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The aim of this study was to evaluate the baseline demographics and real-life efficacy of direct acting antivirals (DAAs) in HIV–HCV-positive patients as compared to patients with HCV monoinfection. The analysis included 5690 subjects who were treated with DAAs: 5533 were HCV-positive and 157 were HIV–HCV-positive. Patients with HCV-monoinfection were older (p <.0001) and in HIV–HCV group there were more men (p <.0001). Prevalence of genotype 1a (p =.002), as well as of genotypes 3 and 4 (p <.0001) was higher in HIV–HCV-coinfected patients. Genotype 1b was more frequent (p <.0001) in the HCV-mono-infection group. Patients with HCV-monoinfection had a higher proportion of fibrosis F4 (p =.0004) and lower proportion of fibrosis F2 (p <.0001). HIV–HCV-coinfected individuals were more often treatment-naïve (p <.0001). Rates of sustained viral response after 12 weeks did not differ significantly between both groups (95.9% versus 97.3% in coinfection and monoinfection group, respectively; p >.05). They were, however, influenced by HCV genotype (p <.0001), stage of hepatic fibrosis (p <.0001), male sex (p <.0001), BMI (p =.0001) and treatment regimen modifications (p <.0001). Although factors associated with worse response to therapy (male sex, genotype 3) occurred more often in the HIV coinfection group, real-life results of DAAs did not differ significantly between both populations. [ABSTRACT FROM AUTHOR]

Background: Over the past years, the introduction of direct-acting antivirals (DAAs) revolutionized chronic hepatitis C treatment. We aimed to characterize and assess treatment efficacy in three specific groups of patients treated with DAAs: those with active solid malignant tumors (SMTs), hematological diseases (HDs) and hepatocellular carcinomas (HCCs)., Methods: A total of 203 patients with active oncological disease (SMT n = 61, HD = 67, HCC n = 74) during DAA treatment in 2015-2020 selected from the EpiTer-2 database were analyzed retrospectively and compared to 12,983 patients without any active malignancy., Results: Extrahepatic symptoms were more frequent in HD patients (17.2% vs. SMT = 10.3%, HCC = 8.2%, without = 7.8%, p = 0.004). HCC patients characterized with the highest ALT activity (81 IU/L vs. SMT = 59.5 IU/L, HD = 52 IU/L, without = 58 IU/L, p = 0.001) more often had F4 fibrosis as well (86.11% vs. SMT = 23.3%, HD = 28.8%, controls = 24.4%, p = 0.001). A significant majority of subjects in HCC, HD and SMT populations completed the full treatment plan (HCC = 91%; n = 67, HD = 97%; n = 65, SMT = 100%; n = 62). Concerning the treatment efficacy, the overall sustained virologic response, excluding non-virologic failures, was reported in 93.6% HD, 90.16% SMT and 80.6% in HCC patients., Conclusions: As presented in our study, DAA therapy has proven to be highly effective and safe in patients with active SMTs and HDs. However, therapy discontinuations resulting from liver disease progression remain to be the major concern in HCC patients.

Background: The aim of this study was to evaluate the real-life efficacy of pangenotypic antivirals in HIV-HCV-positive patients., Research Design and Methods: The analysis included 5650 subjects who were treated with pangenotypic anti-HCV drugs: 5142 were HCV-positive and 508 were HIV-HCV-positive., Results: Patients with HCV-monoinfection were older ( p  < 0.0001), however patients with HCV-monoinfection had a higher proportion of advanced fibrosis F4 ( p  < 0.0001). There were no differences between the study groups in the rate of SVR12 in ITT-analysis (87,6% versus 93,9% in coinfection and monoinfection group, respectively; p  > 0.05). However, there was a difference between study groups in PP-analysis, HIV/HCV and HCV, respectively 95.9% vs 97.9%, p  = 0.0323. Additionally, there were a higher rate of patients who did not apply for follow-up (SVR12) in coinfected patients (7,9% vs 3,6% respectively p  = 0.0001). In multivariante analysis, factors associated with worse response to the pangenotypic anti-HCV therapy included male sex, HCV genotype 3, stage of fibrosis and decompensation of liver function and HIV coinfection., Conclusions: The real-life results of pangenotypic anti-HCV treatment are veryeffective in the group of HIV-HCV-coinfected patients. However, the finaleffectiveness is slightly lower than that obtained in HCV monoinfectedpatients.

Eliminating hepatitis C virus (HCV) infection in the population of women of reproductive age is important not only for the health of women themselves but also for the health of newborns. This study aimed to evaluate the implementation of this goal by analysing the effectiveness of contemporary therapy in a large cohort from everyday clinical practice along with identifying factors reducing therapeutic success. The analysed population consisted of 7861 patients, including 3388 women aged 15-49, treated in 2015-2022 in 26 hepatology centres. Data were collected retrospectively using a nationwide EpiTer-2 database. Females were significantly less often infected with HCV genotype 3 compared to males (11.2% vs. 15.7%) and less frequently showed comorbidities (40.5% vs. 44.2%) and comedications (37.2% vs. 45.2%). Hepatocellular carcinoma, liver transplantation, HIV and HBV coinfections were reported significantly less frequently in women. Regardless of the treatment type, females significantly more often reached sustained virologic response (98.8%) compared to males (96.8%). Regardless of gender, genotype 3 and cirrhosis were independent factors increasing the risk of treatment failure. Women more commonly reported adverse events, but death occurred significantly more frequently in men (0.3% vs. 0.1%), usually related to underlying advanced liver disease. We have demonstrated excellent effectiveness and safety profiles for treating HCV infection in women. This gives hope for the micro-elimination of HCV infections in women, translating into a reduced risk of severe disease in both women and their children., (© 2024 John Wiley & Sons Ltd.)

