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Good SS, Luo S, Lin K, Vo A, Agrawal NGB, Sommadossi JP. Bemnifosbuvir and ruzasvir in combination exhibit potent synergistic antiviral activity in vitro while maintaining a favorable nonclinical safety profile in vivo. Antiviral Res 2025; 237:106137. [PMID: 40054502 DOI: 10.1016/j.antiviral.2025.106137] [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: 12/03/2024] [Revised: 02/17/2025] [Accepted: 03/02/2025] [Indexed: 03/14/2025]
Abstract
Bemnifosbuvir (BEM), the orally available hemisulfate salt of the double prodrug of a guanosine nucleotide analog, is a potent, selective, and pan-genotypic inhibitor of HCV nonstructural protein 5B, an RNA-dependent RNA polymerase necessary for viral replication. Similarly, ruzasvir (RZR) is an orally available, highly potent, selective, and pan-genotypic inhibitor of HCV nonstructural protein 5A, an essential component of the viral replication complex. The antiviral effects of the combination of these two complementary direct-acting antivirals were determined in HCV GT1b Huh-7 replicon cells. Two independent in vitro evaluations suggested that BEM and RZR act synergistically to inhibit HCV replication without accompanying cytotoxicity. Additionally, the toxicity and toxicokinetic properties of BEM and RZR administered individually or in combination were investigated in rats given daily oral doses at 500 mg/kg of each drug for 13 weeks, with an interim analysis at 4 weeks. All doses were well tolerated with no test article-related adverse effects identified in either the separate or combined dose groups. Moreover, toxicokinetic analyses conducted on dose days 1, 28 and 84 indicated minimal pharmacokinetic interactions between the two drugs in rats, with AUC values for AT-511 (free base form of BEM), its major circulating metabolites, and RZR being similar, regardless of separate or co-administration.
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Affiliation(s)
- Steven S Good
- Atea Pharmaceuticals, Inc., 225 Franklin Street, Ste 2100, Boston, MA, 02110, United States.
| | - Shouqi Luo
- Atea Pharmaceuticals, Inc., 225 Franklin Street, Ste 2100, Boston, MA, 02110, United States.
| | - Kai Lin
- Atea Pharmaceuticals, Inc., 225 Franklin Street, Ste 2100, Boston, MA, 02110, United States.
| | - Alex Vo
- Atea Pharmaceuticals, Inc., 225 Franklin Street, Ste 2100, Boston, MA, 02110, United States.
| | - Nancy G B Agrawal
- Atea Pharmaceuticals, Inc., 225 Franklin Street, Ste 2100, Boston, MA, 02110, United States.
| | - Jean-Pierre Sommadossi
- Atea Pharmaceuticals, Inc., 225 Franklin Street, Ste 2100, Boston, MA, 02110, United States.
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Linas BP, Weitz M, Pramanick T, Sulkowski M, Smeaton LM, Cardoso SW, Solomon S. Health economic outcomes of a minimal monitoring approach to providing HCV therapy. Hepatol Commun 2025; 9:e0579. [PMID: 40257357 PMCID: PMC12014070 DOI: 10.1097/hc9.0000000000000579] [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: 12/13/2023] [Accepted: 04/27/2024] [Indexed: 04/22/2025] Open
Abstract
BACKGROUND The ACTG A5360 trial demonstrated that HCV treatment without planned on-treatment monitoring is safe and effective. We report the health economic outcomes of MINMON. METHODS A5360 was a 5-country, single-arm trial providing sofosbuvir/velpatasvir to people with HCV infection with no planned clinic visits between treatment initiation and week 24 sustained virologic response (SVR) evaluation. Trial records included planned/and most unplanned lab tests and visits. Participants completed a 4-week recall questionnaire at weeks 0, 24, 48, and 72 reporting hospital nights, emergency department visits, and ambulatory visits. We tabulated consumption and multiplied units of consumption by country-specific cost. We report the cost and cost per SVR of MINMON (2020 US$) from program and health sector perspectives. Sensitivity analyses compared MINMON costs to the standard of care (SoC). We consulted in-country experts to develop country-specific SoC treatment protocols and used micro-costing to estimate their costs. We compare the cost/SVR in MINMON with that of the simulated SoC, varying the expected SVR with the SoC. RESULTS MINMON cost/SVR (program perspective) varied by country from $1692/SVR (Thailand) to $27,632/SVR (United States). The cost/SVR (health sector perspective) ranged from $6273/SVR (South Africa) to $123,974/SVR (United States) MINMON had a lower cost/SVR than SoC across broad assumptions about SVR proportions, especially in low- and middle-income countries. In the United States-, MINMON had an appealing cost per cure compared to the SoC, unless retention on treatment fell below the SoC. CONCLUSIONS MINMON is a cost-saving strategy for HCV treatment, particularly in low- and middle-income country settings.
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Affiliation(s)
- Benjamin P. Linas
- Boston University School of Medicine, Boston, Massachusetts, USA
- Boston Medical Center, Section of Infectious Diseases, Boston, Massachusetts, USA
| | - Michelle Weitz
- Boston Medical Center, Section of Infectious Diseases, Boston, Massachusetts, USA
| | - Tannishtha Pramanick
- Boston Medical Center, Section of Infectious Diseases, Boston, Massachusetts, USA
| | - Mark Sulkowski
- John Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Laura M. Smeaton
- Center for Biostatistics in AIDS Research, Harvard TH Chan School of Public Health, Boston, Massachusetts, USA
| | - Sandra W. Cardoso
- Oswaldo Cruz Foundation, National Institute of Infectology (INI)- STDs/AIDS Clinical Research Laboratory-Rio De Janeiro, Brazil
| | - Sunil Solomon
- John Hopkins University School of Medicine, Baltimore, Maryland, USA
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Nicolas C, Domas Q, Pol S, Bardou-Jacquet E, Loustaud-Ratti V, Métivier S, Asselah T, Thabut D, Bourlière M, Mathurin P, Foucher J, Larrey D, Varaut A, Alric L, Bailly F, Muti L, Buchard B, Abergel A. Direct Antivirals Can Achieve a Cure in All Patients With Chronic Hepatitis C due to Genotype 5: A French Multicentre Study. Liver Int 2025; 45:e16158. [PMID: 39530494 DOI: 10.1111/liv.16158] [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: 07/08/2024] [Revised: 10/04/2024] [Accepted: 10/25/2024] [Indexed: 11/16/2024]
Abstract
BACKGROUND Hepatitis C virus genotype 5 (HCV-GT-5) is found mainly in South Africa. In our area in central France, the prevalence of HCV-GT-5 is 14%. METHODS AND RESULTS Here we evaluated sustained virological response at week 12 post-treatment (SVR12) in 147 HCV-GT-5 patients from 14 French university hospitals (2014-2021) treated with direct-acting antivirals (DAA) in real-life. Patients had mainly received sofosbuvir/ledipasvir ± ribavirin, sofosbuvir/velpatasvir, and glecaprevir/pibrentasvir. Overall SVR12 was 98% (144/147). Two patients experienced relapse: one was successfully retreated with the same DAAs (sofosbuvir/ledipasvir) plus ribavirin, and the other refused further DAA treatment. One patient with virological failure (sofosbuvir/velpatasvir) had received a second treatment (sofosbuvir/velpatasvir/voxilaprevir) and progressed to cure. CONCLUSIONS HCV-GT-5 patients treated with a DAA regimen had a 99% SVR12 in intention-to-treat (including initial therapy and retreatment) and 100% SVR12 per protocol. Sofosbuvir/ledipasvir, sofosbuvir/velpatasvir, and glecaprevir/pibrentasvir show very good efficacy in real-world HCV-GT-5 patients.
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Affiliation(s)
- Carine Nicolas
- Department of Digestive and Hepatobiliary Medicine, CHU Clermont-Ferrand, Clermont-Ferrand, France
| | - Quentin Domas
- Department of Digestive and Hepatobiliary Medicine, CHU Clermont-Ferrand, Clermont-Ferrand, France
| | - Stanislas Pol
- Oncology and Medical-Surgical Specialities, Department of Hepatology, AP-HP/Hôpital Cochin, Paris-Cité University/INSERM U1223-U1016, Paris, France
| | - Edouard Bardou-Jacquet
- Department of Liver Diseases, CHU Rennes, Rennes University/UMR124/INSERM CIC1414, Institut NUMECAN, Rennes, France
| | - Véronique Loustaud-Ratti
- Department of Hepato-Gastroenterology, CHU Limoges, Limoges University/INSERM U1248, Limoges, France
| | | | - Tarik Asselah
- Department of Hepato-Gastroenterology, AP-HP/Hôpital Beaujon, Paris-Cité University/CRI/INSERM UMR1149, Paris, France
| | - Dominique Thabut
- Department of Hepato-Gastroenterology, AP-HP/Hôpital La Pitié Salpétrière, Sorbonne University/INSERM UMR-S938/CRSA/ICAN, Paris, France
| | - Marc Bourlière
- Department of Hepato-Gastroenterology, Hôpital Saint-Joseph, Aix-Marseille University/INSERM UMR1252 IRD/SESSTIM/ISSPAM, Marseille, France
| | - Philippe Mathurin
- Department of Hepato-Gastroenterology, CHU Lille, Lille University/INSERM INFINITE-U1286, Lille, France
| | | | - Dominique Larrey
- Department of Hepato-Gastroenterology, CHU Montpellier, Montpellier University/INSERM U1183, Montpellier, France
| | - Anne Varaut
- Department of Hepatology, AP-HP/Hôpital Henri Mondor, Créteil, France
| | - Laurent Alric
- Department of Internal Medicine-Clinical Immunology, CHU Toulouse, Toulouse III University/RESTORE INSERM UMR-1301/CNRS-5070/FLAMES Team, Toulouse, France
| | - François Bailly
- Department of Hepatology, HCL/Hopital Croix Rousse, INSERM U1052, Institut EVEREST, Lyon, France
| | - Léon Muti
- Department of Digestive and Hepatobiliary Medicine, CHU Clermont-Ferrand, Clermont-Ferrand, France
| | - Benjamin Buchard
- Department of Digestive and Hepatobiliary Medicine, CHU Clermont-Ferrand, Clermont-Ferrand, France
| | - Armando Abergel
- Department of Digestive and Hepatobiliary Medicine, CHU Clermont-Ferrand, Clermont-Ferrand, France
- Clermont-Auvergne University/CNRS/Clermont-Auvergne INP/Institut Pascal, Clermont-Ferrand, France
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Piazzolla AV, Resta D, Greco M, Comes V, Vassalli T, Mengoli F, Memoli E, Checchia D, Migliorelli N, Giuliani G, Giannattasio G, Checchia RM, Giannone A, Noya A, Pugliese D, Carrisi C, Murgo G, Carretta V, Gentile L, Ongaro L, Parisi G, Costantino D, Giubba A, Squillante MM, Mangia A. Micro-elimination initiative for hepatitis C screening: insight into gender gaps and undiagnosed individuals. Sci Rep 2025; 15:9289. [PMID: 40102477 PMCID: PMC11920028 DOI: 10.1038/s41598-025-91696-4] [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: 09/13/2024] [Accepted: 02/21/2025] [Indexed: 03/20/2025] Open
Abstract
In 2023, the Italian healthcare system launched HCV screening targeting subjects born in 1968-1989. However, subjects > 50 yrs also need screening. In addition, existence of gender gaps in HCV diagnosis and treatment has been suggested. Our aim was to identify undiagnosed individuals outside the age groups to whom the screening is offered and to gather data about gender gaps. This is a prospective, opportunistic micro-elimination initiative based on a network between 24 Apulian pharmacies and our center. Between 01/07/2022 and 01/03/2024, subjects aged 55 to 85, accessing pharmacies were offered HCVOraQuick tests (F/M 1:1) and administered ad-hoc questionnaires. In total, 13,042 screening were carried out. Mean age was 64.9 (± 7.6), 51.1% females. Overall, 1.1% were anti-HCV positive: mean age 68.3 (± 10.3), 44.9% females. Seroprevalence was higher in males (p < 0.00001), elderly (p < 0.00001) and unknown transmission route (p = 0.0009). HCV-RNA was detectable in 67.4% of seropositive. They were 67.5 (± 10.7) yrs old, mainly males (55.1%). HCV-RNA prevalence was 0.8%, higher in elderly (p = 0.0003) and unknown transmission route (p = 0.0007). Overall, 90% were linked-to-treatment. Differences in patients profiles should be considered to guide policy and more inclusive treatment approaches. Gender differences in screening response and rates of active infections underscore the need for gender-targeted intervention.
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Affiliation(s)
| | | | | | - Vito Comes
- Farmacia Gentile, Farmacia Bellisario, Monopoli, Bari, Italy
| | | | | | | | | | | | | | | | | | | | - Attilio Noya
- Farmacia Dottor Attilio Noya Monopoli, Monopoli, Italy
| | | | | | | | | | | | | | - Giacomo Parisi
- Farmacia Porta Reale Palo del Colle, Palo del Colle, Italy
| | | | | | | | - Alessandra Mangia
- Liver Unit, Fondazione "Casa Sollievo della Sofferenza", IRCCS San Giovanni Rotondo, Rotondo, Italy.
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Lybeck C, Bruce D, Szulkin R, Montgomery S, Aleman S, Duberg AS. Long-term risk of HCC in a DAA-treated national hepatitis C cohort, and a proposed risk score. Infect Dis (Lond) 2025; 57:211-223. [PMID: 39319565 DOI: 10.1080/23744235.2024.2403703] [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: 05/21/2024] [Revised: 09/02/2024] [Accepted: 09/09/2024] [Indexed: 09/26/2024] Open
Abstract
BACKGROUND The risk of hepatocellular carcinoma (HCC) remains elevated in cirrhotic hepatitis C patients with sustained virological response (SVR) after DAA treatment. We assessed long-term HCC risk stratified by pretreatment liver stiffness measurement (LSM) and developed a risk score algorithm. METHODS This register-based nationwide cohort study of 7,227 DAA-treated patients with SVR evaluated annual HCC incidence rates (IRs) and cumulative incidences stratified by pretreatment LSM. The association between LSM and HCC risk was analyzed using multivariate Cox regression. A risk score algorithm was developed and internally validated in 2,664 individuals with LSM >9.5 kPa, assigning each patient a score based on risk factors, proportionally weighted by the association with HCC risk. RESULTS During a median follow-up of 1.8 years (3.2 years for LSM ≥12.5 kPa), 92 patients (1.3%) developed HCC. The IRs for LSM 9.5-12.4, 12.5-19.9 and ≥20 kPa were 0.21, 0.99 and 2.20 HCC/100 PY, respectively, with no significant risk reduction during follow-up. The HRs (and 95% CI) for LSM 9.5-12.5, 12.5-19.9 and ≥20 kPa are 1.19 (0.43-3.28), 4.66 (2.17-10.01) and 10.53 (5.26-21.08), respectively. Risk score models including FIB-4, alcohol, diabetes, age and LSM effectively stratified patients with LSM >9.5 kPa into low-, intermediate- and high-risk groups, with a Harrell's C of 0.799. Notably, 48% with LSM ≥9.5 kPa and 27% ≥12.5 kPa were classified as low-risk. CONCLUSION Pretreatment LSM is associated with HCC risk, which remains stable during the initial five years post-SVR. The HCC risk score algorithm effectively identifies low-risk patients, who may not require HCC surveillance.
