The hepatitis C virus genotype and subtype frequency in hepatitis C virus RNA-positive, hepatitis C virus antibody-negative blood donors identified in the nucleic acid test screening program in Poland.

BACKGROUND: Since 2002, blood donors in Poland have been tested not only for hepatitis C virus antibodies (anti-HCV) but also for HCV RNA or HCV core antigen. This screening program identifies asymptomatic, recently infected individuals with no anti-HCV (in the "window period"). The aim of this study was to compare HCV genotype and subtype distribution in window-period (wp) donors, anti-HCV-positive donors, and chronic hepatitis C (CHC) patients. STUDY DESIGN AND METHODS: A total of 2.37 million donors were investigated for HCV RNA, and 340,000 for HCV core antigen. HCV genotypes and subtypes were investigated in 50 HCV RNA-positive, anti-HCV-negative donors; in 70 anti-HCV-positive donors; and in 170 CHC patients. Re-questioning of wp donors for probable risk factors was introduced. RESULTS: HCV RNA was detected in 50 donors of 2.71 million (1:54,200) anti-HCV-negative blood donations. Of these 50 donors, 36 percent exhibited Subtype 1b, whereas Subtypes 3a and 4c/d were identified in 40 and 14 percent, respectively. In anti-HCV-positive donors and CHC patients, the frequency of Subtype 1b was significantly higher (75.7 and 85.3%, respectively); in both groups the lower frequency of Subtypes 3a (14.3 and 10.6%, respectively) and 4c/d (4.3 and 1.2%, respectively) was found. The probable source of infection was identified in 9 wp donors. CONCLUSIONS: The frequency of wp donors is 18.5 per 1 million. The unexpected high frequency of Genotype 4 and Subtype 3a and the low frequency of Subtype 1b was observed in wp donors compared to anti-HCV-positive individuals. Additional epidemiologic questioning introduced after HCV RNA detection may help to identify infection source.

Factors influencing natural history of chronic hepatitis C.

The aim of the study was to asses influence of selected epidemiologic and virusologic factors on the course of chronic hepatitis C (CHC). Data obtained from 550 CHC patients was analyzed (F/M: 241/309; age: 14-87, average age: 44.9 +/- 15.6). HbsAg and HIV-positive, as well as patients taking drugs were excluded from the study. Progression of the liver disease was assessed by the maximal ALT activity, presence of clinical or histopathological symptoms of hepatic cirrhosis, and 363 liver biopsy results. Clinical and histological data was analyzed depending on: patients sex, age (= 40, and > 40 years old), portal of infection (history data on transfusion or another source of infection), history of HBV infection (presence or absence of anti-HBc antibodies), and HCV genotype (1b or no-1b group). HCV genotype was determined in 170 patients by the use of commercial InnoLipa kit (Innogenetics). Statistical analysis was based on t-Student test and chi-squared test with or without Yates correction. It was proved that in patients over 40 years old or with history of transfusion inflammatory activity and liver fibrosis activity are significantly higher than in the rest of patients. More advanced age, transfusion and history of HBV infection are risk factors for hepatic cirrhosis development in CHC patients. Neither patient's sex nor HCV genotype were found to have significant influence on the course of CHC.

Anti-HCV RIBA/LiaTek reactivity and HCV genotype in EIA-negative patients with viremia.

Individuals infected with hepatitis C virus (HCV) usually produce anti-HCV antibodies detectable by enzyme immunoassay (EIA); however, in certain viremic cases this antibody does not appear. To investigate whether anti-HCV in these cases is detectable by Western blot (WB), 38 HCV RNA positive/anti-HCV EIA-negative sera were tested by RIBA 3.0 or LiaTek III. The HCV genotypes (INNO-LiPA) were analyzed to determine whether the variance in these genotypes can be the reason for the late, weak antibody production or its absence. As the control group, 282 EIA-positive/HCV RNA-positive patients were examined. A single band reactivity of various intensities by RIBA or LiaTek was observed in 16/38 EIA negative sera. Positive results with NS3 were detected in 4 sera and weak positive (+/-) with core, NS3, and NS5 in 5, 6, and 1 sera, respectively. In 3 cases with anti-NS3, the seroreversion was observed in follow-up. The distribution of genotypes in anti-HCV-negative versus anti-HCV-positive groups was: 1b alone, 50.0% vs. 78.0%; 3a alone, 13.2% vs. 15.6%; and mixed (1b+3a), 36.8% vs. 5.0%, respectively. The follow-up studies showed that viremia was lost spontaneously in 12/35 patients. In some patients infected with two genotypes, the spontaneous loss of the 3a genotype was observed. The study showed that WB tests are useful for serological confirmation of HCV infection in some EIA negative/HCV RNA-positive patients but, because seroreversion may occur, sequential sera samples should be tested. No unusual HCV genotype was detected in anti-HCV-negative/HCV RNA-positive cases, but the frequency of mixed infection with the 1b+3a genotypes in this group was found to be higher than that in anti-HCV-positive hepatitis patients.