Non-Alcoholic Fatty Liver Disease and other Non-Communicable Diseases: Time for an Integrated Approach


  • Aayushi Rastogi Institute of Liver and Biliary Sciences, New Delhi
  • Manya Prasad Institute of Liver and Biliary Sciences, New Delhi
  • Archana Ramalingam Institute of Liver and Biliary Sciences, New Delhi
  • Umesh Kapil Institute of Liver and Biliary Sciences, New Delhi



NAFLD, Non-Communicable Diseases, Diabetes Mellitus, Metabolic Syndrome, Obesity


Non-Alcoholic fatty liver disease (NAFLD) is a broad term covering a spectrum of conditions ranging from hepatic steatosis, steatohepatitis and cirrhosis. NAFLD is highly prevalent across all regions of the world with its global prevalence of 25.2%(95%CI:22.1-28.7). It is commonly referred as the ‘hepatic manifestation’ of metabolic syndrome (MetS). Moreover, it is strongly associated with the individual components as well as MetS as a whole. NAFLD has been independently associated with other non-communicable diseases (NCDs) like chronic kidney disease (CKD), Polycystic ovary Syndrome (PCOS), Stroke and Cancers. This strong association of NCDs with NAFLD not only affects the prevalence but also the progression and management of the disease. Thus, this review aims at highlighting the association of NAFLD with other NCDs. A literature search was undertaken in the MEDLINE database using the necessary MeSH terms. The review concludes NAFLD is a systemic disease, not just confined to liver-specific morbidity and mortality, but also associated with numerous extra-hepatic manifestations, such as metabolic syndrome, cardiovascular diseases, chronic renal diseases, and malignancy. With co-existence of NAFLD with various NCDs it is expected to become the most overwhelming liver disease in the world in coming years. Hence, to reduce medical and economic impact associated with these comorbidities, it is recommended that all countries should estimate and predict the burden on comorbidities associated with NAFLD and galvanize its health resources in providing integrated therapeutic approaches for management of NAFLD and related comorbidities at an early stage.


Download data is not yet available.


Chalasani N, Younossi Z, Lavine JE, Charlton M, Cusi K, Rinella M, et al. The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases. Hepatol Baltim Md. 2018;67(1):328–57.

Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention | Nature Reviews Gastroenterology & Hepatology [Internet]. [cited 2020 Apr 9]. Available from:

Duseja A, Khaliq A, Choubal CC, Sonawane D, Roy DS, Gadhikar H, et al. Prevalence and Clinico-Epidemiology of Nonalcoholic Fatty Liver Disease (NAFLD) in Patients With Metabolic Syndrome. J Clin Exp Hepatol [Internet]. 2017 Jul 1 [cited 2020 Apr 19];7:S44–5. Available from:

Liver Fat in the Metabolic Syndrome | The Journal of Clinical Endocrinology & Metabolism | Oxford Academic [Internet]. [cited 2020 Apr 19]. Available from:

Fan J-G, Zhu J, Li X-J, Chen L, Lu Y-S, Li L, et al. Fatty liver and the metabolic syndrome among Shanghai adults. J Gastroenterol Hepatol [Internet]. 2005 [cited 2020 Apr 19];20(12):1825–32. Available from:

Boursier J, Chaigneau J, Roullier V, Lainé F, Sandrini J, Michalak S, et al. Steatosis degree, measured by morphometry, is linked to other liver lesions and metabolic syndrome components in patients with NAFLD. Eur J Gastroenterol Hepatol. 2011 Nov;23(11):974–81.

