• Alcohol-related liver disease accounts for approximately 50% of all cirrhosis-related deaths worldwide ^[3].
• The WHO estimates that harmful alcohol use contributes to > 3 million deaths annually; liver disease is the leading cause of alcohol-attributable mortality.
• ALD is the most common cause of cirrhosis in Western countries (Europe, North America, Australia).

• In Hong Kong, HBV is by far the most common cause of cirrhosis (~64–75% by WHO pooled estimates and local expert opinion), with HCV closer to 5–10%, and alcohol/drinking probably > 5%. ^[4]
• However, ALD prevalence is rising in HK due to changing social habits, increased per-capita alcohol consumption, and Westernization of lifestyle.
• The concept of concomitant liver disease is important: many patients with HBV overlap and also possess MAFLD ^[4]. Similarly, a patient labelled as "alcoholic hepatitis" may also have chronic HBV — anyone presenting with chronic liver disease and a history of alcoholism must have other causes excluded ^[5].
• Alcoholic liver disease accounts for ~4% of cirrhosis in HK ^[6].

• Women are more susceptible to alcohol-related liver injury than men at lower cumulative doses. This is due to:
  • Lower gastric alcohol dehydrogenase (ADH) activity → higher effective blood alcohol level per unit consumed.
  • Higher body fat percentage → lower volume of distribution for ethanol.
  • Estrogen increases gut permeability → enhanced endotoxin translocation → greater Kupffer cell activation.
• Threshold for ALD: typically > 40 g/day in men and > 20 g/day in women over a prolonged period, though individual susceptibility varies enormously.

One standard drink ≈ 10 g pure ethanol (HK/Australian standard) ≈ a 330 mL can of beer (5%), 100 mL wine (12%), or 30 mL spirits (40%).

Prolonged heavy drinking (> 50–60 g/day) is associated with alcoholic hepatitis; the patient may cut down recently due to symptoms. ^[7]

• The liver is organised into hexagonal lobules centred on a central vein (terminal hepatic venule), with portal triads at the periphery.
• Rappaport's acinus divides the parenchyma into three zones based on proximity to the portal triad (oxygen-rich blood source):
  • Zone 1 (periportal): Closest to portal triad; highest O₂, receives blood first; site of gluconeogenesis, β-oxidation, urea synthesis.
  • Zone 2 (mid-zone): Intermediate.
  • Zone 3 (pericentral/centrilobular): Closest to central vein; lowest O₂; site of lipogenesis, drug metabolism (CYP450), ketogenesis.

Why does this matter for ALD? Alcohol is primarily metabolised in Zone 3 hepatocytes, which are richest in CYP2E1. This is why alcoholic liver injury (steatosis, steatohepatitis, fibrosis) characteristically begins in the centrilobular/perivenular (Zone 3) region, producing pericellular and perivenular fibrosis — a hallmark histological pattern.

• The liver has a dual blood supply: ~75% from portal vein (nutrient-rich, oxygen-poor) and ~25% from hepatic artery (oxygen-rich).
• Portal hypertension develops when fibrosis distorts sinusoidal architecture, increasing intrahepatic resistance → this drives many complications (ascites, varices, splenomegaly).

Alcoholic fatty liver develops within 2 weeks of regular alcohol ingestion and resolves rapidly (≤ 3 months) with abstinence. ^[2] 8–20% lifetime risk of progressing into cirrhosis, especially if liver biopsy shows marked fatty infiltration, Mallory bodies, or pericellular/perivenular fibrosis. ^[2]

1. Alcoholic Fatty Liver Disease (AFLD) — Usually asymptomatic, incidental finding.
2. Alcoholic Hepatitis (AH) — An acute clinical syndrome; may occur de novo or superimposed on pre-existing cirrhosis; has its own prognostic scoring.
3. Alcoholic Cirrhosis — The end-stage; presents with decompensation (ascites, variceal bleed, encephalopathy, jaundice).

