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

Kalliopi Zachou; Kalliopi Azariadis; Ellina Lytvyak; Romée J A L M Snijders; Atsushi Takahashi; Nikolaos K Gatselis; Mercedes Robles; Raul J Andrade; Christoph Schramm; Ansgar W Lohse; Atsushi Tanaka; Joost P H Drenth; Aldo J Montano-Loza; George N Dalekos; International Autoimmune Hepatitis Group (IAIHG)

doi:10.1016/j.jhepr.2023.100778

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

JHEP Rep. 2023 Apr 22;5(8):100778. doi: 10.1016/j.jhepr.2023.100778. eCollection 2023 Aug.

Authors

Kalliopi Zachou^{1

2}, Kalliopi Azariadis^{1

2}, Ellina Lytvyak³, Romée J A L M Snijders⁴, Atsushi Takahashi⁵, Nikolaos K Gatselis^{1

2}, Mercedes Robles⁶, Raul J Andrade⁶, Christoph Schramm⁷, Ansgar W Lohse⁷, Atsushi Tanaka⁸, Joost P H Drenth⁴, Aldo J Montano-Loza⁹, George N Dalekos^{1

2}; International Autoimmune Hepatitis Group (IAIHG)

Affiliations

¹ Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa, Greece.
² European Reference Network on Hepatological Diseases (ERN RARE-LIVER), General University Hospital of Larissa, Larissa, Greece.
³ Division of Preventive Medicine, University of Alberta, Edmonton, Alberta, Canada.
⁴ Department of Gastroenterology and Hepatology, European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Radboud UMC, Nijmegen, The Netherlands.
⁵ Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan.
⁶ Unidad De Gestión Clínica De Aparato Digestivo, Servicio De Farmacología Clínica, Hospital Universitario Virgen De La Visctoria, Universidad De Malaga, Malaga, Spain.
⁷ Department of Medicine and Martin Zeitz Centre for Rare Diseases, University Medical Centre Hamburg-Eppendorf, European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany.
⁸ Department of Medicine, Tokyo University, School of Medicine, Itabashi-Ku, Tokyo, Japan.
⁹ Division of Gastroenterology and Liver Unit, University of Alberta, Edmonton, Alberta, Canada.

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.