Demographics and outcomes of hepatitis B and D: A 10-year retrospective analysis in a Swiss tertiary referral center.

Hepatitis B virus (HBV) is a major global health challenge with approximately 250-350 million chronically infected individuals. An improved understanding of the demographic features and outcomes of chronic HBV infection and hepatitis D virus (HDV) infection in low-endemic areas may improve prevention, early identification and management both at individual and community levels. Here, we retrospectively analyzed the demographic and clinical characteristics, treatment rates and outcomes of adult patients with chronic HBV infection with or without HDV coinfection examined at Lausanne University Hospital, Switzerland over a 10-year period. We analyzed the medical records of all adult patients with chronic HBV and HDV infection examined in our center between 2007 and 2016. Liver-related outcome was defined as the occurrence of cirrhosis, hepatocellular carcinoma, liver transplantation or liver-related death. Analyses were performed using logistic regression and results were reported as odds ratio (OR) and 95% confidence interval (CI). Of 672 consecutive patients, 421 (62.6%) were male, median age was 36 years (interquartile range, 28-46 years), and 233 (34.7%) were of African origin. The prevalence of HDV coinfection was 7.1% and the proportion of anti-HDV-positive patients with detectable HDV RNA was 70.0%. In multivariate analysis, HDV coinfection was the strongest predictor for liver-related outcome (OR 6.06, 95% CI 2.93-12.54, p<0.001), followed by HBeAg positivity (OR 2.47, 95% CI 1.30-4.69, p = 0.006), age (OR per 10-year increase 2.03, 95% CI 1.63-2.52, p<0.001) and sex (OR for female 0.39, 95% CI 0.22-0.71, p = 0.002). The predictive accuracy of the multivariate model was high (receiver operator characteristic area under the curve 0.81). This retrospective study underscores the importance of migration in the epidemiology of chronic hepatitis B in low-endemic areas. HDV coinfection, HBeAg positivity and age predicted liver-related outcomes while female sex had a protective effect

Sofosbuvir add-on to ribavirin for chronic hepatitis E in a cirrhotic liver transplant recipient: a case report.

Chronic hepatitis E represents an emerging challenge in organ transplantation, as there are currently no established treatment options for patients who fail to clear hepatitis E virus (HEV) following reduction of immunosuppressive therapy and/or treatment with ribavirin. Sofosbuvir has shown antiviral activity against HEV in vitro but clinical utility in vivo is unknown. We describe a 57-year-old liver transplant recipient with decompensated graft cirrhosis due to chronic hepatitis E. Reduction of immunosuppressive treatment as well ribavirin alone for 4 months did not result in viral clearance. Add-on of sofosbuvir for 6 months was associated with HEV RNA becoming undetectable in plasma. However, sustained viral clearance could not be achieved. Sofosbuvir may have some antiviral activity against HEV when added to ribavirin. However, this did not suffice to yield sustained viral clearance. Our well-characterized observation emphasizes the need for new treatment options to cure chronic hepatitis E in the setting of organ transplantation

Clinical validation of Anyplex? II HPV HR Detection according to the guidelines for HPV test requirements for cervical cancer screening.

