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Christodoulou I, Rothenberger S, Ragni MV. Predictors of liver disease outcomes in individuals with hemophilia and HCV infection. Blood Adv 2024; 8:5767-5772. [PMID: 39361728 PMCID: PMC11605336 DOI: 10.1182/bloodadvances.2024014350] [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: 07/26/2024] [Revised: 09/13/2024] [Accepted: 09/17/2024] [Indexed: 10/05/2024] Open
Abstract
ABSTRACT Hemophilia is an X-linked congenital bleeding disorder for which factor replacement is life-saving but complicated by the sequelae of chronic hepatitis C virus (HCV) infection acquired decades ago. Although antiviral therapy clears HCV and reduces end-stage liver disease (ESLD), it may not reverse cirrhosis or prevent hepatocellular cancer (HCC). This was a retrospective cohort study of 121 men with hemophilia and HCV infection cared for at the Hemophilia Center of Western Pennsylvania to determine the incidence and predictors of ESLD and HCC. ESLD and HCC predictors were analyzed using Fisher exact test, and HCV-associated outcomes by Kaplan-Meier time-to-event and Cox proportional hazards regression analyses. At a mean 54 years (36-80) duration of HCV, ESLD occurred in 24 (19.8%), 0.365 per 100 person-years (py); and HCC in 7 (5.8%), 0.106 per 100 py. All 46 (38.0%) alive when HCV antiviral therapy became available, received it. Overall, 31 (25.6%) were HIV+. The leading causes of death were ESLD in 11 (32.3%), bleeding in 9 (26.5%), and HCC in 6 (17.6%). Major risk factors for ESLD included platelets <100 × 103/μL (odds ratio [OR], 6.009; P = .012) and HIV infection (OR, 3.883; P = .001). The major predictors of HCC were ESLD (OR, 11.476; P = .003) and platelets <100 000/μL (OR, 6.159; P = .014). No antiviral-treated patient developed ESLD, P = .001. For men with hemophilia, the sequelae of chronic HCV infection were significant. The major risk factors for ESLD were platelets <100 000/μL and HIV infection. Despite antiviral therapy, ESLD is the most significant predictor of HCC, and ESLD is the leading cause of death.
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Affiliation(s)
- Ilias Christodoulou
- Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA
| | - Scott Rothenberger
- Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA
- Department of Medicine and Center for Research on Healthcare, University of Pittsburgh Medical Center, Pittsburgh, PA
| | - Margaret V. Ragni
- Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA
- Department of Medicine and Center for Research on Healthcare, University of Pittsburgh Medical Center, Pittsburgh, PA
- Division Classical Hematology, Department of Medicine, University of Pittsburgh Medical Center, and The Hemophilia Center of Western Pennsylvania, Pittsburgh, PA
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2
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Ragni MV, Mead H, de Jong YP, Kaczmarek R, Leavitt AD, Long B, Nugent DJ, Sabatino DE, Fong S, von Drygalski A, Walsh CE, Luxon BA. Optimizing liver health before and after gene therapy for hemophilia A. Blood Adv 2024; 8:5203-5212. [PMID: 38843379 PMCID: PMC11530393 DOI: 10.1182/bloodadvances.2024013059] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2024] [Accepted: 05/27/2024] [Indexed: 10/09/2024] Open
Abstract
ABSTRACT Gene therapy for severe hemophilia A uses an adeno-associated virus (AAV) vector and liver-specific promoters that depend on healthy hepatocyte function to achieve safe and long-lasting increases in factor VIII (FVIII) activity. Thus, hepatocyte health is an essential aspect of safe and successful gene therapy. Many people living with hemophilia A have current or past chronic hepatitis C virus infection, metabolic dysfunction-associated steatosis or steatohepatitis, or other conditions that may compromise the efficacy and safety of AAV-mediated gene therapy. In addition, gene therapy may induce an immune response to transduced hepatocytes, leading to liver inflammation and reduced FVIII activity. The immune response can be treated with immunosuppression, but close monitoring of liver function tests and factor levels is necessary. The long-term risk of hepatocellular carcinoma associated with gene therapy is unknown. Routine screening by imaging for hepatocellular carcinoma, preferable every 6 months, is essential in patients at high risk and recommended in all recipients of hemophilia A gene therapy. This paper describes our current understanding of the biologic underpinnings of how liver health affects hemophilia A gene therapy, and provides practical clinical guidance for assessing, monitoring, and managing liver health both before and after gene therapy.
