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Influence of alpha-1 antitrypsin heterozygosity on treatment efficacy of HCV combination therapy.

Abstract：

BACKGROUND:The role of heterozygosity for alpha-1 antitrypsin (A1AT) alleles in patients with chronic hepatitis C virus (HCV) is unclear. There is limited evidence to suggest that there is an increased prevalence of heterozygous A1AT carriers in HCV, but it is unclear how this affects treatment success. AIM:To investigate the (i) prevalence of A1AT heterozygosity among two HCV cohorts and (ii) its effect on treatment outcome. METHODS:We performed a retrospective cohort study using two different cohorts. Cohort 1 consisted of 678 German HCV patients, 507 of them were treated for HCV with standard therapy. Cohort 2 consisted of 370 Dutch HCV patients of which 252 were part of a clinical trial (treatment with amantadine or placebo, in combination with pegylated interferon alpha-2b and ribavirin) whereas 37 HCV patients received standard therapy. We analyzed A1AT status using direct sequencing of the A1AT gene (cohort 1) or isoelectric focusing of serum (cohort 2). In addition, we measured A1AT serum levels (cohort 2). RESULTS:In total, we included 1048 HCV patients; 986 (94%) were wildtype [protease inhibitor (Pi) MM], whereas 61 (6%) were heterozygous for a mutant A1AT allele (41 Pi MS, 20 Pi MZ). Mean A1AT serum levels (370 patients) were lower in A1AT heterozygous patients (1.68 vs. 1.36 g/l), (P<0.05) compared with wildtypes. Sustained viral response (SVR) after treatment was equal between the wildtypes and heterozygotes (54 vs. 56%). CONCLUSION:We found a heterozygosity rate of 0.06, in line with healthy controls in other studies. Serum A1AT levels from A1AT heterozygous HCV patients are significantly lower compared with wildtype patients, although they do not discriminate on an individual level. Finally, SVR in A1AT wildtypes was not different from SVR in A1AT heterozygotes.

journal_name

Eur J Gastroenterol Hepatol

journal_title

European journal of gastroenterology & hepatology

authors

Kok KF,van Soest H,van Herwaarden AE,van Oijen MG,Boland GJ,Halangk J,Berg T,de Vries RA,Drenth JP

doi

10.1097/MEG.0b013e3283320113

subject

Has Abstract

pub_date

2010-07-01 00:00:00

pages

808-12

issue

eissn

0954-691X

issn

1473-5687

journal_volume

pub_type

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Influence of alpha-1 antitrypsin heterozygosity on treatment efficacy of HCV combination therapy.