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Affiliation(s)
- Charlotte Lybeck
- Department of Infectious Diseases, Faculty of Medicine and Health, School of Medical Sciences, Örebro University, Örebro, Sweden
| | | | - Robert Szulkin
- Cytel Inc, Stockholm, Sweden
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Scott Montgomery
- Clinical Epidemiology and Biostatistics, School of Medical Sciences, Örebro University, Örebro, Sweden
- Clinical Epidemiology Division, Karolinska Institutet, Stockholm, Sweden
- Department of Epidemiology and Public Health, University College London, London, United Kingdom
| | - Soo Aleman
- Department of Infectious Diseases, Karolinska Institutet, Stockholm, Sweden
- Department of Gastroenterology and Hepatology, Karolinska Institutet, Stockholm, Sweden
| | - Ann-Sofi Duberg
- Department of Infectious Diseases, Faculty of Medicine and Health, School of Medical Sciences, Örebro University, Örebro, Sweden
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Fedorchenko SV, Klimenko Z, Martynovich T, Solianyk I, Suprunenko T. Retreatment of patients with chronic hepatitis C, subtype 3a, and cirrhosis, who previously failed a regimen containing second-generation NS5A inhibitors with sofosbuvir + glecaprevir/pibrentasvir and ribavirin for 16-24 weeks. J Virol 2025; 99:e0184324. [PMID: 39840947 PMCID: PMC11852967 DOI: 10.1128/jvi.01843-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2025] Open
Abstract
The outcomes of retreatment patients infected with hepatitis C virus genotype 3, cirrhosis, with velpatasvir may be affected by treatment failure with velpatasvir. The efficacy of SOF+GLE/PIB+RIB 16-24 weeks of treatment has been shown. The presence of NS5A resistance-associated substitution mutations, including Y93H, and the number and regimens of the past failed therapy do not influence the likelihood of achieving sustained virological response. When velpatasvir treatment fails, pibrentasvir should be used as the first choice for retreatment.
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Affiliation(s)
- Sergii V. Fedorchenko
- Department of Viral Hepatitis and AIDS, The L.V. Gromashevskyi Institute of Epidemiology and Infectious Disease, Kyiv, Ukraine
| | - Zhanna Klimenko
- Department of Viral Hepatitis and AIDS, The L.V. Gromashevskyi Institute of Epidemiology and Infectious Disease, Kyiv, Ukraine
| | - Tatiana Martynovich
- Department of Viral Hepatitis and AIDS, The L.V. Gromashevskyi Institute of Epidemiology and Infectious Disease, Kyiv, Ukraine
| | - Iryna Solianyk
- Department of Viral Hepatitis and AIDS, The L.V. Gromashevskyi Institute of Epidemiology and Infectious Disease, Kyiv, Ukraine
| | - Tatiana Suprunenko
- Department of Viral Hepatitis and AIDS, The L.V. Gromashevskyi Institute of Epidemiology and Infectious Disease, Kyiv, Ukraine
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Icole F, Haghnejad V, Jeannoel C, Besançon P, Boulanger F, Bronowicki JP. Prevalence of hepatitis C, hepatitis B and HIV and their therapeutic management in a French public psychiatric hospital. L'ENCEPHALE 2025; 51:9-14. [PMID: 38368186 DOI: 10.1016/j.encep.2023.11.023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Revised: 10/23/2023] [Accepted: 11/08/2023] [Indexed: 02/19/2024]
Abstract
INTRODUCTION Several studies suggest that the prevalence of hepatitis C, hepatitis B and HIV are higher in psychiatric patients than in the general population; however, few French studies have been published. The aims of this study were to determine the seroprevalence of the three viruses, describe the profile of infected patients and evaluate the initiation of antiviral treatment in a population of patients hospitalized in a psychiatric hospital. METHOD Between January and October 2020, screening for hepatitis C virus, hepatitis B virus and HIV was systematically offered to all patients admitted to the intersectoral reception and orientation unit of a psychiatric hospital. If serology was positive, viral load was automatically determined from the same blood sample. As direct-acting antivirals (DAAs) are not financed "in addition" to hospital charges, it was decided a priori to start treatment for HCV immediately before discharge. RESULTS Between January 7 and October 1, 2020, 407 patients accepted screening. Of these patients, 17 (4.2%; 95% CI: 2.2-6.1%) were anti-HCV positive and two were anti-HIV+/anti-HCV- (0.49%). HCV RNA was detectable in 9/17 anti-HCV+ patients, with a prevalence of infection of 2.2% (CI: 0.8-3.6%). Drug use was identified in 16 anti-HCV+ patients (94%), ten with active drug use. Of the nine viraemic patients, only four received a prescription for DAA treatment at the end of hospitalization, and only one was followed up by his general practitioner with the confirmation of virological cure three months after treatment cessation. No patient tested positive for hepatitis B surface antigen, but 3% had serological markers indicating HBV past infection. The anti-HBV vaccination coverage rate was only 39% in the entire population and only 41% for patients with a history of drug use. CONCLUSION Our study confirms that the prevalence of HCV infection is significantly higher in the psychiatric population than in the general population. By far, the main risk factor for HCV infection is drug use. This justifies the systematic performance of regular screening in this population. The way in which DAAs are financed in psychiatric hospitals seems to be a major obstacle to the initiation of treatment for chronic HCV infection during hospitalization and therefore to the elimination of HCV infection in the psychiatric population.
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Affiliation(s)
| | - Vincent Haghnejad
- SELHV Lorraine, 54500 Vandœuvre-lès-Nancy, France; Service hépato-gastroentérologie, CHRU de Nancy, 54500 Vandœuvre-lès-Nancy, France; Inserm U1256, 54500 Vandœuvre-lès-Nancy, France
| | | | | | | | - Jean-Pierre Bronowicki
- SELHV Lorraine, 54500 Vandœuvre-lès-Nancy, France; Service hépato-gastroentérologie, CHRU de Nancy, 54500 Vandœuvre-lès-Nancy, France; Inserm U1256, 54500 Vandœuvre-lès-Nancy, France.
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Pokorska-Śpiewak M, Talarek E, Aniszewska M, Pluta M, Dobrzeniecka A, Marczyńska M, Indolfi G. The Influence of Treatment With Sofosbuvir/Velpatasvir on Children's Growth-Results of the PANDAA-PED Study. Pediatr Infect Dis J 2025; 44:1-5. [PMID: 39230270 PMCID: PMC11627321 DOI: 10.1097/inf.0000000000004504] [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] [Accepted: 07/16/2024] [Indexed: 09/05/2024]
Abstract
BACKGROUND The aim of this study was to evaluate the influence of treatment of hepatitis C with sofosbuvir and velpatasvir (SOF/VEL) on children's growth. METHODS Fifty children 6-18 years of age were successfully treated for hepatitis C with a 12-week course of SOF/VEL fixed dose adjusted to the body weight in the PANDAA-PED (Treatment of chronic hepatitis C in children 6-18 years of age using a pangenotypic direct-acting antiviral sofosbuvir/velpatasvir) project. Growth parameters were compared at 1 year after treatment with baseline (at the start of treatment) and 12-week-posttreatment values. Body mass index (BMI), weight and height Z scores adjusted to sex and age were calculated according to the World Health Organization reference data. RESULTS Forty-nine participants (23 boys and 26 girls) completed all the visits. The mean age at 1 year after treatment was 10.9 ± 2.5 years, and all children had undetectable hepatitis C virus RNA at this point. Significant weight and height gains were observed after treatment irrespective of the patients' age and sex. Height Z scores did not vary significantly both at 12 weeks and 1 year after treatment, confirming a normal increase in participants' height. Weight Z scores for 16 children below 10 years of age decreased at 1 year after treatment. BMI Z score values decreased at 12 weeks after treatment compared to the baseline in boys, but no difference was found between 1-year posttreatment and baseline BMI Z scores in both girls and boys. CONCLUSIONS Results of the PANDAA-PED study showed normal growth up to 1 year after successful treatment with SOF/VEL in children 6-18 years of age. Despite the decrease in BMI Z score in boys observed at 12 weeks after treatment, no differences were found between baseline and 1-year posttreatment values. Our observations confirm the long-term safety of the SOF/VEL treatment in children 6-18 years of age.
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Affiliation(s)
- Maria Pokorska-Śpiewak
- From the Department of Children’s Infectious Diseases, Medical University of Warsaw, Warsaw, Poland
- Department of Pediatric Infectious Diseases, Regional Hospital of Infectious Diseases in Warsaw, Warsaw, Poland
| | - Ewa Talarek
- From the Department of Children’s Infectious Diseases, Medical University of Warsaw, Warsaw, Poland
- Department of Pediatric Infectious Diseases, Regional Hospital of Infectious Diseases in Warsaw, Warsaw, Poland
| | - Małgorzata Aniszewska
- From the Department of Children’s Infectious Diseases, Medical University of Warsaw, Warsaw, Poland
- Department of Pediatric Infectious Diseases, Regional Hospital of Infectious Diseases in Warsaw, Warsaw, Poland
| | - Magdalena Pluta
- From the Department of Children’s Infectious Diseases, Medical University of Warsaw, Warsaw, Poland
- Department of Pediatric Infectious Diseases, Regional Hospital of Infectious Diseases in Warsaw, Warsaw, Poland
| | - Anna Dobrzeniecka
- Department of Pediatric Infectious Diseases, Regional Hospital of Infectious Diseases in Warsaw, Warsaw, Poland
| | - Magdalena Marczyńska
- From the Department of Children’s Infectious Diseases, Medical University of Warsaw, Warsaw, Poland
- Department of Pediatric Infectious Diseases, Regional Hospital of Infectious Diseases in Warsaw, Warsaw, Poland
| | - Giuseppe Indolfi
- Department of Neurofarba, Meyer Children’s University of Florence, Florence, Italy
- Meyer Children’s Hospital, Istituto di Ricerca e Cura a Carattere Scientifico, Florence, Italy
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Vilar FC, Donadi E, da Fonseca BAL, Freitas JCDOC, Borducchi ALGZ, Santana RDC. HLA-G liver expression in chronically HIV/hepatitis C-coinfected individuals. Ann Hepatol 2024; 30:101755. [PMID: 39631457 DOI: 10.1016/j.aohep.2024.101755] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2024] [Revised: 09/04/2024] [Accepted: 10/23/2024] [Indexed: 12/07/2024]
Abstract
INTRODUCTION AND OBJECTIVES Hepatitis C-induced liver disease represents a significant threat to the survival of people living with HIV. HIV/HCV-coinfected individuals have a more rapid progression to cirrhosis and its complications than HCV monoinfected patients. Although the underlying mechanisms remain unclear, HLA-G, a non-classical class I HLA molecule, has a well-recognized property to down-regulate the immune response against viruses and may favor the progression of chronic hepatitis C. MATERIALS AND METHODS We analyzed HLA-G expression in 59 liver specimens of patients harboring chronic HCV and HIV coinfection and stratified the findings according to clinical and histopathological features. RESULTS Genotype 1 was the most prevalent (88%); the HLA-G expression was observed in 38 (64%) liver specimens, and it was more frequent in more severe stages than in milder stages of chronic hepatitis (94,1% x 55%; p<0.01). HLA-G expression in the liver was not correlated to antiviral response to hepatitis C therapy with pegylated-IFN-α plus ribavirin. CONCLUSIONS HLA-G expression in the context of HCV/HIV coinfection is a complex process modulated by many factors. HLA-G expression may play a role in the mechanisms that facilitate disease progression and may contribute to the deterioration of the immune response against HCV in individuals living with HIV.
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Affiliation(s)
- Fernando Crivelenti Vilar
- Department of Internal Medicine, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil
| | - Eduardo Donadi
- Department of Internal Medicine, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil
| | | | | | | | - Rodrigo de Carvalho Santana
- Department of Internal Medicine, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil.
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Yao X, Gao S, Yan N. Structural biology of voltage-gated calcium channels. Channels (Austin) 2024; 18:2290807. [PMID: 38062897 PMCID: PMC10761187 DOI: 10.1080/19336950.2023.2290807] [Citation(s) in RCA: 11] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2023] [Accepted: 11/27/2023] [Indexed: 12/18/2023] Open
Abstract
Voltage-gated calcium (Cav) channels mediate Ca2+ influx in response to membrane depolarization, playing critical roles in diverse physiological processes. Dysfunction or aberrant regulation of Cav channels can lead to life-threatening consequences. Cav-targeting drugs have been clinically used to treat cardiovascular and neuronal disorders for several decades. This review aims to provide an account of recent developments in the structural dissection of Cav channels. High-resolution structures have significantly advanced our understanding of the working and disease mechanisms of Cav channels, shed light on the molecular basis for their modulation, and elucidated the modes of actions (MOAs) of representative drugs and toxins. The progress in structural studies of Cav channels lays the foundation for future drug discovery efforts targeting Cav channelopathies.
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Affiliation(s)
- Xia Yao
- TaiKang Center for Life and Medical Sciences, School of Pharmaceutical Sciences, Wuhan University, Wuhan, China
| | - Shuai Gao
- TaiKang Center for Life and Medical Sciences, School of Pharmaceutical Sciences, Wuhan University, Wuhan, China
| | - Nieng Yan
- Beijing Frontier Research Center for Biological Structures, State Key Laboratory of Membrane Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China
- Shenzhen Medical Academy of Research and Translation, Shenzhen, China
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11
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Jiang FR, Ye XT, Huang HQ, Hu YT, Wang DH, Jiang SW, Wang JL, Hu AR. Effectiveness of sofosbuvir-based treatments for patients with hepatitis C virus genotype 6 infection: a real-world study from East China. Front Med (Lausanne) 2024; 11:1462706. [PMID: 39659627 PMCID: PMC11628284 DOI: 10.3389/fmed.2024.1462706] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2024] [Accepted: 11/08/2024] [Indexed: 12/12/2024] Open
Abstract
Background Over the past decade, the proportion of hepatitis C virus (HCV) genotypes (GT) 1 and 2 has decreased in almost all regions of China, while GT 3 and 6 have emerged as new challenges. GT 6 is unique in many respects, like high genetic variability and emerging resistant variants. This study aims to assess the efficacy of sofosbuvir (SOF)-based treatments in patients with GT 6 chronic hepatitis C (CHC). Methods A retrospective analysis was conducted on patients with GT 6 HCV infection, who were diagnosed between July 2018 and May 2023. All patients received a 12-week course of SOF-based treatments. The primary efficacy endpoint was sustained virologic response (SVR), which is defined as having undetectable HCV RNA at 12 weeks after treatment completion (SVR12). The efficacy data for SVR12 were analyzed using both the evaluated population (EP) and per-protocol population (PP). For the PP populations, efficacy data were stratified using Forrester plots. Results A total of 201 patients were included in the study. In PP population, the end of treatment virological response rate was 99.48% (190/191), the SVR12 rate was 99.31% (143/144), and the SVR24 rate was 100.00% (75/75). Only one patient with genotype 6a experienced a relapse 12 weeks after the completion of treatment, but her HCV RNA was undetectable both at the end of treatment and 24 weeks after the end of treatment. Additionally, the normalization rates of alanine transaminase (ALT) and aspartate aminotransferase (AST) were significantly higher at the end of treatment (EOT) compared to baseline (27.36% vs. 93.03%, 36.32% vs. 95.02%, p < 0.001). Significant improvements were observed in the levels of total bilirubin, ALT, AST, albumin, globulin, albumin/globulin ratio, gamma-glutamyl transferase, alkaline phosphatase, platelet, fibrosis-4 (FIB-4), and aspartate transaminase to platelet ratio index (APRI) between baseline and EOT (p < 0.05). Conclusion SOF-based treatments achieved high virological and biochemical response rates in patients with HCV GT 6 infection.