Background & Aims: The study aimed to assess the phenomenon of achieving sustained virologic response (SVR) in patients with detectable ribonucleic acid (RNA) of hepatitis C virus (HCV) at the end of treatment (ET) with direct-acting antivirals (DAA), find how this is affected by the type of regimen, and how patients experiencing this differed from non-responders with detectable HCV RNA at the ET., Methods: The study included all consecutive patients with detectable HCV RNA at the ET selected from the EpiTer-2 database, a retrospective national multicentre project evaluating antiviral treatment in HCV-infected patients in 2015-2023., Results: Of the 16106 patients treated with IFN-free regimens with available HCV RNA assessment at the ET and at follow-up 12 weeks after treatment completion (FU), 1253 (7.8%) had detectable HCV RNA at the ET, and 1120 of them (89%) finally achieved SVR. This phenomenon was significantly more frequent in pangenotypic regimens, 10.3% vs. 4.7% in genotype-specific options (p < 0.001), and the highest proportion was documented for glecaprevir/pibrentasvir (13.7%), and velpatasvir/sofosbuvir ± ribavirin (6.9%). Patients ET + FU- treated with these two pangenotypic regimens (n = 668) had less advanced liver disease, were less frequently infected with genotype (GT) 3, and were significantly more likely to be treatment-naïve than 61 non-responders., Conclusions: We documented 7.8% rate of patients with detectable HCV RNA at the ET, of whom 89% subsequently achieved SVR, significantly more frequently in the population treated with pangenotypic regimens. Less severe liver disease, more often GT3 infection, and a higher percentage of treatment-naive patients distinguished this group from non-responders., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Aims: The aim of this study was to assess the real-life effectiveness and safety of direct acting antivirals (DAAs) in patients with cirrhosis and history of hepatic decompensation compared to those with compensated cirrhosis., Method: Data of patients treated with DAAs and included in the EpiTer-2 database (N = 10 152) were collected retrospectively. The primary endpoint was sustained viral response (SVR) at 12 weeks posttreatment. Patients were also evaluated in terms of liver-related adverse events and treatment modification/discontinuation., Results: The overall SVR rate was 91.4% in the intent to treat (ITT) analysis and 95.2% in the per-protocol (PP) analysis (P < .001). Patients with decompensated cirrhosis had lower SVR rates compared to those with compensated cirrhosis in ITT analysis (86.4% vs 92.0%, P < .001), while not in PP analysis (92.9% vs 95.5%, P > .05). Adverse events (AE) occurred 45.6% and 29.3% of patients with decompensated and compensated cirrhosis (P < .001). Patients with decompensated cirrhosis were at higher risk of death (5.4% vs 0.9%; P < .0001) or liver decompensation (21.5% vs 1.3%; P < .0001). Treatment with protease inhibitors was not associated with hepatic decompensation (P = .3). Only 82.6% of patients with decompensated cirrhosis completed DAA treatment (vs 92.8% in compensated cirrhotics; P < .0001)., Conclusion: Despite higher frequency of AE and treatment modifications, once completed, DAAs yield comparable results for patients with decompensated and compensated cirrhosis. High rate of serious adverse events in patients with advanced liver disease treated with PI may not be related to the detrimental effect of the medications, but rather to the disease itself., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

There is still limited data available from real-world experience studies on the pangenotypic regimens in patients with genotype (GT) 3 hepatitis C virus (HCV) infection and liver cirrhosis. The current study aimed to evaluate the efficacy and safety of pangenotypic regimens in this difficult-to-treat population. A total of 236 patients with mean age 52.3 ± 11.3 years and male predominance (72%) selected from EpiTer-2 database were included in the analysis; 72% of them were treatment-naïve. The majority of patients (55%) received the combination of sofosbuvir/velpatasvir (SOF/VEL), 71 without and 58 with ribavirin (RBV), whereas the remaining 107 individuals were assigned to glecaprevir/pibrentasvir (GLE/PIB). The effectiveness of the treatment following GLE/PIB and SOF/VEL regimens (96% and 93%) was higher compared to SOF/VEL + RBV option (79%). The univariate analysis demonstrated the significantly lower sustained virologic response in males, in patients with baseline HCV RNA ≥ 1,000,000 IU/mL, and among those who failed previous DAA-based therapy. The multivariate logistic regression analysis recognized only the male gender and presence of ascites at baseline as the independent factors of non-response to treatment. It should be emphasized that despite the availability of pangenotypic, strong therapeutic options, GT3 infected patients with cirrhosis still remain difficult-to-treat, especially those with hepatic impairment and DAA-experienced.

