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Marsh TL, Johnston JM, Homan C, Townshend-Bulson LJ, Kim NJ, VoPham T, Li X, He Q, McMahon BJ, Ioannou GN, Feng Z. HCC surveillance in hepatitis C: A longitudinal algorithm improves alpha-fetoprotein screening. Hepatol Commun 2025; 9:e0719. [PMID: 40408282 PMCID: PMC12106215 DOI: 10.1097/hc9.0000000000000719] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2025] [Accepted: 03/26/2025] [Indexed: 05/25/2025] Open
Abstract
BACKGROUND Surveillance for HCC remains important after hepatitis C cure. Improved sensitivity of screening with alpha-fetoprotein (AFP) by using a parametric empirical Bayes (PEB) algorithm, which incorporates an individual patient's longitudinal AFP measurements, was previously demonstrated in a retrospective analysis of clinical trial data prior to widespread hepatitis C cure. METHODS We analyzed de-identified data extracted from the medical records of participants in the Alaska Hepatitis C Study, which aims to enroll all Alaska Native persons living in Alaska with a history of hepatitis C.We compared the performance characteristics of AFP as a screening test using the PEB method versus a fixed cutoff (FC) method in an observational setting, separately for HCC surveillance in active and cured hepatitis C. RESULTS The PEB and FC methods were applied to AFP levels from participants with F3/F4 fibrosis who had active hepatitis C (173 no HCC, 14 HCC) or after they achieved hepatitis C cure (162 no HCC, 12 HCC). Compared to a fixed 20 ng/mL cutoff, demonstrating 91.2% specificity in active hepatitis C, PEB increased sensitivity from 64.3% to 71.4%. After cure, a fixed 7.2 ng/mL cutoff demonstrated 91.2% specificity, and PEB increased sensitivity from 58.3% to 91.7%. CONCLUSIONS The PEB algorithm can increase sensitivity and lead to earlier detection of HCC among patients with F3/F4 fibrosis, both in active and even more so in cured hepatitis C. Lower AFP levels after cure indicate that for either PEB or FC methods, screening parameters, such as cutoffs for a target specificity, should be specified separately by hepatitis C treatment status for HCC surveillance.
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Affiliation(s)
- Tracey L. Marsh
- Biostatistics Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
| | - Janet M. Johnston
- Liver Disease and Hepatitis Program, Alaska Native Tribal Health Consortium, Anchorage, Alaska, USA
| | - Chriss Homan
- Liver Disease and Hepatitis Program, Alaska Native Tribal Health Consortium, Anchorage, Alaska, USA
| | - Lisa J. Townshend-Bulson
- Liver Disease and Hepatitis Program, Alaska Native Tribal Health Consortium, Anchorage, Alaska, USA
| | - Nicole J. Kim
- Division of Gastroenterology, Department of Medicine, University of Washington, Seattle, Washington, USA
| | - Trang VoPham
- Epidemiology Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
| | - Xiaohong Li
- Bioinformatics and Epidemiology Program, Vaccine and Infection Disease Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
| | - Qianchuan He
- Biostatistics Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
| | - Brian J. McMahon
- Liver Disease and Hepatitis Program, Alaska Native Tribal Health Consortium, Anchorage, Alaska, USA
| | - George N. Ioannou
- Division of Gastroenterology, Department of Medicine, University of Washington, Seattle, Washington, USA
- Division of Gastroenterology, Department of Medicine, Veterans Affairs, Puget Sound Health Care System, Seattle, Washington, USA
| | - Ziding Feng
- Biostatistics Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
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Cutting RB, Muscat DM, Patel P, De La Mata NL, Irish GL, Wyld M, White S, Webster AC. Values, Preferences, and Risk Tolerance of People Waitlisted for a Kidney Transplant Regarding Potential Deceased Donor Organ Profiles: A Systematic Review. Transplantation 2025; 109:e326-e339. [PMID: 40020169 DOI: 10.1097/tp.0000000000005267] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/23/2025]
Abstract
BACKGROUND Incorporating the views of people waitlisted for a kidney transplant is important when clinicians consider any donor kidney offer. METHODS We conducted a systematic review of quantitative and qualitative studies in adult patients on, or under assessment for, the kidney waitlist. We focused on views of extended criteria, increased viral (blood-borne virus), or increased cancer risk in deceased donor kidneys. We systematically searched databases and conference proceedings until April 2024, excluding studies of children, case reports, and commentaries. Studies were appraised using the Johanna Briggs Institute checklists and synthesized using a convergent segregated approach, incorporating narrative and thematic methods. RESULTS We included 25 studies (2630 participants) comprising quantitative surveys, questionnaires, conjoint analysis, and discrete choice experiments (n = 16; 64%) and qualitative semi-structured, in-depth interviews and focus groups (n = 9; 36%). Most studies were from the United States (n = 19; 76%) and focused on extended criteria and increased viral risk donors (n = 24; 96%), with 1 study considering general risks (4%). None focused on increased cancer-risk donors. We identified 4 themes and 2 subthemes: (1) I want to be free from dialysis, (2) I do not want more health problems, (3) I might not get another chance, (4) I desire shared decision-making but feel powerless to contribute, (4a) I need more information about my health status, prognosis and the transplant process, and (4b) I need more information about donor risk factors. CONCLUSIONS Waitlist patients desired information and involvement in decision-making, yet individual prognoses were not fully understood. Integrating shared decision-making from pre- to post-offer will increase knowledge and enhance treatment satisfaction.
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Affiliation(s)
- Rachel B Cutting
- Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, Camperdown, NSW, Australia
| | - Danielle M Muscat
- Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, Camperdown, NSW, Australia
- Sydney Health Literacy Lab, Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, Camperdown, NSW, Australia
| | - Pinika Patel
- Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, Camperdown, NSW, Australia
| | - Nicole L De La Mata
- Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, Camperdown, NSW, Australia
| | - Georgina L Irish
- Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry, South Australian Health and Medical Research Institute (SAHMRI), Adelaide, SA, Australia
- Central and Northern Adelaide Renal and Transplantation Service, Royal Adelaide Hospital, Adelaide, SA, Australia
| | - Melanie Wyld
- Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, Camperdown, NSW, Australia
- Department of Renal and Transplant Medicine, Westmead Hospital, Westmead, NSW, Australia
| | - Sarah White
- Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, Camperdown, NSW, Australia
| | - Angela C Webster
- Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, Camperdown, NSW, Australia
- National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Camperdown, NSW, Australia
- Westmead Applied Research Centre, Westmead Hospital, Westmead, NSW, Australia
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3
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Kalam N, Ali R, Balasubramaniam VR. Exploring the potential of direct-acting antivirals against Chikungunya virus through structure-based drug repositioning and molecular dynamic simulations. Comput Biol Med 2025; 189:109989. [PMID: 40056839 DOI: 10.1016/j.compbiomed.2025.109989] [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: 08/14/2024] [Revised: 03/01/2025] [Accepted: 03/03/2025] [Indexed: 03/10/2025]
Abstract
The Chikungunya virus (CHIKV) represents a significant global health threat, particularly in tropical regions, and no FDA-approved antiviral treatments are currently available. This study investigates the potential of Direct-Acting Antivirals (DAAs) and protease inhibitors (PIs) that have been developed for the hepatitis C virus (HCV) in treating CHIKV. We analyzed the binding of eight HCV DAAs to the nsP2 protease of CHIKV, which is essential for viral replication. Our findings suggest repurposing hepatitis C virus (HCV) antivirals, specifically Simeprevir (SIM) and voxilaprevir (VOX), could be effective against CHIKV. Through computational analyses, we observed their strong binding affinity to CHIKV's nsP2 protease, indicating the promising potential of repositioning these drugs for CHIKV treatment. To validate the results of our computational study, we evaluated the antiviral efficacy of SIM and VOX in vitro, both as monotherapies and in combination with ribavirin (RIBA). Our findings revealed that DAAs exert a multifaced effect by targeting different stages of the CHIKV life cycle. Furthermore, the synergistic effects suggest that combining SIM and VOX with RIBA may provide a more effective therapeutic strategy than using either drug alone. Further research is necessary to optimize treatment protocols and improve outcomes for patients affected by CHIKV.
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Affiliation(s)
- Nida Kalam
- Infection and Immunity Research Strength, Jeffrey Cheah School of Medicine & Health Sciences, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway, 47500, Malaysia
| | - Rafat Ali
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, 110025, India
| | - Vinod Rmt Balasubramaniam
- Infection and Immunity Research Strength, Jeffrey Cheah School of Medicine & Health Sciences, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway, 47500, Malaysia.
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Scicluna J, Di Napoli R, Pirozzi D, Fraenza F, Cardillo M, Scavone C, Capuano A. Hepatobiliary disorders and Direct-Acting Antiviral (DAA) therapies: real-world evidence and insights from the EudraVigilance database. Expert Opin Drug Saf 2025:1-8. [PMID: 40243008 DOI: 10.1080/14740338.2025.2495180] [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: 10/03/2024] [Revised: 03/06/2025] [Accepted: 03/17/2025] [Indexed: 04/18/2025]
Abstract
BACKGROUND The introduction of Direct-Acting Antivirals (DAA) brought about a breakthrough in the treatment of HCV. This study aims to analyze the hepatic safety profile of Harvoni® (sofosbuvir/ledipasvir), Epclusa® (sofosbuvir/velpatasvir), and Vosevi® (sofosbuvir/velpatasvir/voxilaprevir) through a review of the Individual Case Safety Reports (ICSRs) reported in EudraVigilance (EV). RESEARCH DESIGN AND METHODS ICSRs with adverse events (AE) belonging to the system organ class (SOC) hepatobiliary disorders were retrieved from the EV database. A descriptive analysis was performed. Reporting odds ratios (ROR) were calculated to assess the reporting frequency of hepatobiliary disorders among the DAA combinations. RESULTS Out of 5,552 ICSRs reported between January 2018 and December 2023, 1,942 were for Harvoni®, 3,180 for Epclusa® and 430 for Vosevi®. Three hundred and thirty-nine ICSRs reported 1,616 PT within the SOC hepatobiliary disorders. Harvoni® showed a statistically significant lower frequency of reporting for the hepatobiliary disorders SOC when compared to Epclusa® and Vosevi® (ROR, 0.33; 95% CI [0.26-0.41] and ROR 0.31; 95% CI [0.19-0.48], respectively). CONCLUSION Harvoni® showed a lower reporting frequency of hepatobiliary disorders and fewer drug ineffectiveness reports, suggesting it may be preferred over Epclusa® and Vosevi® in patients with preexisting liver or biliary conditions.
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Affiliation(s)
- John Scicluna
- Eu2P Programme, University of Bordeaux, Bordeaux, France
| | - Raffaella Di Napoli
- Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, Naples, Italy
- Department of Experimental Medicine - Section of Pharmacology "L. Donatelli", University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Daniele Pirozzi
- Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, Naples, Italy
| | - Federica Fraenza
- Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, Naples, Italy
- Department of Experimental Medicine - Section of Pharmacology "L. Donatelli", University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Mirko Cardillo
- Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, Naples, Italy
| | - Cristina Scavone
- Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, Naples, Italy
- Department of Experimental Medicine - Section of Pharmacology "L. Donatelli", University of Campania "Luigi Vanvitelli", Naples, Italy
- Department of Life Sciences, Health, and Health Professions, Link Campus University, Rome, Italy
| | - Annalisa Capuano
- Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, Naples, Italy
- Department of Experimental Medicine - Section of Pharmacology "L. Donatelli", University of Campania "Luigi Vanvitelli", Naples, Italy
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5
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Chang SH, Cabrera R, Heo J, Park C, Guo J, Park H. Real-World Effectiveness of All-Oral Direct-Acting Antivirals in Patients With Hepatitis C Virus-Related HCC. Clin Pharmacol Ther 2025; 117:1030-1038. [PMID: 39489881 DOI: 10.1002/cpt.3481] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Accepted: 10/08/2024] [Indexed: 11/05/2024]
Abstract
The association between direct-acting antiviral (DAA) treatment and hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) is currently unclear. Hence, we aim to assess the association between DAA treatment and mortality rate among Medicare beneficiaries with HCV-related HCC. This retrospective cohort study screened 19,813 adults in 2013-2019 Surveillance, Epidemiology, and End Results data linked with Medicare data. Patients with HCV-related HCC initiating DAA therapy after their first HCC diagnosis were compared with patients with HCV-related HCC who received no HCV treatment. After inverse probability treatment weighting, multivariable Cox proportional hazards models compared mortality rates between the groups. Subgroup and sensitivity analyses were based on HCC stage (early vs. advanced), type of HCC treatment (curative, palliative, none), and DAA treatment duration. In total 3,777 patients with HCV-related HCC were identified (mean age: 68.2 years, 75.2% male, 61.8% White), of whom 19% initiated DAA therapy. Crude incidence mortality rates were 17.9 and 90.7 deaths per 100 person-years in the DAA and HCV-untreated groups, respectively. Cox regression models indicated that DAA therapy was associated with decreased risk of all-cause mortality (adjusted hazard ratio, 0.33; 95% CI 0.31-0.36). Median survival time was 45.7 (95% CI 40.9-57.9) months in the DAA group and 7.7 (95% CI 7.3-8.2) months in the HCV-untreated group (P < 0.001). All subgroup and sensitivity analyses were consistent with the main analyses. DAA therapy was associated with survival benefits for patients with HCV-related HCC regardless of the stage or type of HCC treatment and should not be withheld from this population of Medicare beneficiaries.
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Affiliation(s)
- Shao-Hsuan Chang
- Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, Florida, USA
| | - Roniel Cabrera
- Division of Gastroenterology, Hepatology, and Nutrition, College of Medicine, University of Florida, Gainesville, Florida, USA
| | - Jihaeng Heo
- Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, Florida, USA
| | - Chanhyun Park
- Health Outcomes Division, College of Pharmacy, University of Texas at Austin, Austin, Texas, USA
| | - Jingchuan Guo
- Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, Florida, USA
| | - Haesuk Park
- Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, Florida, USA
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Kattel HP, Sharma S, Alfsnes K, Pettersson JHO, Pathak R, Engebretsen SB, Rijal KR, Ghimire P, Andreassen ÅK, Banjara MR. The Genotypes/Subtypes and Antiviral Drug Resistance of the Hepatitis C Virus from Patients in a Tertiary Care Hospital in Nepal. Viruses 2025; 17:377. [PMID: 40143305 PMCID: PMC11946309 DOI: 10.3390/v17030377] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2025] [Revised: 03/03/2025] [Accepted: 03/04/2025] [Indexed: 03/28/2025] Open
Abstract
While direct-acting antivirals (DAAs) are available for the treatment of chronic Hepatitis C virus (HCV) patients in Nepal, knowledge of the circulating genotypes/subtypes and drug target gene mutations of HCV is currently unavailable. Here, we describe HCV genotypes/subtypes and identify antiviral target gene mutations in patients at a tertiary care hospital using genome data. A cross-sectional study was conducted from December 2019 to February 2024, where PCR followed by whole genome sequencing was performed to identify HCV genotypes/subtypes and drug target gene mutations. Among all the patients who tested positive for anti-HCV, 70.6% (149/211) were HCV RNA positive, while 68.2% (30/44) were genotype/subtype 3a, followed by 1a (18.2%, 8/44) and others (13.6%, 6/44), including new subtypes 3g and 3i from Nepal. Subtype 3a was also the dominant subtype (≥70%) among intravenous drug users and sexual routes of transmission. We found 70.5% of the samples with resistant mutations in the NS3/4A region, 22.7% in NS5A, and 45.5% in NS5B. Resistant mutations against sofosbuvir, pibrentasvir, velpatasvir, daclatasvir, and dasabuvir were found at 25%, 18%, 16%, 16%, and 2%, respectively, mostly on subtype 3a. The predominant HCV genotype/subtype in our patient group was 3a, and resistance mutations against direct-acting antivirals were found in most untreated patients.
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Affiliation(s)
- Hari Prasad Kattel
- Central Department of Microbiology, Tribhuvan University, Kathmandu 44601, Nepal; (H.P.K.); (K.R.R.); (P.G.)
| | - Sangita Sharma
- Tribhuvan University Teaching Hospital, Kathmandu 44601, Nepal; (S.S.); (R.P.)
| | - Kristian Alfsnes
- Norwegian Institute of Public Health, P.O. Box 222, NO-0213 Oslo, Norway; (K.A.); (S.B.E.); (Å.K.A.)
| | - John H.-O. Pettersson
- Zoonosis Science Center, Clinical Microbiology, Department of Medical Sciences, Uppsala University, SE-751 05 Uppsala, Sweden;
- Department of Microbiology, Swedish Veterinary Agency, SE-751 05 Uppsala, Sweden
- Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC 3121, Australia
| | - Rahul Pathak
- Tribhuvan University Teaching Hospital, Kathmandu 44601, Nepal; (S.S.); (R.P.)
| | - Serina Beate Engebretsen
- Norwegian Institute of Public Health, P.O. Box 222, NO-0213 Oslo, Norway; (K.A.); (S.B.E.); (Å.K.A.)
| | - Komal Raj Rijal
- Central Department of Microbiology, Tribhuvan University, Kathmandu 44601, Nepal; (H.P.K.); (K.R.R.); (P.G.)
| | - Prakash Ghimire
- Central Department of Microbiology, Tribhuvan University, Kathmandu 44601, Nepal; (H.P.K.); (K.R.R.); (P.G.)
| | - Åshild K. Andreassen
- Norwegian Institute of Public Health, P.O. Box 222, NO-0213 Oslo, Norway; (K.A.); (S.B.E.); (Å.K.A.)
| | - Megha Raj Banjara
- Central Department of Microbiology, Tribhuvan University, Kathmandu 44601, Nepal; (H.P.K.); (K.R.R.); (P.G.)
