Aspartate Aminotransferase/alanine Aminotransferase Research Articles

Endothelin/Nitric Oxide Balance Influences Hepatic Ischemia-Reperfusion Injury

Summary: During ischemia-reperfusion an imbalance between endothelin (ET) and nitric oxide (NO) can be responsible for microcirculatory disturbances. The aim of this study was to restore the ET/NO balance to reduce the ischemia-reperfusion injury. Hepatic ischemia was induced for 30 min in 56 Wistar rats. Sham operation, ischemia and treatment groups with the ET receptor antagonist (ERA) bosentan (1 mg/kg body weight i.v.) and the NO donor L-arginine (400 mg/kg body weight i.v.) were performed. For evaluation of hepatic microcirculation in vivo microscopy was carried out 30-90 min after reperfusion. Local hepatic tissue PO2, laser Doppler flow and aspartate aminotransferase/alanine aminotransferase (AST/ALT) levels were measured. Increased ET caused sinusoidal constriction after reperfusion to 76% of the sham group (p < 0.05), leading to significant decrease in perfusion rate (82%), liver tissue PO2 (6.9 mmHg) and erythrocyte flux (45.2% of sham group). Hepatocellular damage could be detected 6 h after reperfusion by AST/ALT increase (p < 0.05). Sinusoidal diameters were maintained at baseline in the ERA (98%) and NO (102%) groups (p < 0.05). Increased percentage of leukocytes sticking in sinusoids (144%) and venules (435%) was reduced by therapy to 110/253% (ERA) and 111/324% (NO), respectively (p < 0.05). Perfusion rate was increased to 93 and 94% (p < 0.05 vs ischemia). Local hepatic tissue PO2 was improved 30 min after reperfusion in the ERA (11.0 mmHg) as well as in the NO group (11.5 mmHg; p < 0.05 vs ischemia). Measurement with a laser Doppler flow meter revealed significant improved erythrocyte flux in both therapy groups (p < 0.05 vs ischemia). Also, the post-ischemic AST/ALT increase was reduced by therapy. In conclusion, ET evokes strong constriction of post-ischemic sinusoids, leading to microcirculatory disturbances. The maintenance of the ET/NO balance by blocking ET receptors, or providing an NO donor, protects liver microcirculation and reduces hepatic ischemia-reperfusion injury.

Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis.

Nonalcoholic steatohepatitis (NASH) may present with increased hepatic fibrosis progressing to end-stage liver disease. No factors that determine increasing fibrosis and histologically advanced disease have been recognized, thus, liver biopsy is recommended in all patients for diagnosis and prognosis. Our aim was to identify independent predictors of severe hepatic fibrosis in patients with NASH. One hundred and forty-four patients were studied. All patients underwent liver biopsy. Clinical and biochemical variables were examined with univariate and multivariate analysis. Thirty-seven (26%) patients had no abnormal fibrosis, 53 (37%) had mild fibrosis, 15 (10%) had moderate fibrosis, 14 (10%) had bridging fibrosis, and 25 (17%) had cirrhosis. In multivariate analysis, older age (P =. 001), obesity (P =.002), diabetes mellitus (P =.009), and aspartate transaminase/alanine transaminase (AST/ALT) ratio greater than 1 (P =.03) were significant predictors of severe liver fibrosis (bridging/cirrhosis). Body mass index (P =.003) was the only independent predictor of the degree of fat infiltration. Increased transferrin saturation correlated positively with the severity of fibrosis (P =.02) in univariate analysis, and there was a trend for more female patients among those with more advanced fibrosis (P =. 09). However, iron studies or gender were not significant when controlled for age, obesity, diabetes, and AST/ALT ratio. In conclusion, older age, obesity, and presence of diabetes mellitus help identify those NASH patients who might have severe liver fibrosis. This is the subgroup of patients with NASH who would be expected to derive the most benefit from having a liver biopsy and considering investigational therapies.

