An overview of recent treatment options for primary sclerosing cholangitis.

Primary sclerosing cholangitis (PSC) is a chronic hepatic dysfunction characterized by inflammatory and tissue-degenerative strictures of the biliary tree, leading to cirrhosis and cholangiocarcinoma. The pathophysiological mechanisms involve immune-mediated responses. Numerous treatment modalities targeting the inflammatory aspects have been suggested, but a consensus on the best treatment option is lacking.

Inhibition of phosphodiesterase 12 results in antiviral activity against several RNA viruses including SARS-CoV-2.

The 2',5'- oligoadenylate synthetase (OAS) - ribonuclease L (RNAseL) - phosphodiesterase 12 (PDE12) pathway is an essential interferon-induced effector mechanism against RNA virus infection. Inhibition of PDE12 leads to selective amplification of RNAseL activity in infected cells. We aimed to investigate PDE12 as a potential pan-RNA virus antiviral drug target and develop PDE12 inhibitors that elicit antiviral activity against a range of viruses.

Re-engineering the Cypriot General Healthcare System for Syndemics.

To date in Cyprus, there is no dedicated "Quality Improvement" body or Public Health authority. The long-awaited general healthcare system (known as GeSy or GHS) has been completed, mid-stream of the COVID-19 pandemic. A recently proposed resilience plan in response to the lessons learnt from the pandemic was put forward by the Government of the Republic of Cyprus to strengthen the capacity of the GHS and support public health defense.

Circulating IgG Levels in SARS-CoV-2 Convalescent Individuals in Cyprus.

Long-term persistence and the heterogeneity of humoral response to SARS-CoV-2 have not yet been thoroughly investigated. The aim of this work is to study the production of circulating immunoglobulin class G (IgG) antibodies against SARS-CoV-2 in individuals with past infection in Cyprus. Individuals of the general population, with or without previous SARS-CoV-2 infection, were invited to visit the Biobank at the Center of Excellence in Biobanking and Biomedical Research of the University of Cyprus.

Extensive Testing and Public Health Interventions for the Control of COVID-19 in the Republic of Cyprus between March and May 2020.

Coronavirus disease 2019 (COVID-19) has significantly affected the well-being of individuals worldwide. We herein describe the epidemiology of COVID-19 in the Republic of Cyprus during the first epidemic wave (9 March-3 May 2020). We analyzed surveillance data from laboratory-confirmed cases, including targeted testing and population screening.

New Approaches to the Treatment of Chronic Hepatitis B.

The currently recommended treatment for chronic hepatitis B virus (HBV) infection achieves only viral suppression whilst on therapy, but rarely hepatitis B surface antigen (HBsAg) loss. The ultimate therapeutic endpoint is the combination of HBsAg loss, inhibition of new hepatocyte infection, elimination of the covalently closed circular DNA (cccDNA) pool, and restoration of immune function in order to achieve virus control. This review concentrates on new antiviral drugs that target different stages of the HBV life cycle (direct acting antivirals) and others that enhance both innate and adaptive immunity against HBV (immunotherapy).

Developing a holistic contingency plan: Challenges and dilemmas for cancer patients during the COVID-19.

During the first quarter of 2020 the world is experiencing a pandemic of Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2), a novel beta coronavirus that is responsible for the 2019 novel coronavirus disease (COVID-19). The COVID-19 pandemic revealed that healthcare systems around the world were not prepared to deal with either the direct effects of the pandemic or with the indirect effects that are imposed on the health of patients with chronic disorders such as cancer patients. Some challenges and dilemmas currently faced during the pandemic include the management of cancer patients during the treatment and follow-up phases, the assessment of the safety of treatments currently used for the management of SARS-CoV-2 for use in cancer patients, the development of psychoeducation and emotional support for cancer patients and the safe conduct of clinical trials involving participation of cancer patients.

Development of hepatic pathology in GBV-B-infected red-bellied tamarins (Saguinus labiatus).

GB virus B (GBV-B) is a new world monkey-associated flavivirus used to model acute hepatitis C virus (HCV) infection. Critical for evaluation of antiviral or vaccine approaches is an understanding of the effect of HCV on the liver at different stages of infection. In the absence of longitudinal human tissue samples at defined time points, we have characterized changes in tamarins.

