Tratamiento de la hepatitis alcohólica / No disponible

No disponible

Short- and long-term outcome of severe alcohol-induced hepatitis treated with steroids or enteral nutrition: a multicenter randomized trial.

Steroids are recommended in severe alcohol-induced hepatitis, but some data suggest that artificial nutrition could also be effective. We conducted a randomized trial comparing the short- and long-term effects of total enteral nutrition or steroids in these patients. A total of 71 patients (80% cirrhotic) were randomized to receive 40 mg/d prednisolone (n = 36) or enteral tube feeding (2,000 kcal/d) for 28 days (n = 35), and were followed for 1 year or until death. Side effects of treatment occurred in 5 patients on steroids and 10 on enteral nutrition (not significant). Eight enterally fed patients were prematurely withdrawn from the trial. Mortality during treatment was similar in both groups (9 of 36 vs. 11 of 35, intention-to-treat) but occurred earlier with enteral feeding (median 7 vs. 23 days; P =.025). Mortality during follow-up was higher with steroids (10 of 27 vs. 2 of 24 intention-to-treat; P =. 04). Seven steroid patients died within the first 1.5 months of follow-up. In contrast to total enteral nutrition (TEN), infections accounted for 9 of 10 follow-up deaths in the steroid group. In conclusion, enteral feeding does not seem to be worse than steroids in the short-term treatment of severe alcohol-induced hepatitis, although death occurs earlier with enteral nutrition. However, steroid therapy is associated with a higher mortality rate in the immediate weeks after treatment, mainly because of infections. A possible synergistic effect of both treatments should be investigated.

Treatment of primary biliary cirrhosis.

Primary biliary cirrhosis is a chronic liver disease of unknown etiology, characterized by inflammation and destruction of the intrahepatic biliary ducts, resulting in chronic cholestasis and eventually cirrhosis. The main clinical manifestations consists of pruritus, jaundice, xanthomas, and the consequences of intestinal malabsorption, including vitamin deficiencies and osteodystrophy. Treatment of PBC is addressed at preventing or relieving the symptoms and clinical consequences of chronic cholestasis, and also at correcting the bile duct abnormalities by specific treatments. Pruritus is treated with cholestyramine, but in some cases other drugs, such as rifampicin or opioid antagonists are needed. Bisphosphanates are effective for increasing bone mass in osteopenic patients. Vitamin D and cAlcium supplements are also recommended, particularly in patients with severe cholestasis. Ursodeoxycholic acid (UDCA) has become the standard treatment (13-15 mg/kg/day), resulting in marked relieving of cholestasis. UDCA also prevents the histological progression of the disease, although the effects on survival are less apparent. Small trials of combination therapy using UDCA with methotrexate, colchicine, or prednisone, have been reported but have not shown any increased efficacy over UDCA therapy. Liver transplantation is the only treatment available when cholestasis progresses, with very good survival rates.

Zinc administration improves gastric alcohol dehydrogenase activity and first-pass metabolism of ethanol in alcohol-fed rats.

The effects of zinc on first-pass metabolism (FPM) of ethanol and gastric and hepatic alcohol dehydrogenase (ADH) activities have been investigated in two groups of male Wistar rats fed a liquid ethanol diet with normal zinc content (7.6 mg/liter), or zinc supplemented (76 mg/liter), for 21 days, and in two pair-fed groups receiving the same diets without ethanol. Alcoholic rats with normal dietary zinc had lower FPM (1.64 +/- 0.25 vs. 2.43 +/- 0.20 mM x hr, p < 0.05) and gastric ADH activity (184 +/- 7 vs. 335 +/- 41 micromol/min/mg protein, p < 0.01) than control rats. Zinc supplementation did not produce any change in FPM or in gastric ADH activity in control rats. By contrast, in alcoholic rats, the zinc supplement increased gastric ADH activity (247 +/- 31 vs. 184 +/- 7 micromol/min/mg protein, p < 0.05) and decreased the areas under the curve of blood ethanol concentrations after the intragastric administration of 0.25 g/kg of body weight of ethanol (0.78 +/- 0.07 vs. 1.71 +/- 0.24 mM x hr, p < 0.05), thereby increasing the FPM. In conclusion, in alcohol-fed rats, the administration of zinc supplements restores gastric ADH activity and improves the FPM of ethanol. These effects may be one of the mechanisms in which zinc has a beneficial role in preventing the development of alcoholic hepatic lesions.

