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1
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Fuster D, So-Armah K, Cheng DM, Blokhina E, Patts G, Lioznov D, Gnatienko N, Long MT, Freiberg MS, Tindle H, Samet JH. Is There an Association Between Cigarette Smoking and Advanced Liver Fibrosis in Smokers with HIV, Heavy Drinking and High Prevalence of HCV? J Clin Med 2025; 14:1169. [PMID: 40004700 PMCID: PMC11856725 DOI: 10.3390/jcm14041169] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2024] [Revised: 01/20/2025] [Accepted: 02/07/2025] [Indexed: 02/27/2025] Open
Abstract
Background: Cigarette smoking has been associated with liver fibrosis in the setting of hepatitis C virus (HCV) infection but has not been studied among people with HIV (PWH) who consume alcohol. Methods: This is a cross-sectional study of PWH with heavy drinking and daily smoking in St. Petersburg, Russia. The primary independent variable was past 30-day cigarettes per day (cpd), and the secondary independent variable was pack-years at study entry. Advanced liver fibrosis was defined as FIB-4 > 3.25. Analyses were adjusted for gender, body mass index (BMI), past 30-day number of heavy drinking days, HCV and CD4 count. Results: Participants (n = 400) were two-thirds male (67.3%), young (median age 38 years), lean (median BMI 22), HCV antibody positive (84.5%) and not severely immune suppressed (median CD4 count 351). The median number of past-month cpd was 20 (IQR: 15-25), and the median pack-years was 24 (IQR: 17-31.8). The prevalence of advanced liver fibrosis was 11.3% (45/400). In the adjusted logistic regression analyses, we did not observe a significant association between cpd [middle (10.1-20 cigarettes) vs. lowest (5-10 cigarettes) category (adjusted odds ratio [aOR] (95% confidence interval [CI]): 1.06 (0.40-2.83), highest (>20.0 cigarettes) vs. lowest category aOR (95% CI): 0.65 (0.21-1.99), global p-value = 0.62]. The secondary analysis with pack-years yielded similar results [middle (20.1-30 pack-years) vs. lowest category (≤20 pack-years) aOR (95% CI): 0.81 (0.33-1.99), highest category (>30 pack-years) vs. lowest category aOR (95% CI): 0.91 (0.38-2.19); global p-value = 0.58]. Conclusions: In this Russian cohort of PWH, we did not detect an association between recent cigarette use or mean pack-years and advanced liver fibrosis.
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Affiliation(s)
- Daniel Fuster
- Addiction Unit, Internal Medicine Department, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, 08916 Badalona, Spain
| | - Kaku So-Armah
- Clinical Addiction Research and Education Unit, Section of General Internal Medicine, Department of Medicine, Boston University School of Medicine/Boston Medical Center, Boston, MA 02118, USA; (K.S.-A.); (J.H.S.)
| | - Debbie M. Cheng
- Biostatistics Department, Boston University School of Public Health, Boston, MA 02118, USA;
| | - Elena Blokhina
- Laboratory of Clinical Psychopharmacology of Addictions, First Pavlov State Medical University, 197022 St. Petersburg, Russia;
| | - Gregory Patts
- Biostatistics and Epidemiology Data Analytics Center, Boston University School of Public Health, Boston, MA 02118, USA;
| | - Dmitry Lioznov
- Department of Infectious Diseases and Epidemiology, First Pavlov State Medical University, 197022 St. Petersburg, Russia;
- Smorodintsev Research Institute of Influenza, 197022 St. Petersburg, Russia
| | - Natalia Gnatienko
- Clinical Addiction Research and Education Unit, Section of General Internal Medicine, Department of Medicine, Boston Medical Center, Boston, MA 02118, USA;
| | - Michelle T. Long
- Gastroenterology Section, Department of Medicine, Boston University School of Medicine/Boston Medical Center, Boston, MA 02118, USA;
| | - Matthew S. Freiberg
- Cardiovascular Medicine Division, Vanderbilt University Medical Center, Nashville, TN 37232, USA;
| | - Hilary Tindle
- ViTAL, the Vanderbilt Center for Tobacco, Addiction and Lifestyle, Vanderbilt University Medical Center, Nashville, TN 37232, USA;
| | - Jeffrey H. Samet
- Clinical Addiction Research and Education Unit, Section of General Internal Medicine, Department of Medicine, Boston University School of Medicine/Boston Medical Center, Boston, MA 02118, USA; (K.S.-A.); (J.H.S.)
- Department of Community Health Sciences, Boston University School of Public Health, Boston, MA 02118, USA
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2
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Konishi K, Matsuo H, Shirano M. Current management and awareness of hepatitis coinfection in HIV care: A single-center retrospective study in Japan. J Infect Chemother 2025; 31:102557. [PMID: 39536987 DOI: 10.1016/j.jiac.2024.11.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2024] [Revised: 10/18/2024] [Accepted: 11/08/2024] [Indexed: 11/16/2024]
Abstract
BACKGROUND Liver disease remains a significant concern for people living with HIV (PLWH), especially in those with hepatitis B virus (HBV) and hepatitis C virus (HCV) coinfection. This study assessed the prevalence of viral hepatitis coinfections and evaluated the current state of hepatitis management by HIV care providers in Japan. METHODS This single-center, retrospective, observational study analyzed data from PLWH treated with antiretroviral therapy between April 1, 2023 and March 31, 2024. Data included demographics, ART regimen, hepatitis status, and screening practices of 811 PLWH treated with antiretroviral therapy. RESULTS The median age of the study population was 48 years, and 97.8 % were men. The HBV status was as follows: chronic HBV, 6.5 %; clinical remission, 34.0 %; uninfected, 30.9 %; unknown, 14.2 %. The HCV antibody positivity rate was 3.2 %. Substantial gaps in hepatitis screening and monitoring were identified. Specifically, we found inadequate rates of abdominal ultrasound examinations and HCC screening among patients with HIV and viral hepatitis coinfection. Moreover, only 71.7 % of patients chronically infected with HBV and 61.5 % with HCV underwent abdominal ultrasound examinations in the preceding 12 months-only 5.7 % and 3.8 % of the participants in these groups had had received tumor marker testing in the previous 12 months. CONCLUSION There are challenges in hepatitis and HCC screening and monitoring among patients with HIV and viral hepatitis coinfection in Japan. These findings underscore the need to improve adherence to clinical practice guidelines and implement integrated care models to enhance hepatitis management in PLWH.
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Affiliation(s)
- Keiji Konishi
- Department of Infectious Diseases, Osaka City General Hospital, Osaka, Japan; Department of Post-infectious Disease Therapeutics, Graduate School of Medicine, Osaka University, Osaka, Japan; Department of Infection Control and Prevention, Graduate School of Medicine, Osaka University, Osaka, Japan.
| | - Hiroo Matsuo
- Department of Infection Control and Prevention, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Michinori Shirano
- Department of Infectious Diseases, Osaka City General Hospital, Osaka, Japan
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3
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Maekawa S, Takano S, Enomoto N. Risk of hepatocellular carcinoma after viral clearance achieved by DAA treatment. J Formos Med Assoc 2024; 123:1124-1130. [PMID: 38245398 DOI: 10.1016/j.jfma.2024.01.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Revised: 12/18/2023] [Accepted: 01/09/2024] [Indexed: 01/22/2024] Open
Abstract
The advent of direct-acting antiviral (DAA) therapy has revolutionized hepatitis C virus (HCV) treatment, enabling most HCV-infected patients to achieve a sustained viral response (SVR) easily and safely in a short period. On the other hand, it is gradually being recognized that a significant proportion of patients are still at risk of developing de novo and recurrent hepatocellular carcinoma (HCC), even after HCV elimination, and therefore, elucidation of the risk of de novo and recurrent HCC, investigation of its molecular basis, and construction of accurate prediction models are emerging as new important clinical topics. In this review, we present recent advances regarding these issues.
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Affiliation(s)
- Shinya Maekawa
- Department of Gastroenterology and Hepatology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
| | - Shinichi Takano
- Department of Gastroenterology and Hepatology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan
| | - Nobuyuki Enomoto
- Department of Gastroenterology and Hepatology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan
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4
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Lee S, Lee JE, Lee SO, Lee SH. Treatment Outcomes of HCV Infection in People Living with HIV: A Case Series from a Single Center in Korea. Infect Chemother 2024; 56:386-394. [PMID: 39370124 PMCID: PMC11458507 DOI: 10.3947/ic.2024.0074] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2024] [Accepted: 08/26/2024] [Indexed: 10/08/2024] Open
Abstract
BACKGROUND Limited information is available on the clinical course and treatment outcomes of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) coinfection in Korea. MATERIALS AND METHODS A retrospective case series was conducted of patients with HIV-HCV coinfection who received interferon (IFN)-based or direct-acting antiviral (DAA) treatment for HCV at a tertiary care hospital between 2000 and 2023. Early virological response (EVR) was defined as a 2-log reduction in HCV RNA levels or undetectable HCV RNA levels at treatment week 12. A sustained virologic response (SVR) was defined as undetectable HCV RNA at 12 weeks after treatment completion. RESULTS Of the 33 patients with HIV-HCV coinfection, 19 received anti-HCV treatment, of whom 12 received IFN-based treatment and 10 received DAA treatment. The median age at the time of anti-HCV treatment was 49 years (interquartile range, 42-57 years) and 15 patients (79%) were male. Of the 12 patients who received IFN-based anti-HCV treatment, 10 showed EVR and 8 achieved SVR. However, 2 patients who achieved SVR experienced recurrence of HCV infection during follow-up; therefore, the overall success rate of IFN-based treatment was 50% (6/12). All 10 patients (including 3 in whom IFN-based treatment failed) who received DAA treatment (5 with previous anti-HCV treatment and 5 treatment-naïve), achieved SVR and did not experience recurrence of HCV infection during follow-up; therefore, the overall success rate of DAA treatment was 100%. CONCLUSION In Korean patients with HIV-HCV coinfection, treatment outcomes were better with DAA treatment than with IFN-based treatment.
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Affiliation(s)
- Shinwon Lee
- Department of Internal Medicine, Pusan National University School of Medicine and Medical Research Institute, Pusan National University Hospital, Busan, Korea
| | - Jeong Eun Lee
- Department of Internal Medicine, Pusan National University School of Medicine and Medical Research Institute, Pusan National University Hospital, Busan, Korea
| | - Soon Ok Lee
- Department of Internal Medicine, Pusan National University School of Medicine and Medical Research Institute, Pusan National University Hospital, Busan, Korea
| | - Sun Hee Lee
- Department of Internal Medicine, Pusan National University School of Medicine and Medical Research Institute, Pusan National University Hospital, Busan, Korea.
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Fahmy AM, Hammad MS, Mabrouk MS, Al-Atabany WI. On leveraging self-supervised learning for accurate HCV genotyping. Sci Rep 2024; 14:15463. [PMID: 38965254 PMCID: PMC11224313 DOI: 10.1038/s41598-024-64209-y] [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: 03/11/2024] [Accepted: 06/06/2024] [Indexed: 07/06/2024] Open
Abstract
Hepatitis C virus (HCV) is a major global health concern, affecting millions of individuals worldwide. While existing literature predominantly focuses on disease classification using clinical data, there exists a critical research gap concerning HCV genotyping based on genomic sequences. Accurate HCV genotyping is essential for patient management and treatment decisions. While the neural models excel at capturing complex patterns, they still face challenges, such as data scarcity, that exist a lot in computational genomics. To overcome this challenges, this paper introduces an advanced deep learning approach for HCV genotyping based on the graphical representation of nucleotide sequences that outperforms classical approaches. Notably, it is effective for both partial and complete HCV genomes and addresses challenges associated with imbalanced datasets. In this work, ten HCV genotypes: 1a, 1b, 2a, 2b, 2c, 3a, 3b, 4, 5, and 6 were used in the analysis. This study utilizes Chaos Game Representation for 2D mapping of genomic sequences, employing self-supervised learning using convolutional autoencoder for deep feature extraction, resulting in an outstanding performance for HCV genotyping compared to various machine learning and deep learning models. This baseline provides a benchmark against which the performance of the proposed approach and other models can be evaluated. The experimental results showcase a remarkable classification accuracy of over 99%, outperforming traditional deep learning models. This performance demonstrates the capability of the proposed model to accurately identify HCV genotypes in both partial and complete sequences and in dealing with data scarcity for certain genotypes. The results of the proposed model are compared to NCBI genotyping tool.
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Affiliation(s)
- Ahmed M Fahmy
- Computer Science program, School of Information Technology and Computer Science (ITCS), Nile University, Sheikh Zayed City, Egypt.
| | - Muhammed S Hammad
- Biomedical Engineering Department, Faculty of Engineering, Helwan University, Cairo, Egypt
| | - Mai S Mabrouk
- Biomedical informatics program, School of Information Technology and Computer Science (ITCS), Nile University, Sheikh Zayed City, Egypt
| | - Walid I Al-Atabany
- Biomedical informatics program, School of Information Technology and Computer Science (ITCS), Nile University, Sheikh Zayed City, Egypt
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6
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Breitschwerdt S, Boesecke C. [HIV and hepatitis B and hepatitis C coinfection: Treatment and practical experiences]. MMW Fortschr Med 2024; 166:38-43. [PMID: 38980616 DOI: 10.1007/s15006-024-3937-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/10/2024]
Affiliation(s)
- Sven Breitschwerdt
- nfektionsambulanz/HIV, Medizinische Klinik I, Universitätsklinikum Bonn, Bonn, Deutschland
| | - Christoph Boesecke
- Infektiologie, Medizinische Klinik I, Universitätsklinikum Bonn, Venusberg-Campus 1, Gebäude 26, 53127, Bonn, Deutschland.
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López CAM, Freiberger RN, Sviercz FA, Jarmoluk P, Cevallos C, Quarleri J, Delpino MV. HIV and gp120-induced lipid droplets loss in hepatic stellate cells contribute to profibrotic profile. Biochim Biophys Acta Mol Basis Dis 2024; 1870:167084. [PMID: 38368823 DOI: 10.1016/j.bbadis.2024.167084] [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: 10/06/2023] [Revised: 01/24/2024] [Accepted: 02/12/2024] [Indexed: 02/20/2024]
Abstract
Liver fibrosis is the excessive accumulation of extracellular matrix proteins, primarily collagen, in response to liver injury caused by chronic liver diseases. HIV infection accelerates the progression of liver fibrosis in patients co-infected with HCV or HBV compared to those who are only mono-infected. The early event in the progression of liver fibrosis involves the activation of hepatic stellate cells (HSCs), which entails the loss of lipid droplets (LD) to fuel the production of extracellular matrix components crucial for liver tissue healing. Thus, we are examining the mechanism by which HIV stimulates the progression of liver fibrosis. HIV-R5 tropic infection was unable to induce the expression of TGF-β, collagen deposition, α-smooth muscle actin (α-SMA), and cellular proliferation. However, this infection induced the secretion of the profibrogenic cytokine IL-6 and the loss of LD. This process involved the participation of peroxisome proliferator-activated receptor (PPAR)-α and an increase in lysosomal acid lipase (LAL), along with the involvement of Microtubule-associated protein 1 A/1B-light chain 3 (LC3), strongly suggesting that LD loss could occur through acid lipolysis. These phenomena were mimicked by the gp120 protein from the R5 tropic strain of HIV. Preincubation of HSCs with the CCR5 receptor antagonist, TAK-779, blocked gp120 activity. Additionally, experiments performed with pseudotyped-HIV revealed that HIV replication could also contribute to LD loss. These results demonstrate that the cross-talk between HSCs and HIV involves a series of interactions that help explain some of the mechanisms involved in the exacerbation of liver damage observed in co-infected individuals.