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Danpanichkul P, Duangsonk K, Kalligeros M, Fallon MB, Vuthithammee C, Pan CW, Saokhieo P, Derrick W, Pang Y, Chen VL, Kim D, Singal AG, Yang JD, Wijarnpreecha K. Alcohol-Related Liver Disease, Followed by Metabolic Dysfunction-Associated Steatotic Liver Disease, Emerges as the Fastest-Growing Aetiologies for Primary Liver Cancer in the United States. Aliment Pharmacol Ther 2025; 61:959-970. [PMID: 39757456 DOI: 10.1111/apt.18473] [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: 10/14/2024] [Revised: 11/27/2024] [Accepted: 12/20/2024] [Indexed: 01/07/2025]
Abstract
OBJECTIVE Primary liver cancer (PLC) is projected to be the third leading cause of cancer mortality in the United States in 2040. We examine the burden of PLC in the United States, stratified by sex, state and aetiological risk factors. METHODS Data on PLC prevalence, incidence, death and disability-adjusted life years (DALYs) were extracted from the Global Burden of Disease Study 2021. Changes in these parameters were calculated using the Joinpoint regression model. RESULTS There were 47,970 cases, 31,450 incident cases, 24,770 deaths and 576,920 DALYs from PLC in the United States. The highest prevalence (16,980), incidence (12,040), death (9840) and DALYs (213,410) from PLC were due to chronic hepatitis C virus infection. From 2000 to 2021, PLC incidences increased by 141%, and PLC deaths increased by 136%. Age-standardised incidence rates (ASIRs) and death rates (ASDRs) per 100,000 population for PLC increased, primarily driven by alcohol-related liver disease (ALD) (ASIR: annual percent change [APC]: +2.40%; ASDR: APC: +2.22%) and metabolic dysfunction-associated steatotic liver disease (MASLD) (ASIR: APC: +2.32%; ASDR: APC: +2.04%). CONCLUSION The burden of PLC in the United States has risen in the past two decades, driven mainly by ALD and followed by MASLD. These findings offer policymakers an accurate assessment of the PLC burden and emphasise the need for targeted risk factor mitigation, especially regarding alcohol related policy.
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Affiliation(s)
- Pojsakorn Danpanichkul
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, Texas, USA
| | - Kwanjit Duangsonk
- Department of Microbiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Markos Kalligeros
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Michael B Fallon
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Arizona College of Medicine, Phoenix, Arizona, USA
- Department of Internal Medicine, Banner University Medical Center, Phoenix, Arizona, USA
| | | | - Chun Wei Pan
- Department of Medicine, John H. Stroger Jr Hospital of Cook County, Chicago, Illinois, USA
| | | | - William Derrick
- Texas Tech University Health Sciences Center School of Medicine, Lubbock, Texas, USA
| | - Yanfang Pang
- Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, China
- National Immunological Laboratory of Traditional Chinese Medicine, Baise, Guangxi, China
- Center for Medical Laboratory Science, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, China
| | - Vincent L Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Donghee Kim
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California, USA
| | - Amit G Singal
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Ju Dong Yang
- Karsh Division of Gastroenterology and Hepatology, Comprehensive Transplant Center, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, California, Los Angeles, USA
| | - Karn Wijarnpreecha
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Arizona College of Medicine, Phoenix, Arizona, USA
- Department of Internal Medicine, Banner University Medical Center, Phoenix, Arizona, USA
- BIO5 Institute, University of Arizona College of Medicine-Phoenix, Phoenix, Arizona, USA
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8
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Gaikwad M, George A, Sivadas A, Karunakaran K, N S, Byradeddy SN, Mukhopadhyay C, Mudgal PP, Kulkarni M. Development and characterization of formulations based on combinatorial potential of antivirals against genital herpes. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2025; 398:3103-3117. [PMID: 39347802 PMCID: PMC11919951 DOI: 10.1007/s00210-024-03468-y] [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: 07/27/2024] [Accepted: 09/17/2024] [Indexed: 10/01/2024]
Abstract
Herpes simplex virus type 2 (HSV-2) treatment faces challenges due to antiviral resistance and systemic side effects of oral therapies. Local delivery of antiviral agents, such as tenofovir (TDF) and zinc acetate dihydrate (ZAD), may offer improved efficacy and reduced systemic toxicity. This study's objective is to develop and evaluate local unit dose formulations of TDF and ZAD combination for local treatment of HSV-2 infection and exploring their individual and combinatory effects in vitro. The study involved the development of immediate-release film and pessary formulations containing TDF and ZAD. These formulations were characterized for physicochemical properties and in vitro drug release profiles. Cytotoxicity and antiviral activity assays were conducted to evaluate the individual and combinatory effects of TDF and ZAD. Film formulations released over 90% of the drugs within 1 h, and pessary formulations within 90 min, ensuring effective local drug delivery. ZAD showed moderate antiviral activity while TDF exhibited significant antiviral activity at non-cytotoxic concentrations. The combination of TDF and ZAD demonstrated synergistic effects in co-infection treatments, reducing the concentration required for 50% inhibition of HSV-2. Developed film and pessary formulations offer consistent and predictable local drug delivery, enhancing antiviral efficacy while minimizing systemic side effects. The combination of TDF and ZAD showed potential synergy against HSV-2, particularly in co-infection treatments. Further preclinical studies on pharmacokinetics, safety, and efficacy are necessary to advance these formulations toward clinical application.
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Affiliation(s)
- Mahesh Gaikwad
- SCES's Indira College of Pharmacy, New Mumbai Pune Highway, Tathawade, Pune, India
| | - Amal George
- Manipal Institute of Virology, Manipal Academy of Higher Education, Manipal, India
| | - Aparna Sivadas
- Manipal Institute of Virology, Manipal Academy of Higher Education, Manipal, India
| | - Kavitha Karunakaran
- Manipal Institute of Virology, Manipal Academy of Higher Education, Manipal, India
| | - Sudheesh N
- Manipal Institute of Virology, Manipal Academy of Higher Education, Manipal, India
| | - Siddappa N Byradeddy
- Manipal Institute of Virology, Manipal Academy of Higher Education, Manipal, India
- Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Centre, Omaha, NE, USA
| | | | - Piya Paul Mudgal
- Manipal Institute of Virology, Manipal Academy of Higher Education, Manipal, India.
| | - Madhur Kulkarni
- SCES's Indira College of Pharmacy, New Mumbai Pune Highway, Tathawade, Pune, India.
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Ocampo F, Sacdalan C, Pinyakorn S, Paudel M, Wansom T, Poltubtim N, Sriplienchan S, Phanuphak N, Paul R, Hsu D, Colby D, Trautmann L, Spudich S, Chan P. Neuropsychiatric and laboratory outcomes of hepatitis C treatment in an early-treated HIV cohort in Thailand. AIDS Res Ther 2025; 22:20. [PMID: 39972347 PMCID: PMC11841302 DOI: 10.1186/s12981-025-00707-x] [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: 03/29/2024] [Accepted: 01/17/2025] [Indexed: 02/21/2025] Open
Abstract
BACKGROUND Hepatitis C virus (HCV) coinfection may further compromise immunological and cognitive function in people with HIV (PWH). This study compared laboratory and neuropsychiatric measures across the periods of HCV seroconversion and direct-acting antiviral (DAA) therapy with sustained virologic response (SVR) among PWH who initiated antiretroviral therapy (ART) during acute HIV infection (AHI) and acquired HCV after 24 weeks of ART. METHODS Participants from the RV254 AHI cohort underwent paired laboratory and neuropsychiatric assessments during follow-up visits. The former included measurements of CD4 + and CD8 + T-cell counts, HIV RNA, liver enzymes, and lipid profiles. The latter included the Patient Health Questionnaire-9 (PHQ-9), Distress Thermometer (DT), and a 4-test cognitive battery that evaluated psychomotor speed, executive function, fine motor speed, and dexterity. The raw scores in the battery were standardized and averaged to create an aggregate performance (NPZ-4) score. Parameters of HCV-coinfected participants were compared across the periods of HCV seroconversion and DAA treatment. RESULTS Between 2009 and 2022, 79 of 703 RV254 participants acquired HCV after ≥ 24 weeks of ART; 53 received DAA, and 50 (94%) achieved SVR. All participants were Thai males (median age: 30 years); 34 (68%) denied past intravenous drug use, and 41 (82%) had a history of other sexually transmitted infections during follow-up. Following SVR, aspartate transferase (AST) and alanine transaminase (ALT) decreased (p < 0.001), while total cholesterol, low-density lipoprotein, and triglycerides increased (p < 0.01). The median CD4 + /CD8 + ratio increased from 0.91 to 0.97 (p = 0.012). NPZ-4 improved from 0.75 to 0.91 (p = 0.004). The median DT score increased from 1.7 to 2.7 (p = 0.045), but the PHQ-9 score remained unchanged. CONCLUSION HCV coinfection is common in this group of high-risk PWH, highlighting the need for regular screening, early diagnosis, and treatment. The study participants exhibited a modest improvement in the CD4 + /CD8 + T-cell ratio and cognitive performance following DAA therapy and SVR. Future studies should examine potential neuropsychiatric impacts during early HCV infection as well as the longer-term neuropsychiatric outcomes after DAA treatment with SVR.
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Affiliation(s)
- Ferron Ocampo
- SEARCH Research Foundation, Block 28, 926 Tower C Room C114-C115 Soi Chula 7, Wang Mai, Pathum Wan, Bangkok, 10330, Thailand.
| | - Carlo Sacdalan
- SEARCH Research Foundation, Block 28, 926 Tower C Room C114-C115 Soi Chula 7, Wang Mai, Pathum Wan, Bangkok, 10330, Thailand
- Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Suteeraporn Pinyakorn
- U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA
| | - Misti Paudel
- U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA
| | | | - Nathornsorn Poltubtim
- SEARCH Research Foundation, Block 28, 926 Tower C Room C114-C115 Soi Chula 7, Wang Mai, Pathum Wan, Bangkok, 10330, Thailand
| | - Somchai Sriplienchan
- SEARCH Research Foundation, Block 28, 926 Tower C Room C114-C115 Soi Chula 7, Wang Mai, Pathum Wan, Bangkok, 10330, Thailand
| | | | | | - Denise Hsu
- U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA
| | - Donn Colby
- U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA
| | - Lydie Trautmann
- U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA
| | - Serena Spudich
- Department of Neurology, Yale University, New Haven, CT, USA
- Yale Center for Brain and Mind Health, Yale University, New Haven, CT, USA
| | - Phillip Chan
- Department of Neurology, Yale University, New Haven, CT, USA
- Yale Center for Brain and Mind Health, Yale University, New Haven, CT, USA
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10
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Ramzy S, Alshehri S, Abduljabbar MH, Althobaiti YS, Alzhrani RM, Almalki AH. An environmentally sustainable synchronous spectrofluorimetric method coupled with second derivative signal processing for simultaneous determination of velpatasvir and simeprevir in pharmaceutical and plasma samples. SPECTROCHIMICA ACTA. PART A, MOLECULAR AND BIOMOLECULAR SPECTROSCOPY 2025; 326:125202. [PMID: 39332169 DOI: 10.1016/j.saa.2024.125202] [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: 08/07/2024] [Revised: 09/03/2024] [Accepted: 09/22/2024] [Indexed: 09/29/2024]
Abstract
Velpatasvir and simeprevir are two direct acting antivirals that are often used in combination with sofosbuvir to treat HCV infections. Herein, an environmentally benign spectrofluorimetric method was developed for simultaneous quantification of velpatasvir and simeprevir in pharmaceutical and plasma samples. To address the issue of overlapping fluorescence spectra presented by these compounds, this method integrates synchronous fluorescence and second-derivative spectroscopy. By employing the second derivative of the synchronous fluorescence spectra measured at Δλ of 140 nm, the accurate determination of velpatasvir at 400 nm and simeprevir at 426 nm was achieved without any interference. Different experimental parameters affecting the synchronous fluorescence of the studied drugs were carefully optimized. The plots of second-derivative amplitudes against concentrations showed linearity in the range of 5-400 ng/mL for velpatasvir and 80-800 ng/mL for simeprevir. The method was very sensitive, with lower detection limits of 1.11 ng/mL and 25.40 ng/mL, and quantification limits of 3.36 ng/mL and 76.96 ng/mL for velpatasvir and simeprevir, respectively.The method was effectively used to determine velpatasvir and simeprevir simultaneously in their pure forms, pharmaceutical dosage forms, and human plasma with no interference. The suggested technique was additionally evaluated for its eco-friendliness through the utilization of the Analytical GREEnness (AGREE) and Green Analytical Procedure Index (GAPI) evaluation metrics, revealing that the method is indeed sustainable.
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Affiliation(s)
- Sherif Ramzy
- Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy, Al-Azhar University, 11751 Nasr City, Cairo, Egypt.
| | - Sameer Alshehri
- Department of Pharmaceutics and Industrial Pharmacy, College of Pharmacy, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia
| | - Maram H Abduljabbar
- Department of Pharmacology and Toxicology, College of Pharmacy, Taif University, Taif 21944, Saudi Arabia
| | - Yusuf S Althobaiti
- Department of Pharmacology and Toxicology, College of Pharmacy, Taif University, Taif 21944, Saudi Arabia; Addiction and Neuroscience Research Unit, Health Science Campus, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia
| | - Rami M Alzhrani
- Department of Pharmaceutics and Industrial Pharmacy, College of Pharmacy, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia
| | - Atiah H Almalki
- Addiction and Neuroscience Research Unit, Health Science Campus, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia; Department of Pharmaceutical Chemistry, College of Pharmacy, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
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11
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Gujarathi R, Klein JA, Liao CY, Pillai A. The Changing Demographics and Epidemiology of Hepatocellular Carcinoma. Clin Liver Dis 2025; 29:1-15. [PMID: 39608950 DOI: 10.1016/j.cld.2024.08.001] [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] [Indexed: 11/30/2024]
Abstract
The epidemiology of hepatocellular carcinoma (HCC) has shifted significantly in the last 2 decades with non-viral etiologies such as metabolic dysfunction-associated steatotic liver disease and alcohol-associated liver disease on the rise. Key factors include the global obesity epidemic and the resurgence of alcohol use disorder, both of which were exacerbated by the coronavirus disease 2019 pandemic. While these non-viral etiologies of HCC are becoming the leading cause in developed countries, the potential impact of immigration patterns on Hepatitis B virus epidemiology cannot be ignored. The risk of HCC remains significant in individuals with cirrhosis and viral hepatitis after curative treatments.
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Affiliation(s)
- Rushabh Gujarathi
- Department of Internal Medicine, University of Chicago, Chicago, IL, USA
| | - Jeremy A Klein
- Department of Internal Medicine, University of Chicago, Chicago, IL, USA
| | - Chih-Yi Liao
- Department of Internal Medicine, University of Chicago, Chicago, IL, USA
| | - Anjana Pillai
- Department of Internal Medicine, University of Chicago, Chicago, IL, USA.
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12
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Tan M, Kuncio D, Addish E, Nassau T, Higgins D, Miller M, Brady K. People With HIV Are More Likely to Clear Hepatitis C: Role of Ryan White Services, Philadelphia, Pennsylvania, United States. Open Forum Infect Dis 2025; 12:ofaf043. [PMID: 39935962 PMCID: PMC11811900 DOI: 10.1093/ofid/ofaf043] [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: 11/15/2024] [Accepted: 01/24/2025] [Indexed: 02/13/2025] Open
Abstract
Background HIV coinfection worsens health outcomes for persons with chronic hepatitis C virus (HCV) infection; however, access to comprehensive Ryan White (RW) HIV care may improve the health of persons with HIV and HCV. Methods In a retrospective cohort study, we used surveillance data from Philadelphia's hepatitis and HIV registries for newly reported HCV infections from November 2015 to October 2021. We plotted Kaplan-Meier curves and performed Cox regressions on time to HCV clearance by HIV coinfection status, adjusting for demographic characteristics and HCV report year. Results A total of 10 251 persons with newly reported HCV infection were included, of whom 9898 (96.6%) had HCV monoinfection and 353 (3.4%) had HIV coinfection. HCV reports were mostly among residents who were non-Hispanic/Latine White (n = 3609, 35.2%) and non-Hispanic/Latine Black (n = 3221, 31.4%) and assigned male sex at birth (n = 6931, 67.8%). At every month of follow-up, having HIV was associated with a higher likelihood of HCV clearance as compared with HCV monoinfection (adjusted hazard ratio, 1.2; 95% CI, 1.1-1.4; P < .05). For persons with HIV coinfection, participation in RW support services 2 to 6 times monthly was associated with an increased likelihood (adjusted hazard ratio, 1.7-3.1) of HCV clearance at every month of follow-up as compared with persons without RW participation (P < .05). Conclusions Among newly reported HCV infections, the likelihood of HCV clearance was higher among persons with HIV coinfection who participated in RW support services. Frequent receipt of supportive services, such as those provided by the national, federally funded RW system, is crucial for HCV elimination.
