Hepatitis A
Hepatitis A is an acute, self-limited viral infection of the liver caused by the hepatitis A virus, transmitted via the fecal-oral route.
Hepatitis A
Hepatitis A is an acute, self-limiting infection of the liver caused by the Hepatitis A Virus (HAV), a non-enveloped, single-stranded RNA virus belonging to the genus Hepatovirus within the family Picornaviridae [1][2]. The name "hepatitis" breaks down from Greek: hepar (ἧπαρ) = liver + -itis = inflammation. So, hepatitis A is literally "liver inflammation caused by agent A."
Key defining features that distinguish HAV from other hepatitis viruses:
- Humans are the only known reservoir [3]
- Transmitted via the faecal-oral route [1][2]
- Self-limiting in > 95% of cases [1]
- Does NOT cause chronic infection — there is no carrier state and no chronicity [1][2][3]
- Lifelong immunity develops after recovery — an individual cannot become reinfected [3]
- It is a notifiable disease in Hong Kong (as are all viral hepatitides) [2]
High Yield - GC Lecture
"Incubation period 14–28 days. Largely asymptomatic; but adults are more symptomatic than children. Self-limiting > 95%; but can result in acute liver failure in rare cases." [1]
Epidemiology
- Approximately 1.4 million new cases per year worldwide [4]
- More common in developing countries due to overcrowding and poor sanitation, where it occurs in an endemic or epidemic pattern [4]
- In highly endemic areas (sub-Saharan Africa, South/Southeast Asia), most children are infected by age 10 — infections are largely asymptomatic, and nearly all adults have natural immunity
- In low-endemicity areas (Western Europe, Australasia), infection shifts to older age groups, paradoxically leading to more symptomatic and more severe disease when it does occur
- Decreasing incidence over the last decades [3][4]
- Why? Improved sanitation, clean water supply, and food safety measures mean fewer people are exposed in childhood
- Paradox of declining endemicity: As fewer young people are exposed, the pool of susceptible adults grows. When these susceptible adults eventually encounter HAV (e.g. travel, contaminated shellfish outbreaks), they present with more symptomatic and potentially severe disease
- By age 55, approximately 61.7% of the Hong Kong population has serological evidence of prior HAV infection (anti-HAV IgG positivity) [4]
- Mortality increases with age [3][4]:
- 0.1% in ≤ 14 years old
- 0.4% in 15–39 years old
- 1.1% in ≥ 40 years old
Why does HAV mortality increase with age?
In children, the immune response to HAV is relatively restrained — most infections are subclinical or anicteric. In adults, the immune response is more vigorous, causing greater hepatocyte destruction (immunopathology). Older adults also have less hepatic regenerative reserve and are more likely to have pre-existing liver disease (e.g. chronic HBV — extremely relevant in Hong Kong where ~8% of the population are HBV carriers). The combination of superimposed HAV on chronic HBV significantly increases the risk of fulminant hepatic failure.
Risk Factors
Risk factors essentially map to the routes of transmission:
- Household contacts of an infected individual [3]
- Sexual transmission — particularly men who have sex with men (MSM) due to oro-anal contact [1][3][4]
- Residential institutions (e.g. care homes, prisons) [3]
- Daycare centres — young children are often asymptomatic shedders [3]
- Healthcare workers — exposure to faecal material [4]
- Consumption of raw or undercooked shellfish — especially bivalve molluscs (clams, oysters, mussels) harvested from sewage-contaminated waters [4][5]
- Why shellfish? Bivalves are filter feeders — they concentrate viral particles from surrounding water as they filter large volumes through their gills
- Uncooked vegetables washed with contaminated water [3][4]
- Contaminated food prepared by infected food handlers [3]
- Travel to areas of poor sanitation [3]
- Blood transfusion — rare because viraemia is transient and low-titre [3][4]
- Acupuncture, tattooing [3][4]
- Illicit drug use (both injection and non-injection routes) [3]
High Yield Mnemonic - HAV = Shellfish
As the senior notes memorably put it: "HAV = shellfish, HEV = pork liver congee" [5]. This is a useful Hong Kong–specific association for exams.
Anatomy and Function: The Liver in Context
To understand why HAV causes the clinical features it does, a brief review of relevant hepatic anatomy and function is essential.
- The liver is composed of ~1 million lobules, each centred on a central vein (draining into hepatic veins → IVC)
- At the periphery of each lobule lie the portal triads (hepatic artery, portal vein, bile duct)
- Hepatocytes are arranged in plates radiating from the central vein, bathed by sinusoidal blood flowing from portal triad → central vein
- Kupffer cells (resident macrophages) line the sinusoids and serve as the liver's first-line immune defence, filtering gut-derived pathogens and endotoxins from portal blood
- Bile canaliculi run between hepatocytes, collecting bile and draining into bile ductules → interlobular bile ducts → common hepatic duct
| Function | Normal Role | Clinical Consequence When Disrupted |
|---|---|---|
| Bilirubin conjugation & excretion | Hepatocytes conjugate indirect bilirubin → direct bilirubin, excrete into bile | Jaundice, dark urine (conjugated bilirubin in urine), pale stools (lack of stercobilinogen) |
| Protein synthesis | Albumin, clotting factors (I, II, V, VII, IX, X), complement | Coagulopathy (↑ INR/PT), hypoalbuminaemia |
| Bile flow | Bile salts emulsify fats, excrete cholesterol and bilirubin | Cholestasis → pruritus (bile salt deposition in skin), steatorrhoea |
| Detoxification | Ammonia → urea, drug metabolism | Hepatic encephalopathy (in fulminant cases) |
| Immune function | Kupffer cells, complement, acute-phase proteins | Increased susceptibility to secondary infection |
| Glucose metabolism | Glycogenolysis, gluconeogenesis | Hypoglycaemia (in severe/fulminant cases) |
The Hepatitis A Virus (HAV)
- Non-enveloped, single-stranded RNA (ssRNA) virus [1][2]
- Genus: Hepatovirus; Family: Picornaviridae [2][3]
- "Picorna" = pico (small) + RNA → small RNA virus
- Only one serotype exists → this is why infection confers lifelong immunity and why a single vaccine works globally
- The virus is remarkably stable in the environment:
- Survives on surfaces for weeks
- Resistant to acid (pH 1) → survives gastric acid (this is how faecal-oral transmission works)
- Resistant to drying, detergents, and moderate heat
- Inactivated by temperatures > 85°C for 1 minute, or by chlorine/bleach → hence why thorough cooking of shellfish eliminates risk
- Non-enveloped nature makes it resistant to bile salts (unlike enveloped viruses), allowing it to survive in the GI tract
Why is HAV non-enveloped? Clinical significance
Non-enveloped viruses are inherently more environmentally stable than enveloped ones (envelopes are lipid bilayers easily disrupted by detergents, drying, and bile). This is precisely why HAV survives the harsh GI environment and why it spreads so effectively via the faecal-oral route. Compare this with HBV (enveloped, blood-borne) — HBV would be inactivated in the GI tract.
Pathophysiology
Understanding the pathophysiology of HAV infection explains every clinical feature, investigation finding, and complication. Let's walk through it chronologically:
- HAV is ingested (contaminated food/water)
- Survives gastric acid (non-enveloped, acid-resistant)
- Reaches the small intestinal epithelium → crosses the mucosa into the portal circulation
- HAV travels via the portal vein to the liver
- Binds to HAV cellular receptor 1 (HAVcr-1/TIM-1) on hepatocyte surfaces
- Enters hepatocytes by receptor-mediated endocytosis
- Replicates within hepatocytes using the host cell's translational machinery
- Newly synthesised viral particles are released into bile canaliculi → shed into the gut → excreted in faeces
- Also released into the bloodstream (transient, low-level viraemia)
Critical concept: HAV is not directly cytopathic (or only minimally so). The liver damage in hepatitis A is primarily immune-mediated — it is the host's immune response attacking infected hepatocytes that causes hepatitis [4].
- Innate immunity: Kupffer cells and NK cells recognise infected hepatocytes → initial inflammatory response
- Adaptive immunity:
- CD8+ cytotoxic T lymphocytes (CTLs) are the main effectors → they recognise HAV antigens presented on MHC class I on infected hepatocytes and kill them
- CD4+ T-helper cells activate B cells → antibody production
- Anti-HAV IgM appears early (coincides with symptom onset) → marker of acute infection
- Anti-HAV IgG appears later → confers lifelong protective immunity
The immune-mediated destruction of hepatocytes leads to:
-
Release of intracellular enzymes → elevated ALT and AST (typically 200–2000 IU/L) [2][4]
-
Impaired bilirubin metabolism:
- Swollen, damaged hepatocytes compress bile canaliculi → intrahepatic cholestasis
- Reduced conjugation capacity
- Result: predominantly conjugated (direct) hyperbilirubinaemia [4]
- Dark/tea-coloured urine (conjugated bilirubin is water-soluble → filtered by kidneys)
- Pale stools (less bilirubin reaching the gut → less stercobilinogen)
- Pruritus (retained bile salts deposited in skin → this mimics obstructive jaundice and is due to hepatocyte swelling compressing canaliculi) [5]
-
Impaired synthetic function (in severe cases):
-
Inflammatory cytokine release → fever, malaise, myalgia, anorexia [1][5]
-
Hepatocyte swelling → stretching of Glisson's capsule → right upper quadrant dull ache [5]
- In > 95% of cases, the immune system successfully clears HAV
- Hepatocytes regenerate; liver architecture is restored
- Anti-HAV IgM wanes over 3–6 months; anti-HAV IgG persists for life
- No chronic infection develops — this is fundamentally different from HBV and HCV
Why does HAV never become chronic?
Several factors contribute: (1) HAV does not integrate into the host genome (unlike HBV). (2) HAV does not have effective immune evasion mechanisms. (3) The robust T-cell and antibody response in immunocompetent hosts efficiently clears the virus. (4) There is only one serotype, so once antibodies develop, they are universally protective. This is in stark contrast to HCV, which has extreme genetic variability allowing immune escape.
This is crucial for understanding public health measures:
Key points:
- HAV replicates in the liver and is shed in the stool in high concentration from 2–3 weeks before to 1 week after onset of clinical illness [3]
- Therefore, patients are most infectious BEFORE they become jaundiced — by the time they present with jaundice, infectivity is already waning
- Transient viraemia occurs during the incubation phase — this is the window for (rare) parenteral transmission [4]
Classification
| Level | Anti-HAV Seroprevalence by Age 10 | Examples |
|---|---|---|
| High | > 90% | Sub-Saharan Africa, South Asia |
| Intermediate | 50–90% | China (rural), Middle East, Latin America |
| Low | 15–50% | East Asia (including HK), Southern Europe |
| Very low | < 15% | Northern Europe, USA, Japan, Australia |
Hong Kong sits in the low endemicity zone — most infections occur in adolescents/adults rather than in early childhood.
| Pattern | Description |
|---|---|
| Typical acute hepatitis | Pre-icteric → icteric → convalescence; resolves in 4–6 weeks; > 95% of cases [4] |
| Cholestatic hepatitis | Prolonged cholestasis (up to 12–24 weeks); < 5% of cases; always resolves [4] |
| Relapsing hepatitis | Apparent recovery followed by biochemical ± clinical relapse; 6–10%; always resolves [4] |
| Fulminant hepatitis | < 1% overall; higher in patients > 50 or with underlying liver disease; significant mortality [1][4] |
| Severity | Features |
|---|---|
| Asymptomatic/subclinical | No symptoms; only detected by serology; more common in children |
| Mild | Prodromal symptoms only; anicteric |
| Moderate | Typical icteric hepatitis |
| Severe/Fulminant | Coagulopathy (INR > 1.5), encephalopathy, multi-organ failure |
Clinical Features
Natural History Phases
The clinical course of symptomatic HAV infection follows three distinct phases [5]:
| Symptom/Sign | Pathophysiological Basis |
|---|---|
| Low-grade fever (usually < 39°C) [5] | Cytokine release (IL-1, IL-6, TNF-α) from Kupffer cells and immune cells in response to viral replication |
| Severe loss of appetite (anorexia) [1][5] | Cytokine-mediated (TNF-α suppresses appetite centre in hypothalamus); also bile salt-mediated nausea |
| Nausea and vomiting [1] | Hepatic inflammation → altered bile metabolism; cytokine-mediated effect on chemoreceptor trigger zone |
| Severe fatigue/malaise [1][5] | Systemic inflammatory response; cytokine-mediated "sickness behaviour" |
| Myalgia [5] | Cytokine-mediated (similar to flu-like illness) |
| Diarrhoea [1][5] | Comparatively more common in HAV than other hepatitides [4]; likely due to direct viral effect on GI epithelium (HAV replicates in intestinal crypt cells before reaching the liver) |
| Right upper quadrant dull ache [5] | Hepatocyte swelling → stretching of Glisson's capsule (the liver parenchyma itself has no pain fibres; the capsule does) |
| Darkening of urine (tea-coloured) [5] | Conjugated bilirubin is water-soluble → filtered by kidneys — appears before jaundice becomes clinically evident |
| Transient pruritus [5] | Hepatocyte swelling compresses bile canaliculi → intrahepatic cholestasis → bile salt retention → deposition in skin → itch |
Teaching point: The pre-icteric phase is the most infectious period, yet patients are often not yet diagnosed. Dark urine is often the first clue that something is wrong — patients notice their urine looks like "tea" or "Coca-Cola" before they or anyone else notices their skin turning yellow.