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Affiliation(s)
- Cinthya Alicia Marcela López
- Instituto de Investigaciones Biomédicas en Retrovirus y Sida (INBIRS), Facultad de Medicina, Consejo de Investigaciones Científicas y Técnicas (CONICET), Universidad de Buenos Aires, Buenos Aires, Argentina
| | - Rosa Nicole Freiberger
- Instituto de Investigaciones Biomédicas en Retrovirus y Sida (INBIRS), Facultad de Medicina, Consejo de Investigaciones Científicas y Técnicas (CONICET), Universidad de Buenos Aires, Buenos Aires, Argentina
| | - Franco Agustín Sviercz
- Instituto de Investigaciones Biomédicas en Retrovirus y Sida (INBIRS), Facultad de Medicina, Consejo de Investigaciones Científicas y Técnicas (CONICET), Universidad de Buenos Aires, Buenos Aires, Argentina
| | - Patricio Jarmoluk
- Instituto de Investigaciones Biomédicas en Retrovirus y Sida (INBIRS), Facultad de Medicina, Consejo de Investigaciones Científicas y Técnicas (CONICET), Universidad de Buenos Aires, Buenos Aires, Argentina
| | - Cintia Cevallos
- Instituto de Investigaciones Biomédicas en Retrovirus y Sida (INBIRS), Facultad de Medicina, Consejo de Investigaciones Científicas y Técnicas (CONICET), Universidad de Buenos Aires, Buenos Aires, Argentina
| | - Jorge Quarleri
- Instituto de Investigaciones Biomédicas en Retrovirus y Sida (INBIRS), Facultad de Medicina, Consejo de Investigaciones Científicas y Técnicas (CONICET), Universidad de Buenos Aires, Buenos Aires, Argentina
| | - María Victoria Delpino
- Instituto de Investigaciones Biomédicas en Retrovirus y Sida (INBIRS), Facultad de Medicina, Consejo de Investigaciones Científicas y Técnicas (CONICET), Universidad de Buenos Aires, Buenos Aires, Argentina.
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8
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Falade-Nwulia O, Lesko CR, Fojo AT, Keruly JC, Moore RD, Sutcliffe CG, Mehta SH, Chander G, Thomas DL, Sulkowski M. Hepatitis C Treatment in People With HIV: Potential to Eliminate Disease and Disparity. J Infect Dis 2024; 229:775-779. [PMID: 37793170 PMCID: PMC10938212 DOI: 10.1093/infdis/jiad433] [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: 05/21/2023] [Revised: 09/20/2023] [Accepted: 10/02/2023] [Indexed: 10/06/2023] Open
Abstract
Access to direct acting antivirals (DAAs) may be associated with reductions in hepatitis C virus (HCV) viremia prevalence among people with human immunodeficiency virus (PWH). Among 3755 PWH, estimated HCV viremia prevalence decreased by 94.0% from 36% (95% confidence interval [CI], 27%-46%) in 2009 (pre-DAA era) to 2% (95% CI, 0%-4%) in 2021 (DAA era). Male sex, black race, and older age were associated with HCV viremia in 2009 but not in 2021. Injection drug use remained associated with HCV viremia in 2009 and 2021. Targeted interventions are needed to meet the HCV care needs of PWH who use drugs.
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Affiliation(s)
- Oluwaseun Falade-Nwulia
- Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Catherine R Lesko
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
| | - Anthony T Fojo
- Division of General Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Jeanne C Keruly
- Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Richard D Moore
- Division of General Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Catherine G Sutcliffe
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
| | - Shruti H Mehta
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
| | - Geetanjali Chander
- Division of General Internal Medicine, University of Washington, Seattle, Washington, USA
| | - David L Thomas
- Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Mark Sulkowski
- Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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Andaloro S, Mancuso F, Miele L, Addolorato G, Gasbarrini A, Ponziani FR. Effect of Low-Dose Alcohol Consumption on Chronic Liver Disease. Nutrients 2024; 16:613. [PMID: 38474740 DOI: 10.3390/nu16050613] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2024] [Revised: 02/16/2024] [Accepted: 02/18/2024] [Indexed: 03/14/2024] Open
Abstract
Although alcohol is one of the most important etiologic agents in the development of chronic liver disease worldwide, also recognized as a promoter of carcinogenesis, several studies have shown a beneficial effect of moderate consumption in terms of reduced cardiovascular morbidity and mortality. Whether this benefit is also present in patients with liver disease due to other causes (viral, metabolic, and others) is still debated. Although there is no clear evidence emerging from guidelines and scientific literature, total abstention from drinking is usually prescribed in clinical practice. In this review, we highlight the results of the most recent evidence on this controversial topic, in order to understand the effect of mild alcohol use in this category of individuals. The quantification of alcohol intake, the composition of the tested populations, and the discrepancy between different works in relation to the outcomes represent important limitations emerging from the scientific literature. In patients with NAFLD, a beneficial effect is demonstrated only in a few works. Even if there is limited evidence in patients affected by chronic viral hepatitis, a clear deleterious effect of drinking in determining disease progression in a dose-dependent manner emerges. Poor data are available about more uncommon pathologies such as hemochromatosis. Overall, based on available data, it is not possible to establish a safe threshold for alcohol intake in patients with liver disease.
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Affiliation(s)
- Silvia Andaloro
- Liver Unit, CEMAD Centro Malattie dell'Apparato Digerente, Medicina Interna e Gastroenterologia, Catholic University, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Fabrizio Mancuso
- Liver Unit, CEMAD Centro Malattie dell'Apparato Digerente, Medicina Interna e Gastroenterologia, Catholic University, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Luca Miele
- Department of Abdominal, Endocrine and Metabolic Medical and Surgical Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
- Department of Translational Medicine and Surgery, Catholic University, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
- CEMAD Unit, Digestive Disease Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
- Internal Medicine and Liver Transplant Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Giovanni Addolorato
- Department of Translational Medicine and Surgery, Catholic University, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
- CEMAD Unit, Digestive Disease Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
- Internal Medicine and Alcohol Related Disease Unit, Columbus-Gemelli Hospital, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Antonio Gasbarrini
- Liver Unit, CEMAD Centro Malattie dell'Apparato Digerente, Medicina Interna e Gastroenterologia, Catholic University, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
- Department of Translational Medicine and Surgery, Catholic University, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Francesca Romana Ponziani
- Liver Unit, CEMAD Centro Malattie dell'Apparato Digerente, Medicina Interna e Gastroenterologia, Catholic University, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
- Department of Translational Medicine and Surgery, Catholic University, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
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10
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Odeghe E, Oyeleke G, Odofin M, Duguru M, Davwar P, Nyam D, Lesi O, Okeke E, Adelabu H, Odukoya O, Akanmu A, Adeyemo W, Abdulkareem F, Imade G, Joyce B, Khan I, Chandler A, Sagay A, Murphy R, Hou L, Hawkins C. Hepatitis B and C Virus Co-Infection and Their Association With Liver Disease in Persons With HIV in Nigeria. J Int Assoc Provid AIDS Care 2024; 23:23259582241292511. [PMID: 39469965 PMCID: PMC11528674 DOI: 10.1177/23259582241292511] [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: 05/15/2024] [Revised: 09/11/2024] [Accepted: 09/28/2024] [Indexed: 10/30/2024] Open
Abstract
PLAIN LANGUAGE SUMMARY Hepatitis B and C infection and liver disease in people with HIV infection in NigeriaPeople living with human immunodeficiency virus (HIV) infection who have hepatitis B or C infection have a higher chance of developing advanced liver disease than those who do not have either of the hepatitis infections. This finding highlights the importance of awareness, screening, and treatment of the hepatitis viruses in HIV programs in order to reduce the risk of liver disease in this population.
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Affiliation(s)
- Emuobor Odeghe
- Department of Medicine, University of Lagos/Lagos University Teaching Hospital, Lagos, Nigeria
| | - Ganiyat Oyeleke
- Department of Medicine, University of Lagos/Lagos University Teaching Hospital, Lagos, Nigeria
| | - Mayowa Odofin
- Department of Haematology and Blood Transfusion, University of Lagos/Lagos University Teaching Hospital, Lagos, Nigeria
| | - Mary Duguru
- Department of Medicine, University of Jos/Jos University Teaching Hospital, Plateau, Nigeria
| | - Pantong Davwar
- Department of Medicine, University of Jos/Jos University Teaching Hospital, Plateau, Nigeria
| | - David Nyam
- Department of Medicine, University of Jos/Jos University Teaching Hospital, Plateau, Nigeria
| | - Olufunmilayo Lesi
- Department of Medicine, University of Lagos/Lagos University Teaching Hospital, Lagos, Nigeria
| | - Edith Okeke
- Department of Medicine, University of Jos/Jos University Teaching Hospital, Plateau, Nigeria
| | - Hameed Adelabu
- Department of Haematology and Blood Transfusion, University of Lagos/Lagos University Teaching Hospital, Lagos, Nigeria
| | - Oluwakemi Odukoya
- Department of Community Health and Primary Care, University of Lagos/Lagos University Teaching Hospital, Lagos, Nigeria
| | - Alani Akanmu
- Department of Haematology and Blood Transfusion, University of Lagos/Lagos University Teaching Hospital, Lagos, Nigeria
| | - Wasiu Adeyemo
- Department of Oral and Maxillofacial Surgery, University of Lagos/Lagos University Teaching Hospital, Lagos, Nigeria
| | - Fatimah Abdulkareem
- Department of Anatomic and Molecular Pathology, University of Lagos/Lagos University Teaching Hospital, Lagos, Nigeria
| | - Godwin Imade
- Department of Obstetrics and Gynaecology, University of Jos/Jos University Teaching Hospital, Plateau, Nigeria
| | - Brian Joyce
- Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Imran Khan
- School of Professional Studies, Northwestern University, Evanston, IL, USA
| | - Ariel Chandler
- School of Professional Studies, Northwestern University, Evanston, IL, USA
| | - Atiene Sagay
- Department of Obstetrics and Gynaecology, University of Jos/Jos University Teaching Hospital, Plateau, Nigeria
| | - Robert Murphy
- Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Lifang Hou
- Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Claudia Hawkins
- Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
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Villar LM, da Silva LL, do Lago BV, Pereira JG, Guimarães ACS, Mello FCDA, de Paula VS. Could Herpesviridae be the cause of severe acute hepatitis of unknown origin in children? Expert Rev Anti Infect Ther 2024; 22:5-17. [PMID: 38224018 DOI: 10.1080/14787210.2024.2304637] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2023] [Accepted: 01/09/2024] [Indexed: 01/16/2024]
Abstract
INTRODUCTION Severe acute hepatitis (SAH) is defined by a severe inflammation of hepatocytes in the liver parenchyma which can lead to an acute liver failure, a clinical condition with high mortality rate that can be triggered by several factors but is usually associated to hepatotropic viruses' infection. In 2022, cases of children with severe acute hepatitis of unknown origin hospitalized in Glasgow, Scotland, were reported. Possible causes of this condition include, but are not limited to, undiagnosed viral (and non-viral) infections, autoimmune hepatitis, drug and/or chemical toxicity, mitochondrial chain respiratory and metabolic disorders. AREAS COVERED Herpesviruses can cause severe acute hepatitis, but little is known about the role and the mechanisms of herpesviruses as a causative agent of this type of hepatitis. We review the role of herpesviruses as causative agent of SAH in children and other possible mechanisms involved in this disease. EXPERT OPINION Differential diagnosis for herpesvirus in SAH should be implemented in all settings. Alternative fluids, such as saliva and dried blood, could be used in the diagnosis to overwhelm the availability of biological specimens at sufficient volume. In the future, genetic studies could also be added to increase the knowledge about severe acute hepatitis in children.
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Affiliation(s)
- Livia Melo Villar
- Viral Hepatitis Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
| | - Lucas Lima da Silva
- Viral Hepatitis Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
| | - Barbara Vieira do Lago
- Viral Hepatitis Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
| | - Jessica Gonçalves Pereira
- Laboratory of Molecular Virology and Parasitology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
| | - Ana Carolina Silva Guimarães
- Laboratory of Molecular Virology and Parasitology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
| | | | - Vanessa Salete de Paula
- Laboratory of Molecular Virology and Parasitology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
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Allison WE. Special Projects of National Significance Curing Hepatitis C (HCV) Among People of Color Living With HIV Initiative: Improving Linkage to and Retention in HCV, Behavioral Health and Substance Use Disorder (SUD) Care. Health Promot Pract 2023; 24:969-972. [PMID: 37440614 DOI: 10.1177/15248399231169785] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/15/2023]
Affiliation(s)
- Waridibo E Allison
- The University of North Texas Health Science Center at Fort Worth, Fort Worth, TX, USA
- The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
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Moorman AC, Bixler D, Teshale EH, Hofmeister M, Roberts H, Chapin-Bardales J, Gupta N. Hepatitis C Virus-HIV Coinfection in the United States Among People Who Inject Drugs: Data Needed for Ending Dual Epidemics. Public Health Rep 2023:333549231181348. [PMID: 37480274 PMCID: PMC12075850 DOI: 10.1177/00333549231181348] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/23/2023] Open
Abstract
The overlapping epidemics of hepatitis C virus (HCV) and HIV infection stem from underlying behaviors and health disparities among disproportionately affected populations, especially people who inject drugs (PWID). Characterizing the prevalence of HCV-HIV coinfection offers improved data to address these underlying determinants of health. We performed a literature search for articles that describe US populations, were published during 2005-2021, and summarized evidence of the prevalence of HCV infection in recent HIV clusters and outbreaks among PWID. In population- and community-based studies, HCV antibody prevalence among PWID with HIV ranged from 10.7% to 71.4%, depending on the setting and study design. HCV-HIV coinfection ranged from 70% to 94% among 5 larger HIV clusters or outbreaks among PWID during 2014-2021; where characterized, HCV diagnosis preceded HIV detection by a median of 4 to 5 years. Robust modernized surveillance is needed to support and measure the progress of city, state, and national activities for ending the HIV epidemic and eliminating hepatitis C. Developing and leveraging surveillance systems can identify missed opportunities for prevention, evaluate care, and build capacity for outbreak investigation. In addition, improved data on injection drug use are crucial to inform efforts for improved HCV and HIV testing, prevention, and treatment in settings that serve PWID. By providing data in a wholistic, integrated manner, public health surveillance programs can support efforts to overcome inefficiencies of disease-specific silos, accelerate delivery of preventive and clinical services, and address the excess disease burden and health disparities associated with HCV-HIV coinfection.
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Affiliation(s)
- Anne C. Moorman
- Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Danae Bixler
- Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Eyasu H. Teshale
- Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Megan Hofmeister
- Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Henry Roberts
- Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Johanna Chapin-Bardales
- Division of HIV Prevention, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Neil Gupta
- Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA
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Çapan İ, Hawash M, Jaradat N, Sert Y, Servi R, Koca İ. Design, synthesis, molecular docking and biological evaluation of new carbazole derivatives as anticancer, and antioxidant agents. BMC Chem 2023; 17:60. [PMID: 37328860 DOI: 10.1186/s13065-023-00961-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Accepted: 05/25/2023] [Indexed: 06/18/2023] Open
Abstract
BACKGROUND The carbazole skeleton is an important structural motif occurring naturally or synthesized chemically and has antihistaminic, antioxidant, antitumor, antimicrobial, and anti-inflammatory activities. OBJECTIVES This study aimed to design and synthesize a novel series of carbazole derivatives and evaluate their antiproliferative and antioxidant activities. METHODS The synthesized compounds were characterized utilizing HRMS, 1H-, and 13CAPT-NMR, and assessed for their anticancer, antifibrotic, and antioxidant effects utilizing reference biomedical procedures. In addition, the AutoDock Vina application was used to perform in-silico docking computations. RESULTS A series of carbazole derivatives were synthesized and characterized in the current study. Compounds 10 and 11 were found to have a stronger antiproliferative effect than compounds 2-5 against HepG2, HeLa, and MCF7 cancer cell lines with IC50 values of 7.68, 10.09, and 6.44 µM, respectively. Moreover, compound 9 showed potent antiproliferative activity against HeLa cancer cell lines with an IC50 value of 7.59 µM. However, except for compound 5, all of the synthesized compounds showed moderate antiproliferative activities against CaCo-2 with IC50 values in the range of 43.7-187.23 µM. All of these values were compared with the positive control anticancer drug 5-Fluorouracil (5-FU). In addition, compound 9 showed the most potent anti-fibrotic compound, and the cellular viability of LX-2 was found 57.96% at 1 µM concentration in comparison with the positive control 5-FU. Moreover, 4 and 9 compounds showed potent antioxidant activities with IC50 values of 1.05 ± 0.77 and 5.15 ± 1.01 µM, respectively. CONCLUSION Most of the synthesized carbazole derivatives showed promising antiproliferative, antioxidant, and antifibrotic biological effects, and further in-vivo investigations are needed to approve or disapprove these results.
