What is the treatment for hepatitis?

Treatment for Hepatitis

The preferred first-line treatments for chronic hepatitis B (CHB) are entecavir, tenofovir, and peginterferon alfa-2a, with entecavir and tenofovir being the preferred oral nucleos(t)ide analogues due to their high potency and low resistance profiles. 1, 2

Types of Hepatitis and Treatment Approaches

Hepatitis B Treatment

Patient Selection for Treatment

• Treatment is indicated for patients with HBV DNA ≥2,000 IU/mL, elevated ALT and/or at least moderate histological lesions 2, 3
• All patients with cirrhosis and detectable HBV DNA should receive treatment, regardless of ALT levels 2, 4
• For HBeAg-positive patients, treatment is recommended with HBV DNA >20,000 IU/mL AND serum ALT >2× ULN or significant inflammation/fibrosis on biopsy 2
• For HBeAg-negative patients, treatment is recommended with HBV DNA >2,000 IU/mL AND serum ALT >2× ULN or significant inflammation/fibrosis on biopsy 2

First-Line Treatment Options

• Nucleos(t)ide analogues (NAs) with high genetic barrier to resistance are preferred: 1, 2
  • Entecavir
  • Tenofovir disoproxil fumarate (TDF)
  • Tenofovir alafenamide fumarate (TAF)
• Peginterferon alfa-2a can be considered for a finite duration in selected patients 2
• First-generation NAs (lamivudine, adefovir) are not recommended due to low potency and high resistance rates 4

Treatment Monitoring

• Monitor HBV DNA levels every 3-6 months to assess virologic response 4
• Monitor liver function tests every 3-6 months 4
• Virologic response is defined as undetectable HBV DNA by PCR assay 4
• Biochemical response is defined as normalization of ALT levels 4

Treatment Duration and Goals

• Long-term, potentially indefinite treatment is typically required with NAs 2, 4
• HBsAg loss is considered the optimal endpoint but is rarely achieved 4
• Short-term goals include HBV DNA suppression, ALT normalization, and HBeAg seroconversion (in HBeAg-positive patients) 2
• Long-term goals include prevention of cirrhosis, hepatic decompensation, and hepatocellular carcinoma 2

Special Populations

• For pregnant women: Tenofovir DF is the preferred agent during pregnancy 2, 4
• For patients with renal dysfunction or bone disease: Entecavir, TAF, or besifovir are preferred 2
• For patients with decompensated cirrhosis: Combination therapy with lamivudine or entecavir plus tenofovir may be preferred 1

Hepatitis C Treatment

• Direct-acting antivirals (DAAs) are the standard of care for hepatitis C treatment 2
• Recommended regimens based on genotype include: 2
  • Genotype 1,4,5,6: Ledipasvir/sofosbuvir (12 weeks)
  • Genotype 2,3: Sofosbuvir/velpatasvir (12 weeks) or Daclatasvir+sofosbuvir (12 weeks)
  • For decompensated cirrhosis: Ledipasvir/sofosbuvir+ribavirin or Sofosbuvir/velpatasvir+ribavirin (12-24 weeks)
• Treatment monitoring should include repeated measurements of HCV RNA levels 2
• Assess for sustained virologic response (SVR) 24 weeks after the end of therapy 2

Management of Resistance and Treatment Failure

• For patients with lamivudine resistance, tenofovir monotherapy is sufficient 1
• For patients with adefovir resistance, tenofovir may also be sufficient 1
• For patients with partial response to entecavir but HBV DNA <1000 IU/mL after 1 year, continuing entecavir through at least 2 years total may achieve viral suppression 1
• For patients with partial response to entecavir and higher residual HBV DNA level after 1 year, switching to tenofovir monotherapy or tenofovir plus entecavir combination therapy is recommended 1

Important Considerations and Precautions

• Severe acute exacerbations of hepatitis have been reported in patients who are infected with HBV or coinfected with HBV and HIV-1 and have discontinued tenofovir disoproxil fumarate 5
• Renal impairment, including cases of acute renal failure, has been reported with tenofovir use 5
• Bone mineral density monitoring should be considered in patients on tenofovir who have a history of pathologic bone fracture or are at risk for osteopenia 5
• In the treatment of chronic hepatitis B, the optimal duration of treatment is unknown, and the relationship between response and long-term prevention of outcomes such as hepatocellular carcinoma is not established 5

Emerging Therapies

• New approaches to HBV treatment aim to achieve HBsAg loss, inhibition of new hepatocyte infection, elimination of cccDNA, and restoration of immune function 6
• Emerging therapies include drugs that target different stages of the HBV life cycle and immunotherapies that enhance both innate and adaptive immunity against HBV 6
• Future therapeutic trends will likely involve combinations of drugs that target the viral life cycle and at least one immunomodulator 6