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Smirne C, Crobu MG, Landi I, Vercellino N, Apostolo D, Pinato DJ, Vincenzi F, Minisini R, Tonello S, D’Onghia D, Ottobrelli A, Martini S, Bracco C, Fenoglio LM, Campanini M, Berton AM, Ciancio A, Pirisi M. Chronic Hepatitis C Infection Treated with Direct-Acting Antiviral Agents and Occurrence/Recurrence of Hepatocellular Carcinoma: Does It Still Matter? Viruses 2024; 16:1899. [PMID: 39772206 PMCID: PMC11680226 DOI: 10.3390/v16121899] [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: 10/09/2024] [Revised: 12/05/2024] [Accepted: 12/06/2024] [Indexed: 01/03/2025] Open
Abstract
Hepatitis C virus (HCV) infection is a significant risk factor for liver cirrhosis and hepatocellular carcinoma (HCC). Traditionally, the primary prevention strategy for HCV-associated HCC has focused on removing infection through antiviral regimes. Currently, highly effective direct-acting antivirals (DAAs) offer extraordinary success across all patient categories, including cirrhotics. Despite these advancements, recent studies have reported that even after sustained virologic response (SVR), individuals with advanced liver disease/cirrhosis at the time of DAA treatment may still face risks of HCC occurrence or recurrence. Based on this premise, this review tries to shed light on the multiple mechanisms that establish a tumorigenic environment, first, during chronic HCV infection and then, after eventual viral eradication by DAAs. Furthermore, it reviews evidence reported by recent observational studies stating that the use of DAAs is not associated with an increased risk of HCC development but rather, with a significantly lower chance of liver cancer compared with DAA-untreated patients. In addition, it seeks to provide some practical guidance for clinicians, helping them to manage HCC surveillance of patients who have achieved SVR with DAAs.
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Affiliation(s)
- Carlo Smirne
- Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy; (N.V.); (D.A.); (D.J.P.); (F.V.); (R.M.); (S.T.); (D.D.); (M.C.); (M.P.)
- Internal Medicine Unit, Maggiore della Carità Hospital, 28100 Novara, Italy
| | - Maria Grazia Crobu
- Laboratory of Molecular Virology, Maggiore della Carità Hospital, 28100 Novara, Italy;
- Clinical Biochemistry Laboratory, City of Health and Science University Hospital, 10126 Turin, Italy
| | - Irene Landi
- Emergency Medicine Department, Michele e Pietro Ferrero Hospital, 12060 Verduno, Italy;
| | - Nicole Vercellino
- Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy; (N.V.); (D.A.); (D.J.P.); (F.V.); (R.M.); (S.T.); (D.D.); (M.C.); (M.P.)
| | - Daria Apostolo
- Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy; (N.V.); (D.A.); (D.J.P.); (F.V.); (R.M.); (S.T.); (D.D.); (M.C.); (M.P.)
| | - David James Pinato
- Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy; (N.V.); (D.A.); (D.J.P.); (F.V.); (R.M.); (S.T.); (D.D.); (M.C.); (M.P.)
- Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, London SW7 2AZ, UK
| | - Federica Vincenzi
- Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy; (N.V.); (D.A.); (D.J.P.); (F.V.); (R.M.); (S.T.); (D.D.); (M.C.); (M.P.)
| | - Rosalba Minisini
- Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy; (N.V.); (D.A.); (D.J.P.); (F.V.); (R.M.); (S.T.); (D.D.); (M.C.); (M.P.)
| | - Stelvio Tonello
- Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy; (N.V.); (D.A.); (D.J.P.); (F.V.); (R.M.); (S.T.); (D.D.); (M.C.); (M.P.)
| | - Davide D’Onghia
- Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy; (N.V.); (D.A.); (D.J.P.); (F.V.); (R.M.); (S.T.); (D.D.); (M.C.); (M.P.)
| | - Antonio Ottobrelli
- Gastroenterology Unit, City of Health and Science University Hospital, 10126 Turin, Italy; (A.O.); (S.M.); (A.C.)
| | - Silvia Martini
- Gastroenterology Unit, City of Health and Science University Hospital, 10126 Turin, Italy; (A.O.); (S.M.); (A.C.)
| | - Christian Bracco
- Department of Internal Medicine, Santa Croce e Carle Hospital, 12100 Cuneo, Italy; (C.B.); (L.M.F.)
| | - Luigi Maria Fenoglio
- Department of Internal Medicine, Santa Croce e Carle Hospital, 12100 Cuneo, Italy; (C.B.); (L.M.F.)
| | - Mauro Campanini
- Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy; (N.V.); (D.A.); (D.J.P.); (F.V.); (R.M.); (S.T.); (D.D.); (M.C.); (M.P.)
