Human leukocyte antigen DRB1 1302 protects against bile duct damage and portal lymphocyte infiltration in patients with chronic hepatitis C

Background/Aims: To confirm the immune reaction of hosts in chronic hepatitis C, we examined the association of human leukocyte antigen (HLA) DR with the histopathological outcome including bile duct damage and steatosis, which are characteristic of hepatitis C virus (HCV) infection. Methods: One hundred and fifty-five patients with chronic HCV infection were examined. The pathological appearance of liver biopsy specimens was evaluated by both Knodellʹs histological activity index and examination of bile duct damage and steatosis. HLA DRB1 was determined by the polymerase chain reaction sequence-specific oligonucleotide probe method. Results: HLA DRB1 1302 was found with significantly higher frequency in patients without than with bile duct damage (34.8% vs. 4.7%, p=0.0001, p corrected by Bonferroniʹs inequality METHOD=0.002). It was also found more frequently in patients without marked portal lymphocyte infiltration (28.6% vs. 7.7%, p=0.0015, p corrected by Bonferroniʹs METHOD=0.03). HLA DRB1 1101 was found more frequently in patients without than with piecemeal necrosis (p=0.004). In contrast, the frequency of HLA DRB1 1502 tended to be higher in patients with than without piecemeal necrosis and marked portal lymphocyte infiltration (p=0.015 and p=0.03, respectively). HLA DRB1 1201 and 0802 were seen more frequently in bile duct damage-negative (p=0.02) and piecemeal necrosis-negative patients (p=0.03), respectively. Interestingly, serum HCV levels of HLA DRB1 1302-positive patients were significantly higher than those of 1302-negative patients (mean: 7.7Meq/ml vs. 3.1Meq/ml, p=0.0007). Conclusion: These findings suggest that some histopathological changes in chronically HCV-infected livers could be caused by the hostʹs immune reaction regulated by HLA DR.