Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA.
Venebio Corporation, Richmond, VA.
Hepatology. 2018 Feb;67(2):534-548. doi: 10.1002/hep.29359. Epub 2017 Dec 23.
The histologic spectrum of nonalcoholic fatty liver disease (NAFLD) includes fatty liver (NAFL) and steatohepatitis (NASH), which can progress to cirrhosis in up to 20% of NASH patients. Bile acids (BA) are linked to the pathogenesis and therapy of NASH. We (1) characterized the plasma BA profile in biopsy-proven NAFL and NASH and compared to controls and (2) related the plasma BA profile to liver histologic features, disease activity, and fibrosis. Liquid chromatography/mass spectrometry quantified BAs. Descriptive statistics, paired and multiple group comparisons, and regression analyses were performed. Of 86 patients (24 controls, 25 NAFL, and 37 NASH; mean age 51.8 years and body mass index 31.9 kg/m ), 66% were women. Increased total primary BAs and decreased secondary BAs (both P < 0.05) characterized NASH. Total conjugated primary BAs were significantly higher in NASH versus NAFL (P = 0.047) and versus controls (P < 0.0001). NASH had higher conjugated to unconjugated chenodeoxycholate (P = 0.04), cholate (P = 0.0004), and total primary BAs (P < 0.0001). The total cholate to chenodeoxycholate ratio was significantly higher in NAFLD without (P = 0.005) and with (P = 0.02) diabetes. Increased key BAs were associated with higher grades of steatosis (taurocholate), lobular (glycocholate) and portal inflammation (taurolithocholate), and hepatocyte ballooning (taurocholate). Conjugated cholate and taurocholate directly and secondary to primary BA ratio inversely correlated to NAFLD activity score. A higher ratio of total secondary to primary BA decreased (odds ratio, 0.57; P = 0.004) and higher conjugated cholate increased the likelihood of significant fibrosis (F≥2) (P = 0.007). Conclusion: NAFLD is associated with significantly altered circulating BA composition, likely unaffected by type 2 diabetes, and correlated with histological features of NASH; these observations provide the foundation for future hypothesis-driven studies of specific effects of BAs on specific aspects of NASH. (Hepatology 2018;67:534-548).
非酒精性脂肪性肝病 (NAFLD) 的组织学谱包括脂肪肝 (NAFL) 和脂肪性肝炎 (NASH)，其中多达 20%的 NASH 患者会进展为肝硬化。胆汁酸 (BA) 与 NASH 的发病机制和治疗有关。我们 (1) 描述了经活检证实的 NAFL 和 NASH 患者的血浆 BA 谱，并与对照组进行了比较，以及 (2) 将血浆 BA 谱与肝组织学特征、疾病活动度和纤维化相关联。采用液相色谱/质谱法对 BA 进行定量分析。采用描述性统计、配对和多组比较以及回归分析。86 例患者（24 例对照组，25 例 NAFL，37 例 NASH；平均年龄 51.8 岁，体重指数 31.9kg/m）中，女性占 66%。NASH 以总初级 BA 增加和次级 BA 减少为特征（均 P<0.05）。NASH 患者的总结合初级 BA 显著高于 NAFL（P=0.047）和对照组（P<0.0001）。NASH 患者的结合胆汁酸与未结合胆汁酸的比值明显高于 NAFL（P=0.04）、对照组（P=0.0004）和总初级 BA（P<0.0001）。总胆酸与鹅脱氧胆酸比值在无（P=0.005）和有（P=0.02）糖尿病的 NAFLD 中显著升高。增加的关键 BA 与更高的脂肪变性（胆酸）、小叶（甘胆酸）和门脉炎症（牛磺胆酸）和肝细胞气球样变（胆酸）等级相关。结合胆酸和牛磺胆酸直接与初级 BA 比值呈负相关，与 NAFLD 活动评分呈负相关。总次级 BA 与初级 BA 的比值升高（比值比，0.57；P=0.004）和结合胆酸升高增加了显著纤维化（F≥2）的可能性（P=0.007）。结论：NAFLD 与循环 BA 组成明显改变有关，可能不受 2 型糖尿病影响，并与 NASH 的组织学特征相关；这些观察结果为未来基于假说的研究提供了基础，以研究 BA 对 NASH 特定方面的具体影响。（《肝脏病学》2018；67：534-548）。
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