GC239 Viral Hepatitis HAV: HBV: HCV: HEV
Viral hepatitis encompasses liver inflammation caused by hepatotropic viruses, including HAV (fecal-oral, acute, self-limited), HBV (bloodborne/sexual, can become chronic with risk of cirrhosis and hepatocellular carcinoma), HCV (bloodborne, frequently chronic leading to cirrhosis), and HEV (fecal-oral, usually self-limited but potentially fulminant in pregnancy).
This lecture, delivered by Dr. Loey Mak (GC 239), provides a comprehensive overview of the four hepatitis viruses that are clinically most important in Hong Kong: HAV, HBV, HCV, and HEV. The lecture is structured around two major clinical scenarios: acute viral hepatitis (primarily HAV, HEV, and sometimes acute HBV) and chronic viral hepatitis (HBV and HCV). HDV is mentioned briefly but is not a focus because it is rare in Chinese populations. [1]
Why this matters for exams: Viral hepatitis is a perennial favorite in HKU summative exams — it bridges gastroenterology/hepatology, microbiology, public health, pathology, and surgery (HCC). Questions appear as MCQs, SAQs, and minicases. The lecture gives you the exact framework examiners use: epidemiology → transmission → clinical features → serological diagnosis → management → prevention.
Learning Objectives [1]
Describe the epidemiology of viral hepatitis in Hong Kong; Differentiate the route of transmission: blood-borne vs food-borne; Recognize the clinical consequence of acute and chronic viral hepatitis; Appreciate the blood tests that are helpful to confirm the diagnosis; Understand the measures for treatment and prevention.
A total of 5 types of viral hepatitis can affect humans. HAV and HEV are food-borne (fecal-oral). HBV, HCV, and HDV are blood-borne. Only HBV and HCV can become chronic infections. [1]
| Feature | HAV | HBV | HCV | HDV | HEV |
|---|---|---|---|---|---|
| Genome | ssRNA | dsDNA | ssRNA | ssRNA | ssRNA |
| Family | Picornaviridae | Hepadnaviridae | Flaviviridae | Incomplete virus | Hepeviridae |
| Transmission | Fecal-oral | Blood-borne, sexual, vertical | Blood-borne | Blood-borne (needs HBV) | Fecal-oral, zoonotic |
| Incubation | 14–28 days | 4–20 weeks | 2–26 weeks | 6–9 weeks | 2–10 weeks (mean 5–6 wk) |
| Chronicity | Never | Yes (highest in neonates >90%) | Yes (~55–85% adults) | Yes (depends on HBV) | No (except immunosuppressed/transplant) |
| Vaccine | Yes | Yes | No | HBV vaccine | Hecolin (China only) |
| Notifiable in HK | Yes | Yes | Yes | Yes | Yes |
All viral hepatitis are notifiable diseases in Hong Kong. [2]
PART 1: ACUTE VIRAL HEPATITIS
Hepatitis A (HAV)
Hepatitis A is a notifiable disease in Hong Kong. Overall anti-HAV seroprevalence in HK is ~52.2%. [1]
- This means about half of the HK population has been exposed at some point. Seroprevalence is age-dependent — older adults have higher rates because they grew up when sanitation was poorer.
- Why does this matter clinically? If an adult in HK has never been exposed (no anti-HAV IgG), they are susceptible and more likely to be symptomatic if infected (adults are more symptomatic than children).
Fecal-oral route: ingestion or direct contact of food, water, or objects contaminated by feces of affected person, or sexual contact (including MSM). HAV can persist in feces and soil for a prolonged period. Resistant to acidic environment and heat (60°C for 60 minutes) and freezing temperatures. [1]
Common food culprits: Raw or undercooked bivalve shell seafood — e.g., oysters, clams, scallops. [1]
Why oysters? Bivalve shellfish are filter feeders — they concentrate virus particles from contaminated water. Cooking to high temperature (boiling >90°C for several minutes) inactivates HAV, but 60°C for 60 minutes is NOT enough. This is why "lightly steamed" oysters can still transmit HAV.
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]
Symptoms (when present):
- Pre-icteric phase (~1–2 weeks): fever, malaise, nausea, loss of appetite, abdominal pain, vomiting, diarrhea [1]
- Icteric phase (~1–2 weeks): jaundice appears, other symptoms begin to subside [3]
- Convalescent phase (4+ weeks): gradual recovery [3]
Clinical Pearl
Dark urine (tea-colored) often appears before jaundice — this is conjugated bilirubin being excreted renally because the swollen hepatocytes cannot excrete it into bile efficiently. Pale stools occur because less bilirubin reaches the gut.
Acute hepatitis A shows a parenchymal pattern: ALT & AST >> ALP & GGT. Level of elevation: in the range of 1000s. [1]
The "parenchymal pattern" means the transaminases (ALT/AST) are disproportionately elevated compared to cholestatic markers (ALP/GGT). This is because HAV causes direct hepatocyte damage (necroinflammation), not biliary obstruction.
