Introduction: Autoimmune hepatitis (AIH) is a chronic liver disease that affects both men and women, with about 30% of AIH cases occurring in individuals over 60 years old. Metabolic syndrome, a group of metabolic abnormalities including central obesity, type 2 diabetes (T2DM), hypertension (HT), and dyslipidemia, promotes the development of metabolic-associated fatty liver disease (MAFLD). Managing liver cirrhosis in AIH patients presents a significant challenge for clinicians. However, it remains unclear whether metabolic-associated diseases (MADs) increase the risk of liver cirrhosis in AIH patients compared to those with AIH alone. Recently, a cross-sectional study led by Professor Wang Hui's team from Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, published in Hepatology International, explored the impact of MADs on AIH patients. The study identified MADs, particularly diabetes (DM) and/or MAFLD, as significant risk factors for liver fibrosis in AIH patients.Study Overview: The study analyzed the clinical characteristics of 283 AIH patients who underwent liver biopsies at Ruijin Hospital between January 2016 and February 2022.
Prevalence of MADs in AIH Patients
The prevalence of MADs among AIH patients was high (87.3%), with most patients having multiple MADs. The prevalence of obesity, DM, HT, and dyslipidemia was 25.8%, 23.7%, 50.9%, and 51.7%, respectively. Notably, the proportion of patients with DM was significantly higher in those with severe liver fibrosis compared to those with mild or moderate fibrosis (31.1% vs. 18.0%, P < 0.05). Furthermore, the prevalence of MADs was significantly higher in the group with severe inflammation than in the mild or moderate inflammation group, with MADs being 1.2 times more prevalent in the severe inflammation group (90.7% vs. 75%, P < 0.05).
Comparison of AIH Patients With and Without MAFLD
Using the FLIP algorithm, 84.8%, 13.4%, and 1.8% of AIH patients were classified as having no MAFLD, NAFL, and NASH, respectively. The prevalence of MAFLD confirmed via liver biopsy or ultrasound/CT was 23.0%.
1. Clinical Characteristics of AIH Patients with MAFLD Compared to AIH patients without MAFLD, those with MAFLD had significantly higher average age and BMI (P < 0.05). Specifically, the proportion of MAFLD patients aged 60-69 was significantly higher. Additionally, the percentage of MAFLD patients with a BMI ≥ 25 was notably higher. The proportion of patients with severe fibrosis was also significantly higher in the MAFLD group.
2. Correlation Between MAFLD and MADs Compared to AIH patients without MAFLD, those with MAFLD had a higher proportion of MADs (93.1% vs. 85.6%, P < 0.01). Moreover, there was a positive correlation between MAFLD and the increased frequency of obesity and DM in AIH patients. However, no significant differences were observed between AIH patients with or without MAFLD in other laboratory findings, such as ALT, AST, γ-GT, Cr, ANA positivity, and IgG levels.
Factors Associated with Liver Fibrosis and Inflammation Severity
Through Spearman correlation analysis, the researchers investigated the potential relationship between MADs or MAFLD and the severity of fibrosis or inflammation in AIH patients, as well as other clinical factors. The results indicated that liver inflammation was significantly correlated with male sex, age, ALT, AST, TB, Alb, BA, Cr, TC, LDL, WBC, platelets, PT, AFP, ANA positivity, IgG levels, MADs, DM, and the number of MADs. Additionally, the severity of liver fibrosis was significantly correlated with age, AKP, γ-GT, TB, BA, platelets, PT, AFP, ANA positivity, IgG levels, DM, HT, and MAFLD.
Risk Factors for Severe Liver Fibrosis or Inflammation
Multivariate analysis identified age, platelet count, IgG levels, and MADs as independent predictors of inflammation severity in AIH patients. Male sex and γ-GT levels were independently associated with severe fibrosis. Furthermore, MADs were identified as an independent predictor of severe liver fibrosis in AIH patients (OR 4.917; P < 0.05), indicating that AIH patients with MADs had at least four times the risk of developing severe fibrosis compared to those without MADs. Further analysis showed that DM was also an independent predictor of severe liver fibrosis in AIH patients (OR 2.445; P < 0.05), suggesting that patients with DM had more than twice the risk of developing severe fibrosis compared to those without DM.
Expert Commentary
The study underscores that MADs are common among AIH patients and serve as independent risk factors for severe fibrosis or inflammation. Notably, DM is also an independent predictor of severe liver fibrosis in AIH patients. Routine evaluation of coexisting MADs, especially DM, is crucial when managing AIH patients.
