Liver Failure: Trends

In many areas of the world, liver failure results primarily from hepatitis virus infection and alcohol abuse.  However, following widespread vaccination of children and adults for two of the three most common hepatitis virus culprits (hepatitis A and hepatitis B), the incidence of virally-induced acute liver failure has significantly decreased in the United States.  Hepatitis C, however, remains a risk factor for liver disease pending approval of a new vaccine against this virus by the FDA. 

A new study in the Annals of Internal Medicine looked at more than 300 patients admitted to 17 major medical centers in the United States with a new diagnosis of acute liver failure.  The study found that 73% of the new liver failure patients were women, with a median age of only 38 years.  Overdose with acetaminophen (the active drug in Tylenol) was the single most common cause of acute liver failure, accounting for 39% of all cases.  Unusual reactions to other medications were suspected in an additional 13% of liver failure cases.  Hepatitis A or B viral infections accounted for 12% of cases, while 17% of cases were of undetermined causes.  Three weeks after diagnosis, 67% of all study patients were still alive.  Among the acetaminophen overdose patients, 68% were alive at three weeks, while patients with liver failure from other causes had a much poorer short-term survival rate (17-25%).  Liver transplantation was undertaken in 29% of patients. 

The authors of this study note that acetaminophen poisoning has replaced hepatitis A and hepatitis B as the most common causes of acute liver failure in the United States, which is, in turn, almost certainly due to the widespread administration of vaccines against these viral offenders.  At the same time, patients admitted with acute liver failure due to acetaminophen appeared to have a greater chance of recovery—and of avoiding liver transplantation—than patients admitted with liver disease due to other causes.  This study emphasizes the seldom-discussed potential toxicity of acetaminophen when not used according to recommendations.  Literally hundreds of millions of doses of acetaminophen have been taken by patients of all ages without side effects.  However, when taken in excessively large doses, this ubiquitous over-the-counter medication can seriously harm the liver.  (The concomitant use of acetaminophen with alcohol further increases the risk of liver injury.)  Acetaminophen is very safe for use in patients without preexisting liver disease, but only when used according to directions.  The results of this study serve as a reminder that even seemingly innocuous over-the-counter medications can be harmful if abused.

One Less Reason to be Depressed

In this week’s issue of the Journal of the American Medical Association (JAMA) is an interesting study that looked at the impact of the anti-impotence medication Viagra (sildenafil) on male patients taking antidepressant medications.  A troublesome side effect of the serotonin uptake inhibitor (SRI) antidepressants has been their negative effects of libido and erectile function in men.  Needless to say, patient compliance with SRIs is often adversely affected when such side effects are present.  A total of 90 male patients with depression were evaluated at three different university medical centers in the United States.  All 90 patients were considered to have major depression which was in remission on SRI therapy.  All patients developed sexual dysfunction after starting SRI therapy.  Half of the patients were randomly assigned to take Viagra for six weeks while the other half received a blue placebo pill (sugar pill).  The study found that 55% of the patients who had received the Viagra pills experienced significant improvement in libido and erectile function.  Only 4% of the patients taking the placebo pills reported any significant improvements in sexual desire and function.  When comparing the two groups, the researchers found no significant differences in symptoms of depression.  The study, therefore, concluded that the adverse effects of SRI drugs on male libido and sexual function could be significantly improved with Viagra.  The findings of this study may encourage men with major depression to continue with SRI therapy despite the association of this class of drugs with reduced libido and sexual function.

