Skip to main content
Top
Published in: BMC Medicine 1/2017

Open Access 01-12-2017 | Minireview

Non-alcoholic fatty liver disease

Author: Brent A. Neuschwander-Tetri

Published in: BMC Medicine | Issue 1/2017

Login to get access

Abstract

Non-alcoholic fatty liver disease has emerged a major challenge because of it prevalence, difficulties in diagnosis, complex pathogenesis, and lack of approved therapies. As the burden of hepatitis C abates over the next decade, non-alcoholic fatty liver disease will become the major form of chronic liver disease in adults and children and could become the leading indication for liver transplantation. This overview briefly summarizes the most recent data on the pathophysiology, diagnosis, and treatment of non-alcoholic fatty liver disease. Ongoing clinical trials are focused on an array of disease mechanisms and reviewed here are how these treatments fit into the current paradigm of substrate overload lipotoxic liver injury. Many of the approaches are directed at downstream events such as inflammation, injury and fibrogenesis. Addressing more proximal processes such as dysfunctional satiety mechanisms and inappropriately parsimonious energy dissipation are potential therapeutic opportunities that if successfully understood and exploited would not only address fatty liver disease but also the other components of the metabolic syndrome such as obesity, diabetes and dyslipidemia.
Literature
1.
2.
go back to reference Brunt EM, Wong VW, Nobili V, Day CP, Sookoian S, Maher JJ, Bugianesi E, Sirlin CB, Neuschwander-Tetri BA, Rinella ME. Nonalcoholic fatty liver disease. Nat Rev Dis Primers. 2015;1:15080.CrossRefPubMed Brunt EM, Wong VW, Nobili V, Day CP, Sookoian S, Maher JJ, Bugianesi E, Sirlin CB, Neuschwander-Tetri BA, Rinella ME. Nonalcoholic fatty liver disease. Nat Rev Dis Primers. 2015;1:15080.CrossRefPubMed
3.
go back to reference Wong RJ, Aguilar M, Cheung R, Perumpail RB, Harrison SA, Younossi ZM, Ahmed A. Nonalcoholic steatohepatitis is the second leading etiology of liver disease among adults awaiting liver transplantation in the United States. Gastroenterology. 2015;148:547–55.CrossRefPubMed Wong RJ, Aguilar M, Cheung R, Perumpail RB, Harrison SA, Younossi ZM, Ahmed A. Nonalcoholic steatohepatitis is the second leading etiology of liver disease among adults awaiting liver transplantation in the United States. Gastroenterology. 2015;148:547–55.CrossRefPubMed
4.
go back to reference Goh GB, McCullough AJ. Natural history of nonalcoholic fatty liver disease. Dig Dis Sci. 2016;61:1226–33.CrossRefPubMed Goh GB, McCullough AJ. Natural history of nonalcoholic fatty liver disease. Dig Dis Sci. 2016;61:1226–33.CrossRefPubMed
5.
go back to reference Younossi ZM, Blissett D, Blissett R, Henry L, Stepanova M, Younossi Y, Racila A, Hunt S, Beckerman R. The economic and clinical burden of nonalcoholic fatty liver disease in the United States and Europe. Hepatology. 2016;64:1577–86.CrossRefPubMed Younossi ZM, Blissett D, Blissett R, Henry L, Stepanova M, Younossi Y, Racila A, Hunt S, Beckerman R. The economic and clinical burden of nonalcoholic fatty liver disease in the United States and Europe. Hepatology. 2016;64:1577–86.CrossRefPubMed
6.
go back to reference Angulo P, Kleiner DE, Dam-Larsen S, Adams LA, Bjornsson ES, Charatcharoenwitthaya P, Mills PR, Keach JC, Lafferty HD, Stahler A, Haflidadottir S, Bendtsen F. Liver fibrosis, but no other histologic features, is associated with long-term outcomes of patients with nonalcoholic fatty liver disease. Gastroenterology. 2015;149:389–97.CrossRefPubMedPubMedCentral Angulo P, Kleiner DE, Dam-Larsen S, Adams LA, Bjornsson ES, Charatcharoenwitthaya P, Mills PR, Keach JC, Lafferty HD, Stahler A, Haflidadottir S, Bendtsen F. Liver fibrosis, but no other histologic features, is associated with long-term outcomes of patients with nonalcoholic fatty liver disease. Gastroenterology. 2015;149:389–97.CrossRefPubMedPubMedCentral
7.