- Internal Medicine Unit, Maggiore della Carità Hospital, 28100 Novara, Italy
| | - Alessandro Maria Berton
- Division of Endocrinology, Diabetes and Metabolism, City of Health and Science University Hospital, 10126 Turin, Italy;
| | - Alessia Ciancio
- Gastroenterology Unit, City of Health and Science University Hospital, 10126 Turin, Italy; (A.O.); (S.M.); (A.C.)
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy
| | - Mario Pirisi
- Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy; (N.V.); (D.A.); (D.J.P.); (F.V.); (R.M.); (S.T.); (D.D.); (M.C.); (M.P.)
- Internal Medicine Unit, Maggiore della Carità Hospital, 28100 Novara, Italy
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2
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Tang J, Weng R, Fang T, Zhang K, Yan X, Jin X, Xie L, Zhao D. Clinical outcomes of liver transplantation in human immunodeficiency virus/hepatitis B virus coinfected patients in China. BMC Infect Dis 2024; 24:383. [PMID: 38589801 PMCID: PMC11003048 DOI: 10.1186/s12879-024-09284-2] [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: 10/27/2023] [Accepted: 04/03/2024] [Indexed: 04/10/2024] Open
Abstract
BACKGROUND Highly active antiretroviral therapy (HAART) has been able to improve the immune system function and survival of human immunodeficiency virus (HIV) patients. However, Patients coinfected with HIV and hepatitis B virus (HBV) are more likely to develop end-stage liver disease (ESLD) than those infected with HBV alone. Consequently, liver transplantation is often required for these patients. This study evaluates the outcomes of orthotopic liver transplantation (OLT) of HIV-HBV coinfected patients in China. METHODS We conducted a retrospective analysis on all HIV-HBV coinfected patients that underwent OLT from April 1, 2019 to December 31, 2021 and their outcomes were compared to all HBV monoinfected patients undergoing OLT during the same period. Patient outcomes were determined, including cumulative survival, viral load, CD4 T-cell count and postoperative complications. RESULTS The median follow-up of HIV recipients was 36 months after OLT (interquartile range 12-39 months). Almost all patients had stable CD4 T-cell count (> 200 copies/ul), undetectable HBV DNA levels, and undetectable HIV RNA load during follow-up. The 1-, 2-, and 3-year posttransplant survival rates were 85.7% for the HIV group (unchanged from 1 to 3 years) versus 82.2%, 81.2%, and 78.8% for the non-HIV group. Cumulative survival among HIV-HBV coinfected recipients was not significantly different from the HBV monoinfected recipients (log-rank test P = 0.692). The percentage of deaths attributed to infection was comparable between the HIV and non-HIV groups (14.3% vs. 9.32%, P = 0.665). Post OLT, there was no significant difference in acute rejection, cytomegalovirus infection, bacteremia, pulmonary infection, acute kidney injury, de novo tumor and vascular and biliary complications. CONCLUSIONS Liver transplantation in patients with HIV-HBV coinfection yields excellent outcomes in terms of intermediate- or long-term survival rate and low incidence of postoperative complications in China. These findings suggest that OLT is safe and feasible for HIV-HBV coinfected patients with ESLD. TRIAL REGISTRATION Chinese Clinical Trial Registry (ChiCTR2300067631), registered 11 January 2023.
