University of California San Francisco, San Francisco, CA, USA.
University of California San Diego, San Diego, CA, USA.
Aliment Pharmacol Ther. 2018 Mar;47(5):645-656. doi: 10.1111/apt.14492. Epub 2018 Jan 14.
In a 72-week, randomised controlled trial of obeticholic acid (OCA) in non-alcoholic steatohepatitis (NASH), OCA was superior to placebo in improving serum ALT levels and liver histology. OCA therapy also reduced weight.
Because weight loss by itself can improve histology, to perform a post hoc analysis of the effects of weight loss and OCA treatment in improving clinical and metabolic features of NASH.
The analysis was limited to the 200 patients with baseline and end-of-treatment liver biopsies. Weight loss was defined as a relative decline from baseline of 2% or more at treatment end.
Weight loss occurred in 44% (45/102) of OCA and 32% (31/98) of placebo-treated patients (P = 0.08). The NAFLD Activity score (NAS) improved more in those with than without weight loss in both the OCA- (-2.4 vs -1.2, P<0.001) and placebo-treated patients (-1.2 vs -0.5, P = 0.03). ALT levels also improved in those with vs without weight loss in OCA- (-43 vs -34 U/L, P = 0.12) and placebo-treated patients (-29 vs -10 U/L, P = 0.02). However, among those who lost weight, OCA was associated with opposite effects from placebo on changes in alkaline phosphatase (+21 vs -12 U/L, P<0.001), total (+13 vs -14 mg/dL, P = 0.02) and LDL cholesterol (+18 vs -12 mg/dL, P = 0.01), and HbA1c (+0.1 vs -0.4%, P = 0.01).
OCA leads to weight loss in up to 44% of patients with NASH, and OCA therapy and weight loss have additive benefits on serum aminotransferases and histology. However, favourable effects of weight loss on alkaline phosphatase, lipids and blood glucose seen in placebo-treated patients were absent or reversed on OCA treatment. These findings stress the importance of assessing concomitant metabolic effects of new therapies of NASH. Clinical trial number: NCT01265498.
在一项为期 72 周的非酒精性脂肪性肝炎（NASH）奥贝胆酸（OCA）随机对照试验中，OCA 在改善血清 ALT 水平和肝脏组织学方面优于安慰剂。OCA 治疗还可减轻体重。
因为体重减轻本身可以改善组织学，因此进行了一项事后分析，以研究体重减轻和 OCA 治疗对 NASH 的临床和代谢特征的改善作用。
该分析仅限于基线和治疗结束时具有肝脏活检的 200 例患者。体重减轻定义为治疗结束时与基线相比相对下降 2%或更多。
在 OCA 治疗组（45/102）和安慰剂治疗组（31/98）中，分别有 44%（45/102）和 32%（31/98）的患者体重减轻（P=0.08）。在 OCA 治疗组（-2.4 比-1.2，P<0.001）和安慰剂治疗组（-1.2 比-0.5，P=0.03）中，与体重未减轻的患者相比，体重减轻的患者的非酒精性脂肪性肝病活动评分（NAS）改善更明显。在 OCA 治疗组（-43 比-34 U/L，P=0.12）和安慰剂治疗组（-29 比-10 U/L，P=0.02）中，与体重未减轻的患者相比，体重减轻的患者的 ALT 水平也有所改善。然而，在体重减轻的患者中，与安慰剂相比，OCA 治疗对碱性磷酸酶（+21 比-12 U/L，P<0.001）、总胆固醇（+13 比-14 mg/dL，P=0.02）和 LDL 胆固醇（+18 比-12 mg/dL，P=0.01）以及 HbA1c（+0.1 比-0.4%，P=0.01）的变化有相反的影响。
OCA 可导致高达 44%的 NASH 患者体重减轻，OCA 治疗和体重减轻对血清氨基转移酶和组织学均有附加益处。然而，在安慰剂治疗的患者中，体重减轻对碱性磷酸酶、脂质和血糖的有利影响在 OCA 治疗中不存在或逆转。这些发现强调了评估新的 NASH 治疗方法伴随的代谢影响的重要性。临床试验编号：NCT01265498。