Serological diagnosis: Anti-HAV IgM positive = acute HAV infection. [1]
The investigation flowchart from the lecture for acute hepatitis [1]:
| Test | Expected in HAV | Purpose |
|---|---|---|
| Anti-HAV IgM | Positive | Confirms acute HAV |
| HBsAg | Negative | Rules out HBV |
| Anti-HCV | Negative | Rules out HCV |
| Anti-HEV IgM | Negative | Rules out HEV |
| ANA, anti-smooth muscle, anti-LKM-1 | Negative | Rules out autoimmune hepatitis |
| Ultrasound | No biliary obstruction, liver normal, no splenomegaly | Excludes other causes |
| Toxicology screen / Paracetamol levels | Normal | Rules out drug-induced |
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. [1]
- No antivirals exist for HAV. This is purely supportive.
- Recovery confers lifelong immunity — the IgG anti-HAV persists indefinitely.
- Relapsing hepatitis occurs in ~10% of patients within 6 months, but still self-resolves [4].
- Fulminant hepatic failure is rare but more common in patients > 50 years old or those with pre-existing liver disease (e.g., chronic HBV carriers getting superinfected with HAV) [4].
- No alcohol for 6 months after acute hepatitis [4].
Very safe and effective. 95% seroconversion after 1st dose. Needs 2 doses, 6–18 months apart. [1]
High-risk people who should be vaccinated: Travelers to endemic areas; persons living with chronic liver disease; MSM; persons requiring regular clotting factor replacement. [1]
Why vaccinate patients with chronic liver disease? They already have compromised hepatic reserve — a superimposed acute HAV infection could precipitate acute-on-chronic liver failure and death.
Hepatitis E (HEV)
A notifiable disease in Hong Kong. The annual number of reported cases of hepatitis E is less than 100 in recent years in Hong Kong. Anti-HEV IgG+: 26.5% in HK. [1]
- HEV incidence has actually surpassed HAV incidence in HK in recent years [5]. This is partly because HAV vaccination has reduced HAV cases, while HEV exposure continues through pork consumption.
- Global HEV-related mortality is significant — it is a leading cause of acute viral hepatitis death worldwide.
Fecal-oral route. HEV can be transmitted through ingestion of undercooked meat or meat products, such as pig liver, of infected animals. Common food culprits (for high-income regions): Raw or undercooked meat or meat products — e.g., pig liver, pork, boar, salami. [1]
For sliced pig liver, depending on thickness and quantity, boil at 100°C or stir-fry in hot skillet/wok for at least three to five minutes. [1]
Other rare transmission routes include transfusion of infected blood products, organ transplant and vertical transmission from a pregnant woman to her foetus. [1]
Why is HEV zoonotic but HAV is not? HEV genotypes 3 and 4 infect both animals and humans (pigs are the main animal reservoir in developed countries). HAV has no significant animal reservoir.
Incubation period 2–10 weeks; mean 5–6 weeks. Largely asymptomatic; adults more symptomatic than children. Self-limiting >95%. Symptoms largely similar to hepatitis A. [1]
HIGH YIELD: HEV in Pregnancy
Pregnant women with hepatitis E are at increased risk of acute liver failure and fetal loss. 20–25% maternal mortality if acute HEV during the 3rd trimester. [1] This is a classic exam fact. The mechanism is thought to involve hormonal and immunological changes in pregnancy that impair viral clearance. This risk is primarily associated with HEV genotype 1.
Patients with major underlying illness or chronic liver disease can develop severe liver consequences. [1]
Cases of chronic HEV (caused by rat-HEV) in immunosuppressed patients. [1]
This is an important nuance: while HEV is generally self-limiting, transplant recipients on immunosuppressive drugs can develop chronic HEV infection (defined as HEV RNA detectable > 6 months). Treatment for chronic HEV involves reducing immunosuppression and/or ribavirin [5].
Acute hepatitis E shows a parenchymal pattern identical to HAV: ALT & AST >> ALP & GGT, in the range of 1000s. [1]
Serological diagnosis:
| Test | Finding | Interpretation |
|---|---|---|
| Anti-HEV IgM | Positive | Acute HEV infection |
| HEV RNA | Positive | Confirms active infection (especially useful when serology equivocal) |
The investigation flowchart is identical to HAV except Anti-HEV IgM and HEV RNA are the confirmatory tests [1].
No specific treatment. Supportive measures. Long-term immunity after recovery. Immunosuppressed patients can develop chronic hepatitis E. [1]
For chronic HEV in immunosuppressed patients:
Hecolin® (recombinant vaccine) developed in China, licensed in China since 2011, licensed in Pakistan in 2020. Clinical trials in USA being conducted. Not widely available. [1]
Practical prevention in HK: Cook pork and pig liver thoroughly. No widely available vaccine.