go back to reference Singh S, Allen AM, Wang Z, Prokop LJ, Murad MH, Loomba R. Fibrosis progression in nonalcoholic fatty liver vs nonalcoholic steatohepatitis: A systematic review and meta-analysis of paired-biopsy studies. Clin Gastroenterol Hepatol. 2015;13:643–54.CrossRefPubMed Singh S, Allen AM, Wang Z, Prokop LJ, Murad MH, Loomba R. Fibrosis progression in nonalcoholic fatty liver vs nonalcoholic steatohepatitis: A systematic review and meta-analysis of paired-biopsy studies. Clin Gastroenterol Hepatol. 2015;13:643–54.CrossRefPubMed
8.
go back to reference Kwok R, Choi KC, Wong GL, Zhang Y, Chan HL, Luk AO, Shu SS, Chan AW, Yeung MW, Chan JC, Kong AP, Wong VW. Screening diabetic patients for non-alcoholic fatty liver disease with controlled attenuation parameter and liver stiffness measurements: a prospective cohort study. Gut. 2016;65:1359–68.CrossRefPubMed Kwok R, Choi KC, Wong GL, Zhang Y, Chan HL, Luk AO, Shu SS, Chan AW, Yeung MW, Chan JC, Kong AP, Wong VW. Screening diabetic patients for non-alcoholic fatty liver disease with controlled attenuation parameter and liver stiffness measurements: a prospective cohort study. Gut. 2016;65:1359–68.CrossRefPubMed
9.
go back to reference Koehler EM, Plompen EP, Schouten JN, Hansen BE, Darwish Murad S, Taimr P, Leebeek FW, Hofman A, Stricker BH, Castera L, Janssen HL. Presence of diabetes mellitus and steatosis is associated with liver stiffness in a general population: The Rotterdam study. Hepatology. 2016;63:138–47.CrossRefPubMed Koehler EM, Plompen EP, Schouten JN, Hansen BE, Darwish Murad S, Taimr P, Leebeek FW, Hofman A, Stricker BH, Castera L, Janssen HL. Presence of diabetes mellitus and steatosis is associated with liver stiffness in a general population: The Rotterdam study. Hepatology. 2016;63:138–47.CrossRefPubMed
10.
go back to reference Unalp-Arida A, Ruhl CE. Noninvasive fatty liver markers predict liver disease mortality in the U.S. population. Hepatology. 2016;63:1170–83.CrossRefPubMed Unalp-Arida A, Ruhl CE. Noninvasive fatty liver markers predict liver disease mortality in the U.S. population. Hepatology. 2016;63:1170–83.CrossRefPubMed
11.
go back to reference Reeves HL, Zaki MY, Day CP. Hepatocellular carcinoma in obesity, type 2 diabetes, and NAFLD. Dig Dis Sci. 2016;61:1234–45.CrossRefPubMed Reeves HL, Zaki MY, Day CP. Hepatocellular carcinoma in obesity, type 2 diabetes, and NAFLD. Dig Dis Sci. 2016;61:1234–45.CrossRefPubMed
12.
go back to reference Mittal S, El-Serag HB, Sada YH, Kanwal F, Duan Z, Temple S, May SB, Kramer JR, Richardson PA, Davila JA. Hepatocellular carcinoma in the absence of cirrhosis in United States veterans is associated with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2016;14:124–31.CrossRefPubMed Mittal S, El-Serag HB, Sada YH, Kanwal F, Duan Z, Temple S, May SB, Kramer JR, Richardson PA, Davila JA. Hepatocellular carcinoma in the absence of cirrhosis in United States veterans is associated with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2016;14:124–31.CrossRefPubMed
13.
go back to reference European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD), European Association for the Study of Obesity (EASO). EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol. 2016;64:1388–402. European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD), European Association for the Study of Obesity (EASO). EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol. 2016;64:1388–402.