Yang KC, Hung H-F, Lu C-W, Chang H-H, Lee L-T, Huang K-C. Association of Non-alcoholic Fatty Liver Disease with Metabolic Syndrome Independently of Central Obesity and Insulin Resistance. Sci Rep [Internet]. 2016 Jun 1 [cited 2020 Apr 18];6(1):1–10. Available from:

Musso G, Gambino R, Bo S, Uberti B, Biroli G, Pagano G, et al. Should Nonalcoholic Fatty Liver Disease Be Included in the Definition of Metabolic Syndrome?: A cross-sectional comparison with Adult Treatment Panel III criteria in nonobese nondiabetic subjects. Diabetes Care [Internet]. 2008 Mar 1 [cited 2020 Apr 19];31(3):562–8. Available from:

Ballestri S, Zona S, Targher G, Romagnoli D, Baldelli E, Nascimbeni F, et al. Nonalcoholic fatty liver disease is associated with an almost twofold increased risk of incident type 2 diabetes and metabolic syndrome. Evidence from a systematic review and meta-analysis. J Gastroenterol Hepatol. 2016 May;31(5):936–44.

Younossi ZM, Golabi P, Avila L de, Paik JM, Srishord M, Fukui N, et al. The global epidemiology of NAFLD and NASH in patients with type 2 diabetes: A systematic review and meta-analysis. J Hepatol [Internet]. 2019 Oct 1 [cited 2020 Apr 19];71(4):793–801. Available from:

Portillo-Sanchez P, Bril F, Maximos M, Lomonaco R, Biernacki D, Orsak B, et al. High Prevalence of Nonalcoholic Fatty Liver Disease in Patients With Type 2 Diabetes Mellitus and Normal Plasma Aminotransferase Levels. J Clin Endocrinol Metab [Internet]. 2015 Jun 1 [cited 2020 Apr 19];100(6):2231–8. Available from:

Fracanzani AL, Valenti L, Bugianesi E, Andreoletti M, Colli A, Vanni E, et al. Risk of severe liver disease in nonalcoholic fatty liver disease with normal aminotransferase levels: a role for insulin resistance and diabetes. Hepatol Baltim Md. 2008 Sep;48(3):792–8.

Lonardo A, Ballestri S, Guaraldi G, Nascimbeni F, Romagnoli D, Zona S, et al. Fatty liver is associated with an increased risk of diabetes and cardiovascular disease - Evidence from three different disease models: NAFLD, HCV and HIV. World J Gastroenterol. 2016 Nov 28;22(44):9674–93.

Xia M-F, Bian H, Gao X. NAFLD and Diabetes: Two Sides of the Same Coin? Rationale for Gene-Based Personalized NAFLD Treatment. Front Pharmacol [Internet]. 2019 Aug 6 [cited 2020 Jan 26];10. Available from:

van der Poorten D, Milner K-L, Hui J, Hodge A, Trenell MI, Kench JG, et al. Visceral fat: a key mediator of steatohepatitis in metabolic liver disease. Hepatol Baltim Md. 2008 Aug;48(2):449–57.

Katsuki A, Sumida Y, Urakawa H, Gabazza EC, Murashima S, Maruyama N, et al. Increased visceral fat and serum levels of triglyceride are associated with insulin resistance in Japanese metabolically obese, normal weight subjects with normal glucose tolerance. Diabetes Care. 2003 Aug;26(8):2341–4.

Agbim U, Carr RM, Pickett-Blakely O, Dagogo-Jack S. Ethnic Disparities in Adiposity: Focus on Non-alcoholic Fatty Liver Disease, Visceral, and Generalized Obesity. Curr Obes Rep. 2019 Sep;8(3):243–54.

Yu SJ, Kim W, Kim D, Yoon J-H, Lee K, Kim JH, et al. Visceral Obesity Predicts Significant Fibrosis in Patients With Nonalcoholic Fatty Liver Disease. Medicine (Baltimore). 2015 Dec;94(48):e2159.

Kim D, Chung GE, Kwak M-S, Seo HB, Kang JH, Kim W, et al. Body Fat Distribution and Risk of Incident and Regressed Nonalcoholic Fatty Liver Disease. Clin Gastroenterol Hepatol [Internet]. 2016 Jan 1 [cited 2020 Apr 20];14(1):132-138.e4. Available from:

Caro-Sabido EA, Larrosa-Haro A. Efficacy of dietary intervention and physical activity in children and adolescents with nonalcoholic fatty liver disease associated with obesity: A scoping review. Rev Gastroenterol Mex. 2019 Jun;84(2):185–94.

