Intended for healthcare professionals

Clinical Review State of the Art Review

Management of non-alcoholic fatty liver disease

BMJ 2021; 372 doi: (Published 18 January 2021) Cite this as: BMJ 2021;372:m4747
  1. Maria Letizia Petroni, doctor1,
  2. Lucia Brodosi, doctor1,
  3. Elisabetta Bugianesi, professor2*,
  4. Giulio Marchesini, professor1*
  1. 1Department of Medical and Surgical Sciences, “Alma Mater” University, IRCCS Policlinico Sant’Orsola, Bologna, Italy
  2. 2Division of Gastro-Hepatology, University of Turin, Turin, Italy
  3. *Contributed equally
  1. Correspondence to: G Marchesini giulio.marchesini{at}


Non-alcoholic fatty liver disease is a very common medical condition, driven by a combination of genetic and lifestyle factors, ultimately producing a severe chronic liver disease and increased cardiovascular risk. Most people are asymptomatic for a long time, and their daily life is unaffected, leading to difficulty in identifying and managing people who slowly progress to non-alcoholic steatohepatitis (NASH), NASH-cirrhosis, and eventually hepatocellular carcinoma. Despite advances in the understanding of pathogenic mechanisms and the identification of liver fibrosis as the strongest factor in predicting disease progression, no specific treatments have been approved by regulatory agencies. Outside controlled trials, treatment is generally limited to lifestyle intervention aimed at weight loss. Pioglitazone remains the drug of choice to reduce progression of fibrosis in people with diabetes, although it is often used off-label in the absence of diabetes. Vitamin E is mainly used in children and may be considered in adults without diabetes. Several drugs are under investigation according to the agreed targets of reduced NASH activity without worsening of fibrosis or improving fibrosis without worsening of NASH. Anti-inflammatory, anti-fibrotic agents and metabolism modulators have been tested in either phase III or phase IIb randomized controlled trials; a few failed, and others have produced marginally positive results, but only a few are being tested in extension studies. The development of non-invasive, easily repeatable surrogate biomarkers and/or imaging tools is crucial to facilitate clinical studies and limit liver biopsy.


  • Series explanation: State of the Art Reviews are commissioned on the basis of their relevance to academics and specialists in the US and internationally. For this reason they are written predominantly by US authors

  • Contributors: MLP and LB searched the literature and drafted parts of manuscript; EB and GM planned the review, drafted parts of manuscript, and critically revised the manuscript; all authors approved the final version. GM is the guarantor.

  • Competing interests: We have read and understood the BMJ policy on declaration of interests and declare the following interests: MLP has participated in an advisory board of Novo Nordisk; EB has received a grant from Gilead and participated in advisory boards of BMS, GENFIT, Gilead, Intercept, Inventiva, Novo-Nordisk, and Pfizer; GM has received honorariums from Eli Lilly and participated in advisory boards of Gilead, Novartis, Astra-Zeneca, Pfizer, and Mundipharma.

  • Provenance and peer review: Commissioned; externally peer reviewed.

View Full Text

Log in

Log in through your institution


* For online subscription