Recurrent Pyogenic Cholangitis

Recurrent pyogenic cholangitis is a chronic biliary condition characterized by recurrent episodes of bacterial cholangitis associated with intrahepatic pigment stone formation and biliary strictures, predominantly affecting East Asian populations.

Definition

Recurrent Pyogenic Cholangitis (RPC) is a chronic biliary disease characterised by recurrent bouts of bacterial cholangitis arising from de novo formation of intrahepatic pigment stones within a biliary tree that is progressively damaged by stricturing and dilatation ^[1]^[2]. The name tells you everything:

Recurrent = episodic, comes back again and again
Pyogenic = "pyo" (pus) + "genic" (producing) — pus-forming bacterial infection
Cholangitis = "chol" (bile) + "ang" (vessel) + "itis" (inflammation) — inflammation of the bile ducts

It is also historically known as "Hong Kong disease", oriental cholangiohepatitis, biliary obstruction syndrome of the Chinese, reflecting its strong geographic predilection for Southeast Asia ^[1]^[2].

Key Distinguishing Concept

RPC is fundamentally different from the more common Western pattern of gallstone disease. In typical gallstone disease, cholesterol stones form in the gallbladder and may migrate into the CBD. In RPC, brown pigment (calcium bilirubinate) stones form de novo within the intrahepatic bile ducts — the gallbladder is often a bystander. This distinction is critical for understanding the pathophysiology, clinical approach, and surgical management ^[1]^[2].

Epidemiology

Feature	Detail
Geographic distribution	*Southeast Asia* — Hong Kong, Southern China, Taiwan, Korea, Japan, Vietnam; rare in Western countries ^[1]^[2]
Sex ratio	Equal frequency in males and females ^[1]
Peak age	*30–40 years* (middle-age onset) ^[1]^[2]
Socioeconomic association	Historically linked to lower socioeconomic status, poor sanitation, and dietary factors (raw freshwater fish consumption); incidence declining with improved hygiene but still prevalent in Hong Kong ^[2]
Trend	Decreasing incidence in younger generations due to improved nutrition, sanitation, and public health measures; however, established cases in older patients continue to present

The disease earned the moniker "Hong Kong disease" because of its striking prevalence in Hong Kong and southern China. Any middle-aged patient from Southeast Asia presenting with recurrent cholangitis and intrahepatic stones should have RPC high on the differential.

Risk Factors

Understanding the risk factors requires understanding the two "hits" needed for RPC: something that damages the biliary epithelium and something that promotes biliary stasis and stone formation.

Risk Factor	Mechanism
*Parasitic infestation (Clonorchis sinensis)*	Flukes inhabit biliary tree → chronic epithelial damage → stricture formation → stasis → stone formation ^[1]^[2]^[3]
Low socioeconomic status / malnutrition	Low-protein diet → relative enzyme deficiency → altered bile composition → promotes unconjugated bilirubin precipitation ^[2]
Poor sanitation	Faecal-oral transmission of parasites; consumption of raw/undercooked freshwater fish ^[2]^[3]
Previous biliary instrumentation	ERCP, sphincterotomy, stenting → disruption of Sphincter of Oddi barrier → ascending bacterial colonisation ^[1]
Biliary anomalies	Choledochal cysts, Caroli's disease → congenital biliary stasis → predisposition to stone formation and infection ^[1]

Anatomy and Function — The Biliary Tree

To understand RPC you must understand the biliary tree's anatomy and its normal defence mechanisms, because RPC systematically destroys both.

Biliary Anatomy

Intrahepatic ducts: Small peripheral ducts → segmental ducts → sectoral ducts → right and left hepatic ducts
Extrahepatic ducts: Common hepatic duct (CHD) → joined by cystic duct → common bile duct (CBD) → ampulla of Vater → duodenum
Sphincter of Oddi: Muscular valve at the ampulla that controls bile flow into the duodenum and prevents duodenal reflux — this is critical for understanding ascending infection

Normal Biliary Defence Mechanisms [1]

The bile duct is NOT a sterile pipe — it has active defences:

Continuous flushing action of bile flow — laminar flow physically washes bacteria downstream
Bacteriostatic activity of bile salts — bile salts are detergents that disrupt bacterial cell membranes
Biliary mucous and secretory IgA — act as anti-adherence factors preventing bacterial colonisation of epithelium
Sphincter of Oddi — acts as a mechanical barrier to duodenal reflux and ascending bacterial infection

In RPC, all four mechanisms are compromised: strictures impede flow (loss of flushing), altered bile composition reduces bacteriostatic activity, chronic inflammation damages the mucosa (loss of IgA), and repeated instrumentation may disrupt the sphincter.

Why the Left Lobe?

RPC has a striking predilection for the left intrahepatic ducts ^[2]. Why? The left hepatic duct has a more acute angle of drainage and a longer intrahepatic course compared to the right. This anatomy promotes relative stasis in the left system, making it more susceptible to stone formation and stricturing. Additionally, the left duct is more prone to compression at the umbilical fissure. This is why, in advanced disease, left hepatic lobe atrophy is commonly seen on CT.

Etiology

1. Parasitic Infection (The Historical "First Hit")

Parasitic infestation is considered the initiating event in many cases of RPC, particularly in endemic areas ^[1]^[2]^[3].

Liver Flukes (Trematodes)

Parasite	Transmission	Pathological Mechanism
*Clonorchis sinensis* (Chinese liver fluke)	Consumption of *raw or undercooked freshwater fish* (淡水魚) ^[2]^[3]	Adult flukes inhabit biliary tract → mechanical damage to biliary epithelium → chronic inflammation → stricture formation → eggs deposited in bile ducts serve as nidus for stone formation
*Opisthorchis viverrini*	Raw freshwater fish (mainly Thailand/Laos)	Same mechanism as above
*Fasciola hepatica*	Contaminated watercress/water plants	Migrates through liver parenchyma → biliary tract inflammation

Life cycle of Clonorchis sinensis (relevant for understanding pathogenesis) ^[3]:

Humans = definitive host; adult flukes reside in biliary tract
Embryonated eggs passed in faeces into freshwater
Eggs ingested by freshwater snail (first intermediate host)
Cercariae released → penetrate freshwater fish (second intermediate host) → encysted metacercariae in fish flesh
Humans consume raw/undercooked fish → metacercariae excyst in duodenum → migrate up through ampulla of Vater into bile ducts → mature into adults

Roundworms

Parasite	Mechanism
*Ascaris lumbricoides*	Adult worms can migrate into CBD through ampulla → mechanical obstruction → dead worm/eggs become nidus for stone formation

2. Bacterial Infection (The "Second Hit" and Perpetuator)

Once biliary stasis and epithelial damage are established, bacterial colonisation drives the ongoing cycle of stone formation and recurrent cholangitis ^[1]^[2].

Common organisms:

Category	Organisms
*Gram-negative bacilli* (predominant)	*Escherichia coli, Klebsiella* sp., Proteus sp., *Pseudomonas aeruginosa* ^[1]
*Anaerobes*	Bacteroides fragilis, Clostridium sp. ^[1]
Gram-positive	Enterococcus sp.

Why gram-negatives? Because these are gut organisms. The infection is ascending — bacteria reflux from the duodenum into the biliary tree, especially when the sphincter of Oddi is compromised or when there is stasis.

3. Dietary / Nutritional Factors

Low-protein diet (historically prevalent in Southeast Asian populations) → relative deficiency of glucuronidase inhibitors → allows bacterial β-glucuronidase to act unopposed → promotes deconjugation of bilirubin → unconjugated bilirubin precipitates with calcium → brown pigment stone formation ^[2].

Pathophysiology

This is the crux of understanding RPC. The disease follows a self-perpetuating vicious cycle of Stasis + Stricturing + Recurrent infection ^[1]^[2].

The Vicious Cycle of RPC

Step-by-Step Pathophysiology

Step 1 — Initiating Event: Epithelial Damage

Parasitic infestation (Clonorchis sinensis) or bacterial infection damages the biliary epithelium
The damaged epithelium triggers an inflammatory cascade

Step 2 — Stricture Formation

Repeated cycles of inflammation → healing → fibrosis
Fibrotic strictures develop, predominantly in the small intrahepatic ducts (small ducts are more affected than large ducts) ^[1]
Strictures narrow the duct lumen → obstruction to bile flow

Step 3 — Biliary Stasis

Bile cannot flow past the strictures efficiently
Stagnant bile loses its normal flushing action → bacteria are not cleared

Step 4 — Bacterial Colonisation and Stone Formation

Bacteria (especially E. coli, Klebsiella) produce the enzyme β-glucuronidase
β-glucuronidase hydrolyses conjugated bilirubin (bilirubin diglucuronide) in bile back to unconjugated bilirubin
Unconjugated bilirubin is insoluble and complexes with calcium ions → precipitation as calcium bilirubinate
These aggregates, combined with bacterial cell bodies and cellular debris, form brown pigment stones
Stones contain bacterial cell bodies embedded within them — this is why they are inherently infected stones

Step 5 — Further Obstruction and Recurrence

Stones cause additional obstruction → more stasis → more infection → more stones → more strictures
The cycle is self-perpetuating and progressive

Why Brown Pigment Stones, Not Cholesterol Stones?

In Western gallstone disease, the problem is cholesterol supersaturation in bile → cholesterol stones form in the gallbladder. In RPC, the problem is bacterial enzymatic deconjugation of bilirubin → calcium bilirubinate precipitates → brown pigment stones form de novo within the bile ducts. The stones are soft, earthy, crumbly (because they contain bacterial debris), in contrast to hard cholesterol stones. They are also radio-opaque (contain calcium) versus cholesterol stones which are radiolucent ^[2]^[4].

Brown Pigment Stone Formation — Biochemistry

\text{Conjugated bilirubin (soluble)} \xrightarrow{\text{bacterial } \beta\text{-glucuronidase}} \text{Unconjugated bilirubin (insoluble)} + \text{Glucuronic acid}

\text{Unconjugated bilirubin} + \text{Ca}^{2+} \rightarrow \text{Calcium bilirubinate (precipitate)} \rightarrow \text{Brown pigment stone}

Comparison: RPC vs Western Gallstone Disease

Feature	RPC	Western Gallstone Disease
Stone location	*Intrahepatic bile ducts* (de novo)	Gallbladder (may migrate to CBD)
Stone type	*Brown pigment / Ca bilirubinate*	Cholesterol (85%)
Stone composition	Unconjugated bilirubin + calcium + bacterial debris	Cholesterol crystals
Pathogenic mechanism	Bacterial β-glucuronidase	Cholesterol supersaturation
Radiodensity	*Radio-opaque*	Radiolucent (80%)
Gallbladder involvement	Usually spared (gallbladder is a bystander)	Primary site
Biliary strictures	Present (part of the disease)	Not typical
Geographic distribution	Southeast Asia	Western countries
Sex predilection	Equal M:F	Female predominance (Fat, Female, Forty, Fertile)

Classification

RPC can be classified by several schemes:

1. By Anatomical Distribution

Pattern	Description	Significance
*Left-sided predominant*	Stones and strictures mainly in left hepatic duct system	Most common pattern; left lobe atrophy frequently develops ^[2]
Right-sided predominant	Stones and strictures mainly in right hepatic duct system	Less common
Bilateral	Both left and right systems involved	More advanced disease; surgical options more limited
Extrahepatic involvement	CBD stones and strictures (often secondary)	May coexist with intrahepatic disease

2. By Disease Stage / Severity

Stage	Features
Early	Recurrent cholangitis episodes, intrahepatic stones, mild stricturing
Established	Multiple strictures, segmental/lobar atrophy, recurrent sepsis
Advanced / Complicated	Cirrhosis (secondary biliary), liver abscess, cholangiocarcinoma

3. By Complications

Complication Category	Examples
Acute infectious	Biliary sepsis, liver abscess, pyogenic cholangitis
Chronic structural	Secondary biliary cirrhosis, hepatic atrophy, portal hypertension
Neoplastic	*Cholangiocarcinoma* (major long-term concern) ^[1]^[3]^[5]

Clinical Features

The clinical presentation of RPC reflects the underlying cycle of biliary obstruction and infection.

Typical Clinical Pattern [2]

Middle-aged patient (30–40 years) from Southeast Asia
Recurrent episodes of acute cholangitis — typically 1–2 episodes per year ^[2]
Between episodes, patients may be relatively well
Progressive deterioration over years with accumulating strictures, atrophy, and complications

Symptoms

Symptom	Pathophysiological Basis
*Fever* (with or without chills and rigors) ^[1]	Bacterial infection of bile → endotoxin and bacterial products enter bloodstream → systemic inflammatory response (SIRS) → fever via IL-1, IL-6, TNF-α acting on hypothalamic thermoregulatory centre
*Right upper quadrant (RUQ) or epigastric pain* ^[1]	Biliary obstruction → ductal distension proximal to stone/stricture → stretching of the biliary epithelium and periductal tissues → visceral pain referred to the RUQ/epigastrium via T7-T9 splanchnic afferents. Unlike biliary colic (which is intermittent), RPC pain may be more sustained due to active infection
*Jaundice* ^[1]	Obstruction of bile ducts → impaired excretion of conjugated bilirubin → reflux into bloodstream → conjugated hyperbilirubinaemia → yellow sclera and skin. Degree depends on level and completeness of obstruction
Pruritus	Retained bile salts deposited in skin → stimulation of cutaneous nerve endings. More prominent with prolonged obstruction
Dark urine (tea-coloured)	Conjugated bilirubin is water-soluble → filtered by kidneys → bilirubinuria → dark urine
Pale/clay-coloured stools (acholic)	No bilirubin reaching the gut → no stercobilinogen production → pale stools
Malaise, anorexia, weight loss	Chronic infection, recurrent sepsis, and malabsorption of fat-soluble vitamins (A, D, E, K) due to impaired bile flow
Nausea and vomiting	Visceral irritation from biliary inflammation; may be exacerbated by associated pancreatitis

Signs

Sign	Pathophysiological Basis
*Charcot's triad* (Fever + RUQ pain + Jaundice)	The classic triad of acute cholangitis — present in majority of RPC flares. Fever = infection; pain = obstruction/distension; jaundice = biliary obstruction ^[1]^[2]
Reynold's pentad (Charcot's triad + shock + altered mental status)	Indicates suppurative cholangitis / biliary sepsis — bacteria and endotoxin overwhelm host defences → septic shock (hypotension) + encephalopathy. This is a surgical emergency < 10% of presentations ^[2]
RUQ tenderness	Periductal and hepatic capsular inflammation → localised tenderness on palpation
Hepatomegaly	Biliary obstruction → intrahepatic ductal dilatation → liver swelling; chronic disease → regenerative nodular hyperplasia
*Palpable gallbladder* (exception to Courvoisier's law) ^[4]	In RPC, the essential pathology is in the bile ducts, not the gallbladder. The gallbladder itself does not undergo chronic cholecystitis → it is NOT fibrosed → it CAN distend when the CBD is obstructed. This is why RPC is a classic exception to Courvoisier's law ^[1]^[4]
Jaundice (icterus)	Yellow discolouration of sclera (best detected in natural light) and skin; indicates bilirubin > 34 μmol/L (approximately 2 mg/dL)
Excoriations	Secondary to pruritus from bile salt deposition in skin
Signs of chronic liver disease (in advanced cases)	Spider naevi, palmar erythema, ascites, splenomegaly — develop if secondary biliary cirrhosis has occurred from chronic obstruction

