Distribution of copper, iron, and zinc in biological samples (scalp hair, serum, blood, and urine) of Pakistani viral hepatitis (A-E) patients and controls.

The aim of the present study was to compare the level of copper (Cu), iron (Fe) and zinc (Zn) in biological samples (serum, blood, urine, and scalp hair) of patients suffering from different viral hepatitis (A, B, C, D, and E; n = 521) of both gender age ranged 31-45 years. For comparative study, 255 age-matched control subjects, of both genders residing in the same city were selected as referents. The elements in the biological samples were analyzed by flame atomic absorption spectrophotometry, prior to microwave-assisted acid digestion. The validity and accuracy of the methodology was checked by using certified reference materials (CRMs) and with those values obtained by conventional wet acid digestion method on same CRMs. The results of this study showed that the mean values of Cu and Fe were higher in blood, sera, and scalp hair samples of hepatitis patients, while Zn level was found to be lower than age-matched control subjects. The urinary levels of these elements were found to be higher in the hepatitis patients than in the age-matched healthy controls (p < 0.05). These results are consistent with literature-reported data, confirming that the deficiency of zinc and hepatic iron and copper overload can directly cause lipid peroxidation and eventually hepatic damage.

[The reassessment of the diagnostic value of 24-hour urinary copper excretion in children with Wilson's disease].

OBJECTIVE: To reassess the diagnostic value of 24 hour urinary copper excretion in children with Wilson disease (WD). METHODS: From July 2005 to June 2007, inpatients over three years old in a pediatric liver center were assigned into WD and non-WD group. RESULTS: 94 patients, including 26 cases in WD and 68 in non-WD group, were enrolled in this study. The median of 24 h urinary copper excretion was 98.5 microg in WD group and 25.8 microg in the non-WD group (Z = -6.111, P equal to 0.000). The area under receiver operator curve (ROC) was 0.909 (95% CI: 0.839-0.979, P equal to 0.000). The sensitivity, specificity, accuracy, positive predictive value and negative predictive value were 84.6%, 91.2%, 89.4%, 78.6% and 93.9% respectively using 52.0 ug as a cutoff value, and 50.0%, 97.1%, 84.0%, 86.7% and 83.5% using 100 microg as a cutoff value. The goodness of fitness of 52 microg criteria was significantly higher than 100 microg criteria (kappacoefficient 0.760, 0.541 respectively, P equal to 0.000). CONCLUSION: Comparing to 100, 52 microg of 24 h urinary copper excretion as a cutoff value significantly improves the sensitivity and accuracy for diagnosing WD in children.

Evaluation of urine as a clinical specimen for diagnosis of hepatitis a.

The present study pertains to the evaluation of urine as a specimen for detection of anti-hepatitis A virus (anti-HAV) antibodies. Immunoglobulin M (IgM), IgG, and IgA capture enzyme-linked immunosorbent assays for hepatitis A were performed on paired serum and urine specimens collected from hepatitis A patients (n = 92), healthy individuals (n = 100), non-A hepatitis patients (n = 70), and patients with nonhepatic diseases (n = 64, including 37 renal disease patients). Hepatitis A patients seropositive for anti-HAV IgM showed 95.65% uropositivity. No false-positive reactions were observed in control groups. The uropositivity of anti-HAV IgM persisted during the convalescent phase of the disease. Anti-HAV IgG uropositivity correlated well with corresponding seropositivity in all groups (P > 0.05 for each). No significant difference between the proportions of serum and urine positivity for anti-HAV IgA was noted (P > 0.05 for each). Using seroreactivity as a "gold standard," the sensitivity and specificity for anti-HAV IgM, anti-HAV IgG, and anti-HAV IgA tests with urine as a specimen were found to be 95.65 and 100%, 97.76 and 76.47%, and 92.23 and 88.18%, respectively. Urine appears to be comparable to serum for diagnosis of recent and past infection with hepatitis A.

Hepatitis A impairs the function of human hepatic CYP2A6 in vivo.

Hepatitis virus A (HVA) is a worldwide sporadic disease but its effects on pharmacokinetics and individual drug responses have not been studied. In this study, the 7-hydroxycoumarin (7OHC) excretion test used in vivo as a bioindex of hepatic CYP2A6 activity was performed in 20, previously healthy, acute jaundice HVA patients. Volunteers with an acute HVA were treated with one p.o. administration of 5 mg coumarin (Venalot). Among the patients, 11 were children (6-10 years; two girls and nine boys), the rest (15-40 years old) consisted of two men and seven women. Urinary excretion of 7OHC was measured after overnight fasting in four fractions: 0 h before any medication (to detect if any basal 7OHC excretion exits), and after a 5-mg coumarin capsule p.o., 0-2, 2-4 and 4-8 h fractions were collected and urine volumes were recorded. Urinary excretion of 7-hydroxycoumarin occurred to a similar extent in healthy adults and children. The first 2-h 7OHC excretion was decreased by 26% (P < 0.05) and total (0-8 h) 7OHC excretion was decreased by 37% (P<0.01) among HVA-positive adults (age range 15-40 years) compared with the values obtained from healthy volunteers. In 11 HVA-positive children (age 6-10 years), the first 2-h 7OHC excretion was only 20% (P < 0.0001) and the total 7OHC excretion 28% (P < 0.0001) of the value observed in healthy controls. These results suggest that (i) an acute HVA decreases the metabolic clearance of drugs such as coumarin which are rapidly metabolised by CYP2A6 and (ii) this decrease is even more prominent in children. Such metabolic responses may be of clinical importance and may also interfere with other drug therapy in these patients.