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Affiliation(s)
- Jianxin Tang
- Department of Liver Surgery & Organ Transplantation Center, Shenzhen Third People's Hospital, The Second Affiliated Hospital of Southern University of Science and Technology, National Clinical Research Center for Infectious Disease, Longgang District, Bulan Road 29#, 518000, Shenzhen, China
| | - Ruihui Weng
- Department of Neurology, Shenzhen Third People's Hospital, The Second Affiliated Hospital of Southern, University of Science and Technology, 518000, Shenzhen, China
| | - Taishi Fang
- Department of Liver Surgery & Organ Transplantation Center, Shenzhen Third People's Hospital, The Second Affiliated Hospital of Southern University of Science and Technology, National Clinical Research Center for Infectious Disease, Longgang District, Bulan Road 29#, 518000, Shenzhen, China
| | - Kangjun Zhang
- Department of Liver Surgery & Organ Transplantation Center, Shenzhen Third People's Hospital, The Second Affiliated Hospital of Southern University of Science and Technology, National Clinical Research Center for Infectious Disease, Longgang District, Bulan Road 29#, 518000, Shenzhen, China
| | - Xu Yan
- Department of Liver Surgery & Organ Transplantation Center, Shenzhen Third People's Hospital, The Second Affiliated Hospital of Southern University of Science and Technology, National Clinical Research Center for Infectious Disease, Longgang District, Bulan Road 29#, 518000, Shenzhen, China
| | - Xin Jin
- Department of Liver Surgery & Organ Transplantation Center, Shenzhen Third People's Hospital, The Second Affiliated Hospital of Southern University of Science and Technology, National Clinical Research Center for Infectious Disease, Longgang District, Bulan Road 29#, 518000, Shenzhen, China
| | - Linjie Xie
- Department of Liver Surgery & Organ Transplantation Center, Shenzhen Third People's Hospital, The Second Affiliated Hospital of Southern University of Science and Technology, National Clinical Research Center for Infectious Disease, Longgang District, Bulan Road 29#, 518000, Shenzhen, China
| | - Dong Zhao
- Department of Liver Surgery & Organ Transplantation Center, Shenzhen Third People's Hospital, The Second Affiliated Hospital of Southern University of Science and Technology, National Clinical Research Center for Infectious Disease, Longgang District, Bulan Road 29#, 518000, Shenzhen, China.
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3
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Chandran S, Stock PG, Roll GR. Expanding Access to Organ Transplant for People Living With HIV: Can Policy Catch Up to Outcomes Data? Transplantation 2024; 108:874-883. [PMID: 37723620 DOI: 10.1097/tp.0000000000004794] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/20/2023]
Abstract
Advances in antiretroviral and immunosuppressive regimens have improved outcomes following solid organ transplantation in people living with HIV (PLWH). The HIV Organ Policy and Equity Act was conceived to reduce the discard of HIV-positive organs and improve access to transplant for PLWH. Nevertheless, PLWH continue to experience disproportionately low rates of transplant. This overview examines the hurdles to transplantation in PLWH with end-organ disease, the potential and realized impact of the HIV Organ Policy and Equity Act, and changes that could permit expanded access to organ transplant in this population.
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Affiliation(s)
- Sindhu Chandran
- Department of Medicine, University of California-San Francisco (UCSF), San Francisco, CA
| | - Peter G Stock
- Department of Surgery, University of California-San Francisco (UCSF), San Francisco, CA
| | - Garrett R Roll
- Department of Surgery, University of California-San Francisco (UCSF), San Francisco, CA
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4
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Zhou S, Qi K, Bersoff-Matcha SJ, Mishra P, Struble K. Sex-related difference analyses of efficacy and safety in clinical trials of direct-acting antivirals to treat chronic HCV genotype 1 and 3 infections. J Viral Hepat 2024; 31:78-87. [PMID: 38111976 DOI: 10.1111/jvh.13901] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2023] [Accepted: 11/19/2023] [Indexed: 12/20/2023]
Abstract
This study aims to identify clinically meaningful sex differences in efficacy and selected safety adverse events for the treatment of chronic hepatitis C virus infection (HCV) or HIV/HCV co-infection in those receiving combination direct-acting antiviral (DAA) regimens. Our assessment was based on adult trial participants treated at the approved DAA dosage and treatment duration from 40 phase 3 clinical trials submitted to the FDA. Female enrollment ranged from 11% to 54% (overall mean 38%). Females with HCV genotype (GT) 1 or 3 infection had statistically significant higher unadjusted or covariant-adjusted odds of achieving sustained virologic response at post-treatment Week 12 (SVR12) compared with males. Odds ratios favouring females were observed among Whites and those ≥40 years of age with HCV GT1 or 3 infections, and among those ≥50 years of age, non-cirrhotic and those with HCV GT3 infection who were treatment-experienced. These differences were not clinically relevant due to the high SVR12 rate achieved by females and males, overall or in subgroups. No differences were observed in SVR12 rates between HCV GT1 mono-infected and HCV GT1/ HIV-1 co-infected participants. Numerically, more females reported headache, fatigue and nausea compared to males, but the differences were small and predominately Grade 1 or 2 severity. Discontinuation rates for any reason or due to an adverse event were low and similar between the sexes. Our study demonstrated females successfully complete DAA regimens and achieve high SVR12 rates despite numerically higher adverse events for certain commonly reported events.