These overlap considerably ^[2] — a patient with alcoholic hepatitis may already have underlying cirrhosis, and the acute hepatitis episode may be the precipitant for decompensation.

Several scores predict prognosis in acute alcoholic hepatitis:

Child-Pugh score (5 parameters: albumin, bilirubin, INR/PT, ascites, encephalopathy) and MELD score (3 parameters: bilirubin, INR, creatinine) are used for cirrhosis staging. MELD is used for transplantation priority — in HK, it is not first come first served. ^[5]

The clinical features of ALD depend on which stage the patient is at. Remember the overlap: a patient may have features of more than one stage simultaneously.

In alcoholic hepatitis: ^[7][8][9]

May have hepatic decompensation (↑INR, Bilirubin) ^[7]

Assessment of liver steatosis requires: ^[15]

• Detailed drinking history
• Cardiometabolic risk factors
• Drugs (corticosteroids / tamoxifen / valproate / methotrexate etc.)
• Concomitant liver disease
• Others (hypothyroid / PCOS / panhypopituitarism / bypass surgery / genetic)
• LFTs (ALT / AST)
• Platelet count! (to be explained later — low platelets suggest advanced fibrosis/portal hypertension)

On abdominal examination of a patient with suspected ALD: ^[16]

• Inspection: Jaundice, spider naevi (upper body), gynaecomastia, caput medusae, abdominal distension, muscle wasting.
• Palpation: Hepatomegaly (assess size, consistency, tenderness, surface — smooth vs nodular, edge), splenomegaly (Traube's space dull), ascites (shifting dullness, fluid thrill).
• Percussion: Liver span (normal 6–12 cm in MCL), shifting dullness.
• Auscultation: Hepatic bruit (HCC?), venous hum over caput medusae.

Also look for enlarged parotid gland, Dupuytren's contracture, peripheral neuropathy, and proximal myopathy — signs of chronic alcohol misuse.

The lecture slides emphasise that fatty liver is classified into: Alcoholic fatty liver and NASH/MAFLD. ^[17]

In HK, many patients have BOTH — concomitant ALD and MASLD, or HBV + MASLD. This "dual liver disease" concept is increasingly recognised and affects management strategy. ^[4][17]

Must exclude: ^[7]

• Biliary obstruction (imaging)
• Other types of hepatitis (viral, drug-induced, autoimmune)

This is critical: anyone presenting with chronic liver disease and a history of alcoholism must exclude other causes ^[5]:

• Check viral hepatitis markers (HBsAg, anti-HCV)
• Check autoimmune markers (ANA, ASMA, anti-LKM)
• Check drug/toxin exposure
• Check metabolic causes (ferritin/transferrin saturation for haemochromatosis, ceruloplasmin for Wilson's)

Apart from CAD, other cardiovascular conditions associated with high alcohol content include: ^[18]

• Coronary artery disease
• Atrial fibrillation → cardiac arrhythmias
• Alcoholic dilated cardiomyopathy (ACM)
• Hypertension

Alcohol and the brain — from psychiatric to neuropsychiatric perspectives: ^[19]

• Alcohol use disorder, dependence, withdrawal (seizures, delirium tremens)
• Wernicke-Korsakoff syndrome
• Cerebellar degeneration
• Alcoholic dementia
• Peripheral neuropathy
• Central pontine myelinolysis (if sodium corrected too rapidly during management)

Drug-induced hepatic injury, including alcohol, TCM/herbal tea is listed as a cause of hepatitis flare-up in chronic HBV patients ^[20].

When a patient has raised ALT/AST, you must first determine the pattern:

In usual circumstances, ALT level > AST level in diseases primarily affecting the liver, except: ^[8][9]

So when you see AST > ALT, your differential immediately narrows to these four. The absolute level, clinical context, and ancillary tests help you distinguish further.

Alcoholic hepatitis: AST almost never greater than 500 U/L. Isolated rise in GGT with relatively normal ALP. Increase in MCV. ^[8][9] If transaminases are > 500 or > 1000, think viral hepatitis, ischaemic hepatitis, drug/toxin (paracetamol), or autoimmune hepatitis flare — NOT alcoholic hepatitis.