The detection in urine specimens of IgG and IgM antibodies to hepatitis A and hepatitis B core antigens.

The use of urine as a noninvasive specimen for the diagnosis of hepatitis A (HAV) and hepatitis B (HBV) virus infections was investigated. Specimens of urine were collected at the same time as blood or saliva specimens, or singly in cases of previously serologically confirmed recent infection. The specimens were tested for IgG and IgM anti-HAV and anti-HBc by immunoglobulin class-specific capture radioimmunoassays (GACRIA and MACRIA). On the basis of assays on urine specimens it was possible to distinguish between individuals who were susceptible or immune to HAV or who had recently been infected with HAV. Using assays on 327 corresponding saliva specimens as reference tests, the observed sensitivity and specificity of tests on urine specimens by anti-HAV GACRIA were 98.9% and 99.1%, respectively, and by anti-HAV MACRIA were 95.8% and 99.6%, respectively. IgM and IgG anti-HBc were detected readily in the urine of 35 acute or recent cases of hepatitis B but were not found in the urine of seronegative individuals. Of the urine specimens from 52 individuals who were HBsAg carriers or who had had long past HBV infections, 49 contained detectable IgG anti-HBc. Of urine specimens from 42 HBsAg carriers, 11 contained raised IgM anti-HBc levels. Urine, which is a convenient specimen to collect, can be used to study outbreaks of hepatitis A, to ascertain the HAV immune status of individuals, to differentiate hepatitis A from hepatitis B, and to identify individuals who have been naturally exposed to HBV.

Urinary neopterin levels in acute viral hepatitis.

Elevated neopterin levels in blood or urine have been shown to be a marker for the activation of cell-mediated immunity in vitro and in vivo. To evaluate whether neopterin levels are elevated in patients with acute viral hepatitis, we measured urinary levels in 13 patients with hepatitis A, 26 with hepatitis B, 12 with non-A, non-B hepatitis, 8 with jaundice and/or cholestasis due to biliary and pancreatic disorders and 3 with alcoholic hepatitis and in 62 apparently healthy HBsAg carriers. Neopterin levels in patients with virus-induced hepatitis were significantly higher than those in patients with other diagnoses. Urinary neopterin levels were above normal in 49 of 51 patients with viral hepatitis and elevations during the course of hepatitis showed a pattern similar to that of the usual liver biochemical tests, suggesting that neopterin levels were related to the clinical activity of the viral disease. In patients with nonviral biliary and hepatic disorders, neopterin levels were usually normal and did not correlate with other liver biochemical tests. These findings suggest that cell-mediated immune mechanisms are activated during viral hepatitis and that neopterin measurement may be of value as an additional surrogate marker for non-A, non-B hepatitis.

[Urinary excretion of microbiologically detectable forms of pantothenic acid in viral hepatitis]. / Vyvedenie s mochoi mikrobiologicheski opredeliaemykh form pantotenovoi kisloty u bol'nykh virusnym gepatitom.

The content of free and total pantothenic acid (PA) in the daily urine was studied microbiologically in 55 patients with virus hepatitis. At the height of the disease the excretion of the test vitamin forms with the urine noticeably decreased whatever the disease severity. During reconvalescence PA excretion rose because of the increase diuresis. However, the concentration of the vitamin in the urine did not reach normal. No disorders in PA metabolism were found in patients with hyperbilirubinemia of non-infectious genesis. Unlike normal subjects, oral administration of calcium pantothenate (50 ng) to patients with hepatitis results in a decrease of the excretion of the free form of PA. It is suggested that disorders in PA metabolism in patients with virus hepatitis are manifestations of functional vitamin deficiency which is a consequence of its reduced utilization.

Detection of hepatitis A virus in the feces of patients with naturally acquired infections.

A prospective study was carried out on 200 patients admitted to Fairfield Hospital, Melbourne, Australia, with acute hepatitis A to determine the frequency with which virus could be detected in their feces. Evidence of infection with hepatitis A virus (HAV) was obtained by detecting IgM specific for HAV in a single serum sample or by demonstrating a rising titer of antibody in paired sera by solid-phase radioimmunoassay. HAV was detected in the feces of 59 of the 200 patients by solid-phase radioimmunoassay and immune electron microscopy. When patients were admitted within one week of the onset of dark urine, 45% were found to be shedding HAV, whereas only 11% of specimens obtained from patients admitted during the second week contained virus. HAV was not detected in fecal specimens collected more than 14 days after the onset of dark urine. These findings suggest that patients admitted to hospital with hepatitis A may still be infectious and that appropriate precautions against fecal contamination should be maintained.

