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1
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Flisiak R, Zarębska-Michaluk D, Janczewska E, Parfieniuk-Kowerda A, Mazur W, Sitko M, Janocha-Litwin J, Krygier R, Lorenc B, Piekarska A, Sobala-Szczygieł B, Dobrowolska K, Socha Ł, Jaroszewicz J. Sustained Virological Response After Early Discontinuation of Hepatitis C Treatment. J Viral Hepat 2024; 31:677-685. [PMID: 39109641 DOI: 10.1111/jvh.13991] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2024] [Revised: 06/26/2024] [Accepted: 07/18/2024] [Indexed: 10/23/2024]
Abstract
To date, the effectiveness of direct-acting antivirals (DAAs) discontinued before 4 weeks has not been analysed in routine clinical practice. The study aimed to determine whether such a short therapy will enable achieving a sustained virological response under real-world experience. The study population of 97 patients who discontinued DAA therapy and had data enabling analysis of patient and disease characteristics, and assessment of treatment effectiveness was selected from 16,815 patients registered in the EpiTer-2 database. The most common reason for discontinuation was hepatic decompensation (20.6%) or the patient's personal decision (18.6%). Patients who discontinued treatment were significantly older, more frequently therapy-experienced, more likely to have cirrhosis, a history of decompensation and a Child-Pugh B or C classification than those who completed treatment. SVR was achieved by 93.5% of patients who discontinued treatment after 4 weeks, 60.9% if discontinued at 3 or 4 week and 33.3% at Week 1 or 2. Patients receiving pangenotypic but not genotype-specific treatment who discontinued after 4 weeks were as likely to achieve SVR as those who completed therapy. Patients who responded to treatment that lasted no longer than 2 weeks had a low baseline viral load (<400,000 IU/mL). Despite discontinuation of therapy after Week 4, the chances of SVR are high. Very early discontinuation does not preclude therapeutic success, especially in patients with low baseline viral load.
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Affiliation(s)
- Robert Flisiak
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, Białystok, Poland
| | | | - Ewa Janczewska
- Department of Basic Medical Sciences, School of Public Health in Bytom, Medical University of Silesia, Katowice, Poland
| | - Anna Parfieniuk-Kowerda
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, Białystok, Poland
| | - Włodzimierz Mazur
- Clinical Department of Infectious Diseases, Medical University of Silesia, Chorzów, Poland
| | - Marek Sitko
- Department of Infectious and Tropical Diseases, Jagiellonian University, Kraków, Poland
| | - Justyna Janocha-Litwin
- Department of Infectious Diseases and Hepatology, Wrocław Medical University, Wrocław, Poland
| | - Rafał Krygier
- Infectious Diseases and Hepatology Outpatient Clinic NZOZ "Gemini", Żychlin, Poland
| | - Beata Lorenc
- Pomeranian Center of Infectious Diseases, Medical University Gdańsk, Gdańsk, Poland
| | - Anna Piekarska
- Department of Infectious Diseases and Hepatology, Medical University of Łódź, Łódź, Poland
| | - Barbara Sobala-Szczygieł
- Department of Infectious Diseases and Hepatology, Medical University of Silesia in Katowice, Bytom, Poland
| | | | - Łukasz Socha
- Department of Infectious Diseases, Hepatology and Liver Transplantation, Pomeranian Medical University, Szczecin, Poland
| | - Jerzy Jaroszewicz
- Department of Infectious Diseases and Hepatology, Medical University of Silesia in Katowice, Bytom, Poland
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Zarębska-Michaluk D, Brzdęk M, Tronina O, Janocha-Litwin J, Sitko M, Piekarska A, Klapaczyński J, Parfieniuk-Kowerda A, Sobala-Szczygieł B, Tudrujek-Zdunek M, Laurans Ł, Flisiak R. Loss to follow-up of patients after antiviral treatment as an additional barrier to HCV elimination. BMC Med 2024; 22:486. [PMID: 39444018 PMCID: PMC11515622 DOI: 10.1186/s12916-024-03699-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2024] [Accepted: 10/10/2024] [Indexed: 10/25/2024] Open
Abstract
BACKGROUND Eliminating hepatitis C virus (HCV) infections is a goal set by the World Health Organization. This has become possible with the introduction of highly effective and safe direct-acting antivirals (DAA) but limitations remain due to undiagnosed HCV infections and loss of patients from the cascade of care at various stages, including those lost to follow-up (LTFU) before the assessment of the effectiveness of the therapy. The aim of our study was to determine the extent of this loss and to establish the characteristics of patients experiencing it. METHODS Patients with chronic HCV infection from the Polish retrospective multicenter EpiTer-2 database who were treated with DAA therapies between 2015 and 2023 were included in the study. RESULTS In the study population of 18,968 patients, 106 had died by the end of the 12-week post-treatment follow-up period, and 509 patients did not report for evaluation of therapy effectiveness while alive and were considered LTFU. Among patients with available assessment of sustained virological response (SVR), the effectiveness of therapy was 97.5%. A significantly higher percentage of men (p<0.0001) and a lower median age (p=0.0001) were documented in LTFU compared to the group with available SVR assessment. In LTFU patients, comorbidities such as alcohol (p<0.0001) and drug addiction (p=0.0005), depression (p=0.0449) or other mental disorders (p<0.0001), and co-infection with human immunodeficiency virus (HIV) (p<0.0001) were significantly more common as compared to those with SVR assessment. They were also significantly more often infected with genotype (GT) 3, less likely to be treatment-experienced and more likely to discontinue DAA therapy. CONCLUSIONS In a real-world population of nearly 19,000 HCV-infected patients, we documented a 2.7% loss to follow-up rate. Independent predictors of this phenomenon were male gender, GT3 infection, HIV co-infection, alcohol addiction, mental illnesses, lack of prior antiviral treatment and discontinuation of DAA therapy.
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Affiliation(s)
- Dorota Zarębska-Michaluk
- Department of Infectious Diseases and Allergology, Jan Kochanowski University, Kielce, 25-317, Poland
| | - Michał Brzdęk
- Collegium Medicum, Jan Kochanowski University, aleja IX Wieków Kielc 19A, Kielce, 25-317, Poland.
| | - Olga Tronina
- Department of Transplantology, Immunology, Nephrology and Internal Diseases, Medical University of Warsaw, Warsaw, Mazowieckie, 02-006, Poland
| | - Justyna Janocha-Litwin
- Department of Infectious Diseases and Hepatology, Wrocław Medical University, Wrocław, 50-367, Poland
| | - Marek Sitko
- Department of Infectious and Tropical Diseases, Jagiellonian University, Kraków, 31-088, Poland
| | - Anna Piekarska
- Department of Infectious Diseases and Hepatology, Medical University of Łódź, Łódź, 90-419, Poland
| | - Jakub Klapaczyński
- Department of Internal Medicine and Hepatology, The National Institute of Medicine of the Ministry of Interior and Administration, Warszawa, 02-507, Poland
| | - Anna Parfieniuk-Kowerda
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, Białystok, 15-089, Poland
| | - Barbara Sobala-Szczygieł
- Department of Infectious Diseases and Hepatology, Medical University of Silesia in Katowice, Katowice, 40-635, Poland
| | | | - Łukasz Laurans
- Department of Infectious Diseases, Hepatology and Liver Transplantation, Pomeranian Medical University, Szczecin, 70-204, Poland
- Multidisciplinary Regional Hospital in Gorzów Wielkopolski, Gorzów Wielkopolski, 66-400, Poland
| | - Robert Flisiak
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, Białystok, 15-089, Poland
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Brzdęk M, Zarębska-Michaluk D, Kukla M, Janocha-Litwin J, Dybowska D, Janczewska E, Lorenc B, Berak H, Mazur W, Tudrujek-Zdunek M, Klapaczyński J, Piekarska A, Sitko M, Laurans Ł, Parfieniuk-Kowerda A, Flisiak R. Real-world experience with direct-acting antiviral therapy in HCV-infected patients with cirrhosis and esophageal varices. Pharmacol Rep 2024; 76:1114-1129. [PMID: 39162985 PMCID: PMC11387439 DOI: 10.1007/s43440-024-00639-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2024] [Revised: 08/11/2024] [Accepted: 08/12/2024] [Indexed: 08/21/2024]
Abstract
BACKGROUND Hepatitis C virus (HCV) infection affects 50 million people worldwide with around 242,000 deaths annually, mainly due to complications such as cirrhosis and hepatocellular carcinoma (HCC). Portal hypertension (PH) caused by cirrhosis leads to severe consequences, including esophageal varices (EV). This study aimed to evaluate the effectiveness and safety of direct-acting antiviral (DAA) treatment in patients with and without EV. METHODS This retrospective analysis involved consecutive HCV-infected adults undergoing DAA therapy at 22 Polish hepatology centers from July 1, 2015, to December 31, 2022. Patients with cirrhosis were categorized based on the presence of EV diagnosed by gastroscopy. Treatment effectiveness was measured by sustained virologic response (SVR), with safety outcomes monitored for 12 weeks post-treatment. RESULTS A population of 3393 HCV-infected patients with cirrhosis was divided into groups with (A, n = 976) and without (B, n = 2417) EV. Group A showed a significantly higher prevalence of comorbidities and concomitant medications. Genotype (GT)1b infections predominated in both groups, and GT3 infections were more common in the EV group. Group A exhibited more severe liver disease, and higher rates of decompensation, HCC, and HBV co-infection. SVR was significantly higher in group B (91.5% vs. 96.3%, p < 0.0001). Male gender, GT3, EV presence, and Child-Pugh grade B were identified as independent negative SVR predictors. Group A had a worse safety profile, with notably higher adverse event incidence and mortality. CONCLUSIONS DAA therapies are highly effective and well tolerated in patients with cirrhosis, but EV presence predicts poorer virologic responses.
