What is the treatment for viral hepatitis?

Treatment of Viral Hepatitis

For chronic hepatitis B, first-line treatment consists of nucleos(t)ide analogues with high genetic barrier to resistance—specifically entecavir, tenofovir disoproxil fumarate (TDF), or tenofovir alafenamide (TAF)—while for hepatitis C, pangenotypic direct-acting antivirals (DAAs) such as ledipasvir/sofosbuvir or sofosbuvir/velpatasvir achieve cure rates exceeding 95%. 1, 2

Hepatitis B Treatment

First-Line Agents

• Entecavir, TDF, or TAF are the only recommended first-line therapies due to their high potency and minimal resistance development (entecavir resistance <1% at 4 years, TDF resistance 0% at 8 years). 1, 2, 3
• Lamivudine is explicitly avoided due to resistance rates reaching 70% within 5 years. 1
• TAF demonstrates superior renal and bone safety compared to TDF through 96 weeks of treatment. 3

Treatment Indications by Clinical Scenario

Immediate treatment required (start within 24-48 hours):

• Any patient with decompensated cirrhosis and detectable HBV DNA, regardless of ALT level 1, 3
• Acute liver failure or severe acute hepatitis B 1, 3
• Patients requiring liver transplantation 3

Standard treatment thresholds for non-cirrhotic patients:

• HBV DNA ≥20,000 IU/mL AND ALT ≥2× upper limit of normal (ULN): treat immediately without biopsy 1, 3
• HBV DNA ≥2,000 IU/mL AND ALT >40 IU/L (>1× ULN) AND moderate-to-severe necroinflammation or fibrosis on assessment: initiate treatment 1, 2, 3
• HBV DNA ≥2,000 IU/mL with at least moderate fibrosis: consider treatment even with normal ALT 1, 3

Compensated cirrhosis:

• Any detectable HBV DNA (>2,000 IU/mL) requires treatment regardless of ALT level 1, 2, 3

Special Populations

Pregnancy:

• TDF is the preferred agent during pregnancy (not entecavir or TAF). 1, 2, 3
• Prophylactic TDF should begin at 24-32 weeks gestation for women with HBV DNA >200,000 IU/mL to prevent mother-to-child transmission. 2, 3

HIV-HBV coinfection:

• All coinfected patients require TDF- or TAF-based antiretroviral therapy regardless of CD4 count. 3
• Avoid lamivudine monotherapy due to rapid resistance development. 1

Renal dysfunction or bone disease:

• Entecavir, TAF, or besifovir are preferred over TDF. 2

Treatment Duration and Monitoring

• Long-term, potentially indefinite treatment is required with nucleos(t)ide analogues. 1, 2, 3
• HBsAg loss (with or without anti-HBs seroconversion) represents the optimal endpoint but is rarely achieved. 1, 2, 3
• Monitor HBV DNA and liver function tests every 3-6 months during treatment. 2, 3
• For HBeAg-positive patients achieving HBeAg seroconversion with undetectable HBV DNA, consider stopping after ≥12 months of consolidation therapy, though relapse risk remains high. 1, 3

Peginterferon Considerations

• Peginterferon alfa-2a can be considered for finite-duration therapy (48 weeks) in selected patients with mild-to-moderate disease, particularly those with genotype A or B, high ALT (>2× ULN), and low HBV DNA. 1, 3
• Peginterferon is absolutely contraindicated in decompensated cirrhosis. 1, 3

Hepatitis C Treatment

First-Line Direct-Acting Antiviral Regimens

Genotype 1,4,5,6:

• Ledipasvir/sofosbuvir 90mg/400mg once daily for 12 weeks achieves SVR12 rates of 94-96% in treatment-naïve non-cirrhotic patients. 2, 4
• For patients with baseline HCV RNA <6 million IU/mL, 8-week treatment achieves 97% SVR12. 4

Genotype 2,3:

• Sofosbuvir/velpatasvir for 12 weeks 2
• Sofosbuvir plus ribavirin: 12 weeks for genotype 2,24 weeks for genotype 3 2, 5

Decompensated cirrhosis:

• Ledipasvir/sofosbuvir plus weight-based ribavirin for 12-24 weeks 2, 4
• Sofosbuvir/velpatasvir plus ribavirin for 12-24 weeks 2
• Ribavirin starting dose is 600 mg daily regardless of weight in decompensated patients, with dose adjustments based on tolerance. 4

Treatment Monitoring

• Assess HCV RNA at weeks 4 and 12 during treatment, then every 12 weeks until treatment completion. 2
• Measure sustained virologic response (SVR12) at 24 weeks post-treatment. 2, 4
• For genotype 1 or 4 patients, discontinue therapy at 12 weeks if HCV RNA has not decreased by ≥2 log units from baseline. 1

Special Populations

Renal impairment:

• Glecaprevir/pibrentasvir for 8 weeks or grazoprevir/elbasvir for 12 weeks in patients with chronic kidney disease requiring dialysis. 2
• Ledipasvir/sofosbuvir is safe in end-stage renal disease requiring dialysis: 8-24 weeks depending on treatment history. 4

HIV-HCV coinfection:

• Same DAA regimens as HIV-negative patients 1
• Sofosbuvir plus ribavirin: 24 weeks for genotype 1,12 weeks for genotype 2/3 treatment-naïve, 24 weeks for genotype 2/3 treatment-experienced. 5

Pediatric patients ≥3 years:

• Ledipasvir/sofosbuvir for 12 weeks (genotype 1 or 4) or 24 weeks based on treatment history. 4
• Sofosbuvir plus ribavirin: 12 weeks for genotype 2,24 weeks for genotype 3. 5

Acute Viral Hepatitis

Hepatitis A and E

• Treatment is entirely supportive: rest, hydration, symptomatic relief, and avoidance of hepatotoxic medications including alcohol. 1, 6
• Hospitalization is indicated for severe nausea/vomiting preventing oral intake or any mental status changes suggesting fulminant hepatic failure. 6

Acute Hepatitis B

• More than 95% of immunocompetent adults recover spontaneously without antiviral therapy. 3
• Antiviral therapy with entecavir or tenofovir is indicated for severe acute hepatitis B (significant coagulopathy, encephalopathy, or prolonged jaundice). 1, 3
• For fulminant hepatitis B, immediately start nucleos(t)ide analogues and evaluate for liver transplantation. 3
• Continue treatment for ≥3 months after anti-HBs seroconversion or ≥12 months after anti-HBe seroconversion if HBsAg persists. 3

Acute Hepatitis C

• Interferon-alpha therapy during acute hepatitis C may decrease progression to chronic infection, though this is not standard practice with current DAA availability. 6

Critical Pitfalls to Avoid

• Never use lamivudine as first-line therapy for hepatitis B—resistance develops in up to 70% of patients within 5 years. 1
• Do not delay treatment in decompensated cirrhosis—any detectable HBV DNA requires immediate nucleos(t)ide analogue therapy. 1, 3
• Never use peginterferon in decompensated cirrhosis—it is absolutely contraindicated and can precipitate liver failure. 1, 3
• Do not rely on normal ALT to exclude significant liver disease—patients with HBV DNA ≥2,000 IU/mL and normal ALT may still have moderate-to-severe fibrosis requiring treatment. 3
• Avoid nephrotoxic drugs (NSAIDs) and excessive acetaminophen (>2g/day) in all patients with cirrhosis. 1
• Screen all hepatitis B patients for HBsAg before starting immunosuppressive or cancer therapy—reactivation can be fatal without prophylaxis. 1