Metabolism and hepatotoxicity of acetaminophen in mice fed on a liquid glucose diet

The role of dietary factors in the toxicity and metabolism of acetaminophen (APAP) was examined using male ICR mice. A 5 % ( w v ) liquid glucose solution replaced a regular lab chow and water exactly for 24 or 48 hr prior to measurement of hepatic glutathione (GSH) contents at 8 am, 2 pm, or 8 pm of a day. The characteristic temporal variation in hepatic GSH contents disappeared in mice provided with the glucose diet for 24 hr or longer. The microsomal p-nitrophenol hydroxylase and ethoxyresorufin O-deethylase activities, most responsible for metabolic activation of this drug, were examined in mice fed on the glucose diet for 24 hr. There were no differences in either enzyme activity between 8 am and 8 pm. Mice were injected with a 200 mg/kg dose of APAP, ip, 24 hr following initiation of the glucose diet supply and the plasma concentrations of this drug and its metabolites were monitored for 3 hr. There were no significant differences in plasma level of APAP or the major metabolites, APAP-glucuronide and APAP-sulfate, between the mice treated with this drug at 8 am and at 8 pm. However, the plasma concentrations of metabolites generated via the conjugation reaction with GSH were lower in mice treated with APAP at 8 pm. The APAP-induced hepatotoxicity was determined by increases in serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) activities and by decreases in hepatic glucose-6-phosphatase (G-6-Pase) activity 24 hr following the treatment. Significant differences in the AST ALT and G-6-Pase activities were observed between 8 am, 2 pm and 8 pm in mice fed on the glucose solution for 24 hr. However, supply of the glucose diet for 48 hr abolished the time-dependent differences in serum AST ALT and hepatic G-6-Pase activities resulting from a dose of APAP. The results indicate that supply of a glucose diet for 24 hr may eliminate the temporal variation in hepatic GSH contents, but the glucose diet supply should continue at least for 48 hr to effectively diminish the fluctuation in the toxicity of chemicals dependent on the availability of this endogenous tripeptide.

Heightened suspicion and rapid evaluation with CT for early diagnosis of partial renal infarction.

Although renal infarction has been well studied and clearly defined, it remains greatly underdiagnosed, resulting in significant morbidity. Acute segmental renal infarction is a diagnosis even more problematic, as the problem can appear insidiously and masquerade as other entities including stone, infection, and even tumor. The clinical manifestations and evaluation of partial renal infarction in our patients were reviewed. Seven patients presenting to the emergency department who were subsequently found to have partial renal infarction were identified from the 5-year records of a single institution. Patients were evaluated for presenting complaints, physical findings, temperature, and blood pressure. Laboratory analysis consisted of a complete blood count (CBC); measurements of creatinine, lactate dehydrogenase (LDH), aspartate transaminase/alanine transaminase (AST/ALT), and alkaline phosphatase; and urinalysis. The sequence of the work-up was recorded, as well as time to diagnosis. The etiology of infarction was identified for all patients. All seven patients were eventually discovered to have partial renal infarction as a result of dysrhythmia (N = 4), mural thrombus (N = 2), or septic emboli (N = 1). The average time to diagnosis was 65.2 hours with a range of 9.5 to 168 hours. The chief complaint was flank pain (N = 3), nonspecific abdominal pain (N = 2), left lower-quadrant pain (N = 1), and mental status change (N = 1). The presenting signs and symptoms included abdominal tenderness (N = 4), nausea and vomiting (N = 4), temperature >100.5 degrees F (N = 3), and hypertension (N = 3). Laboratory studies revealed a white cell count >11,000/microL in six, microhematuria in four, proteinuria in four, elevated LDH in all patients, elevated AST/ALT in two, and elevated alkaline phosphatase in one. The work-up varied by presentation, but definitive diagnosis was made by CT in all five patients scanned and by angiography in two. Angiography confirmed the CT findings in four of the five patients. In evaluating partial renal infarction, a strong clinical suspicion is necessary. We found a history of dysrhythmia or other cardiac disease, the presence of abdominal or flank pain, fever with an elevated white cell count, and an elevated LDH to be clinically significant, and their presence should alert the clinician to the possibility of renal infarction. Once a degree of suspicion exists, early evaluation with CT should speed the diagnosis and effect decreased morbidity.

