Interferon and ribavirin therapy for chronic hepatitis C virus genotype 6: A comparison with genotype 1

Because there is a lack of data on the treatment outcome of patients who carry hepatitis C virus (HCV) genotype 6, we conducted a prospective study, to compare the effect of interferon and ribavirin therapy in HCV genotypes 1 and 6, of patients with seropositive anti-HCV, persistently elevated alanine transaminase levels, and detectable HCV RNA. Patients were treated with subcutaneous recombinant interferon α-2b and ribavirin for 12 months. Of 40 patients, 16 had genotype 6, and 24 had genotype 1. An end-of-treatment response was detected in 12 (75%) patients with genotype 6 and in 10 (41.6%) patients with genotype 1 (P = .05). A sustained virological response (SVR) was present in 10 (62.5%) patients with genotype 6 and in 7 (29.2%) patients with genotype 1 (P = .04). Genotype 6 has a better response than genotype 1 and is associated with a higher SVR.published_or_final_versio

Role of hepatitis B virus genotypes in chronic hepatitis B exacerbation

Hepatitis B virus (HBV) genotypes and precore and core promoter mutations were determined in 318 patients with HBV. Patients infected with HBV genotype B had a higher median alanine aminotransferase level and bilirubin level and a lower median albumin level during exacerbations of disease, compared with patients infected with HBV genotype C (all P < .001). By logistic regression analysis, HBV genotype B infection (P = .014) and low albumin levels (P = .006) were independently associated with a higher risk of hepatic decompensation during severe exacerbations of disease. Patients infected with genotype B had a significantly higher mortality due to hepatic decompensation than did patients with genotype C (70% vs. 27.8%; P = .05).published_or_final_versio

Relationship between the development of precore and core promoter mutations and hepatitis B e antigen seroconversion in patients with chronic hepatitis B virus

Chinese patients with chronic hepatitis B virus (332 with and 44 without cirrhosis-related complications) were studied. Fifty percent of patients <30 years old had precore mutations. The prevalence of precore mutations among hepatitis B e antigen (HBeAg)-positive patients, although lower than that among anti-HBe-positive patients (P = .031), was already high (44.2%). Median HBV DNA level in anti-HBe-positive patients was 1.5 × 106-1.55 × 106 copies/mL, irrespective of the presence or absence of precore mutations. There was no difference in the prevalence of precore mutations between patients with and without complications (P, not significant). However the prevalence of core promoter mutations was higher among patients with complications than among those without complications (90.5% vs. 69.3%, respectively; P = .003). In conclusion, precore mutations occurred in a large proportion of Chinese patients with chronic hepatitis B virus before HBeAg seroconversion. The development of complications was not related to precore mutations but was probably due to the persistence of significant viremia after HBeAg seroconversion.published_or_final_versio

Development and application of cytotoxic T lymphocyte-associated antigen 4 as a protein scaffold for the generation of novel binding ligands

AbstractWe have explored the possibilities of using human cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) as a single immunoglobulin fold-based scaffold for the generation of novel binding ligands. To obtain a suitable protein library selection system, the extracellular domain of CTLA-4 was first displayed on the surface of a filamentous phage as a fusion product of the phage coat protein p3. CTLA-4 was shown to be functionally intact by binding to its natural ligands B7-1 (CD80) and B7-2 (CD86) both in vitro and in situ. Secondly, the complementarity determining region 3 (CDR3) loop of the CTLA-4 extracellular domain was evaluated as a permissive site. We replaced the nine amino acid CDR3-like loop of CTLA-4 with the sequence XXX-RGD-XXX (where X represents any amino acid). Using phage display we selected several CTLA-4-based variants capable of binding to human αvβ3 integrin, one of which showed binding to integrins in situ. To explore the construction of bispecific molecules we also evaluated one other potential permissive site diametrically opposite the natural CDR-like loops, which was found to be tolerant of peptide insertion. Our data suggest that CTLA-4 is a suitable human scaffold for engineering single-domain molecules with one or possibly more binding specificities

Prognostic factors in severe exacerbation of chronic hepatitis B

Forty-seven patients with severe hepatitis B exacerbation were compared with patients who had mild exacerbation (n = 96) or no exacerbation (n = 96). Seventeen patients (36.2%) died or underwent liver transplantation. Preexisting cirrhosis and a prothrombin time (PT) of >30 s were associated with adverse outcome in 60.9% and 87.5% of patients, respectively. The rate of adverse outcome increased to 92.3% when albumin levels of ≤35 g/L and bilirubin levels of >200 μM were present. Other factors associated with adverse outcomes included peak bilirubin level, peak PT, time to reach peak PT, and the presence of encephalopathy and/or ascites. There was no difference in the frequency of precore mutations in patients with severe or mild exacerbation or without exacerbation. A significantly lower prevalence of core promoter mutants was found in patients with severe exacerbation (50%), compared with those who had mild exacerbation (81.3%; P = .004). Patients with severe exacerbation of hepatitis B with poor prognostic factors should be considered for early liver transplantation.published_or_final_versio

