What is the management approach for a patient with viral hepatitis, specifically hepatitis A, B, or C?

Management of Viral Hepatitis

Hepatitis A

Hepatitis A is self-limiting and requires only supportive care—no antiviral therapy is indicated. 1

• Acute hepatitis A resolves spontaneously in the vast majority of cases without specific treatment 2
• Management focuses on symptom relief, adequate hydration, and nutritional support
• Monitor for rare complications such as acute liver failure, which may require transplant evaluation 3
• Prevention through vaccination is the cornerstone of control 4

Common pitfall: Do not delay recognition of acute liver failure in the rare severe cases—monitor coagulation parameters and mental status closely in patients with jaundice and elevated transaminases.

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Hepatitis B

For chronic hepatitis B requiring treatment, initiate first-line therapy with high genetic barrier nucleos(t)ide analogues: entecavir, tenofovir disoproxil fumarate (TDF), or tenofovir alafenamide (TAF). 5

Treatment Indications

Treatment decisions are based on HBV DNA levels, ALT elevation, HBeAg status, and fibrosis stage 6:

• HBeAg-positive patients: Treat if HBV DNA >20,000 IU/mL AND ALT >2× upper limit of normal (ULN) OR significant inflammation/fibrosis on biopsy 5, 1
• HBeAg-negative patients: Treat if HBV DNA >2,000 IU/mL AND ALT >2× ULN OR significant inflammation/fibrosis 5, 1
• All cirrhotic patients: Treat if HBV DNA is detectable, regardless of ALT level 5
• Patients >30 years with normal ALT: Consider treatment if HBV DNA >1,000 IU/mL 5
• Life-threatening disease: Initiate treatment immediately in acute liver failure, decompensated cirrhosis, or severe hepatitis exacerbation regardless of HBV DNA or ALT 6

First-Line Agents

Entecavir, TDF, or TAF are the preferred agents due to high potency and low resistance rates (<1% at 2 years). 5, 7

• Entecavir: Preferred for patients with renal dysfunction or bone disease 5
• TDF: Preferred during pregnancy for prevention of mother-to-child transmission 5
• TAF: Preferred for patients with renal dysfunction or bone disease 5

Critical consideration: Older agents like lamivudine have unacceptably high resistance rates (up to 76% at 5 years) and should be avoided 7

Special Populations

• Pregnancy: Use TDF in the third trimester for mothers with high viral load (>200,000 IU/mL) to prevent vertical transmission 5
• Renal impairment: Prefer entecavir or TAF; monitor creatinine every 12 weeks if using TDF 5, 1
• Coinfection (HIV/HDV): Requires specialized management with attention to drug interactions 1

Treatment Duration and Monitoring

• Long-term, potentially indefinite treatment is typically required 5
• Optimal endpoint: HBsAg loss (functional cure) 5
• Monitoring: Check HBV DNA every 3-6 months, ALT regularly, and assess for virologic breakthrough 1
• Monitor renal function every 12 weeks in patients on TDF 1

Common pitfall: Do not use peginterferon as first-line therapy except in highly selected young patients with mild disease who desire finite treatment duration—nucleos(t)ide analogues are superior for most patients 5

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Hepatitis C

All patients with chronic hepatitis C should be treated with pangenotypic direct-acting antiviral (DAA) regimens, with sofosbuvir/velpatasvir 400mg/100mg once daily for 12 weeks as the preferred first-line option. 8

First-Line Treatment Regimens

Sofosbuvir/velpatasvir achieves 98% sustained virologic response (SVR) rates across all genotypes. 8

• Sofosbuvir/velpatasvir: Single tablet (400mg/100mg) once daily for 12 weeks 8
• Glecaprevir/pibrentasvir: Alternative pangenotypic regimen
  • 8 weeks for patients without cirrhosis 8
  • 12 weeks for patients with compensated cirrhosis (Child-Pugh A) 8

Pre-Treatment Assessment

Mandatory testing before initiating DAAs 8, 1:

• HCV RNA quantitative testing (confirm active infection)
• HCV genotype and subtype determination
• Fibrosis staging using non-invasive methods (FIB-4, transient elastography)
• Screen for HBV coinfection (HBsAg, anti-HBc) to prevent HBV reactivation 1
• Comprehensive drug-drug interaction screening 8

Treatment Prioritization

Immediate treatment priority for: 8

• Advanced fibrosis (≥F3) or any cirrhosis
• Pre- and post-liver transplant patients
• Severe extrahepatic manifestations (vasculitis, cryoglobulinemia, nephropathy)
• Hepatocellular carcinoma

Do not defer treatment in patients with minimal fibrosis (F0-F2)—modern DAAs are highly effective and safe. 8

Special Populations

• Compensated cirrhosis (Child-Pugh A): Use same regimens; extend glecaprevir/pibrentasvir to 12 weeks 8
• Decompensated cirrhosis: Coordinate with transplant center; use sofosbuvir/velpatasvir plus ribavirin for 12 weeks 8, 5
• Liver transplant recipients: Sofosbuvir/velpatasvir plus ribavirin for 12 weeks 8
• HIV coinfection: Treat with same regimens as HCV mono-infected patients with identical outcomes 8
• Active substance use: Not a contraindication to treatment—treat and refer to addiction services 1
• Renal impairment: Use glecaprevir/pibrentasvir (8 weeks) or grazoprevir/elbasvir (12 weeks) for patients with chronic kidney disease 5

Critical Drug-Drug Interactions

Absolute contraindications: P-glycoprotein (P-gp) inducers and moderate-to-strong CYP inducers significantly decrease DAA concentrations and must be avoided 8

Monitoring Protocol

• During treatment: HCV RNA at baseline, weeks 4 and 12, and end of treatment 8
• Post-treatment: HCV RNA at 12 weeks post-treatment (SVR12) 8
• SVR12 (undetectable HCV RNA 12 weeks after treatment completion) represents cure and is achieved in >99% of patients 8
• No routine laboratory monitoring required for most patients on modern DAAs 1
• Monitor for hypoglycemia in diabetic patients and INR in patients on warfarin 1

Retreatment After DAA Failure

• Failed sofosbuvir monotherapy or sofosbuvir/ribavirin: Retreat with sofosbuvir/ledipasvir, sofosbuvir/velpatasvir, or sofosbuvir/daclatasvir with ribavirin for 12 weeks (F0-F2) or 24 weeks (F3-F4) 8
• Failed NS5A inhibitor-containing regimen: Use sofosbuvir with protease inhibitor (grazoprevir/elbasvir or simeprevir) plus ribavirin for 12-24 weeks depending on genotype and cirrhosis 8

Acute Hepatitis C

For acute hepatitis C, initiate pegylated interferon-α monotherapy (pegylated IFN-α2a 180 µg/week or pegylated IFN-α2b 1.5 µg/kg/week) for 24 weeks if HCV RNA remains positive 2-4 months after onset. 6

• Achieves >90% SVR rates in acute infection 6
• Modern DAA regimens are increasingly used off-label for acute HCV with excellent results 4

Common pitfall: Do not use older interferon/ribavirin regimens for chronic hepatitis C—DAAs have replaced them entirely due to superior efficacy (>95% vs. 40-50%), shorter duration, and minimal side effects 6, 8

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Key Counseling Points

Hepatitis B 6

• Natural history is slowly progressive (median time to cirrhosis 28-32 years)
• Do not donate blood, organs, tissues, or semen
• Sexual transmission risk is small (maximum 5%)—barrier contraception in new relationships
• Vertical transmission is rare (maximum 6%) but higher in HIV-positive mothers
• Household contacts should avoid sharing toothbrushes and razors

Hepatitis C 6

• Natural history is slowly progressive (median time to cirrhosis 28-32 years)
• Do not donate blood, organs, tissues, or semen
• Sexual transmission risk is small (maximum 5%)
• Vertical transmission is rare (maximum 6%) but higher in HIV-positive mothers
• Breastfeeding is not contraindicated
• Household contacts should avoid sharing toothbrushes and razors