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Affiliation(s)
- Margaret V Ragni
- Division of Hematology/ Oncology, Department of Medicine, University of Pittsburgh Medical Center, and Hemophilia Center of Western Pennsylvania, Pittsburgh, PA
| | - Henry Mead
- BioMarin Pharmaceutical Inc, San Rafael, CA
| | - Ype P de Jong
- Division of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, NY
| | - Radoslaw Kaczmarek
- Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN
| | - Andrew D Leavitt
- Department of Laboratory Medicine and Medicine, University of California San Francisco Hemophilia Treatment Center, San Francisco, CA
| | - Brian Long
- BioMarin Pharmaceutical Inc, San Rafael, CA
| | - Diane J Nugent
- Department of Pediatrics, Division of Hematology Oncology, Children's Hospital of Orange County, University of California Los Angeles, Los Angeles, CA
| | - Denise E Sabatino
- Department of Pediatrics, Perlman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | | | | | - Christopher E Walsh
- Department of Medicine, Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Bruce A Luxon
- Department of Medicine, Division of Gastroenterology, Medstar Washington Hospital Center and Medstar Georgetown University Hospital, Washington, DC
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3
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Yang X, Jeong K, Yabes JG, Ragni MV. Prevalence and risk factors for hepatocellular carcinoma in individuals with haemophilia in the era of direct-acting antiviral agents: A national inpatient sample study. Haemophilia 2022; 28:769-775. [PMID: 35727998 DOI: 10.1111/hae.14607] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2022] [Revised: 05/08/2022] [Accepted: 06/01/2022] [Indexed: 12/17/2022]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is a major complication of chronic hepatitis C virus (HCV) infection. Among haemophilic (H) men, HCV is the leading cause of liver disease. Direct-acting antiviral agents (DAA) reduce HCV viral load, but impact on HCC is unknown. METHODS This was a retrospective study of adult H and nonhaemophilic (NH) male discharges, with and without HCC, identified by ICD-10 codes in the National Inpatient Sample (NIS) database, 2016-2018, with DAA availability. Analyses included discharge-level weights to reflect national estimates. Categorical variables were assessed by Rao-Scott chi-square and continuous variables by weighted simple linear regression. HCC correlates were determined by weighted multivariable logistic regression. RESULTS Among 7,674,969 adult male discharges, 3730 H (.04%) were identified in 2016-2018, of whom 10.06% had HCV and 1.07% had HCC, significantly higher than NH (1.22% and .27%, respectively) all P < .001. Annual HCC rates were similar during the 3-year period (2016-2018) in H and NH. Among H, HCC is associated with older age and higher rates of HCV, HBV, NASH, end-stage liver disease, and Charlson comorbidity (CCI), each P < .001. Among HCC, H were younger and more likely HIV+, each P < .001, but less likely alcoholic (P = .018) or hyperlipidaemic (P = .008) compared to NH. In multivariable regression, risk factors for HCC among H included NASH (OR 21.6), HCV (OR 3.96), CCI (OR1.54), all P < .001, while HIV and hyperlipidaemia were protective. CONCLUSION From 2016 to 2018, HCC rates did not change significantly in haemophilia discharges. NASH, HCV, and CCI are significant risks for HCC in haemophilia during the DAA-era.
