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Bakshi S, Chattopadhyay P, Ahammed M, Das R, Majumdar M, Dutta S, Nath S, Ghosh A, Bhattacharjee U, Baskey U, Sadhukhan PC. Efficacy of Different Combinations of Direct-Acting Antivirals Against Different Hepatitis C Virus-Infected Population Groups: An Experience in Tertiary Care Hospitals in West Bengal, India. Viruses 2025; 17:269. [PMID: 40007024 PMCID: PMC11861515 DOI: 10.3390/v17020269] [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: 01/07/2025] [Revised: 02/03/2025] [Accepted: 02/05/2025] [Indexed: 02/27/2025] Open
Abstract
Hepatitis C virus (HCV) is a global public health problem, but advancements in HCV treatment have improved the cure rate. This study evaluated the effectiveness of direct-acting antivirals (DAAs) in HCV-infected patients from May 2021 to April 2023 in collaboration with tertiary care hospitals in West Bengal. The HCV viral load was monitored via qRT-PCR. Sanger sequencing was performed to determine the HCV genotypes. The clinicians prescribed the patient treatment regime. The maximum number of patients in the study population (N = 398) were compensated cirrhosis patients (46.28%). The overall SVR rate of the study population was 94.47%. The decompensated cirrhosis patients experienced the lowest SVR rate (88.89%). The maximum number of patients were prescribed sofosbuvir/daclatasvir (63.77%), and the lowest SVR rate (93.23%) was observed with this treatment regime. In the study population, GT-3 was the predominant (67.43%) circulating genotype, followed by GT-1 and -4. Among 398 patients, 22 (5.53%) were non-responsive to DAA treatment. Out of these 22 non-responder patients, 77.27% (n = 17) were GT-3-infected (3a:10; 3b:07), followed by GT-1 (1c: 04; 1b: 01). Thus, increasing numbers of DAA non-responsive cases among HCV GT-3-infected and decompensated cirrhosis patients may pose serious threats in the future.
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Affiliation(s)
- Sagnik Bakshi
- Indian Council of Medical Research, National Institute for Research in Bacterial Infections P-33, Scheme XM, CIT Road, Beliaghata, Kolkata 700010, West Bengal, India; (S.B.); (R.D.); (M.M.); (S.D.); (S.N.); (A.G.); (U.B.); (U.B.)
| | - Partha Chattopadhyay
- College of Medicine & Sagore Dutta Hospital, 578 B.T Road, Kolkata 700058, West Bengal, India;
| | - Mahiuddin Ahammed
- IPGME&R and SSKM Hospital, SSKM Hospital Rd, Bhowanipore, Kolkata 700020, West Bengal, India;
| | - Raina Das
- Indian Council of Medical Research, National Institute for Research in Bacterial Infections P-33, Scheme XM, CIT Road, Beliaghata, Kolkata 700010, West Bengal, India; (S.B.); (R.D.); (M.M.); (S.D.); (S.N.); (A.G.); (U.B.); (U.B.)
| | - Moumita Majumdar
- Indian Council of Medical Research, National Institute for Research in Bacterial Infections P-33, Scheme XM, CIT Road, Beliaghata, Kolkata 700010, West Bengal, India; (S.B.); (R.D.); (M.M.); (S.D.); (S.N.); (A.G.); (U.B.); (U.B.)
| | - Supradip Dutta
- Indian Council of Medical Research, National Institute for Research in Bacterial Infections P-33, Scheme XM, CIT Road, Beliaghata, Kolkata 700010, West Bengal, India; (S.B.); (R.D.); (M.M.); (S.D.); (S.N.); (A.G.); (U.B.); (U.B.)
| | - Shreyasi Nath
- Indian Council of Medical Research, National Institute for Research in Bacterial Infections P-33, Scheme XM, CIT Road, Beliaghata, Kolkata 700010, West Bengal, India; (S.B.); (R.D.); (M.M.); (S.D.); (S.N.); (A.G.); (U.B.); (U.B.)
| | - Anwesha Ghosh
- Indian Council of Medical Research, National Institute for Research in Bacterial Infections P-33, Scheme XM, CIT Road, Beliaghata, Kolkata 700010, West Bengal, India; (S.B.); (R.D.); (M.M.); (S.D.); (S.N.); (A.G.); (U.B.); (U.B.)
| | - Uttaran Bhattacharjee
- Indian Council of Medical Research, National Institute for Research in Bacterial Infections P-33, Scheme XM, CIT Road, Beliaghata, Kolkata 700010, West Bengal, India; (S.B.); (R.D.); (M.M.); (S.D.); (S.N.); (A.G.); (U.B.); (U.B.)
| | - Upasana Baskey
- Indian Council of Medical Research, National Institute for Research in Bacterial Infections P-33, Scheme XM, CIT Road, Beliaghata, Kolkata 700010, West Bengal, India; (S.B.); (R.D.); (M.M.); (S.D.); (S.N.); (A.G.); (U.B.); (U.B.)
| | - Provash Chandra Sadhukhan
- Indian Council of Medical Research, National Institute for Research in Bacterial Infections P-33, Scheme XM, CIT Road, Beliaghata, Kolkata 700010, West Bengal, India; (S.B.); (R.D.); (M.M.); (S.D.); (S.N.); (A.G.); (U.B.); (U.B.)
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Kowo MP, Coyer L, Sini V, Kafack CA, Metomo GY, Wafeu GS, Njouom R, Boers A, Coutinho R, Njoya O, Kouanfack C, the DHEPC project team. Integrating hepatitis C testing and treatment into routine HIV care in Cameroon is feasible. J Int AIDS Soc 2025; 28:e26417. [PMID: 39943742 PMCID: PMC11822197 DOI: 10.1002/jia2.26417] [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] [Indexed: 02/16/2025] Open
Abstract
INTRODUCTION Hepatitis C virus (HCV) prevalence and adverse outcomes are higher among people with human immunodeficiency virus (HIV) than people without HIV. Yet, HCV prevalence among people with HIV in Cameroon remains unknown, with HCV diagnosis and treatment largely inaccessible due to care centralization by specialists with high out-of-pocket costs. Integration of HCV services into routine HIV care by general practitioners could improve diagnosis and treatment coverage. We aimed to examine HCV prevalence and treatment cure rate among people with HIV attending 11 HIV clinics in the Centre Region of Cameroon. METHODS We offered HCV rapid antibody testing, and, if positive, RNA testing to all persons ≥21 years, on HIV ART for ≥6 months and with suppressed HIV RNA (<1000 copies) who attended HIV counselling and treatment appointments between 20 April 2021 and 31 May 2022. Participants with an HCV RNA positive test received 12 weeks of pangenotypic sofosbuvir/velpatasvir. We calculated the cure rate as the proportion of participants with a sustained virological response 12 weeks after treatment completion (SVR12) among all starting and completing treatment. RESULTS We tested 8266 persons for HCV antibodies, 316 (3.8%, 95% CI = 3.4-4.3%) of whom were anti-HCV positive. Of these, 286 (90.5%) were sampled for HCV RNA, 20 (6.3%) ineligible, 5 (1.6%) declined, 4 (1.3%) left before sampling and 1 (0.3%) had an unknown reason. Among 286 sampled, 251 (87.8%) had detectable HCV RNA. Of these, 173 (68.9%) enrolled for treatment, 55 (21.9%) were eligible but not enrolled (49 lost-to-follow-up, 6 denied) and 23 (9.2%) were ineligible. Of 173 enrolled, 165 completed treatment, 6 were lost-to-follow-up and 2 were excluded due to treatment interruption. SVR12 was achieved in 93.6% (n = 162; 95% CI: 88.9-96.8%) of those enrolled and 98.2% (95% CI: 94.8-99.6%) of treatment completers. All three initially not achieving SVR12 were cured with second-line treatment (sofosbuvir/velpatasvir/voxilaprevir). CONCLUSIONS Our study demonstrates the viability of integrating HCV testing and treatment into routine HIV care in Cameroon, yielding new HCV diagnoses and high cure rates. Cameroon can use this strategy to achieve HCV elimination goals, although improvements in testing uptake, diagnosis and treatment access, and laboratory capacity are needed.
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Affiliation(s)
- Mathurin Pierre Kowo
- Research Laboratory on Viral Hepatitis and Health CommunicationUniversity of Yaoundé IYaoundéCameroon
| | - Liza Coyer
- ECDC Fellowship Programme, Field Epidemiology path (EPIET), European Centre for Disease Prevention and Control (ECDC)StockholmSweden
- State Institute for Health II, Task Force for Infectious Diseases (GI), Bavarian Health and Food Safety Authority (LGL)MunichGermany
| | - Victor Sini
- HIV/AIDS Approved Treatment CenterYaounde General HospitalYaoundeCameroon
- Department of Clinical SciencesHigher Institute of Medical Technology of NkolodomYaoundeCameroon
| | - Carole Assontsa Kafack
- Faculty of Medicine and Pharmaceutical SciencesUniversity of DschangDschangCameroon
- French National Agency for Research on AIDS and Infectious Diseases, Cameroon Site, Central Hospital of YaoundéYaoundéCameroon
| | | | - Guy S. Wafeu
- Research Laboratory on Viral Hepatitis and Health CommunicationUniversity of Yaoundé IYaoundéCameroon
| | | | | | - Roel Coutinho
- PharmAccess FoundationAmsterdamthe Netherlands
- Joep Lange InstituteAmsterdamthe Netherlands
| | - Oudou Njoya
- Research Laboratory on Viral Hepatitis and Health CommunicationUniversity of Yaoundé IYaoundéCameroon
| | - Charles Kouanfack
- Faculty of Medicine and Pharmaceutical SciencesUniversity of DschangDschangCameroon
- French National Agency for Research on AIDS and Infectious Diseases, Cameroon Site, Central Hospital of YaoundéYaoundéCameroon
- Centre for Research of Emergency and Re‐emergency DiseasesYaoundéCameroon
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Badshah Y, Shabbir M, Khan K, Zafar S, Afsar T, Husain FM, Amor H, Razak S. HCV and HBV genotypes: vital in the progression of HCV/ HBV co-infection. BMC Gastroenterol 2025; 25:6. [PMID: 39780058 PMCID: PMC11708002 DOI: 10.1186/s12876-025-03587-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2024] [Accepted: 01/01/2025] [Indexed: 01/11/2025] Open
Abstract
BACKGROUND Viral hepatitis is the major contributor to liver cirrhosis and hepatocellular carcinoma (HCC). Studies indicated that the co-infection of hepatitis C and hepatitis B virus also prompts liver damage progression. Therefore, in the present study, the prevalence of HCV-HBV co-infection and the impact of HCV-HBV co-infection on the progression of liver damage was evaluated amongst the HCV-infected patients in Pakistan. METHODS In this study 2500 HCV-positive patients were recruited from Pakistan. The presence and prevalence of HCV and HBV was confirmed through ELISA and nested PCR. To determine the liver damage due to viral infection levels of ALT, ALP, and total bilirubin were also determined. Diagnostic history of patients was thoroughly documented through serological tests and liver biopsy reports. Viral genotypes and viral loads were determined through multiplex polymerase chain reaction (PCR) and time PCR, respectively. RESULTS The study outcomes showed that 12.5% of the HCV-infected patients were co-infected with HBV. Co-infection development was more common in females than in males, and females were at a higher risk of developing the infection (p-value = < 0.0001, OR = 2.437). Despite the variation among different age groups, there was no significant difference in co-infection prevalence. HCV genotype 3a was found to be most prevalent while in HBV genotype D was found to be prevalent among the patients. The HCV patients frequently developed co-infection with HBV genotype D. It was also determined that viral load for HBV genotype D was higher compared to non-D genotypes while for HCV viral load was higher in non-3a genotypes. CONCLUSIONS This study evaluated the prevalence of HCV and HBV co-infection among HCV-positive patients, revealing that 12.5% patients were co-infected with HBV. Co-infection was more common in females, who had a higher risk of developing it. The study also revealed that HBV genotype D was the most prevalent in co-infected patients, with no significant age-related differences in co-infection rates.