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Affiliation(s)
- İrfan Çapan
- Department of Material and Material Processing Technologies, Gazi University, Technical Sciences Vocational College, 06560, Ankara, Turkey.
| | - Mohammed Hawash
- Department of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, 00970, Nablus, Palestine.
| | - Nidal Jaradat
- Department of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, 00970, Nablus, Palestine
| | - Yusuf Sert
- Yozgat Bozok University, Sorgun Vocational School, Yozgat, Turkey
| | - Refik Servi
- Department of Anatomy, Faculty of Medicine, Firat University, Elazig, Turkey
| | - İrfan Koca
- Department of Chemistry, Faculty of Art & Sciences, Yozgat Bozok University, Yozgat, Turkey
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Kayesh MEH, Kohara M, Tsukiyama-Kohara K. Toll-like Receptor Response to Human Immunodeficiency Virus Type 1 or Co-Infection with Hepatitis B or C Virus: An Overview. Int J Mol Sci 2023; 24:ijms24119624. [PMID: 37298575 DOI: 10.3390/ijms24119624] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Revised: 05/29/2023] [Accepted: 05/31/2023] [Indexed: 06/12/2023] Open
Abstract
Toll-like receptors (TLRs) are evolutionarily conserved pattern recognition receptors that play important roles in the early detection of pathogen-associated molecular patterns and shaping innate and adaptive immune responses, which may influence the consequences of infection. Similarly to other viral infections, human immunodeficiency virus type 1 (HIV-1) also modulates the host TLR response; therefore, a proper understanding of the response induced by human HIV-1 or co-infection with hepatitis B virus (HBV) or hepatitis C virus (HCV), due to the common mode of transmission of these viruses, is essential for understanding HIV-1 pathogenesis during mono- or co-infection with HBV or HCV, as well as for HIV-1 cure strategies. In this review, we discuss the host TLR response during HIV-1 infection and the innate immune evasion mechanisms adopted by HIV-1 for infection establishment. We also examine changes in the host TLR response during HIV-1 co-infection with HBV or HCV; however, this type of study is extremely scarce. Moreover, we discuss studies investigating TLR agonists as latency-reverting agents and immune stimulators towards new strategies for curing HIV. This understanding will help develop a new strategy for curing HIV-1 mono-infection or co-infection with HBV or HCV.
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Affiliation(s)
- Mohammad Enamul Hoque Kayesh
- Department of Microbiology and Public Health, Faculty of Animal Science and Veterinary Medicine, Patuakhali Science and Technology University, Barishal 8210, Bangladesh
| | - Michinori Kohara
- Department of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan
| | - Kyoko Tsukiyama-Kohara
- Transboundary Animal Diseases Centre, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima 890-0065, Japan
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16
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Isfordink CJ, Boyd A, Sacks-Davis R, van Santen DK, Smit C, Martinello M, Stoove M, Berenguer J, Wittkop L, Klein MB, Rauch A, Salmon D, Lacombe K, Stewart A, Schinkel J, Doyle JS, Hellard M, van der Valk M, Matthews GV. Reasons for not commencing direct-acting antiviral treatment despite unrestricted access for individuals with HIV and hepatitis C virus: a multinational, prospective cohort study. Lancet Public Health 2023; 8:e294-e304. [PMID: 36965984 DOI: 10.1016/s2468-2667(23)00056-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Revised: 01/23/2023] [Accepted: 02/27/2023] [Indexed: 03/27/2023]
Abstract
BACKGROUND Individuals with HIV and hepatitis C virus (HCV) who remain untreated with direct-acting antivirals can contribute to HCV transmission and HCV-related mortality. We aimed to compare rates of uptake of direct-acting antivirals following unrestricted access to this treatment in high-income countries and examine factors associated with remaining untreated. METHODS This multinational, prospective cohort study used data from the International Collaboration on Hepatitis C Elimination in HIV Cohorts (InCHEHC). We analysed data from nine observational cohorts participating in the InCHEHC, including data from six high-income countries (Australia, Canada, France, the Netherlands, Spain, and Switzerland). We included individuals aged 18 years and older, with HIV and HCV (ie, HCV-RNA positive without evidence of spontaneous clearance) during unrestricted access to interferon-free direct-acting antiviral treatment in each country. We calculated the cumulative proportion of participants who remained untreated with direct-acting antivirals, with follow-up starting after the date of unrestricted access or cohort inclusion, whichever occurred most recently. Factors associated with the commencement rate of direct-acting antiviral treatment were assessed using competing-risks regression with the Fine-Gray method. FINDINGS The date of unrestricted access to direct-acting antiviral treatment for people with HIV ranged from Nov 1, 2014, in France to Nov 1, 2017, in Switzerland. We included 4552 individuals with HIV-HCV, mainly men who have sex with men (MSM; n=2156 [47%]) and people who inject or have injected drugs (n=1453 [32%]). 1365 (30%) of 4552 participants remained untreated with direct-acting antivirals. For individuals treated with direct-acting antivirals, median time from start of follow-up to treatment was 5 months (IQR 2-12). For individuals who were not treated with direct-acting antivirals, median follow-up was 22 months (8-30). Being linked to care in Australia, France, or the Netherlands, on antiretroviral therapy, having undetectable HIV RNA, and shorter duration since first positive HCV test were independently associated with higher commencement rate of direct-acting antiviral treatment. Compared with MSM, male heterosexuals and females with unknown or other routes of HIV transmission (ie, neither injection drug use nor heterosexual transmission) had lower rates of commencement. INTERPRETATION Despite unrestricted access, almost a third of individuals with HIV-HCV remained untreated with direct-acting antivirals during follow-up, with variation in commencement rate of HCV treatment between countries and key populations. Increased efforts are required to reach the remaining individuals with HIV who are HCV-viraemic to achieve HIV-HCV micro-elimination. FUNDING None.
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Affiliation(s)
- Cas J Isfordink
- Department of Internal Medicine, Division of Infectious Diseases, Amsterdam Institute for Infection and Immunity, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands
| | - Anders Boyd
- Stichting HIV Monitoring, Amsterdam, Netherlands; Department of Infectious Diseases, Research, and Prevention, Public Health Service of Amsterdam, Amsterdam, Netherlands
| | - Rachel Sacks-Davis
- Disease Elimination Program, Burnet Institute, Melbourne, VIC, Australia; Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia; Doherty Institute and School of Population and Global Health, University of Melbourne, Melbourne, VIC, Australia
| | - Daniela K van Santen
- Department of Internal Medicine, Division of Infectious Diseases, Amsterdam Institute for Infection and Immunity, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands; Department of Infectious Diseases, Research, and Prevention, Public Health Service of Amsterdam, Amsterdam, Netherlands; Disease Elimination Program, Burnet Institute, Melbourne, VIC, Australia; Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia
| | - Colette Smit
- Stichting HIV Monitoring, Amsterdam, Netherlands
| | | | - Mark Stoove
- Disease Elimination Program, Burnet Institute, Melbourne, VIC, Australia; Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia; School of Psychology and Public Health, La Trobe University, Melbourne, VIC, Australia
| | - Juan Berenguer
- Infectious Diseases, Hospital General Universitario Gregorio Marañón (IiSGM), Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Madrid, Spain
| | - Linda Wittkop
- University of Bordeaux, INSERM, Institut Bergonié, BPH, U1219, CIC-EC 1401, Bordeaux, France; INRIA, Talence, France; CHU de Bordeaux, Service d'Information Médicale, INSERM, Institut Bergonié, CIC-EC 1401, Bordeaux, France
| | - Marina B Klein
- Division of Infectious Diseases and Chronic Viral Illness Service, Department of Medicine, McGill University Health Centre, Montreal, QC, Canada
| | - Andri Rauch
- Department of Infectious Diseases, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Dominique Salmon
- Service Maladies Infectieuses et Tropicales, AP-HP Centre, Hôspital Cochin Hôtel Dieu, Paris, France
| | - Karine Lacombe
- Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, IPLESP, Paris, France
| | - Ashleigh Stewart
- Disease Elimination Program, Burnet Institute, Melbourne, VIC, Australia
| | - Janke Schinkel
- Department of Medical Microbiology and Infection Prevention, Section of Clinical Virology, Amsterdam Infection and Immunity Institute, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands
| | - Joseph S Doyle
- Disease Elimination Program, Burnet Institute, Melbourne, VIC, Australia; Department of Infectious Diseases, The Alfred Hospital, Melbourne, VIC, Australia
| | - Margaret Hellard
- Disease Elimination Program, Burnet Institute, Melbourne, VIC, Australia; Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia; Doherty Institute and School of Population and Global Health, University of Melbourne, Melbourne, VIC, Australia; Department of Infectious Diseases, The Alfred Hospital, Melbourne, VIC, Australia
| | - Marc van der Valk
- Department of Internal Medicine, Division of Infectious Diseases, Amsterdam Institute for Infection and Immunity, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands; Stichting HIV Monitoring, Amsterdam, Netherlands.
| | - Gail V Matthews
- Kirby Institute, University of New South Wales, Sydney, NSW, Australia
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Nickbakhsh S, McWilliam Leitch EC, Smith S, Davis C, Hutchinson S, Irving WL, McLauchlan J, Thomson EC. Geographical variation in hepatitis C-related severe liver disease and patient risk factors: a multicentre cross-sectional study. Epidemiol Infect 2023; 151:e59. [PMID: 36915219 PMCID: PMC10126891 DOI: 10.1017/s0950268823000377] [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: 07/23/2022] [Revised: 02/05/2023] [Accepted: 03/02/2023] [Indexed: 03/15/2023] Open
Abstract
Despite promising steps towards the elimination of hepatitis C virus (HCV) in the UK, several indicators provide a cause for concern for future disease burden. We aimed to improve understanding of geographical variation in HCV-related severe liver disease and historic risk factor prevalence among clinic attendees in England and Scotland. We used metadata from 3829 HCV-positive patients consecutively enrolled into HCV Research UK from 48 hospital centres in England and Scotland during 2012-2014. Employing mixed-effects statistical modelling, several independent risk factors were identified: age 46-59 y (ORadj 3.06) and ≥60 y (ORadj 5.64) relative to <46 y, male relative to female sex (ORadj 1.58), high BMI (ORadj 1.73) and obesity (ORadj 2.81) relative to normal BMI, diabetes relative to no diabetes (ORadj 2.75), infection with HCV genotype (GT)-3 relative to GT-1 (ORadj 1.75), route of infection through blood products relative to injecting drug use (ORadj 1.40), and lower odds were associated with black ethnicity (ORadj 0.31) relative to white ethnicity. A small proportion of unexplained variation was attributed to differences between hospital centres and local health authorities. Our study provides a baseline measure of historic risk factor prevalence and potential geographical variation in healthcare provision, to support ongoing monitoring of HCV-related disease burden and the design of risk prevention measures.
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Affiliation(s)
- Sema Nickbakhsh
- MRC-University of Glasgow Centre for Virus Research, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G61 1QH, UK
| | - E. Carol McWilliam Leitch
- MRC-University of Glasgow Centre for Virus Research, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G61 1QH, UK
| | - Shanley Smith
- Public Health Scotland, Meridian Court, 5 Cadogan Street, Glasgow G2 6QE, UK
| | - Chris Davis
- MRC-University of Glasgow Centre for Virus Research, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G61 1QH, UK
| | - Sharon Hutchinson
- Public Health Scotland, Meridian Court, 5 Cadogan Street, Glasgow G2 6QE, UK
| | - William L. Irving
- NIHR Nottingham Digestive Diseases Biomedical Research Unit, University of Nottingham, Nottingham NG7 2RD, UK
| | - John McLauchlan
- MRC-University of Glasgow Centre for Virus Research, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G61 1QH, UK
| | - Emma C. Thomson
- MRC-University of Glasgow Centre for Virus Research, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G61 1QH, UK
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Nishikawa K, Kimura M, Imamura J, Kimura K. Prevalence of hepatitis C virus infection among men who have sex with men with human immunodeficiency virus-1 infection between 2010 and 2020 in Japan: A single-center retrospective cohort study. J Infect Chemother 2023; 29:263-268. [PMID: 36585274 DOI: 10.1016/j.jiac.2022.11.009] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Revised: 11/06/2022] [Accepted: 11/20/2022] [Indexed: 12/29/2022]
Abstract
INTRODUCTION The high prevalence of hepatitis C virus (HCV) infection in human immunodeficiency virus (HIV)-positive men who have sex with men (MSM) is an important health issue. The purpose of this study is to investigate the actual prevalence of HCV infection among HIV-positive MSM in Japan. METHODS This study is a single-center retrospective cohort study. We collected data of HIV-infected MSM who visited our hospital from January 2010 to December 2020, and evaluated HCV prevalence, course of HCV infection, and direct-acting antiviral (DAA) treatment efficacy in HIV-infected MSM. RESULTS Overall, 1135 HIV-infected MSM had HCV antibody (Ab) tests during the observation period. The first anti-HCV Ab positive rate in HIV-infected MSM was 4% (45/1135), and the seroconversion rate of HCV antibody was 3.6% (39/1090). Treponema pallidum hemagglutination antigen positivity (odds ratio [OR], 5.28; 95% confidence interval [CI], 2.9 to 10.5) and intravenous drug injection (OR, 19; 95% CI, 3.4 to 149) were identified as factors associated with HCV Ab positivity. Spontaneous elimination of HCV infection was observed in 17.9% (7/39) of patients. DAA treatment was performed in 43 cases, and the overall sustained virologic response 12 (SVR12) rate for DAA treatment was 93% (40/43). CONCLUSION A high HCV infection rate among HIV-infected MSM was observed in Japan. The DAA treatment response rate in patients with HIV/HCV co-infection was the high response rate.
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Affiliation(s)
- Koji Nishikawa
- Department of Hepatology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
| | - Masamichi Kimura
- Department of Hepatology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
| | - Jun Imamura
- Department of Hepatology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
| | - Kiminori Kimura
- Department of Hepatology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan.
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Lin W, Wang X, Zhang J, Wen C, Kang W, Mao L, Yang J, Dou Y, Shi L, Dang B, Lan Y, Li H, Li Y, Chen X, He H, Xu M, He Y, Hu F, Lu R, Cai W, Li L. A simple, feasible, efficient and safe treatment strategy of sofosbuvir/velpatasvir for chronic HCV/HIV-1 coinfected patients regardless of HCV genotypes: a multicenter, open-label study in China. THE LANCET REGIONAL HEALTH - WESTERN PACIFIC 2023. [PMID: 37547041 PMCID: PMC10398601 DOI: 10.1016/j.lanwpc.2023.100749] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/29/2023]
Abstract
Background The direct-acting antiviral agents (DAAs) have revolutionized the treatment of Hepatitis C Virus (HCV) infection. However, a simple and feasible treatment strategy with high efficacy and safety for HCV in patients coinfected with Human Immunodeficiency Virus (HIV) remains an unmet medical need, especially in areas with limited health resource. This study aims to assess the efficacy and safety of 12 weeks of treatment with sofosbuvir and velpatasvir in patients with chronic HCV/HIV-1 coinfection. Methods We conducted a multicenter, single-arm, open-label study in China, which involved chronic HCV/HIV-1 coinfected patients who are receiving an antiretroviral regimen of a combination tablet consisting of elvitegravir, cobicistat, emtricitabine, tenofovir alafenamide, (EVG/c/FTC/TAF) once daily. Patients with liver cirrhosis or experienced to DAAs treatment were excluded. All patients received combined sofosbuvir (400 mg) and velpatasvir (100 mg) tablet once daily for 12 weeks regardless of HCV genotype. The primary efficacy endpoint was sustained virologic response, defined as HCV RNA <15 IU/mL at 12 weeks after completion of treatment (SVR12). The primary safety endpoint was the proportion of patients who prematurely discontinued treatment because of adverse events. Safety and efficacy data were analyzed with an intention-to-treat (ITT) population (last observation carried forward) and per-protocol (PP) population. This trial is registered on ChiCTR.org.cn with number being ChiCTR1800020246. Findings Of the 243 patients enrolled, 78% were male, 9% had been previously treated for HCV with interferon, and none had pre-defined cirrhosis, although 8% had Fibrosis 4 score (FIB-4) >3.25. A total of 233 patients completed 12-week post-treatment follow-up. Overall, 227/233 patients (97%) achieved SVR12: 100% (63/63) in those with HCV genotype 1, 67% (2/3) in those with genotype 2, 95% (84/88) in those with genotype 3, 99% (78/79) in those with genotype 6. Rates of SVR12 were lower among those with baseline FIB-4 >3.25 than those without (78% [14/18] vs. 99% [211/212], P < 0.001). HIV-1 suppression was not compromised. The most common adverse events were upper respiratory tract infection (5%), cough (3%), abnormal renal function (2%), abnormal liver function (2%), constipation (2%), urinary tract infection (2%) and sleep disorders (2%). No participant discontinued treatment because of adverse events or death. Interpretation Twelve weeks of treatment with sofosbuvir/velpatasvir provide high rates of SVR and is well-tolerated in patients coinfected with HIV-1 and HCV regardless of HCV genotypes. Non-invasive liver fibrosis score may help to further distinguish patients at greater likelihood of a suboptimal response. Funding The 13th Five Year Plan of the Ministry of Science and Technology of China for the prevention and treatment of major infectious diseases such as AIDS and viral hepatitis, the National Key Research and Development Program of China, Medical Key Discipline Program of Guangzhou-Viral Infectious Diseases (2021-2023), Basic research program on people's Livelihood Science and technology of Guangzhou, and National Natural Science Foundation of China.
