59 Intrafamilial transmission of hepatitis C virus in patients with acute hepatitis C: correlation with virological and immunological parameters

HEPATOLOGY, Vol. 38, No. 4, Suppl. 1, 2003

AASLD ABSTRACTS

183A

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SEXUAL TRANSMISSION OF HEPATITIS C VIRUS IN HETEROSEXUAL MONOGAMOUS COUPLES - T H E H C V PARTNERS STUDY. Norah A Terrault, University of California

INTRAFAMILIAL TRANSMISSION OF HEPATITIS C VIRUS IN PATIENTS WITH ACUTE HEPATITIS C: CORRELATION WITH VIROLOGICAL AND IMMUNOLOGICAL PARAMETERS. Sanaa M Kamal, Harvard Institutes of Medicine,

San Francisco, San Francisco, CA; Michael Busch, ~ dward Murphy, Blood Centers of the Pacific, San Francisco, CA; Maria Tong, Jenya Dvorkin, University of California San Francisco, San Francisco, CA; Miriam J Alter, Centers for Disease Control and Prevention, Altanta, GA Prior studies on sexual transmission of HCV in heterosexual couples have been limited by small sample size, failure to exclude non-sexual routes of HCV transmission, and failure to characterize anti-HCV concordant couples virologically. Aims: To determine the potential for sexual transmission of HCV among monogamous heterosexual couples by identifying the factors (sexual and non-sexual) associated with anti-HCV positivity among partners, and the relatedness of virus strains among concordant couples. Methods: Anti-HCV positive persons (without HIV and HBV coinfection) with a monogamous heterosexual partner for at least 3 years and no history of injection drug use (IDU) in both partners were eligible. Partners were tested for anti-HCV (EIA-2, RIBA-3), qualitative HCV RNA and HCV genotype/serotype ( - t y p e ) as appropriate. HCV type concordant couples underwent sequencing and phylogenetic analysis (pending). Detailed information on HCV risk factors and sexual practices were obtained by interviewing the partners separately. Results: Of 2077 couples screened, 672 were eligible, 552 enrolled and 500 completed the study. The most common reasons for study ineligibility were lack of sexual partner (40%), prior organ transplant (15%), HIV or HBV coinfection (10%), partnership <3 years or non-monogamous (8%), and IDU in both partners (8%). The median age of partners was 49 yrs (range 27-79) and 75% were Caucasian. The median duration of sexual contact was 16 yrs (range 3-52); the median number of sexual contacts per month per couple ranged from 0.3 to 24.4. The proportions of couples engaging in vaginal a n a l oral active and oral receptive sex were 98.3%, 12.5%, 77%, and 76%, respectively. Use of condoms was reported by 80%, but only 17% reported frequent or regular condom use. A total of 20 (4%) partners tested positive for anti-HCV (EIA and RIBA) and 12 had detectable HCV RNA. The type and frequency of sexual contacts and frequency of sharing personal items (e.g. razors) did not differ between anti-HCV positive and negative partners (all p>0.05). Anti-HCV positive partners had higher rates of IDU (45% vs 1%, P<0.001), tattoos (45% vs 15%, P-0.007), blood brother rituals (37% vs 12%, p-0.0015), bloody needlestick injury (60% vs 14% (p-0.005), and total number of sex partners (p-0.005). In multivariate analysis, only IDU, tattoos and needlestick injury were independently associated with anti-HCV positivity in the partners. Genotypes/serotypes were discordant in 6 couples and concordant in 9 couples tested to date. Sexual contact rates of type concordant couples tended to be higher than type discordant couples (median I vs 0.25 contact per mos, p-0.07) but with no differences in types of sexual practices. The frequency of percutaneous risk factors for HCV in both partners t e n d e d to be higher in discordant than concordant couples (3/5 vs 1/9, p-0.09). Conclusions: The prevalence of anti-HCV among sexual partners of persons with HCV was 4% (95% CI: 2.3%-5.7%) but 40% of partners had discordant types indicating lack of sexual transmission. The majority of type concordant couples lacked percutaneous risk factors for HCV, suggesting sex may be the route of transmission but phylogenetic analysis of viral strains will ultimately determine whether sexual transmission occurred. Disclosures: Miriam J Alter - No relationships to disclose Michael Busch - No relationships to disclose Jenya Dvorkin - No relationships to disclose Edward Murphy - No relationships to disclose Norah A Terrault - No relationships to disclose Maria Tong - No relationships to disclose

