The MHC is a major determinant of viral status, but not fibrotic stage, in individuals infected with hepatitis C

McKiernan, Susan; Hagan, Richard; Curry, Michael P.; McDonald, G. S. A.; Nolan, Niamh; Crowley, John P.; Hegarty, John E.; Lawlor, Emer; Kelleher, Dermot

doi:10.1016/s0016-5085(00)70365-9

Cited by 53 publications

(62 citation statements)

References 32 publications

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“…The host immune response might play an important role in such different outcomes. Many studies assessed an association between HLA Class II and severity of liver injury or favourable outcomes of chronic HCV infection [37][38][39][40]. On the other hand, studies about Class I association with HCV disease patterns is relatively poor.…”

Section: Discussionmentioning

confidence: 99%

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: 99%

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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“…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%

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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“…Other factors such as younger age [3,20] , female gender [21,22] , presence of hepatitis B surface antigen (HBsAg) [3,23] , certain HLA alleles [6,[24][25][26][27][28][29] , and low viral quasispecies diversity [30] have been linked to increased HCV RNA clearance. While African American ethnicity [3,25] , HCV genotype 1 [31][32][33] and co-infections with human immunodeficiency virus-1 (HIV-1) [3] , Human T-Lymphotropic Virus-1 [34] and Schistosoma mansoni [35] have been associated with lower HCV RNA clearance and higher HCV RNA levels.…”

Section: Introductionmentioning

confidence: 99%

Factors influencing a low rate of hepatitis C viral RNA clearance in heroin users from Southern China

Garten¹,

Lai²,

Zhang³

et al. 2008

WJG

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INTRODUCTIONThe hepatitis C virus (HCV) epidemic now affects over 200 million people worldwide. HCV is a single-stranded RNA flavivirus that is responsible for the majority of non-A-non-B hepatitis infections [1,2] . Natural history studies have found that 15%-59% of people who are infected with HCV will undergo spontaneous viral clearance with no further liver disease due to HCV [3][4][5][6][7][8][9][10][11] . The remaining will develop chronic HCV infection that can lead to cirrhosis, hepatocellular carcinoma and the need for a liver transplant.The exact mechanism of HCV RNA clearance is not well understood although recent studies have shown that clearance is associated with strong, broad cellular immune responses [12][13][14][15][16][17][18][19] . Other factors such as younger age [3,20] , female gender [21,22] , presence of hepatitis B surface antigen (HBsAg) [3,23] , certain HLA alleles [6,[24][25][26][27][28][29] , and low viral quasispecies diversity [30] have been linked to increased HCV RNA clearance. While African American ethnicity [3,25] , HCV genotype 1 [31][32][33] and co-infections with human immunodeficiency virus-1 (HIV-1) [3] , Human T-Lymphotropic Virus-1 [34] and Schistosoma mansoni [35] have been associated with lower HCV RNA clearance and higher HCV RNA levels. Understanding why and how individuals clear HCV is the key to developing new drugs and an effective vaccine [21] .Studies of heroin users from Guangxi Zhuang Autonomous Region in southern China have attributed the appearance and spread of HIV, HCV and other infectious agents to the change in heroin using patterns from smoking to injection [36] . Abstract AIM: To s t u d y t h e v i r o l o g i c a l a n d h o s t fa c t o r s influencing hepatitis C infection outcomes in heroin users in southern China. METHODS:HCV RNA and associated factors were analyzed among 347 heroin users from Guangxi Zhuang Autonomous Region, southern China who were hepatitis C virus (HCV) EIA positive for two or more consecutive visits. RESULTS:Using the COBAS AMPLICOR HCV TEST, a remarkably low HCV RNA negative rate of 8.6% was detected. After multivariate logistic regression analysis, HCV RNA clearance was significantly associated with the presence of HBsAg (OR = 8.436, P < 0.0001), the lack of HIV-1 infection (OR = 0.256, P = 0.038) and age younger than 25 (OR = 0.400, P = 0.029). CONCLUSION:Our study suggests HCV infection among Chinese heroin users results in high levels of viral persistence even amidst factors previously found to enhance viral clearance. Prospective studies of a possible genetic component within the Chinese population and the pathogenicity of non-genotype 1 HCV infections are needed. heroin trafficking routes into the province [37,38] . It is not clear how widespread the HCV epidemic is in China. Little seroprevalence data exists, mostly from the major cities of Beijing, Shanghai and Hong Kong and to our knowledge; no studies on HCV RNA clearance in China have been done. Studies in Yunnan Province, which borders Guangxi Zhuang Autonomous...

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The MHC is a major determinant of viral status, but not fibrotic stage, in individuals infected with hepatitis C

Cited by 53 publications

References 32 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

Host genetic determinants in hepatitis C virus infection

Factors influencing a low rate of hepatitis C viral RNA clearance in heroin users from Southern China

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