Background and Aims: The revolution of the antiviral treatment of hepatitis C virus (HCV) infection resulting in higher effectiveness came with the introduction of direct-acting antivirals with pangenotypic regimens as a final touch. Among them, the combination of glecaprevir (GLE) and pibrentasvir (PIB) provides the opportunity for shortening therapy to 8 weeks in the majority of patients. Because of still insufficient evaluation of this regimen in the real-world experience, our study aimed to assess the efficacy and safety of 8-week GLE/PIB in chronic hepatitis C patients depending on liver fibrosis and genotype (GT)., Methods: The analysis included patients who received GLE/PIB for 8 weeks selected from the EpiTer-2 database, large retrospective national real-world study evaluating antiviral treatment in 12 584 individuals in 22 Polish hepatology centers., Results: A total of 1034 patients with female predominance (52%) were enrolled in the analysis. The majority of them were treatment naïve (94%), presented liver fibrosis (F) of F0-F3 (92%), with the most common GT1b, followed by GT3. The overall sustained virologic response after exclusion of nonvirologic failures was achieved in 95.8% and 98%, respectively (P = 0.19). In multivariate logistic regression HCV GT-3 (beta = 0.07, P = 0.02) and HIV infection (beta = -0.14, P < 0.001) were independent predictors of nonresponse., Conclusions: We demonstrated high effectiveness of 8-week GLE/PIB treatment in a non-GT3 population irrespective of liver fibrosis stage. Comparable efficacy was achieved in non-cirrhotic patients regardless of the genotype, including GT3 HCV., (© 2020 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: The introduction of direct-acting antiviral drugs into clinical practice has revolutionized the treatment of chronic hepatitis C, making it highly effective and safe for patients. However, few researchers have analyzed the factors causing therapy failure in some patients., Aim: To analyze factors influencing the failure of direct antiviral drugs in the large, multicenter EpiTer-2 cohort in a real-world setting., Methods: The study cohort consisted of patients with chronic hepatitis C treated at 22 Polish centers from 2016-2020. Data collected from the online EpiTer-2 database included the following: hepatitis C virus (HCV) genotype, stage of fibrosis, hematology and liver function parameters, Child-Turcotte-Pugh and Model for End-stage Liver Disease scores, prior antiviral therapy, concomitant diseases, and drugs used in relation to hepatitis B virus (HBV) and/or human immunodeficiency virus (HIV) coinfections. Adverse events observed during the treatment and follow-up period were reported. Both standard and machine learning methods were used for statistical analysis., Results: During analysis, 12614 patients with chronic hepatitis C were registered, of which 11938 (mean age: 52 years) had available sustained virologic response (SVR) data [11629 (97%) achieved SVR and 309 (3%) did not]. Most patients (78.1%) were infected with HCV genotype 1b. Liver cirrhosis was diagnosed in 2974 patients, while advanced fibrosis (F3) was diagnosed in 1717 patients. We included patients with features of hepatic failure at baseline [ascites in 142 (1.2%) and encephalopathy in 68 (0.6%) patients]. The most important host factors negatively influencing treatment efficacy were liver cirrhosis, clinical and laboratory features of liver failure, history of hepatocellular carcinoma, and higher body mass index. Among viral factors, genotype 3 and viral load also exerted an influence on treatment efficacy. Classical statistical analysis revealed that treatment ineffectiveness seemed to be influenced by the male sex, which was not confirmed by the multivariate analysis using the machine learning algorithm (random forest). Coinfection with HBV (including patients with on-treatment reactivation of HBV infection) or HIV, extrahepatic manifestations, and renal failure did not significantly affect the treatment efficacy., Conclusion: In patients with advanced liver disease, individualized therapy (testing for resistance-associated variants and response-guided treatment) should be considered to maximize the chance of achieving SVR., Competing Interests: Conflict-of-interest statement: Janczewska E has acted as a speaker and/or advisor for AbbVie, Gilead, MSD, Ipsen, and has received funding for clinical trials from AbbVie, Allergan, BMS, Celgene, Cymabay, Dr Falk Pharma, Exelixis, GSK, and MSD. Jakub Klapaczyński has acted as a speaker for Gilead and AbbVie. Mazur W has acted as a speaker and/or advisor for AbbVie, Gilead, Merck, and has received funding for clinical trials from AbbVie, Gilead, and Janssen. Zarębska-Michaluk D has acted as a speaker for AbbVie and Gilead. Dybowska D has received funding for participation in the conference: from AbbVie. Czauż-Andrzejuk A has received funding for clinical trials from AbbVie and Merck. Berak H has acted as a speaker and/or advisor for Gilead, Abbvie, and MSD. Krygier R has acted as a consultant for AbbVie and Gilead. Jaroszewicz J has acted as a speaker and/or advisor for AbbVie, Gilead, Merck, Roche, Alfasigma, MSD, Gilead and PRO.MED. CS. Piekarska A has acted as a speaker and/or advisor for AbbVie, Gilead, Merck, and Roche. Socha Ł has acted as a consultant for BMS. Brygida Adamek has acted as a speaker for AbbVie, Gilead, and MSD. Tomasiewicz K has acted as a speaker and/or advisor AbbVie, Alfa Wasserman, BMS, Gilead, Janssen, Merck, Roche, and has received funding for clinical trials from AbbVie, BMS, Gilead, Janssen, Merck, and Roche. Simon K has acted as a speaker and/or advisor: AbbVie, Gilead, Merck, Alfa-Wassermann, Novartis, Lilly, Bayer, and has received funding for clinical trials from: AbbVie, Allergan, Bayer, EISAI, Gilead, Intercept, Pfizer. Pawłowska M has acted as a speaker and/or advisor for AbbVie, Gilead, Merck, Roche and has received funding for clinical trials from AbbVie, Gilead, and Roche. Halota W has acted as a speaker and/or advisor for AbbVie, BMS, Gilead, Janssen, Merck, Roche, and has received funding for clinical trials from AbbVie, Gilead, and Roche. Flisiak R has acted as a speaker and/or advisor, and has received funding for clinical trials from AbbVie, Gilead, Merck, and Roche. Lorenc B, Kołek MF, Tudrujek-Zdunek M, Sitko M, Buczyńska I, Citko J, Dobracka B, Deroń Z, Laurans Ł, Białkowska-Warzecha J and Tronina O have no conflict of interest to declare., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Patients who undergo hemodialysis (HD) or kidney transplantation (KTx) previously had limited possibilities for treatment of hepatitis C virus (HCV) infection. Direct-acting antivirals (DAA) give these patients a chance of virus eradication and safe transplantation. The aim of this study was to evaluate the effectiveness and safety of DAA in KTx and HD patients in real-world settings., Methods: Sustained virologic response (SVR) and treatment safety were analyzed in KTx and HD patients from the EpiTer-2 database, which included HCV-infected subjects treated with DAA between 2015 and 2019. Additionally, for KTx patients, changes in creatinine concentration, estimated glomerular filtration rate (eGFR), proteinuria within a year after treatment, and changes in the need for calcineurin inhibitors were assessed., Results: Among 10,152 patients from the EpiTer-2 database 148 were selected, 85 after KTx and 63 undergoing HD. The most common genotype, 1b HCV, was found in 73% and 86% of patients, respectively. Cirrhosis was noted in 10% and 19%, respectively. The most common DAA regimen after KTx was sofosbuvir/ledipasvir (54%), whereas in HD patients it was ombitasvir/paritaprevir/ritonavir +/- dasabuvir (56%). All patients with available follow-up results achieved SVR. No deaths, kidney loss or acute rejection episodes were noted. The most common adverse effects in both groups were anemia and weakness. One year after treatment, creatinine concentration, eGFR and proteinuria remained stable in the majority of patients., Conclusion: DAA treatment of HCV infection demonstrated high effectiveness and safety in hemodialyzed patients and patients who had undergone KTx in this real-world study., Competing Interests: Conflict of Interest: Dorota Zarębska-Michaluk: Sponsored Lectures: AbbVie, Gilead, Merck Jerzy Jaroszewicz: Sponsored lectures: AbbVie, Bristol-Myers Squib, DiaSorin, Gilead, Grifols, Roche, Woerwag, MSD Sharp&Dohme/Merck; Member of the scientific advisory boards of AbbVie, Bristol-Myers Squib, Gilead Sciences, MSD Sharp & Dohme/ Merck and Roche Krzysztof Simon: Consultancy: AbbVie, Abbott, Gilead, MSD, GSK, Janssen, AlfaSigma, Baxter, Promed; Research Funding: Bayer, Gilead, EISAI, AbbVie, Tobira, Intercept, MSD, Janssen, Takeda, Actelion, GSK, Pfizer, BeiGene, Allergan, Summit (Oxford) Małgorzata Pawłowska: Consultancy: AbbVie, Gilead, Merck, Roche; Sponsored Lectures: AbbVie, Gilead, Merck Krzysztof Tomasiewicz: Consultancy: AbbVie, Alfa Wasserman, BMS, Gilead, Janssen, Merck, Roche; Research funding: AbbVie, BMS, Gilead, Janssen, Merck, Roche Robert Flisiak: Consultancy and Research funding: AbbVie, Gilead, Janssen, Merck, Roche, (Copyright: © 2021 Hellenic Society of Gastroenterology.)

