The Natural History of Advanced Fibrosis Due to Nonalcoholic Steatohepatitis: Data From the Simtuzumab Trials

被引：249

作者：

Sanyal, Arun J. ^{[1
]}

Harrison, Stephen A. ^{[2
]}

Ratziu, Vlad ^{[3
]}

Abdelmalek, Manal F. ^{[4
]}

Diehl, Anna Mae ^{[4
]}

Caldwell, Stephen ^{[5
]}

Shiffman, Mitchell L. ^{[6
]}

Aguilar Schall, Raul ^{[7
]}

Jia, Catherine ^{[7
]}

McColgan, Bryan ^{[7
]}

Djedjos, C. Stephen ^{[7
]}

McHutchison, John G. ^{[7
]}

Subramanian, G. Mani ^{[7
]}

Myers, Robert P. ^{[7
]}

Younossi, Zobair ^{[8
]}

Muir, Andrew J. ^{[4
]}

Afdhal, Nezam H. ^{[9
]}

Bosch, Jaime ^{[10
,11
]}

Goodman, Zachary ^{[8
]}

机构：

[1] Virginia Commonwealth Univ, Richmond, VA USA

[2] Pinnacle Clin Res, San Antonio, TX USA

[3] Hop Univ Pitie Salpetriere, Paris, France

[4] Duke Clin Res Inst, Durham, NC USA

[5] Univ Virginia, Charlottesville, VA USA

[6] Liver Inst Virginia, Richmond, VA USA

[7] Gilead Sci Inc, 353 Lakeside Dr, Foster City, CA 94404 USA

[8] Inova Fairfax Hosp, Falls Church, VA USA

[9] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA

[10] Bern Univ, Inselspital, Bern, Switzerland

[11] Univ Barcelona, IDIBAPS, Barcelona, Spain

来源：

HEPATOLOGY | 2019年 / 70卷 / 06期

关键词：

FATTY LIVER-DISEASE; SIMPLE NONINVASIVE INDEX; WEIGHT-REDUCTION; UNITED-STATES; CIRRHOSIS; NAFLD; MORTALITY; OUTCOMES; PREDICT; BURDEN;

D O I：

10.1002/hep.30664

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Progression of nonalcoholic steatohepatitis (NASH) is incompletely characterized. We analyzed data on longitudinal changes in liver histology, hepatic venous pressure gradient (HVPG), and serum markers of fibrosis in 475 patients with NASH with bridging fibrosis (F3) or compensated cirrhosis (F4) enrolled in two phase 2b, placebo-controlled trials of simtuzumab. The trials were terminated after 96 weeks because of lack of efficacy, so data from treatment groups were combined. Liver biopsies and HVPG measurements (only for patients with F4 fibrosis) were collected at screening and at weeks 48 and 96. Patients were assessed for Ishak fibrosis stage, hepatic collagen content and alpha-smooth muscle actin (by morphometry), NAFLD Activity Score (NAS), and serum markers of fibrosis. Associations with progression to cirrhosis (in patients with F3 fibrosis) and liver-related clinical events (in patients with F4 fibrosis) were determined. Progression to cirrhosis occurred in 22% (48/217) of F3 patients, and liver-related clinical events occurred in 19% (50/258) of patients with cirrhosis. Factors significantly associated with progression to cirrhosis included higher baseline values of and greater increases in hepatic collagen content, level of alpha-smooth muscle actin, and Enhanced Liver Fibrosis score. Similar factors, plus lack of fibrosis stage improvement (hazard ratio, 9.30; 95% confidence interval, 1.28-67.37), higher HVPG at baseline, and greater increase in HVPG over time, were associated with an increased risk of liver-related clinical events in patients with cirrhosis. Disease progression was not associated with the NAS at baseline or changes in NAS during treatment after adjustment for fibrosis stage. Conclusion: In patients with advanced fibrosis due to NASH, the primary determinant of clinical disease progression is fibrosis and its change over time.

引用

页码：1913 / 1927

页数：15

共 27 条

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