Spontaneous Clearance After Relapse Following Direct-Acting Antiviral Treatment for Chronic HCV Infection.

Background & Aims: Direct-acting antivirals (DAAs) cure most cases of chronic hepatitis C virus (HCV) infection. However, a small percentage of patients relapse with reappearance of viremia after a full course of therapy. Although most who relapse require retreatment, some patients spontaneously clear HCV without additional therapy.

Goals of Treatment for Improved Survival in Primary Biliary Cholangitis: Treatment Target Should Be Bilirubin Within the Normal Range and Normalization of Alkaline Phosphatase.

Introduction: In primary biliary cholangitis (PBC), bilirubin and alkaline phosphatase (ALP) are widely established as independent predictors of prognosis. Current treatment goals do not aim for normalization of surrogate markers because their association with survival has not been defined.

Methods: The patient cohort from the GLOBAL PBC Study Group was used, comprising of long-term follow-up data from European and North American centers.

A Phosphanyl-Phosphagallene that Functions as a Frustrated Lewis Pair.

Phosphagallenes (1 a/1 b) featuring double bonds between phosphorus and gallium were synthesized by reaction of (phosphanyl)phosphaketenes with the gallium carbenoid Ga(Nacnac) (Nacnac=HC[C(Me)N(2,6-i-Pr C H )] ). The stability of these species is dependent on the saturation of the phosphanyl moiety. 1 a, which bears an unsaturated phosphanyl ring, rearranges in solution to yield a spirocyclic compound (2) which contains a P=P bond.

Hepatitis C models of care: approaches to elimination.

Hepatitis C direct-acting antivirals (DAAs) have an efficacy of 95% or greater, with pangenotypic options. Many regions in Canada have recently abolished the need to demonstrate fibrosis before treatment with DAAs, and several combination therapies are available under public and private insurance coverage. As a result, efforts to increase treatment are largely focused on engaging specific populations and providers.

Nonsurgical management of advanced hepatocellular carcinoma: a clinical practice guideline.

Background: Practice guidelines based on a systematic review of the literature regarding the nonsurgical management of hepatocellular carcinoma (hcc) in North America are lacking. Resection and transplantation are the foundations for cure of hcc; however, most patients are diagnosed at an advanced stage, precluding those curative treatments. A number of local or regional therapies are used and are followed by systemic therapy for advanced or progressive disease.

Myelodysplastic syndromes: a review of therapeutic progress over the past 10 years.

Introduction: Myelodysplastic syndromes (MDS) represent a range of bone marrow disorders, with patients affected by cytopenias and risk of progression to AML. There are limited therapeutic options available for patients, including hypomethylating agents (azacitidine/decitabine), growth factor support, lenalidomide, and allogeneic stem cell transplant.

Areas Covered: This review provides an overview of the progress made over the past decade for emerging therapies for lower- and higher-risk MDS (MDS-HR).

The impact of tocilizumab on anxiety and depression in patients with rheumatoid arthritis.

Background: Mood disorders, such as anxiety and depression, are extremely prevalent among patients with rheumatoid arthritis (RA). In this study, we assessed the impact of treatment with tocilizumab (TCZ), an IL-6 antagonist, upon anxiety and depressive symptoms in a cohort of RA patients.

Materials And Methods: Study participants were adults diagnosed with RA who received a weekly subcutaneous injection of tocilizumab for 24 weeks.

Short-course, direct-acting antivirals and ezetimibe to prevent HCV infection in recipients of organs from HCV-infected donors: a phase 3, single-centre, open-label study.

Background: An increasing percentage of potential organ donors are infected with hepatitis C virus (HCV). After transplantation from an infected donor, establishment of HCV infection in uninfected recipients is near-universal, with the requirement for post-transplant antiviral treatment. The aim of this study was to determine if antiviral drugs combined with an HCV entry blocker given before and for 7 days after transplant would be safe and reduce the likelihood of HCV infection in recipients of organs from HCV-infected donors.

Assessment of Treatment Strategies to Achieve Hepatitis C Elimination in Canada Using a Validated Model.

Importance: Achievement of the World Health Organization (WHO) target of eliminating hepatitis C virus (HCV) by 2030 will require an increase in key services, including harm reduction, HCV screening, and HCV treatment initiatives in member countries. These data are not available for Canada but are important for informing a national HCV elimination strategy.

Objective: To use a decision analytical model to explore the association of different treatment strategies with HCV epidemiology and HCV-associated mortality in Canada and to assess the levels of service increase needed to meet the WHO elimination targets by 2030.

Attentional prioritization in dual-task walking: Effects of stroke, environment, and instructed focus.

Background: The impact of high distraction, real-world environments on dual-task interference and flexibility of attentional prioritization during dual-task walking in people with stroke is unknown.

Research Question: How does a real-world environment affect dual-task performance and flexible task prioritization during dual-task walking in adults with and without stroke?

Methods: Adults with stroke (n = 29) as well as age-, gender-, and education-matched adults without stroke (n = 23) participated. Single and dual-task walking were examined in two different environments (lab hallway, hospital lobby).

The emergency department as a setting-specific opportunity for population-based hepatitis C screening: An economic evaluation.

Background And Aims: The World Health Organization's hepatitis C virus (HCV) elimination strategy recognizes the need for interventions that identify populations most affected by infection. The emergency department (ED) has been suggested as a setting for HCV screening. The study objective was to explore the health and economic impact of HCV screening in the ED setting.

