With its merits identified by Plato and detriments characterized by Mr. Simpson, alcohol remains ingrained within the fabric of most modern cultures. The origins of alcohol consumption are controversial (with many cultures taking credit for this invention), but it probably dates back to the Paleolithic era in China when cavemen became inebriated after eating fermented fruit.1, 2 Over the ensuing millennia, a number of other liver scourges have emerged because of the genetic susceptibilities and behavioral foibles of mankind. Concurrently, the prevalence rate of alcoholic liver disease may have declined because of a decline in alcohol consumption in many societies.3 However, recent studies have demonstrated that alcoholic liver disease continues to be the major driver of liver-related mortality in the United States and in many other parts of the world.3 In fact, despite a reduction in alcoholic liver disease prevalence in some parts of the world, its prevalence and the number of associated deaths are actually increasing to record levels in other areas, one notable location being the United Kingdom, in which binge drinking may account for this Scottish bragging right.4 Despite these sobering statistics, many other liver afflictions receive an inordinate amount of research attention and financial interest despite their lower impact on human health. Are these musings just sour, fermented grapes, or is there really objective evidence? Table 1 shows the ratio of the estimated death rate attributed to each of four different liver diseases to the number of trials focused on each of these liver diseases; which we can refer to as the dEath-TO-trial ratio (ETOh) score. A high ETOh score reflects inadequate clinical trials for a relatively morbid condition, and a lower score reflects a greater density of treatment trials for a less morbid condition. The four conditions were chosen on the basis of availability of data from Vong et al.,5 whereas the clinical trial numbers were compiled from the government registered-trial Web site ClinicalTrials.gov (compiled on February 15, 2010).
|Liver Disease||Number of Trials (2/10/10)||Age-Adjusted Deaths* Rate (per 100,000)||ETOh Score|
|Alcoholic liver disease||34||12,185||358|
|Primary biliary cirrhosis||32||485||15.2|
|Hepatitis C virus||911||4443||4.9|
|Hepatitis B virus||850||1161||1.4|
The cursory yet informative ETOh score confirms that alcoholic liver disease is indeed clinically understudied in comparison with other less morbid liver diseases. In fact, the number of registered trials for the high-mortality syndrome of alcoholic hepatitis (n = 21) was similar to the number for genetic hemochromatosis (n = 27) and not much more than the number for primary sclerosing cholangitis (n = 15). Why is this? Perhaps the lack of clinical research attention reflects the fact that alcoholic liver disease affects a less affluent and less influential population of our society. This hypothesis is difficult to justify because we do have an entire institute at the National Institutes of Health focused on alcohol afflictions. However, my general reflection as a peer reviewer in National Institute on Alcohol Abuse and Alcoholism study sections is that the volume of submitted clinical trial studies dedicated to liver complications of alcohol is relatively low. Thus, rather than a lack of available resources, the dearth of clinical investigations of alcoholic liver disease may actually reflect a lack of an adequate investigator pipeline focused on the field. Indeed, when “the giants ruled the earth,” the best clinical trials in liver disease focused on alcoholic liver disease.6, 7
However, there is hope that the alcohol treatment trial machine, which has fallen off the wagon, can recover from this slip. Indeed, there has been a recent treatment trial binge led by the French and their lovely Rhone Viogniers,8-13 which has refilled the relative gap in practice-modifying treatment trials that has occurred since the pentoxifylline study was published in 2002.14 Indeed, many of our best and brightest new trainees are now going bottoms up to make a career out of alcoholic liver disease investigation (e.g., Winston Dunn and Sumeet Asrani at the Mayo Clinic in Rochester, MN). Especially with its important links to metabolic syndrome and viral hepatitis, which increase the risk for hepatocellular cancer, alcoholic liver disease could once again become a trendy liver disease. Furthermore, major advances are now also occurring on the genetic front with the identification of a gene linked to alcoholic liver disease that is conserved all the way from potatoes to humans (perhaps this is a clue about the link between obesity and alcoholic liver disease).15 These advances are essential because with alcohol indelibly integrated into our culture, it is not likely that alcoholic liver disease will be going anywhere anytime soon. If I am wrong, then the next round is on me!