High rate of GB virus type C/HGV transmission from mother to infant: possible implications for the prevalence of infection in blood donors

BACKGROUND: Because GB virus type C(GBV-C)/HGV (GBV-C/HGV) is blood-borne and sexually transmitted, persons at risk of infection with such viruses have a high prevalence of GBV-C/HGV markers. However, adults with no apparent risk factors, such as blood donors, frequently are positive for GBV-C/HGV markers. Mother-to-infant transmission could explain this high prevalence, but it has been studied only through small series of GBV-C/HGV-infected mothers co-infected with HCV or HIV. STUDY DESIGN AND METHODS: To determine the rate of mother-to-infant transmission of GBV-C/HGV RNA in women who are HCV- or HIV-negative, a prospective study was performed in a cohort of 288 mothers screened for viral RNA and in the infants born to GBV-C/HGV-infected mothers. RESULTS: Thirteen mothers (4.5%) were found positive for GBV-C/HGV RNA. Of the infants in whom at least one blood sample was collected between the third and the ninth months of life, 89 percent were positive for viral RNA. The majority of these newborns were negative for GBV-C/HGV RNA at birth and positive after the third month. The viral RNA titers of infants born to GBV-C/HGV-infected mothers appeared as elevated as those of their mothers. All the GBV-C/HGV-infected infants remained positive for viral RNA during the entire study period. No clinical events possibly linked to a primary GBV-C/HGV infection were reported in infants. Serum ALT level and blood count remained within normal values throughout the follow-up of all GBV-C/HGV-infected infants. CONCLUSION: The frequency of mother-to-infant GBV-C/HGV transmission is elevated and could explain the high prevalence of GBV-C/HGV markers (viral RNA and E2 antibody) in adults at low risk for blood-borne or sexually transmitted viruses, such as blood donors.     

GB virus type C/HGV markers in HCV RNA-positive French blood donors: correlation with HCV genotypes and risk factors

BACKGROUND: Exposure to GB virus type C/HGV (GBV-C/HGV) could be determined by detection either of RNA by RT-PCR or of antibodies of the envelope protein E2. STUDY DESIGN AND METHODS: The aim of the study was to determine the proportion of the GBV-C/HGV markers of infection in a blood donor population infected with HCV and to identify GBV-C/HGV routes of transmission that are associated with HCV genotypes and risk factors. RESULTS: Among 306 HCV RNA-positive blood donors, the proportion of GBV-C/HGV RNA-positive donors and anti-E2-positive donors was 19.3 percent (95% CI = 15.0-24.2%) and 42.1 percent (95% CI = 36.6-47.9%), respectively. Exposure to GBV-C/HGV (RNA or anti-E2) was significantly associated with the risk factor of IV drug use. There was a trend toward association with HCV subtypes 1a and 3a, probably because these HCV subtypes are the most frequent in IV drug users. No correlation was observed between ALT elevation and the presence of GBV-C/HGV RNA. CONCLUSION: In persons with HCV infection, IV drug use seems to be a major route of GBV-C/HGV transmission. Precautions taken to avoid HCV infection will probably also decrease GBV-C/HGV transmission.     

Hepatitis G virus biology, epidemiology, and clinical manifestations: Implications for blood safety

Hepatitis G virus (HGV), also called GBV-C, is a single positive-standard RNA virus belonging to the Flaviviridae family. In 50% to 75% of infections, HGV is cleared with plasma RNA disappearing as anti-E2 becomes detectable; in other cases, HGV infection becomes chronic. The prevalence of HGV RNA in blood donors ranges from 1% to 4%, and the rate of anti-E2, indicating resolved infection, ranges from 3% to 14%. HGV is transmitted by transfusion of blood components and has been transmitted by nonvirally inactivated factor VIII concentrate. Despite extensive study, HGV has not been identified as a causative agent of any type of liver disease or any other known clinical condition. Molecular biology data show a lack of hepatotropism; preliminary data indicate that the site of HGV replication may be in mononuclear cells in bone marrow or spleen but not in peripheral blood or lymph nodes. The combined clinical and laboratory data strongly support the contention that HGV is not a hepatotropic virus and that this virus was inappropriately named hepatitis G. Because the data do not indicate any pathologic effects of HGV, it is not appropriate to screen the blood supply for HGV RNA.     

