Long-term outcomes of patients with hepatitis C virus-related liver transplantation in a high-volume transplant center.

BACKGROUND AND

aimHepatitis C virus (HCV) infection remains a major indication for liver transplantation (LT) worldwide despite the availability of highly effective direct-acting antivirals (DAAs). Reinfection of the graft is almost universal in viremic patients at the time of LT; however, long-term real-world data from predominantly living-donor programs in the DAA era are limited. We evaluated long-term patient and graft outcomes, identified predictors of post-transplant HCV recurrence, and assessed the impact of pre- and post-transplant antiviral strategies in a high-volume transplant center.

methodsIn this single-center retrospective cohort study, 98 adults underwent primary LT for HCV-related cirrhosis and/or hepatocellular carcinoma between 2007 and 2022. Demographic, clinical, virological, histological and therapeutic data were obtained from electronic records. Outcomes included overall survival, HCV recurrence-free survival, HCV recurrence, fibrosing cholestatic hepatitis (FCH), graft failure, and sustained virological response (SVR). Predictors of recurrence were examined using univariate and multivariable logistic regression, and predictors of mortality were evaluated using Cox proportional-hazards models. Model discrimination for recurrence was assessed using receiver-operating characteristic (ROC) analysis. An exploratory propensity score-matched analysis assessing pre-transplant DAA exposure was performed and is reported in the Supplementary Appendix due to the very small treated subgroup (n = 8).

resultsThe cohort included 59 women (60.2%) and 39 men; 90.8% received living-donor grafts. Genotype 1b predominated (80.4%). Pre-transplant DAA therapy was administered to 8 patients (8.2%), whereas 78 (85.7%) received no antiviral treatment prior to LT and the remainder received interferon-based regimens. Mean overall survival after LT was 145.0 ± 6.8 months. One-, 3-, 5- and 10-year overall survival rates were 95.7%, 88.3%, 83.5% and 75.0%, respectively; HCV recurrence-free survival rates were 78.7%, 54.3% and 39.6% at 1, 3 and 5 years. HCV recurrence occurred in 49 patients (50.0%) after a mean of 18.3 months. In multivariable logistic regression, pre-transplant HCV RNA positivity (OR 7.9; 95% CI 2.8-22.3; p < 0.001) and absence of pre-transplant DAA therapy (OR 5.4; 95% CI 1.5-20.3; p = 0.009) were independent predictors of recurrence. The recurrence model yielded an AUC of 0.832 with 78.2% sensitivity and 80.5% specificity. Among recurrent cases, 44/49 (89.7%) achieved SVR24; regimen-specific SVR24 was 100% with glecaprevir/pibrentasvir and 96.9% with ledipasvir/sofosbuvir. In multivariable Cox regression, FCH was independently associated with mortality (HR 2.9; 95% CI 1.1-7.8; p = 0.03). Overall survival did not differ significantly between patients with and without recurrence.

conclusionIn this long-term, predominantly living-donor cohort, HCV-related LT provided excellent survival, exceeding 80% at 5 years and 75% at 10 years. Although virological recurrence remained common, the combination of pre-transplant DAA therapy and highly effective post-transplant regimens minimized its clinical consequences, yielding survival comparable to that of non-recurrent patients. Pre-transplant viremia and lack of DAA exposure were powerful predictors of recurrence, whereas FCH was the main determinant of late mortality. Systematic use of DAA therapy before and after LT should be considered standard of care in HCV-infected transplant candidates.