Final analysis of the international observational S-Collate study of peginterferon alfa-2a in patients with chronic hepatitis B

Background and aims Sustained off-treatment immune control is achievable in a proportion of patients with chronic hepatitis B treated with peginterferon alfa-2a. We evaluated on-treatment predictors of hepatitis B surface antigen (HBsAg) clearance 3 years after peginterferon alfa-2a treatment and determined the incidence of hepatocellular carcinoma. Methods A prospective, international, multicenter, observational study in patients with chronic hepatitis B who have been prescribed peginterferon alfa-2a (40KD) in a real-world setting. The primary endpoint was HBsAg clearance after 3 years' follow-up. Results The modified intention-to-treat population comprised 844 hepatitis B e antigen (HBeAg)positive patients (540 [64%] completed 3 years' follow-up), and 872 HBeAg-negative patients (614 [70%] completed 3 years' follow-up). At 3 years' follow-up, HBsAg clearance rates in HBeAg-positive and HBeAg-negative populations, respectively, were 2% (16/844) and 5% (41/872) in the modified intention-to-treat population and 5% [16/328] and 10% [41/ 394] in those with available data. In HBeAg-positive patients with data, Week 12 HBsAg levels <1500, 1500-20,000, and >20,000 IU/mL were associated with HBsAg clearance rates at 3 years' follow-up of 11%, 1%, and 5%, respectively (Week 24 predictability was similar). In HBeAg-negative patients with available data, a 6510% decline vs a <10% decline in HBsAg at Week 12 was associated with HBsAg clearance rates of 16% vs 4%. Hepatocellular carcinoma incidence was lower than REACH-B (Risk Estimation for Hepatocellular Carcinoma in Chronic Hepatitis B) model predictions. Conclusions Sustained off-treatment immune control is achieved with peginterferon alfa-2a in a real-world setting. HBsAg clearance 3 years after completion of peginterferon alfa-2a can be predicted on the basis of on-treatment HBsAg kinetics

Structure of the retinal chromophore in halorhodopsin: A resonance Raman study.

AbstractResonance Raman (RR) spectra of the light-driven chloride pump halorhodopsin (HR) were recorded after isolation of the protein from cell membranes of Halobacterium halobium. The spectra of the unphotolyzed state HR578 were compared with those of two unphotolyzed species of the light-driven proton pump bacteriorhodopsin, BR570 and BR548, which were obtained from light- and dark-adapted purple membranes. Identical structural components in the retinal chromophores of HR578 and BR570 are found, both having the all-trans configuration of the retinal chain and a protonated Schiff base linkage to the protein with anti-position of the two hydrogens. Only minor conformational differences between the chromophoric structures in the two proteins could be inferred from the vibrational structure of the RR spectra. The function of the two chromophores as triggers of light-induced chloride or proton transport emphasizes the role of the protein part in the ion specificity of the pumps