Quasispecies Changes with Distinctive Point Mutations in the Hepatitis C Virus Internal Ribosome Entry Site (IRES) Derived from PBMCs and Plasma.

The 5' untranslated region (UTR) of the hepatitis C virus (HCV) genome contains the internal ribosome entry site (IRES), a highly conserved RNA structure essential for cap-independent translation of the viral polyprotein. HCV, apart from the liver, is thought to be associated with lymphocyte subpopulations of peripheral blood mononuclear cells (PBMCs), in lymph nodes and brain tissue. In this study, RT-PCR, cloning, and sequence analysis were employed to investigate the quasispecies nature of the 5'UTR following extraction of viral RNA from PBMCs and plasma of HCV infected individuals.

Demographic changes of hepatitis B virus infection in Iran for the last two decades.

Aim: The objective of this study was to evaluate the impact of the hepatitis B virus (HBV) vaccination program, 24 years after its implementation, by analyzing patients with hepatitis B surface antigen (HBsAg) infection based on gender and age group.

Background: Since the launch of the first universal vaccination program against HBV in Iran in 1993, the epidemiological pattern of HBV prevalence may have changed in our country.

Methods: All data for this cross-sectional study were collected from medical records of HBsAg positive patients, who were referred to the Golhak and Armin private laboratories and also to the Gastrointestinal Department of Tehran's Taleghani Hospital and Day Hospital in Iran over a period of 5 years (2011-2016).

Hepatitis B viral replication influences the expression of natural killer cell ligands.

Background: Hepatitis B virus (HBV) is accounting for over one million deaths annually due to immune-mediated chronic liver damage. Natural killer (NK) cells are abundant in the liver and contribute in HBV persistence. NK cytotoxic effects are controlled by signals from activating and inhibitory receptors.

Hepatitis B virus basal core promoter mutations show lower replication fitness associated with cccDNA acetylation status.

In chronic hepatitis B virus (HBV) infection, variants with mutations in the basal core promoter (BCP) and precore region predominate and associate with more severe disease forms. Studies on their effect on viral replication remain controversial. Increasing evidence shows that epigenetic modifications of cccDNA regulate HBV replication and disease outcome.

The Epigenetic Control of Hepatitis B Virus Modulates the Outcome of Infection.

Epigenetic modifications are stable alterations in gene expression that do not involve mutations of the genetic sequence itself. It has become increasingly clear that epigenetic factors contribute to the outcome of chronic hepatitis B virus (HBV) infection by affecting cellular and virion gene expression, viral replication and the development of hepatocellular carcinoma. HBV persists in the nucleus of infected hepatocytes as a stable non-integrated covalently closed circular DNA (cccDNA) which functions as a minichromosome.

Determinants Involved in Hepatitis C Virus and GB Virus B Primate Host Restriction.

Unlabelled: Hepatitis C virus (HCV) only infects humans and chimpanzees, while GB virus B (GBV-B), another hepatotropic hepacivirus, infects small New World primates (tamarins and marmosets). In an effort to develop an immunocompetent small primate model for HCV infection to study HCV pathogenesis and vaccine approaches, we investigated the HCV life cycle step(s) that may be restricted in small primate hepatocytes. First, we found that replication-competent, genome-length chimeric HCV RNAs encoding GBV-B structural proteins in place of equivalent HCV sequences designed to allow entry into simian hepatocytes failed to induce viremia in tamarins following intrahepatic inoculation, nor did they lead to progeny virus in permissive, transfected human Huh7.

Interferon-based combination treatment for chronic hepatitis C in the era of direct acting antivirals.

The development of protease inhibitors (PIs) such as telaprevir and boceprevir constitutes a milestone in chronic hepatitis C antiviral treatment since it has achieved sustained virological response (SVR) rates of up to 75% in naïve and 29-88% in treatment-experienced patients with genotype 1 infection. Both require combination treatment with pegylated interferon (PEG-IFN) plus ribavirin (RBV) as PI monotherapy results in resistant mutations. New direct acting antiviral agents (DAAs) have recently been approved or their approval is imminent.

HBeAg negative variants and their role in the natural history of chronic hepatitis B virus infection.

