Liver transplantation in Latin America: reality and challenges.

Healthcare systems in Latin America are broadly heterogeneous, but all of them are burdened by a dramatic rise in liver disease. Some challenges that these countries face include an increase in patients requiring a transplant, insufficient rates of organ donation, delayed referral, and inequitable or suboptimal access to liver transplant programs and post-transplant care. This could be improved by expanding the donor pool through the implementation of education programs for citizens and referring physicians, as well as the inclusion of extended criteria donors, living donors and split liver transplantation.

Sofosbuvir plus glecaprevir/pibrentasvir as salvage therapy after liver transplantation in NS5A inhibitor-experienced patients. A case series.

Background: Treatment of chronic hepatitis C virus (HCV) infection with direct-acting antivirals achieves a sustained virologic response rate higher than 95%. However, virologic failure remains a clinical challenge, and data on retreatment are limited, especially in special populations such as liver transplant (LT) recipients.

Objectives: This study evaluated the sofosbuvir plus glecaprevir-pibrentasvir (GLE/PIB) regimen in LT recipients who had failed to a nonstructural protein 5A (NS5A) inhibitor-based regimen.

International survey among hepatologists and pulmonologists on the hepatic hydrothorax: plea for recommendations.

Background: The Hepatic hydrothorax is a pleural effusion related to portal hypertension; its diagnosis and therapeutic management may be difficult. The aims of this article are which follows: To gather the practices of hepatogastroenterologists or pulmonologists practitioners regarding the diagnosis and management of the hepatic hydrothorax.

Methods: Practitioners from 13 French- speaking countries were invited to answer an online questionnaire on the hepatic hydrothorax diagnosis and its management.

Portopulmonary Hypertension: An Updated Review.

Portal hypertension may have major consequences on the pulmonary vasculature due to the complex pathophysiological interactions between the liver and lungs. Portopulmonary hypertension (PoPH), a subset of group 1 pulmonary hypertension (PH), is a serious pulmonary vascular disease secondary to portal hypertension, and is the fourth most common subtype of pulmonary arterial hypertension. It is most commonly observed in cirrhotic patients; however, patients with noncirrhotic portal hypertension can also develop it.

A real-world experience of SARS-CoV-2 infection in a tertiary referral centre of Montréal: Unexpected low prevalence and low mortality.

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with chronic liver disease (CLD) and liver transplant (LT) recipients remains a concern. The aim of this study was to report the impact of coronavirus disease 2019 (COVID-19) infection among patients at the tertiary health care centre (CHUM) during the first wave of the SARS-CoV-2 pandemic.

Methods: This real-world, retrospective cohort included all patients admitted to our liver unit and/or seen as an outpatient with CLD with or without cirrhosis and/or LT recipients who tested positive to SARS-CoV-2 infection.

Cirrhosis etiology trends in developing countries: Transition from infectious to metabolic conditions. Report from a multicentric cohort in central Mexico.

Background: Cirrhosis is a public health threat associated with high mortality. Alcoholic Liver Disease (ALD) is the leading cause in Latin America and Metabolic Associated Fatty Liver Disease (MAFLD) in western countries. In Mexico, ALD and chronic Hepatitis C Virus infection (HCV) were the most frequent aetiologies during the past decades.

One-year outcome of patients with cirrhosis who developed spontaneous bacterial empyema: A cohort study.

Objective: This study aimed to evaluate outcomes in cirrhotic patients diagnosed with spontaneous bacterial empyema (SBE) compared with those without this complication.

Methods: We performed a retrospective cohort study of cirrhotic patients from a tertiary care center. The primary outcome was time to death or liver transplantation (LT) within one year after diagnosis of infection.

Macrophage autophagy protects against hepatocellular carcinogenesis in mice.

Autophagy is a lysosomal degradation pathway of cellular components that regulates macrophage properties. Macrophages are critically involved in tumor growth, metastasis, angiogenesis and immune suppression. Here, we investigated whether macrophage autophagy may protect against hepatocellular carcinoma (HCC).

Non-invasive diagnosis and follow-up of chronic infection with Hepatitis C Virus.