PART 2: CHRONIC VIRAL HEPATITIS
Hepatitis B (HBV)
HBV is a partially double-stranded DNA virus (unique among hepatitis viruses). It replicates via reverse transcription, producing covalently closed circular DNA (cccDNA) in the hepatocyte nucleus. This cccDNA is why HBV is essentially impossible to completely eradicate — it persists as a "minichromosome" even when HBV DNA is undetectable in blood. [6]
Overall crude prevalence of HBsAg was 7.8% in 2017. Lower in < 26 years (2.6%) compared to 36–45 years (10.9%). [1]
Why the age gradient? Hong Kong introduced universal neonatal HBV vaccination in 1988. Those born after 1988 have much lower carrier rates (~2.6% in < 26 years) compared to older cohorts who were infected before vaccination was available. The 36–45 age group (born 1970s–1980s) has the highest prevalence because they were born before universal vaccination and acquired HBV perinatally (vertical/MTCT).
>90% of infants (MTCT) develop chronic infection vs < 5% of adults. Among those with chronic infection: ~30% develop chronic hepatitis +/- fibrosis → 5–15% develop cirrhosis → hepatocellular carcinoma or liver failure → potential need for liver transplantation or death. [1]
For adults with acute HBV: 70–80% self-resolution. < 5% develop chronic infection. [1]
Why do infants become chronic carriers but adults usually clear the virus?
- Neonatal immune systems are immature — specifically, there is relative deficiency of cytotoxic T cells and IFN-γ, plus excessive immune tolerance. HBeAg can cross the placenta and induce tolerance in the fetal immune system. [6]
- Adult immune systems mount a robust T-cell response that usually clears the virus but also causes the symptomatic hepatitis (the liver damage is immune-mediated, not directly cytopathic).
Not all patients need antiviral treatment. [1]
The phases of chronic HBV (from the Yuen MF / EASL framework shown in the lecture) [1]:
| Phase | Old Name | HBeAg | ALT | HBV DNA | Liver Damage | Treatment? |
|---|---|---|---|---|---|---|
| Phase 1 | Immune tolerant | + | Normal | Very high (> 10⁸ IU/mL) | Minimal | Generally No |
| Phase 2 | Immune clearance / HBeAg+ chronic hepatitis | + | Elevated | High | Active inflammation/fibrosis | Yes |
| Phase 3 | Inactive carrier | − | Normal | Low/undetectable | Minimal | No (monitor) |
| Phase 4 | HBeAg− chronic hepatitis (reactivation) | − | Elevated | Moderate | Active inflammation/fibrosis | Yes |
| Phase 5 | HBsAg loss (functional cure) | − | Normal | Undetectable | Variable | No |
Key clinical point: Treatment is indicated during immune-active phases (Phase 2 and Phase 4), NOT during immune-tolerant phase (Phase 1) or inactive carrier state (Phase 3).
Signs to look for: Jaundice, finger clubbing, ankle edema, xanthelasma, palmar erythema, Dupuytren's contracture, testicular atrophy, splenomegaly, fetor hepaticus, muscle wasting, scratch marks, caput medusae, gynecomastia, flapping tremor, spider naevi, ecchymosis, leukonychia. [1]
Pattern recognition is key — most of these signs have multiple possible disease associations, but finding multiple signs together in a patient with known chronic hepatitis B strongly suggests cirrhosis.
- Spider naevi = arteriolar vasodilation from hyperestrogenism (liver cannot metabolize estrogen)
- Palmar erythema = same mechanism
- Gynecomastia = same mechanism
- Flapping tremor (asterixis) = hepatic encephalopathy
- Caput medusae = portal hypertension → paraumbilical vein dilation
- Leukonychia = hypoalbuminemia
Blood tests: HBsAg (positive), HBeAg (positive), Anti-HBc IgM (positive), HBV DNA level (> 10⁸ IU/mL). [1]
How to differentiate acute hepatitis B vs chronic hepatitis B with acute flare:
| Feature | Acute HBV | Chronic HBV with flare |
|---|---|---|
| HBsAg | + | + |
| Anti-HBc IgM | + (high titre) | + (lower titre) |
| IgG anti-HBc | − or just rising | + (already established) |
| HBV DNA | Very high | Variable |
| History | No prior HBV known | Known carrier or risk factors |
Anti-HBc IgM is positive in BOTH acute HBV and acute flare of chronic HBV — but in acute HBV, IgG anti-HBc has not yet risen, whereas in chronic HBV with flare, IgG anti-HBc is already positive. [6][7]
| Scenario | HBsAg | Anti-HBs | HBeAg | Anti-HBe | Anti-HBc IgM | Anti-HBc IgG | HBV DNA |
|---|---|---|---|---|---|---|---|
| Acute HBV (early) | + | − | + | − | + | − | +++ |
| Acute HBV (window) | − | − | − | − | + | + | ± |
| Acute HBV (recovery) | − | + | − | + | ± | + | − |
| Chronic HBV (HBeAg+) | + | − | + | − | − | + | +++ |
| Chronic HBV (HBeAg−) | + | − | − | + | − | + | ++ |
| Inactive carrier | + | − | − | + | − | + | ±/Low |
| Chronic HBV flare | + | − | ± | ± | + | + | Variable |
| Occult HBV | − | ± | − | ± | − | ± | + |
| Immune (past infection) | − | + | − | − | − | + | − |
| Immune (vaccination) | − | + | − | − | − | − | − |
Treatment of Chronic HBV
↓ cirrhosis, hepatic decompensation, liver failure, HCC. ↑ survival. Functional cure (finite treatment). Prevention of transmission or reactivation. [1]
Entecavir (ETV), Tenofovir disoproxil fumarate (TDF), Tenofovir alafenamide (TAF). These are nucleos(t)ide analogues (NUCs). [1]
The lecture shows data that introduction of NUCs in HK led to observed HCC incidence being lower than predicted, demonstrating the real-world benefit of antiviral treatment [1].
