studies

1114A AASLD ABSTRACTS HEPATOLOGY, October, 2015
1854
Modeling the probability of hepatitis C virus transmission
in injecting drug users as a function of viral load
Qingwen Cui 1 , Alexander Gufraind 2,3 , Basmattee Boodram 3 ,
Scott Cotler 2 , Harel Dahari 2,4 , Marian E. Major 1 ; 1 CBER/FDA,
Alexandria, VA; 2 Department of Medicine, Loyola University, Maywood,
IL; 3 Epidemiology & Biostatistics, University of Illinois at
Chicago, Chicago, IL; 4 Theoretical Biology and Biophysics, Los
Alamos National Laboratory, Los Alamos, NM
Background: The major route of hepatitis C virus (HCV) transmission
in the USA is through injecting drug use. It has been
proposed that vaccines would not need to achieve sterilizing
immunity in injecting drug user (IDU) populations in order to
reduce disease spread, but this has not been tested empirically.
We aimed to simulate HCV transmission through contaminated
syringe sharing, apply this to a mathematical model to determine
infection probabilities relative to HCV RNA and assess
the impact of measures that reduce titers (e.g. vaccines or antivirals)
in IDU populations. Method: HCV RNA positive (HCVpos)
plasma was drawn into an insulin syringe and expelled.
Negative plasma (NEG-pre) was drawn into the same syringe
and expelled (NEG-post). Aliquots of HCV-pos, NEG-pre, and
NEG-post were tested for RNA titer. This was repeated employing
a water rinse of the syringe after expulsion of the HCV-pos
sample. A binomial model was used to estimate the probability
of infection with and without syringe rinse, assuming an RNA to
HCV infectivity ratio of 12:1 [range=10:1-20:1]. Results: We
found that 0.5% [range 0.05%-1.16%] of an HCV-pos sample
could be transferred if a syringe is not rinsed or 0.07% [range
0-0.18%] when rinsing is employed. Predicted probabilities
of infection from syringe sharing as a function of RNA titer
are shown in Fig.1. Risk of transmission increases 11-fold as
titers (log10 IU/mL) rise from 2.6 to 4.0 (unrinsed) and 3.6 to
5.0 (rinsed). Conclusions: IDUs experience a risk of transmission
even with syringe rinsing. However, if titers are reduced
below 2 log10 IU/mL transmission via syringe sharing could
be prevented. Overall, a vaccine would not need to achieve
sterilizing immunity to reduce disease spread in IDUs. Similarly,
antiviral treatment could impact spread before sustained
response is achieved.
Fig1:Grey bands: Interquartile ranges based on Monte Carlo
sensitivity analysis.
Disclosures:
The following authors have nothing to disclose: Qingwen Cui, Alexander
Gufraind, Basmattee Boodram, Scott Cotler, Harel Dahari, Marian E. Major
1855
Heterogeneous IL28B/IFNL4 distribution and association
of the C/TT/T haplotype with spontaneous clearance
and less liver damage in Mexican patients with chronic
hepatitis C virus infection
Karina Gonzalez-Aldaco 1,2 , João Renato R. Pinho 3 , Sonia
Roman 1,2 , Ketti G. Oliveira 3 , Nora A Fierro 1,2 , Leticia Oyakawa 3 ,
Rubia A. Santana 3 , Erika Martinez-Lopez 1,2 , Roberta Sitnik 3 ,
Arturo Panduro 1,2 ; 1 University of Guadalajara, Jalisco, Mexico;
2 Molecular Biology in Medicine, Civil Hospital of Guadalajara,
Guadalajara, Mexico; 3 Hospital Israelita Albert Einstein, Sao
Paulo, Brazil
Background & aims. Recently, genetic polymorphisms of interleukin-28B
(IL28B) (rs12979860 C allele and rs8099917 T
allele) and interferon-lambda 4 (IFNL4) (ss469415590 TT
allele) have been associated with spontaneous clearance (SC)
of hepatitis C virus (HCV) infection among distinct populations
worldwide. However, data regarding admixed and Amerindian
populations from Latin America are lacking. This study aimed
to analyze the genetic admixture of the West Mexico population
based on the distribution of the IL28B (rs12979860C>T,
rs8099917G>T) and IFNL4 (ss469415590∆G>TT) polymorphisms,
and the association between the IL28B/IFNL4 haplotypes
with SC and liver damage. Methods. In a cross-sectional
study, 711 unrelated individuals from West Mexico, including
Amerindians (86 Nahuas/95 Huicholes) and Mestizo populations
(32 from Villa Purificación (VP), 172 from Guadalajara,
Jalisco and 326 from Tepic, Nayarit) were genotyped. In a
case-control study, 234 treatment-naïve HCV-infected Mestizo
patients (149 with chronic hepatitis C (CHC) and 85 with SC)
were included for the association of haplotypes with SC and
liver damage. A Real-Time PCR assay perfomed genotyping,
and transitional elastography (FibroScan ) staged liver damage.
Genetic relatedness was evaluated by pairwise comparisons
(exact tests). Both, genetic distances (Fst) and haplotypes
were inferred by using Arlequin software (version 3.1). Linkage
disequilibrium (LD) was calculated by GDA software (version
1.0). All subjects signed an informed consent. The study protocol
conformed to the Declaration of Helsinki and was approved
by the Ethical Committee. Results. Three different clusters
(p