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Affiliation(s)
- Michał Brzdęk
- Collegium Medicum, Jan Kochanowski University, aleja IX Wieków Kielc 19A, Kielce, 25-317, Poland.
| | - Dorota Zarębska-Michaluk
- Department of Infectious Diseases and Allergology, Jan Kochanowski University, Kielce, 25- 317, Poland
| | - Michał Kukla
- Department of Internal Medicine and Geriatrics, Faculty of Medicine, Jagiellonian University Medical College, Kraków, 31-688, Poland
- Department of Endoscopy, University Hospital, Kraków, 30-688, Poland
| | - Justyna Janocha-Litwin
- Department of Infectious Diseases and Hepatology, Wrocław Medical University, Wrocław, 50- 367, Poland
| | - Dorota Dybowska
- Department of Infectious Diseases and Hepatology, Faculty of Medicine, Collegium Medicum Bydgoszcz, Nicolaus Copernicus University, Toruń, 87-100, Poland
- Voivodeship Infectious Observation Hospital in Bydgoszcz, Bydgoszcz, 85-030, Poland
| | - Ewa Janczewska
- Department of Basic Medical Sciences, School of Public Health in Bytom, Medical University of Silesia, Katowice, 40-055, Poland
| | - Beata Lorenc
- Pomeranian Center of Infectious Diseases, Medical University, Gdańsk, 80-214, Poland
| | - Hanna Berak
- Outpatient Clinic, Hospital for Infectious Diseases in Warsaw, Warsaw, 01-201, Poland
| | - Włodzimierz Mazur
- Clinical Department of Infectious Diseases in Chorzów, Medical University of Silesia, Katowice, 40-055, Poland
| | | | - Jakub Klapaczyński
- Department of Internal Medicine and Hepatology, The National Institute of Medicine of the Ministry of Interior and Administration, Warszawa, 02-507, Poland
| | - Anna Piekarska
- Department of Infectious Diseases and Hepatology, Medical University of Łódź, Łódź, 90- 419, Poland
| | - Marek Sitko
- Department of Infectious and Tropical Diseases, Jagiellonian University, Kraków, 31- 088, Poland
| | - Łukasz Laurans
- Department of Infectious Diseases, Hepatology and Liver Transplantation, Pomeranian Medical University, Szczecin, 70-204, Poland
- Multidisciplinary Regional Hospital in Gorzów Wielkopolski, Gorzów Wielkopolski, 66-400, Poland
| | - Anna Parfieniuk-Kowerda
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, Białystok, 15-089, Poland
| | - Robert Flisiak
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, Białystok, 15-089, Poland
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Brzdęk M, Zarębska-Michaluk D, Tomasiewicz K, Tudrujek-Zdunek M, Lorenc B, Mazur W, Berak H, Janocha-Litwin J, Klapaczyński J, Sitko M, Janczewska E, Dybowska D, Parfieniuk-Kowerda A, Piekarska A, Jaroszewicz J, Flisiak R. Effectiveness and safety of direct-acting antivirals in the therapy of HCV-infected elderly people. Minerva Med 2024; 115:266-276. [PMID: 38591836 DOI: 10.23736/s0026-4806.24.09238-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/10/2024]
Abstract
BACKGROUND The introduction of direct-acting antivirals (DAAs) with their effectiveness and safety has revolutionized the approach to treating hepatitis C virus (HCV) infections. Nevertheless, elderly patients have often been excluded from clinical trials, so the results of real-world studies are particularly important in the context of the geriatric population. The study aimed to analyze the effectiveness and safety of antiviral DAA treatment in HCV-infected patients over the age of 65, with notable inclusion of those over the age of 85. METHODS The analyzed patients were divided by age into three groups: group A (65-74 years), group B (75-84 years) and group C (85 years or older). Patients started DAA based therapy at 22 hepatology centers between July 2015 and December 2022. RESULTS A total of 3505 elderly patients were included in the analysis, and this group consisted of 2501 patients in group A, 893 in group B, and 111 in group C. The study population, regardless of age, was dominated by women. Patients had a high prevalence of comorbidities (84.9%, 92.2%, and 93.7%, respectively) as well as a high rate of concomitant medications. The sustained virological response was 97.9% in groups A and B and 100% in group C. The therapy was well-tolerated, with a comparable safety profile observed in all analyzed groups. CONCLUSIONS DAA-based therapies are highly effective and well tolerated by the elderly patients, including those over 85. Age should not be a barrier to treatment, but careful management is necessary.
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Affiliation(s)
- Michał Brzdęk
- Department of Infectious Diseases and Allergology, Jan Kochanowski University, Kielce, Poland -
| | | | | | | | - Beata Lorenc
- Pomeranian Center of Infectious Diseases, Medical University Gdansk, Gdansk, Poland
| | - Włodzimierz Mazur
- Clinical Department of Infectious Diseases, Clinical University of Silesia in Katowice, Chorzów, Poland
| | - Hanna Berak
- Daily Department, Hospital for Infectious Diseases, Warsaw, Poland
| | - Justyna Janocha-Litwin
- Department of Infectious Diseases and Hepatology, Wroclaw Medical University, Wroclaw, Poland
| | - Jakub Klapaczyński
- Department of Internal Medicine and Hepatology, The National Institute of Medicine of the Ministry of Interior and Administration, Warsaw, Poland
| | - Marek Sitko
- Department of Infectious and Tropical Diseases, Jagiellonian University, Krakow, Poland
| | - Ewa Janczewska
- Department of Basic Medical Sciences, Faculty of Public Health in Bytom, Medical University of Silesia in Katowice, Bytom, Poland
| | - Dorota Dybowska
- Department of Infectious Diseases and Hepatology, Faculty of Medicine, Nicolaus Copernicus University, Bydgoszcz, Poland
| | - Anna Parfieniuk-Kowerda
- Department of Infectious Diseases and Hepatology, Medical University of Bialystok, Bialystok, Poland
| | - Anna Piekarska
- Department of Infectious Diseases and Hepatology, Medical University of Lodz, Lodz, Poland
| | - Jerzy Jaroszewicz
- Department of Infectious Diseases and Hepatology, Medical University of Silesia in Katowice, Bytom, Poland
| | - Robert Flisiak
- Department of Infectious Diseases and Hepatology, Medical University of Bialystok, Bialystok, Poland
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5
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Dobrowolska K, Pawłowska M, Zarębska-Michaluk D, Rzymski P, Janczewska E, Tudrujek-Zdunek M, Berak H, Mazur W, Klapaczyński J, Lorenc B, Janocha-Litwin J, Parfieniuk-Kowerda A, Dybowska D, Piekarska A, Krygier R, Dobracka B, Jaroszewicz J, Flisiak R. Direct-acting antivirals in women of reproductive age infected with hepatitis C virus. J Viral Hepat 2024; 31:309-319. [PMID: 38483035 DOI: 10.1111/jvh.13936] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2024] [Revised: 02/16/2024] [Accepted: 03/03/2024] [Indexed: 05/18/2024]
Abstract
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.
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Affiliation(s)
| | - Małgorzata Pawłowska
- Department of Infectious Diseases and Hepatology, Faculty of Medicine, Collegium Medicum Bydgoszcz, Nicolaus Copernicus University, Toruń, Poland
| | | | - Piotr Rzymski
- Department of Environmental Medicine, Poznań University of Medical Sciences, Poznań, Poland
| | - Ewa Janczewska
- Department of Basic Medical Sciences, School of Public Health in Bytom, Medical University of Silesia, Katowice, Poland
| | | | - Hanna Berak
- Outpatient Clinic, Hospital for Infectious Diseases in Warsaw, Warsaw, Poland
| | - Włodzimierz Mazur
- Clinical Department of Infectious Diseases in Chorzów, Medical University of Silesia, Katowice, Poland
| | - Jakub Klapaczyński
- Department of Internal Medicine and Hepatology, The National Institute of Medicine of the Ministry of Interior and Administration, Warszawa, Poland
| | - Beata Lorenc
- Pomeranian Center of Infectious Diseases, Medical University, Gdańsk, Poland
| | - Justyna Janocha-Litwin
- Department of Infectious Diseases and Hepatology, Wrocław Medical University, Wrocław, Poland
| | - Anna Parfieniuk-Kowerda
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, Białystok, Poland
| | - Dorota Dybowska
- Department of Infectious Diseases and Hepatology, Faculty of Medicine, Collegium Medicum Bydgoszcz, Nicolaus Copernicus University, Toruń, Poland
| | - Anna Piekarska
- Department of Infectious Diseases and Hepatology, Medical University of Łódź, Łódź, Poland
| | - Rafał Krygier
- Outpatients Hepatology Department, State University of Applied Sciences, Konin, Poland
| | | | - Jerzy Jaroszewicz
- Department of Infectious Diseases and Hepatology, Medical University of Silesia in Katowice, Bytom, Poland
| | - Robert Flisiak
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, Białystok, Poland
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6
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Zarębska-Michaluk D, Flisiak R, Janczewska E, Berak H, Mazur W, Janocha-Litwin J, Krygier R, Dobracka B, Jaroszewicz J, Parfieniuk-Kowerda A, Dobrowolska K, Rzymski P. Does a detectable HCV RNA at the end of DAA therapy herald treatment failure? Antiviral Res 2023; 220:105742. [PMID: 37944825 DOI: 10.1016/j.antiviral.2023.105742] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2023] [Revised: 10/23/2023] [Accepted: 10/29/2023] [Indexed: 11/12/2023]
Abstract
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.