| Symptom/Sign | Pathophysiological Basis |
|---|---|
| Jaundice [1][5] | Accumulation of bilirubin (predominantly conjugated) in skin, sclera, and mucous membranes when serum bilirubin > 34–51 µmol/L (2–3 mg/dL). Scleral icterus appears first because scleral tissue has high elastin content with high affinity for bilirubin |
| Pale/clay-coloured stools | Reduced bilirubin excretion into gut → less stercobilinogen |
| Hepatomegaly (mild, tender) | Hepatocyte swelling and inflammatory infiltrate → enlargement of liver |
| Improvement of prodromal symptoms [5] | As antibody response matures (IgM/IgG), viral clearance begins → reduction in systemic cytokine levels |
Important Clinical Pearl
"All pre-icteric symptoms begin to subside" during the icteric phase [5]. This is a classic teaching point — paradoxically, patients often feel better just as they look worse (more jaundiced). The reason is that the development of effective adaptive immunity (which causes jaundice by destroying infected hepatocytes) simultaneously starts clearing the virus and reducing systemic inflammation.
| Feature | Details |
|---|---|
| Clinical recovery | Symptoms resolve; appetite returns |
| Biochemical recovery | Transaminases normalise over weeks; bilirubin may remain elevated long after clinical and essential histological recovery [4] |
| Duration | Recovery usually occurs within 4–6 weeks [4], though full biochemical normalisation may take longer |
| Immunity | Anti-HAV IgG persists for life → lifelong immunity |
| Sign | Pathophysiological Basis |
|---|---|
| Jaundice (scleral → skin → sublingual) | Conjugated hyperbilirubinaemia |
| Tender hepatomegaly | Inflammatory infiltrate + hepatocyte swelling stretching capsule |
| Mild splenomegaly (occasional) | Reticuloendothelial hyperplasia in response to infection |
| Cervical lymphadenopathy (occasional) | Immune activation |
| Scratch marks | Pruritus from cholestasis |
| Bradycardia (relative to fever) | A classic but often-forgotten sign of acute hepatitis; mechanism not fully understood but possibly vagal-mediated due to bile salt effects |
| Spider naevi / palmar erythema | Absent — these are signs of chronic liver disease; HAV does NOT cause chronic hepatitis |
Common Exam Mistake
Do NOT describe signs of chronic liver disease (spider naevi, palmar erythema, gynaecomastia, Dupuytren's contracture, caput medusae) in a case of acute hepatitis A. HAV never causes chronic infection. If these signs are present, think of underlying chronic liver disease (e.g. chronic HBV) with superimposed acute HAV.
Atypical/Special Clinical Presentations
- Very common, especially in children
- Only detected if transaminases are checked (e.g. during outbreak investigation)
- Still infectious despite lack of jaundice
- < 1% of cases overall [1][4]
- Especially in patients > 50 years old or with pre-existing liver disease (e.g. chronic HBV) [4]
- Defined as onset of hepatic encephalopathy within 8 weeks of symptom onset in a patient without pre-existing liver disease
- Features: coagulopathy (INR > 1.5), encephalopathy, cerebral oedema, renal failure, hypoglycaemia, sepsis
- HAV is listed as a cause of acute liver failure alongside HEV, acute HBV, drugs (paracetamol), and pregnancy-related causes [6]
HAV Superinfection on Chronic HBV — Hong Kong Relevance
In Hong Kong, where chronic HBV prevalence is ~8%, a patient with chronic hepatitis B who acquires HAV superinfection has a significantly elevated risk of fulminant hepatic failure. This is why HAV vaccination is specifically recommended for all chronic HBV carriers [1][5]. Think of it this way: the liver is already under chronic siege from HBV; adding acute HAV-mediated immune destruction is like pouring petrol on a smouldering fire.
| Marker | Appears | Disappears | Significance |
|---|---|---|---|
| HAV in stool | 2–3 weeks before symptoms | ~1 week after jaundice onset | Period of infectivity |
| Anti-HAV IgM | At or just before symptom onset | 3–6 months | Diagnostic of acute HAV infection [1][2] |
| Anti-HAV IgG | 1–2 weeks after IgM | Lifelong | Marker of past infection or vaccination; confers lifelong immunity |
| Anti-HAV total (IgM + IgG) | — | — | Used for seroprevalence studies, not acute diagnosis |
| Parameter | Typical Finding | Explanation |
|---|---|---|
| ALT | 200–2000 IU/L [2][4] | Released from damaged hepatocytes; ALT more liver-specific |
| AST | Elevated but usually < ALT | ALT > AST in viral hepatitis (unlike alcoholic hepatitis where AST > ALT) |
| Bilirubin | Elevated, predominantly direct (conjugated) [4] | Hepatocyte dysfunction + intrahepatic cholestasis |
| ALP | Mildly elevated or normal | Can be moderately elevated in cholestatic variant |
| GGT | Mildly elevated or normal | Non-specific marker of hepatobiliary disease |
| Albumin | Usually normal acutely | Long half-life (~20 days); may drop in prolonged/severe cases |
| PT/INR | Normal in mild cases; elevated in severe/fulminant cases | Best index for progress and prognosis [4] — Factor VII half-life only ~6 hours |
High Yield — The Paradox of Low Transaminases in Fulminant Hepatitis
Transaminases can be LOW in fulminant hepatitis [2][4]. This seems counterintuitive — if the liver is failing catastrophically, shouldn't enzymes be sky-high? The answer is that in fulminant hepatitis, there is massive hepatocyte necrosis with so few viable hepatocytes remaining that there simply aren't enough cells left to leak enzymes. In this scenario, look at PT/INR and bilirubin instead — these will be markedly abnormal. A falling ALT with a rising INR is an ominous combination.
- WBC: usually normal with relative lymphocytosis [2][4]
- Why lymphocytosis? The adaptive immune response to HAV is predominantly T-cell mediated
- A markedly elevated WCC with neutrophilia should prompt consideration of bacterial superinfection or an alternative diagnosis
- Mild thrombocytopenia may occur (immune-mediated)
- Haemoglobin usually normal unless complicated by haemolysis (rare extrahepatic manifestation)
This is heavily tested in HKUMed exams [1][5]:
| Feature | HAV | HEV |
|---|---|---|
| Transmission | Faecal-oral (shellfish) | Faecal-oral (genotypes 1&2: water; genotypes 3&4: zoonotic — pigs, shellfish) |
| Incubation | 14–28 days [1] | 2–10 weeks (mean 5–6 weeks) [1] |
| Chronic infection | Never | No (except in immunosuppressed/transplant patients — genotype 3) |
| Fulminant hepatitis risk | < 1% | 1–2% in normal; 20–25% maternal mortality if acute HEV in 3rd trimester [1] |
| Cholestatic variant | < 5% [4] | ~20% — more common [4] |
| Lifelong immunity | Yes | No — can be reinfected [4] |
| Vaccine available | Yes | No (one licensed in China but not widely used) |
| Diagnosis | Anti-HAV IgM | Anti-HEV IgM ± stool HEV RNA RT-PCR |
| HK food association | Shellfish (oysters, clams) [5] | Pork liver, pig offal [5] |
GC Lecture — HAV vs HEV
Both HAV and HEV present with identical symptoms: fever, malaise, nausea, loss of appetite, jaundice, abdominal pain, vomiting, diarrhoea [1]. The key clinical differentiators are pregnancy risk (HEV), chronicity in immunosuppressed (HEV), and available vaccination (HAV).
Prevention — Briefly (Full Detail in Management Section)
- Inactivated whole-virus vaccine
- Given as 2 doses (0 and 6–12 months apart)
- Highly effective (> 95% seroconversion after 1 dose; near 100% after 2 doses)
- Indicated for: travellers to endemic areas, MSM, chronic liver disease patients (especially chronic HBV carriers), food handlers, healthcare workers, IVDU
- Pooled human immunoglobulin containing anti-HAV antibodies
- Provides immediate but temporary protection (~3 months)
- Used for post-exposure prophylaxis within 2 weeks of exposure, especially in those who cannot receive vaccine (e.g. < 12 months old, immunocompromised, allergy to vaccine components)
High Yield Summary
Hepatitis A — Key Take-Home Points
- HAV = non-enveloped ssRNA virus, Picornaviridae family; transmitted faecal-oral; incubation 14–28 days [1][2]
- Self-limiting > 95%; NO chronic infection, NO carrier state; lifelong immunity after recovery [1][3]
- Largely asymptomatic; adults more symptomatic than children [1]
- Mortality increases with age (0.1% in children → 1.1% in ≥ 40 years) [4]
- Clinical phases: Pre-icteric (fever, anorexia, nausea, dark urine) → Icteric (jaundice, symptoms improve) → Convalescence (4–6 weeks)
- Liver damage is immune-mediated, not directly cytopathic — CD8+ CTLs destroy infected hepatocytes
- LFT: ALT 200–2000; predominantly conjugated hyperbilirubinaemia; PT/INR = best prognostic marker [2][4]
- Fulminant hepatitis < 1% but increased risk in elderly and those with underlying chronic liver disease (especially chronic HBV — very relevant in HK) [4][6]
- Diagnosis: Anti-HAV IgM [1][2]
- Prevention: HAV vaccine (active) + immunoglobulin (passive post-exposure) [2]
- Notifiable disease in Hong Kong [2]
- HAV = shellfish; HEV = pork liver congee [5]
Active Recall - Hepatitis A (Definition, Epidemiology, Pathophysiology, Clinical Features)
[1] Lecture slides: GC 239. Viral hepatitis HAV_HBV_HCV_HEV.pdf (pages on HAV symptoms, incubation, HEV comparison) [2] Senior notes: Maksim Medicine Notes.pdf (p.141, viral hepatitis overview table, approach to acute hepatitis) [3] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (p.736–738, hepatitis A infection overview) [4] Senior notes: Ryan Ho GI.pdf (p.214–215, p.235, hepatitis A epidemiology, clinical features, complications) [5] Senior notes: Block A - Jaundice after raw oysters_ acute hepatitis.pdf (clinical phases, HAV vs HEV) [6] Senior notes: Block A - A jaundiced and incoherent patient_ liver failure.pdf (causes of acute liver failure)
Differential Diagnosis of Hepatitis A
When a patient presents with the classic clinical picture — acute onset of jaundice, fever, malaise, anorexia, nausea/vomiting, right upper quadrant pain, dark urine, and elevated transaminases — you are not just asking "is this hepatitis A?" You are really asking two nested questions:
- Is this acute hepatitis at all? (vs. other causes of jaundice, vs. other causes of RUQ pain, vs. other causes of fever with deranged LFTs)
- If it IS acute hepatitis, what is the aetiology? (viral vs. drug-induced vs. autoimmune vs. ischaemic vs. metabolic)
The differential diagnosis therefore operates at two levels: mimics of acute hepatitis and other causes of acute hepatitis itself.
GC Lecture High Yield — Top 4 Diagnoses for Markedly Elevated Transaminases
When presented with strikingly elevated ALT/AST, the top differential diagnoses are: (1) Acute viral hepatitis, (2) Ischaemic hepatitis ("shock liver"), (3) Drug-induced hepatitis, (4) Hepatitis B reactivation [7]. This is directly from the GC interactive tutorial / data interpretation slides and is extremely high yield for in-house exams.
The approach should be organ-based and mechanism-based. Think of it as: "What can make the liver angry (hepatocellular), what can block the plumbing (cholestatic), and what can look like liver disease but isn't?"