14.
go back to reference Zhou Y, Orešič M, Leivonen M, Gopalacharyulu P, Hyysalo J, Arola J, Verrijken A, Francque S, Van Gaal L, Hyötyläinen T, Yki-Järvinen H. Noninvasive detection of nonalcoholic steatohepatitis using clinical markers and circulating levels of lipids and metabolites. Clin Gastroenterol Hepatol. 2016;14:1463–72.CrossRefPubMed Zhou Y, Orešič M, Leivonen M, Gopalacharyulu P, Hyysalo J, Arola J, Verrijken A, Francque S, Van Gaal L, Hyötyläinen T, Yki-Järvinen H. Noninvasive detection of nonalcoholic steatohepatitis using clinical markers and circulating levels of lipids and metabolites. Clin Gastroenterol Hepatol. 2016;14:1463–72.CrossRefPubMed
15.
go back to reference Loomba R, Quehenberger O, Armando A, Dennis EA. Polyunsaturated fatty acid metabolites as novel lipidomic biomarkers for noninvasive diagnosis of nonalcoholic steatohepatitis. J Lipid Res. 2015;56:185–92.CrossRefPubMedPubMedCentral Loomba R, Quehenberger O, Armando A, Dennis EA. Polyunsaturated fatty acid metabolites as novel lipidomic biomarkers for noninvasive diagnosis of nonalcoholic steatohepatitis. J Lipid Res. 2015;56:185–92.CrossRefPubMedPubMedCentral
16.
go back to reference Kaswala DH, Lai M, Afdhal NH. Fibrosis assessment in nonalcoholic fatty liver disease (NAFLD) in 2016. Dig Dis Sci. 2016;61:1356–64.CrossRefPubMed Kaswala DH, Lai M, Afdhal NH. Fibrosis assessment in nonalcoholic fatty liver disease (NAFLD) in 2016. Dig Dis Sci. 2016;61:1356–64.CrossRefPubMed
17.
go back to reference Boursier J, Vergniol J, Guillet A, Hiriart JB, Lannes A, Le Bail B, Michalak S, Chermak F, Bertrais S, Foucher J, Oberti F, Charbonnier M, Fouchard-Hubert I, Rousselet MC, Calès P, de Lédinghen V. Diagnostic accuracy and prognostic significance of blood fibrosis tests and liver stiffness measurement by FibroScan in non-alcoholic fatty liver disease. J Hepatol. 2016;65:570–8.CrossRefPubMed Boursier J, Vergniol J, Guillet A, Hiriart JB, Lannes A, Le Bail B, Michalak S, Chermak F, Bertrais S, Foucher J, Oberti F, Charbonnier M, Fouchard-Hubert I, Rousselet MC, Calès P, de Lédinghen V. Diagnostic accuracy and prognostic significance of blood fibrosis tests and liver stiffness measurement by FibroScan in non-alcoholic fatty liver disease. J Hepatol. 2016;65:570–8.CrossRefPubMed
18.
go back to reference Cassinotto C, Boursier J, de Ledinghen V, Lebigot J, Lapuyade B, Cales P, Hiriart JB, Michalak S, Bail BL, Cartier V, Mouries A, Oberti F, Fouchard-Hubert I, Vergniol J, Aube C. Liver stiffness in nonalcoholic fatty liver disease: A comparison of supersonic shear imaging, FibroScan, and ARFI with liver biopsy. Hepatology. 2016;63:1817–27.CrossRefPubMed Cassinotto C, Boursier J, de Ledinghen V, Lebigot J, Lapuyade B, Cales P, Hiriart JB, Michalak S, Bail BL, Cartier V, Mouries A, Oberti F, Fouchard-Hubert I, Vergniol J, Aube C. Liver stiffness in nonalcoholic fatty liver disease: A comparison of supersonic shear imaging, FibroScan, and ARFI with liver biopsy. Hepatology. 2016;63:1817–27.CrossRefPubMed
19.
