---

HEPATITIS B & C - RESIDENT HANDOUT

Screening | Natural History | Treatment | Prevention | Surveillance

Based on AASLD 2025 Guidelines + Harrison's 22E + Katzung 16E

---

PART 1: HEPATITIS B VIRUS (HBV)

---

1. VIROLOGY - QUICK FACTS

---

2. SEROLOGIC MARKERS - THE ROADMAP

Mnemonic: "SCA - Surface, Core, Antigen/Antibody"

AASLD 2025 TRIPLE PANEL SCREENING

CDC now recommends: All adults screened at least once in lifetime, all pregnant persons each pregnancy (first trimester preferred) using:

---

3. NATURAL HISTORY OF CHRONIC HBV INFECTION

Mnemonic: "IT-IH-IC-HBsAg-" = Immune Tolerant → Immune Active/Hepatitic → Inactive Carrier → Functional Cure

---

4. TREATMENT OF CHRONIC HBV

GOALS OF TREATMENT

Mnemonic: "SNIFF"

• S - Suppress HBV DNA to undetectable
• N - Normalize ALT
• I - Induce HBeAg seroconversion (eAg → eAb)
• F - Fibrosis regression / prevent cirrhosis
• F - Functional cure (HBsAg loss = ultimate goal)

---

WHO TO TREAT (AASLD 2025 Integrated Algorithm)

1. HBV DNA ≥2000 IU/mL AND ALT >2× ULN (persisting >6 months)
2. HBV DNA ≥20,000 IU/mL with ALT >ULN and age >40 OR ≥F2 fibrosis
3. HBeAg(+) with HBV DNA ≥10,000 IU/mL regardless of ALT (NEW 2025)
4. Cirrhosis (compensated or decompensated) - treat regardless of HBV DNA
5. HCC, liver transplant, immunosuppressive therapy planned
6. Extrahepatic manifestations (polyarteritis nodosa, membranous nephropathy)

---

DRUGS FOR CHRONIC HBV

Mnemonic: "ELATE" = Entecavir, Lamivudine (avoid), Adefovir (avoid), Tenofovir (TAF/TDF), interferons

PREFERRED ORAL AGENTS (AASLD 2025): "The 3 E-T-T"

Mnemonic for preferred agents: "ETA" = Entecavir, Tenofovir (TDF), Alafenamide (TAF)

IFN vs Nucleos(t)ide Analogs - Quick Comparison:

Mnemonic: "IFN = Immune, Finite, Needle; NUCs = Oral, Lifelong, Tolerant"

---

WHEN TO STOP NUC THERAPY

• HBeAg(+): After HBeAg seroconversion + ≥12 months consolidation therapy, if ALT normal and HBV DNA undetectable
• HBeAg(-): After HBsAg loss (functional cure)
• Cirrhosis: Do NOT stop therapy

Mnemonic: "DNA-ALT-BILI-DECOMP" = restart if ANY:

• HBV DNA ≥10,000 IU/mL (at any time)
• ALT >5× ULN
• Total bilirubin >2.5 mg/dL
• Hepatic decompensation
• Patient's own desire / extrahepatic manifestations

---

SPECIAL SITUATIONS IN HBV TREATMENT

Pregnancy

• Screen all pregnant women (first trimester) - triple panel
• HBsAg+ mother with HBV DNA ≥200,000 IU/mL: Start TDF in 3rd trimester (28 weeks) to prevent MTCT
• Neonatal prophylaxis: HBIG + HBV vaccine within 12 hours of birth
• TDF preferred in pregnancy (safest NUC)
• Breastfeeding allowed on TDF

HIV/HBV Co-infection

• Use TDF or TAF + emtricitabine (FTC) as part of ART
• Avoid entecavir alone (has anti-HIV activity → monotherapy risks resistance)
• Do NOT stop anti-HBV drugs abruptly (risk of severe hepatitis flare)

Immunosuppression/Chemotherapy

• Screen all patients for HBsAg AND anti-HBc before starting immunosuppressives/biologic agents
• HBsAg(+): Start prophylactic ETV or TDF before therapy
• Anti-HBc(+)/HBsAg(-): Pre-emptive treatment or close monitoring

---

5. HCC SURVEILLANCE IN HBV

Mnemonic: "CHAIR" = Cirrhosis, High-risk ethnicity (Asian M>40/F>50), Africa (any age), Immunosuppressed, Relative with HCC