Level 1: Other Causes of Acute Hepatitis (The Main Differential)
This is the most important level. When you see a patient with acute hepatitis, the key differentials for the aetiology are:
| Virus | Key Differentiating Features from HAV | Diagnostic Test |
|---|---|---|
| Hepatitis E (HEV) | Faecal-oral like HAV but: longer incubation (2–10 weeks vs 2–4 weeks), zoonotic transmission (pork liver, pig offal), dangerous in pregnancy (20–25% mortality in 3rd trimester), can cause chronicity in immunosuppressed/transplant patients, more cholestatic variant (~20% vs < 5%) [1][4][5] | Anti-HEV IgM ± stool HEV RNA RT-PCR [1][2] |
| Hepatitis B (HBV) — acute | Blood-borne transmission (not faecal-oral); longer incubation (4–20 weeks); can become chronic (especially neonatal infection); HBsAg positive, anti-HBc IgM positive [2][8] | HBsAg, anti-HBc IgM [2] |
| Hepatitis B reactivation | History of known chronic HBV carrier; often triggered by immunosuppressant withdrawal (especially corticosteroids, anti-CD20); IgM anti-HBc may be positive but not as high as in acute HBV [8][9] | HBsAg, HBV DNA, anti-HBc IgM (lower titre than acute) [8] |
| Hepatitis C (HCV) | Blood-borne; usually insidious onset; acute HCV is rarely caught because it's often asymptomatic; anti-HCV may take up to 12 weeks to appear [2][8] | Anti-HCV ± HCV RNA [2] |
| Hepatitis D (HDV) | Only occurs as co-infection or superinfection with HBV; very rare in Chinese populations [9] | Anti-HDV, HDV RNA |
HBV Reactivation — A Hong Kong Favourite
In Hong Kong where ~8% of the population are chronic HBV carriers, hepatitis B reactivation is a critical differential for acute hepatitis. It often occurs after withdrawal of immunosuppressants (especially corticosteroids or anti-CD20 agents like rituximab) [9]. The mechanism: during immunosuppression, HBV replicates unchecked; when the immune system recovers after drug withdrawal, it mounts a massive attack on HBV-infected hepatocytes → fulminant flare. The clinical presentation can be identical to acute viral hepatitis.
These viruses are not primarily "hepatitis viruses" but can cause hepatitis as part of systemic infection:
| Virus | Clinical Clue | How it Differs from HAV |
|---|---|---|
| Epstein-Barr Virus (EBV) [3] | Fever, fatigue, pharyngitis, lymphadenopathy (especially posterior cervical), splenomegaly, atypical lymphocytes on blood film; LFTs often only mildly deranged; may have positive heterophile antibody (Monospot) | Prominent pharyngitis and lymphadenopathy uncommon in HAV; EBV rarely causes significant jaundice |
| Cytomegalovirus (CMV) [3] | Similar to EBV but typically without pharyngitis; more common in immunocompromised; atypical lymphocytes on film | Fever and LFT derangement can mimic HAV; key is lymphadenopathy and atypical lymphocytes |
| Herpes Simplex Virus (HSV) [3] | Rare cause of hepatitis, mainly in immunocompromised; can cause fulminant hepatic failure; look for mucocutaneous vesicles; markedly elevated AST/ALT with low bilirubin is classic | Extremely rare in immunocompetent; vesicular lesions are the clue |
| HIV (acute seroconversion) [3] | Acute retroviral syndrome: fever, rash, pharyngitis, lymphadenopathy, nausea, anorexia, diarrhoea; transaminases mildly elevated | Ask about risk factors (unprotected sex, IVDU, MSM); HIV p24 antigen/Ab combo test |
| Adenovirus [3] | Primarily respiratory/GI tract involvement; hepatitis mainly in immunocompromised | Rare in immunocompetent adults |
Teaching point: Both EBV and CMV infection can present with liver function abnormalities as well as fever, fatigue and lymphadenopathy [3]. The presence of atypical lymphocytes on peripheral blood film is a hallmark of these infections and helps differentiate them from HAV (where WCC is usually normal with only relative lymphocytosis).
Drug-induced hepatitis is one of the top 4 differentials for markedly elevated transaminases [7].
| Subtype | Key Features | How to Differentiate from HAV |
|---|---|---|
| Paracetamol (acetaminophen) overdose | History of ingestion; acute toxic dose > 150 mg/kg; classic triphasic course: nausea/vomiting (0–24h) → asymptomatic (24–48h) → resolution or fulminant failure ( > 48h); check paracetamol level at 4 hours [10] | Directed history of overdose; paracetamol level; no viral prodrome |
| Idiosyncratic DILI | Any drug — common culprits: antibiotics (amoxicillin-clavulanate, isoniazid, flucloxacillin), NSAIDs, anticonvulsants, statins, TCM/herbal remedies [7][9] | Temporal relationship with drug initiation (typically weeks to months); resolution on drug withdrawal; no positive viral serology |
| Herbal/TCM-related | Very relevant in Hong Kong; patients may not volunteer herbal use unless specifically asked | Always ask about TCM and supplements — this is a common exam pitfall |
Common Exam Mistake — Always Ask About Drugs and TCM
Drug history including over-the-counter medications, supplements, and Traditional Chinese Medicine (TCM) / herbal tea must be specifically elicited [9]. Patients often do not consider these as "drugs." In Hong Kong exams, DILI from TCM is a favourite differential.
Ischaemic hepatitis is a critical differential, especially in the acute setting [7][11].
- Mechanism: Hepatic hypoperfusion (cardiogenic shock, septic shock, hypovolaemia) → centrilobular hepatocyte necrosis
- LFT pattern: Brisk rise and rapid resolution of LDH; ALT/AST strikingly elevated, peak within 1–3 days, then fall rapidly; ALT/LDH ratio < 1.5 early in course [7]
- How to differentiate from HAV:
GC High Yield — Identifying Shock Liver
Ischaemic hepatitis is identified by: brisk rise and rapid resolution of LDH, ALT/AST strikingly elevated peaking within 1–3 days then falling rapidly, ALT/LDH ratio < 1.5 early in course, other evidence of end-organ damage (e.g. acute renal failure), and diagnosis based on clinical features [7]. This is directly from GC lecture slides.
| Feature | Details |
|---|---|
| Demographics | Bimodal age distribution: young and middle-aged females [10] |
| Clinical clues | Association with other autoimmune diseases (Graves', Hashimoto's, T1DM, UC, RA/SLE); can present as acute liver failure (25%) or chronic liver disease [10] |
| Key investigations | ↑ total IgG; autoantibodies (Type 1: ANA, ASMA, atypical pANCA; Type 2: anti-LKM1) [10][12] |
| Differentiation from HAV | Diagnosis by exclusion — must rule out viral hepatitis, DILI, and alcoholic liver disease first [10]; negative viral serology; positive autoantibodies; elevated IgG |
Immunoglobulin pattern in liver diseases: ↑ IgG = Autoimmune hepatitis; ↑ IgM = Primary biliary cholangitis (PBC); ↑ IgA = Alcoholic hepatitis [12]. This is a classic exam question.
| Feature | Details |
|---|---|
| Clinical context | History of heavy alcohol use; AST > ALT (typically 2:1 ratio) — opposite to viral hepatitis where ALT > AST |
| ALT/AST levels | AST usually does not exceed 500 IU/L (unlike viral/ischaemic hepatitis which can reach thousands) [11] |
| Other features | Hepatomegaly (mild, soft), enlarged parotid glands, spider naevi, palmar erythema, Dupuytren's contracture [11] |
| Differentiation | History, AST > ALT pattern, AST < 500, elevated GGT (marker of alcohol use), MCV often elevated |
| Feature | Details |
|---|---|
| Demographics | Young patients (typically 5–40 years old) |
| Clinical clues | Can present as acute hepatitis with jaundice, abdominal pain, and deranged LFT [3]; Kayser-Fleischer rings on slit-lamp examination; neuropsychiatric features (can mimic Parkinson's — extrapyramidal copper deposition) [13] |
| Key investigations | Low serum caeruloplasmin, elevated 24-hour urine copper, Kayser-Fleischer rings, genetic testing (ATP7B mutations — but genetic test does not have to be positive to diagnose) [13] |
| Fulminant presentation | Young patients with fulminant liver failure of no obvious cause + Coombs-negative haemolytic anaemia — classic Wilson's presentation [13] |
| Condition | Key Features |
|---|---|
| Acute Fatty Liver of Pregnancy (AFLP) | 3rd trimester; nausea, vomiting, abdominal pain, jaundice; can progress to fulminant liver failure; hypoglycaemia and coagulopathy out of proportion to transaminase elevation |
| HELLP Syndrome | Haemolysis, Elevated Liver enzymes, Low Platelets [6]; associated with pre-eclampsia; RUQ pain, hypertension, proteinuria |
| Condition | Key Differentiating Features |
|---|---|
| Malaria [3] | Fever and jaundice due to haemolysis (unconjugated hyperbilirubinaemia, NOT hepatocellular); travel to endemic area; thick and thin blood films; rapid diagnostic test |
| Budd-Chiari Syndrome [3] | Hepatic venous outflow obstruction; acute or subacute liver disease; ascites, hepatomegaly, abdominal pain; thrombophilia workup; Doppler USS showing absent hepatic vein flow |
| Leptospirosis | Travel/occupational history (contact with contaminated water/animal urine); Weil's disease with jaundice, renal failure, haemorrhage; conjunctival suffusion is classic |
These are the "look-alikes" — conditions that can present with some overlap but have fundamentally different pathology:
| Condition | How it Mimics HAV | Key Differentiator |
|---|---|---|
| Pre-hepatic jaundice (haemolysis) | Jaundice, fatigue, malaise | Unconjugated hyperbilirubinaemia; normal/near-normal transaminases; elevated LDH, reticulocytes, low haptoglobin; no dark urine (unconjugated bilirubin is NOT water-soluble → not excreted in urine) |
| Post-hepatic (obstructive) jaundice | Jaundice, dark urine, pale stools, pruritus | ALP and GGT markedly elevated (cholestatic pattern); transaminases only mildly elevated; biliary dilatation on USS; causes include gallstones, pancreatic head cancer, cholangiocarcinoma |
| Gilbert syndrome | Jaundice during stress/fasting | Isolated unconjugated hyperbilirubinaemia; normal transaminases; normal LFT otherwise; prevalence ~5% population; triggered by fasting, stress, or intercurrent illness [10] |
| Sepsis | Fever, jaundice, deranged LFTs | Typically cholestatic pattern; elevated WCC/CRP/procalcitonin; source of infection identified |
The key to narrowing the differential in acute hepatitis rests on:
-
History:
- Dietary exposure: raw shellfish → HAV; pork liver → HEV; undercooked food in endemic area
- Travel history: to endemic area for HAV/HEV/malaria
- Drug history: especially paracetamol, antibiotics, TCM/herbal [7][9]
- Alcohol history: quantity, pattern, duration
- Sexual/blood-borne risk factors: MSM, IVDU, transfusion, needlestick → HAV (MSM), HBV, HCV, HIV
- Pregnancy: AFLP, HELLP
- Known chronic liver disease: HBV reactivation, Wilson's
- Immunosuppression: recent chemotherapy/immunosuppressant withdrawal → HBV reactivation; HSV/adenovirus hepatitis
- Haemodynamic instability: shock liver
-
Laboratory pattern:
- Hepatocellular pattern (ALT/AST >> ALP): viral hepatitis, DILI, ischaemic, autoimmune, Wilson's
- Cholestatic pattern (ALP >> ALT): obstruction, PBC, PSC, drug-induced cholestasis, cholestatic variant of viral hepatitis
- AST > ALT: alcoholic hepatitis; also ischaemic hepatitis, cirrhosis
- ALT > AST: viral hepatitis (HAV, HBV, HCV), DILI, MASLD
-
Serology panel — the definitive differentiator:
| Test | What It Confirms |
|---|---|
| Anti-HAV IgM | Acute hepatitis A [1][2] |
| Anti-HEV IgM ± HEV RNA | Acute hepatitis E [1][2] |
| HBsAg + anti-HBc IgM | Acute HBV or HBV reactivation [2][8] |
| Anti-HCV ± HCV RNA | HCV (note: anti-HCV may take 12 weeks to appear) [2] |
| EBV VCA IgM / CMV IgM | EBV/CMV hepatitis |
| ANA, ASMA, IgG levels | Autoimmune hepatitis [10][12] |
| Caeruloplasmin, urine copper | Wilson disease [13] |
| Paracetamol level | Paracetamol overdose |
GC High Yield — Conclusions for Acute Hepatitis Workup
"Different liver diseases have different patterns of abnormalities of the liver function test. Determining the final diagnosis requires: history (drug history), clinical presentation, other investigations. Liver biopsy may be required" [7]. The lecture emphasises that urgent imaging may not be necessary in many cases of acute hepatitis — the diagnosis is often made on clinical grounds plus serology.
| Feature | HAV | HEV | Acute HBV | Ischaemic Hepatitis | DILI | Autoimmune Hepatitis |
|---|---|---|---|---|---|---|
| Transmission | Faecal-oral (shellfish) | Faecal-oral / zoonotic (pork) | Blood-borne | Haemodynamic | Drug exposure | None (autoimmune) |
| Incubation | 14–28 days | 2–10 weeks | 4–20 weeks | Hours | Days–weeks | Variable |
| Prodrome | Typical pre-icteric | Similar to HAV | Similar | None (acute shock) | Variable | Variable |
| ALT peak | 200–2000 | 200–2000 | 200–2000+ | Can be > 5000 | Variable | Variable |
| LDH | Mildly ↑ | Mildly ↑ | Mildly ↑ | Massively ↑ | Variable | Normal/mild ↑ |
| ALT/LDH ratio | > 1.5 | > 1.5 | > 1.5 | < 1.5 | Variable | > 1.5 |
| Resolution | Weeks | Weeks | Variable | 1–3 days (rapid fall) | On drug withdrawal | Requires immunosuppression |
| Chronicity | Never | Transplant only | Yes (neonates > adults) | No | No (unless re-exposed) | Yes |
| Diagnostic test | Anti-HAV IgM | Anti-HEV IgM | HBsAg + anti-HBc IgM | Clinical context + LDH | Temporal drug hx | ANA/ASMA/IgG |
In Hong Kong, a very important differential diagnosis scenario is:
A known chronic HBV carrier presents with acute hepatitis — is this HBV reactivation (spontaneous or drug-induced) or superinfection with HAV/HEV?