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Affiliation(s)
- Dorota Zarębska-Michaluk
- Department of Infectious Diseases and Allergology, Jan Kochanowski University, 25-317, Kielce, Poland.
| | - Robert Flisiak
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, 15-540, Białystok, Poland
| | - Ewa Janczewska
- Department of Basic Medical Sciences, School of Public Health in Bytom, Medical University of Silesia, 40-055, Katowice, Poland
| | - Hanna Berak
- Outpatient Clinic, Hospital for Infectious Diseases in Warsaw, 01-201, Warsaw, Poland
| | - Włodzimierz Mazur
- Clinical Department of Infectious Diseases in Chorzów, Medical University of Silesia, 40-055, Katowice, Poland
| | - Justyna Janocha-Litwin
- Department of Infectious Diseases and Hepatology, Wrocław Medical University, 50-367, Wrocław, Poland
| | - Rafał Krygier
- Infectious Diseases and Hepatology Outpatient Clinic NZOZ "Gemini", 62-571, Żychlin, Poland
| | | | - Jerzy Jaroszewicz
- Department of Infectious Diseases and Hepatology, Medical University of Silesia, 40-055, Katowice, Poland
| | - Anna Parfieniuk-Kowerda
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, 15-540, Białystok, Poland
| | | | - Piotr Rzymski
- Department of Environmental Medicine, Poznań University of Medical Sciences, 60-806, Poznań, Poland
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7
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Tronina O, Brzdęk M, Zarębska-Michaluk D, Lorenc B, Janocha-Litwin J, Berak H, Sitko M, Dybowska D, Mazur W, Tudrujek-Zdunek M, Janczewska E, Klapaczyński J, Dobracki W, Parfieniuk-Kowerda A, Krygier R, Socha Ł, Flisiak R. Real-world effectiveness of genotype-specific and pangenotypic direct-acting antivirals in HCV-infected patients with renal failure. Clin Exp Hepatol 2023; 9:320-334. [PMID: 38774196 PMCID: PMC11103803 DOI: 10.5114/ceh.2023.133307] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2023] [Accepted: 11/16/2023] [Indexed: 05/24/2024] Open
Abstract
Aim of the study The aim is to summarize the effectiveness and safety of genotype-specific and pangenotypic hepatitis C virus (HCV) treatments in patients with renal failure. Material and methods In the EpiTer-2 database, which includes data from 22 hepatology centers in Poland, 593 patients with HCV infection and kidney failure were identified. According to KDIGO 2022, they fulfilled the criteria of chronic kidney disease. Patients were divided into two groups: treated with genotype-specific regimens (n = 428) and pangenotypic options (n = 165), in relation to the stage of kidney disease determined using the glomerular filtration rate (GFR) (Cockcroft and Gault equation). Two separate groups were created for hemodialyzed patients (n = 134) and patients after kidney transplantation (n = 89). Results In a total of 593 patients, 78.7% were treatment-naïve and 23.9% had liver cirrhosis, in 27.5% of cases decompensated. In both groups, the dominant genotype was GT1b. Among patients treated with genotype-specific regimens, LDV/SOF ± RBV, OBV/PTV/r + DSV ± RBV, and GZR/EBR ± RBV treatments were given to 31.5%, 31.5%, and 34.8% of patients respectively. In pangenotypic regimens, GLE/PIB was chosen in 50.3%. Ninety-six percent and 98.8% of patients in the genotype-specific regimen and 88.5% and 94.8% in the pangenotypic regimen achieved a sustained virologic response at 12 weeks (SVR12) in the intention-to-treat and per protocol population respectively. Liver cirrhosis was identified as a risk factor for virological failure. During the study, 14 patients died, 7 in each of the two groups, none related to the antiviral treatment. Conclusions Both types of treatment regimens are equally effective and safe in patients with renal failure. The stage of renal failure or transplant does not influence the antiviral response.
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Affiliation(s)
- Olga Tronina
- Department of Transplantation Medicine, Nephrology, and Internal Diseases, Medical University of Warsaw, Warsaw, Poland
| | - Michał Brzdęk
- Collegium Medicum, Jan Kochanowski University, Kielce, Poland
| | | | - Beata Lorenc
- Pomeranian Center of Infectious Diseases, Medical University Gdańsk, Gdańsk, Poland
| | - Justyna Janocha-Litwin
- Department of Infectious Diseases and Hepatology, Wrocław Medical University, Wrocław, Poland
| | - Hanna Berak
- Outpatient Clinic, Hospital for Infectious Diseases in Warsaw, Warsaw, Poland
| | - Marek Sitko
- Department of Infectious and Tropical Diseases, Jagiellonian University, Kraków, Poland
| | - Dorota Dybowska
- Department of Infectious Diseases and Hepatology, Faculty of Medicine, Nicolaus Copernicus University, Bydgoszcz, Poland
| | - Włodzimierz Mazur
- Clinical Department of Infectious Diseases, Medical University of Silesia, Chorzów, Poland
| | | | - Ewa Janczewska
- Department of Basic Medical Sciences, School of Public Health in Bytom, Medical University of Silesia, Katowice, Poland
| | - Jakub Klapaczyński
- Department of Internal Medicine and Hepatology, The National Institute of Medicine of the Ministry of Interior and Administration, Warsaw, Poland
| | | | - Anna Parfieniuk-Kowerda
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, Białystok, Poland
| | - Rafał Krygier
- Outpatients Hepatology Department, NZOZ GEMINI, Żychlin, Poland
| | - Łukasz Socha
- Department of Infectious Diseases, Hepatology, and Liver Transplantation, Pomeranian Medical University, Szczecin, Poland
| | - Robert Flisiak
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, Białystok, Poland
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8
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Pawlowska M, Dobrowolska K, Moppert J, Pokorska-Śpiewak M, Purzynska M, Marczynska M, Zarebska-Michaluk D, Flisiak R. Real-World Efficacy and Safety of an 8-Week Glecaprevir/Pibrentasvir Regimen in Children and Adolescents with Chronic Hepatitis C-Results of a Multicenter EpiTer-2 Study. J Clin Med 2023; 12:6949. [PMID: 37959413 PMCID: PMC10647729 DOI: 10.3390/jcm12216949] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2023] [Revised: 09/26/2023] [Accepted: 11/03/2023] [Indexed: 11/15/2023] Open
Abstract
The aim of the study was to analyze the effectiveness and safety of anti-HCV treatment based on a pangenotypic direct-acting antiviral (DAA) regimen with glecaprevir/pibrentasvir (GLE/PIB) in children. The multi-center study was conducted in HCV-infected children who were treated in the period from November 2022 to January 2023. The analysis included 23 pediatric patients with a mean (SD) age of 9.61 (3.68) years. The cohort included 13 girls and 10 boys. The most common HCV genotypes were GT1b (n = 9, 39.1%), GT1a (n = 6, 26.1%) and GT3 (n = 5, 21.7%). The SVR was assessed at 12 weeks after the end of treatment and was 100% for both girls and boys. The conducted study showed a very good tolerance of the treatment in the entire analyzed group and confirmed a very high efficacy and safety for 8-week treatment with GLE/PIB in children over three years of age. It seems that our study is the first on the real-world use of an 8-week GLE/PIB pangenotypic therapy in a group of children aged 3-12 years and the first in Europe for adolescents aged 12-17.
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Affiliation(s)
- Malgorzata Pawlowska
- Department of Infectious Diseases and Hepatology, Faculty of Medicine, Collegium Medicum Bydgoszcz, Nicolaus Copernicus University, 87-100 Torun, Poland;
- Department of Paediatrics, Infectious Diseases and Hepatology, Voivodeship Infectious Observation Hospital in Bydgoszcz, 85-030 Bydgoszcz, Poland
| | | | - Justyna Moppert
- Department of Infectious Diseases and Hepatology, Faculty of Medicine, Collegium Medicum Bydgoszcz, Nicolaus Copernicus University, 87-100 Torun, Poland;
- Department of Paediatrics, Infectious Diseases and Hepatology, Voivodeship Infectious Observation Hospital in Bydgoszcz, 85-030 Bydgoszcz, Poland
| | - Maria Pokorska-Śpiewak
- Department of Children’s Infectious Diseases, Medical University of Warsaw, 01-201 Warsaw, Poland; (M.P.-Ś.); (M.M.)
- Department of Pediatric Infectious Diseases, Regional Hospital of Infectious Diseases in Warsaw, 01-201 Warsaw, Poland
| | - Mariola Purzynska
- Pomeranian Centre of Department of Infectious Diseases and Observation for Children, Smoluchowskiego 18, 80-214 Gdansk, Poland;
| | - Magdalena Marczynska
- Department of Children’s Infectious Diseases, Medical University of Warsaw, 01-201 Warsaw, Poland; (M.P.-Ś.); (M.M.)
- Department of Pediatric Infectious Diseases, Regional Hospital of Infectious Diseases in Warsaw, 01-201 Warsaw, Poland
| | - Dorota Zarebska-Michaluk
- Department of Infectious Diseases and Allergology, Jan Kochanowski University, 25-317 Kielce, Poland;
| | - Robert Flisiak
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, 15-540 Bialystok, Poland;
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9
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Flisiak R, Zarębska-Michaluk D, Berak H, Dybowska D, Sitko M, Parfieniuk-Kowerda A, Janocha-Litwin J, Janczewska E, Piekarska A, Lorenc B, Mazur W, Dobrowolska K, Tudrujek-Zdunek M, Klapaczyński J, Jaroszewicz J. Pangenotypic triple versus double therapy in HCV-infected patients after prior failure of direct-acting antivirals. Clin Exp Hepatol 2023; 9:193-201. [PMID: 37790681 PMCID: PMC10544061 DOI: 10.5114/ceh.2023.130935] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2023] [Accepted: 08/20/2023] [Indexed: 10/05/2023] Open
Abstract
Aim of the study Despite the excellent effectiveness of direct-acting antivirals (DAA) in the treatment of hepatitis C virus (HCV) infection, still a few percent of patients fail therapy. The study aimed to determine the effectiveness of triple vs double rescue treatment in such a population. Material and methods The study included all consecutive DAA-experienced patients retreated with pangenotypic options from the EpiTer-2 database, a retrospective national multicenter real-world project evaluating antiviral treatment in HCV-infected patients in 2015-2023. Results The studied population consisted of 269 patients, of whom 208 were treated with the double (P2) and 61 with the triple (P3) pangenotypic option. No statistically significant differences were found between these subpopulations, except a significantly more frequent history of liver transplantation in the P3 group (6.6% vs. 0.5%, p = 0.01). In the P2 group, two-thirds of patients were treated with velpatasvir/sofosbuvir, while in the P3 group the majority of patients received a combination of velpatasvir/sofosbuvir/voxilaprevir. Virological response at the end of therapy was comparable in both analyzed subpopulations, but the sustained virologic response (SVR) rate was significantly higher in triple retherapy, 98.3% vs. 88.7%, p = 0.02, calculated after exclusion of patients lost to follow-up. Lower SVR was achieved in genotype 3-infected men with cirrhosis, 88.9% and 80% in P3 and P2, respectively. Conclusions A comparison of double and triple pangenotypic retherapy in patients after failure of DAA therapy showed a higher sustained virological response in the triple option with a comparable response at the end of therapy. The factors reducing the chances of cure were cirrhosis, genotype 3 infection and male gender.