Brunner KT, Henneberg CJ, Wilechansky RM, Long MT. Nonalcoholic Fatty Liver Disease and Obesity Treatment. Curr Obes Rep. 2019 Sep;8(3):220–8.

Wang Y, Zeng Y, Lin C, Chen Z. Hypertension and non-alcoholic fatty liver disease proven by transient elastography. Hepatol Res [Internet]. 2016 [cited 2020 Apr 21];46(13):1304–10. Available from:

Donati G, Stagni B, Piscaglia F, Venturoli N, Morselli-Labate AM, Rasciti L, et al. Increased prevalence of fatty liver in arterial hypertensive patients with normal liver enzymes: role of insulin resistance. Gut [Internet]. 2004 Jul 1 [cited 2020 Apr 21];53(7):1020–3. Available from:

Dai W, Ye L, Liu A, Wen SW, Deng J, Wu X, et al. Prevalence of nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus. Medicine (Baltimore) [Internet]. 2017 Sep 29 [cited 2020 Apr 21];96(39). Available from:

Feng R-N, Du S-S, Wang C, Li Y-C, Liu L-Y, Guo F-C, et al. Lean-non-alcoholic fatty liver disease increases risk for metabolic disorders in a normal weight Chinese population. World J Gastroenterol. 2014 Dec 21;20(47):17932–40.

Zhang T, Zhang C, Zhang Y, Tang F, Li H, Zhang Q, et al. Metabolic syndrome and its components as predictors of nonalcoholic fatty liver disease in a northern urban Han Chinese population: a prospective cohort study. Atherosclerosis. 2015 May;240(1):144–8.

Aneni EC, Oni ET, Martin SS, Blaha MJ, Agatston AS, Feldman T, et al. Blood pressure is associated with the presence and severity of nonalcoholic fatty liver disease across the spectrum of cardiometabolic risk. J Hypertens. 2015 Jun;33(6):1207–14.

Sorrentino P, Terracciano L, D’Angelo S, Ferbo U, Bracigliano A, Vecchione R. Predicting fibrosis worsening in obese patients with NASH through parenchymal fibronectin, HOMA-IR, and hypertension. Am J Gastroenterol. 2010 Feb;105(2):336–44.

Long MT, Pedley A, Massaro JM, Hoffmann U, Fox CS. The Association between Non-Invasive Hepatic Fibrosis Markers and Cardiometabolic Risk Factors in the Framingham Heart Study. PloS One. 2016;11(6):e0157517.

Ryoo J-H, Suh YJ, Shin HC, Cho YK, Choi J-M, Park SK. Clinical association between non-alcoholic fatty liver disease and the development of hypertension. J Gastroenterol Hepatol. 2014 Nov;29(11):1926–31.

Huh JH, Ahn SV, Koh SB, Choi E, Kim JY, Sung K-C, et al. A Prospective Study of Fatty Liver Index and Incident Hypertension: The KoGES-ARIRANG Study. PLoS ONE [Internet]. 2015 Nov 30 [cited 2020 Apr 21];10(11). Available from:

Ren XY, Shi D, Ding J, Cheng ZY, Li HY, Li JS, et al. Total cholesterol to high-density lipoprotein cholesterol ratio is a significant predictor of nonalcoholic fatty liver: Jinchang cohort study. Lipids Health Dis [Internet]. 2019 Feb 11 [cited 2020 Apr 21];18. Available from:

Du T, Sun X, Yuan G, Zhou X, Lu H, Lin X, et al. Lipid phenotypes in patients with nonalcoholic fatty liver disease. Metabolism. 2016;65(9):1391–8.

Nemes K, Åberg F. Interpreting lipoproteins in nonalcoholic fatty liver disease. Curr Opin Lipidol. 2017 Aug;28(4):355–60.

Katsiki N, Mikhailidis DP, Mantzoros CS. Non-alcoholic fatty liver disease and dyslipidemia: An update. Metab - Clin Exp [Internet]. 2016 Aug 1 [cited 2020 Apr 21];65(8):1109–23. Available from:

Kirpich IA, Marsano LS, McClain CJ. Gut-liver axis, nutrition, and non-alcoholic fatty liver disease. Clin Biochem. 2015 Sep;48(13–14):923–30.