Hepatitis C virus (HCV) infection is a major cause of chronic liver disease. Clinical care for patients with HCV-related liver disease has advanced considerably with developments in screening, diagnostic procedures to evaluate liver fibrosis and improvements in therapy with pangenotypic direct antivirals and prevention. These AFEF guidelines on the non-invasive diagnosis and follow up of chronic infection with HCV describe the optimal management of HCV positive patients with non-invasive methods in screening, in assessing viral disease and liver fibrosis and the follow-up of these patients according to the value of FibroScan®, Fibrotest® or Fibrometer®.

Hepatocellular carcinoma: French Intergroup Clinical Practice Guidelines for diagnosis, treatment and follow-up (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO, AFEF, SIAD, SFR/FRI).

Introduction: This document is a summary of the French Intergroup guidelines regarding the management of hepatocellular carcinoma (HCC) published in March 2019.

Method: It is a collaborative work under the auspices of most of the French medical societies involved in the management of HCC. It is based on the previous guidelines published in 2017.

A Phenyl-Pyrrolidine Derivative Reveals a Dual Inhibition Mechanism of Myocardial Mitochondrial Permeability Transition Pore, Which Is Limited by Its Myocardial Distribution.

Mitochondrial permeability transition pore (mPTP) opening is a key event in cell death during myocardial ischemia reperfusion. Inhibition of its modulator cyclophilin D (CypD) by cyclosporine A (CsA) reduces ischemia-reperfusion injury. The use of cyclosporine A in this indication is debated; however, targeting mPTP remains a major goal to achieve.

Real-world efficacy and safety of direct-acting antiviral drugs in patients with chronic hepatitis C and inherited blood disorders.

Background: Patients with inherited blood disorders (IBLD) have a high risk of hepatitis C virus (HCV) infection. The aim of this work was to assess the efficacy and safety of HCV direct-acting antiviral (DAA)-based treatment in patients with IBLD and chronic HCV infection.

Methods: Twenty-seven patients (25 with sickle cell disease, 1 with β-thalassemia and 1 with hemoglobin D-Punjab), including 3 with compensated cirrhosis, were included.

Outcomes following SARS-CoV-2 infection in liver transplant recipients: an international registry study.

Background: Despite concerns that patients with liver transplants might be at increased risk of adverse outcomes from COVID-19 because of coexisting comorbidities and use of immunosuppressants, the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on this patient group remains unclear. We aimed to assess the clinical outcomes in these patients.

Methods: In this multicentre cohort study, we collected data on patients with laboratory-confirmed SARS-CoV-2 infection, who were older than 18 years, who had previously received a liver transplant, and for whom data had been submitted by clinicians to one of two international registries (COVID-Hep and SECURE-Cirrhosis) at the end of the patient's disease course.

Cerebrovascular events and outcomes in hospitalized patients with COVID-19: The SVIN COVID-19 Multinational Registry.

Background: Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has been associated with a significant risk of thrombotic events in critically ill patients.

Aim: To summarize the findings of a multinational observational cohort of patients with SARS-CoV-2 and cerebrovascular disease.

Methods: Retrospective observational cohort of consecutive adults evaluated in the emergency department and/or admitted with coronavirus disease 2019 (COVID-19) across 31 hospitals in four countries (1 February 2020-16 June 2020).

MK-571, a Cysteinyl Leukotriene Receptor 1 Antagonist, Inhibits Hepatitis C Virus Replication.

The quinoline MK-571 is the most commonly used inhibitor of multidrug resistance protein-1 (MRP-1) but was originally developed as a cysteinyl leukotriene receptor 1 (CysLTR1) antagonist. While studying the modulatory effect of MRP-1 on anti-hepatitis C virus (HCV) direct-acting antiviral (DAA) efficiency, we observed an unexpected anti-HCV effect of compound MK-571 alone. This anti-HCV activity was characterized in Huh7.

Small-Molecule Inhibitors of Cyclophilins Block Opening of the Mitochondrial Permeability Transition Pore and Protect Mice From Hepatic Ischemia/Reperfusion Injury.