- Superinfection with other viral agents, especially HAV and HEV, is more important than HDV in Hong Kong [9]
- HEV is more common now as a superinfecting agent [9]
- The distinction matters because:
- HBV reactivation may require antiviral therapy (entecavir/tenofovir)
- HAV/HEV superinfection is self-limiting but carries increased risk of fulminant failure in chronic HBV
- How to differentiate: Anti-HAV IgM and anti-HEV IgM will be positive in superinfection; HBV DNA levels and anti-HBc IgM titre help assess HBV reactivation [8][9]
High Yield — Aplastic Anaemia Post-Hepatitis
Hepatitis is a well-known antecedent to aplastic anaemia [14]. This is not caused by HAV specifically (the responsible virus is often unidentified — "seronegative hepatitis-associated aplastic anaemia"), but it's worth knowing in the differential of pancytopenia following an episode of hepatitis. The mechanism involves T-cell mediated destruction of haematopoietic stem cells [14].
High Yield Summary — Differential Diagnosis of Hepatitis A
- Top 4 differentials for markedly elevated transaminases: Acute viral hepatitis, ischaemic hepatitis, drug-induced hepatitis, HBV reactivation [7]
- Closest viral mimics: HEV (faecal-oral, similar presentation), acute HBV, EBV/CMV (look for lymphadenopathy + atypical lymphocytes)
- Always exclude: DILI (especially paracetamol and TCM/herbal), alcoholic hepatitis (AST > ALT, AST < 500), autoimmune hepatitis (young females, ↑ IgG, autoantibodies)
- Shock liver clues: haemodynamic instability, massively elevated LDH, ALT/LDH ratio < 1.5, rapid resolution in 1–3 days [7]
- Wilson disease: young patient, Coombs-negative haemolytic anaemia + fulminant liver failure = pathognomonic [13]
- In HK: always consider HBV reactivation and HAV/HEV superinfection on chronic HBV [9]
- Definitive differentiation: serology panel (anti-HAV IgM, anti-HEV IgM, HBsAg, anti-HBc IgM, anti-HCV) [2]
- Diagnosis requires: history (drug history), clinical presentation, other investigations; liver biopsy may be required [7]
Active Recall - Differential Diagnosis of Hepatitis A
References
[1] Lecture slides: GC 239. Viral hepatitis HAV_HBV_HCV_HEV.pdf (pages on HAV/HEV symptoms, incubation, clinical consequences) [2] Senior notes: Maksim Medicine Notes.pdf (p.141, viral hepatitis overview table, serology, approach) [3] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (p.738, 767, differential diagnosis of hepatitis A and E) [4] Senior notes: Ryan Ho GI.pdf (p.214–215, p.235, hepatitis A/E epidemiology and clinical features) [5] Senior notes: Block A - Jaundice after raw oysters_ acute hepatitis.pdf (HAV vs HEV, clinical phases) [6] Senior notes: Block A - A jaundiced and incoherent patient_ liver failure.pdf (causes of acute liver failure, HELLP) [7] Lecture slides: Gastroenterology Hepatology Introduction to GI:Hepatology investigations from the abnormal.pdf (p.38, 40, 49 — top 4 DDx, shock liver identification, conclusions) [8] Senior notes: Block A - Gastrointestinal Data Interpretation.pdf (p.2–3, HBV serology interpretation, acute vs chronic flare) [9] Senior notes: Block A - I am a hepatitis B carrier.pdf (p.25, 28 — hepatitis flare causes, superinfection with HAV/HEV) [10] Senior notes: Maksim Medicine Notes.pdf (p.148, 150 — autoimmune hepatitis, DILI, Gilbert syndrome) [11] Senior notes: Block A - Introduction to GI_Hepatology investigations (LFT, Endoscopy).pdf (p.16–17, ischaemic hepatitis, alcoholic hepatitis patterns) [12] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (p.732, 734 — AIH diagnosis, immunoglobulin patterns) [13] Senior notes: Block A - Patients with non-viral chronic liver diseases.pdf (p.2, Wilson disease features) [14] Senior notes: Block A - Hematology Data Interpretation.pdf (p.1, hepatitis preceding aplastic anaemia)
Diagnostic Criteria, Algorithm, and Investigations for Hepatitis A
Diagnostic Criteria
Hepatitis A does not have a complex scoring-based diagnostic criteria like autoimmune hepatitis or SLE. The diagnosis is straightforward and rests on two pillars:
- Compatible clinical picture — acute hepatitis syndrome (fever, malaise, anorexia, jaundice, dark urine, RUQ pain, elevated transaminases)
- Positive anti-HAV IgM serology — the single definitive diagnostic test [1][2][5]
GC Lecture High Yield — Diagnostic Approach to Acute Viral Hepatitis
Investigations for acute viral hepatitis require three components: (1) Markedly elevated ALT and AST, (2) Specific serological test, (3) Exclusion of other causes [1]. This three-part framework is directly from the GC 239 lecture slide and is the backbone of the diagnostic approach.
| Feature | Detail |
|---|---|
| When it appears | Can be detected early: 1–2 weeks after jaundice, or 2–3 weeks after ALT/AST elevation [5] |
| When it peaks | Acute stage / early convalescent stage [5] |
| Duration | Usually persists 3–4 months; 25% persist > 6 months; very rarely > 12 months [5] |
| False negatives | Occasionally delayed — if negative in a clinically suspicious case, recheck at a later stage [5] |
| Interpretation pitfall | A positive anti-HAV IgG alone does NOT mean acute infection — it indicates past infection or prior vaccination. About half the HK population will have positive IgG for HAV [8] |
Important — IgM Can Be Delayed
Anti-HAV IgM is occasionally delayed [5]. So if you have a highly suspicious clinical picture (e.g. recent raw shellfish consumption, typical prodrome, markedly elevated ALT) but the initial anti-HAV IgM is negative, do NOT rule out HAV — recheck the patient at a later stage. The IgM may simply not have risen yet.
The diagnostic algorithm for acute hepatitis A is best understood as a systematic exclusion approach embedded within the general workup for acute viral hepatitis. The GC lecture provides a clear stepwise algorithm [1]:
GC Lecture High Yield — The Diagnostic Flowchart
The GC 239 lecture slide presents this exact stepwise algorithm [1]:
- HBsAg → Positive → HBV
- Anti-HAV IgM → Positive → HAV
- Anti-HCV → Negative (hard to catch acute phase unless needlestick injury)
- Anti-HEV IgM → Negative; then HEV RNA → Positive → HEV (note the extra step for HEV — IgM may be negative, so RNA PCR is needed)
- ANA, anti-smooth muscle, anti-LKM-1 → Negative → excludes autoimmune hepatitis
- Ultrasound → No biliary obstruction / liver normal / no splenomegaly
- Toxicology screen / Paracetamol levels → Normal
If ALL of the above are negative, you have seronegative hepatitis — consider rarer causes or liver biopsy.
Investigation Modalities: Detailed Interpretation
1. Liver Function Tests (LFTs)
LFTs are the first-line blood tests and must be interpreted systematically. The GC/DI lectures emphasise that LFTs assess three distinct aspects of hepatic function [15]:
| Aspect | Markers | What They Test |
|---|---|---|
| Cellular integrity ("liver damage markers") | ALT, AST | Leakage from damaged hepatocytes |
| Excretory function | Bilirubin, ALP, GGT | Ability to conjugate and excrete bile |
| Synthetic function ("actual liver function") | Albumin, PT/INR | Ability to manufacture proteins |
GC High Yield — ALT/AST Are NOT 'Liver Function Tests'
Albumin and PT are the actual liver function tests — they measure what the liver can DO (synthesise proteins). ALT and AST are liver damage markers — they tell you hepatocytes are being injured, not whether the liver is functioning [8][15]. This distinction matters clinically: a patient can have ALT of 2000 but perfectly preserved synthetic function (mild hepatitis A), while another can have ALT of 50 but disastrous PT and albumin (end-stage cirrhosis with few remaining hepatocytes).
| Parameter | Expected Finding | Pathophysiological Explanation |
|---|---|---|
| ALT | 200–2000 IU/L (markedly elevated) [2] | Released from damaged hepatocytes; ALT is more liver-specific than AST (ALT is almost exclusively hepatic, while AST is also found in heart, muscle, RBCs) |
| AST | Elevated, but ALT > AST [15] | In primary liver pathology, ALT rise is generally greater than AST. The reverse (AST > ALT) occurs in 4 conditions: alcoholic hepatitis, HCC, congestive heart failure, ischaemic hepatitis [15] |
| Bilirubin | Elevated, predominantly conjugated (direct) [4] | Hepatocyte swelling compresses canaliculi → intrahepatic cholestasis; also impaired conjugation capacity, but overall the bilirubin that accumulates is mainly conjugated because the hepatocytes that are still working can conjugate but cannot excrete |
| ALP | Normal or mildly elevated | ALP rises significantly only with biliary obstruction or cholestatic variants; in straightforward HAV, the pathology is hepatocellular, not cholestatic |
| GGT | Normal or mildly elevated | GGT is a microsomal, inducible enzyme — rises with alcohol, drugs, fatty liver, and cholestasis; mild elevation in HAV is non-specific [15] |
| Albumin | Usually normal | Half-life ~20 days — too long to drop acutely; only falls in prolonged or severe cases |
| PT/INR | Normal in mild–moderate cases; elevated in severe/fulminant cases | PT/INR is the best index for progress and prognosis — because Factor VII has the shortest half-life (~6 hours) of all clotting factors, PT is the first synthetic marker to deteriorate [2][4] |
Different liver diseases have different patterns of abnormalities [7]. Serial LFTs reveal the trajectory:
- Viral hepatitis (HAV): ALT/AST peak over days to weeks → gradually decline over weeks → bilirubin lags behind → complete normalisation over weeks to months
- Ischaemic hepatitis: ALT/AST peak within 1–3 days → fall rapidly [7]; LDH is disproportionately elevated
- Bile duct obstruction: AST/ALT may reach up to 500 in the first few hours → then decrease rapidly; ALP and GGT take several days to rise [15]
- Alcoholic hepatitis: AST > ALT (>2:1 ratio); AST almost never > 500 [15]
The AST:ALT ratio provides crucial diagnostic clues beyond absolute enzyme levels. A ratio exceeding 2:1 strongly suggests alcoholic hepatitis, while ratios approaching 1:1 with markedly elevated transaminases and LDH indicate ischaemic hepatitis [15].
| Finding | Expected in HAV | Explanation |
|---|---|---|
| WCC | Usually normal [2] | Viral infections typically do not cause marked leukocytosis (unlike bacterial infections) |
| Differential | Relative lymphocytosis | T-cell mediated immune response; NK cell activation |
| Atypical lymphocytes | Absent or rare in HAV | If prominent → think EBV/CMV (infectious mononucleosis-like syndrome) |
| Platelets | Usually normal; mild thrombocytopenia possible | Immune-mediated; also, liver produces thrombopoietin (TPO) — acute injury may transiently reduce TPO |
| Hb | Normal | Unless complicated by haemolysis (rare extrahepatic complication) or underlying condition |
| Test | Significance in HAV |
|---|---|
| PT/INR | Best index for progress and prognosis [2][4]. Normal → reassuring. INR ≥ 1.5 → defines acute liver failure [4]. Factor VII (half-life ~6 hours) is the first to drop |
| APTT | Less sensitive than PT for liver synthetic function; may be elevated in severe cases |
| Fibrinogen | May be low in fulminant cases (DIC); fibrinogen is an acute-phase reactant so may paradoxically be normal or elevated in mild hepatitis |
Why PT and Not APTT?
The extrinsic pathway (measured by PT) depends heavily on Factor VII, which is exclusively synthesised by the liver and has the shortest half-life of any clotting factor (~6 hours). In acute liver injury, Factor VII is the first to fall, making PT the earliest and most sensitive marker of deteriorating hepatic synthetic function [2]. APTT measures the intrinsic pathway — these factors have longer half-lives and are less sensitive to acute hepatocyte loss.
