Recommendations for research

The guideline committee has made the following recommendations for research. The guideline committee's full set of research recommendations is detailed in the full guideline.

1 Non-invasive tests for diagnosing NAFLD in adults

Which non-invasive tests are most accurate and cost-effective in identifying non-alcoholic fatty liver disease (NAFLD) in adults with risk factors, type 2 diabetes and metabolic syndrome?

Why this is important

Non-alcoholic fatty liver disease (NAFLD) is present in over 50% of adults with type 2 diabetes mellitus or metabolic syndrome. Untreated it can progress to fibrosis, cirrhosis and hepatocellular cancer. In most patients NAFLD is asymptomatic and is only detected incidentally when liver blood tests or abdominal ultrasound are performed for some other reason. Even then, more than 80% of patients with NAFLD have normal routine liver blood tests. There is an urgent need for a simple, accessible, cost-effective, non-invasive test capable of case-finding NAFLD in the huge numbers of people at risk.

The 'gold standard' for diagnosis is liver biopsy. It is not feasible to perform liver biopsy in large numbers of at risk patients, so magnetic resonance based techniques are increasingly used as the comparison in studies assessing non-invasive tests for NAFLD. These demonstrate high diagnostic accuracy but are impractical or too expensive for large scale case finding.

2 Non-invasive tests for diagnosing NASH

Which non-invasive tests most accurately identify non-alcoholic steatohepatitis (NASH) in people with non-alcoholic fatty liver disease (NAFLD)?

Why this is important

NASH develops in only a minority of people with NAFLD. It is thought to be the precursor of liver fibrosis, which is associated with morbidity and mortality. As a result, NASH has been the main target for treatment in NAFLD. This is because reducing the severity of NASH would reduce the risk of a person progressing to fibrosis and advanced liver disease. However, the only way to identify people with NASH is by performing an invasive liver biopsy which is impractical in view of its risks to health and cost. Given that between 20 and 30% of the population have NAFLD, it is important that we have a simple non-invasive method for determining which people have NASH. Then they can start treatment to reduce the risk of developing fibrosis and complications of end-stage liver disease.

3 Non-invasive tests for diagnosing NAFLD and advanced liver fibrosis in children and young people

Which non-invasive tests most accurately diagnose NAFLD and advanced liver fibrosis in children and young people?

Why this is important

NAFLD has become the most common chronic liver disease in children and young people in industrialised countries, mainly as a result of obesity.

NAFLD is often suspected in children and young people with abnormal liver tests or evidence of fatty changes on ultrasound. However, the spectrum of NAFLD (from simple steatosis to steatohepatitis, fibrosis, cirrhosis and liver-related morbidity) can be present in the absence of abnormal liver tests. Early detection and assessment of severity of NAFLD would help identify potential silent progressive fatty liver disease.

Diagnostic practice varies and includes clinical, biochemical and radiographic tests. The evidence review showed that few diagnostic techniques have been assessed in children and young people. There is some evidence for ELF in diagnosing advanced liver fibrosis in children and young people with NAFLD, but only from 1 study. Further research is needed to confirm the most accurate tests in this group.

4 Probiotic and prebiotic supplements

What is the clinical and cost effectiveness of probiotics or prebiotics to treat NAFLD in adults, young people and children?

Why this is important

NAFLD is the most common metabolic liver disease, occurring in approximately 30% of all adults, around 46% of obese people and around 53% of people with type 2 diabetes. Liver fat accumulation is the first stage of more serious chronic liver disease in NAFLD. A small body of evidence supports the use of probiotics in NAFLD but the data are inconclusive and high-quality double-blind randomised placebo-controlled trials are needed. The evidence from cross-sectional studies suggests associations between unfavourable disturbance in gut microbiota and obesity or type 2 diabetes, but there is very limited evidence on whether modifying the gut microbiota influences NAFLD.

5 Pharmacological therapy for advanced liver fibrosis in children and young people

What is the clinical and cost effectiveness of pharmacological therapy in children and young people with advanced liver fibrosis?

Why this is important

Observational studies reported that up to 10% of children and young people diagnosed with NAFLD progress to advanced liver fibrosis and are at risk of developing advanced stages of liver disease. Pharmacological treatment (for example, pioglitazone or vitamin E) could prevent progression to advanced liver fibrosis or end-stage liver disease, as has been reported in a number of high quality studies in adults with confirmed NAFLD. There are insufficient data on the efficacy of similar pharmacological treatment in children and young people with NAFLD to make clear treatment recommendations.