Objectives: The aim of the study was to analyze the prevalence and clinical characteristics of HCV/HBV coinfection and to evaluate the rate of HBV-reactivation during anti-HCV therapy in a large real-world study., Methods: Analyzed population consisted of 10,152 chronic hepatitis C patients treated with DAA between 2015 and 2019 in a nationwide study. Prior to the DAA all subjects had HBsAg and 60% anti-HBc testing., Results: 111 of 10,152 patients (1.1%) had detectable HBsAg and 1239 of 6139 (20.2%) anti-HBcAb. The prevalence of occult hepatitis B was 0.48%. HCV/HBV patients were younger with a higher proportion of males, HIV-coinfected, and advanced fibrosis. They were less often diagnosed with diabetes but more often with chronic kidney disease. In HBsAg(+) subjects with baseline HBV-DNA available 6/102 (5.9%) HBV-reactivations during or after DAA therapy were observed, and in two (1.9%) significant hepatic flares were noted. In HBsAg(-)/anti-HBc(+) group 2 (0.16%) reactivations were observed only in patients undergoing immunosuppressive therapy., Discussion: Data from a large European cohort suggest a relatively low risk of HBV-reactivation during DAA-therapy for HCV infection in HBsAg(+) patients. In HBsAg(-)/anti-HBc(+) HBV-reactivation seems to be limited to subjects with immunodeficiency. Importantly, previous exposure to HBV and occult hepatitis B is present in a significant proportion of HCV-infected.

