Association of Weight Loss Interventions With Changes in Biomarkers of Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-analysis

Dimitrios A Koutoukidis, Nerys M Astbury, Kate E Tudor, Elizabeth Morris, John A Henry, Michaela Noreik, Susan A Jebb, Paul Aveyard, Dimitrios A Koutoukidis, Nerys M Astbury, Kate E Tudor, Elizabeth Morris, John A Henry, Michaela Noreik, Susan A Jebb, Paul Aveyard

Abstract

Importance: Nonalcoholic fatty liver disease (NAFLD) affects about 25% of adults worldwide and is associated with obesity. Weight loss may improve biomarkers of liver disease, but its implications have not been systematically reviewed and quantified.

Objective: To estimate the association of weight loss interventions with biomarkers of liver disease in NAFLD.

Data sources: MEDLINE, Embase, PsycINFO, CINAHL, Cochrane, and Web of Science databases along with 3 trial registries were searched from inception through January 2019.

Study selection: Randomized clinical trials of people with NAFLD were included if they compared any intervention aiming to reduce weight (behavioral weight loss programs [BWLPs], pharmacotherapy, and surgical procedures) with no or lower-intensity weight loss intervention. The review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines.

Data extraction and synthesis: Two independent reviewers screened the studies, extracted the data, and assessed the risk of bias using the Cochrane tool. Pooled mean differences or odds ratios (ORs) were obtained from random-effects meta-analyses.

Main outcomes and measures: Blood, radiologic, and histologic biomarkers of liver disease.

Results: Twenty-two studies with 2588 participants (with a mean [SD] age of 45 [14] years and with approximately 66% male) were included. Fifteen studies tested BWLPs, 6 tested pharmacotherapy, and 1 tested a surgical procedure. The median (interquartile range) intervention duration was 6 (3-8) months. Compared with no or lower-intensity weight loss interventions, more-intensive weight loss interventions were statistically significantly associated with greater weight change (-3.61 kg; 95% CI, -5.11 to -2.12; I2 = 95%). Weight loss interventions were statistically significantly associated with improvements in biomarkers, including alanine aminotransferase (-9.81 U/L; 95% CI, -13.12 to -6.50; I2 = 97%), histologically or radiologically measured liver steatosis (standardized mean difference: -1.48; 95% CI, -2.27 to -0.70; I2 = 94%), histologic NAFLD activity score (-0.92; 95% CI, -1.75 to -0.09; I2 = 95%), and presence of nonalcoholic steatohepatitis (OR, 0.14; 95% CI, 0.04-0.49; I2 = 0%). No statistically significant change in histologic liver fibrosis was found (-0.13; 95% CI, -0.54 to 0.27; I2 = 68%). Twelve studies were at high risk of bias in at least 1 domain. In a sensitivity analysis of the 3 trials at low risk of bias, the estimates and precision of most outcomes did not materially change.

Conclusions and relevance: The trials, despite some heterogeneity, consistently showed evidence of the association between weight loss interventions and improved biomarkers of liver disease in NAFLD in the short to medium term, although evidence on long-term health outcomes was limited. These findings appear to support the need to change the clinical guidelines and to recommend formal weight loss programs for people with NAFLD.

Conflict of interest statement

Conflict of Interest Disclosures: Drs Astbury, Jebb, and Aveyard reported receiving grants from Cambridge Weight Plan outside of the submitted work. No other disclosures were reported.

Figures

Figure 1.. Association Between Weight Loss Intervention…
Figure 1.. Association Between Weight Loss Intervention (WLI) and Weight Loss (WL)
D indicates diet group; D+E, diet and exercise group; L, low-intensity intervention group; LF, low-fat diet group; M, moderate-intensity intervention group; and MF, moderate-fat diet group.
Figure 2.. Association Between Weight Loss Intervention…
Figure 2.. Association Between Weight Loss Intervention (WLI) and Alanine Aminotransferase (ALT)
D indicates diet group; D+E, diet and exercise group; L, low-intensity intervention group; LF, low-fat diet group; M, moderate-intensity intervention group; and MF, moderate-fat diet group.
Figure 3.. Association Between Weight Loss Intervention…
Figure 3.. Association Between Weight Loss Intervention (WLI) and Liver Steatosis
Standardized mean difference was assessed by histologic examination, magnetic resonance imaging, or ultrasonography. D indicates diet group; D+E, diet and exercise group.
Figure 4.. Association Between Weight Loss Intervention…
Figure 4.. Association Between Weight Loss Intervention (WLI) and NAS (Nonalcoholic Fatty Liver Disease Activity Score)
The NAS range is 0-8, with the highest score indicating more severe disease. LF indicates low-fat diet group; MF, moderate-fat diet group.