go back to reference Yoneda M, Thomas E, Sclair SN, Grant TT, Schiff ER. Supersonic shear imaging and transient elastography with the XL probe accurately detect fibrosis in overweight or obese patients with chronic liver disease. Clin Gastroenterol Hepatol. 2015;13:1502–9.CrossRefPubMed Yoneda M, Thomas E, Sclair SN, Grant TT, Schiff ER. Supersonic shear imaging and transient elastography with the XL probe accurately detect fibrosis in overweight or obese patients with chronic liver disease. Clin Gastroenterol Hepatol. 2015;13:1502–9.CrossRefPubMed
20.
go back to reference Decaris ML, Li KW, Emson CL, Gatmaitan M, Liu S, Wang Y, Nyangau E, Colangelo M, Angel TE, Beysen C, Cui J, Hernandez C, Lazaro L, Brenner DA, Turner SM, Hellerstein MK, Loomba R. Identifying nonalcoholic fatty liver disease patients with active fibrosis by measuring extracellular matrix remodeling rates in tissue and blood. Hepatology. 2017;65:78–88.CrossRefPubMed Decaris ML, Li KW, Emson CL, Gatmaitan M, Liu S, Wang Y, Nyangau E, Colangelo M, Angel TE, Beysen C, Cui J, Hernandez C, Lazaro L, Brenner DA, Turner SM, Hellerstein MK, Loomba R. Identifying nonalcoholic fatty liver disease patients with active fibrosis by measuring extracellular matrix remodeling rates in tissue and blood. Hepatology. 2017;65:78–88.CrossRefPubMed
21.
go back to reference Neuschwander-Tetri BA. Hepatic lipotoxicity and the pathogenesis of nonalcoholic steatohepatitis: the central role of nontriglyceride fatty acid metabolites. Hepatology. 2010;52:774–88.CrossRefPubMed Neuschwander-Tetri BA. Hepatic lipotoxicity and the pathogenesis of nonalcoholic steatohepatitis: the central role of nontriglyceride fatty acid metabolites. Hepatology. 2010;52:774–88.CrossRefPubMed
22.
go back to reference Cusi K. Role of obesity and lipotoxicity in the development of nonalcoholic steatohepatitis: pathophysiology and clinical implications. Gastroenterology. 2012;142:711–25.CrossRefPubMed Cusi K. Role of obesity and lipotoxicity in the development of nonalcoholic steatohepatitis: pathophysiology and clinical implications. Gastroenterology. 2012;142:711–25.CrossRefPubMed
23.
go back to reference Szabo G, Petrasek J. Inflammasome activation and function in liver disease. Nat Rev Gastroenterol Hepatol. 2015;12:387–400.CrossRefPubMed Szabo G, Petrasek J. Inflammasome activation and function in liver disease. Nat Rev Gastroenterol Hepatol. 2015;12:387–400.CrossRefPubMed
24.
go back to reference Machado MV, Diehl AM. Pathogenesis of nonalcoholic steatohepatitis. Gastroenterology. 2016;150:1769–77.CrossRefPubMed Machado MV, Diehl AM. Pathogenesis of nonalcoholic steatohepatitis. Gastroenterology. 2016;150:1769–77.CrossRefPubMed
25.
go back to reference Hirsova P, Ibrahim SH, Gores GJ, Malhi H. Lipotoxic lethal and sublethal stress signaling in hepatocytes: relevance to NASH pathogenesis. J Lipid Res. 2016;57:1758–70.CrossRefPubMed Hirsova P, Ibrahim SH, Gores GJ, Malhi H. Lipotoxic lethal and sublethal stress signaling in hepatocytes: relevance to NASH pathogenesis. J Lipid Res. 2016;57:1758–70.CrossRefPubMed
26.
go back to reference Ertunc ME, Hotamisligil GS. Lipid signaling and lipotoxicity in metabolic inflammation: indications for metabolic disease pathogenesis and treatment. J Lipid Res. 2016;57:2099–114.CrossRefPubMed Ertunc ME, Hotamisligil GS. Lipid signaling and lipotoxicity in metabolic inflammation: indications for metabolic disease pathogenesis and treatment. J Lipid Res. 2016;57:2099–114.CrossRefPubMed
27.
go back to reference Bouret S, Levin BE, Ozanne SE. Gene-environment interactions controlling energy and glucose homeostasis and the developmental origins of obesity. Physiol Rev. 2015;95:47–82.CrossRefPubMedPubMedCentral Bouret S, Levin BE, Ozanne SE. Gene-environment interactions controlling energy and glucose homeostasis and the developmental origins of obesity. Physiol Rev. 2015;95:47–82.CrossRefPubMedPubMedCentral
28.
