Mesenchymal stem cells for hepatitis B patients with acute on chronic liver failure—are we there?

Potential conflict of interest: Nothing to report. TO THE EDITOR: We read with great interest regarding the recent publication by Lin et al.1 Recently, there has been increasing interest in the utilization of stem cells and growth factors as a salvage therapy for severe liver diseases, such as alcoholic hepatitis and acute on chronic liver failure (ACLF), despite a limited supporting mechanism.2 Although most studies demonstrated that such a practice appeared to be tolerable and safe, its long‐term benefits remains unclear. In this article, the investigators demonstrated significant survival benefit of mesenchymal stem cells (MSCs) among hepatitis B patients with ACLF compared with standard medical treatment (SMT) attributed to decreased serious infection. The patients appeared to be properly randomized and there were no significant differences in baseline characteristic between both groups; however, there were a few aspects worthy for discussion. First, all patients in this study received entecavir as a part of SMT, and information regarding previous exposure to lamivudine or entecavir was not available. These pieces of information are, in fact, crucially important in this study, considering that several studies have demonstrated that effectiveness of entecavir is significantly lower when patients are previously treated with lamivudine.4 Second, although viral load appeared similar between the two groups, subsequent viral load is important in determining response to antivirals. Last, serious infection appeared to be the cause of lower survival in the SMT group; however, the patients in both groups were not blinded as mentioned in the weakness of this study. As a result, antibiotic stewardship of patients in each group could be distinctly managed and respectively created bias in this study. In summary, providing some information regarding previous antiviral use, viral load, and antibiotic use might alleviate these problems and help readers interpreting the result of this study. Regardless, this study proved that MSC infusion is safe, but potential benefit needs to be confirmed in a double‐blind fashion.