Diagnosis and management of secondary causes of steatohepatitis

J Hepatol. 2021 Jun;74(6):1455-1471. doi: 10.1016/j.jhep.2021.01.045. Epub 2021 Feb 10.


The term non-alcoholic fatty liver disease (NAFLD) was originally coined to describe hepatic fat deposition as part of the metabolic syndrome. However, a variety of rare hereditary liver and metabolic diseases, intestinal diseases, endocrine disorders and drugs may underlie, mimic, or aggravate NAFLD. In contrast to primary NAFLD, therapeutic interventions are available for many secondary causes of NAFLD. Accordingly, secondary causes of fatty liver disease should be considered during the diagnostic workup of patients with fatty liver disease, and treatment of the underlying disease should be started to halt disease progression. Common genetic variants in several genes involved in lipid handling and metabolism modulate the risk of progression from steatosis to fibrosis, cirrhosis and hepatocellular carcinoma development in NAFLD, alcohol-related liver disease and viral hepatitis. Hence, we speculate that genotyping of common risk variants for liver disease progression may be equally useful to gauge the likelihood of developing advanced liver disease in patients with secondary fatty liver disease.

Keywords: NAFLD progression; PNPLA3; endocrine disruptors; inborn errors associated with NAFLD; intestinal failure-associated liver disease; nutrition-associated; secondary NAFLD; toxicant-associated.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adult
  • Chemical and Drug Induced Liver Injury / epidemiology*
  • Child
  • Comorbidity
  • Endocrine System Diseases / drug therapy
  • Endocrine System Diseases / epidemiology*
  • Female
  • Gastrointestinal Diseases / diet therapy
  • Gastrointestinal Diseases / drug therapy
  • Gastrointestinal Diseases / epidemiology*
  • Genetic Diseases, Inborn / diet therapy
  • Genetic Diseases, Inborn / epidemiology*
  • Genetic Predisposition to Disease / genetics
  • Hepacivirus*
  • Hepatitis C, Chronic / drug therapy
  • Hepatitis C, Chronic / epidemiology*
  • Hepatitis C, Chronic / virology
  • Humans
  • Male
  • Metabolic Syndrome / diet therapy
  • Metabolic Syndrome / drug therapy
  • Metabolic Syndrome / epidemiology*
  • Non-alcoholic Fatty Liver Disease / epidemiology*
  • Non-alcoholic Fatty Liver Disease / genetics
  • Obesity, Abdominal / complications
  • Obesity, Abdominal / diet therapy
  • Obesity, Abdominal / epidemiology*
  • Pregnancy
  • Pregnancy Complications / epidemiology*
  • Risk Factors
  • Young Adult