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Affiliation(s)
- Xi Yang
- University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.,Hemophilia Center of Western Pennsylvania, Pittsburgh, Pennsylvania, USA
| | - Kwonho Jeong
- Center for Research on Health Care Data Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Jonathan G Yabes
- Center for Research on Health Care Data Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.,Division of General Internal Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.,Department of Biostatistics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Margaret V Ragni
- University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.,Hemophilia Center of Western Pennsylvania, Pittsburgh, Pennsylvania, USA
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4
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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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Hepatitis C Virus Infection among HIV-Infected Patients Attending Dessie Referral Hospital, Northeastern Ethiopia. Int J Microbiol 2021; 2021:6675851. [PMID: 33552160 PMCID: PMC7846398 DOI: 10.1155/2021/6675851] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2020] [Revised: 12/22/2020] [Accepted: 01/15/2021] [Indexed: 12/09/2022] Open
Abstract
Objective Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV) coinfection increases the incidence of end-stage liver disease which is more severe in immune-compromised HIV-infected patients than HCV infection alone. The aim of this study was to assess HCV infection and the associated risk factors among HIV/AIDS patients attending Dessie Referral Hospital, Northeastern Ethiopia. Methods A hospital-based cross-sectional study was conducted among 249 HIV-infected adults selected by a systematic random sampling technique from January to March 2018. A structured questionnaire was used to collect sociodemographic and risk factor data. Moreover, the blood specimen was collected and tested for CD4 count and anti-HCV antibody detection according to standard operating procedures. The data obtained were entered into SPSS version 20, and descriptive statistics, bivariate and multivariate logistic regression analyses were performed. A P value ≤0.05 with a corresponding 95% confidence interval was considered as statistically significant. Result Of a total of 249 HIV-infected study subjects, 120 (48.2%) were male and 129 (51.8%) were females, while the mean (±SD) age and CD4+ cells/mm3 were 39.10 (±11.507) years and 316.08 + 290.607 cells/mm3, respectively. Anti-HCV antibody was detected in 13 (5.2%) patients with higher prevalence rate found in males (P=0.078) and elders >50 years of age (P=0.013) than their counterparts. Age group of >50 years of age (AOR = 9.070, 95% CI: 1.578, 52.117, P=0.013), longer duration of HIV treatment (AOR = 5.490, 95% CI: 1.341, 34.458, P=0.041), WHO clinical stage III/IV (AOR = 12.768, 95% CI: 2.293, 71.106, P=0.004), previous history of hospitalization (AOR = 10.234, 95% CI: 2.049, 51.118, P=0.005), tooth extraction (AOR = 6.016, 95% CI: 1.137, 36.837, P=0.048), and liver disease (AOR = 11.398, 95% CI: 1.275, 101.930, P=0.029) were statistically significant predictors of HCV infection. Conclusion The prevalence of HCV infection is still higher and causes concern. Therefore, screening of these high-risk groups should be critical to reduce mortality and to improve clinical outcomes.
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Sun J, Althoff KN, Jing Y, Horberg MA, Buchacz K, Gill MJ, Justice AC, Rabkin CS, Goedert JJ, Sigel K, Cachay E, Park L, Lim JK, Kim HN, Lo Re V, Moore R, Sterling T, Peters MG, Achenbach CJ, Silverberg M, Thorne JE, Mayor AM, Crane HM, Kitahata MM, Klein M, Kirk GD. Trends in Hepatocellular Carcinoma Incidence and Risk Among Persons With HIV in the US and Canada, 1996-2015. JAMA Netw Open 2021; 4:e2037512. [PMID: 33595662 PMCID: PMC7890526 DOI: 10.1001/jamanetworkopen.2020.37512] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2020] [Accepted: 12/28/2020] [Indexed: 12/29/2022] Open
Abstract
IMPORTANCE People with HIV (PWH) are often coinfected with hepatitis B virus (HBV) and/or hepatitis C virus (HCV), leading to increased risk of developing hepatocellular carcinoma (HCC), but few cohort studies have had sufficient power to describe the trends of HCC incidence and risk among PWH in the combination antiretroviral therapy (cART) era. OBJECTIVE To determine the temporal trends of HCC incidence rates (IRs) and to compare rates by risk factors among PWH in the cART era. DESIGN, SETTING, AND PARTICIPANTS This cohort study used data from the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) study, which was conducted between 1996 and 2015. NA-ACCORD pooled individual-level data from 22 HIV clinical and interval cohorts of PWH in the US and Canada. PWH aged 18 years or older with available CD4 cell counts and HIV RNA data were enrolled. Data analyses were completed in March 2020. EXPOSURES HBV infection was defined as detection of either HBV surface antigen, HBV e antigen, or HBV DNA in serum or plasma any time during observation. HCV infection was defined by detection of anti-HCV seropositivity, HCV RNA, or detectable genotype in serum or plasma at any time under observation. MAIN OUTCOMES AND MEASURES HCC diagnoses were identified on the basis of review of medical records or cancer registry linkage. RESULTS Of 109 283 PWH with 723 441 person-years of follow-up, the median (interquartile range) age at baseline was 43 (36-51) years, 93 017 (85.1%) were male, 44 752 (40.9%) were White, 44 322 (40.6%) were Black, 21 343 (19.5%) had HCV coinfection, 6348 (5.8%) had HBV coinfection, and 2082 (1.9%) had triple infection; 451 individuals received a diagnosis of HCC by 2015. Between the early (1996-2000) and modern (2006-2015) cART eras, the crude HCC IR increased from 0.28 to 0.75 case per 1000 person-years. HCC IRs remained constant among HIV-monoinfected persons or those coinfected with HBV, but from 1996 to 2015, IRs increased among PWH coinfected with HCV (from 0.34 cases/1000 person-years in 1996 to 2.39 cases/1000 person-years in 2015) or those with triple infection (from 0.65 cases/1000 person-years in 1996 to 4.49 cases/1000 person-years in 2015). Recent HIV RNA levels greater than or equal to 500 copies/mL (IR ratio, 1.8; 95% CI, 1.4-2.4) and CD4 cell counts less than or equal to 500 cells/μL (IR ratio, 1.3; 95% CI, 1.0-1.6) were associated with higher HCC risk in the modern cART era. People who injected drugs had higher HCC risk compared with men who had sex with men (IR ratio, 2.0; 95% CI, 1.3-2.9), adjusted for HBV-HCV coinfection. CONCLUSIONS AND RELEVANCE HCC rates among PWH increased significantly over time from 1996 to 2015. PWH coinfected with viral hepatitis, those with higher HIV RNA levels or lower CD4 cell counts, and those who inject drugs had higher HCC risk.