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Affiliation(s)
- Fan-Rong Jiang
- Department of Pharmacy, Ningbo No. 2 Hospital, Ningbo, China
| | - Xiao-Ting Ye
- Department of Infectious Diseases, Ruian People’s Hospital, Ruian, China
| | - He-Qing Huang
- Department of Infectious Diseases, Zhuji People’s Hospital, Zhuji, China
| | - Yu-Tao Hu
- Department of Infectious Diseases, Xiangshan Hospital Affiliated to Wenzhou Medical University, Ningbo, China
| | - Dong-Hui Wang
- Liver Diseases Center, Ningbo No. 2 Hospital, Ningbo, China
| | - Su-Wen Jiang
- Liver Diseases Center, Ningbo No. 2 Hospital, Ningbo, China
| | - Jia-Lan Wang
- Cixi Biomedical Research Institute, Wenzhou Medical University, Wenzhou, China
| | - Ai-Rong Hu
- Liver Diseases Center, Ningbo No. 2 Hospital, Ningbo, China
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12
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Olafsson S, Love TJ, Fridriksdottir RH, Tyrfingsson T, Runarsdottir V, Hansdottir I, Bergmann OM, Björnsson ES, Johannsson B, Sigurdardottir B, Löve A, Baldvinsdottir GE, Thordardottir M, Hernandez UB, Heimisdottir M, Hellard M, Gottfredsson M. Predictors of treatment outcomes for Hepatitis C infection in a nationwide elimination program in Iceland: The treatment as prevention for Hepatitis C (TraP HepC) study. THE INTERNATIONAL JOURNAL OF DRUG POLICY 2024; 133:104616. [PMID: 39454253 DOI: 10.1016/j.drugpo.2024.104616] [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: 05/07/2024] [Revised: 10/02/2024] [Accepted: 10/05/2024] [Indexed: 10/28/2024]
Abstract
BACKGROUND Limited data exists about treatment outcomes in nationwide hepatitis C virus (HCV) elimination programs where injection drug use (IDU) is the main mode of transmission. In 2016 Iceland initiated the HCV elimination program known as Treatment as Prevention for Hepatitis C (TraP HepC). Factors associated with HCV cure in this population are examined. METHODS Unrestricted access was offered to direct acting antiviral agents (DAAs). Testing and harm reduction was scaled up and re-treatments were offered for those who did not attain cure. Cure rates for the first 36 months were assessed and factors associated with failure to achieve cure analysed using multivariable logistic regression. RESULTS Treatment was initiated for 718; 705 consented for the study. Median age was 44 years (IQR 35-56), history of IDU reported by 593 (84.1 %), recent IDU by 234 (33.2 %); 48 (6.8 %) were homeless. Of 705 patients, 635 achieved cure (90.1 %) during the first treatment. A total of 70 (9.9 %) patients initiated two or more treatments, resulting in 673 participants cured (95.5 %). By multivariable analysis, homelessness was the only statistically significant independent factor associated with not achieving cure (OR 2.67, 95 % CI 1.32-5.41) after first treatment attempt. CONCLUSION By reengagement in care and prompt retreatment when needed, a cure rate of 95.5 % was achieved. Unstable housing, a potentially actionable factor is associated with poor outcome.
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Affiliation(s)
- Sigurdur Olafsson
- Department of Gastroenterology and Hepatology, Landspitali University Hospital, Iceland; Faculty of Medicine, School of Health Sciences, University of Iceland, Iceland.
| | - Thorvardur Jon Love
- Faculty of Medicine, School of Health Sciences, University of Iceland, Iceland; Department of Science, Landspitali University Hospital, Reykjavik, Iceland
| | | | | | | | - Ingunn Hansdottir
- SAA National Center for Addiction Medicine - Reykjavik Iceland, Iceland; Faculty of Psychology, School of Health Sciences, University of Iceland, Iceland
| | - Ottar Mar Bergmann
- Department of Gastroenterology and Hepatology, Landspitali University Hospital, Iceland
| | - Einar Stefan Björnsson
- Department of Gastroenterology and Hepatology, Landspitali University Hospital, Iceland; Faculty of Medicine, School of Health Sciences, University of Iceland, Iceland
| | - Birgir Johannsson
- Department of Infectious Diseases, Landspitali University Hospital, Iceland
| | | | - Arthur Löve
- Faculty of Medicine, School of Health Sciences, University of Iceland, Iceland; Department of Virology, Landspitali University Hospital, Iceland
| | | | | | | | - Maria Heimisdottir
- Faculty of Medicine, School of Health Sciences, University of Iceland, Iceland; Icelandic Health Insurance, Iceland
| | - Margaret Hellard
- Burnet Institute, Melbourne Australia; Department of Infectious Diseases, The Alfred Hospital, Melbourne, Australia
| | - Magnus Gottfredsson
- Faculty of Medicine, School of Health Sciences, University of Iceland, Iceland; Department of Infectious Diseases, Landspitali University Hospital, Iceland; Department of Science, Landspitali University Hospital, Reykjavik, Iceland
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13
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Choi SA, Umashankar K, Maheswaran A, Martin MT, Lee J, Odishoo M, Lin JY, Touchette DR. Cost-effectiveness analysis of emergency department-based hepatitis C screening and linkage-to-care program. BMC Health Serv Res 2024; 24:1308. [PMID: 39472900 PMCID: PMC11523774 DOI: 10.1186/s12913-024-11793-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2023] [Accepted: 10/18/2024] [Indexed: 11/02/2024] Open
Abstract
BACKGROUND In the United States (US), hepatitis C virus (HCV) screening is not covered by payers in settings outside of primary care. A non-traditional, emergency department (ED)-based HCV screening program can be cost-effective and identify infection in vulnerable populations with a high HCV risk. This study examined the long-term cost-effectiveness of routine HCV screening and linkage-to-care for high-risk patients in the ED from the payer's perspective. METHODS The University of Illinois Hospital and Health Sciences System (UIH) implemented Project HEAL (HIV & HCV Screening, Education, Awareness, Linkage-to-Care). Under this initiative, patients who presented to the ED received opt-out HCV screening if they were at high risk for HCV infection (birth cohort between 1945 and 1964, persons who inject drugs, and HIV infection) with subsequent linkage-to-care if infected. Using the summary data from Project HEAL, a hybrid decision-analytic Markov model was developed based on the HCV screening procedure in the ED and the natural history of HCV. A 30-year time horizon and 1-year cycle length were used. All patients who received the ED-based HCV screening were referred for treatment with direct-acting antiviral (DAA) regardless of their fibrosis stage. RESULTS When unscreened/untreated patients received DAA treatment at F1, F2, F3, and compensated cirrhosis stages, the incremental cost-effectiveness ratio (ICER) ranged from $6,084 to $77,063 per quality-adjusted life year (QALY) gained. When unscreened/untreated patients received DAA treatment at the decompensated cirrhosis stage, no HCV screening was dominated. CONCLUSION ED-based HCV screening and linkage-to-care was cost-effective at the willingness-to-pay (WTP) threshold of $100,000/QALY in all scenarios. A reduction in infected persons in the community may provide additional benefits not evaluated in this study.
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Affiliation(s)
- Sun A Choi
- Department of Pharmacy Systems, Outcomes and Policy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA
| | - Kandavadivu Umashankar
- Department of Pharmacy Systems, Outcomes and Policy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA
| | - Anjana Maheswaran
- Department of Emergency Medicine, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA
| | - Michelle T Martin
- Liver Clinic, University of Illinois Hospital and Health Sciences System, Chicago, IL, USA
- Department of Pharmacy Practice College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA
| | - Jean Lee
- Department of Pharmacy Systems, Outcomes and Policy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA
| | - Matt Odishoo
- Department of Pharmacy Systems, Outcomes and Policy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA
| | - Janet Y Lin
- Department of Emergency Medicine, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA
| | - Daniel R Touchette
- Department of Pharmacy Systems, Outcomes and Policy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA.
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14
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Liu CH, Chang YP, Kao JH. Cutting-edge pharmacotherapy for hepatitis C virus infection: a comprehensive review. Expert Opin Pharmacother 2024; 25:1691-1706. [PMID: 39169665 DOI: 10.1080/14656566.2024.2396024] [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: 07/17/2024] [Revised: 08/17/2024] [Accepted: 08/20/2024] [Indexed: 08/23/2024]
Abstract
INTRODUCTION Pharmacotherapy against hepatitis C virus (HCV) infection has tremendously improved since the advent of interferon (IFN)-free direct-acting antivirals (DAAs). Additionally, fixed-dose pangenotypic DAAs, which are safe, potent, easy for use, and can cover a wide spectrum of patients, have been recommended by professional guidelines for DAA-naïve and DAA-experienced patients with HCV. AREAS COVERED We review the pharmacokinetics, pharmacodynamics, and potential drug-drug interactions (DDIs) of fixed-dose pangenotypic DAA regimens, including glecaprevir/pibrentasvir (GLE/PIB), sofosbuvir/velpatasvir (SOF/VEL), and sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX). Additionally, we summarize the efficacy and safety of these regimens in clinical trials as well as real-world studies for treating different populations. Lastly, we discuss unmet medical needs in managing HCV in the era of fixed-dose pangenotypic DAAs. EXPERT OPINION Protease inhibitors (PIs), including GLE and VOX, are prone to have more frequent DDIs, compared to the non-structural (NS) 5A and 5B inhibitors. These regimens are generally well tolerated and can be applied to different populations, except for the contraindicated use of PI-containing DAA regimens in decompensated cirrhosis. Using the first-line GLE/PIB and SOF/VEL can eradicate HCV in more than 95% of DAA-naïve patients across different populations. The viral cure usually exceeds 95% when using the rescue SOF/VEL/VOX regimen for prior DAA failures.
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Affiliation(s)
- Chen-Hua Liu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, Douliou, Taiwan
| | - Yu-Ping Chang
- Department of Internal Medicine, National Taiwan University Biomedical Park Hospital, Hsin-Chu, Taiwan
| | - Jia-Horng Kao
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
- Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
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15
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Gonzales-Zamora JA, Quispe-Vicuña C, Reategui-Garcia ME, Araoz-Salinas JM, Ccami-Bernal F, Morocho-Alburqueque N, Espinoza-Herreros JP, Layme J, Aquino-Sandoval G, Campos VYM, Alave J. Identifying Gaps in the Treatment Guidelines for Hepatitis C in Peru to Meet International Standards: A Narrative Review. J Clin Med 2024; 13:3867. [PMID: 38999433 PMCID: PMC11242551 DOI: 10.3390/jcm13133867] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2024] [Revised: 06/16/2024] [Accepted: 06/25/2024] [Indexed: 07/14/2024] Open
Abstract
Hepatitis C virus still represents a major cause of morbidity and mortality worldwide. In Peru, two national practice guidelines for the management of this infection were published more than 5 years ago; however, the latest breakthroughs in the treatment make it necessary to update these guidelines. We reviewed the most recent recommendations of the international guidelines and compared them with the current Peruvian guidelines. We found major differences, such as the use of Glecaprevir/Pibrentasvir as a first-line therapy, which is contemplated in the World Health Organization guideline, and recommended by American and European guidelines, but is not considered in the Peruvian guidelines. Another crucial difference lies in the management of patients with chronic kidney disease, who are treated nowadays with a variety of direct-acting antivirals, with no restrictions on the use of Sofosbuvir-based regimens in first-world countries, an approach that has not been adopted in Peru. We believe that standardization of the recommendations of the Peruvian guidelines is imperative, including the new therapeutic strategies that have emerged in recent years. We also suggest conducting a cost effectiveness analysis in the Peruvian context to allow for the implementation of new antivirals, and to achieve a better control of hepatitis C in the country.
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Affiliation(s)
- Jose A. Gonzales-Zamora
- Division of Infectious Diseases, Department of Medicine, Miller School of Medicine, University of Miami, Miami, FL 33136, USA;
- Peruvian American Medical Society (PAMS), Albuquerque, NM 87111, USA; (J.M.A.-S.); (J.L.); (V.Y.M.C.)
| | | | - Martín E. Reategui-Garcia
- School of Medicine, Universidad Nacional de la Amazonía Peruana, Iquitos 16000, Peru; (M.E.R.-G.); (G.A.-S.)
| | - Julieta M. Araoz-Salinas
- Peruvian American Medical Society (PAMS), Albuquerque, NM 87111, USA; (J.M.A.-S.); (J.L.); (V.Y.M.C.)
| | - Fabricio Ccami-Bernal
- School of Medicine, Universidad Nacional de San Agustín de Arequipa, Arequipa 04001, Peru;
| | | | | | - Josue Layme
- Peruvian American Medical Society (PAMS), Albuquerque, NM 87111, USA; (J.M.A.-S.); (J.L.); (V.Y.M.C.)
- School of Medicine, Universidad Nacional Mayor de San Marcos, Lima 15001, Peru
| | - Gabriel Aquino-Sandoval
- School of Medicine, Universidad Nacional de la Amazonía Peruana, Iquitos 16000, Peru; (M.E.R.-G.); (G.A.-S.)
- Sociedad Científica de Estudiantes de Medicina de la Amazonía Peruana (SOCIEMAP), Universidad Nacional de la Amazonía Peruana, Iquitos 16000, Peru
| | - Victor Y. Melt Campos
- Peruvian American Medical Society (PAMS), Albuquerque, NM 87111, USA; (J.M.A.-S.); (J.L.); (V.Y.M.C.)
- Department of Community Health and Family Medicine, College of Medicine, University of Florida, Jacksonville, FL 32209, USA
| | - Jorge Alave
- School of Medicine, Universidad Peruana Union, Lima 15464, Peru
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16
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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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17
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Dobrowolska K, Brzdęk M, Rzymski P, Flisiak R, Pawłowska M, Janczura J, Brzdęk K, Zarębska-Michaluk D. Revolutionizing hepatitis C treatment: next-gen direct-acting antivirals. Expert Opin Pharmacother 2024; 25:833-852. [PMID: 38768013 DOI: 10.1080/14656566.2024.2358139] [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: 04/11/2024] [Accepted: 05/17/2024] [Indexed: 05/22/2024]
Abstract
INTRODUCTION With the introduction of highly effective and safe therapies with next-generation direct-acting antivirals (DAAs), that act without interferon, hepatitis C virus (HCV) infection remains the only treatable chronic infectious disease. AREAS COVERED The review aims to provide an overview of the therapy revolution with a description of specific DAAs, their mechanisms of action, a summary of the safety and efficacy of specific regimens, and a discussion of populations requiring special therapeutic approaches. EXPERT OPINION DAAs are highly effective, safe, and easy to use. However, challenges such as access to health services and loss of patients from the cascade of care, especially in groups disproportionately affected by HCV infection, such as substance abusers, make it difficult to achieve the WHO's goal of HCV elimination. The proposed strategy to combat these difficulties involves a one-step approach to diagnosing and treating the infection, the availability of long-lasting forms of medication, and the development of an effective vaccine. The aforementioned opportunities are all the more important as the world is facing an opioid epidemic that is translating into an increase in HCV prevalence. This phenomenon is of greatest concern in women of childbearing age and in those already pregnant due to treatment limitations.
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Affiliation(s)
| | - Michał Brzdęk
- Collegium Medicum, Jan Kochanowski University, Kielce, Poland
| | - Piotr Rzymski
- Department of Environmental Medicine, Poznan University of Medical Sciences, Poznan, Poland
| | - Robert Flisiak
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, Białystok, Poland
| | - Małgorzata Pawłowska
- Department of Infectious Diseases and Hepatology, Faculty of Medicine, Collegium Medicum Bydgoszcz, Nicolaus Copernicus University, Toruń, Poland
| | - Jakub Janczura
- Collegium Medicum, Jan Kochanowski University, Kielce, Poland
| | - Kinga Brzdęk
- Collegium Medicum, Jan Kochanowski University, Kielce, Poland
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18
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Nagao Y, Kimura T, Tomooka K, Wakita H. Hepatitis B and C infections among Japanese dental health workers: Insights from vaccination rates and screening results in the Oita prefecture. Clin Exp Dent Res 2024; 10:e871. [PMID: 38506300 PMCID: PMC10952116 DOI: 10.1002/cre2.871] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2023] [Revised: 02/09/2024] [Accepted: 02/25/2024] [Indexed: 03/21/2024] Open
Abstract
OBJECTIVE This study examined the hepatitis B virus (HBV) and hepatitis C virus (HCV) infection rates and vaccination rates for hepatitis B (HB) among dental healthcare workers (DHCWs) in the Oita prefecture, Japan. METHODS Hepatitis virus testing was conducted on 1920 participants (486 dentists and 1434 dental staff). Anonymous data on age, gender, occupation, hepatitis B surface antigen (HBsAg), antibodies to hepatitis B surface antigen (anti-HBs), antibodies to HCV (anti-HCV), history of HB vaccination, and antiviral treatment for individuals with positive anti-HCV were collected. RESULTS The positivity rates for HBsAg, anti-HBs, and anti-HCV were 0.5%, 39.7%, and 0.6%, respectively. Dentists had significantly higher rates of anti-HBs positivity (53.9% vs. 34.9%; p < .0001) and anti-HCV positivity (1.4% vs. 0.3%; p = .0080) compared to dental staff. The vaccination and non-vaccination rates among 1395 with a known HB vaccination history were 59.1% and 40.9%, respectively. Dentists had a significantly higher HB vaccine vaccination rate than the dental staff (73.6% vs. 54.0%; p < .0001). Those in the vaccination group were younger (p < .0001), had a higher proportion of males (p = .0022) and dentists (p < .0001), a lower HBsAg positivity rate (p < .0097), and a higher anti-HBs positivity rate (p < .0001) compared to those in the non-vaccination group. The positivity rate of HBsAg and anti-HBs in the unvaccinated group increased with age, with HBsAg positivity reaching 3.8% in the 70s and anti-HBs positivity reaching 40.4% in the 70s and 66.7% in the 80s. CONCLUSIONS This study highlights the need to raise awareness about hepatitis prevention vaccination, particularly among dental staff, due to differences in HB vaccination rates across occupations. In particular, they indicated that elderly DHCWs may be more vulnerable to HBV infection. Regular monitoring of the vaccination rate and infection risk is crucial.