go back to reference Vilar-Gomez E, Martinez-Perez Y, Calzadilla-Bertot L, Torres-Gonzalez A, Gra-Oramas B, Gonzalez-Fabian L, Friedman SL, Diago M, Romero-Gomez M. Weight loss through lifestyle modification significantly reduces features of nonalcoholic steatohepatitis. Gastroenterology. 2015;149:367–78.CrossRefPubMed Vilar-Gomez E, Martinez-Perez Y, Calzadilla-Bertot L, Torres-Gonzalez A, Gra-Oramas B, Gonzalez-Fabian L, Friedman SL, Diago M, Romero-Gomez M. Weight loss through lifestyle modification significantly reduces features of nonalcoholic steatohepatitis. Gastroenterology. 2015;149:367–78.CrossRefPubMed
29.
go back to reference Zelber-Sagi S, Godos J, Salomone F. Lifestyle changes for the treatment of nonalcoholic fatty liver disease: a review of observational studies and intervention trials. Therap Adv Gastroenterol. 2016;9:392–407.CrossRefPubMedPubMedCentral Zelber-Sagi S, Godos J, Salomone F. Lifestyle changes for the treatment of nonalcoholic fatty liver disease: a review of observational studies and intervention trials. Therap Adv Gastroenterol. 2016;9:392–407.CrossRefPubMedPubMedCentral
30.
go back to reference Orci LA, Gariani K, Oldani G, Delaune V, Morel P, Toso C. Exercise-based interventions for nonalcoholic fatty liver disease: A meta-analysis and meta-regression. Clin Gastroenterol Hepatol. 2016;14:1398–411.CrossRefPubMed Orci LA, Gariani K, Oldani G, Delaune V, Morel P, Toso C. Exercise-based interventions for nonalcoholic fatty liver disease: A meta-analysis and meta-regression. Clin Gastroenterol Hepatol. 2016;14:1398–411.CrossRefPubMed
31.
go back to reference Hannah Jr WN, Harrison SA. Lifestyle and dietary interventions in the management of nonalcoholic fatty liver disease. Dig Dis Sci. 2016;61:1365–74.CrossRefPubMed Hannah Jr WN, Harrison SA. Lifestyle and dietary interventions in the management of nonalcoholic fatty liver disease. Dig Dis Sci. 2016;61:1365–74.CrossRefPubMed
32.
go back to reference Africa JA, Newton KP, Schwimmer JB. Lifestyle interventions including nutrition, exercise, and supplements for nonalcoholic fatty liver disease in children. Dig Dis Sci. 2016;61:1375–86.CrossRefPubMed Africa JA, Newton KP, Schwimmer JB. Lifestyle interventions including nutrition, exercise, and supplements for nonalcoholic fatty liver disease in children. Dig Dis Sci. 2016;61:1375–86.CrossRefPubMed
33.
go back to reference Abenavoli L, Milic N, Peta V, Alfieri F, De Lorenzo A, Bellentani S. Alimentary regimen in non-alcoholic fatty liver disease: Mediterranean diet. World J Gastroenterol. 2014;20:16831–40.CrossRefPubMedPubMedCentral Abenavoli L, Milic N, Peta V, Alfieri F, De Lorenzo A, Bellentani S. Alimentary regimen in non-alcoholic fatty liver disease: Mediterranean diet. World J Gastroenterol. 2014;20:16831–40.CrossRefPubMedPubMedCentral
34.
go back to reference Lassailly G, Caiazzo R, Buob D, Pigeyre M, Verkindt H, Labreuche J, Raverdy V, Leteurtre E, Dharancy S, Louvet A, Romon M, Duhamel A, Pattou F, Mathurin P. Bariatric surgery reduces features of nonalcoholic steatohepatitis in morbidly obese patients. Gastroenterology. 2015;149:379–88.CrossRefPubMed Lassailly G, Caiazzo R, Buob D, Pigeyre M, Verkindt H, Labreuche J, Raverdy V, Leteurtre E, Dharancy S, Louvet A, Romon M, Duhamel A, Pattou F, Mathurin P. Bariatric surgery reduces features of nonalcoholic steatohepatitis in morbidly obese patients. Gastroenterology. 2015;149:379–88.CrossRefPubMed
35.
