Low frequency of HLA-DRB1*11 in hepatitis C virus induced end stage liver disease

Abstract

Hepatitis C virus (HCV) infection becomes chronic in more than 70% of patients, leading to end stage liver disease in about 20-30% of these patients. Apart from the virus itself, host factors that modulate the immune response are likely to be involved in determining the outcome of HCV infection. Studies on the association of human leucocyte antigens (HLAs) and HCV infection have shown inconsistent results. Selection of patient subgroups may be crucial. However, any association relevant to HCV disease progression will become evident, especially in those patients with end stage liver disease. Therefore, we analysed the phenotype frequencies of HLA antigens in two groups of 69 and 39 patients with HCV induced liver cirrhosis who had received a transplant or were awaiting liver transplantation. The first group was typed serologically and compared with 331 blood and liver donors. The second group, prospectively HLA typed by a polymerase chain reaction-sequence specific oligonucleotide (PCR-SSO) procedure for HLA-DRB and DQB alleles, was compared with another 170 PCR-SSO typed and randomly selected blood donors. Decreased frequencies for HLA-DR5 and HLA-DQ3 were found in one group of patients with HCV induced liver cirrhosis compared with the control groups. In the second analysis comparing 39 patients with end stage liver cirrhosis with blood donors, we confirmed the significant decrease in HLA-DRB1*11 and HLA-DQB1*03, which corresponded to serological HLA-DR5 and HLA-DQ3 antigens, respectively. Our results show that the presence of HLA-DRB1*11 and HLA-DQB1*03 alleles is associated with a reduced risk for the development of HCV induced end stage liver disease. (Gut 2001;48:714-718)

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

“…Minton et al (1998) observed that patients with the HLA-DRB1*11 allele cleared the virus more effectively, and this remained statistically significant even after correction for multiple testing. Similar results have been reported in various other studies (Tillmann et al, 2001;Yenigun & Durupinar, 2002). It is worth mentioning that the HENCORE group did not see any significant association (after Bonferroni correction) between any MHC class II allele and the response of patients to IFN therapy (Thursz et al, 1999).…”

Natural history of chronic hepatitis C

“…71 Several other groups have studied a variety of alleles, identifying some to be associated with progression and others to be associated with benign chronic liver disease. [72][73][74][75] Other host genetic factors that have been linked to progressive liver fibrosis are polymorphisms in the genes of transforming growth factor-␤1 and angiotensin II. 76,77 Finally, the biochemical expression of chronic HCV infection appears to play a role in disease progression, whether as cause or effect.…”

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

“…10 Numerous reports have failed to show an association between individual HLA class I antigens and the course of disease in HCV infection. [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.…”