Non-alcoholic fatty liver disease (NAFLD) represents a broad spectrum of liver damage, ranging from simple steatosis to steatohepatitis and fibrosis; as well, there is a close association between NAFLD, obesity, metabolic syndrome and type 2 diabetes mellitus. There is a certain degree of uncertainty regarding the natural history and prognosis of NAFLD; however, several methods are currently used for its diagnostic approach. In the first instance, non-invasive tests could be used to identify patients at low risk of developing fibrosis and to establish more easily the need for a liver biopsy, whose accuracy in the evaluation of fibrosis has been questioned, mainly due to errors of intra and interobserver sampling, technical problems and cost, which limits its use. Therefore, it is essential to determine the diagnostic strategy for patients with NAFLD.
Keywords: Fibrosis, Liver, Steatohepatitis, Steatosis.
(Please cite as Salva-Pastor N, Chávez-Tapia NC, Uribe M, Nuño-Lámbarri N. Diagnostic and initial approach of the patient with non-alcoholic fatty liver disease: role of the primary care provider. Gastroenterol Hepatol Bed Bench 2019;12(4):267-277).
Chalasani N, Younossi Z, Lavine J, Charlton Mc, 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 2017;67:328–57.
Valenti L, Bugianesi E, Pajvani U, Targher G. Nonalcoholic fatty liver disease: cause or consequence of type 2 diabetes? Liver Int 2016;36:1563–79.
Lomonaco R, Sunny NE, Bril F, Cusi K. Nonalcoholic fatty liver disease: Current issues and novel treatment approaches. Drug 2013;73:1–14.
Nuño-Lámbarri N, Barbero-Becerra V, Uribe M, Chávez-Tapia N. Mitochondrial molecular pathophysiology of nonalcoholic fatty liver disease: a proteomics approach. Int J Mol Sci 2016;17:281.
Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease—Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatol 2016;64:73–84.
Maurice J, Manousou P. Non-Alcoholic Fatty Liver Disease. Clin Med 2018;18:245–50.
Sinn DH, Kang D, Chang Y, Ryu S, Gu S, Kim H, et al. Non-alcoholic fatty liver disease and progression of coronary artery calcium score: a retrospective cohort study. Gut 2017;66:323–9.
Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, et al. 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. Hepatol 2012;55:2005–23.
Marengo A, Jouness RIK, Bugianesi E. Progression and Natural History of Nonalcoholic Fatty Liver Disease in Adults. Clin Liver Dis 2016;20:313–24.
Mantovani A, Byrne CD, Bonora E, Targher G. Nonalcoholic fatty liver disease and risk of incident type 2 diabetes: a meta-analysis. Diabetes Care 2018;41:372–82.
Nderitu P, Bosco C, Garmo H, Holmberg L, Malmström H, Hammar N, et al. The association between individual metabolic syndrome components, primary liver cancer and cirrhosis: A study in the Swedish AMORIS cohort. Int J Cancer 2017;141:1148–60.
Gutiérrez-Grobe Y, Juárez-Hernández E, Sánchez-Jiménez BA, Uribe-Ramos MH, Ramos-Ostos MH, Uribe M, et al. Less liver fibrosis in metabolically healthy compared with metabolically unhealthy obese patients with non-alcoholic fatty liver disease. Diabetes Metab 2017;43:332–7.
Lee MK, Rhee EJ, Kim MC, Moon BS, Lee JI, Song YS, et al. Metabolic Health is More Important than Obesity in the Development of Non-Alcoholic Fatty Liver Disease: A Four-Year Retrospective Study. Endocrinol Metab 2015;522–30.
Wree A, Broderick L, Canbay A, Hoffman HM, Feldstein AE. From NAFLD to NASH to cirrhosis-new insights into disease mechanisms. Nat Rev Gastroenterol Hepatol 2013;10:627–36.
Nath P, Singh SP. Nonalcoholic fatty liver disease: time to take the bull by the horns. Euroasian J Hepatol Gastroenterol 2018;8:47–51.
Guo Y, Lin H, Dong C, Zhang X, Wen H, Shen Y, et al. Role of acoustic radiation force impulse imaging elastography in the assessment of steatohepatitis and fibrosis in rat models. Med Eng Phys 2018;1:30-35.
Stine JG, Wentworth BJ, Zimmet A, Rinella ME, Loomba R, Caldwell SH, et al. Systematic review with meta-analysis: risk of hepatocellular carcinoma in non-alcoholic steatohepatitis without cirrhosis compared to other liver diseases. Aliment Pharmacol Ther 2018;48:696-703.