Pegylated interferon is also an approved agent but is less commonly used now due to side effects and finite duration. NUCs are oral, well-tolerated, and highly effective at viral suppression.
Old EASL 2017 guideline framework (shown in lecture) [1]:
- Treat if: HBV DNA > 2,000 IU/mL AND ALT elevated AND/OR significant fibrosis
- No treatment if: Low HBV DNA, normal ALT, no significant fibrosis
Rationale for 2,000 IU/mL cut-off: REVEAL-HBV study showed that HBV DNA levels ≥ 2,000 IU/mL were associated with significantly increased risk of cirrhosis and HCC. [1]
New EASL 2025 guideline (also shown in lecture):
In principle, all HBsAg-positive individuals with detectable HBV DNA are candidates for antiviral therapy. The indication is primarily based on HBV DNA and ALT levels, fibrosis stage, and risk of liver disease progression and HCC. [1]
This represents a shift toward broader treatment — the trend is to treat more patients earlier.
ETV or TAF are preferred over TDF when there is renal impairment (eGFR concerns) or bone disease. TAF should be preferred over ETV in patients with previous exposure to nucleoside analogues (risk of ETV resistance). ETV dose needs adjustment by renal function. [1]
| Drug | Pros | Cons/Cautions |
|---|---|---|
| ETV | Potent, high barrier to resistance (if treatment-naive) | Dose adjustment for renal impairment; risk of lactic acidosis in decompensated cirrhosis (rare) |
| TDF | Potent, no resistance reported | Nephrotoxic, bone density loss |
| TAF | Potent, renal/bone-safe profile | More expensive; newer agent |
Comorbidities such as diabetes mellitus and hepatic steatosis (MASLD) are increasingly recognized as factors that influence HBV disease progression and should be considered in treatment decisions. [1]
Special Populations
Treat with any detectable HBV DNA levels. For decompensated cirrhosis, watch out for risk of lactic acidosis with entecavir (rare). [1]
Why treat at any DNA level? Cirrhotic patients have no hepatic reserve — even low-level viral replication can cause further decompensation.
Risk of MTCT of HBV increases with maternal HBV DNA levels during pregnancy. Highly viremic defined as HBV DNA > 200,000 IU/mL (5.3 log IU/mL). [1]
Management protocol: Antenatal visits → HBsAg+ → Check HBV DNA at 24–28 weeks → Start tenofovir if highly viremic → Delivery → Stop tenofovir 0–12 weeks postpartum (without maternal indications for antiviral) → Birth dose HBV vaccine + HBIG for baby → Complete HBV vaccine series. [1]
HIGH YIELD: MTCT Prevention Protocol
This is a classic SAQ topic (see 2023 SAQ Q5 below). The key steps are:
- Screen all pregnant women for HBsAg
- Check HBV DNA if HBsAg+
- Start tenofovir at 24–28 weeks if HBV DNA > 200,000 IU/mL
- Give baby birth-dose HBV vaccine + HBIG within 24 hours
- Complete 3-dose HBV vaccination series for baby
- Post-vaccination serologic testing for baby
Why tenofovir and not entecavir in pregnancy? Tenofovir (TDF) has extensive safety data in pregnancy (from HIV treatment experience). Entecavir is FDA category C with less pregnancy safety data.
Why HBIG? Hepatitis B immunoglobulin provides immediate passive immunity to cover the window before the vaccine generates active immunity.
