Mitchell Mack C, Kerr Thomas, Herlong H Franklin
Dr Mitchell is the Nancy S. and Jeremy L. Halbreich Professor of Gastroenterology and vice president of medical affairs at the University of Texas Southwestern Medical Center in Dallas, Texas. Dr Kerr is an associate professor and Dr Herlong is a professor in the Division of Digestive and Liver Diseases at the University of Texas Southwestern Medical Center.
Gastroenterol Hepatol (N Y). 2020 Apr;16(4):178-189.
Excessive alcohol consumption is responsible for approximately 50% of all deaths due to cirrhosis. Although the duration and amount of alcohol consumption are the primary factors responsible for the liver injury caused by consuming alcohol, the pathogenesis of the 3 stages of alcohol-associated liver disease (ALD)-fatty liver, alcoholic hepatitis (AH), and cirrhosis- is likely multifactorial. Preexisting obesity, dysbiosis of the gut microbiome, activation of proinflammatory cytokines, and genetic factors can all contribute to the risk of developing ALD. The cornerstone of therapy for all stages of ALD is abstinence from drinking alcoholic beverages. Severe AH, defined by a Maddrey discriminant function greater than 32, warrants additional therapy. The results of multiple studies evaluating the use of glucocorticoids in the treatment of severe AH led to guidelines from international societies that recommend glucocorticoid therapy in patients with severe AH without active infection. Liver transplantation provides an effective treatment option for patients who fail glucocorticoid therapy. Recent advances in understanding the pathogenesis of AH have led to the investigation of potential therapies directed at preventing the development of steatosis, inhibiting the innate immune response, modifying the gut microbiome, and stimulating liver regeneration.
约50%的肝硬化所致死亡都与过量饮酒有关。虽然饮酒的持续时间和饮酒量是饮酒导致肝损伤的主要因素,但酒精性肝病(ALD)三个阶段——脂肪肝、酒精性肝炎(AH)和肝硬化——的发病机制可能是多因素的。既往肥胖、肠道微生物群失调、促炎细胞因子激活以及遗传因素都可能增加患ALD的风险。ALD各阶段治疗的基石是戒酒。Maddrey判别函数大于32定义的重度AH需要额外治疗。多项评估糖皮质激素治疗重度AH的研究结果促成了国际学会的指南,该指南建议在无活动性感染的重度AH患者中使用糖皮质激素治疗。肝移植为糖皮质激素治疗失败的患者提供了一种有效的治疗选择。最近在理解AH发病机制方面的进展促使人们对旨在预防脂肪变性发展、抑制先天免疫反应、改变肠道微生物群和刺激肝脏再生的潜在疗法进行研究。