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Affiliation(s)
- Robert Flisiak
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, Białystok, Poland
| | | | - Hanna Berak
- Outpatient Clinic, Hospital for Infectious Diseases in Warsaw, Warsaw, Poland
| | - Dorota Dybowska
- Department of Infectious Diseases and Hepatology, Faculty of Medicine, Nicolaus Copernicus University, Bydgoszcz, Poland
| | - Marek Sitko
- Department of Infectious and Tropical Diseases, Jagiellonian University, Kraków, Poland
| | - Anna Parfieniuk-Kowerda
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, Białystok, Poland
| | - Justyna Janocha-Litwin
- Department of Infectious Diseases and Hepatology, Wrocław Medical University, Wrocław, Poland
| | - Ewa Janczewska
- Department of Basic Medical Sciences, School of Public Health in Bytom, Medical University of Silesia, Katowice, Poland
| | - Anna Piekarska
- Department of Infectious Diseases and Hepatology, Medical University of Łódź, Poland
| | - Beata Lorenc
- Pomeranian Center of Infectious Diseases, Medical University of Gdańsk, Gdańsk, Poland
| | - Włodzimierz Mazur
- Clinical Department of Infectious Diseases, Medical University of Silesia, Chorzów, Poland
| | | | | | - Jakub Klapaczyński
- Department of Internal Medicine and Hepatology, The National Institute of Medicine of the Ministry of Interior and Administration, Warsaw, Poland
| | - Jerzy Jaroszewicz
- Department of Infectious Diseases and Hepatology, Medical University of Silesia, Katowice, Poland
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10
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Wróblewska A, Woziwodzka A, Rybicka M, Bielawski KP, Sikorska K. Polymorphisms Related to Iron Homeostasis Associate with Liver Disease in Chronic Hepatitis C. Viruses 2023; 15:1710. [PMID: 37632052 PMCID: PMC10457817 DOI: 10.3390/v15081710] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2023] [Revised: 08/01/2023] [Accepted: 08/05/2023] [Indexed: 08/27/2023] Open
Abstract
Dysregulation of iron metabolism in chronic hepatitis C (CHC) is a significant risk factor for hepatic cirrhosis and cancer. We studied if known genetic variants related to iron homeostasis associate with liver disease progression in CHC. Retrospective analysis included 249 CHC patients qualified for antiviral therapy between 2004 and 2014. For all patients, nine SNPs within HFE, TFR2, HDAC2, HDAC3, HDAC5, TMPRSS6, and CYBRD1 genes were genotyped. Expression of selected iron-related genes, was determined with qRT-PCR in 124 liver biopsies, and mRNA expression of co-inhibitory receptors (PD-1, Tim3, CTLA4) was measured in 79 liver samples. CYBRD1 rs884409, HDAC5 rs368328, TFR2 rs7385804, and TMPRSS6 rs855791 associated with histopathological changes in liver tissue at baseline. The combination of minor allele in HDAC3 rs976552 and CYBRD1 rs884409 linked with higher prevalence of hepatocellular carcinoma (HCC) during follow up (OR 8.1 CI 2.2-29.2; p = 0.001). Minor allele in HDAC3 rs976552 associated with lower hepatic expression of CTLA4. Tested polymorphisms related to iron homeostasis associate with histopathological changes in the liver. The presence of both HDAC3 rs976552 G and CYBRD1 rs884409 G alleles correlates with HCC occurrence, especially in the group of patients with elevated AST (>129 IU/L). rs976552 in HDAC3 could impact immunological processes associated with carcinogenesis in CHC.
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Affiliation(s)
- Anna Wróblewska
- Laboratory of Photobiology and Molecular Diagnostics, Intercollegiate Faculty of Biotechnology University of Gdansk and Medical University of Gdansk, 80-307 Gdansk, Poland; (A.W.); (A.W.); (M.R.); (K.P.B.)
| | - Anna Woziwodzka
- Laboratory of Photobiology and Molecular Diagnostics, Intercollegiate Faculty of Biotechnology University of Gdansk and Medical University of Gdansk, 80-307 Gdansk, Poland; (A.W.); (A.W.); (M.R.); (K.P.B.)
| | - Magda Rybicka
- Laboratory of Photobiology and Molecular Diagnostics, Intercollegiate Faculty of Biotechnology University of Gdansk and Medical University of Gdansk, 80-307 Gdansk, Poland; (A.W.); (A.W.); (M.R.); (K.P.B.)
| | - Krzysztof P. Bielawski
- Laboratory of Photobiology and Molecular Diagnostics, Intercollegiate Faculty of Biotechnology University of Gdansk and Medical University of Gdansk, 80-307 Gdansk, Poland; (A.W.); (A.W.); (M.R.); (K.P.B.)
| | - Katarzyna Sikorska
- Division of Tropical Medicine and Epidemiology, Faculty of Health Sciences, Institute of Maritime and Tropical Medicine, Medical University of Gdansk, 81-519 Gdynia, Poland
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Brzdęk M, Zarębska-Michaluk D, Rzymski P, Lorenc B, Kazek A, Tudrujek-Zdunek M, Janocha-Litwin J, Mazur W, Dybowska D, Berak H, Parfieniuk-Kowerda A, Klapaczyński J, Sitko M, Sobala-Szczygieł B, Piekarska A, Flisiak R. Changes in characteristics of patients with hepatitis C virus-related cirrhosis from the beginning of the interferon-free era. World J Gastroenterol 2023; 29:2015-2033. [PMID: 37155527 PMCID: PMC10122793 DOI: 10.3748/wjg.v29.i13.2015] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Revised: 01/16/2023] [Accepted: 03/20/2023] [Indexed: 04/06/2023] Open
Abstract
BACKGROUND Nearly 290000 patients with chronic hepatitis C die annually from the most severe complications of the disease. One of them is liver cirrhosis, which occurs in about 20% of patients chronically infected with the hepatitis C virus (HCV). Direct-acting antivirals (DAAs), which replaced interferon (IFN)-based regimens, significantly improved the prognosis of this group of patients, increasing HCV eradication rates and tolerability of therapy. Our study is the first to assess changes in patient profile, effectiveness, and safety in the HCV-infected cirrhotic population in the IFN-free era.
AIM To document changes in patient characteristics and treatment regimens along with their effectiveness and safety profile over the years.
METHODS The studied patients were selected from 14801 chronically HCV-infected individuals who started IFN-free therapy between July 2015 and December 2021 in 22 Polish hepatology centers. The retrospective analysis was conducted in real-world clinical practice based on the EpiTer-2 multicenter database. The measure of treatment effectiveness was the percentage of sustained virologic response (SVR) calculated after excluding patients lost to follow-up. Safety data collected during therapy and the 12-wk post-treatment period included information on adverse events, including serious ones, deaths, and treatment course.
RESULTS The studied population (n = 3577) was balanced in terms of gender in 2015-2017, while the following years showed the dominance of men. The decline in the median age from 60 in 2015-2016 to 57 years in 2021 was accompanied by a decrease in the percentage of patients with comorbidities and comedications. Treatment-experienced patients dominated in 2015-2016, while treatment-naive individuals gained an advantage in 2017 and reached 93.2% in 2021. Genotype (GT)-specific options were more prevalent in treatment in 2015-2018 and were supplanted by pangenotypic combinations in subsequent years. The effectiveness of the therapy was comparable regardless of the period analyzed, and patients achieved an overall response rate of 95%, with an SVR range of 72.9%-100% for the different therapeutic regimens. Male gender, GT3 infection, and prior treatment failure were identified as independent negative predictors of therapeutic success.
CONCLUSION We have documented changes in the profile of HCV-infected cirrhotic patients over the years of accessibility to changing DAA regimens, confirming the high effectiveness of IFN-free therapy in all analyzed periods.
