Multicenter study of intrafamilial transmission of hepatitis C virus in human immunodeficiency virus infection

OBJECTIVE: Intrafamilial transmission of hepatitis C virus in human immunodeficiency virus and hepatitis C virus co-infections is not well documented. This cross-sectional study evaluated the transmission of hepatitis C virus in the sexual partners of hepatitis C virus and human immunodeficiency virus co-infected patients. METHODS: Hemophiliacs and transfused hepatitis C virus and human immunodeficiency virus co-infected patients who were being seen in three French university hospitals, and their sexual partners were studied by a face-to-face interview using an epidemiological questionnaire and by biological tests: antibodies against hepatitis C virus, hepatitis C virus RNA, and ALT activity. RESULT: Fifty-two subjects were included: 26 cases and their 26 sexual partners. Three sexual partners (11.5 %) had anti-hepatitis C virus antibodies, two of whom had an undetermined RIBA test. All three had a risk factor for hepatitis C virus infection (transfusion, intra-muscular injections with re-usable needles). Two of these three partners were also human immunodeficiency virus antibody positive. Hepatitis C virus RNA was negative in all sexual partners. CONCLUSION: This study provides evidence of a low prevalence of anti-hepatitis C virus antibodies in sexual partners of hepatitis C virus and human immunodeficiency virus co-infected patients. It does not support intra-familial transmission of hepatitis C virus.     

Prevalence and risk factors for intrafamilial transmission of hepatitis C virus in Karachi,Pakistan

Household contacts of hepatitis C virus (HCV)-positive patients are considered at increased risk of HCV infection. This cross-sectional study during April through June 1999 assessed the prevalence and risk behaviours associated with HCV seropositivity among the household contacts of HCV seropositive thalassaemic children in Karachi, Pakistan. Among the 341 household contacts of 86 thalassaemic HCV seropositive children who were tested, 70 (20.5%) were positive for anti-HCV antibodies. The stratified analysis showed that HCV seroprevalence among the contacts did not differ significantly by the gender of the index patient and the type of relationship of contact with the index patient. However, HCV seroprevalences among the fathers and mothers of male index patients was substantially higher compared to those of female index patients. HCV RNA was recovered and genotyped from nine index patients and corresponding nine HCV-seropositive household contacts. HCV genotype 3a and 3b were found in 89% (8/9) and 11% (1/9) of the pairs, respectively. The final multivariable conditional logistic regression model revealed that after adjusting for the effect of ethnicity and past hospital admission history, the HCV-seropositive household contacts were more likely than HCV seronegative household contacts to have been bitten by the carrier [adjusted matched odds ratio (mOR)=2.6, 95% CI 1.3–5.2] or have shared a toothbrush with the carrier (adjusted mOR=8.2; 95% CI 1.56–43.5). Control efforts should focus on the risk behaviours.     

Absence of intrafamilial transmission of hepatitis C in patients with inherited bleeding disorders

Summary . Hepatitis 'C' virus (HCV) infection has caused significant anxiety in patients with inherited bleeding disorders. A significant number of patients with HCV have developed chronic liver disease, cirrhosis and hepatocellular carcinoma. The exact risk of heterosexual and contact transmission is unclear at the moment. A test for antibody to hepatitis 'C' was offered, after counselling, to spouses and family members of 118 known hepatitis 'C' antibody positive patients with inherited bleeding disorders. Two hundred and fifteen family members were tested, 73 partners and 142 household contacts; all were found negative for hepatitis 'C'. Our experience confirms the low risk of heterosexual and contact transmission of hepatitis 'C' virus.     

