Antiviral therapy in neonatal cholestatic cytomegalovirus hepatitis

BACKGROUND: Neonatal hepatitis refers to a heterogeneous group of disorders, caused by many factors including cytomegalovirus infection, revealing similar morphologic changes in the liver of an infant less than 3 months of age. Approximately 40% of cholestasis in infants is due to neonatal hepatitis. It may cause latent or acute cholestatic or chronic hepatitis, including cirrhosis in immunocompetant infant. METHODS: Twelve infants diagnosed with neonatal cytomegalovirus hepatitis in the last one year were included in the study. Group 1 consisted of seven babies treated with ganciclovir for 21 days. Group 2 included five cases who did not receive antiviral treatment. Physical examination, biochemical, serologic and virologic tests were done for both groups at the time of diagnosis and in the third month. RESULTS: Initial levels of total bilirubin, aminotransferases, gamma glutamyl transpeptidase, and alkaline phosphatase revealed a significant decrease after the treatment in Group 1 (p < 0.05) when compared with Group 2. This study revealed that ganciclovir treatment is a safe and effective in cases with cholestatic hepatitis. Similarly, all the patients in the treatment group had evidence of improvement serologically and virologically, while the comparison group did not reveal any significant change(p < 0.01). CONCLUSION: The clinical spectrum of perinatal infection varies from an asymptomatic infection or a mild disease to a severe systemic involvement, including central nervous system. The treatment in the early period of infection improved serologic markers and cholestatic parameters significantly. Further studies will lead us to clarify the efficacy of ganciclovir treatment in the early period of cytomegalovirus hepatitis, and the preventive role of anti-viral therapy on progressive liver disease due to cholestasis and hepatitis in neonatal cytomegalovirus infection

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

WOS: 000388326300001PubMed: 27401586Background: 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-naive 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. (C) 2016 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.Department of Scientific Research Project of Kocaeli University; Turkish Society of Clinic Microbiology and Infectious DiseasesThis study was funded by Department of Scientific Research Project of Kocaeli University and Turkish Society of Clinic Microbiology and Infectious Diseases

Management of Fulminant Hepatitis B: A Consensus Report of the Study Group for Viral Hepatitis of the Turkish Society of Clinical Microbiology and Infectious Diseases

Study Group for Viral Hepatitis of the Turkish Society of Clinical Microbiology and Infectious Diseases set up a task force to develop a consensus report focused on fulminant hepatitis B, the only infection for which an effective antiviral approach is available. Both antiviral and non-antiviral therapies were reviewed in the report. Some practical recommendations from relevant guidelines of three international associations (i.e., European Association for the Study of the Liver, American Association for the Study of Liver Disease, and Asian Pacific Association for the Study of the Liver) were adopted, and listed with the level of evidence and the grade of recommendation at the end of the report

Real-world efficacy, safety, and clinical outcomes of ombitasvir/paritaprevir/ritonavir +/- dasabuvir +/- ribavirin combination therapy in patients with hepatitis C virus genotype 1 or 4 infection: The Turkey experience experience

Background/Aims: mbitasvir/paritaprevir/ritonavir (OMV/PTV/r) +/- dasabuvir (DSV) +/- ribavirin (RBV) combination has demonstrated excellent rates of sustained virologic response (SVR) and a very good safety profile in patients with the chronic hepatitis C virus (HCV) genotype 1 or 4 infections. We aimed to investigate the effectiveness and safety of OMV/PTV/r +/- DSV +/- RBV combination regimen in a real-world clinical practice

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

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

Demographic Characteristics and Transmission Risk Factors of Patients with Hepatitis C Virus in Turkey: The EPI-C, A Multicenter and Cross-sectional Trial

Objectives: To describe the prevalence of risk factors in patients infected with hepatitis C virus (HCV)