Increase In ALT Activity Research Articles

Dehydroepiandrosterone restores hepatocellular function and prevents liver damage in estrogen-deficient females following trauma and hemorrhage.

Recent studies have shown that administration of the sex steroid dehydroepiandrosterone (DHEA) in males following trauma-hemorrhagic shock has salutary effects on the depressed cardiovascular and immunological functions under those conditions. Since the effects of sex steroids are gender specific, we examined whether administration of DHEA has any beneficial effects on hepatocellular function in female rats with low estrogen levels following trauma-hemorrhage. Ovariectomy was performed in female Sprague-Dawley rats 14 days prior to the experiments. The animals then underwent a 5-cm midline laparotomy and were subjected to hemorrhagic shock (40 mm Hg for 90 min). This was followed by fluid resuscitation (Ringer's lactate over 60 min) and administration of DHEA (30 mg/kg BW) or vehicle subcutaneously at the end of resuscitation. At 24 h after resuscitation hepatocellular function, i.e., clearance of indocyanine green (ICG), and hepatocyte damage (serum alanine aminotransferase) were measured. Plasma levels of DHEA and 17beta-estradiol were also assayed. Vehicle-treated rats had significantly reduced hepatocellular function, increased ALT activity, and decreased levels of 17beta-estradiol following trauma-hemorrhage compared to sham-operated animals (P < 0.05, ANOVA and Student-Newman-Keuls test). In animals receiving DHEA following trauma-hemorrhage, hepatocellular function and ALT activity were similar to those of shams. However, administration of DHEA did not influence the plasma levels of 17beta-estradiol. Administration of DHEA following trauma-hemorrhage restored hepatocellular function and reduced hepatic damage that was observed in ovariectomized female rats under such conditions. This salutary effect of DHEA did not appear to be due to elevated levels of plasma 17beta-estradiol. We therefore propose that DHEA should be considered a novel, safe, and useful adjunct in the treatment of trauma-induced hepatocellular dysfunction in ovariectomized and postmenopausal females.

Absence of antitrifluoroacetate antibody after halothane anaesthesia in patients exhibiting no or mild liver damage

It has been shown that the circulating antibodies, which bind to rat hepatic microsomal proteins obtained after in vivo exposure to halothane, are detectable by immunoblotting in patients with "halothane hepatitis (HH)," and that rabbit immunized anti-sera against trifluoroacetylated rabbit serum albumin (TFA-RSA) recognizes rat microsomal distorted polypeptides in almost the same way as do sera from patients with HH. In this paper, we report first the development of a novel method of synthesizing TFA-RSA using p-nitrophenyl TFA, and second the results of tests for circulating anti-TFA antibodies in the serum of 86 patients who had received halothane anaesthesia and developed no (67 patients) or mild (19 patients, the maximum activity of serum alanine aminotransaminase 519 IU.L-1) liver damage. Serum was selected from stored sera of post-transfusion patients. The new method of synthesizing TFA-RSA was convenient and was able to be done at neutral pH. Rabbit sera obtained after immunization with the newly synthesized TFA-RSA recognized the same polypeptides (109 kDa, 92 kDa, 80 kDa, 76 kDa, 64 kDa and 59 kDa) as the established anti-sera against TFA-RSA, and these reactions were inhibited in the presence of TFA-lysine. Circulating antibodies were not detected in our patients who had developed no or mild liver damage. The present finding supports the hypothesis that the appearance of circulating antibodies against microsomal distorted proteins are specific to patients with HH. Furthermore, we have shown here that the halothane-induced mild increase in ALT activity is not associated with the appearance of those circulating antibodies, supporting the pathophysiological difference between HH and halothane-induced mild hepatic damage.

Surrogate tests and the risk of posttransfusion hepatitis; their time has come

A total of 481 recipients of blood transfusions who had received 6,295 units of blood were followed for 6-9 months in order to evaluate the relationship between posttransfusion hepatitis (PTH) and transfusion of blood that is positive for antibody to hepatitis B core antigen (anti-HBc). The incidence of non-A, non-B PTH (NANB-PTH) was 11.9% among the 193 recipients who received one or more units of anti-HBc-positive blood compared to only 3.2% of the 288 recipients of only anti-HBc-negative blood (p &lt; 0.001). There was, however, no statistically significant difference in the prevalence of hepatitis B virus or hepatitis B serological response following transfusion of anti-HBc-positive blood compared to anti-HBc negative blood. The relationship of NANB-PTH following receipt of anti-HBc-positive blood and/or blood with an elevated ALT level was studied in a subset of 230 recipients and their 1,549 donors. Donor anti-HBc appeared to be more closely associated with an increased rate of NANB-PTH than an elevated donor ALT level, or with the volume of blood transfused. Donor blood that was anti-HBc-positive and blood with increased ALT activity behaved as independent variables with respect to the development of NANB-PTH. Although only 15% of the units that were anti-HBc-positive were associated with NANB-PTH, calculation of maxi-mal correlated efficacy predicted that exclusion of the 4% of the units that were anti-HBc-positive might have prevented 43% of the cases of NANB-PTH. The authors conclude that screening donors with surrogate tests should be seriously considered because of the serious complications of NANB-PTH.

Measuring bile-salt concentrations lacks clinical value for detecting hepatic dysfunction in infants receiving parenteral nutrition.

Concentrations of conjugated cholate, chenodeoxycholate, direct bilirubin, and alanine aminotransferase (ALT, EC 2.6.1.2) were measured in plasma of 122 low-birthweight infants receiving parenteral nutrition. Eighteen (15%) of them developed hepatic dysfunction. We observed two distinct biochemical patterns in these infants. In the Type A pattern (12 infants), concentrations of direct-reading bilirubin and bile salts increased with no change in ALT activity. In the Type B pattern (six infants), increases in the concentrations of bile salt and direct bilirubin were followed by increases in ALT activity. Hepatic dysfunction persisted significantly longer in infants who developed the Type B pattern. The two patterns did not differ significantly in the times at which values for bile salts or direct bilirubin in plasma became abnormal or became normal at resolution, nor did maximal concentrations of bile salts in plasma differ significantly. Maximal concentrations of direct bilirubin were higher in the Type B infants. We conclude that, in such infants, measurement of bile-salt concentrations in plasma offers no advantages for detecting hepatic dysfunction over the more conventional measurement of direct bilirubin in plasma.