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Background: To evaluate the effectiveness and safety of ledipasvir/sofosbuvir (LDV/SOF)±ribavirin (RBV) regimen in a real-world setting., Methods: Patients received a fixed-dose combination tablet containing LDV and SOF with or without RBV, for 8, 12 or 24 weeks. Patients were assessed at baseline, end of treatment, and 12 weeks after the end of treatment. The primary effectiveness endpoint was sustained virologic response 12 weeks after the end of treatment (SVR12)., Results: Of the 86 patients, aged 20-80 years, 82.6% were HCV genotype 1b-infected and 50.0% were cirrhotic. More than half (52.3%) had previously followed pegylated interferon-containing (PEG-IFN) treatment regimens, and 38.5% were null-responders. SVR12 was achieved by 94.2% of patients. All non-responders were cirrhotic: two demonstrated virologic breakthrough and the remaining three relapsed. All patients treated with an 8-week regimen achieved SVR12 despite having high viral load at baseline (HCV RNA of >1 million IU/mL in 8/10 patients, including one with a viral load of >6 million IU/mL). Adverse events were generally mild and transient. Most frequently, fatigue (22.1%), headache (15.1%), and arthralgia (7.0%) were observed. Laboratory abnormalities included anemia and hyperbilirubinemia., Conclusions: Treatment with LDV/SOF±RBV is an effective and safe option for patients with HCV, including those with advanced liver disease or a history of non-response to PEG-IFN-based therapy., (Copyright © 2017 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.)

Background: Virologic and safety outcomes of ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin (OBV/PTV/r ± DSV ± RBV) therapy have shown high sustained virologic response (SVR) rates and good tolerability in most patient populations in pre-registration studies., Aim: To confirm these clinical trial findings in the treatment of genotype 1 and 4 hepatitis C under real-world conditions., Methods: Patients enrolled for treatment with OBV/PTV/r ± DSV ± RBV based on therapeutic guidelines were included, and the regimen was administered according to product characteristics. Clinical and laboratory data, including virologic response, were collected at baseline, end of treatment (EOT) and 12 weeks after EOT., Results: A total of 209 patients with chronic hepatitis C were enrolled, most were genotype 1b-infected (84.2%) and 119 (56.9%) had liver cirrhosis. Among these, 150 (71.7%) had failed previous anti-viral therapies and 84 (40.2%) were null-responders. At 12 weeks after EOT, SVR was achieved by 207 (99.0%) patients, ranging from 96.4% to 100.0% across subgroups. All Child-Pugh B and post-orthotopic liver transplantation patients achieved SVR. Adverse events occurred in 151 (72.2%) patients and were mostly mild and associated with the use of RBV. Serious adverse events, including hepatic decompensation, renal insufficiency, anaemia, hepatotoxicity and diarrhoea, were reported in eight (3.8%) patients. In five (2.4%) patients, adverse events led to treatment discontinuation. On-treatment decompensation was experienced by seven (3.3%) patients., Conclusions: The results of our study confirm previous findings. They demonstrate excellent effectiveness and a good safety profile of OBV/PTV/r± DSV±RBV in HCV genotype 1-infected patients treated in the real-world setting., (© 2016 John Wiley & Sons Ltd.)