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Affiliation(s)
- Marissa Tan
- Cooper Center for Healing, Cooper University Health Care, Camden, New Jersey, USA
- Epidemiology Intelligence Service, Division of Workforce Development, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
- Hepatitis, Division of Disease Control, Philadelphia Department of Public Health, Philadelphia, Pennsylvania, USA
| | - Danica Kuncio
- Hepatitis, Division of Disease Control, Philadelphia Department of Public Health, Philadelphia, Pennsylvania, USA
| | - Eman Addish
- Hepatitis, Division of Disease Control, Philadelphia Department of Public Health, Philadelphia, Pennsylvania, USA
| | - Tanner Nassau
- Division of HIV Health, Philadelphia Department of Public Health, Philadelphia, Pennsylvania, USA
| | - Dana Higgins
- Division of Substance Use Prevention and Harm Reduction, Philadelphia Department of Public Health, Philadelphia, Pennsylvania, USA
| | - Melissa Miller
- Division of HIV Health, Philadelphia Department of Public Health, Philadelphia, Pennsylvania, USA
| | - Kathleen Brady
- Division of HIV Health, Philadelphia Department of Public Health, Philadelphia, Pennsylvania, USA
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13
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Rosendahl A, Uth LMK, Weis N, Smerup M, Ellesøe SG. Detection of Hepatitis C Virus Infection in Patients Undergoing Open Heart Surgery in Childhood Prior to 1992: A Danish Nationwide Cross-Sectional Study. Clin Med Insights Pediatr 2025; 19:11795565251315722. [PMID: 39885994 PMCID: PMC11776013 DOI: 10.1177/11795565251315722] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2024] [Accepted: 01/09/2025] [Indexed: 02/01/2025] Open
Abstract
Background and aim Pediatric patients undergoing cardiac surgery prior to 1992 in Denmark were at risk of hepatitis C virus (HCV) infection through donor blood used in extracorporeal circulation. HCV screening became possible in donors in 1991, eliminating the risk of iatrogenic infections. No formalized screening has been conducted for patients receiving non-screened blood, potentially leaving some with undetected HCV infection. Objectives This study aimed to determine the prevalence of chronic HCV infection in this group of patients and offer treatment to those affected. Design Nationwide cross-sectional study. Methods Between 2020 and 2023, 1645 individuals who underwent pediatric heart surgery before 1992 in Denmark were identified. Participants were invited for HCV screening using anti-HCV-antibody and HCV-RNA tests. Patients testing positive for HCV were referred to direct-acting antiviral (DAA) treatment. Results Of 1645 patients identified, 571 consented to participate, and 246 completed HCV screening. Two individuals tested positive for chronic HCV infection, resulting in a prevalence of 0.8%. Both patients were asymptomatic for many years before treatment and successfully cleared the virus after DAA treatment. Conclusions The 0.8% prevalence of HCV in this cohort is higher than in the general Danish population although lower than in similar studies from the U.S. and Germany. This may reflect Denmark's practice of unpaid blood donation, reducing infection risks. Targeted screening for at-risk cohorts exposed to transfusions before 1992 could aid in HCV detection and treatment, potentially preventing long-term liver complications. Registration The study was approved by the Capital Region Ethics Board in Denmark (j.nr. H-18062088).
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Affiliation(s)
- Amalie Rosendahl
- Department of Anaesthesiology, Herlev and Gentofte Hospital, Copenhagen, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Louise Margrethe Kiær Uth
- Department of Cardiothoracic Surgery, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Nina Weis
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Copenhagen, Denmark
| | - Morten Smerup
- Department of Cardiothoracic Surgery, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Sabrina Gade Ellesøe
- Department of Cardiothoracic Surgery, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
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14
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Jose-Abrego A, Laguna-Meraz S, Roman S, Mariscal-Martinez IM, Panduro A. Hepatitis C Virus Resistance-Associated Substitutions in Mexico. Viruses 2025; 17:169. [PMID: 40006924 PMCID: PMC11860613 DOI: 10.3390/v17020169] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2024] [Revised: 01/10/2025] [Accepted: 01/13/2025] [Indexed: 02/27/2025] Open
Abstract
Hepatitis C virus (HCV) is susceptible to resistance-associated substitutions (RASs) in the NS3, NS5A, and NS5B nonstructural genes, key targets of the direct-acting antivirals (DAAs). This study aimed to assess the prevalence and distribution of RASs across different HCV subtypes in Mexico. A Genbank dataset of 566 HCV sequences was analyzed. Most sequences were from Mexico City (49.1%, 278/566) and Jalisco (39.4%, 223/566). The NS5B region was the most sequenced (59.7%, 338/566). The most frequent HCV subtypes were 1a (44.0%, 249/566), 1b (28.6%, 162/566), 2b (9.5%, 54/566), and 3a (6.2%, 35/566). Subtypes 1a (57.4%, 128/223) and 3a (12.6%, 28/223) were significantly higher in Jalisco than in Mexico City (34.2%, 95/278 and 2.5%, 7/278), whereas subtype 1b was higher in Mexico City (34.5%, 96/278 vs. 14.8%, 33/223). Subtype 1a increased from 2019 to 2024, representing 49.4% (123/249) of all reported cases. RASs were detected in NS3 (6.7%, 1/15), NS5A (2.9%, 3/102), and NS5B (0.3%, 1/349), with the most frequent mutations being Q80K, Y93H, and S282T, respectively, and detected in subtypes 1b (n = 3), 1a (n = 1), and 2a (n = 1). In conclusion, Mexico's HCV sequencing-based surveillance is limited. Subtype 1a predominated, but frequencies varied across states. The prevalence of RASs varied by gene from 0.3% to 6.7%. Establishing regional sequencing centers for NS3, NS5A, and NS5B is crucial to monitoring Mexico's DAA-resistant mutations and HCV subtype genetic diversity.
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Affiliation(s)
- Alexis Jose-Abrego
- Department of Genomic Medicine in Hepatology, Civil Hospital of Guadalajara, Fray Antonio Alcalde, Guadalajara 44280, Mexico; (A.J.-A.); (S.L.-M.); (S.R.); (I.M.M.-M.)
- Health Sciences Center, University of Guadalajara, Guadalajara 44340, Mexico
| | - Saul Laguna-Meraz
- Department of Genomic Medicine in Hepatology, Civil Hospital of Guadalajara, Fray Antonio Alcalde, Guadalajara 44280, Mexico; (A.J.-A.); (S.L.-M.); (S.R.); (I.M.M.-M.)
- Health Sciences Center, University of Guadalajara, Guadalajara 44340, Mexico
| | - Sonia Roman
- Department of Genomic Medicine in Hepatology, Civil Hospital of Guadalajara, Fray Antonio Alcalde, Guadalajara 44280, Mexico; (A.J.-A.); (S.L.-M.); (S.R.); (I.M.M.-M.)
- Health Sciences Center, University of Guadalajara, Guadalajara 44340, Mexico
| | - Irene M. Mariscal-Martinez
- Department of Genomic Medicine in Hepatology, Civil Hospital of Guadalajara, Fray Antonio Alcalde, Guadalajara 44280, Mexico; (A.J.-A.); (S.L.-M.); (S.R.); (I.M.M.-M.)
- Health Sciences Center, University of Guadalajara, Guadalajara 44340, Mexico
- Doctoral Program Molecular Biology in Medicine, Health Sciences Center, University of Guadalajara, Guadalajara 44340, Mexico
| | - Arturo Panduro
- Department of Genomic Medicine in Hepatology, Civil Hospital of Guadalajara, Fray Antonio Alcalde, Guadalajara 44280, Mexico; (A.J.-A.); (S.L.-M.); (S.R.); (I.M.M.-M.)
- Health Sciences Center, University of Guadalajara, Guadalajara 44340, Mexico
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15
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Chen L, Elizalde M, Alvarez-Sola G. The Role of Sulfatides in Liver Health and Disease. FRONT BIOSCI-LANDMRK 2025; 30:25077. [PMID: 39862071 DOI: 10.31083/fbl25077] [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: 06/01/2024] [Revised: 07/31/2024] [Accepted: 08/07/2024] [Indexed: 01/27/2025]
Abstract
Sulfatides or 3-O-sulfogalactosylceramide are negatively charged sulfated glycosphingolipids abundant in the brain and kidneys and play crucial roles in nerve impulse conduction and urinary pH regulation. Sulfatides are present in the liver, specifically in the biliary tract. Sulfatides are self-lipid antigens presented by cholangiocytes to activate cluster of differentiation 1d (CD1d)-restricted type II natural killer T (NKT) cells. These cells are involved in alcohol-related liver disease (ArLD) and ischemic liver injury and exert anti-inflammatory effects by regulating the activity of pro-inflammatory type I NKT cells. Loss of sulfatides has been implicated in the chronic inflammatory disorder of the liver known as primary sclerosing cholangitis (PSC); bile ducts deficient in sulfatides increase their permeability, resulting in the spread of bile into the liver parenchyma. Previous studies have shown elevated levels of sulfatides in hepatocellular carcinoma (HCC), where sulfatides could act as adhesive molecules that contribute to cancer metastasis. We have recently demonstrated how loss of function of GAL3ST1, a limiting enzyme involved in sulfatide synthesis, reduces tumorigenic capacity in cholangiocarcinoma (CCA) cells. The biological function of sulfatides in the liver is still unclear; however, this review aims to summarize the existing findings on the topic.
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Affiliation(s)
- Lin Chen
- Department of Surgery, School of Nutrition and Translational Research in Metabolism, Maastricht University, 6200 MD Maastricht, The Netherlands
| | - Montserrat Elizalde
- Division of Gastroenterology-Hepatology, Department of Internal Medicine, Maastricht University, 6200 MD Maastricht, The Netherlands
| | - Gloria Alvarez-Sola
- Department of Surgery, School of Nutrition and Translational Research in Metabolism, Maastricht University, 6200 MD Maastricht, The Netherlands
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16
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Lane BL, Seal DW, Robertson DJ, Kendall C, Xavier Hall CD, Mgbere O, Kissinger PJ. Hepatitis C Care in the Greater New Orleans Area: Patient Perspectives on the Barriers and Facilitators to Care. J Health Care Poor Underserved 2025; 36:257-283. [PMID: 39957649 PMCID: PMC11932733 DOI: 10.1353/hpu.2025.a951596] [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: 02/18/2025]
Abstract
Increasing engagement in hepatitis C virus (HCV) care and treatment will help mitigate HCV incidence, morbidity, and mortality in the United States. This study aimed to understand the multilevel factors affecting engagement in HCV care after implementation of a subscription-based payment model for HCV treatment. Semi-structured interviews were conducted with patients with chronic HCV from a federally qualified health center in New Orleans, Louisiana. We used a convenience sampling method to recruit patients for the study. The interviews conducted between May 2020 and February 2021 explored factors influencing linkage to and retention in HCV care, using the socio-ecological model as the guiding framework. An analysis of the interviews with 39 patients revealed multilevel barriers to care, including instability, provider attitudes, prior care experiences, and the corrections system. Facilitators identified included personal health journey, network HCV experiences, and HCV awareness. A multilevel approach to facilitate engagement in HCV care is imperative.
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Affiliation(s)
- Brittany L. Lane
- Florida State University, College of Nursing, 98 Varsity Way, Tallahassee, Florida, 32306, United States
- Center of Population Sciences for Health Equity, Florida State University, College of Nursing, 2010 Levy Avenue, Innovation Park, Building B, Suite 3600, Tallahassee, Florida, 32310, United States
| | - David W. Seal
- Tulane University, Celia Scott Weatherhead School Public Health and Tropical Medicine, Department of Social, Behavioral, and Population Sciences, 1440 Canal Street, New Orleans, Louisiana, 70112, United States
| | - Dielda J. Robertson
- Louisiana Office of Public Health, Immunization Program, 1450 Poydras Street, #400 New Orleans, Louisiana, 70112, United States
| | - Carl Kendall
- Tulane University, Celia Scott Weatherhead School Public Health and Tropical Medicine, Department of Social, Behavioral, and Population Sciences, 1440 Canal Street, New Orleans, Louisiana, 70112, United States
| | - Casey D. Xavier Hall
- Florida State University, College of Nursing, 98 Varsity Way, Tallahassee, Florida, 32306, United States
- Center of Population Sciences for Health Equity, Florida State University, College of Nursing, 2010 Levy Avenue, Innovation Park, Building B, Suite 3600, Tallahassee, Florida, 32310, United States
- Florida State University, College of Social Work, 296 Champions Way, Tallahassee, FL, 32304, United States
| | - Osaro Mgbere
- Tilman J. Fertitta Family College of Medicine, Department of Health Systems and Population Health Sciences, University of Houston, 5055 Medical Circle, Houston, Texas, 77204, United States
| | - Patricia J. Kissinger
- Tulane University, Celia Scott Weatherhead School Public Health and Tropical Medicine, Department of Epidemiology, 1440 Canal Street, 70112 New Orleans, Louisiana, United States
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17
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Yilmaz O, Onder A. The Role of Epigallocatechin Gallate (EGCG) in Treatment and Management of Sexually Transmitted Viral Infections. Infect Disord Drug Targets 2025; 25:e18715265319110. [PMID: 39482915 DOI: 10.2174/0118715265319110240916061200] [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: 03/25/2024] [Revised: 07/29/2024] [Accepted: 08/22/2024] [Indexed: 11/03/2024]
Abstract
Tea is obtained from the young leaves and shoots of the evergreen perennial plant Camellia sinensis (L.) Kuntze, the most popular and frequently consumed product using a natural beverage worldwide. Some kinds of tea products, such as green tea, black tea, and oolong tea, have assorted flavors depending on the manufacturing techniques. Green tea has been studied for many years for its important beneficial effects, including anticancer, antiobesity, anti-diabetes, anti-inflammatory, neuroprotective, and cardiovascular effects. These effects are primarily associated with tea polyphenols, and regular consumption has been reported to decrease the incidence of some chronic diseases. Current studies support that green tea catechins play an important role in healing and improving the pathology of many diseases. Epigallocatechin-3-gallate (EGCG) is the most a highly found polyphenol in the leaves and is of great interest for its protective role in the prevention of diseases. Therefore, this review presents the efficacy and possible mechanisms of EGCG against sexually transmitted viruses. Moreover, EGCG and its derivatives are recognized as safe bioactive phytochemicals for external and internal use in preventing and treating viral STIs and other concurrent infections. Multidisciplinary studies are essential to discover cheaper, safer, and more effective treatments using EGCG and its derivatives to improve the toxicity and formulations of viral STI medications.
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Affiliation(s)
- Ozge Yilmaz
- Department of Pharmacognosy, Faculty of Pharmacy, Ankara University, 06100, Ankara, Türkiye
| | - Alev Onder
- Department of Pharmacognosy, Faculty of Pharmacy, Ankara University, 06100, Ankara, Türkiye
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18
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Román López CG, Triana González S, Cano Díaz AL, Lopez DDF, Mata Marín JA, Gaytán Martínez JE. Effectiveness of Direct Antiviral Agents in People with HCV-Monoinfection Compared to HCV/HIV Coinfection in a Real Life Setting. Viruses 2024; 16:1724. [PMID: 39599839 PMCID: PMC11599026 DOI: 10.3390/v16111724] [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: 09/01/2024] [Revised: 10/14/2024] [Accepted: 10/26/2024] [Indexed: 11/29/2024] Open
Abstract
Direct-acting antivirals (DAA) are effective in patients with hepatitis C virus (HCV) infection, but there is little information about real-world effectiveness in people living with human immunodeficiency virus (PLH). The aim of this study was to determinate the effectiveness of DAA to achieve sustained virologic response at week 12 post-treatment (SVR12) in PLH with HCV coinfection and in people with HCV-monoinfection. We conducted a prospective cohort. The full analysis set (FAS) included all subjects enrolled in the study; the modified analysis set (MAS) excluded cases with missing data to evaluate SVR12. A total of 278 people were included, 130 (46.7%) with HCV/HIV-coinfection and 148 (53.2%) with HCV-monoinfection. In the HCV/HIV-coinfection group, 82 (63%) received GLE/PIB for 8 weeks, 45 (34.6%) received SOF/VEL for 12 weeks, and 3 (2.3%) were treated with SOF/VEL + RBV for 12 weeks. In the HCV-monoinfection group, 62 (41.8%) received GLE/PIB for 8 weeks, 28 (18.9%) received SOF/VEL for 12 weeks, and 58 (39.1%) participants were treated with SOF/VEL + RBV for 12 weeks. In the FAS analysis, SVR12 was 81.6% in the HCV/HIV-coinfection group and 86.4% in the HCV-monoinfection group (p = 0.128). In the MAS analysis, both groups achieved 100% of SVR12. In this cohort, the effectiveness of DAA to achieve SVR12 was similar between HCV/HIV-coinfection and HCV-monoinfection cases, regardless of advanced liver disease with no differences between treatment regimens.
