Autoimmune Features in Metabolic Liver Disease: A Single-Center Experience and Review of the Literature

Abstract

Non-alcoholic steatohepatitis (NASH) is the progressive phenotype of non-alcoholic fatty liver disease associated with the metabolic syndrome. The existence of autoimmune features in NASH has been reported, but its significance remains unclear. We herein report the autoantibody profile of 54 patients with histologically proven NASH and further determined the development of autoimmunity in three different murine NASH models (monosodium glutamate, CDAA (choline-deficient L-amino acid-defined), and TSOD (Tsumura Suzuki, Obese Diabetes)) at 48 weeks of age. Forty-eight percent (26/54) of NASH cases were positive for antinuclear (ANA) or antimitochondrial antibody and manifested histological signs of overlap with autoimmune hepatitis and primary biliary cirrhosis, respectively. These patients were significantly older (60 ± 10 versus 50 ± 16 years), more frequently women (81 % versus 43 %), and with more severe portal inflammatory infiltrate compared with patients without autoimmunity. In one third of mice, regardless of the model, we observed a marked lymphoid infiltrate with non-suppurative cholangitis, and several cases were ANA-positive, but none AMA-positive. Our data suggest that autoimmunity may share some pathogenetic traits with the chronic inflammation of NASH, possibly related to advanced age.

Autoimmune Markers Do Not Impact Clinical Presentation or Natural History of Steatohepatitis-Related Liver Disease

“…[1,2,3-7] Prevalence of these markers in NAFLD patients ranges from 12 to 48%. [1,2,3,7] Data are conflicting on the clinical and pathological importance of these markers in NAFLD patients. While some studies report no difference in the clinical implication of the autoimmune markers [3,7], others report worse outcomes in patients with positive autoimmune markers.…”

“…[1,2,3,7] Data are conflicting on the clinical and pathological importance of these markers in NAFLD patients. While some studies report no difference in the clinical implication of the autoimmune markers [3,7], others report worse outcomes in patients with positive autoimmune markers. [1,5] However, in the presence of high titers of autoimmune markers along with signs suggestive of autoimmune liver disease, AASLD recommends complete work up for autoimmune liver disease with a liver biopsy.…”

Immunopathogenic Mechanisms of Autoimmune Hepatitis: How Much Do We Know from Animal Models?

“…External triggers for a pro-inflammatory milieu in the liver can be manifold, including pathogen infections, drugs, alcohol, and obesity. It has been reported that 26 of 54 patients with NASH also carried ANA or anti-mitochondrial antibodies (AMA) and manifested histological signs of an overlap with AIH or PBC, respectively [53]. In a larger study, it was found that 23% of 225 patients with non-alcoholic fatty liver disease (NAFLD) carried ANA or SMA and the majority (88%) of such autoantibody-positive NAFLD patients fulfilled the diagnostic criteria for AIH [54].…”

Thymic NF-κB-inducing kinase regulates CD4+ T cell-elicited liver injury and fibrosis in mice

“…However, liver self-tolerance is compromised in autoimmune liver diseases, including primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), and autoimmune hepatitis (AIH) (1, 2). Hepatic infiltration by T cells, particularly the CD4 + subpopulation, is reported to be associated with alcoholic liver disease, nonalcoholic steatohepatitis (NASH), and hepatotoxin-induced chronic liver injury in rodents and humans (3–7); however, the underlying mechanism responsible for the breakdown of liver immunological privilege is largely unknown. The contribution of adaptive immunity to liver disease progression is also poorly understood.…”