BACKGROUND: Anyplex? II HPV HR Detection (Seegene, Seoul, Korea) is a multiplex real-time PCR using tagging oligonucleotide cleavage and extension (TOCE) technology for simultaneous detection and genotyping of 14 high-risk (HR) HPV types, including HPV16 and HPV18. OBJECTIVES: To evaluate whether the clinical performance and reproducibility of Anyplex? II HPV HR Detection meet the international consensus guidelines for HPV test requirements for cervical cancer screening [1]. STUDY DESIGN: The clinical performance of Anyplex? II HPV HR Detection for detecting cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was determined relative to that of the reference assay, i.e., HR HPV GP5+/6+-PCR-EIA, by analysis of a total of 879 cervical liquid based cytology (LBC) specimens from a screening population, of which 60 were from women with CIN2+. The intra-laboratory reproducibility and inter-laboratory agreement were determined on 509 LBC samples, of which 172 were positive by the reference assay. RESULTS: Anyplex? II HPV HR Detection showed a clinical sensitivity for CIN2+ of 98.3% (59/60; 95% CI: 89.1-99.8) and a clinical specificity for CIN2+ of 93.6% (764/816; 95% CI: 89.8-96.1). The clinical sensitivity and specificity were non-inferior to those of HR HPV GP5+/6+-PCR-EIA (non-inferiority score test: P=0.005 and P=0.023, respectively). Both intra-laboratory reproducibility (96.8%; 95% CI: 95.3-98.1; kappa value of 0.93) and inter-laboratory agreement (96.0%; 95% CI: 94.3-97.4; kappa value of 0.91) were high. CONCLUSIONS: Anyplex? II HPV HR Detection performs clinically non-inferior to HR HPV GP5+/6+-PCR-EIA. Anyplex? II HPV HR Detection complies with international consensus validation metrics for HPV DNA tests for cervical cancer screening [1]

Predicting Survival for Veno-Arterial ECMO Using Conditional Inference Trees-A Multicenter Study

BACKGROUND Despite increasing use and understanding of the process, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) therapy is still associated with considerable mortality. Personalized and quick survival predictions using machine learning methods can assist in clinical decision making before ECMO insertion. METHODS This is a multicenter study to develop and validate an easy-to-use prognostic model to predict in-hospital mortality of VA-ECMO therapy, using unbiased recursive partitioning with conditional inference trees. We compared two sets with different numbers of variables (small and comprehensive), all of which were available just before ECMO initiation. The area under the curve (AUC), the cross-validated Brier score, and the error rate were applied to assess model performance. Data were collected retrospectively between 2007 and 2019. RESULTS 837 patients were eligible for this study; 679 patients in the derivation cohort (median (IQR) age 60 (49 to 69) years; 187 (28%) female patients) and a total of 158 patients in two external validation cohorts (median (IQR) age 57 (49 to 65) and 70 (63 to 76) years). For the small data set, the model showed a cross-validated error rate of 35.79% and an AUC of 0.70 (95% confidence interval from 0.66 to 0.74). In the comprehensive data set, the error rate was the same with a value of 35.35%, with an AUC of 0.71 (95% confidence interval from 0.67 to 0.75). The mean Brier scores of the two models were 0.210 (small data set) and 0.211 (comprehensive data set). External validation showed an error rate of 43% and AUC of 0.60 (95% confidence interval from 0.52 to 0.69) using the small tree and an error rate of 35% with an AUC of 0.63 (95% confidence interval from 0.54 to 0.72) using the comprehensive tree. There were large differences between the two validation sets. CONCLUSIONS Conditional inference trees are able to augment prognostic clinical decision making for patients undergoing ECMO treatment. They may provide a degree of accuracy in mortality prediction and prognostic stratification using readily available variables

A humanized monoclonal antibody that inhibits platelet-surface ERp72 reveals a role for ERp72 in thrombosis

Background: Within the endoplasmic reticulum, thiol isomerase enzymes modulate the formation and rearrangement of disulphide bonds in newly folded proteins entering the secretory pathway to ensure correct protein folding. In addition to their intracellular importance, thiol isomerases have been recently identified to be present on the surface of a number of cell types where they are important for cell function. Several thiol isomerases are known to be present on the resting platelet surface including PDI, ERp5 and ERp57 and levels are increased following platelet activation. Inhibition of the catalytic activity of these enzymes results in diminished platelet function and thrombosis. Aim: We previously determined that ERp72 is present at the resting platelet surface and levels increase upon platelet activation, however its functional role on the cell surface was unclear. We aimed to investigate the role of ERp72 in platelet function and its role in thrombosis. Methods: Using HuCAL technology, fully humanised Fc-null anti-ERp72 antibodies were generated. Eleven antibodies were screened for their ability to inhibit ERp72 activity and the most potent inhibitory antibody (anti-ERp72) selected for further testing in platelet functional assays. Results and conclusions: Anti-ERp72 inhibited platelet aggregation, granule secretion, calcium mobilisation and integrin activation revealing an important role for extracellular ERp72 in the regulation of platelet activation. Consistent with this, infusion of anti-ERp72 into mice protected against thrombosis