Boston, MA; Nakano Tatsarouni, CDC, Atlanta, GA; Jens Rasenack, University of Freiburg, Freiburg, Germany; Qi He, Cami Graham, Harvard Institutes of Medicine, Boston, MA; Alaa Ismail, Ahmed Al Tawil, Mahmoud Massoud, Ain Shams University, Cairo, ~ gypt; Margaret J Koziel, Harvard Institutes of Medicine, Boston, MA Background/Aims: The role of intrafamilial transmission (sexual and asexual) in the spread of HCV infection is still debated and the factors that increase the risk of HCV intrafamilial transmission are poorly understood. Objectives: The aim of this study was to determine the risk of intrafamilial transmission of HCV from index cases with acute hepatitis C and to identify the specific factors promoting HCV transmission. Patients and Methods: The study cohort (n-347) included 55 index cases (health workers; M: F: 31:24) with proven acute hepatitis C following occupational exposure and their family members (n-102; 50 spouses) in addition to 60 index cases with chronic hepatitis C and 128 (55 spouses) family members who served as a control group. Subjects, controls, spouses and family m e m b e r s were prospectively followed for a mean of 4 8+- 7 months. All index acute HCV cases and their family members had archived HCV negative serum specimens and were interviewed with special stress on potential sexual and asexual risk factors for HCV transmission; however no risk factors for HCV transmission were identified other than contact with the index case. Screening for HCV (ELISA) was performed at enrollment. Positive cases were confirmed by polymerase chain reaction and tested for genotype, HCV RNA viral load, HVR1 (nucleotide positions 1156 to 1234) sequence analysis, HCV specific peripheral and intrahepatic HCV specific CD4+-T cell proliferative & CTL responses and cytokines (ELISpot). RESULTS: The risk of sexual transmission was higher in spouses of acutely infected subjects where seroconversion was detected in 2% of spouses of HCVchronically infected index cases versus 14% of spouses of acutely infected index cases (p<0.01). Asexual transmission was detected in 3 children of acutely infected index cases. Genotype and nudeotide sequencing of the HVR1 region showed that the index patients and their spouses and/or family members were infected by the same isolate with > 95% homology. Females were at higher risk of sexual HCV acquisition than males, however 4/7 sexually infected females had self-limited disease. Viral load was significanfiy higher in acutely infected index cases (3.2 x 106 cop/ml) compared with chronic infection (1.2 x 10 6 cop/ml, p - 0.01). Multivariate-analysis identified acute hepatitis C, high viral load, and vaginal infections as important variables of sexual transmission. CD4 + proliferative and CTL responses were detected in index cases and HCV positive family m e m b e r s and was maintained indefinitely after recovery from HCV infection whereas it was weak and narrowly focused in persistently infected patients. Interestingly, CD4+ responses could be detected in 12/50 spouses of acutely infected subjects despite being seronegative with no apparent viremia. Conclusion: Our data demonstrate that acute hepatitis C and high HCV RNA levels increase the risk of sexual transmission. The observation that HCV-specific CD4 + and CTL responses exist in apparently HCV negative subjects may have implications for vaccine development and epidemiological studies. Disclosures: A h m e d AI Tawil - No relationships to disclose Cami Graham - No relationships to disclose Qi He - No relationships to disclose Alaa Ismail - No relationships to disclose Sanaa M Kamal - No relationships to disclose Margaret J Koziel - No relationships to disclose Mahmoud Massoud - No relationships to disclose Jens Rasenack - No relationships to disclose Nakano Tatsarouni - No relationships to disclose