What is the initial approach to treating hepatitis and what medications are used for different types of hepatitis?

Initial Treatment Approach for Hepatitis

The initial approach to treating hepatitis depends critically on the specific virus type (A, B, C, D, or E), with hepatitis C now treated with direct-acting antivirals (DAAs) achieving >90% cure rates, while hepatitis B requires long-term nucleos(t)ide analogue therapy for viral suppression rather than cure. 1

Immediate Diagnostic Steps

Before initiating any treatment, confirm the specific hepatitis virus and assess disease severity:

• Test for active infection: HCV RNA for hepatitis C; HBsAg, HBeAg, and HBV DNA for hepatitis B 1
• Assess liver fibrosis stage: Use FIB-4 score, transient elastography, or serologic tests to determine treatment urgency 1
• Screen for coinfections: Test for HIV and other hepatitis viruses, as coinfection worsens prognosis 1
• Evaluate liver function: Measure bilirubin, INR, albumin, and platelet count to distinguish compensated from decompensated cirrhosis 1
• For HCV patients: Test all patients for current or prior HBV infection (HBsAg and anti-HBc) before starting DAA therapy to prevent HBV reactivation 2

Hepatitis C Treatment

Treatment-Naïve Patients Without Cirrhosis

Genotype 1a:

• Ledipasvir/sofosbuvir (90 mg/400 mg) once daily for 12 weeks 3
• Alternative: Paritaprevir/ritonavir/ombitasvir plus dasabuvir with weight-based ribavirin for 12 weeks 3
• Alternative: Sofosbuvir (400 mg) plus simeprevir (150 mg) daily for 12 weeks (only if Q80K variant negative) 3

Genotype 1b:

• Ledipasvir/sofosbuvir (90 mg/400 mg) once daily for 12 weeks 3
• Alternative: Paritaprevir/ritonavir/ombitasvir plus dasabuvir for 12 weeks (no ribavirin needed) 3
• Alternative: Sofosbuvir plus simeprevir for 12 weeks 3

Genotype 2:

• Sofosbuvir (400 mg) plus weight-based ribavirin (1000-1200 mg) daily for 12 weeks 3
• Extend to 16 weeks if cirrhosis present 3

Genotype 3:

• Sofosbuvir/velpatasvir for 12 weeks 3
• Alternative: Glecaprevir/pibrentasvir for 8 weeks 3
• Alternative: Daclatasvir plus sofosbuvir for 12 weeks 3

Genotype 4:

• Ledipasvir/sofosbuvir for 12 weeks 3
• Alternative: Elbasvir/grazoprevir for 12 weeks 3
• Alternative: Glecaprevir/pibrentasvir for 8 weeks 3
• Alternative: Ombitasvir/paritaprevir/ritonavir plus ribavirin for 12 weeks 3

Genotypes 5 or 6:

• Ledipasvir/sofosbuvir for 12 weeks 3

Patients With Compensated Cirrhosis

Genotype 1a with cirrhosis:

• Ledipasvir/sofosbuvir for 24 weeks 3
• Alternative: Ledipasvir/sofosbuvir plus weight-based ribavirin for 12 weeks 3
• Alternative: Sofosbuvir plus simeprevir for 24 weeks (if Q80K negative) 3

Genotype 1b with cirrhosis:

• Ledipasvir/sofosbuvir for 12 weeks 3

Genotype 3 with cirrhosis:

• Sofosbuvir/velpatasvir plus ribavirin for 12 weeks 3
• Alternative: Sofosbuvir/velpatasvir/voxilaprevir for 8 weeks 3
• Alternative: Glecaprevir/pibrentasvir for 12 weeks 3

Genotype 4 with cirrhosis:

• Glecaprevir/pibrentasvir for 12 weeks 3
• Alternative: Ledipasvir/sofosbuvir for 12 weeks 3

Decompensated Cirrhosis (Child-Pugh B or C)

• Ledipasvir/sofosbuvir plus ribavirin (starting at 600 mg, titrate as tolerated) for 12 weeks 3
• Coordinate treatment with a transplant center 1

Hepatitis B Treatment

Treatment Indications

HBeAg-positive patients:

• Treat when HBV DNA >20,000 IU/mL AND ALT >2× upper limit of normal 4, 5

HBeAg-negative patients:

• Treat when HBV DNA >2,000 IU/mL AND ALT >2× upper limit of normal 4, 5

Compensated cirrhosis:

• Treat if HBV DNA ≥2,000 IU/mL, regardless of ALT level 4, 5

Decompensated cirrhosis:

• Immediately treat all patients with any detectable HBV DNA, regardless of viral load, HBeAg status, or ALT 4

First-Line Medications

Preferred agents (choose one):

• Entecavir 0.5 mg once daily (achieves 83% viral suppression at 96 weeks, no resistance after 8 years in treatment-naïve patients) 4
• Tenofovir disoproxil fumarate (TDF) 300 mg once daily (93% viral suppression at 48 weeks, no resistance after 8 years) 4
• Tenofovir alafenamide (TAF) (equal efficacy to TDF with better renal and bone safety profile) 4

Avoid as first-line:

• Do NOT use lamivudine (70% resistance rate over 5 years) 4
• Do NOT use adefovir (inferior efficacy to tenofovir) 4
• Do NOT use telbivudine (high resistance rates despite potency) 4

Special Considerations for Drug Selection

• Lamivudine-experienced patients: Use tenofovir (TDF or TAF), NOT entecavir, due to archived resistance mutations 4
• Renal dysfunction or bone disease risk: Prefer tenofovir TAF or entecavir over tenofovir TDF 4
• Decompensated cirrhosis: Consider combination therapy with tenofovir plus lamivudine or entecavir monotherapy; peginterferon is absolutely contraindicated 4

Treatment Duration

HBeAg-positive patients:

• Continue for at least 1 year, then 3-6 months after HBeAg seroconversion 4

HBeAg-negative patients:

• Long-term or indefinite treatment required (80-90% relapse if stopped within 1-2 years) 4

Cirrhotic patients:

• Continue until HBsAg loss occurs; do NOT discontinue even after HBeAg seroconversion 4

Monitoring During Treatment

Hepatitis C (DAA regimens):

• No routine laboratory monitoring required for most patients on modern DAAs 1
• Monitor for hypoglycemia in diabetic patients and INR in those on warfarin 1

Hepatitis B:

• Test HBV DNA and ALT every 3-6 months 4
• Monitor HBeAg status regularly in HBeAg-positive patients 4
• Check serum creatinine every 12 weeks for patients on adefovir or tenofovir 3, 4
• Verify medication adherence if virologic breakthrough occurs (most common cause rather than true resistance) 4

Critical Pitfalls to Avoid

• Do NOT delay HCV treatment in patients with advanced fibrosis - modern treatments are highly effective regardless of fibrosis stage 1
• Do NOT use entecavir in any patient with prior lamivudine exposure, even if brief, due to archived resistance mutations 4
• Do NOT assume virologic breakthrough in HBV represents resistance without first confirming medication adherence 4
• Do NOT discontinue HBV therapy prematurely in HBeAg-negative patients or those with cirrhosis (can cause severe hepatitis flares) 4
• Do NOT overlook HBV testing before starting HCV treatment - HBV reactivation during DAA therapy can cause fulminant hepatitis, hepatic failure, and death 2
• Active substance use is NOT a contraindication to HCV treatment - refer to addiction specialists but proceed with DAA therapy 1
• Do NOT use peginterferon in decompensated cirrhosis - risk of further decompensation 4