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Affiliation(s)
- Yasmin Badshah
- Department of Healthcare Biotechnology, Atta ur Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, 44000, Pakistan.
| | - Maria Shabbir
- Department of Healthcare Biotechnology, Atta ur Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, 44000, Pakistan
| | - Khushbukhat Khan
- Department of Healthcare Biotechnology, Atta ur Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, 44000, Pakistan
| | - Sameen Zafar
- Department of Healthcare Biotechnology, Atta ur Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, 44000, Pakistan
| | - Tayyaba Afsar
- Department of Community Health Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, 11433, Saudi Arabia
| | - Fohad Mabood Husain
- Department of Food Science and Nutrition, College of Food and Agriculture Sciences, King Saud University, Riyadh, 11433, Saudi Arabia
| | - Houda Amor
- Department of Obstetrics, Gynecology and Reproductive Medicine, Saarland University Clinic, Homburg, Germany
| | - Suhail Razak
- Department of Community Health Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, 11433, Saudi Arabia.
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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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Nakano S, Suzuki M, Hatori R, Mizuochi T, Etani Y, Tajiri H. Natural history and clinical features of hepatitis C virus infection during childhood: A nationwide, observational survey in Japan. Hepatol Res 2024; 54:795-806. [PMID: 38459826 DOI: 10.1111/hepr.14032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2023] [Revised: 01/26/2024] [Accepted: 02/12/2024] [Indexed: 03/10/2024]
Abstract
AIM Few data on spontaneous clearance rates of cases of mother-to-child transmission of hepatitis C viral (HCV) infection are available in Japan. Furthermore, the treatment courses of interferon-based and direct-acting antiviral agent (DAA) therapies for children are also unclear. Our aim was thus to clarify the long-term natural progression of HCV infection and the treatment outcomes of children in Japan. METHODS We conducted a combined multicenter, observational survey involving 65 pediatric institutions in Japan. Pediatric HCV infection cases with patients born between 1973 and 2021 were collected over the 11-year period from 2012 to 2022. A total of 563 patients were enrolled, with 190 excluded for having insufficient laboratory data or treatment information, resulting in 373 eligible cases. RESULTS Of 328 cases of mother-to-child infection, 34 (10.4%) had spontaneous clearance, with a median time to spontaneous clearance of 3.1 years (range 0.9-7.2 years). Of the total 373 eligible cases, 190 received antiviral therapy (interferon-based therapy, 158; DAA therapy, 32). Sustained virologic response rates after first-line treatment were 75.3% (119/158) and 100% (32/32) for interferon-based therapy and DAA therapy, respectively, with the DAA group showing a shorter time from therapy initiation to viral negativity (2.7 vs. 1.0 months; p = 0.0031). CONCLUSIONS Approximately 10% of Japanese children infected by mother-to-child transmission achieve spontaneous resolution of HCV infection. Our findings indicate that DAA therapy is safe and highly effective in Japanese children, achieving higher sustained virologic response rates and shorter time to clearance of the virus compared with interferon-based therapy.
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Affiliation(s)
- Satoshi Nakano
- Department of Pediatrics, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Mitsuyoshi Suzuki
- Department of Pediatrics, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Reiko Hatori
- Department of Pediatrics, Gunma University Graduate School of Medicine, Gunma, Japan
| | - Tatsuki Mizuochi
- Department of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, Japan
| | - Yuri Etani
- Department of Gastroenterology, Nutrition and Endocrinology, Research Institute Osaka Women's and Children's Hospital, Osaka, Japan
| | - Hitoshi Tajiri
- Department of Pediatrics, Wakayama Medical University, Wakayama, Japan
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Rollin F, McNamara M, Aleuy L, Lom J, Chirumamilla S, Molinari A, Miller L, Fluker SA. Real world experience in treatment of chronic hepatitis C in patients with compensated and decompensated cirrhosis. Future Virol 2024; 19:393-399. [DOI: 10.1080/17460794.2024.2415213] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Accepted: 10/08/2024] [Indexed: 01/03/2025]
Affiliation(s)
- Francois Rollin
- Department of Medicine, Emory University School of Medicine
- Grady Liver Clinic, Grady Health Systems, Atlanta, GA 30303, USA
| | - Maeve McNamara
- Emory University School of Medicine, Atlanta, GA 30303, USA
| | - Lana Aleuy
- Department of Medicine, Emory University School of Medicine
| | - Jennifer Lom
- Department of Medicine, Emory University School of Medicine
- Grady Liver Clinic, Grady Health Systems, Atlanta, GA 30303, USA
| | - Siri Chirumamilla
- Family and Preventive Medicine, Emory University School of Medicine, Atlanta, GA 30303, USA
| | - Alexander Molinari
- Family and Preventive Medicine, Emory University School of Medicine, Atlanta, GA 30303, USA
| | - Lesley Miller
- Department of Medicine, Emory University School of Medicine
- Grady Liver Clinic, Grady Health Systems, Atlanta, GA 30303, USA
| | - Shelly-Ann Fluker
- Department of Medicine, Emory University School of Medicine
- Grady Liver Clinic, Grady Health Systems, Atlanta, GA 30303, USA
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Burton MJ, Voluse AC, Patel AB. Supporting direct acting antiviral medication adherence and treatment completion in a sample of predominantly rural veterans with hepatitis C and substance use disorders. Addict Sci Clin Pract 2024; 19:51. [PMID: 38918869 PMCID: PMC11197191 DOI: 10.1186/s13722-024-00480-8] [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: 03/18/2022] [Accepted: 06/12/2024] [Indexed: 06/27/2024] Open
Abstract
BACKGROUND Clinic-based interventions are needed to promote successful direct acting antiviral (DAA) treatment for chronic hepatitis C virus (HCV) infection in patients with substance use disorders (SUDs) among rural Veterans. METHODS We implemented a clinic-based intervention which used motivational interviewing (MI) techniques to promote medication adherence and treatment completion with 12 weeks of DAA treatment among rural Veterans with chronic HCV and SUDs. Patients received an MI session with a licensed psychologist at baseline and at each two-week follow-up visit during DAA treatment. Patients received $25 per study visit completed. Patients were to attend a laboratory visit 12 weeks after treatment completion to assess for sustained virologic response (SVR). RESULTS Of the 20 participants who enrolled, 75% (n = 15) completed the planned 12-week course of treatment. Average adherence by pill count was 92% (SD = 3%). Overall SVR was 95% (19/20). CONCLUSIONS We demonstrated that a clinic-based intervention which incorporated frequent follow up visits and MI techniques was feasible and acceptable to a sample of predominantly rural Veterans with chronic HCV and SUDs. CLINICAL TRIAL REGISTRATION Registered at ClinicalTrials.gov (NCT02823457) on July 1, 2016. https://clinicaltrials.gov .
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Affiliation(s)
- Mary Jane Burton
- G.V. (Sonny) Montgomery VA Medical Center, University of Mississippi Medical Center, 1500 E. Woodrow Wilson Avenue, Jackson, MS, 39216, USA.
| | - Andrew C Voluse
- G.V. (Sonny) Montgomery VA Medical Center, University of Mississippi Medical Center, 1500 E. Woodrow Wilson Avenue, Jackson, MS, 39216, USA
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Kimball S, Reynoso M, McKnight C, Des Jarlais D. Hepatitis C treatment outcomes among people who inject drugs experiencing unstable versus stable housing: Systematic review and meta-analysis. PLoS One 2024; 19:e0302471. [PMID: 38669250 PMCID: PMC11051606 DOI: 10.1371/journal.pone.0302471] [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: 02/15/2024] [Accepted: 04/04/2024] [Indexed: 04/28/2024] Open
Abstract
BACKGROUND The prevalence of hepatitis C virus (HCV) among people who inject drugs (PWID) is between 50-70%. Prior systematic reviews demonstrated that PWID have similar direct acting antiviral treatment outcomes compared to non-PWID; however, reviews have not examined treatment outcomes by housing status. Given the links between housing and health, identifying gaps in HCV treatment can guide future interventions. METHODS We conducted a systematic review using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched six databases for articles from 2014 onward. Two reviewers conducted title/abstract screenings, full-text review, and data extraction. We extracted effect measures for treatment initiation, adherence, completion, success, and reinfection by housing status. Studies underwent quality and certainty assessments, and we performed meta-analyses as appropriate. RESULTS Our search yielded 473 studies, eight of which met inclusion criteria. Only the treatment initiation outcome had sufficient measures for meta-analysis. Using a random-effects model, we found those with unstable housing had 0.40 (0.26, 0.62) times the odds of initiating treatment compared to those with stable housing. Other outcomes were not amenable for meta-analysis due to a limited number of studies or differing outcome definitions. CONCLUSIONS Among PWID, unstable housing appears to be a barrier to HCV treatment initiation; however, the existing data is limited for treatment initiation and the other outcomes we examined. There is a need for more informative studies to better understand HCV treatment among those with unstable housing. Specifically, future studies should better define housing status beyond a binary, static measure to capture the nuances and complexity of housing and its subsequent impact on HCV treatment. Additionally, researchers should meaningfully consider whether the outcome(s) of interest are being accurately measured for individuals experiencing unstable housing.
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Affiliation(s)
- Sarah Kimball
- Department of Epidemiology, New York University School of Global Public Health, New York, NY, United States of America
| | - Marley Reynoso
- Department of Epidemiology, New York University School of Global Public Health, New York, NY, United States of America
| | - Courtney McKnight
- Department of Epidemiology, New York University School of Global Public Health, New York, NY, United States of America
- Center for Drug Use and HIV/HCV Research, New York, NY, United States of America
| | - Don Des Jarlais
- Department of Epidemiology, New York University School of Global Public Health, New York, NY, United States of America
- Center for Drug Use and HIV/HCV Research, New York, NY, United States of America
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Schiano Moriello N, Pinchera B, Gentile I. Personalized care approaches to hepatitis C therapy: recent advances and future directions. Expert Rev Anti Infect Ther 2024; 22:139-151. [PMID: 38459735 DOI: 10.1080/14787210.2024.2328336] [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: 05/31/2023] [Accepted: 03/05/2024] [Indexed: 03/10/2024]
Abstract
INTRODUCTION The introduction of direct-acting antivirals (DAAs) has significantly transformed the therapeutic landscape for chronic C hepatitis virus (HCV) infection. However, there is still room for further improvement in optimizing therapy efficacy and minimizing adverse effects. AREAS COVERED This review is devoted to the rationale for adopting a personalized approach to HCV therapy. Specifically, we explore the role of host-related factors, such as sex or the presence of comorbidities. We thoroughly examine the implications of commonly encountered comorbidities, including HIV infection, chronic renal disease, liver cirrhosis, and other chronic viral hepatitis infections. Additionally, we discuss the prevalent drug-to-drug interactions between DAAs and other medications, while providing guidance on their management. Finally, we investigate viral-related issues that can influence treatment outcomes, such as viral genotype, quasi-species, and the presence of resistance-associated mutations. EXPERT OPINION Despite pivotal trials demonstrating efficacy rates exceeding 90% for currently available DAA regimens, there are still opportunities to optimize therapy outcomes and tailor treatment to each patient. This can be achieved through a meticulous evaluation of the patient's specific clinical conditions and comorbidities, a vigilant approach to manage potential drug interactions, and diligent patient follow-up.