Background and Aim: Grazoprevir/elbasvir (GZR/EBR) was approved for the treatment of chronic hepatitis C virus (HCV) genotype 1 and 4 infected patients with or without compensated liver cirrhosis. The aim of this study was to assess GZR/EBR regimen in the real-world experience, particularly in previously "difficult-to-treat" patients with chronic kidney diseases, human immunodeficiency virus-coinfected, cirrhotics, and treatment-experienced., Methods: The analysis included patients treated with GZR/EBR selected from 10 152 individuals from the EpiTer-2 database, large national real-world study evaluating antiviral treatment in 22 Polish hepatology centers between 2015 and 2018. Data were completed retrospectively and submitted online., Results: A total of 1615 patients who started GZR/EBR therapy in 2017 and 2018 with a female predominance (54%) and median age of 54 years were analyzed. The majority were infected with GT1b (89%) and treatment naïve (81%). Liver cirrhosis was diagnosed in 19%, and 70% of patients had comorbidities, of which chronic renal disease was present in 7% and HIV-coinfection in 4%. Overall, a sustained virologic response (SVR) was achieved by 95% according to intent-to-treat (ITT) and 98% after exclusion of lost to follow up (modified ITT). No differences were found in cure rate between all included patients and subpopulations previously considered as difficult-to-treat. Majority of patients completed the treatment course as scheduled, adverse events were mostly mild and did not lead to therapy discontinuation., Conclusions: GZR/EBR treatment carried-out in patients infected with HCV genotype 1 and 4 demonstrated good tolerability and an excellent SVR rate with no effectiveness reduction in so called difficult-to-treat populations., (© 2019 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Purpose: Since 2017 treatment-naïve patients infected with genotype 1b of hepatitis C virus and minimal or moderate fibrosis can be treated with Ombitasvir/Paritaprevir/ritonavir + Dasabuvir (OPrD) for 8 weeks according to updated Summary of Product Characteristics. The aim of our study was to assess the comparative efficacy of 8 and 12-weeks therapy with OPrD in large cohort of patients eligible for 8 weeks regimen treated in real-world setting., Materials and Methods: We analysed data of 3067 HCV genotype 1b infected patients treated with OPrD between 2015 and 2017. Final analysis included patients with none, minimal or moderate fibrosis (F0-F2)., Results: A total of 771 patients were enrolled in the study, including 197 (26%) treated for 8-weeks and 574 patients fulfilling criteria for 8-weeks but assigned to 12-weeks regimen. Majority of patients had no or minimal fibrosis (F0-F1). Longer treatment duration was more often administered in patients with moderate fibrosis, comorbidities, concomitant medications. SVR was achieved in 186 (94%) patients treated for 8 weeks and 558 (97%) for 12 weeks (p = 0.07). After exclusion of lost to follow-up patients, sustained virological response (SVR) rate reached 95% and 99%, respectively (p = 0.01). We were not able to identify factors associated with non-response., Conclusions: This real-word experience study confirmed similar, high effectiveness of 8 and 12-weeks regimens of OPrD in genotype 1b HCV infected patients with non-advanced fibrosis. Despite of reduced SVR rate after 8-weeks regimen, there is no need to extend therapy to 12-weeks in vast majority of such patients and no need to add ribavirin., Competing Interests: Declaration of competing interest Dorota Zarębska-Michaluk – Sponsored Lectures: AbbVie, Gilead, Merck; Anna Piekarska – Consultancy: AbbVie, Gilead, Merck, Roche; Jerzy Jaroszewicz – Consultancy: AbbVie, BMS, Gilead; Research funding: Merz, Roche; Jakub Klapaczyński – Sponsored Lectures Gilead; Włodzimierz Mazur – Consultancy: AbbVie, BMS, Gilead, Janssen, Merck, Roche; Research funding: AbbVie, Gilead, Merck, Roche; Rafał Krygier – Consultancy - AbbVie, Gilead, Promed; Teresa Belica-Wdowik – Consultancy: AbbVie, Gilead; Research funding: AbbVie; Barbara Baka-Ćwierz – Consultancy: AbbVie, Gilead, Roche; Research funding: AbbVie, Roche; Ewa Janczewska – Consultancy: AbbVie, BMS, Gilead, Janssen, Roche; Research funding: AbbVie, Allergan, BMS, Gilead, Janssen, Merck, Roche, Vertex, Tobira; Krzysztof Tomasiewicz – Consultancy: AbbVie, Alfa Wasserman, BMS, Gilead, Janssen, Merck, Roche; Research funding: AbbVie, BMS, Gilead, Janssen, Merck, Roche; Aleksander Garlicki – Consultancy: AbbVie, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Janssen, Roche, Sanofi Pasteur; Research funding: Amgen, Janssen, Pfizer; Agnieszka Czauż-Andrzejuk – Research funding: AbbVie, Merck; Dorota Dybowska – Sponsored Lectures: Abbvie. Waldemar Halota – Consultancy: AbbVie, BMS, Gilead, Janssen, Merck, Roche; Research funding: AbbVie, Gilead, Roche; Małgorzata Pawłowska – Consultancy: AbbVie, BMS, Gilead, Janssen, Merck, Roche; Research funding: AbbVie, Gilead, Roche; Krzysztof Simon – Consultancy: AbbVie, Gilead, BMS, Merck, Janssen, Alfa-Wassermann, Baxter, Bayer, Roche; Research funding: AbbVie, Allergan, Bayer, EISAI, Gilead, Intercept, Janssen, Tobira, Pfizer; Olga Tronina – Consultancy: AbbVie; Research funding: Janssen; Robert Flisiak—Consultancy: AbbVie, Alfa Wasserman, BMS, Gilead, Janssen, Merck, Roche; Research funding: AbbVie, Gilead, Janssen, Merck, Roche; Paweł Pabjan, Beata Dobracka, Beata Lorenc, Magdalena Tudrujek-Zdunek, Marek Sitko, Jolanta Citko, Łukasz Laurans, Zbigniew Deroń, Iwona Buczyńska, Jolanta Białkowska – none declared., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Aim: The development of interferon- (IFN-) free regimens substantially improved efficacy of treatment for HCV, but despite excellent effectiveness the failures still occur. The aim of our study was to evaluate the efficacy of retreatment with genotype specific direct acting antivirals- (DAA-) based regimens in nonresponders to previous IFN-free therapy., Materials and Methods: Analysed population consisted of 31 nonresponders to IFN-free regimen, which received second IFN-free rescue therapy, selected from 6228 patients included in a national database EpiTer-2., Results: Age and gender distribution were similar, whereas proportion of genotype 1b was slightly higher and genotype 4 lower in the whole population compared to studied one. Patients included in the study demonstrated much more advanced fibrosis. Primary therapy was discontinued in 12 patients, which were recognized as failures due to nonvirologic reason, whereas virologic reason of therapeutic failure was recognized in 19 patients which completed therapy. Overall sustained virologic response (SVR) rate was 81% and 86% in intent-to-treat (ITT) and modified ITT analysis, respectively (74% and 78% in virologic failures, 92% and 100% in nonvirologic failures). Resistance-associated substitutions (RAS) testing was carried out in 8 patients from the group of completed primary therapy and three of them had potential risk for failure of rescue therapy due to NS5A association, while two of them achieved SVR., Conclusions: We demonstrated moderate effectiveness of genotype specific rescue therapy in failures due to virologic reason and high in those who discontinued primary therapy. Therefore rescue therapy with genotype specific regimens should be considered always if more potent regimens are not available.

