Keshavarzian A, Holmes E W, Patel M, Iber F, Fields J Z, Pethkar S
Department of Medicine (Division of Gastroenterology), Loyola University Medical School, Maywood, Illinois 60153, USA.
Am J Gastroenterol. 1999 Jan;94(1):200-7. doi: 10.1111/j.1572-0241.1999.00797.x.
Only 30% of alcoholics develop cirrhosis, suggesting that the development of alcohol-induced liver injury requires one or more additional factors. Animal studies have shown that gut-derived endotoxin is one such factor. Because increased intestinal permeability has been shown to cause endotoxemia, we hypothesized that increased gastrointestinal permeability contributes to the pathogenesis of alcoholic liver disease. This study aimed to measure gastroduodenal and intestinal permeability in alcoholics with and without chronic liver disease and in nonalcoholic subjects with chronic liver disease.
Gastroduodenal permeability was assessed by measurement of urinary excretion of sucrose after oral administration. Intestinal permeability was assessed by measurement of urinary lactulose and mannitol after oral administration of these sugars.
Alcoholics with no liver disease showed a small but significant increase in sucrose excretion. Alcoholics with chronic liver disease demonstrated a marked and highly significant increase in urinary sucrose excretion relative to the controls, to the alcoholics with no liver disease, and to the nonalcoholics with liver disease. Alcoholics with chronic liver disease demonstrated a marked and highly significant increase in both lactulose absorption and in the urinary lactulose/mannitol ratio (alcoholics 0.703 vs controls 0.019, p = 0.01). In contrast, alcoholics with no liver disease and nonalcoholics with liver disease showed normal lactulose absorption and normal lactulose/mannitol ratio.
Because only the alcoholics with chronic liver disease had increased intestinal permeability, we conclude that a "leaky" gut may be a necessary cofactor for the development of chronic liver injury in heavy drinkers.
仅有30%的酗酒者会发展为肝硬化，这表明酒精性肝损伤的发生需要一个或多个其他因素。动物研究表明，源自肠道的内毒素就是这样一个因素。由于已证实肠道通透性增加会导致内毒素血症，我们推测胃肠道通透性增加有助于酒精性肝病的发病机制。本研究旨在测量患有和未患有慢性肝病的酗酒者以及患有慢性肝病的非酗酒者的胃十二指肠和肠道通透性。
通过口服后测量尿中蔗糖排泄量来评估胃十二指肠通透性。通过口服这些糖类后测量尿中乳果糖和甘露醇排泄量来评估肠道通透性。
无肝病的酗酒者蔗糖排泄量有小幅但显著增加。患有慢性肝病的酗酒者相对于对照组、无肝病的酗酒者以及患有肝病的非酗酒者，尿中蔗糖排泄量有显著且高度显著的增加。患有慢性肝病的酗酒者乳果糖吸收以及尿中乳果糖/甘露醇比值均有显著且高度显著的增加（酗酒者为0.703，对照组为0.019，p = 0.01）。相比之下，无肝病的酗酒者和患有肝病的非酗酒者乳果糖吸收及乳果糖/甘露醇比值均正常。
由于只有患有慢性肝病的酗酒者肠道通透性增加，我们得出结论，“渗漏”的肠道可能是重度饮酒者发生慢性肝损伤的必要辅助因素。
