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Abstract：
OBJECTIVE: Nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NASH) is one of the primary causes of chronic liver disease worldwide. Obeticholic acid (OCA), a potent farnesoid X nuclear receptor activator, has shown promise for treating NASH-related fibrosis due to its anti-fibrotic effects. This study aimed to examine the efficacy of OCA for patients with NASH as well as to investigate its impact on dyslipidemia.
METHODS: A search of databases including PubMed, Embase, and Cochrane Library from January 1, 2010, to November 1, 2022, was conducted to identify systematic reviews of randomized controlled trials involving NASH patients. Inclusion criteria comprised randomized controlled trials that specifically addressed NASH as diagnosed through magnetic resonance imaging, computed tomography, or histology. The results were then categorized, with consideration given to both biochemical and histological outcomes.
RESULTS: Five NASH studies were ultimately selected for further analysis. In terms of biochemical indicators, patients receiving OCA treatment showed improvements in alanine transaminase (mean difference: -19.48, 95% confidence interval [CI]: -24.39 to 14.58; P < .05) and aspartate aminotransferase (mean difference: -9.22, 95% CI: -12.70 to 5.74; P < .05). As for histological improvement, OCA treatment reduced fibrosis (odds ratio [OR]: 1.95, 95% CI: 1.47-2.59; P = .001) and steatosis (OR: 1.95, 95% CI: 1.47-2.59; P = .001). No significant differences were observed regarding adverse events (1.44, 95% CI: 0.57-3.62; P > .001). Regarding dyslipidemia, mean differences between total cholesterol and low-density lipoprotein were found to be high (0.33, 95% CI: 0.01-0.64, P < .05; 0.39, 95% CI: 0.04-0.73, P < .05). In the case of pruritus, OCA achieved a high OR (3.22, 95% CI: 2.22-4.74) compared with placebo.
CONCLUSIONS: OCA also reduced several liver test markers compared to placebo, including the biochemical indicators alanine transaminase, aspartate aminotransferase, alkaline phosphatase, and γ-glutamyl transpeptidase, and improved hepatocellular ballooning, fibrosis, steatosis, and lobular inflammation. Although the incidence of adverse events did not significantly differ between OCA and placebo groups among NASH patients, OCA treatment was found to elevate total cholesterol and low-density lipoprotein levels, and the reported severity of pruritus increased with higher doses of OCA.
METHODS: A search of databases including PubMed, Embase, and Cochrane Library from January 1, 2010, to November 1, 2022, was conducted to identify systematic reviews of randomized controlled trials involving NASH patients. Inclusion criteria comprised randomized controlled trials that specifically addressed NASH as diagnosed through magnetic resonance imaging, computed tomography, or histology. The results were then categorized, with consideration given to both biochemical and histological outcomes.
RESULTS: Five NASH studies were ultimately selected for further analysis. In terms of biochemical indicators, patients receiving OCA treatment showed improvements in alanine transaminase (mean difference: -19.48, 95% confidence interval [CI]: -24.39 to 14.58; P < .05) and aspartate aminotransferase (mean difference: -9.22, 95% CI: -12.70 to 5.74; P < .05). As for histological improvement, OCA treatment reduced fibrosis (odds ratio [OR]: 1.95, 95% CI: 1.47-2.59; P = .001) and steatosis (OR: 1.95, 95% CI: 1.47-2.59; P = .001). No significant differences were observed regarding adverse events (1.44, 95% CI: 0.57-3.62; P > .001). Regarding dyslipidemia, mean differences between total cholesterol and low-density lipoprotein were found to be high (0.33, 95% CI: 0.01-0.64, P < .05; 0.39, 95% CI: 0.04-0.73, P < .05). In the case of pruritus, OCA achieved a high OR (3.22, 95% CI: 2.22-4.74) compared with placebo.
CONCLUSIONS: OCA also reduced several liver test markers compared to placebo, including the biochemical indicators alanine transaminase, aspartate aminotransferase, alkaline phosphatase, and γ-glutamyl transpeptidase, and improved hepatocellular ballooning, fibrosis, steatosis, and lobular inflammation. Although the incidence of adverse events did not significantly differ between OCA and placebo groups among NASH patients, OCA treatment was found to elevate total cholesterol and low-density lipoprotein levels, and the reported severity of pruritus increased with higher doses of OCA.
