Abstract：Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in developed countries. The current treatment strategy focused on weight lose through lifestyle management and on the optimization of the components of metabolic syndrome. Various hypothetical pathogenic mechanisms have been proposed to develop new drug targets with potential for effective treatment of non-alcoholic steatohepatitis (NASH) patients. These experimental drugs and molecules that target specific mechanism pathways are used to effectively treat NASH. Currently, clinical trials of many drugs are underway. This article focuses on the current status of treatment of NAFLD and the progress of new drug research.
[1] Romero-Gomez M，Zelber-Sagi S，Trenell M. Treatment of NAFLD with diet，physical activity and exercise [J]. J Hepatol，2017，67（4）：829-846.
[2] Dibba P，Li AA，Perumpail BJ，et al. Emerging Therapeutic Targets and Experimental Drugs for the Treatment of NAFLD [J]. Diseases，2018，6（3）：pii: E83.
[3] Machado MV，Diehl AM. Pathogenesis of Nonalcoholic Steatohepatitis [J]. Gastroenterology，2016，150（8）：1769-1777.
[4] Brunt EM，Wong VW，Nobili V，et al. Nonalcoholic fatty liver disease [J]. Nat Rev Dis Primers，2015，1：15080.
[5] Musso G，Cassader M，Rosina F，et al. Impact of current treatments on liver disease，glucose metabolism and cardiovascular risk in non-alcoholic fatty liver disease （NAFLD）：a systematic review and meta-analysis of randomised trials [J]. Diabetologia，2012，55（4）：885-904.
[6] Vilar-Gomez E，Martinez-Perez Y，Calzadilla-Bertot L，et al. Weight Loss Through Lifestyle Modification Significantly Reduces Features of Nonalcoholic Steatohepatitis [J]. Gastroenterology，2015，149（2）：367-378，e14-e15.
[7] George ES，Forsyth A，Itsiopoulos C，et al. Practical Dietary Recommendations for the Prevention and Management of Nonalcoholic Fatty Liver Disease in Adults [J]. Adv Nutr，2018，9（1）：30-40.
[8] Winn NC，Liu Y，Rector RS，et al. Energy-matched moderate and high intensity exercise training improves nonalcoholic fatty liver disease risk independent of changes in body mass or abdominal adiposity-A randomized trial [J]. Metabolism，2018，78：128-140.
[9] Byrne CD, Targher G. EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease [J]. J Hepatol，2016，64（6）：1388-1402.
[10] Sato K，Gosho M，Yamamoto T，et al. Vitamin E has a beneficial effect on nonalcoholic fatty liver disease：a meta-analysis of randomized controlled trials [J]. Nutrition，2015，31（7-8）：923-930.
[11] Hadi H，Vettor R，Rossato M. Vitamin E as a Treatment for Nonalcoholic Fatty Liver Disease：Reality or Myth? [J]. Antioxidants （Basel），2018，7（1）：pii: E12.
[12] Violi F，Cangemi R. Pioglitazone，vitamin E，or placebo for nonalcoholic steatohepatitis [J]. N Engl J Med，2010，363（12）：1185-1186.
[13] Lewis JD，Habel LA，Quesenberry CP，et al. Pioglitazone Use and Risk of Bladder Cancer and Other Common Cancers in Persons With Diabetes [J]. JAMA，2015，314（3）：265-277.
[14] Cegla J. Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis（LEAN）：a multicentre，double-blind，randomized，placebo-controlled phase 2 study [J]. Ann Clin Biochem，2016，53（4）：518.
[15] Armstrong MJ，Hull D，Guo K，et al. Glucagon-like peptide 1 decreases lipotoxicity in non-alcoholic steatohepatitis [J]. J Hepatol，2016，64（2）：399-408.
[16] Wong VW. Current Prevention and Treatment Options for NAFLD [J]. Adv Exp Med Biol，2018，1061：149-157.
[17] Visseaux B，Charpentier C，Collin G，et al. Cenicriviroc，a Novel CCR5 （R5） and CCR2 Antagonist，Shows In Vitro Activity against R5 Tropic HIV-2 Clinical Isolates [J]. PLoS One，2015，10（8）：e134904.
[18] Friedman S，Sanyal A，Goodman Z，et al. Efficacy and safety study of cenicriviroc for the treatment of non-alcoholic steatohepatitis in adult subjects with liver fibrosis：CENTAUR Phase 2b study design [J]. Contemp Clin Trials，2016，47：356-365.
[19] Friedman SL，Ratziu V，Harrison SA，et al. A randomized，placebo-controlled trial of cenicriviroc for treatment of nonalcoholic steatohepatitis with fibrosis [J]. Hepatology，2018，67（5）：1754-1767.
[20] Lefebvre E，Moyle G，Reshef R，et al. Antifibrotic Effects of the Dual CCR2/CCR5 Antagonist Cenicriviroc in Animal Models of Liver and Kidney Fibrosis [J]. PLoS One，2016，11（6）：e158156.
