Review identifies factors tied to PSC recurrence after liver transplant

Various factors, including male sex and younger age, were associated with an increased risk of primary sclerosing cholangitis (PSC) recurrence after liver transplant, according to a review study.

Rates of post-transplant recurrence varied by geographic region, but the overall rate of nearly 19% is in line with other recent estimates.

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June 23, 2026 News by Margarida Maia, PhD

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“These findings provide valuable insights that may inform clinical practice and contribute to guideline development in the management of PSC,” the researchers wrote. “However, further high-quality, multicentre studies are needed to strengthen the evidence base and support more definitive recommendations for clinical decision-making.”

The study, “Primary Sclerosing Cholangitis Recurrence After Liver Transplantation: A Systematic Review and Updated Meta-Analysis,” was published in Liver International.

In PSC, the immune system mistakenly attacks healthy cells in and around the bile ducts, which are responsible for carrying the digestive fluid bile from the liver to the small intestine. The ducts become inflamed (cholangitis) and bile flow is impaired (cholestasis), causing bile to build up harmfully in the liver. Ultimately, the organ can become very seriously damaged and fail.

There is currently no treatment that can slow or stop this process. For people with advanced PSC, liver transplant is the only curative treatment. However, it’s estimated that the disease will recur in up to a quarter of patients within the decade after transplant. Knowledge on why this happens and how to prevent it is limited.

Here, a team of researchers in Brazil and the U.K. systematically analyzed studies published up to December 2025 to assess the rates of PSC recurrence after liver transplant and identify factors associated with recurrence.

PSC returned in about 19% of adults after transplant

A total of 29 studies were included in the final meta-analysis. These covered 4,682 adults (63.7% men) with PSC who underwent liver transplant from 1980 to 2024. More than three-quarters of the data came from Europe (51.7%) and North America (29.2%).

Reported rates of post-transplant PSC recurrence varied across studies, but the pooled recurrence rate was 18.66%. In the available data, the highest rate was observed in Oceania, where more than 30% of patients experienced disease recurrence after transplant. In other regions, rates ranged from about 17% to 19%.

The pooled incidence, or rate of new cases, of recurrent PSC was around 26 new cases per 1,000 person-years — a measure that combines the number of patients and their observation time. That’s roughly the same as saying that there would be about two to three new cases of recurrent disease each year for every 100 PSC patients who had a liver transplant.

Among the available regional estimates, the highest incidence was seen in South America, at nearly 40 cases per 1,000 person-years, and the lowest in Europe, at nearly 22 cases per 1,000 person-years.

Geographic differences can be influenced by many things, the researchers noted, including race and ethnicity, healthcare systems, transplant practices, diagnostic approaches, and reporting practices. For example, regions that have adopted advanced imaging techniques in recent years may be better equipped to recognize recurrent PSC and diagnose it.

“Accordingly, the available data do not allow definitive attribution of these geographic differences to specific causes,” the team wrote.

Reported recurrence incidence rose in newer studies

Reported recurrence incidence also increased over time across the included patient cohorts. With each later publication year, the number of new post-transplant PSC recurrence cases increased by 0.7 events per 1,000 person-years.

“This … likely reflects changes in survival, diagnostic sensitivity, disease definitions and post-treatment surveillance across decades,” the researchers wrote. However, additional variability between studies suggests that “recurrence risk is influenced by additional study and population-level factors beyond calendar time.”

Additional statistical analyses showed that younger age at transplant, male sex, and use of the immunosuppressant cyclosporine after transplant were significantly associated with an increased risk of recurrence.

People who developed inflammatory bowel disease (IBD) — an umbrella term for diseases marked by gastrointestinal tract inflammation that commonly co-occur with PSC — after transplant were also at a higher risk of PSC recurrence. The same was seen for patients who experienced acute transplant rejection, when the immune system recognizes the new liver as foreign and attacks it.

The researchers indicated that more work is needed to fully understand how these various factors may be related to an increased recurrence risk. Moreover, certain factors, including immune-related genetic factors, were not accounted for in this study, which limited interpretation of the results. Also, because the included studies only covered adult patients, the findings cannot be generalized to children with PSC.

“Additional large-scale, multicentre studies are needed to generate more robust evidence and support the development of refined clinical approaches and recommendations for managing [PSC recurrence],” the team concluded.