To estimate the Lyme borreliosis (LB) risk for forest workers, totally 646 blood samples were tested for IgG and IgM anti-Borrelia burgdorferi s.l. (anti-B.b.) antibody occurrence using ELISA tests confirmed with western blot. To clarify the varied LB risk, additionally, the data from the Forest Data Bank determining the detailed forest habitat type in particular forest inspectorates were used. The occurrence of the anti-B.b. antibody was confirmed in 22% (8.7% IgM, 17.8% IgG) of forest workers. Analysis of the influence of the habitat type (forest types) indicated the significant positive impact of the occurrence of the deciduous and mixed-deciduous forests on the seroprevalence of anti-B.b. IgG level among forestry workers. However, the share of forest type cannot be the only factor taken into account when assessing risk.

The aim of the study is to analyze treatments available for patients infected with genotype (G) 3 hepatitis C virus (HCV) in Poland at the beginning of the interferon (IFN)-free era and evaluate the efficacy and safety of different therapeutic options administered in a real-world setting. We analyzed data of 198 patients who started antiviral therapy after July 1, 2015, and completed it before December 31, 2016; 57.6% of them had liver cirrhosis and 46% were treatment experienced. Fifty percent of patients were assigned to sofosbuvir (SOF)+pegylated IFN alfa (PegIFNa)+ribavirin (RBV), 9% to PegIFNa+RBV, 36% received SOF+RBV, and 5% SOF+daclatasvir (DCV)±RBV. Cirrhotic patients were assigned more frequently to IFN-free regimens. Overall, a sustained virological response was achieved by 84.3% of patients in intent-to-treat (ITT) analysis and 87% in modified ITT analysis. For SOF+PegIFNa+RBV and SOF+DCV±RBV regimens, the sustained virologic response (SVR) rate reached at least 90%, whereas the two other therapeutic options demonstrated efficacy <80%. The SVR rate in noncirrhotics was higher than in cirrhotics, irrespective of regimen. Adverse events were documented in 52.5%, with the most common being weakness/fatigue and anemia. We confirmed effectiveness and safety of the SOF-based treatment in a real-world cohort of patients with chronic HCV G3 infection. Most notably, we demonstrated good tolerability and high efficacy of the SOF+PegIFNa+RBV regimen.