Increased D-glucaric acid excretion by jaundiced patients.

The urinary excretion of D-glucaric acid, a catabolite of glucuronic acid, is considered to be a reliable index of the state of hepatic microsomal enzyme activity. Because enzyme activity may be altered in liver disease, we examined the effect of liver disease on the excretion of this metabolite and its correlation with liver function tests. We studied 89 patients with nonhemolytic jaundice, 39 with viral hepatitis, 33 with obstructive jaundice, six with cirrhosis, and 11 patients with jaundice of mixed etiology. Glucaric acid excretion was significantly increased in all these patients as compared to controls, most pronounced in the obstructive jaundice group. No correlation was found between glucaric acid excretion and concentrations of bilirubin, albumin, globulin, aspartate aminotransferase, alkaline phosphatase, cholesterol, or gamma-glutamyltransferase in serum, even though the concentrations of these analytes did vary with the type of liver disease. We suggest that this increase in glucaric acid excretion is an indication of normal or even increased glucuronidation (UDP-glucuronosyltransferase activity), which occurs in liver disease.

Diagnosis of infectious hepatitis by multicomponent analysis with use of field ionization mass spectrometry.

Field ionization mass spectrometry has been applied to multicomponent analysis of metabolites in human urine for the diagnosis of metabolic disorders, exemplified here by infectious hepatitis. The molecular weight profiles of carboxylic acids and of "neutral" metabolites in the urine of patients with infectious hepatitis were compared with those in urine of normals. The "neutral" metabolites showed 24 characteristic spectral differences in the range 68 to 215 atomic mass units, which provided correct diagnoses in 100% of the cases and a "diagnostic power" of unity. These results are even more encouraging than those obtained earlier with the acidic metabolites, where 11 mass numbers were found in the same mass range to be useful for correct diagnoses in 91% of the cases. The measurements were performed on urine samples preextracted on Amberlite XAD-2 columns. We used a quadrupole mass spectrometer interfaced with a multichannel analyzer for mass analyses.

[Pseudouridine and uric acid excretion in patients with viral hepatitis]. / Issledovanie ékskretsii psevdouridina i mochevoi kisloty u bol'nykh virusnym gepatitom

Daily excretion of pseudouridine and uric acid with urine was studied in healthy persons and in patients with viral hepatitis during various periods of the disease. Excretion of pseudouridine was increased 2.5-fold and of uric acid--2-fold within the acute period of the disease. The degree of impairment in nucleic acids metabolism could be estimated by measuring of excretion of pseudouridine and uric acid and by calculation of their ratio during various periods of the disease.

Paradoxical urinary excretion of D-glucaric acid in acute viral hepatitis.

The urinary excretion of D-glucaric acid and the plasma clearance of antipyrine were estimated during the acute phase of viral hepatitis and again during recovery. The plasma clearance of antipyrine was impaired during the acute stage of hepatitis, while the urinary excretion of D-glucaric acid was paradoxically high. Both parameters returned to normal during recovery. These findings suggest that the use of urinary D-glucaric acid excretion as an index of microsomal enzyme induction is unreliable when there is liver injury.

Immunoglobinuria in the acute phase of viral hepatitis in children and the influence of HBAg antigen.

Urinary excretion of immunoglobulins of the A, G and M classes was studied in 14 children suffering from viral hepatitis without HBAg antigenemia, and in 12 children with viral hepatitis accompanied by HBAg antigenemia. The control group consisted of 11 healthy children. Over fourfold increase in excretion of IgA, and only twofold increase in IgG were observed. The difference in excretion of A and G immunoglobulins, despite their similar molecular weight, was attributed to increased active excretion of IgA by the kidneys, probably due to stimulation by the virusemia. In no case were immunoglobulins of the M class encountered in the urine.

Proteinuria in the acute phase of viral hepatitis in children and the influence of HBAg antigen.

In 55 children in the acute phase of viral hepatitis with HB Ag antigenemia, and in 24 without antigenemia, total urinary protein excretion and frequency of excretion of the following serum proteins in urine were studied: alpha1-glycoprotein, haptoglobin, transferrin, A, G and M immunoglobulins, light immunoglobulin chains of the phi and gamma types, and Fc and Fab fragments of immunoglobulin G. The control group consisted of 15 healthy children without HB Ag antigenemia and 8 with antigenemia. The type of proteinuria was determined by electrophoresis of serum proteins excreted in the urine on Cellogen-RS. In children suffering from viral hepatitis the urine contained serum proteins significantly more often than in healthy children. HB ag antigenemia had no influence on the degree or type of proteinuria. In children suffering from viral hepatitis with and without HG Ag antigenemia, proteinuria was of the selectively glomerular type, and less often of mixed glomerulo-tubular type with selective glomerular component. It follows that the HB Ag antigen has np distinctly detrimental effect on the renal glomeruli in the acute phase of viral hepatitis, in which the vascular endothelium of renal glomerular blood vessels is probably injured. Less ofter, in children in the acute phase of viral hepatitis function of the proximal segment of the tubules is damaged with appearance in the proteinogram of Berggard's microglobulins.