Ten-Year Outcomes in Liver Transplantation for HBV/HDV Coinfection: A Romanian Single-Center Cohort Study

Background/Objectives: Chronic hepatitis B virus (HBV)/hepatitis D virus (HDV) coinfection is a major cause of cirrhosis and hepatocellular carcinoma (HCC) and remains a disproportionately frequent indication for liver transplantation (LT) in Romania, one of the highest-HDV-prevalence countries in Europe, yet patient-level outcome data from this high-burden Eastern European setting are lacking. We report the ten-year outcomes of LT for HBV/HDV-related cirrhosis in a large single-centre Romanian cohort. Methods: We retrospectively analysed 236 adults transplanted for HBV/HDV-related cirrhosis at a single tertiary centre. Survival was estimated by the Kaplan-Meier method and predictors were assessed by Cox regression. HBV, HDV and HCC recurrence, and anti-HBs kinetics under combined hepatitis B immunoglobulin (HBIG)/nucleos(t)ide-analogue prophylaxis, were analysed. Results: Over a median follow-up of 8.1 years (maximum 14.4), overall survival was 89.8%, 82.8% and 79.5% at 1, 5 and 10 years; among 90-day survivors, conditional survival reached 86.9% at 10 years. Under an “on-demand” low-dose HBIG protocol combined with nucleos(t)ide analogues, HBV recurrence (HBsAg reappearance) occurred in 4.7% and HDV recurrence in 1.7% of patients, without graft dysfunction or death attributable to viral recurrence; anti-HBs titres stabilised at 120–140 IU/L beyond the first year, with approximately 60% of patients maintaining levels above 100 IU/L long-term. HBsAg reappearance occurred exclusively in HCC recipients (11/87 vs. 0/149, p < 0.001) and clustered in patients with tumour recurrence (9/17 vs. 2/70, p < 0.001), preceding the radiological diagnosis of recurrence in six of the nine patients concerned. Mortality was concentrated in the perioperative period (90-day mortality 8.5%), driven mainly by sepsis and surgical complications, and recurrent HCC was the most common recorded cause of late death. Neither the severity of liver disease at listing (MELD, ALBI) nor any viral variable was associated with survival; HCC as indication was associated with survival in univariable analysis and beyond-Milan tumour burden independently (HR 2.74, 95% CI 1.36–5.54). Conclusions: LT for HBV/HDV-related cirrhosis achieves excellent long-term survival and very low viral recurrence under combined prophylaxis, even in this HDV-hyperendemic setting; beyond the perioperative period, viral factors were not associated with survival, whereas beyond-Milan tumour burden was associated with worse survival in one of the sensitivity analyses. In this HBV/HDV cohort, HBsAg reappearance after transplantation for HCC was associated with tumour recurrence and may be regarded as a warning sign prompting oncological reassessment; whether it represents a true early marker requires prospective validation.