Noninvasive Models to Predict Liver Fibrosis in Patients with Chronic Hepatitis B: A Study from Turkey

WOS: 000429311600004Background: Manynoninvasive methods, including aspartateaminotransaminase (AST)/alanineaminotransaminase (ALT) ratio (AAR), AST-to-platelet ratio index (APRI), Bonacini cirrhosis discriminant score (CDS), fibrosis-4 (FIB4) index, and age-platelet index (API), have been described to determine the stage of hepatic fibrosis. However, thesemethodsare developed for patients with chronic hepatitisC(CHC) andproduce conflicting results in the prediction of liver fibrosis in patients with chronic hepatitis B (CHB). Objectives: The aim of this study was to evaluate the relationship between 7 noninvasive models, including AAR, APRI, CDS, API, FIB-4, neutrophil-to-lymphocyte ratio (NLR), and red cell distribution width (RDW)-to-platelet ratio (RPR) in patients with CHB. Methods: The study population included all patients with CHB, undergoing liver biopsy to determine HBsAg and HBV DNA positivity in more than 6 months. Results: A total of 2520 treatment-naive CHB patients from 40 different centers were included in the study. In total, 62.6% of the patients were male, and the mean age was 40.60 +/- 12.34 years (minimum, 18 years; maximum, 77 years). The Ishak fibrosis score was >= 3 in 29.8% of the patients, indicating significant fibrosis. The mean API, APRI, CDS, NLR, FIB4, and RPR scores in the noninvasive models were significantly different between the groups with significant and low fibrosis (P < 0.05). All the noninvave models (API, APRI, AAR, CDS, NLR, RPR, and FIB4) were found to be significant in the discrimination of cirrhosis (P < 0.05). In the multiple logistic regression analysis, CDS, albumin, alkaline phosphatase (ALP), total bilirubin, neutrophil count, NLR, mean platelet volume (MPV), and FIB4 were independent indices for cirrhosis. Conclusions: In the present study, the role of noninvasive tests in the prediction of liver fibrosis stage and cirrhosis was evaluated in a large cohort of CHB patients. Overall, noninvasive models are gradually becoming more promising. Accordingly, the need for liver biopsy can be reduced with a combination of noninvasive methods in the future

Atypical Acinetobacter baumannii Meningitis: Case Report

A patient with an unusual clinical form of acinetobacter meningitis is presented. A 42-year-old female patient who was a victim of domestic violence 1.5 months before was admitted to the emergency department with the complaints of fever, nausea, vomiting, and confusion. The cerebrospinal fluid (CSF) obtained from lumbar puncture (LP), showed normal pressure and appearance. No cells were found on microscopic examination of the CSF. CSF biochemistry revealed protein: 18 mg/dL, glucose: 75 mg/dL (concurrent blood glucose level: 102 mg/dL) and lactate dehydrogenase (LDH) < 30 U/L. A. baumannii was isolated from the CSF culture. Since all CSF parameters were within normal range and bedside CSF culture was not performed, a contamination was suspected, and LP was repeated. Follow-up LP also revealed normal CSF pressure, clear CSF, and no cells on microscopic examination. Biochemical examination revealed protein: 25.2 mg/dL, glucose: 84 mg/dL (concurrent blood glucose level: 118 mg/ dL) and, LDH: 44 U/L; A. baumannii grew on CSF culture. Growth on culture despite normal CSF findings prompted LP to be repeated once again. The last LP revealed normal CSF pressure and appearance and no cells on microscopic examination, but biochemical tests showed protein level of 25 mg/dL and glucose level of 82 mg/dL, with concurrent blood glucose level of 106 mg/dL. LDH was 30 U/L, and A. baumannii grew for the third time. The patient was diagnosed as acinetobacter meningitis, and treatment consisting of intrathecal and intravenous colistin together with meropenem was started. CSF culture after intrathecal colistin treatment on consecutive days yielded no growth. There was improvement regarding consciousness after this treatment. We emphasize that CSF culture is more valuable in the diagnosis of meningitis, and that meningitis, albeit rarely, can have an uncommon presentation

