Hepatitis G virus infection in hemodialysis patients and the effects of interferon treatment.

OBJECTIVE: To characterize the nature of hepatitis G virus (HGV) infections in hemodialysis patients and to determine the responsiveness of HGV to antiviral therapy in these patients. METHODS: HGV, a recently identified flavivirus, is associated with non-A-E viral hepatitis infections. We studied HGV infections in hepatitis C virus (HCV)-infected hemodialysis patients over a 1-yr period, using two independent PCR assays and nucleic acid sequencing. Thirty-four of 63 study patients were treated with interferon. RESULTS: We observed a 27% prevalence (17/63 patients) and a 4% annual incidence of HGV infections in the study population. HGV was not detected in any of the 10 HGV-infected patients immediately after interferon therapy. Although seven of these 10 patients developed HGV relapses, three had long-term responses. The interferon responsiveness of HGV and HCV appeared to be unrelated. In contrast, all seven untreated HGV-infected patients remained viremic. Sequence analyses of the different HGV isolates revealed only very limited genetic variability in the polymerase chain reaction-amplified regions of HGV during 1 yr of observation. CONCLUSIONS: Our data suggest that HCV-infected hemodialysis patients are at substantial risk of acquiring HGV infection and that HGV infections are prevalent in this population. In addition, HGV infections become chronic but are responsive to interferon treatment.

Patterns of hepatitis C viremia in patients receiving hemodialysis.

OBJECTIVES: Chronic hepatitis C virus (HCV) infection is common in patients who receive hemodialysis (HD). The aim of this study was to determine the natural history of hepatitis C viremia and the clinical utility of quantitation and genotyping of HCV in this population of patients. METHODS: Consecutive sera from two groups of HD patients who were HCV RNA positive, a group of 33 patients treated with interferon alfa (5 MU, three times a week for 4 months) and a group of 31 untreated patients, were analyzed by qualitative polymerase chain reaction, quantitative polymerase chain reaction, and a line probe assay for genotyping. RESULTS: Serum HCV RNA was detected continuously in 20 of 31 untreated patients (65%), and 11 patients (35%) showed a fluctuating pattern of viremia with virus-free intervals of up to 4 wk. Twenty-five of 33 patients (76%) treated with interferon alfa became HCV RNA negative during therapy; eight of these 25 patients had a breakthrough, which was transient in seven patients and persistent in one. Of the remaining 24 end-of-treatment responders, 17 relapsed after completion of therapy, and seven (21%) had a sustained response with undetectable serum HCV RNA for 1 yr of follow-up. Initial serum HCV RNA levels in HD patients were generally low (median, 1 x 10(5) genome eq/ml). Sustained responders had significantly lower median levels of viremia (4 x 10(4) eq/ml) than relapsers and nonresponders (9 x 10(4) and 1.8 x 10(5) eq/ml, respectively). Genotyping revealed a predominance of genotype 1a (33%) and 1b (48%). CONCLUSIONS: This study documents that fluctuating hepatitis C viremia with periods of undetectable HCV RNA is common and that low viral load predicts a sustained response to interferon therapy in HD patients. Diagnosis of chronic hepatitis C and monitoring of interferon therapy in HD patients should include initial HCV RNA quantitation and repeated qualitative measurements of HCV RNA.

Hepatitis C virus detection by single-round PCR specific for the terminal 3' noncoding region.

A single-round PCR method with primers specific for the 3' noncoding region (NCR) of hepatitis C virus (HCV) has been developed. Using a double RNAzol-B extraction, a high-temperature reverse-transcription step with SuperScript II reverse transcriptase, and a 40-cycle two-temperature PCR with a TaqStart antibody hot-start procedure, we were able to detect a 92-nucleotide fragment of the recently discovered 98-nucleotide highly conserved sequence at the 3' terminus of the HCV genome. Direct sequencing of the PCR products confirmed the specificity of the PCR and demonstrated conservation in this region. Only one nucleotide change in 14 specimens was found. End point dilution titration of sera with known viral RNA titers showed the sensitivity of the single-round 3' NCR PCR to be comparable to those of the established nested 5' NCR assays (fewer than 25 HCV genome equivalents). To evaluate specificity and sensitivity, a panel of 116 serum samples characterized by nested 5'-end PCR, genotyping, and quantitative assays was tested. A high degree of concordance (96%) between the 3' NCR and 5' NCR PCR results was found. The sequence conservation at the 3' end of the HCV genome among common genotypes and the savings in time, labor, and reagents from a single-round PCR make this assay a useful addition to the detection systems available to identify and monitor HCV infection.

Hemangiopericytoma of the heart following treatment of Hodgkin's disease. A case report.

During the autopsy of a 24 year old woman, who died of cardiorespiratory insufficiency a large solitary tumour was found extending into the right ventricle of the heart and obstructing the pulmonary valve subtotally. Histologically the tumour showed a vascular pattern of differentiation typical of a hemangiopericytoma with almost uniform cellularity and a dense reticulin meshwork surrounding the individual tumour cells. Ten years before death the patient had been diagnosed as having Hodgkin's disease treated with an unusually high dose of radiotherapy combined with chemotherapy. Although tumours have been known to arise following radiation and chemotherapy and hemangiopericytomas of almost all parts of the body have been described, to our knowledge this is the first case of an (iatrogenically induced) hemangiopericytoma of the heart.