Nonalcoholic Fatty Liver Disease: Epidemiology, Pathogenesis, Natural History, Diagnosis, and Current Treatment Options

Abstract

Nonalcoholic fatty liver disease (NAFLD) is on the rise and has become a major etiology for chronic liver disease. It is frequently associated with obesity, insulin resistance, hypertension, and dyslipidemia and is considered the hepatic manifestation of metabolic syndrome. In this review, we present a summary of the epidemiology and pathogenesis of NAFLD, and discuss the clinical evaluation and stratification of NAFLD patients into low, intermediate, and high risk with respect to liver-related outcomes. While diet and exercise are the cornerstone of treatment in all patients, the low rate of adherence and inadequacy of these recommendations necessitate pharmacologic intervention, especially in intermediate- and high-risk patients. We discuss vitamin E and pioglitazone which are often used as first-line therapy by many practitioners, with pentoxifylline and liraglutide as backup agents. Several drugs are in advanced-phase clinical trials and will likely change the landscape for management of NAFLD in the very near future.

Keywords: hepatocellular carcinoma; metabolic syndrome; nonalcoholic fatty liver disease; nonalcoholic steatohepatitis; obeticholic acid; risk stratification; vitamin E.

Figure 1

Assessment and management of NAFLD. Patients with NAFLD typically come to the clinician’s attention due to elevated alanine aminotransferase (ALT) or steatosis on imaging usually done for unrelated indications. These patients should undergo evaluation to rule out alcoholic liver disease and etiologies other than NAFLD that could cause chronic liver disease. Diagnosis of NAFLD is confirmed using biochemical panels and imaging studies aimed at assessing steatosis and fibrosis. These confirmatory studies, together with NAFLD risk factors, are used for patient stratification into low-, intermediate-, and high-risk categories for liver-related outcomes. Recommendations are provided for management of patients in the different risk categories. Notes: Cutoff values for APRI, FIB-4, and NFS are reported by Angulo et al. ^*APRI formula: ((AST/AST upper limit of normal)/platelet [10⁹/L]) × 100. ^‡FIB-4 formula: (Age [years] × AST [U/L])/(platelet [10⁹/L] × √ALT [U/L]). ^#NFS formula: −1.675 + 0.037 × age [years] + 0.094 × BMI [kg/m²] + 1.13 × hyperglycemia/diabetes [yes = 1, no = 0] + 0.99 × AST/ALT ratio − 0.013 × platelet [10⁹/L] − 0.66 × albumin [g/dL]. Abbreviations: ALT, alanine aminotransferase; APRI, aspartate aminotransferase to platelet ratio index; AST, aspartate aminotransferase; CBT, cognitive behavioral therapy; CT, computed tomography; CV, cardiovascular; FIB-4, fibrosis 4; Hep, hepatitis; HCC, hepatocellular carcinoma; MRI, magnetic resonance imaging; NAFLD, nonalcoholic fatty liver disease; NFS, NAFLD fibrosis score.