References

    1. Younossi Z, Anstee QM, Marietti M, et al. . Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol. 2018;15(1):11-20. doi:10.1038/nrgastro.2017.109
    1. Polyzos SA, Kountouras J, Mantzoros CS. Obesity and nonalcoholic fatty liver disease: from pathophysiology to therapeutics. Metabolism. 2019;92:82-97. doi:10.1016/j.metabol.2018.11.014
    1. Leung JC, Loong TC, Wei JL, et al. . Histological severity and clinical outcomes of nonalcoholic fatty liver disease in nonobese patients. Hepatology. 2017;65(1):54-64. doi:10.1002/hep.28697
    1. Younossi ZM, Blissett D, Blissett R, et al. . The economic and clinical burden of nonalcoholic fatty liver disease in the United States and Europe. Hepatology. 2016;64(5):1577-1586. doi:10.1002/hep.28785
    1. Targher G, Byrne CD, Lonardo A, Zoppini G, Barbui C. Non-alcoholic fatty liver disease and risk of incident cardiovascular disease: a meta-analysis. J Hepatol. 2016;65(3):589-600. doi:10.1016/j.jhep.2016.05.013
    1. Dyson J, Jaques B, Chattopadyhay D, et al. . Hepatocellular cancer: the impact of obesity, type 2 diabetes and a multidisciplinary team. J Hepatol. 2014;60(1):110-117. doi:10.1016/j.jhep.2013.08.011
    1. Noureddin M, Vipani A, Bresee C, et al. . NASH leading cause of liver transplant in women: updated analysis of indications for liver transplant and ethnic and gender variances. Am J Gastroenterol. 2018;113(11):1649-1659. doi:10.1038/s41395-018-0088-6
    1. Ekstedt M, Hagström H, Nasr P, et al. . Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up. Hepatology. 2015;61(5):1547-1554. doi:10.1002/hep.27368
    1. Angulo P, Kleiner DE, Dam-Larsen S, et al. . Liver fibrosis, but no other histologic features, is associated with long-term outcomes of patients with nonalcoholic fatty liver disease. Gastroenterology. 2015;149(2):389-97.e10. doi:10.1053/j.gastro.2015.04.043
    1. Chalasani N, Younossi Z, Lavine JE, et al. . The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2018;67(1):328-357. doi:10.1002/hep.29367
    1. 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(6):1388-1402. doi:10.1016/j.jhep.2015.11.004
    1. NICE Non-Alcoholic Fatty Liver Disease (NAFLD): Assessment and Management. London, UK: National Institute for Health and Care Excellence; 2016.
    1. Italian Association for the Study of the Liver (AISF) AISF position paper on nonalcoholic fatty liver disease (NAFLD): updates and future directions. Dig Liver Dis. 2017;49(5):471-483. doi:10.1016/j.dld.2017.01.147
    1. Chitturi S, Wong VW, Chan WK, et al. . The Asia-Pacific Working Party on Non-alcoholic Fatty Liver Disease guidelines 2017–part 2: management and special groups. J Gastroenterol Hepatol. 2018;33(1):86-98. doi:10.1111/jgh.13856
    1. Sheridan DA, Aithal G, Alazawi W, et al. . Care standards for non-alcoholic fatty liver disease in the United Kingdom 2016: a cross-sectional survey. Frontline Gastroenterol. 2017;8(4):252-259. doi:10.1136/flgastro-2017-100806
    1. Sisti LG, Dajko M, Campanella P, Shkurti E, Ricciardi W, de Waure C. The effect of multifactorial lifestyle interventions on cardiovascular risk factors: a systematic review and meta-analysis of trials conducted in the general population and high risk groups. Prev Med. 2018;109:82-97. doi:10.1016/j.ypmed.2017.12.027
    1. Yanovski SZ, Yanovski JA. Long-term drug treatment for obesity: a systematic and clinical review. JAMA. 2014;311(1):74-86. doi:10.1001/jama.2013.281361
    1. Zhou X, Yu J, Li L, et al. . Effects of bariatric surgery on mortality, cardiovascular events, and cancer outcomes in obese patients: systematic review and meta-analysis. Obes Surg. 2016;26(11):2590-2601. doi:10.1007/s11695-016-2144-x