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Affiliation(s)
| | - Biagio Pinchera
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - Ivan Gentile
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
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Requena MB, Protopopescu C, Stewart AC, van Santen DK, Klein MB, Jarrin I, Berenguer J, Wittkop L, Salmon D, Rauch A, Prins M, van der Valk M, Sacks-Davis R, Hellard ME, Carrieri P, Lacombe K. All-cause mortality before and after DAA availability among people living with HIV and HCV: An international comparison between 2010 and 2019. THE INTERNATIONAL JOURNAL OF DRUG POLICY 2024; 124:104311. [PMID: 38184902 DOI: 10.1016/j.drugpo.2023.104311] [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: 07/10/2023] [Revised: 12/18/2023] [Accepted: 12/21/2023] [Indexed: 01/09/2024]
Abstract
BACKGROUND Among people living with HIV and hepatitis C virus (HCV), people who inject drugs (PWID) have historically experienced higher mortality rates. Direct-acting antivirals (DAA), which have led to a 90 % HCV cure rate independently of HIV co-infection, have improved mortality rates. However, DAA era mortality trends among PWID with HIV/HCV remain unknown. Using data from the International Collaboration on Hepatitis C Elimination in HIV Cohorts (InCHEHC), we compared pre/post-DAA availability mortality changes in three groups: PWID, men who have sex with men (MSM), and all other participants. METHODS We included InCHEHC participants with HIV/HCV followed between 2010 and 2019 in Canada, France, the Netherlands, Spain, and Switzerland. All-cause mortality hazard was compared in the three groups, using Cox proportional hazards regression models adjusted for sex, age, advanced fibrosis/cirrhosis, and pre/post DAA availability. RESULTS Of the 11,029 participants, 76 % were men, 46 % were PWID, baseline median age was 46 years (interquartile range [IQR] = 40;51), and median CD4 T-cell count was 490 cells/mm3 (IQR = 327;689). Over the study period (median follow-up = 7.2 years (IQR = 3.7;10.0)), 6143 (56 %) participants received HCV treatment, 4880 (44 %) were cured, and 1322 participants died (mortality rate = 1.81/100 person-years (PY) [95 % confidence interval (CI)=1.72-1.91]). Overall, PWID had higher mortality rates than MSM (2.5/100 PY [95 % CI = 2.3-2.6] vs. 0.8/100 PY [95 % CI = 0.7-0.9], respectively). Unlike women with other transmission modes, those who injected drugs had a higher mortality hazard than men who did not inject drugs and men who were not MSM (adjusted Hazard-Ratio (aHR) [95 % CI] = 1.3[1.0-1.6]). Post-DAA availability, mortality decreased among MSM in the Netherlands, Spain, and Switzerland and increased among PWID in Canada (aHR [95 % CI] = 1.73 [1.15-2.61]). CONCLUSION Post-DAA availability, all-cause mortality did not decrease in PWID. Determinants of cause-specific deaths (drug-related, HIV-related, or HCV-related) need to be identified to explain persistently high mortality among PWID in the DAA era.
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Affiliation(s)
- Maria-Bernarda Requena
- Sorbonne Université, INSERM, Pierre Louis Institute of Epidemiology and Public Health, iPLESP, Paris, France
| | - Camelia Protopopescu
- Aix Marseille Univ, INSERM, IRD, SESSTIM, Sciences Economiques & Sociales de la Santé & Traitement de l'Information Médicale, ISSPAM, Marseille, France.
| | - Ashleigh C Stewart
- Disease Elimination Program, Burnet Institute, Melbourne, Australia; School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
| | - Daniela K van Santen
- Department of Infectious Diseases, Public Health Service of Amsterdam, Amsterdam, the Netherlands
| | - Marina B Klein
- Division of Infectious Diseases, McGill University Health Centre, Montreal, Canada
| | - Inmaculada Jarrin
- Instituto de Salud Carlos III, Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Infecciosas, CIBERINFEC, Madrid, Spain
| | - Juan Berenguer
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas, CIBERINFEC, Madrid, Spain; Infectious Diseases. Hospital General Universitario Gregorio Marañón, IiSGM, Madrid, Spain
| | - Linda Wittkop
- Université de Bordeaux, ISPED, INSERM, Bordeaux Population Health Research Center, U1219, CIC-EC 1401, Bordeaux, France; Inria équipe SISTM, Talence, France; CHU de Bordeaux, Service d'information médicale, INSERM, Institut Bergonié, CIC-EC 1401, Bordeaux, France
| | - Dominique Salmon
- Université Paris Descartes, Service Maladies Infectieuses et Tropicales, AP-HP, Hôpital Cochin, Paris, France
| | - Andri Rauch
- Department of Infectious Diseases, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Maria Prins
- Department of Infectious Diseases, Public Health Service of Amsterdam, Amsterdam, the Netherlands; Department of Infectious Diseases, Amsterdam Infection and Immunity Institute, AI&II, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
| | - Marc van der Valk
- Department of Infectious Diseases, Amsterdam Infection and Immunity Institute, AI&II, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands; Stichting HIV Monitoring, Amsterdam, the Netherlands
| | - Rachel Sacks-Davis
- Disease Elimination Program, Burnet Institute, Melbourne, Australia; School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia; Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia
| | - Margaret E Hellard
- Disease Elimination Program, Burnet Institute, Melbourne, Australia; School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia; Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia; Department of Infectious Diseases, The Alfred and Monash University, Melbourne, Australia
| | - Patrizia Carrieri
- Aix Marseille Univ, INSERM, IRD, SESSTIM, Sciences Economiques & Sociales de la Santé & Traitement de l'Information Médicale, ISSPAM, Marseille, France
| | - Karine Lacombe
- Sorbonne Université, INSERM, Pierre Louis Institute of Epidemiology and Public Health, iPLESP, Paris, France; AP-HP, Department of Infectious Diseases, Saint-Antoine Hospital, Paris, France
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11
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McGee-Avila JK, Argirion I, Engels EA, O’Brien TR, Horner MJ, Qiao B, Monterosso A, Luo Q, Shiels MS. Risk of hepatocellular carcinoma in people with HIV in the United States, 2001-2019. J Natl Cancer Inst 2024; 116:61-68. [PMID: 37610358 PMCID: PMC10777672 DOI: 10.1093/jnci/djad172] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Revised: 07/06/2023] [Accepted: 08/17/2023] [Indexed: 08/24/2023] Open
Abstract
BACKGROUND People with HIV have higher risk of hepatocellular carcinoma than the general population, partly because of higher prevalence of coinfection with hepatitis B virus (HBV) or hepatitis C virus (HCV). METHODS We calculated standardized incidence ratios for hepatocellular carcinoma in people with HIV by comparing rates from people with HIV in the HIV/AIDS Cancer Match Study, a population-based HIV and cancer registry linkage, to those in the general population. We used multivariable Poisson regression to estimate adjusted incidence rate ratios among people with HIV and linked the Texas HIV registry with medical claims data to estimate adjusted odds ratios (AORs) of HBV and HCV in hepatocellular carcinoma patients with logistic regression. RESULTS Compared with the general population, hepatocellular carcinoma rates in people with HIV were elevated 2.79-fold (n = 1736; 95% confidence interval [CI] = 2.66 to 2.92). Hepatocellular carcinoma rates decreased statistically significantly from 2001-2004 to 2015-2019 (P < .001). Compared with men who have sex with men, hepatocellular carcinoma risk was elevated 4.28-fold among men who injected drugs (95% CI = 3.72 to 4.93) and 1.83-fold among women who injected drugs (95% CI = 1.49 to 2.26). In Texas, 146 hepatocellular carcinoma cases among people with HIV were linked to claims data: 25% HBV positive, 59% HCV positive, and 13% coinfected with HBV and HCV. Compared with men who had sex with men, people who inject drugs had 82% decreased odds of HBV (AOR = 0.18, 95% CI = 0.05 to 0.63) and 2 times the odds of HCV (AOR = 20.4, 95% CI = 3.32 to 125.3). CONCLUSIONS During 2001-2019, hepatocellular carcinoma risk declined among people with HIV, though rates remain statistically significantly elevated compared with the general population, particularly among people who inject drugs. Prevention and treatment of HBV/HCV are needed to reduce hepatocellular carcinoma risk among people with HIV.
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Affiliation(s)
- Jennifer K McGee-Avila
- Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
| | - Ilona Argirion
- Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
| | - Eric A Engels
- Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
| | - Thomas R O’Brien
- Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
| | - Marie-Josèphe Horner
- Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
- Trans-Divisional Research Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
| | - Baozhen Qiao
- Bureau of Cancer Epidemiology, New York State Department of Health, Albany, NY, USA
| | - Analise Monterosso
- HIV/STD/HCV Epidemiology and Surveillance Unit, Texas Department of State Health Services, Austin, TX, USA
| | - Qianlai Luo
- Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
| | - Meredith S Shiels
- Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
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12
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Zhou J, Wang FD, Li LQ, Li JY, Chen EQ. Decreased Efficacy of Sofosbuvir/Velpatasvir in HIV Patients Coinfected with HCV Genotype 3b. Future Virol 2024; 19:33-45. [DOI: 10.2217/fvl-2023-0112] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Accepted: 01/29/2024] [Indexed: 01/13/2025]
Affiliation(s)
- Jing Zhou
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Fa-Da Wang
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Lan-Qing Li
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Jing-Yu Li
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - En-Qiang Chen
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, 610041, China
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13
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Volesky-Avellaneda KD, Morais S, Walter SD, O’Brien TR, Hildesheim A, Engels EA, El-Zein M, Franco EL. Cancers Attributable to Infections in the US in 2017: A Meta-Analysis. JAMA Oncol 2023; 9:1678-1687. [PMID: 37856141 PMCID: PMC10587828 DOI: 10.1001/jamaoncol.2023.4273] [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: 04/25/2023] [Accepted: 07/09/2023] [Indexed: 10/20/2023]
Abstract
Importance Infections are largely modifiable causes of cancer. However, there remains untapped potential for preventing and treating carcinogenic infections in the US. Objective To estimate the percentage and number of incident cancers attributable to infections in the US among adults and children for the most recent year cancer incidence data were available (2017). Data Sources A literature search from 1946 onward was performed in MEDLINE on January 6, 2023, to obtain the data required to calculate population attributable fractions for 31 infection-cancer pairs. National Health and Nutrition Examination Survey data were used to estimate the population prevalence of hepatitis B and C viruses and Helicobacter pylori. Study Selection Studies conducted in the US or other Western countries were selected according to specific infection-cancer criteria. Data Extraction and Synthesis Data from 128 studies were meta-analyzed to obtain the magnitude of an infection-cancer association or prevalence of the infection within cancer cells. Main Outcomes and Measures The proportion of cancer incidence attributable to 8 infections. Results Of the 1 666 102 cancers diagnosed in 2017 among individuals aged 20 years or older in the US, 71 485 (4.3%; 95% CI, 3.1%-5.3%) were attributable to infections. Human papillomavirus (n = 38 230) was responsible for the most cancers, followed by H pylori (n = 10 624), hepatitis C virus (n = 9006), Epstein-Barr virus (n = 7581), hepatitis B virus (n = 2310), Merkel cell polyomavirus (n = 2000), Kaposi sarcoma-associated herpesvirus (n = 1075), and human T-cell lymphotropic virus type 1 (n = 659). Cancers with the most infection-attributable cases were cervical (human papillomavirus; n = 12 829), gastric (H pylori and Epstein-Barr virus; n = 12 565), oropharynx (human papillomavirus; n = 12 430), and hepatocellular carcinoma (hepatitis B and C viruses; n = 10 017). The burden of infection-attributable cancers as a proportion of total cancer incidence ranged from 9.6% (95% CI, 9.2%-10.0%) for women aged 20 to 34 years to 3.2% (95% CI, 2.4%-3.8%) for women aged 65 years or older and from 6.1% (95% CI, 5.2%-7.0%) for men aged 20 to 34 years to 3.3% (95% CI, 1.9%-4.4%) for men aged 65 years or older. Among those aged 19 years or younger, 2.2% (95% CI, 1.3%-3.0%) of cancers diagnosed in 2017 were attributable to Epstein-Barr virus. Conclusions and Relevance Infections were estimated to be responsible for 4.3% of cancers diagnosed among adults in the US in 2017 and, therefore, represent an important target for cancer prevention efforts.