The Aim of the Study: Was to analyze the efficacy achieved with regimens available for chronic hepatitis C (CHC) in Poland between 2013 and 2016., Material and Methods: Data were collected from 29 centers and included 6786 patients with available sustained virologic response (SVR) data between 1 January 2013 and 31 March 2016., Results: The sustained virologic response rate for genotypes (G) 1a, 1b, 2, 3 and 4 was 62%, 56%, 92%, 67% and 56% respectively; 71% patients ( n = 4832) were treated with pegylated interferon α (Peg-IFNα) and ribavirin (RBV), with SVR rates of 58%, 49%, 92%, 67% and 55% respectively. The sustained virologic response among 5646 G1 infected patients was the lowest with natural interferon α (7%, n = 70) or PegIFN (50%, n = 3779) with RBV, and improved in those receiving triple regimens of Peg-IFN + RBV combined with boceprevir (47%, n = 485), telaprevir (64%, n = 805), simeprevir (73%, n = 132) or sofosbuvir (70%, n = 23). The sustained virologic response with interferon-free regimens of sofosbuvir and RBV ( n = 7), sofosbuvir and simeprevir ( n = 53), and ledipasvir and sofosbuvir ( n = 64) achieved 86%, 89% and 94% respectively. The highest SVR of 98% was observed with ombitasvir/paritaprevir combined with dasabuvir ( n = 227). Patients infected with G3 ( n = 896) and G4 ( n = 220) received mostly Peg-IFN + RBV with SVR of 67% and 56% respectively. Interferon-free regimens were administered in 18 G3/G4 patients and all achieved an SVR. Sofosbuvir combined with Peg-IFN and RBV was administered to 33 patients with an SVR rate of 94%, and a similar rate was achieved among 13 G2 patients treated with interferon and RBV., Conclusions: We observed significant differences in efficacy of HCV regimens available in Poland at the turn of the interferon era. The data will be useful as a comparison for therapeutic options expected in the next few years.

The Aim of the Study: Was to assess current prevalence of hepatitis C virus (HCV) genotypes in Poland, including their geographic distribution and changes in a given period of time., Material and Methods: Data were collected with questionnaires from 29 Polish centers and included data of patients diagnosed with HCV infection between 1 January 2013 and 31 March 2016., Results: In total, data of 9800 patients were reported. The highest prevalence was estimated for genotype 1b (81.7%), followed by 3 (11.3%), 4 (3.5%), 1a (3.2%) and 2 (0.2%). Genotype 5 or 6 was reported in 6 patients only (0.1%). The highest prevalence of genotype 1 was observed in central (łódzkie, mazowieckie, świętokrzyskie), eastern (lubelskie) and southern (małopolskie, śląskie) Poland. The highest rate for genotype 3 was observed in south-western (dolnośląskie, lubuskie) and eastern (podlaskie, warmińsko-mazurskie and podkarpackie) Poland. Compared to historical data, we observed an increasing tendency of G1 prevalence from 72.0% in 2003 to 87.5% in 2016, which was accompanied by a decrease of G3 (17.9% vs. 9.1%) and G4 (9.0% vs. 3.1%)., Conclusions: Almost 85% of patients with HCV in Poland are infected with genotype 1 (almost exclusively subgenotype 1b), and its prevalence shows an increasing tendency, accompanied by a decrease of genotypes 3 and 4.

We investigated the safety, efficacy, and impact of ribavirin and peginterferon dose reduction on complete early virologic response and sustained virologic response (SVR) to triple therapy with telaprevir in treatment-experienced patients with advanced liver fibrosis.Treatment was initiated for 211 patients who failed treatment with peginterferon and ribavirin, with bridging fibrosis (F3, n = 68) or cirrhosis (F4, n = 143), including 103 (49%) null-responders (NR), 30 (14%) partial responders (PR), and 78 (37%) relapsers (REL). Impaired liver function (ILF) platelets <100,000/mm or albumin <35 g/L were present in 40 patients. The distribution of hepatitis C virus subtypes was: 1a, 1b, or 1, with undetermined subtype for 10 (5%), 187 (89%), and 14 (6%) patients, respectively. Treatment was started with peginterferon alpha-2a or alpha-2b, ribavirin, and telaprevir at standard doses.The overall SVR24 rate was 56% and was lower in cirrhotic patients (NR: 35%, PR: 40%, and REL: 63%, respectively) than in patients with bridging fibrosis (NR: 50%, PR: 75%, and REL: 75%, respectively). The lowest probability of SVR24 was in NRs with ILF (26%). The SVR24 rate significantly decreased in NRs receiving <60% vs >60% of the total ribavirin dose (23% vs 44%, respectively) or <80% vs >80% of the total ribavirin dose (33% vs 48%, respectively). A significant SVR24 decrease was noted subsequent to a total peginterferon dose reduction, both when comparing patients who received <60% vs >60% of the total dose (NR: 0% vs 44%; REL: 33% vs 68%) and patients who received <80% vs >80% of the total dose (NR: 17% vs 50%; REL: 46% vs 71%).Serious adverse events were observed in 31 patients (15%). Deaths occurred in 4 patients. All of the deceased subjects were cirrhotic members of the ILF (baseline serum albumin level <35 g/L and/or platelet count <100,000/mm) group.Ribavirin dose reduction did not affect efficacy in REL but did in NR. Peginterferon dose reduction decreased the SVR24 rate for all groups, particularly in prior NR. ILF increased the risk of fatal complications with a low probability to achieve SVR24. One solution might be to provide wide and early access to novel, efficient, and safe interferon-free combinations to treatment-experienced patients, particularly those with liver cirrhosis.

