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

Patel, Keyur; Norris, Suzanne; Lebeck, Lauralynn K.; Feng, Anne C.; Clare, Michael; Pianko, Stephen; Portmann, Bernard; Blatt, Lawrence M.; Koziol, James A.; Conrad, Andrew; McHutchison, John G.

doi:10.1002/hep.21040

Cited by 41 publications

(38 citation statements)

References 41 publications

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“…In this study, no statistically significant association was found between different HLA-A and HLA-B antigens and elevated ALT level, HCV viral load, grades of activity or degree of fibrosis except for association between HLA-A9 and low HCV viral load. HLA Class I alleles were not associated with viral load, fibrosis stage, liver inflammation or treatment outcome in Irish and American studies [25,41]. However, in a Taiwanese study [42], patients with chronic HCV infection with HLA alleles (A*34, B*56) have significantly lower viral load than those without these alleles, while those with HLA-B*4001 have significantly higher viral load.…”

Section: Discussionmentioning

confidence: 86%

Association of Human Leucocyte Antigen Class I (HLA-A and HLA-B) With Chronic Hepatitis C Virus Infection in Egyptian Patients

Mosaad

Farag

Arafa

et al. 2010

Scandinavian Journal of Immunology

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Egypt has the highest prevalence of hepatitis C virus (HCV) in the world, ranging from 6% to 28% with an average of approximately 13.8% in the general population. It has been reported that human leucocyte antigen (HLA) alleles are associated with the outcome of HCV infection, but this associations showed ethnic and geographical differences. The objective of this study is to investigate the association between the frequencies of HLA Class I and chronic HCV infection in Egyptian patients and to find out whether there is a relation between certain HLA Class I antigens and HCV viral load, degree of fibrosis, activity and alanine aminotransferase (ALT) level. A case control study was conducted on 100 patients with chronic HCV infection and 150 healthy controls. HLA‐A and HLA‐B typing by complement‐dependent micro‐lympho‐cytotoxicity assay was performed for both groups. HLA‐A11 antigen was significantly increased in patients with chronic HCV infection versus controls (OR 3.98; 95% CI = 1.85–8.89; P = 0.001; and Pc = 0.021). HLA‐B12, HLA‐B13, HLA‐B17 and HLA‐B40 were higher in patients, and HLA‐A32 and HLA‐B14 were higher in controls, although the significance was lost after correction for multiple testing. HLA‐A9 was significantly associated with low viral load (P = 0.008, Pc = 0.048). The results of this work implicate that HLA‐A11 antigen may influence chronic HCV infection and may play a role in viral persistence. Different HLA Class I antigens are not associated with degree of liver fibrosis, grades of activity or level of ALT. However, HLA‐A9 is associated with low HCV viral load in chronic HCV Egyptian patients.

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Section: Discussionmentioning

confidence: 86%

Association of Human Leucocyte Antigen Class I (HLA-A and HLA-B) With Chronic Hepatitis C Virus Infection in Egyptian Patients

Mosaad

Farag

Arafa

et al. 2010

Scandinavian Journal of Immunology

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“…The study population consisted of 670 adults with chronic HCV infection, including 155 with advanced cirrhosis and 237 non-HCV controls. 78 These results suggest that hepatic injury is more likely to be determined by a complex interplay between host, viral and genetic factors. They also suggest while genetic restriction may play an important role in the early phase of infection that determines the outcome, once viral persistence is established specific genetic restrictions of virus-specific CD8 þ T-cell responses may not be of any significant relevance.…”

Section: Role Of Class I Alleles In Hcv Infectionmentioning

confidence: 92%

Impact of the genetic restriction of virus-specific T-cell responses in hepatitis C virus infection

Thimme

2007

Genes Immun

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The immunobiology of hepatitis C virus (HCV) is significantly influenced by the host immune response to the virus, especially by virus-specific T-cell responses. Virus-specific T cells are restricted by human leucocyte antigen class I and II molecules. Of note, associations between these polymorphic loci and outcome and course of HCV infection have been reported in large and well-documented cohorts. This review will briefly summarize these studies and focus especially on the immunological and virological basis for the reported associations. The outcome and course of HCV infection is most likely determined by a complex interplay of genetic, immunological and virological factors. A better understanding of these host-virus interactions is essential not only to gain better insights into the mechanisms of viral clearance and persistence but also for the development of new antiviral vaccine strategies.

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“…Associations with HLA class Ⅱ genes are reported more often than HLA class I . HLA class I allelic diversity is suggested to have little influence on fibrosis and disease severity associated with chronic HCV infections [53] . HLA class I allele associations: Susceptibility to HCV infections is associated with A*19 in Saudi people [54] and with HLA A*28, A*29, B*14, DR7 in Egyptians [55] .…”

Section: Viral Persistence and Viral Clearancementioning

confidence: 99%

A comparative review of HLA associations with hepatitis B and C viral infections across global populations

Singh

Kaul

et al. 2007

WJG

202

175

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Hepatitis B (HBV) and hepatitis C (HCV) viral infection or co-infection leads to risk of development of chronic infection, cirrhosis and hepatocellular carcinoma (HCC).Immigration and globalization have added to the challenges of public health concerns regarding chronic HBV and HCV infections worldwide. The aim of this study is to review existing global literature across ethnic populations on HBV and HCV related human leukocyte antigen (HLA) associations in relation to susceptibility, viral persistence and treatment. Extensive literature search was conducted to explore the HLA associations in HBV and HCV infections reported across global populations over the past decade to understand the knowledge status, weaknesses and strengths of this information in different ethnic populations. HLA DR13 is consistently associated with HBV clearance globally. HLADRB1*11/*12 alleles and DQB1*0301 are associated with HBV persistence but with HCV clearance worldwide. Consistent association of DRB1*03 and *07 is observed with HCV susceptibility and non-responsiveness to HBV vaccination across the population. HLA DR13 is protective for vertical HBV and HCV transmission in Chinese and Italian neonates, but different alleles are associated with their susceptibility in these populations. HLA class Ⅰmolecule interactions with Killer cell immunoglobulin like receptors (KIR) of natural killer (NK) cells modulate HCV infection outcome via regulating immune regulatory cells and molecules. HLA associations with HBV vaccination, interferon therapy in HBV and HCV, and with extra hepatic manifestations of viral hepatitis are also discussed. Systematic studies in compliance with global regulatory standards are required to identify the HLA specific viral epitope, stage specific T cell populations interacting with different HLA alleles during disease progression and viral clearance of chronic HBV or HCV infections among different ethnic populations. These studies would facilitate stage specific therapeutic strategies for clearance of HBV and HCV infections or co-infections across global populations and aid in identification of HBV-HCV combined vaccine. HLA associations of chronic HBV or HCV development with confounding host factors including alcohol, drug abuse, insulin resistance, age and gender are lacking and warrant detailed investigation across global populations.

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

Cited by 41 publications

References 41 publications

Association of Human Leucocyte Antigen Class I (HLA-A and HLA-B) With Chronic Hepatitis C Virus Infection in Egyptian Patients

Association of Human Leucocyte Antigen Class I (HLA-A and HLA-B) With Chronic Hepatitis C Virus Infection in Egyptian Patients

Impact of the genetic restriction of virus-specific T-cell responses in hepatitis C virus infection

A comparative review of HLA associations with hepatitis B and C viral infections across global populations

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