4. Viral Serology — The Definitive Tests
This is the core of the diagnostic workup. The GC lecture provides the serological approach [1]:
| Test | What It Detects | Notes |
|---|---|---|
| Anti-HAV IgM | Acute HAV | Appears at symptom onset; persists 3–6 months [5] |
| HBsAg | HBV infection (acute or chronic) | If positive → need further workup (HBeAg, HBV DNA, anti-HBc IgM) [1][16] |
| Anti-HBc IgM | Acute HBV infection | Only marker positive during the "window period" (when HBsAg has cleared but anti-HBs hasn't appeared yet) [2]; also positive in HBV reactivation but at lower titre [8] |
| Anti-HCV | HCV exposure | May take up to 12 weeks to appear [2]; if strong suspicion (e.g. needlestick), check HCV RNA directly [8] |
| Anti-HEV IgM | Acute HEV | Coincides with symptoms; persists ~3 months [5] |
| HEV RNA | Active HEV infection | Important because anti-HEV IgM may be negative in a proportion of patients → HEV RNA is more sensitive [1][5] |
GC Lecture High Yield — The HEV Diagnostic Pitfall
The GC 239 slide shows that when anti-HEV IgM is negative, you should still check HEV RNA if clinical suspicion is high [1]. This is because anti-HEV IgM can be falsely negative in early infection or in immunocompromised patients. This is a favourite exam testing point.
This is a classic data interpretation question [1][8][16]:
| Feature | Acute HBV | Chronic HBV with Acute Flare |
|---|---|---|
| HBsAg | Positive (clears within 6 months) | Persistently positive > 6 months |
| HBeAg | Usually positive | May be positive or negative (if already seroconverted → negative) |
| Anti-HBc IgM | Strongly positive (high titre) | Positive but lower titre [8] |
| HBV DNA | Very high (often > 10^8 IU/mL) [16] | Variable; may be very high during flare |
| Definitive differentiation | HBsAg clears within 6 months [8] | HBsAg persists > 6 months |
"Sometimes we can't differentiate acutely. Definition of chronic hepatitis B requires elevation of HBsAg over 6 months. So how to differentiate — if the patient doesn't die, do a surface antigen in 6 months" [8].
| Test | Purpose | Interpretation |
|---|---|---|
| INR/PT | Best prognostic marker [2][4] | Rising INR = deteriorating synthetic function = more severe disease |
| Serum bilirubin | Severity and trajectory | May remain elevated long after clinical and histological recovery [4] — don't panic if bilirubin is slow to normalise; follow the trend |
| Arterial ammonia | Hepatic encephalopathy assessment | Elevated in fulminant cases with encephalopathy; not always correlated with severity [6] |
| Serum glucose (H'stix) | Hypoglycaemia detection | Liver failure can cause hypoglycaemia — impaired glycogenolysis and gluconeogenesis [2] |
| Renal function (RFT) | AKI detection | AKI complicates 30–70% of acute liver injury [4] — hepatorenal syndrome or ATN |
| AFP | Not a diagnostic test for HAV | High inflammation in the liver can cause marked elevation of AFP — this does NOT automatically mean malignancy. Key: does AFP come down after symptoms disappear? If it doesn't and keeps rising, worry about cancer [8] |
AFP Pitfall in Acute Hepatitis
AFP elevated in acute hepatitis is NOT always a tumour marker [8]. Acute hepatocyte regeneration and inflammation can release AFP. The critical question is trajectory — if AFP falls as hepatitis resolves, it was regeneration-related. If it persists or rises, investigate for HCC. This is a common exam pitfall — do not reflexively diagnose malignancy from an elevated AFP in the context of acute hepatitis.
As per the GC diagnostic algorithm [1]:
| Investigation | Purpose | Expected Finding in HAV |
|---|---|---|
| ANA, anti-smooth muscle antibody, anti-LKM-1 | Exclude autoimmune hepatitis [1] | Negative |
| Ultrasound liver | Exclude biliary obstruction, Budd-Chiari, hepatic steatosis, splenomegaly [1][4] | No biliary obstruction / liver normal / no splenomegaly [1]; may show mild hepatomegaly |
| Toxicology screen / Paracetamol level | Exclude drug-induced hepatitis [1] | Paracetamol levels normal [1] |
| Serum caeruloplasmin, urine copper | Exclude Wilson disease (in young patients) | Normal |
| Serum IgG level | AIH screening | Normal in HAV (elevated in AIH) |
GC Lecture High Yield — When is Imaging Useful?
"Urgent imaging may not be necessary" in many cases of acute hepatitis [7]. Imaging (ultrasound) is useful only to exclude biliary obstruction or structural abnormalities. In cases like acute hepatitis A, acute HEV, ischaemic hepatitis, and alcoholic hepatitis, the diagnosis is made on clinical grounds plus laboratory tests [7]. Don't order unnecessary CT scans or MRIs in straightforward acute viral hepatitis.
| Modality | Indication | Findings in HAV |
|---|---|---|
| Ultrasound abdomen | First-line imaging; rule out obstruction, assess liver echotexture | Usually normal or mildly enlarged liver; no biliary dilatation; normal spleen (vs. cirrhosis where spleen may be enlarged); no focal lesion |
| FibroScan (liver elastography) | NOT indicated in acute HAV | Falsely elevated during acute inflammation — do not interpret as fibrosis/cirrhosis |
| CT / MRI | NOT routinely indicated | Only if ultrasound findings are equivocal or Budd-Chiari/vascular cause suspected |
| MRCP/ERCP | Only if biliary obstruction suspected | Not needed for HAV |
Liver biopsy is NOT routinely required for the diagnosis of hepatitis A [7].
Indications for liver biopsy in the context of acute hepatitis:
- When the diagnosis remains unclear after full serological and biochemical workup [7]
- When autoimmune hepatitis is suspected but autoantibodies are inconclusive (AIH can be a diagnosis of exclusion; autoantibodies are not specific, require diagnostic criteria) [8]
- Atypical clinical course (e.g. prolonged cholestasis, failure to improve)
- When liver transplant is being considered → transjugular liver biopsy (percutaneous is contraindicated due to coagulopathy in fulminant cases) [4]
"Determining the final diagnosis requires: history (drug history), clinical presentation, other investigations. Liver biopsy may be required" — but it is "only useful" when the above non-invasive methods fail [7].
If performed, histological findings in acute hepatitis A:
- Lobular disarray: loss of normal hepatocyte plate architecture
- Hepatocyte ballooning and necrosis: primarily periportal and centrilobular
- Councilman bodies (acidophilic bodies): eosinophilic remnants of apoptotic hepatocytes
- Portal and lobular inflammation: predominantly lymphocytic infiltrate (CD8+ T cells)
- Kupffer cell hyperplasia: activated macrophages clearing debris
- Cholestasis: bile plugs in canaliculi (especially in cholestatic variant)
- NO fibrosis (unlike chronic hepatitis)
- NO plasma cell infiltrate (if plasma cells are prominent → think autoimmune hepatitis) [13]
This is a classic DI exam question [16]:
| Marker Combination | Interpretation |
|---|---|
| Anti-HAV IgM positive | Acute hepatitis A [16] |
| Anti-HAV IgG positive, IgM negative | Past HAV infection or vaccination [16] |
| HBsAg positive, anti-HBc IgM positive | Acute hepatitis B [16] |
| HBsAg positive, anti-HBc IgG positive, IgM negative | Chronic hepatitis B |
| Anti-HBs positive, anti-HBc IgG positive | Recovered HBV infection [16] |
| Anti-HBs positive, anti-HBc negative | Prior HBV vaccination (never infected) |
| Anti-HCV positive, HCV RNA negative | Prior HCV infection (cleared or treated) [16] |
| Anti-HCV positive, HCV RNA positive | Active/chronic HCV infection |
| Anti-HEV IgM positive | Acute hepatitis E |
| All markers negative | Seronegative hepatitis — consider DILI, AIH, Wilson's, ischaemic, rarer viral causes |
GC Lecture High Yield — Viral Marker Interpretation
From the DI lecture [16]:
- Acute HAV = IgM anti-HAV
- Acute HBV = HBsAg + IgM anti-HBc
- Acute HEV = IgM anti-HEV
- Acute HCV = No reliable acute marker (anti-HCV takes up to 12 weeks; HCV RNA is the only way to catch it early, typically only done after needlestick injury) [8]
- Past HAV = IgG anti-HAV positive
- Recovered HBV = Anti-HBs positive + IgG anti-HBc positive
- Prior HCV = Anti-HCV positive + HCV RNA negative
For patients admitted with acute hepatitis (including HAV), the initial management/monitoring workup includes [2]:
| Action | Rationale |
|---|---|
| DAT (diet as tolerated) | No specific dietary restriction needed |
| Observations Q4h | Monitor for clinical deterioration (encephalopathy, haemodynamic instability) |
| H'stix BD (capillary blood glucose twice daily) | Liver failure can cause hypoglycaemia — impaired gluconeogenesis and glycogenolysis [2] |
| Bloods: CBC, LRFT, INR, NH3 — daily | Track trajectory of liver damage (ALT/AST), synthetic function (INR, albumin), and complications (ammonia, renal function) [2] |
High Yield Summary — Diagnosis of Hepatitis A
- Diagnosis = compatible clinical picture + positive anti-HAV IgM [1][2][5]
- Three pillars of acute hepatitis investigation: markedly elevated ALT/AST + specific serology + exclusion of other causes [1]
- Anti-HAV IgM appears 1–2 weeks after jaundice, persists 3–4 months; can be occasionally delayed — recheck if negative but clinically suspicious [5]
- LFT pattern: hepatocellular (ALT > AST, ALT 200–2000); ALT/AST are damage markers, NOT function tests; albumin and PT/INR are the true liver function tests [15]
- PT/INR = best prognostic marker (Factor VII half-life ~6 hours); INR ≥ 1.5 defines acute liver failure [2][4]
- Urgent imaging often not necessary — diagnosis made on clinical + laboratory grounds [7]
- Liver biopsy only when diagnosis unclear after full workup [7]
- AFP can be elevated in acute hepatitis without malignancy — follow the trajectory [8]
- Monitor admitted patients with daily CBC, LRFT, INR, NH3, and BD H'stix [2]
- Acute HCV has no reliable acute serological marker — HCV RNA is needed (typically only post-needlestick) [8]
Active Recall - Diagnosis and Investigations of Hepatitis A
References
[1] Lecture slides: GC 239. Viral hepatitis HAV_HBV_HCV_HEV.pdf (p.11, 20, 32 — diagnostic algorithm, serological tests, HBV differentiation) [2] Senior notes: Maksim Medicine Notes.pdf (p.141 — viral hepatitis overview, approach, initial management) [4] Senior notes: Ryan Ho GI.pdf (p.206, 214–215 — acute liver failure evaluation, hepatitis A workup, bilirubin interpretation) [5] Senior notes: Block A - Jaundice after raw oysters_ acute hepatitis.pdf (p.13, 20 — anti-HAV IgM timing, HEV diagnosis) [6] Senior notes: Block A - A jaundiced and incoherent patient_ liver failure.pdf (p.4, 17 — ACLF, ammonia interpretation, HE diagnosis) [7] Lecture slides: Gastroenterology Hepatology Introduction to GI:Hepatology investigations from the abnormal.pdf (p.49 — conclusions, imaging utility, liver biopsy indication) [8] Senior notes: Block A - Gastrointestinal Data Interpretation.pdf (p.2 — serology interpretation, AFP pitfall, HCV acute marker limitation) [13] Senior notes: Block A - Patients with non-viral chronic liver diseases.pdf (p.1 — AIH histology, plasma cells) [15] Senior notes: Block A - Introduction to GI_Hepatology investigations (LFT, Endoscopy).pdf (p.5, 10 — LFT framework, AST > ALT conditions, ALP/GGT interpretation) [16] Lecture slides: 1213_DI_GI_Prof_WK_Leung.ppt.pdf (p.14 — viral hepatitis marker interpretation table); Data Interpretation (M24 slides) LFT.pdf (p.4 — acute HBV vs chronic HBV with flare)
Management of Hepatitis A
The most important thing to understand about managing hepatitis A is this: there is no specific treatment [1][17]. HAV infection is self-limiting in > 95% of cases. Management is therefore overwhelmingly supportive, with the critical clinical skill being the ability to (a) recognise the rare cases progressing to fulminant hepatic failure and (b) implement prevention to stop further spread.
GC Lecture High Yield — Treatment of Hepatitis A
"No specific treatment. Supportive measures: maintaining hydration, electrolyte balance, nutritional balance. Long-term immunity after recovery from acute hepatitis A. Will not evolve into chronic viral hepatitis." [17] — This is directly from the GC 239 lecture slide.
1. Supportive Management (The Mainstay)
This is the bread and butter of HAV management. There are several key principles, each worth understanding from first principles:
- If extremely tired, rest — but rest does not shorten the course of hepatitis [5]
- The evidence for this comes from studies on US soldiers in the Vietnam War who developed hepatitis — soldiers who rested and soldiers who continued active duty had the same prognosis and disease duration [5]
- So rest is for symptom relief, not disease modification
- No alcohol for 6 months for acute hepatitis [2][4][5]
- No alcohol for life for chronic hepatitis [4]
- Why? Alcohol is directly hepatotoxic (metabolised to acetaldehyde → oxidative stress, lipid peroxidation, mitochondrial injury). Adding alcohol to an already inflamed liver compounds the injury and impairs hepatocyte regeneration. The 6-month period allows full resolution of hepatic inflammation and normalisation of liver function.