Courvoisier's Law and RPC — A Classic Exception

Courvoisier's Law states: "In painless obstructive jaundice, if the gallbladder is palpable, the cause is unlikely to be gallstones" ^[4]. The reasoning is that chronic gallstones → repeated cholecystitis → fibrosed, contracted gallbladder → cannot distend. In RPC, however: - The pathology is in the bile ducts (not gallbladder) - The gallbladder has NOT undergone chronic cholecystitis - Therefore the gallbladder CAN distend when the CBD is obstructed - RPC is one of three classic exceptions to Courvoisier's law: 1. Double impaction (stone in CBD + stone in cystic duct) 2. Mirizzi syndrome 3. Recurrent pyogenic cholangitis (RPC) ^[1]^[4]

Complications (Overview — will be covered in detail later)

Category	Complications	Mechanism
Acute infectious	*Biliary sepsis, liver abscess*	Infected bile → bacteraemia → sepsis; walled-off intrahepatic infection
Pancreatitis	*Acute biliary pancreatitis*	Stone/sludge impaction at ampulla → pancreatic duct obstruction
Chronic structural	*Secondary biliary cirrhosis, hepatic atrophy*	Chronic obstruction → cholestasis → progressive fibrosis; chronic inflammation → parenchymal loss with compensatory atrophy ^[2]
Fistula	Biliary-enteric fistula	Chronic inflammation eroding through duct wall into adjacent bowel
*Neoplastic*	*Cholangiocarcinoma*	Chronic inflammation → dysplasia-carcinoma sequence; chronic biliary stasis → prolonged exposure to carcinogens in bile ^[1]^[2]^[3]^[5]

The Cholangiocarcinoma Risk

RPC is a well-established risk factor for cholangiocarcinoma ^[3]^[5]. The mechanism is a chronic inflammation-driven dysplasia → carcinoma sequence — analogous to how ulcerative colitis predisposes to colorectal cancer. The association with cholangiocarcinoma is common in Orientals while PSC-associated cholangiocarcinoma is more common in Western populations ^[5]. Any patient with RPC who develops worsening obstructive symptoms, new weight loss, or rising CA 19-9 should be evaluated for superimposed malignancy.

Clonorchis sinensis — Focused Discussion

Given its central role in RPC pathogenesis, Clonorchis sinensis deserves special attention ^[3]:

Feature	Detail
Common name	Chinese liver fluke
Definitive host	Humans
First intermediate host	Freshwater snail
Second intermediate host	*Freshwater fish*
Transmission	*Consumption of raw/undercooked freshwater fish* (淡水魚)
Adult habitat	Biliary tract (intrahepatic bile ducts)
Eggs	Passed in faeces; embryonated
Clinical spectrum	Asymptomatic → acute cholangitis → *RPC* → *increased risk of cholangiocarcinoma* ^[3]
Diagnosis	Stool microscopy for eggs, duodenal aspirate for eggs, USG for adult flukes, intraoperative choledochoscopy for adult flukes ^[3]
Treatment	*Praziquantel 25 mg/kg PO TDS × 1 day* ^[3]

Praziquantel works by increasing cell membrane permeability to calcium in the parasite → tetanic muscle contraction → paralysis and death of the fluke. It is the drug of choice for all trematode infections.

Relevance to Hong Kong

RPC remains highly relevant to clinical practice in Hong Kong:

Historical burden: Hong Kong was historically one of the highest-prevalence areas, hence the name "Hong Kong disease"
Current epidemiology: While incidence is declining due to improved sanitation and nutrition, established cases continue to present, particularly in older patients
Dietary practices: Consumption of raw freshwater fish (sashimi, congee with raw fish) persists in some communities
Association with cholangiocarcinoma — long-term surveillance is essential
Surgical expertise: HKU and other Hong Kong centres have extensive experience in hepatobiliary surgery for RPC, including hepatic resection with biliary-enteric anastomosis

Key Concepts to Remember Before Moving to DDx/Diagnosis/Management:

RPC = intrahepatic pigment stones + strictures + recurrent cholangitis

Vicious cycle: stasis → infection → stone formation → more obstruction → more stasis

Left lobe predilection

Brown pigment stones (NOT cholesterol)

Exception to Courvoisier's law

Long-term risk of cholangiocarcinoma

Clonorchis sinensis is the key parasitic trigger in Hong Kong

High Yield Summary

Definition: RPC = recurrent bacterial cholangitis + intrahepatic pigment stone formation + intrahepatic biliary strictures; also called "Hong Kong disease"
Epidemiology: Southeast Asia, equal M:F, peak 30–40 years
Pathophysiology — Vicious Cycle: Parasitic/bacterial damage → strictures → stasis → bacterial β-glucuronidase deconjugates bilirubin → Ca bilirubinate (brown pigment) stones → further obstruction → recurrent infection
Key Differences from Western Gallstone Disease: Stones form de novo in intrahepatic ducts (not gallbladder); composed of brown pigment (not cholesterol); radio-opaque (not radiolucent)
Left lobe predilection — due to anatomical factors promoting stasis
Clinical Features: Charcot's triad (fever + RUQ pain + jaundice); 1–2 episodes/year; Reynold's pentad if severe sepsis
Exception to Courvoisier's Law: Gallbladder NOT fibrosed (pathology is in ducts) → CAN distend
Clonorchis sinensis: Chinese liver fluke, transmitted by raw freshwater fish, initiates epithelial damage; treated with praziquantel
Major Long-term Complications: Secondary biliary cirrhosis, hepatic atrophy, cholangiocarcinoma
Organisms: E. coli, Klebsiella, Pseudomonas (gram-negatives); anaerobes; Enterococcus

Active Recall - Recurrent Pyogenic Cholangitis

1. What is the fundamental difference between stone formation in RPC versus Western gallstone disease? Explain the mechanism of stone formation in RPC.

Your answer

Show mark scheme

RPC: stones form de novo in intrahepatic bile ducts (not gallbladder); composed of brown pigment (calcium bilirubinate), not cholesterol. Mechanism: bacterial beta-glucuronidase deconjugates bilirubin glucuronide to unconjugated bilirubin, which is insoluble and complexes with calcium to form calcium bilirubinate stones.

2. Describe the vicious cycle of pathogenesis in RPC using three key components.

Your answer

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Stasis + Stricturing + Recurrent infection. Parasitic or bacterial damage causes epithelial injury and stricture formation (fibrosis from repeated inflammation-healing). Strictures cause biliary stasis, promoting bacterial colonisation and beta-glucuronidase-mediated stone formation. Stones cause further obstruction, perpetuating the cycle.

3. Why is RPC a classic exception to Courvoisier's Law?

Your answer

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Courvoisier's Law states palpable gallbladder in painless jaundice is unlikely due to gallstones (because chronic cholecystitis fibroses the gallbladder). In RPC, pathology is in bile ducts, not gallbladder. The gallbladder has not undergone chronic cholecystitis, is not fibrosed, and therefore CAN distend when CBD is obstructed.

4. Name the parasitic organism most commonly implicated in RPC in Hong Kong, its transmission route, and the recommended treatment.

Your answer

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Clonorchis sinensis (Chinese liver fluke). Transmission: consumption of raw or undercooked freshwater fish. Treatment: Praziquantel 25 mg/kg PO TDS for 1 day.

5. Why does RPC have a predilection for the left hepatic lobe?

Your answer

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The left hepatic duct has a more acute angle of drainage and a longer intrahepatic course compared to the right, promoting relative biliary stasis. This makes the left system more susceptible to stone formation and stricturing, leading to left lobe atrophy in advanced disease.

6. What are the three major categories of long-term complications of RPC?

Your answer

Show mark scheme

1. Chronic structural: secondary biliary cirrhosis, hepatic atrophy. 2. Acute infectious: biliary sepsis, liver abscess, pancreatitis. 3. Neoplastic: cholangiocarcinoma (chronic inflammation-driven dysplasia-carcinoma sequence).

References

^[1] Senior notes: felixlai.md (Recurrent pyogenic cholangitis section, pp. 526–528) ^[2] Senior notes: maxim.md (Recurrent pyogenic cholangitis section, pp. 136–137) ^[3] Senior notes: maxim.md (Clonorchis sinensis infection section, p. 138) ^[4] Senior notes: felixlai.md (Courvoisier's law section, p. 568); maxim.md (Courvoisier's Law note, p. 130) ^[5] Lecture slides: WCS 064 - A large liver - by Prof R Poon ^[20191108].doc.pdf (p. 5, Cholangiocarcinoma — association with RPC in Orientals)

Differential Diagnosis of Recurrent Pyogenic Cholangitis

The clinical presentation of RPC — recurrent episodes of fever, RUQ pain, and jaundice (Charcot's triad) — is shared by a number of hepatobiliary conditions. The differential diagnosis should be approached systematically. Think of it this way: any condition that causes biliary obstruction + infection or biliary obstruction + inflammation can mimic RPC. The key is figuring out where the obstruction is, what is causing it, and whether the pattern is truly recurrent with intrahepatic stones ^[1]^[2]^[6].

Framework for Differential Diagnosis

The DDx of RPC is essentially the DDx of recurrent cholangitis and/or intrahepatic biliary disease. We can organise it by:

Conditions presenting with Charcot's triad (fever + RUQ pain + jaundice)
Conditions causing intrahepatic biliary strictures and stones (mimicking the imaging pattern of RPC)
Conditions that are complications of or evolve from RPC itself

Differential Diagnosis Decision Framework

Detailed Differential Diagnosis

1. Choledocholithiasis with Acute Cholangitis (Most Common DDx)

This is the single most important differential and the most common cause of acute cholangitis worldwide ^[6]^[7].

Feature	Choledocholithiasis + Cholangitis	RPC
Stone origin	Gallbladder → migrates to CBD	De novo in intrahepatic ducts ^[1]^[2]
Stone type	Usually cholesterol (mixed)	Brown pigment (Ca bilirubinate) ^[1]
Gallbladder	Often contains stones; may be fibrosed from chronic cholecystitis	Usually spared; NOT fibrosed (exception to Courvoisier's law) ^[4]
Biliary strictures	Not a primary feature	Hallmark feature — intrahepatic strictures with dilatation ^[1]^[2]
Pattern	Usually single episode or few recurrences; resolves after cholecystectomy + CBD clearance	Recurrent (1–2 episodes/year); persists even after stone clearance because strictures reform ^[2]
Imaging	CBD dilatation ± CBD stone; gallstones in GB	Intrahepatic ductal dilatation with focal stricturing, left lobe predilection, ± hepatic atrophy ^[2]
Geography	Worldwide	Southeast Asia ^[1]

Why this distinction matters: In choledocholithiasis, cholecystectomy + CBD clearance is usually curative. In RPC, the disease is in the intrahepatic ducts — simply removing CBD stones does NOT address the underlying strictures and intrahepatic stone burden. Missing RPC and treating it as simple choledocholithiasis leads to persistent recurrence ^[1]^[2].

How to Tell Them Apart

The key distinguishing features of RPC versus simple choledocholithiasis are: (1) intrahepatic stones (not just CBD), (2) intrahepatic strictures, (3) left lobe predilection, (4) pigment stones (not cholesterol), (5) recurrent pattern despite treatment, and (6) patient from Southeast Asia. If the imaging shows a clean gallbladder but intrahepatic ductal dilatation with strictures and stones — think RPC.

2. Liver Abscess (Pyogenic or Amoebic)

Liver abscess can present very similarly to RPC, and indeed liver abscess is also a complication of RPC — so they can coexist ^[8]^[2].

Feature	Liver Abscess	RPC
Fever pattern	Swinging fever, chills and rigors, septic-looking ^[8]	Fever with or without chills; episodic pattern
Jaundice	Not significant (mainly parenchymal disease) ^[8]	Prominent (biliary obstruction)
Hepatomegaly	Tender hepatomegaly ^[8]	May have hepatomegaly but tenderness is RUQ-focused
Key imaging finding	USG: multiloculated cystic mass, no vascularity; CT: double-target sign (rim-enhancing with central hypodensity) ^[8]	USG/CT: dilated ducts with strictures and intrahepatic stones; atrophy
Blood culture	Often positive (Klebsiella, E. coli, Strep milleri) ^[8]	May be positive during acute episodes
Amoebic abscess	Bloody dysentery history; travel to endemic area; anchovy paste-like aspirate; no eosinophilia ^[8]	No dysentery
Biliary stones	Not a primary feature	Hallmark

Why this is important: Liver abscess from RPC is caused by ascending biliary infection (20–30% of pyogenic liver abscess cases arise from biliary sources, including RPC, cholecystitis, and cholangitis) ^[8]. Always look for underlying RPC when you find a liver abscess in a Southeast Asian patient with intrahepatic duct abnormalities.

3. Acute Cholecystitis

Feature	Acute Cholecystitis	RPC
Pain	RUQ pain > 6 hours, positive Murphy's sign ^[9]	RUQ pain, but Murphy's sign typically negative (gallbladder not primarily inflamed)
Fever	Present	Present
Jaundice	Uncommon (unless Mirizzi syndrome or choledocholithiasis coexists)	Prominent
Imaging	USG: distended GB, GB wall thickening > 3mm, pericholecystic fluid, positive sonographic Murphy's sign ^[9]	USG: intrahepatic duct dilatation with stones and strictures; GB usually normal
Key distinction	Pathology is in the gallbladder	Pathology is in the intrahepatic bile ducts

4. Primary Sclerosing Cholangitis (PSC)

PSC and RPC can look remarkably similar on imaging — both cause biliary strictures and dilatation. However, they are fundamentally different diseases ^[6]^[10].

Feature	PSC	RPC
Definition	Chronic progressive inflammation, fibrosis, and stricturing of bile ducts — large ducts more affected than small ducts ^[10]	Recurrent infection-driven stricturing — small intrahepatic ducts more affected ^[1]
Etiology	Autoimmune / unknown	Infectious (parasitic + bacterial)
Geographic predilection	Western countries (rare in Asia) ^[7]^[10]	Southeast Asia ^[1]^[2]
Associated conditions	Strong association with ulcerative colitis (majority of PSC patients have UC) ^[10]	Associated with parasitic infection (Clonorchis sinensis)
IBD association	Yes — ulcerative colitis ^[5]^[10]	No
Stone formation	Not a primary feature (but secondary stones can form)	Primary feature — de novo pigment stones
Cholangiogram appearance	"Beaded" appearance — diffuse multifocal strictures with intervening dilatation, both intrahepatic and extrahepatic	Intrahepatic strictures with left lobe predilection; central dilatation with peripheral tapering ^[2]
Serology	p-ANCA may be positive; ↑ IgG; ANA may be positive	Stool ova and parasites may be positive
Cancer risk	Cholangiocarcinoma (especially perihilar) ^[10]	Cholangiocarcinoma ^[2]^[5]

Why distinguish them: Treatment is completely different. PSC has no proven medical therapy (ursodeoxycholic acid is controversial); management focuses on endoscopic treatment of dominant strictures and liver transplantation for end-stage disease. RPC management centres on stone clearance, biliary drainage, and hepatic resection ^[2]^[10].

