HLA class II favors clearance of HCV infection and progression of the chronic liver damage

Mangia, Alessandra; Gentile, Raffaela; Cascavilla, I.; Margaglione, Maurizio; Villani, M; Stella, Francesco; Modola, Giovanni; Agostiano, Valeria; Gaudiano, Carlo; Andriulli, Angelo

doi:10.1016/s0168-8278(99)80250-5

Cited by 107 publications

(92 citation statements)

References 18 publications

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“…23,26,35,36 However, DRB1*1104 is reported to have an association with viral persistence in a recently reported investigation. 27 This apparent lack of agreement among studies may reflect both viral and study group heterogeneity and/or the influence of specific polymorphisms in immunoregulatory genes in linkage disequilibrium with the HLA class II alleles. 26,37 Evidence from the study presented here and others may lead to the identification of crucial T-cell epitopes presented by HCV 1b-infected cells, which stimulate virus clearance.…”

Section: Discussionmentioning

confidence: 99%

Viral clearance in hepatitis C (1b) infection: Relationship with human leukocyte antigen class II in a homogeneous population

Fanning¹,

Levis²,

Kenny-Walsh³

et al. 2000

Hepatology

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Hepatitis C virus (HCV) infection is the main cause of non-A, non-B hepatitis. 1-5 HCV consists of a heterogeneous mix of isolates defined by genotype, each of which is further classified into subtypes. 6,7 A number of factors have been considered in terms of their potential to predict the outcome of the disease. These include age of infection, viral typesubtype, quasispecies, viral load, and mode of infection. [8][9][10][11][12][13] Clinical heterogeneity in disease progression may reflect viral heterogeneity and variations in host response. 14-17 The human leukocyte antigen (HLA) has been shown to influence host response to infection. [18][19][20][21][22] Although HLA class II genes have shown associations with viral clearance or persistence of the HCV these findings are not uniform. [23][24][25][26][27][28] In addition, direct comparisons between studies is often difficult because of heterogeneity of ethnic background, viral genotype, phenotype frequencies of individual alleles between populations, gender, and duration of disease. To avoid heterogeneity of risk factors and confounding variables in viral type/subtype we studied a unique cohort of individuals all infected by anti-D contaminated from a single source of HCV 1b. The patients were of similar ethnogeographic background and had an absence of competing risk factors for liver disease.The present study is a follow-up investigation of the well-documented series of Irish women who were inadvertently infected with HCV as a result of receiving contaminated anti-D immunoglobulin (from a single source) in 1977 to 1978. [29][30][31] The contaminating HCV 1b was derived from a single infected donor. [30][31][32][33] The homogeneity of this group allows one to examine variation in host response to HCV infection without the potentially confounding influence of factors such as gender, specific HCV genotype, age range, and general health status. The purpose of the present study was to address whether particular HLA class II alleles are associated with clearance or persistence of HCV type 1b. PATIENTS AND METHODSThe study group consisted of 156 female individuals all of whom were iatrogenically infected between May 1977 and November 1978 with HCV type 1b from a single source. All 156 cases tested positive for antibodies to HCV (by recombinant immunoblot assay; Chiron Corporation, Emeryville, CA) and 46% (n ϭ 72) were positive for HCV RNA by qualitative reverse transcriptase-polymerase chain reaction (RT-PCR) using the Roche AMPLICOR test (F. Hoffmann-La Roche Ltd., CH-4070 Basel, Switzerland). The HCV status of the 84 patients who tested negative on initial qualitative HCV RT-PCR screening was confirmed by retesting within an 18-month period. The HCV genotype of the 72 virus-positive individuals was confirmed to be HCV 1b by reverse line probe assay (Inno-Lipa HCV II, INNOGENETICS N.V., Zwijndrecht, Belgium).Investigations were performed with informed consent and complied with a standardized protocol in compliance with standard of care and in accordance hospital eth...

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Section: Discussionmentioning

confidence: 99%

Viral clearance in hepatitis C (1b) infection: Relationship with human leukocyte antigen class II in a homogeneous population

Fanning¹,

Levis²,

Kenny-Walsh³

et al. 2000

Hepatology

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“…4,16,17,25,32,35,39,41,52 One study, however, reported an opposite effect for DQB1*0301. 48 Several of these studies on susceptibility to HCV compared individuals with chronic HCV infection to healthy controls.…”

Section: Susceptibility To Persistent Hcv Infectionmentioning

confidence: 97%

“…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.…”

