Noninvasive approach to indicate risk factors of nonalcoholic steatohepatitis overlapping autoimmune hepatitis based on peripheral lymphocyte pattern

• Published in: Journal of gastroenterology Vol. 58; no. 12; pp. 1237 - 1251
• Main Authors: Kado, Akira, Tsutsumi, Takeya, Yotsuyanagi, Hiroshi, Ikeuchi, Kazuhiko, Okushin, Kazuya, Moriya, Kyoji, Koike, Kazuhiko, Fujishiro, Mitsuhiro
• Format: Journal Article
• Language: English
• Published: Singapore Springer Nature Singapore 01.12.2023; Springer; Springer Nature B.V
• Subjects: Abdominal Surgery; Antinuclear antibodies; Apoptosis; Autoantibodies; Autoimmune diseases; Autoimmunity; B cells; Biliary Tract; Biopsy; CD8 antigen; Cell death; Chronic active hepatitis; Colorectal Surgery; Cytotoxicity; Fatty liver; Flow cytometry; Gastroenterology; Helper cells; Hepatitis; Hepatitis, Autoimmune - complications; Hepatology; Humans; Hyaluronic acid; Immunity; Immunoregulation; Liver; Liver diseases; Lymphocytes; Lymphocytes B; Lymphocytes T; Medical research; Medicine; Medicine & Public Health; Medicine, Experimental; Natural killer cells; Non-alcoholic Fatty Liver Disease - complications; Original Article―Liver; Pancreas; PD-1 protein; Risk Factors; Surgical Oncology; T cells; Peripheral blood mononuclear cells; Flow cytometry; Peripheral lymphocyte frequency; Nonalcoholic steatohepatitis; Autoimmune hepatitis
• DOI: 10.1007/s00535-023-02038-y
• ISSN: 0944-1174; 1435-5922

Background Nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) clinically includes autoimmunity as indicated by antinuclear antibody (ANA) positivity and overlap of autoimmune hepatitis (AIH). Discriminating AIH-overlap NASH from NAFLD/NASH is required for proper treatment, and typically involves pathological diagnosis by invasive liver biopsy. Differential patterns of peripheral lymphocytes in NAFLD and AIH were assessed to noninvasively indicate risk factors of AIH-overlap NASH by flow cytometry (FCM). Methods We assessed the differential frequencies of peripheral lymphocytes in 115 patients: 70 NASH (ANA negative:positive:AIH-overlap = 36:20:14), 18 NAFL, and 27 AIH (acute:chronic = 12:15) patients diagnosed by FCM. We focused on the following populations of lymphocytes: T cells, B cells, natural killer (NK) cells, NKT cells, helper T cell (Th) subsets (Th1, Th2, and Th17), and regulatory T cells; we also examined programmed cell death (PD) 1 and cytotoxic T-lymphocyte antigen levels. Results Several significant differences in laboratory parameters and peripheral lymphocyte frequencies were found among the NAFLD and AIH subgroups. In univariate and multivariate analyses, hyaluronic acid level, liver stiffness, and the frequencies of Th17 and CD8 + PD1 + T cells were independent risk factors of NASH in NAFLD. Regarding overlap of AIH, only the frequency of CD8 + PD1 + T cells (odds ratio, 0.01; 95% CI 0.00–38.9, p  = 0.004) was an independent risk factor in NASH and significantly decreased in AIH. Conclusions The decreased frequency of peripheral CD8 + PD1 + T cells is an independent risk factor of NASH overlapping with AIH in the present cohort. Our findings will facilitate development of a new noninvasive FCM method for indicating risk factors of NASH, including autoimmunity.