go back to reference Corey KE, Rinella ME. Medical and surgical treatment options for nonalcoholic steatohepatitis. Dig Dis Sci. 2016;61:1387–97.CrossRefPubMed Corey KE, Rinella ME. Medical and surgical treatment options for nonalcoholic steatohepatitis. Dig Dis Sci. 2016;61:1387–97.CrossRefPubMed
37.
go back to reference Musso G, Cassader M, Gambino R. Non-alcoholic steatohepatitis: emerging molecular targets and therapeutic strategies. Nat Rev Drug Discov. 2016;15:249–74.CrossRefPubMed Musso G, Cassader M, Gambino R. Non-alcoholic steatohepatitis: emerging molecular targets and therapeutic strategies. Nat Rev Drug Discov. 2016;15:249–74.CrossRefPubMed
38.
go back to reference Sanyal AJ, Chalasani N, Kowdley KV, McCullough A, Diehl AM, Bass NM, Neuschwander-Tetri BA, Lavine JE, Tonascia J, Unalp A, Van Natta M, Clark J, Brunt EM, Kleiner DE, Hoofnagle JH, Robuck PR, for the NASH CRN. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med. 2010;362:1675–85.CrossRefPubMedPubMedCentral Sanyal AJ, Chalasani N, Kowdley KV, McCullough A, Diehl AM, Bass NM, Neuschwander-Tetri BA, Lavine JE, Tonascia J, Unalp A, Van Natta M, Clark J, Brunt EM, Kleiner DE, Hoofnagle JH, Robuck PR, for the NASH CRN. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med. 2010;362:1675–85.CrossRefPubMedPubMedCentral
39.
go back to reference Cusi K, Orsak B, Bril F, Lomonaco R, Hecht J, Ortiz-Lopez C, Tio F, Hardies J, Darland C, Musi N, Webb A, Portillo-Sanchez P. Long-term pioglitazone treatment for patients with nonalcoholic steatohepatitis and prediabetes or type 2 diabetes mellitus: a randomized trial. Ann Intern Med. 2016;165:305–15.CrossRefPubMed Cusi K, Orsak B, Bril F, Lomonaco R, Hecht J, Ortiz-Lopez C, Tio F, Hardies J, Darland C, Musi N, Webb A, Portillo-Sanchez P. Long-term pioglitazone treatment for patients with nonalcoholic steatohepatitis and prediabetes or type 2 diabetes mellitus: a randomized trial. Ann Intern Med. 2016;165:305–15.CrossRefPubMed
40.
go back to reference Sanyal AJ, Friedman SL, McCullough AJ, Dimick-Santos L. Challenges and opportunities in drug and biomarker development for nonalcoholic steatohepatitis: findings and recommendations from an American Association for the Study of Liver Diseases-U.S. Food and Drug Administration Joint Workshop. Hepatology. 2015;61:1392–405.CrossRefPubMedPubMedCentral Sanyal AJ, Friedman SL, McCullough AJ, Dimick-Santos L. Challenges and opportunities in drug and biomarker development for nonalcoholic steatohepatitis: findings and recommendations from an American Association for the Study of Liver Diseases-U.S. Food and Drug Administration Joint Workshop. Hepatology. 2015;61:1392–405.CrossRefPubMedPubMedCentral
41.
go back to reference Ratziu V, Harrison SA, Francque S, Bedossa P, Lehert P, Serfaty L, Romero-Gomez M, Boursier J, Abdelmalek M, Caldwell S, Drenth J, Anstee QM, Hum D, Hanf R, Roudot A, Megnien S, Staels B, Sanyal A, on behalf of the Golden-505 Investigator Study Group. Elafibranor, an agonist of the peroxisome proliferator-activated receptor-α and -δ, induces resolution of nonalcoholic steatohepatitis without fibrosis worsening. Gastroenterology. 2016;150:1147–59.CrossRefPubMed Ratziu V, Harrison SA, Francque S, Bedossa P, Lehert P, Serfaty L, Romero-Gomez M, Boursier J, Abdelmalek M, Caldwell S, Drenth J, Anstee QM, Hum D, Hanf R, Roudot A, Megnien S, Staels B, Sanyal A, on behalf of the Golden-505 Investigator Study Group. Elafibranor, an agonist of the peroxisome proliferator-activated receptor-α and -δ, induces resolution of nonalcoholic steatohepatitis without fibrosis worsening. Gastroenterology. 2016;150:1147–59.CrossRefPubMed
42.