PSC vs RPC — The Two Great Biliary Stricturing Diseases

A common exam pitfall is confusing PSC and RPC. Remember: PSC = Western, autoimmune, associated with UC, large ducts primarily affected, rare in Asia ^[7]^[10]. RPC = Oriental, infectious, associated with parasites, small intrahepatic ducts primarily affected, common in Hong Kong ^[1]^[2]. Both predispose to cholangiocarcinoma. PSC is listed as a cause of secondary sclerosing cholangitis when RPC causes similar-looking cholangiographic changes ^[10].

5. Cholangiocarcinoma

This is both a differential diagnosis of RPC and a complication of RPC — the two are intertwined ^[2]^[5]^[11].

Feature	Cholangiocarcinoma	RPC
Presentation	Painless progressive obstructive jaundice in elderly ( > 50 years); RUQ pain, hepatomegaly, jaundice; anorexia, weight loss, fever ^[5]^[11]	Recurrent episodes of painful jaundice with fever in middle-aged patients
Pattern	Progressive, worsening	Episodic, recurrent
Risk factors	Association with UC (common in Westerners) and RPC (common in Orientals) ^[5]; PSC; choledochal cysts; Caroli's disease; thorium dioxide (Thorotrast) ^[11]	Parasitic infection, low socioeconomic status
Tumour markers	CEA and CA 19-9 may be elevated (but nonspecific) ^[5]^[11]	Not elevated (unless cholangiocarcinoma has developed)
Histology	> 90% adenocarcinoma; CK7 positive ^[11]	N/A (no neoplasm)
Key imaging distinction	Mass lesion, hilar obstruction (Klatskin tumour), vascular encasement	Stones + strictures without mass (unless superimposed cholangioCA)

Clinical pearl: Any RPC patient with progressive worsening of jaundice, new weight loss, or rising CA 19-9 should be evaluated urgently for superimposed cholangiocarcinoma ^[2]^[5].

Cholangiocarcinoma: association with ulcerative colitis (common in Westerners) and recurrent pyogenic cholangitis (common in Orientals). Mostly occurs in patients > 50 years. ^[5]

6. Mirizzi Syndrome

Feature	Mirizzi Syndrome	RPC
Definition	Common hepatic duct obstruction caused by extrinsic compression from an impacted stone in Hartmann's pouch/cystic duct ^[4]^[12]	Intrahepatic biliary strictures + stones from chronic infection
Jaundice	Present (CHD obstruction)	Present (intrahepatic obstruction)
Palpable GB	Jaundice with palpable GB — exception to Courvoisier's law ^[12]	Also exception to Courvoisier's law ^[4]
Imaging	USG: dilated biliary tree above stone impaction at GB neck; contracted GB ^[12]	USG: intrahepatic duct dilatation with stones and strictures
Cholecystobiliary fistula	Can develop (Csendes type 2–5) ^[12]	Not a feature
Key distinction	Pathology is at the cystic duct/Hartmann's pouch level; gallbladder is the culprit	Pathology is in the intrahepatic ducts; gallbladder is a bystander

7. Acute Biliary Pancreatitis

Feature	Biliary Pancreatitis	RPC
Pain	Severe epigastric pain radiating to the back	RUQ/epigastric pain
Amylase/Lipase	Markedly elevated ( > 3× ULN)	Normal or mildly elevated
Jaundice	May be present (if stone at ampulla)	Present
Mechanism	Stone impacts at ampulla → pancreatic duct obstruction	Intrahepatic stones + strictures
Key distinction	Elevated pancreatic enzymes; pancreatic inflammation on CT	Intrahepatic ductal disease on imaging

Note: Pancreatitis can also be a complication of RPC if stones/sludge migrate to the ampulla ^[2].

8. Caroli's Disease and Choledochal Cysts

These congenital biliary anomalies can mimic RPC on imaging and also predispose to RPC ^[11]^[13].

Feature	Caroli's Disease	Choledochal Cyst	RPC
Definition	Multiple cystic dilatations of intrahepatic bile ducts (Todani type V) ^[13]	Congenital cystic dilatation of intra/extrahepatic biliary system ^[13]	Acquired intrahepatic strictures + stones
Age at diagnosis	Usually childhood ( < 10 years in 60%) ^[13]	Usually childhood	Middle age (30–40 years)
Complications	Stone formation, cholangitis, cholangiocarcinoma ^[11]^[13]	Pancreatitis, cholangitis, cholangiocarcinoma ^[11]^[13]	Biliary sepsis, cirrhosis, cholangiocarcinoma
Imaging	Saccular intrahepatic duct dilatation ("central dot sign" on CT)	Extrahepatic cystic dilatation (type I most common) ^[13]	Strictures + dilatation + stones, left lobe predilection
Key distinction	Congenital; no strictures per se; saccular dilatation	Congenital; predominantly extrahepatic	Acquired; strictures are the hallmark

9. IgG4-Associated Cholangitis (IAC)

Feature	IgG4-Associated Cholangitis	RPC
Demographics	Mostly elderly male ^[7]	Equal sex, middle-age, Southeast Asian
Mechanism	Infiltration of biliary system with IgG4-positive plasma cells ^[7]	Infectious — parasitic + bacterial
Associated conditions	Autoimmune pancreatitis (type 1); may have multi-organ IgG4 disease	Parasitic infection
Serology	Elevated serum IgG4	Normal IgG4; stool ova and parasites may be positive
Response to steroids	Dramatic response to corticosteroids	No response to steroids
Imaging	Diffuse or segmental bile duct wall thickening; can mimic cholangioCA	Strictures + dilatation + stones

10. Biliary Leaks

Post-operative biliary leaks (e.g., after cholecystectomy or liver surgery) can present with fever, abdominal pain, and jaundice, and should be considered in the post-surgical patient ^[6].

Feature	Biliary Leak	RPC
Context	Post-operative	No surgical history required
Onset	Acute, days after surgery	Chronic, recurrent
Imaging	HIDA scan or MRCP showing biliary leak; biloma on CT/USG	Intrahepatic stones + strictures

Summary Table: Key Differentiating Features

Differential	Key Distinguishing Feature(s) from RPC
Choledocholithiasis + cholangitis	CBD stones from GB migration; cholesterol stones; no intrahepatic strictures; resolves after cholecystectomy
Liver abscess	Focal hepatic lesion; swinging fever; jaundice not prominent; double-target sign on CT
Acute cholecystitis	Murphy's sign positive; GB wall thickening; no intrahepatic duct disease
PSC	Western; autoimmune; UC association; large ducts; beaded cholangiogram; no stones primarily
Cholangiocarcinoma	Progressive painless jaundice; mass lesion; > 50 years; weight loss
Mirizzi syndrome	Stone impacted at Hartmann's pouch/cystic duct; CHD obstruction; cholecystobiliary fistula
Biliary pancreatitis	Markedly elevated amylase/lipase; pancreatic inflammation
Caroli's disease	Congenital; saccular intrahepatic dilatation; childhood presentation
Choledochal cyst	Congenital; predominantly extrahepatic cystic dilatation; childhood
IgG4-associated cholangitis	Elderly male; elevated IgG4; steroid-responsive; autoimmune pancreatitis
Biliary leak	Post-operative context; acute onset

DDx Based on Level of Biliary Obstruction

When you see biliary dilatation on imaging, the level of obstruction guides your differential ^[6]:

Level	Differentials
Hilum	RPC, Klatskin tumour (cholangioCA), CA gallbladder, HCC (segments 4/5), Mirizzi syndrome, porta hepatis lymphadenopathy, PSC ^[6]
Mid-CBD	CA CBD, CA head of pancreas, lymphadenopathy ^[6]
Distal CBD	Bile duct strictures, periampullary carcinoma (duodenum, distal CBD, pancreatic head, ampulla of Vater), choledochal cysts, pancreatic cysts, chronic pancreatitis ^[6]

RPC characteristically causes hilar and intrahepatic obstruction. If you see isolated distal CBD obstruction, think of other diagnoses first (periampullary tumour, choledocholithiasis, chronic pancreatitis).

History-Taking Approach to Narrow the DDx

When faced with a patient presenting with Charcot's triad, the following history points help narrow the differential ^[7]:

Question	Purpose
Ethnicity / country of origin	Southeast Asian → RPC; Western → PSC, choledocholithiasis
Dietary history — raw freshwater fish?	Clonorchis sinensis exposure → RPC
Recurrence pattern — how many episodes?	Recurrent (1–2/year) → RPC; single episode → choledocholithiasis
Previous biliary surgery or ERCP	Post-procedural → biliary leak, stent occlusion, iatrogenic stricture
IBD history (bloody diarrhoea, UC)	PSC is strongly associated with UC ^[10]
Weight loss, progressive jaundice	Malignancy (cholangioCA, pancreatic CA)
Stool colour / urine colour	Tea-coloured urine + pale stool = obstructive jaundice (surgical cause) ^[7]; normal coloured = medical cause
Pain character	Colicky → stone; dull persistent → abscess/tumour; radiating to back → pancreatitis
Age	Middle-age → RPC; elderly with painless jaundice → malignant biliary obstruction until proven otherwise ^[7]

Painless Progressive Obstructive Jaundice in the Elderly

Painless progressive obstructive jaundice in elderly is malignant biliary obstruction until proven otherwise ^[7]. This is a crucial clinical pearl. RPC typically presents with painful jaundice and fever in a middle-aged patient. If the jaundice is painless, progressive, and the patient is > 50, think cholangiocarcinoma, pancreatic head CA, or periampullary tumour first.

High Yield Summary — Differential Diagnosis

Most important DDx: Choledocholithiasis with acute cholangitis — differentiate by stone location (CBD vs intrahepatic), stone type (cholesterol vs pigment), presence of strictures, and recurrence pattern
Liver abscess can mimic AND complicate RPC — look for swinging fever, tender hepatomegaly, double-target sign on CT; jaundice is NOT prominent in isolated liver abscess
PSC vs RPC: PSC = Western, autoimmune, UC association, large duct disease, rare in Asia. RPC = Oriental, infectious, parasitic association, small duct disease, common in Hong Kong
Cholangiocarcinoma is both a DDx and a complication — progressive painless jaundice + weight loss in a patient > 50; associated with UC (Westerners) and RPC (Orientals)
Congenital causes (Caroli's disease, choledochal cysts) present in childhood; can predispose to RPC
Level of obstruction guides DDx: RPC causes hilar/intrahepatic obstruction; distal obstruction → think periampullary tumours
Exception to Courvoisier's law: Both RPC and Mirizzi syndrome are exceptions — but the mechanism differs (RPC: gallbladder not fibrosed because pathology is in ducts; Mirizzi: stone at Hartmann's pouch compresses CHD)

Active Recall - DDx of Recurrent Pyogenic Cholangitis

1. Name 6 conditions in the differential diagnosis of a patient presenting with recurrent fever, RUQ pain, and jaundice.

Your answer

Show mark scheme

Any 6 of: (1) Choledocholithiasis with acute cholangitis, (2) Liver abscess, (3) Acute cholecystitis, (4) PSC, (5) Cholangiocarcinoma, (6) Mirizzi syndrome, (7) Biliary pancreatitis, (8) Caroli's disease, (9) Choledochal cyst, (10) IgG4-associated cholangitis, (11) Biliary leak.

2. How do you differentiate PSC from RPC? Give 4 distinguishing features.

Your answer

Show mark scheme

PSC: (1) Western population, rare in Asia; (2) Autoimmune etiology; (3) Strong association with UC; (4) Large ducts more affected than small ducts; (5) No primary stone formation. RPC: (1) Southeast Asian; (2) Infectious etiology (parasitic/bacterial); (3) Small intrahepatic ducts more affected; (4) De novo pigment stone formation; (5) Left lobe predilection.

3. A 65-year-old man presents with painless progressive jaundice and weight loss. What is the most likely category of diagnosis, and why does this differ from RPC?

Your answer

Show mark scheme

Malignant biliary obstruction until proven otherwise (e.g. cholangiocarcinoma, pancreatic head CA, periampullary tumour). Differs from RPC because RPC presents with PAINFUL jaundice + fever in MIDDLE-AGED patients (30-40 years) from Southeast Asia, with a recurrent episodic pattern rather than progressive worsening.

4. Liver abscess can both mimic and complicate RPC. Name 3 clinical features that help distinguish an isolated liver abscess from an acute RPC flare.

Your answer

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(1) Swinging fever pattern (vs episodic fever in RPC); (2) Tender hepatomegaly is dominant sign (vs RUQ pain + jaundice in RPC); (3) Jaundice is NOT prominent in isolated liver abscess (parenchymal disease) vs prominent in RPC (biliary obstruction); (4) CT shows double-target sign (rim-enhancing lesion) vs dilated ducts with stones and strictures.

5. What is the significance of the level of biliary obstruction in differential diagnosis? Where does RPC typically cause obstruction?

Your answer

Show mark scheme

Level of obstruction narrows the DDx. RPC typically causes HILAR and INTRAHEPATIC obstruction (strictures in small intrahepatic ducts, left lobe predilection). Hilar DDx includes: Klatskin tumour, CA gallbladder, HCC, Mirizzi syndrome, PSC, porta hepatis LN. Isolated DISTAL CBD obstruction suggests periampullary tumours, chronic pancreatitis, or choledocholithiasis instead.

References

^[1] Senior notes: felixlai.md (Recurrent pyogenic cholangitis section, pp. 526–527) ^[2] Senior notes: maxim.md (Recurrent pyogenic cholangitis section, pp. 136–137) ^[4] Senior notes: felixlai.md (Courvoisier's law section, p. 568); Senior notes: maxim.md (Courvoisier's Law note, p. 130) ^[5] Lecture slides: WCS 064 - A large liver - by Prof R Poon ^[20191108].doc.pdf (p. 5, Cholangiocarcinoma) ^[6] Senior notes: felixlai.md (Causes of biliary obstruction and level of obstruction, pp. 499–501) ^[7] Senior notes: maxim.md (Obstructive jaundice differential diagnosis, p. 135; Acute cholangitis section, pp. 135–136) ^[8] Senior notes: maxim.md (Liver abscess section, p. 125); Senior notes: felixlai.md (Liver abscess section, p. 436) ^[9] Senior notes: maxim.md (Symptomatic gallstones summary table, p. 130) ^[10] Senior notes: felixlai.md (Primary sclerosing cholangitis section, pp. 529–530) ^[11] Senior notes: felixlai.md (Cholangiocarcinoma etiology and pathogenesis, pp. 547–548); Senior notes: maxim.md (Cholangiocarcinoma risk factors, p. 139) ^[12] Senior notes: maxim.md (Mirizzi syndrome section, p. 132) ^[13] Senior notes: maxim.md (Choledochal cyst section, p. 138)

Diagnostic Criteria for Acute Cholangitis (Applied to RPC)

There is no standalone "diagnostic criteria" set for RPC per se — instead, the diagnosis of an acute RPC flare uses the diagnostic criteria for acute cholangitis (based on the Tokyo Guidelines, TG18/TG13), combined with imaging findings that are characteristic of the underlying RPC disease pattern. Think of it in two layers:

Layer 1: Is this acute cholangitis? → Apply the Tokyo Guidelines criteria
Layer 2: Is the underlying cause RPC? → Look for the characteristic imaging triad of intrahepatic stones + intrahepatic strictures + left lobe predilection

Tokyo Guidelines Diagnostic Criteria for Acute Cholangitis [6][7]

These criteria apply to any acute cholangitis episode, including those caused by RPC.

