Obesity and Alcohol May Interact to Increase Risk for Liver Disease

Laurie Barclay, MD

March 22, 2010

March 22, 2010 — Obesity and alcohol act together to increase the risk for liver disease in both men and women, according to the results of 2 prospective studies reported online in the March 11 issue of the BMJ.

Study 1: Liu and Colleagues

"Cirrhosis of the liver is a growing health problem in the United Kingdom, and deaths from this condition are increasing rapidly among both men and women," write Dr. Bette Liu, from the University of Oxford, United Kingdom, and colleagues from the Million Women Study Collaborators. "Alcohol is a well established cause of cirrhosis, and, although increases in alcohol consumption over the past 10 years are likely to have contributed to the observed rise in rates, other factors may also have a role. Evidence from prospective studies suggests that excess body weight may result in a substantial increase in the risk of death from liver cirrhosis."

The goal of the study was to examine the association between body mass index (BMI) and liver cirrhosis and the effect of BMI and alcohol consumption on the incidence of liver cirrhosis in middle-aged women in the United Kingdom. The study cohort consisted of 1,230,662 women participating in the Million Women Study who were recruited from 1996 to 2001 in National Health Service breast screening centers, and who were monitored by record linkage to routinely collected data regarding hospital admissions and deaths.

Mean age at recruitment was 56 years, and mean duration of follow-up was 6.2 years. The primary study endpoints were relative risk and absolute risk for first hospital admission with or death from liver cirrhosis, after adjustment for age, recruitment region, alcohol intake, smoking, socioeconomic status, and physical activity.

During follow-up, 1811 women had a first hospital admission with or died from liver cirrhosis. Increasing BMI was associated with increased incidence of liver cirrhosis among women with a BMI of 22.5 kg/m2 or more. For every 5-unit increase in BMI, the adjusted relative risk for cirrhosis increased by 28% (relative risk [RR], 1.28; 95% confidence interval [CI], 1.19 - 1.38; P < .001).

The relative increase in the risk for liver cirrhosis per 5-unit increase in BMI was not significantly different based on the amount of alcohol intake, but the absolute risk was significantly different. Among women with reported alcohol consumption of less than 70 g per week, the absolute risk for liver cirrhosis per 1000 women at 5 years was 0.8 (95% CI, 0.7 - 0.9) for those with a BMI of 22.5 to 25 kg/m2 and 1.0 (95% CI, 0.9 - 1.2) for those with a BMI of 30 kg/m2 or more. Among women with reported alcohol consumption of 150 g or more per week, the corresponding risks were 2.7 (95% CI, 2.1 - 3.4) and 5.0 (95% CI, 3.8 - 6.6), respectively.

"Excess body weight increases the incidence of liver cirrhosis," the study authors write. "In middle aged women in the UK, an estimated 17% of incident or fatal liver cirrhosis is attributable to excess body weight. This compares with an estimated 42% attributable to alcohol."

Limitations of the study include possible reporting errors in BMI and alcohol consumption and possible lack of generalizability to heavy drinkers.

"From a public health perspective, reducing both excessive alcohol consumption and excessive body weight should lead to a reduction in the incidence of liver cirrhosis," the study authors conclude.

Study 2: Hart and Colleagues

In the second study, Carole L. Hart, from University of Glasgow, Scotland, and colleagues analyzed data from 2 prospective cohort studies ("Main" and "Collaborative") enrolling a total of 9559 men. The goal was to determine whether alcohol intake and increased BMI acted together to increase the risk for liver disease. Average duration of follow-up was 29 years. Participants were divided into 9 groups based on BMI and alcohol intake, and the main endpoints were morbidity and mortality from liver disease.

There were 80 deaths (0.8%) from liver disease as the main cause and 146 deaths (1.5%) from liver disease as any contributing cause. Liver disease defined by a death, admission, or cancer registration occurred in 196 men (3.3%) in the Collaborative study.

After adjustment for other confounders, BMI and alcohol intake were strongly associated with liver disease mortality (P = .001 and P < .0001, respectively). Compared with underweight/normal-weight nondrinkers, drinkers of at least 15 units per week in any BMI category and obese drinkers had raised relative rates for all definitions of liver disease.

Men who drank at least 15 units per week had adjusted relative rates for liver disease mortality of 3.16 (95% CI, 1.28 - 7.8) for underweight/normal-weight men, 7.01 (95% CI, 3.02 - 16.3) for overweight men, and 18.9 (95% CI, 6.84 - 52.4) for obese men. Obese men reporting alcohol intake of 1 to 14 units per week had a relative rate of 5.3 (95% CI, 1.36 - 20.7). Relative excess risk caused by the interaction between BMI and alcohol drinking was 5.58 (95% CI, 1.09 - 10.1); synergy index = 2.89 (95% CI, 1.29 - 6.47).

"Raised BMI and alcohol consumption are both related to liver disease, with evidence of a supraadditive interaction between the two," the study authors write. "The occurrence of both factors in the same populations should inform health promotion and public health policies."

Limitations of this study include the possibility that BMI and alcohol consumption could have changed in the follow-up period, reliance on self-reported weight and height in the Main study, lack of waist and hip measurements, and lack of data on frequency of drinking or binge drinking. In addition, women could not be included because of small numbers and lack of events, and no clinical measurements of liver function were recorded.

Editorial: Prevention Better Than Cure

In an accompanying editorial, Dr. Christopher D. Byrne, from the University of Southampton, and Dr. S. H. Wild, from the University of Edinburgh, recommend further research on improved diagnosis and treatment of nonalcoholic fatty liver disease.

"In the meantime, the old adage of 'prevention is better than cure' remains pertinent to dealing with the problem of non-alcoholic fatty liver disease," Drs. Byrne and Wild write. "The increasing prevalence of obesity and alcohol consumption over time, together with the increasing prevalence of hepatitis C, are contributing to the increasing incidence and prevalence of liver disease."

"Reducing alcohol consumption and obesity are, at present, our only weapons against non-viral liver disease," Drs. Byrne and Wild conclude. "The progression of non-alcoholic fatty liver disease to end stage liver disease can now be added to the list of the undesirable consequences of modern lifestyles."

The Million Women Study was funded by Cancer Research UK, the NHS Breast Screening Programme, and the Medical Research Council. The Scottish study and 3 of its authors were supported by the Chief Scientist Office of the Scottish Government. The authors from both studies and Drs. Byrne and Wild have disclosed no relevant financial relationships.

BMJ. 2010;340:c912, c1240. Abstract

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