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Affiliation(s)
- Shuang Zhou
- Center for Drug Evaluation and Research, Division of Antivirals, FDA, Silver Spring, Maryland, USA
| | - Karen Qi
- Center for Drug Evaluation and Research, Office of Biostatistician, FDA, Silver Spring, Maryland, USA
| | | | - Poonam Mishra
- Center for Drug Evaluation and Research, Division of Antivirals, FDA, Silver Spring, Maryland, USA
| | - Kimberly Struble
- Center for Drug Evaluation and Research, Division of Antivirals, FDA, Silver Spring, Maryland, USA
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5
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Lynch EN, Russo FP. Liver Transplantation in People Living with HIV: Still an Experimental Procedure or Standard of Care? Life (Basel) 2023; 13:1975. [PMID: 37895356 PMCID: PMC10608432 DOI: 10.3390/life13101975] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Revised: 09/21/2023] [Accepted: 09/25/2023] [Indexed: 10/29/2023] Open
Abstract
Liver transplantation (LT) is the only curative treatment for various liver diseases, including acute liver failure, end-stage liver disease, and selected unresectable liver malignancies. Combination antiretroviral therapy has improved outcomes for people living with HIV (PLWH), transforming the status of acquired immune deficiency syndrome from a fatal disease to a chronic and manageable condition. These powerful antiviral therapies have not only increased the number of HIV+ enlisted patients by improving their survival but also made the use of HIV+ organs a viable option. In this review, we summarise current knowledge on the peculiarities of liver transplantation in PLWH. In particular, we focus on the indications, contraindications, specific considerations for treatment, and outcomes of LT in PLWH. Finally, we present available preliminary data on the use of HIV+ liver allografts.
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Affiliation(s)
- Erica Nicola Lynch
- Department of Surgery, Oncology and Gastroenterology, Gastroenterology/Multivisceral Transplant Section, Padua University Hospital, 35128 Padua, Italy;
- Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, 50134 Florence, Italy
| | - Francesco Paolo Russo
- Department of Surgery, Oncology and Gastroenterology, Gastroenterology/Multivisceral Transplant Section, Padua University Hospital, 35128 Padua, Italy;
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6
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Bertoni C, Galli L, Lolatto R, Hasson H, Siribelli A, Messina E, Castagna A, Uberti Foppa C, Morsica G. Survival in People Living with HIV with or without Recurrence of Hepatocellular Carcinoma after Invasive Therapy. Cancers (Basel) 2023; 15:cancers15061653. [PMID: 36980538 PMCID: PMC10046370 DOI: 10.3390/cancers15061653] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2023] [Revised: 03/02/2023] [Accepted: 03/04/2023] [Indexed: 03/11/2023] Open
Abstract
Background and Aims: To address the overall survival (OS) and recurrence (RE) in people living with HIV (PLWH) treated with invasive therapy (IT) for hepatocellular carcinoma (HCC). Methods: This is a retrospective cohort study on 41 PLWH with HCC receiving IT, defined as liver resection (LR), orthotopic liver transplantation (OLT), radiofrequency thermo-ablation (RFTA) trans arterial chemo, or radioembolization (CRE). OS and RE were investigated by Kaplan–Meier curves. The Cox proportional hazard regression model was used for multivariate analyses. Results: Recurrence occurred in 46.3% PLWH; in 36.7% of participants at 2 years and in 52% at 5 years from HCC diagnosis; it was less frequent in males, p = 0.036. Overall, 2- and 5-year survival after HCC diagnosis was 72% and 48%, respectively. Two-and five-year survival was 100% and 90.9%, respectively, in PLWH receiving OLT, compared to other IT (60.9% and 30.6%, respectively) log-rank p = 0.0006. Two- and five-year survival in participants with no-RE was 70.5% and 54.6%, respectively, and 73.7% and 42.1% among RE, respectively, log-rank p = 0.7772. By multivariate analysis, AFP at values < 28.8 ng/mL, at HCC diagnosis, was the only factor predicting survival. Conclusions: Fifty percent of PLWH survived five years after HCC diagnosis; 90.9% among OLT patients. Recurrence after IT was observed in 46% of HCC/PLWH. AFP cut-off levels of 28.8 ng/mL were the only independent variable associated with survival.
