Higher Serum Alanine Aminotransferase Levels Research Articles

Prevalence patterns and genotypes of GB Virus C/hepatitis G virus among imprisoned intravenous drug users

An RT-PCR assay using primers from the 5'-UTR of the GBV-C/HGV genome was used to detect viremia, and a serological assay was used to detect past exposure to GBV-C/HGV, in sera from 106 imprisoned Greek intravenous drug users. High seroprevalence rates indicative of the parenteral route of transmission of the virus were found (32.1% for GBV-C RNA and 46.2% for anti-GBV-C E2). These rates were nonetheless lower in comparison to the corresponding rates of HCV infection markers (64.2% for HCV RNA and 77.4% for anti-HCV). Statistically significant univariate associations were observed between GBV-C-RNA positivity and younger age (P=0.006) and HCV-RNA positivity (P=0.024), as well as with higher serum alanine aminotransferase levels (P< 0.001); this latter association was shown to be independent of coinfection with HCV and of age by a multiple logistic regression model. Apparently, GBV-C/HGV had spread readily by needle-sharing in prison, while causing acute subclinical hepatitis in infected inmates. Phylogenetic analysis of the partial 5'-UTR of the GBV-C/HGV genome from 16 seropositive individuals, which delineated their grouping within genotype 2, also revealed a close genetic relationship between two sets of sequences from 4 drug addicts, 3 of whom admitted to sharing needles while imprisoned.

EFFICACY AND SAFETY OF LAMIVUDINE ON REPLICATION OF RECURRENT HEPATITIS B AFTER CADAVERIC RENAL TRANSPLANTATION

The aim of this pilot study was to evaluate the efficacy and the safety of lamivudine therapy in hepatitis B virus (HBV)-positive/DNA-positive renal transplant recipients. Six HBV DNA-positive cadaveric renal transplant recipients ranging in age from 49+/-6 years were administered lamivudine, at 100 mg/day for a period of at least 6 months, on a compassionate-use basis. Lamivudine is the (-) enantiomer of 3'-thiacytidine, which is known to be a potent inhibitor of HBV replication. All of the patients but one were on cyclosporine-based immunosuppression. The mean serum creatinine was 134+/-44 micromol/L. The mean duration of HBV infection was 230+/-54 months (156-288). All of the patients but one had high serum alanine aminotransferase levels (122+/-52 IU/L; range, 45-243). Histological evaluation showed the presence of either chronic active hepatitis (n=4) or cirrhosis (n=2). All of the patients but one were hepatitis B e antigen negative/hepatitis B e antibody positive, but none were coinfected with either hepatitis C virus or hepatitis D virus. Lamivudine therapy was associated with (i) a normalization of alanine aminotransferase levels in four of five patients when these levels were increased at the beginning (n=5); (ii) a rapid disappearance of HBV DNA from the serum (detected by hybridization) in all of the patients; (iii) the negativity of HBV DNA by polymerase chain reaction in four patients; and (iv) no change in renal function and in proteinuria when present (one patient). Finally, no adverse effects were noted. When lamivudine therapy was stopped for four patients after 6 months, it was associated with a biochemical and virological relapse within the weeks that followed. Lamivudine therapy was therefore resumed for these patients.

Serum alanine aminotransferase level in relation to hepatitis B and C virus infections among blood donors.

To assess the serum alanine aminotransferase (ALT) activity in relation to hepatitis B virus (HBV) and hepatitis C virus (HCV) infections among blood donors, antibodies to HCV (anti-HCV) and hepatitis B surface antigen (HBsAg) were detected in 400 blood donors with normal ALT level (< or = 750 mumol/s per liter), and 76 blood donors with raised ALT level. The prevalence of anti-HCV (10.5%) and HBsAg (28.9%) in the latter was higher than that (2.0% and 17.5%, respectively) in the former (p < 0.001 and p < 0.03, respectively). There was a trend that indicated that the risk of anti-HCV positivity increased with increasing age (p < 0.001). Thirty of 76 (39.5%) donors with raised ALT level were positive for anti-HCV or HBsAg. Compared with HBsAg-positive donors, donors with anti-HCV had higher serum ALT levels (p < 0.01) and greater mean age (p < 0.01). Multivariate analysis indicated that both anti-HCV (odds ratio: 6.2; 95% confidence interval: 2.2-17.8) and HBsAg (odds ratio: 2.2; 95% confidence interval: 1.3-3.9) were significantly associated with raised serum ALT activity. The estimated population-attributable risk was 8.6% for anti-HCV, and 13.8% for HBsAg. In conclusion, although HBV and HCV infections are independent risk factors of raised ALT activity among blood donors, they play a minor role in the etiology of raised ALT activity.

The precore/core promoter mutant (T1762A1764) of hepatitis B virus: clinical significance and an easy method for detection.

