A case‐control study of factors associated with resolution of hepatitis C viremia in former blood donors (CME)

Tobler, Leslie H.; Bahrami, Shrein H.; Kaidarova, Zhanna; Pitina, Lubov; Winkelman, Valarie K.; Vanderpool, Sandra; Guiltinan, Anne M.; Cooper, Stewart; Busch, Michael P.; Murphy, Edward L.

doi:10.1111/j.1537-2995.2010.02634.x

Cited by 15 publications

(15 citation statements)

References 45 publications

(49 reference statements)

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“…While it is possible that body mass index, baseline alcohol use, or baseline HCV RNA may account for differences seen among racial/ethnic groups, studies adjusting for these factors, including our study which accounted for a host of potential confounders, continue to observe marked racial/ethnic differences [18, 19]. Recent data show that immunogenetics explain a large part of spontaneous HCV clearance.…”

Section: Discussionmentioning

confidence: 80%

Racial/Ethnic Differences in Spontaneous HCV Clearance in HIV Infected and Uninfected Women

et al. 2012

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Background/Aims Among individuals without human immunodeficiency virus (HIV), African Americans have lower spontaneous clearance of hepatitis C virus (HCV) than Caucasians, and women have higher clearance than men. Few studies report racial/ethnic differences in acute HCV in HIV infected, or Hispanic women. We examined racial/ethnic differences in spontaneous HCV clearance in a population of HCV mono- and co-infected women. Methods We conducted a cross sectional study of HCV seropositive women (897 HIV infected and 168 HIV uninfected) followed in the US multicenter, NIH-funded Women's Interagency HIV Study (WIHS), to determine the association of race/ethnicity with spontaneous HCV clearance, as defined by undetectable HCV RNA at study entry. Results Among HIV and HCV seropositive women, 18.7 % were HCV RNA negative, 60.9 % were African American, 19.3 % Hispanic and 17.7 % Caucasian. HIV infected African American women were less likely to spontaneously clear HCV than Hispanic (OR 0.59, 95 % CI 0.38–0.93, p = 0.022) or Caucasian women (OR 0.57, 95 % CI 0.36–0.93, p = 0.023). Among HIV uninfected women, African Americans had less HCV clearance than Hispanics (OR 0.18, 95 % CI 0.07–0.48, p = 0.001) or Caucasians (OR 0.26, 95 % CI 0.09–0.79, p = 0.017). There were no significant differences in HCV clearance between Hispanics and Caucasians, among either HIV infected (OR 0.97, 95 % CI 0.57–1.66, p = 0.91) or uninfected (OR 1.45, 95 % CI 0.56–3.8, p = 0.45) women. Conclusions African Americans were less likely to spontaneously clear HCV than Hispanics or Caucasians, regardless of HIV status. No significant differences in spontaneous HCV clearance were observed between Caucasian and Hispanic women. Future studies incorporating IL28B genotype may further explain these observed racial/ethnic differences in spontaneous HCV clearance.

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Section: Discussionmentioning

confidence: 80%

Racial/Ethnic Differences in Spontaneous HCV Clearance in HIV Infected and Uninfected Women

et al. 2012

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“…The study sites include the AIDS Link to the Intravenous Experience (ALIVE)(8), Baltimore Before and After Acute Study of Hepatitis (BBAASH)(9), Boston Area HCV Study Transmission, Immunity, Outcomes Network (BAHSTION)(10), Cramp (11), Hemophilia Growth and Development Cohort (HGDS)(12), Mangia(13), Multicenter Hemophilia Cohort Studies (MHCS I and II)(14), Correlates of Resolved Versus Low-Level Viremic Hepatitis C Infection in Blood Donors (REVELL Study) (15), The Swan Project(16), Toulouse cohort(17), Women’s Interagency HIV Study (WIHS)(18), and United Kingdom Drug Use cohort(19). Study sites were selected because they had well established HCV outcomes, available DNA and permission for genetic testing.…”

Section: Methodsmentioning

confidence: 99%

Genome-Wide Association Study of Spontaneous Resolution of Hepatitis C Virus Infection: Data From Multiple Cohorts

