Combination therapy for non-alcoholic steatohepatitis: rationale, opportunities and challenges

被引：151

作者：

Dufour, Jean-Francois ^{[1
,2
]}

Caussy, Cyrielle ^{[3
,4
]}

Loomba, Rohit ^{[5
]}

机构：

[1] Univ Bern, Dept Clin Res, Hepatol, CH-3010 Bern, Switzerland

[2] Inselspital Bern, Univ Clin Visceral Surg & Med, Bern, Switzerland

[3] Univ Lyon 1, Hosp Civils Lyon, Ctr Hosp Lyon Sud Endocrinol Diabete & Nutr, Lyon, France

[4] Univ Calif San Diego, NAFLD Res Ctr, La Jolla, CA 92093 USA

[5] Univ Calif San Diego, NAFLD Res Ctr, Dept Med, Div Gastroenterol & Hepatol, La Jolla, CA 92093 USA

来源：

GUT | 2020年 / 69卷 / 10期

基金：

瑞士国家科学基金会;

关键词：

nonalcoholic steatohepatitis; hepatobiliary disease; liver; FATTY LIVER-DISEASE; TYPE-2; DIABETES-MELLITUS; CHRONIC KIDNEY-DISEASE; CARDIOVASCULAR OUTCOMES; INSULIN-RESISTANCE; ADVANCED FIBROSIS; HIGH PREVALENCE; OBESE-PATIENTS; PLACEBO; ASSOCIATION;

D O I：

10.1136/gutjnl-2019-319104

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Non-alcoholic steatohepatitis (NASH) is becoming a leading cause of cirrhosis with the burden of NASH-related complications projected to increase massively over the coming years. Several molecules with different mechanisms of action are currently in development to treat NASH, although reported efficacy to date has been limited. Given the complexity of the pathophysiology of NASH, it will take the engagement of several targets and pathways to improve the results of pharmacological intervention, which provides a rationale for combination therapies in the treatment of NASH. As the field is moving towards combination therapy, this article reviews the rationale for such combination therapies to treat NASH based on the current therapeutic landscape as well as the advantages and limitations of this approach.

引用

页码：1877 / 1884

页数：8

共 69 条

[61] Diabetes mellitus and risk of hepatocellular carcinoma: a systematic review and meta-analysis [J].

Wang, Ping ;

Kang, Donghong ;

Cao, Wei ;

Wang, Yan ;

Liu, Zhiwen .

DIABETES-METABOLISM RESEARCH AND REVIEWS, 2012, 28 (02) :109-122

[62] Prevalence of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis Among a Largely Middle-Aged Population Utilizing Ultrasound and Liver Biopsy: A Prospective Study [J].

Williams, Christopher D. ;

Stengel, Joel ;

Asike, Michael I. ;

Torres, Dawn M. ;

Shaw, Janet ;

Contreras, Maricela ;

Landt, Cristy L. ;

Harrison, Stephen A. .

GASTROENTEROLOGY, 2011, 140 (01) :124-131

[63] Prevalence and markers of advanced liver disease in type 2 diabetes [J].

Williamson, R. M. ;

Price, J. F. ;

Hayes, P. C. ;

Glancy, S. ;

Frier, B. M. ;

Johnston, G. I. ;

Reynolds, R. M. ;

Strachan, M. W. J. .

QJM-AN INTERNATIONAL JOURNAL OF MEDICINE, 2012, 105 (05) :425-432

[64]

Wiviott SD, 2019, NEW ENGL J MED, V380, P347, DOI [10.1056/NEJMc1902837, 10.1056/NEJMoa1812389]

[65] Advanced liver fibrosis but not steatosis is independently associated with albuminuria in Chinese patients with type 2 diabetes [J].

Yeung, Ming-Wai ;

Wong, Grace Lai-Hung ;

Choi, Kai Chow ;

Luk, Andrea On-Yan ;

Kwok, Raymond ;

Shu, Sally She-Ting ;

Chan, Anthony Wing-Hung ;

Lau, Eric Siu Him ;

Ma, Ronald Ching Wan ;

Chan, Henry Lik-Yuen ;

Chan, Juliana Chung-Ngor ;

Wong, Vincent Wai-Sun ;

Kong, Alice Pik-Shan .

JOURNAL OF HEPATOLOGY, 2018, 68 (01) :147-156

[66] Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial [J].

Younossi, Zobair M. ;

Ratziu, Vlad ;

Loomba, Rohit ;

Rinella, Mary ;

Anstee, Quentin M. ;

Goodman, Zachary ;

Bedossa, Pierre ;

Geier, Andreas ;

Beckebaum, Susanne ;

Newsome, Philip N. ;

Sheridan, David ;

Sheikh, Muhammad Y. ;

Trotter, James ;

Knapple, Whitfield ;

Lawitz, Eric ;

Abdelmalek, Manal F. ;

Kowdley, Kris V. ;

Montano-Loza, Aldo J. ;

Boursier, Jerome ;

Mathurin, Philippe ;

Bugianesi, Elisabetta ;

Mazzella, Giuseppe ;

Olveira, Antonio ;

Cortez-Pinto, Helena ;

Graupera, Isabel ;

Orr, David ;

Gluud, Lise Lotte ;

Dufour, Jean-Francois ;

Shapiro, David ;

Campagna, Jason ;

Zaru, Luna ;

MacConell, Leigh ;

Shringarpure, Reshma ;

Harrison, Stephen ;

Sanyal, Arun J. .

LANCET, 2019, 394 (10215) :2184-2196

[67] Nonalcoholic Fatty Liver Disease in Patients With Type 2 Diabetes [J].

Younossi, Zobair M. ;

Gramlich, Terry ;

Matteoni, Christi A. ;

Boparai, Navdeep ;

Mccullough, Arthur J. .

CLINICAL GASTROENTEROLOGY AND HEPATOLOGY, 2004, 2 (03) :262-265

[68] SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials [J].

Zelniker, Thomas A. ;

Wiviott, Stephen D. ;

Raz, Itamar ;

Im, Kyungah ;

Goodrich, Erica L. ;

Bonaca, Marc P. ;

Mosenzon, Ofri ;

Kato, Eri T. ;

Cahn, Avivit ;

Furtado, Remo H. M. ;

Bhatt, Deepak L. ;

Leiter, Lawrence A. ;

McGuire, Darren K. ;

Wilding, John P. H. ;

Sabatine, Marc S. .

LANCET, 2019, 393 (10166) :31-39

[69] Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes [J].

Fischereder, Michael ;

Schoenermarck, Ulf .

NEW ENGLAND JOURNAL OF MEDICINE, 2016, 374 (11) :1092-1093

← 1 2 3 4 5 6 7 →