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Affiliation(s)
- Cristina Guadalupe Román López
- Internal Medicine Department, Hospital Regional No. 1 “Ignacio García Tellez”, Instituto Mexicano del Seguro Social, Mérida 97150, Yucatán, Mexico;
| | - Salma Triana González
- Infectious Diseases Department, Hospital de Infectologia “La Raza” National Medical Center, Instituto Mexicano del Seguro Social, Mexico City 02990, Mexico; (S.T.G.); (A.L.C.D.); (D.D.F.L.); (J.E.G.M.)
| | - Ana Luz Cano Díaz
- Infectious Diseases Department, Hospital de Infectologia “La Raza” National Medical Center, Instituto Mexicano del Seguro Social, Mexico City 02990, Mexico; (S.T.G.); (A.L.C.D.); (D.D.F.L.); (J.E.G.M.)
| | - Dulce Daniela Flores Lopez
- Infectious Diseases Department, Hospital de Infectologia “La Raza” National Medical Center, Instituto Mexicano del Seguro Social, Mexico City 02990, Mexico; (S.T.G.); (A.L.C.D.); (D.D.F.L.); (J.E.G.M.)
| | - José Antonio Mata Marín
- Infectious Diseases Department, Hospital de Infectologia “La Raza” National Medical Center, Instituto Mexicano del Seguro Social, Mexico City 02990, Mexico; (S.T.G.); (A.L.C.D.); (D.D.F.L.); (J.E.G.M.)
| | - Jesús Enrique Gaytán Martínez
- Infectious Diseases Department, Hospital de Infectologia “La Raza” National Medical Center, Instituto Mexicano del Seguro Social, Mexico City 02990, Mexico; (S.T.G.); (A.L.C.D.); (D.D.F.L.); (J.E.G.M.)
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19
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McKinley L, Acen IK, Alshannaq A, Christensen L, Dolan K, Kates A, Keating J, Musuuza J, Hollnagel F, Safdar N. Antiviral potential of spirulina in individuals with human immunodeficiency virus or Hepatis C virus infections: A systematic review and meta-analysis. Clin Nutr ESPEN 2024; 63:440-446. [PMID: 39003731 DOI: 10.1016/j.clnesp.2024.06.049] [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: 05/29/2024] [Revised: 06/21/2024] [Accepted: 06/27/2024] [Indexed: 07/16/2024]
Abstract
BACKGROUND Spirulina, a cyanobacterium or blue-green algae that contains phycocyanin, nutritional supplementation has been evaluated in patients living with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) due to its antiviral properties. This supplementation may be beneficial in low resource settings when awaiting antiretroviral therapy (ART) for HIV. This review aimed to evaluate the effectiveness of Spirulina supplement in antiviral-naïve HIV- and HCV-infected patients by assessing its immunological effect (Cluster of Differentiation 4 or CD-4 T-cell count) and disease progression (viral load). METHODS We searched PubMed, Cochrane Library, Scopus, and Web of Science from inception through January 23, 2024. Two authors independently performed the study selection, data extraction, and risk of bias assessment. We pooled data by using a random-effects model and evaluated publication bias by a funnel plot. RESULTS We identified 5552 articles, 5509 excluded at the title and abstract stage with 44 studies making it to the full text review. Of these 6 studies met the eligibility for inclusion in the final analysis as follows: 4 randomized controlled trials (RCTs) and 2 non-RCTs. The pooled results of the Spirulina intervention found significant improvements in biomarkers of clinical outcomes, viral load (VL) and CD4 T-cell (CD4) counts, in participants of the treatment group compared to controls; the VL had an overall Cohen's d effect size decrease of -2.49 (-4.80, -0.18) and CD4 had an overall effect size increase of 4.09 (0.75, 7.43). [Cohen's d benchmark: 0.2 = small effect; 0.5 = medium effect; 0.8 = large effect]. CONCLUSIONS Findings from this systematic review showed a potential beneficial effect of Spirulina supplementation in HIV- and HCV-infected patients by increasing CD4 counts and decreasing viral load. However, further research in larger controlled clinical trials is needed to fully investigate the effect of this nutritional supplement on clinically relevant outcomes, opportunities for intervention, optimal dose, and cost-benefit of Spirulina supplementation.
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Affiliation(s)
- Linda McKinley
- William S. Middleton Memorial Veterans Hospital, Madison, WI, USA.
| | | | - Ahmad Alshannaq
- University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Leslie Christensen
- University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Katherine Dolan
- University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Ashley Kates
- University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Julie Keating
- William S. Middleton Memorial Veterans Hospital, Madison, WI, USA; University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | | | - Fauzia Hollnagel
- University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Nasia Safdar
- William S. Middleton Memorial Veterans Hospital, Madison, WI, USA; University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
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20
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Dinh DA, Tan Y, Saeed S. Disengagement from Care Among People Co-Infected with HIV and HCV: A Scoping Review. AIDS Behav 2024; 28:3381-3403. [PMID: 38992228 DOI: 10.1007/s10461-024-04436-6] [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] [Accepted: 06/27/2024] [Indexed: 07/13/2024]
Abstract
Disengagement from care among people with HIV (PWH) and hepatitis C (HCV) increases the risks of adverse health outcomes and poses significant barriers to achieving global HIV and HCV elimination goals. In accordance with the Joanna Briggs Institute framework, a scoping review was conducted to synthesize and highlight existing gaps in the literature on (dis)engagement in care among PWH and HCV. We searched for original studies on (dis)engagement in care among PWH and HCV in high-income countries using eight electronic databases from inception to May 2023. Our search yielded 4462 non-duplicated records, which were scoped to 27 studies. Definitions of (dis)engagement in care were diverse, with considerable heterogeneity in how retention was operationalized and temporally measured. Studies identified predictors of (dis)engagement to be related to drug and substance use (n = 5 articles), clinical factors (n = 5), social and welfare (n = 4), and demographic characteristics (n = 2). When engagement in care was treated as an exposure, it was associated with HCV treatment initiation (n = 3), achieving sustained virological response (n = 2), and maintaining HIV viral suppression (n = 1). Interventions to improve care engagement among PWH and HCV were limited to five studies using cash incentives (n = 1) and individual case management (n = 4). (Dis)engagement in care is a dynamic process influenced by shifting priorities that may 'tip the balance' towards or away from regularly interacting with healthcare professionals. However, inconsistent definitions render cross-study comparisons and meta-analyses virtually impossible. Further research needs to establish a standardized definition to identify patients at high risk of disengagement and develop interventions that leverage the nested HIV/HCV care cascades to retain and recover patients lost from care.
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Affiliation(s)
- Duy A Dinh
- Faculty of Health Sciences, Queen's University, Kingston, ON, Canada
| | - Yvonne Tan
- Department of Medicine, Queen's University, Kingston, ON, Canada
| | - Sahar Saeed
- Department of Public Health Sciences, Queen's University, 203 Carruthers Hall 62 Fifth Field Company Lane, Kingston, ON, K7L 3N6, Canada.
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21
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Chiu I, Cano D, Leathers M, Turner CM, Trujillo D, Sicro S, Arayasirikul S, Taylor KD, Wilson EC, McFarland W. HIV and hepatitis C virus infection and co-infection among trans women in San Francisco, 2020. PLoS One 2024; 19:e0307990. [PMID: 39312538 PMCID: PMC11419358 DOI: 10.1371/journal.pone.0307990] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2023] [Accepted: 07/11/2024] [Indexed: 09/25/2024] Open
Abstract
BACKGROUND Transgender women (hereafter "trans women") face social marginalization, stigma, and discrimination and experience a high burden of HIV. More recently, trans women have been identified as having a high risk for hepatitis C (HCV) infection. The interaction between these two diseases and the risks for HIV/HCV co-infection among trans women are understudied. OBJECTIVE To characterize epidemiological, behavioral, and socio-structural interactions between HIV and HCV infections among trans women. METHODS This cross-sectional study examined data from a community-based survey of trans women in San Francisco recruited through respondent-driven sampling (RDS) in 2019/2020. Face-to-face interviews collected data on demographics, medical history, drug injection practices, sexual behavior, and socio-structural factors (e.g., poverty, housing insecurity, incarceration, social support). HIV and HCV antibodies were detected using oral fluid rapid tests and prior diagnosis and treatment were collected by self-report. Blood specimens were collected to confirm antibodies using ELISA. Multinomial logistic regression analysis characterized factors associated with HIV infection alone, HCV infection alone, and HIV/HCV co-infection compared to neither infection. RESULTS Among 201 trans women recruited, HIV prevalence was 42.3%; HCV infection by history or current seroprevalence was 28.9%; evidence for both HIV and HCV infection was present for 18.9%. Two-thirds of trans women (67.2%) had been incarcerated; 30.8% had ever injected drugs. History of injection drug use and receiving emotional support from family were factors found in common for HIV infection, HCV infection, and HIV/HCV co-infection compared to no infection. Having a sexual partner who injects drugs was associated with HIV infection alone. Not lacking care due to cost and older age were associated with co-infection. Older age was also associated with HCV infection. Of trans women with HIV infection, 91.8% had accessed HIV care, whereas only 62% with HCV had accessed some form of care. CONCLUSIONS Our study found high levels of HIV, HCV, and HIV/HCV co-infection among trans women in San Francisco. We found common associations between HIV and HCV through injection practices and emotional support, but having a sexual partner who injects drugs was not associated with HCV infection alone or co-infection. We note a substantial gap in the treatment of HCV for trans women, including those in HIV care, that needs to be urgently addressed.
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Affiliation(s)
- Izzy Chiu
- Fielding School of Public Health, University of California Los Angeles, Los Angeles, CA, United States of America
- Center for Public Health Research, San Francisco Department of Public Health, San Francisco, CA, United States of America
| | - Damiana Cano
- Center for Public Health Research, San Francisco Department of Public Health, San Francisco, CA, United States of America
- University of California Berkeley, Berkeley, CA, United States of America
| | - Matisse Leathers
- Center for Public Health Research, San Francisco Department of Public Health, San Francisco, CA, United States of America
- University of California Berkeley, Berkeley, CA, United States of America
| | - Caitlin M. Turner
- Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, United States of America
| | - Dillon Trujillo
- Fielding School of Public Health, University of California Los Angeles, Los Angeles, CA, United States of America
| | - Sofia Sicro
- Center for Public Health Research, San Francisco Department of Public Health, San Francisco, CA, United States of America
| | - Sean Arayasirikul
- Department of Health, Society, & Behavior, University of California, Irvine, Irvine, CA, United States of America
| | - Kelly D. Taylor
- Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, United States of America
| | - Erin C. Wilson
- Center for Public Health Research, San Francisco Department of Public Health, San Francisco, CA, United States of America
| | - Willi McFarland
- Center for Public Health Research, San Francisco Department of Public Health, San Francisco, CA, United States of America
- Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, United States of America
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22
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Dąbrowska M, Jaroszewicz J, Sitko M, Janocha-Litwin J, Zarębska-Michaluk D, Janczewska E, Lorenc B, Tudrujek-Zdunek M, Parfieniuk-Kowerda A, Klapaczyński J, Berak H, Socha Ł, Dobracka B, Dybowska D, Mazur W, Ważny Ł, Flisiak R. The Real-World Efficacy and Safety of Direct-Acting Antivirals for Chronic Hepatitis C in Patients Active Malignancies. Cancers (Basel) 2024; 16:3114. [PMID: 39272972 PMCID: PMC11394372 DOI: 10.3390/cancers16173114] [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: 08/11/2024] [Revised: 08/30/2024] [Accepted: 09/02/2024] [Indexed: 09/15/2024] Open
Abstract
BACKGROUND Over the past years, the introduction of direct-acting antivirals (DAAs) revolutionized chronic hepatitis C treatment. We aimed to characterize and assess treatment efficacy in three specific groups of patients treated with DAAs: those with active solid malignant tumors (SMTs), hematological diseases (HDs) and hepatocellular carcinomas (HCCs). METHODS A total of 203 patients with active oncological disease (SMT n = 61, HD = 67, HCC n = 74) during DAA treatment in 2015-2020 selected from the EpiTer-2 database were analyzed retrospectively and compared to 12,983 patients without any active malignancy. RESULTS Extrahepatic symptoms were more frequent in HD patients (17.2% vs. SMT = 10.3%, HCC = 8.2%, without = 7.8%, p = 0.004). HCC patients characterized with the highest ALT activity (81 IU/L vs. SMT = 59.5 IU/L, HD = 52 IU/L, without = 58 IU/L, p = 0.001) more often had F4 fibrosis as well (86.11% vs. SMT = 23.3%, HD = 28.8%, controls = 24.4%, p = 0.001). A significant majority of subjects in HCC, HD and SMT populations completed the full treatment plan (HCC = 91%; n = 67, HD = 97%; n = 65, SMT = 100%; n = 62). Concerning the treatment efficacy, the overall sustained virologic response, excluding non-virologic failures, was reported in 93.6% HD, 90.16% SMT and 80.6% in HCC patients. CONCLUSIONS As presented in our study, DAA therapy has proven to be highly effective and safe in patients with active SMTs and HDs. However, therapy discontinuations resulting from liver disease progression remain to be the major concern in HCC patients.
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Affiliation(s)
- Maria Dąbrowska
- Department of Infectious Diseases and Hepatology, Medical University of Silesia, 40-635 Katowice, Poland
| | - Jerzy Jaroszewicz
- Department of Infectious Diseases and Hepatology, Medical University of Silesia, 40-635 Katowice, Poland
| | - Marek Sitko
- Department of Infectious and Tropical Diseases, Jagiellonian University, 30-688 Kraków, Poland
| | - Justyna Janocha-Litwin
- Department of Infectious Diseases and Hepatology, Medical University Wroclaw, 51-149 Wroclaw, Poland
| | - Dorota Zarębska-Michaluk
- Department of Infectious Diseases and Allergology, Jan Kochanowski University, 25-317 Kielce, Poland
| | - Ewa Janczewska
- Department of Basic Medical Sciences, Faculty of Health Sciences, Medical University of Silesia, 41-902 Bytom, Poland
| | - Beata Lorenc
- Pomeranian Center of Infectious Diseases, Department of Infectious Diseases, Medical University of Gdańsk, 80-214 Gdańsk, Poland
| | - Magdalena Tudrujek-Zdunek
- Department of Infectious Diseases and Hepatology, Medical University of Lublin, 20-081 Lublin, Poland
| | - Anna Parfieniuk-Kowerda
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, 15-569 Białystok, Poland
| | - Jakub Klapaczyński
- Department of Internal Medicine and Hepatology, The National Institute of Medicine of the Ministry of Interior and Administration, 02-507 Warszawa, Poland
| | - Hanna Berak
- Daily Department of Hospital for Infectious Diseases in Warsaw, 01-201 Warszawa, Poland
| | - Łukasz Socha
- Department of Infectious Diseases, Hepatology and Liver Transplantation, Pomeranian Medical University, 71-455 Szczecin, Poland
| | | | - Dorota Dybowska
- Department of Infectious Diseases and Hepatology, Faculty of Medicine, Collegium Medicum Bydgoszcz, Nicolaus Copernicus University, 87-100 Toruń, Poland
| | - Włodzimierz Mazur
- Clinical Department of Infectious Diseases, Specialist Hospital in Chorzów, Medical University of Silesia, 41-500 Katowice, Poland
| | - Łukasz Ważny
- Department of Infectious Diseases and Hepatology, Medical University of Silesia, 40-635 Katowice, Poland
| | - Robert Flisiak
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, 15-569 Białystok, Poland
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23
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Yilma M, Houhong Xu R, Saxena V, Muzzin M, Tucker LY, Lee J, Mehta N, Mukhtar N. Survival Outcomes Among Patients With Hepatocellular Carcinoma in a Large Integrated US Health System. JAMA Netw Open 2024; 7:e2435066. [PMID: 39316399 PMCID: PMC11423175 DOI: 10.1001/jamanetworkopen.2024.35066] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 09/25/2024] Open
Abstract
Importance Hepatocellular carcinoma (HCC) is the leading oncologic cause of death among patients with cirrhosis, but large studies examining mortality trends are lacking. Objective To evaluate survival among patients with HCC in one of the largest integrated health care systems in the US. Design, Setting, and Participants This retrospective cohort study included 3441 adult patients who received a diagnosis of HCC between January 1, 2006, and December 31, 2019, with end of follow-up on December 31, 2020. The study period was further categorized as era 1, defined as 2006 to 2012, and era 2, defined as 2013 to 2019. Statistical analysis was conducted from January 2021 to June 2024. Exposures Patient demographic characteristics and disease factors. Main Outcomes and Measures All-cause and HCC-specific mortality were used as primary end points, and survival probabilities were estimated using the Kaplan-Meier method. Cox proportional hazards regression analyses were adjusted for age at diagnosis, sex, race and ethnicity, cause of disease, Barcelona Clinic Liver Cancer (BCLC) stage, alpha-fetoprotein level, and treatment type. Results Of 3441 patients with HCC, 2581 (75.0%) were men, and the median age was 65 years (IQR, 58-73 years). A total of 1195 patients (34.7%) received curative treatment, 1374 (39.9%) received noncurative treatment, and 872 (25.3%) received no treatment. During the study period, 2500 patients (72.7%) experienced all-cause mortality, and 1809 (52.6%) had HCC-specific mortality. In multivariable analysis, being 70 years of age or older (adjusted hazard ratio [AHR], 1.39; 95% CI, 1.22-1.59), male sex (AHR, 1.20; 95% CI, 1.07-1.35), BCLC stage C or D (AHR, 2.40; 95% CI, 2.15-2.67), increasing alpha-fetoprotein level (vs <20 ng/mL; 20-99 ng/mL: AHR, 1.20; 95% CI, 1.04-1.38; ≥1000 ng/mL: AHR, 2.84; 95% CI, 2.45-3.25), noncurative treatment (AHR, 2.51; 95% CI, 2.16-2.90), and no treatment (AHR, 3.15; 95% CI, 2.64-3.76) were associated with higher all-cause mortality, while Asian or Other Pacific Islander race and ethnicity (vs non-Hispanic White; AHR, 0.76; 95% CI, 0.65-0.88) was associated with lower all-cause mortality. Survival improved in diagnosis era 2 (2013-2019; n = 2007) compared with diagnosis era 1 (2006-2012; n = 1434). Conclusions and Relevance This large, racially and ethnically diverse cohort study of patients with HCC found improving survival over time, especially among individuals with early-stage HCC receiving potentially curative treatments. This study highlights the importance of surveillance for detection of HCC at early stages, particularly among groups at risk for poorer outcomes.
