Non-alcoholic hepatic steatosis, or non-alcoholic fatty liver disease (NAFLD), is one of the most common causes of chronic liver disease in the developed world.
It is a spectrum of disease, ranging from hepatic fat accumulation without inflammation to steatohepatitis, fibrosis, cirrhosis, and end-stage liver disease.
NAFLD is considered the hepatic manifestation of metabolic syndrome and is associated with obesity, dyslipidaemia, and type 2 diabetes mellitus.
The diagnosis of non-alcoholic fatty liver disease is based on exclusion of other aetiologies of hepatic steatosis, such as alcohol use, and supportive laboratory tests and imaging. Liver biopsy and histology is the gold standard for diagnosis, and is performed for patients at higher risk of fibrosis or steatohepatitis.
Lifestyle modification, including weight loss, physical activity, and dietary changes, is the first-line therapy. There are no licensed drug treatments, although use of pioglitazone or vitamin E may be considered for selected patients.
Hepatic steatosis occurs when intrahepatic fat is ≥5% of liver weight.
Non-alcoholic fatty liver disease (NAFLD) is evidence of hepatic steatosis (imaging or histological) in the absence of secondary causes of hepatic fat accumulation, such as significant alcohol consumption.
NAFLD can be categorised as non-alcoholic fatty liver (NAFL) or non-alcoholic steatohepatitis (NASH), depending on histological features. NAFL is the presence of hepatic steatosis without evidence of hepatocellular injury in the form of hepatocyte ballooning. NASH is the presence of hepatic steatosis and inflammation with hepatocyte injury (e.g., ballooning), with or without fibrosis. This distinction is important for prognosis because NASH may progress to cirrhosis and liver failure. The risk of NAFL progressing to cirrhosis or liver failure is minimal.
To more accurately reflect the pathogenesis of fatty liver, a new nomenclature of metabolic associated fatty liver disease (MAFLD) has been suggested.
This topic focuses on NAFLD. See also Alcoholic liver disease.
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
- signs of chronic liver disease
- insulin resistance or diabetes
- metabolic syndrome
- rapid weight loss
- total parenteral nutrition (TPN)
- diseases associated with hepatic steatosis
1st investigations to order
- serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT)
- total bilirubin
- alkaline phosphatase
- gamma glutamyl transferase
- 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
- liver biopsy
- HFE gene mutation testing
- anti-M2 mitochondrial antibody
- cytokeratin-18 fragments
without end-stage liver disease
end-stage liver disease
- Alcoholic liver disease
- Cryptogenic cirrhosis
- Autoimmune hepatitis
- Non-alcoholic fatty liver disease (NAFLD): assessment and management
- EASL-EASD-EASO clinical practice guidelines for the management of non-alcoholic fatty liver disease
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