Hepatitis, alcoholic

Propylene glycol is partially excreted by the kidney unchanged and partially metabolized by hepatic alcohol dehydrogenase to lactic acid and pyruvate. 

The first human hver transplantations were performed in 1963 by Starzl and colleagues. Until the application of immune system suppressants, the long-term survival rate of transplant recipients was poor. Continued improvements in surgical techniques, organ preservation, and immune suppression led to I-year survival rates of 85% to 90%. The most common indications for the need for a hver transplantation are chronic hepatitis, alcoholic hver disease, and cirrhosis. The widening gap between the need for transplant material and the supply has caused the medical research community to search for alternatives to transplantation. 

Kemper and Elfarra (1996) demonstrated the oxidation of butenediol by hepatic alcohol dehydrogenase (ADH), yielding 1-hydroxy-2-butanone as a single stable metabolite various intermediates have been proposed. For the ADH-dependent oxidation of racemic butenediol in liver cytosol of male B6C3Fj mice, male Sprague-Dawley rats and three humans, saturation kinetics were found. The ratio was similar in these... 

Milk thistle has been used to treat acute and chronic viral hepatitis, alcoholic liver disease, and toxin-induced liver injury in human patients. Milk thistle has most often been studied in the treatment of alcoholic hepatitis and cirrhosis. In both of these disorders, outcomes have been mixed and reports include significant reductions in markers of liver dysfunction and in mortality, as well as no effect. In acute viral hepatitis, studies have generally involved small sample sizes and have shown mixed outcomes of improved liver function (eg, aminotransferase values, bilirubin, prothrombin time) or no effect. Studies in chronic viral hepatitis and toxin-induced injury have also been of small size but have reported mostly favorable results. Parenteral silybin is marketed and used in Europe as an antidote in Amanitaphalloides mushroom poisoning, based on favorable outcomes reported in case-control studies. 

Lee TD, Sadda MR, Mendler MJ, et al. Abnormal hepatic methionine and glutathione metabolism in patients with alcoholic hepatitis. Alcohol Clin Exp Res 2004 28 173-181. 

Panes J, Soler X, Pares A, et al. (1989) Influence of liver disease on hepatic alcohol and aldehyde dehydrogenases. Gastroenterology 97 708-714. 

Bautista, A.P. (2002). Neutrophilic infiltration in alcoholic hepatitis. Alcohol 27 17-21. 

Methanol is widely available as a solvent and in paints and antifreezes, and may be consumed as a cheap substitute for ethanol. As little as 10 ml may cause permanent blindness and 30 ml may kill, through its toxic metabolites. Methanol, like ethanol, is metabolised by zero-order processes that involve the hepatic alcohol and aldehyde dehydrogenases, but whereas ethanol forms acetaldehyde and acetic acid which are partly responsible for the unpleasant effects of hangover, methanol forms formaldehyde and formic acid. Blindness may occur because aldehyde dehydrogenase present in the retina (for the interconversion of retinol and retinene) allows the local formation of formaldehyde. Acidosis is due to the formic acid, which itself enhances pH-dependent hepatic lactate production, so that lactic acidosis is added. 

Liver disease progresses more rapidly in women, with the incidence of cirrhosis being 2 or 3 times higher than in men. Gender-specific differences in the gastric and hepatic alcohol metabolism are thought to be the factors responsible for this. 

Acute and chronic hepatitis, alcohol-induced fatty liver, cirrhosis, cholestasis, haemochromatosis... 

Tshii K, Furudera S, Kumashiro R, Koga Y, Hamada T, Sata M, et al. Clinical and pathological features, and the mechanism of development in severe alcoholic hepatitis, especially in comparison with acute type fulminant hepatitis. Alcohol Alcohol Suppl 1993 1B 97-103. 

Felver, M. E., Mezey, E., McGuire, M., Mitchell, M. C., Herlong, H. F., Veech, G. A., and Veech, R. L. Plasma tumor necrosis factor alpha predicts decreased long-term survival in severe alcoholic hepatitis. Alcohol. Clin. Exp. Res. 14, 255-259 (1990). 

Calcium-channel blockers Nifedipine and verapamil can increase alcohol serum levels by about 15-50%. The mechanism is speculated to be via inhibition of hepatic alcohol metabolism. Some data suggest that alcohol might also inhibit the metabolism of nifedipine, thus raising its serum levels with consequent effects. 

Ethanol is a dietary fuel that is metabolized to acetate principally in the liver, with the generation ofNADH. The principal route for metabolism of ethanol is through hepatic alcohol dehydrogenases, which oxidize ethanol to acetaldehyde in the cytosol (Fig. 25.1). Acetaldehyde is further oxidized by acetaldehyde dehydrogenases to acetate, principally in mitochondria. Acetaldehyde, which is toxic, also may enter the blood. NADH produced by these reactions is used for adenosine triphosphate (ATP) generation through oxidative phosphorylation. Most of the acetate enters the blood and is taken up by skeletal muscles and other tissues, where it is activated to acetyl CoA and is oxidized in the TCA cycle. 

Choi CW, Lee SI, Huh K. Effect of ginseng on the hepatic alcohol metabolizing enz3nne system activity in chronic alcohol-treated mice. Korean JPharmacol (1984) 20, 13-21. 

In conlcusion, the rates of ethanol metabolism and the activity of hepatic alcohol dehydrogenase are both reduced in fetal life and in the newborn when compared with values obtained in the adult. Significant microsomal ethanol oxidizing system and catalase activities are detected early in fetal life and do not increase during further fetal development However, the contribution of these two enzymes to the m vivo metabolism of ethanol during development remains to be evaluated. 

In that It markedly Inhibits hepatic alcohol dehydrogenase l. This action of butyraldoxlme Is not unexpected in view of the earlier observation that hydroa lanlne and pyruvoxlne Inhibit alc< ol dehydrogenase in vitro, Witii a short interval between administratlm of butyral-doxime and alcohol, acetaldehyde accumulation is suppressed and alcohol disappearance is ratarded, because of the concomitant inhibition of the rate-limiting alcohol dehydrogenase step. 

The authors highlighted the need for liver function monitoring in the first few weeks of buprenorphine treatment in susceptible patients, such as those with hepatitis, alcohol abuse, or concomitant use of drugs that cause mitochondrial toxicity. 

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