Suspected Diagnosis

The patient must have BOTH of the following ^[6]:

Criterion A (Systemic inflammation)	Criterion B (Cholestasis/biliary injury)
ONE of: Fever or shaking chills OR Laboratory evidence of inflammatory response (abnormal WBC, ↑ CRP, or other inflammatory markers)	ONE of: Jaundice OR Abnormal liver chemistries (↑ AST/ALT/ALP/GGT)

Definite Diagnosis

In addition to meeting criteria for suspected diagnosis, the patient must have BOTH of the following ^[6]:

Criterion C (Biliary dilatation)	Criterion D (Etiology identified)
Biliary dilatation on imaging	Evidence of an etiology on imaging: stone, stricture, or stent

Applying TG18 to RPC

In RPC, the "definite diagnosis" criteria are almost always met during acute flares because imaging shows both biliary dilatation (from stricture-induced obstruction) and the etiology (intrahepatic stones and strictures). The challenge is not whether the patient has cholangitis — it's recognising that the underlying pattern is RPC rather than simple choledocholithiasis. This requires careful imaging interpretation.

Severity Grading (TG18) — Important for Guiding Urgency of Drainage

Grade	Criteria	Clinical Significance
Grade I (Mild)	Does not meet criteria for Grade II or III; responds to initial antibiotic therapy	Conservative management
Grade II (Moderate)	Any 2 of: WBC > 12 or < 4 ×10⁹/L, fever ≥ 39°C, age ≥ 75, bilirubin ≥ 85 μmol/L (5 mg/dL), albumin < 0.7× lower limit of normal	Early biliary drainage recommended
Grade III (Severe)	Organ dysfunction in any ONE system: cardiovascular (hypotension requiring vasopressors), neurological (altered consciousness), respiratory, renal (oliguria, Cr > 176 μmol/L), hepatic (PT-INR > 1.5), haematological (platelets < 100 ×10⁹/L)	Urgent biliary drainage — this is Reynold's pentad territory ^[6]^[7]

Reynold's pentad (Charcot's triad + shock + altered mental status) corresponds to Grade III severity and requires emergent biliary drainage — delay leads to multiorgan failure and death ^[6]^[7].

Diagnostic Features Specific to RPC (Layer 2)

Once acute cholangitis is confirmed, the following features on investigation point specifically to RPC rather than other causes ^[1]^[2]:

Feature	Explanation
Intrahepatic stones (not just CBD stones)	Stones formed de novo within intrahepatic ducts — pathognomonic
Intrahepatic biliary strictures with proximal dilatation	Fibrotic narrowing from repeated infection-healing cycles
Central dilated bile ducts with peripheral tapering	Classic CT finding — central ducts dilated, peripheral ducts narrowed by strictures ^[2]
Left lobe predilection	Due to anatomical drainage angle promoting stasis ^[2]
Hepatic atrophy (usually left lobe)	Chronic obstruction and parenchymal destruction ^[2]
Absence of gallbladder stones (typically)	Stones form in ducts, not gallbladder — distinguishes from choledocholithiasis
Brown pigment stones (on ERCP/choledochoscopy)	Soft, earthy, calcium bilirubinate — not cholesterol
Recurrent history	1–2 episodes per year over many years ^[2]
Southeast Asian ethnicity	Strong geographic predilection ^[1]

Diagnostic Algorithm

Overall Approach

The diagnostic workup of a suspected RPC flare follows a logical stepwise approach: clinical assessment → bloods → initial imaging (USG) → advanced imaging (CT/MRCP) → cholangiography (ERCP/PTC) if therapeutic intervention needed ^[1]^[2]^[6]^[7]^[14].

Investigation Modalities — Detailed Breakdown

A. Bedside and Physical Examination

Before any bloods or imaging, the clinical examination itself provides crucial information:

Finding	Significance	Pathophysiological Basis
Charcot's triad (fever + RUQ pain + jaundice)	Strongly suggests acute cholangitis ^[6]	Infection + obstruction + biliary backflow
Reynold's pentad (+ shock + confusion)	Grade III severity — needs urgent drainage ^[6]^[7]	Sepsis → endotoxaemia → cardiovascular collapse + encephalopathy
Palpable gallbladder	Exception to Courvoisier's law — suggests RPC (not chronic cholecystitis) ^[4]	Gallbladder not fibrosed (disease is in ducts) → can distend with CBD obstruction
Hepatomegaly	Intrahepatic ductal dilatation; may also indicate abscess	Biliary obstruction → back-pressure → liver swelling
Signs of chronic liver disease	Suggests secondary biliary cirrhosis (advanced RPC)	Chronic biliary obstruction → progressive fibrosis

B. Laboratory Investigations

B1. Blood Tests

Test	Expected Findings in RPC	Why This Test? (Pathophysiological Rationale)
CBC with differentials	Leukocytosis with neutrophil predominance ^[6]^[14]	Bacterial infection → bone marrow releases neutrophils → left shift. Thrombocytopenia if sepsis-associated DIC or hypersplenism from cirrhosis
CRP / ESR	↑ ESR and CRP ^[6]	Acute phase reactants produced by the liver in response to IL-6; CRP useful for monitoring treatment response
LFT	↑ ALP and GGT (cholestatic pattern); ↑ conjugated bilirubin; mild ↑ AST/ALT ^[6]^[14]	ALP and GGT are enzymes concentrated in the biliary epithelium — obstruction causes back-pressure and induction of these enzymes. Conjugated bilirubin rises because it is synthesised but cannot be excreted past the obstruction. AST/ALT may be mildly elevated from hepatocellular injury secondary to cholestasis
RFT	May show ↑ creatinine in severe cases	Renal impairment from sepsis (hepatorenal syndrome in cirrhotic patients) or direct nephrotoxicity from cholestasis
Clotting profile	Coagulopathy (prolonged PT/INR) ^[4]^[14]	Why? Bile cannot reach the intestine → cannot emulsify fats → cannot absorb fat-soluble vitamins (A, D, E, K) → Vitamin K is a co-factor for factors II, VII, IX, X → deficiency causes prolonged PT. This is critical to check before any invasive procedure like ERCP or PTBD
Blood culture (×2 sets BEFORE antibiotics)	May grow E. coli, Klebsiella, Enterococcus, Pseudomonas ^[7]	Blood culture is essential — guides targeted antibiotic therapy. Take before starting empirical antibiotics. Positive bile cultures are common with bile duct stones and other causes of obstruction ^[6]
Amylase / Lipase	Usually normal; elevated if concurrent pancreatitis	Rule out biliary pancreatitis (stone at ampulla → pancreatic duct obstruction) ^[7]
Stool for ova and parasites	May detect Clonorchis sinensis eggs ^[2]^[3]	Identifies the parasitic trigger — important for targeted treatment (praziquantel) and epidemiological understanding

The Cholestatic Pattern — Explained from First Principles

Why ALP and GGT rise more than AST/ALT in biliary obstruction:

ALP (alkaline phosphatase) is an enzyme found on the canalicular surface of hepatocytes (the bile duct-facing surface). When bile backs up, this membrane is disrupted → ALP leaks into blood. Additionally, bile acids that accumulate act as detergents that solubilise ALP from the membrane.
GGT (gamma-glutamyl transferase) is concentrated in the biliary epithelium itself. Obstruction → epithelial damage → GGT release. GGT is also induced by bile acids.
AST/ALT are cytoplasmic enzymes of hepatocytes — they rise primarily with hepatocellular damage (e.g., hepatitis). In cholestasis, the hepatocyte itself is not the primary target, so these rise only mildly from secondary back-pressure injury.
Conjugated (direct) bilirubin rises because the hepatocyte conjugates bilirubin normally, but the conjugated product cannot be excreted through the obstructed ducts → refluxes back into the bloodstream → conjugated hyperbilirubinaemia.

B2. Tumour Markers (When Cholangiocarcinoma is Suspected)

Marker	Interpretation
CEA and CA 19-9	May or may not be elevated; nonspecific ^[5]^[14]
Serial assay after resection	Might aid in diagnosis of persistent or recurrent disease ^[14]

Tumour Markers — NOT for Screening

CEA and CA 19-9 are NOT useful as screening tools for malignant biliary obstruction ^[14]. They are neither sensitive nor specific. The absence of an elevated tumour marker does NOT exclude underlying malignancy ^[14]. Their role is in serial monitoring after resection to detect recurrence.

B3. Urinalysis

Finding	Significance
Bile in urine (conjugated bilirubin)	Conjugated bilirubin is water-soluble → filtered by kidneys when serum levels rise → bilirubinuria → dark "tea-coloured" urine. Confirms obstructive (post-hepatic) jaundice ^[6]
Absent urobilinogen	No bilirubin reaching the gut → no urobilinogen produced → none reabsorbed → absent in urine. Helps distinguish obstructive from hepatocellular jaundice

C. Imaging Investigations

This is the cornerstone of RPC diagnosis. The goals of imaging are:

Confirm biliary obstruction (dilatation)
Identify the cause (stones, strictures)
Map the extent of disease (which segments affected, atrophy)
Detect complications (abscess, cholangiocarcinoma)
Plan intervention (drainage route, surgical resection)

C1. Transabdominal Ultrasound (USG) — First-Line Imaging

USG is the initial imaging modality for any patient with suspected biliary disease ^[1]^[2]^[7].

Finding	Description	Significance
Dilated intrahepatic ducts	Parallel channel sign (dilated duct running alongside portal vein branches); intrahepatic ducts normally < 2–3 mm and not visible on USG ^[14]	Confirms biliary obstruction
Intrahepatic stones	Hyperechoic foci within dilated ducts ± posterior acoustic shadowing	Direct visualisation of RPC stones; brown pigment stones may be less echogenic than cholesterol stones
Liver abscess	Hypoechoic or complex cystic lesion within liver parenchyma	Complication of RPC — must rule out ^[1]^[2]
Gallbladder	Usually normal (no stones, no wall thickening)	Helps distinguish from cholecystitis/choledocholithiasis
CBD dilatation	CBD > 8 mm (or > 0.1 cm per decade of age) ^[14]	May be present if extrahepatic component exists

Limitations of USG:

Distal CBD often obscured by bowel gas ^[14] — cannot reliably see ampullary pathology
May miss small intrahepatic stones
Operator-dependent
Acute obstruction — duct may not yet have time to dilate → false negative ^[6]

C2. CT Abdomen (with Contrast) — Second-Line / Staging

CT provides more anatomical detail than USG and is critical for surgical planning and complication detection ^[1]^[2].

Finding	Description	Significance
Central dilated bile ducts with peripheral tapering	Dilated central intrahepatic ducts that narrow peripherally due to strictures	Classic CT finding of RPC ^[2] — the strictures are peripheral, so central ducts dilate while peripheral ducts are narrowed
Left lobe predilection	Disease predominantly affecting left hepatic lobe	Characteristic of RPC ^[2]
Hepatic atrophy (usually left lobe)	Volume loss of the affected hepatic lobe	Chronic obstruction → parenchymal destruction → atrophy with compensatory hypertrophy of the contralateral lobe ^[1]^[2]
Intrahepatic calculi	Hyperdense foci within dilated ducts	Brown pigment stones are radio-opaque (contain calcium)
Liver abscess	Rim-enhancing hypodense lesion (double-target sign) ^[8]	Complication
Suspicious mass	Irregular enhancing mass within or adjacent to strictured duct	Raises concern for superimposed cholangiocarcinoma ^[5]

Why CT is important in RPC specifically: CT demonstrates whether disease is localised (usually to the left lobe) and whether atrophy has developed ^[1] — both critical factors in deciding whether hepatic resection is indicated.

C3. Magnetic Resonance Cholangiopancreatography (MRCP) — Biliary Mapping

MRCP is a non-contrast, T2-weighted MRI sequence that provides exquisite detail of the biliary tree without any invasive intervention ^[14].

Feature	Detail
Technique	Non-contrast, T2-weighted — bile appears bright (hyperintense) because it is fluid ^[14]
Advantages	Non-invasive; permits detailed visualisation of extent of biliary involvement which may not be possible by ERCP when there are extensively occluded segments ^[1]; no radiation; no contrast needed
Limitations	Does NOT permit therapeutic interventions ^[1] — purely diagnostic
Key findings in RPC	Intrahepatic duct dilatation and strictures; stone burden mapping; extent of disease (unilateral vs bilateral); biliary anatomy before surgery
When to use	When USG is equivocal but clinical suspicion remains high; for preoperative biliary mapping; when ERCP cannot access occluded segments ^[1]^[6]

MRCP vs ERCP — Understanding the Trade-off

MRCP has largely replaced ERCP as a diagnostic tool ^[14]. ERCP carries procedural risks (pancreatitis, perforation, bacteraemia), so it should be reserved for when therapeutic intervention is planned. MRCP gives you the anatomy for free — use it first for mapping, then deploy ERCP when you need to drain, stent, or extract stones.

C4. Endoscopic Retrograde Cholangiopancreatography (ERCP) — Diagnostic AND Therapeutic

ERCP is both diagnostic and therapeutic and is the first-line intervention for acute biliary drainage ^[1]^[6]^[7].

Feature	Detail
Technique	Endoscope advanced to duodenum → cannulation of ampulla of Vater → contrast injection → fluoroscopic visualisation of biliary tree
Diagnostic role	Confirm diagnosis; show level and cause of obstruction; delineate biliary anatomy ^[6]
Therapeutic role	Biliary drainage and decompression (the primary goal in acute setting); sphincterotomy; stricture balloon dilatation; stone extraction; stent placement ^[1]^[7]
Key RPC-specific finding	Multiple intrahepatic and extrahepatic stones; strictures; soft brown pigment stones
Prophylactic antibiotics required	Due to risk of inciting cholangitis or sepsis following manipulation of bile ducts ^[1]
Bile culture	Can aspirate bile during ERCP for culture and sensitivity — guides antibiotic therapy ^[6]

Challenges of ERCP in RPC ^[1]:

Endoscopic intervention is challenging due to multiple intrahepatic and extrahepatic stones as well as stricturing ^[1]
ERCP accesses the biliary tree from below (retrograde) — it is inherently limited in reaching intrahepatic ducts, especially those above tight strictures
ERCP difficult to access intrahepatic drainage ^[2] — this is why PTBD is often needed

ERCP procedure in acute cholangitis ^[7]:

Aspirate bile duct to remove bile and pus → decompress biliary tree → reduces risk of bacteraemia during contrast injection
Then inject contrast and visualise anatomy
Place plastic stent (temporary, requires scheduled change) with or without sphincterotomy
Stone removal can be done now or deferred (interval ERCP after sepsis resolves)

Role of ERCP in unstable patients is biliary drainage and decompression — NOT stone removal ^[7]. The priority is to relieve obstruction and control sepsis. Definitive stone clearance comes later.