Hepatitis C virus and GB virus C/hepatitis G virus viremia in Swedish blood donors with different alanine aminotransferase levels

BACKGROUND: Hepatitis C virus (HCV) is a known blood-borne hepatotropic virus for which antibody screening of blood donors is universally practiced. The newly identified GB virus C (GBV-C) and its strain variant hepatitis G virus (HGV) are of unknown pathogenic significance, and screening of blood donors for this agent has not yet been implemented. Polymerase chain reaction (PCR) is the most sensitive method for detecting HCV viremia and is the only method presently available for the diagnosis of GBV-C/HGV infection. STUDY DESIGN AND METHODS: RNA extracts of sera from 577 anti-HCV-negative blood donors (393 with elevated alanine aminotransferase [ALT] levels, 184 with normal ALT levels) were tested with nested PCR for HCV and GBV-C/HGV directed at the 5'-noncoding regions of the two viruses. RESULTS: One donor with elevated ALT was HCV PCR positive. This donor was anti-HCV negative when recruited to the study but subsequently developed anti- HCV. Of the 19 donors with GBV-C/HGV viremia in the series as a whole, 16 belonged to the group with elevated ALT levels and 3 to the group with normal ALT levels; the group difference in prevalence was nonsignificant (4.1% [16/393] vs. 1.6% [3/184; p = 0.20]). Phylogenetic analysis showed 16 of the GBV-C/HGV isolates to be classifiable as subtype 2a and three as subtype 2b. At follow-up 3 to 5 years later, 11 of 18 donors were still viremic. CONCLUSION: There was no significant difference in GBV-C/HGV viremia in the group with elevated ALT levels and the group with normal ALT levels. The frequency and subtype distribution in the present series were similar to those in other Western countries.     

High prevalence of GBV-C/HGV among relatives of GBV-C/HGV-positive blood donors in blood recipients and in patients with aplastic anemia

BACKGROUND: The prevalence of GB virus C (GBV-C)/HGV is high in individuals with parenteral risk factors. The frequency of GBV-C/HGV in blood donors is significantly lower, however it is still far above other parenterally transmitted viruses like HBV and HCV. Therefore, transmission routes apart from parenteral transmission must be considered. STUDY DESIGN AND METHODS: The purpose of the study was to evaluate the prevalence of GBV-C/HGV in blood donors and relatives of GBV-C/HGV-positive and -negative blood donors. Prevalence was also analyzed in aplastic anemia patients. Samples were tested by RT-PCR and partially by ELISA. Positive isolates were sequenced and phylogenetically analyzed. RESULTS: A total of 5733 blood donors were PCR tested and 90 were positive (1.6%). Of these, 98 relatives could be tested. Viremia was found in 14.3 percent and anti-E2 in 29.5 percent, whereas only 1.1 percent of the relatives of PCR-negative donors were viremic and 8.5 percent were anti-E2 positive. Probable virus transmission could be shown in two couples and in six mother-child pairs by sequencing of isolates indicating horizontal and vertical virus transmission, respectively. Recipients of GBV-C/HGV RNA-positive blood products were shown to be infected at a rate of 58 percent (18/31). Aplastic anemia patients were positive at a rate of 32 percent (17/53). CONCLUSION: The high percentage of 14.3 percent of GBV-C/HGV PCR-positive relatives of GBV-C/HGV-positive blood donors suggests intrafamilial transmission. Sequence analyses revealed vertical and horizontal transmission. Although parenteral transmission is highly efficient for GBV-C/HGV (58% of recipients of GBV-C/HGV RNA-positive blood products and 32% of aplastic anemia patients), it appears that sexual and vertical transmission are the most common transmission routes.     

GB virus C/hepatitis G virus infection in Indian blood donors and high-risk groups.

The hepatitis G virus (HGV) or GB virus C (GBV-C) was discovered in 1995 as a putative agent of post-transfusion, non-A-E hepatitis. The present study was carried out with the aim to find the prevalence of this virus among various subject groups at risk for parenteral transmission as well as in healthy control subjects both individually and along with other parenterally transmitted hepatitis viruses. Of the 402 subjects tested, 6.22% were positive for the HBsAg surface antigen, 7.21% were positive for HCV RNA while only 2.24% were seen to be carriers of the HGV/GBV-C RNA. All the HGV/GBV-C positive cases were either multi-transfused thalassaemic subjects or hemodialysis patients. None of the healthy control subjects showed presence of the virus. Seven of the HGV/GBV-C positive subjects showed co-infection with one or more additional virological markers. Also, of the 9 HGV/GBV-C positive subjects, 5 showed elevated ALT levels while 4 showed elevated alkaline phosphatase levels. Overall our findings seem to indicate that HGV infections generally are asymptomatic, transient and self-limiting and the virus does not seem to show a very high prevalence among the Indian population.     