Quantitative Assessment of HCV Load in Chronic Hemodialysis Patients: A Cross-Sectional Survey

Recent evidence has been accumulated showing that chronic hemodialysis (HD) patients have a very high prevalence of antibodies to hepatitis C virus (HCV). In contrast, there is little information addressing the virological characteristics of HCV infection in this population. Aim: To measure HCV viral load and to correlate this with demographic, biochemical, and clinical features of a large cohort of HCV-infected patients on chronic HD. Methods: 394 chronic HD patients were tested by branched-DNA signal amplification assay, anti-HCV enzyme-linked immunosorbent assay 2.0, and on the basis of the aspartate aminotransferase/alanine aminotransferase (AST/ALT) activity. Multivariate analysis by ordinal logistic regression model was performed: age, gender, race, time on HD, allocation of the patients among the HD units, etiology of end-stage renal disease, HBsAg status, anti-HCV positivity, HCV genotype, and AST/ALT levels were independent factors, and viremic levels of HCV in serum were assumed as dependent variables. Results: 88 (22.3%) patients showed serological and/or virological signs of HCV infection. 59 (15%) out of 394 had detectable HCV RNA in serum, the mean HCV load was 19.4 × 10⁵ (95% CI, 6.06 × 10⁷ to 6.2 × 10⁴) Eq/ml. According to the criteria suggested by others [J Infect Dis 1994;169:1219–1225], there were 8 (13.5%) individuals with high-titer viremia (>1 × 10⁷ Eq/ml) in the subset of viremic patients. A small subset (8/394 or 2%) of individuals was seronegative, but viremic; 29 (7%) out of 394 were seropositive without detectable HCV RNA in serum. Univariate analysis showed that the frequency of anti-HCV positivity was significantly higher in viremic patients as compared with individuals with no detectable HCV viremia: 51/59 (86%) vs. 29/335 (8.6%), p = 0.0001. Serum AST and ALT levels were significantly higher in viremic patients than in individuals with no detectable HCV RNA in serum: 23.8 (95% CI 60.8–9.3) vs. 17.1 (95% CI 50.4–5.8) U/l (p = 0.009) and 14.4 (95% CI 48.9–4.3) vs. 9.8 (95% CI, 37.3– 2.5) U/l (p = 0.008). Logistic regression analysis showed an association between HCV viremia and anti-HCV positivity (p = 0.00001) and ALT activity (p = 0.01). Conclusions: Hepatitis C virus infection is highly prevalent in the HD population; the viral load is relatively low, and it was associated with elevated hepatic enzyme levels and anti-HCV positivity. No other clinical characteristics were associated with HCV RNA levels. Seronegative but viremic patients were also found. Longitudinal studies with long follow-up periods are necessary to evaluate the course of HCV load over time in this population.

Liver and renal function after repeated sevoflurane or isoflurane anaesthesia.

To compare retrospectively liver and renal function after repeated exposure (twice) to sevoflurane or isoflurane. Sixty patients were studied for liver and renal function after repeated exposure within 30 to 180 days to sevoflurane (30 patients) or isoflurane (30 patients). Serum concentrations of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TBil), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GTP), blood urea nitrogen (BUN) and creatinine (Cr) were measured before and, 1, 3, 7, and 14 days after surgery. Qualitative analyses of urinary protein and glucose were done 1, 3, and 7 days after surgery. The number of patients with abnormal values in AST, ALT and GTP was larger in the isoflurane than in the sevoflurane group. BUN and Cr were within normal range after anaesthesia in either group. Renal excretion of protein and glucose increased one and three days after anaesthesia with no difference between the anaesthetics. None of the variables showed differences between the first and second anaesthesia after either anaesthetic. Repeat exposure to sevoflurane or isoflurane within 30 to 180 days had no additional risk of increasing serum concentration of liver enzymes or increasing urinary excretion of protein and glucose compared with the first exposure to the same anaesthetic.

Prevalence of chronic hepatic disease in Portugal. Apropos of a review carried out in a hepatology unit