Risk stratification based on HBV serology and type of immunosuppressive therapy. [1]
Why does this matter? Immunosuppressive drugs (especially rituximab/anti-CD20, corticosteroids) can cause HBV reactivation — even in patients with "resolved" or "occult" HBV (HBsAg−, anti-HBc+). [6]
Mechanism of steroid-induced reactivation [6]:
- HBV contains a glucocorticoid-responsive element → steroids directly enhance viral replication
- During steroid use: HBV DNA rises silently
- Upon steroid withdrawal: immune rebound → massive T-cell attack on HBV-infected hepatocytes → severe hepatic flare → potentially fatal
Anti-CD20 (rituximab) reactivation [6]:
- Profound B-cell depletion → HBcAg-binding B cells normally prime cytotoxic T cells → loss of immune surveillance → HBV reactivation
Clinical implication: ALL patients should be screened for HBsAg and anti-HBc before starting immunosuppressive therapy. Prophylactic antivirals (e.g., entecavir) should be given to at-risk patients.
- Universal neonatal vaccination in HK since 1988: 3 doses (birth, 1 month, 6 months) [1]
- No booster dose required — anamnestic (memory) response means even if anti-HBs falls to undetectable levels, the immune system will mount a response upon re-exposure [6]
- HBsAg+ mothers' babies: HBIG + HBV vaccine within 24 hours → 95% protection [6]
- Post-vaccination serologic testing recommended for babies born to HBV-infected mothers [1]
Hong Kong Viral Hepatitis Action Plan 2020–2024 [1]:
- Four strategic axes: awareness, surveillance, prevention, treatment
- Universal screening for pregnant women and neonatal vaccination
- Antivirals for pregnant women with high viral load
- Enhancement of treatment via HA (laboratory, equipment, drug formulary, model of care)
Hepatitis C (HCV)
An estimated 0.3% of Hong Kong population are infected with HCV (~22,000/7.5 million people). In view of low overall prevalence, population-based screening is not practiced in Hong Kong. [1]
High-risk groups in HK [1]:
- People who inject drugs (PWID) — most common mode of HCV transmission in HK (36.7%)
- Blood product transfusion (30.0%) — historically important but now extremely rare due to screening
- People living with HIV
- MSM
- Tattoo/piercing with unsterilized needles
- Hemodialysis patients
- Persons ever incarcerated
Blood product safety: Starting from July 1991, each unit of collected blood is routinely tested for anti-HCV, NAT, etc. Risk of acquiring HCV from blood product is < 1 in 10,000,000. [1]
No baby boomers cohort in Hong Kong — unlike the US, HK does not have a specific age cohort with disproportionately high HCV prevalence [1].
Healthy liver → Liver infected with HCV → 20% develop cirrhosis in 20–30 years → From cirrhosis: 1–5% per year develop liver cancer; 3–6% per year develop liver decompensation. [1]
Key differences from HBV:
- HCV can be CURED (with DAAs) — HBV generally cannot (functional cure with HBsAg loss is rare)
- HCV causes HCC almost exclusively through cirrhosis — unlike HBV which has direct oncogenic effects and can cause HCC even without cirrhosis [6]
- 55–85% of HCV-infected adults develop chronic infection vs < 5% of adults with HBV [5]
Strongly associated: Mixed cryoglobulinemia (≤50%), Sjögren syndrome (10%), Lymphoproliferative disorders (≤6%), Porphyria cutanea tarda (< 5%), Neuropathy, Membranoproliferative glomerulonephritis (10–20%), Cryoglobulinemic vasculitis. [1]
Possibly associated: Corneal ulcers, thyroid disease, lichen planus, pulmonary fibrosis, type 2 diabetes, systemic vasculitis, arthralgias/myalgias, autoimmune thrombocytopenia. [1]
Why so many extrahepatic manifestations? HCV triggers chronic immune stimulation → B-cell activation → cryoglobulin production → immune complex deposition in vessels, glomeruli, nerves.
Step 1: Anti-HCV antibody test. Step 2 (if anti-HCV+): HCV RNA (reflex RNA testing). If HCV RNA+: current infection. If HCV RNA−: past resolved infection or false-positive antibody. [1]
| Anti-HCV | HCV RNA | Interpretation |
|---|---|---|
| + | + | Current infection (acute or chronic) |
| + | − | Past resolved infection OR false-positive antibody |
| − | + | Very early acute infection (before antibody develops) OR immunocompromised |
| − | − | No infection |
Window period for anti-HCV: Anti-HCV can take up to 12 weeks to appear after infection. In suspected recent exposure (e.g., needlestick injury), test HCV RNA directly [7].
Evaluate comorbidities contributing to liver disease progression. Assess liver disease severity/fibrosis stage prior to therapy (FIB-4, APRI, FibroScan, or biopsy if uncertain). Identify cirrhosis — adjust treatment accordingly. Mandatory post-treatment HCC surveillance for patients with cirrhosis (F4) or advanced fibrosis (F3). Renal function (creatinine/eGFR). Identify extrahepatic manifestations. HBV and HAV vaccination should be proposed to patients who are not protected. [1]
Why HBV vaccination before HCV treatment?