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Affiliation(s)
- Yumiko Nagao
- Department of Public Health, Graduate School of MedicineJuntendo UniversityTokyoJapan
- Liver CenterSaga University HospitalSagaJapan
| | | | - Kiyohide Tomooka
- Department of Public Health, Graduate School of MedicineJuntendo UniversityTokyoJapan
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19
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Brigham D, Narkewicz MR. Profile of Sofosbuvir and Velpatasvir Combination in the Treatment of Chronic Hepatitis C in Children and Adolescents: Current Evidence. Ther Clin Risk Manag 2024; 20:1-7. [PMID: 38230373 PMCID: PMC10789568 DOI: 10.2147/tcrm.s326099] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2023] [Accepted: 12/28/2023] [Indexed: 01/18/2024] Open
Abstract
Chronic hepatitis C (HCV) affects up to 3.25 million children and adolescents. Early treatment of HCV in children and adolescents reduces progression to advanced liver disease and cancer. Treatment for HCV has evolved to highly effective direct acting antiviral therapy in adults and now in children ≥3 years of age. This review focuses on the role of sofosbuvir and velpatasvir (SOF/VEL), a newer treatment of children and adolescents with chronic HCV. SOF/VEL is a pangenotypic DAA with primary clearance via the liver and biliary excretion. It has been studied in children and adolescents and is approved in the US for use in children and adolescents ≥3 years of age. Although the data are currently limited, SOF/VEL has demonstrated sustained viral response rates similar to comparable DAAs in the range of 95-98%. To date, side effects have been minimal.
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Affiliation(s)
- Dania Brigham
- Digestive Health Institute, Pediatric Liver Center, Children’s Hospital Colorado and University of Colorado School of Medicine, Section of Pediatric Gastroenterology, Hepatology and Nutrition, Aurora, CO, USA
| | - Michael R Narkewicz
- Digestive Health Institute, Pediatric Liver Center, Children’s Hospital Colorado and University of Colorado School of Medicine, Section of Pediatric Gastroenterology, Hepatology and Nutrition, Aurora, CO, USA
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Alghamdi AS, Alghamdi H, Alserehi HA, Babatin MA, Alswat KA, Alghamdi M, AlQutub A, Abaalkhail F, Altraif I, Alfaleh FZ, Sanai FM. SASLT guidelines: Update in treatment of hepatitis C virus infection, 2024. Saudi J Gastroenterol 2024; 30:S1-S42. [PMID: 38167232 PMCID: PMC10856511 DOI: 10.4103/sjg.sjg_333_23] [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: 09/20/2023] [Revised: 11/27/2023] [Accepted: 12/03/2023] [Indexed: 01/05/2024] Open
Abstract
ABSTRACT Hepatitis C virus (HCV) infection has been a major global health concern, with a significant impact on public health. In recent years, there have been remarkable advancements in our understanding of HCV and the development of novel therapeutic agents. The Saudi Society for the Study of Liver Disease and Transplantation formed a working group to develop HCV practice guidelines in Saudi Arabia. The methodology used to create these guidelines involved a comprehensive review of available evidence, local data, and major international practice guidelines regarding HCV management. This updated guideline encompasses critical aspects of HCV care, including screening and diagnosis, assessing the severity of liver disease, and treatment strategies. The aim of this updated guideline is to assist healthcare providers in the management of HCV in Saudi Arabia. It summarizes the latest local studies on HCV epidemiology, significant changes in virus prevalence, and the importance of universal screening, particularly among high-risk populations. Moreover, it discusses the promising potential for HCV elimination as a public health threat by 2030, driven by effective treatment and comprehensive prevention strategies. This guideline also highlights evolving recommendations for advancing disease management, including the treatment of HCV patients with decompensated cirrhosis, treatment of those who have previously failed treatment with the newer medications, management in the context of liver transplantation and hepatocellular carcinoma, and treatment for special populations.
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Affiliation(s)
- Abdullah S. Alghamdi
- Department of Medicine, Gastroenterology Unit, King Fahad Hospital, Jeddah, Saudi Arabia
| | - Hamdan Alghamdi
- Hepatology Section, Hepatobiliary Sciences and Organs Transplant Center, King Abdulaziz Medical City, Riyadh, Saudi Arabia
- King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
- King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia
| | - Haleema A. Alserehi
- General Directorate of Communicable Diseases, Ministry of Health, Riyadh, Saudi Arabia
| | - Mohammed A. Babatin
- Department of Medicine, Gastroenterology Unit, King Fahad Hospital, Jeddah, Saudi Arabia
| | - Khalid A. Alswat
- Liver Disease Research Center, and Riyadh, Saudi Arabia
- College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Mohammed Alghamdi
- Department of Medicine, Division of Gastroenterology, King Fahd Military Complex, Dhahran, Saudi Arabia
| | - Adel AlQutub
- Department of Gastroenterology and Hepatology, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Faisal Abaalkhail
- Department of Medicine, Section of Gastroenterology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
- College of Medicine, Al Faisal University, Riyadh, Saudi Arabia
| | - Ibrahim Altraif
- Hepatology Section, Hepatobiliary Sciences and Organs Transplant Center, King Abdulaziz Medical City, Riyadh, Saudi Arabia
- King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
- King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia
| | | | - Faisal M. Sanai
- Liver Disease Research Center, and Riyadh, Saudi Arabia
- Gastroenterology Section, Department of Medicine, King Abdulaziz Medical City, Jeddah, Saudi Arabia
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21
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Zhou J, Wang FD, Li LQ, Li JY, Chen EQ. Decreased Efficacy of Sofosbuvir/Velpatasvir in HIV Patients Coinfected with HCV Genotype 3b. Future Virol 2024; 19:33-45. [DOI: 10.2217/fvl-2023-0112] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Accepted: 01/29/2024] [Indexed: 01/13/2025]
Affiliation(s)
- Jing Zhou
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Fa-Da Wang
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Lan-Qing Li
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Jing-Yu Li
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - En-Qiang Chen
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, 610041, China
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Westin J, Ydreborg M, Kampmann C, Wejstål R, Weiland O. Dismal prognosis for cirrhotic patients with hepatitis C after initial failure of direct acting anti-virals, but salvage therapy may be life-saving. Infect Dis (Lond) 2023; 55:786-793. [PMID: 37561507 DOI: 10.1080/23744235.2023.2244069] [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: 03/31/2023] [Revised: 07/24/2023] [Accepted: 07/27/2023] [Indexed: 08/11/2023] Open
Abstract
BACKGROUND Effective direct-acting antiviral treatment against hepatitis C virus infection is available in many countries worldwide. Despite good treatment results, a proportion of patients does not respond to treatment. The aim of this study was to investigate the long-term prognosis and the outcome of salvage therapy, after an initial treatment failure, in a nation-wide real-life setting. METHOD Data from all adult patients registered in the national Swedish hepatitis C treatment register who did not achieve sustained virological response after initial antiviral treatment, was retrieved from 2014 through 2018. RESULTS In total, 288 patients with primary treatment failure were included, of whom 236 underwent a second treatment course as salvage therapy after a median delay of 353 (IQR: 215-650) days. Fifteen patients received a third treatment course as second salvage treatment after a further median delay of 193 (IQR: 160-378) days. One-hundred-eleven out of 124 (90%) non-cirrhotic and 62/79 (78%) cirrhotic patients achieved sustained virological response following the first salvage treatment. Sustained virological response was achieved by 108/112 (96%) patients who received a triple antiviral regimen. In total 69 patients were lost to follow-up or died waiting for salvage treatment. Baseline cirrhosis was associated with poor long-term survival. CONCLUSION Our study indicates that salvage therapy was effective in most patients with primary treatment failure, in particular when a triple direct acting antiviral regimen was given. To avoid the risk of death or complications, patients with primary treatment failure should be offered salvage therapy with a triple regimen, as soon as possible.
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Affiliation(s)
- Johan Westin
- Department of Infectious Diseases, Insitute of Biomedicine, University of Gothenburg, Gothenburg, Sweden
- Department of Infectious Diseases, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Magdalena Ydreborg
- Department of Infectious Diseases, Insitute of Biomedicine, University of Gothenburg, Gothenburg, Sweden
- Department of Infectious Diseases, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Christian Kampmann
- Department of Infectious Diseases, Skåne University Hospital, Lund, Sweden
| | - Rune Wejstål
- Department of Infectious Diseases, Insitute of Biomedicine, University of Gothenburg, Gothenburg, Sweden
- Department of Infectious Diseases, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Ola Weiland
- Department of Medicine, Division of Infectious Diseases, Karolinska Institutet and Karolinska University Hospital Huddinge, Stockholm, Sweden
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23
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Flamm S, Lawitz E, Borg B, Charlton M, Landis C, Reddy KR, Shiffman M, Alsina A, Chang C, Ravendhran N, Hernandez C, Hézode C, Scherbakovsky S, Mercier RC, Samuel D. Efficacy and Safety of Sofosbuvir/Velpatasvir Plus Ribavirin in Patients with Hepatitis C Virus-Related Decompensated Cirrhosis. Viruses 2023; 15:2026. [PMID: 37896803 PMCID: PMC10611233 DOI: 10.3390/v15102026] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2023] [Revised: 08/18/2023] [Accepted: 08/22/2023] [Indexed: 10/29/2023] Open
Abstract
A fixed-dose combination of sofosbuvir/velpatasvir (SOF/VEL) plus weight-based ribavirin (RBV) for 12 weeks is recommended for the treatment of patients with hepatitis C virus (HCV)-associated decompensated cirrhosis. However, large global studies, while confirming the effectiveness of SOF/VEL in a broad range of patients, often exclude these patients. This Phase 2, single-arm, open-label study in adult patients with HCV-associated decompensated cirrhosis in France and the USA aimed to provide further data on the safety and efficacy of SOF/VEL plus RBV for 12 weeks in this population. Patients were treated with a fixed-dose combination of SOF 400 mg/VEL 100 mg plus weight-based RBV once daily for 12 weeks. The inclusion criteria were chronic HCV infection (≥6 months), quantifiable HCV RNA at screening, Child-Turcotte-Pugh class B or C cirrhosis, and liver imaging within 6 months of Day 1 to exclude hepatocellular carcinoma. Among 32 patients who initiated treatment, 78.1% achieved sustained virologic response 12 weeks after the end of treatment (SVR12). Failure to achieve SVR12 was due to non-virologic reasons (investigator discretion, n = 1; death, n = 6). All 25 patients in the per-protocol population achieved SVR12 and all but one achieved sustained virologic response 24 weeks after the end of treatment. Adverse events (AEs) were as expected for a patient population with advanced liver disease. All Grade 3-4 and serious AEs and deaths were deemed unrelated to treatment. In patients with HCV-associated decompensated cirrhosis, SOF/VEL plus RBV achieved high SVR12 rates and was generally well tolerated.
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Affiliation(s)
- Steven Flamm
- Department of Internal Medicine, Division of Digestive Diseases and Nutrition, Rush University Medical Center, Chicago, IL 60612, USA
| | - Eric Lawitz
- Texas Liver Institute, University of Texas Health San Antonio, San Antonio, TX 78215, USA
| | - Brian Borg
- Southern Therapy and Advanced Research LLC, Jackson, MS 39216, USA
| | | | - Charles Landis
- Division of Gastroenterology and Hepatology, University of Washington, Seattle, WA 98101, USA
| | - K. Rajender Reddy
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Mitchell Shiffman
- Bon Secours Mercy Health, Liver Institute of Virginia, Richmond, VA 23226, USA
| | - Angel Alsina
- Tampa General Medical Group, Tampa, FL 33609, USA
| | - Charissa Chang
- Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | | | | | | | | | | | - Didier Samuel
- Centre Hépatobiliaire, Hôpital Paul-Brousse, Inserm Research Unit 1193, Université Paris-Saclay, 94800 Villejuif, France
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De A, Charak S, Bhagat N, Rathi S, Verma N, Premkumar M, Taneja S, Sharma A, Goel K, Singh V, Duseja A. Efficacy and safety of pan-genotypic sofosbuvir and velpatasvir in patients with hepatitis C and HIV coinfection on dolutegravir-based antiretroviral therapy. J Viral Hepat 2023; 30:740-745. [PMID: 37260083 DOI: 10.1111/jvh.13844] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Revised: 04/30/2023] [Accepted: 05/13/2023] [Indexed: 06/02/2023]
Abstract
Hepatitis C virus (HCV) infection is more prevalent in people living with HIV-AIDS (PLHA) and portends a poorer prognosis. Pharmacokinetic studies suggest the absence of significant interaction between velpatasvir and dolutegravir which has been recently recommended as part of preferred first-line antiretroviral therapy (ART) regimens by WHO. However, clinical data on the use of velpatasvir-based regimen in PLHA taking dolutegavir is lacking. Hence, we aimed to assess the efficacy and safety of sofosbuvir and velpatasvir (SOF + VEL) in HCV and HIV coinfected patients on dolutegravir-based ART. Forty-five consecutive PLHA with HCV coinfection on dolutegravir-based ART were prospectively enrolled. All patients were treated SOF + VEL for 12 weeks. Complete haemogram, liver and renal function tests were assessed at baseline, 4 weeks and at end of treatment. Sustained virological response (SVR) was assessed at 12 weeks after end of treatment. The majority were males (95.5%) with a mean age of 32.8 ± 12.3 years. Cirrhosis was present in 6 (13.3%) patients. All patients completed 12 weeks of therapy with SOF + VEL, but SVR could not be assessed in two patients. Forty-two (97.7%) of the remaining 43 patients attained SVR-12. SVR-12 rate was 97.7% and 93.3% by per protocol and intention to treat analysis, respectively. No grade III/IV adverse events were reported, and there was no worsening of blood counts, liver or renal function test parameters. The pan-genotypic regimen of SOF + VEL is safe and effective in PLHA with HCV coinfection who are on dolutegravir-based ART.
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Affiliation(s)
- Arka De
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Swati Charak
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Naveen Bhagat
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Sahaj Rathi
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Nipun Verma
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Madhumita Premkumar
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Sunil Taneja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Aman Sharma
- Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Kapil Goel
- Department of Community Medicine and School of Public Health, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Virendra Singh
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Ajay Duseja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
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Konishi F, Miyake T, Watanabe T, Tokumoto Y, Furukawa S, Matsuura B, Yoshida O, Miyazaki M, Shiomi A, Kanzaki S, Nakaguchi H, Nakamura Y, Imai Y, Koizumi M, Yamamoto Y, Koizumi Y, Hirooka M, Takeshita E, Kumagi T, Ikeda Y, Abe M, Hiasa Y. Association of abnormal glucose tolerance with liver-related disease and cardiovascular diseases in patients with chronic hepatitis C. Hepatol Res 2023; 53:806-814. [PMID: 37183992 DOI: 10.1111/hepr.13925] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Revised: 05/06/2023] [Accepted: 05/08/2023] [Indexed: 05/16/2023]
Abstract
AIM Hepatitis C complicated by diabetes mellitus (DM) is considered a risk factor for the progression of fibrosis and development of hepatocellular carcinoma (HCC) and cardiovascular diseases. However, several studies may have lacked appropriate diagnosis of glucose intolerance. We aimed to examine the risk associated with abnormal glucose intolerance in the development of liver-related diseases, including HCC and complications of liver cirrhosis, such as ascites, esophageal and gastric varices, and hepatic encephalopathy, and cardiovascular diseases in patients with hepatitis C accurately diagnosed with impaired glucose tolerance. METHODS This longitudinal retrospective study included 365 patients with chronic hepatitis C admitted to Ehime University Hospital for anti-hepatitis C therapy between September 1991 and January 2015. Patients were classified into normal glucose tolerance (NGT), prediabetes, and DM groups based on 75-g oral glucose tolerance test results. RESULTS Both univariate and multivariate (adjusted for potential confounders) analyses revealed a significantly higher risk of developing HCC and cardiovascular events in the DM group than in the NGT group. However, in multivariate analysis, liver-related events, particularly liver cirrhosis complications, revealed no significant association. In addition, the prediabetes group had no significant risk of any outcome. CONCLUSIONS Patients with hepatitis C complicated by DM, compared with patients with hepatitis C with NGT or complicated with prediabetes, have a higher risk of HCC and cardiovascular disease events, but not liver-related events, particularly in not developing liver cirrhosis complications. Therefore, appropriate follow-up is required for patients with hepatitis C based on their glucose tolerance status.
