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Critique 156: The pattern of alcohol consumption and risk of cirrhosis – 10 February 2015

This paper, from a group of experienced investigators in Denmark using data from a large population-based cohort, attempted to judge how drinking pattern affects the risk of a subject developing alcoholic cirrhosis. From a cohort study of 55,917 participants (aged 50–64 years), the authors calculated hazard ratios (HRs) for alcoholic cirrhosis in relation to drinking frequency, lifetime alcohol amount, and beverage type. A total of 342 subjects developed alcoholic cirrhosis. The authors concluded that, in men, daily drinking was associated with an increased risk of alcoholic cirrhosis as compared with less frequent consumption; they also concluded that wine consumption might be associated with a lower risk of alcoholic cirrhosis that associated with the consumption of beer or liquor.

The major concern of Forum reviewers regarding this paper was the use of a diagnosis of “alcoholic cirrhosis” to judge the effects of alcohol on the disease; this was considered a type of circular reasoning. A diagnosis of alcoholic cirrhosis generally requires a history of alcoholism or heavy drinking, and subjects given that diagnosis would essentially be limited to those who were heavy drinkers. Thus, it would be no surprise to find a history of heavy drinking when evaluating alcohol as an exposure.

There was also concern about the implications of the author regarding frequency of drinking. The authors’ described in detail the relation of drinking pattern to liver cirrhosis, differentiating, in particular, effects associated with drinking daily versus drinking on 4-5, or 6 days a week. However, Forum members were concerned that as the overall average amount of alcohol for the daily drinkers exceeded that of those drinking less frequently, it was difficult to know if it was primarily the frequency of drinking (as concluded by the authors) or the total amount of alcohol consumed by subjects. The authors stated that they wanted to “execute evidence-based counselling,” which of course is praiseworthy, but Forum members had difficulty understanding why the effect of drinking 5-6 days/week should differ much from 7 days/week, especially if the usual amount was moderate. Indeed, the investigators state: “The mean alcohol amounts for daily drinkers were somewhat higher compared to those drinking less frequently in each category of alcohol amount, making it difficult to detangle the effect of drinking frequency and alcohol amount.” Forum members noted that the authors conclude that “daily drinking” was associated with increased cirrhosis, but they do not state daily drinking of how many drinks, which would be especially important. The study did not provide reliable data that would support alcohol-free days during the week.

The referent group in this study was made up of subjects reporting < 0 to 14 drinks/week, which would consist of light-to-moderate drinkers, those considered to be “sensible drinkers” in most cultures. Hence, it is no surprise that as subjects reported greater amounts of alcohol in the study, the risk of alcoholic cirrhosis increased. No one advises people to drink more than sensible limits. Further, there was a much higher risk of of cirrhosis among “current abstainers” than in the referent group, undoubtedly indicating that the current abstainers group included many former heavy drinkers.

Overall, the Forum thought that this paper raises, but does not answer, a number of questions about the relation of alcohol to the risk of cirrhosis: (1) Is wine really less liver-toxic than beer or liquor? (2) Should we really tell everyone to have one day each week without wine being included with their meal, or on which to avoid any alcohol? (3) Why is daily drinking, rather than 5 or 6 days per week dangerous for men but tends to be even slightly protective in women regarding liver disease? Because of concerns due to problems with bias from the diagnostic approach, the probability of under-reporting of alcohol consumption, and the lack of biological plausibility, we will need further scientific data to answer these important questions.

Reference: Askgaard G, Grønbæk M, Kjær MS, Tjønneland A, Tolstrup JS. Alcohol drinking pattern and risk of alcoholic liver cirrhosis: A prospective cohort study. Pre-publication. J Hepatol (2015) http://dx.doi.org/10.1016/j.jhep.2014.12.005

For the full critique of this paper by members of the International Scientific Forum on Alcohol Research, please click here
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