Polymeric Nanocapsule from Silica Nanoparticle@Cross-linked Polymer Nanoparticles via One-Pot Approach

A facile strategy was developed here to prepare cross-linked polymeric nanocapsules (CP nanocapsules) with silica nanoparticles as templates. The silica nanoparticle@cross-linked polymer nanoparticles were prepared by the encapsulation of the silica nanoparticles by the one-pot approach via surface-initiated atom transfer radical polymerization of hydroxyethyl acrylate in the presence ofN,N′-methylenebisacrylamide as a cross-linker from the initiator-modified silica nanoparticles. After the silica nanoparticle templates were etched with hydrofluoric acid, the CP nanocapsules with particle size of about 100 nm were obtained. The strategy developed was confirmed with Fourier transform infrared, thermogravimetric analysis and transmission electron microscopy

Viral Resistance in Hepatitis B: Prevalence and Management

Hepatitis B is a DNA virus affecting hundreds of millions of individuals worldwide. As the clinical sequelae of cirrhosis and hepatocellular cancer are increasingly recognized to be related to viral levels, the impetus increases to offer treatment to those previously not treated. With the development of more robust antivirals with reasonable safety profiles, long-term treatment is becoming more common. The oral nucleos(t)ide analogs have become the preferred first-line therapies for most genotypes of hepatitis B. Five are now available, all with different potencies and resistance profiles. Long-term data spanning several years are now available for most compounds in this arena. This article focuses on the common natural variants and those secondary to nucleos(t)ide therapy, as well as diagnostic methods to detect resistance

Genetic variability in the precore and core promoter regions of hepatitis B virus strains in Karachi

BACKGROUND: Hepatitis B virus (HBV) genotypes have distinct geographic distribution. Moreover, much genetic variability has been described in the precore (PC) and basal core promoter (BCP) regions of the HBV genome. The local prevalence of HBV genotypes and mutations has not been well studied. The aim of the present study is to determine the prevalence of HBV genotypes and mutations in the PC and BCP region in HBV strains in Karachi. METHODS: A total of 109 chronic hepatitis B patients with detectable HBV DNA by a PCR assay were enrolled in the study. Sera were tested for HBeAg, anti-HBe antibody and liver profile. HBV genotypes and mutations in the PC and BCP regions were detected by INNO-LiPA line-probe assays. RESULTS: Of the 109 patients investigated, 38 (35%) were HBeAg positive while 71 (65%) were HBeAg negative. Genotype D was present in 100% of the patients. Two patients had co-infection with genotype A. There was no significant difference in the baseline characteristics, mean ALT levels, and presence of clinical cirrhosis in patients with HBeAg positive or negative strains with or without PC and BCP mutations. Of the 38 HBeAg positive patients, 9 (24%) had PC and BCP mutations. In the HBeAg negative patient group, mutations were detected in 44 (62%) of the strains investigated. More than one mutation was common, seen in 26 (37%) patients with HBeAg negative disease and 6 (16%) patients with HBeAg positive disease. Twelve (17%) HBeAg negative patients had dual T1762 and A1764 mutations. None of the HBeAg positive patients had T1762 mutation. Mutations were undetectable in 27 (38%) of patients with HBeAg negative disease. CONCLUSION: Our study shows that type D is the main HBV genotype in Karachi, Pakistan. Significant numbers of patients infected with this genotype have PC and BCP variants. Mutations at more than one site are common. Patients harboring these mutants do not differ significantly in their clinical presentation from patients having wild type infection

Standardization of the Fully Stapled Laparoscopic Roux-en-Y Gastric Bypass for Obesity Reduces Early Immediate Postoperative Morbidity and Mortality: A Single Center Study on 2606 Patients

Various techniques of laparoscopic Roux-en-Y gastric bypass have been described. We completely standardized this procedure to minimize its sometimes substantial morbidity and mortality. This study describes our experience with the standardized fully stapled laparoscopic Roux-en-Y gastric bypass (FS-LRYGB) and its influence on the 30-day morbidity and mortality.status: publishe