A LONG-TERM single-centre study has revealed that cirrhosis after liver transplantation can arise from two distinct pathways, recurrence of the original liver disease or a new, de novo disease in the graft, with recurrence accounting for the large majority of cases.
Liver transplantation is often curative for patients with cirrhosis, yet some recipients go on to develop cirrhosis after liver transplantation. Researchers hypothesised that this could stem from either recurrence of the primary liver disease that originally caused cirrhosis, or from a different, de novo aetiology emerging in the transplanted graft, a distinction that has remained poorly characterised over long-term follow-up.
Researchers examined consecutive adult patients who underwent liver transplantation for cirrhosis at their institution between January 1987 and December 2023. Patients transplanted for indications other than cirrhosis, including acute liver failure, and those with active hepatitis C at transplantation, were excluded from the primary analysis. Cirrhosis after transplant was defined histologically or by clinical complications of portal hypertension. Propensity score matching and Kaplan-Meier analysis assessed mortality risk between recipients with and without post-transplant cirrhosis.
Of 937 patients included, 107 (11.4%) developed cirrhosis after liver transplantation, at a median 7.8 years (interquartile range, 8.3) post-transplant. Recurrence of the original disease accounted for 89 of 107 cases (83.2%), most commonly autoimmune hepatitis (16/55, 29.1%) and primary biliary cholangitis (11/52, 21.2%).
De novo cirrhosis, arising from a different aetiology than the original disease, occurred in 18 of 937 patients overall (1.9%), representing 16.8% (18/107) of post-transplant cirrhosis cases, driven mainly by chronic rejection (9/18) and metabolic dysfunction-associated steatohepatitis (4/18).
Twenty-year survival was significantly lower in patients with cirrhosis after transplant than in those without (50.6% versus 70.7%; hazard ratio, 1.77; 95% CI, 1.09 to 2.88; p<0.05).
These findings have shown that recurrence of the primary liver disease, rather than de novo disease, is the dominant driver of cirrhosis after liver transplantation, with recurrence risk highest in patients transplanted for autoimmune hepatitis or primary biliary cholangitis. The authors have suggested that disease-permissive factors present before transplantation may persist and drive graft injury in these patients. Distinguishing recurrent from de novo cirrhosis could help clinicians tailor post-transplant surveillance according to a patient’s original diagnosis.
Reference
Rao AK et al. Recurrent and de novo cirrhosis after liver transplantation. Portal Hypertension & Cirrhosis. 2026;5:207-13.
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