Q&A: Obesity, fatty liver play role in increased risk for COVID-19
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Data from the UK BioBank demonstrated patients with obesity and fatty liver had an increased risk for symptomatic COVID-19 infection, according to a release from Perspectum.
However, patients with obesity, but normal liver fat had no increased risk.
Healio Gastroenterology spoke with Matt Kelly, PhD, chief innovation officer at Perspectum, about results from the study that comprised over 40,000 participants from the UK BioBank. Investigators used MRI scanning with Perspectum’s LiverMultiScan to determine if patients had fatty liver disease. They combined these results with those from COVID-19 testing to determine risk factors correlated with severe COVID-19 infection.
Healio: What was the purpose and design of the study?
Kelly: The purpose was to understand how key measures of liver health may impact COVID-19 and the likelihood of infection, or the severity of the infection once they become infected. Like a lot of organizations, at the start of the pandemic, we looked at what we could do to contribute to the efforts to combat COVID-19. The UK BioBank is a 500,000-patient study in the United Kingdom where they are collecting detailed phenotypical and genotypical information from volunteers and following up with healthcare records. Over 42,000 people in the UK BioBank have LiverMultiScan data. When they released COVID-19 test data for these people, we were in a unique position to look at various characteristics including those from the LiverMultiScan and determine how they correlate to the likelihood of having a positive test.
Healio: What were the results?
Kelly: If you had a lot of fat in your liver, above 10%, then you were about two times more likely to have symptomatic COVID. Initially only those symptomatic and hospitalized were tested for COVID-19, that allowed us to determine from the data that if patients had a positive test then they would have been quite severe to require hospitalization. Now, testing is far more widespread, lot more people were tested with only mild symptoms. We were able to see a link between positive test results and symptomatic or severe COVID-19. We looked at a sub-analysis of obesity and liver fat to see if they are correlated; a lot of people who are obese do not have liver fat above 10%. We found that people who are obese and had liver fat above 10% were at increased risk. In that sub-analysis, the risk went up nearly three-fold. When you compare people, who are obese and have liver fat below 5%, they are not at increased risk and although it was not significant it was pointing to a slightly protective effect. So, you were less likely to have a positive test if you were obese but had a low or healthy liver fat.
Healio: What is the conclusion?
Kelly: The link between liver fat and the severity of the COVID-19 is important information for resource planning because we know there are certain populations right now that are shielded or known to be at increased risk for the disease. Fatty liver puts you in a high-risk category and is something that should be considered. You can’t determine someone’s body fat based on a person’s size. Just because someone may be obese, there is only about a 30% chance that they are in the high-risk category.
Healio: What is the take-home message of the study?
Kelly: As more data become available from the UK BioBank, we will have more concrete information. Fatty liver disease appears to play a role in the severity of COVID-19 infection. Greater liver fat correlated with more severe disease and that is independent of obesity. Something about the mechanism in fatty liver disease increases their susceptibility to COVID-19. We hope the results, as we get more data, have the potential to inform health policies around this at-risk population.
Healio: What is the next step in research?
Kelly: The UK BioBank is still releasing more test data for their patients. We are getting a higher proportion of test data as more people are being tested in the population. We will also be adding richer data regarding hospital admissions. As these data become available, we will be able to look more at the detail and the role of other conditions such as hypertension or diabetes.
We can assess genetic risk factors as well. We are expanding on the study on the UK BioBank, with people we know have been hospitalized for COVID-19. They are getting very detailed scanning after the infection, so we can see if there is evidence of damage that has happened as a result of the infection. We are looking at the risk and pre-risk and the impact of COVID-19 on organ health and function after an infection and how well they recover. This will give us a comprehensive assessment of the interplay between multi-organ disease, liver disease and COVID-19.
These data are preliminary, so it is not a complete study that has been peer-reviewed yet. They are exciting results that are aligned with other data that we are seeing coming from Asia — from China in particular — a French study in patients with diabetes and a U.K. study with the open safety organization that is looking at deaths links to COVID-19. All those studies identified liver disease as a risk factor. A lot of patients do not realize they have increased liver fat because it is generally pre-symptomatic.
Perspective
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Shreya Sengupta, MD
This is an interesting study. The UK Biobank enrolled 500,000 people between 2006-2010 and continues to prospectively follow them. It was remarkable to see that 40,000 people who underwent a specific liver imaging test to look at fatty liver were then followed to look at COVID-19 symptoms. The investigators found that even 10% of fat in the liver was linked to a two-fold increase in the chance of having symptomatic COVID-19 infection. When we see patients with fatty liver, one of the tests we use is FibroScan and 10% fat in the liver is considered early stage or lower level steatosis. One item that I want clarification on is how investigators used MRI scanning with Perspectum’ s LiverMultiScan and which protocol was used for the MRI. We use different ones in hepatology that provide varying degrees and different types of information. Having an understanding of this protocol, what specific information it provides, and how it compares to the in-office tools we use in hepatology would be helpful.
The article does a good job of making the point that obesity and fatty liver are not synonymous and not everyone who is obese has fatty liver. It should also be noted that not everyone who has fatty liver is obese. While the general definition for obesity uses a BMI greater than 30 kg/m2 , this may not be accurate for all ethnicities. For example, in Asian populations, obesity or being overweight has a much lower BMI cutoff of 23 kg/m2 to 25 kg/m2. Obesity isn’t the same for everyone. Fatty liver is a heterogenous description which encompasses a lot of different phenotypes. Some people are obese and have fatty liver and high blood pressure and high cholesterol, and some people do not have those risk factors. The patients followed in this study should be further categorized and stratified by BMI, presence of co-morbidities like diabetes, high blood pressure, high cholesterol, etc. That would be helpful to know when interpreting this data. It would be particularly interesting to know how diabetes impacts outcomes of COVID-19 in this prospective cohort because there seems to be mixed data in the literature. Some studies would indicate diabetes and fatty liver is a risk factor for COVID-19 and some studies indicate fatty liver without diabetes is at higher risk. These data would be able to give some of those answers.
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