Alcohol intake and obesity are independent risk factors for morbidity among patients with cirrhosis, but the two factors do not appear to combine for a stronger effect (supra-additive), according to conclusions from a new analysis of participants in the UK Biobank study published in Hepatology.
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The researchers analyzed data from the records of 489,285 individuals in the UK Biobank from May 2006 to July 2010. Researchers defined morbidity as first-time hospitalization for cirrhosis and calculated the cumulative incidence at 10 years among included individuals. The researchers defined obesity as body mass index of at least 30 kg/m2 and healthy BMI as 20-25. Safe drinking was defined as having fewer than 22 units per week for males or fewer than 15 units for females, harmful drinking was defined as more than 50 units per week for males or more than 35 for females, and hazardous drinking was defined as 22-49 units per week for males and 15-35 for females. The researchers assumed 2 units in a pint of beer or cider, 1.5 units in a glass of wine and “other” drinks, and 1 unit per measure of spirits.
The mean age was 57.0 years, and 45.4% were male. Overall, 24.3% of subjects were obese, 76.5% had safe levels of alcohol consumption, 19.7% had hazardous alcohol consumption, and 3.8% were classified as harmful drinkers.
Overall, harmful drinking was associated with 5.0 times the 10-year cumulative incidence of cirrhosis morbidity among harmful versus safe drinkers (1.51% vs. 0.30%). However, among those with a healthy BMI, harmful was associated with an 8.6-fold increase of cirrhosis morbidity, compared with safe drinkers (1.38% vs. 0.16%). On the other hand, obese patients with harmful drinking habits had a 3.6-fold increase over obese safe drinkers (1.99% vs. 0.56%).
When looked at according to BMI, 10-year cumulative incidence was 3.1 times higher in patients who with obesity versus those who with healthy BMI (0.65% vs. 0.21%). This varied strongly with drinking: Safe drinkers who with obesity had 3.7 times the incidence, compared with safe drinkers with healthy BMI (0.56% vs. 0.15%), and harmful drinkers who were obese had a 1.4-fold increased incidence, compared with harmful drinkers of a healthy weight (1.99% vs. 1.38%).
“In contrast to some previous studies, we found little evidence that [obesity and drinking] interacted supra-additively to modulate the risk of cirrhosis morbidity,” the authors wrote. “On the contrary, through a relative risk lens, the association between alcohol intake and cirrhosis morbidity was actually weaker for individuals with obesity than for individuals with a healthy BMI (indicating a sub-additive relationship).”
Fine-Gray regression modelling seemed to confirm that the relationship was sub-additive. After controlling for various factors, researchers found that harmful drinkers had a 6.84-fold increased risk at a healthy BMI, while the risk was only 3.14 times higher in obese patients (P interaction = 3.53 x 10–6).
The findings contradict previous studies, which suggested that high BMI and harmful drinking combined may produce much higher risk than either factor alone, possibly because obesity might “prime” the liver to be vulnerable to the effects of alcohol.
The authors suggest that the differences in findings may be caused by methodological limitations of the earlier studies, such as reliance on self-reported BMI data; small sample sizes and a relatively small number of liver events among those with obesity and harmful alcohol consumption; and the failure to use a competing risk perspective. The latter is relevant because alcohol and obesity are risk factors for other potentially fatal health conditions.
But the current study is not without its own limitations, according to Nancy Reau, MD, who is a professor of medicine and chair of hepatology at Rush University Medical Center in Chicago, who was asked to comment on the findings. Dr. Reau pointed out that the authors found the highest frequency of complications was observed in people with harmful alcohol intake whose BMI was under 20. That group may be composed of subjects with sarcopenia and end-stage liver disease from alcohol use. “Until you can separate these from the truly healthy BMI but [with harmful alcohol use], you can’t interpret this arm,” said Dr. Reau.
Beyond that, the researchers found increased risks of harm among individuals regardless of BMI, but the risks were highest among those with BMI over 30. Dr. Reau posited that the frequency might have been significantly greater at BMI higher than 35 and 40, but the researchers didn’t report results among these subcategories.
“In no way does this suggest that we need to ignore alcohol use in our patients with NAFLD [nonalcoholic fatty liver disease] or [nonalcoholic steatohepatitis],” said Dr. Reau.
In fact, she pointed to a figure in the paper that showed the highest increase in frequency among those with harmful alcohol use and obesity. “It’s clear that both conditions are much more serious than just obesity alone. It is incredibly important to council our NAFLD patients on appropriate alcohol use, [since] problematic drinking increases their risk. Problematic drinking remains a serious problem and increased awareness and linking to addiction services is important,” she said.
The authors reported no conflicts of interest. Dr. Reau has no relevant financial disclosures.