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Affiliation(s)
- Mignote Yilma
- General Surgery, University of California, San Francisco
- National Clinician Scholars Program, San Francisco, California
| | | | - Varun Saxena
- Department of Gastroenterology, Kaiser Permanente South San Francisco Medical Center, San Francisco, California
- Department of Medicine, University of California, San Francisco
| | - Monica Muzzin
- Department of Gastroenterology, Kaiser Permanente San Francisco Medical Center, San Francisco
| | - Lue-Yen Tucker
- Division of Research, Kaiser Permanente, Oakland, California
| | - Jeffrey Lee
- Division of Research, Kaiser Permanente, Oakland, California
- Department of Gastroenterology, Kaiser Permanente San Francisco Medical Center, San Francisco
| | - Neil Mehta
- Department of Medicine, University of California, San Francisco
| | - Nizar Mukhtar
- Department of Gastroenterology, Kaiser Permanente San Francisco Medical Center, San Francisco
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24
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Smirne C, Crobu MG, Gerevini C, Berton AM, Rapetti R, Pasini B, Ravanini P, Pirisi M. The Impact of the G6PD Gene Mutations in Patients with Chronic Hepatitis C Infection Treated with Direct-Acting Antivirals: A Multicenter Observational Study. Genes (Basel) 2024; 15:1116. [PMID: 39336707 PMCID: PMC11431558 DOI: 10.3390/genes15091116] [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: 07/22/2024] [Revised: 08/20/2024] [Accepted: 08/22/2024] [Indexed: 09/30/2024] Open
Abstract
Following the advent of direct-acting antivirals (DAAs), the treatment of hepatitis C virus (HCV) infection is now rarely challenging. However, data are still limited concerning DAA use in patients affected by glucose-6-phosphate dehydrogenase deficiency (G6PDd). Based on these considerations, the goal of this study was to evaluate the effectiveness and safety of DAAs in this subpopulation. A retrospective multicenter observational study (2015-2023) was conducted on all 2754 consecutive HCV-positive patients treated with first- and second-generation all-oral DAAs, and with a G6PDd diagnosis confirmed by quantitative testing (n = 38). At the treating clinician's discretion, an enhanced clinical and laboratory follow-up was performed, generally on a monthly basis both during treatment and up to six months after the end of it. Concerning hematochemical parameters, no significant differences were found between any considered time point. In all cases, no treatment-related adverse events were reported, and virologic response rates were as expected without G6PDd. In conclusion, in a large experience which, to the best of our knowledge, is unprecedented in the literature, the treatment of HCV hepatitis with nearly all available DAAs in patients with G6PDd as a comorbidity-a common occurrence in countries such as Italy-proved to be highly effective and safe.
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Affiliation(s)
- Carlo Smirne
- Internal Medicine Unit, Maggiore della Carità Hospital, 28100 Novara, Italy; (C.G.); (R.R.); (M.P.)
- Department of Translational Medicine, University of Piemonte Orientale, 28100 Novara, Italy
| | - Maria Grazia Crobu
- Laboratory of Molecular Virology, Maggiore della Carità Hospital, 28100 Novara, Italy; (M.G.C.); (P.R.)
- Clinical Biochemistry Laboratory, City of Health and Science University Hospital, 10126 Turin, Italy
| | - Chiara Gerevini
- Internal Medicine Unit, Maggiore della Carità Hospital, 28100 Novara, Italy; (C.G.); (R.R.); (M.P.)
| | - Alessandro Maria Berton
- Division of Endocrinology, Diabetes and Metabolism, City of Health and Science University Hospital, 10126 Turin, Italy;
| | - Rachele Rapetti
- Internal Medicine Unit, Maggiore della Carità Hospital, 28100 Novara, Italy; (C.G.); (R.R.); (M.P.)
| | - Barbara Pasini
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy;
- Division of Medical Genetics, City of Health and Science University Hospital, 10126 Turin, Italy
| | - Paolo Ravanini
- Laboratory of Molecular Virology, Maggiore della Carità Hospital, 28100 Novara, Italy; (M.G.C.); (P.R.)
| | - Mario Pirisi
- Internal Medicine Unit, Maggiore della Carità Hospital, 28100 Novara, Italy; (C.G.); (R.R.); (M.P.)
- Department of Translational Medicine, University of Piemonte Orientale, 28100 Novara, Italy
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25
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Khalil R, Al-Mahzoum K, Barakat M, Sallam M. An Increase in the Prevalence of Clinically Relevant Resistance-Associated Substitutions in Four Direct-Acting Antiviral Regimens: A Study Using GenBank HCV Sequences. Pathogens 2024; 13:674. [PMID: 39204274 PMCID: PMC11356961 DOI: 10.3390/pathogens13080674] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2024] [Revised: 08/01/2024] [Accepted: 08/08/2024] [Indexed: 09/03/2024] Open
Abstract
Direct-acting antivirals (DAAs) revolutionized the therapeutics of chronic hepatitis C. The emergence and transmission of HCV variants with resistance-associated substitutions (RASs) can undermine HCV treatment. This study aimed to assess the prevalence and temporal trends of RASs in HCV, with a particular focus on clinically relevant RASs (cr-RASs). Near-complete HCV GenBank sequences archived in the Los Alamos HCV Database were analyzed. The study period was divided into two phases: before 2011 and from 2011 onward. Identification of RASs across three DAA classes (NS3, NS5A, and NS5B inhibitors) was based on the 2020 EASL guidelines. The AASLD-IDSA recommendations were used to identify cr-RASs for three HCV genotypes/subtypes (1a, 1b, and 3) and four DAA regimens: ledipasvir/sofosbuvir; elbasvir/grazoprevir; sofosbuvir/velpatasvir; and glecaprevir/pibrentasvir. The final HCV dataset comprised 3443 sequences, and the prevalence of RASs was 50.4%, 60.2%, and 25.3% in NS3, NS5A, and NS5B, respectively. In subtype 1a, resistance to ledipasvir/sofosbuvir was 32.8%, while resistance to elbasvir/grazoprevir was 33.0%. For genotype 3, resistance to sofosbuvir/velpatasvir and glecaprevir/pibrentasvir was 4.2% and 24.9%, respectively. A significant increase in cr-RASs was observed across the two study phases as follows: for ledipasvir/sofosbuvir in subtype 1a, cr-RASs increased from 30.2% to 35.8% (p = 0.019); for elbasvir/grazoprevir in subtype 1a, cr-RASs increased from 30.4% to 36.1% (p = 0.018); In subtype 1b, neither ledipasvir/sofosbuvir nor elbasvir/grazoprevir showed any cr-RASs in the first phase, but both were present at a prevalence of 6.5% in the second phase (p < 0.001); for sofosbuvir/velpatasvir in genotype 3, cr-RASs increased from 0.9% to 5.2% (p = 0.006); and for glecaprevir/pibrentasvir, cr-RASs increased from 12.0% to 29.1% (p < 0.001). The rising prevalence of HCV RASs and cr-RASs was discernible. This highlights the necessity for ongoing surveillance and adaptation of novel therapeutics to manage HCV resistance effectively. Updating the clinical guidelines and treatment regimens is recommended to counteract the evolving HCV resistance to DAAs.
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Affiliation(s)
- Roaa Khalil
- Department of Pathology, Microbiology and Forensic Medicine, School of Medicine, The University of Jordan, Amman 11942, Jordan
| | - Kholoud Al-Mahzoum
- Department of Pathology, Microbiology and Forensic Medicine, School of Medicine, The University of Jordan, Amman 11942, Jordan
| | - Muna Barakat
- Department of Clinical Pharmacy and Therapeutics, Faculty of Pharmacy, Applied Science Private University, Amman 11931, Jordan
| | - Malik Sallam
- Department of Pathology, Microbiology and Forensic Medicine, School of Medicine, The University of Jordan, Amman 11942, Jordan
- Department of Clinical Laboratories and Forensic Medicine, Jordan University Hospital, Amman 11942, Jordan
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26
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Fahmy SN, Khedr LH, Wahdan SA, Menze ET, Azab SS, El-Demerdash E. Effect of carvedilol on pharmacokinetics of sofosbuvir and its metabolite GS-331007: role of P-glycoprotein. J Pharm Pharmacol 2024; 76:1051-1064. [PMID: 38850570 DOI: 10.1093/jpp/rgae070] [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: 02/15/2024] [Accepted: 05/31/2024] [Indexed: 06/10/2024]
Abstract
Sofosbuvir (SOF) is a P-glycoprotein (P-gp) substrate, and carvedilol (CAR) is an inhibitor of P-gp, suggesting that it may affect the oral pharmacokinetics and safety of SOF. The current study investigated the pharmacokinetic interaction of CAR with SOF and its metabolite, GS-331007, and the possible consequent toxicities in rats. To assess the pharmacokinetics of SOF and GS-331007, rats were divided into three groups; all received a single oral dose of SOF preceded with saline (SAL), verapamil (VER) as a standard P-gp inhibitor, or CAR, respectively. The serosal, plasma, and hepatic tissue contents of SOF and GS-331007 were assessed using LC-MS/MS. Renal and hepatic toxicities were assessed using biochemical and histopathological tests. Serosal and plasma concentrations of SOF and GS-331007 were increased in the presence of CAR, suggesting a significant inhibitory effect of CAR on intestinal P-gp. Simultaneously, the pharmacokinetic profile of SOF showed a significant increase in the Cmax, AUC(0-t), AUC (0-∞), t1/2, and a reduction in its apparent oral clearance. While the pharmacokinetic profile of GS-331007 was not significantly affected. However, this notable elevation in drug oral bioavailability was corroborated by a significant alteration in renal functions. Hence, further clinical investigations are recommended to ensure the safety and dosing of CAR/SOF combination.
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Affiliation(s)
- Salma N Fahmy
- Pharmacology & Toxicology Department, Faculty of Pharmacy, Misr International University (MIU), Cairo, Egypt
| | - Lobna H Khedr
- Pharmacology & Toxicology Department, Faculty of Pharmacy, Misr International University (MIU), Cairo, Egypt
| | - Sara A Wahdan
- Pharmacology & Toxicology Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt
- Preclinical & Translational Research Center, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt
| | - Esther T Menze
- Pharmacology & Toxicology Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt
| | - Samar S Azab
- Pharmacology & Toxicology Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt
| | - Ebtehal El-Demerdash
- Pharmacology & Toxicology Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt
- Preclinical & Translational Research Center, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt
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27
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Tok D. Analysis of articles on hepatitis C by scientific mapping: 1989-2022. World J Clin Cases 2024; 12:4301-4316. [PMID: 39015889 PMCID: PMC11235547 DOI: 10.12998/wjcc.v12.i20.4301] [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: 02/22/2024] [Revised: 05/01/2024] [Accepted: 05/24/2024] [Indexed: 06/30/2024] Open
Abstract
BACKGROUND Hepatitis C virus (HCV) poses a significant quandary about public health. It is challenging to study the literature in a particular discipline comprehensively today. One solution is bibliometric analysis, which is often used to track the attributes and evolutionary trajectories of scientific outputs. AIM To examine the 35-year scientific evolution of articles focused on HCV. METHODS This study examined the 35-year scientific evolution of articles focused on HCV. Our study utilized the Web of Science database. The study encompassed a total of 11930 articles. RESULTS Regarding the cumulative count of articles, the leading countries are the United States, Japan, and Italy. Rice CM is the author with the highest recorded H-index and G-index values. The journal with the highest recorded H-index and G-index values is the Journal of Virology. The Journal of Viral Hepatitis contributed 10.94% of the articles, whereas the Journal of Virology published 9.68%. According to the strategic diagram, the keywords most frequently used in 2020-2022 are HCV, epidemiology, and sofosbuvir. CONCLUSION This study provides valuable information about 40 years of academic knowledge on HCV.
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Affiliation(s)
- Duran Tok
- Department of Infectious Diseases, Liv Hospital, Ankara 06100, Türkiye
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28
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Seurre C, Roca Suarez AA, Testoni B, Zoulim F, Grigorov B. After the Storm: Persistent Molecular Alterations Following HCV Cure. Int J Mol Sci 2024; 25:7073. [PMID: 39000179 PMCID: PMC11241208 DOI: 10.3390/ijms25137073] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2024] [Revised: 06/24/2024] [Accepted: 06/26/2024] [Indexed: 07/16/2024] Open
Abstract
The development of direct-acting antivirals (DAAs) against hepatitis C virus (HCV) has revolutionized the management of this pathology, as their use allows viral elimination in a large majority of patients. Nonetheless, HCV remains a major public health problem due to the multiple challenges associated with its diagnosis, treatment availability and development of a prophylactic vaccine. Moreover, HCV-cured patients still present an increased risk of developing hepatic complications such as hepatocellular carcinoma. In the present review, we aim to summarize the impact that HCV infection has on a wide variety of peripheral and intrahepatic cell populations, the alterations that remain following DAA treatment and the potential molecular mechanisms implicated in their long-term persistence. Finally, we consider how recent developments in single-cell multiomics could refine our understanding of this disease in each specific intrahepatic cell population and drive the field to explore new directions for the development of chemo-preventive strategies.
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Affiliation(s)
- Coline Seurre
- INSERM U1052, CNRS 5286, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Université Claude Bernard Lyon 1, 69434 Lyon, France; (C.S.); (A.A.R.S.); (B.T.); (F.Z.)
- The Lyon Hepatology Institute EVEREST, 69003 Lyon, France
| | - Armando Andres Roca Suarez
- INSERM U1052, CNRS 5286, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Université Claude Bernard Lyon 1, 69434 Lyon, France; (C.S.); (A.A.R.S.); (B.T.); (F.Z.)
- The Lyon Hepatology Institute EVEREST, 69003 Lyon, France
| | - Barbara Testoni
- INSERM U1052, CNRS 5286, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Université Claude Bernard Lyon 1, 69434 Lyon, France; (C.S.); (A.A.R.S.); (B.T.); (F.Z.)
- The Lyon Hepatology Institute EVEREST, 69003 Lyon, France
| | - Fabien Zoulim
- INSERM U1052, CNRS 5286, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Université Claude Bernard Lyon 1, 69434 Lyon, France; (C.S.); (A.A.R.S.); (B.T.); (F.Z.)
- The Lyon Hepatology Institute EVEREST, 69003 Lyon, France
- Hospices Civils de Lyon, 69002 Lyon, France
| | - Boyan Grigorov
- INSERM U1052, CNRS 5286, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Université Claude Bernard Lyon 1, 69434 Lyon, France; (C.S.); (A.A.R.S.); (B.T.); (F.Z.)
- The Lyon Hepatology Institute EVEREST, 69003 Lyon, France
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29
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Sallam M, Khalil R. Contemporary Insights into Hepatitis C Virus: A Comprehensive Review. Microorganisms 2024; 12:1035. [PMID: 38930417 PMCID: PMC11205832 DOI: 10.3390/microorganisms12061035] [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: 04/30/2024] [Revised: 05/15/2024] [Accepted: 05/20/2024] [Indexed: 06/28/2024] Open
Abstract
Hepatitis C virus (HCV) remains a significant global health challenge. Approximately 50 million people were living with chronic hepatitis C based on the World Health Organization as of 2024, contributing extensively to global morbidity and mortality. The advent and approval of several direct-acting antiviral (DAA) regimens significantly improved HCV treatment, offering potentially high rates of cure for chronic hepatitis C. However, the promising aim of eventual HCV eradication remains challenging. Key challenges include the variability in DAA access across different regions, slightly variable response rates to DAAs across diverse patient populations and HCV genotypes/subtypes, and the emergence of resistance-associated substitutions (RASs), potentially conferring resistance to DAAs. Therefore, periodic reassessment of current HCV knowledge is needed. An up-to-date review on HCV is also necessitated based on the observed shifts in HCV epidemiological trends, continuous development and approval of therapeutic strategies, and changes in public health policies. Thus, the current comprehensive review aimed to integrate the latest knowledge on the epidemiology, pathophysiology, diagnostic approaches, treatment options and preventive strategies for HCV, with a particular focus on the current challenges associated with RASs and ongoing efforts in vaccine development. This review sought to provide healthcare professionals, researchers, and policymakers with the necessary insights to address the HCV burden more effectively. We aimed to highlight the progress made in managing and preventing HCV infection and to highlight the persistent barriers challenging the prevention of HCV infection. The overarching goal was to align with global health objectives towards reducing the burden of chronic hepatitis, aiming for its eventual elimination as a public health threat by 2030.