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Affiliation(s)
- Jing Sun
- Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland
| | - Keri N. Althoff
- Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland
| | - Yuezhou Jing
- Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland
| | - Michael A. Horberg
- Kaiser Permanente Mid-Atlantic States, Mid-Atlantic Permanente Research Institute, Rockville, Maryland
| | - Kate Buchacz
- Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - M. John Gill
- Department of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Amy C. Justice
- Department of Medicine, Yale University, West Haven, Connecticut
| | | | | | - Keith Sigel
- Division of General Internal Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
- Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Edward Cachay
- Department of Medicine, University of California, San Diego, San Diego
| | - Lesley Park
- Center for Population Health Sciences, Stanford University School of Medicine, Stanford, California
| | - Joseph K. Lim
- Department of Medicine, Yale University School of Medicine, New Haven, Connecticut
| | - H. Nina Kim
- Department of Medicine, University of Washington, Seattle
| | - Vincent Lo Re
- Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia
- Center for Pharmacoepidemiology Research and Training, Perelman School of Medicine, Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia
- Perelman School of Medicine, Department of Medicine, University of Pennsylvania, Philadelphia
| | - Richard Moore
- Department of Medicine, Johns Hopkins University, Baltimore, Maryland
| | - Timothy Sterling
- Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee
| | - Marion G. Peters
- Department of Medicine, University of California, San Francisco, San Francisco
| | - Chad J. Achenbach
- Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | | | | | - Angel M. Mayor
- Retrovirus Research Center, Department of Medicine, Universidad Central del Caribe School of Medicine, Bayamon, Puerto Rico
| | - Heidi M. Crane
- Department of Medicine, University of Washington School of Medicine, Seattle
| | - Mari M. Kitahata
- Department of Medicine, University of Washington School of Medicine, Seattle
| | - Marina Klein
- Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada
- Division of Infectious Diseases and Chronic Viral Illness Service, McGill University Health Centre, Montreal, Quebec, Canada
| | - Gregory D. Kirk
- Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland
- Department of Medicine, Johns Hopkins University, Baltimore, Maryland
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7
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Death after diagnosis of noncommunicable disease comorbid conditions, stratified by injection drug use. AIDS 2019; 33:285-293. [PMID: 30325772 DOI: 10.1097/qad.0000000000002054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVE Describe all-cause mortality associated with history of injection drug use (IDU) after a validated diagnosis of four noncommunicable disease (NCD) diagnoses: end-stage liver disease (ESLD); end-stage renal disease (ESRD); cancer; or myocardial infarction (MI) or stroke. DESIGN We followed four cohorts of persons in continuity HIV care in the Johns Hopkins HIV Clinic with a validated diagnosis of ESLD (n = 67), ESRD (n = 187), cancer (n = 424), and MI or stroke (n = 213) from 1996 through approximately 2014. METHODS Crude and adjusted Cox proportional hazards models to estimate hazard ratios for death after a validated diagnosis of one of four NCD diagnoses associated with history of IDU as an HIV acquisition risk factor. RESULTS History of IDU was not associated with death after ESRD (adjusted hazard ratio 0.98, 95% confidence interval (CI) 0.57-1.68). Associations between history of IDU and death after ESLD and MI or stroke were weak, imprecise and not statistically significant (hazard ratio 1.17, 95% CI 0.63-2.19; hazard ratio 1.21, 95% CI 0.80-1.83). History of IDU was not associated with death after cancer in the first 6 months, but subsequently, the adjusted hazard ratio was 2.03 (95% CI 1.26-3.27). CONCLUSION Persons with a history of injection drug use and non-IDU had strikingly similar risk and hazard of mortality after several major NCD diagnoses. Mortality after cancer diagnosis in this cohort was higher for persons with a history of IDU than those without; this may be because of being diagnosed with a different mix of specific sites and stages of cancers.
