自身免疫性肝炎合并非酒精性脂肪性肝病研究进展

摘要/Abstract

摘要： 非酒精性脂肪性肝病(NAFLD)等代谢综合征的发病率近年来不断增长,合并自身免疫性肝炎(AIH)的临床病例报道也日益增多。AIH与NAFLD的诊疗方案大相径庭,但该合并症在流行病学、病因、发病机制、临床特征、诊断及治疗方案均未完全明确,致使二者合并诊疗困难。本文对该合并症的以上方面进行了最新研究进展综述,并提出面临的诊治挑战及应对策略,以期能够为今后提高AIH合并NAFLD的诊断技巧和临床诊疗提供参考借鉴。

关键词: 自身免疫性肝炎, 非酒精性脂肪性肝病, 合并症, 诊断, 治疗

苟悦, 孙鑫, 杨娜, 刘杨, 刘成海. 自身免疫性肝炎合并非酒精性脂肪性肝病研究进展[J]. 肝脏, 2023, 28(12): 1509-1513.

参考文献

[1] Younossi ZM, Marchesini G, Pinto-Cortez H, et al. Epidemiology of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: implications for liver transplantation.Transplantation,2019, 103(1): 22-27.
[2] Matsumoto T, Yamasaki S, Arakawa A, et al. Exposure to a high total dosage of glucocorticoids produces non-alcoholic steatohepatits. Pathol Int, 2007, 57(6): 388-389.
[3] Van Heyningen C. Drug-induced acute autoimmune hepatitis during combination therapy with atorvastatin and ezetimibe. Ann Clin Biochem, 2005, 42(Pt 5): 402-404.
[4] Graziadei IW, Obermoser GE, Sepp NT, et al. Drug-induced lupus-like syndrome associated with severe autoimmune hepatitis. Lupus, 2003, 12(5): 409-412.
[5] Alla V, Abraham J, Siddiqui J, et al. Autoimmune hepatitis triggered by statins. J Clin Gastroenterol, 2006, 40(8): 757-761.
[6] Tan CK, Ho D, Wang LM, et al. Drug-induced autoimmune hepatitis: a minireview. World J Gastroenterol, 2022, 28(24): 2654-2666.
[7] Takahashi A, Abe K, Ohira H. Nonalcoholic steatohepatitis-autoimmune hepatitis overlap. Autoimmune Liver Diseases, 2014: 127-136.
[8] Loria P, Lonardo A, Leonardi F, et al. Non-organ-specific autoantibodies in nonalcoholic fatty liver disease: prevalence and correlates. Dig Dis Sci, 2003, 48(11): 2173-2181.
[9] De Luca-Johnson J, Wangensteen KJ, Hanson J, et al. Natural history of patients presenting with autoimmune hepatitis and coincident nonalcoholic fatty liver disease. Dig Dis Sci, 2016, 61(9): 2710-2720.
[10] Dalekos GN, Gatselis NK, Zachou K, et al. NAFLD and autoimmune hepatitis: do not judge a book by its cover. Eur J Intern Med, 2020, 75: 1-9.
[11] Gaber Y, Abdallah M, Salama A, et al. Metabolic-associated fatty liver disease and autoimmune hepatitis: an overlooked interaction. Expert Rev Gastroenterol Hepatol, 2021, 15(10): 1181-1189.
[12] Takahashi A, Arinaga-Hino T, Ohira H, et al. Non-alcoholic fatty liver disease in patients with autoimmune hepatitis. JGH open, 2018, 2(2): 54-58.
[13] Zachou K, Azariadi K, Lytvtak E, et al. FRI-029-Non-alcoholic fatty liver disease and steatohepatitis in autoimmune hepatitis: important player or innocent bystander? J Hepatol, 2019, 70(1, Supplement): e396-e397.
[14] Chalasani S, Mathur K, Shammas N, et al. Hepatic steatosis is highly prevalent but is not correlated with stiffness in autoimmune hepatitis. Medicine, 2020, 99(42): e22805.
[15] Tsuneyama K, Baba H, Kikuchi K, et al. Autoimmune features in metabolic liver disease: a single-center experience and review of the literature. Clin Rev Allergy Immunol, 2013, 45(1): 143-148.
[16] 曹俊英, 卢君瑶, 白玉盘, 等. 自身免疫性肝病患者合并非酒精性脂肪性肝病的临床及病理特征. 肝脏, 2019, 24(6): 643-645.
[17] 朱敏. 自身免疫性肝炎合并非酒精性脂肪性肝病患者的临床特点及预后分析. 重庆医科大学, 2022.
[18] Gatselis NK, Ntaios G, Makaritsis K, et al. Adiponectin: a key playmaker adipocytokine in non-alcoholic fatty liver disease. Clin Exp Med, 2014, 14(2): 121-131.
[19] Masalkar PD, Abhang SA. Oxidative stress and antioxidant status in patients with alcoholic liver disease. Clin Chim Acta, 2005, 355(1): 61-65.
[20] Tilg H, Adolph TE, Dudek M, et al. Non-alcoholic fatty liver disease: the interplay between metabolism, microbes and immunity. Nat Metab, 2021, 3(12): 1596-1607.
