[Viral co-infections in hepatitis C: HBV, HBV-C/HGV and TTV studies]. / Víruskoinfekciók krónikus hepatitis C-vírus-fertózésben: HBV-, GBV-C/HGV- és TTV-vizsgálatok.

BACKGROUND/AIMS: The prevalence of co-infections with hepatitis B virus (HBV) and novel hepatitis viruses GBV-C (Hepatitis G virus, HGV) and TT virus (TTV) in chronic hepatitis C (HCV) infection has been studied. In patients with chronic hepatitis C and in asymptomatic healthy HCV carriers, the influence of these agents on the course of HCV infection was assessed. METHODS: a total of 110 HCV-positive individuals, among them 77 patients with chronic hepatitis C--50 of them treated with interferon (IFN)--and 33 HCV carriers with normal alanine aminotransferase have been investigated. HBV-DNA, HGV RNA and TTV DNA were detected by PCR, to determine HBsAg and anti-HBc ELISA technic has been used. RESULTS: In the healthy population, the prevalence of anti-HCV was 0.3%, HBsAg 0.09%, anti-HBc 2.5%, HGV RNA 8.0% and TTV DNA 18.5%, respectively. In chronic hepatitis C HBsAg (accompanied with HBV-DNA) occurred in 1.29%, anti-HBc 25.97%, HGV RNA in 9.09% and TTV DNA in 40.25% of cases. In IFN-treated patients with sustained remission, the frequency of TTV was 20% vs. 45.7% found in non-responders. Among asymptomatic HCV-carriers, the prevalence of anti-HBc was 27.27%, HGV RNA 9.09% and TTV DNA 75.7% respectively. CONCLUSIONS: Neither previous HBV infection, nor HGV RNA and TTV DNA had apparent effect on the course of chronic HCV infection. TTV was detected with the lowest frequency in persons with sustained remission due to IFN, suggesting antiviral effect of IFN on TTV.

Co-infections with hepatitis G and TT virus in patients with chronic hepatitis C in Hungary.

The significance of co-infections with novel hepatitis viruses Hepatitis G (GBV-C, HGV) and TT virus (TTV) in chronic hepatitis C is not clear. We determined the prevalence of HGV RNA and TTV DNA in chronic hepatitis C patients and in asymptomatic hepatitis C virus (HCV) carriers, and assessed the influence of these agents on the course of HCV infection. Seventy-seven patients with chronic hepatitis C--50 of them treated with interferon (IFN)--and 33 HCV carriers with normal alanine aminotransferase have been investigated. Previous HBV infection was detected by testing serum HBsAg and aHBc. HGV RNA and TTV DNA were detected by PCR. In the healthy population, the prevalence of anti-HCV was 0.3%, HGV RNA 8.0% and TTV DNA 18.5%. In chronic hepatitis C HGV RNA occurred in 9.09% and TTV DNA in 40.25% of cases. In IFN-treated patients with sustained remission, the frequency of TTV was 20% vs. 45.7% found in non-responders. Among asymptomatic HCV-carriers, the prevalence of HGV RNA was 9.09% and TTV DNA 75.7%. Neither HGV RNA nor TTV DNA had apparent effect on the HCV infection. TTV was detected with the lowest frequency in persons with sustained remission due to IFN, suggesting antiviral effect of IFN on TTV.

Retrospective detection of a subclinical hepatitis A virus (HAV) epidemic affecting juvenile cohorts of the Hungarian population.

Sero-epidemiological surveys of serum samples taken in 1982, 1987, 1994 and 1999 have been performed with hepatitis A virus-specific (HAV-specific) serological tests. Results obtained during these surveys show that the proportion of seropositive blood donors decreased from 69% to 18% within 17 years. The authors have recognised a (mainly subclinical) epidemic, affecting about 115000 teenagers in 1992-1994 in Hungary, is a threatening phenomenon. It was calculated that only about 3600 clinical diseases were associated with the epidemic, recognised retrospectively from the findings of the four sero-epidemiological surveys. Epidemiological data indicated that the excess clinical diseases caused by HAV concentrated in the southern counties of Hungary, which have been affected by the social and military activities between 1992 and 1994. Due to the decrease of subjects seropositive for HAV, sera from preselected or actively immunised donors will be required in the future and vaccination against HAV with killed virus is likely to be recommended for risk groups. Furthermore, health authorities might promote active immunisation of young children against HAV infection; for that, promotion of manufacturing combination vaccines of HAV/HBV/DPT or, for certain countries, HAV/DPT would be desirable.