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8
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Thalappillil A, Ragni MV, Comer DM, Yabes JG. Incidence and risk factors for hepatocellular cancer in individuals with haemophilia: A National Inpatient Sample Study. Haemophilia 2019; 25:221-228. [PMID: 30615816 DOI: 10.1111/hae.13668] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2018] [Revised: 11/09/2018] [Accepted: 11/28/2018] [Indexed: 11/28/2022]
Abstract
INTRODUCTION Among haemophilic (H) men, hepatitis C virus (HCV) is the leading cause of liver disease and mortality, but demographics and risks of hepatocellular carcinoma (HCC) in H are not well known. METHODS Adult discharges in H and non-haemophilic (NH) men, with and without HCC were identified in the National Inpatient Sample (NIS) between 1998 and 2014, using ICD-9 codes. Analyses included NIS-provided discharge-level weights to reflect national estimates. Categorical variables were assessed by Rao-Scott chi-square and continuous variables by weighted simple linear regression. HCC predictors were determined by weighted multivariable logistic regression. RESULTS Of 18 098 H, 144 (0.79%) had HCC between 1998 and 2014. Adjusted rates of HCC increased 3.0-fold in H vs 1.7-fold in NH (P = 0.484). Among HCV+, HCC rates adjusted for HIV, increased 2.2-fold in H vs 1.7-fold in NH (P = 0.740), while among HIV+, HCC increased 1.4-fold in H vs 0.2-fold in NH (P = 0.448). Among those with HCC, H were older than NH (P < 0.001), Caucasian (P = 0.006), platelet transfusion recipients (P < 0.001), with greater comorbidity (P < 0.001) and mortality (P < 0.006). H with HCC also had greater rates of HCV and HIV (each P < 0.001), lower rates of alcoholism and hyperlipidemia (each P < 0.001), and similar rates of HBV (P = 0.866), smoking (P = 0.507) and obesity (P = 0.502). In multivariable logistic regression, HCV was a strong predictor for HCC in haemophilia, (OR: 15.42, 95% CI: 8.75-27.16). DISCUSSION Haemophilic men have increasing rates of HCC, similar to men without haemophilia. HCV is the major predictor of HCC in haemophilia. Future trends in HCC will depend on the impact of newer HCV antiviral therapy.
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Affiliation(s)
- Alvin Thalappillil
- University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.,Haemophilia Center of Western Pennsylvania, Pittsburgh, Pennsylvania
| | - Margaret V Ragni
- University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.,Haemophilia Center of Western Pennsylvania, Pittsburgh, Pennsylvania
| | - Diane M Comer
- Center for Research on Health Care Data Center, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Jonathan G Yabes
- Center for Research on Health Care Data Center, University of Pittsburgh, Pittsburgh, Pennsylvania.,Division of General Internal Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.,Department of Biostatistics, University of Pittsburgh, Pittsburgh, Pennsylvania
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9
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Qvigstad C, Tait RC, Rauchensteiner S, Berntorp E, de Moerloose P, Schutgens RE, Holme PA. The elevated prevalence of risk factors for chronic liver disease among ageing people with hemophilia and implications for treatment. Medicine (Baltimore) 2018; 97:e12551. [PMID: 30278553 PMCID: PMC6181599 DOI: 10.1097/md.0000000000012551] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Chronic liver disease (CLD) is frequently seen in the hemophilia population. The ADVANCE Working Group conducted a cross-sectional study in which people with hemophilia (PWH) aged ≥40 years were included. This study aimed to assess the associations between CLD and its risk factors using data from the H3 study, and to suggest implications for optimal care.Data from 13 European countries were collected at a single time-point (2011-2013). Univariate and multivariate logistic regression (MLR) analyses were performed.A total of 532 PWH were included with either hemophilia A (n = 467) or hemophilia B (n = 65). A total of 127 (24%) were diagnosed with CLD. Hepatitis C virus (HCV), human immunodeficiency virus (HIV), total cholesterol, and severe hemophilia were significant risk factors in univariate logistic regressions. In MLR, HCV Ab+/PCR+ (OR = 17.6, P < .001), diabetes (OR = 3.0, P = .02), and HIV (OR = 1.9, P = .049) were positively associated with CLD. Total cholesterol (OR = 0.6, P = .002) was negatively associated with CLD. We found no evidence of interaction effects among the explanatory variables. No significant associations with age and type of or severity of hemophilia were observed in MLR.The main risk factors for CLD in this European cohort also apply to the general population, but the prevalence of HCV and HIV is considerably larger in this cohort. With new and improved treatment options, intensified eradication therapy for HCV seems justified to prevent CLD. Similarly, intensified monitoring and treatment of diabetes seem warranted.
