Skin advanced glycation end-products as indicators of the metabolic profile in diabetes mellitus: correlations with glycemic control, liver phenotypes and metabolic biomarkers.

Introduction: The production of advanced glycation end-products (AGEs) is a key pathomechanism related to the complications of diabetes mellitus. The measurement of HbA1c as one of the AGEs is widely used in the clinic, but also other proteins undergo glycation in the course of diabetes. Here, we measure skin AGEs (SAGEs) in patients with diabetes type 1 (DM1) and type 2 (DM2) and correlate them with metabolic markers as well as non-invasively measured liver fibrosis and steatosis.

A phase 2 dose-finding study of lonafarnib and ritonavir with or without interferon alpha for chronic delta hepatitis.

Background And Aims: Proof-of-concept studies demonstrated lonafarnib (LNF), a first-in-class oral prenylation inhibitor, efficacy in patients infected with HDV. The lonafarnib with ritonavir for HDV-2 (LOWR-2) study's aim was to identify optimal combination regimens of LNF + ritonavir (RTV) ± pegylated interferon alpha (PEG-IFNα) with efficacy and tolerability for longer-term dosing. Here we report the safety and efficacy at end of treatment for up to 24 weeks.

Fibroblast Growth Factor 21 Response in a Preclinical Alcohol Model of Acute-on-Chronic Liver Injury.

Background And Aims: Fibroblast growth factor (FGF) 21 has recently been shown to play a potential role in bile acid metabolism. We aimed to investigate the FGF21 response in an ethanol-induced acute-on-chronic liver injury (ACLI) model in mice with deficiency of the hepatobiliary phospholipid transporter.

Methods: Total RNA was extracted from wild-type (WT, C57BL/6J) and (KO) mice, which were either fed a control diet (WT-Cont and KO-Cont groups; = 28/group) or ethanol diet, followed by an acute ethanol binge (WT-EtOH and KO-EtOH groups; = 28/group).

Vitamin D in Preclinical Models of Fatty Liver Disease.

Simple steatosis in non-alcoholic fatty liver disease (NAFLD) progresses to non-alcoholic steatohepatitis (NASH) when excessive fat accumulation is accompanied by ballooning, inflammation, and progressive hepatocellular injury. Due to the increasing global incidence of NAFLD/NASH and the lack of effective drugs, current treatment options are currently dominated by lifestyle interventions, including dietary and physical activity modifications. In this regard, vitamin D has received widespread attention in recent years.

Evaluation of the results of MOTAKK hepatitis C virus RNA genotyping and hepatitis delta virus external quality assessment programs during 2015-2016.

Background/aims: To evaluate the HCV RNA genotyping and HDV RNA tests that are performed in molecular microbiology laboratories in Turkey as part of a national external quality assessment programme, MOTAKK (Moleküler Tanıda Kalite Kontrol) (English translation: Quality control in molecular diagnostics).

Materials And Methods: Plasmas having different HCV RNA genotypes were used to prepare HCV genotype control sera. The HDV RNA main stock was prepared from patients with chronic delta hepatitis who had a significant amount of viral load detected, as per the WHO reference materials on viral load studies that were compiled for the purpose of developing HDV RNA control sera.

HEV seroprevalence in blood donors in Turkey by two commercial total anti-HEV Ab ELISA kits.

Previous hepatitis E virus (HEV) seroprevalence studies in Turkey have shown high variabilities, leading to conflicting results. We aimed to re-evaluate HEV seroprevalence among blood donors in Turkey using the Wantai (Beijing, China) and the Dia.Pro (Milan, Italy) total anti-HEV antibody (Ab) enzyme-linked immunosorbent assay (ELISA) kits and compare their performances and to investigate the presence of HEV RNA in blood donors.

[Evaluation of 2015-2016 MOTAKK HBV DNA and HCV RNA external quality assessment national program results].

MOTAKK, as a national external quality control program has been launched to evaluate the molecular detection of viral infections including HBV DNA and HCV RNA in molecular microbiology diagnostic laboratories in Turkey. This program is prepared in compliance with ISO 17043:2010 (Conformity assessment general requirements for proficiency testing) standards, and aims to take the place of external quality control programs from abroad, contributing to standardization and accuracy of molecular diagnostic tests in our country. The aim of this study was to evaluate 2015 and 2016 results of the MOTAKK External Quality Control Program for HBV DNA and HCV RNA viral load .

