Treatment responses and outcomes in patients with autoimmune hepatitis and concomitant features of non-alcoholic fatty liver disease

Abstract

Background & aims: Non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) affect 17-46% of Western countries, making coexistence with other liver diseases inevitable. We investigated the prevalence and clinical significance of NAFLD/NASH or the components of metabolic syndrome (MetS) in a large multicentric cohort of patients with autoimmune hepatitis (AIH).

Methods: Data from six academic centres (Greece, Canada, Japan, Germany, The Netherlands, and Spain) were evaluated. The presence of NAFLD/NASH in liver biopsy, MetS components, and clinical and laboratory parameters were recorded.

Results: A total of 640 patients (474 females, age 49 [4-87] years; follow-up 78 [1-521] months) were included. NAFLD was present in 146 (22.8%) patients (AIH/non-alcoholic fatty liver [NAFL] 115 [18%], AIH/NASH 31 [4.8%]). AIH/NAFL patients were older (p = 0.017), more frequently overweight or obese (p = 0.002), had hypertension (p = 0.001), and had diabetes (p = 0.016), whereas they less frequently had acute presentation (p = 0.002) and soluble liver antigen/liver pancreas positivity (p <0.05), lower transaminases (p <0.001), ALP (p = 0.028) and IgG (p = 0.004) and higher albumin (p <0.001) than patients with AIH only. Patients with AIH/NASH more frequently had cirrhosis at diagnosis (p = 0.036) and higher IgG (p = 0.009). Response to treatment did not differ between groups. Patients with cirrhosis with AIH/NAFL had higher frequency of decompensation compared with patients with AIH only (p <0.05). Patients with type 2 diabetes mellitus and dyslipidaemia had increased hazard of disease progression (p <0.05 for each).

Conclusions: The prevalence of NAFLD in AIH is similar to the general population. Concurrence of NASH in patients with AIH signifies a more severe disease, whereas that of NAFL may indicate a worse prognosis in patients with cirrhosis. T2DM and dyslipidaemia in AIH patients are associated with dismal parameters of outcome. Our findings suggest that NAFLD presence or even components of MetS in patients with AIH may affect prognosis, so closer follow-up of such patients is warranted.

Impact and implications: Non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) affect many people, making coexistence with other liver diseases inevitable. We investigated the prevalence and clinical significance of NAFLD/NASH or the components of metabolic syndrome (MetS) in patients with autoimmune hepatitis (AIH). NAFLD and NASH presence in patients with AIH is as frequent as in the general population. The concurrence of NASH in patients with AIH seems to signify a more severe disease, whereas that of non-alcoholic fatty liver may indicate a worse prognosis in a specific subgroup of patients who already have cirrhosis at diagnosis. Diabetes or dyslipidaemia in patients with AIH were associated with worse prognosis. Therefore, it seems that closer follow-up of patients with concurrent AIH and NAFLD or AIH and components of MetS is needed.

Keywords: Autoimmune hepatitis; Metabolic dysfunction-associated fatty liver disease; Non-alcoholic fatty liver disease; Non-alcoholic steatohepatitis.

Graphical abstract

Fig. 1

Frequency (%) of autoimmune hepatitis (AIH) only and AIH with non-alcoholic fatty liver disease (AIH/NAFLD) according to nationality.

Fig. 2

Differences between AIH patients according to the NAFL, NASH or Mets status. (A) Patients with AIH/NAFL more frequently were overweight or obese and had T2DM compared with patients with AIH but without NAFL (p = 0.002 and p = 0.016, respectively; Χ² test with Yates’ correction). In addition, patients with AIH/NAFL with cirrhosis at baseline decompensated more frequently compared with patients with AIH and cirrhosis but without NAFL (p = 0.003; Χ² test with Yates’ correction). (B) Patients with AIH/NASH more frequently were overweight or obese, and had T2DM and cirrhosis at diagnosis compared with AIH patients without NASH (p = 0.041, p = 0.003, and p = 0.036, respectively; Χ² test with Yates’ correction). (C) Patients with AIH/MetS more frequently were overweight or obese and had T2DM compared with patients with AIH but without MetS (p <0.001 for each; Χ² test with Yates’ correction). In addition, patients with AIH/MetS with cirrhosis at baseline decompensated more frequently compared with patients with AIH and cirrhosis but without MetS (p = 0.027; Χ² test with Yates’ correction). (D) Patients with AIH with dyslipidaemia more frequently were overweight or obese, had T2DM, developed cirrhosis more frequently during follow-up, and underwent OLT more frequently compared with patients with AIH without dyslipidaemia (p = 0.046, p <0.001, p <0.001 and p <0.001, respectively; Χ² test with Yates’ correction). AIH, autoimmune hepatitis; MetS, metabolic syndrome; NAFL, non-alcoholic fatty liver; NASH, non-alcoholic steatohepatitis; OLT, orthotopic liver transplantation; T2DM: type 2 diabetes mellitus.

Fig. 3

Cox regression analysis regarding overall autoimmune hepatitis progression. Patients with type 2 diabetes mellitus (T2DM) had an increased hazard ratio of disease progression compared with patients without T2DM (p = 0.013).

Fig. 4

Cox regression analysis regarding overall autoimmune hepatitis progression. Patients with dyslipidaemia had an increased hazard ratio of disease progression compared with patients without dyslipidaemia (p = 0.003).