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Affiliation(s)
| | - Teruki Miyake
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
| | - Takao Watanabe
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
| | - Yoshio Tokumoto
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
| | - Shinya Furukawa
- Health Services Center, Ehime University, Matsuyama, Ehime, Japan
| | - Bunzo Matsuura
- Department of Lifestyle-related Medicine and Endocrinology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
| | - Osamu Yoshida
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
| | - Masumi Miyazaki
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
| | - Akihito Shiomi
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
| | - Sayaka Kanzaki
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
| | - Hironobu Nakaguchi
- Department of Lifestyle-related Medicine and Endocrinology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
| | - Yoshiko Nakamura
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
| | - Yusuke Imai
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
| | - Mitsuhito Koizumi
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
| | - Yasunori Yamamoto
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
| | - Yohei Koizumi
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
| | - Masashi Hirooka
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
| | - Eiji Takeshita
- Department of Inflammatory Bowel Diseases and Therapeutics, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
| | - Teru Kumagi
- Postgraduate Medical Education Center, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
| | - Yoshio Ikeda
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
| | - Masanori Abe
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
| | - Yoichi Hiasa
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
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Bositis CM, Tana MM. Timely Treatment Translates: A Vision for Eradicating HCV. NAM Perspect 2023; 2023:202307b. [PMID: 37916069 PMCID: PMC10617995 DOI: 10.31478/202307b] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2023]
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Heo J, Kim YJ, Lee SW, Lee YJ, Yoon KT, Byun KS, Jung YJ, Tak WY, Jeong SH, Kwon KM, Suri V, Wu P, Jang BK, Lee BS, Cho JY, Jang JW, Yang SH, Paik SW, Kim HJ, Kwon JH, Park NH, Kim JH, Kim IH, Ahn SH, Lim YS. Efficacy and safety of sofosbuvir-velpatasvir and sofosbuvir-velpatasvir-voxilaprevir for hepatitis C in Korea: a Phase 3b study. Korean J Intern Med 2023; 38:504-513. [PMID: 37424500 PMCID: PMC10338242 DOI: 10.3904/kjim.2022.252] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2022] [Revised: 01/31/2023] [Accepted: 04/15/2023] [Indexed: 07/11/2023] Open
Abstract
BACKGROUND/AIMS Despite the availability of direct-acting antivirals (DAAs) for chronic hepatitis C virus (HCV) infection in Korea, need remains for pangenotypic regimens that can be used in the presence of hepatic impairment, comorbidities, or prior treatment failure. We investigated the efficacy and safety of sofosbuvir-velpatasvir and sofosbuvir-velpatasvir-voxilaprevir for 12 weeks in HCV-infected Korean adults. METHODS This Phase 3b, multicenter, open-label study included 2 cohorts. In Cohort 1, participants with HCV genotype 1 or 2 and who were treatment-naive or treatment-experienced with interferon-based treatments, received sofosbuvir-velpatasvir 400/100 mg/day. In Cohort 2, HCV genotype 1 infected individuals who previously received an NS5A inhibitor-containing regimen ≥ 4 weeks received sofosbuvir-velpatasvir-voxilaprevir 400/100/100 mg/day. Decompensated cirrhosis was an exclusion criterion. The primary endpoint was SVR12, defined as HCV RNA < 15 IU/mL 12 weeks following treatment. RESULTS Of 53 participants receiving sofosbuvir-velpatasvir, 52 (98.1%) achieved SVR12. The single participant who did not achieve SVR12 experienced an asymptomatic Grade 3 ASL/ALT elevation on day 15 and discontinued treatment. The event resolved without intervention. All 33 participants (100%) treated with sofosbuvir-velpatasvir-voxilaprevir achieved SVR 12. Overall, sofosbuvir-velpatasvir and sofosbuvir-velpatasvir-voxilaprevir were safe and well tolerated. Three participants (5.6%) in Cohort 1 and 1 participant (3.0%) in Cohort 2 had serious adverse events, but none were considered treatment-related. No deaths or grade 4 laboratory abnormalities were reported. CONCLUSION Treatment with sofosbuvir-velpatasvir or sofosbuvir-velpatasvir-voxilaprevir was safe and resulted in high SVR12 rates in Korean HCV patients.
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Affiliation(s)
- Jeong Heo
- Department of Internal Medicine, College of Medicine, Pusan National University and Biomedical Research Institute, Pusan National University Hospital, Busan, Korea
| | - Yoon Jun Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Sung Wook Lee
- Department of Internal Medicine, Dong-A University Hospital, Dong-A University College of Medicine, Busan, Korea
| | - Youn-Jae Lee
- Department of Internal Medicine, Inje University Busan Paik Hospital, Inje University College of Medicine, Busan, Korea
| | - Ki Tae Yoon
- Department of Internal Medicine, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, Korea
| | - Kwan Soo Byun
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Yong Jin Jung
- Division of Gastroenterology, Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
| | - Won Young Tak
- Department of Internal Medicine, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Sook-Hyang Jeong
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | | | | | - Peiwen Wu
- Gilead Sciences, Inc., Foster City, CA, USA
| | - Byoung Kuk Jang
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Byung Seok Lee
- Department of Internal Medicine, School of Medicine, Chungnam National University, Daejeon, Korea
| | - Ju-Yeon Cho
- Department of Internal Medicine, College of Medicine, Chosun University, Gwangju, Korea
| | - Jeong Won Jang
- Division of Hepatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Soo Hyun Yang
- Department of Internal Medicine, Veterans Health Service Medical Center, Seoul, Korea
| | - Seung Woon Paik
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Hyung Joon Kim
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
| | - Jung Hyun Kwon
- Division of Hepatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Neung Hwa Park
- Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea
| | - Ju Hyun Kim
- Department of Internal Medicine, Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon, Korea
| | - In Hee Kim
- Department of Internal Medicine, Jeonbuk National University Hospital, Jeonju, Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - Young-Suk Lim
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Ivashkin VT, Chulanov VP, Mamonova NA, Maevskaya MV, Zharkova MS, Tikhonov IN, Bogomolov PO, Volchkova EV, Dmitriev AS, Znojko OO, Klimova EA, Kozlov KV, Kravchenko IE, Malinnikova EY, Maslennikov RV, Mikhailov MI, Novak KE, Nikitin IG, Syutkin VE, Esaulenko EV, Sheptulin AA, Shirokova EN, Yushchuk ND. Clinical Practice Guidelines of the Russian Society for the Study of the Liver, the Russian Gastroenterological Association, the National Scientific Society of Infectious Disease Specialists for the Diagnosis and Treatment of Chronic Hepatitis C. RUSSIAN JOURNAL OF GASTROENTEROLOGY, HEPATOLOGY, COLOPROCTOLOGY 2023; 33:84-124. [DOI: 10.22416/1382-4376-2023-33-1-84-124] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/26/2024]
Abstract
Аim:diagnosis and treatment algorithms in the clinical recommendations intended for general practitioners, gastroenterologists, infectious disease specialists, hepatologists on the of chronic hepatitis C are presented.Summary.Chronic viral hepatitis C is a socially significant infection, the incidence of which in the Russian Federation remains significantly high. Over the past 10 years, great progress has been made in the treatment of hepatitis C — direct acting antiviral drugs have appeared. The spectrum of their effectiveness allows to achieve a sustained virological response in more than 90 % of cases, even in groups that were not previously considered even as candidates for therapy or were difficult to treat — patients receiving renal replacement therapy, after liver transplantation (or other organs), at the stage of decompensated liver cirrhosis, HIV co-infected, etc. Interferons are excluded from the recommendations due to their low effectiveness and a wide range of adverse events. The indications for the treatment have been expanded, namely, the fact of confirmation of viral replication. The terms of dispensary observation of patients without cirrhosis of the liver have been reduced (up to 12 weeks after the end of therapy). Also, these recommendations present approaches to active screening of hepatitis in risk groups, preventive and rehabilitation measures after the end of treatment.Conclusion.Great success has been achieved in the treatment of chronic hepatitis C. In most cases, eradication of viral HCV infection is a real task even in patients at the stage of cirrhosis of the liver, with impaired renal function, HIV co-infection, after solid organs transplantation.
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Affiliation(s)
- V. T. Ivashkin
- Sechenov First Moscow State Medical University (Sechenov University)
| | - V. P. Chulanov
- Center for Epidemiologically Significant Infectious Diseases, National Medical Research Center for Phthisiopulmonology and Infectious Diseases
| | - N. A. Mamonova
- Center for Epidemiologically Significant Infectious Diseases, National Medical Research Center for Phthisiopulmonology and Infectious Diseases
| | - M. V. Maevskaya
- Sechenov First Moscow State Medical University (Sechenov University)
| | - M. S. Zharkova
- Sechenov First Moscow State Medical University (Sechenov University)
| | - I. N. Tikhonov
- Sechenov First Moscow State Medical University (Sechenov University)
| | - P. O. Bogomolov
- M.F. Vladimirsky Moscow Regional Research Clinical Institute
| | - E. V. Volchkova
- Sechenov First Moscow State Medical University (Sechenov University)
| | - A. S. Dmitriev
- Sechenov First Moscow State Medical University (Sechenov University)
| | - O. O. Znojko
- Moscow State University of Medicine and Dentistry
| | | | | | | | - E. Yu. Malinnikova
- Department of Virology, Russian Medical Academy of Continuing Professional Education
| | - R. V. Maslennikov
- Sechenov First Moscow State Medical University (Sechenov University)
| | - M. I. Mikhailov
- North-Western State Medical University named after I.I. Mechnikov
| | | | | | - V. E. Syutkin
- Sklifosovsky Clinical and Research Institute for Emergency Medicine; Russian State Research Center — Burnazyan Federal Medical Biophysical Center
| | | | - A. A. Sheptulin
- Sechenov First Moscow State Medical University (Sechenov University)
| | - E. N. Shirokova
- Sechenov First Moscow State Medical University (Sechenov University)
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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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30
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Abi-Saleh SP, Ghazal F, Urtasun Sotil E. Achieving the Sustained Virologic Response With a Short-Course Treatment of Sofosbuvir/Velpatasvir. Cureus 2023; 15:e37126. [PMID: 37168177 PMCID: PMC10166273 DOI: 10.7759/cureus.37126] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/04/2023] [Indexed: 04/07/2023] Open
Abstract
Hepatitis C, a single-stranded RNA virus officially discovered in 1989, is one of the most known viruses of the Flaviviridae family. Direct-acting antiviral drugs helped revolutionize the management of hepatitis C infection by guaranteeing higher cure rates. The medical field has strived to optimize the management of this disease, with recent reports proposing a shorter treatment duration to achieve the sustained virologic response (SVR). We present a case of a patient diagnosed with hepatitis C decompensated liver cirrhosis who achieved the SVR after only two weeks of treatment with sofosbuvir/velpatasvir, suggesting that short-term therapy might be beneficial for these patients.
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31
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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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Lin W, Wang X, Zhang J, Wen C, Kang W, Mao L, Yang J, Dou Y, Shi L, Dang B, Lan Y, Li H, Li Y, Chen X, He H, Xu M, He Y, Hu F, Lu R, Cai W, Li L. A simple, feasible, efficient and safe treatment strategy of sofosbuvir/velpatasvir for chronic HCV/HIV-1 coinfected patients regardless of HCV genotypes: a multicenter, open-label study in China. THE LANCET REGIONAL HEALTH - WESTERN PACIFIC 2023. [PMID: 37547041 PMCID: PMC10398601 DOI: 10.1016/j.lanwpc.2023.100749] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/29/2023]
Abstract
Background The direct-acting antiviral agents (DAAs) have revolutionized the treatment of Hepatitis C Virus (HCV) infection. However, a simple and feasible treatment strategy with high efficacy and safety for HCV in patients coinfected with Human Immunodeficiency Virus (HIV) remains an unmet medical need, especially in areas with limited health resource. This study aims to assess the efficacy and safety of 12 weeks of treatment with sofosbuvir and velpatasvir in patients with chronic HCV/HIV-1 coinfection. Methods We conducted a multicenter, single-arm, open-label study in China, which involved chronic HCV/HIV-1 coinfected patients who are receiving an antiretroviral regimen of a combination tablet consisting of elvitegravir, cobicistat, emtricitabine, tenofovir alafenamide, (EVG/c/FTC/TAF) once daily. Patients with liver cirrhosis or experienced to DAAs treatment were excluded. All patients received combined sofosbuvir (400 mg) and velpatasvir (100 mg) tablet once daily for 12 weeks regardless of HCV genotype. The primary efficacy endpoint was sustained virologic response, defined as HCV RNA <15 IU/mL at 12 weeks after completion of treatment (SVR12). The primary safety endpoint was the proportion of patients who prematurely discontinued treatment because of adverse events. Safety and efficacy data were analyzed with an intention-to-treat (ITT) population (last observation carried forward) and per-protocol (PP) population. This trial is registered on ChiCTR.org.cn with number being ChiCTR1800020246. Findings Of the 243 patients enrolled, 78% were male, 9% had been previously treated for HCV with interferon, and none had pre-defined cirrhosis, although 8% had Fibrosis 4 score (FIB-4) >3.25. A total of 233 patients completed 12-week post-treatment follow-up. Overall, 227/233 patients (97%) achieved SVR12: 100% (63/63) in those with HCV genotype 1, 67% (2/3) in those with genotype 2, 95% (84/88) in those with genotype 3, 99% (78/79) in those with genotype 6. Rates of SVR12 were lower among those with baseline FIB-4 >3.25 than those without (78% [14/18] vs. 99% [211/212], P < 0.001). HIV-1 suppression was not compromised. The most common adverse events were upper respiratory tract infection (5%), cough (3%), abnormal renal function (2%), abnormal liver function (2%), constipation (2%), urinary tract infection (2%) and sleep disorders (2%). No participant discontinued treatment because of adverse events or death. Interpretation Twelve weeks of treatment with sofosbuvir/velpatasvir provide high rates of SVR and is well-tolerated in patients coinfected with HIV-1 and HCV regardless of HCV genotypes. Non-invasive liver fibrosis score may help to further distinguish patients at greater likelihood of a suboptimal response. Funding The 13th Five Year Plan of the Ministry of Science and Technology of China for the prevention and treatment of major infectious diseases such as AIDS and viral hepatitis, the National Key Research and Development Program of China, Medical Key Discipline Program of Guangzhou-Viral Infectious Diseases (2021-2023), Basic research program on people's Livelihood Science and technology of Guangzhou, and National Natural Science Foundation of China.
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Brzdęk M, Zarębska-Michaluk D, Invernizzi F, Cilla M, Dobrowolska K, Flisiak R. Decade of optimizing therapy with direct-acting antiviral drugs and the changing profile of patients with chronic hepatitis C. World J Gastroenterol 2023; 29:949-966. [PMID: 36844142 PMCID: PMC9950869 DOI: 10.3748/wjg.v29.i6.949] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Revised: 11/22/2022] [Accepted: 01/09/2023] [Indexed: 02/10/2023] Open
Abstract
Chronic infection with the hepatitis C virus (HCV) remains a major health problem affecting approximately 58 million people worldwide. In the era of interferon (IFN)-based regimens, patients particularly infected with genotypes 1 and 4 achieved a low response rate. The implementation of direct-acting antivirals changed the landscape of HCV treatment. The increase in effectiveness provided us with the hope of eliminating HCV as a significant public threat by 2030. In the following years, there was an observed improvement in the treatment of HCV with genotype-specific regimens and highly effective pangenotypic options that are the most recent stage of the revolution. The optimization of therapy was accompanied by changes in the patient profile from the beginning of the IFN-free era over time. Patients treated with antiviral therapies were younger in successive periods, less burdened with comorbidities and comedications, more frequently treatment-naïve and had less advanced liver disease. Before the IFN-free era, specific subpopulations such as patients with HCV/HIV coinfection, those with a history of previous treatment, patients with renal impairment or with cirrhosis had lower chances for a virologic response. Currently, these populations should no longer be considered difficult to treat. Despite the high effectiveness of HCV therapy, there is a small percentage of patients with treatment failure. However, they can be effectively retreated with pangenotypic rescue regimens.
