Management of NAFLD in primary care settings.
cirrhosis
general practice
liver fibrosis
non-alcoholic fatty liver disease
non-alcoholic steatohepatitis
Journal
Liver international : official journal of the International Association for the Study of the Liver
ISSN: 1478-3231
Titre abrégé: Liver Int
Pays: United States
ID NLM: 101160857
Informations de publication
Date de publication:
11 2022
11 2022
Historique:
revised:
23
07
2022
received:
20
05
2022
accepted:
10
08
2022
pubmed:
21
8
2022
medline:
28
9
2022
entrez:
20
8
2022
Statut:
ppublish
Résumé
Non-alcoholic fatty liver disease (NAFLD) affects at least 25% of the general population and is an increasingly important cause of cirrhosis and hepatocellular carcinoma. Although it is the research focus of the hepatology field, it is clear that primary care physicians are seeing the majority of NAFLD patients and are in a pivotal position to provide quality care. In this article, we review the role of primary care in the management of NAFLD. NAFLD is common in patients with diabetes, obesity and other metabolic risk factors. Abdominal ultrasonography is the most commonly used method to diagnose fatty liver. Simple fibrosis scores have high negative predictive values in excluding advanced liver fibrosis and future liver-related events and can be used in primary care as initial evaluation. An abnormal result should be followed by subsequent workup or specialist referral. Primary care is the ideal setting to institute multidisciplinary care, especially the involvement of dietitians and physical activity trainers in lifestyle intervention, as well as initiating the discussion of bariatric surgery in patients with severe obesity. Although specific drug treatment for steatohepatitis would require a more precise diagnosis, metabolic drugs that improve both steatohepatitis and cardiovascular outcomes (e.g. glucagon-like peptide-1 receptor agonists) may be considered in patients with NAFLD.
Substances chimiques
Glucagon-Like Peptide-1 Receptor
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
2377-2389Informations de copyright
© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Références
Powell EE, Wong VW-S, Rinella M. Non-alcoholic fatty liver disease. Lancet. 2021;397:2212-2224.
Tilg H, Moschen AR. Evolution of inflammation in nonalcoholic fatty liver disease: the multiple parallel hits hypothesis. Hepatology. 2010;52:1836-1846.
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;64:1577-1586.
Karlsen TH, Sheron N, Zelber-Sagi S, et al. The EASL-lancet liver commission: protecting the next generation of Europeans against liver disease complications and premature mortality. Lancet. 2022;399:61-116.
Lazarus JV, Mark HE, Villota-Rivas M, et al. The global NAFLD policy review and preparedness index: are countries ready to address this silent public health challenge? J Hepatol. 2022;76:771-780.
Lazarus JV, Anstee QM, Hagström H, et al. Defining comprehensive models of care for NAFLD. Nat Rev Gastroenterol Hepatol. 2021;18:717-729.
Mantovani A, Csermely A, Petracca G, et al. Non-alcoholic fatty liver disease and risk of fatal and non-fatal cardiovascular events: an updated systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2021;6:903-913.
Mantovani A, Byrne CD, Benfari G, Bonapace S, Simon TG, Targher G. Risk of heart failure in patients with nonalcoholic fatty liver disease: JACC review topic of the week. J Am Coll Cardiol. 2022;79:180-191.
Carrieri P, Mourad A, Marcellin F, et al. Knowledge of liver fibrosis stage among adults with NAFLD/NASH improves adherence to lifestyle changes. Liver Int. 2022;42:984-994. doi:10.1111/liv.15209
Mari A, Omari S, Abu Baker F, et al. Non-alcoholic fatty liver disease: a survey of involvement of primary care physicians. Minerva Gastroenterol Dietol. 2019;65:255-258.
Duell PB, Welty FK, Miller M, et al. Nonalcoholic fatty liver disease and cardiovascular risk: a scientific statement from the American Heart Association. Arterioscler Thromb Vasc Biol. 2022;42:e168-e185.
Santos-Laso A, Gutiérrez-Larrañaga M, Alonso-Peña M, et al. Pathophysiological mechanisms in non-alcoholic fatty liver disease: from drivers to targets. Biomedicine. 2021;10:46.
Mazier W, Saucisse N, Gatta-Cherifi B, Cota D. The endocannabinoid system: pivotal orchestrator of obesity and metabolic disease. Trends Endocrinol Metab. 2015;26:524-537.