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Affiliation(s)
- Christian Qvigstad
- Department of Haematology, Oslo University Hospital
- Institute of Clinical Medicine University of Oslo, Oslo, Norway
| | | | | | | | | | - Roger E. Schutgens
- Department of Hematology Van Creveldkliniek, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Pål Andre Holme
- Department of Haematology, Oslo University Hospital
- Institute of Clinical Medicine University of Oslo, Oslo, Norway
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10
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Ragni MV, Humar A, Stock PG, Blumberg EA, Eghtesad B, Fung JJ, Stosor V, Nissen N, Wong MT, Sherman KE, Stablein DM, Barin B. Hemophilia Liver Transplantation Observational Study. Liver Transpl 2017; 23:762-768. [PMID: 27935212 PMCID: PMC5449207 DOI: 10.1002/lt.24688] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2016] [Accepted: 11/20/2016] [Indexed: 01/13/2023]
Abstract
Hepatitis C virus (HCV) infection is the leading cause of liver disease in hemophilia patients. In those with human immunodeficiency virus (HIV)/HCV coinfection, the rate of liver disease progression is greater than in HCV monoinfected individuals. Despite antiretroviral therapy, which slows HCV liver disease progression, some require transplantation. Whether transplant outcomes are worse in hemophilic (H) rather than nonhemophilic (NH) candidates is unknown. In order to determine rates and predictors of pretransplant and posttransplant survival, we conducted a retrospective observational study using United Network for Organ Sharing national transplant registry data, comparing HCV+ H and NH candidates. We identified 2502 HCV+ liver transplant candidates from 8 US university-based transplant centers, between January 1, 2004 to December 31, 2010, including 144 HIV+ (6%) and 2358 HIV-; 36 H (1%) and 2466 NH; 1213 (48%) transplanted and 1289 not transplanted. Other than male predominance and younger age, each were P < 0.001. Baseline data were comparable between H and NH. In univariate analysis, 90-day pretransplant mortality was associated with higher baseline Model for End-Stage Liver Disease (MELD; hazard ratio [HR] = 1.15; P < 0.001), lower baseline platelet count (HR = 0.9 per 25,000/µL; P = 0.04), and having HIV/HCV+ hemophilia (P = 0.003). In multivariate analysis, pretransplant mortality was associated with higher MELD (P < 0.001) and was significantly greater in HIV+ than HIV- groups (P = 0.001). However, it did not differ between HIV+ H and NH (HR = 1.7; P = 0.36). Among HIV/HCV+, posttransplant mortality was similar between H and NH, despite lower CD4 in H (P = 0.04). In conclusion, this observational study confirms that hemophilia per se does not have a specific influence on transplant outcomes and that HIV infection increases the risk of mortality in both H and NH patients. Liver Transplantation 23 762-768 2017 AASLD.
