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Aims To investigate an optimal long-term prophylactic strategy for prevention of hepatitis B virus (HBV) recurrence after liver transplantation, we conducted a randomized study of 29 transplant recipients receiving a short course of hepatitis B immune globulin ( HBIg) + lamivudine ( LAM), followed by randomization to long-term prophylaxis with LAM with or without HBIg. Methods The efficacy and safety, and impact on survival and HBV recurrence of these 2 prophylactic regimens were compared over a mean period of 10 years. In patients with viral recurrence, the HBV quasispecies in the surface/polymerase region were studied by ultra-deep pyrosequencing ( UDPS). Results The 10-year survival rate was 76% and was not affected by the type of prophylaxis. Four patients had hepatitis B surface antigen ( HBsAg) recurrence within the first 48 months after orthotopic liver transplantation ( OLT). HBsAg-positive and -negative patients showed similar mean survival times, with no differences between the 2 regimens. Low HBV DNA levels were transiently detected in 32% of HBsAg-negative patients. UDPS showed major changes after OLT in the HBV quasispecies of patients with viral recurrence, which may be explained by a 'bottleneck' effect of OLT together with prophylactic therapy. Conclusion Long-term survival after OLT in end-stage chronic hepatitis B patients was good with both prophylactic strategies. However, low, transient HBV DNA levels were detected even in the absence of HBsAg, showing the importance of continuing HBV prophylaxis. [ABSTRACT FROM AUTHOR]

The success of current antiviral treatment for hepatitis C virus ( HCV) recurrence in liver transplant ( LT) recipients remains limited. We aimed at evaluating the value of IL28 B genotype and early viral kinetics to predict response to standard treatment in the transplant setting. We retrospectively evaluated 104 LT recipients treated for HCV genotype 1 recurrence between 2001 and 2010. Baseline variables, including IL28 B genotype, and early viral kinetics were compared among patients who did or did not achieve a sustained virological response ( SVR). Logistic regression analyses of candidate variables were conducted to generate a reliable predictive model based on the minimum set of variables. Twenty-nine (28%) achieved an SVR. On multivariate analysis, the magnitude of HCV RNA decline at 4 weeks ( OR: 3.74, 95% CI: 1.64-9.39; P = 0.003) and treatment compliance ( OR: 35.27, 95% CI: 3.35-365.54; P = 0.003) were the only independent predictors of SVR. Favourable recipient IL28 B genotype significantly correlates with virological response at week 4 ( OR 3.23; 95% CI, 1.12-9.15; P = 0.03). By logistic regression analysis, a model including donor age, recipient rs12979860 genotype and viral load at 4 weeks showed the best predictive value for SVR with an area under the receiver operating curve of 0.861. Favourable recipient IL28 B genotype strongly correlates with the viral response at week 4 which is the strongest predictor of response. The combination of recipient IL28 B genotype and donor age with the week 4 response reliably estimates the probability of SVR early on-treatment and may facilitate therapeutic strategies incorporating new antiviral agents. [ABSTRACT FROM AUTHOR]

Aliment Pharmacol Ther 2010; 32: 97–104 Background Some patients continue to have detectable HBV-DNA levels with liver disease progression after hepatitis B e antigen (HBeAg) loss. It is important to identify these patients, candidates for long-term treatment. Aims To evaluate hepatitis B virus (HBV) genotype and the main mutations in the basic core promoter (BCP, A1762T/G1764A) and precore (G1896A) sequences as markers of persistent HBV-DNA after HBeAg loss. Methods We analysed 60 serum samples from 20 Caucasian, HBeAg-positive, chronic hepatitis B patients, who lost HBeAg and were followed-up longitudinally. HBV genotype and precore and BCP mutations were determined before, at the time of, and after HBeAg loss. Results After HBeAg loss, eight (40%) patients continued to have undetectable HBV-DNA and 12 (60%) had persistent HBV-DNA (median level 4.7 log10 copies/mL). The presence of BCP mutations prior to therapy was the only variable associated with persistently detectable viraemia ( P = 0.017). Four patients with genotype A and no mutations in the BCP region experienced hepatitis B surface antigen (HBsAg) loss after a mean period of 35 months from baseline. Conclusions Main BCP mutations in HBeAg-positive patients are useful markers to identify patients who will not have sustained virological suppression after HBeAg loss and therapy discontinuation and could benefit from long-term treatment. [ABSTRACT FROM AUTHOR]

A 39-year-old female patient, an ex-smoker with an 8-pack-year smoking history and severe pulmonary emphysema of early onset, received a diagnosis of alpha(1)-antitrypsin (AAT) deficiency and proved to be a carrier of a new deficient variant, YBARCELONA, derived from the normal M1 variant with two substitutions: one in exon III and the other in exon V. AAT genotype of eight members of the same family and study of lung function of the index case and family members at baseline and after 6 years of follow-up were performed. Five subjects were PiYM, with intermediate serum AAT concentrations and normal pulmonary function. No changes were observed over 6 years in pulmonary function of the PiYM patients who were nonsmokers; however, the PiYY index case presented worsening of pulmonary function with FEV(1) of 33%. The heterozygotes PiYM have AAT concentrations similar to the PiMZ and, at 6 years, the nonsmokers presented no worsening in pulmonary function. The risk associated with this variant in its heterozygous form may be similar to that described for PiMZ. [ABSTRACT FROM AUTHOR]