What are the indications to start Direct-Acting Antivirals (DAAs) in Hepatitis B surface antigen (HBsAg) positive patients?

Indications to Start Direct-Acting Antivirals (DAAs) in HBsAg Positive Patients

Direct-Acting Antivirals (DAAs) should be started in all HBsAg-positive patients with detectable HCV RNA who have HBV/HCV coinfection, with concurrent nucleos(t)ide analogue therapy for HBV if treatment for HBV is independently indicated. 1

Primary Indications for DAA Therapy in HBsAg-Positive Patients

HBV/HCV Coinfection

• Detectable HCV RNA: If HCV RNA is detectable in patients with HBV/HCV coinfection, antiviral treatment for HCV with DAAs should be initiated 1
• Concurrent HBV Treatment: If HBV treatment is independently indicated based on HBV DNA levels, ALT, and liver fibrosis assessment, nucleos(t)ide analogue therapy for HBV should be started along with DAA therapy 1
• Risk of HBV Reactivation: There is a significant risk of HBV reactivation during or after DAA therapy (14.1% of patients may experience increased HBV DNA levels and 12.2% may develop active hepatitis) 1

Special Populations Requiring DAAs

• Cirrhosis or HCC History: Patients with history of cirrhosis or hepatocellular carcinoma should receive simultaneous nucleos(t)ide analogue therapy for HBV along with DAA therapy for HCV to reduce the risk of liver failure from HBV reactivation 1
• Solid Organ Transplant Recipients: All HBsAg-positive solid organ transplant recipients should start prophylactic antiviral treatment at the time of transplantation with potent antivirals such as entecavir, tenofovir DF, or tenofovir AF 1

Pre-Treatment Assessment and Monitoring

Required Testing Before Starting DAAs

• HBV Status: Test all patients for HBsAg and anti-HBc before initiating HCV treatment with DAAs 2, 3
• Viral Replication: Check HBV DNA and HCV RNA levels before starting antiviral treatment 1
• Liver Assessment: Evaluate ALT levels and presence of liver cirrhosis 1

Monitoring During and After DAA Therapy

• Regular Monitoring: All HBV/HCV coinfected patients should be monitored for HBV reactivation by checking ALT and HBV DNA levels during and after DAA therapy 1
• HBsAg-Negative, Anti-HBc-Positive Patients: Although the risk of reactivation is very low (0-0.1%), HBsAg and HBV DNA should be tested if ALT elevation occurs 1

Choice of Antiviral Agents

Preferred DAA Regimens

• First-line Options: Sofosbuvir-based regimens are recommended for HCV treatment in HBV/HCV coinfection 4
• Treatment Duration: 8-12 weeks depending on HCV genotype and cirrhosis status 4

HBV Therapy When Indicated

• Preferred Agents: Entecavir, tenofovir DF, or tenofovir AF are preferred choices for HBV treatment 1, 4
• Drug Interactions: No significant drug-drug interactions exist between nucleos(t)ide analogues for HBV and DAAs for HCV, except in HBV/HCV/HIV triple infection where interactions should be considered 1

Special Considerations

Decompensated Cirrhosis

• Treatment Approach: Patients with decompensated cirrhosis and mild to moderate renal impairment should receive sofosbuvir and velpatasvir with ribavirin for 12 weeks 1
• Severe Renal Impairment: Those with severe renal impairment should receive sofosbuvir and velpatasvir without ribavirin for 24 weeks 1

Common Pitfalls to Avoid

• Failure to Screen: Not testing for HBV before starting HCV treatment 4
• Inadequate Monitoring: Not monitoring for HBV reactivation during and after DAA therapy 4
• Premature Discontinuation: Stopping HBV therapy too early in coinfected patients 4
• Ignoring Risk Factors: Not considering prophylactic HBV therapy in cirrhotic patients regardless of baseline HBV DNA levels 5

Outcomes and Prognosis

• HBsAg Clearance: DAA-treated HBV/HCV coinfected patients may have higher rates of HBsAg clearance, particularly those with low pre-treatment HBsAg titers 5
• Reactivation Risk: Higher risk of HBV reactivation exists, especially in patients with higher pre-treatment HBsAg titers 5
• Mortality Risk: Some cases of HBV reactivation have resulted in fulminant hepatitis, hepatic failure, and death when not properly managed 2, 3

By following these guidelines, clinicians can effectively manage HBsAg-positive patients requiring DAA therapy while minimizing the risk of HBV reactivation and associated complications.