Based on investigations of liver biopsy material, certain cellular genes have been implicated as correlates of success or failure to interferon alpha-ribavirin (IFN/RBV) therapy against hepatitis C. The current study aimed at determining whether expression of host genes thought to be relevant to HCV replication in the liver would be correlated with HCV infection status in peripheral blood mononuclear cells (PBMCs) and also with patient responsiveness to IFN/RBV treatment. Therefore, PBMCs from patients with chronic hepatitis C responding (n = 35) or not (n = 49) to IFN/RBV and from healthy controls (n = 15) were evaluated for HCV RNA load and cellular gene expression. Non-responders had 3- to 10-fold higher basal levels of interleukin (IL)-8, IFN-stimulated gene 15 (ISG15), 2',5'-oligoadenylate synthetase (OAS), and Toll-like receptors (TLR)-4, -5, and -7 compared to responders. Non-responders with similar post-treatment follow-ups as responders persistently expressed 6- to 20-fold greater levels of IL-8, ISG15, and OAS after therapy. Higher expression of IFN-α, IFN-γ, and IFN-λ was found in PBMCs of individuals achieving sustained virological response, either before or after therapy. Pre-treatment HCV RNA loads in PBMCs of non-responders were significantly higher (P = 0.016) than those of responders. In conclusion, the data indicate that immune cells of responders and non-responders to IFN/RBV therapy exhibited significantly different virological and host gene expression profiles. Elevated baseline HCV loads and TLR-4, -5, and -7 levels, and persistently high levels of IL-8, ISG15, and OAS were correlated with IFN non-responsiveness. The results warrant further investigations on the utilization of PBMCs for predicting success or failure to IFN-based therapies., (Copyright © 2012 Wiley Periodicals, Inc.)

Introduction: Hepatitis C virus (HCV) infection in Poland affects approximately 750 thousand persons. The prevention of cirrhosis and hepatocellular carcinoma, of which approximately 20% of patients with chronic hepatitis C virus are at risk, aims at eradication of the virus by applying antiviral treatment with pegylated interferon alpha with ribavirin., Material/methods: In this paper the results of the standard treatment of chronic hepatitis C in a population of 169 adult patients in whom it was started in the period of 01.01.2007-30.06.2008 are analyzed. Moreover, the influence of various clinical, biochemical and viral factors on achieving therapeutic success in the form of the sustained virological response (SVR) was studied., Results: In the group of 128 patients who received the full course of antiviral treatment, the SVR was achieved by 67.2% of patients (86 persons), whereas regarding all 169 patients who started the therapy, the sustained disappearance of viremia was found in 53.2% of patients (90 persons). Regarding 155 persons in whom the treatment was not interrupted for reasons others than virology, this value was 55.5%. For the sustained disappearance of viremia the following was favorable: genotype 3 virus, age under 40 years, body mass up to 75 kg, correct value of body mass index (BMI), low gamma-glutamyl transpeptidase (GGTP) activity before the treatment, minimum advancement of liver fibrosis in a liver biopsy (S1), complete early biochemical response (cEBR), and moreover, the achievement of negation of viremia after 12 weeks of the treatment in a group of patients infected with genotype 1 (complete early virological response, cEVR). These factors were strongly correlated with each other and that is why an analysis by the method of logistic multiple regression was impossible. Adverse reactions to the treatment and other health problems were the reasons for earlier discontinuation of the standard therapeutic scheme in 14 patients, whereby the lack of an SVR occurred in 10 of them (71.5% which is 5.9% of the studied population).

Pegylated interferon α and ribavirin in treatment of chronic hepatitis C in children is used rarely. The aim of the study was to find prognostic factors for sustained virological response and to analyze the safety of pegylated interferon α2a and ribavirin in children with chronic hepatitis C. The study covered a group of 44 children, mean age 14 years, with diagnosed chronic hepatitis C. Clinical, biochemical and virological parameters, as well as side effects were evaluated. Combined treatment allowed to obtain sustained virological response in a total of 77.5% of the treated children. Lower viral load and lower fibrosis grade contributed to sustained virological response. The response was not gender-related. The best response is obtained in children whose treatment was started after they attained the age of 10 years. Therapy with pegylated interferon α2a and ribavirin is well tolerated by pediatric patients.

The authors described a case of a 30 year-old man with chronic hepatitis C (G1,S1) complicated by pulmonary embolism (PE), preceded by symptoms of respiratory system infection, which occurred after 6 months of combination therapy with pegylated interferon-α and ribavirin. Right sided nonbacterial thrombotic endocarditis as a source of segmental/subsegmental PE was found. Hemostatic work up showed increased activated protein C resistance, elevated factor VIII activity and fibrinogen concentration as well as hyperhomocysteinaemia (all these disturbances returned to normal 3-6 months later). The patient's clinical status improved during anticoagulation therapy. Antiviral treatment was not continued as virological response was achieved.