Sinner MF, Wang N, Fox CS, Fontes JD, Rienstra M, Magnani JW, et al. Relation of Circulating Liver Transaminase Concentrations to Risk of New-Onset Atrial Fibrillation. Am J Cardiol [Internet]. 2013 Jan 15 [cited 2020 Apr 23];111(2):219–24. Available from:

Alonso A, Misialek JR, Amiin MA, Hoogeveen RC, Chen LY, Agarwal SK, et al. Circulating levels of liver enzymes and incidence of atrial fibrillation: the Atherosclerosis Risk in Communities cohort. Heart [Internet]. 2014 Oct 1 [cited 2020 Apr 23];100(19):1511–6. Available from:

Targher G, Valbusa F, Bonapace S, Bertolini L, Zenari L, Rodella S, et al. Non-Alcoholic Fatty Liver Disease Is Associated with an Increased Incidence of Atrial Fibrillation in Patients with Type 2 Diabetes. PLOS ONE [Internet]. 2013 Feb 22 [cited 2020 Apr 23];8(2):e57183. Available from:

Käräjämäki AJ, Pätsi O-P, Savolainen M, Kesäniemi YA, Huikuri H, Ukkola O. Non-Alcoholic Fatty Liver Disease as a Predictor of Atrial Fibrillation in Middle-Aged Population (OPERA Study). PLOS ONE [Internet]. 2015 Nov 16 [cited 2020 Apr 23];10(11):e0142937. Available from:

Wijarnpreecha K, Boonpheng B, Thongprayoon C, Jaruvongvanich V, Ungprasert P. The association between non-alcoholic fatty liver disease and atrial fibrillation: A meta-analysis. Clin Res Hepatol Gastroenterol [Internet]. 2017 Oct 1 [cited 2020 Apr 23];41(5):525–32. Available from:

Ampuero J, Gallego-Durán R, Romero-Gómez M. Association of NAFLD with subclinical atherosclerosis and coronary-artery disease: meta-analysis. Rev Espanola Enfermedades Dig Organo Of Soc Espanola Patol Dig. 2015 Jan;107(1):10–6.

Madan SA, John F, Pyrsopoulos N, Pitchumoni CS. Nonalcoholic fatty liver disease and carotid artery atherosclerosis in children and adults: a meta-analysis. Eur J Gastroenterol Hepatol. 2015 Nov;27(11):1237–48.

Saltiel AR, Olefsky JM. Inflammatory mechanisms linking obesity and metabolic disease. J Clin Invest [Internet]. 2017 Jan 3 [cited 2020 Apr 23];127(1):1–4. Available from:

Luo K, Bian J, Wang Q, Wang J, Chen F, Li H, et al. Association of obesity with chronic kidney disease in elderly patients with nonalcoholic fatty liver disease. Turk J Gastroenterol [Internet]. 2019 Jul [cited 2020 Apr 21];30(7):611–5. Available from:

Musso G, Gambino R, Tabibian JH, Ekstedt M, Kechagias S, Hamaguchi M, et al. Association of non-alcoholic fatty liver disease with chronic kidney disease: a systematic review and meta-analysis. PLoS Med. 2014 Jul;11(7):e1001680.

Paik J, Golabi P, Younoszai Z, Mishra A, Trimble G, Younossi ZM. Chronic kidney disease is independently associated with increased mortality in patients with nonalcoholic fatty liver disease. Liver Int Off J Int Assoc Study Liver. 2019;39(2):342–52.

Chinnadurai R, Ritchie J, Green D, Kalra PA. Non-alcoholic fatty liver disease and clinical outcomes in chronic kidney disease. Nephrol Dial Transplant Off Publ Eur Dial Transpl Assoc - Eur Ren Assoc. 2019 01;34(3):449–57.