The chronic elevation of Aminotransferases is one of the most frequent indications for percutaneous Liver Biopsy (LB). From a retrospective study of LB performed in the Hepatology liver Unit of Santa Maria Hospital, between 1989 and 1993, we correlated the histologic diagnosis with the etiology of liver disease, sex, age and the Aspartate aminotransferase/Alanine aminotransferase (AST/ALT) and Gama-Glutamyl transpeptidase (gamma GT) index in patients with chronic liver test abnormalities. 790 LB were reviewed retrospectively, of patients aged between 11 and 78 years, 68% males and 32% females. The most common etiology was Hepatitis C (34.6%), followed by Hepatitis B (20.1%) and alcohol (15.8%). Autoimmune diseases (Primary Biliary Cirrhosis and Autoimmune Hepatitis) were present in 3% of cases, and metabolic liver diseases in 1.4%. The distribution by sex revealed a predominance of Hepatitis C in both, alcoholic liver disease being more frequent in males (21.5% vs 3.9%). The main histological diagnoses were Chronic Active Hepatitis (27.2%), Liver Cirrhosis (19.5%), Steatohepatitis (9.5%) and minor lesions (24.6%). In alcoholic liver disease, 47.2% had Liver Cirrhosis and 16% Steatohepatitis; in Hepatitis B, Liver Cirrhosis was found in 12.6% and in Hepatitis C in 11.4%. Liver Cirrhosis had a prevalence between the 4th and 6th decade of life (82%) with a peak incidence in the 5th, and appeared earlier in Hepatitis B and later in Hepatitis C. The prevalence between sexes was similar. The main etiology of Liver Cirrhosis was alcohol (38.3%). The gamma GT index was greater in alcoholic liver disease (average 4.1) and was nearly twice in Hepatitis C than in Hepatitis B (1.7 vs 0.8). 1) Hepatitis C in our Hepatology Unit was the main indication for Liver biopsy. 2) The prevalence of alcoholic liver disease is greater in males, being the main etiology of Liver Cirrhosis. 3) The progression to Liver Cirrhosis seems to be similar in Hepatitis B and C. 4) The progression to Liver Cirrhosis is similar in both sexes, being dominant in the 5th decade of life. 5) The progression to Liver Cirrhosis is earlier in Hepatitis B than in Hepatitis C. 6) A gamma GT index elevation, without alcohol abuse, is suggestive of Hepatitis C. 7) Autoimmune and metabolic liver diseases seem to be rare in Portugal.

Aminotransferase as a prognostic index in infants with liver disease

To assess the utility of the serum aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio in a group of infants with liver disorders, we retrospectively analyzed the charts of 73 infants with chronic liver disorders. Patients were considered as having either a good outcome (n = 40) or a poor outcome (n = 33), based upon the clinical course. AST and ALT in serum were measured simultaneously at the time of initial presentation and at various follow-up visits during the first 13 months after birth. At presentation (mean age 1.65 months), there was no difference in the AST/ALT ratios between the good (1.61 +/- 0.62; mean +/- SD) and poor (1.65 +/- 0.78) outcome groups (P = 0.81). However, over time, the AST/ALT ratio increased in patients in the poor-outcome group and decreased in patients in the good-outcome group. Calculating the AST/ALT ratio appears to be an easy, early, and reliable prognostic indicator for infants with hepatic disease, and may be a useful measure for evaluating liver-disease patients.

Clinical Significance of Ultrasonography, Computed Tomography, and Biochemical Tests in the Rapid Diagnosis of Gallstone-Related Pancreatitis

Real-time ultrasonography (US), computed tomography (CT), and biochemical tests were prospectively performed to detect gallstones in 88 consecutive patients immediately after the onset of an attack of acute pancreatitis. The sensitivity of biochemical tests was 84.6% when the patients had three or more positives of five parameters [including serum bilirubin, alkaline phosphatase (AP), gamma-glutamyl transpeptidase (GGT), alanine transaminase (ALT), and alanine transaminase-aspartate transaminase (ALT-AST) ratio]. The sensitivity, specificity, and accuracy were 71.8, 98.0, and 86.4% for US, and 52.9%, 100%, and 79.5% for CT. The sensitivity, specificity, and accuracy were improved to 82.1, 100, and 93.2% by the combination of US and CT, and 94.9, 100, and 97.7% by the combination of US and biochemical tests. Adding CT to the combination of US and biochemical tests resulted in only a slight improvement in sensitivity and accuracy. In conclusion, a combination of US and biochemical tests can provide the best noninvasive method in rapidly detecting gallstones as an etiological factor in acute pancreatitis. Computed tomography is not cost-effective. A positive result of biochemical tests despite a negative finding in US calls for an intensive search for gallstones by further investigation with endoscopic retrograde cholangiography or repeated US examinations.