Background/Aims: This study was aimed to determine whether host-dependent genetic factors modulate the outcome of HCV infection. Methods HLA class II DRB and DQB typing was performed in 184 infected patients and 200 healthy volunteers. Among the patients, 149 subjects had persistent HCV viremia (Group I) and 35 subjects underwent spontaneous viral clearance (Group 2), Group 1 included cirrhotic patients with transfusion-acquired infections (n=79), asymptomatic MCV carriers (n= 42), and patients with chronic hepatitis C responsive to interferon therapy (n=28), Results: Spontaneous viral clearance was associated with HLA DRB1*1104 (pc=0.054, OR=4.51, 95% C,I, 2.02 10.1) and HLA DQB1*0301 (pc=0.0039, OR=4.52, 95% C,I, 2.15-9.51), In Group 1 the haplotype DRB1*1104/DQB1*0301 was less frequent (4.8%) than in Group 2 (18.3%) (pc=0.009, OR= 7.38, 95% C,I, 2.58-21.59), At the HLA levels cirhotic patients were not different from asymptomatic HCV carriers and patients with interferon-induced viral clearance, In cirrhotic patients infected with genotype Ib, the DQB1*0502 allele was more frequently found in those with rapidly progressive liver damage (OR=8.15, 95% C,I, 1.49-4.44),but the corrected p-value was not significant (pc=0.09), Conclusions: The HLA haplotype DRB1*1104/DQB1*0301 appears Co contribute to the spontaneous clearance of HCV infection. The predominance of the DQB1*0502 allele in cirrhotic patients with arapidly progressive disease possibly reflects an influence of this allele on the progression of the HCV-related liver disease.