go back to reference Neuschwander-Tetri BA, Loomba R, Sanyal AJ, Lavine JE, Van Natta ML, Abdelmalek MF, Chalasani N, Dasarathy S, Diehl AM, Hameed B, Kowdley KV, McCullough A, Terrault N, Clark JM, Tonascia J, Brunt EM, Kleiner DE, Doo E, for the Nash Clinical Research Network. Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo-controlled trial. Lancet. 2015;385:956–65.CrossRefPubMed Neuschwander-Tetri BA, Loomba R, Sanyal AJ, Lavine JE, Van Natta ML, Abdelmalek MF, Chalasani N, Dasarathy S, Diehl AM, Hameed B, Kowdley KV, McCullough A, Terrault N, Clark JM, Tonascia J, Brunt EM, Kleiner DE, Doo E, for the Nash Clinical Research Network. Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo-controlled trial. Lancet. 2015;385:956–65.CrossRefPubMed
43.
go back to reference Armstrong MJ, Gaunt P, Aithal GP, Barton D, Hull D, Parker R, Hazlehurst JM, Guo K, team Lt, Abouda G, Aldersley MA, Stocken D, Gough SC, Tomlinson JW, Brown RM, Hubscher SG, Newsome PN. Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (LEAN): a multicentre, double-blind, randomised, placebo-controlled phase 2 study. Lancet. 2016;387:679–90.CrossRefPubMed Armstrong MJ, Gaunt P, Aithal GP, Barton D, Hull D, Parker R, Hazlehurst JM, Guo K, team Lt, Abouda G, Aldersley MA, Stocken D, Gough SC, Tomlinson JW, Brown RM, Hubscher SG, Newsome PN. Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (LEAN): a multicentre, double-blind, randomised, placebo-controlled phase 2 study. Lancet. 2016;387:679–90.CrossRefPubMed
44.
go back to reference Cui J, Philo L, Nguyen P, Hofflich H, Hernandez C, Bettencourt R, Richards L, Salotti J, Bhatt A, Hooker J, Haufe W, Hooker C, Brenner DA, Sirlin CB, Loomba R. Sitagliptin vs. placebo for non-alcoholic fatty liver disease: A randomized controlled trial. J Hepatol. 2016;65:369–76.CrossRefPubMed Cui J, Philo L, Nguyen P, Hofflich H, Hernandez C, Bettencourt R, Richards L, Salotti J, Bhatt A, Hooker J, Haufe W, Hooker C, Brenner DA, Sirlin CB, Loomba R. Sitagliptin vs. placebo for non-alcoholic fatty liver disease: A randomized controlled trial. J Hepatol. 2016;65:369–76.CrossRefPubMed
45.
go back to reference Wree A, Mehal WZ, Feldstein AE. Targeting cell death and sterile inflammation loop for the treatment of nonalcoholic steatohepatitis. Semin Liver Dis. 2016;36:27–36.CrossRefPubMedPubMedCentral Wree A, Mehal WZ, Feldstein AE. Targeting cell death and sterile inflammation loop for the treatment of nonalcoholic steatohepatitis. Semin Liver Dis. 2016;36:27–36.CrossRefPubMedPubMedCentral
46.
go back to reference Zein CO, Yerian LM, Gogate P, Lopez R, Kirwan JP, Feldstein AE, McCullough AJ. Pentoxifylline improves nonalcoholic steatohepatitis: a randomized placebo-controlled trial. Hepatology. 2011;54:1610–9.CrossRefPubMedPubMedCentral Zein CO, Yerian LM, Gogate P, Lopez R, Kirwan JP, Feldstein AE, McCullough AJ. Pentoxifylline improves nonalcoholic steatohepatitis: a randomized placebo-controlled trial. Hepatology. 2011;54:1610–9.CrossRefPubMedPubMedCentral
47.