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Affiliation(s)
- Margaret V. Ragni
- Division Hematology/Oncology, University of Pittsburgh and Hemophilia Center of Western Pennsylvania, Pittsburgh, PA
| | - Abhinav Humar
- Division of Transplant Surgery, Starzl Transplant Institute, University of Pittsburgh
| | - Peter G. Stock
- Division of Transplant Surgery, University of California, San Francisco, CA
| | - Emily A. Blumberg
- Division of Infectious Diseases, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Bijan Eghtesad
- Transplant Center and Department of General Surgery, Cleveland Clinic Foundation, Cleveland, OH
| | - John J. Fung
- Transplant Center and Department of General Surgery, Cleveland Clinic Foundation, Cleveland, OH
| | - Valentina Stosor
- Divisions of Infectious Diseases and Organ Transplantation, Northwestern University, Feinberg School of Medicine, Chicago, IL
| | - Nicholas Nissen
- Division Transplant Surgery, Cedars-Sinai Medical Center, Los Angeles, CA
| | - Michael T. Wong
- Division of Transplant Medicine, Beth Israel Deaconess Medical Center, Boston MA
| | - Kenneth E. Sherman
- Division of Digestive Disorders, University of Cincinnati, Cincinnati OH
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11
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Walsh CE, Workowski K, Terrault NA, Sax PE, Cohen A, Bowlus CL, Kim AY, Hyland RH, Han B, Wang J, Stamm LM, Brainard DM, McHutchison JG, von Drygalski A, Rhame F, Fried MW, Kouides P, Balba G, Reddy KR. Ledipasvir-sofosbuvir and sofosbuvir plus ribavirin in patients with chronic hepatitis C and bleeding disorders. Haemophilia 2017; 23:198-206. [PMID: 28124511 DOI: 10.1111/hae.13178] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/20/2016] [Indexed: 11/29/2022]
Abstract
INTRODUCTION Chronic hepatitis C virus (HCV) infection is prevalent among patients with inherited bleeding disorders and is a leading cause of mortality in those with haemophilia. AIM We evaluated the efficacy and safety of ledipasvir-sofosbuvir and sofosbuvir plus ribavirin in patients with chronic HCV genotype 1-4 infection and an inherited bleeding disorder. METHODS Ledipasvir-sofosbuvir was administered for 12 weeks to patients with genotype 1 or 4 infection and for 12 or 24 weeks to treatment-experienced cirrhotic patients with genotype 1 infection. Patients with genotype 2 and 3 infection received sofosbuvir plus ribavirin for 12 and 24 weeks respectively. RESULTS The majority of the 120 treated patients had a severe bleeding disorder (55%); overall, 65% of patients had haemophilia A and 26% of patients had haemophilia B; 22% were HIV coinfected. Sustained virologic response at 12 weeks posttreatment was 99% (98/99) in patients with genotype 1 or 4 infection; 100% (5/5) in treatment-experienced cirrhotic patients with genotype 1 infection; 100% (10/10) in patients with genotype 2 infection; and 83% (5/6) in patients with genotype 3 infection. There were no treatment discontinuations due to adverse events (AEs). The most frequent non-bleeding AEs were fatigue, headache, diarrhoea, nausea and insomnia. Bleeding AEs occurred in 22 patients, of which all but one were considered unrelated to treatment. CONCLUSION Treatment with ledipasvir-sofosbuvir for patients with HCV genotype 1 or 4 infection or sofosbuvir plus ribavirin for patients with genotype 2 or 3 infection was highly effective and well tolerated among those with inherited bleeding disorders.
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Affiliation(s)
- C E Walsh
- Icahn School of Medicine at Mount Sinai, Mount Sinai Hospital, New York, NY, USA
| | | | - N A Terrault
- University of California at San Francisco, San Francisco, CA, USA
| | - P E Sax
- Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - A Cohen
- Newark Beth Israel Medical Center, Barnabas Health, Newark, NJ, USA
| | - C L Bowlus
- University of California at Davis, Davis, CA, USA
| | - A Y Kim
- Massachusetts General Hospital, Boston, MA, USA
| | - R H Hyland
- Gilead Sciences Inc., Foster City, CA, USA
| | - B Han
- Gilead Sciences Inc., Foster City, CA, USA
| | - J Wang
- Gilead Sciences Inc., Foster City, CA, USA
| | - L M Stamm
- Gilead Sciences Inc., Foster City, CA, USA
| | | | | | | | - F Rhame
- Abbott Northwestern Hospital, Minneapolis, MN, USA
| | - M W Fried
- University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - P Kouides
- The Mary M. Gooley Hemophilia Center, Rochester, NY, USA
| | - G Balba
- MedStar Georgetown University Hospital, Washington, DC, USA
| | - K R Reddy
- University of Pennsylvania, Philadelphia, PA, USA
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12
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Mehta KD, Ragni MV. Bleeding and liver transplantation outcomes in haemophilia. Haemophilia 2016; 23:230-237. [PMID: 27813318 DOI: 10.1111/hae.13104] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/25/2016] [Indexed: 11/30/2022]
