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A successful strategy for the treatment of hepatic damage should be based on the use of nontoxic drugs with a high therapeutic index and safety profile, as well as selective targeting delivery. To achieve these goals, several biological and synthetic vehicles have been formulated with a wide range of chemical and physical properties. These vectors allow the delivery of either traditional drugs or genetic material to the cells. Despite remarkable progress, the design of an ideal carrier is still to be accomplished. Safety issues concerning viral vectors and low efficiency of synthetic delivery systems are the main limitations of present vectors. Once these problems are overcome, the liver-specific targeting systems will provide new opportunities to treat a vast range of hepatic diseases.

Molecular biological investigations have become a predominant methodology applied to the study of alcohol-induced liver disease. The enzymatic pathways responsible for ethanol metabolism, and their genetic as well as environmental control, have become the focus of detailed investigation. More recently, the significance of cytokines in the pathogenesis of alcohol-induced liver disease has also become a major area of speculation. This review focuses on the advances made in studies of two important enzymes responsible for alcohol metabolism, alcohol dehydrogenase and aldehyde dehydrogenase, as well as the investigation of the proinflammatory and profibrogenic cytokines involved in the process of hepatic fibrogenesis. The quality and quantity of new discoveries made in the field of alcohol-induced liver disease is impressive, especially when one realizes that molecular biological approaches have been employed in this area for only 15 years. However, in most cases the studies have been predominantly descriptive, with little direct relevance to the therapeutics of alcoholism and alcohol-induced organ injury. Because the groundwork has been laid, one hopes that the next 15 years will rectify this failure.

High levels of serum cortisol or abnormal dexamethasone suppression tests may be helpful in diagnosing major depressive disorder. However, a controversy exists as to whether abnormal liver function associated with alcohol abuse may negate the diagnostic value of the dexamethasone suppression test in alcoholics. We investigated the value of the dexamethasone suppression test in alcoholics by analyzing the liver function, cortisol levels, and psychiatric status of inpatients from an alcohol detoxification treatment center. The subjects met the DSM III criteria for alcohol dependence but took no chronic medication and had negative screening for substance abuse. They had routine blood screening to evaluate liver function, the afternoon cortisol test and dexamethasone suppression test to study glucocorticoid activity, and a structured evaluation to determine psychiatric diagnoses. The blood chemistry findings demonstrated a lack of significant liver synthetic dysfunction in this group, although 43% of the subjects had some elevation of their liver enzymes. We did not find differences in the liver function between patients with normal and abnormal cortisol levels. However, subjects with endogenous depression did have significantly elevated afternoon cortisol levels, and they tended to have more normal liver tests. These results indicate that modest liver dysfunction does not contaminate the validity of the plasma cortisol tests or the dexamethasone suppression test as diagnostic tools for assessing depression in this group of detoxified alcoholics. In addition, they demonstrate an association between depression and plasma cortisol levels and suggest a correlation between depression and better liver function in alcoholics who seek detoxification.