- No known drugs or herbs hasten the recovery of acute hepatitis [5]
- "Definitely do not try TCM" [5] — there are no double-blind, placebo-controlled trials demonstrating any herbal remedy accelerates recovery from acute viral hepatitis. TCM/herbal remedies carry the additional risk of drug-induced liver injury (DILI), which would be catastrophic in a patient with active hepatitis
- Steroids are specifically NOT recommended even in cholestatic or relapsing variants (see complications section later): steroids may quickly "whitewash" the cholestatic picture but increase relapse rate [4]
Exam Favourite — What NOT to Give in Acute Hepatitis A
Common mistakes include:
- Giving IV glucose drip → does not help, may cause fatty liver [5]
- Prescribing steroids for cholestatic variant → increases relapse [4]
- Recommending TCM/herbal remedies → no evidence, risk of DILI [5]
- Restricting fat in diet → fatty diet is harmless [5]
- Enforcing strict bed rest → does not alter course [5]
- Avoid elective surgery — risk of post-operative liver failure when hepatocytes are already compromised [4]
- Avoid or minimise hepatotoxic drugs (paracetamol at high doses, certain antibiotics, statins)
- Avoid alcohol (as above)
- Review all current medications for hepatotoxic potential
For patients admitted with acute hepatitis A [2]:
| Action | Rationale | Frequency |
|---|---|---|
| DAT (diet as tolerated) | No dietary restriction needed | Continuous |
| Observations Q4h | Monitor for encephalopathy (confusion, drowsiness), haemodynamic instability | Every 4 hours |
| H'stix BD | Liver failure can cause hypoglycaemia — impaired gluconeogenesis and glycogenolysis | Twice daily |
| CBC, LRFT, INR, NH3 | Track trajectory: ALT/AST (liver damage), INR (synthetic function → prognosis), bilirubin (cholestasis), ammonia (encephalopathy risk), renal function (hepatorenal syndrome) | Daily [2] |
What are we watching for? The key is to detect the rare progression to fulminant hepatic failure EARLY. Warning signs include:
- Rising INR despite supportive care
- Falling ALT with rising bilirubin (paradoxical improvement in "damage" markers but worsening function → massive hepatocyte loss)
- Altered mental status (encephalopathy)
- Hypoglycaemia
- Oliguria / rising creatinine (hepatorenal syndrome)
All viral hepatitides are notifiable diseases in Hong Kong [2]. Upon confirming acute hepatitis A:
- Notify the Centre for Health Protection (CHP) within 24 hours
- Contact tracing: identify household contacts, sexual contacts, and potential food-borne exposure sources
- Post-exposure prophylaxis for close contacts (see below)
- Source identification: if linked to a restaurant/food premises → public health investigation
4. Management of Fulminant Hepatic Failure (< 1% of HAV Cases)
When hepatitis A progresses to fulminant hepatic failure (defined as hepatic encephalopathy within 8 weeks of onset in a patient without pre-existing liver disease, with INR ≥ 1.5), management escalates dramatically:
| Principle | Details |
|---|---|
| 1. Supportive — Standard ICU care | Haemodynamic monitoring, fluid resuscitation, ventilatory support if needed |
| 2. Identify and remove/treat the insult | In HAV → supportive (no specific antiviral); in other causes: N-acetylcysteine for paracetamol, antivirals for HBV, activated charcoal for mushroom poisoning [6] |
| 3. Manage complications | See below |
| 4. High volume plasma exchange | "Wash away all the cytokines causing the liver failure" [6] — proven treatment; very expensive but effective as combination therapy |
| 5. Liver transplantation | The final line — after exhausting all other treatments [6] |
| Complication | Management | Key Notes |
|---|---|---|
| Hepatic encephalopathy | Lactulose (enteral); rifaximin controversial, may not be useful in acute liver failure [4] | Dexamethasone is NOT useful for raised ICP in acute liver failure [4] |
| Raised ICP / cerebral oedema | Mannitol, hyperventilation, barbiturate coma if refractory [4] | Cerebral oedema is the leading cause of death in fulminant hepatic failure |
| Coagulopathy | FFP, cryoprecipitate, vitamin K (if cholestasis-related), platelets | Only correct if actively bleeding or before invasive procedures — coagulopathy is also a prognostic marker, so "correcting" it masks deterioration |
| Hypoglycaemia | IV dextrose infusion (10% dextrose), frequent H'stix | Impaired gluconeogenesis and glycogenolysis |
| Acute kidney injury | Usually requires continuous renal replacement therapy (CRRT) [4] | AKI complicates 30–70% of acute liver injury; intermittent haemodialysis may worsen haemodynamic instability |
| Sepsis | Broad-spectrum antibiotics; low threshold for cultures | Immunoparesis from liver failure → increased infection risk |
| Seizures | Usually phenytoin or short-acting benzodiazepines [4] | Avoid long-acting sedatives — impaired hepatic metabolism |
| Respiratory failure | Mechanical ventilation | ARDS may occur as part of multi-organ failure |
The King's College Criteria are the most widely used criteria to predict poor prognosis in acute liver failure and guide transplant listing [4]:
For Non-Paracetamol Causes (including HAV):
- INR > 6.5 (PT > 100 seconds)
- OR any 3 of the following 5:
- Age < 10 or > 40 years
- Aetiology: non-A, non-B hepatitis, drug-induced, or halothane
- Duration of jaundice before encephalopathy > 7 days
- INR > 3.5 (PT > 50 seconds)
- Serum bilirubin > 300 µmol/L
For Paracetamol Causes (for comparison):
- Arterial pH < 7.3 (after resuscitation)
- OR all of: INR > 6.5 AND creatinine > 300 µmol/L AND grade III/IV encephalopathy
High Yield — Liver Transplant is the Final Line
Liver transplantation is the LAST resort after exhausting all other treatments [6]. It is not a first-line intervention. The sequence is: supportive care → treat cause → manage complications → plasma exchange → transplant only if unlikely to recover spontaneously based on King's College Criteria.
5. Prevention — Active and Passive Immunisation
Prevention is arguably the most clinically important and most testable aspect of HAV management.
A. Active Immunisation: HAV Vaccine
| Feature | Details |
|---|---|
| Type | Inactivated whole virus vaccine (IMI) [2][4] |
| Regimen | 2 doses intramuscularly, 6–12 months apart (2nd dose is booster) [2][4] |
| Efficacy | Immunogenicity 99%, protective efficacy 100% [4] |
| Onset of protection | Effective protection ≤ 3–4 weeks after 1st dose [4]; effective around 4 weeks after 1st dose [2] |
| Duration of protection | Long-lasting (likely lifelong after 2-dose series); current evidence suggests ≥ 25 years |
| Alternative | Combined bivalent vaccine (HAV + HBV) — Twinrix; 3-dose schedule (0, 1, 6 months) [2] |
| Indication | Rationale |
|---|---|
| Travellers to endemic areas | High exposure risk in areas with poor sanitation |
| Men who have sex with men (MSM) | Faecal-oral transmission via oro-anal contact |
| Patients with chronic liver disease (CLD) | Superinfection HAV on chronic HBV/HCV increases risk of fulminant hepatic failure — this is especially important in Hong Kong |
| Intravenous drug users (IVDU) | Shared drug paraphernalia; poor hygiene |
| Food handlers | Prevent transmission to public |
| Healthcare workers | Occupational exposure risk |
| Residents/staff of institutions | Crowding facilitates transmission |
| Post-exposure prophylaxis | Can be given within 2 weeks of exposure (alongside or instead of IVIg depending on age/health) |
GC Lecture High Yield — HAV Vaccine for Chronic Liver Disease Patients
In Hong Kong, where chronic HBV is extremely prevalent (~8% of population), HAV vaccination is specifically indicated for all patients with chronic liver disease [2][17]. The reason is simple: acute HAV superinfection on chronic HBV dramatically increases the risk of fulminant failure — the liver is already compromised, and the additional immune-mediated assault from HAV can be catastrophic.
| Absolute | Relative |
|---|---|
| Severe allergic reaction (anaphylaxis) to previous dose or vaccine component | Moderate-to-severe acute illness (defer until recovery) |
| Pregnancy (theoretical concern — but inactivated vaccines are generally considered safe; weigh risk vs benefit) |
| Feature | Details |
|---|---|
| Type | Pooled human immunoglobulin containing anti-HAV antibodies |
| Efficacy | Up to 90% — prevents or reduces severity of infection; dose-dependent [4] |
| Duration of effect | Effective for up to 6 months [4] |
| Onset | Immediate (provides pre-formed antibodies) |
| Primary indication | Urgent travellers who need protection before vaccine takes effect [2][4] — because the vaccine takes 3–4 weeks to be effective, IVIg bridges this gap |
| Post-exposure prophylaxis | Within 2 weeks of exposure, especially for: infants < 12 months (too young for vaccine), immunocompromised patients (poor vaccine response), those with vaccine allergy |
Post-Exposure Prophylaxis Strategy:
| Patient Category | Recommended PEP |
|---|---|
| Healthy person aged 1–40 years | HAV vaccine alone (single dose within 2 weeks of exposure) |
| Healthy person aged > 40 years | HAV vaccine + IVIg (older patients may have suboptimal vaccine response and higher risk of severe disease) |
| Infant < 12 months | IVIg alone (vaccine not licensed for this age) |
| Immunocompromised | IVIg ± vaccine (impaired immune response to vaccine alone) |
| Chronic liver disease | IVIg + vaccine (high-risk group) |
| Vaccine allergy | IVIg alone |
| Measure | Mechanism |
|---|---|
| Careful cooking of shelled seafood | Virus killed by dry heat at 100°C in 1 minute, wet heat at 100°C in 5–10 minutes [4]; NOT killed at 60°C even in 12 hours [4] — this is why steaming shellfish may NOT be sufficient if internal temperature doesn't reach 100°C |
| Chlorination of drinking water [4] | Chlorine inactivates HAV |
| Hand hygiene | Standard infection control; HAV is shed in faeces |
| Sanitary food handling | Infected food handlers must be excluded from work until no longer infectious (typically 1 week after jaundice onset) |
| Avoid raw/undercooked shellfish | Bivalve molluscs concentrate HAV from contaminated water |
Temperature Matters — Cooking HAV
HAV is NOT killed at 60°C even after 12 hours [4]. This is critical — many cooking methods (e.g. brief steaming, light stir-frying of shellfish) may not reach sufficient internal temperatures. The virus requires 100°C for at least 1 minute (dry heat) or 5–10 minutes (wet heat) to be inactivated. Simply "cooking" shellfish is not enough — it must be thoroughly cooked to a high internal temperature.