Differential diagnosis of hepatomegaly ^[22][23][24]:

On abdominal examination, describe the hepatomegaly: ^[25]

• Irregular/hard → cancer (not only HCC!)
• Nodular → polycystic kidney and liver disease
• Smooth → fatty liver, alcoholic cirrhosis, primary biliary cholangitis (NOT chronic viral hepatitis unless superimposed pathology)

Alcoholic hepatitis is a known cause of hepatomegaly → usually a mild, soft hepatomegaly. Also try to look for enlarged parotid gland. ^[12] Alcoholic cirrhosis also causes hepatomegaly — hepatomegaly is common even with presence of cirrhosis ^[2] — this is unusual because most other forms of cirrhosis produce a shrunken liver.

When a patient presents with acute jaundice, you must differentiate alcoholic hepatitis from other causes of acute hepatitis:

The lecture slides list four conditions where urgent imaging may NOT be necessary to make a diagnosis based on LFT pattern + clinical context: ^[8]

• Cholangiohepatitis
• Acute hepatitis E
• Ischaemic hepatitis
• Alcoholic hepatitis

For alcoholic hepatitis, must exclude: biliary obstruction (imaging) and other types of hepatitis ^[7].

When a patient presents with established cirrhosis, you need to identify the cause — and crucially, more than one cause may coexist (concept of concomitant liver disease ^[4]).

Causes of cirrhosis ^[6][4]:

Isolated increase in GGT → inducible enzyme → think alcohol ^[5]. An isolated GGT elevation with normal ALP in a patient with cirrhosis is a strong clue to alcohol as the aetiology (or at least a contributory factor).

When USS or CT shows steatosis:

Fatty liver classification: ^[17]

• Alcoholic fatty liver
• NASH / MAFLD (MASLD)

ALD to NAFLD Index (ANI) = −58.5 + 0.637 × MCV + 3.91 × AST/ALT − 0.406 × BMI + 6.35 if male ^[2]. A score > 0 favours ALD; < 0 favours NAFLD. This is useful when the history is unreliable.

Other causes of hepatic steatosis to exclude:

• Drug-related: corticosteroids, tamoxifen, valproate, methotrexate ^[15]
• HCV-related steatosis ^[2]
• Endocrine: hypothyroidism, PCOS, panhypopituitarism ^[15]
• Others: bypass surgery, genetic (e.g., PNPLA3 polymorphism) ^[15]

Key concept: confusion in cirrhosis does NOT mean hepatic encephalopathy. HE is a less common cause of confusion in cirrhosis. Confusion is still most commonly caused by head injury and drug-related causes ^[29].

Other differentials for confusion in cirrhosis:

• Head injury (alcoholics are prone to falls)
• Drug effects (benzodiazepines, opioids, sedatives)
• Alcohol withdrawal / delirium tremens
• Wernicke's encephalopathy (thiamine deficiency)
• Infection (SBP, pneumonia, UTI → septic encephalopathy)
• Metabolic disturbance (hypoglycaemia, hyponatraemia, hypokalaemia)
• Intracranial bleed (subdural haematoma — coagulopathy + falls)
• Hepatic encephalopathy (diagnosis by exclusion; no single diagnostic test; arterial ammonia is not diagnostic — not always raised, may not correlate with severity) ^[29]

For any patient with cirrhosis and confusion, must order CT brain and electrolyte panel, maybe even urine toxicology to exclude other causes ^[29].