go back to reference Ratziu V, Bedossa P, Francque SM, Larrey D, Aithal GP, Serfaty L, Voiculescu M, Preotescu L, Nevens F, De Lédinghen V, Kirchner GI, Trunecka P, Ryder SD, Day CP, Takeda J, Traudtner K. Lack of efficacy of an inhibitor of PDE4 in phase 1 and 2 trials of patients with nonalcoholic steatohepatitis. Clin Gastroenterol Hepatol. 2014;12:1724–30.CrossRefPubMed Ratziu V, Bedossa P, Francque SM, Larrey D, Aithal GP, Serfaty L, Voiculescu M, Preotescu L, Nevens F, De Lédinghen V, Kirchner GI, Trunecka P, Ryder SD, Day CP, Takeda J, Traudtner K. Lack of efficacy of an inhibitor of PDE4 in phase 1 and 2 trials of patients with nonalcoholic steatohepatitis. Clin Gastroenterol Hepatol. 2014;12:1724–30.CrossRefPubMed
48.
go back to reference Sanyal A, Ratziu V, Harrison S, Abdelmalek M, Aithal GP, Caballeria J, Francque SM, Farrell GC, Kowdley KV, Craxi A, Krzysztof S, Fischer L, Melchor-Khan L, Vest J, Weins BL, Vig P, Seyedkazem S, Goodman ZD, Wong VW, Loomba R, Tacke F, Friedman SL, Lefebvre E. Cenicriviroc placebo for the treatment of non-alcoholic steatohepatitis with liver fibrosis: Results from the year 1 primary analysis of the phase 2b CENTAUR study (abstract). Hepatology. 2016;64:1118A.CrossRef Sanyal A, Ratziu V, Harrison S, Abdelmalek M, Aithal GP, Caballeria J, Francque SM, Farrell GC, Kowdley KV, Craxi A, Krzysztof S, Fischer L, Melchor-Khan L, Vest J, Weins BL, Vig P, Seyedkazem S, Goodman ZD, Wong VW, Loomba R, Tacke F, Friedman SL, Lefebvre E. Cenicriviroc placebo for the treatment of non-alcoholic steatohepatitis with liver fibrosis: Results from the year 1 primary analysis of the phase 2b CENTAUR study (abstract). Hepatology. 2016;64:1118A.CrossRef
49.
51.
go back to reference Sevgi M, Rigoux L, Kühn AB, Mauer J, Schilbach L, Hess ME, Gruendler TO, Ullsperger M, Stephan KE, Brüning JC, Tittgemeyer M. An obesity-predisposing variant of the FTO gene regulates D2R-dependent reward learning. J Neurosci. 2015;35:12584–92.CrossRefPubMed Sevgi M, Rigoux L, Kühn AB, Mauer J, Schilbach L, Hess ME, Gruendler TO, Ullsperger M, Stephan KE, Brüning JC, Tittgemeyer M. An obesity-predisposing variant of the FTO gene regulates D2R-dependent reward learning. J Neurosci. 2015;35:12584–92.CrossRefPubMed
52.
go back to reference Acosta A, Camilleri M, Shin A, Vazquez-Roque MI, Iturrino J, Burton D, O'Neill J, Eckert D, Zinsmeister AR. Quantitative gastrointestinal and psychological traits associated with obesity and response to weight-loss therapy. Gastroenterology. 2015;148:537–46.CrossRefPubMed Acosta A, Camilleri M, Shin A, Vazquez-Roque MI, Iturrino J, Burton D, O'Neill J, Eckert D, Zinsmeister AR. Quantitative gastrointestinal and psychological traits associated with obesity and response to weight-loss therapy. Gastroenterology. 2015;148:537–46.CrossRefPubMed
Metadata
Title
Non-alcoholic fatty liver disease
Author
Brent A. Neuschwander-Tetri
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Medicine / Issue 1/2017
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/s12916-017-0806-8

Other articles of this Issue 1/2017

BMC Medicine 1/2017 Go to the issue