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Affiliation(s)
- Michał Brzdęk
- Department of Infectious Diseases, Jan Kochanowski University, Kielce 25-317, Poland
| | | | - Piotr Rzymski
- Department of Environmental Medicine, Poznan University of Medical Sciences, Poznań 60-806, Poland
- Integrated Science Association, Universal Scientific Education and Research Network, Poznań 60-806, Poland
| | - Beata Lorenc
- Pomeranian Center of Infectious Diseases, Medical University Gdańsk, Gdańsk 80-214, Poland
| | | | | | - Justyna Janocha-Litwin
- Department of Infectious Diseases and Hepatology, Medical University Wrocław, Wrocław 50-367, Poland
| | - Włodzimierz Mazur
- Clinical Department of Infectious Diseases, Clinical University of Silesia in Katowice, Chorzów 41-500, Poland
| | - Dorota Dybowska
- Department of Infectious Diseases and Hepatology, Faculty of Medicine, Nicolaus Copernicus University, Bydgoszcz 85-030, Poland
| | - Hanna Berak
- Daily Department, Hospital for Infectious Diseases in Warsaw, Warszawa 01-201, Poland
| | - Anna Parfieniuk-Kowerda
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, Białystok 15-089, Poland
| | - Jakub Klapaczyński
- Department of Internal Medicine and Hepatology, Central Clinical Hospital of the Ministry of Internal Affairs and Administration, Warszawa 00-241, Poland
| | - Marek Sitko
- Department of Infectious and Tropical Diseases, Jagiellonian University, Kraków 31-088, Poland
| | - Barbara Sobala-Szczygieł
- Department of Infectious Diseases, Medical University of Silesia in Katowice, Bytom 41-902, Poland
| | - Anna Piekarska
- Department of Infectious Diseases and Hepatology, Medical University of Łódź, Łódź 90-419, Poland
| | - Robert Flisiak
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, Białystok 15-089, Poland
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12
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Tronina O, Brzdęk M, Zarębska-Michaluk D, Dybowska D, Lorenc B, Janczewska E, Mazur W, Parfieniuk-Kowerda A, Piekarska A, Krygier R, Klapaczyński J, Berak H, Jaroszewicz J, Garlicki A, Tomasiewicz K, Citko J, Flisiak R. Rescue Therapy after Failure of HCV Antiviral Treatment with Interferon-Free Regimens. Viruses 2023; 15:677. [PMID: 36992388 PMCID: PMC10055110 DOI: 10.3390/v15030677] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2023] [Revised: 03/01/2023] [Accepted: 03/03/2023] [Indexed: 03/08/2023] Open
Abstract
Direct-acting antivirals (DAA) regimens have provided hope for eliminating hepatitis C virus (HCV) infection. Patients following ineffective therapy with DAA, especially those previously treated with inhibitors of non-structural protein 5A (NS5A), remain a challenge. The study aimed to assess the effectiveness of DAA pangenotypic options in patients after failure of NS5A containing genotype-specific regimens. The analysis included 120 patients selected from the EpiTer-2 database with data on 15675 HCV-infected individuals treated with IFN-free therapies from 1 July 2015 to 30 June 2022 at 22 Polish hepatology centres. The majority of them were infected with genotype (GT) 1b (85.8%) and one-third was diagnosed with fibrosis F4. Among the rescue pangenotypic regimens, the most commonly used was the sofosbuvir/velpatasvir (SOF/VEL) ± ribavirin (RBV) combination. The sustained virologic response, which was a measure of treatment effectiveness, was achieved by 102 patients, resulting in cure rate of 90.3% in the per protocol analysis. All 11 non-responders were infected with GT1b, 7 were diagnosed with cirrhosis, and 9 were treated with SOF/VEL±RBV. We demonstrated the high effectiveness of the pangenotypic rescue options in patients after genotype specific NS5A-containing regimens failures, identifying cirrhosis as a negative prognostic factor of treatment effectiveness.
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Affiliation(s)
- Olga Tronina
- Department of Transplantation Medicine, Nephrology, and Internal Diseases, Medical University of Warsaw, 02-091 Warsaw, Poland
| | - Michał Brzdęk
- Collegium Medicum, Jan Kochanowski University, 25-317 Kielce, Poland
| | - Dorota Zarębska-Michaluk
- Collegium Medicum, Jan Kochanowski University, 25-317 Kielce, Poland
- Department of Infectious Diseases, Voivodship Hospital, 25-317 Kielce, Poland
| | - Dorota Dybowska
- Department of Infectious Diseases and Hepatology, Faculty of Medicine, Collegium Medicum Bydgoszcz, Nicolaus Copernicus University, 87-100 Toruń, Poland
| | - Beata Lorenc
- Pomeranian Center of Infectious Diseases, Medical University of Gdańsk, 80-210 Gdańsk, Poland
| | - Ewa Janczewska
- Department of Basic Medical Sciences, School of Public Health in Bytom, Medical University of Silesia, 40-055 Katowice, Poland
- ID Clinic, Hepatology Outpatient Department, 41-400 Bytom, Poland
| | - Włodzimierz Mazur
- Clinical Department of Infectious Diseases, Medical University of Silesia, 41-500 Chorzów, Poland
| | - Anna Parfieniuk-Kowerda
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, 15-540 Białystok, Poland
| | - Anna Piekarska
- Department of Infectious Diseases and Hepatology, Medical University of Łódź, 90-419 Łódź, Poland
| | - Rafał Krygier
- Outpatients Hepatology Department, State University of Applied Sciences, 62-510 Konin, Poland
| | - Jakub Klapaczyński
- Department of Internal Medicine and Hepatology, Central Clinical Hospital of the Ministry of Internal Affairs and Administration, 02-241 Warszawa, Poland
| | - Hanna Berak
- Outpatient Clinic, Hospital for Infectious Diseases, 02-091 Warsaw, Poland
| | - Jerzy Jaroszewicz
- Department of Infectious Diseases and Hepatology, Medical University of Silesia in Katowice, 41-902 Bytom, Poland
| | - Aleksander Garlicki
- Department of Infectious and Tropical Diseases, Jagiellonian University Collegium Medicum, 30-252 Kraków, Poland
| | - Krzysztof Tomasiewicz
- Department of Infectious Diseases, Medical University of Lublin, 20-059 Lublin, Poland
| | | | - Robert Flisiak
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, 15-540 Białystok, Poland
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13
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Brzdęk M, Dobrowolska K, Flisiak R, Zarębska-Michaluk D. Genotype 4 hepatitis C virus-a review of a diverse genotype. Adv Med Sci 2023; 68:54-59. [PMID: 36640687 DOI: 10.1016/j.advms.2022.12.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2022] [Revised: 12/02/2022] [Accepted: 12/21/2022] [Indexed: 01/15/2023]
Abstract
PURPOSE Hepatitis C virus (HCV) infection remains a major health problem and one of the leading causes of chronic liver disease worldwide. The purpose of this paper was to summarize knowledge about the epidemiology of HCV genotype (GT) 4 infection, similarities and differences with other genotypes, specific problems associated with this genotype, and treatment regimens used to treat GT4-infected patients. METHODS We performed an accurate search for literature using the PubMed database to select high-quality reviews and original articles concerning this topic. RESULTS GT4 with a global prevalence of 8% takes third place, closing the global HCV podium in terms of frequency. However, there are regions where GT4 infections are dominant, such as sub-Saharan and North Africa, and the Middle East. The disease course and complications are generally similar to those of chronic hepatitis C caused by other genotypes, although the faster progression of fibrosis was demonstrated in patients with coexisting schistosomiasis. In the era of interferon-based therapy, GT4-infected patients were described as difficult to treat due to suboptimal response. A breakthrough in the treatment of HCV-infected patients, including those with GT4 infection, was the introduction of direct-acting antiviral drugs. CONCLUSIONS The availability of safe and effective therapy has created a real opportunity for HCV eradication in line with the goal set by the World Health Organization. An example of a country where this is happening is Egypt, where GT4 accounts for more than 90% of HCV infections. There, broad access to therapy has been effectively supported by population-based screening.
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Affiliation(s)
- Michał Brzdęk
- Collegium Medicum, Jan Kochanowski University, Kielce, Poland.
| | | | - Robert Flisiak
- Department of Infectious Diseases and Hepatology, Medical University of Bialystok, Bialystok, Poland
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Zarębska-Michaluk D, Brzdęk M, Jaroszewicz J, Tudrujek-Zdunek M, Lorenc B, Klapaczyński J, Mazur W, Kazek A, Sitko M, Berak H, Janocha-Litwin J, Dybowska D, Supronowicz Ł, Krygier R, Citko J, Piekarska A, Flisiak R. Best therapy for the easiest to treat hepatitis C virus genotype 1b-infected patients. World J Gastroenterol 2022; 28:6380-6396. [PMID: 36533109 PMCID: PMC9753050 DOI: 10.3748/wjg.v28.i45.6380] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2022] [Revised: 10/01/2022] [Accepted: 11/19/2022] [Indexed: 12/02/2022] Open
Abstract
BACKGROUND The revolution in treatment of patients with chronic hepatitis C virus (HCV) infection dates back to the introduction of direct-acting antivirals (DAAs). The increase in efficacy was most pronounced in patients infected with genotype (GT) 1b, as this was the most poorly responsive population to treatment during the interferon era.
AIM To identify the most effective interferon-free therapy for GT1b-infected patients and to determine positive and negative predictors of virological response.
METHODS This real-world retrospective analysis included patients chronically infected with GT1b HCV whose data were obtained from the multicenter observational EpiTer-2 database. Treatment effectiveness was evaluated for each therapeutic regimen as the percentage of sustained virological responses (SVR). Assessment of the safety was based on the evaluation of the course of therapy, the occurrence of adverse events including serious ones, deaths during treatment and in the post 12-wk follow-up period.
RESULTS The studied population consisted of 11385 patients with a mean age of 53 ± 14.8 years and a female predominance (53.4%). The majority of them were treatment-naïve (74.6%) and patients with cirrhosis accounted for 24.3%. Of the DAA regimens used, 76.9% were GT-specific with ombitasvir/paritaprevir/ritonavir + dasabuvir ± ribavirin being the most used option (32.4%). A total of 10903 patients responded to treatment resulting in a 98.1% in the per-protocol analysis after excluding 273 patients without SVR data. The effectiveness of all regimens exceeded 90% and the highest SVR of 98.9% was achieved in patients treated with a combination of glecaprevir/pibrentasvir. Logistic regression analyses showed that the virologic response was independently associated with female sex [odds ratio (OR) = 1.67], absence of decompensated cirrhosis at baseline (OR = 2.42) and higher baseline platelets (OR = 1.004 per 1000/μL increase), while the presence of human immunodeficiency virus (HIV) coinfection significantly decreased the odds of response (OR = 0.39). About 95%-100% of patients completed therapy irrespective of the drug regimen. At least one adverse effect occurred in 10.9%-36.3% and most of them were mild. No treatment related deaths have been reported.
