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Younger age and use of a certain immunosuppressive agent were more than three times as likely to be associated with higher risk of recurrent autoimmune hepatitis (AIH) after liver transplantation, researchers found.

Among 736 AIH patients who received a liver transplant over a 33-year period, adjusted analyses showed the following factors were associated with a greater risk of recurrent disease:

• Age 42 or younger at transplantation (HR 3.15, 95% CI 1.22-8.16, P=0.02)
• Using mycophenolate mofetil after transplantation (HR 3.06, 95% CI 1.39-6.73, P=0.005)
• Sex mismatch between donor and recipient (HR 2.57, 95% CI 1.39-4.76, P=0.003)
• High IgG levels before transplantation (HR 1.04, 95% CI 1.01-1.06, P=0.004)

In a time-dependent multivariate regression analysis, recurrent AIH was also significantly associated with graft loss (HR 10.79, 95% CI 5.37-21.66, P<0.001) and mortality (HR 2.53, 95% CI 1.48-4.33, P=0.001), reported Aldo Montano-Loza, MD, PhD, of the University of Alberta in Edmonton, Canada, and colleagues in the .

At diagnosis, those with bilirubin levels above 50 μmol/L had a greater risk of graft loss (HR 4.21, 95% CI 2.13-8.34, P<0.001), and bilirubin levels were linked to a greater mortality risk as well (HR 1.003, 95% CI 1.001-1.005, P=0.04).

"We knew that people who get transplanted for autoimmune hepatitis do have recurrences, I don't think we knew some of these risk factors -- like high IgG, liver from a different sex," said Douglas Dieterich, MD, of Mount Sinai Hospital in New York City, who was not involved in this study. "So that's kind of the new 'news', even the bilirubin."

The researchers found that the probability of recurrent AIH increased from 24% at 5 years to 55% at 20 years, with an annual increase in recurrence rate up to 10%. The probability of graft survival was 88% at 5 years, but down to 68% at 20 years.

Recurrent AIH, often occurring after a liver transplant, is a multifaceted liver disease. It is a leading cause of allograft dysfunction and is associated with reduced graft survival, patient survival, and greater need for re-transplantation, the authors noted.

For their study, Montano-Loza and colleagues examined data on 736 AIH patients who received a liver transplant at 33 international centers from 1987 to 2020.

Researchers analyzed clinical data prior to and after transplantation, biochemical data within 12 months of transplantation, in addition to immunosuppression after transplantation. Those at high-risk for recurrent AIH were identified by histological diagnoses, based on .

Main outcomes assessed probability and risk factors related to recurrent AIH, in addition to its effect on patient and graft survival.

Over three-quarters (77%) of patients were women. Mean age was 42. Common transplant indications included decompensated cirrhosis (76%), acute liver failure caused by AIH (19%), and hepatocellular carcinoma (5%). Recurrent AIH was diagnosed in 20% of patients overall, and in 28% of those who had a liver biopsy after liver transplant. After transplant, the average time to AIH recurrence was 2.6 years and median survival was 23 years.

"Regular autoimmune hepatitis patients definitely relapse a lot, depending on their age, when they are younger we can get them off immunosuppressants more than when they are older," Dieterich told 番茄社区app. "You just have to take each individual patient as they go to get them off their immunosuppressive regimen, we catch them pretty early these days because we monitor liver enzymes."

The authors acknowledged several limitations to the data, including its retrospective design. AIH recurrence incidence may have been underestimated since not all patients underwent a liver biopsy to confirm their diagnosis. Time-to-diagnosis may have varied across centers because of inconsistencies in "clinical-driven" versus "protocol-driven" liver biopsies. The frequency of recurrent AIH and annual recurrence rates also varied widely across centers.

For future research, Montano-Loza told 番茄社区app that more studies are needed "to better delineate treatment strategies for patients with an established diagnosis of recurrent AIH."

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