Rifaximin-α in alcohol-associated liver disease.
Rifaximin-α in alcohol-associated liver disease.
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利福昔明-α 治疗酒精相关性肝病。
DOI：
10.1016/s2468-1253(23)00033-x
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Singal,AshwaniK
中科院分区：
文献类型：
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作者：
Xie,Chencheng;Singal,AshwaniK
www.496.com我的天使com/gastrohep 2023年6月8日酒精相关性肝病。作者得出结论，利福昔明-α不能逆转肝纤维化，但似乎能有效预防纤维化进展。利福昔明-α在本研究中耐受性良好。5这是第一项显示利福昔明-α在预防肝纤维化进展中的益处的研究。在排除肥胖的饮酒者后，结果保持不变，这是相关的，因为非酒精性脂肪性肝炎（NASH）与酒精相关性肝病具有相同的疾病途径和组织学特征。此外，非酒精性脂肪性肝病小鼠模型的数据显示，利福昔明-α改善了生态失调，并降低了肠道通透性和肝脏炎症。然而，Israelsen及其同事没有研究利福昔明-α对临床结果的益处，证据仍然相互矛盾。在一项对32名酒精相关性肝炎患者进行的随机对照研究中，利福昔明-α在28天或90天内没有改善患者的生存率，也没有改变代谢或炎症。8在另一项对63例酒精相关性肝炎患者进行的多中心、开放标签、比较研究（RIFA-AH）中，21例患者使用利福昔明-α与42例患者使用标准治疗相比，减少了每例患者的感染（每例患者0· 29 vs 0· 62感染; p= 0· 049）和急性和慢性肝衰竭（每例患者0.62 vs 1.26次发作; p= 0.01），患者死亡率在数值上降低（14.2% vs 30.9%; p= 0.15）。9 Israelsen及其同事的研究还有其他局限性，例如纳入了具有广泛纤维化谱（F0-F4）的患者，这妨碍了对无纤维化患者的纤维化消退和肝硬化患者的纤维化进展进行分析;缺乏对细胞周纤维化的评估，这是酒精相关性肝病患者的重要组织学发现;以及与非侵入性血清生物标志物（细菌DNA、细胞因子和脂多糖以及巨噬细胞表型）的机械相关性的缺乏。此外，通过磷脂酰乙醇测量监测的酒精使用，尽管利福昔明和安慰剂组的纤维化进展者和非进展者相似，但仅在基线、1个月和18个月进行，限制了独立于持续酒精使用的利福昔明对纤维化的影响的颗粒评估。尽管存在局限性，但这项研究的结果与临床医生相关，因为酒精相关性肝病是肝硬化的最常见原因，利福昔明-α通常用于肝性脑病。未来需要进行多中心研究，其研究设计克服了本研究的局限性，以检查利福昔明-α在早期酒精相关性肝病患者中的临床相关结局中的获益，这些患者伴有轻微或无纤维化，以评估其在预防肝硬化和晚期纤维化方面的作用。未来的研究还应该检查利福昔明-α在晚期酒精相关性肝纤维化伴肝硬化和酒精相关性肝炎患者中的应用，以评估其对改善肝移植患者生存率和纤维化消退的影响。Israelsen及其同事的这项研究提供了重要的数据，表明利福昔明-α是一种潜在的治疗药物，可以预防酒精相关性肝病患者的纤维化进展。此外，利福昔明-α的可用性和安全性特征可以支持这种药物治疗的设备。
Comment496 www. thelancet. com/gastrohep Vol 8 June 2023 alcohol-associated liver disease. The authors conclude that rifaximin-α did not reverse liver fibrosis but seemed efficacious in preventing fibrosis progression. Rifaximin-α was well tolerated in this study. 5 This is the first study showing benefits of rifaximin-α in preventing progression of hepatic fibrosis. The results remained unchanged after excluding alcohol drinkers with obesity, which is relevant given that non-alcoholic steatohepatitis (NASH) shares disease pathways and histological features with alcohol-associated liver disease. Furthermore, data in mouse models of nonalcoholic fatty liver disease show that rifaximin-α improves dysbiosis, and reduces intestinal permeability and hepatic inflammation. 6, 7 However, Israelsen and colleagues did not examine benefits of rifaximin-α on clinical outcomes, evidence for which remains conflicting. In a randomised controlled study of 32 patients with alcohol-related hepatitis, rifaximin-α did not improve patient survival at 28 days or 90 days, and did not change metabolism or inflammation. 8 In another multicentre, open-label, comparative study (RIFA-AH) in 63 patients with alcoholrelated hepatitis, rifaximin-α use in 21 patients versus standard of care in 42 patients reduced per-patient infections (0· 29 vs 0· 62 infections per patient; p= 0· 049) and acute and chronic liver failure (0· 62 vs 1· 26 episodes per patient; p= 0· 01), with a numerically reduced patient mortality (14· 2% vs30· 9%; p= 0· 15). 9 The study by Israelsen and colleagues had other limitations, such as the inclusion of patients with a broad fibrosis spectrum (F0–F4), which prevented analysis of fibrosis regression in patients with no fibrosis and fibrosis progression in patients with cirrhosis; absence of evaluation of pericellular fibrosis, an important histological finding in patients with alcoholassociated liver disease; and an absence of mechanistic correlation with non-invasive serum biomarkers (bacterial DNA, cytokines, and lipopolysaccharide, and macrophage phenotype). Moreover, alcohol use monitored by phosphatidylethanol measurement, although similar among fibrosis progressors and nonprogressors in rifaximin and placebo groups, was done only at baseline, 1 month, and 18 months, limiting the granular assessment of the effect of rifaximin on fibrosis independent of ongoing alcohol use. Despite limitations, the findings in this study are relevant to clinicians because alcohol-associated liver disease is the most common cause of cirrhosis, a condition in which rifaximin-α is commonly used for hepatic encephalopathy. Future multicentre studies with study designs that overcome the limitations of this study are needed to examine the benefits of rifaximin-α in clinically relevant outcomes in patients with early alcohol-associated liver disease with minimal or no fibrosis to assess its effect in the prevention of cirrhosis and advanced fibrosis. Future studies should also examine the use of rifaximin-α in patients with advanced alcoholassociated liver fibrosis with cirrhosis and alcohol-related hepatitis to assess its impact in improving liver transplantfree patient survival and regression of fibrosis. The study by Israelsen and colleagues provides important data suggesting rifaximin-α as a potential therapeutic to prevent fibrosis progression in patients with alcohol-associated liver disease. Furthermore, the availability and safety profile of rifaximin-α could bolster the armamentarium of pharmacotherapies in this