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20
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Wang Y, Zhou C, Fu Y, Zhang L, Liu S, Cai L, Jiang Z, Xu X, Feng L, Gao Y. Establishment of acute liver failure model in Tibetan miniature pig and verified by dual plasma molecular adsorption system. Int J Artif Organs 2023; 46:141-152. [PMID: 36600401 DOI: 10.1177/03913988221145501] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
BACKGROUND Acute liver failure (ALF) is a severe liver disease with high morbidity and mortality rates. Animal models are important for research on ALF. This study aimed to establish a reproducible, Tibetan miniature pig model of D-galactosamine-induced ALF and verify it using a dual plasma molecular adsorption system (DPMAS). METHODS Tibet miniature pigs were randomly divided into four groups (A, B, C, D) after catheterization. D-galactosamine (D-gal) at 0.45, 0.40, 0.35, and 0.35 g/kg body weight, respectively, was injected through the catheter. Group D was treated with DPMAS 48 h after D-gal administration. Vital signs and blood index values were recorded every 12 h after D-gal administration. H&E, TUNEL, Ki67, and Masson staining tests were performed. RESULTS After D-gal administration, Tibetan miniature pigs developed different degrees of debilitation, loss of appetite, and jaundice. Survival times of groups A, B, C, and D were 39.7 ± 5.9, 53.0 ± 12.5,61.3 ± 8.1, and 61 ± 7 h, respectively. Blood levels of ALT, AST, TBIL, ammonia, PT, and inflammation factors significantly increased compared with baseline levels in the different groups (Ps < 0.05). Pathological results revealed a clear liver cell necrosis positive correlation with D-gal dose. However, DPMAS did not increase the survival time in ALF, ammonia, or liver cell necrosis. CONCLUSION We successfully established a reproducible Tibetan miniature pig model of d-galactosamine-induced ALF, and we believe that a dosage of 0.35 g/kg is optimal.
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Affiliation(s)
- Yi Wang
- Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Chenjie Zhou
- Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Yu Fu
- Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Linya Zhang
- Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Shusong Liu
- Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Lei Cai
- Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Zesheng Jiang
- Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Xiaoping Xu
- Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Lei Feng
- Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Yi Gao
- Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.,State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou, Guangdong, China
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21
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Monin MB, Ingiliz P, Lutz T, Scholten S, Cordes C, Martínez-Rebollar M, Spinner CD, Nelson M, Rausch M, Bhagani S, Peters L, Reiberger T, Mauss S, Rockstroh JK, Boesecke C. Low Spontaneous Clearance Rates of Recently Acquired Hepatitis C Virus in Human Immunodeficiency Virus-Positive Men Who Have Sex With Men (PROBE-C Study). Clin Infect Dis 2023; 76:e607-e612. [PMID: 36004410 DOI: 10.1093/cid/ciac680] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2022] [Revised: 08/10/2022] [Accepted: 08/19/2022] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND Using direct-acting antivirals (DAAs) for recently acquired hepatitis C virus (RAHCV) infections, particularly in human immunodeficiency virus (HIV)-positive men who have sex with men (MSM), dramatically reduced the incidence of hepatitis C. However, implementation into clinical practice is challenging. The aim of this study was to analyze spontaneous clearance (SC) rates of RAHCV and to identify predictors of SC. METHODS The PROBE-C study is an observational European cohort on RAHCV infections in HIV-positive MSM. Between 2007 and 2017, RAHCV infections were documented with ≥12 months of follow-up. Fisher exact, χ2, and Mann-Whitney U tests were used for statistical analysis. RESULTS A total of 464 RAHCV infections were documented; 457 of 464 patients (98%) were male, and the median age (interquartile range [IQR]) was 41 (38-46) years. The main risk group for hepatitis C virus (HCV) transmission was MSM (98.9%). Most participants were infected with HCV genotype 1 (78.3%). The median baseline HCV RNA level (IQR) was 230 000 (135 000-474 432) IU/mL, and the median CD4+ T-cell count was 574/µL (547-604/µL. Of all cases, 92% received combination antiretroviral therapy, with 91% showing suppressed HIV RNA levels (<200 copies/mL). The median maximum alanine aminotransferase level (IQR) was 445 (402-522) U/L. SC of RAHCV infection occurred in 55 of 464 cases (11.9%). A >2-log decline in HCV RNA levels 4 weeks after diagnosis of RAHCV infection was the strongest predictor of SC (P < .001; sensitivity, 96.4%; specificity, 97.5%; positive predictive value, 84.1%; negative predictive value, 99.5%). CONCLUSIONS SC of RAHCV in HIV-positive MSM is found in only 11.9% of cases and a <2-log drop in HCV RNA level at week 4 after diagnosis should prompt early DAA-based treatment. However, immediate DAA treatment for RAHCV infection may also be favored in patients with ongoing transmission risk behavior.
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Affiliation(s)
- Malte B Monin
- University Hospital Bonn, Bonn, Germany.,German Centre for Infection Research (DZIF), Partner Site Cologne-Bonn, Bonn, Germany
| | - Patrick Ingiliz
- University Hospital Henri-Mondor, Inserm U955-Virus, Hepatology, Cancer, Paris, France
| | | | | | | | - Maria Martínez-Rebollar
- HIV Unit, Infectious Diseases Service, Hospital Clinic de Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Christoph D Spinner
- Department of Internal Medicine II, School of Medicine, University Hospital Rechts der Isar, Technical University of Munich, Munich, Germany
| | - Mark Nelson
- Chelsea and Westminster Hospital, London, United Kingdom
| | | | | | - Lars Peters
- CHIP, Department of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark
| | - Thomas Reiberger
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Stefan Mauss
- Center for HIV and Hepatogastroenterology, Düsseldorf, Germany
| | - Jürgen K Rockstroh
- University Hospital Bonn, Bonn, Germany.,German Centre for Infection Research (DZIF), Partner Site Cologne-Bonn, Bonn, Germany.,European AIDS Treatment Network Infectious Disease (NEAT ID) Foundation, London, United Kingdom
| | - Christoph Boesecke
- University Hospital Bonn, Bonn, Germany.,German Centre for Infection Research (DZIF), Partner Site Cologne-Bonn, Bonn, Germany.,European AIDS Treatment Network Infectious Disease (NEAT ID) Foundation, London, United Kingdom
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22
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Price JC, Ma Y, Kuniholm MH, Adimora AA, Fischl M, French AL, Golub ET, Konkle-Parker D, Minkoff H, Ofotokun I, Plankey M, Sharma A, Tien PC. Human Immunodeficiency Virus Is Associated With Elevated FibroScan-Aspartate Aminotransferase (FAST) Score. Clin Infect Dis 2022; 75:2119-2127. [PMID: 35511608 PMCID: PMC10200299 DOI: 10.1093/cid/ciac337] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Revised: 04/06/2022] [Accepted: 04/27/2022] [Indexed: 01/19/2023] Open
Abstract
BACKGROUND Whether human immunodeficiency virus (HIV) infection is associated with the development of nonalcoholic steatohepatitis (NASH) remains unclear. The FibroScan-aspartate aminotransferase (FAST) score was developed to identify patients who have histologic NASH with high nonalcoholic fatty liver disease activity score (NAS ≥4) and significant liver fibrosis (≥F2), which has been associated with higher risk of end-stage liver disease. We examined whether HIV infection is associated with elevated FAST score in a large United States (US) cohort. METHODS Vibration-controlled transient elastography was performed in 1309 women without history of chronic viral hepatitis enrolled from 10 US sites: 928 women with HIV (WWH) and 381 women without HIV (WWOH). We used multivariable logistic regression to evaluate associations of HIV, demographic, lifestyle, and metabolic factors with an elevated (>0.35) FAST score. RESULTS Median age of WWH and WWOH was 51 years and 48 years, respectively. Most (90%) WWH were on antiretroviral therapy and 72% had undetectable HIV RNA. Prevalence of elevated FAST score was higher among WWH compared to WWOH (6.3% vs 1.8%, respectively; P = .001). On multivariable analysis, HIV infection was associated with 3.7-fold higher odds of elevated FAST score (P = .002), and greater waist circumference (per 10 cm) was associated with 1.7-fold higher odds (P < .001). In analysis limited to WWH, undetectable HIV RNA and current protease inhibitor use were independently associated with lower odds of elevated FAST score. CONCLUSIONS Our findings suggest that HIV is an independent risk factor for NASH with significant activity and fibrosis. Studies validating FAST score in persons with HIV are warranted.
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Grants
- U01 AI031834 NIAID NIH HHS
- U01 HL146208 NHLBI NIH HHS
- U01 HL146192 NHLBI NIH HHS
- U01 HL146242 NHLBI NIH HHS
- R01 DA044111 NIDA NIH HHS
- U01 HL146193 NHLBI NIH HHS
- R01 DK109823 NIDDK NIH HHS
- U01 HL146194 NHLBI NIH HHS
- U01 HL146241 NHLBI NIH HHS
- P30 AI027767 NIAID NIH HHS
- P30 AI050409 NIAID NIH HHS
- U01 HL146333 NHLBI NIH HHS
- U01 HL146245 NHLBI NIH HHS
- K24 AI108516 NIAID NIH HHS
- U01 HL146205 NHLBI NIH HHS
- P30 MH116867 NIMH NIH HHS
- P30 AI073961 NIAID NIH HHS
- U01 HL146201 NHLBI NIH HHS
- U01 HL146204 NHLBI NIH HHS
- U01 HL146202 NHLBI NIH HHS
- UL1 TR001881 NCATS NIH HHS
- U01 HL146240 NHLBI NIH HHS
- U01 HL146203 NHLBI NIH HHS
- UL1 TR003098 NCATS NIH HHS
- P30 AI050410 NIAID NIH HHS
- Women’s Interagency HIV Study
- Multicenter AIDS Cohort Study
- WIHS Combined Cohort Study
- Atlanta Clinical Research Site
- Ighovwerha Ofotokun, Anandi Sheth, and Gina Wingood
- Baltimore CRS (Todd Brown and Joseph Margolick)
- Bronx CRS (Kathryn Anastos and Anjali Sharma)
- Brooklyn CRS (Deborah Gustafson and Tracey Wilson)
- Data Analysis and Coordination Center (Gypsyamber D’Souza, Stephen Gange, and Elizabeth Golub)
- Chicago–Cook County CRS (Mardge Cohen and Audrey French)
- Chicago-Northwestern CRS (Steven Wolinsky)
- Northern California CRS (Bradley Aouizerat, Jennifer Price, and Phyllis Tien)
- Los Angeles CRS (Roger Detels and Matthew Mimiaga)
- Metropolitan Washington CRS (Seble Kassaye and Daniel Merenstein)
- Miami CRS (Maria Alcaide, Margaret Fischl, and Deborah Jones)
- Pittsburgh CRS (Jeremy Martinson and Charles Rinaldo)
- University of Alabama at Birmingham
- University of North Carolina CRS (Adaora Adimora)
- National Heart, Lung, and Blood Institute
- Eunice Kennedy Shriver National Institute of Child Health and Human Development
- National Institute on Aging
- National Institute of Dental and Craniofacial Research
- National Institute of Allergy and Infectious Diseases
- National Institute of Neurological Disorders and Stroke
- National Institute of Mental Health
- National Institute on Drug Abuse
- National Institute of Nursing Research
- National Cancer Institute
- National Institute on Alcohol Abuse and Alcoholism
- National Institute on Deafness and Other Communication Disorders
- National Institute of Diabetes and Digestive and Kidney Diseases
- National Institute on Minority Health and Health Disparities
- University of California, San Francisco
- Clinical and Translational Science Award
- Johns Hopkins University, Institute for Clinical and Translational Research
- University of California, Los Angeles, Clinical and Translational Science Institute
- Atlanta, Center for AIDS Research
- Miami CFAR
- University of North Carolina CFAR
- University of Alabama at Birmingham CFAR
- Miami, Center for HIV and Research in Mental Health
- NIAID
- NIDDK
- American College of Gastroenterology Junior Faculty Development Award
- NIH
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Affiliation(s)
- Jennifer C Price
- Department of Medicine, University of California, San Francisco, San Francisco, California, USA
| | - Yifei Ma
- Department of Medicine, University of California, San Francisco, San Francisco, California, USA
| | - Mark H Kuniholm
- Department of Epidemiology and Biostatistics, University at Albany, State University of New York, Rensselaer, New York, USA
| | - Adaora A Adimora
- Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Margaret Fischl
- Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Audrey L French
- Department of Medicine, CORE Center/Stroger Hospital of Cook County, Chicago, Illinois, USA
| | - Elizabeth T Golub
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
| | - Deborah Konkle-Parker
- Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi, USA
| | - Howard Minkoff
- Department of Obstetrics and Gynecology, State University of New York Downstate Health Sciences University, Brooklyn, New York, USA
| | - Ighovwerha Ofotokun
- Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Michael Plankey
- Department of Medicine, Georgetown University Medical Center, Washington, District of Columbia, USA
| | - Anjali Sharma
- Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, USA
| | - Phyllis C Tien
- Department of Medicine, University of California, San Francisco, San Francisco, California, USA
- Department of Veterans Affairs, San Francisco, California, USA
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23
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Lin W, Zhong H, Wen C, He Y, Zheng X, Li H, Chen X, He H, Chen J, Chen L, Liu C, Tang X, Cai W, Li L. Persistently low CD4 cell counts are associated with hepatic events in HCV/HIV coinfected patients: data from the national free antiretroviral treatment program of China. Chin Med J (Engl) 2022; 135:2699-2705. [PMID: 36574222 PMCID: PMC9943990 DOI: 10.1097/cm9.0000000000002502] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND Chronic liver disease has emerged as a leading cause of non-acquired immune deficiency syndrome (AIDS)-related mortality in hepatitis C virus (HCV)/human immunodeficiency virus (HIV)-coinfected patients. The relationship between CD4 cell count and HIV-related opportunistic infections and tumors has been well characterized; however, it is unclear whether CD4 cell count is associated with HCV-related hepatic events. METHODS This observational cohort study enrolled HCV/HIV-coinfected patients from the National Free Antiretroviral Treatment Program of China from 2004 to 2019 in Guangzhou. The primary outcome was a composite of hepatic events, including cirrhosis complications, hepatocellular carcinoma (HCC), and liver-related mortality. Kaplan-Meier survival and multivariate logistic regression analyses were performed. RESULTS Among the 793 patients, 43 developed hepatic events during a median follow-up of 6.7 years, including 35 cirrhosis complications, 13 HCC cases, and 14 cases of liver-related mortality. The 5-year and 10-year cumulative incidences of hepatic events were 4.2% and 9.3%, respectively. Patients who developed hepatic events had a less satisfactory increase in CD4 cell count, lower peak CD4 (354.5 cells/μL vs. 560.0 cells/μL, P < 0.001), and lower percentage of peak CD4 > 500 cells/μL (30.2% vs. 60.7%, P < 0.001) after the initiation of antiretroviral therapy (ART) than those who did not. The cumulative incidences of hepatic events were higher in patients with lower peak CD4 levels with adjusted odds ratios of 3.96 (95% confidence interval [CI]: 1.51-10.40), 2.25 (95% CI: 0.87-5.86), and 0.98 (95% CI: 0.35-2.74) for patients with peak CD4 at <200 cells/μL, 200-350 cells/μL, and 351 to 500 cells/μL, respectively, relative to those with peak CD4 > 500 cells/μL. Peak CD4 was negatively associated with the risk of hepatic events in a dose-response manner ( P -value for trend = 0.004). CONCLUSION Persistently low CD4 cell counts after ART are independently associated with a high risk of hepatic events in HCV/HIV-coinfected patients, highlighting the important role of immune reconstitution in improving liver outcomes.