6. Specific Clinical Scenarios and Their Management
- Presentation: Prolonged, marked jaundice, pruritus for up to 12–24 weeks; high bilirubin (10× ULN) but with decreasing AST/ALT
- Management: ALWAYS complete resolution [4]
- Symptomatic management of pruritus (cholestyramine, ursodeoxycholic acid, antihistamines)
- Steroids are NOT used — they quickly "whitewash" the cholestatic picture but increase relapse rate [4]
- Presentation: Apparent clinical recovery followed by biochemical ± clinical relapse; can be biphasic or polyphasic, lasting 3–12 months
- Key findings: AST/ALT > 1000 IU/L again; IgM anti-HAV remains positive; HAV identified in stools and HAV RNA in serum
- Management: ALWAYS complete resolution — steroids can increase relapse [4]
- Reassurance and monitoring; no specific treatment required
- Increased risk of fulminant hepatic failure
- Management: supportive care with heightened vigilance; early hepatology/transplant team involvement
- Prevention is key: vaccinate all chronic HBV carriers against HAV [2]
| ✅ DO | ❌ DO NOT |
|---|---|
| Supportive care: hydration, nutrition, electrolyte balance | Give glucose drip ("does not help, may cause fatty liver") [5] |
| Alcohol abstinence × 6 months [2][5] | Give alcohol ("obvious but worth stating") |
| Monitor daily: CBC, LRFT, INR, NH3 | Give steroids (even for cholestatic variant — increases relapse) [4] |
| H'stix BD for hypoglycaemia | Prescribe TCM/herbal remedies (no evidence, risk of DILI) [5] |
| Notify CHP | Perform elective surgery (risk of post-operative liver failure) [4] |
| Vaccinate contacts and high-risk groups | Give unnecessary IV fluids or restrict diet |
| Escalate to ICU if INR ≥ 1.5 or encephalopathy develops | Discharge prematurely without confirming improving trajectory |
| Consider transplant if King's College Criteria met | Use transplant as first-line |
High Yield Summary — Management of Hepatitis A
- No specific treatment exists — management is entirely supportive [5][17]
- Supportive measures: hydration, electrolyte balance, nutritional balance [17]
- Rest does not shorten disease course; diet is unrestricted; fatty diet is harmless; glucose drip does NOT help [5]
- Alcohol abstinence for 6 months (acute) or lifelong (chronic hepatitis) [2][5]
- No drugs hasten recovery — avoid TCM/herbal remedies [5]
- Steroids are contraindicated in cholestatic and relapsing variants — they increase relapse [4]
- Monitor: daily CBC, LRFT, INR, NH3; H'stix BD [2]
- Fulminant hepatic failure management (5 principles): supportive ICU care → identify/treat cause → manage complications → high volume plasma exchange → liver transplantation (final line) [6]
- King's College Criteria guide transplant listing; for non-paracetamol causes: INR > 6.5 OR any 3 of 5 criteria [4]
- Prevention: HAV vaccine (inactivated whole virus, 2 doses 6–12 months apart; effective ≤ 3–4 weeks after 1st dose; immunogenicity 99%) [2][4]
- Passive immunisation: IVIg (up to 90% efficacy, lasts up to 6 months; for urgent travellers or those unable to receive vaccine) [4]
- HAV vaccination indicated for: travellers, MSM, chronic liver disease, IVDU, food handlers [2]
- Cooking: HAV killed at 100°C in 1 min (dry) or 5–10 min (wet); NOT killed at 60°C even in 12 hours [4]
- Notifiable disease — notify CHP, contact tracing, post-exposure prophylaxis [2]
Active Recall - Management of Hepatitis A
References
[2] Senior notes: Maksim Medicine Notes.pdf (p.141 — HAV prevention, vaccine indications, alcohol abstinence, monitoring) [4] Senior notes: Ryan Ho GI.pdf (p.207, 216 — supportive management, cooking temperatures, vaccine regimen, IVIg, King's College Criteria, cholestatic/relapsing variant management) [5] Senior notes: Block A - Jaundice after raw oysters_ acute hepatitis.pdf (p.3 — no specific treatment, rest futility, diet, glucose drip, TCM, alcohol abstinence) [6] Senior notes: Block A - A jaundiced and incoherent patient_ liver failure.pdf (p.24 — five principles of ALF management, plasma exchange, transplant as final line) [17] Lecture slides: GC 239. Viral hepatitis HAV_HBV_HCV_HEV.pdf (p.12 — treatment: no specific treatment, supportive measures, long-term immunity, no chronicity)
Complications of Hepatitis A
Before diving into individual complications, it's worth understanding the overarching principle: hepatitis A is self-limiting in > 95% of cases and NEVER becomes chronic. This fundamentally distinguishes it from HBV and HCV, where the major complications (cirrhosis, HCC, decompensation) arise from decades of chronic inflammation. The complications of HAV are therefore either:
- Atypical clinical courses of the acute infection itself (cholestatic, relapsing)
- Fulminant hepatic failure — the life-threatening complication
- Extrahepatic manifestations — immune-mediated phenomena
- Rare associations (e.g. aplastic anaemia)
HAV will NOT evolve into chronic viral hepatitis [17] — this means there are no long-term complications of cirrhosis, portal hypertension, variceal bleeding, ascites, hepatorenal syndrome, or HCC attributable to hepatitis A alone.
GC Lecture High Yield — No Chronicity
"Long-term immunity after recovery from acute hepatitis A. Will not evolve into chronic viral hepatitis." [17] — This is directly from the GC 239 lecture slide. Understanding this principle immediately tells you that the complications of HAV are confined to the acute phase and its aftermath.
1. Cholestatic Hepatitis A (< 5%)
Prolonged cholestasis occurring in < 5% of acute HAV infections [4].
- Characterised by very high bilirubin (up to 10× ULN) but with decreasing AST/ALT [4]
- This pattern is the key to recognising it: the "damage" markers (transaminases) are resolving, but bilirubin remains stubbornly elevated. Why? The hepatocytes are recovering from the acute injury, but the intrahepatic cholestasis (from hepatocyte swelling compressing canaliculi and from bile duct inflammation) takes much longer to resolve. Think of it as: the fire is going out, but the smoke lingers.
- ALWAYS achieves complete resolution [4][3]
- Steroids are NOT used — they may quickly "whitewash" the cholestatic picture (i.e. make the jaundice improve transiently) but increase the relapse rate [4]
- Symptomatic management of pruritus: cholestyramine (bile acid sequestrant), ursodeoxycholic acid, antihistamines
- Reassurance is the most important intervention — patients and families may panic at weeks of persistent jaundice
Why Do Steroids Increase Relapse?
Steroids suppress the immune response that is clearing the virus. By dampening the immune attack on infected hepatocytes, steroids allow HAV to persist longer. When steroids are withdrawn, the immune system ramps up again → another round of immune-mediated hepatocyte destruction → relapse. This is analogous to the concept of HBV reactivation after steroid withdrawal — the immune "rebound" causes the damage.
2. Relapsing Hepatitis A (6–10%)
- Can be biphasic or polyphasic [4]
- Duration may last 3–12 months [4]
- Typically, the patient recovers from the initial episode (transaminases normalise, symptoms resolve), then weeks later develops a second (or occasionally third) episode of transaminase elevation ± recurrence of jaundice and symptoms
- Related to immune reaction towards HAV [4]
- The virus is not completely cleared during the initial immune response. Residual viral antigens trigger a second wave of immune-mediated hepatocyte destruction. The patient remains infectious during relapse because:
- ALWAYS achieves complete resolution [4]
- Steroids can increase relapse — do NOT use [4]
- The duration of clinical relapse is usually less than 3 weeks [3]
- Management: supportive care, reassurance, monitor LFTs
Important — Relapsing HAV Patients Remain Infectious
Because HAV is still present in stools and serum during relapse, these patients can transmit the virus. This has public health implications — they may need to be re-counselled about hygiene measures and excluded from food handling.
3. Fulminant Hepatic Failure (< 1%)
This is the most feared complication and the only one that carries significant mortality.
- < 1% of all HAV infections [4]
- Occurs especially in patients > 50 years old and individuals with other liver diseases such as chronic hepatitis B or C [4][3]
- This is profoundly relevant in Hong Kong: a chronic HBV carrier who acquires HAV superinfection has a dramatically increased risk of fulminant failure
The immune response to HAV is the double-edged sword. In most patients, the immune attack on infected hepatocytes is measured and proportional — enough to clear the virus but not enough to destroy the entire liver. In fulminant failure, the immune response is excessively vigorous — massive hepatocyte necrosis occurs faster than the liver can regenerate. Contributing factors include:
- Age-related factors: older adults mount stronger but less well-regulated immune responses
- Pre-existing liver disease: fewer reserve hepatocytes → less capacity to withstand immune-mediated destruction + less regenerative capacity
- Genetic/host factors: likely variation in HLA types and cytokine responses
| Subtype | Jaundice-to-Encephalopathy Interval | Cerebral Oedema | INR | Bilirubin | Prognosis |
|---|---|---|---|---|---|
| Hyperacute | 0–1 week | Common | Prolonged | Least raised | Moderate |
| Acute | > 1–4 weeks | Common | Prolonged | Raised | Poor |
| Subacute | > 4–26 weeks | Infrequent | Less prolonged | Raised | Poor |
These are the complications OF the complication — multi-organ failure cascading from hepatic failure:
| Complication | Mechanism | Key Features |
|---|---|---|
| Hepatic encephalopathy | Failure to clear ammonia and other nitrogenous toxins → neurotoxicity; cerebral astrocyte swelling → cerebral oedema | Confusion, drowsiness → coma; cerebral oedema is the leading cause of death in fulminant hepatic failure; dexamethasone is NOT useful for raised ICP in acute liver failure [4] |
| Coagulopathy | Failed synthesis of clotting factors (especially Factor VII); DIC from release of tissue factor from necrotic hepatocytes | Bleeding tendency; but paradoxically, also at risk of thrombosis (reduced antithrombin III, protein C, protein S) |
| Infections / Sepsis | Reticuloendothelial dysfunction and reduced opsonisation [6]; impaired Kupffer cell function; reduced complement production; bacteraemia in up to 25% of fulminant hepatic failure patients [6] | Bacteria from respiratory and urinary tracts (Staph, Strep, Gram-negative rods); fungal infection especially Candida [6] |
| Acute kidney injury | Hepatorenal syndrome (splanchnic vasodilation → renal hypoperfusion); acute tubular necrosis; AKI complicates 30–70% of acute liver injury [4] | Oliguria, rising creatinine; often requires CRRT |
| Hypoglycaemia | Impaired gluconeogenesis and glycogenolysis; depleted hepatic glycogen stores | Insidious onset; can worsen encephalopathy; requires regular H'stix monitoring |
| Metabolic derangements | Hyponatraemia (dilutional), hypokalaemia, metabolic acidosis (lactic acidosis from impaired hepatic lactate clearance), respiratory alkalosis (hyperventilation from encephalopathy) | Multiple electrolyte disturbances requiring serial monitoring |
| Multi-organ failure | Systemic inflammatory response; circulatory failure (high-output state); ARDS | Haemodynamic instability requiring vasopressors; mechanical ventilation |
Why Are Infections So Common in Liver Failure?
The liver is the body's largest reticuloendothelial organ. Kupffer cells (resident hepatic macrophages) normally filter ~99% of gut-derived bacteria and endotoxins from portal blood. When the liver fails: (1) Kupffer cell function is impaired → bacteria "escape" into the systemic circulation, (2) complement and opsonin production falls → impaired bacterial killing, (3) immune cell function is generally depressed (immunoparesis). The result is that infections — especially from respiratory and urinary tracts — are extremely common, and fungal infections (especially Candida) become a significant threat [6].
As covered in the management section, the King's College Criteria guide transplant listing:
- INR > 6.5
- OR any 3 of: age < 10 or > 40, non-A non-B/drug aetiology, jaundice-to-encephalopathy > 7 days, INR > 3.5, bilirubin > 300 µmol/L
Variceal bleeding is uncommon in acute liver failure [18]. If variceal bleeding is present, suspect Budd-Chiari syndrome as an alternative diagnosis rather than straightforward acute liver failure.
4. Extrahepatic Manifestations (< 15%)
- Characterised by immune complex-mediated disease [4]
- During active HAV infection, circulating immune complexes (HAV antigen + anti-HAV antibodies) deposit in various tissues → activate complement → tissue damage
- This is a type III hypersensitivity reaction (Arthus-type/serum sickness-like)
| Manifestation | Mechanism | Clinical Features |
|---|---|---|
| Skin rash / Urticaria | Immune complex deposition in dermal vessels → complement activation → vasculitis / urticaria | Maculopapular rash, urticaria, or rarely leukocytoclastic vasculitis |
| Arthralgia / Arthritis | Immune complex deposition in synovium → synovitis | Polyarthralgias or frank polyarthritis; typically symmetric, involving small joints; occurs in pre-icteric or early icteric phase |
| Vasculitis | Immune complex deposition in vessel walls → inflammation | Cutaneous vasculitis; rarely systemic vasculitis |
| Cryoglobulinaemia | Circulating cryoglobulins (immunoglobulins that precipitate at cold temperatures) | Palpable purpura, arthralgias, renal involvement (rare) |
| Glomerulonephritis | Immune complex deposition in glomeruli → mesangial proliferative or membranoproliferative GN | Haematuria, proteinuria; typically resolves with viral clearance |
| Haemolytic anaemia | Autoimmune haemolysis triggered by molecular mimicry or immune dysregulation | Positive direct Coombs test; reticulocytosis; ↑ LDH, ↓ haptoglobin |
| Aplastic anaemia | See below — discussed separately as a distinct and important complication | |
| Guillain-Barré syndrome | Post-infectious immune-mediated demyelination of peripheral nerves | Ascending weakness, areflexia; rare but documented |
| Acute pancreatitis | Immune-mediated or direct viral effect on pancreas | Epigastric pain radiating to back; elevated amylase/lipase |
| Myocarditis / Pericarditis | Immune-mediated cardiac inflammation | Chest pain, ST changes, elevated troponin; rare |
All extrahepatic manifestations of HAV are self-limiting and resolve with viral clearance. No specific treatment beyond supportive care is usually required.
5. Post-Hepatitis Aplastic Anaemia (Rare but Important)
Hepatitis is a well-known antecedent to aplastic anaemia [14]. This is sometimes called hepatitis-associated aplastic anaemia (HAAA).
- T-cell mediated destruction of haematopoietic stem cells [14]
- The hepatitis triggers an aberrant immune response where activated T cells (specifically CD8+ cytotoxic T cells and γδ T cells) attack not only infected hepatocytes but also haematopoietic stem cells in the bone marrow
- Interestingly, the responsible virus in most cases of HAAA is never identified — most are "seronegative" (all standard hepatitis viral markers are negative). HAV, HBV, and HCV are rarely the direct cause, but the association highlights the concept that viral hepatitis can trigger immune-mediated bone marrow failure
- While most cases of HAAA are seronegative, HAV has been documented as a trigger in case reports
- If a patient develops pancytopenia after recovering from hepatitis A, think of aplastic anaemia
- This is important because aplastic anaemia requires urgent haematological management (immunosuppressive therapy with ATG + ciclosporin, or bone marrow transplant)
6. Triggering of Autoimmune Hepatitis (Rare)
Autoimmune hepatitis has been reported as a complication following acute hepatitis A [3].
