비알코올 지방간 질환의 약물치료
Pharmacologic Therapy for Nonalcoholic Fatty Liver Disease
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Weight loss via lifestyle modification remains the most efficient treatment for NAFLD. Weight loss and exercise are thecornerstones of therapy, but achieving long-term lifestyle modification is not free from difficulties. Pharmacologic therapy shouldbe considered for patients with NAFLD unable to achieve or maintain lifestyle-induced weight loss. Unfortunately, there is noapproved drug for NAFLD currently. Current treatment methods for NAFLD can be divided roughly into those methods that targetcomponents of metabolic syndrome using weight reduction and insulin sensitizers (pioglitazone) and those that use antioxidants(Vitamin E) to benefit the liver. Pioglitazone has been shown to improve steatosis, hepatocellular ballooning, and inflammation andalso to reduce the risk of fibrosis progression in several randomized-controlled trials (RCTs). In a large RCT, large doses of vitaminE improved all histological lesions except for fibrosis. Compared with a placebo, Metformin lowered ALT, but did not improveliver histology. Recently, novel anti-diabetic agents (GLP-1 analogues, DPP IV inhibitors) and probiotics that alter the gutmicrobiome were shown to mildly benefit ALT and liver histology. In this report, we systemically review current pharmacologictherapies and other promising agents that were not considered in the most recent guidelines for the treatment of NAFLD.
Abstract
Weight loss via lifestyle modification remains the most efficient treatment for NAFLD. Weight loss and exercise are thecornerstones of therapy, but achieving long-term lifestyle modification is not free from difficulties. Pharmacologic therapy shouldbe considered for patients with NAFLD unable to achieve or maintain lifestyle-induced weight loss. Unfortunately, there is noapproved drug for NAFLD currently. Current treatment methods for NAFLD can be divided roughly into those methods that targetcomponents of metabolic syndrome using weight reduction and insulin sensitizers (pioglitazone) and those that use antioxidants(Vitamin E) to benefit the liver. Pioglitazone has been shown to improve steatosis, hepatocellular ballooning, and inflammation andalso to reduce the risk of fibrosis progression in several randomized-controlled trials (RCTs). In a large RCT, large doses of vitaminE improved all histological lesions except for fibrosis. Compared with a placebo, Metformin lowered ALT, but did not improveliver histology. Recently, novel anti-diabetic agents (GLP-1 analogues, DPP IV inhibitors) and probiotics that alter the gutmicrobiome were shown to mildly benefit ALT and liver histology. In this report, we systemically review current pharmacologictherapies and other promising agents that were not considered in the most recent guidelines for the treatment of NAFLD.
참고문헌 (60)
- Starley BQ, "Nonalcoholic fatty liver disease and hepatocellular carcinoma: a weighty connection", Hepatology, 51, pp.1820~1832 (2010)
- Bellentani S, "Fatty Liver Italian Network. Behavior therapy for nonalcoholic fatty liver disease: the need for a multidisciplinary approach", Hepatology, 47, pp.746~754 (2008)
- Torres DM, "Features, diagnosis, and treatment of nonalcoholic fatty liver disease", Clin Gastroenterol Hepatol, 10, pp.837~858 (2012)
- Schuppan D, "Non-alcoholic steatohepatitis: pathogenesis and novel therapeutic approaches", J Gastroenterol Hepatol, 28(1), pp.68~76 (2013)
- Jourdan T, "Antagonism of peripheral hepatic cannabinoid receptor-1 improves liver lipid metabolism in mice: evidence from cultured explants", Hepatology, 55, pp.790~799 (2012)
- Tam J, "Peripheral cannabinoid-1 receptor inverse agonism reduces obesity by reversing leptin resistance", Cell Metab, 16, pp.167~179 (2012)
- Smith SR, "Multicenter, placebo-controlled trial of lorcaserin for weight management", N Engl J Med, 363, pp.245~256 (2010)
- Gadde KM, "Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial", Lancet, 377, pp.1341~1352 (2011)
- Belfort R, "A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis", N Engl J Med, 355, pp.2297~2307 (2006)