C5. Percutaneous Transhepatic Cholangiography / Biliary Drainage (PTC/PTBD)

PTBD is preferred to ERCP when the obstruction is at or above the level of confluence of hepatic ducts — which is often the case in RPC ^[14].

Feature	Detail
Technique	Percutaneous needle inserted through the liver parenchyma into a dilated intrahepatic duct → contrast injection for cholangiography → guidewire → catheter placement for drainage
Diagnostic role	Visualisation of biliary tree above the obstruction (where ERCP cannot reach) ^[14]
Therapeutic role	Bile drainage by catheter (PTBD) or insertion of indwelling stents ^[14]
When preferred over ERCP	Stricture/obstruction at or above the level of confluence of hepatic ducts ^[14]; ERCP unsuccessful or contraindicated; examples include cholangiocarcinoma, PSC, RPC ^[14]
Advantage over ERCP for RPC	Transhepatic insertion of intrahepatic bile duct (directly accesses the intrahepatic disease, not limited by retrograde access) ^[7]; easy output monitoring (external drainage) ^[7]
Complications	Bacteraemia (thus antibiotic prophylaxis required) ^[14]; haemobilia; bile leak; pneumothorax (if right-sided approach)
Disadvantage	Risk of fluid and electrolyte loss (external drainage) ^[7]; patient discomfort from external catheter

C6. Choledochoscopy (Intraoperative or Percutaneous)

Feature	Detail
Technique	Direct endoscopic visualisation of bile duct lumen — either during surgery (intraoperative choledochoscopy) or percutaneously through a mature PTBD tract
Role in RPC	Direct visualisation and removal of intrahepatic stones; inspection for strictures; detection of adult Clonorchis sinensis flukes ^[3]; biopsy of suspicious lesions (r/o cholangiocarcinoma)
Advantage	Can reach intrahepatic ducts that ERCP and PTBD cannot; allows direct stone fragmentation and extraction

C7. Endoscopic Ultrasound (EUS)

Feature	Detail
Role	Useful adjunct for choledocholithiasis detection; staging periampullary and pancreatic cancers ^[14]; therapeutic EUS (EUS-guided cholangiopancreatography) as alternative drainage when ERCP fails ^[7]
Limitation in RPC	Less useful for mapping intrahepatic disease specifically; better for extrahepatic and periampullary pathology

C8. Other Imaging

Modality	Role
Erect CXR	Aerobilia (air in biliary tree — suggests prior sphincterotomy or biliary-enteric fistula); right basal effusion/collapse (if liver abscess present) ^[7]
AXR (Abdominal X-ray)	Radio-opaque calculi in RUQ (brown pigment stones contain calcium → may be visible); aerobilia ^[7]
MRI liver with contrast	Liver-specific contrast (e.g., Primovist/gadoxetic acid) — superior to CT in detecting small hepatocellular lesions; useful if cholangiocarcinoma suspected

Summary: Imaging Modalities Comparison for RPC

Modality	Pros	Cons	When to Use
USG	Non-invasive, bedside, cheap, no radiation, first-line	Operator-dependent; misses distal CBD; misses small stones	Always first
CT	Anatomical detail; detects atrophy, abscess, mass; staging	Radiation; IV contrast needed; less biliary detail than MRCP	Surgical planning; r/o complications
MRCP	Best non-invasive biliary mapping; no contrast/radiation	Not therapeutic; cannot intervene	Biliary anatomy mapping; pre-op planning
ERCP	Diagnostic AND therapeutic; gold standard for drainage	Invasive; risks (pancreatitis, perforation, sepsis); limited intrahepatic access	Acute drainage; stone removal
PTBD	Directly accesses intrahepatic ducts; external drainage	Invasive; bacteraemia risk; fluid/electrolyte loss	When ERCP fails or obstruction at/above confluence
Choledochoscopy	Direct visualisation; stone removal; biopsy capability	Requires mature tract or surgical access	Intraoperative; complex stone disease
EUS	Good for CBD/periampullary; therapeutic alternative	Limited intrahepatic reach	Adjunct; ERCP failure

QMH Practice Algorithm for Biliary Drainage [6]

The Queen Mary Hospital (HKU-affiliated) approach to biliary drainage in cholangitis follows this stepwise escalation:

QMH practice: ERCP → PTBD → ECBD ^[6]

ERCP — first attempt at biliary decompression
PTBD — if ERCP fails (e.g., cannot access intrahepatic ducts through strictures) or contraindicated
ECBD (Exploration of CBD) — surgical exploration with T-tube placement if both ERCP and PTBD fail; high mortality (~30%) ^[7] — reserved as last resort

Investigation Checklist for RPC — Practical Summary

When you see a patient with suspected RPC, here is the complete workup:

Immediate (Acute presentation):

Blood culture ×2 (BEFORE antibiotics) ^[7]
CBC D/C, CRP
LFT (ALP, GGT, bilirubin, AST, ALT)
RFT
Clotting profile (PT/INR)
Amylase (r/o pancreatitis)
USG abdomen (first-line imaging) ^[1]^[2]
Erect CXR (r/o perforation, right basal pathology) ^[7]

After initial stabilisation:

Stool for ova and parasites ^[2]
CT abdomen with contrast (if surgical planning needed or suspecting complications) ^[1]^[2]
MRCP (biliary mapping, especially if ERCP cannot visualise occluded segments) ^[1]

For therapeutic intervention / acute drainage:

ERCP (first-line for drainage; prophylactic antibiotics required) ^[1]^[6]
PTBD (if ERCP fails or obstruction above confluence) ^[7]^[14]

For suspected superimposed malignancy:

CEA and CA 19-9 (nonspecific; serial monitoring more useful) ^[5]^[14]
CT/MRI for mass characterisation
FNAC or Trucut biopsy (ONLY for unresectable cases) ^[5]
Choledochoscopy with biopsy

For long-term surveillance:

Regular USG surveillance ^[2]
Serial tumour markers if cholangiocarcinoma risk is high

High Yield Summary — Diagnosis of RPC

Diagnostic criteria: Use Tokyo Guidelines (TG18) for acute cholangitis — Suspected: systemic inflammation + cholestasis; Definite: + biliary dilatation + etiology on imaging
Severity grading matters: Grade III (organ dysfunction / Reynold's pentad) → urgent biliary drainage
RPC-specific imaging pattern: Intrahepatic stones + strictures + central dilatation with peripheral tapering + left lobe predilection + hepatic atrophy
Blood tests: Cholestatic pattern LFT (↑ ALP, GGT, conjugated bilirubin); leukocytosis; blood culture BEFORE antibiotics; clotting (Vitamin K deficiency); stool ova and parasites
Imaging hierarchy: USG first → CT for staging/complications → MRCP for biliary mapping → ERCP for therapeutic drainage
MRCP does NOT permit therapeutic interventions — use it for mapping, not treatment
ERCP prophylactic antibiotics required due to risk of inciting cholangitis
PTBD preferred over ERCP when obstruction at or above hepatic duct confluence — directly accesses intrahepatic disease
QMH practice: ERCP → PTBD → ECBD (stepwise escalation)
Tumour markers (CEA, CA 19-9) are NOT useful for screening — absence does not exclude malignancy; useful for serial monitoring post-resection

Active Recall - Diagnosis of RPC

1. State the Tokyo Guidelines diagnostic criteria for 'suspected' and 'definite' acute cholangitis.

Your answer

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Suspected: (A) ONE of fever/chills OR lab evidence of inflammation (abnormal WBC/raised CRP) AND (B) ONE of jaundice OR abnormal liver chemistries (raised AST/ALT/ALP/GGT). Definite: meets suspected criteria PLUS BOTH biliary dilatation on imaging AND evidence of etiology (stone, stricture, or stent) on imaging.

2. What is the classic CT finding in RPC and why does it occur?

Your answer

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Central dilated bile ducts with peripheral tapering, with left lobe predilection and hepatic atrophy. Occurs because fibrotic strictures narrow the peripheral intrahepatic ducts (from repeated inflammation-healing), causing proximal central duct dilatation. Left lobe is preferentially affected due to anatomical angle promoting stasis.

3. Why must prophylactic antibiotics be given before ERCP in RPC patients?

Your answer

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Manipulation of bile ducts during ERCP can incite cholangitis or sepsis by introducing contrast under pressure into an already infected and obstructed biliary system, promoting bacteraemia. The obstructed biliary tree contains infected bile, and instrumentation disrupts barriers. Antibiotics reduce the risk of iatrogenic sepsis.

4. Explain why PTBD is preferred over ERCP when biliary obstruction is at or above the hepatic duct confluence. Give a clinical example.

Your answer

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ERCP accesses the biliary tree retrogradely from below (via duodenum and ampulla) and is limited in reaching intrahepatic ducts above tight strictures. PTBD is inserted percutaneously through the liver directly into dilated intrahepatic ducts, providing direct access above the obstruction. Examples: RPC (intrahepatic strictures), cholangiocarcinoma (Klatskin tumour), PSC.

5. A patient with RPC has prolonged PT/INR. Explain the mechanism and why this is important to check before ERCP.

Your answer

Show mark scheme

Biliary obstruction prevents bile from reaching intestine, impairing fat emulsification and absorption of fat-soluble vitamins (A, D, E, K). Vitamin K is a co-factor for synthesis of clotting factors II, VII, IX, X. Deficiency leads to coagulopathy (prolonged PT/INR). Must be corrected before invasive procedures like ERCP or PTBD to prevent haemorrhagic complications.

6. Compare the roles of MRCP and ERCP in the investigation of RPC.

Your answer

Show mark scheme

MRCP: Non-invasive, non-contrast T2-weighted MRI. Best for detailed biliary mapping, especially occluded segments ERCP cannot reach. Does NOT permit therapeutic interventions. ERCP: Invasive but both diagnostic AND therapeutic. Gold standard for biliary drainage, sphincterotomy, stent placement, stone removal. Limited intrahepatic access. Requires prophylactic antibiotics. MRCP is used for mapping; ERCP is reserved for intervention.

References

^[1] Senior notes: felixlai.md (Recurrent pyogenic cholangitis — Diagnosis section, pp. 526–528) ^[2] Senior notes: maxim.md (Recurrent pyogenic cholangitis section, pp. 136–137) ^[3] Senior notes: maxim.md (Clonorchis sinensis infection section, p. 138) ^[4] Senior notes: felixlai.md (Courvoisier's law section, p. 568); Senior notes: maxim.md (Courvoisier's Law note, p. 130) ^[5] Lecture slides: WCS 064 - A large liver - by Prof R Poon ^[20191108].doc.pdf (p. 5, Cholangiocarcinoma diagnosis — tumour markers, USG, CT, MRI, FNAC) ^[6] Senior notes: felixlai.md (Acute cholangitis — Diagnosis and Treatment, pp. 520–523) ^[7] Senior notes: maxim.md (Acute cholangitis — Investigations and acute management, pp. 135–136) ^[8] Senior notes: maxim.md (Liver abscess section, p. 125) ^[14] Senior notes: felixlai.md (MBO — Biochemical and Radiological tests, pp. 502–503); Senior notes: maxim.md (HBP investigations, pp. 121–122)

Management of Recurrent Pyogenic Cholangitis

The management of RPC must be understood in two distinct phases, because the disease has two faces:

Acute phase: Treat the cholangitis flare — this is an emergency
Long-term phase: Break the vicious cycle of stasis → infection → stones → strictures → more stasis — this requires definitive intervention

The fundamental principle is that you cannot cure RPC with antibiotics alone. Why? Because the underlying problem is mechanical — strictures and stones cause obstruction and stasis, and antibiotics cannot clear stones or open strictures. Furthermore, excretion of antibiotics is impaired in biliary obstruction ^[15]^[16] — the very antibiotics you give cannot reach therapeutic concentrations in the obstructed bile, making biliary drainage mandatory ^[16].

Management Algorithm — Overview

Phase 1: Acute Management — "RAD"

The mnemonic RAD captures the three pillars of acute cholangitis management ^[7]:

R = Resuscitation, A = Antibiotics, D = Drainage — must know! ^[7]

1. Resuscitation

Component	Detail	Rationale
NPO (Nil per os)	Keep patient fasting	Reduces biliary stimulation (CCK release → gallbladder contraction → increased biliary pressure); prepares for potential emergency ERCP
IV fluids	Aggressive crystalloid resuscitation (e.g., Ringer's lactate / normal saline)	Biliary sepsis → vasodilatation + third-spacing → intravascular volume depletion → organ hypoperfusion. Fluids restore circulating volume
Monitor vitals and I/O Q1h ^[7]	Continuous monitoring of temperature, pulse, BP, consciousness level, urine output ^[6]	Detects signs of failure of conservative treatment: ↑ temperature/pulse, ↓ BP/consciousness/urine output, increased abdominal tenderness and guarding ^[6]
Correct coagulopathy	IV Vitamin K (phytomenadione 10 mg slow IV)	Obstructive jaundice → impaired fat-soluble vitamin absorption → Vitamin K deficiency → coagulopathy. Must correct before any invasive procedure

Why Monitor So Closely?

15% of patients will NOT respond to antibiotics and will require emergency biliary decompression ^[6]. You need to catch this deterioration early. The signs of failure include rising temperature, tachycardia, falling BP, falling urine output, worsening tenderness, and altered consciousness — essentially progression towards Reynold's pentad.

2. Antibiotics

Principles of Antibiotic Selection

The empirical regimen must cover the organisms that cause RPC cholangitis: Gram-negative aerobes (E. coli, Klebsiella, Pseudomonas) and anaerobes (Bacteroides) ^[1]^[6].

Why not just one antibiotic? Because the bile duct in RPC harbours a polymicrobial environment, and inadequate coverage leads to treatment failure and fulminant sepsis.

Empirical Antibiotic Regimens

Regimen	Coverage	When to Use
IV Cefuroxime + Metronidazole ^[15]	Cefuroxime: Gram-negative aerobes; Metronidazole: anaerobes	Standard HK regimen for mild–moderate disease
IV Piperacillin-Tazobactam (Tazocin) ^[7]^[15]	Broad-spectrum: Gram-negatives including Pseudomonas + anaerobes	Severe disease or Reynold's pentad
IV Ampicillin-Sulbactam (Augmentin)	Gram-negatives + anaerobes	Mild disease ^[7]
IV Metronidazole + 3rd-gen cephalosporin (e.g., Ceftriaxone) ^[6]	Ceftriaxone: Gram-negatives; Metronidazole: anaerobes	Alternative regimen
IV Metronidazole + Fluoroquinolone (e.g., Ciprofloxacin/Levofloxacin) ^[6]	Fluoroquinolone: Gram-negatives; Metronidazole: anaerobes	Penicillin allergy

Duration: Typically 7 days of IV antibiotics ^[7], then step down to oral based on culture and sensitivity results.

Why Antibiotics Alone Are Not Enough

Biliary obstruction impairs the excretion of antibiotics into bile ^[16]. Normal biliary pressure is 7–14 cm H₂O. When pressure rises > 25 cm H₂O (due to obstruction), bacteria reflux into hepatic veins and lymphatics → bacteraemia and septic shock ^[16]. Even high-dose IV antibiotics cannot achieve adequate biliary concentrations when the duct is obstructed. This is why biliary drainage is mandatory ^[16] — you must physically decompress the system.

