Related Experiment Videos
Serine protease inhibitors in patients with chronic viral hepatitis
A N Elzouki1, H Verbaan, S Lindgren
1Department of Medicine, University of Lund, University Hospital, Malmo, Sweden.
Insights
Alpha-1-antitrypsin (AAT) deficiency is not linked to higher hepatitis B or C virus (HBV/HCV) risk. However, low alpha1-antichymotrypsin (ACT) levels are frequent in HCV infection, suggesting a potential association.
Area of Science:
- Hepatology
- Virology
- Genetics
- Immunology
Background:
- Serine protease inhibitors, alpha1-antitrypsin (AAT) and alpha1-antichymotrypsin (ACT), play roles in immune regulation.
- Chronic viral hepatitis B (HBV) and C (HCV) are significant causes of liver disease.
- The potential association between deficiencies in AAT or ACT and the risk of chronic HBV/HCV infection requires investigation.
Purpose of the Study:
- To investigate the association between deficiencies in alpha1-antitrypsin (AAT) and alpha1-antichymotrypsin (ACT) and the risk of chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
- To determine if genetic variations in AAT and ACT influence susceptibility or progression of chronic liver disease caused by HBV or HCV.
Main Methods:
- A cohort of 709 adults with chronic liver disease was studied retrospectively (1978-1992).
- Hepatitis C virus (HCV) infection was assessed using ELISA and RIBA 2 assays.
- Hepatitis B virus (HBV) infection markers were tested via radioimmunoassays.
- Plasma concentrations of AAT and ACT were quantified using electroimmunoassay and immune nephelometry.
- AAT PiZ deficiency was screened by ELISA and phenotyped by isoelectric focusing.
- The 229Pro-->Ala mutation for ACT deficiency was identified using PCR techniques.
Main Results:
- HCV infection was detected in 18.6% of patients.
- PiZ AAT deficiency (6.2%) and subnormal ACT levels (4.6%) were found at higher frequencies than expected in the general population.
- No significant association was observed between PiZ AAT deficiency and HCV or HBV infection.
- A significant association was found between subnormal ACT levels and HCV infection (51.5% of patients with low ACT were anti-HCV positive; OR=5.2).
- No relationship was identified between HBV infection and either AAT deficiency or subnormal ACT levels.
Conclusions:
- Heterozygous alpha1-antitrypsin (AAT) deficiency is not associated with an increased risk of chronic hepatitis B or C virus (HBV/HCV) infection.
- Low plasma levels of alpha1-antichymotrypsin (ACT), potentially acquired or hereditary (excluding the 229Pro-->Ala mutation), are frequently observed in patients with HCV infection.
- Further research is warranted to explore the potential link between AAT deficiency and more severe liver disease, and the implications of low ACT levels in HCV infection.
Background/Aims:
This study aimed to determine whether deficiency of the major serine protease inhibitors (alpha1-antitrypsin (AAT) or alpha1-antichymotrypsin (ACT)) is associated with increased risk for chronic hepatitis B or C virus (HBV or HCV) infection.
Methods:
We studied 709 adults with chronic liver disease who had undergone liver biopsy during the 14-year period 1978-92. Anti-HCV testing was carried out with second-generation ELISA and immunoblot assays (RIBA 2). HBV markers were tested with commercially available radioimmunoassays. ACT and AAT concentrations in plasma were measured with electroimmunoassay and immune nephelometry. Plasma samples were screened for the AAT PiZ deficiency with ELISA technique and phenotyped by isoelectric focusing. The 229Pro-->Ala mutation for ACT deficiency was identified by PCR techniques.
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 levels were found in 33 (4.6%) patients, frequencies that were higher than expected in the general population (p=0.0375 and p<0.0001, respectively). Of the PiZ-carriers, 8/44 (18%) were found to be anti-HCV positive 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 hepatitis, 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 infection and AAT deficiency or subnormal ACT levels. Only one patient with subnormal ACT levels was heterozygous for the 229Pro-->Ala mutation of ACT deficiency. There was no significant difference in the histological findings when the patients with subnormal ACT levels or PiZ allele were subgrouped according to HCV status.
Conclusions:
There is no overrepresentation of chronic HBV or HCV in heterozygous AAT deficiency, although an association with more severe liver disease in such patients cannot be excluded. In contrast, low plasma levels of ACT that may be acquired or hereditary, due to mutations other than 229Pro-->Ala, are frequent in HCV infection.