Purpose: Administration of pegylated interferon-alpha (IFN-alpha) and ribavirin in adults with chronic hepatitis C (CHC) is a recommended therapeutic standard. Nevertheless, this therapeutic regimen rises numerous controversies. The aim of this study was to analyze adverse effects during the treatment with pegylated IFN-alpha and ribavirin in children with CHC., Methods: Study group comprised 30 children with CHC, age 8-19 years (mean 13,6 years), 9 girls and 21 boys. All patients were administered two medication therapy with pegylated IFN-alpha-2b in the dose of 1.5 microg/kg of body weight 1x/week subcutaneously and daily oral ribavirin 15 mg/kg of bodyweight for 48 weeks. Blood samples were taken at baseline and every 4 weeks during the whole treatment and 24 weeks of follow-up period. Panel of test included: cellular blood count and smear, ALT activity, bilirubin level. Patients complaints were noticed during every visit. Thyroid hormones and antibodies were checked every 3 months. Children were divided into group A that responded to treatment and group B-nonresponders., Results: Abnormalities in laboratory tests (white blood cells, neutrophils, haemoglobin) were observed mainly during first weeks of treatment. Mean bilirubin level and platelets were normal. Mean ALT normalized during the treatment. After 12-16 weeks of the therapy somatic adverse effects decreased significantly., Conclusions: Administration of pegylated IFN-alpha and ribavirin in children with CHC is related to characteristic adverse effects. Periodical dose reduction was necessary. Although side effects and subjective patient complaints were present, children attended school without difficulties. Constant monitoring is required during the whole treatment.

Objective: Infection with hepatitis C virus (HCV) is widespread worldwide. It is estimated that this problem affects approximately 3% of global population. By introducing weekly doses of pegylated interferon (IFN) alfa in combination with ribavirin, given daily, to chronic hepatitis C (CHC) treatment one can achieve a full inhibition of HCV replication in 54-56% of adult patients. The aim of this study was to examine the relationship between prognostic factors and early virological response (EVR) after combination treatment with peginterferon alfa- 2a or alfa-2b and ribavirin in children with CHC., Methods: Twenty-three children with chronic HCV were treated with a combination of peginterferon alfa-2a or alfa-2b once a week and ribavirin twice a day. Assessment included age at the time of infection, the length of infection, HCV genotype, viral load in serum and HCV RNA level in peripheral blood mononuclear cells (PBMCs), alanine aminotransferase (ALT) activity and adherence to therapy. The efficacy endpoint was EVR defined as undetectable HCV RNA in serum or >2 log10 decrease in HCV RNA compared with baseline values., Results: An EVR was achieved in 15 out of 23 patients (65.3%) after 12 weeks of therapy., Conclusions: Lower HCV RNA viral load have positive influence on EVR. HCV RNA presence in PBMCs and lower ALT activity do not influence the achievement of EVR. Oncologic history does not bear any influence on EVR. Adherence to the therapy has an unclear influence on the achievement of EVR in children with CHC.

Objective: Assessment of the effect of anti-viral therapy in children affected by chronic hepatitis C on the expression of Toll-like receptors (TLR) on blood leucocytes, Methods: A cohort of children (n=24) infected with C virus with completed anti-viral therapy with interferon-alpha + ribavirin and another group of children HCV+ (n=23) awaiting for treatment entered this study. Three ml of blood was drawn from each child, divided on 100 ml aliquots and incubated with the panel offluorochrome labelled monoclonal antibodies versus differentiation antigens of leucocytes, anti - TLR2 and TLR4. After washing samples were subjected to acquisition in flow cytometer FACScan (Becton Dickinson). Data were analyzed by means of BD FACS Diva version 4.1.2 software., Results: It was found that blood leucocytes of HCV+ children which completed anti-viral therapy, show significantly higher expression of TLR2 and TLR4. This rise was evident not only in percentage of cells, but also in mean fluorescence intensity (MFI). It was true in the case of granulocytes, T, B lymphocytes and monocytes, but the latter did not differ significantly from their counterparts derived from untreated children., Conclusion: Anti-viral treatment of children infected with C virus results in heightened expression of Toll-like receptors on blood leucocytes.

