SERINE-PROTEASE INHIBITORS IN PATIENTS WITH CHRONIC VIRAL-HEPATITIS

Background/Aims: This study aimed to determine whether deficiency of t he major serine protease inhibitors (alpha(1)-antitrypsin (AAT) or alp ha(1)-antichymotrypsin (ACT)) is associated with increased risk for ch ronic hepatitis B or C virus (HBV or HCV) infection. Methods: We studi ed 709 adults with chronic liver disease who had undergone liver biops y during the 14-year period 1978-92. Anti-HCV testing was carried out with second-generation ELISA. and immunoblot assays (RIBA 2). HBV mark ers were tested with commercially available radioimmunoassays. ACT and AAT concentrations in plasma were measured with electroimmunoassay an d immune nephelometry. Plasma samples were screened for the AAT PiZ de ficiency with ELISA technique and phenotyped by isoelectric focusing, The (229)Pro-->Ala mutation for ACT deficiency was identified by PCR t echniques. Results: Of the 709 patients, 132 (18.6%) were positive for anti-HCV according to RIBA 2. PiZ AAT deficiency was found in 44 (6.2 %) of patients (one PiZZ, 38 PiMZ, and PiSZ), while subnormal ACT leve ls were found in 33 (4.6%) patients, frequencies that were higher than expected in the general population (p=0.0375 and p<0.0001, respective ly). Of the PiZ-carriers, 8/44 (18%) were found to be anti-HCV positiv e according to RIBA 2, as compared to 123/662 (19%) non-PiZ-carriers ( p>0.05). One of these patients had cirrhosis, four chronic active hepa titis, and three chronic persistent hepatitis, In contrast, 17/33 (51. 5%) of the patients with subnormal ACT were anti-HCV positive (OR=5.2, CI=2.6-10.6; p<0.0001). No relationship was found between HBV infecti on and AAT deficiency or subnormal ACT levels, Only one patient with s ubnormal ACT levels was heterozygous for the (229)Pro-->Ala mutation o f ACT deficiency. There was no significant difference in the histologi cal findings when the patients with subnormal ACT levels or PiZ allele were subgrouped according to HCV status. Conclusions: There is no ove rrepresentation of chronic HBV or HCV in heterozygous AAT deficiency, although an association with more severe liver disease in such patient s cannot be excluded. In contrast, low plasma levels of ACT that mag b e acquired or hereditary due to mutations other than (229)Pro-->Ala, a re frequent in HCV infection.