HLA class II genes determine the natural variance of hepatitis C viral load

Abstract

The aim of this study was to investigate the relationship between human leukocyte antigen (HLA) class II genes and the natural fluctuations in hepatitis C viral load in a homogeneous patient population. The study group consisted of 57 viremic (hepatitis C virus [HCV] 1b) women for whom HLA class II DRB1 and DQB1 haplotyping, virologic, histologic, and biochemical markers of disease activity were available. All patients were infected with HCV 1b from the same source of hepatitis C-contaminated anti-D immunoglobulin during the period from May 1977 to November 1978. The mean slope of change of viral load was 0.34 (SD ؎ 0.73) log 10 viral copies/mL/year, which is significantly different from zero, P < 10 ؊9 . Analysis of the relationship between the slope of change of viral load and HLA class II haplotype indicated a significantly different slope of change of viral load between the alleles of (1) DRB1*15 and DRB1*0701, and (2) DQB1*0602 and DQB1*0201, P c ‫؍‬ .036 and P c ‫؍‬ .026 after Bonferroni correction for multiple comparisons, respectively. Significant differences for grade and stage of disease at liver biopsy were observed for DQB1*0501 and DQB1*0201 alleles; P ‫؍‬ .019, r s ‫؍‬ .64, and P ‫؍‬ .047, r s ‫؍‬ .57, respectively. In addition, significant differences in stage of disease were found to exist between DRB1*13 and DRB1*0701, P ‫؍‬ .031, r s ‫؍‬ ؊.71. The rate of disease progression in chronic hepatitis C is variable and influenced by both viral and host-related factors. Relevant virus-related factors might include size of inoculum, quasispecies diversity, and genotype. Transfusion-associated infection has a more rapid progression to active liver disease than needle stick-associated infection. 1,2 This is presumably related to the smaller viral burden at exposure for the latter case. Hepatitis C viral production is estimated to reach 10 10 to 10 13 virions/day with a short half-life of several hours. [3][4][5][6] The magnitude of the serum viral load has relevance for the success of antiviral therapy. Serum viremia at or below the threshold of 6.3 log 10 viral copies/mL is a good prognostic indicator of likely response to either interferon monotherapy or interferon and ribavirin combination therapy. 7-9 Similar to the human immunodeficiency virus (HIV), the high turnover rates and error-prone replication exhibited by the hepatitis C virus (HCV) provides a mechanism for the generation of immune escape and antiviral therapy-resistant mutants. [10][11][12][13] Host factors that influence disease progression in individuals infected with HCV include age at exposure, excessive alcohol consumption, and the presence of competing causes for liver disease such as the hepatitis B virus and hepatitis A virus superinfection. Individuals infected with HCV who are greater than 50 years of age have a more severe disease and higher mortality rate than younger individuals. 14,15 The genetic background of the host as assessed by human leukocyteassociated antigen (HLA) typing has shown some associations with clearance of ...

Patient HLA-DRB1* and -DQB1* allele and haplotype association with hepatitis C virus persistence and clearance

“…This is an important finding as, to date, we have not come across any report that has demonstrated the association of an HLA-DRB1-DQB1 haplotype with persistence of HCV in Pakistani patients. However, Fanning et al (2001) reported a positive response to IFN therapy in patients from Ireland with the haplotype HLA-DRB*0701-DQB1*02, again indicating the need to conduct such studies in ethnically different patient populations. In agreement with the data of Correa et al (2002), we also found this haplotype to be the most common in non-responders and in linkage disequilibrium in our population.…”

“…In seropositive individuals exhibiting spontaneous viral clearance, the CD4 + T-cell response is mostly against non-structural proteins (NS3, NS4 and NS5) with the predominant response being against NS3 (Lloyd et al, 2007). An epitope in the NS3 region shows high affinity for HLA-DR, indicating the possible involvement of HLA class II in virus clearance (Fanning et al, 2001). …”

Host genetic determinants in hepatitis C virus infection

“…71,72 Studies of HCV progression or severity of disease A total of 44 studies were found to address the topic of host genetics and HCV progression, severity or activity of disease, and have largely been inconsistent. 16,18,27,29,32,34,37,39,47,[68][69][70]80, There is a trend with DRB1*11 alleles and less severe liver disease. Asti 68 reported an association between DRB1*1201 with less severe liver disease (OR not reported) as well.…”

Factors Affecting the Response to Interferon Alpha Therapy in Egyptian HCV Patients

“…Fanning et al (2001) reported that individuals who possess the alleles DRB1*0701 and/or DQB1*0201 have a relatively stable viral load over time. Also DRB1*07 and DQB1*02 were found by Wawrzynowicz-Syczewska et al (2000) in responsive patients and Jiao and Wang (2003) found a higher response rate to IFN in patients with the HLA-DRB1*07 allele where Martinetti et al (2006) reported that DRB1*13 allele was significant in protection from chronic HCV especially the protection from vertical transmission in infants born to HCV positive mothers.…”