Singh S, Allen AM, Wang Z, Prokop LJ, Murad MH, Loomba R. Fibrosis progression in nonalcoholic fatty liver versus nonalcoholic steatohepatitis: a systematic review and meta- analysis of paired-biopsy studies. Clin Gastroenterol Hepatol 2015;13:643–54.
Castera L. Diagnosis of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis: non-invasive tests are enough. Liver Int 2018;38:67–70.
Wang X, Zhang X. Diagnostic performance of magnetic resonance technology in detecting steatosis or fi brosis in patients with nonalcoholic fatty liver disease: a meta-analysis. Med 2018;97.
Mayo R, Crespo J, Martínez-Arranz I, Banales JM, Arias M, Mincholé I, et al. Metabolomic-based noninvasive serum test to diagnose nonalcoholic steatohepatitis: Results from discovery and validation cohorts. Hepatol Commun 2018;2:807–20.
Fujita N, Nishie A, Asayama Y, Ishigami K, Ushijima Y, Takayama Y, et al. Fibrosis in nonalcoholic fatty liver disease: Noninvasive assessment using computed tomography volumetry. World J Gastroenterol 2016;22:8949–55.
Liu C, Yu J, Li H, Liu J, Xu Y, Song P, et al. Comparison of laboratory tests, ultrasound, or MRE to detect fibrosis in patients with non-alcoholic fatty liver disease: a meta-analysis. Hepatol 2017;66:1–47.
Kleiner DE, Makhlouf HR, Program D, Investigation P, Branch R, Shams A. Histology of NAFLD and NASH in adults and children. Clin Liver Dis 2017;20:293–312.
Alempijevic TM, Stojkovic Lalosevic M, Dumic I, Jocic N, Markovic AP, Dragasevic S, et al. Diagnostic accuracy of platelet count and platelet indices in noninvasive assessment of fibrosis in nonalcoholic fatty liver disease patients. Can J Gastroenterol Hepatol 2017;2017.
Yoneda M, Fujii H, Sumida Y, Hyogo H, Itoh Y, Ono M, et al. Platelet count for predicting fibrosis in nonalcoholic fatty liver disease. J Gastroenterol 2011;46:1300–6.
Vilar-Gomez E, Chalasani N. Non-invasive assessment of non-alcoholic fatty liver disease: Clinical prediction rules and blood-based biomarkers. J Hepatol 2018;68:305–15.
Castera L, Yuen Chan HL, Arrese M, Afdhal N, Bedossa P, Friedrich-Rust M, et al. EASL-ALEH Clinical Practice Guidelines: non-invasive tests for evaluation of liver disease severity and prognosis. J Hepatol 2015;63:237–64.
McPherson S, Anstee QM, Henderson E, Day CP, Burt AD. Are simple noninvasive scoring systems for fibrosis reliable in patients with NAFLD and normal ALT levels? Eur J Gastroenterol Hepatol 2013;25:652–8.
Enomoto H, Bando Y, Nakamura H, Nishiguchi S, Koga M. Liver fibrosis markers of nonalcoholic steatohepatitis. World J Gastroenterol 2015;21:7427–35.
Pérez-Gutiérrez OZ, Hernández-Rocha C, Candia-Balboa RA, Arrese MA, Benítez C, Brizuela-Alcántara DC, et al. Validation study of systems for noninvasive diagnosis of fibrosis in nonalcoholic fatty liver disease in Latin population. Ann Hepatol 2013;12:416–24.
Ishiba H, Sumida Y, Tanaka S, Yoneda M, Hyogo H, Ono M, et al. The novel cutoff points for the FIB4 index categorized by age increase the diagnostic accuracy in NAFLD: a multi-center study. J Gastroenterol 2018;1.
Esterson YB, Grimaldi GM. Radiologic imaging in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Clin Liver Dis 2018;22:93–108.
Lee SS, Park SH. Radiologic evaluation of nonalcoholic fatty liver disease. World J Gastroenterol 2014;20:7392–402.
Castera L, Vilgrain V, Angulo P. Noninvasive evaluation of NAFLD. Nat Rev Gastroenterol Hepatol 2013;10:666–75.
Mikolasevic I, Milic S, Orlic L, Stimac D, Franjic N, Targher G. Factors associated with significant liver steatosis and fibrosis as assessed by transient elastography in patients with one or more components of the metabolic syndrome. J Diabetes Complications 2016;30:1347–53.
Abdullah E, Idris A, Saparon A. Concomitant screening for liver fibrosis and steatosis in French type 2 diabetic patients using fibroscan. ARPN J Eng Appl Sci 2017;12:3218–21.