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Affiliation(s)
- Karena D. Volesky-Avellaneda
- Division of Cancer Epidemiology, McGill University, Montreal, Quebec, Canada
- Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada
- Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland
| | - Samantha Morais
- Division of Cancer Epidemiology, McGill University, Montreal, Quebec, Canada
- ICES, Toronto, Ontario, Canada
| | - Stephen D. Walter
- Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada
| | - Thomas R. O’Brien
- Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland
| | - Allan Hildesheim
- Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland
| | - Eric A. Engels
- Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland
| | - Mariam El-Zein
- Division of Cancer Epidemiology, McGill University, Montreal, Quebec, Canada
| | - Eduardo L. Franco
- Division of Cancer Epidemiology, McGill University, Montreal, Quebec, Canada
- Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada
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14
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Nyein PP, Tillakeratne S, Phyu S, Yee MM, Lwin MM, Htike KL, Aung MT, Grebely J, Applegate T, Hanson J, Matthews G, Lin KS. Evaluation of Simplified HCV Diagnostics in HIV/HCV Co-Infected Patients in Myanmar. Viruses 2023; 15:v15020521. [PMID: 36851736 PMCID: PMC9967037 DOI: 10.3390/v15020521] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2022] [Revised: 02/06/2023] [Accepted: 02/08/2023] [Indexed: 02/16/2023] Open
Abstract
To evaluate a decentralised testing model and simplified treatment protocol of hepatitis C virus (HCV) infection to facilitate treatment scale-up in Myanmar, this prospective, observational study recruited HIV-HCV co-infected outpatients receiving sofosbuvir/daclatasvir in Yangon, Myanmar. The study examined the outcomes and factors associated with a sustained virological response (SVR). A decentralised "hub-and-spoke" testing model was evaluated where fingerstick capillary specimens were transported by taxi and processed centrally. The performance of the Xpert HCV VL Fingerstick Assay in detecting HCV RNA was compared to the local standard of care ( plasma HCV RNA collected by venepuncture). Between January 2019 and February 2020, 162 HCV RNA-positive individuals were identified; 154/162 (95%) initiated treatment, and 128/154 (84%) returned for their SVR12 visit. A SVR was achieved in 119/154 (77%) participants in the intent-to-treat population and 119/128 (93%) participants in the modified-intent-to-treat population. Individuals receiving an antiretroviral therapy were more likely to achieve a SVR (with an odds ratio (OR) of 7.16, 95% CI 1.03-49.50), while those with cirrhosis were less likely (OR: 0.26, 95% CI 0.07-0.88). The sensitivity of the Xpert HCV VL Fingerstick Assay was 99.4% (95% CI 96.7-100.0), and the specificity was 99.2% (95% CI 95.9-99.9). A simplified treatment protocol using a hub-and-spoke testing model of fingerstick capillary specimens can achieve an SVR rate in LMIC comparable to well-resourced high-income settings.
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Affiliation(s)
| | - Shane Tillakeratne
- The Kirby Institute, University of New South Wales, Sydney, NSW 2052, Australia
- Correspondence:
| | - Sabai Phyu
- Department of Tropical and Infectious Diseases, Specialist Hospital Waibargi, Yangon W5C4+6J7, Myanmar
| | | | - Mya Mya Lwin
- Department of Microbiology, University of Medicine 2, Yangon 644-704, Myanmar
| | - Kyaw Linn Htike
- Myanmar-Australia Research Collaboration for Health Laboratory, Yangon W5C4+6J7, Myanmar
| | - May Thu Aung
- Myanmar-Australia Research Collaboration for Health Laboratory, Yangon W5C4+6J7, Myanmar
| | - Jason Grebely
- The Kirby Institute, University of New South Wales, Sydney, NSW 2052, Australia
| | - Tanya Applegate
- The Kirby Institute, University of New South Wales, Sydney, NSW 2052, Australia
| | - Josh Hanson
- The Kirby Institute, University of New South Wales, Sydney, NSW 2052, Australia
- Cairns and Hinterland Hospital and Health Service, Cairns North, QLD 4870, Australia
| | - Gail Matthews
- The Kirby Institute, University of New South Wales, Sydney, NSW 2052, Australia
| | - Kyaw Swar Lin
- Specialist Hospital Mingaladon, Yangon X42H+J4, Myanmar
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15
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Khemnark S, Manosuthi W. Real-world treatment outcomes of sofosbuvir-based regimens for treatment of chronic hepatitis C with and without human immunodeficiency virus co-infection. JGH Open 2023; 7:157-162. [PMID: 36852142 PMCID: PMC9958333 DOI: 10.1002/jgh3.12869] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2022] [Revised: 01/09/2023] [Accepted: 01/12/2023] [Indexed: 01/28/2023]
Abstract
Background and Aim The efficacy of sofosbuvir (SOF)-based regimens in the treatment of chronic hepatitis C (HCV) patients with and without human immunodeficiency virus (HIV) co-infected patients in real-world setting is limited. Methods This was a retrospective cohort study, conducted between 1 January 2017 and 31 December 2021 at Bamrasnaradura Infectious Disease Institute, Thailand. All HCV patients received 12 weeks of SOF-based regimens and had follow-up for at least 12 weeks after therapy discontinuation. The primary outcome was sustained virological response (SVR) at 12 weeks after the end of treatment. Treatment outcomes were compared between HCV patients with and without HIV co-infection. Results A total of 163 patients were included in the study, 130 (79.8%) were HCV/HIV co-infected, and 33 (20.2%) were HCV mono-infected. Of all, 106 (64%) patients received SOF and ledipasvir. Genotype 1 (GT1) was predominant at 66.4%, followed by GT3 at 22.2%, and GT6 at 11.4%. Overall SVR was 96.9%. SVR in HCV mono-infected was 96.9% and SVR in HIV-HCV co-infected patients was 96.9%. The factor associated with SVR was HCV genotype (P = 0.001). Patients with HCV GT6 had lower SVR rates compared with GT1 and GT3 patients (83.3%, 100%, and 97.1% [P = 0.000] respectively). There was no association between SVR and other factors such as gender, age, BMI, underlying cirrhosis, baseline HCV viral load, or prior treatment history (all P > 0.05). All patients completed 12-week SOF-based treatment. Conclusion In real-world setting, HCV treatment with SOF-based regimens between patients with and without HIV co-infection showed high rates of SVR. SOF-based regimens were highly efficacious and tolerated.
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Affiliation(s)
- Suparat Khemnark
- Department of MedicineBamrasnaradura Infectious Disease Institute, Ministry of Public HealthNonthaburiThailand
| | - Weerawat Manosuthi
- Department of MedicineBamrasnaradura Infectious Disease Institute, Ministry of Public HealthNonthaburiThailand
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16
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Hidaka M, Eguchi S, Hasegawa K, Shimamura T, Hatano E, Ohdan H, Hibi T, Hasegawa Y, Kaneko J, Goto R, Egawa H, Eguchi H, Tsukada K, Yotsuyanagi H, Soyama A, Hara T, Takatsuki M. Impact of sustained viral response for hepatitis C virus on the outcomes of liver transplantation in hemophilic patients with human immunodeficiency virus/hepatitis C virus co-infection: A nationwide survey in Japan. Hepatol Res 2023; 53:18-25. [PMID: 36002995 DOI: 10.1111/hepr.13833] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2022] [Revised: 08/16/2022] [Accepted: 08/16/2022] [Indexed: 01/03/2023]
Abstract
AIM Human immunodeficiency virus (HIV)/hepatitis C virus (HCV) co-infection from blood products for hemophilia has been a social problem in Japan, and liver transplantation (LT) for these patients has been a challenging procedure. However, with the advent of the direct-acting antiviral agent for HCV and change in the policy for prioritization of deceased donor LT, the results of LT for patients co-infected with HCV/HIV may have improved. METHODS This study was conducted to provide updated results of our nationwide survey of LT for patients co-infected with HCV/HIV, from January 1997 to December 2019. We collected data on 17 patients with HIV/HCV co-infection who underwent either deceased donor LT (n = 5) or living donor LT (n = 12). RESULTS All the patients were men with hemophilia, and the median age was 41 (range, 23-61) years. The median CD4 count before LT was 258 (range, 63-751). Most patients had poor liver function before surgery with Child-Pugh grade C and a Model for End-stage Liver Disease score of 20 (range, 11-48). The right lobe was used for most grafts for living donor liver transplantation (n = 10). Overall survival was significantly better with a sustained viral response (SVR) than without an SVR, and a univariate analysis indicated that SVR after direct-acting antiviral or interferon/ribavirin showed the highest hazard ratio for patient survival after LT. A multivariate analysis was not possible because of the limited number of cases. CONCLUSION SVR for HCV showed the highest impact on the outcome of LT for patients with hemophilia co-infected with HIV/HCV. SVR for HCV should be achieved before or after LT for patients with hemophilia co-infected with HIV/HCV for a better outcome.
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Affiliation(s)
- Masaaki Hidaka
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Susumu Eguchi
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Kiyoshi Hasegawa
- Hepato-Biliary-Pancreatic Surgery Division, Artificial Organ and Transplantation Division, Tokyo, Japan.,Department of Surgery, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan
| | - Tsuyoshi Shimamura
- Division of Organ Transplantation, Hokkaido University Hospital, Sapporo, Japan
| | - Etsuro Hatano
- Division of Hepatobiliary Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine Kyoto University, Kyoto, Japan
| | - Hideki Ohdan
- Department of Gastroenterological and Transplant Surgery Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Taizo Hibi
- Department of Pediatric Surgery and Transplantation, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Yasushi Hasegawa
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Junichi Kaneko
- Hepato-Biliary-Pancreatic Surgery Division, Artificial Organ and Transplantation Division, Tokyo, Japan.,Department of Surgery, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan
| | - Ryoichi Goto
- Division of Organ Transplantation, Hokkaido University Hospital, Sapporo, Japan
| | - Hiroto Egawa
- Department of Surgery, Tokyo Women's Medical University, Tokyo, Japan
| | - Hidetoshi Eguchi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Kunihisa Tsukada
- Institute of Clinical Research, National Hospital Organization Higashisaitama Hospital, Saitama, Japan
| | - Hiroshi Yotsuyanagi
- Department of Infectious Diseases and Applied Immunology, IMSUT Hospital of The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Akihiko Soyama
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Takanobu Hara
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Mitsuhisa Takatsuki
- Department of Digestive and General Surgery, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan
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17
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Huang KY, Kao HJ, Weng TH, Chen CH, Weng SL. iDVIP: identification and characterization of viral integrase inhibitory peptides. Brief Bioinform 2022; 23:6754756. [PMID: 36215051 DOI: 10.1093/bib/bbac406] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2022] [Revised: 08/12/2022] [Accepted: 08/22/2022] [Indexed: 12/14/2022] Open
Abstract
Antiretroviral peptides are a kind of bioactive peptides that present inhibitory activity against retroviruses through various mechanisms. Among them, viral integrase inhibitory peptides (VINIPs) are a class of antiretroviral peptides that have the ability to block the action of integrase proteins, which is essential for retroviral replication. As the number of experimentally verified bioactive peptides has increased significantly, the lack of in silico machine learning approaches can effectively predict the peptides with the integrase inhibitory activity. Here, we have developed the first prediction model for identifying the novel VINIPs using the sequence characteristics, and the hybrid feature set was considered to improve the predictive ability. The performance was evaluated by 5-fold cross-validation based on the training dataset, and the result indicates the proposed model is capable of predicting the VINIPs, with a sensitivity of 85.82%, a specificity of 88.81%, an accuracy of 88.37%, a balanced accuracy of 87.32% and a Matthews correlation coefficient value of 0.64. Most importantly, the model also consistently provides effective performance in independent testing. To sum up, we propose the first computational approach for identifying and characterizing the VINIPs, which can be considered novel antiretroviral therapy agents. Ultimately, to facilitate further research and development, iDVIP, an automatic computational tool that predicts the VINIPs has been developed, which is now freely available at http://mer.hc.mmh.org.tw/iDVIP/.