The impact of SVR from direct-acting antiviral- and interferon-based treatments for HCV on hepatocellular carcinoma risk.

We evaluated the effect of sustained virologic response (SVR) from direct-acting antiviral (DAA)- and interferon-based treatments on hepatocellular carcinoma (HCC) risk in a large population-based cohort in Canada. We used data from the BC Hepatitis Testers Cohort, which includes ~1.3 million individuals tested for HCV since 1990, linked with healthcare administrative and registry datasets.

Reinfection Following Successful Direct-acting Antiviral Therapy for Hepatitis C Virus Infection Among People Who Inject Drugs.

Background: The aim of this analysis was to calculate the incidence of hepatitis C virus (HCV) reinfection and associated factors among 2 clinical trials of HCV direct-acting antiviral treatment in people with recent injecting drug use or currently receiving opioid agonist therapy (OAT).

Methods: Participants who achieved an end-of-treatment response in 2 clinical trials of people with recent injecting drug use or currently receiving OAT (SIMPLIFY and D3FEAT) enrolled between March 2016 and February 2017 in 8 countries were assessed for HCV reinfection, confirmed by viral sequencing. Incidence was calculated using person-time of observation and associated factors were assessed using Cox proportional hazard models.

Risk stratification in primary sclerosing cholangitis: comparison of biliary stricture severity on MRCP versus liver stiffness by MR elastography and vibration-controlled transient elastography.

Objectives: To compare biliary stricture severity on magnetic resonance cholangiopancreatography (MRCP), magnetic resonance elastography (MRE), and vibration-controlled transient elastography (VCTE) liver stiffness (LS) for evaluation of risk stratification and prognostication in primary sclerosing cholangitis (PSC).

Materials And Methods: Eighty-seven patients (31-61 years; 34 female/53 male) prospectively underwent biochemical testing, VCTE, MRCP, and MRE between January 2014 and July 2016. Correlation between the MRCP grading of PSC based on biliary stricture severity, LS on MRE and VCTE, and the Mayo Risk Score as well as the Amsterdam Oxford Prognostic Index (AOPI) were evaluated and compared.

The 8 Canadian Symposium on Hepatitis C virus: "Improving diagnosis and linkage to care".

Hepatitis C virus (HCV) affects approximately 250,000 Canadians. Although safe and effective (>95% cure rates) antiviral therapies have become available within the past 5 years, chronic HCV infection still remains a major driver of end-stage liver disease and liver transplantation. Both the Canadian Institute for Health Research and the Public Health Agency of Canada recognize the impact of HCV-related liver diseases and support the Canadian Network for Hepatitis C (CanHepC), a National network for the scientific study of hepatitis C that organizes an annual symposium as part of its knowledge translation mandate.

Serum alanine aminotransferase flares in chronic hepatitis B infection: the good and the bad.

Chronic hepatitis B virus (HBV) infection follows a dynamic and variable course. At different stages in the disease, hepatitis flares might occur, which can be challenging to predict and manage. Flares are believed to be primarily immune-mediated and might mark transitions to inactive disease or clearance of infection, but in certain scenarios they might also lead to hepatic decompensation or death.

Evaluation of Sustained Virologic Response as a Relevant Surrogate Endpoint for Long-term Outcomes of Hepatitis C Virus Infection.

Background: The causal link of sustained virologic response (SVR) with outcome has been challenged. With improved SVR rates with direct-acting antivirals (DAAs), the benefit of SVR would be expected to diminish if the association with outcome is not causal.

Methods: Data were collected for patients starting treatment with interferon (IFN) or DAAs between June 2006 and December 2016.

A Systematic Review and Meta-Analysis of Health Utilities in Patients With Chronic Hepatitis C.

Background: Chronic hepatitis C (CHC) is among the most burdensome infectious diseases in the world. Health utilities are a valuable tool for quantifying this burden and conducting cost-utility analysis.

Objective: Our study summarizes the available data on utilities in CHC patients.

Development of the Functional Assessment of Cancer Therapy-Immune Checkpoint Modulator (FACT-ICM): A toxicity subscale to measure quality of life in patients with cancer who are treated with ICMs.

Background: Patients with cancer who are treated with immune checkpoint modulators (ICMs) have their health-related quality of life (HRQOL) measured using general patient-reported outcome (PRO) tools. To the authors' knowledge, no instrument has been developed to date specifically for patients treated with ICMs. The objective of the current study was to develop a toxicity subscale PRO instrument for patients treated with ICMs to assess HRQOL.

Hepatitis B Virus RNA as Early Predictor for Response to Pegylated Interferon Alpha in HBeAg-Negative Chronic Hepatitis B.

Background: Hepatitis B virus RNA (HBV-RNA) is a novel serum biomarker that correlates with transcription of intrahepatic covalently closed circular (cccDNA), which is an important target for pegylated interferon (PEG-IFN) and novel therapies for functional cure. We studied HBV-RNA kinetics following PEG-IFN treatment and its potential role as a predictor to response in HBeAg-negative chronic hepatitis B (CHB) patients.

Methods: HBV-RNA levels were measured in 133 HBeAg-negative CHB patients treated in an international randomized controlled trial (PARC study).