• All cirrhotic HBsAg(+) patients
• Non-cirrhotic HBsAg(+) Asian males >40, Asian females >50
• Non-cirrhotic HBsAg(+) Africans any age
• Family history of HCC + HBsAg(+)
• HBsAg-negative but anti-HBc(+) + cirrhosis or co-infection (HDV/HCV/HIV) - per AASLD 2025

---

6. PREVENTION OF HBV

Mnemonic: "3-V-P" = Vaccination, Vertical transmission prevention, Post-exposure prophylaxis

Vaccination

• Universal birth dose within 12-24 hours
• 3-dose series (0, 1, 6 months) - for adults and children
• Post-vaccination serology: Check anti-HBs 1-2 months post series; titre ≥10 mIU/mL = protective
• Non-responders (<10 mIU/mL): Repeat 3-dose series; if still negative, check HBsAg
• High-risk groups: healthcare workers, IVDU, sexual partners of HBsAg(+), dialysis patients

Post-Exposure Prophylaxis (PEP)

• Unvaccinated exposure to HBsAg(+) source: HBIG 0.06 mL/kg IM + start vaccine series within 24 hours
• Perinatal: HBIG 0.5 mL IM + vaccine within 12 hours of birth

---

PART 2: HEPATITIS C VIRUS (HCV)

---

1. VIROLOGY - QUICK FACTS

Mnemonic for HCV DAA targets: "P-R-A" = Protease (NS3/4A), RNA-polymerase (NS5B), Assembly/replication complex (NS5A)

---

2. NATURAL HISTORY OF HCV

Acute HCV (6 months)
    ↓ 20-35% spontaneous clearance
Chronic HCV (65-80%)
    ↓ 15-20% over 20-30 years
Cirrhosis
    ↓ 1-5% per year
HCC / Decompensation

• SVR (Sustained Virologic Response) = CURE - defined as undetectable HCV RNA 12 weeks after completing therapy (SVR12)
• SVR12 = 97-100% long-term HCV RNA negativity
• SVR associated with regression of cirrhosis, reduced HCC risk, reduced liver-related mortality

---

3. DIAGNOSIS AND SCREENING

1. Anti-HCV antibody (ELISA) - initial test
2. If reactive → HCV RNA by PCR (confirms active infection)
3. If RNA positive → HCV genotype (guides treatment duration)
4. Assess fibrosis: FibroScan (elastography), FIB-4 score, or biopsy

• All adults aged 18-79 (one-time screening)
• All pregnant women (each pregnancy)
• IVDU (annually)
• Prior to biologic therapy or immunosuppression
• HIV-infected persons
• Born 1945-1965 (baby boomer generation - US guideline)

Note on HCV testing after exposure: Anti-HCV may be negative in early acute HCV (window period 8-12 weeks). Check HCV RNA directly if high clinical suspicion.

---

4. HCV TREATMENT - DIRECT ACTING ANTIVIRALS (DAAs)

GOAL: CURE (SVR12 = HCV RNA undetectable 12 weeks post-treatment)

THE 4 DAA CLASSES

Mnemonic: "PNNA" = Protease inhibitors, NS5A inhibitors, NS5B Nucleoside analogs, NS5B Non-nucleoside (now off market)

Easy recall: "-previr" prevents, "-asvir" assembles, "-buvir" blocks (synthesis)

---

CURRENT PREFERRED DAA REGIMENS (AASLD/EASL 2025)

Mnemonic for pangenotypic regimens: "GS-V" = GleP (Glecaprevir/Pibrentasvir) and SOF-VEL (Sofosbuvir/Velpatasvir)

PANGENOTYPIC (All Genotypes 1-6) - PREFERRED FIRST LINE:

GENOTYPE-SPECIFIC REGIMENS:

---

TREATMENT DURATION CHEATSHEET

Mnemonic: "8-12-16-24 rule"

• 8 weeks: GLE/PIB in naïve, non-cirrhotic (all genotypes); LDV/SOF GT1 (non-cirrhotic, HCV RNA <6 million IU/mL)
• 12 weeks: Most other regimens; GLE/PIB with cirrhosis
• 16 weeks: GLE/PIB in treatment-experienced GT3
• 24 weeks: Decompensated cirrhosis (SOF/VEL + RBV or LDV/SOF + RBV)

---

SPECIAL HCV POPULATIONS

CRITICAL: Before starting any DAA - CHECK FOR HBV CO-INFECTION (HBsAg + anti-HBc). HBV reactivation during DAA therapy can cause fulminant hepatic failure and death. Treat HBV first or concurrently.