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Affiliation(s)
- Kai-Yao Huang
- Department of Medical Research, Hsinchu MacKay Memorial Hospital, Hsinchu city 300, Taiwan.,Department of Medicine, MacKay Medical College, New Taipei City 252, Taiwan
| | - Hui-Ju Kao
- Department of Medical Research, Hsinchu MacKay Memorial Hospital, Hsinchu city 300, Taiwan
| | - Tzu-Hsiang Weng
- Department of Obstetrics and Gynecology, MacKay Memorial Hospital, Taipei city 104, Taiwan
| | - Chia-Hung Chen
- Department of Medical Research, Hsinchu MacKay Memorial Hospital, Hsinchu city 300, Taiwan
| | - Shun-Long Weng
- Department of Medicine, MacKay Medical College, New Taipei City 252, Taiwan.,Department of Obstetrics and Gynecology, Hsinchu MacKay Memorial Hospital, Hsinchu city 300, Taiwan.,MacKay Junior College of Medicine, Nursing and Management, Taipei 112, Taiwan
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Bar N, Bensoussan N, Rabinowich L, Levi S, Houri I, Ben-Ami Shor D, Shibolet O, Mor O, Weitzman E, Turner D, Katchman H. Barriers and Facilitators of Hepatitis C Care in Persons Coinfected with Human Immunodeficiency Virus. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:15237. [PMID: 36429957 PMCID: PMC9690547 DOI: 10.3390/ijerph192215237] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Revised: 11/09/2022] [Accepted: 11/13/2022] [Indexed: 06/16/2023]
Abstract
Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) are often co-transmitted. Viral coinfection results in worse outcomes. Persons who inject drugs (PWIDs) face barriers to medical treatment, but HCV treatment is indicated and effective even with ongoing active drug use. We aimed to assess access to HCV care and treatment results in patients coinfected with HIV-HCV. This is a real-world retrospective single-center study of patients followed in the HIV clinic between 2002 and 2018. Linkage to care was defined as achieving care cascade steps: (1) hepatology clinic visit, (2) receiving prescription of anti-HCV treatment, and (3) documentation of sustained virologic response (SVR). Of 1660 patients with HIV, 254 with HIV-HCV coinfection were included. Only 39% of them achieved SVR. The rate limiting step was the engagement into hepatology care. Being a PWID was associated with ~50% reduced odds of achieving study outcomes, active drug use was associated with ~90% reduced odds. Older age was found to facilitate treatment success. Once treated, the rate of SVR was high in all populations. HCV is undertreated in coinfected young PWIDs. Further efforts should be directed to improve access to care in this marginalized population.
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Affiliation(s)
- Nir Bar
- Gastroenterology and Hepatology Department, Tel Aviv Medical Center, Tel Aviv 6423906, Israel
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6195001, Israel
| | - Noa Bensoussan
- Gastroenterology and Hepatology Department, Tel Aviv Medical Center, Tel Aviv 6423906, Israel
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6195001, Israel
| | - Liane Rabinowich
- Gastroenterology and Hepatology Department, Tel Aviv Medical Center, Tel Aviv 6423906, Israel
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6195001, Israel
| | - Sharon Levi
- Gastroenterology and Hepatology Department, Tel Aviv Medical Center, Tel Aviv 6423906, Israel
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6195001, Israel
| | - Inbal Houri
- Gastroenterology and Hepatology Department, Tel Aviv Medical Center, Tel Aviv 6423906, Israel
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6195001, Israel
| | - Dana Ben-Ami Shor
- Gastroenterology and Hepatology Department, Tel Aviv Medical Center, Tel Aviv 6423906, Israel
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6195001, Israel
| | - Oren Shibolet
- Gastroenterology and Hepatology Department, Tel Aviv Medical Center, Tel Aviv 6423906, Israel
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6195001, Israel
| | - Orna Mor
- Central Virology Laboratory, Ministry of Health, Chaim Sheba Medical Center, Ramat Gan 5262000, Israel
- Department of Epidemiology, School of public health, Faculty of Medicine, Tel Aviv University, Tel Aviv 6195001, Israel
| | - Ella Weitzman
- Center for Liver Disease, Rambam Healthcare Campus, Rappaport Faculty of Medicine, Technion, Haifa 3109601, Israel
| | - Dan Turner
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6195001, Israel
- Crusaid Kobler AIDS Center, Tel Aviv Medical Center, Tel Aviv 6423906, Israel
| | - Helena Katchman
- Gastroenterology and Hepatology Department, Tel Aviv Medical Center, Tel Aviv 6423906, Israel
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6195001, Israel
- Department of Gastroenterology and Hepatology, Tel Aviv Medical Center, Tel Aviv 6423906, Israel
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Hao Y, Chen M, Othman Y, Xie XQ, Feng Z. Virus-CKB 2.0: Viral-Associated Disease-Specific Chemogenomics Knowledgebase. ACS OMEGA 2022; 7:37476-37484. [PMID: 36312370 PMCID: PMC9609052 DOI: 10.1021/acsomega.2c04258] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Accepted: 09/26/2022] [Indexed: 06/16/2023]
Abstract
Transmissible and infectious viruses can cause large-scale epidemics around the world. This is because the virus can constantly mutate and produce different variants and subvariants to counter existing treatments. Therefore, a variety of treatments are urgently needed to keep up with the mutation of the viruses. To facilitate the research of such treatment, we updated our Virus-CKB 1.0 to Virus-CKB 2.0, which contains 10 kinds of viruses, including enterovirus, dengue virus, hepatitis C virus, Zika virus, herpes simplex virus, Andes orthohantavirus, human immunodeficiency virus, Ebola virus, Lassa virus, influenza virus, coronavirus, and norovirus. To date, Virus-CKB 2.0 archived at least 65 antiviral drugs (such as remdesivir, telaprevir, acyclovir, boceprevir, and nelfinavir) in the market, 178 viral-related targets with 292 available 3D crystal or cryo-EM structures, and 3766 chemical agents reported for these target proteins. Virus-CKB 2.0 is integrated with established tools for target prediction and result visualization; these include HTDocking, TargetHunter, blood-brain barrier (BBB) predictor, Spider Plot, etc. The Virus-CKB 2.0 server is accessible at https://www.cbligand.org/g/virus-ckb. By using the established chemogenomic tools and algorithms and newly developed tools, we can screen FDA-approved drugs and chemical compounds that may bind to these proteins involved in viral-associated disease regulation. If the virus strain mutates and the vaccine loses its effect, we can still screen drugs that can be used to treat the mutated virus in a fleeting time. In some cases, we can even repurpose FDA-approved drugs through Virus-CKB 2.0.
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Affiliation(s)
| | | | - Yasmin Othman
- Department of Pharmaceutical
Sciences and Computational Chemical Genomics Screening Center, School
of Pharmacy; National Center of Excellence for Computational Drug
Abuse Research; Drug Discovery Institute; Departments of Computational
Biology and Structural Biology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, United States
| | - Xiang-Qun Xie
- Department of Pharmaceutical
Sciences and Computational Chemical Genomics Screening Center, School
of Pharmacy; National Center of Excellence for Computational Drug
Abuse Research; Drug Discovery Institute; Departments of Computational
Biology and Structural Biology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, United States
| | - Zhiwei Feng
- Department of Pharmaceutical
Sciences and Computational Chemical Genomics Screening Center, School
of Pharmacy; National Center of Excellence for Computational Drug
Abuse Research; Drug Discovery Institute; Departments of Computational
Biology and Structural Biology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, United States
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Proulx J, Ghaly M, Park IW, Borgmann K. HIV-1-Mediated Acceleration of Oncovirus-Related Non-AIDS-Defining Cancers. Biomedicines 2022; 10:biomedicines10040768. [PMID: 35453518 PMCID: PMC9024568 DOI: 10.3390/biomedicines10040768] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Revised: 03/22/2022] [Accepted: 03/22/2022] [Indexed: 11/25/2022] Open
Abstract
With the advent of combination antiretroviral therapy (cART), overall survival has been improved, and the incidence of acquired immunodeficiency syndrome (AIDS)-defining cancers has also been remarkably reduced. However, non-AIDS-defining cancers among human immunodeficiency virus-1 (HIV-1)-associated malignancies have increased significantly so that cancer is the leading cause of death in people living with HIV in certain highly developed countries, such as France. However, it is currently unknown how HIV-1 infection raises oncogenic virus-mediated cancer risks in the HIV-1 and oncogenic virus co-infected patients, and thus elucidation of the molecular mechanisms for how HIV-1 expedites the oncogenic viruses-triggered tumorigenesis in the co-infected hosts is imperative for developing therapeutics to cure or impede the carcinogenesis. Hence, this review is focused on HIV-1 and oncogenic virus co-infection-mediated molecular processes in the acceleration of non-AIDS-defining cancers.
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21
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Kouroumalis E, Voumvouraki A. Hepatitis C virus: A critical approach to who really needs treatment. World J Hepatol 2022; 14:1-44. [PMID: 35126838 PMCID: PMC8790391 DOI: 10.4254/wjh.v14.i1.1] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Revised: 04/14/2021] [Accepted: 12/31/2021] [Indexed: 02/06/2023] Open
Abstract
Introduction of effective drugs in the treatment of hepatitis C virus (HCV) infection has prompted the World Health Organization to declare a global eradication target by 2030. Propositions have been made to screen the general population and treat all HCV carriers irrespective of the disease status. A year ago the new severe acute respiratory syndrome coronavirus 2 virus appeared causing a worldwide pandemic of coronavirus disease 2019 disease. Huge financial resources were redirected, and the pandemic became the first priority in every country. In this review, we examined the feasibility of the World Health Organization elimination program and the actual natural course of HCV infection. We also identified and analyzed certain comorbidity factors that may aggravate the progress of HCV and some marginalized subpopulations with characteristics favoring HCV dissemination. Alcohol consumption, HIV coinfection and the presence of components of metabolic syndrome including obesity, hyperuricemia and overt diabetes were comorbidities mostly responsible for increased liver-related morbidity and mortality of HCV. We also examined the significance of special subpopulations like people who inject drugs and males having sex with males. Finally, we proposed a different micro-elimination screening and treatment program that can be implemented in all countries irrespective of income. We suggest that screening and treatment of HCV carriers should be limited only in these particular groups.