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Affiliation(s)
- Weiyin Lin
- Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510060, China
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24
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Krings A, Schmidt D, Meixenberger K, Bannert N, Münstermann D, Tiemann C, Kollan C, Gunsenheimer-Bartmeyer B. Decreasing prevalence and stagnating incidence of Hepatitis C-co-infection among a cohort of HIV-1-positive patients, with a majority of men who have sex with men, in Germany, 1996-2019. J Viral Hepat 2022; 29:465-473. [PMID: 35302675 DOI: 10.1111/jvh.13670] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2021] [Revised: 02/08/2022] [Accepted: 02/16/2022] [Indexed: 12/09/2022]
Abstract
Co-infection with Hepatitis C virus (HCV) among HIV-positive patients leads to accelerated progression of liver disease and AIDS. Due to increased HCV prevalence and incidence, co-infection requires monitoring trends among HIV-positive individuals. This will help target prevention strategies and support to reach the global goals of eliminating viral hepatitis as a public health threat. In this analysis HCV prevalence and incidence were determined for the years 1996-2019 from yearly blood samples and questionnaire details among HIV-1-positive patients, with a majority of men who have sex with men, belonging to a nationwide, multicentre observational, prospective cohort study. The results show that HCV prevalence for acute/chronic and resolved infection increased until 2014 to 12%. Since then, prevalence of acute/chronic HCV infection rapidly decreased and prevalence of resolved infections showed a steady increase. HCV incidence was highest in 2010 and lowest in 2017; however, no significant change in HCV incidence could be seen over the years. Therefore, the introduction of directly-acting antiviral agents for HCV treatment notably decreased prevalence and potentially incidence of acute/chronic HCV infection. Nevertheless, prevalence and incidence of HCV among these HIV-1-positive study participants remain high compared with the general population and justify the need for continuous HCV prevention and treatment efforts among HIV-positive individuals.
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Affiliation(s)
- Amrei Krings
- Department of Infectious Disease Epidemiology, Robert Koch Institute, Berlin, Germany.,Postgraduate Training for Applied Epidemiology, Robert Koch Institute, Berlin, Germany.,European Program for Intervention Epidemiology Training, European Centre for Disease Prevention and Control, Stockholm, Sweden
| | - Daniel Schmidt
- Department of Infectious Disease Epidemiology, Robert Koch Institute, Berlin, Germany
| | | | - Norbert Bannert
- Department of Infectious Diseases, Robert Koch Institute, Berlin, Germany
| | | | | | - Christian Kollan
- Department of Infectious Disease Epidemiology, Robert Koch Institute, Berlin, Germany
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25
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McCain JD, Chascsa DM. Special Considerations in the Management of HIV and Viral Hepatitis Coinfections in Liver Transplantation. Hepat Med 2022; 14:27-36. [PMID: 35514530 PMCID: PMC9063796 DOI: 10.2147/hmer.s282662] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Accepted: 04/07/2022] [Indexed: 11/26/2022] Open
Abstract
Modern therapies for hepatitis B virus, hepatitis C virus, and human immunodeficiency virus have become so effective that patients treated for these conditions can have normal life-expectancies. Suitable livers for transplantation remain a scarce and valuable resource. As such, significant efforts have been made to expand donation criteria at many centers. This constant pressure, coupled with the increasing effectiveness of antiviral therapies, has meant that more and more patients infected with hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) may be considered appropriate donors in the right circumstances. Patients with these infections are also more likely to be considered appropriate transplantation recipients than in the past. The treatment of HBV, HCV, and HIV after liver transplantation (LT) can be challenging and complicated by viral coinfections. The various pharmaceutical agents used to treat these infections, as well as the immunosuppressants used post-LT must be carefully balanced for maximum efficacy, and to avoid resistance and drug–drug interactions.
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Affiliation(s)
- Josiah D McCain
- Department of Gastroenterology & Hepatology, Mayo Clinic, Phoenix, AZ, USA
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26
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O'Shea J, Oliver N, Cartwright EJ. Diagnosis and Clinical Manifestations of Acute Hepatitis C Infection in People Living with HIV. AIDS Patient Care STDS 2022; 36:172-177. [PMID: 35507325 DOI: 10.1089/apc.2022.0021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
HIV/hepatitis C virus (HCV) coinfection is a global health problem with overlapping modes of transmission. We performed a single-center retrospective case series of acute HCV infections at the Atlanta Veterans Affairs Health Care System between January 2001 and June 2020 to better characterize the presentation and clinical course of acute HCV among veterans with HIV. Cases were discovered through routine clinical care. We identified 29 cases of acute HCV: all men. Risk for HCV acquisition included men who have sex with men (MSM; 93%) and injection drug use (17%). Thirteen (45%) had a concurrent sexually transmitted infection (STI). Symptoms were seen in 76% of acute HCV cases and resulted in hospitalization in 59% of symptomatic cases. Seven (24%) presented as HCV antibody seronegative. Three never seroconverted, all with CD4 T cell counts <200. Spontaneous HCV clearance occurred in 21% (n = 6) and was more common in those who developed jaundice (p = 0.01). Time to treatment was significantly reduced in the direct-acting antivirals (DAAs) era versus the interferon era (300 vs. 1631 days, p < 0.01). Of those who did not spontaneously clear, 87% were treated (n = 20/23) and 95% (n = 19/20) achieved sustained virological response. Three patients died before HCV treatment, all in the pre-DAA period (one death was liver related). In this case series of acute HCV infection in persons with HIV, many were symptomatic MSM who had a concurrent STI, suggesting sexual HCV transmission. Some presented as HCV antibody negative, highlighting the role of enhanced HCV screening and treatment in MSM with HIV to prevent HCV transmission in sexual networks.
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Affiliation(s)
- Jesse O'Shea
- Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Nora Oliver
- Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, Georgia, USA
- Infectious Diseases, Atlanta VA Health Care System, Decatur, Georgia, USA
| | - Emily J. Cartwright
- Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, Georgia, USA
- Infectious Diseases, Atlanta VA Health Care System, Decatur, Georgia, USA
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27
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Inukai Y, Imai N, Yamamoto K, Ito T, Ishizu Y, Honda T, Okamoto S, Kanematsu T, Suzuki N, Matsushita T, Ishigami M, Fujishiro M. The influence of hepatitis C virus eradication on hepatocarcinogenesis in patients with hemophilia. Ann Hepatol 2022; 27:100545. [PMID: 34571264 DOI: 10.1016/j.aohep.2021.100545] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2021] [Revised: 05/21/2021] [Accepted: 05/24/2021] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND OBJECTIVES Hepatitis C virus (HCV) infections in patients with hemophilia lead to the development of hepatocellular carcinoma (HCC) at a relatively younger age than that in patients without hemophilia. Although recent progress in direct-acting-antivirals has facilitated a high rate of sustained virological response (SVR), the clinical influence of HCV eradication in hemophilia patients remains unclear. This study aimed to compare the clinical outcomes of SVR against HCV in patients with and without hemophilia. PATIENTS AND METHODS The study enrolled 699 patients who achieved SVR after HCV antiviral treatment. Patients were divided into two groups: 78 patients with hemophilia (H group) and 621 patients without hemophilia (NH group). We evaluated patient characteristics, clinical outcomes, and the cumulative incidence of HCC after SVR. RESULTS Compared with the NH group, patients in the H-group were significantly younger and had a lower hepatic fibrosis score. No difference was found in the incidence of liver-related disease or overall death between the two groups over a mean follow-up period of 7 years. Four patients in the H group and 36 patients in the NH group were diagnosed with HCC after SVR. Multivariate analysis showed that male sex, age, and cirrhosis were significant risk factors for HCC incidence. There was no significant difference in the cumulative incidence of HCC after propensity-score matching adjusting for the risk factors of HCC between the two groups. CONCLUSION Hemophilia is not a significant risk factor for hepatocarcinogenesis after SVR against HCV.
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Affiliation(s)
- Yosuke Inukai
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine
| | - Norihiro Imai
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine.
| | - Kenta Yamamoto
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine
| | - Takanori Ito
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine
| | - Yoji Ishizu
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine
| | - Takashi Honda
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine
| | - Shuichi Okamoto
- Department of Hematology and Oncology, Nagoya University Graduate School of Medicine
| | | | - Nobuaki Suzuki
- Department of Transfusion Medicine, Nagoya University Hospital
| | - Tadashi Matsushita
- Department of Clinical Laboratory, Nagoya University Hospital; Department of Transfusion Medicine, Nagoya University Hospital
| | - Masatoshi Ishigami
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine
| | - Mitsuhiro Fujishiro
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine
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28
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Venkatesh SK, Torbenson MS. Liver fibrosis quantification. Abdom Radiol (NY) 2022; 47:1032-1052. [PMID: 35022806 PMCID: PMC9538706 DOI: 10.1007/s00261-021-03396-y] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2021] [Revised: 12/19/2021] [Accepted: 12/20/2021] [Indexed: 12/14/2022]
Abstract
Liver fibrosis (LF) is the wound healing response to chronic liver injury. LF is the endpoint of chronic liver disease (CLD) regardless of etiology and the single most important determinant of long-term liver-related clinical outcomes. Quantification of LF is important for staging, to evaluate response to treatment and to predict outcomes. LF is traditionally staged by liver biopsy. However, liver biopsy is invasive and suffers from sampling errors when biopsy size is inadequate; therefore, non-invasive tests (NITs) have found important roles in clinical care. NITs include simple laboratory-based serum tests, panels of serum tests, and imaging biomarkers. NITs are validated against the liver biopsy and will be used in the future for evaluation of nearly all CLDs with invasive liver biopsy reserved for some cases. Both serum tests and some imaging biomarkers such as elastography are currently used clinically as surrogate markers for LF. Several other imaging biomarkers are still considered research and awaiting clinical application in the future. As the evaluation of imaging biomarkers will likely become the norm in the future, understanding pathogenesis of LF is important. Knowledge of properties measured by imaging biomarkers and its correlation with LF is important to understand the application of NITs by abdominal radiologists. In this review, we present a brief overview of pathogenesis of LF, spatiotemporal evolution of LF in different CLD, and severity assessment with liver biopsy. This will be followed by a brief discussion on properties measured by imaging biomarkers and their relationship to the LF.
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Affiliation(s)
- Sudhakar K Venkatesh
- Abdominal Imaging Division, Department of Radiology, Mayo Clinic, 200, First Street SW, Rochester, MN, 55905, USA.
| | - Michael S Torbenson
- Anatomic Pathology Division, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
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29
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Wasuwanich P, Striley CW, Kamili S, Teshale EH, Seaberg EC, Karnsakul W. Hepatitis D-associated hospitalizations in the United States: 2010-2018. J Viral Hepat 2022; 29:218-226. [PMID: 35075719 PMCID: PMC9304186 DOI: 10.1111/jvh.13645] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Revised: 12/01/2021] [Accepted: 01/03/2022] [Indexed: 12/09/2022]
Abstract
In the United States, hepatitis D is not a reportable condition, leading to gaps in epidemiological and clinical knowledge. We aim to estimate the incidence of hepatitis D-associated hospitalizations in the United States and describe the clinical, demographic and geographic characteristics of those hospitalizations. We utilized hospitalization data from the 2010-2018 National Inpatient Sample from the Healthcare Cost and Utilization Project. Hepatitis D and hepatitis B only (HBV only) hospitalizations were identified by International Classification of Diseases, Ninth Revision (ICD-9) and International Classification of Diseases, Tenth Revision (ICD-10) codes. We identified 3825 hepatitis D-associated hospitalizations. The hospitalization rate of hepatitis D was between 6.9 and 20.7 per 10,000,000 but did not change significantly over time. Compared to HBV only, the hepatitis D cohort had a greater proportion of males, Hispanics, hospitalizations in the Northeast region. The hepatitis D-associated hospitalizations also had significantly greater frequencies of liver failure, non-alcoholic cirrhosis, portal hypertension, ascites and thrombocytopenia. While mortality in hepatitis D was similar to that of HBV only, age >65 years (odds ratio [OR] = 3.79; p = .020) and having a diagnosis of alcoholic cirrhosis (OR = 3.37; p = .044) increased the odds of mortality within the hepatitis D cohort. Although the hepatitis D-associated hospitalizations were relatively uncommon, they were associated with severe complications.
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Affiliation(s)
- Paul Wasuwanich
- University of Florida College of MedicineGainesvilleFloridaUSA
| | - Catherine W. Striley
- Department of EpidemiologyCollege of Public Health and Health ProfessionsUniversity of FloridaGainesvilleFloridaUSA
| | - Saleem Kamili
- Division of Viral HepatitisNational Center for HIV, Viral Hepatitis, STD and TB PreventionCenters for Disease Control and PreventionAtlantaGeorgiaUSA
| | - Eyasu H. Teshale
- Division of Viral HepatitisNational Center for HIV, Viral Hepatitis, STD and TB PreventionCenters for Disease Control and PreventionAtlantaGeorgiaUSA
| | - Eric C. Seaberg
- Department of EpidemiologyJohns Hopkins University Bloomberg School of Public HealthBaltimoreMarylandUSA
| | - Wikrom Karnsakul
- Division of Pediatric Gastroenterology, Hepatology, and NutritionDepartment of PediatricsJohns Hopkins University School of MedicineBaltimoreMarylandUSA
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30
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Mawatari S, Kumagai K, Oda K, Tabu K, Ijuin S, Fujisaki K, Tashima S, Inada Y, Uto H, Saisyoji A, Hiramine Y, Hashiguchi M, Tamai T, Hori T, Taniyama O, Toyodome A, Sakae H, Kure T, Sakurai K, Moriuchi A, Kanmura S, Ido A. Features of patients who developed hepatocellular carcinoma after direct-acting antiviral treatment for hepatitis C Virus. PLoS One 2022; 17:e0262267. [PMID: 35020772 PMCID: PMC8754290 DOI: 10.1371/journal.pone.0262267] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2021] [Accepted: 12/21/2021] [Indexed: 02/07/2023] Open
Abstract
Background The features of hepatitis C virus patients with a sustained virologic response (SVR) who developed hepatocellular carcinoma (HCC) after direct-acting antiviral (DAA) therapy are unclear. Methods The study population included 1494 DAA-SVR patients without a history of HCC. The cumulative carcinogenesis rate after the end of treatment (EOT) and factors related to HCC were analyzed. Results Sixty (4.0%) patients developed HCC during a median observation period of 47.6 months. At four years, the cumulative carcinogenesis rate was 4.7%. A Cox proportional hazards analysis showed that age ≥73 years (hazard ratio [HR]: 2.148), male sex (HR: 3.060), hyaluronic acid (HA) ≥75 ng/mL (HR: 3.996), alpha-fetoprotein at EOT (EOT-AFP) ≥5.3 ng/mL (HR: 4.773), and albumin at EOT (EOT-Alb) <3.9 g/dL (HR: 2.305) were associated with HCC development. Especially, EOT-AFP ≥5.3 ng/mL was associated with HCC development after 3 years from EOT (HR: 6.237). Among patients who developed HCC, AFP did not increase in patients with EOT-AFP <5.3 ng/mL at the onset of HCC. Of these 5 factors, EOT-AFP ≥5.3 ng/mL was scored as 2 points; the others were scored as 1 point. The 4-year cumulative carcinogenesis rate for patients with total scores of 0–2, 3–4, and 5–6 points were 0.6%, 11.9%, and 27.1%, respectively (p<0.001). Conclusions EOT-AFP ≥5.3 ng/mL is useful for predicting HCC development after an SVR. However, AFP does not increase in patients with EOT-AFP <5.3 ng/mL at the onset of HCC. The combination of EOT-AFP, age, sex, HA, and EOT-Alb is important for predicting carcinogenesis.