- Sanyal AJ, "Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis", N Engl J Med, 362, pp.1675~1685 (2010)
- Aithal GP, "Randomized, placebo- controlled trial of pioglitazone in nondiabetic subjects with nonalcoholic steatohepatitis", Gastroenterology, 138, pp.1176~1184 (2008)
- Mahady SE, "The role of thiazolidinediones in non-alcoholic steatohepatitis- a systematic review and meta analysis", J Hepatol, 55, pp.1383~1390 (2011)
- Kahn SE, "Rosiglitazone-associated fractures in type 2 diabetes: an Analysis from A Diabetes Outcome Progression Trial (ADOPT)", Diabetes Care, 31, pp.845~851 (2008)
- Lewis JD, "Risk of bladder cancer among diabetic patients treated with pioglitazone: interim report of a longitudinal cohort study", Diabetes Care, 34, pp.916~922 (2011)
- Lincoff AM, "Pioglitazone and risk of cardiovascular events in patients with type 2 diabetes mellitus: a meta-analysis of randomized trials", JAMA, 298, pp.1180~1188 (2007)
- Lipscombe LL, "Thiazolidinediones and cardiovascular outcomes in older patients with diabetes", JAMA, 298, pp.2634~2643 (2007)
- Korean Association for the Study of the Liver (KASL), "KASL clinical practice guidelines: management of nonalcoholic fatty liver disease", Clin Mol Hepatol, 19, pp.325~348 (2013)
- Marchesini G, "Metformin in non-alcoholic steatohepatitis", Lancet, 358, pp.893~894 (2001)
- Bugianesi E, "A randomized controlled trial of metformin versus vitamin E or prescriptive diet in nonalcoholic fatty liver disease", Am J Gastroenterol, 100, pp.1082~1090 (2005)
- Uygun A, "Metformin in the treatment of patients with non-alcoholic steatohepatitis", Aliment Pharmacol Ther, 19, pp.537~544 (2004)
- Torres DM, "Rosiglitazone versus rosiglitazone and metformin versus rosiglitazone and losartan in the treatment of nonalcoholic steatohepatitis in humans: a 12-month randomized, prospective, open-label trial", Hepatology, 54, pp.1631~1639 (2011)
- Vernon G, "Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults", Aliment Pharmacol Ther, 34, pp.274~285 (2011)
- Musso G, "A meta-analysis of randomized trials for the treatment of nonalcoholic fatty liver disease", Hepatology, 52, pp.79~104 (2010)
- Bjelakovic G, "Meta-analysis: antioxidant supplements for liver diseases-the Cochrane Hepato-Biliary Group", Aliment Pharmacol Ther, 32, pp.356~367 (2010)
- Miller ER, "Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality", Ann Intern Med, 142, pp.37~46 (2005)
- Lavine JE, "Effect of vitamin E or metformin for treatment of nonalcoholic fatty liver disease in children and adolescents: the TONIC randomized controlled trial", JAMA, 305, pp.1659~1668 (2011)
- Klein EA, "Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT)", JAMA, 306, pp.1549~1556 (2011)
- Ratziu V, "A randomized controlled trial of high-dose ursodesoxycholic acid for nonalcoholic steatohepatitis", J Hepatol, 54, pp.1011~1019 (2011)
- Leuschner UF, "High-dose ursodeoxycholic acid therapy for nonalcoholic steatohepatitis: a double-blind, randomized, placebo-controlled trial", Hepatology, 52, pp.472~479 (2010)
- Lindor KD, "High-dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis", Hepatology, 50, pp.808~814 (2009)
- Xiang Z, "The role of Ursodeoxycholic acid in non-alcoholic steatohepatitis: a systematic review", BMC Gastroenterol, 13, pp.140~ (2013)
- Chalasani N, "The diagnosis and management of non-alcoholic fatty liver disease: practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association", Hepatology, 55, pp.2005~2023 (2012)
- Strieter RM, "Cellular and molecular regulation of tumor necrosis factor-alpha production by pentoxifylline", Biochem Biophys Res Commun, 155, pp.1230~1236 (1988)
- Zein CO, "Pentoxifylline decreases oxidized lipid products in nonalcoholic steatohepatitis: new evidence on the potential therapeutic mechanism", Hepatology, 56, pp.1291~1299 (2012)
- Zein CO, "Pentoxifylline improves nonalcoholic steatohepatitis: a randomized placebo- controlled trial", Hepatology, 54, pp.1610~1619 (2011)
- Van Wagner LB, "Pentoxifylline for the treatment of non-alcoholic steatohepatitis: a randomized controlled trial", Ann Hepatol, 10, pp.277~286 (2011)