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Affiliation(s)
- Elias Kouroumalis
- Department of Gastroenterology, University of Crete Medical School, Heraklion 71500, Crete, Greece
| | - Argyro Voumvouraki
- First Department of Internal Medicine, AHEPA University Hospital, Thessaloniki 54621, Greece
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22
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Tripathi G, Rooge S, Yadav M, Mathew B, Sharma N, Bindal V, Hemati H, Singh Maras J, Gupta E. Baseline Plasma Metabotype Correlates With Direct-Acting Antiviral Therapy Nonresponse for HCV in HIV–HCV Coinfected Patients. Front Mol Biosci 2022; 8:748014. [PMID: 35083276 PMCID: PMC8784690 DOI: 10.3389/fmolb.2021.748014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Accepted: 12/15/2021] [Indexed: 11/22/2022] Open
Abstract
Introduction: With the advent of direct-acting antiviral (DAA) therapy for HCV, the cure is achieved at similar rates among HIV–HCV coinfected patients as in HCV mono-infected patients. The present study evaluates host plasma metabolites as putative indicators in predicting the treatment response in baseline HIV–HCV patients. Methods: Non-cirrhotic HIV–HCV (N = 43) coinfected patients were treated with sofosbuvir and daclatasvir for 12 weeks. Plasma metabolite profiling of pre- and post-therapy was analyzed in 20/43 patients. Of the 20 selected, 10 (50%) attained the sustained viral response [(SVR) (responders)] as defined by the absence of HCV RNA at 12 weeks after the treatment, and 10 (50%) did not attain the cure for HCV (nonresponders). Results: A total of 563 features were annotated (metabolomic/spectral databases). Before therapy, 39 metabolites differentiated (FC ±1.5, p < 0.05) nonresponders from responders. Of these, 20 upregulated and 19 downregulated were associated with tryptophan metabolism, nicotinamide metabolism, and others. Post therapy, 62 plasma metabolites (12 upregulated and 50 downregulated, FC±1.5, p < 0.05) differentiated nonresponders from responders and highlighted a significant increase in the steroid and histidine metabolism and significant decrease in tryptophan metabolism and ascorbate and pyruvate metabolism in the nonresponders. Based on random forest and multivariate linear regression analysis, the baseline level of N-acetylspermidine (FC > 2, AUC = 0.940, Bfactor = −0.267) and 2-acetolactate (FC > 2, AUC = 0.880, Bfactor = −0.713) significantly differentiated between nonresponders from responders in HIV–HCV coinfected patients and was able to predict the failure of treatment response. Conclusion: Increased baseline levels of N-acetylspermidine and 2-acetolactate levels are associated with the likeliness of failure to attain the cure for HCV in HIV–HCV coinfected patients.
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Affiliation(s)
- Gaurav Tripathi
- Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Sheetalnath Rooge
- Department of Clinical Virology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Manisha Yadav
- Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Babu Mathew
- Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Nupur Sharma
- Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Vasundhra Bindal
- Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Hamed Hemati
- Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Jaswinder Singh Maras
- Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
- *Correspondence: Ekta Gupta, ; Jaswinder Singh Maras,
| | - Ekta Gupta
- Department of Clinical Virology, Institute of Liver and Biliary Sciences, New Delhi, India
- *Correspondence: Ekta Gupta, ; Jaswinder Singh Maras,
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23
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Pabjan P, Brzdęk M, Chrapek M, Dziedzic K, Dobrowolska K, Paluch K, Garbat A, Błoniarczyk P, Reczko K, Stępień P, Zarębska-Michaluk D. Are There Still Difficult-to-Treat Patients with Chronic Hepatitis C in the Era of Direct-Acting Antivirals? Viruses 2022; 14:96. [PMID: 35062302 PMCID: PMC8779728 DOI: 10.3390/v14010096] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2021] [Revised: 12/29/2021] [Accepted: 01/04/2022] [Indexed: 12/17/2022] Open
Abstract
Difficult-to-treat populations with chronic hepatitis C (CHC), in the era of interferon treatment, included patients with liver cirrhosis, kidney impairment, treatment-experienced individuals, and those coinfected with the human immunodeficiency virus. The current study aimed to determine whether, in the era of direct-acting antivirals (DAA), there are still patients that are difficult-to-treat. The study included all consecutive patients chronically infected with hepatitis C virus (HCV) who started interferon-free therapy between July 2015 and December 2020 in the Department of Infectious Diseases in Kielce. The analyzed real-world population consisted of 963 patients, and most of them were infected with genotype 1 (87.6%) with the predominance of subtype 1b and were treatment-naïve (78.8%). Liver cirrhosis was determined in 207 individuals (21.5%), of whom 82.6% were compensated. The overall sustained virologic response, after exclusion of non-virologic failures, was achieved in 98.4%. The univariable analysis demonstrated the significantly lower response rates in males, patients with liver cirrhosis, decompensation of hepatic function at baseline, documented esophageal varices, concomitant diabetes, body mass index ≥25, and previous ineffective antiviral treatment. Despite an overall very high effectiveness, some unfavorable factors, including male gender, genotype 3 infection, liver cirrhosis, and treatment experience, significantly reduce the chances for a virologic response were identified.
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Affiliation(s)
- Paweł Pabjan
- Department of Infectious Diseases, Voivodship Hospital, Jan Kochanowski University, 25-317 Kielce, Poland; (P.P.); (K.P.); (A.G.); (P.B.); (K.R.); (P.S.)
| | - Michał Brzdęk
- Collegium Medicum, Jan Kochanowski University, 25-369 Kielce, Poland; (M.B.); (K.D.); (K.D.)
| | - Magdalena Chrapek
- Faculty of Natural Sciences, Jan Kochanowski University, 25-369 Kielce, Poland;
| | - Kacper Dziedzic
- Collegium Medicum, Jan Kochanowski University, 25-369 Kielce, Poland; (M.B.); (K.D.); (K.D.)
| | - Krystyna Dobrowolska
- Collegium Medicum, Jan Kochanowski University, 25-369 Kielce, Poland; (M.B.); (K.D.); (K.D.)
| | - Katarzyna Paluch
- Department of Infectious Diseases, Voivodship Hospital, Jan Kochanowski University, 25-317 Kielce, Poland; (P.P.); (K.P.); (A.G.); (P.B.); (K.R.); (P.S.)
| | - Anna Garbat
- Department of Infectious Diseases, Voivodship Hospital, Jan Kochanowski University, 25-317 Kielce, Poland; (P.P.); (K.P.); (A.G.); (P.B.); (K.R.); (P.S.)
| | - Piotr Błoniarczyk
- Department of Infectious Diseases, Voivodship Hospital, Jan Kochanowski University, 25-317 Kielce, Poland; (P.P.); (K.P.); (A.G.); (P.B.); (K.R.); (P.S.)
| | - Katarzyna Reczko
- Department of Infectious Diseases, Voivodship Hospital, Jan Kochanowski University, 25-317 Kielce, Poland; (P.P.); (K.P.); (A.G.); (P.B.); (K.R.); (P.S.)
| | - Piotr Stępień
- Department of Infectious Diseases, Voivodship Hospital, Jan Kochanowski University, 25-317 Kielce, Poland; (P.P.); (K.P.); (A.G.); (P.B.); (K.R.); (P.S.)
| | - Dorota Zarębska-Michaluk
- Department of Infectious Diseases, Voivodship Hospital, Jan Kochanowski University, 25-317 Kielce, Poland; (P.P.); (K.P.); (A.G.); (P.B.); (K.R.); (P.S.)
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24
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Abdelaziz H, Omar H, Khalil M, Cordie A, Mohamed R, AbdAllah M, Abdel Maksoud MH, El Garhy N, Ali L, El Serafy M, Esmat G, Doss W. Real-life experience of treating HCV co-infection among HIV-infected population in Egypt: single-center experience. Expert Rev Anti Infect Ther 2021; 20:789-795. [PMID: 34751609 DOI: 10.1080/14787210.2022.2004117] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
BACKGROUND Liver disease has emerged as a leading cause of death among PLHIV coinfected with HCV. METHODS A retrospective study involving all HCV viremic patients coinfected with HIV who presented to HCV/HIV multidisciplinary clinics located at Embaba fever hospital. Patients were assigned to receive DAAs according to the national treatment guidelines. The primary endpoint was SVR12. RESULTS Of the 519 patients enrolled, 38.73% LTFU; either not initiated (n = 170) or did not complete the treatment (n = 31). The main identified reasons behind LTFU were schedule conflict (19%) or hospitalization (13%). Among 318 patients who completed their DAAs course, nine patients had a relapse after the end of treatment and 97% had attained SVR12. There were significant differences among different virological response groups in baseline factors including smoking (p = 0.005), history of dental procedure (p = 0.007), CD4 count (p = 0.007), and HIV viral load (p = <0.001). Among responders (n = 309), there was a significant reduction of baseline hemoglobin and significant improvement of baseline platelets (p = 0.005) at on-treatment week 8. Baseline necro-inflammatory markers showed significant improvement across follow-up time points (p < 0.001). CONCLUSIONS DAAs are an effective and safe choice to treat HCV in PLHIV. Social stigma could be a major cause for lacking adherence to follow-up visits.Abbreviations: ALT: Alanine Aminotransferase; ARV: Antiretroviral treatment; AST: Aspartate Aminotransferase; DAAs: Direct acting antivirals; ARVs: antiretroviral therapy; EMR: Eastern Mediterranean region; HCV: Hepatitis C virus; kPa: Kilopascal; LTFU: Patient lost to follow up; NCCVH: The National Committee for Control of Viral Hepatitis; PWID: People who inject drugs; SVR: Sustained virological response;UNAIDS: The Joint United Nations Programme on HIV/AIDS.
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Affiliation(s)
- Hossam Abdelaziz
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Giza, Egypt.,Hepatology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Heba Omar
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Giza, Egypt
| | - Mahmoud Khalil
- Infectious Disease Department, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
| | - Ahmed Cordie
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Giza, Egypt.,Kasr Alainy Hiv and Viral Hepatitis Fighting Group Cairo Egypt
| | - Rahma Mohamed
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Giza, Egypt.,Kasr Alainy Hiv and Viral Hepatitis Fighting Group Cairo Egypt
| | - Mohamed AbdAllah
- Medical Research Division, National Research Center, Cairo, Egypt
| | | | - Naeema El Garhy
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Giza, Egypt
| | - Lamiaa Ali
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Giza, Egypt
| | - Magdy El Serafy
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Giza, Egypt
| | - Gamal Esmat
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Giza, Egypt
| | - Wahid Doss
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Giza, Egypt
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25
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Datfar T, Doulberis M, Papaefthymiou A, Hines IN, Manzini G. Viral Hepatitis and Hepatocellular Carcinoma: State of the Art. Pathogens 2021; 10:pathogens10111366. [PMID: 34832522 PMCID: PMC8619105 DOI: 10.3390/pathogens10111366] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2021] [Revised: 09/26/2021] [Accepted: 10/18/2021] [Indexed: 02/06/2023] Open
Abstract
Viral hepatitis is one of the main causes leading to hepatocellular carcinoma (HCC). The continued rise in incidence of HCC suggests additional factors following infection may be involved. This review examines recent studies investigating the molecular mechanisms of chronic hepatitis and its association with hepatocarcinogenesis. Hepatitis B virus patients with genotype C display an aggressive disease course leading to HCC more than other genotypes. Furthermore, hepatitis B excretory antigen (HBeAg) seems to be a more sensitive predictive tumor marker exhibiting a six-fold higher relative risk in patients with positive HBsAg and HBeAg than those with HBsAg only. Single or combined mutations of viral genome can predict HCC development in up to 80% of patients. Several mutations in HBx-gene are related with higher HCC incidence. Overexpression of the core protein in HCV leads to hepatocellular lipid accumulation associated with oncogenesis. Reduced number and decreased functionality of natural killer cells in chronic HCV individuals dysregulate their surveillance function in tumor and viral cells resulting in HCC. Furthermore, high T-cell immunoglobulin and mucin 3 levels supress CD8+ T-cells, which lead to immunological dysregulation. Hepatitis D promotes HCC development indirectly via modifications to innate immunity, epigenetic alterations and production of reactive oxygen species with the LHDAg being the most highly associated with HCC development. Summarizing the results, HBV and HCV infection represent the most associated forms of viral hepatitis causing HCC. Further studies are warranted to further improve the prediction of high-risk patients and development of targeted therapeutics preventing the transition from hepatic inflammation–fibrosis to cancer.