Unlabelled: Available data on prevalence of HCV genotypes in Poland are insufficient. The aim of the study was the analysis of distribution of HCV genotypes in Poland over the period of recent 10 years regarding the age of patients and the regions of the country., Material and Methods: Analysis of HCV genotypes in Poland was carried out between 2003 and 2012, and included 14 651 patients from 22 centers where patients with chronic viral hepatitis C are diagnosed and treated. Genotypes were analyzed in age groups (< 20 years of age, 20-40 years of age, > 40 years of age) as well as in populations of HBV and HIV co-infections., Results: Genotype (G) 1 infection was demonstrated in 79.4%, G2 -0.1%, G3- 13.8%, G4- 4.9%, G6-0.09% and mixed infections in 1.6%. There was no infection with genotype 5. The highest prevalence of G1 was observed in the Łódzkie voivodship (89.2%) and the Slaskie voivodship (86.7%) while the lowest one in the Warmińsko-mazurskie (62.0%) and the Podlaskie voivodships (68.2%). Genotype 3 most commonly occurs in the Warmińsko-mazurskie (28.1%), and the Podlaskie voivodships (23.0%) and is least common in the Małopolskie (7.9%) and the Łódzkie voivodships (9.0%). Genotype 4 is more common in the Kujawsko-pomorskie (11.7%) and the Podlaskie voivodships (8.6%) and relatively less common in the Lubelskie (1.1%) and the Łódzkie voivodships (1.8%). Prevalence of G1 infection in 2003-2004 was 72% and increased up to 85.6% in 2011-2012, that was accompanied by decrease of G3 prevalence from 17% to 8% in this period. In HBV co-infected (n = 83), G1 infection was demonstrated in 85.5%, G3 - in 7.2%, G4 -4.8%, and mixed genotypes in 6%. Among HIV co-infected (n = 391), a much lower prevalence of G1 (33.0%) and a high of G3 (40.4%) as well as G4 (24.0%) were observed., Conclusions: There is a geographic variability of HCV genotypes prevalence in Poland. Increase of HCV G1 infections and decrease of G3 and G4 were observed in the last 10 years. Genotypes G3 and G4 occur more often in HCV/HIV co-infected than in HCV mono-infected patients.

The work presents epidemiological analysis of Borrelia burgdorferi (B.b.) infections and borreliosis cases in workers of the District Forestry Offices in Lower Silesia in 2003-2005. The infections rate was proved to be high and increasing in time. In 2003-2005 the presence of B.b. antibodies was noted in 672 (35%) examined people. In particular District Forestry Offices the rate of positive results was between 19.42-50.50%. In several District Forestry Offices a marked increase of B.b. infections (above 20%) was noted within two tick seasons (2003-2005). In 2003-2005 796 workers of the District Forestry Offices were under medical care. In this group more than 96% remembered tick bites. 15.6% of them reported the presence of EM. The evidence of borreliosis in almost 67% of examined workers. In clinical picture the symptoms of the locomotor system (83.8%) and the peripheral and vegetative nervous systems (54.1%) were dominating. Almost 1/3, cases were asymptomatic of B.b. infections.

The aim of the study was the analysis of Lyme borreliosis cases notified by Clinic for Infections Diseases in Wrocław in connection with exposure to ticks in year 2002. In the analyzed group of patients tick bites were confirmed in 77.9% and the most common places of exposition were forest regions in Lower Silesia (Masyw Slezy, Wzgórza Twardógorskie, Kotlina Kłodzka, Wzgórza Trzebnickie, Bory Dolnoślaskie) and in Wrocław area. EM appeared in 55.8% cases. In cases of multiple ticks professionally exposured persons EM appeared only in 22.2%.

Binding of antibodies specific to Borrelia burgdorferi in circulating immune complexes can lead to false negative results in serological tests. The aim of our study was to determine the presence of IgM antibodies to Borrelia burgdorferi bound in immune complexes in 52 sera of foresters the National Park in Karkonosze. Free and bound in immune complexes IgM antibodies present in 6 (11.5%) examined sera. In 24 (46.2%) seronegative sera after dissociation of immune complexes IgM antibodies to spirochaeta were found. The rest of the examined seronegative sera we failed to find IgM antibodies to Borrelia burgdorferi. The diagnostic assay, such as antibody analysis of immune components is useful in establishing of the diagnosis of borreliosis in seronegative cases and monitoring of disease activity. That method should be introduced for routine diagnosis of Lyme disease.

We analyzed clinically and epidemiologically 285 patients suffered from chronic brucellosis treated during 12 years. Especially we observed 51 persons with the infection called "brucellosis recens". Comparing both groups, we did not notice any statistically significant differences in the changes of organs and systems. This suggests greater influence of kind and frequency of exposition on pathologic changes than duration of illness.

The purpose of the paper was to evaluate activity of interferon system in a group of patients with chronic brucellosis. Trial was performed in 21 persons: 10-with active and 11-with non active disease. "Whole blood test" was used to induce interferon by peripheral blood leucocytes after stimulation with antigens: non specific (NDV, LPS, PHA + PMA) and specific (Brucella). There was no difference between examined and control groups in interferon induction by non specific factors. This indicates correct functions by interferon system in chronic brucellosis. Relatively, after stimulation by specific antigens 4-fold increase of endogenic interferon (alfa and gamma) was observed. These results suggest that chronic brucellosis (active and non active) in still immunologically active and pathological changes depend on delayed hypersensitivity. We conclude, that this method seems to be deciding diagnostic test in latent brucellosis.