Could genetics improve liver disease diagnosis?
An increasing number of people are dying prematurely from liver disease.
When caught early, liver disease can be treated successfully, but many people are not diagnosed until their condition has reached an advanced stage. At this point, treatments can only manage symptoms rather than provide a cure.
A new study from Glasgow Caledonian University, partly funded by us, highlights the role of genetics in interpreting results from liver blood tests. These findings could have significant implications for the way that liver disease is managed and treated, by making diagnoses more personalised to a patient’s genetic makeup.
[Our findings] could help clinicians to distinguish between patients who are at serious risk of liver disease and those whose results just reflect genetic factors.Dr Hamish Innes
Glasgow Caledonian University
Supported by our Emerging Leaders Prize funding, Dr Hamish Innes’ (Glasgow Caledonian University) new study was published last month in Liver International. His findings could improve the accuracy of early liver disease detection.
Liver disease and liver blood tests (LBTs)
Liver diseases can occur due to a range of factors, from excessive alcohol consumption to viral infections like hepatitis. Over the past 20 years, the number of premature deaths resulting from liver disease has risen by more than 60%, and hospital admissions for the condition remain high. [1]
To examine liver function, healthcare practitioners commonly use liver blood tests (LBTs) to analyse specific substances produced by the organ.
When liver cells are injured or inflamed, larger amounts of certain chemicals are released into the bloodstream, including liver enzymes that may appear higher than usual on blood tests. Until now, elevated liver enzymes were thought to be a sign of a more serious condition (such as liver disease).
The role of genetics in liver blood test results
In healthcare, it is common practice to target interventions towards people who exhibit elevated enzyme levels in liver blood tests. Clinicians commonly refer patients to specialist liver clinics on this basis alone, as it is assumed they have a higher risk of liver disease.
However, recent studies reveal that biomarkers such as enzyme levels can be influenced by other factors as well – such as age, ethnicity, and sample collection methods – not solely by presence of disease.
Genetics is another under-explored potential cause of abnormal enzyme levels. Dr Innes has focused on this very area.
In this study, Dr Innes and his team carried out a genome-wide association analysis of 10 different liver blood tests. The team set out to compare small variations in DNA and identify key genetic markers associated with elevated levels of various enzymes. This analysis was conducted using the UK Biobank, a large-scale biomedical database that contains data on more than half a million people. For this particular study, the team analysed genetic data from over 150,000 people.
Through this analysis, Dr Innes wanted to understand how genetic variability affects liver blood tests, and what implications this could have for how clinical practices identify the most ‘at-risk’ patients for liver disease.
For instance, Gilbert’s syndrome, a genetic disorder that affects the liver’s ability to process a substance called bilirubin, has been found to cause abnormal test results. People with this genetic disorder, despite their higher bilirubin levels, are at no greater risk of developing liver-related illnesses.
Dr Innes and his team were interested in finding out if other common liver blood tests, beyond bilirubin, similarly revealed abnormal results for people with this genetic disorder. Their results indicate that, while a large proportion of liver test abnormalities can be indicators of chronic liver disease, a significant number are not.
Implications for liver disease diagnostics
“Our study suggests that ‘abnormal’ values on LBTs often reflect an individual’s genetic makeup, rather than an increased risk of liver disease,” says Dr Innes.
Dr Innes’ findings reveal that elevated liver enzyme levels vary considerably based on the genes that make up a person’s DNA. In other words, liver test abnormalities could just be influenced by genetic factors that have a neutral effect on disease risk.
“By accounting for this genetic variability, we could help clinicians to distinguish between patients who are at serious risk of liver disease and those whose results just reflect genetic factors. This could, in turn, improve the accuracy of early liver disease detection.”
The study highlights the potential of genetics to improve diagnostic precision and support more personalised patient care. At a time when the NHS faces significant strain, these findings could help clinicians allocate resources more effectively, while also ensuring the best possible care for those suffering from chronic liver conditions.
Dr Innes and his team are now planning to explore this concept on a broader level, to see if other tests beyond those for liver disease are similarly influenced by genetic factors.
Read the full paper: https://doi.org/10.1111/liv.1611
References:
[1] British Liver Trust: Statistics https://britishlivertrust.org.uk/information-and-support/statistics