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Affiliation(s)
- Michał Brzdęk
- Collegium Medicum, Jan Kochanowski University, Kielce 25-516, Poland
| | | | - Federica Invernizzi
- Center for Liver Disease, Division of Internal Medicine and Hepatology, IRCCS Ospedale San Raffaele, Milan 20-132, Italy
| | - Marta Cilla
- Center for Liver Disease, Division of Internal Medicine and Hepatology, IRCCS Ospedale San Raffaele, Milan 20-132, Italy
| | | | - Robert Flisiak
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, Białystok 15-540, Poland
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Lok AS, Moon J, Sherman KE, Khalili M, Fishbein D, Reddy KR. Long-term Follow-up of Hepatitis C Patients Who Achieved Sustained Virologic Response in the Pragmatic PRIORITIZE Study. Clin Gastroenterol Hepatol 2023; 21:546-548.e4. [PMID: 35182741 PMCID: PMC9503088 DOI: 10.1016/j.cgh.2022.01.059] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Revised: 01/24/2022] [Accepted: 01/26/2022] [Indexed: 02/07/2023]
Abstract
Multiple real-world studies have confirmed the safety and efficacy of hepatitis C (HCV) direct-acting antivirals (DAAs); however, few studies have provided data on long-term outcomes of patients without cirrhosis after achieving sustained virologic response (SVR).1-3 The aims of this analysis were to describe, among individuals in the PRIORITIZE Study achieving SVR: (1) the frequency of laboratory testing and imaging during long-term follow-up (LTFU), (2) changes in liver tests, (3) occurrence of hepatic decompensation or hepatocellular carcinoma (HCC) and deaths, and (4) durability of SVR.
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Affiliation(s)
- Anna S Lok
- Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, MI.
| | - Juhi Moon
- Johns Hopkins University School of Medicine, Baltimore, MD
| | | | - Mandana Khalili
- University of California San Francisco, Zuckerberg San Francisco General Hospital and Trauma Center, San Francisco, CA
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Liu CH, Peng CY, Liu CJ, Chen CY, Lo CC, Tseng KC, Su PY, Kao WY, Tsai MC, Tung HD, Cheng HT, Lee FJ, Huang CS, Huang KJ, Shih YL, Yang SS, Wu JH, Lai HC, Fang YJ, Chen PY, Hwang JJ, Tseng CW, Su WW, Chang CC, Lee PL, Chen JJ, Chang CY, Hsieh TY, Chang CH, Huang YJ, Kao JH. Sofosbuvir/velpatasvir/voxilaprevir for patients with chronic hepatitis C virus infection previously treated with NS5A direct-acting antivirals: a real-world multicenter cohort in Taiwan. Hepatol Int 2023; 17:291-302. [PMID: 36701081 DOI: 10.1007/s12072-022-10475-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2022] [Accepted: 12/24/2022] [Indexed: 01/27/2023]
Abstract
BACKGROUND Real-world data are scarce about the effectiveness and safety of sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) for retreating East Asian patients with hepatitis C virus (HCV) infection who previously received NS5A direct-acting antivirals (DAAs). We conducted a multicenter study to assess the performance of SOF/VEL/VOX in patients who were not responsive to prior NS5A inhibitors in Taiwan. METHODS Between September 2021 and May 2022, 107 patients who failed NS5A inhibitor-containing DAAs with SOF/VEL/VOX salvage therapy for 12 weeks were included at 16 academic centers. The sustained virologic response at off-treatment week 12 (SVR12) was assessed in the evaluable (EP) and per-protocol (PP) populations. The safety profiles were also reported. RESULTS All patients completed 12 weeks of treatment and achieved an end-of-treatment virologic response. The SVR12 rates were 97.2% (95% confidence interval (CI) 92.1-99.0%) and 100% (95% CI 96.4-100%) in EP and PP populations. Three (2.8%) patients were lost to off-treatment follow-up and did not meet SVR12 in the EP population. No baseline factors predicted SVR12. Two (1.9%) not-fatal serious adverse events (AE) occurred but were unrelated to SOF/VEL/VOX. Sixteen (15.0%) had grade 2 total bilirubin elevation, and three (2.8%) had grade 2 alanine transaminase (ALT) elevation. Thirteen (81.3%) of the 16 patients with grade 2 total bilirubin elevation had unconjugated hyperbilirubinemia. The estimated glomerular filtration rates (eGFR) were comparable between baseline and SVR12, regardless of baseline renal reserve. CONCLUSIONS SOF/VEL/VOX is highly efficacious and well-tolerated for East Asian HCV patients previously treated with NS5A inhibitor-containing DAAs. CLINICAL TRIALS REGISTRATION The study was not a drug trial. There was no need for clinical trial registration.
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Affiliation(s)
- Chen-Hua Liu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, Yunlin, Taiwan
| | - Cheng-Yuan Peng
- Department of Internal Medicine, Center for Digestive Medicine, China Medical University Hospital, Taichung, Taiwan
- School of Medicine, China Medical University, Taichung, Taiwan
| | - Chun-Jen Liu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine Hospital, Taipei, Taiwan
| | - Chi-Yi Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi, Taiwan
| | - Ching-Chu Lo
- Department of Internal Medicine, St. Martin De Porres Hospital, Daya, Chiayi, Taiwan
| | - Kuo-Chih Tseng
- Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
- School of Medicine, Tzuchi University, Hualien, Taiwan
| | - Pei-Yuan Su
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan
| | - Wei-Yu Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- TMU Research Center for Digestive Medicine, Taipei Medical University, Taipei, Taiwan
- Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan
| | - Ming-Chang Tsai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan
- School of Medicine, Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Hung-Da Tung
- Division of Gastroenterology and Hepatology, Chi-Mei Hospital, Liouying, Taiwan
| | - Hao-Tsai Cheng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, New Taipei Municipal TuCheng Hospital, New Taipei City, Taiwan
- Department of Gastroenterology and Hepatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan
| | - Fu-Jen Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Fu Jen Catholic University Hospital, New Taipei City, Taiwan
| | - Chia-Sheng Huang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Yang Ming Hospital, Chiayi, Taiwan
| | - Ke-Jhang Huang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Beigang Hospital, Yunlin, Taiwan
| | - Yu-Lueng Shih
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Sheng-Shun Yang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
- School of Medicine, Chung Shan Medical University, Taichung, Taiwan
- Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan
| | - Jo-Hsuan Wu
- Shiley Eye Institute and Viterbi Family Department of Ophthalmology, Hamilton Glaucoma Center, University of California, San Diego, CA, USA
| | - Hsueh-Chou Lai
- Department of Internal Medicine, Center for Digestive Medicine, China Medical University Hospital, Taichung, Taiwan
- School of Medicine, China Medical University, Taichung, Taiwan
| | - Yu-Jen Fang
- Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, Yunlin, Taiwan
| | - Po-Yueh Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi, Taiwan
| | - Jow-Jyh Hwang
- Department of Internal Medicine, St. Martin De Porres Hospital, Daya, Chiayi, Taiwan
| | - Chi-Wei Tseng
- Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
- School of Medicine, Tzuchi University, Hualien, Taiwan
| | - Wei-Wen Su
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan
| | - Chun-Chao Chang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- TMU Research Center for Digestive Medicine, Taipei Medical University, Taipei, Taiwan
| | - Pei-Lun Lee
- Division of Gastroenterology and Hepatology, Chi-Mei Hospital, Liouying, Taiwan
| | - Jyh-Jou Chen
- Division of Gastroenterology and Hepatology, Chi-Mei Hospital, Liouying, Taiwan
| | - Chi-Yang Chang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Fu Jen Catholic University Hospital, New Taipei City, Taiwan
| | - Tsai-Yuan Hsieh
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Chung-Hsin Chang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Yi-Jie Huang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Jia-Horng Kao
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine Hospital, Taipei, Taiwan.
- Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan.
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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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Nagao Y, Tsuji M. Onset of Oral Lichen Planus Led to Direct-Acting Antiviral Therapy in a Patient with Long-Term Hepatitis C: The Role of a Dentist as Gatekeeper. Case Rep Gastroenterol 2023; 17:26-33. [PMID: 36742093 PMCID: PMC9893994 DOI: 10.1159/000528681] [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: 10/09/2022] [Accepted: 12/08/2022] [Indexed: 01/10/2023] Open
Abstract
Oral lichen planus (OLP), a chronic inflammatory mucocutaneous disease, is an extrahepatic manifestation of a hepatitis C virus infection. In recent years, direct-acting antivirals (DAAs) have made great strides in the treatment of hepatitis C. However, there might be a lack of information about the treatment strategies available among those with this condition. Herein, we report a case of an 85-year-old female patient who was diagnosed with hepatitis C at the age of 55 but had not received antiviral treatment over the past 30 years. She underwent DAA treatment following a recommendation from her oral surgeon after the onset of OLP. The patient had declined interferon therapy in the past, owing to concerns about its side effects. She was unaware of the benefits of DAA treatment, probably due to communication difficulties caused by senile hearing loss. Consultation with an oral surgeon for an erosive form of OLP led her to receive antiviral therapy for hepatitis C. She achieved a sustained virologic response (SVR) following the DAA treatment, along with improvements in the signs and symptoms of OLP. Oral surgeons play an important role as gatekeepers in guiding untreated hepatitis patients toward appropriate treatment.
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Affiliation(s)
- Yumiko Nagao
- Department of Public Health, Graduate School of Medicine, Juntendo University, Tokyo, Japan,Tsuji Dental and Oral Surgery Clinic, Omuta, Japan
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Ma B, Shang T, Huang J, Tu Z, Wang Y, Han Y, Wang Y, Wen X, Jin Q. A rare case report of iatrogenic Cushing syndrome caused by direct anti-hepatitis C virus therapy with sofosbuvir/velpatasvir. Medicine (Baltimore) 2022; 101:e30294. [PMID: 36595855 PMCID: PMC9794295 DOI: 10.1097/md.0000000000030294] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
RATIONALE Sofosbuvir/velpatasvir (SOF/VEL) is a combination of direct-acting antivirals with pan-genotypic activity that is used to treat chronic hepatitis C virus infection. This was a fixed-dose regimen. SOF is a nucleotide nonstructural 5B polymerase inhibitor and VEL is an nonstructural 5A inhibitor. Side effects of this agent on the endocrine system, particularly iatrogenic Cushing syndrome (ICS), are uncommon. Here, we present a case of ICS with significantly low serum adrenocorticotropic hormone and cortisol levels caused by SOF/VEL. PATIENT CONCERNS A 49-year-old Asian woman with chronic hepatitis C and cirrhosis presented with a round face, fat thickening at the clavicle and back of the neck, mild facial edema, facial congestion, skin ulceration on the hands, central obesity, acne, and general status changes after 3 months of treatment with SOF/VEL (400 mg/dose, 1/day). DIAGNOSES The patient's serum adrenocorticotropic hormone and cortisol levels dropped significantly, and her normal rhythm vanished, with no visible aberrant lesions on computed tomography or across the abdomen. The patient was diagnosed with ICS. OUTCOMES Symptoms improved after withdrawing SOF/VEL and taking low-dose oral hydrocortisone. Thus, the SOF/VEL was suspected to be an offender. To our knowledge, this is the first time that SOF/VEL has been linked to ICS. LESSONS Hepatologists and primary care physicians treating hepatitis C virus should be more aware of this uncommon adverse event so that direct-acting antiviral therapy can be stopped sooner if it recurs. The findings of this study emphasize the importance of collaboration between hepatologists and endocrinologists in co-management of complications.
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Affiliation(s)
- Bo Ma
- Department of Hepatology, The First Hospital of Jilin University, Changchun, Jilin Province, China
| | - Tianling Shang
- Department of Neurology, The First Hospital of Jilin University, Changchun, Jilin Province, China
| | - Jianjie Huang
- Department of Hepatology, The First Hospital of Jilin University, Changchun, Jilin Province, China
| | - Zhixin Tu
- Department of Hepatology, The First Hospital of Jilin University, Changchun, Jilin Province, China
| | - Yan Wang
- Department of Hepatology, The First Hospital of Jilin University, Changchun, Jilin Province, China
| | - Yujin Han
- Department of Hepatology, The First Hospital of Jilin University, Changchun, Jilin Province, China
| | - Yang Wang
- Department of Hepatology, The First Hospital of Jilin University, Changchun, Jilin Province, China
| | - Xiaoyu Wen
- Department of Hepatology, The First Hospital of Jilin University, Changchun, Jilin Province, China
| | - Qinglong Jin
- Department of Hepatology, The First Hospital of Jilin University, Changchun, Jilin Province, China
- * Correspondence: Qinglong Jin, Department of Hepatology, The First Hospital of Jilin University, No. 1, Xinmin Street, Chaoyang District, Changchun, Jilin 130021, China (e-mail: )
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Yao X, Gao S, Wang J, Li Z, Huang J, Wang Y, Wang Z, Chen J, Fan X, Wang W, Jin X, Pan X, Yu Y, Lagrutta A, Yan N. Structural basis for the severe adverse interaction of sofosbuvir and amiodarone on L-type Ca v channels. Cell 2022; 185:4801-4810.e13. [PMID: 36417914 PMCID: PMC9891081 DOI: 10.1016/j.cell.2022.10.024] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2022] [Revised: 08/24/2022] [Accepted: 10/26/2022] [Indexed: 11/23/2022]
Abstract
Drug-drug interaction of the antiviral sofosbuvir and the antiarrhythmics amiodarone has been reported to cause fatal heartbeat slowing. Sofosbuvir and its analog, MNI-1, were reported to potentiate the inhibition of cardiomyocyte calcium handling by amiodarone, which functions as a multi-channel antagonist, and implicate its inhibitory effect on L-type Cav channels, but the molecular mechanism has remained unclear. Here we present systematic cryo-EM structural analysis of Cav1.1 and Cav1.3 treated with amiodarone or sofosbuvir alone, or sofosbuvir/MNI-1 combined with amiodarone. Whereas amiodarone alone occupies the dihydropyridine binding site, sofosbuvir is not found in the channel when applied on its own. In the presence of amiodarone, sofosbuvir/MNI-1 is anchored in the central cavity of the pore domain through specific interaction with amiodarone and directly obstructs the ion permeation path. Our study reveals the molecular basis for the physical, pharmacodynamic interaction of two drugs on the scaffold of Cav channels.