Section: Susceptibility To Persistent Hcv Infectionmentioning

confidence: 99%

“…25 In Italy, two studies have shown an association for DRB1*1104-DQB1*0301 with self-limiting HCV as well. 32,52 The association of the DQB1*0301 allele with self-limiting HCV in the presence of different DRB1 alleles suggests that this particular allele may play an important role in the natural clearance of HCV viraemia. 54 Another allele that has been correlated with selflimiting HCV is DRB1*1101.…”

Section: Susceptibility To Persistent Hcv Infectionmentioning

confidence: 99%

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Host genetic determinants in hepatitis C virus infection

2004

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In addition to viral and environmental/behavioural factors, host genetic diversity is believed to contribute to the spectrum of clinical outcomes in hepatitis C virus (HCV) infection. This paper reviews the literature with respect to studies of host genetic determinants of HCV outcome and attempts to highlight trends and synthesise findings. With respect to the susceptibility to HCV infection, several studies have replicated associations of the HLA class II alleles DQB1*0301 and DRB1*11 with selflimiting infection predominantly in Caucasian populations. Meta-analyses yielded summary estimates of 3.0 (95% CI: 1.8-4.8) and 2.5 (95% CI: 1.7-3.7) for the effects of DQB1*0301 and DRB1*11 on self-limiting HCV, respectively. Studies of genetics and the response to interferon-based therapies have largely concerned single-nucleotide polymorphisms and have been inconsistent. Regarding studies of genetics and the progression of HCV-related disease, there is a trend with DRB1*11 alleles and less severe disease. Studies of extrahepatic manifestations of chronic HCV have shown an association between DQB1*11 and DR3 with the formation of cryoglobulins. Some important initial observations have been made with respect to genetic determinants of HCV outcome. Replication studies are needed for many of these associations, as well as biological data on the function of many of these polymorphisms.

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“…[11][12][13][14] In contrast, several studies have suggested that specific HLA class II alleles may influence outcome parameters in chronic HCV infection such as disease susceptibility, viral clearance, or disease severity. [15][16][17][18][19][20][21] However, many of these studies were small and reported inconsistent findings. Despite the propensity of HCV to present a diverse range of epitopes for T cell recognition, heterozygous advantage has not been addressed or demonstrated in these studies.…”

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confidence: 99%

HLA class I allelic diversity and progression of fibrosis in patients with chronic hepatitis C

et al. 2006

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Patients infected with HIV-1 who are heterozygous at HLA class I loci present greater variety of antigenic peptides to CD8 ؉ cytotoxic T lymphocytes, slowing progression to AIDS. A similar broad immune response in chronic hepatitis C (CHC) infection could result in greater hepatic injury. Although specific HLA class II alleles may influence outcome in CHC patients, the role of HLA class I heterogeneity is generally less clearly defined. Our aims were to determine whether HLA class I allelic diversity is associated with disease severity and progression of fibrosis in CHC. The study population consisted of 670 adults with CHC, including 155 with advanced cirrhosis, and 237 non-HCV-infected controls. Serological testing for HLA class I antigens was performed via microlymphocytotoxicity assay. Peptide expression was defined as heterozygous (i.e., a different allele at each locus) or homozygous. The majority of these patients develop chronic infection, which is characterized by varying degrees of inflammation and hepatic fibrosis. A proportion of patients (Ͻ20%) will develop progressive liver damage with subsequent cirrhosis, end-stage liver disease, and hepatocellular carcinoma over 20 to 40 years. 3 The immunopathogenic mechanisms responsible for viral persistence and varying degrees of hepatic injury in chronic hepatitis C (CHC) are poorly understood. Cellular immune responses probably play an important role in this regard. CD4 ϩ T helper cells recognize HCV-derived peptides in the HLA class II binding groove of antigenpresenting cells such as dendritic cells, macrophages, and B cells. CD8 ϩ cytotoxic T cell lymphocytes (CTL) recognize intracellularly processed HCV proteins presented on HLA class I molecules on virus-infected cells. The HLA class I and II loci contain a highly polymorphic set of genes that appear to have evolved over time through selection pressures, thus allowing the host to resist a variety of pathogens. 4 In comparison with homozygous individuals, persons with overdominant selection or heterozygote advantage at HLA loci may be able to present a greater variety of antigenic peptides to T cells, thus result-

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HLA class II favors clearance of HCV infection and progression of the chronic liver damage

Cited by 107 publications

References 18 publications

Viral clearance in hepatitis C (1b) infection: Relationship with human leukocyte antigen class II in a homogeneous population

Viral clearance in hepatitis C (1b) infection: Relationship with human leukocyte antigen class II in a homogeneous population

Host genetic determinants in hepatitis C virus infection

HLA class I allelic diversity and progression of fibrosis in patients with chronic hepatitis C

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