Tesi etd-10142012-111431 |
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Tipo di tesi
Tesi di specializzazione
Autore
CHERUBINI, BEATRICE
URN
etd-10142012-111431
Titolo
"IL28B polymorphism in chronic HBV infection: the CC allele does not correlate with the phase of the infection nor with HBsAg clearance in IFN treated patients".
Dipartimento
MEDICINA E CHIRURGIA
Corso di studi
GASTROENTEROLOGIA
Relatori
relatore Prof. Bonino, Ferruccio
Parole chiave
- Nessuna parola chiave trovata
Data inizio appello
29/10/2012
Consultabilità
Completa
Riassunto
IL28B polymorphism (IL28Bp) is associated with spontaneous and treatment induced HCV clearance, whereas its role in HBV infection is still debated. We analysed the correlation between IL28Bp and phase and outcome of HBV infection and HBsAg clearance in Interferon (IFN) treated patients.
We studied 525 consecutive chronic HBV carriers (63.4% males; median age 47.3 y., range:16-86, genotype D 88%) followed up at the Hepatology Unit of the University Hospital of Pisa since 1998. They were 71 HBeAg pos and 454 HBeAg neg. During follow-up (fu) 138 patients were treated with IFN +/- nucleos(t)ide analogues (NA). IL28Bp SNP rs12979860 was characterized by allele-specific RT-PCR (LightMix, Roche). Quantitative HBsAg (Architect, Abbott) and HBV-DNA (Cobas TaqMan, Roche) were tested at baseline (BL) in all carriers, during therapy (week 1-4-12-24-48) in 42 Peg-IFN treated pts.
In the overall population IL28Bp was: CC 49.7%, CT 40.4% and TT 9.9%. The CC allele prevalence was not statistically different according to age, gender (males: 49.5%), HBeAg status (pos: 59.2%), HBeAg negative inactive (48.2%) or active (49.7%) infection. Median Log HBV-DNA and HBsAg levels at BL in CC (4.46 and 3.34), CT (4.40 and 3.18) and TT (4.34 and 3.19) carriers were comparable. During fu 14/122 (11.5%) inactive carriers cleared HBsAg: 7.4% CC,14.8% CT, 14.3% TT, n.s. Among IFN+/- NA treated pts, 8/29 (27.6%) HBeAg pos (50% CC) and 21/127 (16.5%) HBeAg neg (33.3% CC) lost HBsAg. At multivariate analysis the only independent factor associated with HBsAg loss was genotype non D (P=0.009). During peg-IFN mono-therapy week 12 HBV-DNA, but not HBsAg, became significantly lower in CC (7) than in CT/TT (7/1) HBeAg pos pts (4.94 vs 7.90, P=0.029). No difference was found in HBeAg negative pts.
The IL28B CC allele does not correlate with the phase and the outcome of HBV infection. HBsAg and HBV-DNA levels at BL and HBsAg clearance in IFN +/-NA treated pts were not influenced by the CC allele, although a faster HBV-DNA was found in HBeAg pos CC pts. These findings underline major differences in the mechanisms of natural and therapy induced control of HBV and HCV infections.
We studied 525 consecutive chronic HBV carriers (63.4% males; median age 47.3 y., range:16-86, genotype D 88%) followed up at the Hepatology Unit of the University Hospital of Pisa since 1998. They were 71 HBeAg pos and 454 HBeAg neg. During follow-up (fu) 138 patients were treated with IFN +/- nucleos(t)ide analogues (NA). IL28Bp SNP rs12979860 was characterized by allele-specific RT-PCR (LightMix, Roche). Quantitative HBsAg (Architect, Abbott) and HBV-DNA (Cobas TaqMan, Roche) were tested at baseline (BL) in all carriers, during therapy (week 1-4-12-24-48) in 42 Peg-IFN treated pts.
In the overall population IL28Bp was: CC 49.7%, CT 40.4% and TT 9.9%. The CC allele prevalence was not statistically different according to age, gender (males: 49.5%), HBeAg status (pos: 59.2%), HBeAg negative inactive (48.2%) or active (49.7%) infection. Median Log HBV-DNA and HBsAg levels at BL in CC (4.46 and 3.34), CT (4.40 and 3.18) and TT (4.34 and 3.19) carriers were comparable. During fu 14/122 (11.5%) inactive carriers cleared HBsAg: 7.4% CC,14.8% CT, 14.3% TT, n.s. Among IFN+/- NA treated pts, 8/29 (27.6%) HBeAg pos (50% CC) and 21/127 (16.5%) HBeAg neg (33.3% CC) lost HBsAg. At multivariate analysis the only independent factor associated with HBsAg loss was genotype non D (P=0.009). During peg-IFN mono-therapy week 12 HBV-DNA, but not HBsAg, became significantly lower in CC (7) than in CT/TT (7/1) HBeAg pos pts (4.94 vs 7.90, P=0.029). No difference was found in HBeAg negative pts.
The IL28B CC allele does not correlate with the phase and the outcome of HBV infection. HBsAg and HBV-DNA levels at BL and HBsAg clearance in IFN +/-NA treated pts were not influenced by the CC allele, although a faster HBV-DNA was found in HBeAg pos CC pts. These findings underline major differences in the mechanisms of natural and therapy induced control of HBV and HCV infections.
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