Clinical importance of HCV confirmatory testing in blood donors.
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Blood Donors↗
Biomedical subjects
M C Kuhns
Publications and source records attributed to M C Kuhns.
Prediction of hepatitis C virus infectivity in seropositive Australian blood donors by supplemental immunoassays and detection of viral RNA.
The prevalence of anti-hepatitis C virus (HCV) enzyme immunoassay (EIA)-positive in 167,511 Australian volunteer blood donors from Adelaide, Melbourne, Perth, and Sydney was 0.78%. One thousand two-hundred and eighteen EIA-positive serum samples were assessed by supplemental tests including a blocking EIA and two peptide EIAs corresponding to major epitopes of the HCV C-100-3 antigen. Seven hundred and eighteen samples (59%) were negative by supplemental testing; no evidence of reactivity with other HCV gene products or HCV RNA detected by cDNA polymerase chain reaction was found in selected samples from this group. In contrast, of 43 samples randomly selected from 400 samples (32.8%) positive by supplemental testing, 88% were reactive with HCV 33-C or core antigens and 52% contained HCV RNA, suggesting contact with HCV and infectivity of most donors in this group. Most samples equivocal by supplemental testing reacted only with C-100 and not with other HCV antigens when tested by dot immunoblot assay. Only 21% had detectable HCV RNA. The battery of assays used in this study indicated that approximately 32% of HCV EIA repeatably reactive serum samples were serologically related to HCV, corresponding to a 0.25% prevalence of potentially infectious donors.
Adult↗
Monitoring hepatitis B virus replication.
Serum hepatitis B virus DNA is the best marker for monitoring hepatitis B virus replication in the liver. Data are presented on the sensitivity, specificity and application of a standardized solution hybridization assay for the quantitation of hepatitis B viral DNA in serum. The assay is linear over several orders of magnitude in sample concentration and is equivalent in sensitivity and specificity to classic filter hybridization methods employing [32P]DNA probes and autoradiography. The assay provides clinically relevant information for monitoring viral replication before, during and after antiviral therapy.
DNA, Viral↗
Prevention of hepatitis B virus carrier state in infants according to maternal serum levels of HBV DNA.
235 infants of HBeAg-carrier mothers in Hong Kong were assigned to four study groups. Groups I, II, and III received hepatitis-B (HB) vaccine at birth and at 1, 2, and 6 months. Group I also received seven monthly injections of HB immunoglobulin (HBIg), and group II received one HBIg injection at birth. Group III received vaccine only and group IV received placebo for both vaccine and HBIg. At the age of 3 years, all infants of the three treatment groups were significantly protected against the HB virus (HBV) carrier state compared with the placebo group (p less than 0.0001); the protective efficacy rates in groups I, II, and III were 87%, 80%, and 65%, respectively. At all times, group I was significantly better protected than group III. In groups III and IV, infants of mothers with serum HBV DNA levels of 5 pg/ml or above were at a significantly higher risk of acquiring the HBV carrier state than those whose mothers had HBV DNA levels below 5 pg/ml. This difference was not significant in groups given HBIg. Of the 183 infants who initially escaped HBV infection, 73 (40%) had transient and 8 (4%) chronic HBV infection between 6 and 36 months. Vaccinated infants who had actively formed anti-HBs remained well protected against the HBV carrier state. However, infants in groups I and II with no active anti-HBs response to vaccine became at risk for the HBV carrier state when the passively acquired anti-HBs antibodies had disappeared. HBIg should be included in HB vaccination schedules for all infants of HBeAg-positive mothers.
Age Factors↗
Quantitation of hepatitis B viral DNA by solution hybridization: comparison with DNA polymerase and hepatitis B e antigen during antiviral therapy.
Serological markers of hepatitis B virus (HBV) replication were assessed in a randomized, controlled trial of prednisone withdrawal followed by alpha-interferon in the treatment of chronic hepatitis B. HBV DNA levels in more than 700 serial serum samples from 41 patients were determined by a sensitive and quantitative solution hybridization assay. Results were compared with HBV DNA polymerase (DNAp) activity and hepatitis B e antigen (HBeAg) in 21 untreated controls and 20 treated patients. Among treated patients, the mean pretherapy HBV DNA values were higher in nonresponders than in responders. During prednisone treatment, DNA levels increased an average of 2.1-fold in responders and 1.4-fold in nonresponders. During the 2-week rest interval between prednisone and interferon, DNA values fell an average of 57% in responders. In contrast, the mean DNA values in nonresponders did not change during the same interval. This early distinction between responders and nonresponders was not apparent from DNAp or HBeAg results. During interferon treatment, HBV DNA became undetectable in responders and remained negative during a 1-year follow-up. DNA in nonresponders declined to 14% of baseline during interferon treatment but increased to pretherapy levels after treatment. DNAp values generally paralleled HBV DNA values, but DNAp activity showed more variability and lower sensitivity than did the hybridization assay results. HBeAg values varied independently of HBV DNA and DNAp with a much delayed decline in responders. These results indicate that HBV DNA, when measured quantitatively by a sensitive solution hybridization assay, is an early predictor of the effects of antiviral agents on replication.