Influence of zinc intake on hepatic lipid peroxidation and metallothioneins in alcoholic rats: relationship to collagen synthesis.

Hepatic lipid peroxidation, metallothioneins, collagen and proline hydroxylase activity were investigated in 16 ethanol-fed rats and in 16 control animals. The rats were further divided into three groups to receive either a standard diet, a zinc-deficient diet or a zinc-supplemented diet. The animals were sacrificed at week 12 of the experiment for histological and biochemical assessments. Hepatic tissue examination indicated that oral zinc supplementation was associated with a decrease in lipid peroxidation, collagen deposition and proline hydroxylase activity together with an increase in metallothionein concentration in alcoholic rats. There were no significant differences in lipid peroxidation in the control group in relation to the diet. Zinc supplementation was associated with increased concentrations of hepatic metallothioneins together with decreased concentrations of proline-hydroxylase and collagen but to a lesser degree than in alcoholic animals. These results indicate that zinc is an efficient hepato-protective agent against lipid peroxidation in alcoholic rats and its effect may be, in part, mediated by the activation of metallothionein synthesis. Also, lipid peroxidation may be related to changes in hepatic collagen synthesis.

Fibrogenic and collagenolytic activity in carbon-tetrachloride-injured rats: beneficial effects of zinc administration.

Collagen synthesis and degradation in normal and carbon-tetrachloride-injured male Wistar rats at early and late stages of liver fibrosis, and the potential beneficial effects of zinc supplementation on liver fibrogenesis and collagenolysis have been assessed by measuring hepatic collagen content and prolyl hydroxylase and collagenase activities. No significant changes in hepatic collagen and prolyl hydroxylase activities were observed between control rats (82 +/- 25 cpm/mg protein) and rats with induced cirrhosis (107 +/- 23 cpm/mg protein) after 4 weeks of carbon tetrachloride injury. By this time, hepatic collagenase activity was significantly lower in rats with induced cirrhosis (61 +/- 9 micro units/mg protein) than in control rats (133 +/- 31 micro units/mg protein) (p < 0.05). This result was prevented by zinc administration, since hepatic collagenase activity was similar in zinc-supplemented, carbon-tetrachloride-injured rats and normal rats (148 +/- 19 micromicrons/mg protein). After 16 weeks, all carbon-tetrachloride-injured rats had cirrhosis. Hepatic collagen content and prolyl hydroxylase activity were significantly higher in carbon-tetrachloride-injured rats than in controls. These effects were partially prevented by zinc administration, since only two of the seven zinc-supplemented, carbon-tetrachloride-injured rats had cirrhosis. Moreover, prolyl hydroxylase activity was significantly lower in zinc-supplemented injured rats (263 +/- 27 cpm/mg protein) than in the non-supplemented respective controls (389 +/- 52 cpm/mg protein) (p < 0.05). No significant changes in hepatic collagenase activity were observed at this stage of liver injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship between hepatic lipid peroxidation and fibrogenesis in carbon tetrachloride-treated rats: effect of zinc administration.

1. Lipid peroxidation and hepatic fibrogenesis were investigated in 25 carbon tetrachloride-treated rats and in 25 control animals. Rats were further divided into two groups to receive either a standard diet or one supplemented with zinc. From each group, animals were killed at weeks 3 and 18 of the experiment for histological and biochemical assessments which included hepatic lipid peroxide and collagen concentrations and plasma zinc concentration as well as the hepatic activities of proline hydroxylase and collagenase. 2. Results indicated that oral zinc supplementation was associated with a decrease in lipid peroxidation (mean 51%; P < 0.05), collagen deposition (mean 32%; P < 0.001) and proline hydroxylase activity (mean 30%; P < 0.05) at week 18, together with an increase in collagenase activity (mean 208%; P < 0.01) at week 3, in carbon tetrachloride-treated rats. 3. There was a significant direct correlation between lipid peroxidation and proline hydroxylase activity in carbon tetrachloride-treated rats (r = 0.52; P < 0.01) and also a significant inverse correlation between lipid peroxidation and plasma zinc concentration in these animals (r = -0.62; P < 0.001). 4. These findings are consistent with the hypothesis that hepatic lipid peroxidation plays an important role in the aetiology of hepatic fibrogenesis and that zinc mitigates the process.

Influence of dietary zinc on hepatic collagen and prolyl hydroxylase activity in alcoholic rats.

