Recurrent and De Novo Cirrhosis After Liver Transplantation

Liver transplantation is often curative for patients with cirrhosis; however, some patients subsequently develop cirrhosis in the transplanted graft, either due to recurrence of the original cause of liver disease or development of a new type of liver disease (de novo). Here, we examined patients who developed recurrent or de novo cirrhosis after undergoing liver transplantation for cirrhosis.

We examined consecutive adult liver transplant patients who underwent liver transplantation for cirrhosis and were followed between January 1, 1987, and December 31, 2023, at our institution. Patients transplanted for indications other than cirrhosis, including acute liver failure, were excluded. Patients with active hepatitis C virus infection at the time of transplantation were excluded from the primary analysis. Cirrhosis after transplant was defined by histology demonstrating bridging fibrosis or the presence of clinical complications of portal hypertension. In the evaluation of mortality risk, propensity score matching was used to compare liver transplant recipients with and without cirrhosis after liver transplant, and survival was assessed using Kaplan-Meier analysis.

In total, 937 unique patients were included; 107 (11.4%) developed cirrhosis subsequent to transplantation with a median (interquartile range) time to cirrhosis of 7.8 (8.3) years after transplant. In total, 89 of 107 (83.2%) patients developed the same liver disease that caused cirrhosis initially and led to transplantation. Autoimmune hepatitis (16/55, 29.1%) and primary biliary cholangitis (11/52, 21.2%) most commonly recurred after liver transplantation. Overall, de novo cirrhosis occurred in 18/937 (1.9%) of all patients, accounting for 16.8% (18/107) of patients who developed cirrhosis, most commonly due to chronic rejection (9/18) or metabolic dysfunction-associated steatohepatitis (4/18). Patients with cirrhosis after transplant had a significantly lower survival rate at 20 years (50.6% vs. 70.7%, hazard ratio: 1.77; 95% confidence interval: 1.09-2.88; log-rank test; p < 0.05) after liver transplantation compared to those without cirrhosis after transplant.

Cirrhosis after transplant is uncommon, but when it occurs, it is most often due to recurrence of the primary liver disease, with the highest recurrence rates observed in patients with autoimmune hepatitis and primary biliary cholangitis. De novo cirrhosis is most commonly associated with chronic rejection or metabolic dysfunction-associated steatohepatitis. Patients developing cirrhosis after transplant have reduced long-term survival.