CONCLUSION We documented very high effectiveness and a good safety profile across all DAA regimens. Positive predictors of SVR were female sex, absence of decompensated cirrhosis at baseline and higher platelet count while HIV coinfection reduced the effectiveness.
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Affiliation(s)
| | - Michał Brzdęk
- Department of Infectious Diseases, Jan Kochanowski University, Kielce 25-317, Poland
| | - Jerzy Jaroszewicz
- Department of Infectious Diseases and Hepatology, Medical University of Silesia, Katowice 40-055, Poland
| | | | - Beata Lorenc
- Pomeranian Center of Infectious Diseases, Medical University Gdańsk, Gdańsk 80-214, Poland
| | - Jakub Klapaczyński
- Department of Internal Medicine and Hepatology, Central Clinical Hospital of the Ministry of Internal Affairs and Administration, Warszawa 00-241, Poland
| | - Włodzimierz Mazur
- Clinical Department of Infectious Diseases, Medical University of Silesia, Chorzów 41-500, Poland
| | | | - Marek Sitko
- Department of Infectious and Tropical Diseases, Jagiellonian University, Kraków 31-088, Poland
| | - Hanna Berak
- Hospital for Infectious Diseases, Hospital for Infectious Diseases, Warszawa 02-091, Poland
| | - Justyna Janocha-Litwin
- Department of Infectious Diseases and Hepatology, Medical University Wrocław, Wrocław 50-367, Poland
| | - Dorota Dybowska
- Department of Infectious Diseases and Hepatology, Faculty of Medicine, Nicolaus Copernicus University, Bydgoszcz 85-030, Poland
| | - Łukasz Supronowicz
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, Białystok 15-089, Poland
| | - Rafał Krygier
- Infectious Diseases and Hepatology Outpatient Clinic, Gemini NZOZ, Żychlin 62-571, Poland
| | - Jolanta Citko
- Medical Practice of Infections, Regional Hospital, Olsztyn 10-561, Poland
| | - Anna Piekarska
- Department of Infectious Diseases and Hepatology, Medical University Łódź, Łódź 90-419, Poland
| | - Robert Flisiak
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, Białystok 15-089, Poland
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Zarębska-Michaluk D, Jaroszewicz J, Parfieniuk-Kowerda A, Pawłowska M, Janczewska E, Berak H, Janocha-Litwin J, Klapaczyński J, Tomasiewicz K, Piekarska A, Krygier R, Citko J, Tronina O, Dobrowolska K, Flisiak R. Pangenotypic and Genotype-Specific Antivirals in the Treatment of HCV Genotype 4 Infected Patients with HCV Monoinfection and HIV/HCV Coinfection. J Clin Med 2022; 11:jcm11020389. [PMID: 35054088 PMCID: PMC8781964 DOI: 10.3390/jcm11020389] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2021] [Revised: 12/29/2021] [Accepted: 01/11/2022] [Indexed: 02/07/2023] Open
Abstract
The introduction of the direct-acting antivirals (DAA) has substantially improved the effectiveness of the therapy in patients with chronic hepatitis C. We aimed to compare the efficacy of pangenotypic and genotype-specific DAA in the cohort of genotype (GT) four patients with HCV monoinfection and HIV coinfection. A total of 662 GT4-infected patients treated in 2015–2020—of whom 168 (25.3%) were coinfected with HIV, selected from the retrospective EpiTer-2 database—were enrolled in the analysis. Among HIV-coinfected patients, 54% (90) were treated with genotype-specific regimens and 46% (78) with pangenotypic options, while among HCV-monoinfected patients, the rates were 72% and 28%, respectively. Significantly higher rate of males (67.9% vs. 57.7%, p = 0.01), a lower rate of liver cirrhosis (10.2% vs. 18.1%, p = 0.02), and higher of treatment-naïve patients (87.5% vs. 76.7%, p = 0.003) were documented in the HIV coinfected population. The overall sustained virologic response after exclusion of non-virologic failures was achieved in 98% with no significant difference between HIV-positive and HIV-negative patients, 96.2% vs. 98.5%, respectively. While the genotype-specific regimens resulted in a similar cure rate regardless of the HIV status, the pangenotypic options were more efficacious in patients with HCV monoinfection (99.3% vs. 94.4%, p = 0.05). Hereby, we demonstrated the high effectiveness and good safety profile of the DAA therapy in the population of HCV GT4 infected patients with HIV coinfection supporting the current recommendations to treat HCV/HIV coinfected patients with the same options as those with HCV monoinfection.
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Affiliation(s)
- Dorota Zarębska-Michaluk
- Department of Infectious Diseases, Jan Kochanowski University Kielce, 25-516 Kielce, Poland
- Correspondence: (D.Z.-M.); (R.F.)
| | - Jerzy Jaroszewicz
- Department of Infectious Diseases and Hepatology, Medical University of Silesia in Katowice, 40-055 Katowice, Poland;
| | - Anna Parfieniuk-Kowerda
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, 15-540 Białystok, Poland;
| | - Małgorzata Pawłowska
- Department of Infectious Diseases and Hepatology, Ludwik Rydygier Collegium Medicum, Bydgoszcz Faculty of Medicine Nicolaus Copernicus University in Toruń, 85-030 Bydgoszcz, Poland;
| | - Ewa Janczewska
- Faculty of Health Sciences in Bytom, Department of Basic Medical Sciences, Medical University of Silesia, ID Clinic, Hepatology Outpatient Department, 41-902 Bytom, Poland;
| | - Hanna Berak
- Hospital for Infectious Diseases in Warszawa, 02-091 Warszawa, Poland;
| | - Justyna Janocha-Litwin
- Department of Infectious Diseases and Hepatology, Medical University Wrocław, 50-367 Wrocław, Poland;
| | - Jakub Klapaczyński
- Department of Internal Medicine and Hepatology, Central Clinical Hospital of the Ministry of Internal Affairs and Administration, 02-507 Warszawa, Poland;
| | - Krzysztof Tomasiewicz
- Department of Infectious Diseases, Medical University of Lublin, 20-059 Lublin, Poland;
| | - Anna Piekarska
- Department of Infectious Diseases and Hepatology, Medical University of Łódź, 90-419 Łódź, Poland;
| | - Rafał Krygier
- Outpatients Hepatology Department, State University of Applied Sciences, 62-510 Konin, Poland;
| | - Jolanta Citko
- Medical Practice of Infections, Regional Hospital, 10-561 Olsztyn, Poland;
| | - Olga Tronina
- Department of Transplantation Medicine, Nephrology, and Internal Diseases, Medical University of Warsaw, 02-006 Warszawa, Poland;
| | | | - Robert Flisiak
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, 15-540 Białystok, Poland;
- Correspondence: (D.Z.-M.); (R.F.)
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16
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Pabjan P, Brzdęk M, Chrapek M, Dziedzic K, Dobrowolska K, Paluch K, Garbat A, Błoniarczyk P, Reczko K, Stępień P, Zarębska-Michaluk D. Are There Still Difficult-to-Treat Patients with Chronic Hepatitis C in the Era of Direct-Acting Antivirals? Viruses 2022; 14:96. [PMID: 35062302 PMCID: PMC8779728 DOI: 10.3390/v14010096] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2021] [Revised: 12/29/2021] [Accepted: 01/04/2022] [Indexed: 12/17/2022] Open
Abstract
Difficult-to-treat populations with chronic hepatitis C (CHC), in the era of interferon treatment, included patients with liver cirrhosis, kidney impairment, treatment-experienced individuals, and those coinfected with the human immunodeficiency virus. The current study aimed to determine whether, in the era of direct-acting antivirals (DAA), there are still patients that are difficult-to-treat. The study included all consecutive patients chronically infected with hepatitis C virus (HCV) who started interferon-free therapy between July 2015 and December 2020 in the Department of Infectious Diseases in Kielce. The analyzed real-world population consisted of 963 patients, and most of them were infected with genotype 1 (87.6%) with the predominance of subtype 1b and were treatment-naïve (78.8%). Liver cirrhosis was determined in 207 individuals (21.5%), of whom 82.6% were compensated. The overall sustained virologic response, after exclusion of non-virologic failures, was achieved in 98.4%. The univariable analysis demonstrated the significantly lower response rates in males, patients with liver cirrhosis, decompensation of hepatic function at baseline, documented esophageal varices, concomitant diabetes, body mass index ≥25, and previous ineffective antiviral treatment. Despite an overall very high effectiveness, some unfavorable factors, including male gender, genotype 3 infection, liver cirrhosis, and treatment experience, significantly reduce the chances for a virologic response were identified.
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Affiliation(s)
- Paweł Pabjan
- Department of Infectious Diseases, Voivodship Hospital, Jan Kochanowski University, 25-317 Kielce, Poland; (P.P.); (K.P.); (A.G.); (P.B.); (K.R.); (P.S.)
| | - Michał Brzdęk
- Collegium Medicum, Jan Kochanowski University, 25-369 Kielce, Poland; (M.B.); (K.D.); (K.D.)
| | - Magdalena Chrapek
- Faculty of Natural Sciences, Jan Kochanowski University, 25-369 Kielce, Poland;
| | - Kacper Dziedzic
- Collegium Medicum, Jan Kochanowski University, 25-369 Kielce, Poland; (M.B.); (K.D.); (K.D.)
| | - Krystyna Dobrowolska
- Collegium Medicum, Jan Kochanowski University, 25-369 Kielce, Poland; (M.B.); (K.D.); (K.D.)
| | - Katarzyna Paluch
- Department of Infectious Diseases, Voivodship Hospital, Jan Kochanowski University, 25-317 Kielce, Poland; (P.P.); (K.P.); (A.G.); (P.B.); (K.R.); (P.S.)
| | - Anna Garbat
- Department of Infectious Diseases, Voivodship Hospital, Jan Kochanowski University, 25-317 Kielce, Poland; (P.P.); (K.P.); (A.G.); (P.B.); (K.R.); (P.S.)
| | - Piotr Błoniarczyk
- Department of Infectious Diseases, Voivodship Hospital, Jan Kochanowski University, 25-317 Kielce, Poland; (P.P.); (K.P.); (A.G.); (P.B.); (K.R.); (P.S.)
| | - Katarzyna Reczko
- Department of Infectious Diseases, Voivodship Hospital, Jan Kochanowski University, 25-317 Kielce, Poland; (P.P.); (K.P.); (A.G.); (P.B.); (K.R.); (P.S.)
| | - Piotr Stępień
- Department of Infectious Diseases, Voivodship Hospital, Jan Kochanowski University, 25-317 Kielce, Poland; (P.P.); (K.P.); (A.G.); (P.B.); (K.R.); (P.S.)
| | - Dorota Zarębska-Michaluk
- Department of Infectious Diseases, Voivodship Hospital, Jan Kochanowski University, 25-317 Kielce, Poland; (P.P.); (K.P.); (A.G.); (P.B.); (K.R.); (P.S.)