Treating HCV with DAAs can cause HBV reactivation in co-infected patients (even if HBsAg−/anti-HBc+). All HCV patients should be tested for HBV markers, and those who are susceptible should be vaccinated. [6]
Fibrosis assessment cut-offs suggesting cirrhosis [1]:
- FIB-4 > 3.25
- APRI > 2.0
- Platelets < 150,000/mm³
- FibroScan > 12.5 kPa
HCV Treatment: Direct-Acting Antivirals (DAAs)
SVR is defined as the absence of detectable HCV RNA for ≥12 weeks after completion of therapy (SVR12), i.e., LLOD ≤15 IU/mL. This represents a CURE. SVR is associated with: improvement in extrahepatic manifestations, improvement/disappearance of liver necroinflammation and fibrosis, regression of advanced fibrosis/cirrhosis, reduced risk of HCC, hepatic decompensation, liver-related and all-cause mortality. [1]
Traditional treatment: PegIFN + ribavirin → ~40% cure rate for major genotype, injection, 24–48 weeks, moderate side effects. Current standard: DAAs → 90–100% cure rate, oral, 8–12 weeks, mild side effects. [1]
Since October 2020, the Hospital Authority has expanded the access of DAA treatment to all hepatitis C patients regardless of disease severity. [1]
| Class | Target | Examples |
|---|---|---|
| NS3/4A protease inhibitors | Protease involved in polyprotein processing | Glecaprevir, voxilaprevir |
| NS5A inhibitors | NS5A protein (replication and assembly) | Pibrentasvir, velpatasvir, ledipasvir |
| NS5B polymerase inhibitors (nucleotide) | RNA-dependent RNA polymerase | Sofosbuvir |
Pan-genotypic regimens effective against all 6 HCV genotypes: SOF/VEL (Epclusa), GLE/PIB (Maviret), SOF/VEL/VOX (Vosevi). [1]
| Regimen | Duration |
|---|---|
| SOF/VEL (sofosbuvir/velpatasvir) | 12 weeks |
| GLE/PIB (glecaprevir/pibrentasvir) — take with food | 8 weeks |
Not eligible for simplified pathway: Prior HCV treatment, cirrhosis, prior liver transplant, HIV or HBsAg+, eGFR < 30, currently pregnant [1].
CYP/P-gp-inducing agents (e.g., carbamazepine, phenytoin) are contraindicated with all regimens. Protease inhibitors must NOT be used in patients with Child-Pugh B or C decompensated cirrhosis. SOF should only be used if no alternative for eGFR < 30. [1]
Drug-drug interaction assessment essential: www.hep-druginteractions.org [1]
Concept: Define and segment high-risk population groups for tailor-made screening and treatment measures to gradually eliminate HCV. Target groups: PWID, illicit drug users, prisoners, hemodialysis patients, transfusion/transplant-acquired. [1]
Why micro-elimination rather than mass screening? HCV prevalence in HK is low (0.3%), so population-level screening is not cost-effective. Instead, focusing on high-prevalence subgroups (e.g., PWID with ~40% HCV prevalence) is more efficient.
Remaining obstacles for HCV elimination: Only 21% are diagnosed. Case finding → Linkage to care → Access to treatment → Reinfection/new infection. [1]
No vaccine for hepatitis C is available. No upcoming treatments breakthroughs for HCV beyond current DAAs. [1]
Prevention relies on:
- Harm reduction (needle exchange programs for PWID)
- Blood product screening
- Universal precautions in healthcare settings
- Condom use
- Education
WHO goal: Eliminate viral hepatitis as a major public health threat by 2030. Targets: 90% diagnosed, 80% treated, 90% cured. Decrease new infections. Decrease deaths. [1]
This is a frequently examined topic. From the lecture and senior notes [1][3][6]:
- Spontaneous reactivation (IgM anti-HBc rises, but not as high as acute HBV)
- HBeAg clearance (spontaneous or during therapy)
- HBeAg seroreversion (HBeAg− → HBeAg+)
- Emergence of resistant variants / non-compliance during NUC therapy
- Corticosteroid or other immunosuppressant withdrawal (especially anti-CD20)
- Superinfection with HAV, HEV, or HDV
- Drug-induced hepatic injury (alcohol, TCM, herbal tea)
Exam Intelligence
| Trap | Correct Understanding |
|---|---|
| "Anti-HBc IgM is only positive in acute HBV" | WRONG — also elevated in chronic HBV flare (just at lower titre) |
| "Anti-HBs positive = vaccinated" | Could also be past natural infection — differentiate by checking anti-HBc (present in natural infection, absent in vaccination) |
| "HCV causes HCC directly" | WRONG — HCC in HCV occurs almost exclusively through cirrhosis. HBV can cause HCC without cirrhosis (direct oncogenic effect via HBV DNA integration) |
| "HAV can become chronic" | NEVER — HAV causes acute infection only |
| "HEV never becomes chronic" | Usually true, but exceptions in immunosuppressed patients (transplant recipients) |
| "All HBV carriers need antiviral treatment" | WRONG — only those in immune-active phases or with cirrhosis/special populations |
| "Acute ischemic hepatitis" vs "Acute viral hepatitis" | Ischemic hepatitis: AST > ALT, rapid rise and fall (hours-days), history of hemodynamic compromise. Viral hepatitis: ALT > AST, more gradual, history of exposure [9] |
| "DAAs can be used safely in decompensated cirrhosis" | Protease inhibitors (NS3/4A) must NOT be used in Child-Pugh B/C |
- HAV vs HEV: Both are fecal-oral, but HAV = shellfish/oysters, HEV = pig liver/pork. HEV dangerous in pregnancy, HAV is not specifically. HAV vaccine widely available; HEV vaccine only in China.