- Chalasani N, "Patients with elevated liver enzymes are not at higher risk for statin hepatotoxicity", Gastroenterology, 126, pp.1287~1292 (2004)
- Nelson A, "A pilot study using simvastatin in the treatment of nonalcoholic steatohepatitis: a randomized placebo-controlled trial", J Clin Gastroenterol, 43, pp.990~994 (2009)
- Yokohama S, "Therapeutic efficacy of an angiotensin II receptor antagonist in patients with nonalcoholic steatohepatitis", Hepatology, 40, pp.1222~1225 (2004)
- Georgescu EF, "Angiotensin-receptor blockers as therapy for mild-to-moderate hypertension-associated non-alcoholic steatohepatitis", World J Gastroenterol, 15, pp.942~954 (2009)
- Vos MB, "Nutrition, nonalcoholic fatty liver disease and the microbiome: recent progress in the field", Curr Opin Lipidol, 25, pp.61~66 (2014)
- Rabot S, "Germ-free C57BL", 6J mice are resistant to high-fat-diet-induced insulin resistance and have altered cholesterol metabolism, 2010, pp.24, 4948~4959
- Zhu L, "Characterization of gut microbiomes in nonalcoholic steatohepatitis (NASH) patients: a connection between endogenous alcohol and NASH", Hepatology, 57, pp.601~609 (2013)
- Wagnerberger S, "Lactobacillus casei Shirota protects from fructose-induced liver steatosis: a mouse model", J Nutr Biochem, 24, pp.531~538 (2013)
- Okubo H, "Lactobacillus casei strain Shirota protects against nonalcoholic steatohepatitis development in a rodent model", Am J Physiol Gastrointest Liver Physiol, 305, pp.G911~918 (2013)
- Mencarelli A, "VSL#3 resets insulin signaling and protects against NASH and atherosclerosis in a model of genetic dyslipidemia and intestinal inflammation", PLoS One, 7, pp.e45425~ (2012)
- Wong VW, "Treatment of nonalcoholic steatohepatitis with probiotics: a proof-of-concept study", Ann Hepatol, 12, pp.256~262 (2013)
- Vrieze A, "Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome", Gastroenterology, 143, pp.913~916.e7 (2012)
- Parnell JA, "The potential role of prebiotic fibre for treatment and management of non-alcoholic fatty liver disease and associated obesity and insulin resistance", Liver Int, 32, pp.701~711 (2012)
- Holst JJ, "Incretin hormones and the satiation signal", Int J Obes (Lond), 37, pp.1161~1168 (2013)
- Bernsmeier C, "Glucose-induced glucagon-like Peptide 1 secretion is deficient in patients with non-alcoholic Fatty liver disease", PLoS One, 9, pp.e87488~ (2014)
- Gupta NA, "Glucagon-like peptide- 1 receptor is present on human hepatocytes and has a direct role in decreasing hepatic steatosis in vitro by modulating elements of the insulin signaling pathway", Hepatology, 51, pp.1584~1592 (2010)
- Svegliati-Baroni G, "Glucagon-like peptide-1 receptor activation stimulates hepatic lipid oxidation and restores hepatic signalling alteration induced by a high-fat diet in nonalcoholic steatohepatitis", Liver Int, 31, pp.1285~1297 (2011)
- Trevaskis JL, "Glucagon-like peptide-1 receptor agonism improves metabolic, biochemical, and histopathological indices of nonalcoholic steatohepatitis in mice", Am J Physiol Gastrointest Liver Physiol, 302, pp.G762~772 (2012)
- Drucker DJ, "The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes", Lancet, 368, pp.1696~1705 (2006)
- Iwasaki T, "Sitagliptin as a novel treatment agent for non-alcoholic Fatty liver disease patients with type 2 diabetes mellitus", Hepatogastroenterology, 58, pp.2103~2105 (2011)
- Kenny PR, "Exenatide in the treatment of diabetic patients with non-alcoholic steatohepatitis: a case series", Am J Gastroenterol, 105, pp.2707~2709 (2010)
- Vilsbøll T, "Effects of glucagon-like peptide-1 receptor agonists on weight loss: systematic review and meta-analyses of randomised controlled trials", BMJ, 344, pp.d7771~ (2012)
- Hollman DA, "Anti-inflammatory and metabolic actions of FXR: insights into molecular mechanisms", Biochim Biophys Acta, 1821, pp.1443~1452 (2012)
- Mudaliar S, "Efficacy and safety of the farnesoid X receptor agonist obeticholic acid in patients with type 2 diabetes and nonalcoholic fatty liver disease", Gastroenterology, 145, pp.574~582.e (2013)