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Affiliation(s)
- Costanza Bertoni
- Division of Infectious Diseases, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy
- Faculty of Medicine and Surgery, Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Laura Galli
- Division of Infectious Diseases, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy
| | - Riccardo Lolatto
- Division of Infectious Diseases, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy
| | - Hamid Hasson
- Division of Infectious Diseases, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy
| | - Alessia Siribelli
- Division of Infectious Diseases, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy
- Faculty of Medicine and Surgery, Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Emanuela Messina
- Division of Infectious Diseases, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy
| | - Antonella Castagna
- Division of Infectious Diseases, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy
- Faculty of Medicine and Surgery, Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Caterina Uberti Foppa
- Division of Infectious Diseases, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy
- Faculty of Medicine and Surgery, Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Giulia Morsica
- Division of Infectious Diseases, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy
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7
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Russo FP, Viganò M, Stock P, Ferrarese A, Pugliese N, Burra P, Aghemo A. HBV-positive and HIV-positive organs in transplantation: A clinical guide for the hepatologist. J Hepatol 2022; 77:503-515. [PMID: 35398460 DOI: 10.1016/j.jhep.2022.03.007] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2021] [Revised: 02/08/2022] [Accepted: 03/02/2022] [Indexed: 12/04/2022]
Abstract
Organ transplantation is a life-saving treatment for patients with end-stage organ disease, a severe condition associated with a high risk of waitlist mortality. It is primarily limited by a shortage of available organs. Maximising available donors can increase access to transplantation. Transplantation from donors positive for HBV and HIV has increased in many countries. However, antiviral therapies need to be readily available for recipients after transplantation to prevent possible reactivation of the virus following the administration of immunosuppressive therapies. Furthermore, the intentional transmission of a virus has practical, ethical, and clinical implications. In this review, we summarise the current research, focusing on grafts from donors positive for the HBV surface antigen, antibodies against the HBV core antigen, and HIV, to help hepatologists and physicians interested in transplantation to select the best antiviral and/or prophylactic regimens for after transplantation.
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Affiliation(s)
- Francesco Paolo Russo
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Italy; Gastroenterology and Multivisceral Transplant Unit, Azienda Ospedale Università-Padova, Italy
| | - Mauro Viganò
- Division of Hepatology, San Giuseppe Hospital, MultiMedica IRCCS, Milan, Italy
| | - Peter Stock
- Department of Surgery, University of California at San Francisco, San Francisco, California, USA
| | - Alberto Ferrarese
- Unit of Gastroenterology, Borgo Trento University Hospital of Verona, Verona, Italy
| | - Nicola Pugliese
- Department of Biomedical Sciences, Humanitas University, Milan, Italy; Division of Internal Medicine and Hepatology, Department of Gastroenterology, Humanitas Research Hospital IRCCS, Milan, Italy
| | - Patrizia Burra
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Italy; Gastroenterology and Multivisceral Transplant Unit, Azienda Ospedale Università-Padova, Italy.
| | - Alessio Aghemo
- Department of Biomedical Sciences, Humanitas University, Milan, Italy; Division of Internal Medicine and Hepatology, Department of Gastroenterology, Humanitas Research Hospital IRCCS, Milan, Italy
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8
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Papp KA, Beecker J, Cooper C, Kirchhof MG, Pozniak AL, Rockstroh JK, Dutz JP, Gooderham MJ, Gniadecki R, Hong CH, Lynde CW, Maari C, Poulin Y, Vender RB, Walmsley SL. Use of Systemic Therapies for Treatment of Psoriasis in People Living with Controlled HIV: Inference-Based Guidance from a Multidisciplinary Expert Panel. Dermatol Ther (Heidelb) 2022; 12:1073-1089. [PMID: 35445963 PMCID: PMC9110627 DOI: 10.1007/s13555-022-00722-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Accepted: 03/30/2022] [Indexed: 11/28/2022] Open
Abstract
