Anne Burke

To address the hypothesis that elevated blood alcohol increases systemic oxidant stress, we measured urinary excretion of isoprostanes (iPs), free radical-catalyzed products of arachidonic acid. Ten healthy volunteers received acute doses of alcohol (Everclear-R) or placebo under randomized, controlled, double-blind conditions. Urinary iPF2a-III increased in a time- and dosage-dependent manner after dosing with alcohol, with the peak urinary iPF2a-III excretion correlating with the rise in blood alcohol. To determine whether oxidant stress was associated with alcohol-induced liver disease (ALD), we then studied the excretion of iP in individuals with a documented history of alcohol-induced hepatitis or alcohol-induced chronic liver disease (AC). Both urinary iPF2a-III and urinary iPF2a-VI were markedly increased in patients with acute alcoholic hepatitis. In general, urinary iPF2a-III was significantly elevated in cirrhotic patients, relative to controls, but excretion was more pronounced when cirrhosis was induced by alcohol than by hepatitis C. Excretion of iPF2a-VI, as well as 4-hydroxynonenal and the iPF2a-III metabolite, 2,3-dinor-5, 6-dihydro-iPF2a-III, was also increased in AC. Vitamin C, but not aspirin, reduced urinary iPs in AC. Thus, vasoactive iPs, which serve as indices of oxidant stress, are elevated in the urine in both acute and chronic ALD. Increased generation of iPs by alcohol in healthy volunteers is consistent with the hypothesis that oxidant stress precedes and contributes to the evolution of ALD.

The majority of candidates with end-stage alcoholic liver disease (ESALD) in the United States who are eligible for referral for liver transplantation (LT) are not being referred. There is a lack of firm consensus for the duration of abstinence from alcohol as well as what constitutes good psychosocial criteria for listing for LT. Evidence shows that the general public and the practicing physicians outside the transplant community perceive that patients with a history of alcohol abuse will make poor transplant candidates. However, physicians in the transplant community perceive selected patients with ESALD as good candidates. When considering patients for listing for LT, 3 months of alcohol abstinence may be more ideal than 6 months. Patients with a lack of social support, active smoking, psychotic or personality disorders, or a pattern of nonadherence should be listed only with reservation. Those who have a diagnosis of alcohol abuse as opposed to alcohol dependence may make better transplant candidates. Patients who have regular appointments with a psychiatrist or psychologist in addictions treatment training also seem to do more favorably.