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Affiliation(s)
- Seiichi Mawatari
- Department of Human and Environmental Sciences, Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
- * E-mail:
| | - Kotaro Kumagai
- Department of Human and Environmental Sciences, Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Kohei Oda
- Department of Human and Environmental Sciences, Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Kazuaki Tabu
- Department of Human and Environmental Sciences, Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Sho Ijuin
- Department of Human and Environmental Sciences, Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Kunio Fujisaki
- Department of Hepatology, Kirishima Medical Center, Hayato-cho, Kirishima, Kagoshima, Japan
| | - Shuzo Tashima
- Department of Human and Environmental Sciences, Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
- Department of Hepatology, Kirishima Medical Center, Hayato-cho, Kirishima, Kagoshima, Japan
| | - Yukiko Inada
- Center for Digestive and Liver Diseases, Miyazaki Medical Center Hospital, Miyazaki, Japan
| | - Hirofumi Uto
- Department of Human and Environmental Sciences, Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
- Center for Digestive and Liver Diseases, Miyazaki Medical Center Hospital, Miyazaki, Japan
| | - Akiko Saisyoji
- Department of Human and Environmental Sciences, Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
- Department of Internal Medicine, Kagoshima Kouseiren Hospital, Kagoshima, Japan
| | - Yasunari Hiramine
- Department of Internal Medicine, Kagoshima Kouseiren Hospital, Kagoshima, Japan
| | - Masafumi Hashiguchi
- Department of Human and Environmental Sciences, Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
- Department of Gastroenterology and Hepatology, Kagoshima City Hospital, Kagoshima, Japan
| | - Tsutomu Tamai
- Department of Human and Environmental Sciences, Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
- Department of Gastroenterology and Hepatology, Kagoshima City Hospital, Kagoshima, Japan
| | - Takeshi Hori
- Department of Gastroenterology and Hepatology, Kagoshima City Hospital, Kagoshima, Japan
| | - Ohki Taniyama
- Department of Human and Environmental Sciences, Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Ai Toyodome
- Department of Human and Environmental Sciences, Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Haruka Sakae
- Department of Human and Environmental Sciences, Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Takeshi Kure
- Department of Human and Environmental Sciences, Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
- Department of Gastroenterology, Kagoshima Medical Association Hospital, Kagoshima, Japan
| | - Kazuhiro Sakurai
- Department of Gastroenterology, National Hospital Organization Kagoshima Medical Center, Kagoshima, Japan
| | - Akihiro Moriuchi
- Department of Human and Environmental Sciences, Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
- Department of Gastroenterology, National Hospital Organization Kagoshima Medical Center, Kagoshima, Japan
| | - Shuji Kanmura
- Department of Human and Environmental Sciences, Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Akio Ido
- Department of Human and Environmental Sciences, Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
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31
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Jones BI, Freedman A, Thomas MJ, Villalba-Mendez C, Sathia L, Flanagan D, Francis S, Currie CJ. Comorbid diseases and conditions in people with HIV in the UK. Curr Med Res Opin 2022; 38:277-285. [PMID: 34761727 DOI: 10.1080/03007995.2021.2003671] [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] [Indexed: 10/19/2022]
Abstract
OBJECTIVES This study aimed to characterize the risk of people living with HIV (PLHIV) in the UK progressing to pre-specified HIV-associated comorbidities, compared with matched, HIV-negative controls. METHODS Primary and secondary care records from the Clinical Practice Research Datalink (CPRD) and linked Hospital Episode Statistics (HES) were used to identify PLHIV, and a matched cohort from the HIV-negative population. Kaplan Meier curves and Cox proportional hazard models were used to evaluate the risk of developing comorbidities including central nervous system (CNS) disorders, end-stage renal disease, osteoporosis, diabetes, cardiovascular disease (CVD), hypertension, stroke and cancer. RESULTS A total of 2945 PLHIV were matched to a cohort of 5890 HIV-negative controls. PLHIV demonstrated an increased hazard ratio (HR) for time to development of incident sleep disorders, depression, osteoporosis, stroke, cancer and renal disease when compared with their matched HIV-negative control. The HRs for anxiety, hypertension, diabetes and CVD were not significantly increased. CONCLUSIONS PLHIV in the UK were at a higher risk of developing a number of comorbid conditions, highlighting the need for regular attendance of health reviews such as the annual health reviews recommended by the British HIV Associations (BHIVA) quality standard for care, which are currently not uniformly conducted.
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Affiliation(s)
| | - Andrew Freedman
- Division of Infection & Immunity, School of Medicine, Cardiff University, Cardiff, UK
| | | | | | | | | | | | - Craig J Currie
- Global Epidemiology, Pharmatelligence, Cardiff, UK
- Division of Population Medicine, School of Medicine, Cardiff University, UK
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32
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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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33
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Fanciulli C, Berenguer J, Busca C, Vivancos MJ, Téllez MJ, Domínguez L, Domingo P, Navarro J, Santos J, Iribarren JA, Morano L, Artero A, Moreno J, Rivero-Román A, Santos I, Giner L, Armiñanzas C, Montero M, Manzardo C, Cifuentes C, García C, Galindo MJ, Ferrero OL, Sanz J, de la Fuente B, Rodríguez C, Gaspar G, Pérez L, Losa JE, Force L, Veloso S, Martínez-Alfaro E, Jarrín I, De Miguel M, González Garcia J. Epidemiological trends of HIV/HCV coinfection in Spain, 2015-2019. HIV Med 2022; 23:705-716. [PMID: 35037379 PMCID: PMC9543728 DOI: 10.1111/hiv.13229] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Revised: 12/17/2021] [Accepted: 12/23/2021] [Indexed: 01/03/2023]
Abstract
Objectives We assessed the prevalence of anti‐hepatitis C virus (HCV) antibodies and active HCV infection (HCV‐RNA‐positive) in people living with HIV (PLWH) in Spain in 2019 and compared the results with those of four similar studies performed during 2015–2018. Methods The study was performed in 41 centres. Sample size was estimated for an accuracy of 1%. Patients were selected by random sampling with proportional allocation. Results The reference population comprised 41 973 PLWH, and the sample size was 1325. HCV serostatus was known in 1316 PLWH (99.3%), of whom 376 (28.6%) were HCV antibody (Ab)‐positive (78.7% were prior injection drug users); 29 were HCV‐RNA‐positive (2.2%). Of the 29 HCV‐RNA‐positive PLWH, infection was chronic in 24, it was acute/recent in one, and it was of unknown duration in four. Cirrhosis was present in 71 (5.4%) PLWH overall, three (10.3%) HCV‐RNA‐positive patients and 68 (23.4%) of those who cleared HCV after anti‐HCV therapy (p = 0.04). The prevalence of anti‐HCV antibodies decreased steadily from 37.7% in 2015 to 28.6% in 2019 (p < 0.001); the prevalence of active HCV infection decreased from 22.1% in 2015 to 2.2% in 2019 (p < 0.001). Uptake of anti‐HCV treatment increased from 53.9% in 2015 to 95.0% in 2019 (p < 0.001). Conclusions In Spain, the prevalence of active HCV infection among PLWH at the end of 2019 was 2.2%, i.e. 90.0% lower than in 2015. Increased exposure to DAAs was probably the main reason for this sharp reduction. Despite the high coverage of treatment with direct‐acting antiviral agents, HCV‐related cirrhosis remains significant in this population.
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Affiliation(s)
- Chiara Fanciulli
- Infectious Diseases and Clinical Microbiology, Hospital General Universitario Gregorio Marañón (IiSGM), Madrid, Spain.,CIBERINFEC, Madrid, Spain
| | - Juan Berenguer
- Infectious Diseases and Clinical Microbiology, Hospital General Universitario Gregorio Marañón (IiSGM), Madrid, Spain.,CIBERINFEC, Madrid, Spain
| | - Carmen Busca
- CIBERINFEC, Madrid, Spain.,HIV Unit, Internal Medicine, Hospital Universitario La Paz (IdiPAZ), Madrid, Spain
| | - María J Vivancos
- CIBERINFEC, Madrid, Spain.,Infectious Diseases, Hospital Ramón y Cajal (Irycis), Madrid, Spain
| | - María J Téllez
- CIBERINFEC, Madrid, Spain.,Infectious Diseases, Hospital Clínico San Carlos, Madrid, Spain
| | - Lourdes Domínguez
- CIBERINFEC, Madrid, Spain.,HIV Unit, Internal Medicine, Hospital Universitario 12 de Octubre, Madrid, Spain
| | - Pere Domingo
- Infectious Diseases, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Jordi Navarro
- CIBERINFEC, Madrid, Spain.,Infectious Diseases, Hospital Universitari Vall d´Hebrón, Barcelona, Spain
| | - Jesús Santos
- Infectious Diseases, Hospital Clínico Universitario Virgen de la Victoria, Málaga, Spain
| | | | - Luis Morano
- Infectious Diseases, Hospital Universitario Álvaro Cunqueiro, Vigo, Spain
| | - Arturo Artero
- Internal Medicine and Infectious Diseases, Hospital Universitario Doctor Peset, Valencia, Spain
| | - Javier Moreno
- Infectious Diseases, Hospital Universitario Miguel Servet, Zaragoza, Spain
| | - Antonio Rivero-Román
- CIBERINFEC, Madrid, Spain.,Infectious Diseases, Hospital Universitario Reina Sofía, Córdoba, Spain
| | - Ignacio Santos
- CIBERINFEC, Madrid, Spain.,Infectious Diseases, Hospital Universitario de la Princesa, Madrid, Spain
| | - Livia Giner
- Infectious Diseases, Hospital General Universitario de Alicante, Alicante, Spain
| | - Carlos Armiñanzas
- CIBERINFEC, Madrid, Spain.,Infectious Diseases, Hospital Universitario Marqués de Valdecilla, Santander, Spain
| | - Marta Montero
- Infectious Diseases, Hospital Universitario y Politécnico La Fe, Valencia, Spain
| | - Christian Manzardo
- Infectious Diseases, Hospital Arnau de Vilanova, Lleida, Spain.,Infectious Diseases, Hospital Santa María, Lleida, Spain
| | - Carmen Cifuentes
- Infectious Diseases, Hospital Son Llàtzer, Palma de Mallorca, Mallorca, Spain
| | - Coral García
- Infectious Diseases, Hospital Universitario Virgen de las Nieves, Granada, Spain
| | - María J Galindo
- Internal Medicine and Infectious Diseases, Hospital Clínico de Valencia, Valencia, Spain
| | - Oscar L Ferrero
- Infectious Diseases, Hospital Universitario de Basurto, Bilbao, Spain
| | - José Sanz
- Infectious Diseases, Hospital Universitario Príncipe de Asturias, Alcalá de Henares, Spain
| | | | | | - Gabriel Gaspar
- Internal Medicine and Infectious Diseases, Hospital Universitario de Getafe, Getafe, Spain
| | - Laura Pérez
- Infectious Diseases, Hospital San Pedro, Logroño, Spain
| | - Juan E Losa
- Infectious Diseases, Fundación Hospital Alcorcón, Alcorcón, Spain
| | - Luis Force
- Internal Medicine and Infectious Diseases, Hospital de Mataró, Mataró, Spain
| | - Sergio Veloso
- Infectious Diseases, Hospital Universitario Joan XXIII, Tarragona, Spain
| | - Elisa Martínez-Alfaro
- Infectious Diseases, Complejo Hospitalario Universitario de Albacete, Albacete, Spain
| | - Inmaculada Jarrín
- CIBERINFEC, Madrid, Spain.,Centro Nacional de Epidemiología, Instituto de Salud Carlos III, Madrid, Spain
| | | | - Juan González Garcia
- CIBERINFEC, Madrid, Spain.,HIV Unit, Internal Medicine, Hospital Universitario La Paz (IdiPAZ), Madrid, Spain
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34
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O’Gurek DT. Diseases of the Liver. Fam Med 2022. [DOI: 10.1007/978-3-030-54441-6_97] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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35
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Skinner NE, Vergara C, El-Diwany R, Paul H, Skaist A, Wheelan SJ, Thomas DL, Ray SC, Balagopal A, Bailey JR. Decreased Activated CD4 + T Cell Repertoire Diversity After Antiretroviral Therapy in HIV-1/HCV Coinfection Correlates with CD4 + T Cell Recovery. Viral Immunol 2021; 34:622-631. [PMID: 34672777 PMCID: PMC8917883 DOI: 10.1089/vim.2021.0027] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Dysfunctional immune activation accumulates during chronic viral infection and contributes to disease pathogenesis. In HIV-1, immune activation is exacerbated by concurrent infection with hepatitis C virus (HCV), accelerating depletion of CD4+ T cells. HIV-1 suppression with antiretroviral therapy (ART) generally reconstitutes CD4+ T cell counts, while also reducing the proportion that is activated. Whether this immune reconstitution also reduces the complexity of the CD4+ T cell population is unknown. We sought to characterize the relationship between activated CD4+ T cell repertoire diversity and immune reconstitution following ART in HIV-1/HCV coinfection. We extracted T cell receptor (TCR) sequences from RNA sequencing data obtained from activated CD4+ T cells of HIV-1/HCV coinfected individuals before and after treatment with ART (clinical trial NCT01285050). There was notable heterogeneity in both the extent of CD4+ T cell reconstitution and in the change in activated CD4+ TCR repertoire diversity following ART. Decreases in activated CD4+ TCR repertoire diversity following ART were predictive of the degree of CD4+ T cell reconstitution. The association of decreased activated CD4+ TCR repertoire diversity and improved CD4+ T cell reconstitution may represent loss of nonspecifically activated TCR clonotypes, and possibly selective expansion of specifically activated CD4+ clones. These results provide insight into the dynamic relationship between activated CD4+ TCR diversity and CD4+ T cell recovery of HIV-1/HCV coinfected individuals after suppression of HIV-1 viremia.
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Affiliation(s)
- Nicole E. Skinner
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Candelaria Vergara
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Ramy El-Diwany
- Department of Surgery, and Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Harry Paul
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Alyza Skaist
- Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Sarah J. Wheelan
- Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - David L. Thomas
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Stuart C. Ray
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Ashwin Balagopal
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Justin R. Bailey
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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36
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Tan Z, Sun H, Xue T, Gan C, Liu H, Xie Y, Yao Y, Ye T. Liver Fibrosis: Therapeutic Targets and Advances in Drug Therapy. Front Cell Dev Biol 2021; 9:730176. [PMID: 34621747 PMCID: PMC8490799 DOI: 10.3389/fcell.2021.730176] [Citation(s) in RCA: 123] [Impact Index Per Article: 30.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2021] [Accepted: 08/31/2021] [Indexed: 02/05/2023] Open
Abstract
Liver fibrosis is an abnormal wound repair response caused by a variety of chronic liver injuries, which is characterized by over-deposition of diffuse extracellular matrix (ECM) and anomalous hyperplasia of connective tissue, and it may further develop into liver cirrhosis, liver failure or liver cancer. To date, chronic liver diseases accompanied with liver fibrosis have caused significant morbidity and mortality in the world with increasing tendency. Although early liver fibrosis has been reported to be reversible, the detailed mechanism of reversing liver fibrosis is still unclear and there is lack of an effective treatment for liver fibrosis. Thus, it is still a top priority for the research and development of anti-fibrosis drugs. In recent years, many strategies have emerged as crucial means to inhibit the occurrence and development of liver fibrosis including anti-inflammation and liver protection, inhibition of hepatic stellate cells (HSCs) activation and proliferation, reduction of ECM overproduction and acceleration of ECM degradation. Moreover, gene therapy has been proved to be a promising anti-fibrosis method. Here, we provide an overview of the relevant targets and drugs under development. We aim to classify and summarize their potential roles in treatment of liver fibrosis, and discuss the challenges and development of anti-fibrosis drugs.
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Affiliation(s)
- Zui Tan
- Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, Frontiers Science Center for Disease-Related Molecular Network, Department of Gastroenterology and Hepatology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Hongbao Sun
- Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, Frontiers Science Center for Disease-Related Molecular Network, Department of Gastroenterology and Hepatology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Taixiong Xue
- Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, Frontiers Science Center for Disease-Related Molecular Network, Department of Gastroenterology and Hepatology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Cailing Gan
- Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, Frontiers Science Center for Disease-Related Molecular Network, Department of Gastroenterology and Hepatology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Hongyao Liu
- Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, Frontiers Science Center for Disease-Related Molecular Network, Department of Gastroenterology and Hepatology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Yuting Xie
- Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, Frontiers Science Center for Disease-Related Molecular Network, Department of Gastroenterology and Hepatology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Yuqin Yao
- West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China
| | - Tinghong Ye
- Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, Frontiers Science Center for Disease-Related Molecular Network, Department of Gastroenterology and Hepatology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
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37
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Ajao S, Roach D, Chan KH, Thimmanagari K, Muhanna A, Mutyala M, Lakasanni S, Slim J. The Roles of Fibrosis Index Based on Four Factors and Aspartate Transaminase-to-Platelet Ratio Index Scoring Systems as an Alternative to Transient Elastography Liver Stiffness in Liver Fibrosis Staging in Human Immunodeficiency Virus and Hepatitis C Virus Co-Infected Patients. Gastroenterology Res 2021; 14:209-213. [PMID: 34527089 PMCID: PMC8425799 DOI: 10.14740/gr1377] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Accepted: 06/26/2021] [Indexed: 11/23/2022] Open
Abstract
Background Liver biopsy used to be the gold standard to assess liver fibrosis in patients infected with hepatitis C virus (HCV). Nonetheless, due to its invasive nature, techniques such as transient elastography liver stiffness (TE-LS), fibrosis index based on four factors (FIB-4) and aspartate transaminase-to-platelet ratio index (APRI) scores are currently being used. FIB-4 and APRI scores have the advantage of low cost and are readily available, compared with TE-LS. Herein, we evaluated the diagnostic performance of these scoring systems as compared to TE-LS in assessing liver fibrosis in patients with human immunodeficiency virus (HIV) and HCV co-infection. Methods The medical records of patients with HIV and HCV co-infection who had TE-LS done at our facility between August 1, 2013 and January 1, 2020 were extracted and analyzed. Exclusion criteria include: 1) patients co-infected with hepatitis B virus; 2) invalid TE-LS assessment; 3) have ≥ 10th upper limit of normal (ULN) alanine aminotransferase (ALT) levels; and 4) excessive alcohol use. Patient demographics, medical history, biochemical and clinical data were retrieved. For each patient, we calculated the FIB-4 and APRI score. Descriptive analysis was performed and correlation of FIB-4 and APRI with TE-LS was assessed with GraphPad Prism statistical software. Results Five hundred forty-seven patients underwent TE-LS during the study period. After excluding those without complete laboratory parameters, the total study population was 344. Their age was 56 ± 10.4 years and 234 (68%) were male. The average aspartate aminotransferase (AST) and ALT were 27.95 and 30.73. The average platelet count was 224 and the average TE-LS was 7.29. Fourteen patients (4.1%) had TE-LS values between 9 and 11.9 kPa and were classified as F3, while 29 (8.5%) had TE-LS ≥ 12 kPa and were classified as F4. With the correlation analysis, both APRI (correlation coefficient, r = 0.1097, 95% confidence interval (CI) 0.0403 - 0.2130; P = 0.042) and FIB-4 (r = 0.0424, 95% CI -0.0634 - 0.1474; P = 0.4335) were not correlated with TE-LS stages of fibrosis. Conclusion In our cohort, we failed to demonstrate that APRI and FIB-4 are reliable alternatives for screening liver fibrosis in patients with HIV and HCV co-infection. Nonetheless, APRI score still has a potential role as a screening tool instead of TE-LS measurement, which is costly and not readily available. It will be important to corroborate these findings in another large cohort, since this may have an important impact on patient management.