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Affiliation(s)
- Xia Yao
- Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA,These authors contribute equally
| | - Shuai Gao
- Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA,These authors contribute equally.,Present address: School of Pharmaceutical Sciences, TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan 430071, China,To whom correspondence should be addressed: N. Yan (); S. Gao ()
| | - Jixin Wang
- Department of Genetic and Cellular Toxicology, ADME & Discovery Toxicology, Preclinical Development, Merck Research Laboratories, Merck & Co., Inc., West Point, PA 19486, USA,These authors contribute equally
| | - Zhangqiang Li
- State Key Laboratory of Membrane Biology, Beijing Advanced Innovation Center for Structural Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China,These authors contribute equally
| | - Jian Huang
- Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA
| | - Yan Wang
- Department of Biological Sciences, St. John’s University, Queens, NY 11439, USA
| | - Zhifei Wang
- Department of Biological Sciences, St. John’s University, Queens, NY 11439, USA
| | - Jiaofeng Chen
- State Key Laboratory of Membrane Biology, Beijing Advanced Innovation Center for Structural Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China
| | - Xiao Fan
- Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA
| | - Weipeng Wang
- State Key Laboratory of Membrane Biology, Beijing Advanced Innovation Center for Structural Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China
| | - Xueqin Jin
- State Key Laboratory of Membrane Biology, Beijing Advanced Innovation Center for Structural Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China
| | - Xiaojing Pan
- State Key Laboratory of Membrane Biology, Beijing Advanced Innovation Center for Structural Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China
| | - Yong Yu
- Department of Biological Sciences, St. John’s University, Queens, NY 11439, USA
| | - Armando Lagrutta
- Department of Genetic and Cellular Toxicology, ADME & Discovery Toxicology, Preclinical Development, Merck Research Laboratories, Merck & Co., Inc., West Point, PA 19486, USA
| | - Nieng Yan
- Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA,Lead contact.,To whom correspondence should be addressed: N. Yan (); S. Gao ()
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Feld JJ, Forns X, Dylla DE, Kumada H, de Ledinghen V, Wei L, Brown RS, Flisiak R, Lampertico P, Thabut D, Bondin M, Tatsch F, Burroughs M, Marcinak J, Zhang Z, Emmett A, Jacobson IM. Safety analysis of glecaprevir/pibrentasvir in patients with markers of advanced liver disease in clinical and real-world cohorts. J Viral Hepat 2022; 29:1050-1061. [PMID: 36036117 PMCID: PMC9827821 DOI: 10.1111/jvh.13738] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Revised: 04/28/2022] [Accepted: 07/06/2022] [Indexed: 01/18/2023]
Abstract
Chronic hepatitis C virus (HCV) infection has the greatest health impact in patients with advanced liver disease. The direct-acting antiviral (DAA) regimen glecaprevir/pibrentasvir (G/P) is approved for treatment of HCV-infected patients without cirrhosis and with compensated cirrhosis. However, events of liver decompensation/failure have been reported in patients treated with protease-inhibitor-containing DAA regimens, often in patients with advanced liver disease. This study examines the safety of on-label G/P treatment in patients with compensated cirrhosis (F4 at baseline) with markers of advanced liver disease. Patients with cirrhosis were categorized into 4 subgroups, based on different noninvasive markers of advanced liver disease identified using laboratory measures: platelet count < or ≥ 100 × 109 /L, and Child-Pugh score 5 or 6. Separate analyses were performed using pooled data from clinical trials and from real-world post-marketing observational studies. G/P was well tolerated in patients with platelet count ≥100 × 109 /L (n = 800), platelet count <100 × 109 /L (n = 215), a Child-Pugh score of 5 (n = 915) and a Child-Pugh score of 6 (n = 95). In the clinical trial and real-world cohorts two patients and no patients experienced a serious adverse event (AE) possibly related to study drug, respectively; three patients and no patients experienced an AE of special interest for hepatic decompensation and hepatic failure. This analysis reaffirms G/P's safety profile in indicated patients with compensated cirrhosis, including those with markers of more advanced liver disease. Increasing the number of patients treated with short-duration G/P therapy may contribute to meeting HCV elimination targets.
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Affiliation(s)
- Jordan J. Feld
- Toronto Centre for Liver DiseaseUniversity Health Network, University of TorontoTorontoOntarioCanada
| | - Xavier Forns
- Liver Unit, Hospital ClinicUniversity of Barcelona, IDIBAPS and CIBEREHDBarcelonaSpain
| | | | | | | | - Lai Wei
- Peking University People's HospitalPeking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver DiseaseBeijingChina,Beijing Tsinghua Changgung HospitalTsinghua UniversityBeijingChina
| | - Robert S. Brown
- Center for Liver Disease and TransplantationWeill Cornell Medical CollegeNew YorkNew YorkUSA
| | - Robert Flisiak
- Department of Infectious Diseases and HepatologyMedical University of Białystok, BiałystokBialystokPoland
| | - Pietro Lampertico
- Division of Gastroenterology and HepatologyFoundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, CRC “A. M. and A. Migliavacca” Center for Liver DiseaseMilanItaly,Department of Pathophysiology and TransplantationUniversity of MilanMilanItaly
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Muacevic A, Adler JR. Direct-Acting Antiviral Treatment in Albanian Patients With Chronic Hepatitis C and Advanced Liver Fibrosis. Cureus 2022; 14:e32646. [PMID: 36540321 PMCID: PMC9759809 DOI: 10.7759/cureus.32646] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/16/2022] [Indexed: 12/23/2022] Open
Abstract
Background Treating chronic hepatitis C (CHC) with direct-acting antiviral (DAA) is very effective at clearing the infection. In Albania treatment with DAA is limited to patients with liver stiffness F3-F4, and with other co-infections. The objective of this study was to evaluate the efficacy of DAA in Albanian patients with genotypes 1-5, who mostly suffer from advanced liver fibrosis. Material and Methods This is a retrospective study carried out at the University Hospital Center "Mother Teresa", Tirana, during 2014-2019, including treatment-naïve and treatment-experienced patients with genotypes 1-5. All patients were evaluated with elastography and most of them were F3-F4. The primary endpoint involved the patients achieving SVR-12, or undetectable hepatitis C virus/ribonucleic acid (HCV RNA) 12 weeks after the end of treatment. In patients without a genotype, we have used a pangenotypic regimen. Results This study included 207 patients with a mean age of 48.9 ± 13.1 years, 56% male and 44% female; 152 (73%) were genotype 1, 24 were (11.5%) genotype 2, nine were (4.3%) genotype 3, 14 were (6.7%) genotype 4, one was (0.4%) genotype 5, and seven (3.8%) unassigned genotypes. The sustained virologic response (SVR) percentage according to genotype is discussed in the article. The overall SVR score of all the patients in our study was >93%. According to elastography, 127 (66%) were F3-F4, and 80 (38.6%) were F1-F2. Conclusion Treatment with DAA proved to be very effective in our patients; most of them had advanced liver fibrosis as well as compensated or decompensated liver cirrhosis. The overall SVR score of the patients in our study was >93%. Our country needs to treat all patients with chronic hepatitis C without limitations to attain the WHO objective of eradicating this disease by 2030.
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Abstract
In 2019, more than 4 years after the widespread availability of safe, oral, curative treatments, an estimated 58 million people were living with hepatitis C virus infections (PLWHC). Additional tools may enable those not yet reached to be treated. One such tool could be long-acting parenteral formulations of HCV treatments, which may allow PLWHC to be diagnosed and cured in a single encounter. Although existing highly effective oral medications might be formulated as long-acting parenteral treatments, pharmacological, regulatory, patent, and medical challenges have to be overcome; this requires the concerted efforts of PLWHC, researchers, funding agencies, industry, the World Health Organization, and other stakeholders.
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Affiliation(s)
- David L Thomas
- Department of Medicine, Division of Infectious Diseases, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Andrew Owen
- Department of Pharmacology and Therapeutics, Centre of Excellence for Long-acting Therapeutics (CELT), University of Liverpool, Liverpool, United Kingdom
| | - Jennifer J Kiser
- Department of Pharmaceutical Sciences, University of Colorado, Aurora, Colorado, USA
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Wedemeyer H, Di Marco V, Garcia-Retortillo M, Teti E, Fraser C, Morano Amado LE, Rodriguez-Tajes S, Acosta-López S, O’Loan J, Milella M, Buti M, Guerra-Veloz MF, Ramji A, Fenech M, Martins A, Borgia SM, Vanstraelen K, Mertens M, Hernández C, Ntalla I, Ramroth H, Milligan S. Global Real-World Evidence of Sofosbuvir/Velpatasvir as a Highly Effective Treatment and Elimination Tool in People with Hepatitis C Infection Experiencing Mental Health Disorders. Viruses 2022; 14:v14112493. [PMID: 36423102 PMCID: PMC9695390 DOI: 10.3390/v14112493] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Revised: 10/28/2022] [Accepted: 11/02/2022] [Indexed: 11/16/2022] Open
Abstract
Hepatitis C virus (HCV) is prevalent in people with mental health disorders, a priority population to diagnose and cure in order to achieve HCV elimination. This integrated analysis pooled data from 20 cohorts in seven countries to evaluate the real-world effectiveness of the pangenotypic direct-acting antiviral (DAA) sofosbuvir/velpatasvir (SOF/VEL) in people with mental health disorders. HCV-infected patients diagnosed with mental health disorders who were treated with SOF/VEL for 12 weeks without ribavirin as part of routine clinical practice were included. The primary outcome was sustained virological response (SVR) in the effectiveness population (EP), defined as patients with an available SVR assessment. Secondary outcomes were reasons for not achieving SVR, characteristics of patients with non-virological failures, adherence, and time from HCV RNA diagnosis to SOF/VEL treatment initiation. A total of 1209 patients were included; 142 did not achieve an SVR for non-virological reasons (n = 112; 83 lost to follow-up, 20 early treatment discontinuations) or unknown reasons (n = 30). Of the 1067 patients in the EP, 97.4% achieved SVR. SVR rates in the EP were ≥95% when stratified by type of mental health disorder and other complicating baseline characteristics, including active injection drug use and antipsychotic drug use. Of 461 patients with data available in the EP, only 2% had an adherence level < 90% and 1% had an adherence level < 80%; all achieved SVR. Patients with mental health disorders can be cured of HCV using a well-tolerated, pangenotypic, protease inhibitor-free SOF/VEL regimen. This DAA allows the implementation of a simple treatment algorithm, with minimal monitoring requirements and fewer interactions with central nervous system drugs compared with protease-inhibitor DAA regimens.
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Affiliation(s)
- Heiner Wedemeyer
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, OE6810, Carl-Neuberg-Str. 1, 30625 Hannover, Germany
- Correspondence: ; Tel.: +49-511-532-3305
| | - Vito Di Marco
- University of Palermo, Piazza Marina, 61, 90133 Palermo, Italy
| | - Montserrat Garcia-Retortillo
- Liver Section, Gastroenterology Department, Hospital del Mar-Parc de Salut Mar, Hospital del Mar Medical Research Institute (IMIM), C/ del Dr. Aiguader, 88, 08003 Barcelona, Spain
| | | | - Chris Fraser
- Cool Aid Community Health Centre, 713 Johnson St, Victoria, BC V8W 1M8, Canada
| | - Luis Enrique Morano Amado
- Unit of Infectious Diseases, Álvaro Cunqueiro University Hospital, Estrada de Clara Campoamor, 341, 36312 Vigo, Spain
| | - Sergio Rodriguez-Tajes
- Liver Unit, Hospital Clinic Barcelona, IDIBAPS, CIBERehd, C. de Villarroel, 170, 08036 Barcelona, Spain
| | - Silvia Acosta-López
- Digestive Diseases, Hospital Nuestra Señora de Candelaria, Ctra. Gral. del Rosario, 145, 38010 Tenerife, Spain
| | - Joss O’Loan
- Medeco Inala & Kombi Clinic, 55b/156 Inala Ave, Brisbane, QLD 4077, Australia
- School of Medicine, University of Queensland, St Lucia, Brisbane, QLD 4072, Australia
| | - Michele Milella
- Clinic of Infectious Diseases, University of Bari, Piazza Umberto I, 1, 70121 Bari, Italy
| | - Maria Buti
- Liver Unit, Vall d’Hebron University Hospital, and CIBEREHD del Instituto Carlos III, Barcelona, Spain
| | - María Fernanda Guerra-Veloz
- Virgen Macarena University Hospital, Av. Dr. Fedriani, 3, 41003 Seville, Spain
- Clinical Research Fellow in Hepatology at King’s College Hospital, Denmark Hill, London SE5 9RS, UK
| | - Alnoor Ramji
- University of British Columbia, Vancouver, BC V6T 1Z4, Canada
| | - Mary Fenech
- Queensland Injectors Health Network (QuIHN), Treatment and Management Programme, 1 Hamilton Pl, Bowen Hills, Brisbane, QLD 4006, Australia
| | - Alexandra Martins
- Hospital Prof. Dr. Fernando Fonseca, IC19, 2720-276 Amadora, Portugal
| | - Sergio M. Borgia
- Infectious Diseases, William Osler Health System, 2100 Bovaird Dr E, Brampton, ON L6R 3J7, Canada
| | - Kim Vanstraelen
- Gilead Sciences Europe Ltd., Stockley Park, 2 Roundwood Ave, Hayes, Uxbridge UB11 1AS, UK
| | - Michael Mertens
- Gilead Sciences Europe Ltd., Stockley Park, 2 Roundwood Ave, Hayes, Uxbridge UB11 1AS, UK
| | - Cándido Hernández
- Gilead Sciences Europe Ltd., Stockley Park, 2 Roundwood Ave, Hayes, Uxbridge UB11 1AS, UK
| | - Ioanna Ntalla
- Gilead Sciences Europe Ltd., Stockley Park, 2 Roundwood Ave, Hayes, Uxbridge UB11 1AS, UK
| | - Heribert Ramroth
- Gilead Sciences Europe Ltd., Stockley Park, 2 Roundwood Ave, Hayes, Uxbridge UB11 1AS, UK
| | - Scott Milligan
- Trio Health Analytics, 1025 Cannon Street, Suite 2C, Louisville, CO 80027, USA
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Su P, Chang T, Tung S, Wei K, Shen C, Hsieh Y, Chen W, Chen Y, Chen C, Yen C, Xu H, Tung W, Chang K. Changes in renal function in patients with chronic hepatitis C treated with sofosbuvir‐velpatasvir. ADVANCES IN DIGESTIVE MEDICINE 2022. [DOI: 10.1002/aid2.13336] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Affiliation(s)
- Pei‐Kai Su
- Division of Hepatology and Gastroenterology, Department of Internal Medicine Chang Gung Memorial Hospital Chiayi Taiwan
| | - Te‐Sheng Chang
- Division of Hepatology and Gastroenterology, Department of Internal Medicine Chang Gung Memorial Hospital Chiayi Taiwan
- College of Medicine, Chang Gung University Taoyuan Taiwan
| | - Shui‐Yi Tung
- Division of Hepatology and Gastroenterology, Department of Internal Medicine Chang Gung Memorial Hospital Chiayi Taiwan
- College of Medicine, Chang Gung University Taoyuan Taiwan
| | - Kuo‐Liang Wei
- Division of Hepatology and Gastroenterology, Department of Internal Medicine Chang Gung Memorial Hospital Chiayi Taiwan
- College of Medicine, Chang Gung University Taoyuan Taiwan
| | - Chien‐Heng Shen
- Division of Hepatology and Gastroenterology, Department of Internal Medicine Chang Gung Memorial Hospital Chiayi Taiwan
| | - Yung‐Yu Hsieh
- Division of Hepatology and Gastroenterology, Department of Internal Medicine Chang Gung Memorial Hospital Chiayi Taiwan
- College of Medicine, Chang Gung University Taoyuan Taiwan
| | - Wei‐Ming Chen
- Division of Hepatology and Gastroenterology, Department of Internal Medicine Chang Gung Memorial Hospital Chiayi Taiwan
| | - Yi‐Hsing Chen
- Division of Hepatology and Gastroenterology, Department of Internal Medicine Chang Gung Memorial Hospital Chiayi Taiwan
| | - Chun‐Hsien Chen
- Division of Hepatology and Gastroenterology, Department of Internal Medicine Chang Gung Memorial Hospital Chiayi Taiwan
| | - Chih‐Wei Yen
- Division of Hepatology and Gastroenterology, Department of Internal Medicine Chang Gung Memorial Hospital Chiayi Taiwan
| | - Huang‐Wei Xu
- Division of Hepatology and Gastroenterology, Department of Internal Medicine Chang Gung Memorial Hospital Chiayi Taiwan
| | - Wei‐Ling Tung
- Division of Hepatology and Gastroenterology, Department of Internal Medicine Chang Gung Memorial Hospital Chiayi Taiwan
| | - Kao‐Chi Chang
- Division of Hepatology and Gastroenterology, Department of Internal Medicine Chang Gung Memorial Hospital Chiayi Taiwan
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Rosati S, Wong A, Marco VD, Pérez-Hernandez P, Macedo G, Brixko C, Ranieri R, Campanale F, Basciá A, Fernández-Rodríguez C, Lédinghen VD, Maida I, Teti E, Mangia A, Vanstraelen K, Hernández C, Mertens M, Ntalla I, Ramroth H, Jiménez E. Real-world Effectiveness of sofosbuvir/velpatasvir for the Treatment of Hepatitis C Virus in Prison Settings. Future Virol 2022; 17:419-428. [DOI: 10.2217/fvl-2022-0016] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Accepted: 03/30/2022] [Indexed: 02/06/2023]
Affiliation(s)
| | | | | | | | | | | | - Roberto Ranieri
- Penitentiary Health Service
San Paolo University Hospital
Milan
Italy
| | | | - Annalisa Basciá
- Polyclinic “Cittadella della Salute” ASL Lecce & Infectious Disease Consultant of San Borgo San Nicola Detention Center
Lecce
Italy
| | | | - Victor de Lédinghen
- Hepatology Unit
CHU Bordeaux
& INSERM U1053
Bordeaux University
Bordeaux
France
| | | | | | | | | | | | | | | | | | - Elena Jiménez
- University Hospital of Gran Canaria
Las Palmas
Spain
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46
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Tasavon Gholamhoseini M, Sharafi H, Hl Borba H, Alavian SM, Sabermahani A, Hajarizadeh B. Economic evaluation of pan-genotypic generic direct-acting antiviral regimens for treatment of chronic hepatitis C in Iran: a cost-effectiveness study. BMJ Open 2022; 12:e058757. [PMID: 35676019 PMCID: PMC9185662 DOI: 10.1136/bmjopen-2021-058757] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
INTRODUCTION Low-cost generic direct-acting antiviral (DAA) regimens for treatment of hepatitis C virus (HCV) are available in several low-income/middle-income countries, important for treatment scale-up. This study evaluated the cost-effectiveness of genotype-dependent and pan-genotypic DAA regimens in Iran as an example of a resource-limited setting. METHODS A Markov model was developed to simulate HCV natural history. A decision tree was developed for HCV treatment, assuming four scenarios, including scenario 1: genotyping, sofosbuvir/ledipasvir (SOF/LDV) for genotype 1, and sofosbuvir/daclatasvir (SOF/DCV) for genotype 3; scenario 2: genotyping, SOF/LDV for genotype 1, and sofosbuvir/velpatasvir (SOF/VEL) for genotype 3; scenario 3: no genotyping and SOF/DCV for all; and scenario 4: no genotyping and SOF/VEL for all. A 1-year cycle length was used to calculate the cumulative cost and effectiveness over a lifetime time horizon. We calculated quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER) using a health system perspective. Costs were converted to US dollars using purchasing power parity exchange rate ($PPP). All costs and outcomes were discounted at an annual rate of 3%. RESULTS Among people with no cirrhosis, scenario 3 had the minimum cost, compared with which scenario 4 was cost-effective with an ICER of 4583 $PPP per QALY (willingness-to-pay threshold: 9,311 $PPP per QALY). Among both people with compensated or decompensated cirrhosis, scenario 4 was cost saving. In sensitivity analysis, scenario 4 would be also cost-saving among people with no cirrhosis provided a 39% reduction in the cost of 12 weeks SOF/VEL. CONCLUSION Initiating all patients on pan-genotypic generic DAA regimens with no pretreatment genotyping was cost-effective compared with scenarios requiring pretreatment HCV genotype tests. Among generic pan-genotypic DAA regimens, SOF/VEL was cost-effective, for people with no cirrhosis and cost-saving for those with cirrhosis.
