Is it necessary to revise the liver transplantation guidelines to meet the current situation?

See article in Hepatology Research Kreitman KR, Kothadia JP, Nair SP, Maliakkal BJ. Unexpected hepatitis B virus transmission after liver transplant from nucleic acid testing‐ and serology‐negative liver donors who are hepatitis C viremic. Hepatol Res. 2021;1–5. https://doi.org/10.1111/hepr.13680 The availability of organs for liver transplantation has indeed increased with the opioid epidemic. Lamentably, these donor livers are often infected with hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV). In cases of coinfection with HBV and HCV, HBV has been shown to be suppressed. In this issue of Hepatology Research, Kreitman et al. reported an unexpected HBV transmission after liver transplantation from nucleic acid testing (NAT)‐ and serology‐negative liver donors who are hepatitis C viremic. The authors speculate that the presence of HCV may have prolonged the NAT window. They therefore suggest that screening for HBV in HCV‐infected donor livers should be improved and extended in the future. Previously, cases of HBV development were observed in patients transplanted with livers from Anti‐HBc‐negative and Anti‐ HBs‐negative donors. These unexpected HBV infections led to a revision of liver transplant guidelines in the United States in 2013 to incorporate NAT. However, there have been occasional reports of HBV infection after liver transplantation. The Centers for Disease Control and Prevention determined that the risk for undetected infection in donors with high‐risk behaviors screened by NAT 30 days after the most recent potential risk behavior was less than one per 1 million for HIV and HCV and close to one per 1 million for HBV. HBV and HCV share a common route of transmission, and both can cause acute and chronic infections. Dual chronic infection with HBV and HCV is fairly frequent, particularly among high‐risk individuals. However, the intracellular interactions of HBV and HCV are not yet fully understood. A few studies have shown that HCV replication was more robust in HBV/HCV dual infection than in HCV single infection. Other studies have suggested that HBV infection suppressed HCV replication, or that reciprocal inhibition manifested between HBV and HCV infection. Mimms et al. studied patients with acute infections with both viruses and compared them with patients who were monoinfected with HBV. They observed decreased levels of alanine aminotransferases, delayed appearance of HBsAg, and a shorter period of HBsAg in coinfected patients than in monoinfected patients, suggesting that HCV suppresses HBV activity. Vionnet et al. reported a case of late HBV reactivation after direct‐acting antiviral (DAA)‐ based treatment of recurrent hepatitis C in an antibody against hepatitis B core antigen‐positive liver transplant recipient. The Food and Drug Administration issued an alert about the risk of HBV reactivation in patients treated with DAAs. The full data were subsequently published. They referred to 29 cases of HBV reactivation in HCV‐HBV patients after treatment with DAAs. The American Association for the Study of Liver Diseases and the Japan Society of Hepatology guidelines for the management of HCV infection also state that patients with HBV coinfection or who have a history of HBV infection must be carefully monitored for HBV reactivation during HCV treatment. Thus, it is now well known that DAA‐ based treatment for HCV in HCV/HBV coinfected patients reactivates HBV. This case would also be classified as HBV reactivation in the broad sense, although it does not specifically fit the definition. Ison et al. also reported that post‐transplant screening for HIV, HBV, and HCV in patients who have received high‐risk donor organs is not universally available, and testing methods vary. Considering the current situation as also suggested by Kreitman KR, there is a good possibility that the number of brain‐dead livers of drug users will increase in the future, thus there will be more similar cases. As a countermeasure, improvement measures such as testing for HBV (e.g., RNA, cccDNA) in the donor liver at the time of transplantation, frequent HBV testing after transplantation, and extending the HBV follow‐up period based on the case in this paper are necessary. Furthermore, it may be necessary to vaccinate the recipient with HBV vaccine in advance, as we do not know who will