- Acute HBV vs Chronic HBV flare: IgG anti-HBc distinguishes (negative/rising in acute, already positive in chronic)
- HBV vs HCV natural history: HBV — high neonatal chronicity, direct oncogenic, functional cure possible but rare. HCV — high adult chronicity, HCC via cirrhosis only, DAA cure achievable in >95%.
Past Paper Questions
Stem: A 30-year-old pregnant lady at 16 weeks of gestation is referred to you for being HBsAg positive following the antenatal clinic assessment. She has known chronic hepatitis B infection for many years, but has defaulted follow-up before the current pregnancy.
(a) Name two blood tests you would arrange for her to decide whether antiviral therapy would be needed. (4 marks)
Answer: HBV DNA level and ALT (or liver function test). These determine viral load and disease activity. HBeAg is also acceptable. The decision to treat is based on whether she is "highly viremic" (HBV DNA > 200,000 IU/mL) for MTCT prevention and whether she has active hepatitis needing treatment for her own health.
(b) Name the drug of choice during pregnancy. (1 mark)
Answer: Tenofovir (TDF) — safe in pregnancy with extensive safety data.
(c) Name two measures to be implemented for the infant within 24 hours of birth. (4 marks)
Answer: Birth-dose hepatitis B vaccination and hepatitis B immunoglobulin (HBIG) — both within 24 hours of delivery.
(d) The patient's husband is tested for HBsAg which is found to be negative. Name one intervention you would advise for her husband. (1 mark)
Answer: Hepatitis B vaccination (check anti-HBs first; if negative, vaccinate with 3-dose series).
Stem: A 68-year-old man with known chronic hepatitis B was previously commenced on entecavir 10 years ago. He has defaulted regular clinic follow-up for the past 6 years. He was now referred for new onset increased abdominal distension. Shifting dullness elicited. Blood tests show Hb 10.5, Plt 51, Alb 33, Bili 25, INR 1.35, ALT 26, AST 48, Cr 97.
(a) What did his physical examination finding suggest? (1 mark)
Answer: Ascites (shifting dullness).
(b) What are the possible causes for this physical examination finding? (2 marks)
Answer: Decompensated liver cirrhosis (portal hypertension causing transudative ascites) and malignancy/peritoneal carcinomatosis (e.g., HCC with peritoneal spread causing exudative ascites). Other causes: nephrotic syndrome, cardiac failure.
(c) Name two prognostic models that can be used to grade severity of cirrhosis. (2 marks)
Answer: Child-Pugh score and MELD score (Model for End-Stage Liver Disease).
(d) Name two other liver-related clinical complications which can occur. (2 marks)
Answer: Variceal bleeding (from portal hypertension) and hepatic encephalopathy. Other acceptable: HCC, spontaneous bacterial peritonitis (SBP), hepatorenal syndrome.
(e) Suggest three additional investigations which will aid further management. (3 marks)
Answer: HBV DNA level (to assess viral suppression/compliance), AFP and ultrasound liver (HCC surveillance), diagnostic paracentesis (cell count, albumin, culture — to rule out SBP and determine SAAG).
Stem: A 45-year-old gentleman presented with palpitation and near loss of consciousness. LFT showed AST 3500 U/L and ALT 2000 U/L on admission. Albumin and bilirubin normal. One day later, AST and ALT decreased to 400 and 1340 respectively. What is the LIKELY diagnosis?
