The ethics of placebo treatment for patients with acute exacerbation of chronic hepatitis B


  • Potential conflict of interest: Nothing to report.

The Ethics of Placebo Treatment for Patients With Acute Exacerbation of Chronic Hepatitis B

To the Editor:

I read with interest the article by Garg et al.,1 who showed that tenofovir improves the outcome in patients with spontaneous reactivation of hepatitis B virus (HBV) presenting as acute-on-chronic liver failure (ACLF). As indicated by the authors, the short-term prognosis of patients with spontaneous severe acute exacerbation of chronic hepatitis B leading to ACLF-like presentation is extremely poor, with a mortality rate ranging from 30%-70%. The current study showed that mortality rate was 43% in the tenofovir group and up to 85% in the placebo group. Prior to the start of the trial by Garg et al., Chien et al.2 demonstrated that the use of lamivudine is definitely beneficial for these patients, with an improved survival compared to historic controls. Moreover, this study showed that patients with serum bilirubin lower than 20 mg/dL could usually be rescued with the use of lamivudine. As a consequence, the HBV management guidelines proposed by organizations such as the Asian Pacific Association for the Study of the Liver (APASL)3 as well as the American Association for the Study of Liver Diseases (AASLD)4 consistently recommend that when patients with HBV who have ACLF are treated, antiviral drugs should be promptly instituted. The trial by Garg et al., which used placebo drug as a control, leading to an appreciably high mortality in this group, in order to demonstrate the efficacy of tenofovir in treating patients with HBV who have ACLF, was apparently medically unethical. Similar studies should be strongly discouraged.

Gin-Ho Lo M.D.*, * Department of Medical Education, Digestive Center, E-Da Hospital, I-Shou University, Kaohsiung City, Taiwan.