Objective: Detection of differences in white blood cell subsets I children with chronic viral hepatitis type C before antiviral treatment., Methods: A cohort of children (n = 52) with proven HCV infection were subjected to flow cytometric analysis of their white blood cells and compared to non-infected control group., Main Observations: It has been found that the hepatitis group has higher number of cells with cytotoxic potential, decreased CD4/CD8 ratio than the other one., Results: Significant rise of CD8+, CD28- cells, NK cells and NKT lymphocytes was demonstrated in hepatitis group. Several correlations were noticed between various cell subsets studied in virus C infected children., Conclusions: This data show that HCV infection affects child immunity at systemic level. Cellular alterations are detectable by means of flow cytometry. Evaluation of its parameters might have predictive value in antiviral treatment.

Objective: The aim of his study is to evaluate the influence of the baseline ALT activity, HCV viral load and genotype on the effects of the treatment with pegylated interferon alpha 2 b and ribavirin in children with CHC., Methods: Twenty children with chronic hepatitis C were enrolled to the study. All were treated with pegylated interferon alpha and ribavirin for 48 weeks. Viral genotype, advancement of changes in histopathological examination and ALT activity with HCV-RNA viral load in respective periods of the treatment were analyzed., Main Observations and Results: All children were infected with genotype 1. The advancement of inflammatory changes and fibrosis in the liver was mediocre. On the basis of the outcome of treatment in the 24th week of the treatment the study group was divided to group A n = 17, which eliminated HCV, and group B n = 3 without elimination. In some of the patients n = 10 viral response was assessed directly after the therapy. In 8 children HCV elimination was confirmed, however in 2 patients replication was still present. ALT activity decreased with the decline of the viral load., Conclusions: During the treatment HCV RNA elimination occurs in 85% of children infected with genotype 1. ETR seem to achieve similar ratio. The influence of ALT activity, HCV viral load and the advancement of changes in histopathological examination on the HCV RNA elimination remains unclear. The adverse-effects are not significant and abnormalities in clinical chemistry do not cause permanent cease of the therapy.

Our aim was to evaluate the recent clinical data concerning the course of chronic hepatitis C in children and the rationale indications for therapy. There is no doubt that in adult group the pegylated interferon is better than standard interferon and results in higher response rate in combination with ribavirin. Actually complicating the issues surrounding hepatitis C in children is the lack of information on the efficacy and safety of this therapy in pediatric age group. The first preliminary data of our clinical study concerning the therapy with pegylated interferon alpha 2b and ribavirin in 10 children with chronic hepatitis C (genotype 1) suggest a good tolerance of this drug and the end of treatment virologic response in 8 children (80%).

The response to viral infections is mediated through the co-operation of cellular and humoral mechanisms. The aim of this study was to seek the correlation between IL-6 and IL-12 level, HCV viral load, ALT activity during the 48-week treatment with interferon-alpha-2b (IFN-alpha-2b) combined with ribavirin in children with diagnosed CHC and to search their influence on positive response to treatment. The group of 27 children with CHC was enrolled into this study. The children were treated with interferon-alpha and ribavirin in the course of 48-week therapy. The results show that both ALT activity and the viral load at the time of implementation of treatment with IFN-alpha and ribavirin is an important prognostic tool when treating children. It has been shown that the levels of IL-6 do not bear any significant prognostic importance to the implemented therapy, yet the increase of IL-12 levels in the 24th week of the treatment may be of prognostic value and may point out the possible elimination of HCV-RNA.