22nd July 2023

Non-alcohol related fatty liver disease (NAFLD)

Background

NAFLD is an increasingly common cause of liver disease in the UK and the Western world, in both adults and children. Prevalence increases with age and NAFLD currently affects ~20% population in developed countries. NAFLD is defined as the accumulation of fat (steatosis) in >5% of hepatocytes, in the absence of significant alcohol consumption or any other secondary cause of hepatic steatosis.

Risk factors include central obesity, impaired glucose tolerance, type 2 diabetes mellitus, hypertension, and hyperlipidaemia. NAFLD itself is also a risk factor for type 2 diabetes, hypertension and chronic kidney disease.

Complications may be liver related, e.g. liver failure, portal hypertension and hepatocellular carcinoma, or metabolic related, with cardiovascular disease being the most common cause of death in people with NAFLD.

Pathophysiology

NAFLD encompasses a spectrum of disease with the following stages: hepatic steatosis, non-alcohol related steatohepatitis (NASH), NASH with fibrosis, and hepatic cirrhosis. The disease often forms part of a wider metabolic syndrome, and it is thought that insulin resistance is one of the key mechanisms in the development of NAFLD.

Histological features are similar to those seen in alcohol-related liver disease and include steatosis, hepatocyte ballooning, inflammation and apoptosis and Mallory-Denk bodies.

Assessment and diagnosis

Many people with NAFLD are asymptomatic, which can make identifying cases challenging. Early recognition and intervention are crucial as, in the early stages, NAFLD is potentially reversible. NAFLD should be suspected in those with features of metabolic syndrome.

NAFLD is one of the most common causes for deranged liver blood tests and so may be picked up incidentally. However, not all those with NAFLD will have abnormal blood tests, so normal results cannot be used to exclude the disease. Imaging carried out for other purposes may also find incidental evidence of NAFLD.

A thorough assessment should be carried out, which covers alcohol intake, risk factors and exclusion of other causes of liver diseases.

Ultrasound imaging can be used to assess for increased hepatic echogenicity  – which is indicative of fatty liver changes. However, ultrasound may be normal in those with NAFLD.

The gold standard for diagnosis is liver biopsy and histology; however, this is invasive and costly. Diagnosis is, therefore, usually based on a combination of elements from the history, examination and investigation.

Non-invasive tests can be used to assess the severity of inflammation and fibrosis. NICE suggests using the enhanced liver fibrosis (ELF) test, which generates a score using a combination of three blood markers of fibrosis: tissue inhibitor of metalloproteinases 1, amino-terminal propeptide of type III procollagen and hyaluronic acid.

Transient elastography is a non-invasive test that is increasingly being used to detect fibrosis and cirrhosis.

If a non-invasive test cannot exclude fibrosis, the diagnosis is uncertain or another coexistent liver disease is suspected, then liver biopsy should be considered.

Management

The mainstay of management centres on lifestyle interventions: including physical activity, diet, preventing excess weight gain and avoiding excess alcohol intake. Other cardiovascular risk factors should be identified and treated appropriately, e.g. hypertension.

Those with advanced liver fibrosis should be referred for specialist assessment. NICE recommends consideration of pioglitazone or vitamin E, however, this an off-label use of both medications. Emerging treatment options include GLP-1 agonists and SGLT2 inhibitors.

Bariatric surgery may be considered in some patients and has the potential to reverse steatosis and fibrosis.

For those with end-stage liver disease, transplantation is the only curative treatment option. However, NAFLD may recur in the transplanted liver, especially if contributory lifestyle factors are not addressed.