Arginine Treatment for Alcoholic Hepatitis

描述(由申请人提供)：酒精性肝炎进展为肝硬变，原因是肠道内的内毒素暴露和肝内微循环一氧化氮(NO)缺乏导致肝脏炎症损害。饮食中精氨酸摄入不足会促进细菌移位、内毒素吸收和减少肝脏内NO的生成。饮食中的精氨酸具有细胞保护作用，减少了内毒素的吸收，并会增加肝脏内NO的生成。增加肝内NO的生成将减轻肝脏炎症、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，这三项试验都表明，随着饮食蛋白质和精氨酸摄入量的增加，肝功能和存活率都有所改善。在第一项研究中，添加额外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，而不是71克。在第二项研究中，肠内营养与类固醇治疗酒精性肝炎进行了比较。与接受类固醇治疗的患者相比，肠内营养(1克蛋白质/公斤/天)可提高随访存活率。在S对245名酒精性肝炎患者进行的第三项研究中，88%的患者在6个月内因摄入34克蛋白质而死亡。相比之下，每天摄入大约95克蛋白质的患者中，100%的人在6个月时还活着。膳食蛋白质的增加也增加了膳食精氨酸的摄入量。众所周知，饮食中添加精氨酸可以减少内毒素对肝脏的损害，提供肠道细胞保护，减少细菌易位，改善肠道结构。这项试点项目(R21)将测试额外的蛋白质(每天94克)和额外的精氨酸(每天额外24克或总卡路里的6%)是否可以改善酒精性肝炎患者的肝脏组织学、减少内毒素产生和改善肝功能。

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.