The effects of dietary zinc on hepatic collagen and prolyl hydroxylase activity in normal and alcoholic rats has been investigated in four groups of pair-fed male Wistar rats given either liquid ethanol or a control diet for 12 wk. Each group of pair-fed animals received a diet with a different zinc concentration (standard diet, 7.6 mg/L; low-zinc diet, 3.4 mg/L; zinc-supplemented diet, 76 mg/L; and zinc-extrasupplemented, 300 mg/L. There were no significant differences in hepatic collagen concentration and prolyl hydroxylase activity between alcoholic and normal rats receiving a standard diet (collagen, 77 +/- 5 and 73 +/- 6 micrograms/mg protein; and prolyl hydroxylase; 37 +/- 26 and 36 +/- 22 cpm/mg protein). Alcoholic rats fed a low-zinc diet showed increased prolyl hydroxylase activity (75 +/- 10 cpm/mg protein, p less than 0.05), although no changes in hepatic collagen (77 +/- 10 micrograms/mg protein) were observed in comparison with rats fed a standard alcoholic diet. By contrast, hepatic collagen was significantly lower in alcoholic rats fed a zinc-supplemented diet (66 +/- 4 and 63 +/- 3 micrograms/mg protein, p less than 0.05 and p less than 0.01, respectively), and hepatic prolyl hydroxylase activity was particularly lower in rats receiving zinc 300 mg/L (18 +/- 20 cpm/mg protein). Similar effects were observed in normal rats. We conclude that dietary zinc influences hepatic prolyl hydroxylase activity and collagen deposition in alcoholic rats, and in consequence, the control of dietary zinc is necessary to assess the effects of alcohol on collagen metabolism in rats.

Sodium fluoride prevents bone loss in primary biliary cirrhosis.

Low-bone-turnover osteoporosis is a common complication of primary biliary cirrhosis (PBC). Since sodium fluoride stimulates bone formation we assessed the effect of this drug on bone mass in a 2-year, prospective, double-blind trial including 22 women with PBC who were randomly assigned to receive sodium fluoride (50 mg/day) or placebo. All received calcium supplements and low doses of vitamin D. Bone mineral density of the lumbar spine was measured by dual-photon absorptiometry initially and every 6 months. Vertebral fractures were evaluated in thoracic and lumbar spine initially, and after 1 and 2 years. Seven patients in the fluoride group and eight in the placebo group completed the trial. In the fluoride group, bone mineral density did not change after 2 years (initial 1.05 +/- 0.07, final 1.07 +/- 0.06 g/cm2; p = n.s.). In the placebo group, however, bone mineral density decreased significantly (initial 1.00 +/- 0.07, final 0.93 +/- 0.06 g/cm2; p = 0.03). Moreover, in the fluoride group bone mineral density increased by 2.9 +/- 3.6%, and in the placebo group decreased by 6.6 +/- 2.6% (p = 0.04). None of the patients developed new vertebral or non-vertebral fractures. Treatment with sodium fluoride did not impair liver function or cholestasis in PBC. These results indicate that sodium fluoride prevents bone loss in PBC and therefore might be considered as a possible therapeutic agent for osteoporosis associated with this liver disease. Since a small number of patients completed the trial, further studies are required.

Effect of parenteral amino acid supplementation on short-term and long-term outcomes in severe alcoholic hepatitis: a randomized controlled trial.

The effect of parenteral amino acid administration on nutritional state, liver function and mortality was assessed in patients with severe alcoholic hepatitis. Twenty-eight patients received 2 l/day of a solution of dextrose (65 gm/L) and amino acids (25.8 gm/L) for 1 mo, whereas 26 received only the dextrose solution. All patients were allowed to eat a standard hospital diet. During the month in the hospital, there were six deaths in the treatment group and five deaths in the control group. Nitrogen balance improved in the treated group, but not in the control group. Creatinine-height index, triceps skin fold measurement and levels of serum albumin and prealbumin increased similarly in both groups. Serum retinol binding protein increased more in the treatment group than it did in the control group, and transferrin was increased only in the treatment group. Serum bilirubin, type III amino-terminal procollagen peptide and aminopyrine clearance improved more in the treatment group than in the control group, whereas serum AST and prothrombin time improved in the treatment group but not in the control group. Cumulative 2-yr survival rates from the day of entry into the study were 42% and 38% in the treatment and control groups, respectively. Patients who survived 2 yr and patients in the treatment group who died during the 2-yr follow-up had continued improvement in serum retinol binding protein, transferrin, bilirubin and prothrombin time. These parameters were unchanged in patients in the control group who died during follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)