Molecular virology methods including polymerase chain reaction, cloning and sequencing have revolutionised our understanding of viral genome variation. In the case of hepatitis B virus (HBV), sequencing studies have identified a number of virus variants normally found during the natural course of chronic infection. The appearance of the precore stop codon (with G-for-A substitution at position 1896) and basal core promoter (BCP) (with A-for-T and G-for-A, at positions 1762 and 1764, respectively) variants which reduce or abrogate hepatitis B e antigen (HBeAg) production, heralds the initiation of the seroconversion phase from HBeAg to anti-HBe positivity.

HCV NS5A co-operates with PKR in modulating HCV IRES-dependent translation.

Translation initiation of the Hepatitis C virus (HCV) genome is driven by an internal ribosome entry site (IRES), located within the 5' non-coding region. Several studies have suggested that different cellular non canonical proteins or viral proteins can regulate the HCV IRES activity. However, the role of the viral proteins on HCV translation remains controversial.

Changes in immune cell populations in the periphery and liver of GBV-B-infected and convalescent tamarins (Saguinus labiatus).

Flaviviruses related to hepatitis C virus (HCV) in suitable animal models may provide further insight into the role that cellular immunity contributes to spontaneous clearance of HCV. We characterised changes in lymphocyte populations in tamarins with an acute GBV-B infection, a hepatitis virus of the flaviviridae. Major immune cell populations were monitored in peripheral and intra-hepatic lymphocytes at high viraemia or following a period when peripheral virus was no longer detected.

Oral conditions associated with hepatitis C virus infection.

Hepatitis C virus (HCV) infection in more than 170 million chronically infected patients with no developed preventive vaccine is a globally important issue. In addition to expected hepatic manifestations, a number of extrahepatic manifestations, such as mixed cryoglobulinemia, glomerulonephritis, polyarteritis nodosa, rashes, renal disease, neuropathy, and lymphoma, have been reported following HCV infection, which are believed to be influenced by the virus or the host immune response. HCV combination therapy with pegylated interferon and ribavirin might be associated with side effects as well.

Dental treatment as a risk factor for hepatitis B and C viral infection. A review of the recent literature.

Background & Aim: Patients chronically infected either with hepatitis B (HBV) or hepatitis C virus (HCV) are at increased risk of developing cirrhosis, end stage liver disease and hepatocellular carcinoma. Different risk factors were found to be associated with the transmission of these viruses in various settings. HBV and HCV transmission seems to be also acquired by non-parenteral and non-sexual routes.

Seroepidemiology of hepatitis A and E virus infections in Tehran, Iran: a population based study.

Hepatitis A virus (HAV) and hepatitis E virus (HEV) are enteric hepatotropic viruses and their prevalence is related to the sanitary conditions of the region under investigation. There are only a few studies on the seroepidemiology of these two viruses in the general Iranian population. The purpose of this investigation was to measure the prevalence of hepatitis A and E infections in the general population.

Direct acting antivirals for the treatment of chronic viral hepatitis.

The development and evaluation of antiviral agents through carefully designed clinical trials over the last 25 years have heralded a new dawn in the treatment of patients chronically infected with the hepatitis B and C viruses, but not so for the D virus (HBV, HCV, and HDV). The introduction of direct acting antivirals (DDAs) for the treatment of HBV carriers has permitted the long-term use of these compounds for the continuous suppression of viral replication, whilst in the case of HCV in combination with the standard of care [SOC, pegylated interferon (PegIFN), and ribavirin] sustained virological responses (SVRs) have been achieved with increasing frequency. Progress in the case of HDV has been slow and lacking in significant breakthroughs.

Oral fluid and hepatitis A, B and C: a literature review.

Background And Aims: Viral hepatitis is a significant global health problem that, depending upon the virus, affects individuals of the developing and/or developed world. In recent years, there has been renewed interest in whether oral fluids can be considered as a source of viral hepatitis transmission and whether oral fluid, in particular, whole saliva, may be a useful source for viral detection as part of the diagnosis and monitoring of viral hepatitis. The aim of this article was to review current data concerning the possible carriage of the hepatitis A, B and C viruses within saliva and gingival crevicular fluid.