Indeterminate results of the second-generation hepatitis C virus (HCV) recombinant immunoblot assay: significance of high-level c22-3 reactivity and influence of HCV genotypes.

A second-generation recombinant immunoblot assay (RIBA 2.0) is used in the United States to confirm infection with hepatitis C virus (HCV) in samples that are anti-HCV (enzyme immunoassay) positive. In some cases, indeterminate results of RIBA 2.0, which are defined as reactivity to a single antigen species or reactivity limited to two proteins derived from the same coding region of the HCV genome, are encountered. This study was performed to establish the significance of indeterminate RIBA 2.0 results in relation to HCV RNA detection, high positivity for the c22-3 band, and the HCV genotype as determined by direct DNA sequencing. Ninety-six samples with indeterminate RIBA 2.0 results were studied. HCV RNA was detected in 21 of 34 (62%) samples with high reactivity to c22-3 and in 8 of 62 (13%) samples with low reactivity to c22-3. The HCV genotype distribution in samples that were RIBA 2.0 indeterminate and HCV RNA positive was significantly different from that in samples of a control group with positive results for both the RIBA 2.0 and HCV PCR. These results suggest that highly positive c22-3 samples are likely to be associated with HCV viremia and that infection with less common HCV genotypes is more commonly associated with indeterminate RIBA 2.0 results.

Increased risk of hepatocellular carcinoma in patients infected with hepatitis C genotype 1b.

UNLABELLED: Infection with hepatitis C virus (HCV) genotype 1b has been reported to be associated with more severe liver disease and an unfavorable outcome. Liver transplantation allows for a complete examination of the explanted liver for the detection of hepatocellular carcinoma (HCC). OBJECTIVE: To study the prevalence of HCC in patients with liver cirrhosis secondary to chronic infection with HCV genotype 1b compared with those infected with other genotypes. METHODS: Sera were collected from 48 consecutive patients undergoing liver transplantation for end stage liver disease secondary to HCV infection. RNA was extracted from serum using chaotropic lysis and isopropanol precipitation. Reverse transcriptase-polymerase chain reaction of the NS5 region was performed, followed by automated sequencing on desalted amplification products. Genotype assignment followed Simmonds's classification. All explanted livers were examined for the presence of HCC. RESULTS: HCV genotypes in our patients were as follows: subtype 1a, 20 patients (42%); 1b, 18 patients (37.5%); 2a, one patient (2%); 2b, six patients (12.5%); 3a, one patient (2%); and 4a, two patients (4%). Although five of 18 patients infected with HCV genotype 1b (28%) had HCC, only one of 30 patients (3%) infected with all other genotypes (1a, 2a, 2b, 3a, and 4a) had HCC (p = 0.02). CONCLUSION: Infection with HCV genotype 1b may carry a higher risk for the development of HCC than infection with other HCV genotypes.

Prevalence and outcome of hepatitis C infection among heart transplant recipients.

BACKGROUND: Hepatitis C virus infection is common in organ transplant recipients, and can be associated with significant morbidity and mortality. A unique feature of this infection among immunosuppressed patients is that it can progress without the development of hepatitis C virus antibodies. METHODS: To define the prevalence of hepatitis C virus infection in patients undergoing heart transplantation and identify clinical syndromes associated with hepatitis C virus infection in heart transplant recipients, we collected sera from 59 consecutive heart transplant recipients and their donors. Samples were tested before and after transplantation for hepatitis C virus antibodies with the use of a second-generation recombinant immunoblot assay and for hepatitis C virus RNA by means of reverse transcriptase polymerase chain reaction. RESULTS: Four of 59 patients (7%) had hepatitis C virus-RNA detected in posttransplantation serum samples; but only one of these was anti-hepatitis C virus antibody positive. Two of the four patients with hepatitis C virus RNA detected after transplantation received organs from donors who were positive for hepatitis C virus RNA/anti-hepatitis C virus. One of these two recipients tested positive for hepatitis C virus antibody and hepatitis C virus RNA before transplantation. The other two patients received organs from hepatitis C virus negative donors and possibly acquired infection after transplantation from blood or immunoglobulin preparations. One patient was anti-hepatitis C virus positive before transplantation but had no detectable hepatitis C virus RNA, and hepatitis C virus infection did not develop after transplantation. Progressive hepatitis C virus-induced cholestatic liver disease that led to hepatic failure and death after heart transplantation occurred in one of the four patients. CONCLUSION: Hepatitis C virus infection may occur after heart transplantation in the absence of anti-hepatitis C virus antibodies, and a syndrome of severe cholestatic liver disease may complicate heart transplantation in the presence of hepatitis C virus infection.