Prevalence of hepatitis C virus antibody in a cohort of hemophilia patients

One hundred thirty-one patients followed at the New England Hemophilia Center (Worcester, MA) were tested for antibody to hepatitis C virus (HCV). All but two had used factor concentrate that had not undergone viral inactivation; two patients had used only cryoprecipitate. The overall prevalence of HCV antibody positivity was 76.3%. There was no significant difference in age or the amount of non-heat-treated factor concentrate used between the group that was HCV antibody positive and negative. There was also no significant difference between aminotransferase levels in the two groups. There was a positive association between HCV antibody and the presence of antibody to hepatitis B core antigen and antibody to human immunodeficiency virus. A group of 31 patients were tested twice for HCV antibody at intervals of 35 to 71 months. In this subset, 25 were repeatedly seropositive, 4 were repeatedly seronegative, and 2 went from seropositive to seronegative. These data confirm the previous impression that non-A, non-B hepatitis is a major sequela to the use of pooled coagulation factor concentrates. HCV infection may account for most of the chronic liver disease observed in this population. Anti-HCV testing of plasma donors and improved methods of viral inactivation should prevent new cases from developing.     

Intrafamilial transmission of hepatitis C virus in patients with hepatitis C and human immunodeficiency virus coinfection

OBJECTIVE: The aim of this study was to determine whether hepatitis C virus (HCV)/HIV coinfection of index cases increases intrafamilial transmission (sexual and nonsexual contacts) of HCV. METHODS: We prospectively enrolled 347 subjects, including 87 family members of 53 HCV/HIV-coinfected index cases and 134 family members of 73 HCV-monoinfected index cases, which served as a control group. All index cases and family members were interviewed, and a screening for HCV and HIV using enzyme-linked immunosorbent assays was performed. Positive samples were confirmed by polymerase chain reaction and tested for genotype and HCV RNA viral load. A meta-analysis designed to assess the pooled risk of sexual transmission of HCV among HCV/HIV-coinfected patients was performed. RESULTS: Anti-HCV was detected in 2.2% of family members of HCV-monoinfected index cases and 2.3% of family members of HCV/HIV-coinfected index cases. Viral load was higher in coinfected index cases (7.2 x 10(6) mEq/ml) compared with HCV alone (1.9 x 10(6) mEq/ml), p = 0.01. HCV genotype concordance was observed in three family members of HCV-monoinfected index cases and in two family members of HCV/HIV-coinfected index cases. The pooled OR of the meta-analysis evaluating HIV as a cofactor of sexual transmission of HCV was 1.54 (95% CI = 0.76-3.12). CONCLUSIONS: Our data demonstrate a low prevalence of intrafamilial transmission of HCV, independent of the presence of HCV/HIV coinfection. This finding is supported by meta-analysis, which failed to identify HIV as an important cofactor of sexual transmission in HCV/HIV-coinfected patients.     

The influence of hepatitis C virus eradication on hepatocarcinogenesis in patients with hemophilia

Introduction and objectivesHepatitis C virus (HCV) infections in patients with hemophilia lead to the development of hepatocellular carcinoma (HCC) at a relatively younger age than that in patients without hemophilia. Although recent progress in direct-acting-antivirals has facilitated a high rate of sustained virological response (SVR), the clinical influence of HCV eradication in hemophilia patients remains unclear. This study aimed to compare the clinical outcomes of SVR against HCV in patients with and without hemophilia.Patients and methodsThe study enrolled 699 patients who achieved SVR after HCV antiviral treatment. Patients were divided into two groups: 78 patients with hemophilia (H group) and 621 patients without hemophilia (NH group). We evaluated patient characteristics, clinical outcomes, and the cumulative incidence of HCC after SVR.ResultsCompared with the NH group, patients in the H-group were significantly younger and had a lower hepatic fibrosis score. No difference was found in the incidence of liver-related disease or overall death between the two groups over a mean follow-up period of 7 years.Four patients in the H group and 36 patients in the NH group were diagnosed with HCC after SVR. Multivariate analysis showed that male sex, age, and cirrhosis were significant risk factors for HCC incidence. There was no significant difference in the cumulative incidence of HCC after propensity-score matching adjusting for the risk factors of HCC between the two groups.ConclusionHemophilia is not a significant risk factor for hepatocarcinogenesis after SVR against HCV.     