Options: A. Acute cholecystitis, B. Acute ischemic hepatitis, C. Acute viral hepatitis, D. Recurrent pyogenic cholangitis
Answer: B. Acute ischemic hepatitis
Rationale: AST > ALT (reversed de Ritis ratio), rapid rise and fall (halving within 24 hours), presentation with hemodynamic compromise (palpitation, near-syncope = cardiac cause), normal albumin/bilirubin (preserved synthetic function). Acute viral hepatitis would show ALT > AST with a more gradual course. Cholecystitis and RPC would show cholestatic pattern (ALP/GGT >> ALT/AST).
Stem: A 42-year-old man who was a chronic hepatitis B carrier had a 6-monthly blood test and ultrasound scan. He was noticed to have a newly-developed 3-cm solid lesion in the right lobe of the liver.
(a) Most likely diagnosis? → Hepatocellular carcinoma (HCC)
(d) Serum tumour marker for screening and monitoring? → AFP (alpha-fetoprotein)
This question demonstrates why HBV carriers need regular HCC surveillance (6-monthly AFP + US).
Stem: Routine LFT of a 55-year-old male asymptomatic hepatitis B carrier: Bilirubin 15, ALT 28, AST 25, ALP 625, GGT 424. Albumin and globulin normal.
(a) Most likely diagnosis? (4 marks)
Answer: This is a cholestatic pattern (ALP/GGT >> ALT/AST) in an HBV carrier. The most likely diagnosis is extrahepatic biliary obstruction or intrahepatic cholestasis — in an HBV carrier with markedly elevated ALP/GGT and normal transaminases, consider bile duct obstruction from cholangiocarcinoma or gallstone, or drug-induced cholestasis. Note: this is NOT typical of HBV hepatitis (which causes parenchymal pattern).
(b) Three investigations? → Ultrasound abdomen (dilated biliary tree?), CT/MRCP, CA19-9.
High Yield Summary
Food-borne (HAV, HEV): Both cause acute hepatitis only (usually self-limiting), diagnosed by IgM antibodies, parenchymal LFT pattern (ALT/AST in 1000s). HAV = oysters/shellfish, HEV = pig liver/pork. HEV is dangerous in pregnancy (20–25% mortality in 3rd trimester). HAV vaccine exists (2 doses); HEV vaccine only in China.
Blood-borne (HBV, HCV): Both can cause chronic infection. HBV prevalence ~7.8% in HK; treated with NUCs (ETV/TDF/TAF) — not all carriers need treatment. HBV cannot be eradicated (cccDNA persists). HBV vaccination since 1988 has dramatically reduced carrier rates in young HK adults. MTCT prevention: screen pregnant women, tenofovir if HBV DNA > 200,000 IU/mL, birth-dose vaccine + HBIG. Screen for HBV before immunosuppression.
HCV prevalence ~0.3% in HK; PWID is the main risk group. DAAs (SOF/VEL or GLE/PIB) achieve > 95% cure (SVR12). No HCV vaccine. Micro-elimination strategy targets high-risk groups. HCC surveillance is mandatory even after SVR in patients with advanced fibrosis/cirrhosis.
All viral hepatitis are notifiable in Hong Kong. WHO 2030 target: eliminate viral hepatitis as a major public health threat (90% diagnosed, 80% treated, 90% cured).
Active Recall - Viral Hepatitis
[1] GC 239. Viral hepatitis HAV_HBV_HCV_HEV.pdf [2] Maksim Medicine Notes.pdf (GI & hepatology section, p.141) [3] Block A - Jaundice after raw oysters_ acute hepatitis.pdf [4] MBBS Final MB (Medicine) (Felix PY Lai).pdf (Hepatitis A infection section, pp.736–742) [5] MBBS Final MB (Medicine) (Felix PY Lai).pdf (Hepatitis E infection section, pp.765–771) [6] MBBS Final MB (Medicine) (Felix PY Lai).pdf (Hepatitis B infection section, pp.741–759) [7] Block A - Gastrointestinal Data Interpretation.pdf (p.2) [8] MBBS Final MB (Surgery) (Felix PY Lai).pdf (HBV serology table, p.484) [9] 2025 Fourth Summative MCQ.pdf (Q38) [10] 2023 Fourth Summative SAQ.pdf (Q5) [11] 2021 Fourth Summative SAQ.pdf (Q5) [12] 2016 Fourth Summative SAQ.pdf (Q8) [13] 2017 Fourth Summative SAQ.pdf (Q4)
GC238 Rare Disease Genetic Testing For Precision Medicine
Genetic testing in rare diseases that identifies specific pathogenic variants to guide individualized diagnosis, management, and targeted therapeutic interventions through precision medicine approaches.
GC240 MASLD And Alcoholic Liver Disease
MASLD (metabolic dysfunction-associated steatotic liver disease) and alcoholic liver disease are chronic hepatic conditions characterized by hepatic steatosis driven by metabolic dysfunction or excessive alcohol consumption, respectively, which can progress through steatohepatitis to fibrosis, cirrhosis, and hepatocellular carcinoma.