Effect of alcohol on the interleukin 6-mediated inflammatory response in a new mouse model of acute-on-chronic liver injury.

Background And Aims: ACLF is usually associated with a precipitant in the setting of a chronically damaged liver. We aim to combine a mouse model with a pre-injured liver (Abcb4/Mdr2) with a recently standardized ethanol feeding model to dissect alcohol-related inflammatory responses in this model.

Method: Ten (n = 64) and 15 (n = 64) week old wild-type (WT) C57BL/6 J and Abcb4 knock-out (KO) mice were either fed control (WT/Cont and KO/Cont groups) or liquid ethanol diet (5% v/v) followed by an ethanol binge (4 mg/kg) (WT/EtOH and KO/EtOH groups).

Interferon Treatment Duration in Patients With Chronic Delta Hepatitis and its Effect on the Natural Course of the Disease.

Background: Interferon is the only treatment option in chronic delta hepatitis (CDH). A CDH database (333 patients, 161 with interferon treatment history) was analyzed for effects of treatment duration on virologic response and clinical outcomes.

Methods: Ninety-nine CDH patients who received at least 6 months of interferon were selected.

Optimizing lonafarnib treatment for the management of chronic delta hepatitis: The LOWR HDV-1 study.

Unlabelled: In a proof-of-concept (POC) study, the oral prenylation inhibitor, lonafarnib (LNF), decreased hepatitis D virus (HDV) RNA during 4 weeks of treatment. Here, we explored optimal LNF regimens. Fifteen patients (five groups; 3 per group) completed dosing as follows: (1) LNF 200 mg twice-daily (BID; 12 weeks); (2) LNF 300 mg BID (12 weeks); (3) LNF 100 mg thrice-daily (5 weeks); (4) LNF 100 mg BID + pegylated interferon alfa (PEG-IFNα) 180 μg once-weekly (QW; 8 weeks); and (5) LNF 100 mg BID + ritonavir (RTV) 100 mg once-daily (QD; 8 weeks).

Clinical and pathological characteristics of gastrointestinal stromal tumor (GIST) metastatic to bone.

Our aim in this study was to describe the clinical, morphological, and molecular profile of gastrointestinal stromal tumor (GIST) metastatic to bone. We analyzed the morphological, phenotypic, and molecular characteristics of seven cases, and in addition reviewed 17 cases from literature. Sequence analysis of KIT and PDGFRA genes was possible for six cases.

Discontinuation of lamivudine treatment in HBeAg-negative chronic hepatitis B: a pilot study with long-term follow-up.

Background: Finite treatment of hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) with nucleoside/nucleotide analogues (NAs) is important in resource-limited countries. Outcome of treatment discontinuation in patients on long-term lamivudine (LVD) was assessed in a single centre observational pilot study in the current study.

Methods: Non-cirrhotic patients on LVD for at least 5 years with undetectable HBV DNA on at least two consecutive assessments were offered to stop treatment.

Investigation of West Nile virus among healthy blood donors in the western part of Turkey.

Background/aim: THE West Nile virus (WNV) is a mosquito-borne flavivirus causing different forms of infection among humans, varying from asymptomatic illness to fetal central nervous system infection. Turkeylies within an endemic region for WNV. Transfusion of infected blood products is another well-documented major route of transmission.

Hepatitis C virus genotype distribution in Turkey remains unchanged after a decade: performance of phylogenetic analysis of the NS5B, E1, and 5'UTR regions in genotyping efficiency.

Background/aims: Hepatitis C virus (HCV) genotyping has a considerable effect on therapy. The aim was to determine the change in prevalence of HCV genotypes in Turkey during the last decade and to compare the performance of DNA sequencing of different targets in the HCV genome (NS5B, E1, and 5'UTR).

Materials And Methods: Five hundred HCV RNA-positive patients (226 males, 274 females) were included in the study.

[Production of a recombinant CagA protein for the detection of Helicobacter pylori CagA antibodies].

At present, Helicobacter pylori infections affect approximately 50% of the world population. It is known that H.pylori is related with several gastric diseases including chronic atrophic gastritis, peptic and gastric ulcers as well as gastric carcinomas.