Targeted Antibiotic Therapy

Adjust based on blood/bile culture and sensitivity results
If Clonorchis sinensis identified on stool O&P: add praziquantel 25 mg/kg PO TDS × 1 day ^[3]

3. Drainage — The Critical Step

Biliary drainage is the definitive acute intervention — it addresses the mechanical obstruction that antibiotics cannot fix ^[16].

Indications for Urgent Drainage [7]

Reynold's pentad (Charcot's triad + shock + altered mental status)
Not responding to antibiotics for 24 hours ^[7]
- Why 24 hours? Because obstruction impairs antibiotic secretion into bile — if there's no improvement in 24h, it means the obstruction is not resolving spontaneously and drainage is mandatory

Drainage Modalities — Stepwise Escalation

The QMH (Queen Mary Hospital) stepwise approach ^[6]:

QMH practice: ERCP → PTBD → ECBD ^[6]

3A. ERCP — First-Line Drainage

ERCP is the first-line approach for biliary drainage in acute cholangitis ^[6]^[7]^[15].

Aspect	Detail
Procedure	Endoscope to D2 → cannulate ampulla → aspirate bile/pus → inject contrast → visualise obstruction → intervene
Role in acute setting	Biliary drainage and decompression in unstable patients — NOT stone removal ^[7]
Step 1	Aspirate bile duct to remove bile and pus → decompress → reduces risk of bacteraemia during contrast injection ^[7]
Step 2	Inject contrast → delineate anatomy
Step 3	Place plastic stent (temporary, requires scheduled change) with or without sphincterotomy ^[7]
Step 4	Remove stone now or interval ERCP after sepsis resolves ^[7]
Mortality	< 5% ^[7]

ERCP Procedures in Detail

a) Endoscopic Sphincterotomy ^[6]

What: Electrocautery incision through the musculature of the biliary portion of the Sphincter of Oddi
Why: Eliminates the principal anatomic barrier impeding stone passage; facilitates stone extraction; allows future access
Complications:
- Short-term: Acute pancreatitis, perforation (intraperitoneal or retroperitoneal), bleeding from papillotomy, infection ^[6]^[15]
  - Intraperitoneal perforation: Perforate the duodenum → free gas under diaphragm on CXR → requires operative treatment (will not seal spontaneously) ^[6]
  - Retroperitoneal perforation: Perforate the bile duct when cutting the ampulla (retroperitoneal portion of D2) → no free gas under diaphragm → retroperitoneal gas may be present → conservative treatment (will seal spontaneously) ^[6]
- Long-term: Acute cholangitis recurrence, stone recurrence, papillary stenosis ^[6]

b) Stricture Balloon Dilatation ^[1]

Balloon inflated across stricture to widen the lumen
Important in RPC because strictures are the primary mechanical problem

c) Biliary Stent Placement ^[1]

Plastic stent (temporary) — requires scheduled exchange (every 3 months typically, as plastic stents occlude with biofilm/sludge)
Purpose: maintains biliary drainage through the strictured segment
Initial biliary decompression is achieved by ERCP with sphincterotomy, stricture dilatation and placement of biliary endoprosthesis (stent) often required ^[1]

d) Stone Extraction Methods ^[15]

Method	Description
Wire basket (Dormia basket)	Wire cage deployed around stone → trapped → extracted through sphincterotomy
Stone extraction balloon	Balloon inflated above stone → swept downward through sphincterotomy
Mechanical lithotripsy	For large stones → mechanical crushing within the duct

Challenges of ERCP in RPC [1]

Endoscopic intervention is challenging due to multiple intrahepatic and extrahepatic stones as well as stricturing ^[1]. Key issues:

ERCP accesses from below (retrograde) → limited access to intrahepatic ducts above tight strictures
ERCP difficult to access intrahepatic drainage ^[2] — the disease in RPC is predominantly intrahepatic
Multiple strictures may prevent passage of the scope or instruments
Patients in whom adequate drainage cannot be achieved during ERCP will require percutaneous or surgical drainage ^[1]

Relative Contraindications for ERCP [15]

Altered GI anatomy e.g. Billroth II gastrectomy, Roux-en-Y ^[15] — the altered anatomy makes cannulation of the ampulla technically very difficult or impossible.

3B. PTBD — Second-Line Drainage

PTBD is indicated when ERCP is unsuccessful, unavailable, or contraindicated ^[6]^[7].

Aspect	Detail
Technique	Percutaneous needle through liver parenchyma → puncture dilated intrahepatic duct under USG/fluoroscopic guidance → confirm position with contrast → insert guidewire → catheter placement ^[6]
Access route	Usually via left hepatic duct (preferred — subcostal approach is less painful than intercostal for right duct; less likely to transgress pleural space) or right hepatic duct; can also access through gallbladder puncture ^[6]
Key advantage for RPC	Transhepatic insertion directly into intrahepatic bile ducts — directly accesses the intrahepatic disease that ERCP cannot reach ^[7]
Therapeutic capabilities	Drainage of infected bile; extraction of biliary stones; dilatation of benign strictures; stent placement across strictures ^[6]
Efficacy	Similar efficacy and rate of complications as ERCP ^[7]
Output monitoring	Easy output monitoring — external drainage ^[7], but can be internalised later (external-internal PTBD)
Complications	Bacteraemia (antibiotic prophylaxis required); haemobilia (puncture of hepatic artery or portal vein); bile leak; pneumothorax ^[6]^[14]
Disadvantages	Risk of fluid and electrolyte loss (external bile drainage) ^[7]; patient discomfort from external catheter; requires patent intrahepatic duct dilatation for safe access

The reason PTBD is particularly useful in RPC compared to simple choledocholithiasis is that the disease is in the intrahepatic ducts, and PTBD goes directly to the problem. ERCP approaches from below and is limited by strictures blocking retrograde access.

3C. Surgical Drainage — Third-Line (Last Resort)

Surgical drainage for acute cholangitis is reserved for patients in whom other methods of biliary drainage cannot be performed or have failed ^[6].

Procedure	Detail
Exploration of Common Bile Duct (ECBD)	Open (emergency) or laparoscopic (selected elective cases) → choledochotomy → stone removal → T-tube placement for ongoing drainage and future cholangiography ^[6]^[15]
Indications	Failure of endoscopic drainage; deterioration despite endoscopic drainage ^[15]
T-tube	Placed in CBD after exploration → provides ongoing bile drainage → allows subsequent cholangiogram to check for residual stones
Mortality	~30% ^[7] — this is why surgery is the last resort for acute cholangitis
Approach	Open approach for emergency case; laparoscopic approach in selected elective case ^[15]

Why Is Surgical Drainage So Dangerous?

The high mortality (~30%) of surgical CBD exploration in acute cholangitis ^[7] is because these patients are already septic, often with organ dysfunction (Grade III severity). General anaesthesia in a septic patient compounds haemodynamic instability. The combination of sepsis + surgical stress + coagulopathy (Vitamin K deficiency from obstruction) + impaired wound healing (from cholestasis-related protein synthesis impairment) makes operative mortality very high. This is why the stepwise escalation ERCP → PTBD → surgery is so important — exhaust less invasive options first.

Other Acute Drainage Options

Modality	Role
T-tube drainage	Can be placed during ECBD or through a mature PTBD tract; allows ongoing external drainage and access for cholangiography ^[2]
Hepaticocutaneojejunostomy (HCJ)	A surgical technique creating a conduit from intrahepatic bile ducts through a Roux-en-Y jejunal loop to the skin surface — allows future percutaneous access for repeat stone clearance without needing ERCP ^[2]. Used in complex RPC with recurrent stone formation
Therapeutic EUS (EUS-guided cholangiopancreatography)	Alternative when ERCP fails — EUS-guided puncture of bile duct from duodenum/stomach → guidewire → stent ^[7]

Phase 2: Long-Term / Definitive Management

Once the acute episode is controlled, the focus shifts to breaking the vicious cycle and preventing long-term complications (cirrhosis, cholangiocarcinoma).

A. Regular Ductal Clearance (Non-Operative)

Strategy	Detail	Rationale
USG surveillance	Regular interval ultrasound (e.g., every 6–12 months) ^[2]	Monitor for stone recurrence, new strictures, hepatic atrophy, suspicious masses (cholangioCA)
Interval ERCP	Scheduled ERCP sessions to remove stones and dilate strictures ^[2]	Reduces stone burden and relieves obstruction — breaks the stasis → infection → stone cycle
Percutaneous choledochoscopy	Through a mature PTBD or HCJ tract → direct visualisation and stone extraction	Allows repeated access to intrahepatic ducts for clearance without repeated ERCP

B. Hepatobiliary Resection + Biliary-Enteric Anastomosis (Definitive Surgery)

This is the cornerstone of definitive management for RPC when disease is localised and the non-operative approach fails or complications arise ^[1]^[2].

Indications for Surgical Resection [2]

Indication	Rationale
Atrophic liver segment	The segment is non-functional, harbours stones and strictures, and serves as a persistent source of infection. Removing it eliminates the diseased reservoir ^[2]
Failed non-operative treatment	Recurrent cholangitis despite regular ERCP/PTBD stone clearance → the strictures and stones are too extensive for endoscopic management alone ^[2]
Suspected cholangiocarcinoma	Chronic inflammation → dysplasia → carcinoma. Resection is both diagnostic and therapeutic — removes the at-risk tissue ^[2]

Surgical Procedures

a) Hepatobiliary Resection ^[1]

Resection of the hepatobiliary segments with the aim to resect areas of recurrent infection, biliary stasis and hepatic atrophy ^[1]
Typically involves left hepatectomy (or left lateral sectionectomy) given the left lobe predilection of RPC
May involve segmentectomy if disease is more localised
Removes the entire diseased segment — strictures, stones, atrophic parenchyma, and potential pre-malignant tissue

b) Biliary-Enteric Anastomosis ^[1]

Procedure	Description	Role in RPC
Hepaticojejunostomy (HJ)	Anastomosis of the hepatic duct to a Roux-en-Y jejunal loop	Frequently required in RPC ^[1] — provides wide drainage of the remaining biliary tree into the jejunum, bypassing any residual extrahepatic strictures
Choledochoduodenostomy	Anastomosis of CBD to duodenum	Contraindicated in RPC — residual strictured biliary segments may not be drained adequately ^[1]
Choledochojejunostomy	Anastomosis of CBD to jejunum	Also contraindicated in RPC — same reason; does not address intrahepatic disease above the anastomosis ^[1]

Why Hepaticojejunostomy and NOT Choledochoduodenostomy/Choledochojejunostomy?

Standard biliary drainage procedures such as choledochoduodenostomy or choledochojejunostomy are contraindicated in RPC since residual strictured biliary segments may not be drained adequately ^[1]. The problem in RPC is intrahepatic — connecting the CBD to the bowel does nothing for strictured intrahepatic segments above the anastomosis. Hepaticojejunostomy connects at a higher level (at the hepatic duct), and when combined with resection of the diseased segments, ensures that the remaining healthy biliary tree drains adequately.

c) Hepaticocutaneojejunostomy (HCJ) ^[2]

A specialised procedure where a Roux-en-Y jejunal loop is brought to the skin (subcutaneous) as a future access loop
Purpose: allows repeated percutaneous access for choledochoscopy and stone clearance through the subcutaneous loop without needing ERCP or reoperation
Particularly useful in patients with diffuse bilateral disease where complete resection is not possible but ongoing stone clearance is needed

C. Anti-Parasitic Treatment

Condition	Treatment	Rationale
Clonorchis sinensis infection	Praziquantel 25 mg/kg PO TDS × 1 day ^[3]	Eliminates the parasitic trigger that initiated and perpetuates epithelial damage → breaks the vicious cycle at its origin

D. Nutritional Support

Intervention	Rationale
Adequate protein intake	Low-protein diet was the historical risk factor → relative enzyme deficiency → promotes stone formation. Improving nutrition may reduce stone recurrence
Fat-soluble vitamin supplementation (A, D, E, K)	Chronic biliary obstruction → malabsorption of fat-soluble vitamins. Vitamin K specifically to prevent coagulopathy

Management Summary by Phase

Phase	Priorities	Key Interventions
Acute (RAD)	Control sepsis, relieve obstruction	Resuscitation (NPO, IV fluids, monitoring); Antibiotics (Augmentin/Tazocin/Cefuroxime+Metro); Drainage (ERCP → PTBD → ECBD) ^[6]^[7]
Subacute (post-sepsis)	Complete stone clearance, map disease extent	Interval ERCP for stone removal; CT/MRCP for surgical planning; stool O&P; anti-parasitic Rx
Long-term (definitive)	Break the vicious cycle, prevent complications	Regular ductal clearance (USG surveillance + ERCP) ^[2]; Hepatobiliary resection + HJ if indicated ^[1]^[2]; anti-parasitic treatment
Surveillance	Detect cholangiocarcinoma early	Regular USG; serial CA 19-9 if indicated; low threshold for CT/MRI if new symptoms

Special Considerations

Monitoring for Treatment Failure [6]

During the acute phase, continuously monitor for signs that conservative treatment is failing:

Sign	Implication
↑ Temperature / Pulse	Worsening sepsis
↓ BP / Consciousness / Urine output	Progression to septic shock (Reynold's pentad)
Increased abdominal tenderness and guarding	Potential biliary perforation, peritonitis, or liver abscess formation

Definitive treatment should be deferred until cholangitis has been treated and the proper diagnosis is established ^[6]. Never rush to definitive surgery during acute sepsis — stabilise first.