Four cases with intrafamilial clustering of hepatitis C virus infection.

Four hepatitis C patients with intrafamilial clustering of hepatitis C virus (HCV) infection are reported. Antibodies to C100-3 antigen, capsid protein of HCV and GOR epitope were tested to detect histories of HCV infection. Transmission of HCV from mother to children, from father to children, and from wife to husband was implicated. Of all family members studied, three were positive for all antibodies, one for only antibody to capsid protein, two for antibodies to capsid protein and GOR epitope but negative for antibody to C100-3 antigen and one vice versa.     

Intrafamilial transmission of hepatitis C virus

Abstract The intrafamilial transmission pattern of hepatitis C virus (HCV) was examined in 118 family members of 61 index patients with type C chronic liver disease using anti-HCV antibodies and HCV RNA assay. The study subjects consisted of eight parents, 49 spouses, 50 children, eight siblings and three other relatives. The positivity rates of anti-C100, anti-JCC, second-generation anti-HCV and HCV RNA were 6.8, 12.7, 12.7 and 11.0%, respectively. Positivity in one or more anti-HCV antibody assay was detected in 3/24 (12.5%) father-child pairs, 3/17 (17.6%) mother-child pairs, 2/8 (25%) sibling pairs, 6/38 (15.8%) husband-wife pairs and 2/13 (15.4%) wife-husband pairs. In spouses, positivity for anti-HCV antibody or HCV RNA was observed after 40 years of age. None of 11 spouses married < 15 years was positive for any anti-HCV assay or HCV RNA. In spouses whose age was > 50 years and duration of marriage was > 25 years, anti-HCV or HCV RNA was frequently detected (32.0%). However, when seven pairs involving four spouses, one mother-daughter pair and two sibling pairs were subtyped, the same HCV subtypes were found in only four pairs (type II in three pairs and type III in one pair). Further, the agreement rate between anti-HCV and HCV RNA was > 90%. These results suggest that intrafamilial transmission of HCV, revealed by the subtyping method, is considered lower than the percentage of positivity for anti-HCV antibodies or HCV RNA in family members of patients with type C chronic liver disease. Thus, the intrafamilial transmission of HCV seems to be quite rare and much less common than that of HBV.     

Mother-to-infant transmission of hepatitis C virus

Since the programme of the hepatitis B virus vaccination started, hepatitis C virus has become the most significant cause of chronic liver disease of infectious aetiology in paediatric age. After the introduction of hepatitis C virus screening of blood units, vertical transmission seems to now be the most common route of hepatitis C virus infection in children. According to studies on infants born to anti-hepatitis C virus positive women, the rate of mother-to-infant transmission is about 5% when the mother is anti-hepatitis C virus positive and anti-HIV negative, but the risk is three-five times higher when the mother is coinfected with HIV. Both viral and host-related factors are of importance as risk factors in vertical hepatitis C virus transmission. Among the first, only viral load has been demonstrated by some authors as a relevant risk factor while genotype seems not to be influent. The importance of quasispecies has been hypothesized but not yet clarified. Among host-related factors, beyond maternal HIV coinfection, maternal drug abuse has certainly an important role. Other factors such as breast feeding and vaginal delivery do not seem to influence the rate of vertical transmission. Progression to chronicity occurs in the majority of perinatally infected children, although hepatitis C virus associated liver disease is usually mild throughout infancy and childhood.     

Nosocomial transmission of hepatitis C virus

Nosocomial transmission of hepatitis C virus (HCV) may occur in a variety of circumstances. This problem is best characterised in haemodialysis units. In this setting, molecular analysis of viral isolates indicates that patient to patient is the most frequent mode of HCV transmission. Spreading of HCV is mainly related to non-strict observance of universal precautionary measures, which are an efficient and, possibly, sufficient means for prevention. Epidemics or single instances of patient-to-patient transmission have only occasionally been reported in hospital settings other than haemodialysis units, and, again, non-observance of universal precautionary measures, or inadequate cleaning or disinfecting of medical instruments was involved. Transmission from an infected surgeon to patients has been reported, but infection from doctors to patients seems to be exceptional. Thus, although prospective studies have not been performed, nosocomial transmission of HCV unrelated to haemodialysis appears to be an infrequent and preventable event.     