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Affiliation(s)
- Susanne Ajao
- Department of Medical Education, Saint Michael's Medical Centre, New York Medical College, Newark, NJ, USA
| | - Dawn Roach
- Department of Medical Education, Saint Michael's Medical Centre, New York Medical College, Newark, NJ, USA
| | - Kok Hoe Chan
- Department of Medical Education, Saint Michael's Medical Centre, New York Medical College, Newark, NJ, USA
| | - Kundana Thimmanagari
- Department of Medical Education, Saint Michael's Medical Centre, New York Medical College, Newark, NJ, USA
| | - Ala Muhanna
- Department of Medical Education, Saint Michael's Medical Centre, New York Medical College, Newark, NJ, USA
| | - Monica Mutyala
- Department of Infectious Disease, Saint Michael's Medical Centre, New York Medical College, Newark, NJ, USA
| | - Saraswathi Lakasanni
- Department of Gastroenterology, Saint Michael's Medical Centre, New York Medical College, Newark, NJ, USA
| | - Jihad Slim
- Department of Medical Education, Saint Michael's Medical Centre, New York Medical College, Newark, NJ, USA.,Department of Infectious Disease, Saint Michael's Medical Centre, New York Medical College, Newark, NJ, USA
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Brochado-Kith Ó, Martínez I, Berenguer J, González-García J, Salgüero S, Sepúlveda-Crespo D, Díez C, Hontañón V, Ibañez-Samaniego L, Pérez-Latorre L, Fernández-Rodríguez A, Ángeles Jiménez-Sousa M, Resino S. HCV Cure With Direct-Acting Antivirals Improves Liver and Immunological Markers in HIV/HCV-Coinfected Patients. Front Immunol 2021; 12:723196. [PMID: 34497613 PMCID: PMC8419228 DOI: 10.3389/fimmu.2021.723196] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Accepted: 08/06/2021] [Indexed: 12/19/2022] Open
Abstract
Hepatitis C virus (HCV) cure after all-oral direct-acting antiviral (DAA) therapy greatly improves the liver and immune system. We aimed to assess the impact of this HCV clearance on immune system-related markers in plasma and the gene expression profile in human immunodeficiency virus (HIV)/HCV-coinfected patients with advanced cirrhosis. We performed a prospective study on 33 HIV/HCV-coinfected patients at baseline and 36 weeks after the sustained virological response. Gene expression was evaluated by RNA-seq analysis on peripheral blood mononuclear cells (PBMCs) and plasma biomarkers by multiplex immunoassays. We found a decrease in plasma biomarkers (PD1, PDL1, CXCL10, CXCL8, IL12p70, IL10, and TGFβ) and liver disease markers (stiffness measurement (LSM), hepatic venous pressure gradient (HVPG), and transaminases, among others). Furthermore, decreased plasma levels of CXCL8, CXCL10, IL10, and PD1 were associated with reduced LSM values. We also found two upregulated (HAS1 and IRG1) and 15 downregulated (CXCL11, CCL8, CCL7, CCL2, ADARB2, RRAD, MX1, SIGLEC1, IFI44L, IFI44, IFI27, IFI6, IFIT3, IFIT1B, and IFIT1) genes at the end of follow-up, all interferon-stimulated genes (ISGs) grouped into four pathways (“cytokine-cytokine receptor interaction”, “viral protein interaction with cytokine and cytokine receptor”, “chemokine signaling pathway”, and “hepatitis C”). Additionally, the decrease in most of these ISGs was significantly related to reduced LSM and HVPG values. In conclusion, HIV/HCV-coinfected patients with advanced-HCV-related cirrhosis who eradicated HCV following DAA therapy exhibited an improvement in liver disease markers and a significant decrease in plasma biomarkers and gene expression related to antiviral/inflammatory response, particularly in levels of several chemokines and ISGs.
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Affiliation(s)
- Óscar Brochado-Kith
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain
| | - Isidoro Martínez
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain
| | - Juan Berenguer
- Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario "Gregorio Marañón", Madrid, Spain.,Instituto de Investigación Sanitaria del Gregorio Marañón, Madrid, Spain
| | - Juan González-García
- Unidad de VIH, Servicio de Medicina Interna, Hospital Universitario "La Paz", Madrid, Spain.,Instituto de Investigación Sanitaria La Paz (IdiPAZ), Madrid, Spain
| | - Sergio Salgüero
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.,Unidad de Análisis Clínicos, Hospital Universitario Fundación Alcorcón, Alcorcón, Spain
| | - Daniel Sepúlveda-Crespo
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain
| | - Cristina Díez
- Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario "Gregorio Marañón", Madrid, Spain.,Instituto de Investigación Sanitaria del Gregorio Marañón, Madrid, Spain
| | - Víctor Hontañón
- Unidad de VIH, Servicio de Medicina Interna, Hospital Universitario "La Paz", Madrid, Spain.,Instituto de Investigación Sanitaria La Paz (IdiPAZ), Madrid, Spain
| | - Luis Ibañez-Samaniego
- Instituto de Investigación Sanitaria del Gregorio Marañón, Madrid, Spain.,Servicio de Aparato Digestivo, Hospital General Universitario Gregorio Marañón, Madrid, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
| | - Leire Pérez-Latorre
- Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario "Gregorio Marañón", Madrid, Spain.,Instituto de Investigación Sanitaria del Gregorio Marañón, Madrid, Spain
| | - Amanda Fernández-Rodríguez
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain
| | - María Ángeles Jiménez-Sousa
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain
| | - Salvador Resino
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain
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Kumar N, Prabhu SS, Monga I, Banerjee I. Influence of IL28B gene polymorphisms on PegINF-RBV-mediated HCV clearance in HIV-HCV co-infected patients: A meta-analysis. Meta Gene 2021. [DOI: 10.1016/j.mgene.2021.100909] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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40
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Ahmadi Gharaei H, Fararouei M, Mirzazadeh A, Sharifnia G, Rohani-Rasaf M, Bastam D, Rahimi J, Kouhestani M, Rezaian S, Dianatinasab M. The global and regional prevalence of hepatitis C and B co-infections among prisoners living with HIV: a systematic review and meta-analysis. Infect Dis Poverty 2021; 10:93. [PMID: 34210349 PMCID: PMC8252262 DOI: 10.1186/s40249-021-00876-7] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2021] [Accepted: 06/16/2021] [Indexed: 01/02/2023] Open
Abstract
BACKGROUND Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are common among individuals with human immune deficiency virus (HIV) infection worldwide. In this study, we did a systematic review and meta-analysis of the published literature to estimate the global and regional prevalence of HCV, HBV and HIV coinfections among HIV-positive prisoners. METHODS We searched PubMed via MEDLINE, Embase, the Cochrane Library, SCOPUS, and Web of science (ISI) to identify studies that reported the prevalence of HBV and HCV among prisoners living with HIV. We used an eight-item checklist for critically appraisal studies of prevalence/incidence of a health problem to assess the quality of publications in the included 48 cross-sectional and 4 cohort studies. We used random-effect models and meta-regression for the meta-analysis of the results of the included studies. RESULTS The number of the included studies were 50 for HCV-HIV, and 23 for HBV-HIV co-infections. The pooled prevalence rates of the coinfections were 12% [95% confidence interval (CI) 9.0-16.0] for HBV-HIV and 62% (95% CI 53.0-71.0) for HCV-HIV. Among HIV-positive prisoners who reported drug injection, the prevalence of HBV increased to 15% (95% CI 5.0-23.0), and the HCV prevalence increased to 78% (95% CI 51.0-100). The prevalence of HBV-HIV coinfection among prisoners ranged from 3% in the East Mediterranean region to 27% in the American region. Also, the prevalence of HCV-HIV coinfections among prisoners ranged from 6% in Europe to 98% in the East Mediterranean regions. CONCLUSIONS Our findings suggested that the high prevalence of HBV and HCV co-infection among HIV-positive prisoners, particularly among those with a history of drug injection, varies significantly across the globe. The results of Meta-regression analysis showed a sliding increase in the prevalence of the studied co-infections among prisoners over the past decades, rising a call for better screening and treatment programs targeting this high-risk population. To prevent the above coinfections among prisoners, aimed public health services (e.g. harm reduction via access to clean needles), human rights, equity, and ethics are to be seriously delivered or practiced in prisons. Protocol registration number: CRD42018115707 (in the PROSPERO international).
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Affiliation(s)
- Hasan Ahmadi Gharaei
- Department of Epidemiology, School of Public Health and Nutrition, Shiraz University of Medical Sciences, Shiraz, Iran
- Department of Health, Faculty of Public Health, Social Determinants of Health Research Center, Gonabad University of Medical Sciences, Gonabad, Iran
| | - Mohammad Fararouei
- Department of Epidemiology, School of Public Health and Nutrition, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Ali Mirzazadeh
- Department of Epidemiology and Biostatistics and Institute for Global Health Sciences, University of California San Francisco, San Francisco, CA, USA
| | - Golnaz Sharifnia
- Department of Epidemiology, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
| | - Marzieh Rohani-Rasaf
- Department of Epidemiology, School of Public Health, Shahroud University of Medical Sciences, Shahroud, Iran
| | - Dariush Bastam
- Medical School, Yasuj University of Medical Sciences, Yasuj, Iran
| | - Jamileh Rahimi
- Department of Epidemiology and Biostatistics, School of Public Health, North Khorasan University of Medical Sciences, Bojnurd, Iran
| | - Mostafa Kouhestani
- Department of Health, Faculty of Public Health, Social Determinants of Health Research Center, Gonabad University of Medical Sciences, Gonabad, Iran
| | - Shahab Rezaian
- Infectious Diseases Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Mostafa Dianatinasab
- Department of Epidemiology, School of Public Health, Shahroud University of Medical Sciences, Shahroud, Iran.
- Department of Complex Genetics and Epidemiology, School of Nutrition and Translational Research in Metabolism, Maastricht University, Universiteitssingel 40 (Room C5.570), 6229 ER, Maastricht, the Netherlands.
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Cross-talk between hepatic stellate cells and T lymphocytes in liver fibrosis. Hepatobiliary Pancreat Dis Int 2021; 20:207-214. [PMID: 33972160 DOI: 10.1016/j.hbpd.2021.04.007] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2020] [Accepted: 04/21/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND Fibrosis results from inflammation and healing following injury. The imbalance between extracellular matrix (ECM) secretion and degradation leads to the ECM accumulation and liver fibrosis. This process is regulated by immune cells. T lymphocytes, including alpha beta (αβ) T cells, which have adaptive immune functions, and gamma delta (γδ) T cells, which have innate immune functions, are considered regulators of liver fibrosis. This review aimed to present the current understanding of the cross-talk between T lymphocytes and hepatic stellate cells (HSCs), which are the key cells in liver fibrosis. DATA SOURCES The keywords "liver fibrosis", "immune", and "T cells" were used to retrieve articles published in PubMed database before January 31, 2020. RESULTS The ratio of CD8+ (suppressor) T cells to CD4+ (helper) T cells is significantly higher in the liver than in the peripheral blood. T cells secrete a series of cytokines and chemokines to regulate the inflammation in the liver and the activation of HSCs to influence the course of liver fibrosis. In addition, HSCs also regulate the differentiation and proliferation of T cells. CONCLUSIONS The cross-talk between T cells and HSCs regulates liver fibrosis progression. The elucidation of this communication process will help us to understand the pathological process of liver fibrosis.
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42
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Solitano V, Plaz Torres MC, Pugliese N, Aghemo A. Management and Treatment of Hepatitis C: Are There Still Unsolved Problems and Unique Populations? Viruses 2021; 13:1048. [PMID: 34205966 PMCID: PMC8228389 DOI: 10.3390/v13061048] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Revised: 05/27/2021] [Accepted: 05/28/2021] [Indexed: 02/07/2023] Open
Abstract
Direct-acting antivirals (DAA) have revolutionized the treatment of patients with chronic hepatitis C virus (HCV) infection, possibly leading to HCV elimination by 2030 as endorsed by the World Health Organization (WHO). However, some patients belonging to the so-called unique or special populations are referred to as difficult-to-treat due to unreached sustained virological response, potential drug side effects or interactions or co-morbidities. Several years after the DAA introduction and on the basis of excellent findings in terms of efficacy and safety, some doubts arise around the exact meaning of the special population designation and whether this group of patients actually exists. The aim of this review is to discuss and analyze current evidence on the management and treatment of the so-called "unique populations". We placed particular emphasis on patients with decompensated cirrhosis, chronic kidney disease (CKD), coinfections, rare genotypes, and previous treatment failure, in order to provide physicians with an updated overview of the actual problems and needs in the current scenario.
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Affiliation(s)
- Virginia Solitano
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20082 Milan, Italy; (V.S.); (N.P.)
- Division of Internal Medicine and Hepatology, Humanitas Research Hospital IRCCS, Rozzano, 20089 Milan, Italy;
| | - Maria Corina Plaz Torres
- Division of Internal Medicine and Hepatology, Humanitas Research Hospital IRCCS, Rozzano, 20089 Milan, Italy;
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS-Ospedale Policlinico San Martino, 16132 Genoa, Italy
| | - Nicola Pugliese
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20082 Milan, Italy; (V.S.); (N.P.)
- Division of Internal Medicine and Hepatology, Humanitas Research Hospital IRCCS, Rozzano, 20089 Milan, Italy;
| | - Alessio Aghemo
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20082 Milan, Italy; (V.S.); (N.P.)
- Division of Internal Medicine and Hepatology, Humanitas Research Hospital IRCCS, Rozzano, 20089 Milan, Italy;
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43
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Liver Fibrosis during Antiretroviral Treatment in HIV-Infected Individuals. Truth or Tale? Cells 2021; 10:cells10051212. [PMID: 34063534 PMCID: PMC8156893 DOI: 10.3390/cells10051212] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Revised: 05/11/2021] [Accepted: 05/13/2021] [Indexed: 12/13/2022] Open
Abstract
After the introduction of antiretroviral treatment (ART) back in 1996, the lifespan of people living with HIV (PLWH) has been substantially increased, while the major causes of morbidity and mortality have switched from opportunistic infections and AIDS-related neoplasms to cardiovascular and liver diseases. HIV itself may lead to liver damage and subsequent liver fibrosis (LF) through multiple pathways. Apart from HIV, viral hepatitis, alcoholic and especially non-alcoholic liver diseases have been implicated in liver involvement among PLWH. Another well known cause of hepatotoxicity is ART, raising clinically significant concerns about LF in long-term treatment. In this review we present the existing data and analyze the association of LF with all ART drug classes. Published data derived from many studies are to some extent controversial and therefore remain inconclusive. Among all the antiretroviral drugs, nucleoside reverse transcriptase inhibitors, especially didanosine and zidovudine, seem to carry the greatest risk for LF, with integrase strand transfer inhibitors and entry inhibitors having minimal risk. Surprisingly, even though protease inhibitors often lead to insulin resistance, they do not seem to be associated with a significant risk of LF. In conclusion, most ART drugs are safe in long-term treatment and seldom lead to severe LF when no liver-related co-morbidities exist.