    1. Peng L, Wang J, Li F. Weight reduction for non-alcoholic fatty liver disease. Cochrane Database Syst Rev. 2011;(6):CD003619.
    1. Paris T, George ES, Roberts SK, Tierney AC. The effects of diet and lifestyle interventions on insulin resistance in patients with nonalcoholic fatty liver disease: a systematic review. Eur J Gastroenterol Hepatol. 2017;29(8):867-878. doi:10.1097/MEG.0000000000000890
    1. Kenneally S, Sier JH, Moore JB. Efficacy of dietary and physical activity intervention in non-alcoholic fatty liver disease: a systematic review. BMJ Open Gastroenterol. 2017;4(1):e000139. doi:10.1136/bmjgast-2017-000139
    1. Katsagoni CN, Georgoulis M, Papatheodoridis GV, Panagiotakos DB, Kontogianni MD. Effects of lifestyle interventions on clinical characteristics of patients with non-alcoholic fatty liver disease: a meta-analysis. Metabolism. 2017;68:119-132. doi:10.1016/j.metabol.2016.12.006
    1. Moher D, Liberati A, Tetzlaff J, Altman DG, Group P; PRISMA Group . Preferred Reporting Items for Systematic Reviews and Meta-analyses: the PRISMA statement. PLoS Med. 2009;6(7):e1000097. doi:10.1371/journal.pmed.1000097
    1. Cochrane. Covidence systematic review software. . Accessed April 15, 2019.
    1. Higgins JPT, Green S, eds. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0. . Updated March 2011. Accessed April 15, 2019.
    1. Collaboration NCDRF; NCD Risk Factor Collaboration (NCD-RisC) . A century of trends in adult human height. Elife. 2016;5:e13410. doi:10.7554/eLife.13410
    1. Lim SL, Loo WM, Ong KW, et al. . Lifestyle intervention enabled by mobile technologies leading to weight loss in patients with non-alcoholic fatty liver disease: a randomized controlled trial. J Gastroenterol Hepatol. 2018;33(suppl 4):94.
    1. Ye J, Yanqin W, Xuan H, Bihui Z. Effect of orlistat on total liver fat quantification by novel magnetic resonance imaging in obese patients with non-alcoholic steatohepatitis: interim analysis of a prospective, randomized, single-center, open-label trial. United European Gastroenterol J. 2017;5(suppl 1):A625.
    1. Asghari S, Asghari-Jafarabadi M, Somi MH, Ghavami SM, Rafraf M. Comparison of calorie-restricted diet and resveratrol supplementation on anthropometric indices, metabolic parameters, and serum sirtuin-1 levels in patients with nonalcoholic fatty liver disease: a randomized controlled clinical trial. J Am Coll Nutr. 2018;37(3):223-233. doi:10.1080/07315724.2017.1392264
    1. Bahmanabadi Z, Ebrahimi-Mamghani M, Arefhosseini SR. Comparison of low-calorie diet with and without sibutramine on body weight and liver function of patients with non-alcoholic fatty liver disease [in Persian]. Armaghane-Danesh. 2011;16(2):101-110.
    1. Cheng S, Ge J, Zhao C, et al. . Effect of aerobic exercise and diet on liver fat in pre-diabetic patients with non-alcoholic-fatty-liver-disease: a randomized controlled trial. Sci Rep. 2017;7(1):15952. doi:10.1038/s41598-017-16159-x
    1. Dong F, Zhang Y, Huang Y, et al. . Long-term lifestyle interventions in middle-aged and elderly men with nonalcoholic fatty liver disease: a randomized controlled trial. Sci Rep. 2016;6:36783. doi:10.1038/srep36783
    1. Selezneva KS, Isakov VA, Sentsova TB, Kirillova OO. An analysis of the efficacy of low-calorie and isocaloric diets in obese patients with nonalcoholic steatohepatitis [in Russian]. Vopr Pitan. 2014;83(5):72-78.
    1. Sun WH, Song MQ, Jiang CQ, et al. . Lifestyle intervention in non-alcoholic fatty liver disease in Chengyang District, Qingdao, China. World J Hepatol. 2012;4(7):224-230. doi:10.4254/wjh.v4.i7.224
    1. Abd El-Kader SM, Al-Shreef FM, Al-Jiffri OH. Biochemical parameters response to weight loss in patients with non-alcoholic steatohepatitis. Afr Health Sci. 2016;16(1):242-249. doi:10.4314/ahs.v16i1.32