Perinatal and intrafamily transmission of hepatitis B virus in three generations of a low-prevalence population.

Family members of 47 hepatitis B virus (HBV)-carrier pregnant women were tested for the presence of hepatitis B surface antigen (HBsAg), other markers of HBV infection, and hepatitis A virus (HAV) antibodies. Eleven members of six families were found to be HBV DNA positive. Five of the anti-HBe-positive persons were found to be HBV DNA carriers, too. The mean age of the HBV DNA carriers was found to be lower than that of Hbe carriers; therefore, it is suggested that seroconversion to HBe occurs before the resolution of HBV DNA carrier state. Superinfection with hepatitis A virus was not found to influence the elimination of HBV-carrier state, as there was no correlation found between the hepatitis A exposure and the hepatitis B virus markers in the families. The low HBV prevalence in the population (0.3%) was in contrast to the high prevalence of the families of the HBV-carrier mothers (27.1%) and family members with HBV markers (50.4%). Significant positive correlation was found in the proportion of HBV-positive children, and the HBV history of their parents. When fathers were shown to be seronegative, the probability of HBV transmission was reduced by a factor of 6 (12.5% instead of 75%) probably due to reduced viral load and possibly by other factors. Several results indicate, that the noncytocidal hepatitis B virus clearing mechanism suggested by Guidotti et al. [1996, 1999] was effective also in the HBV-carrier human population.

TT virus in Hungary: sequence heterogeneity and mixed infections.

The majority of the viral hepatitis cases is caused by five hepatitis viruses (A,B,C,D,E). In 1997, TT virus was discovered. It was supposed that a number of the unknown hepatitis cases was caused by the TT virus. The aim of this study was to characterize TT viruses carried by healthy individuals and patients suffering from hepatitis of unknown origin in Hungary. TTV DNA was detected by seminested PCR with the commonly used N22 primers. Twenty of the 108 sera (18.5%) taken from healthy persons and 115 of the 228 sera (50.4%) of patients with hepatitis of unknown origin were found to be positive. The nucleotide sequences of 26 clones derived from 17 hepatitis patients and 15 clones from nine healthy persons were determined and a phylogenetic tree was constructed. Genotype 2 (group 1) was found to be the most frequent, but other group 1 genotypes (1, 6) and genotypes 8 and 17 of group 2 were also detected. Mixed TTV infections were found in eight cases (two healthy persons and six hepatitis patients). Variants belonging to the same group were carried in seven cases, and the presence of group 1 (genotype 2) and group 2 (genotype 8) TTV sequences were found in one single hepatitis patient.

Prevalence of GB virus C/hepatitis G virus in Hungary.

In 1995 a new flavivirus, GB virus C/hepatitis G virus (GBV-C/HGV), was discovered. The aim of this study was to determine the prevalence of the virus in healthy persons and hepatitis patients in Hungary. The sera of 408 healthy persons older than 60 years were tested for the presence of GBV-C/HGV antibodies, and 113 were positive (28%). Eight of the 71 healthy persons younger than 60 years and twenty of the 51 sera (39%) taken from patients suffering from hepatitis of unknown origin proved to be positive for GBV-C/HGV antibodies. Ten of the 124 sera (8%) of healthy persons and 36 of the 247 sera (14.6%) of hepatitis patients proved to be positive for GBV-C/HGV RNA. Eleven PCR products were sequenced, and the sequences were found to be different from each other and from the previously published ones. However, three sequences taken from the same patient at different times were identical. These results show that GBV-C/HGV is present in Hungary and cannot be considered rare.