Prevalence and infectivity of hepatitis G virus and its strain variant, the GB agent, in volunteer blood donors in Taiwan

BACKGROUND: The prevalence of hepatitis G virus (HGV) and its strain variant, the GB agent (GBV-C) is high in non-virus-inactivated plasma products, but, persistent infection in recipients is relatively low. STUDY DESIGN AND METHODS: Stored samples from transfusion donors and recipients in a prospective study of posttransfusion hepatitis were tested for HGV RNA and antibody to the E2 protein (anti-E2). RESULTS: Thirty-two (2.1%) of the 1500 qualified donors were positive for HGV RNA. Twenty-four persons had received a transfusion of blood from one of these 32 viremic donors. Of these 24 recipients, 3 were positive for HGV RNA before transfusion. Of the remaining 21 recipients, 8 became viremic after transfusion, while the other 13 were not infected. Four of the eight infected recipients were persistently positive for HGV RNA, while four became negative in 1 to 3 years. Three of the four patients with HGV clearance seroconverted to anti-E2 positivity. Comparison of the viral titer, viral sequences at E2, storage period of blood donations, and clinical data in the infected and noninfected recipients revealed no significant differences. However, the noninfected recipients seemed to have a higher prevalence of anti-E2 before transfusion. CONCLUSION: The prevalence of HGV viremia in volunteer blood donors in Taiwan is 2.1 percent, and blood from 0.6 percent of them actually causes HGV infection in the recipients. In half of infected recipients, clearance of HGV occurs. Anti-E2 appears in most recipients whose viremia is cleared.     

The prevalence of serum GB virus C/hepatitis G virus RNA and anti-E2 in Japanese children without a history of blood transfusion

The prevalence of serum GB virus C (GBV-C)/Hepatitis G virus (HGV) RNA and anti-E2 was investigated in Japanese children younger than 16 years of age without a history of blood transfusion and the family members of serum GBV-C/HGV RNA-positive children. The prevalences of serum GBV-C/HGV RNA and anti-E2 were 0.5% (5/1000) and 0% (0/330), respectively. Viral RNA was also detected in the mothers of all five GBV-C/HGV RNA-positive children and in two of their siblings. Sequence determinations indicated the likelihood of mother-to-infant transmission in all cases. The presence of the virus persisted for at least 10-18 months in all 5 children, without any appearance of anti-E2.     

Mother-to-infant transmission of GB virus type C/HGV

BACKGROUND: The potentially hepatotropic flavivirus-like virus, GB virus type C (GBV-C)/HGV, has been detected in a few patients with acute and chronic hepatitis and in a certain proportion of blood donors and recipients of blood or blood components. STUDY DESIGN AND METHODS: Sera from 2979 pregnant Japanese women were examined for the presence of GBV-C/HGV RNA by nested RT-PCR. Mothers who were positive for viral RNA and their 34 infants were followed and tested for infection. RESULTS: Of the 2979 women, 32 (1.1%) were positive for GBV-C/HGV RNA. Twenty-six (76.5%) of 34 babies born to these women were positive for the virus when first tested. A significantly higher titer of viral RNA was observed in mothers whose infants were infected than in those whose infants were uninfected (mean +/- SD, 10(6.3 +/- 0.9) vs. 10(4.6 +/- 0.9)/mL; p<0.001). Twenty-three (96%) of 24 babies born to mothers whose serum viral titers were 10(6) mL or more were infected with the virus. Infants delivered by elective caesarean section had a lower risk (OR, 0.13; 95% CI, 0.02-0.82) than those delivered vaginally or by emergency caesarean section. No other risk factors for mother-to-infant transmission were confirmed. CONCLUSIONS: GBV-C/HGV is frequently transmitted from mothers to infants in the general population. The most critical factor is the titer of viral RNA in the maternal serum. By the use of elective caesarean section in women with high titers of viral RNA, vertical transmission of the virus may be lessened.     