    1. Abenavoli L, Greco M, Milic N, et al. . Effect of Mediterranean diet and antioxidant formulation in non-alcoholic fatty liver disease: a randomized study. Nutrients. 2017;9(8):E870. doi:10.3390/nu9080870
    1. Al-Jiffri O, Al-Sharif FM, Abd El-Kader SM, Ashmawy EM. Weight reduction improves markers of hepatic function and insulin resistance in type-2 diabetic patients with non-alcoholic fatty liver. Afr Health Sci. 2013;13(3):667-672.
    1. Armstrong MJ, Gaunt P, Aithal GP, et al. ; LEAN trial team . Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (LEAN): a multicentre, double-blind, randomised, placebo-controlled phase 2 study. Lancet. 2016;387(10019):679-690. doi:10.1016/S0140-6736(15)00803-X
    1. Axley P, Kodali S, Kuo YF, et al. . Text messaging approach improves weight loss in patients with nonalcoholic fatty liver disease: a randomized study. Liver Int. 2018;38(5):924-931. doi:10.1111/liv.13622
    1. Eckard C, Cole R, Lockwood J, et al. . Prospective histopathologic evaluation of lifestyle modification in nonalcoholic fatty liver disease: a randomized trial. Therap Adv Gastroenterol. 2013;6(4):249-259. doi:10.1177/1756283X13484078
    1. Harrison SA, Fecht W, Brunt EM, Neuschwander-Tetri BA. Orlistat for overweight subjects with nonalcoholic steatohepatitis: a randomized, prospective trial. Hepatology. 2009;49(1):80-86. doi:10.1002/hep.22575
    1. Katsagoni CN, Papatheodoridis GV, Ioannidou P, et al. . Improvements in clinical characteristics of patients with non-alcoholic fatty liver disease, after an intervention based on the Mediterranean lifestyle: a randomised controlled clinical trial. Br J Nutr. 2018;120(2):164-175. doi:10.1017/S000711451800137X
    1. Khoo J, Hsiang J, Taneja R, Law NM, Ang TL. Comparative effects of liraglutide 3 mg vs structured lifestyle modification on body weight, liver fat and liver function in obese patients with non-alcoholic fatty liver disease: a pilot randomized trial. Diabetes Obes Metab. 2017;19(12):1814-1817. doi:10.1111/dom.13007
    1. Lee YM, Low HC, Lim LG, et al. . Intragastric balloon significantly improves nonalcoholic fatty liver disease activity score in obese patients with nonalcoholic steatohepatitis: a pilot study. Gastrointest Endosc. 2012;76(4):756-760. doi:10.1016/j.gie.2012.05.023
    1. Promrat K, Kleiner DE, Niemeier HM, et al. . Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis. Hepatology. 2010;51(1):121-129. doi:10.1002/hep.23276
    1. St George A, Bauman A, Johnston A, Farrell G, Chey T, George J. Effect of a lifestyle intervention in patients with abnormal liver enzymes and metabolic risk factors. J Gastroenterol Hepatol. 2009;24(3):399-407. doi:10.1111/j.1440-1746.2008.05694.x
    1. Wong VW, Chan RS, Wong GL, et al. . Community-based lifestyle modification programme for non-alcoholic fatty liver disease: a randomized controlled trial. J Hepatol. 2013;59(3):536-542. doi:10.1016/j.jhep.2013.04.013
    1. Zelber-Sagi S, Kessler A, Brazowsky E, et al. . A double-blind randomized placebo-controlled trial of orlistat for the treatment of nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2006;4(5):639-644. doi:10.1016/j.cgh.2006.02.004
    1. Khoo J, Hsiang J, Law N, Tao C, Ang T. Effects of lifestyle modification– versus liraglutide-induced weight loss and subsequent weight maintenance on hepatic steatosis and inflammation in obese adults with non-alcoholic fatty liver disease. Obes Facts. 2018;11(suppl 1):238-239.
    1. Wong VW, Wong GL, Chan RS, et al. . Beneficial effects of lifestyle intervention in non-obese patients with non-alcoholic fatty liver disease. J Hepatol. 2018;69(6):1349-1356. doi:10.1016/j.jhep.2018.08.011