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Affiliation(s)
- Mohammad Tasavon Gholamhoseini
- Health Services Management Research Center, Institute for Futures Studies in Health, Kerman University of Medical Sciences, Kerman, Iran
| | | | - Helena Hl Borba
- Department of Pharmacy, Federal University of Parana, Curitiba, Parana, Brazil
| | | | - Asma Sabermahani
- Department of Management, Health Policy and Health Economics, Kerman University of Medical Sciences, Kerman, Iran
| | - Behzad Hajarizadeh
- The Kirby Institute, University of New South Wales (UNSW Sydney), Sydney, New South Wales, Australia
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47
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Kateera F, Shumbusho F, Manirambona L, Kabihizi J, Murangwa A, Serumondo J, Makuza JD, Nsanzimana S, Muvunyi CM, Kabakambira JD, Sylvain H, Camus G, Grant PM, Gupta N. Safety and efficacy of sofosbuvir-velpatasvir to treat chronic hepatitis C virus infection in treatment-naive patients in Rwanda (SHARED-3): a single-arm trial. Lancet Gastroenterol Hepatol 2022; 7:533-541. [DOI: 10.1016/s2468-1253(21)00398-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Revised: 10/25/2021] [Accepted: 10/26/2021] [Indexed: 02/07/2023]
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48
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Cooper MP, Foley H, Damico D, Wright M, Rhudy C, Schadler A, Platt T. Impact of the COVID-19 pandemic on hepatitis C outcomes at a health-system specialty pharmacy. J Manag Care Spec Pharm 2022; 28:667-672. [PMID: 35621721 PMCID: PMC10372976 DOI: 10.18553/jmcp.2022.28.6.667] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
BACKGROUND: The goal of hepatitis C virus (HCV) treatment is to cure the patient of the infection, defined as a nondetectable HCV RNA at least 12 weeks after treatment completion, or sustained virologic response (SVR). The COVID-19 pandemic has presented new barriers to care in the treatment of patients with HCV that resulted in a transition to tele-health services at many health systems to overcome these barriers. OBJECTIVE: To assess the real-world impact of the COVID-19 pandemic and the subsequent shift to a telehealth model on collection of SVR data and other HCV treatment outcomes in a health-system setting. METHODS: Subjects who received a referral for an HCV direct-acting antiviral agent between January 1, 2018, and November 30, 2020, and were aged 18 years or older at time of enrollment were placed in either "pre-COVID-19" or "COVID-19" cohorts based on enrollment date. The primary endpoint of this study evaluated confirmed SVR to treatment determined by the absence of HCV RNA by polymerase chain reaction testing at least 12 weeks after completion of drug therapy. Secondary endpoints evaluated completion of medication therapy and adherence to laboratory appointments. RESULTS: 1,504 patients met study inclusion criteria (pre-COVID-19 cohort, n = 1,230; COVID-19 cohort, n = 274). The COVID-19 cohort demonstrated significantly lower therapy completion rates (P = 0.001), were less likely to obtain SVR laboratory tests (P < 0.001), and had a significantly lower confirmed SVR rate (P < 0.001) compared with the pre-COVID-19 cohort. In a subset of patients who completed therapy and had SVR laboratory tests collected, there were no significant differences observed in the rate of patients who achieved SVR (P = 0.959). CONCLUSIONS: During the COVID-19 pandemic, patients with HCV were significantly less likely to complete therapy or participate in SVR laboratory work. Further studies are needed to determine if offering a telehealth option for our patients in a post-COVID-19 environment would offer any additional advantage in increasing access to care for patients with HCV. DISCLOSURES: No outside funding supported this study. Dr Cooper is an employee of the University of Kentucky whose position was partially funded by Gilead Sciences, Inc.
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Affiliation(s)
| | - Heather Foley
- UK HealthCare Specialty Pharmacy and Infusion Services, Lexington, KY
| | - David Damico
- UK HealthCare Specialty Pharmacy and Infusion Services, Lexington, KY
| | - Maribeth Wright
- UK HealthCare Specialty Pharmacy and Infusion Services, Lexington, KY
| | - Christian Rhudy
- UK HealthCare Specialty Pharmacy and Infusion Services, Lexington, KY
| | | | - Thom Platt
- UK HealthCare Specialty Pharmacy and Infusion Services, Lexington, KY
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49
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Solomon SS, Wagner-Cardoso S, Smeaton L, Sowah LA, Wimbish C, Robbins G, Brates I, Scello C, Son A, Avihingsanon A, Linas B, Anthony D, Nunes EP, Kliemann DA, Supparatpinyo K, Kityo C, Tebas P, Bennet JA, Santana-Bagur J, Benson CA, Van Schalkwyk M, Cheinquer N, Naggie S, Wyles D, Sulkowski M. A minimal monitoring approach for the treatment of hepatitis C virus infection (ACTG A5360 [MINMON]): a phase 4, open-label, single-arm trial. Lancet Gastroenterol Hepatol 2022; 7:307-317. [PMID: 35026142 PMCID: PMC8920770 DOI: 10.1016/s2468-1253(21)00397-6] [Citation(s) in RCA: 49] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Revised: 10/24/2021] [Accepted: 10/25/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND Despite widespread availability of direct-acting antivirals including generic formulations, limited progress has been made in the global adoption of hepatitis C virus (HCV) treatment. Barriers to treatment scale-up include availability and access to diagnostic and monitoring tests, health-care infrastructure, and requirement for frequent visits during treatment. METHODS ACTG A5360 was a phase 4, open-label, single-arm trial across 38 sites in Brazil, South Africa, Thailand, Uganda, and the USA. Key inclusion criteria were age of 18 years or older, evidence of active HCV infection (HCV RNA >1000 IU/mL) and HCV treatment-naive; patients with compensated cirrhosis and HIV/HCV co-infection were included but their enrolment was capped. All participants received a fixed dose combination of oral sofosbuvir (400 mg) and velpatasvir (100 mg) once daily for 12 weeks. The minimal monitoring (MINMON) approach consisted of four components: (1) there was no pre-treatment genotyping; (2) the entire treatment course (84 tablets) was dispensed at entry; (3) there were no scheduled visits or laboratory monitoring; and (4) there were two points of remote contact, at week 4 for adherence and week 22, to schedule outcome assessment at week 24 (-2 weeks to +4 weeks). Participants who missed the week 24 window could return for a visit to assess treatment response any time before week 72. Unplanned visits for any reason were permissible before the week 24 visit. The primary efficacy outcome was sustained virological response (SVR), defined as HCV RNA less than the lower limit of quantification measured at least 22 weeks post-treatment initiation; the primary safety outcome was serious adverse events. The primary efficacy analysis included all participants who initiated treatment, using a missing=failure approach. The primary safety analysis included all participants who initiated treatment and had at least one post-treatment assessment. This trial is registered at ClinicalTrials.gov, NCT03512210. FINDINGS Between Oct 22, 2018, and July 19, 2019, 400 participants were enrolled across all 38 sites; 399 initiated treatment. At the SVR assessment visit, 355 (89%) of 397 participants reported taking 100% of the trial medication during the 12-week treatment period; two patients did not have any follow-up visits after the entry visit and were excluded from the safety analyses. Overall, 379 of the 399 who initiated treatment had an SVR (95·0%, 95% CI 92·4-96·7). 14 (4%) of 397 participants reported serious adverse events between treatment initiation and week 28; none were treatment related or led to treatment discontinuation or death. 15 (4%) of 399 participants had unplanned visits; none were related to treatment. INTERPRETATION In this diverse global population of people with HCV, the MINMON approach with sofosbuvir-velpatasvir treatment was safe and achieved SVR comparable to standard monitoring observed in real-world data. Coupled with innovative case finding strategies, this strategy could be crucial to the global HCV elimination agenda. FUNDING US National Institutes of Health and Gilead Sciences.
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Affiliation(s)
- Sunil S Solomon
- Johns Hopkins University School of Medicine, Baltimore, MD, USA.
| | | | - Laura Smeaton
- Harvard T H Chan School of Public Health, Boston, MA, USA
| | | | | | | | - Irena Brates
- Harvard T H Chan School of Public Health, Boston, MA, USA
| | - Christine Scello
- Frontier Science & Technology Research Foundation, Inc, Amherst, NY, USA
| | - Annie Son
- Gilead Sciences, Foster City, CA, USA
| | - Anchalee Avihingsanon
- HIV-NAT, Thai Red Cross AIDS Research Centre and TB RU, Chulalongkorn University, Bangkok, Thailand
| | | | | | | | | | | | - Cissy Kityo
- Joint Clinical Research Centre, Kampala, Uganda
| | - Pablo Tebas
- Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Jaclyn Ann Bennet
- Clinical HIV Research Unit, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa
| | | | - Constance A Benson
- Department of Medicine, University of California San Diego, San Diego, CA, USA
| | - Marije Van Schalkwyk
- Family Centre for Research with Ubuntu, Stellenbosch University, Cape Town, South Africa
| | | | | | - David Wyles
- Department of Medicine, University of Colorado School of Medicine, Aurora, CO, USA
| | - Mark Sulkowski
- Johns Hopkins University School of Medicine, Baltimore, MD, USA
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50
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Yee J, Carson JM, Hajarizadeh B, Hanson J, O'Beirne J, Iser D, Read P, Balcomb A, Doyle JS, Davies J, Martinello M, Marks P, Dore GJ, Matthews GV. High Effectiveness of Broad Access Direct-Acting Antiviral Therapy for Hepatitis C in an Australian Real-World Cohort: The REACH-C Study. Hepatol Commun 2022; 6:496-512. [PMID: 34729957 PMCID: PMC8870316 DOI: 10.1002/hep4.1826] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Revised: 07/29/2021] [Accepted: 08/24/2021] [Indexed: 12/15/2022] Open
Abstract
Australia was one of the first countries with unrestricted access to government subsidized direct-acting antiviral (DAA) therapy for adults with chronic hepatitis C virus. This study assessed real-world DAA treatment outcomes across a diverse range of Australian clinical services and evaluated factors associated with successful treatment and loss to follow-up. Real-world Effectiveness of Antiviral therapy in Chronic Hepatitis C (REACH-C) consisted a national observational cohort of 96 clinical services including specialist clinics and less traditional settings such as general practice. Data were obtained on consecutive individuals who commenced DAAs from March 2016 to June 2019. Effectiveness was assessed by sustained virological response ≥12 weeks following treatment (SVR) using intention-to-treat (ITT) and per-protocol (PP) analyses. Within REACH-C, 10,843 individuals initiated DAAs (male 69%; ≥50 years 52%; cirrhosis 22%). SVR data were available in 85% (9,174 of 10,843). SVR was 81% (8,750 of 10,843) by ITT and 95% (8,750 of 9,174) by PP. High SVR (≥92%) was observed across all service types and participant characteristics. Male gender (adjusted odds ratio [aOR] 0.56, 95% confidence interval [CI] 0.43-0.72), cirrhosis (aOR 0.52, 95% CI 0.41-0.64), recent injecting drug use (IDU; aOR 0.64, 95% CI 0.46-0.91) and previous DAA treatment (aOR 0.50, 95% CI 0.28-0.90) decreased the likelihood of achieving SVR. Multiple factors modified the likelihood of loss to follow-up including IDU ± opioid agonist therapy (OAT; IDU only: aOR 1.75, 95% CI 1.44-2.11; IDU + OAT: aOR 1.39, 95% CI 1.11-1.74; OAT only, aOR 1.36; 95% CI 1.13-1.68) and age (aOR 0.97, 95% CI 0.97-0.98). Conclusion: Treatment response was high in a diverse population and through a broad range of services following universal access to DAA therapy. Loss to follow-up presents a real-world challenge. Younger people who inject drugs were more likely to disengage from care, requiring innovative strategies to retain them in follow-up.
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Affiliation(s)
- Jasmine Yee
- The Kirby InstituteUNSW AustraliaSydneyNSWAustralia
| | | | | | - Joshua Hanson
- The Kirby InstituteUNSW AustraliaSydneyNSWAustralia.,Cairns HospitalCairnsQLDAustralia
| | - James O'Beirne
- Sunshine Coast University HospitalSunshine CoastQLDAustralia
| | - David Iser
- Scope GastroenterologyMelbourneVICAustralia
| | | | | | - Joseph S Doyle
- Burnet InstituteMelbourneVICAustralia.,The Alfred and Monash UniversityDepartment of Infectious DiseasesMelbourneVICAustralia
| | - Jane Davies
- Royal Darwin HospitalDarwinAustralia.,Menzies School of Health ResearchDarwinAustralia
| | - Marianne Martinello
- The Kirby InstituteUNSW AustraliaSydneyNSWAustralia.,Blacktown Mount Druitt HospitalBlacktownNSWAustralia.,St Vincent's HospitalSydneyNSWAustralia
| | | | - Gregory J Dore
- The Kirby InstituteUNSW AustraliaSydneyNSWAustralia.,St Vincent's HospitalSydneyNSWAustralia
| | - Gail V Matthews
- The Kirby InstituteUNSW AustraliaSydneyNSWAustralia.,St Vincent's HospitalSydneyNSWAustralia
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