Monday, June 19, 2017

Letter: the influence of direct acting agents for hepatitis C, on hepatitis B reactivation

Volume 46, Issue 2
July 2017  Page 208

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Letter: the influence of direct acting agents for hepatitis C, on hepatitis B reactivation
C.-C. Wang, J.-H. Kao
First published: 15 June 2017
Full publication history DOI: 10.1111/apt.14116  

We read with great interest the article by Londono et al.[1] In this study, baseline HBsAg positivity or isolated anti-HBc positivity were 2.8% and 18% in 352 chronic hepatitis C (CHC) patients receiving direct-acting antivirals (DAAs), respectively. They found that 50% of HBsAg-positive and 1.6% of anti-HBc-positive patients had hepatitis B virus (HBV) viral reactivation (> 1 log increase in HBV-DNA level). In addition, the increase in HBV-DNA was modest and early during the course of DAAs treatment. There were no serious clinical events in such patients. They thus suggested that HBV viral reactivation is frequent and early during DAAs treatment; however, the reactivation is modest and without clinical impact. Although these data provide more evidence about the risk of HBV reactivation during DAAs for CHC, several issues are worthy of discussion and further investigations.

First, this study found HBV reactivation is frequent in HBsAg-positive patients receiving DAAs against HCV. However, only 10 HBV/HCV co-infected patients were included, and they had a higher risk of HBV viral reactivation than those positive for anti-HBc antibody. Among these HBsAg-positive patients, six were inactive carriers and four received anti-HBV agents. Therefore, the frequency and severity of HBV viral reactivation may be underestimated as is observed in clinical practice. It is recommended that HBV status, either chronic active infection, inactive carrier or resolved infection, must be confirmed before starting DAAs, especially in HBV endemic area by measuring serum HBsAg, HBV-DNA, anti-HBc, and anti-HBs antibody. On-treatment HBV-DNA monitoring at Week 4 of DAAs treatment is required for early detection of HBV viral reactivation to prompt anti-HBV treatment and prevent the occurrence of hepatitis flare as well as subsequent fulminant hepatic failure.[2, 3] Second, 24.8% of HBV/HCV co-infected patients had HBeAg-negative chronic hepatitis in our previous study.[4] Our data showed that combination of pegylated interferon plus ribavirin is equally effective for patients with HCV mono-infection and those with dual HBV/HCV infection. In addition, post-treatment HBsAg seroclearance was observed in 11.2% of 161 HBV/HCV co-infected patients. Interferon-based regimen is known active against both HBV and HCV; however, DAAs are only effective for HCV. Whether combination of DAAs and anti-HBV agents is cost-effective for HBV/HCV co-infected patients with high HBV-DNA levels (> 2000 IU/mL) deserves additional studies. Third, a recent study showed a high rate of hepatocellular carcinoma (HCC) recurrence in HCV-related HCC patients receiving DAAs after curative treatment.[5] The possible explanation is the disruption of host immune surveillance after HCV clearance. Since host immune responses play an important role in the interaction between HBV and HCV in HBV/HCV co-infected patients, the dynamic change in immune markers during DAAs therapy for CHC deserves further investigations.

Londono MC, Lens S, Marino Z, et al. Hepatitis B reactivation in patients with chronic hepatitis C undergoing anti-viral therapy with interferon-free regimens. Aliment Pharmacol Ther. 2017;45:1156-1161.
  • 2De Monte A, Courjon J, Anty R, et al. Direct-acting antiviral treatment in adults infected with hepatitis C virus: reactivation of hepatitisB virus coinfection as a further challenge. J Clin Virol. 2016;78:27-30.
  • 3Ende AR, Kim NH, Yeh MM, et al. Fulminant hepatitis B reactivation leading to liver transplantation in a patient with chronic hepatitis C treated with simeprevir and sofosbuvir: a case report. J Med Case Rep. 2015;9:164.
  • 4Liu CJ, Chen PJ, Chen DS, Tseng TC, Kao JH. Perspectives on dual hepatitis B and C infection in Taiwan. J Formos Med Assoc. 2016;115:298-305.
  • 5Reig M, Marino Z, Perello C, et al. Unexpected early tumor recurrence in patients with hepatitis C virus –related hepatocellular carcinoma undergoing interferon-free therapy: a note of caution. J Hepatol. 2016;65:719-726.
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