Treatment Options for Hepatitis
Hepatitis C Treatment
Direct-acting antivirals (DAAs) are the standard of care for hepatitis C, achieving sustained virologic response rates exceeding 90% and should be used in all patients with chronic HCV infection regardless of fibrosis stage. 1, 2
First-Line DAA Regimens by Genotype
- Genotype 1,4,5,6: Ledipasvir/sofosbuvir for 12 weeks 2, 3
- Genotype 2,3: Sofosbuvir/velpatasvir for 12 weeks OR daclatasvir plus sofosbuvir for 12 weeks 2
- Treatment-naïve non-cirrhotic genotype 1 patients: 8-week ledipasvir/sofosbuvir regimen achieves 94% SVR12, though 12-week treatment remains standard with 96% SVR12 3
Special Populations
- Decompensated cirrhosis: Ledipasvir/sofosbuvir plus ribavirin OR sofosbuvir/velpatasvir plus ribavirin for 12-24 weeks 2
- Renal impairment (CKD/ESRD): Glecaprevir/pibrentasvir for 8 weeks OR grazoprevir/elbasvir for 12 weeks 2
- Post-transplant patients: Ledipasvir/sofosbuvir plus ribavirin regimens are effective 3
Ribavirin Dosing When Required
- Genotypes 1,4-6: Weight-based dosing at 15 mg/kg per day (1000 mg daily if <75 kg; 1200 mg daily if ≥75 kg) 2, 3
- Genotypes 2,3: Flat dose of 800 mg daily 2
- Decompensated cirrhosis: Start at 600 mg daily regardless of weight, adjust based on tolerance 3
Treatment Monitoring
- Baseline assessment: Confirm diagnosis with nucleic acid testing, determine genotype and viral load, assess liver fibrosis using non-invasive methods 2
- On-treatment: Monitor at weeks 4 and 12 after initiation, then every 12 weeks until treatment completion 2
- Post-treatment: Assess for sustained virologic response (SVR) at 24 weeks after therapy ends 2
Hepatitis B Treatment
Nucleos(t)ide analogues with high genetic barrier to resistance—specifically entecavir, tenofovir disoproxil fumarate (TDF), or tenofovir alafenamide fumarate (TAF)—are first-line treatment for chronic hepatitis B. 2, 4, 5
Treatment Indications
- HBeAg-positive patients: Treat when HBV DNA >20,000 IU/mL AND ALT >2× upper limit of normal OR significant inflammation/fibrosis on biopsy 2, 4
- HBeAg-negative patients: Treat when HBV DNA >2,000 IU/mL AND ALT >2× upper limit of normal OR significant inflammation/fibrosis on biopsy 2, 4
- Patients >30 years with normal ALT: Consider treatment if HBV DNA >1,000 IU/mL 2
- All cirrhotic patients: Treat if HBV DNA is detectable, regardless of ALT levels 2
First-Line Treatment Options
- Entecavir: 0.5 mg daily (1 mg daily in decompensated cirrhosis); achieves >90% virologic remission after 3 years with <1% resistance at 4 years in treatment-naïve patients 4, 5
- Tenofovir (TDF): 300 mg daily; achieves >90% virologic remission after 3 years with minimal resistance 4
- Tenofovir alafenamide (TAF): Preferred for patients with renal dysfunction or bone disease 2
- Peginterferon alfa-2a: 180 mcg weekly subcutaneous for 48 weeks; offers higher rates of HBeAg seroconversion and HBsAg loss, particularly in genotype A or B, high ALT, low HBV DNA, and younger patients 4
Treatment by Clinical Scenario
Compensated cirrhosis:
- Entecavir or tenofovir are preferred first-line agents 1, 4
- Peginterferon may be considered in select patients with well-compensated disease 1, 4
- Long-term, potentially lifelong treatment is required 1, 4
Decompensated cirrhosis:
- Combination therapy with tenofovir plus lamivudine OR entecavir monotherapy (1 mg daily) OR tenofovir monotherapy 1
- Peginterferon is contraindicated 1, 4
- All patients should be wait-listed for liver transplantation 1
- Treatment must be lifelong 4
Pregnancy:
- TDF is the preferred agent during pregnancy 2
- Antiviral therapy in third trimester for mothers with high viral load prevents mother-to-child transmission 2
Lamivudine-experienced patients:
- Avoid entecavir due to resistance risk; use tenofovir instead 4
Treatment Duration and Monitoring
- HBeAg-positive patients: Minimum 1 year, then 3-6 months after HBeAg seroconversion 5
- Cirrhotic patients: Lifelong treatment due to decompensation risk upon discontinuation 5
- Monitoring frequency: HBV DNA and ALT every 3-6 months; assess HBeAg status and renal function regularly 4
- Optimal endpoint: HBsAg loss, though this is rare with nucleos(t)ide analogues 2
On-Treatment Virologic Response Assessment
- Week 12: Assess for primary treatment failure (HBV DNA decline <1 log10 IU/mL) 1
- Week 24: Categorize response as complete (HBV DNA <60 IU/mL), partial (60-2000 IU/mL), or inadequate (>2000 IU/mL) 1
- Every 3-6 months thereafter: Monitor to confirm viral suppression and detect breakthrough 1
Hepatitis D Treatment
Peginterferon alfa remains the primary treatment option for hepatitis D, though relapse rates are high. 6
- Bulevirtide is the first conditionally approved drug in Europe for HDV-associated compensated liver disease 7
- Novel direct-acting agents targeting different steps of the HDV life cycle are under investigation 7, 8
- HDV remains the most challenging chronic viral hepatitis to treat with less favorable response rates compared to HBV and HCV 8
Hepatitis E Treatment
Acute hepatitis E is typically self-limiting and requires no specific antiviral therapy in immunocompetent patients. 6
- Immunocompromised patients (e.g., post-transplant): Reduction of immunosuppression may clear HEV 6
- Chronic HEV in immunosuppressed patients: Ribavirin shows antiviral efficacy as an off-label treatment option 6, 7
HBV-HCV Coinfection Management
Treat HCV with standard DAA regimens while providing concurrent HBV nucleos(t)ide analogue therapy if HBsAg-positive or HBV DNA detectable. 5