    1. Sumida Y, Nakajima A, Itoh Y. Limitations of liver biopsy and non-invasive diagnostic tests for the diagnosis of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. World J Gastroenterol. 2014;20(2):475-485. doi:10.3748/wjg.v20.i2.475
    1. Willis LH, Slentz CA, Bateman LA, et al. . Effects of aerobic and/or resistance training on body mass and fat mass in overweight or obese adults. J Appl Physiol (1985). 2012;113(12):1831-1837.
    1. Thorogood A, Mottillo S, Shimony A, et al. . Isolated aerobic exercise and weight loss: a systematic review and meta-analysis of randomized controlled trials. Am J Med. 2011;124(8):747-755. doi:10.1016/j.amjmed.2011.02.037
    1. Tobias DK, Chen M, Manson JE, Ludwig DS, Willett W, Hu FB. Effect of low-fat diet interventions versus other diet interventions on long-term weight change in adults: a systematic review and meta-analysis. Lancet Diabetes Endocrinol. 2015;3(12):968-979. doi:10.1016/S2213-8587(15)00367-8
    1. Sargeant JA, Gray LJ, Bodicoat DH, et al. . The effect of exercise training on intrahepatic triglyceride and hepatic insulin sensitivity: a systematic review and meta-analysis. Obes Rev. 2018;19(10):1446-1459. doi:10.1111/obr.12719
    1. Ahn J, Jun DW, Lee HY, Moon JH. Critical appraisal for low-carbohydrate diet in nonalcoholic fatty liver disease: review and meta-analyses. Clin Nutr. 2018;S0261-5614(18)32460-9.
    1. Rinella ME, Lominadze Z, Loomba R, et al. . Practice patterns in NAFLD and NASH: real life differs from published guidelines. Therap Adv Gastroenterol. 2016;9(1):4-12. doi:10.1177/1756283X15611581
    1. Ahern AL, Wheeler GM, Aveyard P, et al. . Extended and standard duration weight-loss programme referrals for adults in primary care (WRAP): a randomised controlled trial. Lancet. 2017;389(10085):2214-2225. doi:10.1016/S0140-6736(17)30647-5
    1. Aveyard P, Lewis A, Tearne S, et al. . Screening and brief intervention for obesity in primary care: a parallel, two-arm, randomised trial. Lancet. 2016;388(10059):2492-2500. doi:10.1016/S0140-6736(16)31893-1
    1. Hartmann-Boyce J, Johns DJ, Jebb SA, Summerbell C, Aveyard P; Behavioural Weight Management Review Group . Behavioural weight management programmes for adults assessed by trials conducted in everyday contexts: systematic review and meta-analysis. Obes Rev. 2014;15(11):920-932. doi:10.1111/obr.12220
    1. Center for Drug Evaluation and Research. Noncirrhotic Nonalcoholic Steatohepatitis With Liver Fibrosis: Developing Drugs for Treatment.U.S. Department of Health and Human Services Food and Drug Administration. . Published December 2018. Accessed March 1, 2019
    1. Ma C, Avenell A, Bolland M, et al. . Effects of weight loss interventions for adults who are obese on mortality, cardiovascular disease, and cancer: systematic review and meta-analysis. BMJ. 2017;359:j4849. doi:10.1136/bmj.j4849
    1. Wing RR, Bolin P, Brancati FL, et al. ; Look AHEAD Research Group . Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. N Engl J Med. 2013;369(2):145-154. doi:10.1056/NEJMoa1212914
    1. Utz-Melere M, Targa-Ferreira C, Lessa-Horta B, Epifanio M, Mouzaki M, Mattos AA. Non-alcoholic fatty liver disease in children and adolescents: lifestyle change—a systematic review and meta-analysis. Ann Hepatol. 2018;17(3):345-354. doi:10.5604/01.3001.0011.7380
    1. Anderson EL, Howe LD, Jones HE, Higgins JP, Lawlor DA, Fraser A. The prevalence of non-alcoholic fatty liver disease in children and adolescents: a systematic review and meta-analysis. PLoS One. 2015;10(10):e0140908. doi:10.1371/journal.pone.0140908

Source: PubMed

Sponzoři a spolupracovníci

Zdravotní podmínky

Drogové intervence

3
Předplatit