Retreatment of Chronic Hepatitis C Infection with Telaprevir: Preliminary Results in Turkey

Background: The use of pegylated interferon alpha and ribavirin (PegIFN/RBV) for the retreatment of chronic hepatitis C virus (HCV) infection without a sustained virological response (SVR) prior to PegIFN/RBV treatment has resulted in low success rates. Aims: To investigate the efficacy and safety of telaprevir (TVR) in combination with PegIFN/RBV in patients infected with HCV genotypes 1 and 4 who were previously treated with PegIFN/RBV and failed to achieve SVR. Study Design: Multi-center, retrospective, cross-sectional study. Methods: The study included 111 patients: 80 prior relapsers, 25 prior null responders, and six prior partial responders to PegIFN/RBV treatment. The patients were given TVR/PegIFN/RBV for 12 weeks, followed by a 12-week PegIFN/RBV treatment; virological response results were assessed at weeks 4, 12, and 24. Treatment was discontinued in patients with HCV RNA >1000 IU/mL at week 4 or with negative RNA results at week 4 but >1000 IU/mL at week 12. Rapid virological response (RVR), early virological response (EVR), extended rapid virological response (eRVR), and virological response at 24th week of treatment were evaluated. The side effects of combination therapy and the rates of treatment discontinuation were investigated. Results: The mean age of the patients was 56.02±9.96 years and 45.9% were male. Ninety-one percent of the patients were infected with viral genotype 1, 69.6% with the interleukin (IL) 28B genotype CT and 20.2% were cirrhotic. The RVR rate was 86.3% in prior relapsers, 56% in prior null responders, and 50% in prior partial responders (p=0.002). EVR rates in those groups were 91.3%, 56%, and 83.3%, respectively (p<0.001). eRVR rates were 83.8% in prior relapsers, 48% in prior null responders, and 50% in prior partial responders (<0.001). The virological response at the 24th week of treatment was found to be the highest in prior relapsers (88.8%); it was 56% in prior null responders and 66.7% in prior partial responders (p<0.001). Common side effects were fatigue, headache, anorexia, malaise, anemia, pruritus, dry skin, rash, dyspepsia, nausea, pyrexia, stomachache, and anorectal discomfort. All treatments were discontinued due to side effects in 9.9% of patients. Conclusion: High virological response rates were obtained with TVR/PegIFN/RBV treatment. Although side effects were frequently observed, the discontinuation rate of combination therapy was low

Retreatment of Chronic Hepatitis C Infection with Telaprevir: Preliminary Results in Turkey

Background: The use of pegylated interferon alpha and ribavirin (PegIFN/RBV) for the retreatment of chronic hepatitis C virus (HCV) infection without a sustained virological response (SVR) prior to PegIFN/RBV treatment has resulted in low success rates

Molecular Characterization of Drug Resistance in Hepatitis B Viruses Isolated from Patients with Chronical Infection in Turkey

Background: Hepatitis B virus (HBV) has a high mutation rate due to its unusual replication strategy leading to the production of a large number of virions with single and double mutations. The mutations, in turn, are associated with the development of drug resistance to nucleos(t)ide analogs (NUCs) in patients before and during NUCs therapy. Objectives: The current study aimed at investigating the molecular characterization of HBV in Turkish patients with chronic hepatitis B (CHB) infection. Methods: Polymerase chain reaction (PCR) amplification and direct sequencing procedures were used to analyze mutations. The detected drug resistance mutations were divided into the nucleos(t) ide analogs primary, partial, and compensatory resistance groups. The amino acid substitutions of hepatitis B surface antigen (HBsAg) were categorized into antiviral drug - associated potential vaccine-escape mutations (ADAPVEMs) and typical HBsAg amino acid substitutions, which included hepatitis B hyperimmunoglobulin (HBIg) - selected escape mutation, vaccine escape mutation, hepatitis B misdiagnosis, and immune - selected amino acid substitutions. Results: The number of patients included in the study was 528 out of which 271 (51.3%) were treatment - naive and 351 (66.3%) were hepatitis B e antigen (HBeAg) - negative. Moreover, 325 (61.6%) were males with a mean age of 38 years (range: 18 - 69). Primary, partial, and compensatory resistance to NUCs was reported in 174 (32.9%) patients. Six different ADAPVEM motifs were determined in both treatment - naive and treatment - experienced patients, namely, sF161L/rtI169X, sE164D/rtV173L, sL172L/rtA181T, sL173F/rtA181V, sS195M/rtM204V, and sS196L/rtM204I. The prevalence of ADAPVEMs and typical HBsAg escape mutations was 5.3% (n = 28) and 34.8% (n = 184), respectively. Conclusions: The analysis of drug resistance should constitute a fundamental part of the follow - up period of patients with CHB undergone treatment with NUCs. The surveillance of development of drug resistance mutations, while receiving treatment for hepatitis B is of paramount importance to monitor and control the emerging resistance

