酒精性肝炎的治疗进展

摘要/Abstract

摘要： 我国酒精性肝炎的发病率呈现不断上升趋势。目前,酒精性肝炎的治疗手段主要包括戒酒、营养支持、糖皮质激素及早期肝移植治疗。糖皮质激素治疗重症酒精性肝炎患者具有短期(28 d)生存优势,但对LILLE评分高于0.45的患者,6个月生存率显著降低;同时,尽管早期肝移植对激素无应答的患者有生存获益,但只有较小部分重症酒精性肝炎患者符合早期肝移植的条件。由于药物疗效有限,早期肝移植可及性较低,因此,探索酒精性肝炎治疗新方向及靶点对减轻疾病负担具有重要意义。

关键词: 酒精性肝炎, 治疗, 炎症反应, 细胞因子

孙悦, 孟方圆, 苑广菲, 高沿航. 酒精性肝炎的治疗进展[J]. 肝脏, 2022, 27(8): 849-852.

参考文献

[1] David WC, Ramon B, Naga P, et al.Standard definitions and common data elements for clinical trials in patients with alcoholic hepatitis: Recommendation from the NIAAA alcoholic hepatitis consortia. Gastroenterology,2016,150(4):785-790.
[2] Singal AK,Bataller R,Ahn J, et al. ACG Clinical Guideline: Alcoholic Liver Disease. Am J Gastroenterol, 2018, 113(2):175-194.
[3] Konturek PC, Harsch IA, Konturek K, et al. Gut-liver axis: how do gut bacteria influence the liver? Med Sci (Basel),2018,6(3):79.
[4] Bajaj JS, Idilman R, Mabudian L,et al. Diet affects gut microbiota and modulates hospitalization risk differentially in an international cirrhosis cohort. Hepatology,2018,68:234-247
[5] Vlachogiannakos J, Viazis N, Vasianopoulou P , et al. Long-term administration of rifaximin improves the prognosis of patients with decompensated alcoholic cirrhosis.Gastroenterol Hepatol,2013,28(3):450-455.
[6] Jimenez C ,Ventura M , Sala M, et al. Use of rifaximin in alcoholic hepatitis: Pilot study. J Hepatol, 2018, 68:S816.
[7] Gu Z, Liu Y, Hu S, et al. Probiotics for alleviating alcoholic liver injury. Gastroenterol Res Pract, 2019,2019:1-8.
[8] Philips CA , Pande A , Shasthry SM , et al. Healthy Donor Fecal Microbiota Transplantation in Steroid Ineligible Severe Alcoholic Hepatitis-A Pilot Study.Clin Gastroenterol Hepatol, 2016, 15(4):600.
[9] Bajaj JS, Gavis EA, Fagan A, et al.A randomized clinical trial of fecal microbiota transplant for alcohol use disorder. Hepatology,2021,73:1688-1700.
[10] Singal AK, Shah VH. Current trials and novel therapeutic targets for alcoholic hepatitis .Hepatology,2019,70(2):305-313.
[11] Iracheta-Vellve A, Petrasek J, Gyogyosi B, et al. Interleukin-1 inhibition facilitates recovery from liver injury and promotes regeneration of hepatocytes in alcoholic hepatitis in mice. Liver Int,2017,37(7):968-973.
[12] Szabo G, Mitchell M, McClain CJ,et al. IL-1 receptor antagonist plus pentoxifylline and zinc for severe alcohol-associated hepatitis. Hepatology,2022,5:1-11.
[13] Ambade A, Lowe P , Kodys K, et al. Pharmacological inhibition of CCR2/5 signaling prevents and reverses alcohol-induced liver damage, steatosis, and inflammation in mice. Hepatology, 2019,69(3):1105-1121.
[14] Mandrekar P, Ambade A, Lim A, et al. An essential role for monocyte chemoattractant protein-1 in alcoholic liver injury: regulation of proinflammatory cytokines and hepatic steatosis in mice. Hepatology,2011,54(6):2185-2197.
[15] Lee JS, Mukhopadhyay P , Matyas C, et al. PCSK9 inhibition as a novel therapeu-tic target for alcoholic liver disease. Sci Rep,2019,9(1):17167.
[16] Shi X, Chang CC, Basson MD, et al. Alcohol Disrupts Human Liver Stem/Progenitor Cell Proliferation and Differentiation. Stem Cell Res Ther,2014,4(5):205.
[17] Kong X, Feng D, Mathews S, et al. Hepatoprotective and anti-fibrotic functions of interleukin-22: therapeutic potential for the treatment of alcoholic liver disease.Gastroenterol Hepatol,2013,28 Suppl 1:56-60.
[18] Arab JP, Sehrawat TS, Simonetto DA, et al. An open-label, dose-escalation study to assess the safety and efficacy of IL-22 agonist F-652 in patients with alcohol-associated hepatitis. Hepatology,2020,72:441-453.
[19] Singh V , Sharma AK, Narasimhan RL, et al. Granulocyte colony-stimulating factor in severe alcoholic hepatitis: a randomized pilot study.Am J Gastroenterol,2014,109:1417-1423.
[20] Camilleri M. Bile Acid diarrhea: prevalence, pathogenesis, and therapy.Gut Liver,2015, 9(3):332-339.
[21] Hartmann P , Hochrath K, Horvath A, et al. Modulation of the intestinal bile acid/farnesoid X receptor/fibroblast growth factor 15 axis improves alcoholic liver disease in mice.Hepatology, 2018,67(6):2150-2166.
[22] Harrison SA, Abdelmalek MF, Neff G, et al. Aldafermin in patients with non-alcoholic steatohepatitis (ALPINE 2/3): a randomised, double-blind, placebo-controlled, phase 2b trial. Lancet Gastroenterol Hepatol,2022,7(7):603-616.
[23] Stickel F, Lutz P, Buch S, et al.Genetic variation in HSD17B13 reduces the risk of developing cirrhosisand hepatocellular carcinoma in alcohol misusers. Hepatology,2020,72:88-102.
[24] Wang Y , Lin W , Brown JE , et al. 25-hydroxycholesterol 3-sulfate is an endogenous ligand of DNA methyltransferases in hepatocytes. J Lipid Res, 2021(1):100063.