Lee MJ, Kim E-H, Bae S-J, et al. Age-related decrease in skeletal muscle mass is an independent risk factor for incident nonalcoholic fatty liver disease: a 10-year retrospective cohort study. Gut Liver. 2019;13:67-76.
Sinn DH, Kang D, Kang M, et al. Nonalcoholic fatty liver disease and accelerated loss of skeletal muscle mass: a longitudinal cohort study. Hepatology. 2022. doi:10.1002/hep.32578
Trayhurn P. Hypoxia and adipocyte physiology: implications for adipose tissue dysfunction in obesity. Annu Rev Nutr. 2014;34:207-236.
Tilg H, Hotamisligil GS. Nonalcoholic fatty liver disease: cytokine-adipokine interplay and regulation of insulin resistance. Gastroenterology. 2006;131:934-945.
Ikejima K, Okumura K, Kon K, Takei Y, Sato N. Role of adipocytokines in hepatic fibrogenesis. J Gastroenterol Hepatol. 2007;22(Suppl 1):S87-S92.
Trauner M, Arrese M, Wagner M. Fatty liver and lipotoxicity. Biochim Biophys Acta. 2010;1801:299-310.
Chaurasia B, Tippetts TS, Mayoral Monibas R, et al. Targeting a ceramide double bond improves insulin resistance and hepatic steatosis. Science. 2019;365:386-392.
Wahlström A, Sayin SI, Marschall H-U, Bäckhed F. Intestinal crosstalk between bile acids and microbiota and its impact on host metabolism. Cell Metab. 2016;24:41-50.
Krautkramer KA, Fan J, Bäckhed F. Gut microbial metabolites as multi-kingdom intermediates. Nat Rev Microbiol. 2021;19:77-94.
de Aguiar Vallim TQ, Tarling EJ, Edwards PA. Pleiotropic roles of bile acids in metabolism. Cell Metab. 2013;17:657-669.
Lefebvre P, Cariou B, Lien F, Kuipers F, Staels B. Role of bile acids and bile acid receptors in metabolic regulation. Physiol Rev. 2009;89:147-191.
Eslam M, Newsome PN, Sarin SK, et al. A new definition for metabolic dysfunction-associated fatty liver disease: an international expert consensus statement. J Hepatol. 2020;73:202-209.
Wong VW-S, Adams LA, de Lédinghen V, Wong GL-H, Sookoian S. Noninvasive biomarkers in NAFLD and NASH - current progress and future promise. Nat Rev Gastroenterol Hepatol. 2018;15:461-478.
Wong VW-S, Wong GL-H, Tsang SW-C, et al. Metabolic and histological features of non-alcoholic fatty liver disease patients with different serum alanine aminotransferase levels. Aliment Pharmacol Ther. 2009;29:387-396.
Taylor RS, Taylor RJ, Bayliss S, et al. Association between fibrosis stage and outcomes of patients with nonalcoholic fatty liver disease: a systematic review and meta-analysis. Gastroenterology. 2020;158:1611-1625.e12.
Mahady SE, Macaskill P, Craig JC, et al. Diagnostic accuracy of noninvasive fibrosis scores in a population of individuals with a low prevalence of fibrosis. Clin Gastroenterol Hepatol. 2017;15:1453-1460.e1.
Hagström H, Talbäck M, Andreasson A, Walldius G, Hammar N. Repeated FIB-4 measurements can help identify individuals at risk of severe liver disease. J Hepatol. 2020;73:1023-1029.
Srivastava A, Gailer R, Tanwar S, et al. Prospective evaluation of a primary care referral pathway for patients with non-alcoholic fatty liver disease. J Hepatol. 2019;71:371-378.
Chan W-K, Treeprasertsuk S, Goh GB-B, et al. Optimizing use of nonalcoholic fatty liver disease fibrosis score, fibrosis-4 score, and liver stiffness measurement to identify patients with advanced fibrosis. Clin Gastroenterol Hepatol. 2019;17:2570-2580.e37.
Boursier J, Guillaume M, Leroy V, et al. New sequential combinations of non-invasive fibrosis tests provide an accurate diagnosis of advanced fibrosis in NAFLD. J Hepatol. 2019;71:389-396.
Kanwal F, Shubrook JH, Adams LA, et al. Clinical care pathway for the risk stratification and management of patients with nonalcoholic fatty liver disease. Gastroenterology. 2021;161:1657-1669.
