HBV reactivation in patients with HCV/HBV cirrhosis on treatment with direct-acting antivirals

J Viral Hepat. 2018 Jan;25(1):72-79. doi: 10.1111/jvh.12754. Epub 2017 Aug 9.


Anecdotal reports suggest that patients with chronic hepatitis C virus (HCV) hepatitis and overt or occult hepatitis B virus (HBV) coinfection may reactivate HBV when HCV is suppressed or cleared by direct-acting antivirals (DAAs). We assessed the prevalence of overt or previous HBV coinfection and the risk of HBV reactivation in patients with HCV cirrhosis treated with DAAs. This was a retrospective cohort of 104 consecutive patients with HCV cirrhosis treated with DAAs. Serum HCV-RNA and HBV-DNA were tested at weeks 4, 8 and 12 of DAAs therapy and at week 12 of follow-up. At the start of DAAs, eight patients (7.7%) were HBsAg positive/HBeAg negative with undetectable HBV-DNA and low levels of quantitative HBsAg (four on nucleos(t)ide analogues [NUCs] and four inactive carriers), 37 patients (35.6%) had markers of previous HBV infection (25 anti-HBc positive, 12 anti-HBc/anti-HBs positive) and 59 (56.7%) had no evidence of HBV infection. Sixty-seven patients (64.4%) were HCV-RNA negative at week 4 and 98 (94.2%) achieved sustained virological response. All four HBsAg-positive patients treated with NUCs remained HBV-DNA negative, but three of four untreated patients showed an increase in HBV-DNA of 2-3 log without a biochemical flare and achieved HBV-DNA suppression when given NUCs. During or after DAAs, by conventional assay, HBV-DNA remained not detectable in all 37 anti-HBc-positive patients but in three of them (8.1%) HBV-DNA became detectable with a highly sensitive PCR. HBV reactivation is likely to occur in untreated HBV/HCV-coinfected cirrhotic patients when they undergo HCV treatment with DAAs. Pre-emptive therapy with NUCs should be considered in this setting. Anti-HBc-positive patients rarely reactivate HBV without clinical or virological outcomes.

Keywords: HBV-DNA reactivation; HBV/HCV coinfection; nucleos(t)ide analogues therapy; previous HBV infection; sustained virological response.

MeSH terms

  • Adult
  • Aged
  • Antiviral Agents / administration & dosage*
  • Coinfection / drug therapy*
  • Coinfection / virology
  • DNA, Viral / blood
  • Female
  • Hepacivirus / drug effects
  • Hepacivirus / physiology
  • Hepatitis B virus / drug effects
  • Hepatitis B virus / physiology*
  • Hepatitis B, Chronic / complications
  • Hepatitis B, Chronic / drug therapy*
  • Hepatitis B, Chronic / virology
  • Hepatitis C, Chronic / complications
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / virology
  • Humans
  • Liver Cirrhosis / virology*
  • Male
  • Middle Aged
  • RNA, Viral / blood
  • Retrospective Studies
  • Virus Activation / drug effects*


  • Antiviral Agents
  • DNA, Viral
  • RNA, Viral