Hepatorenal syndrome sounds like the obvious answer, but it is actually NOT the most common cause of AKI in liver disease ^[30]. Must consider:

• Pre-renal: Dehydration, GI bleeding, over-diuresis, sepsis
• Intrinsic renal: ATN, drug nephrotoxicity (NSAIDs, aminoglycosides, contrast), glomerulonephritis (IgA nephropathy in alcoholics; HCV-associated cryoglobulinaemic GN)
• Post-renal: Obstruction (rare in this context)
• Hepatorenal syndrome (HRS): Diagnosis of exclusion; requires absence of structural kidney disease, no improvement with volume expansion

There are no formal "diagnostic criteria" per se. Diagnosis is made when:

• History of significant alcohol intake (typically > 20 g/day women, > 40 g/day men).
• Imaging demonstrates hepatic steatosis (USS: hyperechoic liver; CT: low-attenuation liver).
• Other causes of steatosis are excluded or accounted for.
• Can be detectable by USG, despite liver biopsy showing macrovesicular fat droplets in centrilobular zones being the gold standard ^[31].

Alcoholic hepatitis is the entity where diagnostic criteria matter most, because it has specific prognostic scoring and treatment thresholds.

NIAAA (National Institute on Alcohol Abuse and Alcoholism) Diagnostic Criteria for Alcoholic Hepatitis (2024 ACG/AASLD consensus):

Classification of diagnostic certainty (NIAAA framework):

In clinical practice, most cases are diagnosed as "probable AH" without biopsy, because biopsy carries risks in coagulopathic patients and the clinical-laboratory picture is usually sufficient.

Diagnosis follows the same principles as cirrhosis of any aetiology:

• Clinical: Stigmata of chronic liver disease + signs of portal hypertension + history of heavy alcohol use.
• Laboratory: Features of hepatic decompensation (↑bilirubin, ↓albumin, ↑INR) + ALD pattern (↑GGT, ↑MCV, AST > ALT).
• Imaging: Nodular liver surface, features of portal hypertension.
• Non-invasive fibrosis assessment: Elastography (FibroScan) — liver stiffness > 12 kPa suggestive of cirrhosis ^[17].
• Histological definition: late stage of liver fibrosis (F4) with diffuse distortion of liver architecture and formation of regenerative nodules surrounded by fibrous bands ^[4].

Not for diagnosing ALD per se, but essential in ALD patients with suspected or confirmed cirrhosis:

• Screen for oesophageal and gastric varices — all patients with newly diagnosed alcoholic cirrhosis should undergo OGD for variceal screening.
• Identify sources of upper GI bleeding (variceal vs. non-variceal).
• Low platelet count → hypersplenism → think about variceal bleeding ^[5].

No alcohol for life for chronic hepatitis / chronic liver disease ^[40]. Only modification needed in hepatitis management is ALCOHOL ^[40].

• Reduced food intake: Alcohol suppresses appetite; social dysfunction; gastritis causing nausea.
• Malabsorption: Alcohol damages intestinal mucosa; chronic pancreatitis → exocrine insufficiency → fat malabsorption.
• Impaired hepatic metabolism: Damaged liver cannot process nutrients effectively.
• Increased metabolic demands: Inflammation, infection, regeneration all require energy.

Pentoxifylline: a weak TNF inhibitor ^[39][32]:

• Reduces inpatient mortality, particularly from hepatorenal failure, in patients with severe alcoholic hepatitis ^[39].
• Mechanism: inhibits phosphodiesterase → ↑ cAMP → ↓ TNF-α production.
• However, the STOPAH trial showed no significant benefit → pentoxifylline has fallen out of favour in most guidelines.
• Monoclonal antibodies that neutralise serum TNF-α (e.g., infliximab) should NOT be used in alcoholic hepatitis due to increased death secondary to infection or renal failure ^[39].

The key teaching point: anti-TNF biologics (infliximab, etanercept) are harmful in AH despite the pathophysiology being TNF-driven. This is because complete TNF blockade cripples the immune system → overwhelming sepsis. Pentoxifylline's partial, non-specific anti-TNF effect was thought to be safer, but even that has not shown convincing benefit.

• End-stage alcoholic liver disease with hepatic decompensation (Child C cirrhosis, MELD ≥ 15).
• Unresectable HCC meeting Milan/UCSF criteria in the setting of alcoholic cirrhosis.
• Selected patients with severe alcoholic hepatitis non-responsive to medical therapy — this was previously controversial but increasingly accepted (see below).

