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Last reviewed: 21 Apr 2025
Last updated: 27 Jun 2024

Summary

Definition

History and exam

Key diagnostic factors

  • presence of risk factors
  • absence of significant alcohol use
  • mild abnormality in liver function tests
  • truncal obesity

Other diagnostic factors

  • fatigue and malaise
  • right upper quadrant abdominal discomfort
  • hepatosplenomegaly
  • signs of chronic liver disease

Risk factors

  • obesity
  • insulin resistance or diabetes
  • dyslipidaemia
  • hypertension
  • metabolic syndrome
  • rapid weight loss
  • medications
  • total parenteral nutrition (TPN)
  • diseases associated with SLD

Diagnostic investigations

1st investigations to order

  • serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT)
  • total bilirubin
  • alkaline phosphatase
  • gamma glutamyl transferase
  • FBC
  • metabolic panel
  • lipid panel
  • prothrombin time and INR
  • serum albumin
  • autoimmune liver disease screen
  • iron studies
  • hepatitis B surface antigen, surface antibody, and core antibody
  • hepatitis C virus antibody
  • alpha-1 antitrypsin level and phenotype
  • liver ultrasound

Investigations to consider

  • fasting insulin
  • homeostatic model assessment (HOMA) calculation
  • abdominal MRI
  • elastography
  • liver biopsy
  • ceruloplasmin
  • HFE gene mutation testing
  • anti-M2 mitochondrial antibody

Emerging tests

  • cytokeratin-18 fragments

Treatment algorithm

Contributors

Authors

Shahid M. Malik, MD
Shahid M. Malik

Clinical Associate Professor of Medicine

Division of Gastroenterology, Hepatology and Nutrition

Department of Medicine

Program Director, Transplant Hepatology Fellowship Program

Starzl Transplantation Institute

University of Pittsburgh Medical Center

Pittsburgh

PA

Disclosures

SMM declares that he has no competing interests.

Kapil B. Chopra, MD, FACP, FAASLD, AGAF
Kapil B. Chopra

Professor of Medicine

Medical Director of Comprehensive Liver Program and Liver Pancreas Institute

University of Pittsburgh School of Medicine

University of Pittsburgh Medical Center

Pittsburgh

PA

Disclosures

KBC declares that he has no competing interests.

Acknowledgements

Dr Shahid M. Malik and Dr Kapil B. Chopra would like to gratefully acknowledge Dr Rachel Zhuang, a previous contribution to this topic.

Disclosures

RZ declares no competing interests.

Peer reviewers

Philip Newsome, PhD, FRCPE

Senior Lecturer in Hepatology & Honorary Consultant Physician

Liver Research Group

Institute of Biomedical Research

The Medical School

University of Birmingham

Birmingham

UK

Disclosures

PN declares that he has no competing interests.

Stephen A. Harrison, MD, LTC, MC

Chief of Hepatology

Department of Medicine

Gastroenterology & Hepatology Service

Brooke Army Medical Center

Fort Sam Houston

Associate Professor of Medicine

University of Texas Health Science Center

Houston

TX

Disclosures

SAH is an author of a reference cited in this topic.

Robert D. Goldin, MBCHB, MD, FRCPath

Reader in Liver and GI Pathology

Imperial College at St. Mary's

London

UK

Disclosures

RDG declares that he has no competing interests.

References

Our in-house evidence and editorial teams collaborate with international expert contributors and peer reviewers to ensure that we provide access to the most clinically relevant information possible.

Key articles

Rinella ME, Neuschwander-Tetri BA, Siddiqui MS, et al. AASLD practice guidance on the clinical assessment and management of nonalcoholic fatty liver disease. Hepatology. 2023 May 1;77(5):1797-835.Full text  Abstract

Vos MB, Abrams SH, Barlow SE, et al. NASPGHAN clinical practice guideline for the diagnosis and treatment of nonalcoholic fatty liver disease in children: recommendations from the Expert Committee on NAFLD (ECON) and the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN). J Pediatr Gastroenterol Nutr. 2017 Feb;64(2):319-34.Full text  Abstract

European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD), European Association for the Study of Obesity (EASO). EASL-EASD-EASO clinical practice guidelines for the management of non-alcoholic fatty liver disease. J Hepatol. 2016 Jun;64(6):1388-402.Full text  Abstract

Kwo PY, Cohen SM, Lim JK. ACG clinical guideline: evaluation of abnormal liver chemistries. Am J Gastroenterol. 2017 Jan;112(1):18-35.Full text  Abstract

Reference articles

A full list of sources referenced in this topic is available here.

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