Non-alcoholic fatty liver disease

Abstract

Non-alcoholic fatty liver disease (NAFLD) has a global prevalence of about 25%. Incidence is increasing with rising levels of obesity, type 2 diabetes and the metabolic syndrome, and NAFLD is predicted to become the leading cause of cirrhosis requiring liver transplantation in the next decade. However, the cardiovascular disease is the most common cause of death and only a minority will develop fibrosis and liver-related complications. Therefore, it is imperative to identify patients with advanced disease using non-invasive markers of fibrosis, which include serology-based tests (eg NAFLD Fibrosis Score and ELF test) and imaging (eg transient elastography). This targets appropriate patients for referral to secondary care for additional investigations such as liver biopsy and specialist care. Lifestyle modification and weight loss remains the cornerstone of management, but we are about to enter a new era of promising pharmacotherapies for NASH and fibrosis.

Keywords: diagnosis; fibrosis; liver disease; management; non-alcoholic fatty liver disease.

Fig 1.

Pathophysiology and treatment options in NAFLD. DM = diabetes mellitus; FXR = farsinoid X receptor; HCC = hepatocellular carcinoma; LPS = lipopolysaccharide; NAFLD = non-alcoholic fatty liver; NASH = non-alcoholic steatohepatitis; PNPLA3 = patatin-like phospholipase domain-containing protein 3; TLR = toll-like receptor

Fig 2.

Proposed investigation and management algorithm for NAFLD. NICE guidelines recommend ELF test. Where this is available, cut-off values are: –1.068 (moderate ≥F2 fibrosis) and 0.3576 (advanced fibrosis). FIB-4 is also well validated, with cut-off values ≤1.30 (low risk of significant fibrosis) and ≥2.67 (high risk of significant fibrosis). Further studies are required on the optimal frequency of follow-up; eg clinical stigmata of chronic liver disease, type 2 diabetes and/or obesity (BMI >30), platelets <150 cells/mm³, radiological evidence of cirrhosis. Always consider comorbidities and potential side effects, which include weight gain and congestive cardiac failure (pioglitazone), and possible increased risk of haemorrhagic stroke and prostate cancer (vitamin E). BMI = body mass index; CAP = controlled attenuation parameter; ELF = enhanced liver fibrosis; FLI = fatty liver index; GOV = gastro-oesophageal varices; HCC = hepatocellular carcinoma; MDT = multidisciplinary team; NICE = National Institute for Health and Care Excellence