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Affiliation(s)
- Toofan Datfar
- Department of General and Visceral Surgery, Hospital of Aarau, 5001 Aarau, Switzerland;
- Correspondence: ; Tel.: +41-76-4930834
| | - Michael Doulberis
- Department of Gastroenterology and Hepatology, Hospital of Aarau, 5001 Aarau, Switzerland;
| | | | - Ian N. Hines
- Department of Nutrition Science, East Carolina University, Greenville, NC 27858, USA;
| | - Giulia Manzini
- Department of General and Visceral Surgery, Hospital of Aarau, 5001 Aarau, Switzerland;
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26
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Eames JR, Tran B. Hepatitis C. PHYSICIAN ASSISTANT CLINICS 2021. [DOI: 10.1016/j.cpha.2021.05.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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27
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Fan X, Fang J, Wu X, Poulsen K, Miyata T, Kim A, Yu L, Wang X, Zhang X, Zhang K, Han Q, Liu Z. Effect of HIV infection on pre- and post-liver transplant mortality in patients with organ failure. HIV Med 2021; 22:662-673. [PMID: 33964108 DOI: 10.1111/hiv.13113] [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] [Accepted: 03/31/2021] [Indexed: 11/29/2022]
Abstract
OBJECTIVES Organ failure (OF), a leading cause of death in HIV-positive individuals, is common in patients undergoing liver transplantation (LT). We examined the impact of HIV infection on pre- and post-LT mortalities in cirrhotic patients stratified by the number and type of OFs. METHODS We performed a cross-sectional study and a retrospective cohort study using the US National Inpatient Sample (NIS) and the United Network for Organ Sharing (UNOS) registry data, respectively. Patients who had not yet undergone LT from the NIS database (2010-2014) and patients undergoing LT from the UNOS database (2003-2016) were included in the study. RESULTS Analysis of patients (201 348) from the NIS database showed that one [adjusted odds ratio (aOR) 1.531; 95% confidence interval (CI) 1.160-2.023], two (aOR 1.624; 95% CI 1.266-2.083) or three or more OFs (aOR 1.349; 95% CI 1.165-1.562) were associated with higher pre-LT mortality in HIV-infected patients compared with HIV-negative patients with the corresponding number of OFs. In patients without OF, HIV infection was not associated with increased pre-LT mortality. UNOS data for patients undergoing LT (38 942) showed that the presence of two or more OFs was associated with increased post-LT 1-year mortality in HIV-infected patients compared with non-HIV-infected patients with the corresponding number of OFs (aOR 2.342; 95% CI 1.576-3.480). However, in patients with no OF or only one OF, HIV infection was not associated with increased post-LT 1-year mortality (aOR 1.372; 95% CI 0.911-2.068). CONCLUSIONS The results of this study emphasize the importance of preventing OF development, and justify LT for HIV-infected patients with no or only one OF.
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Affiliation(s)
- X Fan
- Department of Infectious Diseases, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
- Department of Inflammation and Immunity, Center for Liver Disease Research, Cleveland Clinic, Cleveland, OH, USA
| | - J Fang
- Department of Inflammation and Immunity, Center for Liver Disease Research, Cleveland Clinic, Cleveland, OH, USA
| | - X Wu
- Department of Inflammation and Immunity, Center for Liver Disease Research, Cleveland Clinic, Cleveland, OH, USA
| | - K Poulsen
- Department of Inflammation and Immunity, Center for Liver Disease Research, Cleveland Clinic, Cleveland, OH, USA
| | - T Miyata
- Department of Inflammation and Immunity, Center for Liver Disease Research, Cleveland Clinic, Cleveland, OH, USA
| | - A Kim
- Department of Inflammation and Immunity, Center for Liver Disease Research, Cleveland Clinic, Cleveland, OH, USA
| | - L Yu
- Department of Inflammation and Immunity, Center for Liver Disease Research, Cleveland Clinic, Cleveland, OH, USA
| | - X Wang
- Department of Infectious Diseases, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - X Zhang
- Department of Infectious Diseases, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - K Zhang
- Department of Infectious Diseases, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Q Han
- Department of Infectious Diseases, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Z Liu
- Department of Infectious Diseases, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
- Fengdong New Town (International) Hospital, Xi'an, Shaanxi, China
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Yunihastuti E, Hariyanto R, Sulaiman AS, Harimurti K. Hepatitis C continuum of care: Experience of integrative hepatitis C treatment within a human immunodeficiency virus clinic in Indonesia. PLoS One 2021; 16:e0256164. [PMID: 34383853 PMCID: PMC8360535 DOI: 10.1371/journal.pone.0256164] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Accepted: 08/01/2021] [Indexed: 12/24/2022] Open
Abstract
INTRODUCTION Direct-acting antiviral drugs (DAAs) have changed the paradigm of hepatitis C therapy for both HCV/HIV co-infected and HCV mono-infected patients. We aimed to describe the HCV continuum of care of HIV-infected patients treated in an HIV clinic after a free DAA program in Indonesia and identify factors correlated with sofosbuvir-daclatasvir (SOF-DCV) treatment failure. METHODS We did a retrospective cohort study of adult HIV/HCV co-infected patients under routine HIV-care from November 2019 to April 2020 in the HIV integrated clinic of Cipto Mangunkusumo Hospital, Jakarta, Indonesia. We evaluated some factors correlated with sofosbuvir-daclatasvir treatment failure: gender, diabetes mellitus, previous IFN failure, cirrhosis, concomitant ribavirin use, high baseline HCV-RNA, and low CD4 cell count. RESULTS AND DISCUSSION Overall, 640 anti-HCV positive patients were included in the study. Most of them were male (88.3%) and former intravenous drug users (76.6%) with a mean age of 40.95 (SD 4.60) years old. Numbers and percentages for the stages of the HCV continuum of care were as follows: HCV-RNA tested (411; 64.2%), pre-therapeutic evaluation done (271; 42.3%), HCV treatment initiated (210; 32.8%), HCV treatment completed (207; 32.2%), but only 178 of these patients had follow-up HCV-RNA tests to allow SVR assessment; and finally SVR12 achieved (178; 27.8%). For the 184 who completed SOF-DCV treatment, SVR12 was achieved by 95.7%. In multivariate analysis, diabetes mellitus remained a significant factor correlated with SOF-DCV treatment failure (adjusted RR 17.0, 95%CI: 3.28-88.23, p = 0.001). CONCLUSIONS This study found that in the HCV continuum of care for HIV/HCV co-infected patients, gaps still exist at all stages. As the most commonly used DAA combination, sofosbuvir daclatasvir treatment proved to be effective and well-tolerated in HIV/HCV co-infected patients. Diabetes mellitus was significant factor correlated with not achieving SVR12 in this population.
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Affiliation(s)
- Evy Yunihastuti
- Department Internal Medicine, Faculty of Medicine Universitas Indonesia/Cipto Mangunkusumo Hospital, Jakarta, Indonesia
- HIV Integrated Clinic, Cipto Mangunkusumo Hospital, Jakarta, Indonesia
| | - Rahmat Hariyanto
- Department Internal Medicine, Faculty of Medicine Universitas Indonesia/Cipto Mangunkusumo Hospital, Jakarta, Indonesia
| | - Andri Sanityoso Sulaiman
- Department Internal Medicine, Faculty of Medicine Universitas Indonesia/Cipto Mangunkusumo Hospital, Jakarta, Indonesia
| | - Kuntjoro Harimurti
- Department Internal Medicine, Faculty of Medicine Universitas Indonesia/Cipto Mangunkusumo Hospital, Jakarta, Indonesia
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29
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Eguchi S, Egawa H, Eguchi H, Uehira T, Endo T, Genda T, Shinoda M, Hasegawa K, Shimamura T, Tsukada K, Hara T, Nakao K, Yatsuhashi H, Yotsuyanagi H, Natsuda K, Soyama A, Hidaka M, Hara T, Takatsuki M. Indications and waiting list priority for deceased donor liver transplantation in HIV/HCV co-infected hemophilic patients in Japan through contaminated blood product. Hepatol Res 2021; 51:909-914. [PMID: 34132462 DOI: 10.1111/hepr.13686] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Revised: 05/19/2021] [Accepted: 06/02/2021] [Indexed: 12/08/2022]
Abstract
HIV/HCV co-infection from blood products for hemophilia has been a social problem in Japan. Liver transplantation (LT) is an important treatment option for hepatic failure and cirrhosis of the liver in co-infected patients, and appropriate indications for LT, especially organ form deceased donors, are required by society. The aim is to propose priority status for the waiting list for deceased donor (DD) LT in HIV/HCV co-infected patients in Japan based on medical and scientific considerations. Since 2009, we have been working on the subject in research projects under grants-in-aid for health and labour sciences research on AIDS measures provided by the Ministry of Health, Labour and Welfare (the Kanematsu project and Eguchi project). Our research showed that hepatic fibrosis is advanced in HIV/HCV co-infected Japanese patients, especially those with hemophilia who became infected from blood products at a faster rate than HCV mono-infected patients. In addition, those patients who developed portal hypertension had a poor prognosis at a young age. The results of our research contributed to increasing the priority score of those patients on the deceased donor liver transplantation (DDLT) waiting list in 2013 and to establishing a scoring system for DDLT corresponding to the Model for End-stage Liver disease (MELD) score in 2019. This paper introduces changes in priority and the current state of priority of the DDLT waiting list for HIV/HCV co-infected patients in Japan.