[21] Markle JGM, Frank DN, Mortin-Toth S, et al. Sex differences in the gut microbiome drive hormone-dependent regulation of autoimmunity. Science, 2013, 339(6123): 1084-1088.
[22] Atarashi K, Honda K. Microbiota in autoimmunity and tolerance. Curr Opin Immunol, 2011, 23(6): 761-768.
[23] Lathrop SK, Bloom SM, Rao SM, et al. Peripheral education of the immune system by colonic commensal microbiota. Nature, 2011, 478(7368): 250-254.
[24] Muscate F, Woestemeier A, Gagliani N. Functional heterogeneity of CD4+ T cells in liver inflammation. Semin Immunopathol, 2021, 43(4): 549-561.
[25] Fujisaka S, Usui I, Ikutani M, et al. Adipose tissue hypoxia induces inflammatory M1 polarity of macrophages in an HIF-1α-dependent and HIF-1α-independent manner in obese mice. Diabetologia, 2013, 56(6): 1403-1412.
[26] Smorlesi A, Frontini A, Giordano A, et al. The adipose organ: white-brown adipocyte plasticity and metabolic inflammation. Obes Rev, 2012, 13(Suppl 2): 83-96.
[27] Eslam M, George J. Genetic contributions to NAFLD: leveraging shared genetics to uncover systems biology. Nat Rev Gastroenterol Hepatol, 2020, 17(1): 40-52.
[28] Eslam M, Valenti L, Romeo S. Genetics and epigenetics of NAFLD and NASH: clinical impact. J Hepatol, 2018, 68(2): 268-279.
[29] Mederacke YS, Kirstein MM, Grosshennig A, et al. The PNPLA3 rs738409 GG genotype is associated with poorer prognosis in 239 patients with autoimmune hepatitis. Aliment Pharmacol Ther, 2020, 51(11): 1160-1168.
[30] Hiromasa O. Autoimmune liver diseases: perspectives from Japan. Tkyo: Springer, 2014.
[31] 金沛桦, 施军平. 自身免疫性肝炎患者肝脂肪变的发生率及危险因素. 中国现代医生, 2018, 56(12): 8-11.
[32] Yatsuji S, Hashimoto E, Kaneda H, et al. Diagnosing autoimmune hepatitis in nonalcoholic fatty liver disease: is the International Autoimmune Hepatitis Group scoring system useful?. J Gastroenterol, 2005, 40(12): 1130-1138.
[33] Mcpherson S, Henderson E, Burt AD, et al. Serum immunoglobulin levels predict fibrosis in patients with non-alcoholic fatty liver disease. J Hepatol, 2014, 60(5): 1055-1062.
[34] Inamine T, Schnabl B. Immunoglobulin A and liver diseases. J Gastroenterol, 2018, 53(6): 691-700.
[35] Maleki I, Aminafshari MR, Taghvaei T, et al. Serum immunoglobulin A concentration is a reliable biomarker for liver fibrosis in non-alcoholic fatty liver disease. World Journal of Gastroenterology, 2014, 20(35): 12566-12573.
[36] Cotler SJ, Kanji K, Keshavarzian A, et al. Prevalence and significance of autoantibodies in patients with non-alcoholic steatohepatitis. World J Gastroenterol, 2004, 38(9): 801-804.
[37] Takahashi A, Arinaga-Hino T, Ohira H, et al. Non-alcoholic fatty liver disease in patients with autoimmune hepatitis. JGH open, 2018, 2(2): 54-58.
[38] Taratino G, Carmine F. Pathogenesis of hepatic steatosis:the link between hypercortisolism and non-alcoholic fatty liver disease. World J Gastroenterol, 2013,19(40):6735-6743.
[39] European Association For The Study Of The Liver. EASL Clinical Practice Guidelines: autoimmune hepatitis. J Hepatol, 2015, 63(4): 971-1004.
[40] Weiler-Normann C, Lohse AW. Nonalcoholic fatty liver disease in patients with autoimmune hepatitis: further reason for teeth GNASHing? Dig Dis Sci, 2016, 61(9): 2462-2464.
[41] Mack CL, Adams D, Assis DN, et al. Diagnosis and management of autoimmune hepatitis in adults and children: 2019 Practice Guidance and Guidelines From the American Association for the Study of Liver Diseases. Hepatology, 2020, 72(2): 671-722.
[42] Pape S, Gevers TJG, Belias M, et al. Predniso(lo)ne dosage and chance of remission in patients with autoimmune hepatitis. Clin Gastroenterol Hepatol, 2019, 17(10): 2068-2075.e2.