Nosocomial transmission of hepatitis C virus

Summary The nosocomial transmission of hepatitis C involving three subjects participating in a research project in a Swedish hospital is described. One person contracted acute hepatitis C and another participant had an asymptomatic seroconversion. A temporal relationship between participation in the experiments and seroconversion for hepatitis C, and virology with phylogenetic analyses, suggest that they most probably contracted hepatitis C from a third subject who unknowingly had chronic hepatitis C. Faulty nursing and procedural routines were identified as the probable cause of the transmission. Our findings reinforce the need for medical personnel to strictly adhere to universal precautions worked out to prevent the transmission of blood-borne viruses and underline the importance of a continuous supervision of nursing and procedural routines, even in hospitals with well-educated staff and presumably high standards.     

Sexual transmission of hepatitis C virus

Sexual transmission of hepatitis C virus (HCV) occurs; however, to what extent is still unclear. In this presentation relevant data from the literature concerning the following key issues will be presented: presence of HCV in the seminal fluid and vaginal secretions; presence of HCV infection in sexually promiscuous individuals; presence of HCV infection among sexual partners to HCV-infected individuals; and molecular biology evidence of sexual transmission. An anti-HCV prevalence of 2-12% is seen in sexually promiscuous individuals, which is higher than that usually seen among blood donors. In case-control studies, HCV infection is associated with sexual promiscuity and sex with a partner who has a past history of hepatitis. In most studies, HCV infection is common among sexual partners of HCV-infected subjects. Genotyping and genome sequencing provide further evidence for intraspousal transmission of HCV Despite these findings, stable sexual partners of hemophiliacs or recipients of HCV-contaminated immunoglobulin preparations rarely become infected. These discrepancies are not fully understood. Other sexual behaviours or confounding non-sexual transmission routes could play a part.     

Mother-to-infant transmission of hepatitis C virus

The rate of mother-to-infant transmission of hepatitis C virus (HCV) is approximately 5%, but is higher when the mother is co-infected with HIV Vertical transmission is restricted to infants whose mothers are viraemic. The risk of transmission increases with increasing maternal viral load but a specific cut-off value predicting infection cannot be defined. There is no specific HCV genotype which is preferentially transmitted. The mode of delivery (caesarean versus vaginal) does not appear to influence the rate of transmission, but firm evidence is lacking. There is no evidence to suggest an increased risk of HCV transmission through breast feeding. Pregnancy is not contra-indicated in HCV-infected women. Without drugs to treat established infections in mothers and infants and interventions to prevent vertical transmission, routine HCV screening is not recommended in pregnant women.     

Hepatitis C virus infection in patients with hemophilia

After the introduction of second generation ELISA and confirmatory tests clinically available, it was possible to determine that prevalence of infection with HCV was 98% among hemophiliacs exposed to factor VIII concentrates that weren't submitted to viral inactivation. Liver failure is 4.2 times more probable among patients also infected with HIV. The hepatocellular carcinoma studies show similar findings. They report a rate of 1.4 for every 1,000 hemophiliacs, and almost all patients have antibodies for hepatitis C virus. The studies with hemophiliacs exposed to unsafe blood products for HCV showed a significant increase in mortality from different liver diseases, as compared to control subjects. Mortality rate shows an important increase in the hemophiliacs also infected with human immunodeficiency virus. Combination therapy (ribavirin and interferon) doesn't seem to make a difference in the response rate as compared to patients without hemophilia. In spite of the best efforts to improve the safety of factor VIII concentrates, it has been impossible to eliminate the risk of transmission of other infective agents. That's why it seems that recombinant technology will be the answer in obtaining the concentrates.