Hepatitis C virus and GBV-C/hepatitis G virus in Argentine patients with porphyria cutanea tarda

To investigate hepatitis C virus (HCV) and GBV-C/hepatitis G virus (HGV) genotype prevalence among HCV-infected porphyria cutanea tarda (PCT) patients, 19 HCV-infected patients with associated PCT were studied. A control group of 53 age-matched HCV-infected patients without associated PCT was selected. Eighteen of the 19 serologically positive HCV-PCT patients showed HCV RNA in serum. Genotype 1b was the most prevalent among both HCV-PCT patients (72.2%; 13/18) and age-matched HCV controls (50.9%; 27/53). Such different genotypic prevalence failed to reach statistical significance (chi(2) with Yates' correction, p = 0.19). The single HCV-PCT patient without detectable HCV RNA was also infected with genogroup 3 GBV-C/HGV. This GBV-C/HGV RNA prevalence (5.3%) among HCV-PCT patients is not statistically different from that observed among Argentine blood donors (5.5%; 11/200). To our knowledge, these results show for the first time the molecular epidemiology of both HCV and GBV-C/HGV associated to PCT in America.     

Persistent infection mechanism of GB virus C/hepatitis G virus differs from that of hepatitis C virus

OBJECTIVE: Changes in the deduced amino acid sequence of the envelope 2 (E2) region of the GB virus C/hepatitis G virus (GBV-C/HGV) were analyzed to investigate whether or not the region contributes to persistent infection with the virus. METHODS: Eight patients with acute hepatitis C and 1 patient with acute hepatitis of unknown etiology were included in the study. GBV-C/HGV RNA was detected in 6 patients, including the patient with hepatitis of unknown origin. The nucleotide sequence of the E2 region of hepatitis C virus (HCV) and GBV-C/HGV was determined by direct sequencing of polymerase chain reaction products in 5 patients with HCV infection and in 6 patients with GBV-C/HGV infection twice during the period of early infection and several months or years later in each patient. RESULTS: The mean substitution rate of the deduced amino acid sequence in the E2 region was over 100 times lower (p < 0.001) in GBV-C/HGV (0.01 +/- 0.04/month/100 sites) than in HCV (2.4 +/- 1.7/month/100 sites). The amino acid sequence of the loop domain of GBV-C/HGV-E2 did not change in any of the 6 patients. On the other hand, the sequence of the hypervariable region of HCV-E2 changed remarkably (5.9 +/- 4.3/month/100 sites). No amino acid substitution in the loop domain was observed in 7 additional patients who showed persistent GBV-C/HGV viremia for more than 2 years. CONCLUSION: These results indicate that changes in the amino acid sequence of the E2 region are not involved in the mechanism of persistent GBV-C/HGV infection.     

合肥地区献血员庚型肝炎病毒的分子生物学研究

目的了解台肥地区献血员的庚型肝炎病毒(GBV—C／HGV)感染情况。方法应用酶免疫测定法(EIA)和逆转录一套式多聚酶链反应法(RT—PCR)分别检测献血员中的抗-GBV-C/HGV和GBV-C/HGV RNA。结果 献血员中抗-GBV—C/HGV检出率为1．7％(18／1 050)．抗-GBV—C／HGV阳性血清中GBV／HGV RNA占66.7％(12/18)；男性和低年龄组献血员抗-GBV—C／HGV阳性率分别低于女性和高年龄组．两差异有显性(P<0.05)；抗-GBV—C／HGV阴性的献血员有6名转为阳性，2名抗-GBV-C/HGV和GBV-C／HGV RNA阳性的献血员有1名转为阴性。结论GBV—C／HGV在合肥地区献血员中有较高的感染率；献血员中存在着GBV-C／HGV阳性但ALT正常的献血员，应尽快对献血员进行GBV-C／HGV感染指标的检测。     

GB virus type C infection in patients treated for childhood acute lymphoblastic leukemia