Park CC, Nguyen P, Hernandez C, Bettencourt R, Ramirez K, Fortney L, et al. magnetic resonance elastography vs transient elastography in detection of fibrosis and noninvasive measurement of steatosis in patients with biopsy-proven nonalcoholic fatty liver disease. Gastroenterol 2017;152:598–607.
Kamath PS, Mookerjee RP. Expanding consensus in portal hypertension Report of the Baveno VI Consensus Workshop: Stratifying risk and individualizing care for portal hypertension. J Hepatol 2015;63:543–5.
Boursier J, Zarski JP, de Ledinghen V, Rousselet MC, Sturm N, Lebail B, et al. Determination of reliability criteria for liver stiffness evaluation by transient elastography. Hepatol 2013;57:1182–91.
Juárez-Hernández E, Uribe-Ramos MH, Ramos-Ostos MH, López-Ramírez AY, Ornelas-Arroyo S, Romero-Flores JL, et al. Factors associated with the quality of transient elastography. Dig Dis Sci 2015;60:2177–82.
Idilman IS, Tuzun A, Savas B, Elhan AH, Celik A, Idilman R, et al. Quantification of liver, pancreas, kidney, and vertebral body MRI-PDFF in non-alcoholic fatty liver disease. Abdom Imaging 2015;40:1512–9.
Idilman IS, Aniktar H, Idilman R, Kabacam G, Savas B, Elhan A, et al. Hepatic steatosis: quantification by proton density fat fraction with MR imaging versus liver biopsy. Radiol 2013;267:767–75.
Idilman IS, Keskin O, Elhan AH, Idilman R, Karcaaltincaba M. Impact of sequential proton density fat fraction for quantification of hepatic steatosis in nonalcoholic fatty liver disease. Scand J Gastroenterol 2014;49:617–24.
Middleton MS, Heba ER, Hooker CA, Bashir MR, Fowler KJ, Sandrasegaran K, et al. Agreement between magnetic resonance imaging proton density fat fraction measurements and pathologist-assigned steatosis grades of liver biopsies from adults with nonalcoholic steatohepatitis. Gastroenterol 2017;153:753–61.
Bedossa P, Burt AD, Gouw ASH, Biology M, Schirmacher P, Terracciano L, et al. Utility and appropriateness of the FLIP algorithm and SAF score in the evaluation of biopsies of nonalcoholic fatty liver disease. Hepatol 2014;60:565–575.
Rastogi A, Shasthry SM, Agarwal A, Bihari C, Jain P, Jindal A, et al. Non-alcoholic fatty liver disease – histological scoring systems: a large cohort single-center, evaluation study. Apmis 2017;125:962–73.
Musso G, Cassader M, Rosina F, Gambino R. Impact of current treatments on liver disease, glucose metabolism and cardiovascular risk in non-alcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis of randomised trials. Diabetologia 2012;55:885–904.
Povsic M, Oliver L, Jiandani NR, Perry R, Bottomley JA structured literature review of interventions used in the management of nonalcoholic steatohepatitis (NASH). Pharmacol Res Perspect 2019;00.
Tong W, Ju L, Qiu M, Xie Q, Chen Y, Shen W, et al. Liraglutide ameliorates non-alcoholic fatty liver disease by enhancing mitochondrial architecture and promoting autophagy through the SIRT1/SIRT3-FOXO3a pathway. Hepatol Res 2016;46:933–43.
Madsbad S, Dirksen C, Holst JJ. Mechanisms of changes in glucose metabolism and bodyweight after bariatric surgery. lancet Diabetes Endocrinol 2014;2:152–64.
Lassailly G, Caiazzo R, Buob D, Pigeyre M, Verkindt H, Labreuche J, et al. Bariatric surgery reduces features of nonalcoholic steatohepatitis in morbidly obese patients. Gastroenterol 2015;149:379-88.
Méndez-Sánchez N, Chavez-Tapia NC, Almeda-Valdes P, Uribe M. The management of incidental fatty liver found on imaging. What do we need to do? Am J Gastroenterol 2018;1–3.
Sánchez-Jiménez BA, Brizuela-Alcántara D, Ramos-Ostos MH, Alva-López LF, Uribe-Esquivel M, Chávez-Tapia NC. Both alcoholic and non-alcoholic steatohepatitis association with cardiovascular risk and liver fibrosis. Alcohol 2018;69:63–7.
Sarkar M, Terrault N, Duwaerts CC, Tien P, Cedars MI, Huddleston H. The association of hispanic ethnicity with nonalcoholic fatty liver disease in polycystic ovary syndrome. Curr Opin Gynecol Obstet 2018;1:24-33.