Most centres require 6 months of abstinence before consideration for liver transplantation ^[2]:

• Rationale: identify patients at risk for relapse + allow time for liver recovery from ongoing alcohol-related injury ^[2].
• Monitor alcohol use using urine testing ^[2].
• 10–30% will have alcohol relapse after transplantation ^[2].
• Alcohol relapse is associated with graft rejection, recurrent ALD (usually rapidly progressive and may be fatal) ^[2].

The 6-month rule is practical rather than evidence-based. Some patients with severe AH who are steroid non-responders may die within 6 months if not transplanted. Emerging data (the Franco-Belgian trial, 2011) showed that early liver transplant in highly selected patients with severe AH (first episode, strong psychosocial support, no prior liver disease awareness) had 77% 6-month survival vs 23% without transplant. This has led to cautious relaxation of the 6-month rule in some centres, though it remains the standard in HK.

• Active alcohol / substance abuse (the 6-month rule)
• Active uncontrolled extrahepatic infection (e.g., HIV with uncontrolled viraemia)
• Extrahepatic malignancy
• Severe uncontrolled multisystem organ failure
• Inability to comply with transplant medications
• Inadequate psychosocial support

Liver transplantation prognosis: 66–72% 5-year survival (23% if no liver transplant) ^[2].

Liver transplantation is NOT performed for patients with active alcoholic hepatitis due to increased surgical mortality and high rates of recidivism ^[39] — though this is evolving as above.

In the normal liver, blood flows freely through sinusoids from the portal vein to the hepatic veins. In ALD-related cirrhosis:

1. Structural component (75%): Fibrosis, regenerative nodules, and collagen deposition in the space of Disse → increased intrahepatic vascular resistance. The sinusoids lose their fenestrations ("capillarisation"), and pericellular fibrosis compresses them.
2. Dynamic component (25%): Activated stellate cells and sinusoidal endothelial dysfunction → increased intrahepatic vasoconstrictor tone (↑endothelin, ↓nitric oxide production within the liver). Paradoxically, there is splanchnic vasodilatation (↑nitric oxide production in splanchnic circulation) → increased portal venous inflow.

The result: Portal venous pressure rises. When the hepatic venous pressure gradient (HVPG) exceeds 5 mmHg, portal hypertension exists. When it exceeds 10 mmHg, varices begin to form. When it exceeds 12 mmHg, variceal bleeding risk becomes significant.

The body attempts to decompress the portal system by shunting blood through collateral pathways:

50% of patients with alcoholic cirrhosis will develop cirrhotic complications, with 5-year transplant-free survival of only 60% in abstinence and 30% in drinkers ^[2].

Ascites is the most common decompensating event in cirrhosis. The mechanism is a cascade:

1. Portal hypertension → splanchnic vasodilatation (↑NO in mesenteric vessels) → ↓effective arterial blood volume.
2. Effective hypovolaemia activates:
   • RAAS (renin-angiotensin-aldosterone system) → sodium and water retention.
   • Sympathetic nervous system → renal vasoconstriction → ↓GFR.
   • ADH (vasopressin) → free water retention → dilutional hyponatraemia.
3. Hypoalbuminaemia (impaired hepatic synthesis) → ↓oncotic pressure → fluid shifts from intravascular to interstitial/peritoneal space.
4. Portal hypertension increases hydrostatic pressure in splanchnic capillaries → fluid transudation into peritoneal cavity.

The combination of these forces produces a transudative ascites with a SAAG (serum-ascites albumin gradient) ≥ 11 g/L — pathognomonic of portal hypertensive ascites.

Cirrhotic complications listed in the one-slide overview include ascites ^[47]. Protein calorie malnutrition may increase risk of major complications including infection, HE, ascites ^[2].