Antiviral Agents↗
Prednisone withdrawal followed by recombinant alpha interferon in the treatment of chronic type B hepatitis. A randomized, controlled trial.
STUDY OBJECTIVE: To determine the efficacy of a short course of prednisone followed by recombinant interferon treatment in patients with chronic type B hepatitis. DESIGN: Randomized, controlled trial with a 5-month treatment phase and a 9-month observation period after treatment. SETTING: Two referral-based university-affiliated medical centers. PATIENTS: Thirty-nine clinically stable patients with chronic type B hepatitis, all of whom were positive for hepatitis B antigen, hepatitis B virus-associated-DNA (HBV-DNA), and DNA polymerase for at least 6 months before entry. Patients included 20 heterosexuals and 19 male homosexuals. INTERVENTIONS: Eighteen patients were treated with a 6-week tapered regimen of prednisone, followed by 90 days treatment with recombinant interferon alpha-2b; 21 patients were untreated controls. Paired liver biopsy specimens of 27 patients (pretreatment and 9 months after treatment) were blindly evaluated. MEASUREMENTS AND MAIN RESULTS: Nine treated patients had a sustained loss of HBV-DNA. In addition, eight treated patients lost hepatitis B e antigen and four became negative for hepatitis B surface antigen (HBsAg). When compared with controls the differences were statistically significant for clearance of HBV-DNA and HBsAg (P = 0.035 and 0.037, respectively). Treated patients who had a sustained loss of HBV-DNA had higher initial alanine aminotransferase lower initial DNA and DNA polymerase levels, and were more frequently heterosexual. Patients who responded to treatment with the disappearance of hepatitis B e antigen and HBV-DNA had normal liver function tests and markedly improved liver histology during follow-up. CONCLUSIONS: The immunologic priming provided by a short course of prednisone used with alpha interferon may be an effective treatment for selected patients with chronic type B hepatitis.
Adult↗
Nuclear inheritance of oligomycin resistance in mouse L cells.
The inheritance of oligomycin resistance was studied in three mouse L-cell mutants, OLI 2, OLI 4, and OLI 14. All three mutants had previously been shown to have oligomycin-resistant mitochondrial ATPase activity. In addition, OLI 14 has DCCD-resistant mitochondrial ATPase activity and an altered DCCD-binding protein. Oligomycin-resistant cells were enucleated and fused with oligomycin-sensitive cells under a variety of selective regimes designed to allow growth of oligomycin-resistant cybrids. No transfer of oligomycin resistance via the cytoplasm of OLI 2, OLI 4, or OLI 14 was detected. In contrast, oligomycin resistance was transferred with the karyoplasts of OLI 14 in karyoplast-cell fusions. Fusions between OLI 14 cells and oligomycin-sensitive cells also produced oligomycin-resistant hybrids. Transfer of oligomycin resistance in the karyoplast-cell and cell-cell fusions were demonstrated at the level of the mitochondrial ATPase. These results indicate that oligomycin resistance in OLI 14 is most likely under nuclear control. Furthermore, nuclear inheritance of oligomycin resistance in a mutant with a modified DCCD-binding protein suggests that the gene for the DCCD-binding protein is encoded in the nucleus of mammalian cells.
Adenosine Triphosphatases↗
Oligomycin-resistant mitochondrial ATPase from mouse fibroblasts.
Fourteen oligomycin-resistant LM(TK-) clones were isolated following the mutagenesis of minicells. In the absence of oligomycin, the mutants grew with population doubling times similar to that of the wild type (1 day). In 3 or 5 microgram oligomycin/ml the doubling times of the mutants were 1.2-2.5 days. Both stable and unstable classes were represented among the oligomycin-resistant mutants. Mitochondrial ATPase activities of the mutants were 1.3-1130 times more resistant to oligomycin than the wild type. The mitochondrial ATPase of OLI 14 was found to be bound firmly to the mitochondrial membrane, showed no alteration in the pH optimum compared to wild-type, and exhibited increased resistance to DCCD and venturicidin. These results are consistent with the conclusion that oligomycin resistance in these mutants results from altered mitochondrial ATPase.
Adenosine Triphosphatases↗