Post-ERCP Complications to Watch For [15]

Complication	Presentation	Management
Post-ERCP fever and tachycardia	DDx: persistent cholangitis (unsuccessful drainage, migrated/blocked stent, resistant organisms), flare-up sepsis, pancreatitis, perforation ^[15]	AXR (stent position), repeat imaging, consider re-intervention
Post-ERCP abdominal pain	DDx: post-ERCP pancreatitis (elevated amylase/lipase), perforation	CT abdomen (retroperitoneal free gas) ^[15]; conservative vs surgical management depending on type

Issue	Detail
Stent occlusion	Sludge, biofilm, tumour ingrowth (metallic stents) → recurrent cholangitis → requires stent exchange
Stent migration	Stent displaces distally into duodenum or proximally into duct → loss of drainage → recurrent symptoms
Patients with indwelling stents and cholangitis	Usually require repeated imaging and stent removal and replacement ^[6]

Comparison: Drainage Modalities

Feature	ERCP	PTBD	ECBD (Surgical)
Access	Retrograde (from duodenum)	Antegrade (percutaneous through liver)	Direct (open abdomen)
Best for	CBD/extrahepatic stones	Intrahepatic obstruction (above confluence)	Failure of both ERCP and PTBD
Therapeutic capability	Sphincterotomy, stone removal, stent	Drainage, stent, stone removal	Complete exploration + T-tube
RPC-specific limitation	Difficult intrahepatic access ^[1]^[2]	Requires dilated ducts for safe puncture	High mortality (~30%) ^[7]
Relative C/I	Altered GI anatomy (Billroth II, Roux-en-Y) ^[15]	Coagulopathy, ascites, non-dilated ducts	Haemodynamic instability
Mortality	< 5% ^[7]	Similar to ERCP ^[7]	~30% ^[7]

Treatment of Underlying Cause — Cholangitis From Biliary Obstruction (From First Principles)

To truly understand why this management works, recall the pathophysiology from the lecture slides ^[16]:

Normal ductal pressure: 7–14 cm H₂O. Increased biliary pressure > 25 cm H₂O → bacteria reflux to hepatic veins and lymphatics → bacteraemia and septic shock. Excretion of antibiotics impaired in biliary obstruction. Biliary drainage is mandatory. ^[16]

This explains everything:

Why antibiotics alone fail: They cannot be excreted into bile when the ducts are obstructed → cannot achieve therapeutic concentrations at the site of infection
Why drainage is mandatory: Must physically reduce biliary pressure below 25 cm H₂O → stops bacterial reflux into the bloodstream → allows antibiotics to work
Why decompression is urgent in Reynold's pentad: The patient already has bacteraemia and septic shock → every hour of delay worsens outcomes

High Yield Summary — Management of RPC

Acute management = RAD: Resuscitation (NPO, IV fluids, monitor Q1h) → Antibiotics (Augmentin for mild / Tazocin for severe / Cefuroxime + Metronidazole × 7 days) → Drainage (urgent if Reynold's pentad or no response to antibiotics in 24h)
QMH drainage escalation: ERCP → PTBD → ECBD (surgical exploration has ~30% mortality — last resort)
ERCP role in acute setting: Biliary drainage and decompression — NOT stone removal. Aspirate pus/bile first, then contrast, then plastic stent
PTBD preferred when intrahepatic obstruction — directly accesses intrahepatic ducts that ERCP cannot reach
Biliary drainage is mandatory because antibiotic excretion is impaired in biliary obstruction and biliary pressure > 25 cm H₂O causes bacteraemia
15% of patients will NOT respond to antibiotics → need emergency drainage
Definitive surgery: Hepatobiliary resection + hepaticojejunostomy — indications: atrophic segment, failed non-op Tx, suspected cholangioCA
Choledochoduodenostomy and choledochojejunostomy are CONTRAINDICATED in RPC because residual strictured segments are not drained adequately
Definitive treatment deferred until cholangitis resolved — never operate on a septic patient for definitive surgery
Anti-parasitic: Praziquantel 25 mg/kg TDS × 1 day for Clonorchis sinensis
Long-term: Regular ductal clearance (USG surveillance + interval ERCP); HCJ for repeated percutaneous access

Active Recall - Management of RPC

1. State the RAD mnemonic for acute cholangitis management and expand each component with specific details.

Your answer

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R = Resuscitation: NPO, IV fluids, monitor vitals and I/O Q1h, correct coagulopathy with Vitamin K. A = Antibiotics: IV broad-spectrum (Augmentin for mild, Tazocin for severe, or Cefuroxime + Metronidazole) for 7 days, adjust based on culture. D = Drainage: urgent if Reynold's pentad or no response to antibiotics in 24h. Escalation: ERCP 1st line, PTBD 2nd line, ECBD 3rd line.

2. Explain from first principles why biliary drainage is mandatory in acute cholangitis and antibiotics alone are insufficient.

Your answer

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Normal biliary pressure is 7-14 cm H2O. Obstruction raises pressure above 25 cm H2O, causing bacteria to reflux into hepatic veins and lymphatics, leading to bacteraemia and septic shock. Biliary obstruction impairs excretion of antibiotics into bile, so they cannot reach therapeutic concentrations at the infection site. Physical drainage is needed to reduce pressure, stop bacterial reflux, and allow antibiotics to work.

3. Why is hepaticojejunostomy the preferred biliary-enteric anastomosis in RPC, and why are choledochoduodenostomy and choledochojejunostomy contraindicated?

Your answer

Show mark scheme

RPC involves intrahepatic strictured segments. Choledochoduodenostomy and choledochojejunostomy connect at the CBD level, which does not drain residual strictured intrahepatic segments above the anastomosis. Hepaticojejunostomy connects at a higher level (hepatic duct), and when combined with resection of diseased segments, ensures adequate drainage of the remaining healthy biliary tree.

4. List the three indications for hepatobiliary resection with biliary-enteric anastomosis in RPC.

Your answer

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1. Atrophic liver segment (non-functional, harbours stones and infection). 2. Failed non-operative treatment (recurrent cholangitis despite ERCP/PTBD). 3. Suspected cholangiocarcinoma (removes at-risk tissue, both diagnostic and therapeutic).

5. What is the QMH stepwise drainage approach for acute cholangitis, and what is the approximate mortality of each level?

Your answer

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ERCP (1st line, mortality less than 5%) then PTBD (2nd line, similar efficacy and complication rate to ERCP) then ECBD/surgical exploration (3rd line, mortality approximately 30%). Surgery reserved for failure of both ERCP and PTBD.

6. A patient with RPC develops post-ERCP fever and tachycardia. What are the differential diagnoses and how would you investigate?

Your answer

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DDx: (1) Persistent cholangitis from unsuccessful drainage, migrated or blocked stent, resistant organisms; (2) Flare-up sepsis/bacteraemia from biliary manipulation; (3) Post-ERCP pancreatitis; (4) Perforation (intraperitoneal or retroperitoneal). Investigate with: AXR (check stent position, free gas), blood cultures, amylase/lipase, CT abdomen (retroperitoneal free gas if perforation suspected).

References

^[1] Senior notes: felixlai.md (Recurrent pyogenic cholangitis — Treatment section, pp. 527–528) ^[2] Senior notes: maxim.md (Recurrent pyogenic cholangitis — Management section, pp. 136–137) ^[3] Senior notes: maxim.md (Clonorchis sinensis infection — Treatment, p. 138) ^[6] Senior notes: felixlai.md (Acute cholangitis — Treatment section, pp. 522–525) ^[7] Senior notes: maxim.md (Acute cholangitis — Acute management RAD, pp. 135–136) ^[14] Senior notes: felixlai.md (MBO — PTBD section, pp. 504–505) ^[15] Lecture slides: GC 200. RUQ pain, jaundice and fever Cholecytitis and cholangitis Imaging of GI system.pdf (pp. 13–15, Acute cholangitis management, ERCP, surgical treatment) ^[16] Lecture slides: Malignant biliary obstruction.pdf (pp. 15–17, Cholangitis pathophysiology, biliary pressure, antibiotic excretion, management principles)

Complications of Recurrent Pyogenic Cholangitis

The complications of RPC can be understood as the downstream consequences of the disease's vicious cycle — stasis, stricturing, and recurrent infection — playing out across different timescales. Some complications are acute (from each cholangitis flare), some are chronic (from cumulative damage over years), and one is neoplastic (the dreaded end-stage transformation). Additionally, there are complications arising from the treatment itself (iatrogenic) ^[1]^[2]^[17].

A helpful way to organise these is by category and by timeline:

A. Acute Complications

These arise during or shortly after each cholangitis flare. They are direct consequences of acute biliary obstruction + bacterial infection.

1. Biliary Sepsis

Aspect	Detail
Definition	Systemic infection originating from the infected biliary tree — bacteraemia progressing to sepsis and septic shock ^[1]^[2]^[17]
Mechanism	Biliary obstruction → biliary pressure rises above 25 cm H₂O → bacteria reflux into hepatic veins and lymphatics → bacteraemia and septic shock ^[16]. The obstructed biliary system becomes a pressurised reservoir of infected bile. Gram-negative endotoxin enters the systemic circulation → activates complement, coagulation cascades, and inflammatory mediators (TNF-α, IL-1, IL-6) → SIRS → sepsis → multiorgan dysfunction
Clinical presentation	Reynold's pentad: Charcot's triad (fever + RUQ pain + jaundice) + shock (hypotension) + altered mental status (confusion) ^[6]. Present in < 10% of patients but carries very high mortality
Why it's dangerous	Excretion of antibiotics is impaired in biliary obstruction ^[16] — even appropriate antibiotics cannot reach adequate biliary concentrations. Without drainage, antibiotics alone cannot control the infection
Management	Urgent biliary drainage is mandatory ^[16] — ERCP (first-line) → PTBD → ECBD. Aggressive resuscitation, vasopressors if needed, broad-spectrum IV antibiotics

Biliary Sepsis — The Most Feared Acute Complication

Biliary sepsis is the leading cause of acute mortality in RPC. The combination of an obstructed, pressurised biliary system and polymicrobial infection creates a perfect storm for overwhelming sepsis. 15% of patients will NOT respond to antibiotics ^[6] and require emergency drainage. Any RPC patient with Reynold's pentad should be treated as a surgical emergency.

2. Liver Abscess

Aspect	Detail
Definition	Localised collection of pus within the hepatic parenchyma, arising from ascending biliary infection ^[8]^[17]
Mechanism	Infected bile under pressure → bacteria track along intrahepatic biliary radicles → penetrate into adjacent liver parenchyma → walled-off pus collection. Ascending biliary infection accounts for 20–30% of pyogenic liver abscesses ^[8], and RPC is a major cause in Southeast Asia
Common organisms	E. coli, Klebsiella pneumoniae (common in > 60 years + DM), Streptococcus milleri ^[8]
Clinical features	Swinging fever, chills and rigors, septic-looking; tender hepatomegaly; jaundice is not as prominent as in cholangitis alone (the abscess is primarily a parenchymal problem) ^[8]
Diagnosis	USG: hypoechoic/complex cystic mass, no vascularity. CT abdomen with contrast: double-target sign (rim-enhancing with central hypodensity), cluster sign ^[8]. Blood culture, CRP for monitoring
Can be distant	Abscess formation at distant sites including lungs and brain ^[17] — haematogenous seeding from bacteraemia. If the patient develops neurological symptoms or respiratory deterioration during an RPC flare, think of metastatic abscess
Management	IV antibiotics (Augmentin or ceftriaxone + metronidazole for ≥ 4–6 weeks ^[8]); percutaneous drainage (needle aspiration if < 5 cm, catheter if > 5 cm) ^[8]; address the underlying biliary obstruction

Liver Abscess vs Acute Cholangitis — They Often Coexist

In RPC, liver abscess and acute cholangitis frequently coexist. Always perform USG/CT to rule out liver abscess when treating an RPC flare ^[1]^[7]. The management of the abscess (percutaneous drainage + prolonged antibiotics) is in addition to biliary drainage for the cholangitis — missing one while treating the other leads to treatment failure.

3. Acute Biliary Pancreatitis

Aspect	Detail
Definition	Acute pancreatitis triggered by biliary stones/sludge impacting at the ampulla of Vater ^[2]^[17]
Mechanism	Stone or sludge from the intrahepatic/extrahepatic ducts migrates distally → impacts at the ampulla → obstructs the pancreatic duct → premature activation of pancreatic enzymes (trypsinogen → trypsin) within the pancreatic parenchyma → autodigestion → acute pancreatitis
Why it occurs in RPC	Result of passage of biliary stones ^[17]. Although RPC stones primarily form in intrahepatic ducts, fragments or sludge can migrate down into the CBD and impact at the ampulla. The disrupted sphincter from prior ERCPs also facilitates stone passage
Clinical features	Severe epigastric pain radiating to the back, nausea/vomiting, markedly elevated amylase/lipase ( > 3× ULN)
Management	Supportive (NPO, IV fluids, analgesia); early ERCP if concurrent cholangitis; address the underlying biliary pathology

4. Rupture of Obstructed Bile Ducts

Aspect	Detail
Definition	Rupture of obstructed pus-filled bile ducts into the peritoneum ^[17]
Mechanism	Severe obstruction → biliary pressure rises markedly → the wall of a pus-filled, dilated bile duct becomes necrotic from infection and ischaemia → perforation → infected bile and pus leak into the peritoneal cavity → biliary peritonitis
Clinical features	Sudden worsening of abdominal pain, generalised tenderness, guarding, board-like rigidity (peritonism), septic shock
Diagnosis	CT: free fluid in peritoneal cavity, discontinuity of bile duct wall
Management	Surgical emergency — peritoneal lavage + biliary drainage + antibiotics

This is a rare but catastrophic complication. The bile duct is essentially a pressurised tube of pus, and when it bursts, it contaminates the entire peritoneal cavity.

B. Chronic / Progressive Complications

These develop insidiously over years from the cumulative effect of repeated obstruction, infection, and inflammation.

5. Secondary Biliary Cirrhosis

Aspect	Detail
Definition	Cirrhosis (irreversible fibrosis with regenerative nodules) resulting from chronic, prolonged biliary obstruction ^[2]^[17]
Mechanism	Chronic biliary obstruction → persistent cholestasis → bile acids accumulate in hepatocytes → hepatocyte injury → periductal fibrosis → bridging fibrosis → cirrhosis. The bile acids are detergent molecules — when they cannot be excreted, they damage the hepatocyte membranes from within. Additionally, recurrent cholangitis episodes cause periductal inflammation and fibrosis that progressively extends into the parenchyma
Timeline	Takes years to decades of recurrent obstruction. This is why RPC patients who present at age 30–40 may develop cirrhosis by their 50s–60s if the disease is not adequately managed
Consequences	Portal hypertension (varices, ascites, splenomegaly), synthetic failure (hypoalbuminaemia, coagulopathy), hepatorenal syndrome, hepatic encephalopathy
Clinical features	Spider naevi, palmar erythema, ascites, splenomegaly, caput medusae, jaundice (now from hepatocellular failure rather than just obstruction)
Key point	This is a preventable complication — adequate biliary drainage and definitive surgery (hepatic resection + HJ) can arrest progression before cirrhosis develops

6. Hepatic Atrophy

Aspect	Detail
Definition	Volume loss of a hepatic lobe or segment due to chronic obstruction and parenchymal destruction ^[1]^[2]
Mechanism	Chronic obstruction of intrahepatic ducts in a particular segment → persistent cholestasis and ischaemia → hepatocyte death → parenchymal collapse → fibrotic replacement → volume loss. The contralateral lobe undergoes compensatory hypertrophy
Predilection	Left lobe (reflecting the left-sided predominance of RPC) ^[2]
Imaging	CT: small, atrophic left lobe with dilated ducts and stones; hypertrophied right lobe
Significance	An atrophic segment is non-functional, harbours infection and stones, and serves as a persistent source of sepsis. It is also at risk for malignant transformation. This is one of the key indications for hepatic resection ^[2]

7. Portal Vein Thrombosis

Aspect	Detail
Definition	Thrombosis within the portal vein or its branches ^[17]
Mechanism	Chronic periductal inflammation from recurrent cholangitis → inflammatory damage to the portal vein (which runs alongside the bile ducts in the portal triad) → endothelial injury → activation of coagulation cascade → thrombus formation. Additionally, biliary sepsis causes a systemic pro-coagulant state (DIC, sepsis-associated coagulopathy). Hepatic atrophy and fibrosis also reduce portal flow, promoting stasis (Virchow's triad: stasis + endothelial injury + hypercoagulability — all present in RPC)
Consequences	Worsens portal hypertension → variceal bleeding, ascites; can cause mesenteric ischaemia if extension occurs
Diagnosis	Doppler ultrasound; CT with contrast (filling defect in portal vein)
Significance	Complicates surgical planning — portal vein thrombosis may make hepatic resection more technically challenging or preclude it

8. Liver Failure

Aspect	Detail
Definition	End-stage hepatic decompensation ^[17]
Mechanism	Progressive biliary cirrhosis → loss of critical mass of functional hepatocytes → failure of synthetic, excretory, and detoxification functions. Additionally, recurrent sepsis causes cumulative hepatocyte damage
Clinical features	Jaundice (progressive, now hepatocellular), coagulopathy, hypoalbuminaemia, hepatic encephalopathy, ascites, hepatorenal syndrome
Management	Liver transplantation may be considered in advanced cases — though this is rarely performed for RPC specifically, as the disease is typically managed with resection and drainage before it reaches this stage

9. Fistulisation

Aspect	Detail
Definition	Formation of choledocho-duodenal fistula into gastrointestinal tract or abdominal wall ^[17]
Mechanism	Chronic inflammation from recurrent cholangitis → erosion through the bile duct wall into adjacent structures. The continuous cycle of infection and healing weakens the duct wall and surrounding tissues. Stones themselves can erode through the wall by pressure necrosis
Types	Choledocho-duodenal fistula (most common — bile duct erodes into duodenum); cholecysto-enteric fistula; fistula to abdominal wall (rare)
Consequences	Pneumobilia/aerobilia (air in biliary tree — from the GI tract entering through the fistula); may predispose to further ascending infection; rarely, gallstone ileus if a large stone passes through the fistula into the bowel
Diagnosis	Imaging: aerobilia on AXR/CT; contrast studies may demonstrate the fistula tract

C. Neoplastic Complication

10. Cholangiocarcinoma — The Most Important Long-Term Complication

This deserves special emphasis because it is the most feared long-term outcome and directly impacts surveillance strategy.