SBP is a bacterial infection of ascitic fluid without an identifiable intra-abdominal source of infection (no perforation, no abscess). The mechanism involves the gut-liver axis:

1. Cirrhosis → intestinal bacterial overgrowth + ↑intestinal permeability ("leaky gut").
2. Bacterial translocation → Gram-negative organisms (E. coli, Klebsiella) cross the gut wall into mesenteric lymph nodes and then into the bloodstream (bacteraemia) and ascitic fluid.
3. The cirrhotic patient has impaired immune defences: ↓complement and opsonin levels in ascitic fluid (especially when ascitic protein < 10–15 g/L), reticuloendothelial dysfunction, ↓neutrophil function.

SBP requires high clinical suspicion ^[5]. May actually not have a lot of abdominal signs, since no perforation ^[5]. Culture is not useful (usually negative) → defined by checking the neutrophils ^[5].

• Diagnostic paracentesis in any cirrhotic with new/worsening ascites, fever, abdominal pain, encephalopathy, or unexplained clinical deterioration.
• SBP is diagnosed by ascitic fluid PMN ≥ 250/mm³, regardless of culture result ^[5].
• Ascitic fluid should also be sent for: albumin (SAAG), total protein, glucose, LDH, Gram stain, culture (inoculate into blood culture bottles at bedside to improve yield).

Infections in liver failure are very common ^[46]. Bacteria, especially from the respiratory and urinary tract (Staph, Strep, Gram-negative rods). Bacteraemia in up to 25% of fulminant hepatic failure patients. Fungal infection, especially Candida, but bacterial still most common ^[46].

The mechanism behind why liver failure patients are susceptible to infection: reticuloendothelial dysfunction and reduced opsonisation — the liver cannot clear toxins, and production of complement/opsonins is impaired ^[46].

HE is a spectrum of neuropsychiatric abnormalities in patients with liver failure/portal hypertension, caused by accumulation of neurotoxins (principally ammonia) that the liver can no longer metabolise.

1. Ammonia source: Produced by bacterial urease in the gut (40%) and directly from dietary protein breakdown (60%).
2. Normal clearance: Ammonia is converted to urea by the hepatic urea cycle → excreted by kidneys. In liver failure, this cycle is impaired. Portal-systemic shunting also diverts ammonia-rich portal blood away from the liver.
3. Neurotoxicity: Ammonia crosses the blood-brain barrier → astrocytes convert it to glutamine (via glutamine synthetase) → glutamine is osmotically active → astrocyte swelling → cerebral oedema (mainly in acute liver failure); also disrupts neurotransmission (↑GABAergic tone, ↓glutamatergic tone).
4. Other neurotoxins: Manganese (deposits in basal ganglia), mercaptans (fetor hepaticus), short-chain fatty acids, and inflammatory cytokines all contribute.

Hepatic encephalopathy is a diagnosis of exclusion ^[29]:

• Arterial ammonia: not always raised, may not correlate with severity; not diagnostic ^[29].
• EEG abnormalities: for patients where diagnosis is difficult or in ICU ^[29].
• Psychometric tests: constructional apraxia (drawing a 5-point star), Reitan's test (number connection) ^[29].
• Other clinical features: fetor hepaticus, flapping tremor (asterixis) ^[29].

Confusion in cirrhosis does NOT mean HE. HE is a less common cause of confusion in cirrhosis — confusion is still most commonly caused by head injury and drug-related causes ^[29].

HRS is not primary kidney disease — the kidneys are structurally normal. It is a functional renal failure caused by extreme splanchnic vasodilatation in advanced cirrhosis:

1. Progressive splanchnic vasodilatation → ↓↓ effective arterial blood volume.
2. Maximal compensatory activation of RAAS, SNS, and ADH cannot maintain renal perfusion.
3. Intense renal vasoconstriction → ↓↓GFR → oliguric renal failure.
4. If you transplant the liver, the kidneys recover — proving the problem was haemodynamic, not structural.

• No structural kidney disease (normal renal USS).
• No response to 48-hour plasma volume expansion with IV albumin (1 g/kg/day, max 100 g/day).
• No shock, nephrotoxic drugs, or significant proteinuria.
• Urine sodium < 10 mmol/L (kidneys avidly retaining sodium — "pre-renal" physiology).