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Affiliation(s)
- Malik Sallam
- Department of Pathology, Microbiology and Forensic Medicine, School of Medicine, The University of Jordan, Amman 11942, Jordan
- Department of Clinical Laboratories and Forensic Medicine, Jordan University Hospital, Amman 11942, Jordan
| | - Roaa Khalil
- Department of Pathology, Microbiology and Forensic Medicine, School of Medicine, The University of Jordan, Amman 11942, Jordan
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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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31
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Abdelaziz SMH. Morphometric, biochemical and histopathological effects of sofosbuvir (sovaldi) on testes of adult male albino rats. Ultrastruct Pathol 2024; 48:94-107. [PMID: 38160400 DOI: 10.1080/01913123.2023.2295453] [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: 09/19/2023] [Accepted: 12/12/2023] [Indexed: 01/03/2024]
Abstract
Sofosbuvir treatment regimens for chronic HCV infection have recently been linked to extra hepatic side effects. This study aimed to show how sofosbuvir affected the adult male albino rat testis. Forty adult male albino rats were used. The rats were equally split into two main groups (I and II), then each group subdivided into two subgroups (A and B). Each rat in group I (control) received 0.5 ml of distilled water every day for four weeks. Each rat in group II (sofosbuvir-treated) received 0.5 ml of distilled water containing 7.2 mg of sofosbuvir every day for four weeks. After four weeks (subgroups IA and IIA) and eight weeks (subgroups IB and IIB) of treatment, the rats were sacrificed. Histological, biochemical, and morphometric studies on the testes were conducted. The data were analyzed. Examination of testes of sovaldi treated group revealed histopathological changes. Biochemical and morphometric analysis showed reduced levels of reduced glutathione and seminiferous tubule epithelial height respectively. Following a 4-week drug withdrawal period, the testes only partially recovered. We concluded that sofosbuvir induced deteriorating changes in the adult male albino rats' testes. These changes were proved by histological and biochemical studies. These changes were incompletely reversible after cession of treatment. Researches investigating the effect of adding drugs that have antioxidant properties during sofosbuvir therapy are recommended.
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Affiliation(s)
- Safaa M H Abdelaziz
- Department of Anatomy and Physiology, College of Medicine, Imam Mohammad Ibn Saud Islamic University, Riyadh, Saudi Arabia
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32
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Jarasvaraparn C, Hartley C, Karnsakul W. Updated Clinical Guidelines on the Management of Hepatitis C Infection in Children. Pathogens 2024; 13:180. [PMID: 38392918 PMCID: PMC10891648 DOI: 10.3390/pathogens13020180] [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: 12/15/2023] [Revised: 01/30/2024] [Accepted: 02/12/2024] [Indexed: 02/25/2024] Open
Abstract
Children represent only a small proportion of those infected with the hepatitis C virus (HCV) compared to adults. Nevertheless, a substantial number of children have chronic HCV infection and are at risk of complications including cirrhosis, portal hypertension, hepatic decompensation with hepatic encephalopathy, and hepatocellular carcinoma in adulthood. The overall prevalence of the HCV in children was estimated to be 0.87% worldwide. The HCV spreads through the blood. Children born to women with chronic hepatitis C should be evaluated and tested for HCV due to the known risk of infection. The course of treatment for hepatitis C depends on the type of HCV. Currently, there are two pan-genotype HCV treatments (Glecaprevir/pibrentasvir and Sofosbuvir/velpatasvir) for children. We aim to review the updated clinical guidelines on the management of HCV infection in children, including screening, diagnosis, and long-term monitoring, as well as currently published clinical trials and ongoing research on direct acting antiviral hepatitis C treatment in children.
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Affiliation(s)
- Chaowapong Jarasvaraparn
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Indiana University School of Medicine, Indianapolis, IN 46201, USA
| | - Christopher Hartley
- Department of Pharmacy, The Johns Hopkins Hospital, Baltimore, MD 21287, USA;
| | - Wikrom Karnsakul
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA;
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33
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Martino SD, Petri GL, De Rosa M. Hepatitis C: The Story of a Long Journey through First, Second, and Third Generation NS3/4A Peptidomimetic Inhibitors. What Did We Learn? J Med Chem 2024; 67:885-921. [PMID: 38179950 DOI: 10.1021/acs.jmedchem.3c01971] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2024]
Abstract
Hepatitis C viral (HCV) infection is the leading cause of liver failure and still represents a global health burden. Over the past decade, great advancements made HCV curable, and sustained viral remission significantly improved to more than 98%. Historical treatment with pegylated interferon alpha and ribavirin has been displaced by combinations of direct-acting antivirals. These regimens include drugs targeting different stages of the HCV life cycle. However, the emergence of viral resistance remains a big concern. The design of peptidomimetic inhibitors (PIs) able to fit and fill the conserved substrate envelope region within the active site helped avoid contact with the vulnerable sites of the most common resistance-associated substitutions Arg155, Ala156, and Asp168. Herein, we give an overview of HCV NS3 PIs discovered during the past decade, and we deeply discuss the rationale behind the structural optimization efforts essential to achieve pangenotypic activity.
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Affiliation(s)
- Simona Di Martino
- Drug Discovery Unit, Medicinal Chemistry Group, Ri.MED Foundation, Palermo 90133, Italy
| | - Giovanna Li Petri
- Drug Discovery Unit, Medicinal Chemistry Group, Ri.MED Foundation, Palermo 90133, Italy
| | - Maria De Rosa
- Drug Discovery Unit, Medicinal Chemistry Group, Ri.MED Foundation, Palermo 90133, Italy
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34
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Kung VL, Giannini G, Nast CC. Kidney Histopathology of Patients with Hepatitis C Infection and Diabetes Mellitus before and after Availability of Direct-Acting Antiviral Therapy. GLOMERULAR DISEASES 2024; 4:74-83. [PMID: 38623264 PMCID: PMC11018331 DOI: 10.1159/000537977] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/09/2023] [Accepted: 02/19/2024] [Indexed: 04/17/2024]
Abstract
Introduction Type 2 diabetes mellitus (DM) and diabetic kidney disease are increasing. Hepatitis C infection (HCV) occurs in 1% of the world population and can induce several kidney diseases. DM prevalence is increased in individuals with HCV; however, kidney diseases in those with both DM and HCV have not been assessed. Direct-acting antiviral agents (DAAs) became available for HCV treatment in 2014; it is unknown if DAAs altered the spectrum of kidney disease in patients with DM and HCV. Methods Case review identifying patients with kidney biopsy and clinical history of DM and HCV between 2009-2013 (pre-DAA) and 2016-2020 (post-DAA), excluding kidney transplant, hepatitis B, HIV, and inadequate biopsy, identified 245 biopsies. Biopsies were evaluated for diabetic glomerulosclerosis (DGS) class, global and focal segmental glomerulosclerosis (FSGS), other glomerular diseases, interstitial fibrosis/tubular atrophy (IFTA), interstitial nephritis, acute tubular injury and degree of arterial and arteriolar sclerosis. Kidney disease differences in pre-DAA versus post-DAA eras and in mild versus severe DGS were assessed by χ2 and Fisher's exact tests. Results The most common non-DGS lesions were non-collapsing FSGS (41%), HCV-related IgM dominant immune complex glomerulonephritis (IgM-ICGN, 18%), IgA nephropathy (9%), and membranoproliferative glomerulonephritis (MPGN, 7%). Collapsing FSGS was more common pre-DAA versus post-DAA (8% vs. 1%, p = 0.03). Biopsies from patients with HCV and DM were reduced in post-DAA (0.7%) versus pre-DAA (1.3%) (p < 0.0001). Post-DAA there were less MPGN (2% vs. 10%, p = 0.02) and more advanced DGS (85% vs. 61%, p = 0.0002), non-collapsing FSGS (57% vs. 31%, p < 0.0001), IFTA (2.0 vs. 1.6, p = 0.0002), and vascular sclerosis (2.1 vs. 1.6, p < 0.0001). Conclusion Post-DAA there were reduced biopsies and MPGN, with more severe DGS class, non-collapsing FSGS, IFTA, and chronic vascular changes. This suggests a modulating effect of DAAs on HCV-related kidney pathology with DM and chronic changes driving indications for kidney biopsy.
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Affiliation(s)
- Vanderlene L Kung
- Department of Pathology and Laboratory Medicine, Oregon Health and Science University, Portland, OR, USA
| | - Gabriel Giannini
- Department of Pathology, Yosemite Pathology Medical Group, Modesto, CA, USA
| | - Cynthia C Nast
- Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, CA, USA
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35
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Kamal S, Shahzad A, Rehman K, Tariq K, Akash MSH, Imran M, Assiri MA. Therapeutic Intervention of Serine Protease Inhibitors against Hepatitis C Virus. Curr Med Chem 2024; 31:2052-2072. [PMID: 37855348 DOI: 10.2174/0109298673234823230921090431] [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: 11/16/2022] [Revised: 05/12/2023] [Accepted: 05/23/2023] [Indexed: 10/20/2023]
Abstract
Hepatitis C virus (HCV) is a globally prevalent and hazardous disorder that is responsible for inducing several persistent and potentially fatal liver diseases. Current treatment strategies offer limited efficacy, often accompanied by severe and debilitating adverse effects. Consequently, there is an urgent and compelling need to develop novel therapeutic interventions that can provide maximum efficacy in combating HCV while minimizing the burden of adverse effects on patients. One promising target against HCV is the NS3-4A serine protease, a complex composed of two HCV-encoded proteins. This non-covalent heterodimer is crucial in the viral life cycle and has become a primary focus for therapeutic interventions. Although peginterferon, combined with ribavirin, is commonly employed for HCV treatment, its efficacy is hampered by significant adverse effects that can profoundly impact patients' quality of life. In recent years, the development of direct-acting antiviral agents (DAAs) has emerged as a breakthrough in HCV therapy. These agents exhibit remarkable potency against the virus and have demonstrated fewer adverse effects when combined with other DAAs. However, it is important to note that there is a potential for developing resistance to DAAs due to alterations in the amino acid position of the NS3-4A protease. This emphasizes the need for ongoing research to identify strategies that can minimize the emergence of resistance and ensure long-term effectiveness. While the combination of DAAs holds promise for HCV treatment, it is crucial to consider the possibility of drug-drug interactions. These interactions may occur when different DAAs are used concurrently, potentially compromising their therapeutic efficacy. Therefore, carefully evaluating and monitoring potential drug interactions are vital to optimize treatment outcomes. In the pursuit of novel therapeutic interventions for HCV, the field of computational biology and bioinformatics has emerged as a valuable tool. These advanced technologies and methodologies enable the development and design of new drugs and therapeutic agents that exhibit maximum efficacy, reduced risk of resistance, and minimal adverse effects. By leveraging computational approaches, researchers can efficiently screen and optimize potential candidates, accelerating the discovery and development of highly effective treatments for HCV, treatments.
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Affiliation(s)
- Shagufta Kamal
- Department of Biochemistry, Government College University, Faisalabad, Pakistan
| | - Asif Shahzad
- Department of Biochemistry, Government College University, Faisalabad, Pakistan
| | - Kanwal Rehman
- Department of Pharmacy, The Women University, Multan, Pakistan
| | - Komal Tariq
- Department of Biochemistry, Government College University, Faisalabad, Pakistan
| | | | - Muhammad Imran
- Research center for Advanced Materials Science (RCAMS), King Khalid University, Abha, Saudi Arabia
- Department of Chemistry, Faculty of Science, King Khalid University, Abha, Saudi Arabia
| | - Mohammed Ali Assiri
- Research center for Advanced Materials Science (RCAMS), King Khalid University, Abha, Saudi Arabia
- Department of Chemistry, Faculty of Science, King Khalid University, Abha, Saudi Arabia
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36
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Kumar A, Narang RK, Bhatia R. Recent advancements in NS5B inhibitors (2011-2021): Structural insights, SAR studies and clinical status. J Mol Struct 2023; 1293:136272. [DOI: 10.1016/j.molstruc.2023.136272] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/30/2025]
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37
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Garza KY, Pandey A, Marzinke MA. Development and validation of a liquid chromatographic-tandem mass spectrometric assay for the quantification of the direct acting antivirals glecaprevir and pibrentasvir in plasma. J Pharm Biomed Anal 2023; 235:115629. [PMID: 37619293 DOI: 10.1016/j.jpba.2023.115629] [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: 06/27/2023] [Revised: 07/31/2023] [Accepted: 08/04/2023] [Indexed: 08/26/2023]
Abstract
BACKGROUND Direct acting antiviral (DAA) therapies are effective in the treatment and management of chronic HCV infections. Glecaprevir (GLE) and pibrentasvir (PIB) are pangenotypic DAAs that are delivered alone or as a fixed-dose oral formulation to treat chronic HCV infections with or without cirrhosis. Sensitive and dynamic bioanalytical assays are needed to understand the pharmacology of GLE and PIB. METHODS Drug free K2EDTA plasma was spiked with GLE, PIB, and their internal standards. Drugs were extracted from plasma via protein precipitation, and subsequently quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The method was validated according to regulatory recommendations, and evaluated in remnant plasma samples from individuals prescribed GLE and PIB. RESULTS The analytical measuring ranges for GLE and PIB were 0.25-2000 ng/mL and 0.25-1000 ng/mL, respectively. The method showed acceptable accuracy and precision for both DAAs. GLE and PIB in plasma were stable following six freeze thaw cycles and at room temperature for up to 67 h. All analytes were stable in whole blood incubated at room temperature for 24 h, and at 40 °C and 100% humidity for 2 h. Negligible percent matrix effects were observed for PIB and PIB-IS across the measuring range of the assay. Significant ion suppression was observed for GLE, with an average matrix effects of 27.9%. However, relative matrix effects were < 6.3% between drug and internal standard, and deemed acceptable. Assay validation assessments in alternative matrices also met acceptance criteria. Both DAAs were successfully measured in remnant plasma samples from individuals administered GLE and PIB. CONCLUSIONS An LC-MS/MS method for GLE and PIB quantification in plasma has been developed and validated. The assay met acceptable performance criteria and may be used in downstream applications to characterize DAA pharmacology for HCV treatment.
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Affiliation(s)
- Kyana Y Garza
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Aashish Pandey
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Mark A Marzinke
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
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38
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Mandal A, Hazra B. Medicinal plant molecules against hepatitis C virus: Current status and future prospect. Phytother Res 2023; 37:4353-4374. [PMID: 37439007 DOI: 10.1002/ptr.7936] [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: 05/16/2023] [Revised: 06/16/2023] [Accepted: 06/21/2023] [Indexed: 07/14/2023]
Abstract
Hepatitis C virus (HCV), a global malady, causes acute and chronic hepatitis leading to permanent liver damage, hepatocellular carcinoma, and death. Modern anti-HCV therapies are efficient, but mostly inaccessible for residents of underdeveloped regions. To innovate more effective treatments at affordable cost, medicinal plant-based products need to be explored. The aim of this article is to review plant constituents in the light of putative anti-HCV mechanisms of action, and discuss existing problems, challenges, and future directions for their potential application in therapeutic settings. One hundred sixty literatures were collected by using appropriate search strings via scientific search engines: Google Scholar, PubMed, ScienceDirect, and Scopus. Bibliography was prepared using Mendeley desktop software. We found a substantial number of plants that were reported to inhibit different stages of HCV life cycle. Traditional medicinal plants such as Phyllanthus amarus Schumach. and Thonn., Eclipta alba (L.) Hassk., and Acacia nilotica (L.) Delile exhibited strong anti-HCV activities. Again, several phytochemicals such as epigallocatechin-3-gallate, honokilol, punicalagin, and quercetin have shown broad-spectrum anti-HCV effect. We have presented promising phytochemicals like silymarin, curcumin, glycyrrhizin, and camptothecin for nanoparticle-based hepatocyte-targeted drug delivery. Nevertheless, only a few animal studies have been performed to validate the anti-HCV effect of these plant products. Again, insufficient clinical evaluation of the safety and effectiveness of herbal medications remain a problem. Selected plants products could be developed as novel therapeutics for HCV patients only after scrupulous evaluation of their safety and efficacy in a clinical set-up.
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Affiliation(s)
- Anirban Mandal
- Department of Microbiology, Mrinalini Datta Mahavidyapith, Birati, Kolkata, India
| | - Banasri Hazra
- Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India
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Izhari MA. Molecular Mechanisms of Resistance to Direct-Acting Antiviral (DAA) Drugs for the Treatment of Hepatitis C Virus Infections. Diagnostics (Basel) 2023; 13:3102. [PMID: 37835845 PMCID: PMC10572573 DOI: 10.3390/diagnostics13193102] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2023] [Revised: 09/23/2023] [Accepted: 09/28/2023] [Indexed: 10/15/2023] Open
Abstract
Hepatitis C virus (HCV) is a hepatotropic virus that affects millions of human lives worldwide. Direct-acting antiviral (DAA) regimens are the most effective HCV treatment option. However, amino acid substitution-dependent resistance to DAAs has been a major challenge. This study aimed to determine the increasing risk of DAA resistance due to substitutions in DAA target non-structural proteins (NS3/4A, NS5A, and NS5B). Using a Sequence Retrieval System (SRS) at the virus pathogen resource (ViPR/BV-BRC), n = 32763 target protein sequences were retrieved and analyzed for resistance-associated amino acid substitutions (RAASs) by the Sequence Feature Variant Type (SFVT) antiviral-resistance assessment modeling tool. Reference target protein sequences with 100% identity were retried from UniProt following NCBI BLAST. The types and locations of RAASs were identified and visualized by AlphaFold and PyMol. Linux-r-base/R-studio was used for the data presentation. Multi-drug-resistant variants of NS3/4A in genotype 1 (n = 9) and genotype 5 (n = 5) along with DAA-specific NS3/4A, NS5A, and NS5B variants were identified pan-genotypically. A total of 27 variants (RAASs) of all the targets were identified. Fourteen genotype 1-specific substitutions: V1196A, V1158I, D1194A/T/G, R1181K, T1080S, Q1106R, V1062A, S1148G, A1182V, Y2065N, M2000T, and L2003V were identified. The most frequent substitutions were V1062L and L2003M, followed by Q2002H. L2003V, Q2002H, M2000T, Y2065N, and NL2003M of NS5A and L2003M of NS5B conferred resistance to daclatasvir. S2702T NS5B was the sofosbuvir-resistant variant. D1194A NS3/4A was triple DAA (simeprevir, faldaprevir, and asunaprevir) resistant. The double-drug resistant variants R1181K (faldaprevir and asunaprevir), A1182V and Q1106K/R (faldaprevir and simeprevir), T1080S (faldaprevir and telaprevir), and single drug-resistant variants V1062L (telaprevir), D1194E/T (simeprevir), D1194G (asunaprevir), S1148A/G (simeprevir), and Q1106L (Boceprevir) of NS3/4A were determined. The molecular phenomenon of DAA resistance is paramount in the development of HCV drug candidates. RAASs in NS3, NS5A, and NS5B reduce the susceptibility to DAAs; therefore, continuous RAAS-dependent resistance profiling in HCV is recommended to minimize the probability of DAA therapeutic failure.