Thio²,

et al. 2013

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Background Hepatitis C virus (HCV) infections occur worldwide and either spontaneously resolve or persist and markedly increase the person’s lifetime risk of cirrhosis and hepatocellular carcinoma. Although HCV persistence occurs more often in persons of African ancestry and in persons with a genetic variant near IL28B, the genetic basis is not well understood. Objective To evaluate the host genetic basis for spontaneous resolution of HCV infection. Design Two-stage genome wide association study (GWAS). Setting 13 international multicenter study sites. Patients 919 individuals with serum HCV antibodies but no HCV RNA (spontaneous resolution) and 1482 individuals with serum HCV antibodies and RNA (persistence). Measurements Frequencies of 792,721 SNPs. Results Differences in allele frequencies between persons with spontaneous resolution and persistence were identified on chromosomes 19q13.13 and 6p21.32. On chromosome 19, allele frequency differences localized near IL28B and included rs12979860 (overall per-allele OR = 0.45, P = 2.17 × 10−30) and 10 additional SNPs spanning 55,000 bases. On chromosome 6, allele frequency differences localized near genes for class II human leukocyte antigens (HLA) and included rs4273729 (overall per-allele OR= 0.59, P = 1.71 × 10−16) near DQB1*03:01 and an additional 116 SNPs spanning 1,090,000 base pairs. The associations in chromosomes 19 and 6 were independent, additive, and explain an estimated 14.9% (95% CI: 8.5–22.6%) of the variation in HCV resolution in those of European-Ancestry, and 15.8% (95% CI:4.4–31.0%) in individuals of African-Ancestry. Replication of the chromosome 6 SNP, rs4272729 in an additional 746 individuals confirmed the findings (p=0.015). Limitations Epigenetic effects were not studied. Conclusions IL28B and HLA class II are independently associated with spontaneous resolution of HCV infection and SNPs marking IL28B and DQB1*03:01 may explain ~15% of spontaneous resolution of HCV infection.

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“…Some factors have been associated with this situation, such as differences in immune response, ethnic background, and parenteral exposure. 2,3 Recently, single nucleotide polymorphisms (SNP) near the gene of interleukin 28B (IL28B), which encodes a type III interferon (IFN-lambda3), were identified as genetic determinants of spontaneous resolution of HCV infection. Specifically, one polymorphism (rs12979860) was associated with the response to standard treatment for HCV (pegylated interferon plus ribavirin) in coinfected HCV/HIV-1 individuals.…”

Section: Introductionmentioning

confidence: 99%

IL28BPolymorphism Associated with Spontaneous Clearance of Hepatitis C Infection in a Southern Brazilian HIV Type 1 Population

Lunge

Rocha

Béria

et al. 2012

AIDS Research and Human Retroviruses

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About one-third of people infected with human immunodeficiency virus-1 (HIV-1) are coinfected with hepatitis C virus (HCV) because of shared transmission routes. Studies report that HIV-1 complicates hepatitis C infection by increasing HCV viral load and reducing spontaneous clearance. Single nucleotide polymorphisms (SNPs) upstream of the IL28B gene have been associated with spontaneous and treatment-induced clearance of HCV infection. The aim of this study was to evaluate the association between the SNP rs12979860 of the IL28B gene and spontaneous clearance of HCV infection in a Brazilian HIV-1 population. The SNP was analyzed by polymerase chain reaction (PCR) followed by restriction digestion in 138 anti-HCV-positive patients. Spontaneous clearance was observed in 34 subjects (24.6%). Genotype distribution was significantly different between spontaneous clearance and HCV chronic patients. The CT/TT genotypes conferred a nearly 3-fold increased odds to chronic HCV infection relative to the CC genotype (odds ratio, 2.78; 95% confidence interval, 1.16-6.64; p=0.011). In conclusion, the rs12979860 polymorphism is associated with spontaneous clearance of HCV in HIV-1 Brazilian infected patients.

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A case‐control study of factors associated with resolution of hepatitis C viremia in former blood donors (CME)

Cited by 15 publications

References 45 publications

Racial/Ethnic Differences in Spontaneous HCV Clearance in HIV Infected and Uninfected Women

Racial/Ethnic Differences in Spontaneous HCV Clearance in HIV Infected and Uninfected Women

Genome-Wide Association Study of Spontaneous Resolution of Hepatitis C Virus Infection: Data From Multiple Cohorts

IL28BPolymorphism Associated with Spontaneous Clearance of Hepatitis C Infection in a Southern Brazilian HIV Type 1 Population

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