Trends in Liver Transplantation for Chronic Hepatitis B in the Era of Highly Potent Antiviral Therapies

Abstract

Background: Potent nucleos(t)ide analogs with high barrier to resistance have been available for over a decade . Theoretically, this should lead to a decline in the number of chronic hepatitis B (CHB) patients needing liver transplantation (LT) . This study aims to determine the trend of LT indications over the past two decades in an area endemic for CHB infection . Methods: All patients transplanted up to February 2019 were reviewed . The indications for LT and the primary liver disease etiology were recorded. Patients were stratified into lamivudine (LAM), adefovir (ADV), and entecavir (ETV) eras at the time of transplant based on drug availability at the time (pre-2003, 2003-2005, and 2006 onwards respectively) . Results: A total of 1,411 patients underwent LT, of which 815 (57 .8%) were due to CHB . CHB infection was the etiology in 59 .1%, 67 .2%, and 55.5% of all patients transplanted during the LAM, ADV, and ETV era respectively (p=0.010). Of the 815 CHB patients, 383 (47 .0%), 271 (33 .3%) and 161 (19 .8%) were transplanted for decompensated cirrhosis, hepatocellular carcinoma (HCC), and severe acute flares of CHB (AFCOHB) respectively. In the LAM era, significantly higher proportion of CHB patients were transplanted for decompensated cirrhosis compared to the ADV and ETV era (63.5% vs 56.6% vs 39.7% respectively, p<0.001). In contrast, a significantly higher HBV-related HCC was observed in the ETV era compared to LAM and ADV (39 .3%, 22 .0%, and 22 .5% respectively, p<0 .001) . From year 2000 to 2018, a decline in overall transplantation for CHB has been observed from 76% to 43%, which is mostly contributed by the decline in LT for decompensated cirrhosis during this period from 71% to 22% of HBV patients. This decline has been offset by the increase in LT for HBV-related HCC from 29% of CHB patients un 2000 to 52% in 2018 . Severe AFOCHB remains a stable indication for LT, accounting for 26% of LTst in 2018 (see figure 1). Conclusion: In the era of highly potent antiviral therapies with low resistance risk, LT for decompensated cirrhosis is becoming uncommon, likely due to the fact most cirrhotic patients have already been treated with antivirals . Severe AFOCHB remains an important cause, highlighting the fact that significant proportion of persons in the population may be unknown carriers. Finally, HBV-related HCC has now become the leading indication for LT in an area where CHB remains endemic. [https://doi.org/10.1002/hep.30940]