Binge Drinking in the United States

Also in this week’s issue of JAMA is a sobering (no pun intended…) look at the prevalence of binge drinking in the United States.  Defined by this study as the consumption of five or more alcoholic drinks at one time, the study looked at such behavior by performing annual random telephone surveys of adults throughout the US between 1993 and 2001.  In 1993, the first year that the survey was performed, 102,263 adults responded, while the 2001 survey encompassed more than 200,000 respondents.  The study’s researchers found that binge drinking increased an average of 17% during the course of the study.  Between 1995 and 2001, the increase in binge drinking per person surveyed was a whopping 35%.  Not surprisingly, we men accounted for 81% of binge drinking behaviors.  Although binge drinking has been historically most common among the 18-to-25 year-old population, 69% of binge drinking episodes occurred among those aged 26 or older during the study period.  People describing themselves as “moderate drinkers” accounted for 73% of the respondents who admitted to engaging in binge drinking behavior.  Not surprisingly, binge drinking was associated with a 14-fold increase in the likelihood of driving while under the influence of alcohol (when compared with non-binge drinkers).

This study paints a rather disturbing picture of alcohol abuse trends over much of the past decade in the US.  The study, unfortunately, does not address potential explanations for this worrisome shift in alcohol consumption habits.  However, the social, economic and personal ramifications of these disturbing findings are very clear indeed.  Also clear is the importance of effectively intervening to prevent binge drinking, particularly in the under-30 group where most of this behavior takes p lace.  College and university administrations need to be aware of both the prevalence and the danger of binge drinking, and parents must reinforce these concerns to their pre-college sons and daughters.  The cost to society from untreated alcohol abuse runs into the many billions of dollars, and it would appear that this cost will continue to rise if these trends continue unabated.

Obesity & Diabetes Trends in the United States

Also in JAMA is a report on the prevalence of obesity, diabetes, and obesity-related health risk factors in the United States.  This study, along with the binge drinking study reported in JAMA, was part of a larger comprehensive study termed the Behavioral Risk Factor Surveillance System.  In 2001, almost 200,000 people agreed to answer a comprehensive survey after being randomly contacted by telephone.  The volunteers were asked to report their weight and height, and the presence or absence of diabetes.  Body mass index (BMI), a standardized measure of obesity, was then calculated for each respondent based upon their anonymous self-reporting of height and weight.  Based upon the standard definition of obesity as a BMI greater or equal to 30, 21% of respondents could be categorized as obese, a 5.6% increase from 2000.  The prevalence of diabetes also increased more than 8% between 2000 and 2001, with nearly 8% of respondents carrying this diagnosis.  Just over 2% of respondents had a BMI of 40 or higher (morbid obesity) in 2001.  The presence of obesity was significantly associated with diabetes, high blood pressure, elevated cholesterol levels, asthma, arthritis and poor overall health status.  The study concludes that the prevalence of obesity and diabetes in the United States continues to increase from already unprecedented levels.  Moreover, obesity rates have climbed among both sexes, all ages, all races, all educational levels, and all smoking levels in America.  In view of the potentially life-threatening ailments associated with obesity, grater emphasis on educating Americans about eating a healthy diet, and increasing the amount of exercise in our daily routines, should be a high priority.

“The Pill” for Males?

Recent research has identified several effective male contraceptive medications (at least in laboratory rats).  However, almost all of them have nasty side effects, the most common of which are a reduction in blood testosterone levels and an excessively prolonged duration of action.  Needless to say, most men would be rather reluctant to take such an anti-fertility drug.  A new study in the current issue of the Proceedings of the National Academy of Science may improve the outlook for a male “Pill,” however.  Using a modified sugar molecule, scientists in England studied an oral male contraceptive called N-butyldeoxynojirimycin, or NB-DNJ, using laboratory mice.  Basically, NB-DNJ impairs the normal development of sperm, rendering them incapable of normal function.  However, the medication did not appear to reduce testosterone levels. 

Following three weeks of NB-DNJ administration, male mice became sterile, as their sperm became incapable of propelling themselves towards the female’s egg.  Within four weeks of stopping the drug, the male mice regained their prior level of fertility.  This is an interesting development that may hold some promise for humans as well.  Of course, extensive safety and efficacy studies in humans would be a prerequisite before FDA approval could be granted for public use.

Dr. Robert A. Wascher