Introduction: Coexistence of metabolic dysfunction-associated liver disease (MASLD) and autoimmune hepatitis (AIH) could lead to more severe disease with poorer outcomes. We aimed to use our prospective AIH registry to assess prevalence and possible impact of MASLD on AIH treatment course and outcome.

Methods: AIH patients in our cohort, confirmed per accepted simplified critieria, were assessed for steatotic liver disease (SLD) in the absence of significant alcohol use. SLD was defined as steatosis either on liver biopsy, imaging, or CAP score >285 dB/m on liver elastography within 1 year of AIH diagnosis. AIH-MASLD overlap was defined by the presence of SLD and one accepted cardiometabolic criteria for MASLD at the time of AIH diagnosis. Continuous variables were summarized using means and standard deviations (SD). Patient demographic and clinical characteristics were collected and compared using students t and chi-squared tests.

Results: AIH-MASLD overlap was present in 25.3% (136/538) of patients at diagnosis. AIH-MASLD were more likely to have diabetes mellitus type 2 (22.8% vs 8.2%), hypertension (41.2% vs 17.6%), elevated triglycerides (22.8% vs 5.5%), low HDL (10.3% vs 3.5%), and obesity (66.9% vs 17.4%) compared to patients with AIH alone (p<=0.002) (Table 1). The proportion of PNPLA3 GG or CG genotype (rs738409) was no different in AIH-MASLD compared to AIH alone (30.9% vs 41.9%, p=0.19). AIH-MASLD were older (50.4 yrs (SD 14) vs 45.1 (18), p<0.001) with higher BMI (35.6 (8.3) vs 28.2 (6.8), p<0.001) compared to AIH alone. Cirrhosis was present at diagnosis in 28.7% of AIH-MASLD and 24.6% AIH alone (p=0.35). No differences were observed between groups according to other demographics or autoantibody profiles. Lab abnormalities at disease onset and after 1 year of treatment were also similar except AIH alone had higher total bilirubin (1 (1.4) vs 0.7 (0.6), p=0.03) at 1 year compared to AIH-MASLD. There was no difference between AIH-MASLD and AIH alone according to transplant-free survival during follow-up (91.2% vs 85.6%, p=0.09).

We also examined AIH patients that had features consistent with steatohepatitis on biopsy (AIH-MASH). 126 (29%) patients with available biopsy (n=430) had both compatible AIH histology and lobular inflammation (90.5%), Mallory bodies (11.9%), or hepatocyte ballooning (31%). Among AIH-MASLD, AIH-MASH was present in 61.2% whereas in AIH alone, 15.6% had AIH-MASH (p<0.001). Despite similar demographics, duration of follow-up, and biochemical remission (data not shown), there was no difference between AIH-MASH and other AIH according to proportion with transplant-free survival (91.3% vs 88.2%, p=0.35).

Conclusion: In this AIH cohort, both AIH-MASLD overlap and AIH-MASH were prevalent (>25%) and enriched in concurrent metabolic disorders but had minimal impact on AIH-related endpoints or liver related outcomes.

Alexander Kusnik

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