[21] Tacke F. Cenicriviroc for the treatment of non-alcoholic steatohepatitis and liver fibrosis [J]. Expert Opin Investig Drugs，2018，27（3）：301-311.
[22] Harrison SA，Rinella ME，Abdelmalek MF，et al. NGM282 for treatment of non-alcoholic steatohepatitis：a multicentre，randomised，double-blind，placebo-controlled，phase 2 trial [J]. Lancet，2018，391（10126）：1174-1185.
[23] Repana D，Ross P. Targeting FGF19/FGFR4 Pathway：A Novel Therapeutic Strategy for Hepatocellular Carcinoma [J]. Diseases，2015，3（4）：294-305.
[24] Zhou M，Learned RM，Rossi SJ，et al. Engineered FGF19 eliminates bile acid toxicity and lipotoxicity leading to resolution of steatohepatitis and fibrosis in mice [J]. Hepatol Commun，2017，1（10）：1024-1042.
[25] Dickson I. NASH：Successful phase Ⅱtrial of FGF19 analogue [J]. Nat Rev Gastroenterol Hepatol，2018，15（5）：256.
[26] Dabbagh K，Steven DG， Yamamoto L， et al. Preclinical and first-in human development of SGM-1019，a first-in-class novel small molecule modulator of inflammasome activity for the treatment of nonalcoholic steatohepatitis （NASH）[J]. J Hepatol，2018，68：S60.
[27] Borrelli A，Bonelli P，Tuccillo FM，et al. Role of gut microbiota and oxidative stress in the progression of non-alcoholic fatty liver disease to hepatocarcinoma：Current and innovative therapeutic approaches [J]. Redox Biol，2018，15：467-479.
[28] Koopman N，Molinaro A，Nieuwdorp M，et al. Review article：can bugs be drugs? The potential of probiotics and prebiotics as treatment for non-alcoholic fatty liver disease [J]. Aliment Pharmacol Ther，2019，50（6）：628-639.
[29] Aller R，De Luis DA，Izaola O，et al. Effect of a probiotic on liver aminotransferases in nonalcoholic fatty liver disease patients：a double blind randomized clinical trial [J]. Eur Rev Med Pharmacol Sci，2011，15（9）：1090-1095.
[30] Mouzaki M，Comelli EM，Arendt BM，et al. Intestinal microbiota in patients with nonalcoholic fatty liver disease [J]. Hepatology，2013，58（1）：120-127.
[31] Poeta M，Pierri L，Vajro P. Gut-Liver Axis Derangement in Non-Alcoholic Fatty Liver Disease [J]. Children（Basel），2017，4（8）：66.
[32] Ma YY，Li L，Yu CH，et al. Effects of probiotics on nonalcoholic fatty liver disease：a meta-analysis [J]. World J Gastroenterol，2013，19（40）：6911-6918.
[33] S Lavekar A，V Raje D，Manohar T，et al. Role of Probiotics in the Treatment of Nonalcoholic Fatty Liver Disease：A Meta-analysis [J]. Euroasian J Hepatogastroenterol，2017，7（2）：130-137.
[34] Mofidi F，Poustchi H，Yari Z，et al. Synbiotic supplementation in lean patients with non-alcoholic fatty liver disease：a pilot，randomised，double-blind，placebo-controlled，clinical trial [J]. Br J Nutr，2017，117（5）：662-668.
[35] Pan YT，Xu FY，Yu XZ，et al. Research progress on therapeutic targets of active components in Chinese herbs for treatment of nonalcoholic fatty liver disease [J]. Zhongguo Zhong Yao Za Zhi，2017，42（6）：1109-1112.
[36] Cai Y，Liang Q，Chen W，et al. Evaluation of HuoXueHuaYu therapy for nonalcoholic fatty liver disease：a systematic review and meta-analysis of randomized controlled trial [J]. BMC Complement Altern Med，2019，19（1）：178.
[37] Deng Y，Tang K，Chen R，et al. Berberine attenuates hepatic oxidative stress in rats with non-alcoholic fatty liver disease via the Nrf2/ARE signalling pathway [J]. Exp Ther Med，2019，17（3）：2091-2098.
[38] Dang Y，Hao S，Zhou W，et al. The traditional Chinese formulae Ling-gui-zhu-gan decoction alleviated non-alcoholic fatty liver disease via inhibiting PPP1R3C mediated molecules [J]. BMC Complement Altern Med，2019， 19（1）：8.
[39] Zhang M，Yuan Y，Wang Q，et al. The Chinese medicine Chai Hu Li Zhong Tang protects against non-alcoholic fatty liver disease by activating AMPKalpha [J]. Biosci Rep，2018，38（6）：pii：BSR20180644.
2020, Vol. 17 
京公网安备 11010502046598号