Increased Liver-Related Morbidity in Autoimmune Hepatitis-Primary Sclerosing Cholangitis Variant Syndrome: A Propensity-Matched Multicenter Cohort Study.

BACKGROUND AND AIMS: Autoimmune hepatitis-primary sclerosing cholangitis (AIH-PSC) variant syndrome is characterized by concurrent hepatitic and cholestatic liver injury, yet data on long-term outcomes relative to both component diseases remain limited.

METHODS

Using the TriNetX Research Network, we performed 2 separate 1:1 propensity score-matched (PSM) analyses comparing AIH-PSC to AIH alone and to PSC alone, matching on demographics, comorbidities, and baseline laboratory values. A 180-day landmark was applied. Primary outcomes included cirrhosis, hepatocellular carcinoma, liver transplantation, all-cause hospitalization, and long-term steroid use. Cholangiocarcinoma (CCA) was analyzed separately using multivariable Cox regression. Hazard ratios (HRs) served as the primary effect measure.

RESULTS

After matching, 985 patients per cohort were included in the AIH comparison and 961 per cohort in the PSC comparison. Compared with AIH alone, AIH-PSC had significantly higher hazards of cirrhosis (HR: 3.138), hepatocellular carcinoma (HR: 2.360), liver transplantation (HR: 4.351), and long-term steroid use (HR: 1.690; all P ≤ .012). Compared with PSC alone, AIH-PSC carried higher hazards of cirrhosis (HR: 2.361), liver transplantation (HR: 1.400), and long-term steroid use (HR: 2.283; all P ≤ .048). Hospitalization did not differ in either comparison. AIH-PSC was the strongest independent predictor of CCA vs AIH (adjusted HR: 14.546), yet CCA rates were nearly identical between AIH-PSC and PSC (3.6% vs 3.4%; P = .457), indicating CCA risk is attributable to the PSC component.

CONCLUSION

AIH-PSC variant syndrome confers additive liver-related morbidity exceeding either component disease, with significantly higher risks of cirrhosis, hepatobiliary malignancy, liver transplantation, and steroid dependence. CCA risk is driven by the PSC component. These findings support intensified surveillance and early transplant evaluation in this population.