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Intrafamilial Transmission of Hepatitis C Virus in Patients with Acute Hepatitis C: correlation with virologic and immunologic parameters
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Reported by Jules Levin
54th AASLD
Boston, MA
Oct 24-28, 2003
Sanaa M Kamal, Harvard Institutes of Medicine, 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, Egypt; Margaret J Koziel, Harvard Institutes of Medicine, Boston, MA
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.
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.
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 members were prospectively followed for a mean of 48± 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).
The risk of sexual transmission was higher in spouses of acutely infected subjects where seroconversion was detected in 2% of spouses of HCV-chronically 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 nucleotide 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 significantly 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 members 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.
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. |
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