Related Experiment Videos
Increased frequency of HLA DR13 in hepatitis C virus carriers with persistently normal ALT levels
N Kuzushita1, N Hayashi, K Katayama
1First Department of Medicine, Osaka University School of Medicine, Japan.
Insights
Human leukocyte antigen DR13 is associated with a lower immune response in asymptomatic hepatitis C virus (HCV) carriers. This finding suggests a potential link between HLA DR13 and reduced liver injury in HCV infection.
Area of Science:
- Immunogenetics
- Hepatology
- Virology
Background:
- Hepatitis C virus (HCV) infection can lead to varying degrees of liver injury.
- Human leukocyte antigen (HLA) alleles are known to influence immune responses and disease outcomes.
- Understanding the genetic factors associated with HCV carrier states is crucial for predicting disease progression.
Purpose of the Study:
- To investigate the association between HLA DR allele distribution and the severity of liver cell injury in Japanese HCV carriers.
- To explore the relationship between specific HLA DR alleles and the immune response in different HCV infection stages.
Main Methods:
- Sixty-eight HCV carriers were categorized into asymptomatic and chronic active hepatitis groups based on laboratory data and liver histology.
- HLA DR alleles were determined using polymerase chain reaction restriction fragment length polymorphism.
- Expression of HLA class I antigen and intercellular adhesion molecule 1 on hepatocytes was assessed via immunohistochemistry.
Main Results:
- The frequency of HLA DR13 was significantly higher in the asymptomatic carrier group (42.1%) compared to the chronic active hepatitis group (4.1%).
- Asymptomatic carriers showed significantly lower expression of HLA class I antigen and intercellular adhesion molecule 1 on hepatocytes.
- No significant difference in serum HCV-RNA viral load was observed between the groups.
Conclusions:
- HLA DR13 is strongly associated with a less activated cellular immune response in HCV carriers.
- This genetic factor may play a role in maintaining an asymptomatic carrier state with minimal liver damage.
- The findings suggest that HLA DR13 may be a protective factor against severe liver injury in HCV infection.
Abstract:
The aim of this study was to clarify the relationship between human leukocyte antigen DR allele distribution and the degree of liver cell injury of hepatitis C virus (HCV) carriers in Japan. The subjects, 68 HCV carriers, were divided into two groups according to the laboratory data and liver histology. Those in the asymptomatic carrier group (n = 19) had normal ALT levels persistently for 8-153 months (mean 25.7 months) and were diagnosed histologically as normal liver, nonspecific reactive hepatitis or chronic persistent hepatitis. Those in the chronic active hepatitis group (n = 49) had elevated ALT levels and were diagnosed histologically with chronic active hepatitis. The human leukocyte antigen DR alleles of all subjects were defined using the polymerase chain reaction restriction fragment length polymorphism method. The expression of human leukocyte antigen class I antigen and intercellular adhesion molecule 1 on the hepatocyte membrane were also examined in 14 patients from each group using an indirect immunohistochemical method. The frequency of DR13 (42.1%) in the asymptomatic carrier group was significantly higher (Pc < 0.003) than that of the chronic active hepatitis group (4.1%). There were no significant differences for the other DR alleles. The frequencies of expression of human leukocyte antigen class I antigen and intercellular adhesion molecule 1 on the hepatocyte membrane of the asymptomatic carrier group were significantly less than those of the chronic hepatitis group (64% vs. 100% P < 0.05, 29% vs. 71% P < 0.05, respectively), although there was no significant difference in the serum HCV-RNA titer between the two groups (10(6.4 +/- 1.1) vs. 10(6.5 +/- 0.7) copies/mL). These results demonstrate that the cellular immune response of the asymptomatic carrier group is less activated than the response of the chronic active hepatitis group and that HLA DR13 may be closely associated with this low activity of hepatitis among HCV carriers.