---

HCV MONITORING

---

5. HCV PREVENTION

Mnemonic: "SHARP" = Sterile needles, HBIG is NOT for HCV, Avoid sharing, Regular screening, Post-exposure: NO PEP exists

• Harm reduction for IVDU (needle/syringe programs)
• Safe injection practices in healthcare settings
• Blood donor screening (NAT testing)
• No PEP available - early HCV RNA testing post-exposure; treat if chronic
• Treatment as prevention (TasP): treating HCV in high-risk groups reduces transmission

---

6. HCC SURVEILLANCE IN HCV

• Post-SVR patients with cirrhosis: Ultrasound ± AFP every 6 months indefinitely
• Post-SVR non-cirrhotic: surveillance can usually be discontinued (though debate exists in advanced fibrosis F3)

---

PART 3: SIDE-BY-SIDE COMPARISON (HBV vs HCV)

---

PART 4: MASTER MNEMONICS SUMMARY

---

PART 5: CLINICAL PEARLS FOR THE WARD/OPD

1. Do not miss HBsAg reactivation: Screen with TRIPLE PANEL (not just HBsAg alone) before immunosuppression - isolated core antibody (anti-HBc+) can reactivate.
2. "Window period" pearl: In acute HBV, HBsAg may transiently disappear and anti-HBs has not yet appeared - only IgM anti-HBc is positive. This is the "window period" - don't miss it.
3. HBV does NOT need cirrhosis to cause HCC - unlike HCV. Conduct surveillance even in non-cirrhotic HBsAg(+) patients who meet criteria.
4. cccDNA = the enemy in HBV - it persists in hepatocyte nuclei indefinitely; this is why NUC therapy suppresses but does not cure HBV. Stopping treatment risks relapse.
5. HCV is NOW curable - SVR12 with DAAs = 97-99%; don't delay treatment. Every patient with HCV should be offered treatment.
6. Check DDIs before starting HCV DAAs: Rifampicin, carbamazepine, and St. John's Wort can reduce DAA levels (CYP3A4 inducers). Statins + -previr drugs risk myopathy.
7. Genotype 3 HCV = hardest to treat - lower SVR rates, higher fibrosis progression, higher HCC risk even without cirrhosis. Aggressive treatment.
8. AASLD 2025 new threshold: In immune-tolerant phase HBV, treat if HBV DNA ≥10,000 IU/mL (regardless of ALT) - this is a significant expansion from previous "watch and wait" approach.
9. qHBsAg trending (quantitative HBsAg <100 IU/mL) - emerging marker for treatment stopping decisions in HBeAg(-) CHB; do not stop NUCs in cirrhosis regardless.
10. Bulevirtide - new subcutaneous lipopeptide approved for HDV (Hepatitis D co-infection with HBV) - ask your senior if managing HBV/HDV co-infection.

---

---

How to Use This Handout

• Jump to the "WHO TO TREAT" table (Part 1, Section 4) for instant HBV treatment decisions
• Use the "SCA Triad" result interpretation table to decode any serology report in 30 seconds
• The HBV phases table (IT → IH → IC → Cure) explains your patient's current status

• Use the AASLD 2025 triple panel screening algorithm for every new patient with risk factors
• For new HCV diagnoses: Anti-HCV → HCV RNA → Genotype → pick regimen from the DAA table
• The "8-12-16-24 rule" tells you treatment duration at a glance

• "CHAIR" mnemonic for HCC surveillance eligibility
• "3-V-P" for HBV prevention counseling
• "SHARP" for HCV harm reduction

---

Key 2025 Updates You Must Know

1. HBV immune-tolerant phase - AASLD 2025 now recommends treating if HBV DNA ≥10,000 IU/mL regardless of ALT - this is a major shift from prior "watch and wait" for immune-tolerant patients.
2. qHBsAg <100 IU/mL is an emerging threshold for considering NUC discontinuation in selected HBeAg(-) non-cirrhotic patients.
3. GLE/PIB (Glecaprevir/Pibrentasvir) achieves ~99% SVR in just 8 weeks for treatment-naïve non-cirrhotic HCV patients of all genotypes - the shortest curative regimen available.
4. HBV/HCV co-infection during DAA therapy risks HBV reactivation (sometimes fatal) - always screen triple panel before starting DAAs.
5. Bulevirtide is now approved for chronic HDV (hepatitis delta) in HBsAg(+) co-infected patients - ask about HDV testing in your South Asian/Mediterranean/IVDU HBV patients.