Recently, a new hepatitis B virus (HBV) mutant with HBe antigen-negative phenotype has been characterized, in which one TATA box-like motif of the precore/core promoter had degenerated: most frequently by both A-->T and G-->A mutations at positions 1762 and 1764, respectively. The clinical significance of this mutant is as yet unknown. In our present study, the T1762 A1764 mutant was sought in sera from HBV-infected blood donors and chronic liver disease patients by directly sequencing a PCR-amplified region of HBVDNA. Also, because the A1764 mutation generates a Sau3AI cleavage site (GGTC-->GATC), we digested the PCR products with Sau3AI to see if cleavage would occur at this specific site. Our results mostly corroborated the earlier report but we found a higher-than-predicted frequency of HBe antigen-positive blood donors positive for the mutant (22%). The titres of HBe antigen in these mutant-positive sera were slightly decreased compared to the titres in wild-type HBV infection. In addition, these blood donors had relatively high (though within the normal range) serum alanine aminotransferase (ALT) levels, suggesting that the T1762 A1764 mutation could be used as a sensitive laboratory marker for insidious hepatitis in these otherwise 'asymptomatic' carriers. The Sau3AI assay, which is much more convenient than sequencing, was shown to be useful for the detection of the T1762 A1764 mutant in an extensive number of clinical samples.

Variations in the core region of hepatitis C virus genomes in patients with chronic hepatitis.

In each infected patient, the population of hepatitis C virus is composed of quasispecies that differ in their nucleotide sequences. Among regions in hepatitis C virus genomes, nucleotide sequences of the hypervariable region have been shown to change quickly during the course of infection. It is not known, however, whether these variations exist in the core region that has recently been suggested to contain human lymphocyte antigen class 1 restricted sites for cytotoxic T cell recognition. To clarify this, RNA was extracted from the plasma of four patients with chronic hepatitis C. After cDNA synthesis, DNA fragments that contain the core region were amplified by the polymerase chain reaction and the diversity of the core region was analyzed by the single strand conformation polymorphism analysis. Using this method, single or multiple DNA bands were observed in each patient, and representative bands showed different nucleotide sequences. Comparison of single strand conformation polymorphism patterns revealed that the population of quasispecies changed during the course of chronic infection. These changes were more remarkable in patients with high serum alanine aminotransferase levels than those with low serum alanine aminotransferase levels. Thus, sequential variations exist in the core region of hepatitis C virus in same individuals, and the population of quasispecies as determined by the sequence of the core region changes during the course of infection, which might be related to cytopathic effects of hepatitis C virus.

Detection of antibodies to hepatitis C virus (HCV) structural proteins in anti-HCV-positive sera by an enzyme-linked immunosorbent assay using synthetic peptides as antigens

We have defined 10 linear immunogenic regions encoded by the putative hepatitis C virus (HCV) structural proteins (core and envelope) by employing an enzyme-linked immunosorbent assay (ELISA) and by using 17 sequential synthetic peptides covering the N-terminal 330 amino acids of the structural polyproteins as antigens. These peptides correspond to amino acids 1 to 24, 21 to 44, 42 to 68, 64 to 91, and 100 to 120 of the putative core protein and amino acids 192 to 212, 223 to 238, 236 to 258, 250 to 266, and 307 to 330 of the putative envelope protein. In particular, the peptide covering amino acids 21 to 44 of the core protein was reactive with all but one (40 of 41) of the serum samples giving a positive signal in the passive hemagglutination assay (PHA) using the core and nonstructural proteins (NS 3/4) of the virus as antigens. We detected the HCV genome in 25 (61%) of 41 PHA-positive serum samples by the polymerase chain reaction (PCR) test. Of 25 PCR-positive serum samples, 17 serum samples had reactivity to the peptides derived from the envelope protein. On the other hand, only 1 of the 16 PCR-negative serum samples had reactivity to the peptides derived from the envelope protein. Interestingly, we often observed high serum alanine aminotransferase levels in PCR-positive individuals bearing antibodies to the envelope protein.

Prevalence of serum antibodies against lymphocytic choriomeningitis virus in selected populations from two U.S. cities.

An ELISA was developed for measuring serum antibodies against the arenavirus lymphocytic choriomeningitis virus (LCMV) and a closely related isolate termed callitrichid hepatitis virus (CHV). The ELISA was used to test sera from healthy adults and from hepatitis patients. In Birmingham, Alabama, the seropositivity rate for healthy black women was 5.1% (7/138), and the rate for patients with all types of hepatitis or cirrhosis was 4.3% (2/46). In San Antonio, Texas, the seropositivity rate among a clinical series of patients with non-A, non-B hepatitis was 0 (0/20), and the rate among persons rejected from blood donation because of high serum alanine aminotransferase levels was 2.4% (2/82). These results indicate that infection with LCMV or CHV is common in Birmingham but that infection is not associated with hepatitis.