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44
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Isfordink CJ, van Erpecum KJ, van der Valk M, Mauser-Bunschoten EP, Makris M. Viral hepatitis in haemophilia: historical perspective and current management. Br J Haematol 2021; 195:174-185. [PMID: 33955555 DOI: 10.1111/bjh.17438] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The introduction of clotting factor concentrates has substantially improved the lives of people with clotting factor deficiencies. Unfortunately, the transmission of blood-borne viral infections through these plasma-derived products led to a huge epidemic of human immunodeficiency virus and viral hepatitis in people with haemophilia (PWH). In a significant proportion of PWH exposed to these viruses, the ensuing decades-long chronic infection resulted in excess morbidity and mortality. Fortunately, developments in the safety of blood products, as well as vaccination and highly effective antiviral treatments have improved the prospects of PWH. The present article reviews the background of the viral hepatitis epidemic in PWH, the natural history of hepatitis B and C infections and their long-term management.
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Affiliation(s)
- Cas J Isfordink
- Van Creveldkliniek, Department of Benign Haematology, University Medical Center Utrecht, Utrecht, the Netherlands.,Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, the Netherlands.,Department of Internal Medicine, Division of Infectious Diseases, Amsterdam Institute for Infection and Immunity, University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands
| | - Karel J van Erpecum
- Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Marc van der Valk
- Department of Internal Medicine, Division of Infectious Diseases, Amsterdam Institute for Infection and Immunity, University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands
| | - Evelien P Mauser-Bunschoten
- Van Creveldkliniek, Department of Benign Haematology, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Michael Makris
- Sheffield Haemophilia and Thrombosis Centre, Royal Hallamshire Hospital, Sheffield, UK.,Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
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Suda G, Sakamoto N. Recent advances in the treatment of hepatitis C virus infection for special populations and remaining problems. J Gastroenterol Hepatol 2021; 36:1152-1158. [PMID: 32667068 DOI: 10.1111/jgh.15189] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2020] [Revised: 07/02/2020] [Accepted: 07/12/2020] [Indexed: 12/16/2022]
Abstract
Hepatitis C virus (HCV) infection is one of the primary causes of liver cirrhosis, hepatocellular carcinoma (HCC), and liver transplantation (LT). The rate of HCV infection is high in patients on hemodialysis and in patients infected with human immunodeficiency virus (HIV). In liver transplant patients with HCV infection, recurrent HCV infection of the transplanted liver is universal and results in rapid liver fibrosis progression. In patients with HCV/HIV coinfection as well, liver fibrosis advances rapidly. Thus, there is an urgent need for prompt HCV infection treatment in these special populations (i.e. HIV/HCV coinfection, HCV infection after LT, and dialysis patients). Interferon (IFN)-based therapy for HCV infection could not achieve a high rate of sustained viral response and could cause severe adverse events in the aforementioned special populations. Direct-acting antivirals (DAAs) have recently been developed, and clinical trials have shown that IFN-free DAA-based therapies are associated with a significantly better safety and therapeutic profile than IFN-based therapies. However, the majority of the initial DAA trials excluded special populations; thus, the efficacy and safety of IFN-free DAA-based therapy in special populations remained to be clearly established. Although recent clinical trials and clinical studies have shown the high efficacy and safety of this therapy even in special populations, several unresolved problems, including emergence of resistance-associated variants after failure to respond to DAAs and HCC occurrence after DAA therapy, still exist. Hence, in this review, we discuss the recent advances in anti-HCV therapy for special populations and the remaining problems regarding this therapy.
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Affiliation(s)
- Goki Suda
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Naoya Sakamoto
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
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Gupta E, Agarwal R, Rastogi A, Rani N, Jindal A. Naturally Occurring Resistance Associated Substitutions in Non-Cirrhotic, Treatment Naive HCV-HIV Co-Infected Patients Does Not Affect the Treatment Response for Anti-HCV Antiviral Therapy. Infect Drug Resist 2021; 14:1381-1387. [PMID: 33880042 PMCID: PMC8052117 DOI: 10.2147/idr.s301032] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2021] [Accepted: 03/13/2021] [Indexed: 12/27/2022] Open
Abstract
Purpose Limited literature on the prevalence of baseline resistance associated substitutions (BL-RAS) among HCV–HIV co-infected patients and their association with treatment outcomes is available especially from India. Hence, the present study aimed to study naturally occurring RAS among non-cirrhotic HCV–HIV co-infected patients and their impact on the response to anti-HCV therapy. Patients and Methods In this retrospective study, archived blood samples of 80 HCV–HIV co-infected patients, before anti-HCV therapy initiation, were tested for substitutions at the drug acting sites (NS5a and NS5b) in the HCV genome by direct PCR sequencing. Results BL-RAS were seen in 19 (23.7%) patients. As well as BL-RAS, all patients were given sofosbuvir (SOF) 400 mg+ daclatasvir (DCV) 60 mg for 12 weeks. Overall, sustained virological response (SVR) was achieved in 63 (78.8%) patients, in 13 with BL-RAS and in 50 without BL-RAS. All the SVR failure cases (n=17) were retreated with SOF (400 mg) +DCV (60 mg)+ ribavirin (RBV) for 24 weeks. SVR was eventually attained in 14 (82.3%) patients, in 4/6 (66.6%) with BL-RAS and in 10/11 (91%) without BL-RAS. On univariate analysis, age more than 30 years (OR: 11.6; 95% CI: 3.0–45.5, p-value<0.001) and female gender (OR: 8.6; 95% CI: 1.1−69, p-value <0.009) were found to be significant factors associated with the attainment of SVR. Conclusion BL-RAS are common in HCV–HIV co-infected patients. The existence of BL-RAS, however, did not affect the attainment of SVR among non-cirrhotic, treatment naive HCV–HIV co-infected patients.
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Affiliation(s)
- Ekta Gupta
- Department of Clinical Virology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Reshu Agarwal
- Department of Clinical Virology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Aayushi Rastogi
- Department of Epidemiology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Nitiksha Rani
- Department of Clinical Virology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Ankur Jindal
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
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47
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Edsall A, Dinh TTT, Mai PP, Hoffman K, Nguyen HT, Khuyen TT, Trang NT, Bart G, Giang LM, Korthuis PT. Provider Perspectives on Integration of Substance Use Disorder and HIV Care in Vietnam: A Qualitative Study. J Behav Health Serv Res 2021; 48:274-286. [PMID: 32940824 PMCID: PMC7965786 DOI: 10.1007/s11414-020-09730-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
UNAIDS recommends integration of medications for substance use disorders (SUD) with HIV care to improve HIV outcomes. Yet, integration of HIV and SUD services remains limited in many countries. The objective of this study was to assess provider perceptions of care integration in Vietnam. Qualitative interviews were conducted with 43 providers (nurses, physicians, counselors, pharmacists, and clinic managers) in 8 HIV clinics in northern Vietnam, 2013-2015. Providers identified five themes informing HIV and SUD treatment integration: (1) treatment for alcohol use disorder is often neglected compared to other SUD treatment; (2) structural challenges must be addressed to increase integration feasibility; (3) workforce limitations; (4) societal and healthcare stigmatization of SUD; and (5) providers' conflicting views regarding integration challenges. The experience of providers in Vietnam may be useful to other countries attempting to integrate HIV and SUD services.
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Affiliation(s)
- Andrew Edsall
- Oregon Health & Science University School of Medicine, Portland, OR, USA
| | | | | | - Kim Hoffman
- Portland State University-Oregon Health & Science University School of Public Health, Portland, OR, USA.
| | - Hang T Nguyen
- Portland State University-Oregon Health & Science University School of Public Health, Portland, OR, USA
| | | | | | - Gavin Bart
- Hennepin Healthcare and University of Minnesota, Minneapolis, MN, USA
| | | | - P Todd Korthuis
- Department of Medicine, Oregon Health & Science University, Portland, OR, USA
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Patients with chronic hepatitis C receiving treatment with direct acting antivirals: How is this population changing? Dig Liver Dis 2021; 53:456-460. [PMID: 32732070 DOI: 10.1016/j.dld.2020.07.013] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2020] [Revised: 07/08/2020] [Accepted: 07/09/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS Direct acting antiviral agents (DAAs) have revolutionized the landscape of chronic hepatitis C (CHC) enabling treatment of all those infected. It remains to be determined how the characteristics of those receiving treatment are changing. MATERIALS AND METHODS We retrospectively analysed all the patients with CHC who received treatment with DAAs in a large referral centre since 01/01/2015. We stratified their demographic, clinical and virological characteristics at baseline and the sustained virological response (SVR) rates according to the year of treatment. RESULTS In the study were included 2565 patients. During the study period, the yearly proportion of men and cirrhotic patients decreased (p<0.001) whereas mean age increased from 59.8 to 62.2 years old (p=0.04). An increasing trend was observed in the foreign-born patients from 4.3% to 7.9%, without reaching statistical significance. The prevalence of comorbidities had also increased during the study period (p<0.001). Instead, the yearly number of experienced patients decreased significantly (p<0.001) as well as the mean MELD score of cirrhotic patients from 9 to 7.6 (p<0.001). SVR rates increased significantly, from 93.4% in 2015 to 97.1% in 2018 (P<0.05). CONCLUSIONS The population of patients with CHC receiving DAAs is becoming older and with more comorbidities. Nevertheless, this did not impact SVR rates.
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Auma AWN, Shive C, Damjanovska S, Kowal C, Cohen DE, Bhattacharya D, Alston-Smith B, Osborne M, Kalayjian R, Balagopal A, Sulkowski M, Wyles D, Anthony DD. T-cell Activation Is Correlated With Monocyte Activation in HCV/HIV Coinfection and Declines During HCV Direct-Acting Antiviral Therapy. Open Forum Infect Dis 2021; 8:ofab079. [PMID: 33880389 PMCID: PMC8043262 DOI: 10.1093/ofid/ofab079] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Accepted: 02/11/2021] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Immune activation markers associate with morbidity and mortality in HIV and hepatitis C virus (HCV) infection. We investigated how T-cell and monocyte activation are related over the course of HCV direct-acting antiviral (DAA) therapy during HCV/HIV coinfection. METHODS Peripheral blood mononuclear cells from AIDS Clinical Trials Group (ACTG) A5329 participants and a single-site separate cohort treated with DAAs were analyzed for central memory (CM)/effector memory (EM) T-cell subsets, monocyte subsets, and cell activation (CD38 and HLA-DR expression) before, during, and after therapy. RESULTS Before therapy, classical and inflammatory monocyte subset HLA-DR expression positively correlated with absolute counts and frequencies of CD38+HLA-DR+-expressing CD4+ and CD8 T cells and corresponding CM and EM subsets. After therapy initiation, CD38+HLA-DR+ co-expression on CD4+ and CD8+ memory T cells decreased by 12 weeks and 36 weeks, and plasma sCD14 positively correlated with CD38+HLA-DR+ CD4+ and CD4+CM T-cell frequencies. Monocyte subset activation remained similar over time. CONCLUSIONS During HCV/HIV coinfection, memory T-cell activation is associated with monocyte subset activation, consistent with related underlying mechanisms. Following therapy initiation, memory T-cell, but not monocyte, activation decreased. Residual CD4+ T-cell activation after therapy completion is associated with sCD14, potentially linking the remaining CD4+ T-cell activation to residual factors driving activation in antiretroviral therapy-controlled HIV.
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Affiliation(s)
- Ann W N Auma
- Department of Pathology, VA Medical Center, Case Western Reserve University, Cleveland, Ohio, USA
| | - Carey Shive
- Department of Pathology, VA Medical Center, Case Western Reserve University, Cleveland, Ohio, USA
| | - Sofi Damjanovska
- Department of Medicine, MetroHealth Medical Center, Case Western Reserve University, Cleveland, Ohio, USA
| | - Corinne Kowal
- Department of Medicine, MetroHealth Medical Center, Case Western Reserve University, Cleveland, Ohio, USA
| | | | - Debika Bhattacharya
- Division of Infectious Diseases, Department of Medicine David Geffen School of Medicine at UCLA, Los Angeles, California, USA
| | | | - Melissa Osborne
- Department of Medicine, MetroHealth Medical Center, Case Western Reserve University, Cleveland, Ohio, USA
| | - Robert Kalayjian
- Department of Medicine, MetroHealth Medical Center, Case Western Reserve University, Cleveland, Ohio, USA
| | - Ashwin Balagopal
- Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Mark Sulkowski
- Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - David Wyles
- University of Colorado School of Medicine, Denver, Colorado, USA
| | - Donald D Anthony
- Department of Pathology, VA Medical Center, Case Western Reserve University, Cleveland, Ohio, USA
- Department of Medicine, MetroHealth Medical Center, Case Western Reserve University, Cleveland, Ohio, USA
- ACTG Immunology Support Laboratory, Case Western Reserve University, Cleveland, Ohio, USA
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50
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Saud LRC, Chagas AL, Maccali C, Pinto PVA, Horvat N, Alencar RSSM, Tani CM, Abdala E, Carrilho FJ. Hepatocellular carcinoma in patients coinfected with hepatitis B or C and HIV: more aggressive tumor behavior? Eur J Gastroenterol Hepatol 2021; 33:583-588. [PMID: 33560682 PMCID: PMC9446514 DOI: 10.1097/meg.0000000000002057] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
INTRODUCTION AND OBJECTIVES Hepatocellular carcinoma (HCC) is the 6th cause of cancer and hepatitis C (HCV) and B (HBV) viruses are the most frequent risk factors for HCC. Patients coinfected with HCV or HBV and HIV present a faster progression to liver fibrosis and higher incidence of HCC. The aim of this study was to evaluate the survival and clinical outcomes of coinfected patients with HCC comparing with non-HIV patients. METHODS We conducted a retrospective cohort study, including 267 HCC patients with HCV or HBV infection with or without HIV. The primary endpoint was overall survival. A Kaplan-Meier curve was presented to assess survival function. Clinical and radiologic variables, according to HIV status, were compared by logistic regression. RESULTS Among 267 HCC patients, 25 (9.3%) were HIV-positive. In the coinfected group, patients were younger (49.8 vs 61.2 years, P < 0.001), cirrhosis was less predominant (88 vs 96.7%, P = 0.05), a smaller proportion received HCC treatment (60 vs 86.3%, P = 0.001) and the frequency of portal vein tumoral thrombosis was higher (32 vs 11.1%, P = 0.003). The overall mortality rate was higher in the HIV-positive group (92 vs 74.3%), independently of clinical and tumoral variables. CONCLUSION Coinfected patients with HCC presented higher mortality, tumor diagnosis in a younger age, less underlying cirrhosis and a higher frequency of tumoral thrombosis. Further studies are warranted to better understand the role of HIV in hepatocarcinogenesis, in order to improve the management of those patients, particularly regarding screening programs.
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Affiliation(s)
- Lisa R C Saud
- São Paulo Clínicas Liver Cancer Group, Instituto do Cancer do Estado de São Paulo, Division of Clinical Gastroenterology and Hepatology, Hospital das Clínicas, Department of Gastroenterology, University of São Paulo School of Medicine
| | - Aline L Chagas
- São Paulo Clínicas Liver Cancer Group, Instituto do Cancer do Estado de São Paulo, Division of Clinical Gastroenterology and Hepatology, Hospital das Clínicas, Department of Gastroenterology, University of São Paulo School of Medicine
| | - Claudia Maccali
- São Paulo Clínicas Liver Cancer Group, Instituto do Cancer do Estado de São Paulo, Division of Clinical Gastroenterology and Hepatology, Hospital das Clínicas, Department of Gastroenterology, University of São Paulo School of Medicine
| | - Paulo V A Pinto
- São Paulo Clínicas Liver Cancer Group, Hospital das Clínicas, Department of Radiology, University of São Paulo School of Medicine
| | - Natally Horvat
- Radiology Department, Memorial Sloan Kettering Cancer Center, New York
| | - Regiane S S M Alencar
- São Paulo Clínicas Liver Cancer Group, Instituto do Cancer do Estado de São Paulo, Division of Clinical Gastroenterology and Hepatology, Hospital das Clínicas, Department of Gastroenterology, University of São Paulo School of Medicine
| | - Claudia M Tani
- São Paulo Clínicas Liver Cancer Group, Instituto do Cancer do Estado de São Paulo, Division of Clinical Gastroenterology and Hepatology, Hospital das Clínicas, Department of Gastroenterology, University of São Paulo School of Medicine
| | - Edson Abdala
- Instituto do Cancer do Estado de São Paulo, Hospital das Clínicas, Infectious Diseases Department, University of São Paulo School of Medicine, São Paulo, Brazil
| | - Flair J Carrilho
- São Paulo Clínicas Liver Cancer Group, Instituto do Cancer do Estado de São Paulo, Division of Clinical Gastroenterology and Hepatology, Hospital das Clínicas, Department of Gastroenterology, University of São Paulo School of Medicine
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