Lee HW, Wong GL-H, Kwok R, et al. Serial transient elastography examinations to monitor patients with type 2 diabetes: a prospective cohort study. Hepatology. 2020;72:1230-1241.
Wong VW-S, Tak WY, Goh GBB, et al. Performance of noninvasive tests of fibrosis among Asians, Hispanic, and non-Hispanic whites in the STELLAR trials. Clin Gastroenterol Hepatol. 2022;S1542-3565(22)00069-6. doi:10.1016/j.cgh.2022.01.015
de Franchis R, Bosch J, Garcia-Tsao G, Reiberger T, Ripoll C. Baveno VII faculty. Baveno VII - renewing consensus in portal hypertension. J Hepatol. 2022;76:959-974.
Vilar-Gomez E, Martinez-Perez Y, Calzadilla-Bertot L, et al. Weight loss through lifestyle modification significantly reduces features of nonalcoholic steatohepatitis. Gastroenterology. 2015;149:367-378.e5. quiz e14-15.
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. 2019;38:2023-2030.
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. Obes Facts. 2016;9:65-90.
Plauth M, Bernal W, Dasarathy S, et al. ESPEN guideline on clinical nutrition in liver disease. Clin Nutr. 2019;38:485-521.
Malespin MH, Barritt AS, Watkins SE, et al. Weight loss and weight regain in usual clinical practice: results from the TARGET-NASH observational cohort. Clin Gastroenterol Hepatol. 2021;S1542-3565(21)00073-2. doi:10.1016/j.cgh.2021.01.023
Ryan DH, Kahan S. Guideline recommendations for obesity management. Med Clin North Am. 2018;102:49-63.
Wadden TA, Neiberg RH, Wing RR, et al. Four-year weight losses in the look AHEAD study: factors associated with long-term success. Obesity (Silver Spring). 2011;19:1987-1998.
Gepner Y, Shelef I, Schwarzfuchs D, et al. Effect of distinct lifestyle interventions on mobilization of fat storage pools: CENTRAL magnetic resonance imaging randomized controlled trial. Circulation. 2018;137:1143-1157.
Yaskolka Meir A, Rinott E, Tsaban G, et al. Effect of green-Mediterranean diet on intrahepatic fat: the DIRECT PLUS randomised controlled trial. Gut. 2021;70:2085-2095.
Noureddin M, Zelber-Sagi S, Wilkens LR, et al. Diet associations with nonalcoholic fatty liver disease in an ethnically diverse population: the multiethnic cohort. Hepatology. 2020;71:1940-1952.
Salomone F, Ivancovsky-Wajcman D, Fliss-Isakov N, et al. Higher phenolic acid intake independently associates with lower prevalence of insulin resistance and non-alcoholic fatty liver disease. JHEP Rep. 2020;2:100069.
Ivancovsky-Wajcman D, Fliss-Isakov N, Webb M, et al. Ultra-processed food is associated with features of metabolic syndrome and non-alcoholic fatty liver disease. Liver Int. 2021;41:2635-2645.
Yki-Järvinen H, Luukkonen PK, Hodson L, Moore JB. Dietary carbohydrates and fats in nonalcoholic fatty liver disease. Nat Rev Gastroenterol Hepatol. 2021;18:770-786.
Kim D, Vazquez-Montesino LM, Li AA, Cholankeril G, Ahmed A. Inadequate physical activity and sedentary behavior are independent predictors of nonalcoholic fatty liver disease. Hepatology. 2020;72:1556-1568.
Nakanishi N, Hashimoto Y, Okamura T, et al. A weight regain of 1.5 kg or more and lack of exercise are associated with nonalcoholic fatty liver disease recurrence in men. Sci Rep. 2021;11:19992.
Oh S, Tsujimoto T, Kim B, et al. Weight-loss-independent benefits of exercise on liver steatosis and stiffness in Japanese men with NAFLD. JHEP Rep. 2021;3:100253.
Hashida R, Kawaguchi T, Bekki M, et al. Aerobic vs. resistance exercise in non-alcoholic fatty liver disease: a systematic review. J Hepatol. 2017;66:142-152.
Zelber-Sagi S, Bord S, Dror-Lavi G, et al. Role of illness perception and self-efficacy in lifestyle modification among non-alcoholic fatty liver disease patients. World J Gastroenterol. 2017;23:1881-1890.