Background People living with human immunodeficiency virus (PLHIV) have a similar prevalence of psoriasis as the general population, though incidence and severity correlate with HIV viral load. Adequately treating HIV early renders the infection a chronic medical condition and allows PLHIV with a suppressed viral load (PLHIV-s) to live normal lives. Despite this, safety concerns and a lack of high-level data have hindered the use of systemic psoriasis therapies in PLHIV-s. Objectives We aim to provide a structured framework that supports healthcare professionals and patients discussing the risks and benefits of systemic psoriasis therapy in PLHIV-s. Our goal was to address the primary question, are responses to systemic therapies for the treatment of psoriasis in PLHIV-s similar to those in the non-HIV population? Methods We implemented an inference-based approach relying on indirect evidence when direct clinical trial data were absent. In this instance, we reviewed indirect evidence supporting inferences on the status of immune function in PLHIV. Recommendations on systemic treatment for psoriasis in PLHIV were derived using an inferential heuristic. Results We identified seven indirect indicators of immune function informed by largely independent bodies of evidence: (1) functional assays, (2) vaccine response, (3) life expectancy, (4) psoriasis manifestations, (5) rate of infections, (6) rate of malignancies, and (7) organ transplant outcomes. Conclusions Drug-related benefits and risks when treating a patient with systemic psoriasis therapies are similar for non-HIV patients and PLHIV with a suppressed viral load and normalized CD4 counts. Prior to initiating psoriasis treatment in PLHIV, HIV replication should be addressed by an HIV specialist. Exercise additional caution for patients with a suppressed viral load and discordant CD4 responses on antiretroviral therapy. Supplementary Information The online version contains supplementary material available at 10.1007/s13555-022-00722-0. People living with human immunodeficiency virus (PLHIV) develop psoriasis as often as everyone else. We asked: what are effective and safe treatments when PLHIV need systemic therapy (pills or injections) for their psoriasis? HIV infection attacks the immune system. When HIV is not treated, the immune system declines. A less effective immune system makes it harder for the body to fight infections and certain cancers. Psoriasis is a skin condition caused by overactive immune cells. Effective psoriasis treatments reduce immune-cell activity. There are some concerns that treatments for psoriasis may not work and could worsen infections or cancers. To answer the question, we gathered 11 dermatologists and 4 HIV specialists. We reviewed the international scientific literature on PLHIV and psoriasis. The absence of direct evidence and volume of information to review made the process challenging. The end results were worthwhile. We concluded that people who are diagnosed early and take antiretroviral therapy to control their HIV infection (PLHIV-c) can live long, healthy lives. Accordingly, we determined that PLHIV-c can likely expect the same safety and efficacy for systemic psoriasis treatments as the general population. Treatment decisions should be made on a case-by-case basis through consultation with the patient and treating physician(s). Pillars of modern medicine are evidence-based care and collaborative decision-making. Too often, neither care provider nor patient are adequately informed. We have tried to fill one information gap for PLHIV and psoriasis. This process may help answer questions in other disease populations where direct evidence is scarce or absent.
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Affiliation(s)
- Kim A Papp
- Probity Medical Research Inc., Waterloo, ON, Canada. .,K Papp Clinical Research, Waterloo, ON, Canada.
| | - Jennifer Beecker
- Probity Medical Research Inc., Waterloo, ON, Canada.,University of Ottawa, Ottawa, ON, Canada.,Division of Dermatology, The Ottawa Hospital, Ottawa, ON, Canada.,Ottawa Hospital Research Institute, Ottawa, ON, Canada
| | - Curtis Cooper
- University of Ottawa, Ottawa, ON, Canada.,Ottawa Hospital Research Institute, Ottawa, ON, Canada.,The Ottawa Hospital and Regional Hepatitis Program, Ottawa, ON, Canada
| | - Mark G Kirchhof
- University of Ottawa, Ottawa, ON, Canada.,Division of Dermatology, The Ottawa Hospital, Ottawa, ON, Canada
| | - Anton L Pozniak
- Chelsea and Westminster Hospital NHS Foundation Trust, London, UK
| | | | - Jan P Dutz
- Skin Care Center, Vancouver, BC, Canada.,Department of Dermatology and Skin Science, University of British Columbia, Vancouver, BC, Canada.,BC Children's Hospital Research Institute, Vancouver, BC, Canada
| | - Melinda J Gooderham
- Probity Medical Research Inc., Waterloo, ON, Canada.,SKiN Centre for Dermatology, Peterborough, ON, Canada
| | - Robert Gniadecki
- Division of Dermatology, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada
| | - Chih-Ho Hong
- Probity Medical Research Inc., Waterloo, ON, Canada.,Department of Dermatology and Skin Science, University of British Columbia, Vancouver, BC, Canada.,Dr. Chih-Ho Hong Medical Inc., Surrey, BC, Canada
