Background Liver involvement, particularly autoimmune hepatitis (AIH) overlap, is a rare but clinically important manifestation of systemic sclerosis (SSc). This study aimed to assess the prevalence, clinical characteristics, and diagnostic utility of laboratory parameters for identifying AIH in a cohort of patients with SSc. Methods We retrospectively analyzed 111 patients with SSc. Clinical characteristics, autoantibody profiles, and laboratory parameters were compared between patients with and without AIH. AIH diagnosis was confirmed by liver biopsy in all cases. Given the small number of events, Firth’s penalized likelihood logistic regression was applied to identify independent risk factors. The diagnostic performance of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and serum IgG levels was evaluated using receiver operating characteristic (ROC) curve analysis. Prior methotrexate (MTX) exposure was recorded, and the potential confounding effect of MTX-induced liver enzyme elevations was assessed. Results Autoimmune hepatitis (AIH) was identified in 8 of 111 patients (7.2%). All AIH-positive patients showed interface hepatitis on liver biopsy. There were no significant differences between AIH-positive and AIH-negative patients regarding age, systemic sclerosis subtype, or presence of interstitial lung disease (all p > 0.05). Firth’s penalized logistic regression indicated that diffuse cutaneous SSc, anti–Scl-70 positivity, and interstitial lung disease were not independent predictors of AIH overlap. In receiver operating characteristic analysis, alanine aminotransferase (ALT) demonstrated the highest diagnostic performance (AUC 0.88, 95% CI 0.76–0.99; p < 0.001), with a sensitivity of 87.5% and specificity of 85.4% at a cut-off > 34.5 U/L. Aspartate aminotransferase (AST) (AUC 0.86) and serum IgG (AUC 0.74) also showed significant but lower discriminatory ability. ALT retained high specificity for AIH even among patients with prior MTX exposure, supporting its utility as a non-invasive screening tool in SSc. Conclusion Autoimmune hepatitis is a rare overlap syndrome in systemic sclerosis that occurs independently of clinical phenotype. Routine monitoring of liver transaminases, particularly ALT, provides a reliable non-invasive screening tool. Clinicians should consider ALT elevations > 34.5 U/L as a trigger for further AIH evaluation, even in patients with prior MTX exposure.<Table Float="No" ID="Taba"> <tgroup cols="3"> <colspec align="left" colname="c1" colnum="1" /> <colspec align="left" colname="c2" colnum="2" /> <colspec align="left" colname="c3" colnum="3" /> <tbody> <row> <entry nameend="c3" namest="c1"> Key Points • Autoimmune hepatitis (AIH) represents a clinically significant overlap in systemic sclerosis (SSc), with a prevalence of 7.2% in this cohort, indicating that it may be more common than previously reported when systematic screening is implemented. Biochemical screening rather than biopsy-only evaluation improves detection. • The development of AIH in SSc patients appears to be independent of disease subtype (limited vs. diffuse), specific autoantibody profiles (Anti-Scl70, ACA), or major organ involvement, such as interstitial lung disease. • An ALT threshold of > 34.5 U/L provides a practical “red flag” for clinicians, offering high sensitivity and specificity to prompt further diagnostic evaluation, including liver-specific autoantibody testing and liver biopsy when indicated. This threshold should be interpreted cautiously in patients with prior methotrexate (MTX) exposure, as mild ALT elevations may also reflect drug-related hepatotoxicity. • An ALT threshold of > 34.5 U/L provides a practical “red flag” for clinicians, offering high sensitivity and specificity to prompt further diagnostic evaluation, including liver-specific autoantibody testing and liver biopsy when indicated. • Because AIH can develop across the full spectrum of SSc regardless of systemic disease severity, routine monitoring of transaminases is essential for early detection and timely initiation of immunosuppressive therapy. </entry> </row> </tbody> </tgroup> </Table>

Prevalence, clinical features, and laboratory predictors of autoimmune hepatitis in systemic sclerosis: A retrospective single-center cohort study

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2026年3月6日

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Zeynel Abidin Akar,
Dilan Yildirim

摘要

Background

Liver involvement, particularly autoimmune hepatitis (AIH) overlap, is a rare but clinically important manifestation of systemic sclerosis (SSc). This study aimed to assess the prevalence, clinical characteristics, and diagnostic utility of laboratory parameters for identifying AIH in a cohort of patients with SSc.

Methods

We retrospectively analyzed 111 patients with SSc. Clinical characteristics, autoantibody profiles, and laboratory parameters were compared between patients with and without AIH. AIH diagnosis was confirmed by liver biopsy in all cases. Given the small number of events, Firth’s penalized likelihood logistic regression was applied to identify independent risk factors. The diagnostic performance of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and serum IgG levels was evaluated using receiver operating characteristic (ROC) curve analysis. Prior methotrexate (MTX) exposure was recorded, and the potential confounding effect of MTX-induced liver enzyme elevations was assessed.

Results

Autoimmune hepatitis (AIH) was identified in 8 of 111 patients (7.2%). All AIH-positive patients showed interface hepatitis on liver biopsy. There were no significant differences between AIH-positive and AIH-negative patients regarding age, systemic sclerosis subtype, or presence of interstitial lung disease (all p > 0.05). Firth’s penalized logistic regression indicated that diffuse cutaneous SSc, anti–Scl-70 positivity, and interstitial lung disease were not independent predictors of AIH overlap. In receiver operating characteristic analysis, alanine aminotransferase (ALT) demonstrated the highest diagnostic performance (AUC 0.88, 95% CI 0.76–0.99; p < 0.001), with a sensitivity of 87.5% and specificity of 85.4% at a cut-off > 34.5 U/L. Aspartate aminotransferase (AST) (AUC 0.86) and serum IgG (AUC 0.74) also showed significant but lower discriminatory ability. ALT retained high specificity for AIH even among patients with prior MTX exposure, supporting its utility as a non-invasive screening tool in SSc.

Conclusion

Autoimmune hepatitis is a rare overlap syndrome in systemic sclerosis that occurs independently of clinical phenotype. Routine monitoring of liver transaminases, particularly ALT, provides a reliable non-invasive screening tool. Clinicians should consider ALT elevations > 34.5 U/L as a trigger for further AIH evaluation, even in patients with prior MTX exposure.

Key Points

• Autoimmune hepatitis (AIH) represents a clinically significant overlap in systemic sclerosis (SSc), with a prevalence of 7.2% in this cohort, indicating that it may be more common than previously reported when systematic screening is implemented. Biochemical screening rather than biopsy-only evaluation improves detection.

• The development of AIH in SSc patients appears to be independent of disease subtype (limited vs. diffuse), specific autoantibody profiles (Anti-Scl70, ACA), or major organ involvement, such as interstitial lung disease.

• An ALT threshold of > 34.5 U/L provides a practical “red flag” for clinicians, offering high sensitivity and specificity to prompt further diagnostic evaluation, including liver-specific autoantibody testing and liver biopsy when indicated. This threshold should be interpreted cautiously in patients with prior methotrexate (MTX) exposure, as mild ALT elevations may also reflect drug-related hepatotoxicity.

• Because AIH can develop across the full spectrum of SSc regardless of systemic disease severity, routine monitoring of transaminases is essential for early detection and timely initiation of immunosuppressive therapy.