What is the treatment approach for patients with hepatitis B virus (HBV) and hepatitis C virus (HCV) or hepatitis D virus (HDV) coinfection?

Treatment Approach for Hepatitis Coinfection

For patients with HBV/HCV coinfection, antiviral treatment for HCV should be started if HCV RNA is detectable, while HBV treatment should be initiated according to standard HBV treatment criteria with careful monitoring for HBV reactivation during and after HCV therapy. 1

HBV/HCV Coinfection Management

Initial Assessment

• Test for both viruses: HBV DNA, HCV RNA, ALT levels, and liver fibrosis assessment
• Determine which virus is dominant based on viral load and liver enzyme patterns

Treatment Algorithm

1. If HCV RNA is detectable:

   • Start direct-acting antiviral (DAA) therapy for HCV 1
   • Monitor for HBV reactivation by checking ALT and HBV DNA levels during and after DAA therapy 1
   • Preferred DAAs: Follow standard HCV treatment guidelines based on genotype

2. If HBV treatment is indicated (based on standard HBV criteria):

   • Start nucleos(t)ide analogue (NA) therapy for HBV concurrently 1
   • Preferred NAs: Entecavir, tenofovir DF, or tenofovir AF 1

3. Special considerations:

   • For patients with history of cirrhosis or HCC: Consider simultaneous NA therapy for HBV along with DAA therapy for HCV to reduce risk of liver failure from HBV reactivation 1
   • For HBsAg-negative but anti-HBc-positive patients: Risk of HBV reactivation is very low (0-0.1%), but monitor ALT and test for HBsAg and HBV DNA if ALT elevation occurs 1

HBV Reactivation Risk

• Meta-analysis shows HBV DNA was newly detected or increased in 14.1% of patients after 4-12 weeks of DAA therapy 1
• Active hepatitis with ALT elevation occurred in 12.2% of patients 1
• Critical warning: HBV reactivation during HCV treatment can lead to fulminant hepatitis, hepatic failure, and death 2, 3

HDV Coinfection Management

Initial Assessment

• Diagnose HDV infection by detecting anti-HDV or HDV RNA in serum, or HDV antigens in liver tissue 1
• Evaluate degree of hepatic fibrosis using liver biopsy or non-invasive methods 1

Treatment Algorithm

1. All patients with HDV RNA positivity are eligible for treatment regardless of liver disease severity 1

2. First-line therapy:

   • Weekly peginterferon alfa by subcutaneous injection for 48 weeks 1
   • Sustained viral response at 24 weeks reported in 23-28% of patients 1
   • Note: Relapse is frequent during long-term follow-up (sustained response maintained in only 12% after 4.3 years) 1

3. For patients with active HBV replication:

   • Add NA therapy (entecavir, tenofovir DF, or tenofovir AF) if HBV DNA levels are elevated 1
   • Note: NAs alone do not inhibit HDV replication and are not recommended if HBV treatment is not otherwise indicated 1

4. For patients with advanced fibrosis, cirrhosis, or other HBV treatment indications:

   • NA therapy should be administered to prevent progression of liver disease 1

Emerging Therapies

• Bulevirtide (BLV), an entry inhibitor for HDV that acts on sodium taurocholate cotransporting polypeptide (NTCP), is in phase III studies 1

Important Monitoring Considerations

• Before starting treatment:

  • Test all patients for evidence of current or prior HBV infection (HBsAg and anti-HBc) before initiating HCV treatment 2, 3

• During and after HCV treatment:

  • Monitor ALT and HBV DNA levels for potential HBV reactivation 1
  • For HBV/HDV coinfection, monitor for 6 months post-treatment and beyond 1

• Drug interactions:

  • No significant drug-drug interactions between NAs for HBV and DAAs for HCV 1
  • For HBV/HCV/HIV triple infection, carefully consider potential drug interactions 1

Clinical Outcomes and Prognosis

• HBV/HCV coinfection is associated with higher rates of cirrhosis and HCC compared to monoinfection 4
• HBV/HDV coinfection is associated with higher rates of cirrhosis and HCC compared to HBV monoinfection 1
• Successful treatment of HCV may lead to improved outcomes, but vigilance for HBV reactivation is essential 1, 2, 3