Hepatitis B infection in patients with acute liver failure in the United States

Occult hepatitis B virus (HBV) infection has been reported in 30% to 50% of patients with acute liver failure (ALF) in small case series. The aim of this study was to determine the prevalence of occult HBV infection in a large series of ALF patients in the United States and the prevalence of precore and core promoter variants in patients with ALF caused by hepatitis B. Sera from patients in the US ALF study and liver, when available, were tested using nested polymerase chain reaction (PCR) with primers in the HBV S and precore regions. PCR-positive samples were sequenced. Sera and/or liver from 139 patients (39 males, 100 females; mean age, 42 years) enrolled between January 1998 and December 1999 were studied. Twelve patients were diagnosed with hepatitis B, 1 with hepatitis B+C+D coinfection, and 22 had indeterminate etiology. HBV DNA was detected in the sera of 9 (6%) patients; all 9 had ALF caused by hepatitis B. HBV genotypes A, B, C, and D were present in 4, 3, 1, and 1 patients, respectively. Seven of these 9 patients had precore and/or core promoter variants. Liver from 19 patients were examined. HBV DNA was detected in the liver of 3 patients with ALF caused by hepatitis B, but in none of the remaining 16 patients with non-B ALF. Contrary to earlier reports, occult HBV infection was not present in this large series of ALF patients in the United States. HBV precore and/or core promoter variants were common among US patients with ALF caused by hepatitis B. (H EPATOLOGY 2001;33:972-976.)Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34782/1/510330426_ftp.pd

Hepatitis C treatment outcomes in Australian clinics

Objective: To determine hepatitis C (HCV) treatment effectiveness and predictors of response in the “real-world” Australian clinic setting.Design, setting and participants: Patients with chronic HCV, who were HCV-treatment-naive at enrolment, and were then treated with standard therapy (pegylated interferon-α plus ribavirin), were recruited prospectively through a national network of 24 HCV clinics between April 2008 and December 2009. Patients were interviewed and a medical record review was conducted at enrolment and at routine follow-up clinic visits.Main outcome measures: Proportion of patients achieving a sustained virological response (SVR), predictors of SVR, and impact of treatment on biochemical markers of liver disease (alanine aminotransferase levels and aspartate aminotransferase-to-platelet ratio index scores).Results: The SVR by intention to treat was 60% (327/550). Infection with HCV genotype 2 or 3 (compared with genotype 1) was an independent predictor of SVR (odds ratio [OR], 2.45; 95% CI, 1.70–3.52), while HIV coinfection (OR, 0.28; 95% CI, 0.10–0.82), cirrhosis (OR, 0.38; 95% CI, 0.18–0.81), and increased body mass index for ≥ 30 kg/m2 v ≤ 25 kg/m2 (OR, 0.58; 95% CI, 0.35–0.96) were independently associated with lower SVR. There was a significant improvement in biochemical markers of liver disease following SVR (

Non-physician endoscopists: A systematic review

AIM: To examine the available evidence on safety, competency and cost-effectiveness of nursing staff providing gastrointestinal (GI) endoscopy services

Third-generation anti-CD19 chimeric antigen receptor T-cells incorporating a TLR2 domain for relapsed or refractory B-cell lymphoma: a phase I clinical trial protocol (ENABLE).

INTRODUCTION: Autologous T-cells transduced to express a chimeric antigen receptor (CAR) directed against CD19 elicit high response rates in relapsed or refractory (r/r) B-cell non-Hodgkin lymphoma (B-NHL). However, r/r B-NHL remissions are durable in fewer than half of recipients of second-generation CAR T-cells. Third-generation (3G) CARs employ two costimulatory domains, resulting in improved CAR T-cell efficacy in vitro and in animal models in vivo. This investigator-initiated, phase I dose escalation trial, termed ENABLE, will investigate the safety and preliminary efficacy of WZTL-002, comprising autologous T-cells expressing a 3G anti-CD19 CAR incorporating the intracellular signalling domains of CD28 and Toll-like receptor 2 (TLR2) for the treatment of r/r B-NHL. METHODS AND ANALYSIS: Eligible participants will be adults with r/r B-NHL including diffuse large B-cell lymphoma and its variants, follicular lymphoma, transformed follicular lymphoma and mantle cell lymphoma. Participants must have satisfactory organ function, and lack other curative options. Autologous T-cells will be obtained by leukapheresis. Following WZTL-002 manufacture and product release, participants will receive lymphodepleting chemotherapy comprising intravenous fludarabine and cyclophosphamide. A single dose of WZTL-002 will be administered intravenously 2 days later. Targeted assessments for cytokine release syndrome and immune cell effector-associated neurotoxicity syndrome, graded by the American Society Transplantation and Cellular Therapy criteria, will be made. A modified 3+3 dose escalation scheme is planned starting at 5×104 CAR T-cells/kg with a maximum dose of 1×106 CAR T-cells/kg. The primary outcome of this trial is safety of WZTL-002. Secondary outcomes include feasibility of WZTL-002 manufacture and preliminary measures of efficacy. ETHICS AND DISSEMINATION: Ethical approval for the study was granted by the New Zealand Health and Disability Ethics Committee (reference 19/STH/69) on 23 June 2019 for Protocol V.1.2. Trial results will be reported in a peer-reviewed journal, and results presented at scientific conferences or meetings. TRIAL REGISTRATION NUMBER: NCT04049513

Distribution of interferon lambda-3 gene polymorphisms in Australian patients with previously untreated genotype 1 chronic hepatitis C: analysis from the PREDICT and CHARIOT studies

Background and Aims: The aim of this study was to examine the distribution of interferon lambda-3 (IFN-λ3) gene polymorphisms in previously untreated Australian patients with genotype 1 (Gt1) chronic hepatitis C (CHC) and to compare the IFN-λ3 genotype frequency among the different ethnic populations. Methods: This was a prospective, multicenter, observational study undertaken by the Australian Liver Association Clinical Research Network. Eligible subjects had Gt1 CHC and were being considered for and/or undergoing treatment. IFN-λ3 single nucleotide polymorphisms were genotyped by the Applied Biosystems's Taqman single nucleotide polymorphism genotyping assay. Results: Between May 2012 and June 2012, 1132 patients were recruited from 38 treatment clinics across Australia. Also, 561 subjects from the CHARIOT (collaborative group hepatitis C study using high dose Pegasys RBV Induction dose in genotype one) study of high-dose interferon who had baseline serum available were retrospectively tested. The overall frequency of IFN-λ3 rs12979860 CC/CT/TT genotypes was 36%, 52%, and 12%, and that of rs8099917 TT/TG/GG genotypes was 54%, 41%, and 5%, respectively. The prevalence of the favorable IFN-λ3 rs12979860 CC and rs8099917 TT genotypes in Causcasians, Asians, Aboriginals, Maori/Pacific Islanders, and Mediterraneans was 32% and 52%, 80% and 86%, 33% and 63%, 77% and 88%, and 19% and 29%, respectively. Compared with Caucasians, the frequency of IFN-λ3 CC was significantly higher among Asians (P < 0.0001) and Maori/Pacific Islander subjects (P < 0.0001). Conclusions: The distribution of IFN-λ3 polymorphisms among untreated patients with Gt1 CHC in Australia appears similar to that reported from North America. The frequency of the favorable response alleles varies considerably according to ethnicity, being more common in self-reported Asians and Maori/Pacific Islanders than Caucasians, Aboriginals, and Mediterraneans