Predictors associated with mortality of extracorporeal life support therapy for acute heart failure: single-center experience with 679 patients

Background: Extracorporeal life support (ECLS) therapy is increasingly used for cardiac and respiratory support postcardiotomy, refractory cardiogenic shock and cardiopulmonary resuscitation. This study aims to describe in-hospital mortality of patients requiring ECLS, identify independent predictors associated with mortality and analyze changes of mortality over time. Methods: This retrospective study includes all adult ECLS cases at the University Hospital Zurich, a designated ECLS center in Switzerland, in the period 2007 to 2019. Results: ECLS therapy was required in 679 patients (median age 60 years, 27.5% female). In-hospital mortality was 55.5%. Cubic spline interpolation did not detect evidence for a change in mortality over the whole period of 13 years. In-hospital mortality significantly varied between ECLS indications: 70.7% (152/215) for postcardiotomy, 67.9% (108/159) for cardiopulmonary resuscitation, 47.0% (110/234) for refractory cardiogenic shock, and 9.9% (7/71) for lung transplantation and expansive thoracic surgery (P<0.001). Logistic regression modelling showed excellent discrimination in the receiver operating characteristic (ROC) area under the curve (AUC) of 0.89 [95% confidence interval (CI): 0.87-0.92] and identified significant mortality predictors: age, simplified acute physiology score (SAPS) II, as well as new liver failure and each allogenic blood transfusion unit given per day. ECLS after cardiopulmonary resuscitation was associated with significantly higher mortality compared to ECLS for refractory cardiogenic shock. Conclusions: In-hospital mortality of patients treated with ECLS therapy is high. Outcomes have not changed significantly in the observed period. We identified age, SAPS II, new liver failure and each allogenic blood transfusion unit given per day as independent mortality predictors. Knowledge of predictors strongly associated with in-hospital mortality may affect future decisions about ECLS indications and the respective management to use this elaborate therapy more effectively. Keywords: Extracorporeal circulation; extracorporeal life support (ECLS)/extracorporeal membrane oxygenation (ECMO); mortality; outcome; predictor

Absence of hepatitis delta infection in a large rural HIV cohort in Tanzania

OBJECTIVES: The epidemiological and clinical determinants of hepatitis delta virus (HDV) infection in Sub-Saharan Africa are ill-defined. The prevalence of HDV infection was determined in HIV/hepatitis B virus (HBV) co-infected individuals in rural Tanzania. METHODS: All hepatitis B virus (HBV)-infected adults under active follow-up in the Kilombero and Ulanga Antiretroviral Cohort (KIULARCO) were screened for anti-HDV antibodies. For positive samples, a second serological test and nucleic acid amplification were performed. Demographic and clinical characteristics at initiation of antiretroviral therapy (ART) were compared between anti-HDV-negative and positive patients. RESULTS: Among 222 HIV/HBV co-infected patients on ART, 219 (98.6%) had a stored serum sample available and were included in the study. Median age was 37 years, 55% were female, 46% had World Health Organization stage III/IV HIV disease, and the median CD4 count was 179 cells/mul. The prevalence of anti-HDV positivity was 5.0% (95% confidence interval 2.8-8.9%). There was no significant predictor of anti-HDV positivity. HDV could not be amplified in any of the anti-HDV-positive patients and the second serological test was negative in all of them. CONCLUSIONS: No confirmed case of HDV infection was found among over 200 HIV/HBV co-infected patients in Tanzania. As false-positive serology results are common, screening results should be confirmed with a second test