| | - Charles W Lynde
- Probity Medical Research Inc., Waterloo, ON, Canada.,Lynde Institute for Dermatology, Markham, ON, Canada
| | | | - Yves Poulin
- Centre de Recherche Dermatologique du Québec Métropolitain, Quebec, QC, Canada
| | - Ronald B Vender
- Dermatrials Research Inc., Hamilton, ON, Canada.,Department of Medicine, McMaster University, Hamilton, ON, Canada
| | - Sharon L Walmsley
- Toronto General Hospital Research Institute, Toronto, ON, Canada.,University of Toronto, Toronto, ON, Canada.,Department of Medicine, University Health Network, Toronto, ON, Canada
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9
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Kumar RN, Stosor V. Advances in Liver Transplantation for Persons with Human Immunodeficiency Infection. Curr Infect Dis Rep 2022; 24:39-50. [PMID: 35308580 PMCID: PMC8922075 DOI: 10.1007/s11908-022-00776-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/23/2022] [Indexed: 02/06/2023]
Affiliation(s)
- Rebecca N. Kumar
- Division of Infectious Diseases and Travel Medicine, Georgetown University Medical Center, Washington, DC USA
| | - Valentina Stosor
- Divisions of Infectious Diseases and Organ Transplantation and Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, 645 North Michigan Avenue, Suite 900, Chicago, IL 60611 USA
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Werbel WA, Durand CM. Clearing the hepatitis hurdle: Obstacles and opportunities in liver transplantation for people with HIV. Am J Transplant 2021; 21:2931-2932. [PMID: 33856113 DOI: 10.1111/ajt.16608] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Revised: 04/07/2021] [Accepted: 04/07/2021] [Indexed: 01/25/2023]
Affiliation(s)
- William A Werbel
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Christine M Durand
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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Janczewska E, Kołek MF, Lorenc B, Klapaczyński J, Tudrujek-Zdunek M, Sitko M, Mazur W, Zarębska-Michaluk D, Buczyńska I, Dybowska D, Czauż-Andrzejuk A, Berak H, Krygier R, Jaroszewicz J, Citko J, Piekarska A, Dobracka B, Socha Ł, Deroń Z, Laurans Ł, Białkowska-Warzecha J, Tronina O, Adamek B, Tomasiewicz K, Simon K, Pawłowska M, Halota W, Flisiak R. Factors influencing the failure of interferon-free therapy for chronic hepatitis C: Data from the Polish EpiTer-2 cohort study. World J Gastroenterol 2021; 27:2177-2192. [PMID: 34025072 PMCID: PMC8117732 DOI: 10.3748/wjg.v27.i18.2177] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Revised: 03/13/2021] [Accepted: 04/21/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The introduction of direct-acting antiviral drugs into clinical practice has revolutionized the treatment of chronic hepatitis C, making it highly effective and safe for patients. However, few researchers have analyzed the factors causing therapy failure in some patients.
AIM To analyze factors influencing the failure of direct antiviral drugs in the large, multicenter EpiTer-2 cohort in a real-world setting.
METHODS The study cohort consisted of patients with chronic hepatitis C treated at 22 Polish centers from 2016-2020. Data collected from the online EpiTer-2 database included the following: hepatitis C virus (HCV) genotype, stage of fibrosis, hematology and liver function parameters, Child-Turcotte-Pugh and Model for End-stage Liver Disease scores, prior antiviral therapy, concomitant diseases, and drugs used in relation to hepatitis B virus (HBV) and/or human immunodeficiency virus (HIV) coinfections. Adverse events observed during the treatment and follow-up period were reported. Both standard and machine learning methods were used for statistical analysis.
RESULTS During analysis, 12614 patients with chronic hepatitis C were registered, of which 11938 (mean age: 52 years) had available sustained virologic response (SVR) data [11629 (97%) achieved SVR and 309 (3%) did not]. Most patients (78.1%) were infected with HCV genotype 1b. Liver cirrhosis was diagnosed in 2974 patients, while advanced fibrosis (F3) was diagnosed in 1717 patients. We included patients with features of hepatic failure at baseline [ascites in 142 (1.2%) and encephalopathy in 68 (0.6%) patients]. The most important host factors negatively influencing treatment efficacy were liver cirrhosis, clinical and laboratory features of liver failure, history of hepatocellular carcinoma, and higher body mass index. Among viral factors, genotype 3 and viral load also exerted an influence on treatment efficacy. Classical statistical analysis revealed that treatment ineffectiveness seemed to be influenced by the male sex, which was not confirmed by the multivariate analysis using the machine learning algorithm (random forest). Coinfection with HBV (including patients with on-treatment reactivation of HBV infection) or HIV, extrahepatic manifestations, and renal failure did not significantly affect the treatment efficacy.