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Affiliation(s)
- Mohammad Asrar Izhari
- Department of Laboratory Medicine, Faculty of Applied Medical Sciences, Al-Baha University, Al-Baha 65522, Saudi Arabia
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Etoori D, Desai M, Mandal S, Rosenberg W, Sabin CA. A scoping review of media campaign strategies used to reach populations living with or at high risk for Hepatitis C in high income countries to inform future national campaigns in the United Kingdom. BMC Infect Dis 2023; 23:629. [PMID: 37752434 PMCID: PMC10523688 DOI: 10.1186/s12879-023-08603-3] [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: 05/11/2023] [Accepted: 09/12/2023] [Indexed: 09/28/2023] Open
Abstract
BACKGROUND With the advent of direct acting antivirals, the World Health Organisation proposed eliminating Hepatitis C as a public health threat by 2030. To achieve this, countries need to diagnose, engage in care and treat their undiagnosed populations. This will require sensitisation campaigns. However previous media campaigns have had mixed impact. We conducted a scoping review to identify and understand the impact of previous Hepatitis C media campaigns. These findings could inform the delivery of future campaigns. METHODS We searched five electronic databases for published literature on media campaigns conducted for Hepatitis C awareness, testing, and treatment in Organisation for Economic Co-operation and Development (OECD) countries since 2010. Two independent reviewers screened citations for inclusion. Additionally, we spoke to stakeholders in the Hepatitis C field in the UK and conducted a Google search to identify any unpublished literature. A quantitative synthesis was conducted to identify targeted populations, strategies and media used, aims and impact of the campaigns. RESULTS A title and year of publication screening of 3815 citations resulted in 113 papers that had a full abstract screen. This left 50 full-text papers, 18 were included of which 9 (50%) were from Europe. 5 (27.8%) of campaigns targeted minority ethnicities, and 9 (50%) aimed to increase testing. A Google search identified 6 grey literature sources. Most campaigns were not evaluated for impact. Discussions with stakeholders identified several barriers to successful campaigns including lack of targeted messaging, stigmatising or accusatory messaging, and short-lived or intermittent campaign strategies. CONCLUSION Future campaigns will likely need to be multifaceted and have multiple tailored interventions. Campaigns will need to be sizeable and robust, integrated into health systems and viewed as an ongoing service rather than one-offs.
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Affiliation(s)
- David Etoori
- Centre for Clinical Research, Epidemiology, Modelling and Evaluation (CREME), Institute for Global Health, UCL, Royal Free Campus, Rowland Hill Street, London, NW3 2PF, UK.
- National Institute for Health and Care Research (NIHR) Health Protection Research Unit (HPRU) in Blood-borne and Sexually Transmitted Infections at UCL in partnership with the UK Health Security Agency (UKHSA), Royal Free Campus, Rowland Hill Street, London, NW3 2PF, UK.
| | - Monica Desai
- Blood Safety, Hepatitis, Sexually Transmitted Infections and HIV Division, UK Health Security Agency, 61 Colindale Avenue, London, NW9 5EQ, UK
| | - Sema Mandal
- Blood Safety, Hepatitis, Sexually Transmitted Infections and HIV Division, UK Health Security Agency, 61 Colindale Avenue, London, NW9 5EQ, UK
| | - William Rosenberg
- National Institute for Health and Care Research (NIHR) Health Protection Research Unit (HPRU) in Blood-borne and Sexually Transmitted Infections at UCL in partnership with the UK Health Security Agency (UKHSA), Royal Free Campus, Rowland Hill Street, London, NW3 2PF, UK
| | - Caroline A Sabin
- Centre for Clinical Research, Epidemiology, Modelling and Evaluation (CREME), Institute for Global Health, UCL, Royal Free Campus, Rowland Hill Street, London, NW3 2PF, UK
- National Institute for Health and Care Research (NIHR) Health Protection Research Unit (HPRU) in Blood-borne and Sexually Transmitted Infections at UCL in partnership with the UK Health Security Agency (UKHSA), Royal Free Campus, Rowland Hill Street, London, NW3 2PF, UK
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Yasmeen S, Khan A, Anwar F, Akhtar MF, Yasmeen S, Shah SA. An insight into the hepatoprotective role of Velpatasvir and Sofosbuvir per se and in combination against carbon tetrachloride-induced hepatic fibrosis in rats. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2023; 30:95660-95672. [PMID: 37556059 DOI: 10.1007/s11356-023-29134-z] [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: 01/17/2023] [Accepted: 07/30/2023] [Indexed: 08/10/2023]
Abstract
Hepatitis C is a global health issue. Hepatitis C Virus (HCV) induces fibrosis by redox reactions, which involve the deposition of collagen in extracellular matrix (ECM). This study aimed to examine the antifibrotic effect of direct-acting antivirals; Sofosbuvir and Velpatasvir, per se and in combination against carbon tetrachloride (CCl4)-induced fibrosis in rats. Carbon tetrachloride (intraperitoneal; 0.5 ml/kg) twice weekly for six weeks was used to induce hepatic fibrosis in rats. After two weeks of CCl4, oral administration of Sofosbuvir (20 mg/kg/d) and Velpatasvir (10 mg/kg/d) was administered to rats for the last four weeks. Liver function tests (LFTs), renal function tests (RFTs), oxidative stress markers, and the levels of TNF-a, NF-κB, and IL-6 were measured through ELISA and western blotting at the end of the study. CCl4 significantly ameliorated the values of RFTs, LFTs and lipid profiles in the diseased group, which were normalized by the SOF and VEL both alone and in combination. These drugs produced potent antioxidant effects by significantly increasing antioxidant enzymes. From the histopathology of hepatic tissues of rats treated with drugs, the antifibrotic effect was further manifested, which showed suppression of hepatic stellate cells (HSCs) in treated rats, as compared to the disease control group. The antifibrotic effect was further demonstrated by significantly decreasing the levels of TNF-a, NF-κB and IL-6 in serum and hepatic tissues of treated rats as compared to the disease control group. Sofosbuvir and Velpatasvir alone and in combination showed marked inhibition of fibrosis in the CCl4-induced non-HCV rat model, which was mediated by decreased levels of TNF-a/NF-κB and the IL-6 signaling pathway. Thus, it can be concluded that Sofosbuvir and Velpatasvir might have an antifibrotic effect that appears to be independent of their antiviral activity.
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Affiliation(s)
- Sadaf Yasmeen
- Department of Pharmacology, Riphah Institute of Pharmaceutical Sciences, Riphah International University, 13 KM Raiwind Road, Lahore, Pakistan
| | - Aslam Khan
- Department of Pharmacology, Riphah Institute of Pharmaceutical Sciences, Riphah International University, 13 KM Raiwind Road, Lahore, Pakistan.
| | - Fareeha Anwar
- Department of Pharmacology, Riphah Institute of Pharmaceutical Sciences, Riphah International University, 13 KM Raiwind Road, Lahore, Pakistan
| | - Muhammad Furqan Akhtar
- Department of Pharmacology, Riphah Institute of Pharmaceutical Sciences, Riphah International University, 13 KM Raiwind Road, Lahore, Pakistan
| | - Sidra Yasmeen
- Department of Pharmaceutics, Faculty of Pharmacy, Jinnah University for Women, Karachi, Pakistan
| | - Shafeeq Ali Shah
- Faculty of Pharmacy, Superior University, Raiwind Road, Lahore, Pakistan
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Aponte-Meléndez Y, Mateu-Gelabert P, Eckhardt B, Fong C, Padilla A, Trinidad-Martínez W, Maldonado-Rodríguez E, Agront N. Hepatitis C virus care cascade among people who inject drugs in puerto rico: Minimal HCV treatment and substantial barriers to HCV care. DRUG AND ALCOHOL DEPENDENCE REPORTS 2023; 8:100178. [PMID: 37555192 PMCID: PMC10404601 DOI: 10.1016/j.dadr.2023.100178] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/19/2023] [Revised: 07/06/2023] [Accepted: 07/07/2023] [Indexed: 08/10/2023]
Abstract
Background People who inject drugs (PWID) in Puerto Rico are disproportionately affected by the hepatitis C virus (HCV) epidemic. However, there is a scarcity of data on the HCV care cascade among PWID in Puerto Rico. This study aims to describe the HCV cascade of care among PWID in Puerto Rico, identify gaps, and explore barriers to HCV care. Methods Participants were recruited using respondent-driven sampling and tested for both HCV antibodies (Ab) and RNA (ribonucleic acid) using rapid testing and dried blood spot samples (DBS). The cascade of care was estimated based on the DBS HCV Ab and RNA results, as well as self-reported data on HCV screening, linkage to care, treatment uptake and sustained virologic response collected through a questionnaire. The cascade was constructed sequentially, with each step using the number of people from the preceding step as the base denominator. The survey also assessed participants' perceived barriers to HCV care. Results Out of 150 participants, 126 (84%) had previously been HCV screened, 87% (109/126) were HCV Ab positive, 72% (79/109) were RNA positive,48% (38/79) were linked to care, 32% (12/38) initiated treatment, 58% (7/12) finished treatment, and 71% (5/7) achieved SVR. Barriers to HCV care included concerns about drug abstinence requirements, access to transportation, stigma in healthcare settings, and lack of knowledge about HCV treatment sites. Conclusion This study provides insights into the HCV cascade of care among PWID in Puerto Rico for the first time and highlights limited diagnosis, treatment uptake, and barriers to care.
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Affiliation(s)
- Yesenia Aponte-Meléndez
- CUNY Graduate School of Public Health and Health Policy, Institute for Implementation Science in Population Health(ISPH) 55 West 125th street, New York, NY 10027,USA
- NYU Rory Meyers College of Nursing 433 1st Ave., New York, NY 10010
| | - Pedro Mateu-Gelabert
- CUNY Graduate School of Public Health and Health Policy, Institute for Implementation Science in Population Health(ISPH) 55 West 125th street, New York, NY 10027,USA
| | - Benjamin Eckhardt
- New York University School of Medicine, 550 First Avenue, New York, NY, 10016, USA
| | - Chunki Fong
- CUNY Graduate School of Public Health and Health Policy, Institute for Implementation Science in Population Health(ISPH) 55 West 125th street, New York, NY 10027,USA
| | - Adriana Padilla
- CUNY Graduate School of Public Health and Health Policy, Institute for Implementation Science in Population Health(ISPH) 55 West 125th street, New York, NY 10027,USA
| | - Wanda Trinidad-Martínez
- CUNY Graduate School of Public Health and Health Policy, Institute for Implementation Science in Population Health(ISPH) 55 West 125th street, New York, NY 10027,USA
| | - Eric Maldonado-Rodríguez
- CUNY Graduate School of Public Health and Health Policy, Institute for Implementation Science in Population Health(ISPH) 55 West 125th street, New York, NY 10027,USA
| | - Nancy Agront
- AbbVie Corp., Paseo Caribe Building Suite 22415 Ave Munoz Rivera San Juan, 00901, Puerto Rico
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Obradovic B, Roberts O, Owen A, Milosevic I, Milic N, Ranin J, Dragovic G. Expression of CYP2B6 Enzyme in Human Liver Tissue of HIV and HCV Patients. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:1207. [PMID: 37512019 PMCID: PMC10385124 DOI: 10.3390/medicina59071207] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/19/2023] [Revised: 06/15/2023] [Accepted: 06/21/2023] [Indexed: 07/30/2023]
Abstract
Background and Objectives: Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections present significant public health challenges worldwide. The management of these infections is complicated by the need for antiviral and antiretroviral therapies, which are influenced by drug metabolism mediated by metabolic enzymes and transporters. This study focuses on the gene expression of CYP2B6, CYP3A4, and ABCB1 transporters in patients with HIV, HCV, and HIV/HCV co-infection, aiming to assess their potential association with the choice of therapy, patohistological and clinical parameters of liver damage such as the stage of liver fibrosis, serum levels of ALT and AST, as well as the grade of liver inflammation and other available biochemical parameters. Materials and Methods: The study included 54 patients who underwent liver biopsy, divided into HIV-infected, HCV-infected, and co-infected groups. The mRNA levels of CYP2B6, CYP3A4, and ABCB1 was quantified and compared between the groups, along with the analysis of liver fibrosis and inflammation levels. Results: The results indicated a significant increase in CYP2B6 mRNA levels in co-infected patients, a significant association with the presence of HIV infection with an increase in CYP3A4 mRNA levels. A trend towards downregulation of ABCB1 expression was observed in patients using lamivudine. Conclusions: This study provides insight into gene expression of CYP2B6 CYP3A4, and ABCB1 in HIV, HCV, and HIV/HCV co-infected patients. The absence of correlation with liver damage, inflammation, and specific treatment interventions emphasises the need for additional research to elucidate the complex interplay between gene expression, viral co-infection, liver pathology, and therapeutic responses in these particular patients population.
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Affiliation(s)
- Bozana Obradovic
- University of Belgrade, Faculty of Medicine, Department of Pharmacology, Clinical Pharmacology and Toxicology, 11000 Belgrade, Serbia
| | - Owain Roberts
- University of Buckingham Medical School, Faculty of Medicine and Health Sciences, University of Buckingham, Buckingham MK18 1EG, UK
| | - Andrew Owen
- Centre of Excellence in Long-Acting Therapeutics (CELT), Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 3BX, UK
| | - Ivana Milosevic
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia
- Clinic of Infectious and Tropical Diseases, Clinical Centre of Serbia, 11000 Belgrade, Serbia
| | - Natasa Milic
- University of Belgrade, Faculty of Medicine, Department of Medical Statistics & Informatics, 11000 Belgrade, Serbia
| | - Jovan Ranin
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia
- Clinic of Infectious and Tropical Diseases, Clinical Centre of Serbia, 11000 Belgrade, Serbia
| | - Gordana Dragovic
- University of Belgrade, Faculty of Medicine, Department of Pharmacology, Clinical Pharmacology and Toxicology, 11000 Belgrade, Serbia
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Aimla K, Kowalska JD, Matulionyte R, Mulabdic V, Vassilenko A, Bolokadze N, Jilich D, Antoniak S, Oprea C, Balayan T, Harxhi A, Papadopoulos A, Lakatos B, Vasylyev M, Begovac J, Yancheva N, Streinu-Cercel A, Verhaz A, Gokengin D, Dragovic G, Sojak L, Skrzat-Klapaczyńska A. Vaccination against HBV and HAV as Mode of Hepatitis Prevention among People Living with HIV-Data from ECEE Network Group. Vaccines (Basel) 2023; 11:980. [PMID: 37243084 PMCID: PMC10222000 DOI: 10.3390/vaccines11050980] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2023] [Revised: 04/27/2023] [Accepted: 05/11/2023] [Indexed: 05/28/2023] Open
Abstract
(1) Background: Viral hepatitis C (HCV) and viral hepatitis B (HBV) are common co-infections in people living with HIV (PLWH). All PLWH should be vaccinated against HBV and hepatitis A (HAV) and treated for HBV and HCV. We aimed to compare testing, prophylaxis and treatment of viral hepatitis in PLWH in Central and Eastern Europe (CEE) in 2019 and 2022. (2) Methods: Data was collected through two on-line surveys conducted in 2019 and 2022 among 18 countries of the Euroguidelines in CEE (ECEE) Network Group. (3) Results: In all 18 countries the standard of care was to screen all PLWH for HBV and HCV both years; screening of HAV was routine in 2019 in 54.5% and in 2022 47.4% of clinics. Vaccination of PLWH against HAV was available in 2019 in 16.7%, in 2022 in 22.2% countries. Vaccination against HBV was available routinely and free of charge in 50% of clinics both in 2019 and 2022. In HIV/HBV co-infected the choice of NRTI was tenofovir-based in 94.4% of countries in both years. All clinics that responded had access to direct-acting antivirals (DAAs) but 50% still had limitations for treatment. (4) Conclusions: Although testing for HBV and HCV was good, testing for HAV is insufficient. Vaccination against HBV and especially against HAV has room for improvement; furthermore, HCV treatment access needs to overcome restrictions.