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Affiliation(s)
- Susumu Eguchi
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Hiroto Egawa
- Department of Surgery, Tokyo Women's Medical University, Tokyo, Japan
| | - Hidetoshi Eguchi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Tomoko Uehira
- Department of Infectious Diseases, National Hospital Organization Osaka National Hospital, Osaka, Japan
| | - Tomoyuki Endo
- Department of Hematology, Hokkaido University Hospital, Sapporo, Japan
| | - Takuya Genda
- Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Shizuoka, Japan
| | - Masahiro Shinoda
- Department of Hepato-Biliary-Pancreatic and Gastrointesyinal Surgery, International University of Health and Welfare School of Medicine, Tokyo, Japan
| | - Kiyoshi Hasegawa
- Hepato-Biliary-Pancreatic Surgery Division, Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan
| | - Tsuyoshi Shimamura
- Division of Organ Transplantation, Hokkaido University Hospital, Sapporo, Japan
| | - Kunihisa Tsukada
- AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan
| | - Tetsuya Hara
- Department of Anesthesiology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Kazuhiko Nakao
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Hiroshi Yatsuhashi
- Clinical Research Center, Nagasaki Medical Center, National Hospital Organization, Nagasaki, Japan
| | - Hiroshi Yotsuyanagi
- Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan
| | - Koji Natsuda
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Akihiko Soyama
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Masaaki Hidaka
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Takanobu Hara
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Mitsuhisa Takatsuki
- Department of Digestive and General Surgery, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan
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30
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Compartmentalization of Resistance-Associated Substitutions in HIV/HCV-Infected Patients: Possible Correlation with Infecting HCV Genotype. Viruses 2021; 13:v13081486. [PMID: 34452351 PMCID: PMC8402799 DOI: 10.3390/v13081486] [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: 04/22/2021] [Revised: 07/09/2021] [Accepted: 07/22/2021] [Indexed: 11/17/2022] Open
Abstract
Resistance-associated substitutions (RASs) may exist prior to treatment and contribute to the failure of treatment with direct-acting antivirals (DAAs). As the major site of HCV replication, naturally occurring variants with RASs may segregate into the liver. In the present study, we performed viral population sequencing to retrospectively investigate the NS3 and NS5A RAS profiles in 34 HIV/HCV coinfected patients naïve to anti-HCV treatment who underwent diagnostic liver biopsy between 2000 and 2006 and had liver and plasma samples available. Sixteen were infected by HCV genotype (GT) 1a, 11 by GT3a, and 7 by GT4d. The analysis of the NS3 domain in GT1a showed a difference in strain between the liver and plasma in three cases, with a preponderance of specific RASs in the liver compartment. In GT4d samples, 6/7 coupled liver and plasma samples were concordant with no RASs. Sequence analysis of the NS5A domain showed the presence of RASs in the livers of 2/16 patients harboring GT1a but not in the corresponding plasma. In GT4d, NS5A RASs were detected in 7/7 liver tissues and 5/7 plasma samples. NS3 domain and NS5A domain were found to be conserved in plasma and livers of patients infected with GT3a. Thus, RASs within GT1a and GT4d more likely segregate into the liver and may explain the emergence of resistant strains during DAA treatment.
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31
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Saldarriaga OA, Dye B, Pham J, Wanninger TG, Millian D, Kueht M, Freiberg B, Utay N, Stevenson HL. Comparison of liver biopsies before and after direct-acting antiviral therapy for hepatitis C and correlation with clinical outcome. Sci Rep 2021; 11:14506. [PMID: 34267267 PMCID: PMC8282660 DOI: 10.1038/s41598-021-93881-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Accepted: 06/18/2021] [Indexed: 02/07/2023] Open
Abstract
Direct-acting antivirals (DAA) have replaced interferon (IFN)-based therapies for hepatitis C virus. In this retrospective clinical study, we examined differences in histopathologic features in paired liver biopsies collected from the same patient before and after DAA and correlated these findings with clinical outcome. Biopsies (n = 19) were evaluated by quantitative imaging analysis to measure steatosis and fibrosis. Most patients had decreased steatosis in their post-treatment, follow-up biopsies. However, one patient had a striking increase in steatosis (from 0.86 to 6.32%) and later developed decompensated cirrhosis and hepatocellular carcinoma (HCC). This patient had a marked increase in fibrosis between biopsies, with a CPA of 6.74 to 32.02. Another patient, who already had bridging fibrosis at the time of her pre-treatment biopsy, developed cholangiocarcinoma after DAA. Even though the overall inflammatory activity in the post-treatment biopsies significantly decreased after treatment, 60% of patients had persistent portal lymphocytic inflammation. In summary, DAAs decreased steatosis and hepatic inflammation in most patients, although some may have persistence of lymphocytic portal inflammation. Patients known to have advanced fibrosis at treatment initiation and who have other risk factors for ongoing liver injury, such as steatosis, should be followed closely for the development of adverse outcomes, such as portal hypertension and primary liver cancers.
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Affiliation(s)
- Omar A Saldarriaga
- Department of Pathology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX, 77555-0144, USA
| | - Bradley Dye
- School of Medicine, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX, 77555-0144, USA
| | - Judy Pham
- School of Medicine, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX, 77555-0144, USA
| | - Timothy G Wanninger
- School of Medicine, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX, 77555-0144, USA
| | - Daniel Millian
- School of Medicine, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX, 77555-0144, USA
| | - Michael Kueht
- Dept. of Surgery, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX, 77555-0144, USA
| | - Benjamin Freiberg
- Digital Pathology, Araceli Biosciences, 7425 NE Evergreen Pkwy, Hillsboro, OR, 97124, USA
| | - Netanya Utay
- Department of Internal Medicine, University of Texas Health Science Center at Houston, 7000 Fannin St # 1200, Houston, TX, 77030, USA
| | - Heather L Stevenson
- Department of Pathology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX, 77555-0144, USA.
- Department of Pathology, The University of Texas Medical Branch, 712 Texas Avenue, Clinical Services Wing-Room 5.506Q, Galveston, TX, 77555-0416, USA.
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Sarrazin C, Boesecke C, Golsabahi‐Broclawski S, Moog G, Negro F, Silaidos C, Patel P, Lohmann K, Spinner CD, Walcher S, Wedemeyer H, Wörns M. Hepatitis C virus: Current steps toward elimination in Germany and barriers to reaching the 2030 goal. Health Sci Rep 2021; 4:e290. [PMID: 34136654 PMCID: PMC8177898 DOI: 10.1002/hsr2.290] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2020] [Revised: 02/24/2021] [Accepted: 04/13/2021] [Indexed: 11/25/2022] Open
Abstract
Hepatitis C virus (HCV) affects over 70 million people globally, with an estimated 399 000 HCV-related deaths in 2016. The World Health Organization (WHO) has set a goal to eliminate HCV by 2030. Despite the availability of direct-acting antivirals-highly effective and well-tolerated therapies for HCV-many patients infected with HCV in Germany have not initiated treatment, including a majority of those who are aware of their positive diagnosis. Barriers to screening, diagnosis, and treatment are major factors taking many countries off track for HCV elimination by 2030. Identifying country-specific barriers and challenges, particularly in at-risk populations such as people who inject drugs or men who have sex with men, has the potential to create tailored programs and strategies to increase access to screening or treatment and engage at-risk populations. This review aims to report the current steps toward HCV elimination in Germany, the country-specific barriers and challenges that will potentially prevent reaching the 2030 HCV elimination goal and describe good practice examples to overcome these barriers.
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Affiliation(s)
- Christoph Sarrazin
- Department of Internal Medicine and Liver CenterSt. Josefs‐Hospital Wiesbaden and Viral Hepatitis Research Group, Goethe‐University Hospital FrankfurtFrankfurtGermany
| | - Christoph Boesecke
- Department of Medicine IUniversity Hospital BonnBonnGermany
- German Centre for Infection Research (DZIF)Partner‐site Bonn‐CologneBonnGermany
| | | | - Gero Moog
- Gastroenterologische Praxis im MarienkrankenhausKasselGermany
| | - Francesco Negro
- Divisions of Gastroenterology and Hepatology and of Clinical PathologyGeneva University HospitalsGenevaSwitzerland
| | | | | | | | - Christoph D. Spinner
- Department of Internal Medicine II, School of Medicine, University Hospital Rechts der IsarTechnical University of MunichMunichGermany
- German Centre for Infection Research (DZIF), Partner Site MunichMunichGermany
| | | | - Heiner Wedemeyer
- Department of GastroenterologyHepatology and Endocrinology, Hannover Medical SchoolHannoverGermany
- Leberstiftungs‐GmbH DeutschlandHannoverGermany
| | - Marcus‐Alexander Wörns
- First Department of MedicineUniversity Medical Centre of the Johannes Gutenberg‐UniversityMainzGermany
- Cirrhosis Centre Mainz (CCM)University Medical Centre of the Johannes Gutenberg‐UniversityMainzGermany
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Hay CRM, Nissen F, Pipe SW. Mortality in congenital hemophilia A - a systematic literature review. J Thromb Haemost 2021; 19 Suppl 1:6-20. [PMID: 33331043 PMCID: PMC7839505 DOI: 10.1111/jth.15189] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Revised: 10/14/2020] [Accepted: 11/02/2020] [Indexed: 12/20/2022]
Abstract
Against a background of a rapidly evolving treatment landscape, a contemporary, evidence-based consolidated understanding of mortality in people with congenital hemophilia A (PwcHA) is lacking. This systematic literature review examines the available data on mortality and causes of death in PwcHA to enable a better understanding of fatalities in PwcHA and evaluate the impact of new treatment paradigms on mortality. A systematic literature review of observational studies was conducted by searching Medline, Embase, and clinical trials registries for articles published from January 2010 to March 2020, using the search terms: hemophilia A (HA), mortality, cause of death. Interventional studies, studies not reporting fatalities, and those reporting only on hemophilia B, acquired HA, or mixed other coagulopathies were excluded. Overall, 7818 unique records were identified and 17 were analyzed. Of these, six reported mortality rates and five reported mortality ratios. Mortality generally decreased over time, despite a spike associated with human immunodeficiency virus (HIV)/hepatitis C virus (HCV) infection in the 1980s and 1990s. Mortality was strongly correlated with age and hemophilia severity. People with hemophilia had a raised mortality risk compared with the general population, particularly in severe hemophilia, and when infected with HIV or HCV. Causes of death varied across populations, countries, and time in 15 identified studies; however, incomplete and heterogeneous reporting limits evidence. Hemorrhage, HIV, HCV, and hepatic disease were the leading causes of death. A unified approach to reporting mortality and cause of death is needed to understand mortality in PwcHA as treatments continue to advance.
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Affiliation(s)
| | | | - Steven W. Pipe
- Departments of Pediatrics and PathologyUniversity of MichiganAnn ArborMIUSA
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Blanco JR, Negredo E, Bernal E, Blanco J. Impact of HIV infection on aging and immune status. Expert Rev Anti Infect Ther 2020; 19:719-731. [PMID: 33167724 DOI: 10.1080/14787210.2021.1848546] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Introduction: Thanks to antiretroviral therapy (ART), persons living with HIV (PLWH), have a longer life expectancy. However, immune activation and inflammation remain elevated, even after viral suppression, and contribute to morbidity and mortality in these individuals.Areas covered: We review aspects related to immune activation and inflammation in PLWH, their consequences, and the potential strategies to reduce immune activation in HIV-infected individuals on ART.Expert opinion: When addressing a problem, it is necessary to thoroughly understand the topic. This is the main limitation faced when dealing with immune activation and inflammation in PLWH since there is no consensus on the ideal markers to evaluate immune activation or inflammation. To date, the different interventions that have addressed this problem by targeting specific mediators have not been able to significantly reduce immune activation or its consequences. Given that there is currently no curative intervention for HIV infection, more studies are necessary to understand the mechanism underlying immune activation and help to identify potential therapeutic targets that contribute to improving the life expectancy of HIV-infected individuals.
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Affiliation(s)
- Jose-Ramon Blanco
- Servicio de Enfermedades Infecciosas, Hospital Universitario San Pedro- Centro De Investigación Biomédica De La Rioja (CIBIR), La Rioja, Spain
| | - Eugenia Negredo
- Lluita Contra La Sida Foundation, Germans Trias I Pujol University Hospital, Badalona, Spain. Centre for Health and Social Care Research (CESS), Faculty of Medicine, University of Vic - Central University of Catalonia (Uvic - UCC), Catalonia, Spain
| | - Enrique Bernal
- Unidad De Enfermedades Infecciosas, Hospital General Universitario Reina Sofía, Universidad De Murcia, Murcia, Spain
| | - Juliá Blanco
- AIDS Research Institute-IrsiCaixa, Badalona, Barcelona, Spain.,Universitat De Vic-Central De Catalunya (UVIC-UCC), Vic, Spain
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