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17
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Zarębska-Michaluk D, Jaroszewicz J, Parfieniuk-Kowerda A, Janczewska E, Dybowska D, Pawłowska M, Halota W, Mazur W, Lorenc B, Janocha-Litwin J, Simon K, Piekarska A, Berak H, Klapaczyński J, Stępień P, Sobala-Szczygieł B, Citko J, Socha Ł, Tudrujek-Zdunek M, Tomasiewicz K, Sitko M, Dobracka B, Krygier R, Białkowska-Warzecha J, Laurans Ł, Flisiak R. Effectiveness and Safety of Pangenotypic Regimens in the Most Difficult to Treat Population of Genotype 3 HCV Infected Cirrhotics. J Clin Med 2021; 10:jcm10153280. [PMID: 34362064 PMCID: PMC8347334 DOI: 10.3390/jcm10153280] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2021] [Revised: 07/20/2021] [Accepted: 07/22/2021] [Indexed: 12/14/2022] Open
Abstract
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.
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Affiliation(s)
- Dorota Zarębska-Michaluk
- Department of Infectious Diseases, Jan Kochanowski University, 25-317 Kielce, Poland;
- Correspondence: ; Tel.: +48-66-244-1465; Fax: +48-41-368-2262
| | - Jerzy Jaroszewicz
- Department of Infectious Diseases and Hepatology, Medical University of Silesia, 40-055 Katowice, Poland; (J.J.); (B.S.-S.)
| | - Anna Parfieniuk-Kowerda
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, 15-540 Białystok, Poland; (A.P.-K.); (R.F.)
| | - Ewa Janczewska
- Department of Basic Medical Sciences, Faculty of Health Sciences in Bytom, Medical University of Silesia, 41-902 Bytom, Poland;
| | - Dorota Dybowska
- Department of Infectious Diseases and Hepatology, Collegium Medicum, Nicolaus Copernicus University, 87-030 Bydgoszcz, Poland; (D.D.); (M.P.); (W.H.)
| | - Małgorzata Pawłowska
- Department of Infectious Diseases and Hepatology, Collegium Medicum, Nicolaus Copernicus University, 87-030 Bydgoszcz, Poland; (D.D.); (M.P.); (W.H.)
| | - Waldemar Halota
- Department of Infectious Diseases and Hepatology, Collegium Medicum, Nicolaus Copernicus University, 87-030 Bydgoszcz, Poland; (D.D.); (M.P.); (W.H.)
| | - Włodzimierz Mazur
- Clinical Department of Infectious Diseases, Medical University of Silesia in Katowice, 41-500 Chorzów, Poland;
| | - Beata Lorenc
- Pomeranian Center of Infectious Diseases, Medical University Gdańsk, 80-214 Gdańsk, Poland;
| | - Justyna Janocha-Litwin
- Department of Infectious Diseases and Hepatology, Medical University Wrocław, 50-367 Wrocław, Poland; (J.J.-L.); (K.S.)
| | - Krzysztof Simon
- Department of Infectious Diseases and Hepatology, Medical University Wrocław, 50-367 Wrocław, Poland; (J.J.-L.); (K.S.)
| | - Anna Piekarska
- Department of Infectious Diseases and Hepatology, Medical University of Łódź, 90-419 Łódź, Poland;
| | - Hanna Berak
- Hospital for Infectious Diseases in Warszawa, 02-091 Warsaw, Poland;
| | - Jakub Klapaczyński
- Department of Internal Medicine and Hepatology, Central Clinical Hospital of the Ministry of Internal Affairs and Administration, 00-241 Warszawa, Poland;
| | - Piotr Stępień
- Department of Infectious Diseases, Jan Kochanowski University, 25-317 Kielce, Poland;
| | - Barbara Sobala-Szczygieł
- Department of Infectious Diseases and Hepatology, Medical University of Silesia, 40-055 Katowice, Poland; (J.J.); (B.S.-S.)
| | - Jolanta Citko
- Medical Practice of Infections, Regional Hospital, 10-561 Olsztyn, Poland;
| | - Łukasz Socha
- Department of Infectious Diseases, Hepatology and Liver Transplantation, Pomeranian Medical University, 71-455 Szczecin, Poland; (Ł.S.); (Ł.L.)
| | - Magdalena Tudrujek-Zdunek
- Department of Infectious Diseases, Medical University of Lublin, 20-059 Lublin, Poland; (M.T.-Z.); (K.T.)
| | - Krzysztof Tomasiewicz
- Department of Infectious Diseases, Medical University of Lublin, 20-059 Lublin, Poland; (M.T.-Z.); (K.T.)
| | - Marek Sitko
- Department of Infectious and Tropical Diseases, Jagiellonian University, 31-088 Kraków, Poland;
| | | | - Rafał Krygier
- Outpatients Hepatology Department, State University of Applied Sciences, 62-510 Konin, Poland;
| | | | - Łukasz Laurans
- Department of Infectious Diseases, Hepatology and Liver Transplantation, Pomeranian Medical University, 71-455 Szczecin, Poland; (Ł.S.); (Ł.L.)
- Multidisciplinary Regional Hospital, 66-418 Gorzów Wielkopolski, Poland
| | - Robert Flisiak
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, 15-540 Białystok, Poland; (A.P.-K.); (R.F.)
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18
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Flisiak R, Zarębska-Michaluk D, Janczewska E, Łapiński T, Rogalska M, Karpińska E, Mikuła T, Bolewska B, Białkowska J, Flejscher-Stępniewska K, Tomasiewicz K, Karwowska K, Pazgan-Simon M, Piekarska A, Berak H, Tronina O, Garlicki A, Jaroszewicz J. Five-Year Follow-Up of Cured HCV Patients under Real-World Interferon-Free Therapy. Cancers (Basel) 2021; 13:3694. [PMID: 34359594 PMCID: PMC8345092 DOI: 10.3390/cancers13153694] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2021] [Revised: 07/20/2021] [Accepted: 07/21/2021] [Indexed: 12/11/2022] Open
Abstract
(1) Background: Treatment of hepatitis C virus (HCV) infections with direct-acting antivirals (DAA) has demonstrated high efficacy and an excellent safety profile. The cured patients showed a sustained virological response and improved liver function, but also a continued risk of hepatocellular carcinoma (HCC) during the 2-3 years of follow-up after treatment; (2) Methods: A total of 192 patients out of 209 of the primary AMBER study were analyzed five years after treatment with ombitasvir/paritaprevir/ritonavir with or without dasabuvir and with or without ribavirin. Results: We confirmed that HCV clearance after DAA treatment is stable regardless of baseline liver fibrosis. We found that sustained virologic response is associated with a gradual but significant reduction in liver stiffness over 5 years. Liver function improved during the first 2 years of follow-up and remained stable thereafter. The risk of death due to HCC as well as death due to HCV persists through 5 years of follow-up after successful DAA treatment. However, in non-cirrhotic patients, it appears to clear up 3 years after treatment; (3) Conclusions: Monitoring for more than 5 years after curing HCV infection is necessary to assess the long-term risk of possible development of HCC, especially in patients with cirrhosis of the liver.