Cai J, Wu CH, Zhang Y, Wang YY, Xu WD, Lin TC, et al. High-free androgen index is associated with increased risk of non-alcoholic fatty liver disease in women with polycystic ovary syndrome, independent of obesity and insulin resistance. Int J Obes [Internet]. 2017 Sep [cited 2020 Apr 22];41(9):1341–7. Available from:

Jensen T, Wieland A, Cree-Green M, Nadeau K, Sullivan S. Clinical workup of fatty liver for the primary care provider. Postgrad Med [Internet]. 2019 Jan 2 [cited 2020 Apr 22];131(1):19–30. Available from:

Kelley CE, Brown AJ, Diehl AM, Setji TL. Review of nonalcoholic fatty liver disease in women with polycystic ovary syndrome. World J Gastroenterol WJG [Internet]. 2014 Oct 21 [cited 2020 Apr 22];20(39):14172–84. Available from:

Macut D, Tziomalos K, Boži?-Anti? I, Bjeki?-Macut J, Katsikis I, Papadakis E, et al. Non-alcoholic fatty liver disease is associated with insulin resistance and lipid accumulation product in women with polycystic ovary syndrome. Hum Reprod [Internet]. 2016 Jun 1 [cited 2020 Apr 22];31(6):1347–53. Available from:

M S, N T, Cc D, P T, Mi C, H H. The Association of Hispanic Ethnicity with Nonalcoholic Fatty Liver Disease in Polycystic Ovary Syndrome. Curr Opin Gynecol Obstet [Internet]. 2018 Apr 5 [cited 2020 Apr 22];1(1):24–33. Available from:

Kumarendran B, O’Reilly MW, Manolopoulos KN, Toulis KA, Gokhale KM, Sitch AJ, et al. Polycystic ovary syndrome, androgen excess, and the risk of nonalcoholic fatty liver disease in women: A longitudinal study based on a United Kingdom primary care database. PLoS Med. 2018;15(3):e1002542.

Vassilatou E, Vassiliadi DA, Salambasis K, Lazaridou H, Koutsomitopoulos N, Kelekis N, et al. Increased prevalence of polycystic ovary syndrome in premenopausal women with nonalcoholic fatty liver disease. Eur J Endocrinol. 2015 Dec;173(6):739–47.

Ovaries are more vulnerable than hepatocytes for insulin resistance and hyperinsulinemia. - Abstract - Europe PMC [Internet]. [cited 2020 Apr 22]. Available from:

Kim SU, Song D, Heo JH, Yoo J, Kim BK, Park JY, et al. Liver fibrosis assessed with transient elastography is an independent risk factor for ischemic stroke. Atherosclerosis [Internet]. 2017 May 1 [cited 2020 Apr 22];260:156–62. Available from:

Baik M, Kim SU, Kang S, Park HJ, Nam HS, Heo JH, et al. Liver Fibrosis, Not Steatosis, Associates with Long-Term Outcomes in Ischaemic Stroke Patients. Cerebrovasc Dis Basel Switz. 2019;47(1–2):32–9.

Li H, Hu B, Wei L, Zhou L, Zhang L, Lin Y, et al. Non-alcoholic fatty liver disease is associated with stroke severity and progression of brainstem infarctions. Eur J Neurol [Internet]. 2018 [cited 2020 Apr 22];25(3):577-e34. Available from:

Younossi Z, Stepanova M, Ong JP, Jacobson IM, Bugianesi E, Duseja A, et al. Nonalcoholic Steatohepatitis Is the Fastest Growing Cause of Hepatocellular Carcinoma in Liver Transplant Candidates. Clin Gastroenterol Hepatol Off Clin Pract J Am Gastroenterol Assoc. 2019;17(4):748-755.e3.

Estes C, Razavi H, Loomba R, Younossi Z, Sanyal AJ. Modeling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease. Hepatol Baltim Md. 2018;67(1):123–33.

Lee J-M, Park Y-M, Yun J-S, Ahn Y-B, Lee K-M, Kim DB, et al. The association between nonalcoholic fatty liver disease and esophageal, stomach, or colorectal cancer: National population-based cohort study. PloS One. 2020;15(1):e0226351.