CONCLUSION In patients with advanced liver disease, individualized therapy (testing for resistance-associated variants and response-guided treatment) should be considered to maximize the chance of achieving SVR.
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Affiliation(s)
- Ewa Janczewska
- Department of Basic Medical Sciences, The School of Health Sciences in Bytom, Medical University of Silesia, Bytom 41-902, Poland
| | - Mateusz Franciszek Kołek
- Department of Animal Physiology, Faculty of Biology, University of Warsaw, Warszawa 02-096, Poland
| | - Beata Lorenc
- Pomeranian Center of Infectious Diseases, Medical University Gdańsk, Gdańsk 80-214, Poland
| | - Jakub Klapaczyński
- Department of Internal Medicine and Hepatology, Central Clinical Hospital of the Ministry of Internal Affairs and Administration, Warszawa 02-507, Poland
| | | | - Marek Sitko
- Department of Infectious and Tropical Diseases, Jagiellonian University, Kraków 30-688, Poland
| | - Włodzimierz Mazur
- Clinical Department of Infectious Diseases, Medical University of Silesia in Katowice, Chorzów 41-500, Poland
| | | | - Iwona Buczyńska
- Department of Infectious Diseases and Hepatology, Medical University Wrocław, Wrocław 51-149, Poland
| | - Dorota Dybowska
- Department of Infectious Diseases and Hepatology, Ludwik Rydygier Collegium Medicum in Bydgoszcz Faculty of Medicine Nicolaus Copernicus University in Toruń, Bydgoszcz 85-030, Poland
| | - Agnieszka Czauż-Andrzejuk
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, Białystok 15-540, Poland
| | - Hanna Berak
- One-Day Department, Hospital for Infectious Diseases in Warsaw, Warszawa 01-201, Poland
| | - Rafał Krygier
- Outpatient Clinic, State University of Applied Sciences in Konin, Konin 62-510, Poland
| | - Jerzy Jaroszewicz
- Department of Infectious Diseases and Hepatology, Medical University of Silesia in Katowice, Bytom 41-902, Poland
| | - Jolanta Citko
- Department of Medical Practice of Infections, Regional Hospital, Olsztyn 10-561, Poland
| | - Anna Piekarska
- Department of Infectious Diseases and Hepatology, Medical University of Łódź, Łódź 90-419, Poland
| | | | - Łukasz Socha
- Department of Infectious Diseases, Hepatology and Liver Transplantation, Pomeranian Medical University, Szczecin 71-455, Poland
| | - Zbigniew Deroń
- Ward of Infectious Diseases and Hepatology, Biegański Regional Specialist Hospital, Łódź 91-347, Poland
| | - Łukasz Laurans
- Department of Infectious Diseases, Hepatology and Liver Transplantation, Pomeranian Medical University, Szczecin 71-455, Poland
- Infectious and Liver Diseases Clinic, Multidisciplinary Regional Hospital, Gorzów Wielkopolski 66-400, Poland
| | | | - Olga Tronina
- Department of Transplantation Medicine, Nephrology, and Internal Diseases, Medical University of Warsaw, Warszawa 02-091, Poland
| | - Brygida Adamek
- Department of Basic Medical Sciences, The School of Health Sciences in Bytom, Medical University of Silesia, Bytom 41-902, Poland
| | - Krzysztof Tomasiewicz
- Department of Infectious Diseases, Medical University of Lublin, Lublin 20-081, Poland
| | - Krzysztof Simon
- Department of Infectious Diseases and Hepatology, Medical University Wrocław, Wrocław 51-149, Poland
| | - Malgorzata Pawłowska
- Department of Paediatric Infectious Diseases and Hepatology, Faculty of Medicine, Collegium Medicum Bydgoszcz, Nicolaus Copernicus University Toruń, Bydgoszcz 85-030, Poland
| | - Waldemar Halota
- Department of Infectious Diseases and Hepatology, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Faculty of Medicine, Nicolaus Copernicus University in Toruń, Bydgoszcz 85-030, Poland
| | - Robert Flisiak
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, Białystok 15-540, Poland
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