BACKGROUND: The purpose of this study was to determine the prevalence of GB virus type C (GBV-C) infection in subjects treated for childhood acute lymphoblastic leukemia (ALL) or non-Hodgkin's lymphoma. STUDY DESIGN AND METHODS: One hundred forty patients (82 males) aged 4 to 27 years (median, 11) diagnosed with ALL between 1976 and 1993, were prospectively followed for a median of 5 years (range, 0.1-17) after completion of therapy. Stored sera were tested for antibody to hepatitis C virus (HCV), HCV RNA, antibody to GBV-C E2 (anti-E2), and GBV-C RNA. RESULTS: Thirty-eight patients (27%) were exposed to GBV-C: 30 were positive for GBV-C RNA (mostly type 2) and 8 were positive for anti-E2. Anti-E2 and GBV-C RNA were mutually exclusive: 61 patients (43%) were positive for HCV RNA, 16 (11%) were coinfected with GBV-C and HCV. Alanine aminotransferase (ALT) levels were increased (>35 mU/mL) in 32 (23%) of 137: 3 of 20 who were positive for GBV-C and negative for HCV, 7 of 15 who were positive for GBV-C and HCV, 15 of 44 who were negative for GBV-C and positive for HCV, and 7 of 58 who were negative for GBV-C and HCV (p<0.001). Median ALT values were significantly higher in patients positive for GBV-C and HCV than in those who were positive for GBV-C and negative for HCV (35 vs. 13 mU/mL, p = 0.003). Thirty-one of 38 patients with GBV-C markers were retested: GBV-C RNA was lost in 16 of 30 tested, but 7 were still GBV-C RNA positive up to 50 months later, 3 tested positive for anti-E2 up to 27 months later, and 1 was positive for GBV-C RNA and anti-E2 26 months later, while 20 tested negative for both. CONCLUSION: GBV-C did not behave as a liver pathogen, because ALT alterations were unrelated to GBV-C status, but, rather, were related to HCV infection or coinfection. GBV-C RNA was frequently lost over a relatively short period, though in some cases, it was retained for a longer time. Anti-E2 rarely coexisted with GBV-C RNA and might be short-term.     

Evaluation of RNA and E2 antibodies in prospectively followed recipients of hepatitis G virus-infected blood

BACKGROUND: Hepatitis G virus (HGV) has recently been cloned and tests for HGV RNA and envelope antibodies (anti-E2) have been developed. HGV infection is widespread among blood donors worldwide, but the clinical and serologic outcome of transfusion-associated HGV infection has not been fully characterized. STUDY DESIGN AND METHODS: Consecutive blood donors (n = 2210) were investigated for HGV markers (RNA and anti-E2). The recipients of HGV RNA-positive blood were followed for 1 year after transfusion. RESULTS: Forty-two blood donors (1.9%) were positive for HGV RNA. Eight recipients of HGV RNA-positive blood were retrospectively identified within 2 weeks of transfusion and prospectively followed. In four patients, the presence of anti-E2 before transfusion or an early antibody response protected them from reinfection or prevented HGV persistence, while, in the remaining four patients, transient or persistent viremia was detected shortly after exposure. None of the infected recipients had any evidence of liver disease. CONCLUSION: These results do not support the screening of donors to prevent transfusion-associated HGV infection.     

Prevalence of hepatitis G virus RNA and antibodies to HGV envelope protein (anti-E2) in patients with liver injury in Japan]

To assess the role of hepatitis G virus (HGV) in acute and chronic liver diseases, we investigated the prevalence of HGV RNA and antibodies to HGV envelope protein (anti-E2) among patients with liver diseases diagnosed in our hospital from 1992 to 1997. Among 24 patients with acute hepatitis (HAV: 13, HBV: 2, HCV: 3, CMV: 1, non A-C: 5), only 1 patient with non A-C hepatitis (4%) were positive for HGV RNA and none was positive for anti-E2. Among 461 patients with chronic liver diseases (alcohol: 27, HBV: 74, HCV: 297, HBV + HCV: 10, non B non C: 14, autoimmune and metabolic: 39), 40 patients (alcohol: 1, HBV: 3, HCV: 33, HBV + HCV: 3) were positive for HGV RNA(9%) and 48 patients were positive for anti-E2(17%). In the patients with positive for anti-E2, only 8% were positive for HGV RNA. 98% of HGV RNA positive patients were infected with HBV or HCV, and especially 82% were infected with HCV. In patients with non A-C hepatitis, none was positive for HGV RNA, so HGV seems not to have important role in liver diseases.