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Hepatitis B Testing Should Be Done Before and During Hepatitis C Treatment

People considering treatment for hepatitis C should first be tested for hepatitis B virus (HBV) and monitored throughout therapy, as successful elimination of hepatitis C virus (HCV) can reactivate HBV and potentially worsen liver disease, according to recent updates to American and European hepatitis C treatment guidelines.

In people with both HBV and HCV infection, HBV DNA viral load is often low or undetectable and HCV is usually the main driver of active liver disease. Although not fully understood, the 2 viruses seem to keep each other in check. HBV could become more active, however, if HCV is cured with direct-acting antiviral (DAA) therapy.

The American Association for the Study of the Liver (AASLD) and Infectious Diseases Society of America (IDSA) included the recommendation in a September 16 update to its HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C, available at www.hcvguidelines.org.

The revised recommendation states:

All patients initiating HCV direct-acting antiviral therapy should be assessed for HBV coinfection with HBsAg, anti-HBs, and anti-HBc

For HBsAg+ patients who are not already on HBV suppressive. therapy, monitoring of HBV DNA levels during and immediately after DAA therapy for HCV is recommended and antiviral treatment for HBV should be given if treatment criteria for HBV are met.

Updated guidelinesfrom the European Association for the Study of the Liver (EASL), released last week at a special meeting in Paris, likewise state that people coinfected with HBV and HCV can be treated for hepatitis C using the generally recommended regimens, but "If chronic hepatitis B or 'occult' HBV infection is detected, concurrent HBV nucleoside/nucleotide analogue therapy is indicated."

"Cases of HBV reactivation (an increase of the HBV virus) during or after DAA therapy for HCV have been reported in HBV/HCV coinfected patients who were not already on HBV suppressive therapy," Raymond Chung, co-chair of the AASLD/IDSA HCV Guidance Panel, said in a press releaseannouncing the changes. "The severity of these cases have ranged from mild to severe fulminant liver injury that can be life threatening. While we do not know how frequently this occurs, the Guidance Panel recommends HBV testing for all patients beginning DAA treatment for HCV."

Hepatitis B surface antigen (HBsAg) and hepatitis B surface and core antibodies (anti-HBs and anti-HBc, respectively) are measured to determine HBV infection status. People who are HBsAg-positive, meaning they may have active disease, should also be tested for HBV DNA viral load, to see if the virus is actively replicating.

The EASL guidelines also recommend testing for the presence of hepatitis delta virus (which only occurs in people with hepatitis B) and address "occult" HBV infection, when HBV DNA is detectable in HBsAg-negative patients.

The AASLD/IDSA and EASL panels both recommend that patients who meet criteria for treatment of active HBV infection (as described in the AASLD Guidelines for Treatment of Chronic Hepatitis B) should start nucleoside/nucleotide antivirals such as entecavir (Baraclude) or tenofovir (Viread) at the same time as -- or before -- initiating hepatitis C DAA therapy.

People with low or undetectable HBV DNA levels should be monitored at regular intervals (usually not more than every 4 weeks) during and immediately after hepatitis C treatment to check for HBV reactivation, and started on hepatitis B antivirals if they meet treatment criteria, according to the AASLD/IDSA guidelines.

The AASLD/IDSA panel recommends that people who have resolved HBV infection -- either due to spontaneous clearance or successful antiviral therapy -- should also be monitored for HBV reactivation during hepatitis C treatment. The EASL panel advises "assiduous monitoring" of aminotransferase (ALT and AST) liver enzyme levels in people who test positive for hepatitis B antibodies.

"While there currently isn’t enough data to make clear recommendations for patients who have been exposed to HBV and resolved the virus, whether spontaneous or after antiviral therapy, we recommend these patients be monitored for HBV reactivation," said panel co-chair Susanna Naggie. "This is particularly important in the event of unexplained increases in liver enzymes and during and/or after completion of [HCV] DAA therapy."

Finally, the AASLD/IDSA panel recommends that all people with hepatitis C who remain susceptible to hepatitis B should receive HBV vaccination.

9/29/16

References

AASLD/ISDA. HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C. www.hcvguidelines.org. Updated September 16, 2016.

JM Pawlotsky et al (European Association for the Study of the Liver). EASL Recommendations on Treatment of Hepatitis C 2016. Journal of Hepatology, 2016 (in press).

AASLD. People with Hepatitis C Should Be Tested for Hepatitis B Before Starting Antiviral Therapies. Press release. September 16, 2016.