摘要：
目的：非酒精性脂肪性肝病/非酒精性脂肪性肝炎（NASH）是世界范围内慢性肝病的主要原因之一。奥贝胆酸(OCA),一种有效的法尼醇X核受体激活剂，由于其抗纤维化作用，已显示出治疗NASH相关纤维化的希望。本研究旨在研究OCA对NASH患者的疗效，并探讨其对血脂异常的影响。
方法：搜索数据库，包括PubMed，Embase,和CochraneLibrary从2010年1月1日至2022年11月1日,对涉及NASH患者的随机对照试验进行了系统评价.纳入标准包括随机对照试验，这些试验专门针对通过磁共振成像诊断的NASH，计算机断层扫描,或组织学。然后对结果进行分类，同时考虑生化和组织学结果。
结果：最终选择5项NASH研究进行进一步分析。在生化指标方面，接受OCA治疗的患者显示丙氨酸转氨酶(平均差:-19.48,95%置信区间[CI]:-24.39~14.58;P<.05)和天冬氨酸转氨酶(平均差:-9.22,95%CI:-12.70~5.74;P<.05)改善.至于组织学改善，OCA治疗可减少纤维化（比值比[OR]：1.95，95％CI：1.47-2.59；P=.001）和脂肪变性（OR：1.95，95％CI：1.47-2.59；P=.001）。在不良事件方面没有观察到显著差异(1.44,95%CI:0.57-3.62;P>.001)。关于血脂异常，发现总胆固醇和低密度脂蛋白之间的平均差异很大（0.33，95％CI：0.01-0.64，P<0.05；0.39，95％CI：0.04-0.73，P<0.05）。在瘙痒的情况下，与安慰剂相比，OCA获得了较高的OR（3.22，95％CI：2.22-4.74）。
结论：与安慰剂相比，OCA还降低了几种肝脏测试标志物，包括生化指标丙氨酸转氨酶，天冬氨酸转氨酶,碱性磷酸酶,和γ-谷氨酰转肽酶，和改善肝细胞膨胀，纤维化，脂肪变性,和小叶炎症。尽管在NASH患者中，OCA和安慰剂组的不良事件发生率没有显着差异，发现OCA治疗会升高总胆固醇和低密度脂蛋白水平，报告的瘙痒严重程度随着OCA剂量的增加而增加。
方法：搜索数据库，包括PubMed，Embase,和CochraneLibrary从2010年1月1日至2022年11月1日,对涉及NASH患者的随机对照试验进行了系统评价.纳入标准包括随机对照试验，这些试验专门针对通过磁共振成像诊断的NASH，计算机断层扫描,或组织学。然后对结果进行分类，同时考虑生化和组织学结果。
结果：最终选择5项NASH研究进行进一步分析。在生化指标方面，接受OCA治疗的患者显示丙氨酸转氨酶(平均差:-19.48,95%置信区间[CI]:-24.39~14.58;P<.05)和天冬氨酸转氨酶(平均差:-9.22,95%CI:-12.70~5.74;P<.05)改善.至于组织学改善，OCA治疗可减少纤维化（比值比[OR]：1.95，95％CI：1.47-2.59；P=.001）和脂肪变性（OR：1.95，95％CI：1.47-2.59；P=.001）。在不良事件方面没有观察到显著差异(1.44,95%CI:0.57-3.62;P>.001)。关于血脂异常，发现总胆固醇和低密度脂蛋白之间的平均差异很大（0.33，95％CI：0.01-0.64，P<0.05；0.39，95％CI：0.04-0.73，P<0.05）。在瘙痒的情况下，与安慰剂相比，OCA获得了较高的OR（3.22，95％CI：2.22-4.74）。
结论：与安慰剂相比，OCA还降低了几种肝脏测试标志物，包括生化指标丙氨酸转氨酶，天冬氨酸转氨酶,碱性磷酸酶,和γ-谷氨酰转肽酶，和改善肝细胞膨胀，纤维化，脂肪变性,和小叶炎症。尽管在NASH患者中，OCA和安慰剂组的不良事件发生率没有显着差异，发现OCA治疗会升高总胆固醇和低密度脂蛋白水平，报告的瘙痒严重程度随着OCA剂量的增加而增加。