Lee Y-S, Lee HS, Chang SW, Lee CU, Kim JS, Jung YK, et al. Underlying nonalcoholic fatty liver disease is a significant factor for breast cancer recurrence after curative surgery. Medicine (Baltimore). 2019 Sep;98(39):e17277.

Romdhane H, Ayadi S, Cheikh M, Bouchabou B, Ben Nejma H, Ennaifer R. Estimation of the prevalence of obstructive sleep apnea in non alcoholic fatty liver disease. Tunis Med. 2018 Apr;96(4):171–6.

Jin S, Jiang S, Hu A. Association between obstructive sleep apnea and non-alcoholic fatty liver disease: a systematic review and meta-analysis. Sleep Breath Schlaf Atm. 2018;22(3):841–51.

Musso G, Cassader M, Olivetti C, Rosina F, Carbone G, Gambino R. Association of obstructive sleep apnoea with the presence and severity of non-alcoholic fatty liver disease. A systematic review and meta-analysis. Obes Rev Off J Int Assoc Study Obes. 2013 May;14(5):417–31.

Lee D-Y, Park JK, Hur KY, Um SH. Association between nonalcoholic fatty liver disease and bone mineral density in postmenopausal women. Climacteric J Int Menopause Soc. 2018;21(5):498–501.

Lee SH, Yun JM, Kim SH, Seo YG, Min H, Chung E, et al. Association between bone mineral density and nonalcoholic fatty liver disease in Korean adults. J Endocrinol Invest. 2016 Nov;39(11):1329–36.

Li M, Xu Y, Xu M, Ma L, Wang T, Liu Y, et al. Association between nonalcoholic fatty liver disease (NAFLD) and osteoporotic fracture in middle-aged and elderly Chinese. J Clin Endocrinol Metab. 2012 Jun;97(6):2033–8.

Upala S, Jaruvongvanich V, Wijarnpreecha K, Sanguankeo A. Nonalcoholic fatty liver disease and osteoporosis: a systematic review and meta-analysis. J Bone Miner Metab [Internet]. 2017 Nov 1 [cited 2020 Apr 23];35(6):685–93.

Xu X, Su L, Gao Y, Ding Y. The Prevalence of Nonalcoholic Fatty Liver Disease and Related Metabolic Comorbidities Was Associated with Age at Onset of Moderate to Severe Plaque Psoriasis: A Cross-Sectional Study. PloS One. 2017;12(1):e0169952.

Candia R, Ruiz A, Torres-Robles R, Chávez-Tapia N, Méndez-Sánchez N, Arrese M. Risk of non-alcoholic fatty liver disease in patients with psoriasis: a systematic review and meta-analysis. J Eur Acad Dermatol Venereol JEADV. 2015 Apr;29(4):656–62.

Lonardo A, Ballestri S, Mantovani A, Nascimbeni F, Lugari S, Targher G. Pathogenesis of hypothyroidism-induced NAFLD: Evidence for a distinct disease entity? Dig Liver Dis Off J Ital Soc Gastroenterol Ital Assoc Study Liver. 2019;51(4):462–70.

Notariza KR, Wisnu W. The Risk of Developing Non-Alcoholic Fatty Liver Disease in Adult Patients with Subclinical Hypothyroidism Compared to Euthyroid: An Evidence-based Case Report. Acta Medica Indones. 2019 Apr;51(2):179–88.

Mantovani A, Nascimbeni F, Lonardo A, Zoppini G, Bonora E, Mantzoros CS, et al. Association Between Primary Hypothyroidism and Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis. Thyroid Off J Am Thyroid Assoc. 2018;28(10):1270–84.




How to Cite

Rastogi A, Prasad M, Ramalingam A, Kapil U. Non-Alcoholic Fatty Liver Disease and other Non-Communicable Diseases: Time for an Integrated Approach. Indian J Community Health [Internet]. 2022 Mar. 31 [cited 2024 Jun. 21];34(1):03-10. Available from:



Review Article

Most read articles by the same author(s)

1 2 3 > >>