Free circulating nucleic acids in plasma and serum as a novel approach to the use of internal controls in real time PCR based detection.

Internal controls (ICs), are the main components of any real-time PCR based amplification methods, which are co-purified and co-amplified with the actual target. The existence of free circulating nucleic acids in plasma and serum (CNAPS) has been known for many years. The aim of this study was to verify whether CNAPS can be used as ICs in real-time PCR based detection and quantification of DNA or RNA targets in plasma and serum samples.

Interleukin-28 gene polymorphisms may contribute to HBsAg persistence and the development of HBeAg-negative chronic hepatitis B.

Background & Aims: Aim of this study was to investigate whether a potential association exists between several single nucleotide polymorphisms (SNPs) of the IL-28B gene (rs12979860, rs1188122, rs8099917, rs8105790, rs12980275) and HBsAg persistence. Further, a potential effect on the development of HBeAg-negative CHB vs. inactive HBsAg carrier state was assessed in a genotype D HBV cohort.

A one step real time PCR method for the quantification of hepatitis delta virus RNA using an external armored RNA standard and intrinsic internal control.

Background: Hepatitis delta virus (HDV) RNA viral load measurement is critical in diagnosis and monitoring the response to antiviral treatment.

Objectives: Our aim is to design a real time PCR method for accurate quantitation of HDV RNA in clinical specimens using an armored RNA as external standard, and an intrinsic internal control.

Study Design: A plasmid bearing delta antigen region of genotype I HDV genome was used to develop an armored RNA.

Efficacy of tenofovir in adefovir-experienced patients compared with treatment-naive patients with chronic hepatitis B.

Background: Tenofovir (TDF) has similar antiviral efficacy in both treatment-naive and lamivudine-resistant chronic hepatitis B (CHB) patients. Data on TDF use in patients with adefovir (ADV) resistance is inconsistent. The aim of our study was to assess antiviral efficacy of TDF against nucleoside analogue-naive (NN) and ADV-resistant (ADV-R) CHB and suboptimal responders to ADV (ADV-S).

Molecular characterization of hepatitis A virus isolated from acute infections in Turkey.

Background/aims: Hepatitis A virus is a global public health problem, especially in developing countries, and the most common cause of hepatitis in childhood. Hepatitis A virus is a single- stranded positive RNA virus subdivided to 6 genotypes (3 human,3 simian). The aim of this study was to determine the prevalent genotype in Turkey using sera of acute hepatitis A virus-infected patients from different geographical regions of the country.

Clonal analysis of the quasispecies of antiviral-resistant HBV genomes in patients with entecavir resistance during rescue treatment and successful treatment of entecavir resistance with tenofovir.

Background: Clonal analysis of quasispecies of resistant HBV genomes in patients with entecavir (ETV) resistance receiving lamivudine (3TC) plus adefovir (ADV) rescue therapy has never been performed.

Methods: A sample of 10 patients with ETV resistance who were switched to 3TC+ADV treatment were analysed for changes in viral quasispecies. Serum samples at baseline, and at months 3 and 6 of 3TC+ADV treatment could be clonally analysed in 7 of 10 patients; 3-82 clones per sample (total 1,068 clones, mean 63) were sequenced.

Entecavir treatment of chronic hepatitis D.

Background: Hepatitis D virus (HDV) requires hepatitis B surface antigen (HBsAg) to propagate infection and cause disease. Entecavir is a nucleoside analog with potent antiviral efficacy, and in the woodchuck animal model it also decreased hepatitis B virus (HBV) cccDNA and woodchuck surface antigen. The aim of this study was to investigate the efficacy of entecavir in chronic hepatitis D (CHD).

Molecular characterization of a novel entecavir mutation pattern isolated from a multi-drug refractory patient with chronic hepatitis B infection.

Background: Prolonged antiviral treatment results in selection and accumulation of resistant strains in quasispecies pool in hepatitis B virus (HBV) infection.

Objectives: The aim of this study was to characterise a novel HBV pattern which shows resistance to lamivudine, adefovir dipivoxil and entecavir using in vitro phenoyping assay.

Study Design: A male 36 years old patient diagnosed with anti HBe-positive chronic hepatitis B (CHB) had received lamivudine treatment for 7 years following an initial unsuccessfull interferon treatment.