Background & Aims: Hepatic ischemia/reperfusion injury is a complication of liver surgery that involves mitochondrial dysfunction resulting from mitochondrial permeability transition pore (mPTP) opening. Cyclophilin D (PPIF or CypD) is a peptidyl-prolyl cis-trans isomerase that regulates mPTP opening in the inner mitochondrial membrane. We investigated whether and how recently created small-molecule inhibitors of CypD prevent opening of the mPTP in hepatocytes and the resulting effects in cell models and livers of mice undergoing ischemia/reperfusion injury.

Frequent Antiviral Treatment Failures in Patients Infected With Hepatitis C Virus Genotype 4, Subtype 4r.

Hepatitis C virus (HCV) genotype 4 is highly heterogeneous. HCV subtype 4r has been suggested to be less responsive to direct-acting antiviral (DAA) drug treatment than other genotype 4 subtypes. Among 537 DAA-treated patients who experienced a virological failure (VF) in France between 2015 and 2018, 121 (22.

Importance of Evaluating Cardiovascular Risk and Hepatic Fibrosis in Patients With Newly Diagnosed Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is a well-recognized health problem, with an estimated worldwide prevalence of 25%. It is associated with metabolic syndrome (MetSx) and complications such as cirrhosis and hepatocellular carcinoma. However, the main cause of death in patients with NAFLD is derived from cardiovascular disease, and outcome seems to be determined by the degree of hepatic fibrosis.

Characterization of the Anti-Hepatitis C Virus Activity of New Nonpeptidic Small-Molecule Cyclophilin Inhibitors with the Potential for Broad Anti-Flaviviridae Activity.

Although members of the display high incidence, morbidity, and mortality rates, the development of specific antiviral drugs for each virus is unlikely. Cyclophilins, a family of host peptidyl-prolyl isomerases (PPIases), play a pivotal role in the life cycles of many viruses and therefore represent an attractive target for broad-spectrum antiviral development. We report here the pangenotypic anti-hepatitis C virus (HCV) activity of a small-molecule cyclophilin inhibitor (SMCypI).

Tunable dual-band graphene-based infrared reflectance filter.

We experimentally demonstrated an actively tunable optical filter that controls the amplitude of reflected long-wave-infrared light in two separate spectral regions concurrently. Our device exploits the dependence of the excitation energy of plasmons in a continuous and unpatterned sheet of graphene on the Fermi-level, which can be controlled via conventional electrostatic gating. The filter enables simultaneous modification of two distinct spectral bands whose positions are dictated by the device geometry and graphene plasmon dispersion.

Interleukins-17 and 27 promote liver regeneration by sequentially inducing progenitor cell expansion and differentiation.

Liver progenitor cells (LPCs)/ductular reactions (DRs) are associated with inflammation and implicated in the pathogenesis of chronic liver diseases. However, how inflammation regulates LPCs/DRs remains largely unknown. Identification of inflammatory processes that involve LPC activation and expansion represent a key step in understanding the pathogenesis of liver diseases.

Graphene-Insulator-Semiconductor Junction for Hybrid Photodetection Modalities.

A sensitive optical detector is presented based on a deeply depleted graphene-insulator-semiconducting (DGIS) junction, which offers the possibility of simultaneously leveraging the advantages of both charge integration and localized amplification. Direct read-out and built-in amplification are accomplished via photogating of a graphene field-effect transistor (GFET) by carriers generated within a deeply depleted low-doped silicon substrate. Analogous to a depleted metal-oxide-semiconducting junction, photo-generated charge collects in the potential well that forms at the semiconductor/insulator interface and induces charges of opposite polarity within the graphene film modifying its conductivity.

Designing graphene absorption in a multispectral plasmon-enhanced infrared detector.

We have examined graphene absorption in a range of graphene-based infrared devices that combine either monolayer or bilayer graphene with three different gate dielectrics. Electromagnetic simulations show that the optical absorption in graphene in these devices, an important factor in a functional graphene-based detector, is strongly dielectric-dependent. These simulations reveal that plasmonic excitation in graphene can significantly influence the percentage of light absorbed in the entire device, as well as the graphene layer itself, with graphene absorption exceeding 25% in regions where plasmonic excitation occurs.