What are the other causes of steatosis beyond non-alcoholic fatty liver disease (NAFLD)?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: January 10, 2026 • View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

Other Causes of Hepatic Steatosis Beyond NAFLD

When evaluating hepatic steatosis, clinicians must systematically exclude alcohol-related liver disease, medications, viral hepatitis (particularly HCV genotype 3), and rare metabolic/genetic disorders before confirming a diagnosis of NAFLD. 1

Alcohol-Related Steatosis

  • Significant alcohol consumption is defined as >21 drinks per week in men or >14 drinks per week in women, which indicates alcohol-related liver disease rather than NAFLD 1
  • Even alcohol consumption below these thresholds contributes to hepatic fat accumulation, particularly with binge drinking patterns 1
  • Use sensitive biomarkers when alcohol history is unreliable: urine ethyl glucuronide (detects use within 3-5 days) or blood phosphatidylethanol (detects use within 1-2 weeks) 1
  • The AUDIT-C questionnaire should be incorporated to standardize screening for alcohol misuse and binge drinking 1

Medication-Induced Steatosis

Approximately 2% of steatosis cases are attributable to prescribed medications, requiring a comprehensive drug history in all patients 1

High-Risk Medications:

  • Antiarrhythmics: Amiodarone causes hepatotoxicity with acute centrolobular confluent hepatocellular necrosis and chronic liver enzyme elevations 1, 2
  • Anticonvulsants: Carbamazepine, sodium valproate 1
  • Anti-metabolites: Methotrexate (particularly with cumulative doses >1.5 grams), 5-Fluorouracil 1, 3
  • Hormone modulators: Tamoxifen (estrogen receptor modulator), corticosteroids 1, 4
  • Antiretrovirals: Efavirenz and other HIV medications 1
  • Analgesics: NSAIDs 1

Methotrexate requires special attention: hepatotoxicity appears after prolonged use (≥2 years) and total cumulative doses ≥1.5 grams, enhanced by alcoholism, obesity, diabetes, and advanced age 3

Viral Hepatitis

  • Hepatitis C genotype 3 is specifically associated with increased rates of steatosis and must be excluded with viral serology in all patients undergoing evaluation for suspected NAFLD 1
  • HCV-related steatosis impacts both fibrosis progression and treatment response 5

Rare Metabolic and Genetic Causes

These should be considered particularly in lean individuals with steatosis who lack cardiometabolic risk factors 1:

Lipid Metabolism Disorders:

  • Lysosomal acid lipase deficiency (LAL-D) 1
  • Familial hypobetalipoproteinemia 1
  • Abetalipoproteinemia 1

Body Composition Disorders:

  • Lipodystrophy (both HIV-related and non-HIV forms) 1

Other Metabolic Conditions:

  • Wilson's disease (copper metabolism disorder) 1
  • Hemochromatosis (iron overload) - elevated ferritin and transferrin saturation warrant HFE gene testing 1
  • Alpha-1 antitrypsin deficiency 1

Nutritional and Gastrointestinal Causes

  • Total parenteral nutrition 1
  • Severe malnutrition (fully reversible with refeeding and does not cause chronic liver disease) 1, 6

Endocrine Disorders

  • Hypothyroidism should be evaluated as part of the comprehensive metabolic screen 1

Toxin Exposures

  • Vinyl chloride and other industrial toxins 1

Systematic Diagnostic Approach

A comprehensive metabolic and serological screen must be undertaken to consolidate the NAFLD diagnosis and exclude co-existent liver disease 1:

Required Laboratory Evaluation:

  • Autoimmune markers (ANA, anti-smooth muscle antibody) 1
  • Viral serology (hepatitis B surface antigen, hepatitis C antibody) 1
  • Iron studies (ferritin, transferrin saturation) 1
  • Copper studies (ceruloplasmin, 24-hour urine copper) 1
  • Alpha-1 antitrypsin level 1
  • Thyroid function tests 1

Critical Pitfall to Avoid:

Do not rely solely on liver enzyme levels - they can be normal in patients with significant NAFLD, and mildly elevated ferritin is common in NAFLD without indicating iron overload 1, 7

References

1
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

5
Research

Hepatic steatosis: a benign disease or a silent killer.

World journal of gastroenterology, 2008

6
Guideline

Ashwagandha-Induced Liver Injury

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Related Questions

Does hepatic steatosis (fatty liver disease) cause abdominal pain?
What is the relationship between hyponatremia (low sodium levels) and hepatic steatosis (fatty liver disease)?
Does hepatic (liver) steatosis cause pain?
How do I communicate ultrasound findings of questionable mild increased liver echotexture (possibly indicative of hepatic steatosis), a benign hepatic cyst, and a nonspecific hyperechoic structure near the umbilicus (possibly a periumbilical fat-containing hernia) to a patient?
What is the significance of mild hepatic (liver) steatosis with no substantial change from prior ultrasound results, and an otherwise normal abdominal ultrasound?
What is the initial management for a 17-year-old male with orchitis?
What is the recommended dose and administration of diazepam (Diazepam) for a pediatric patient experiencing an active seizure?
What alternative sleep medications do not cause QTc (QT interval corrected) prolongation for an older adult with a history of diabetes mellitus (DM), hypertension (HTN), heart disease, and possible dementia?
What differentiates Acute Motor Axonal Neuropathy (AMAN) from Acute Inflammatory Demyelinating Polyneuropathy (AIDP) in a pediatric patient?
What is the management approach for an older adult with Type 3 diabetes mellitus (associated with Alzheimer's disease) and cognitive decline?
What are the indications for stenting in an adult patient, likely older than 50 years, with a history of hypertension, diabetes, or atherosclerotic disease, and renal artery stenosis?

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.

Ask Question