Approach to the Patient With Nonalcoholic Fatty Liver Disease

J Clin Endocrinol Metab. 2023 Jan 17;108(2):483-495. doi: 10.1210/clinem/dgac624.

Abstract

Context: Nonalcoholic fatty liver disease (NAFLD) is associated with obesity and type 2 diabetes (T2D), causing substantial burden from hepatic and extrahepatic complications. However, endocrinologists often follow people who are at the highest risk of its more severe form with nonalcoholic steatohepatitis or NASH (i.e., T2D or obesity with cardiometabolic risk factors). Endocrinologists are in a unique position to prevent cirrhosis in this population with early diagnosis and treatment.

Objective: This work aims to offer endocrinologists a practical approach for the management of patients with NAFLD, including diagnosis, fibrosis risk stratification, and referral to hepatologists.

Patients: (1) An asymptomatic patient with obesity and cardiometabolic risk factors, found to have hepatic steatosis; (2) a patient with T2D and NASH with clinically significant liver fibrosis; and (3) a liver transplant recipient with a history of NASH cirrhosis, with significant weight regain and with recurrent NAFLD on the transplanted organ.

Conclusion: NASH can be reversed with proper management of obesity and of T2D. While no agents are currently approved for the treatment of NASH, treatment should include lifestyle changes and a broader use of structured weight-loss programs, obesity pharmacotherapy, and bariatric surgery. Diabetes medications such as pioglitazone and some glucagon-like peptide 1 receptor agonists may also improve liver histology and cardiometabolic health. Sodium-glucose cotransporter-2 inhibitors and insulin may ameliorate steatosis, but their effect on steatohepatitis remains unclear. Awareness by endocrinologists about, establishing an early diagnosis of fibrosis (ie, FIB-4, liver elastography) in patients at high-risk of cirrhosis, long-term monitoring, and timely referral to the hepatologist are all critical to curve the looming epidemic of cirrhosis from NAFLD.

Keywords: NAFLD; NASH; cirrhosis; insulin resistance; liver fat; nonalcoholic steatohepatitis; steatosis; type 2 diabetes.

MeSH terms

  • Diabetes Mellitus, Type 2* / drug therapy
  • Diabetes Mellitus, Type 2* / therapy
  • Humans
  • Liver / pathology
  • Liver Cirrhosis / complications
  • Liver Cirrhosis / diagnosis
  • Non-alcoholic Fatty Liver Disease* / complications
  • Non-alcoholic Fatty Liver Disease* / diagnosis
  • Non-alcoholic Fatty Liver Disease* / epidemiology
  • Obesity / drug therapy
  • Obesity / therapy
  • Sodium-Glucose Transporter 2 Inhibitors* / therapeutic use

Substances

  • Sodium-Glucose Transporter 2 Inhibitors