Arginine Treatment for Alcoholic Hepatitis

描述（由申请方提供）：由于肠道内毒素暴露和肝内微循环一氧化氮（NO）缺乏导致肝脏炎症性损伤，酒精性肝炎进展为肝硬化。精氨酸摄入不足会促进细菌移位、内毒素吸收和肝内NO生成减少。饮食精氨酸是细胞保护，减少内毒素吸收，并将增加肝内NO的产生。增加肝内NO的生成可减轻肝脏炎症、肝内血管阻力和肝纤维化。支持额外精氨酸作用的证据来自三项临床试验，这些试验都证明了随着膳食蛋白质和精氨酸摄入量的增加，肝功能和生存率得到改善。在第一项研究中，补充精氨酸和支链氨基酸的肠内营养增加了活动性肝病患者的死亡率。对照组的患者每天摄入44克蛋白质，而对照组的患者每天摄入71克蛋白质。在第二项研究中，将肠内营养与类固醇治疗酒精性肝炎进行了比较。肠内营养（1克蛋白质/公斤/天）改善后续生存相比，类固醇治疗的患者。在第三项对245名酒精性肝炎患者的研究中，88%的患者在6个月内死亡，他们的蛋白质摄入量<34克。相比之下，每天摄入约95克蛋白质的患者在6个月时100%存活。增加膳食蛋白质也增加了膳食精氨酸的摄入量。已知饮食中额外的精氨酸可减少肝脏的内毒素损伤，提供肠道细胞保护，减少细菌移位和改善肠道结构。该试点项目（R21）将测试额外的蛋白质（每天94克与70克）和额外的agrinine（每天额外24克或总热量的6%）是否可以改善酒精性肝炎患者的肝脏组织学，减少内毒素产生并改善肝功能。

DESCRIPTION (provided by applicant): Alcoholic hepatitis progresses to cirrhosis due to inflammatory damage of the liver that occurs as a result of intestinal endotoxin exposure and intrahepatic microcirculatory nitric oxide (NO) deficiency. Insufficient dietary arginine intake promotes bacterial translocation, endotoxin absorption and reduced intrahepatic NO generation. Dietary arginine is cytoprotective, reduces endotoxin absorption and will increase intrahepatic NO generation. Increase intrahepatic NO generation will reduce liver inflammation, intrahepatic vascular resistance and fibrosis. Evidence to support the role of additional arginine comes from three clinical trials that have both demonstrated improved liver function and survival with increased dietary protein and arginine intake. In the first study, enteral nutrition with additional arginine and BCAA added improved mortality in patients with active liver disease. The patients in the control arm consumed 44 vs. 71 grams of protein per day. In a second study, enteral nutrition was compared to steroid therapy for alcoholic hepatitis. Enteral nutrition (1 gm of protein/kg/day) improves follow-up survival compared to steroid treated patients. In a s third study of 245 patients with alcoholic hepatitis, 88% died at 6-months who had <34 grams of protein intake. In contrast, 100% of the patients who ingested approximately 95 grams of protein per day were alive at 6-months. The increased dietary protein also increased the dietary arginine intake. Additional arginine in the diet is known to reduce endotoxin damage of the liver, provide intestinal cytoprotection, reduced bacterial translocation and improved intestinal structure. This pilot project (R21) will test if additional protein (94 vs. 70 grams per day) and additional agrinine (24 additional grams per day or 6% of total calories) can improve liver histology, reduce endotoxin production and improve liver function in patients with alcoholic hepatitis.