Aspect	Detail
Definition	Malignant tumour of the bile duct epithelium — > 90% are adenocarcinoma ^[5]^[11]
Mechanism	Chronic inflammation → repeated epithelial injury and regeneration → accumulation of genetic mutations → dysplasia → carcinoma sequence. This is analogous to the colitis-associated cancer sequence in UC. The bile duct epithelium in RPC is subjected to decades of: (1) direct bacterial damage, (2) bile acid-induced mutagenesis (retained bile acids are genotoxic), (3) parasitic-induced chronic inflammation (Clonorchis sinensis), (4) generation of reactive oxygen species (ROS) from chronic infection
Epidemiological link	Association with ulcerative colitis (common in Westerners) and recurrent pyogenic cholangitis (common in Orientals) ^[5]. Mostly occurs in patients > 50 years ^[5]
Risk factors for cholangioCA in RPC	Duration of disease (longer → higher risk); extent of stricturing; hepatolithiasis; Clonorchis infection; PSC overlap ^[11]
Clinical red flags	New or worsening progressive painless jaundice (different from the episodic painful jaundice of RPC flares); unexplained weight loss; anorexia; rising CA 19-9 on serial measurement; new hepatomegaly; RUQ pain, hepatomegaly, jaundice ^[5]
Diagnosis	Tumour markers: CEA and CA 19-9 (may or may not be elevated, nonspecific) ^[5]; USG, CT scan, MRI ^[5]; FNAC or Trucut biopsy (ONLY for unresectable cases) ^[5]; choledochoscopy with biopsy for histological confirmation
Treatment	Hepatic resection is the treatment of choice (resectability rate about 20%) ^[5]; other treatment: no proven effect ^[5]. The low resectability rate reflects the fact that cholangiocarcinoma is often diagnosed late, especially when superimposed on RPC (the symptoms of malignancy overlap with the symptoms of RPC flares)
Prognosis	Very poor — especially when diagnosed late. This underscores the importance of vigilant surveillance in all RPC patients

Why RPC → Cholangiocarcinoma — The Molecular Rationale

The chronic inflammation-to-cancer pathway in RPC involves several molecular mechanisms:

NF-κB activation by bacterial endotoxin → chronic inflammatory signalling → promotes cell survival and proliferation
Reactive oxygen species (ROS) from activated neutrophils and macrophages → DNA damage → oncogenic mutations
Bile acid genotoxicity — retained bile acids (especially secondary bile acids) cause direct DNA damage and promote apoptosis resistance
IL-6/STAT3 signalling — upregulated in chronic cholangitis → drives cholangiocyte proliferation and survival
Parasite-specific factors — Clonorchis sinensis secretes excretory/secretory products that directly promote cell proliferation via the Wnt/β-catenin pathway

The cumulative effect over decades is a field change in the biliary epithelium — widespread dysplasia from which carcinoma eventually emerges.

Screening and Surveillance for Cholangiocarcinoma in RPC

There is no universally standardised surveillance protocol, but the following approach is widely practiced in Hong Kong centres:

Regular USG (every 6–12 months) — look for new masses, worsening strictures, change in biliary anatomy
Serial CA 19-9 — a rising trend (even if absolute value is within normal range) should prompt further investigation
Low threshold for CT/MRI if any clinical change (new weight loss, worsening jaundice, failure to respond to usual treatment)
Choledochoscopy with biopsy during any planned ERCP/PTBD procedure — direct visualisation and tissue sampling
FNAC or Trucut biopsy should be performed ONLY for unresectable cases ^[5] — in potentially resectable tumours, percutaneous biopsy risks needle-tract seeding

RPC patients undergo frequent invasive procedures (ERCP, PTBD, surgery), each carrying its own complication profile.

11. Post-ERCP Complications

Complication	Mechanism	Features	Management
Acute pancreatitis	Instrumentation near pancreatic duct orifice → traumatic oedema → pancreatic duct obstruction → enzyme activation	Epigastric pain post-procedure; elevated amylase/lipase	Conservative (NPO, IV fluids); usually self-limited
Perforation ^[6]^[15]	Sphincterotomy cuts through duodenal wall or bile duct wall	Intraperitoneal: free gas under diaphragm → requires surgery (will not seal). Retroperitoneal: no free gas under diaphragm, retroperitoneal gas → conservative treatment (will seal spontaneously) ^[6]	Surgery vs conservative based on type
Bleeding from papillotomy ^[15]	Electrocautery damages vessels at the sphincter during sphincterotomy	Haematemesis, melaena, haemobilia	Endoscopic haemostasis (adrenaline injection, cautery, clips); correct coagulopathy
Cholangitis flare	Instrumentation introduces organisms; incomplete drainage; stent occlusion	Fever, tachycardia post-ERCP	Check stent position (AXR); repeat drainage if needed; antibiotics
Stent occlusion/migration	Sludge/biofilm (plastic stents); tumour ingrowth (metallic stents); mechanical displacement	Recurrent jaundice, cholangitis	Stent exchange at scheduled intervals

12. Post-PTBD Complications

Complication	Mechanism
Bacteraemia	Needle traverses infected parenchyma → organisms enter bloodstream. Antibiotic prophylaxis required ^[14]
Haemobilia	Needle punctures a branch of the hepatic artery or portal vein (they travel together in the portal triad) → blood enters bile duct → haemobilia (blood in bile)
Fluid and electrolyte loss	External bile drainage → loss of bile salts, bicarbonate, and fluid → dehydration, electrolyte imbalance, malabsorption
Bile leak / peritonitis	Catheter dislodgement or tract disruption → bile leaks into peritoneal cavity
Pneumothorax	Right-sided approach may transgress the pleural space (the right intrahepatic approach is intercostal). This is why left hepatic duct access is preferred (subcostal, less painful, avoids pleura) ^[6]

13. Post-Surgical Complications

Complication	Mechanism
Anastomotic stricture	Fibrosis at the hepaticojejunostomy site → recurrent biliary obstruction → cholangitis. The most frequent long-term complication of Roux-en-Y hepaticojejunostomy is stenosis of the biliary-enteric anastomosis leading to jaundice, cirrhosis, or cholangitis ^[18]
Bile leak	Anastomotic leak or cut surface leak → biloma → infection
Liver failure (post-resection)	Insufficient future liver remnant after hepatic resection → post-hepatectomy liver failure
Recurrent stone formation	Even after resection, remaining ducts may develop new stones if the underlying stasis-infection cycle is not completely broken
Wound infection / poor wound healing	Cholestasis → impaired protein synthesis → impaired wound healing; nutritional deficiency; immunosuppression from sepsis

Summary: Complications by Timeline

Timeline	Complications
Acute (each flare)	Biliary sepsis, liver abscess (local and distant — lungs, brain), pancreatitis, rupture of bile ducts
Chronic (years)	Secondary biliary cirrhosis, hepatic atrophy, portal vein thrombosis, liver failure, fistulisation
Neoplastic (decades)	Cholangiocarcinoma — the most important long-term complication
Iatrogenic	Post-ERCP (pancreatitis, perforation, bleeding, cholangitis), post-PTBD (haemobilia, bacteraemia), post-surgical (anastomotic stricture, bile leak, liver failure)

High Yield Summary — Complications of RPC

Acute complications arise from each cholangitis flare: biliary sepsis (Reynold's pentad — urgent drainage mandatory), liver abscess (ascending biliary infection; swinging fever, tender hepatomegaly; double-target sign on CT), pancreatitis (stone passage to ampulla), rupture of pus-filled bile ducts into peritoneum
Chronic complications arise from cumulative damage: secondary biliary cirrhosis (chronic cholestasis → fibrosis), hepatic atrophy (left lobe predominant; indication for resection), portal vein thrombosis (periductal inflammation + hypercoagulability), liver failure (end-stage), fistulisation (erosion into bowel/abdominal wall)
Cholangiocarcinoma is the most important long-term neoplastic complication — driven by chronic inflammation → dysplasia → carcinoma sequence. Associated with RPC in Orientals and PSC/UC in Westerners ^[5]. Hepatic resection is the treatment of choice (resectability rate ~20%) ^[5]. FNAC/biopsy ONLY for unresectable cases ^[5]
Iatrogenic complications: Post-ERCP (pancreatitis, perforation — distinguish intraperitoneal from retroperitoneal, bleeding); Post-PTBD (haemobilia, bacteraemia); Post-surgery (anastomotic stricture — most common long-term surgical complication)
Key management principles: Biliary drainage is mandatory for acute sepsis; percutaneous drainage for liver abscess; hepatic resection for atrophic segments and suspected cholangioCA; regular surveillance for malignancy

Active Recall - Complications of RPC

1. List the 4 main acute complications of RPC and explain the pathophysiology of biliary sepsis from first principles.

Your answer

Show mark scheme

Acute complications: (1) Biliary sepsis, (2) Liver abscess, (3) Pancreatitis, (4) Rupture of obstructed bile ducts. Biliary sepsis mechanism: Biliary obstruction raises ductal pressure above 25 cm H2O. At this pressure, bacteria reflux from bile into hepatic veins and lymphatics, causing bacteraemia. Gram-negative endotoxin activates systemic inflammatory response, leading to septic shock. Antibiotic excretion into bile is impaired by obstruction, so biliary drainage is mandatory.

2. Explain why cholangiocarcinoma develops in RPC patients. What is the molecular pathway, and what clinical red flags should prompt investigation?

Your answer

Show mark scheme

Chronic inflammation from recurrent bacterial and parasitic damage leads to repeated epithelial injury and regeneration. This drives a dysplasia-to-carcinoma sequence via NF-kB activation, ROS-mediated DNA damage, bile acid genotoxicity, and IL-6/STAT3 upregulation. Red flags: new progressive painless jaundice (different from episodic painful jaundice of RPC), unexplained weight loss, anorexia, rising CA 19-9 on serial measurements, new hepatomegaly.

3. A post-ERCP patient develops severe abdominal pain. How do you distinguish intraperitoneal from retroperitoneal perforation, and how does management differ?

Your answer

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Intraperitoneal perforation: duodenal perforation. CXR shows free gas under diaphragm. Requires operative treatment because it will NOT seal spontaneously. Retroperitoneal perforation: bile duct perforation at ampulla (retroperitoneal portion of D2). NO free gas under diaphragm; retroperitoneal gas may be present on CT. Managed conservatively because it will seal spontaneously.

4. What are the consequences of secondary biliary cirrhosis in RPC, and why is it considered a preventable complication?

Your answer

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Consequences: Portal hypertension (varices, ascites, splenomegaly), synthetic failure (hypoalbuminaemia, coagulopathy), hepatorenal syndrome, hepatic encephalopathy. It is preventable because adequate biliary drainage (ERCP/PTBD) and definitive surgery (hepatic resection + hepaticojejunostomy) can relieve chronic obstruction and arrest progressive fibrosis before cirrhosis develops.

5. Why is hepatic atrophy an indication for surgical resection in RPC? What is the typical lobe affected and why?

Your answer

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An atrophic hepatic segment is non-functional, harbours stones and strictures, serves as a persistent source of infection and sepsis, and is at increased risk of malignant transformation (cholangioCA). The left lobe is typically affected due to anatomical factors: the left hepatic duct has a more acute drainage angle and longer intrahepatic course, promoting relative biliary stasis and making it more susceptible to stone formation and stricturing.

6. Regarding cholangiocarcinoma complicating RPC, state the treatment of choice and its resectability rate. When is FNAC or Trucut biopsy indicated?

Your answer

Show mark scheme

Hepatic resection is the treatment of choice. Resectability rate is approximately 20%. FNAC or Trucut biopsy is indicated ONLY for unresectable cases — in potentially resectable tumours, percutaneous biopsy risks needle-tract seeding and should be avoided.

References

^[1] Senior notes: felixlai.md (Recurrent pyogenic cholangitis — Complications section, p. 528) ^[2] Senior notes: maxim.md (Recurrent pyogenic cholangitis — Complications, pp. 136–137) ^[3] Senior notes: maxim.md (Clonorchis sinensis infection, p. 138) ^[5] Lecture slides: WCS 064 - A large liver - by Prof R Poon ^[20191108].doc.pdf (p. 5, Cholangiocarcinoma — aetiology, diagnosis, treatment) ^[6] Senior notes: felixlai.md (Acute cholangitis — Treatment and ERCP complications, pp. 522–525) ^[7] Senior notes: maxim.md (Acute cholangitis — Acute management RAD, pp. 135–136) ^[8] Senior notes: maxim.md (Liver abscess section, p. 125) ^[11] Senior notes: felixlai.md (Cholangiocarcinoma — Etiology and risk factors, pp. 547–548) ^[14] Senior notes: felixlai.md (PTBD section, pp. 504–505, 524) ^[15] Lecture slides: GC 200. RUQ pain, jaundice and fever Cholecytitis and cholangitis Imaging of GI system.pdf (p. 14, ERCP complications) ^[16] Lecture slides: Malignant biliary obstruction.pdf (p. 16, Cholangitis — biliary pressure, antibiotic excretion, drainage mandatory) ^[17] Senior notes: felixlai.md (RPC — Complications, p. 528) ^[18] Senior notes: felixlai.md (Biliary cysts — Complications of Roux-en-Y HJ, p. 544)

Recurrent Pyogenic Cholangitis

Active Recall - Recurrent Pyogenic Cholangitis

Active Recall - DDx of Recurrent Pyogenic Cholangitis

Active Recall - Diagnosis of RPC

Active Recall - Management of RPC

Active Recall - Complications of RPC

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