Nguyen VH, Yeo YH, Zou B, et al. Discrepancies between actual weight, weight perception and weight loss intention amongst persons with NAFLD. J Intern Med. 2021;289:840-850.
Anstee QM, Hallsworth K, Lynch N, et al. Real-world management of non-alcoholic steatohepatitis differs from clinical practice guideline recommendations and across regions. JHEP Rep. 2022;4:100411.
Stefan N, Cusi K. A global view of the interplay between non-alcoholic fatty liver disease and diabetes. Lancet Diabetes Endocrinol. 2022;10:284-296.
Cusi K. Role of obesity and lipotoxicity in the development of nonalcoholic steatohepatitis: pathophysiology and clinical implications. Gastroenterology. 2012;142:711-725.e6.
Mantovani A, Byrne CD, Targher G. Efficacy of peroxisome proliferator-activated receptor agonists, glucagon-like peptide-1 receptor agonists, or sodium-glucose cotransporter-2 inhibitors for treatment of non-alcoholic fatty liver disease: a systematic review. Lancet Gastroenterol Hepatol. 2022;7:367-378.
Cusi K, Bril F, Barb D, et al. Effect of canagliflozin treatment on hepatic triglyceride content and glucose metabolism in patients with type 2 diabetes. Diabetes Obes Metab. 2019;21:812-821.
Kahl S, Gancheva S, Straßburger K, et al. Empagliflozin effectively lowers liver fat content in well-controlled type 2 diabetes: a randomized, double-blind, phase 4, placebo-controlled trial. Diabetes Care. 2020;43:298-305.
Cusi K. Time to include nonalcoholic steatohepatitis in the management of patients with type 2 diabetes. Diabetes Care. 2020;43:275-279.
Pradhan R, Yin H, Yu O, Azoulay L. Glucagon-like peptide 1 receptor agonists and sodium-glucose cotransporter 2 inhibitors and risk of nonalcoholic fatty liver disease among patients with type 2 diabetes. Diabetes Care. 2022;45:819-829.
Takahashi H, Kessoku T, Kawanaka M, et al. Ipragliflozin improves the hepatic outcomes of patients with diabetes with NAFLD. Hepatol Commun. 2022;6:120-132.
Kim RG, Loomba R, Prokop LJ, Singh S. Statin use and risk of cirrhosis and related complications in patients with chronic liver diseases: a systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2017;15:1521-1530.e8.
Sung S, Al-Karaghouli M, Kalainy S, Cabrera Garcia L, Abraldes JG. A systematic review on pharmacokinetics, cardiovascular outcomes and safety profiles of statins in cirrhosis. BMC Gastroenterol. 2021;21:120.
Kusnik A, Hunter N, Rasbach E, et al. Co-medication and nutrition in hepatocellular carcinoma: potentially preventative strategies in hepatocellular carcinoma. Dig Dis. 2021;39:526-533.
Vilar-Gomez E, Calzadilla-Bertot L, Wong VW-S, et al. Type 2 diabetes and metformin use associate with outcomes of patients with nonalcoholic steatohepatitis-related, child-pugh a cirrhosis. Clin Gastroenterol Hepatol. 2021;19:136-145.e6.
Gastaldelli A, Cusi K. From NASH to diabetes and from diabetes to NASH: mechanisms and treatment options. JHEP Rep. 2019;1:312-328.
Belfort R, Harrison SA, Brown K, et al. A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. N Engl J Med. 2006;355:2297-2307.
Aithal GP, Thomas JA, Kaye PV, et al. Randomized, placebo-controlled trial of pioglitazone in nondiabetic subjects with nonalcoholic steatohepatitis. Gastroenterology. 2008;135:1176-1184.
Sanyal AJ, Chalasani N, Kowdley KV, et al. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med. 2010;362:1675-1685.
Cusi K, Orsak B, Bril F, et al. Long-term pioglitazone treatment for patients with nonalcoholic steatohepatitis and prediabetes or type 2 diabetes mellitus: a randomized trial. Ann Intern Med. 2016;165:305-315.
Bril F, Biernacki DM, Kalavalapalli S, et al. Role of vitamin E for nonalcoholic steatohepatitis in patients with type 2 diabetes: a randomized controlled trial. Diabetes Care. 2019;42:1481-1488.
