Liver enzyme levels help diagnose autoimmune hepatitis in SSc: Study

Clinical overlap frequently asymptomatic in early stages, creating challenges
Written by Andrea Lobo, PhD | April 14, 2026

Some people with systemic sclerosis (SSc) have autoimmune hepatitis (AIH), a condition marked by liver inflammation caused by self-reactive antibodies, a study in Turkey shows.

The study also identified the blood levels of the liver enzyme alanine aminotransferase (ALT) as the most accurate predictor of AIH.

“Our findings highlight the critical role of routine biochemical monitoring, with ALT emerging as a highly effective [noninvasive] screening tool to guide clinical decision-making,” researchers wrote.

The study, “Prevalence, clinical features, and laboratory predictors of autoimmune hepatitis in systemic sclerosis: A retrospective single-center cohort study,” was published in Clinical Rheumatology.

Number of reported cases of AIH in people with SSc is low
SSc is an autoimmune disease characterized by the buildup of a protein called collagen, the main component of scar tissue. Liver involvement, particularly AIH, may also be seen in people with SSc.

However, the low number of reported cases of AIH in people with SSc and the fact that this clinical overlap is frequently asymptomatic in early stages represent significant challenges for diagnosis and timely treatment.

To learn more, researchers analyzed the medical records of 111 individuals with SSc followed at a specialized center in Turkey between 2015 and 2025. Participants had a mean age of 52.4 years, a median SSc duration of seven years, and were mostly women (88.3%). Regarding disease types, two-thirds of participants had limited cutaneous SSc, while one-third had diffuse SSc.

Most participants had self-reactive antinuclear antibodies, which target proteins in the cell nucleus (97.1%); interstitial lung disease, diseases that cause inflammation and scarring in the lungs (61.3%); and Raynaud’s phenomenon, when fingers and toes are numb and frigid in response to cold temperatures or stress (95.5%).

Overall, eight participants (7.2%) had AIH, diagnosed at a mean age of 46.5 years. There were no significant differences for age, sex, disease duration, interstitial lung disease, or type of self-reactive antibodies between patients with and without AIH.

Among people with AIH, laboratory tests revealed elevated blood levels of liver enzymes, a potential sign of liver damage, and immunoglobulins (antibodies). Liver biopsy indicated inflammation in all patients with AIH, infiltration of immune cells (75% of patients), and structural reorganization of liver cells (37.5%). One patient had permanent liver scarring, or cirrhosis.
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Further analysis indicated that AIH was not significantly associated with patients’ age, sex, or clinical characteristics.

​Enzyme showed strong accuracy in diagnosing AIH in SSC patients
To assess the accuracy of liver enzymes in diagnosing AIH in SSc patients, the researchers used the area under the curve (AUC) metric. This test assesses how well a measure distinguishes between two groups (in this case, AIH or not). AUC scores range from 0.5 to 1, with higher values indicating greater accuracy.

Both ALT and aspartate aminotransferase (AST) showed high accuracy, with an AUC of 0.88 and 0.86, respectively. Immunoglobulin G, a type of antibody, showed a more moderate diagnostic performance, with an AUC of 0.74.

At an optimal cutoff value of 34.5 U/L, ALT had a sensitivity of 87.5% for detecting AIH and a specificity of 85.4% for ruling it out.

Among all patients, 21 (18.9%) were treated with the immunosuppressant methotrexate, including six with ALT levels higher than 34.5 U/L. None of the AIH-positive patients had been treated with methotrexate.

Further, the positive predictive value of ALT higher than 34.5 U/L in diagnosing AIH was 33.3%, indicating that one-third of SSc patients exceeding this threshold had AIH.

“These findings highlight that while methotrexate-associated liver enzyme elevations must be considered, persistent ALT elevation above the identified threshold warrants evaluation for AIH,” the researchers wrote.

Based on these findings, the researchers proposed “regular ALT assessment for all SSc patients, with elevations above 34.5 U/L prompting consideration of AIH evaluation, including liver-specific autoantibody testing and biopsy when indicated.”
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“While the established diagnostic thresholds in this study provide a practical framework for early detection, further large-scale, prospective, and multi-center studies are required to validate these risk factors, refine ALT [cutoffs], and optimize structured liver monitoring protocols in broader SSc populations,” they added.