The liver synthesises essentially all clotting factors (except vWF and factor VIII, which are made by endothelial cells) and the natural anticoagulants (protein C, protein S, antithrombin). In liver failure:

• ↓ Pro-coagulant factors (II, V, VII, IX, X, XI, fibrinogen) → ↑ bleeding tendency.
• ↓ Anti-coagulant factors (protein C, protein S, antithrombin) → ↑ thrombotic tendency.
• ↓ Fibrinolytic factors (plasminogen) but also ↓ antifibrinolytics (α2-antiplasmin, TAFI).

This creates a "rebalanced haemostasis" — the INR looks terrible, but the patient is not necessarily bleeding because the loss of anticoagulants partially compensates. In fact, cirrhotic patients can develop thrombotic complications (portal vein thrombosis, DVT).

Factor VII has the shortest half-life (6 hours) → PT/INR is the first clotting parameter to become abnormal in liver failure ^[11].

• Thrombocytopenia from hypersplenism (portal hypertension → congestive splenomegaly → platelet sequestration) and ↓hepatic thrombopoietin production.
• Dysfibrinogenaemia — qualitatively abnormal fibrinogen.
• DIC — may be triggered by sepsis or severe AH.
• Vitamin K deficiency — impaired bile salt production → impaired fat-soluble vitamin absorption (K-dependent factors: II, VII, IX, X). Distinguish from true synthetic failure: give IV vitamin K 10 mg × 3 days; if PT corrects → cholestatic cause; if PT does not correct → hepatocellular failure ^[35].

1. Cirrhosis itself is the strongest risk factor — the chronic cycle of hepatocyte death → regeneration → DNA replication errors → dysplastic nodules → HCC.
2. Alcohol-specific carcinogenesis: Acetaldehyde is a carcinogen (forms DNA adducts); CYP2E1-generated ROS cause oxidative DNA damage; chronic inflammation promotes a tumour-permissive microenvironment.
3. 100% of patients with HCV infection or alcoholic liver disease who develop HCC have underlying liver cirrhosis ^[50][51] — unlike HBV, where HCC can occur without cirrhosis due to viral DNA integration. This means that for ALD-related HCC, cirrhosis is a requirement for HCC surveillance indication ^[17].

Surveillance should be performed at intervals of 6 months (doubling time of HCC = 3 months) ^[50][51]:

• AFP + USS liver every 6 months for all cirrhotics.
• USG has higher sensitivity than AFP alone ^[50][51].
• 6-month interval: no difference in outcomes compared with 3-month surveillance; better survival than 12-month surveillance ^[50][51].

1. Present in the late stage — asymptomatic when tumour < 8 cm; NO nerve fibres in the liver.
2. Majority have underlying liver cirrhosis (80–100%) → limits scope for resection.
3. Early venous permeation → high recurrence rate.
4. Field cancerisation effect → whole liver is exposed to oncogenic influence.

Other cardiovascular conditions associated with high alcohol content: ^[18]

• Coronary artery disease
• Atrial fibrillation → cardiac arrhythmias
• Alcoholic dilated cardiomyopathy (ACM) — direct ethanol toxicity to cardiomyocytes → LV dilatation, impaired contractility → heart failure ^[13]. Toxic aetiology of dilated cardiomyopathy ^[13]. Reversible with early abstinence.
• Hypertension

Alcohol is the major aetiology of chronic pancreatitis ^[14]:

• Chronic pancreatitis → exocrine insufficiency (steatorrhoea, malabsorption, fat-soluble vitamin deficiency) + endocrine insufficiency (diabetes mellitus).
• Pathological classification: calcifying pancreatitis — fibrosis with intraductal stones, associated with alcohol ^[14].
• Acute pancreatitis can also be precipitated by alcohol (though gallstones are the more common cause of acute pancreatitis).

Alcoholic hepatitis general management includes: assessing and managing pancreatitis ^[48].