- HAV infection may act as a trigger for autoimmune hepatitis in genetically predisposed individuals
- The viral infection breaks immune tolerance to hepatocyte autoantigens through:
- Molecular mimicry: HAV antigens share epitopes with hepatocyte surface proteins
- Bystander activation: the intense immune response during HAV infection non-specifically activates autoreactive T cells
- Epitope spreading: initial immune response to HAV antigens spreads to target self-antigens on damaged hepatocytes
- If transaminases fail to normalise after expected recovery from HAV, or if they worsen after an initial improvement, consider autoimmune hepatitis
- Investigate with: ANA, ASMA, anti-LKM-1, serum IgG levels, ± liver biopsy
- Management is that of autoimmune hepatitis: corticosteroids + azathioprine
While not a complication of HAV per se, the consequence of HAV superinfection on pre-existing chronic liver disease deserves emphasis:
- HAV superinfection in chronic HBV carriers dramatically increases risk of fulminant hepatic failure [9]
- This is one of the causes of acute-on-chronic liver failure (ACLF) [6]:
- ACLF definition: acute liver insult manifesting jaundice and INR > 1.5, complicating within 4 weeks by ascites and/or encephalopathy in patients with underlying chronic liver disease [6]
- ACLF has 28-day mortality > 20% — much worse than acute liver failure alone [6]
- HAV and HEV superinfection are specifically listed as causes of ACLF [6]
Prevention is Better Than Cure — Vaccinate Chronic HBV Carriers
The management principle for cirrhosis also includes: preventing superimposed insults to the liver — vaccination with hepatitis A and B vaccines if not already immune; avoidance of hepatotoxins (alcohol, paracetamol, NSAIDs, herbal remedies) [4].
| Complication | Incidence | Key Features | Prognosis |
|---|---|---|---|
| Cholestatic hepatitis | < 5% | Prolonged jaundice + pruritus (up to 12–24 weeks); high bilirubin with decreasing ALT/AST; steroids NOT used | Always complete resolution |
| Relapsing hepatitis | 6–10% | Biphasic/polyphasic course; AST/ALT > 1000; IgM anti-HAV remains positive; HAV in stools; steroids NOT used | Always complete resolution |
| Fulminant hepatic failure | < 1% | INR ≥ 1.5 + encephalopathy; risk ↑ in age > 50 and pre-existing liver disease; multi-organ failure; cerebral oedema | Significant mortality; may require liver transplant |
| Extrahepatic manifestations | < 15% | Immune complex-mediated: rash, arthralgia, vasculitis, GN, haemolytic anaemia, GBS | Self-limiting |
| Aplastic anaemia | Rare | Pancytopenia weeks–months after hepatitis; T-cell mediated HSC destruction; usually seronegative | Requires urgent haematological management |
| Autoimmune hepatitis | Rare | Failure of transaminases to normalise; positive autoantibodies; elevated IgG | Requires immunosuppression |
| ACLF (in chronic HBV carriers) | Variable | HAV superinfection on chronic HBV → jaundice + INR > 1.5 → ascites/encephalopathy within 4 weeks; 28-day mortality > 20% | Much worse prognosis than acute liver failure alone |
High Yield Summary — Complications of Hepatitis A
- HAV never becomes chronic — all complications are related to the acute phase [17]
- Cholestatic hepatitis (< 5%): prolonged jaundice up to 12–24 weeks; high bilirubin + decreasing ALT/AST; always resolves; steroids increase relapse — NOT used [4]
- Relapsing hepatitis (6–10%): biphasic/polyphasic relapse lasting 3–12 months; IgM anti-HAV remains positive; HAV still in stools (infectious!); always resolves; steroids increase relapse — NOT used [4]
- Fulminant hepatic failure (< 1%): the only life-threatening complication; risk increased in > 50 years old and pre-existing liver disease (especially chronic HBV); complications include cerebral oedema (leading cause of death), coagulopathy, infections, AKI, hypoglycaemia; managed with ICU care, plasma exchange, liver transplant as final line [4][6]
- Extrahepatic manifestations (< 15%): immune complex-mediated (rash, arthralgia, vasculitis, GN); self-limiting [4]
- Aplastic anaemia: rare; T-cell mediated destruction of haematopoietic stem cells; often seronegative [14]
- ACLF in chronic HBV carriers: HAV superinfection + chronic HBV → fulminant decompensation; 28-day mortality > 20%; prevention by HAV vaccination of all chronic HBV carriers [6]
- Infections in liver failure: Kupffer cell dysfunction + reduced opsonisation → bacterial (Staph, Strep, GNR) and fungal (Candida) infections; bacteraemia in up to 25% [6]
- Variceal bleeding is uncommon in acute liver failure — if present, suspect Budd-Chiari syndrome [18]
Active Recall - Complications of Hepatitis A
References
[3] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (p.740, 742 — complications of HAV: cholestatic, autoimmune, relapsing, fulminant; prevention) [4] Senior notes: Ryan Ho GI.pdf (p.215–216, 315 — complications: cholestatic, relapsing, extrahepatic manifestations; cirrhosis management including HAV vaccination) [5] Senior notes: Block A - Jaundice after raw oysters_ acute hepatitis.pdf (p.2, 3 — management principles, biochemistry of hepatitis) [6] Senior notes: Block A - A jaundiced and incoherent patient_ liver failure.pdf (p.12, 24 — ACLF definition, infections in liver failure, HAV/HEV superinfection, complications of liver failure) [9] Senior notes: Block A - I am a hepatitis B carrier.pdf (p.28 — HAV/HEV superinfection on chronic HBV) [14] Senior notes: Block A - Hematology Data Interpretation.pdf (p.1 — hepatitis preceding aplastic anaemia, T-cell mediated HSC destruction) [17] Lecture slides: GC 239. Viral hepatitis HAV_HBV_HCV_HEV.pdf (p.12 — treatment: no specific treatment, long-term immunity, no chronic viral hepatitis) [18] Senior notes: Maksim Medicine Notes.pdf (p.133–135 — acute liver failure definition, classification, variceal bleeding uncommon in ALF); Handbook of Internal Medicine 2024.pdf (p.88 — ALF definition and classification)
High Yield Summary
Hepatitis A — Key Take-Home Points
- HAV = non-enveloped ssRNA virus, Picornaviridae family; transmitted faecal-oral; incubation 14–28 days [1][2]
- Self-limiting > 95%; NO chronic infection, NO carrier state; lifelong immunity after recovery [1][3]
- Largely asymptomatic; adults more symptomatic than children [1]
- Mortality increases with age (0.1% in children → 1.1% in ≥ 40 years) [4]
- Clinical phases: Pre-icteric (fever, anorexia, nausea, dark urine) → Icteric (jaundice, symptoms improve) → Convalescence (4–6 weeks)
- Liver damage is immune-mediated, not directly cytopathic — CD8+ CTLs destroy infected hepatocytes
- LFT: ALT 200–2000; predominantly conjugated hyperbilirubinaemia; PT/INR = best prognostic marker [2][4]
- Fulminant hepatitis < 1% but increased risk in elderly and those with underlying chronic liver disease (especially chronic HBV — very relevant in HK) [4][6]
- Diagnosis: Anti-HAV IgM [1][2]
- Prevention: HAV vaccine (active) + immunoglobulin (passive post-exposure) [2]
- Notifiable disease in Hong Kong [2]
- HAV = shellfish; HEV = pork liver congee [5]
High Yield Summary — Differential Diagnosis of Hepatitis A
- Top 4 differentials for markedly elevated transaminases: Acute viral hepatitis, ischaemic hepatitis, drug-induced hepatitis, HBV reactivation [7]
- Closest viral mimics: HEV (faecal-oral, similar presentation), acute HBV, EBV/CMV (look for lymphadenopathy + atypical lymphocytes)
- Always exclude: DILI (especially paracetamol and TCM/herbal), alcoholic hepatitis (AST > ALT, AST < 500), autoimmune hepatitis (young females, ↑ IgG, autoantibodies)
- Shock liver clues: haemodynamic instability, massively elevated LDH, ALT/LDH ratio < 1.5, rapid resolution in 1–3 days [7]
- Wilson disease: young patient, Coombs-negative haemolytic anaemia + fulminant liver failure = pathognomonic [13]
- In HK: always consider HBV reactivation and HAV/HEV superinfection on chronic HBV [9]
- Definitive differentiation: serology panel (anti-HAV IgM, anti-HEV IgM, HBsAg, anti-HBc IgM, anti-HCV) [2]
- Diagnosis requires: history (drug history), clinical presentation, other investigations; liver biopsy may be required [7]
High Yield Summary — Diagnosis of Hepatitis A
- Diagnosis = compatible clinical picture + positive anti-HAV IgM [1][2][5]
- Three pillars of acute hepatitis investigation: markedly elevated ALT/AST + specific serology + exclusion of other causes [1]
- Anti-HAV IgM appears 1–2 weeks after jaundice, persists 3–4 months; can be occasionally delayed — recheck if negative but clinically suspicious [5]
- LFT pattern: hepatocellular (ALT > AST, ALT 200–2000); ALT/AST are damage markers, NOT function tests; albumin and PT/INR are the true liver function tests [15]
- PT/INR = best prognostic marker (Factor VII half-life ~6 hours); INR ≥ 1.5 defines acute liver failure [2][4]
- Urgent imaging often not necessary — diagnosis made on clinical + laboratory grounds [7]
- Liver biopsy only when diagnosis unclear after full workup [7]
- AFP can be elevated in acute hepatitis without malignancy — follow the trajectory [8]
- Monitor admitted patients with daily CBC, LRFT, INR, NH3, and BD H'stix [2]
- Acute HCV has no reliable acute serological marker — HCV RNA is needed (typically only post-needlestick) [8]
High Yield Summary — Management of Hepatitis A
- No specific treatment exists — management is entirely supportive [5][17]
- Supportive measures: hydration, electrolyte balance, nutritional balance [17]
- Rest does not shorten disease course; diet is unrestricted; fatty diet is harmless; glucose drip does NOT help [5]
- Alcohol abstinence for 6 months (acute) or lifelong (chronic hepatitis) [2][5]
- No drugs hasten recovery — avoid TCM/herbal remedies [5]
- Steroids are contraindicated in cholestatic and relapsing variants — they increase relapse [4]
- Monitor: daily CBC, LRFT, INR, NH3; H'stix BD [2]
- Fulminant hepatic failure management (5 principles): supportive ICU care → identify/treat cause → manage complications → high volume plasma exchange → liver transplantation (final line) [6]
- King's College Criteria guide transplant listing; for non-paracetamol causes: INR > 6.5 OR any 3 of 5 criteria [4]
- Prevention: HAV vaccine (inactivated whole virus, 2 doses 6–12 months apart; effective ≤ 3–4 weeks after 1st dose; immunogenicity 99%) [2][4]
- Passive immunisation: IVIg (up to 90% efficacy, lasts up to 6 months; for urgent travellers or those unable to receive vaccine) [4]
- HAV vaccination indicated for: travellers, MSM, chronic liver disease, IVDU, food handlers [2]
- Cooking: HAV killed at 100°C in 1 min (dry) or 5–10 min (wet); NOT killed at 60°C even in 12 hours [4]
- Notifiable disease — notify CHP, contact tracing, post-exposure prophylaxis [2]
High Yield Summary — Complications of Hepatitis A
- HAV never becomes chronic — all complications are related to the acute phase [17]
- Cholestatic hepatitis (< 5%): prolonged jaundice up to 12–24 weeks; high bilirubin + decreasing ALT/AST; always resolves; steroids increase relapse — NOT used [4]
- Relapsing hepatitis (6–10%): biphasic/polyphasic relapse lasting 3–12 months; IgM anti-HAV remains positive; HAV still in stools (infectious!); always resolves; steroids increase relapse — NOT used [4]
- Fulminant hepatic failure (< 1%): the only life-threatening complication; risk increased in > 50 years old and pre-existing liver disease (especially chronic HBV); complications include cerebral oedema (leading cause of death), coagulopathy, infections, AKI, hypoglycaemia; managed with ICU care, plasma exchange, liver transplant as final line [4][6]
- Extrahepatic manifestations (< 15%): immune complex-mediated (rash, arthralgia, vasculitis, GN); self-limiting [4]
- Aplastic anaemia: rare; T-cell mediated destruction of haematopoietic stem cells; often seronegative [14]
- ACLF in chronic HBV carriers: HAV superinfection + chronic HBV → fulminant decompensation; 28-day mortality > 20%; prevention by HAV vaccination of all chronic HBV carriers [6]
- Infections in liver failure: Kupffer cell dysfunction + reduced opsonisation → bacterial (Staph, Strep, GNR) and fungal (Candida) infections; bacteraemia in up to 25% [6]
- Variceal bleeding is uncommon in acute liver failure — if present, suspect Budd-Chiari syndrome [18]