B and C hepatitis viruses, HLA-DQ1 and -DR3 alleles and autoimmunity in patients with hepatocellular carcinoma.
OBJECTIVE
Hepatitis B and C involvement in hepatocellular carcinoma has been well established, but as yet not that of the human lymphocyte antigen (HLA) complex. To study viral, HLA and tumour interrelationships, 105 patients were evaluated for prevalence of viral markers and 161 patients, including 99 of the previous ones, for HLA allele frequency; the other 52 patients served as controls.


METHODS
Immunoassays, molecular assays, microlymphocytotoxicity.


RESULTS
Positivity for hepatitis B surface antigen and/or hepatitis C antibodies in 89% cirrhotic, 44% non-cirrhotic vs. 92% control patients (cirrhotic; all hepatitis C antibody positives were viraemic). Recurrent HLA alleles: HLA-Cw7 and -DQ1 in cirrhotic and control patients, HLA-Cw7, -B8 and -DR3 in non-cirrhotic patients compared with healthy controls (Pc=0.0000074, 0.000025, 0.0025, 0.00027 and 0.043, respectively).


CONCLUSIONS
Viral data suggest a high chronic infection rate for cirrhotic patients. Recurrent HLA-Cw7 is compatible with natural killer cell activity inhibition to virus-infected and tumour cells by HLA C molecules. Recurrent HLA-DQ1 and -DR3 suggest the existence of an autoimmune condition with cell destruction in cirrhotic and without cell destruction in non-cirrhotic patients as a consequence of autoreactive DQ-restricted T-helper (Th)1 and DR-restricted Th2 cells response, respectively. HLA-B8-DR3 linkage disequilibrium was possible. Thus, autoimmunity may have contributed to hepatocellular carcinoma development in these patients.
Pellegris
Giuseppe
G
O.U. Immunohaematology and Transfusion Division, Istituto Nazionale per lo Studio e la Cura dei Tumori, Via Venezian 1, 20133 Milan, Italy.
Ravagnani
Fernando
F
Notti
Paola
P
Fissi
Susanna
S
Lombardo
Claudia
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D015551:Autoimmunity; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000276:immunology*; D005260:Female; D005787:Gene Frequency; D006683:HLA-DQ Antigens / Q000235:genetics*; D015803:HLA-DR3 Antigen / Q000235:genetics*; D006514:Hepatitis B Surface Antigens / Q000032:analysis*; D018937:Hepatitis C Antibodies / Q000032:analysis*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000276:immunology*; D008297:Male; D008875:Middle Aged
D006683:HLA-DQ Antigens; C051568:HLA-DQ1 antigen; D015803:HLA-DR3 Antigen; D006514:Hepatitis B Surface Antigens; D018937:Hepatitis C Antibodies