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Affiliation(s)
- Robert Flisiak
- Department of Infectious Diseases and Hepatology, Medical University of Bialystok, 15-540 Bialystok, Poland;
| | | | - Ewa Janczewska
- Department of Basic Medical Sciences, Faculty of Health Sciences in Bytom, Medical University of Silesia, 41-902 Bytom, Poland;
| | - Tadeusz Łapiński
- Department of Infectious Diseases and Hepatology, Medical University of Bialystok, 15-540 Bialystok, Poland;
| | - Magdalena Rogalska
- Department of Infectious Diseases and Hepatology, Medical University of Bialystok, 15-540 Bialystok, Poland;
| | - Ewa Karpińska
- Department of Infectious Diseases, Hepatology and Liver Transplantation, Pomeranian Medical University, 70-204 Szczecin, Poland;
| | - Tomasz Mikuła
- Department of Infectious and Tropical Disease and Hepatology, Medical University of Warsaw, 02-091 Warsaw, Poland;
| | - Beata Bolewska
- Department of Infectious Diseases, Poznan University of Medical Sciences, 61-701 Poznan, Poland;
| | - Jolanta Białkowska
- Department of Infectious and Liver Diseases, Medical University of Lodz, 90-419 Lodz, Poland;
| | - Katarzyna Flejscher-Stępniewska
- Department of Infectious Diseases, Liver Diseases and Immune Deficiencies, Wroclaw Medical University, 50-367 Wroclaw, Poland;
| | - Krzysztof Tomasiewicz
- Department of Infectious Diseases and Hepatology, Medical University of Lublin, 20-059 Lublin, Poland;
| | - Kornelia Karwowska
- Department of Infectious Diseases and Hepatology, Collegium Medicum, Nicolaus Copernicus University, 87-030 Bydgoszcz, Poland;
| | - Monika Pazgan-Simon
- Department of Infectious Diseases and Hepatology, Wroclaw Medical University, 50-367 Wroclaw, Poland;
| | - Anna Piekarska
- Department of Infectious Diseases and Hepatology, Medical University of Lodz, 90-419 Lodz, Poland;
| | - Hanna Berak
- Daily Unit, Hospital of Infectious Diseases in Warsaw, 01-201 Warsaw, Poland;
| | - Olga Tronina
- Department of Transplantation Medicine, Nephrology and Internal Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland;
| | - Aleksander Garlicki
- Department of Infectious and Tropical Diseases, Jagiellonian University Medical College, 31-008 Krakow, Poland;
| | - Jerzy Jaroszewicz
- Department of Infectious Diseases and Hepatology, Medical University of Silesia, 40-055 Katowice, Poland;
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Parczewski M, Janczewska E, Pisula A, Dybowska D, Łojewski W, Witor A, Wawrzynowicz-Syczewska M, Socha Ł, Krygier R, Knysz B, Musialik J, Urbańska A, Scheibe K, Jaroszewicz J. HCV resistance-associated substitutions following direct-acting antiviral therapy failure - Real-life data from Poland. INFECTION GENETICS AND EVOLUTION 2021; 93:104949. [PMID: 34087494 DOI: 10.1016/j.meegid.2021.104949] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Revised: 05/27/2021] [Accepted: 05/30/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND This study analysed the NS3 and NS5A mutation frequencies, persistence and drug susceptibility in a cohort of real-life patients, with failed hepatitis C virus (HCV) therapy following directly acting antiviral (DAA) treatment. METHODS NS3/NS5A Sanger sequences from 105 patients infected with HCV genotype (G) 1a (6,5.7%), G1b (94,89.5%), G3a (4,3.8%), and G4 (1,1.0%) post DAA treatment failure were analysed. NS3 and NS5A resistance-associated substitutions (RASs) were identified using the geno2pheno algorithm and associated with clinical variables. Time trends were examined using logistic regression. RESULTS NS5A RAS were found in 87.9% of sequences derived from patients exposed to this class of agents, whereas NS3 RAS was found in 59.1% of HCV protease-exposed subjects. The frequency of the NS3 RAS increased with fibrosis stage, from 40.0% among F0/F1 individuals to 81.8% among patients with liver cirrhosis (F4, p = 0.094). NS5A mutation frequencies were 7.6% for 28A/V/M, 10.6% for 30 K/Q/R, 42.4% for 31I/F/M/V, and 75.8% for 93H. For NS3, the most common RASs were 56F-23.7%, 168A/E/I/Y/T/V-14.0%, and 117H-5.4%. Susceptibility to glecaprevir/pibrentasvir, velpatasvir/voxlaprevir, and elbasvir/grazoprevir was retained in 92.9%, 43.4%, and, 25.3% of patients, respectively. The frequency of NS3 RAS decreased with time elapsed from failure to sampling (p = 0.034 for trend). NS5A RAS frequency remained stable over the 24-months. CONCLUSIONS Following DAA treatment failure, NS5A and NS3 RASs were common with increasing frequency among patients with advanced liver disease. In most cases, despite the presence of RASs, susceptibility to DAA combinations with higher genetic barrier was retained.
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Affiliation(s)
- Miłosz Parczewski
- Department of Infectious, Tropical Diseases and Immune Deficiency, Pomeranian Medical University in Szczecin, Szczecin, Poland.
| | - Ewa Janczewska
- Department of Basic Medical Sciences, The School of Health Sciences in Bytom, Medical University of Silesia, Bytom, Poland
| | | | - Dorota Dybowska
- Department of Infectious Diseases and Hepatology, Ludwik Rydygier Collegium Medicum, Bydgoszcz Faculty of Medicine, Nicolaus Copernicus University, Toruń, Poland
| | - Władysław Łojewski
- Department of Infectious Diseases, Regional Hospital in Zielona Góra, Zielona Góra, Poland
| | - Adam Witor
- Hospital for Infectious Diseases, Chorzów, Poland
| | - Marta Wawrzynowicz-Syczewska
- Department of Infectious Diseases, Hepatology and Liver Transplantation, Pomeranian Medical University in Szczecin, Szczecin, Poland
| | - Łukasz Socha
- Department of Infectious Diseases, Hepatology and Liver Transplantation, Pomeranian Medical University in Szczecin, Szczecin, Poland
| | - Rafał Krygier
- Outpatients Hepatology Department, State University of Applied Sciences, Konin, Poland
| | - Brygida Knysz
- Department of Infectious Diseases, Liver Diseases and Acquired Immune Deficiencies, Wrocław Medical University, Wrocław, Poland
| | - Joanna Musialik
- Department of Nephrology, Transplantation and Internal Medicine, Medical University of Silesia in Katowice, Katowice, Poland
| | - Anna Urbańska
- Department of Infectious, Tropical Diseases and Immune Deficiency, Pomeranian Medical University in Szczecin, Szczecin, Poland
| | - Kaja Scheibe
- Department of Infectious, Tropical Diseases and Immune Deficiency, Pomeranian Medical University in Szczecin, Szczecin, Poland
| | - Jerzy Jaroszewicz
- Department of Infectious Diseases and Hepatology, Medical University of Silesia, Katowice, Poland
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20
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Tronina O, Durlik M, Orłowska I, Lorenc B, Łapiński TW, Garlicki A, Dybowska D, Zarębska-Michaluk D, Tudrujek-Zdunek M, Citko J, Janczewska E, Kaczmarczyk M, Jaroszewicz J, Krygier R, Klapaczyński J, Dobracka B, Białkowska-Warzecha J, Piekarska A, Simon K, Halota W, Pawłowska M, Tomasiewicz K, Flisiak R. Real-world direct-acting antiviral treatment in kidney transplant and hemodialysis patients: the EpiTer-2 multicenter observational study. Ann Gastroenterol 2021; 34:438-446. [PMID: 33948071 PMCID: PMC8079881 DOI: 10.20524/aog.2021.0595] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2020] [Accepted: 10/22/2020] [Indexed: 12/12/2022] Open
Abstract
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.
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Affiliation(s)
- Olga Tronina
- Department of Transplantation Medicine, Nephrology, and Internal Diseases, Medical University of Warsaw, Warsaw (Olga Tronina, Magdalena Durlik)
| | - Magdalena Durlik
- Department of Transplantation Medicine, Nephrology, and Internal Diseases, Medical University of Warsaw, Warsaw (Olga Tronina, Magdalena Durlik)
| | - Iwona Orłowska
- Department of Infectious Diseases and Hepatology, Wrocław Medical University, Wrocław (Iwona Orłowska, Krzysztof Simon)
| | - Beata Lorenc
- Pomeranian Center of Infectious Diseases, Department of Infectious Diseases, Medical University of Gdańsk, Gdańsk (Beata Lorenc)
| | - Tadeusz W. Łapiński
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, Białystok (Tadeusz W. Łapiński, Robert Flisiak)
| | - Aleksander Garlicki
- Department of Infectious and Tropical Diseases, Jagiellonian University Collegium Medicum, Kraków (Aleksander Garlicki)
| | - Dorota Dybowska
- Department of Infectious Diseases and Hepatology, Faculty of Medicine, Collegium Medicum Bydgoszcz, Nicolaus Copernicus University, Toruń (Dorota Dybowska, Waldemar Halota, Małgorzata Pawłowska)
| | - Dorota Zarębska-Michaluk
- Department of Infectious Diseases, Voivodship Hospital and Jan Kochanowski University, Kielce (Dorota Zarębska-Michaluk)
| | - Magdalena Tudrujek-Zdunek
- Department of Infectious Diseases and Hepatology, Medical University of Lublin, Lublin (Magdalena Tudrujek-Zdunek, Krzysztof Tomasiewicz)
| | - Jolanta Citko
- Medical Practice of Infections, Regional Hospital, Olsztyn, Poland (Jolanta Citko)
| | - Ewa Janczewska
- Hepatology Outpatient Clinic, ID Clinic, Mysłowice, Poland (Ewa Janczewska)
| | - Marcin Kaczmarczyk
- Clinical Department of Infectious Diseases, Specialist Hospital in Chorzów, Medical University of Silesia, Katowice, Poland (Marcin Kaczmarczyk)
| | - Jerzy Jaroszewicz
- Department of Infectious Diseases, Medical University of Silesia in Katowice, Bytom (Jerzy Jaroszewicz)
| | - Rafał Krygier
- Infectious Diseases and Hepatology Outpatient Clinic NZOZ “Gemini”, Żychlin (Rafał Krygier)
| | - Jakub Klapaczyński
- Department of Internal Medicine and Hepatology, Central Clinical Hospital of the Ministry of Internal Affairs and Administration, Warsaw (Jakub Klapaczyński)
| | | | | | - Anna Piekarska
- Department of Infectious Diseases and Hepatology, Medical University of Łódź (Anna Piekarska), Poland
| | - Krzysztof Simon
- Department of Infectious Diseases and Hepatology, Wrocław Medical University, Wrocław (Iwona Orłowska, Krzysztof Simon)
| | - Waldemar Halota
- Department of Infectious Diseases and Hepatology, Faculty of Medicine, Collegium Medicum Bydgoszcz, Nicolaus Copernicus University, Toruń (Dorota Dybowska, Waldemar Halota, Małgorzata Pawłowska)
| | - Małgorzata Pawłowska
- Department of Infectious Diseases and Hepatology, Faculty of Medicine, Collegium Medicum Bydgoszcz, Nicolaus Copernicus University, Toruń (Dorota Dybowska, Waldemar Halota, Małgorzata Pawłowska)
| | - Krzysztof Tomasiewicz
- Department of Infectious Diseases and Hepatology, Medical University of Lublin, Lublin (Magdalena Tudrujek-Zdunek, Krzysztof Tomasiewicz)
| | - Robert Flisiak
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, Białystok (Tadeusz W. Łapiński, Robert Flisiak)
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