Development and validation of a modified quick SOFA scale for risk assessment in sepsis syndrome

Sepsis is a severe clinical syndrome owing to its high mortality. Quick Sequential Organ Failure Assessment (qSOFA) score has been proposed for the prediction of fatal outcomes in sepsis syndrome in emergency departments. Due to the low predictive performance of the qSOFA score, we propose a modification to the score by adding age. We conducted a multicenter, retrospective cohort study among regional referral centers from various regions of the country. Participants recruited data of patients admitted to emergency departments and obtained a diagnosis of sepsis syndrome. Crude in-hospital mortality was the primary endpoint. A generalized mixed-effects model with random intercepts produced estimates for adverse outcomes. Model-based recursive partitioning demonstrated the effects and thresholds of significant covariates. Scores were internally validated. The H measure compared performances of scores. A total of 580 patients from 22 centers were included for further analysis. Stages of sepsis, age, time to antibiotics, and administration of carbapenem for empirical treatment were entered the final model. Among these, severe sepsis (OR, 4.40; CIs, 2.35-8.21), septic shock (OR, 8.78; CIs, 4.37-17.66), age (OR, 1.03; CIs, 1.02-1.05) and time to antibiotics (OR, 1.05; CIs, 1.01-1.10) were significantly associated with fatal outcomes. A decision tree demonstrated the thresholds for age. We modified the quick Sequential Organ Failure Assessment (mod-qSOFA) score by adding age (> 50 years old = one point) and compared this to the conventional score. H-measures for qSOFA and mod-qSOFA were found to be 0.11 and 0.14, respectively, whereas AUCs of both scores were 0.64. We propose the use of the modified qSOFA score for early risk assessment among sepsis patients for improved triage and management of this fatal syndrome

Protease Inhibitors Drug Resistance Mutations in Turkish Patients with Chronic Hepatitis C

Background: Drug resistance development is an expected problem during treatment with protease inhibitors (PIs), this is largely due to the fact that Pls are low-genetic barrier drugs. Resistance-associated variants (RAVs) however may also occur naturally, and prior to treatment with Pls, the clinical impact of this basal resistance remains unknown. In Turkey, there is yet to be an investigation into the hepatitis C (HCV) drug associated resistance to oral antivirals. Materials and methods: 178 antiviral-naïve patients infected with HCV genotype 1 were selected from 27 clinical centers of various geographical regions in Turkey and included in the current study. The basal NS3 Pls resistance mutations of these patients were analyzed. Results: In 33 (18.5%) of the patients included in the study, at least one mutation pattern that can cause drug resistance was identified. The most frequently detected mutation pattern was T54S while R109K was the second most frequently detected. Following a more general examination of the patients studied, telaprevir (TVR) resistance in 27 patients (15.2%), boceprevir (BOC) resistance in 26 (14.6%) patients, simeprevir (SMV) resistance in 11 (6.2%) patients and faldaprevir resistance in 13 (7.3%) patients were detected. Our investigation also revealed that rebound developed in the presence of a Q80K mutation and amongst two V55A mutations following treatment with TVR, while no response to treatment was detected in a patient with a R55K mutation. Conclusion: We are of the opinion that drug resistance analyses can be beneficial and necessary in revealing which variants are responsible for pre-treatment natural resistance and which mutations are responsible for the viral breakthrough that may develop during the treatment