Convincing evidence that antiviral therapy contributes to reduce short-term mortality of patients with hepatitis B virus (HBV)-associated acute-on-chronic liver failure (ACLF) is still unavailable.1, 2 I read with great interest the article by Garg et al.,3 who demonstrated that tenofovir can reduce the mortality of patients with severe spontaneous reactivation of chronic hepatitis B presenting as ACLF. Their optimistic results give us some evidence about antiviral therapy in HBV-associated ACLF. However, a recent prospective cohort study by Wong et al.4 demonstrated that entecavir treatment, as compared to lamivudine treatment, is associated with increased short-term mortality of patients with severe acute exacerbation of chronic hepatitis B.
Both tenofovir and entecavir are now the most effective antiviral agents for chronic hepatitis B. But why did they have converse effects upon the short-term mortality of HBV-associated ACLF? Here, we would like to offer some possible reasons for this interesting question. First, Garg et al. identified patients with HBV-associated ACLF by a high HBV DNA level (>105 copies/mL).3 The criterion on which their previous study is based may be useful, but it is still immature with only 14 patients enrolled in the tenofovir treatment group. There are obviously distinct prognoses between acute hepatitis B–related liver failure and HBV-associated ACLF. Therefore, enrollment of any patients with acute HBV-related liver failure may interfere with the results. Besides, genotype D was the predominant HBV genotype in the Indian study subjects (85.2%), but genotype B or C is the main HBV genotype in China. Also, it is still unknown whether HBV genotype may affect the results of antiviral treatment in ACLF. In addition, Wong et al. speculated that the problem of lactic acidosis or an exaggerated immune response due to rapid virological suppression may lead to and exacerbate liver injury among patients with severe acute exacerbation of chronic hepatitis B.4 However, the latter explanation is contradictory to the opinion of Garg et al., who proposed that rapid reduction in HBV DNA levels independently predicted a good short-term survival rate. Thus, larger prospective and multicentric studies are encouraged to further evaluate the affect of tenofovir and entecavir on short-term mortality of patients with HBV-associated ACLF.