Musso G, Cassader M, Paschetta E, Gambino R. Thiazolidinediones and advanced liver fibrosis in nonalcoholic steatohepatitis: a meta-analysis. JAMA Intern Med. 2017;177:633-640.
DeFronzo RA, Inzucchi S, Abdul-Ghani M, Nissen SE. Pioglitazone: the forgotten, cost-effective cardioprotective drug for type 2 diabetes. Diab Vasc Dis Res. 2019;16:133-143.
Cusi K, Isaacs S, Barb D, et al. American Association of Clinical Endocrinologists (AACE) clinical practice guideline for the diagnosis and management of NAFLD in primary care and endocrinology clinical settings. Endocr Pract. 2022;28:528-562.
Gastaldelli A, Sabatini S, Carli F, et al. PPAR-γ-induced changes in visceral fat and adiponectin levels are associated with improvement of steatohepatitis in patients with NASH. Liver Int. 2021;41:2659-2670.
Vaccaro O, Masulli M, Nicolucci A, et al. Effects on the incidence of cardiovascular events of the addition of pioglitazone versus sulfonylureas in patients with type 2 diabetes inadequately controlled with metformin (TOSCA.IT): a randomised, multicentre trial. Lancet Diabetes Endocrinol. 2017;5:887-897.
Filipova E, Uzunova K, Kalinov K, Vekov T. Pioglitazone and the risk of bladder cancer: a meta-analysis. Diabetes Ther. 2017;8:705-726.
Patel Chavez C, Cusi K, Kadiyala S. The emerging role of glucagon-like peptide-1 receptor agonists for the management of NAFLD. J Clin Endocrinol Metab. 2022;107:29-38.
Armstrong MJ, Gaunt P, Aithal GP, et al. Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (LEAN): a multicentre, double-blind, randomised, placebo-controlled phase 2 study. Lancet. 2016;387:679-690.
Newsome PN, Buchholtz K, Cusi K, et al. A placebo-controlled trial of subcutaneous semaglutide in nonalcoholic steatohepatitis. N Engl J Med. 2021;384:1113-1124.
Gastaldelli A, Cusi K, Fernandez Lando L, et al. Changes in abdominal fat and clinical and analytical parameters in tirzepatide- or insulin degludec-treated patients with type 2 diabetes (SURPASS-3 MRI). Lancet. 2022;10:393-406.
Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide once weekly for the treatment of obesity. N Engl J Med. 2022;387:205-216.
Vilar-Gomez E, Vuppalanchi R, Gawrieh S, et al. Vitamin E improves transplant-free survival and hepatic decompensation among patients with nonalcoholic steatohepatitis and advanced fibrosis. Hepatology. 2020;71:495-509.
Wong VW-S, Singal AK. Emerging medical therapies for non-alcoholic fatty liver disease and for alcoholic hepatitis. Transl Gastroenterol Hepatol. 2019;4:53.
Younossi ZM, Ratziu V, Loomba R, et al. Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial. Lancet. 2019;394:2184-2196.
Francque SM, Bedossa P, Ratziu V, et al. A randomized, controlled trial of the pan-PPAR agonist lanifibranor in NASH. N Engl J Med. 2021;385:1547-1558.
Ratziu V, de Guevara L, Safadi R, et al. Aramchol in patients with nonalcoholic steatohepatitis: a randomized, double-blind, placebo-controlled phase 2b trial. Nat Med. 2021;27:1825-1835.
Harrison SA, Bashir MR, Guy CD, et al. Resmetirom (MGL-3196) for the treatment of non-alcoholic steatohepatitis: a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet. 2019;394:2012-2024.
Lee Y, Doumouras AG, Yu J, et al. Complete resolution of nonalcoholic fatty liver disease after bariatric surgery: a systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2019;17:1040-1060.e11.
Wirth KM, Sheka AC, Kizy S, et al. Bariatric surgery is associated with decreased progression of nonalcoholic fatty liver disease to cirrhosis: a retrospective cohort analysis. Ann Surg. 2020;272:32-39.
Schroeder R, Harrison TD, McGraw SL. Treatment of adult obesity with bariatric surgery. Am Fam Physician. 2016;93:31-37.
NIH conference. Gastrointestinal surgery for severe obesity. Consensus development conference panel. Ann Intern Med. 1991;115:956-961.
Arterburn DE, Telem DA, Kushner RF, Courcoulas AP. Benefits and risks of bariatric surgery in adults: a review. JAMA. 2020;324:879-887.