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Affiliation(s)
- Kerstin Aimla
- Department of Infectious Diseases, Tartu University Hospital, 50406 Tartu, Estonia
| | - Justyna Dominika Kowalska
- Department of Adults’ Infectious Diseases, Hospital for Infectious Diseases, Medical University of Warsaw, 02-091 Warsaw, Poland
| | - Raimonda Matulionyte
- Department of Infectious Diseases and Dermatovenerology, Faculty of Medicine, Vilnius University, Vilnius University Hospital Santaros Klinikos, LT-08410 Vilnius, Lithuania
| | - Velida Mulabdic
- Clinic for Infectious Diseases, University Clinical Center Sarajevo, 71000 Sarajevo, Bosnia and Herzegovina
| | - Anna Vassilenko
- City Clinical Hospital of Infectious Diseases, 220002 Minsk, Belarus
| | - Natalie Bolokadze
- Infectious Diseases, AIDS and Clinical Immunology Research Center, 0160 Tbilisi, Georgia
| | - David Jilich
- Department of Infectious Diseases, 1st Faculty of Medicine, Charles University in Prague and Faculty Hospital Bulovka, 18000 Prague, Czech Republic
| | - Sergii Antoniak
- Clinic of the Gromashevsky Institute of Epidemiology and Infectious Diseases, 01001 Kyiv, Ukraine
| | - Cristiana Oprea
- Victor Babes Clinical Hospital for Infectious and Tropical Diseases, 030303 Bucharest, Romania
| | | | - Arjan Harxhi
- Department of Infectious Disease, Faculty of Medicine, Medical University of Tirana, 1000 Tirana, Albania
| | - Antonios Papadopoulos
- HIV Unit, 4th Department of Internal Medicine, School of Medicine, National and Kapodistrian University of Athens, Attikon University Hospital, 12462 Athens, Greece
| | - Botond Lakatos
- National Instititue of Hematology and Infectious Diseases, National Center of HIV, 1097 Budapest, Hungary
| | - Marta Vasylyev
- Lviv Regional Public Health Center, HIV Unit, 79000 Lviv, Ukraine
| | - Josip Begovac
- University Hospital of Infectious Diseases, 10000 Zagreb, Croatia
| | - Nina Yancheva
- Department for AIDS, Specialized Hospital for Active Treatment of Infectious and Parasitic Diseases, Medical University of Sofia, 1606 Sofia, Bulgaria
| | - Anca Streinu-Cercel
- National Institute of Infectious Diseases “Prof. Dr. Matei Balș”, 021105 Bucharest, Romania
| | - Antonija Verhaz
- Clinic for Infectious Diseases Republic of Srpska Banja Luka, 78000 Banja Luka, Bosnia and Herzegovina
| | - Deniz Gokengin
- Department of Infectious Diseases and Clinical Microbiology, Medical Faculty, Ege University, 35100 Izmir, Turkey
| | - Gordana Dragovic
- Department of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia
| | - Lubomir Sojak
- Department of Infectology and Geographical Medicine, 833 05 Bratislava, Slovakia
| | - Agata Skrzat-Klapaczyńska
- Department of Adults’ Infectious Diseases, Hospital for Infectious Diseases, Medical University of Warsaw, 02-091 Warsaw, Poland
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Riaz HA, Nishwa DE, Fatima A, Wahid B, Ali A, Kumari B, Idrees M. Risk of adverse outcomes following treatment with direct acting antiviral drugs in HCV infected patients with liver cirrhosis. Heliyon 2023; 9:e16169. [PMID: 37234654 PMCID: PMC10205523 DOI: 10.1016/j.heliyon.2023.e16169] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2022] [Revised: 04/23/2023] [Accepted: 05/08/2023] [Indexed: 05/28/2023] Open
Abstract
Introduction Hepatitis C virus (HCV) is the second major cause of death in Pakistan. Previously, interferon-based regimens were considered highly recommended therapy for HCV patients. Since 2015, interferon-based therapy has been replaced with interferon-free therapy also known as Direct Acting Antiviral (DAA) drugs. The treatment response of interferon-free regimens has been reported as highly effective treatment option with more than 90% sustained virological response (SVR) in chronic HCV infected patients in western countries of the world. Objective This study aims to analyze the treatment response of DAA drugs in HCV-infected Pakistani population with liver cirrhosis. Methodology We collected the total 94 sample of the HCV infected patients, from June 2020 to September 2020. Forty-six (46) patients were cirrhotic, and forty-eight (48) patients were non-cirrhotic. Data was analyzed using IBM SPSS version 21 software. Conclusion The findings of our study suggest that the response rate was 82.60% in HCV cirrhotic patients and 68.75% in HCV non-cirrhotic patients. Our study showed that overall treatment response was independent of age and gender. We also observed some adverse effects such as hepatocellular carcinoma, portosystemic encephalopathy (PSE), spontaneous bacterial peritonitis (SBP), hepatorenal syndrome (HRS), upper gastrointestinal bleeding (UGIB), ascites, among patients following treatment with interferon-free regimens.
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Affiliation(s)
- Hafiza Arooba Riaz
- Department of Life Sciences, School of Sciences, University of Management and Technology, Lahore, Pakistan
| | - Dur E. Nishwa
- Department of Life Sciences, School of Sciences, University of Management and Technology, Lahore, Pakistan
| | - Ameer Fatima
- Hepatobiliary and Gastroenterology Unit, Sheikh Zayed Hospital, Lahore, Pakistan
| | - Braira Wahid
- Department of Life Sciences, School of Sciences, University of Management and Technology, Lahore, Pakistan
- Department of Microbiology, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC, 3168, Australia
| | - Akhtar Ali
- School of Agriculture and Food, Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, VIC, 3010, Australia
| | - Babita Kumari
- Department of Microbiology, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC, 3168, Australia
| | - Muhammad Idrees
- Division of Molecular Virology, Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan
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Jones AT, Moreno-Walton L, Sossamon SD, Tahmeena F, Tran T, Briones C, Stevens R, Isaacson K, He H, Rhodes S, Percak J, Kissinger PJ. Delays in fibrosis staging reduce the likelihood of achieving hepatitis C treatment and cure. Infect Dis (Lond) 2023; 55:309-315. [PMID: 36853886 PMCID: PMC10284034 DOI: 10.1080/23744235.2023.2178670] [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: 09/23/2022] [Revised: 01/30/2023] [Accepted: 02/05/2023] [Indexed: 03/01/2023] Open
Abstract
BACKGROUND Updated 2021 hepatitis C virus (HCV) treatment guidelines no longer recommend fibrosis staging for treatment-naïve patients without cirrhosis; however, numerous US state Medicaid plans continue to restrict initiation of HCV therapy by fibrosis stage. The study objective was to determine whether delays from HCV diagnosis to fibrosis staging impact the likelihood of initiating/completing HCV treatment and achieving sustained virologic response (SVR). METHODS A retrospective cohort study was performed among patients diagnosed with chronic HCV by an urban US emergency department who subsequently underwent fibrosis staging. Time elapsed from HCV diagnosis to hepatic fibrosis staging was evaluated on the likelihood of treatment initiation, treatment completion and SVR. RESULTS Among fibrosis staging modalities, hepatic ultrasounds occurred more quickly following HCV diagnosis (3.5 months, IQR = 12.4 months), compared to FibroSure (8.5 months, IQR = 20.4 months) and FibroScan (9.9 months, IQR = 18.0 months) (p<.001). Each six-month delay in fibrosis staging decreased the likelihood of initiating treatment by 5% (adjusted relative risk (aRR)=0.95; 95% confidence interval (CI)=0.91-0.998; p=.04) and the likelihood of SVR by 7% (aRR = 0.93; 95% CI = 0.87-0.995; p=.04) after adjusting for insurance, race/ethnicity and history of HIV testing. CONCLUSIONS Delays in hepatitis fibrosis staging were significantly associated with decreased likelihood of HCV treatment initiation and SVR.
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Affiliation(s)
- Austin T. Jones
- Department of Emergency Medicine, Denver Health Medical Center, Denver, CO, USA
| | - Lisa Moreno-Walton
- Section of Emergency Medicine, Louisiana State University Health Sciences Center, New Orleans, LA, USA
| | - Sierra D. Sossamon
- Section of Emergency Medicine, Louisiana State University Health Sciences Center, New Orleans, LA, USA
| | - Fnu Tahmeena
- Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA
| | - Torrence Tran
- Department of Emergency Medicine, University of California Los Angeles Medical Center, Los Angeles, CA, USA
| | - Christopher Briones
- Department of Emergency Medicine, University of California Los Angeles Medical Center, Los Angeles, CA, USA
| | | | | | - Hua He
- Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA
| | - Stacey Rhodes
- Section of Emergency Medicine, Louisiana State University Health Sciences Center, New Orleans, LA, USA
| | - Jeffrey Percak
- Tulane University School of Medicine, New Orleans, LA, USA
| | - Patricia J. Kissinger
- Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA
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Effectiveness of direct-acting antiviral (DAA) agents on hepatitis C virus-related mixed cryoglobulinemia syndrome: One-year follow-up. THE EGYPTIAN RHEUMATOLOGIST 2023. [DOI: 10.1016/j.ejr.2022.12.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
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Broni E, Ashley C, Adams J, Manu H, Aikins E, Okom M, Miller WA, Wilson MD, Kwofie SK. Cheminformatics-Based Study Identifies Potential Ebola VP40 Inhibitors. Int J Mol Sci 2023; 24:ijms24076298. [PMID: 37047270 PMCID: PMC10094735 DOI: 10.3390/ijms24076298] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Revised: 03/21/2023] [Accepted: 03/24/2023] [Indexed: 03/30/2023] Open
Abstract
The Ebola virus (EBOV) is still highly infectious and causes severe hemorrhagic fevers in primates. However, there are no regulatorily approved drugs against the Ebola virus disease (EVD). The highly virulent and lethal nature of EVD highlights the need to develop therapeutic agents. Viral protein 40 kDa (VP40), the most abundantly expressed protein during infection, coordinates the assembly, budding, and release of viral particles into the host cell. It also regulates viral transcription and RNA replication. This study sought to identify small molecules that could potentially inhibit the VP40 protein by targeting the N-terminal domain using an in silico approach. The statistical quality of AutoDock Vina’s capacity to discriminate between inhibitors and decoys was determined, and an area under the curve of the receiver operating characteristic (AUC-ROC) curve of 0.791 was obtained. A total of 29,519 natural-product-derived compounds from Chinese and African sources as well as 2738 approved drugs were successfully screened against VP40. Using a threshold of −8 kcal/mol, a total of 7, 11, 163, and 30 compounds from the AfroDb, Northern African Natural Products Database (NANPDB), traditional Chinese medicine (TCM), and approved drugs libraries, respectively, were obtained after molecular docking. A biological activity prediction of the lead compounds suggested their potential antiviral properties. In addition, random-forest- and support-vector-machine-based algorithms predicted the compounds to be anti-Ebola with IC50 values in the micromolar range (less than 25 μM). A total of 42 natural-product-derived compounds were identified as potential EBOV inhibitors with desirable ADMET profiles, comprising 1, 2, and 39 compounds from NANPDB (2-hydroxyseneganolide), AfroDb (ZINC000034518176 and ZINC000095485942), and TCM, respectively. A total of 23 approved drugs, including doramectin, glecaprevir, velpatasvir, ledipasvir, avermectin B1, nafarelin acetate, danoprevir, eltrombopag, lanatoside C, and glycyrrhizin, among others, were also predicted to have potential anti-EBOV activity and can be further explored so that they may be repurposed for EVD treatment. Molecular dynamics simulations coupled with molecular mechanics Poisson–Boltzmann surface area calculations corroborated the stability and good binding affinities of the complexes (−46.97 to −118.9 kJ/mol). The potential lead compounds may have the potential to be developed as anti-EBOV drugs after experimental testing.
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Affiliation(s)
- Emmanuel Broni
- Department of Biomedical Engineering, School of Engineering Sciences, College of Basic and Applied Sciences, University of Ghana, Legon, Accra LG 77, Ghana
- Department of Parasitology, Noguchi Memorial Institute for Medical Research (NMIMR), College of Health Sciences (CHS), University of Ghana, Legon, Accra LG 581, Ghana
- Department of Medicine, Loyola University Medical Center, Loyola University Chicago, Maywood, IL 60153, USA
| | - Carolyn Ashley
- Department of Medicine, Loyola University Medical Center, Loyola University Chicago, Maywood, IL 60153, USA
| | - Joseph Adams
- Department of Parasitology, Noguchi Memorial Institute for Medical Research (NMIMR), College of Health Sciences (CHS), University of Ghana, Legon, Accra LG 581, Ghana
| | - Hammond Manu
- Department of Biomedical Engineering, School of Engineering Sciences, College of Basic and Applied Sciences, University of Ghana, Legon, Accra LG 77, Ghana
| | - Ebenezer Aikins
- Department of Biomedical Engineering, School of Engineering Sciences, College of Basic and Applied Sciences, University of Ghana, Legon, Accra LG 77, Ghana
| | - Mary Okom
- Department of Biomedical Engineering, School of Engineering Sciences, College of Basic and Applied Sciences, University of Ghana, Legon, Accra LG 77, Ghana
| | - Whelton A. Miller
- Department of Medicine, Loyola University Medical Center, Loyola University Chicago, Maywood, IL 60153, USA
- Department of Molecular Pharmacology and Neuroscience, Loyola University Medical Center, Maywood, IL 60153, USA
- Department of Chemical and Biomolecular Engineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA 19104, USA
- Correspondence: (W.A.M.III); (S.K.K.); Tel.: +1(708)-2168451 (W.A.M.III); +23-320-3797922 (S.K.K.)
| | - Michael D. Wilson
- Department of Parasitology, Noguchi Memorial Institute for Medical Research (NMIMR), College of Health Sciences (CHS), University of Ghana, Legon, Accra LG 581, Ghana
- Department of Medicine, Loyola University Medical Center, Loyola University Chicago, Maywood, IL 60153, USA
| | - Samuel K. Kwofie
- Department of Biomedical Engineering, School of Engineering Sciences, College of Basic and Applied Sciences, University of Ghana, Legon, Accra LG 77, Ghana
- Department of Biochemistry, Cell and Molecular Biology, West African Centre for Cell Biology of Infectious Pathogens, College of Basic and Applied Sciences, University of Ghana, Accra LG 54, Ghana
- Correspondence: (W.A.M.III); (S.K.K.); Tel.: +1(708)-2168451 (W.A.M.III); +23-320-3797922 (S.K.K.)
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Rizaldi G, Hafid AF, Wahyuni TS. Promising alkaloids and flavonoids compounds as anti-hepatitis c virus agents: a review. J Public Health Afr 2023. [PMID: 37492538 PMCID: PMC10365654 DOI: 10.4081/jphia.2023.2514] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/18/2023] Open
Abstract
Background: Virus infections are presently seen as a major public health problem. Hepatitis C Virus (HCV) is recognized as a “silent killer” because the acute infection has no symptoms, and it develops as a chronic infection that causes hepatocellular carcinoma and liver damage. The World Health Organization (WHO) predicts that between 130-170 million people are estimated to have chronic Hepatitis C. Plants have various phytochemical compounds such as alkaloids and flavonoids that have prominent antiviral effects especially anti-HCV. The current HCV treatment still has limitations related to side effects and can lead to viral resistance. Therefore, it is necessary for the discovery and development of novel anti-HCV drugs for alternative and complementary medicine.
Objective: This review intends to evaluate the alkaloids and flavonoids that have the potential to be used against HCV by looking at their classification and their mechanism of action.
Methods: Twenty-one articles from 2010 to 2022 obtained from PUBMED database using keywords such as isolated compounds, alkaloids, flavonoids, hepatitis C virus.
Results: 21 alkaloids and 37 flavonoids reported active against HCV. Alkaloids include quinoline, quinolizidine and isoquinoline. In addition, flavanone, flavonol, flavone, flavan-3-ol, flavonolignan, anthocyanidin and proanthocyanidin comprise flavonoids. The berberine alkaloids and eriodictyol 7-O-(6′′-caffeoyl)-β-D- glucopyranoside flavonoids had the lowest IC50 with values of 0.49 mM and 0.041 nM.
Conclusions: Alkaloids and flavonoids compound had good activity against HCV with various mechanisms. Our results provide information of alkaloids and flavonoids to the researcher for the development of alternative and complementary medicine of hepatitis C.
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Mahmoud Farhan S, Mahmoud Abd El-Baky R, Mohammad Abdalla SA, Osama El-Gendy A, Farag Azmy A, Department of Microbiology and Immunology, Faculty of Pharmacy, Deraya University, Minia, Egypt, Department of Microbiology and Immunology, Faculty of Pharmacy, Deraya University, Minia, Egypt, Department of Microbiology and Immunology, Faculty of Pharmacy, Suez Canal University, Ismalia, Egypt, Department of Microbiology and Immunology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt, Department of Microbiology and Immunology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt. Efficacy of Amikacin and Imipenem Against Multi-Drug Resistant Gram-Negative Bacteria Isolated from Wound Infections, Egypt. IRANIAN JOURNAL OF MEDICAL MICROBIOLOGY 2023; 17:218-229. [DOI: 10.30699/ijmm.17.2.218] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/02/2023]
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