Abstract
BACKGROUND Hepatitis C is the major cause of end-stage liver disease and the major indication for orthotopic liver transplantation (OLTx) in individuals with haemophilia. AIM To assess the epidemiology and outcomes of OLTx in U.S. haemophilia patients. METHODS We investigated haemophilia liver transplant recipients between 1993 and 2012, using the Nationwide Inpatient Sample, identified by ICD9 code 50.59. RESULTS Of the 11 267 (weighted n = 54 691) patients undergoing OLTx, 44 (0.4%; weighted n = 213) had haemophilia. Those with haemophilia were more likely than non-haemophilic OLTx recipients to have bleeding complications (45.3% vs. 31.5%, P = 0.009) and hypovolemic shock (7.0% vs. 1.1%, P < 0.0001). They also had a significantly higher incidence of HIV (24.8% vs. 0.5%, P < 0.005), hepatitis B (16.2% vs. 7.9%, P = 0.04) and vitamin K deficiency (2.1% vs. 0.02%, P < 0.001). In spite of these differences, there was no difference in in-hospital mortality between haemophilic and non-haemophilic recipients (6.8% vs. 6.2%, P = 0.9). In multivariate logistic regression, bleeding complications in haemophilia increased the risk of in-hospital mortality by more than 3-fold (P < 0.0001), and disseminated intravascular coagulation increased the risk of bleeding complications in haemophilic recipients by over 10-fold (P < 0.0001). CONCLUSIONS Bleeding complications are common in haemophilia OLTx recipients. Thus, aggressive correction of coagulation defects in this group may be a medically sound approach to reduce complications and mortality associated with OLTx.
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Affiliation(s)
- K D Mehta
- Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - M V Ragni
- Hemophilia Center of Western Pennsylvania, Pittsburgh, PA, USA
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13
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Eyster ME, Kong L, Li M, Schreibman IR. Long term survival in persons with hemophilia and chronic hepatitis C: 40 year outcomes of a large single center cohort. Am J Hematol 2016; 91:E335-40. [PMID: 27214557 DOI: 10.1002/ajh.24427] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2016] [Revised: 05/17/2016] [Accepted: 05/19/2016] [Indexed: 12/13/2022]
Abstract
We studied the course of chronic HCV infections in a cohort of 222 persons with hemophilia (PWH) and von Willebrand disease followed at our center since 1973. Twenty two (10%) developed end stage liver disease (ESLD). Forty years after HCV infection, cumulative incidence of ESLD was 12.3% and overall survival was 45.5%. Those who were infected with HCV only (n = 100) had a survival of 75.2%, while those infected with HIV (n = 122) had a survival of 24% (P < 0.001). Survivals were significantly longer for those infected with HCV at younger age (< 15 years) compared to those infected over age 30 years (P = 0.014). Cause specific deaths for ESLD and bleeding were 8.8% and 8.3% respectively. For HIV negative subjects, the annual hazard of death from ESLD and bleeding was near zero for the first 10 years, and then rose slowly over the next 20 years to 0.4/100py for ESLD and 0.2/100py for bleeding. Sixty subjects completed 79 treatment episodes. Sustained viral response rates increased from 7/21 (33%) between 1990 and 2001, to 17/29 (58%) between 2002 and 2011, and to 27/29 (93%), since 2012 with the advent of the directly acting antiviral agents. These results confirm the very slow ESLD progression rate in HIV negative PWH. However, the risk of death from both ESLD and bleeding increases steadily with longer duration of HCV infection. More aggressive surveillance to detect those with early fibrosis is needed now that curative treatment is possible in >95% of individuals. Am. J. Hematol. 91:E335-E340, 2016. © 2016 Wiley Periodicals, Inc.
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Affiliation(s)
- M. Elaine Eyster
- Department of Medicine; Division of Hematology/Oncology; Penn State Milton S. Hershey Medical Center; PO Box 850, 500 University Drive Hershey Pennsylvania
| | - Lan Kong
- Department of Public Health Sciences; Penn State Milton S. Hershey Medical Center; PO Box 850, 500 University Drive Hershey Pennsylvania
| | - Menghan Li
- Department of Public Health Sciences; Penn State Milton S. Hershey Medical Center; PO Box 850, 500 University Drive Hershey Pennsylvania
| | - Ian R. Schreibman
- Department of Medicine; Division of Gastroenterology and Hepatology; Penn State Milton S. Hershey Medical Center; PO Box 850, 500 University Drive Hershey Pennsylvania
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14
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Quon D, Chitlur M, Rajpurkar M, Simpson M, O'Brien S, Flood V, Hsieh L, Acharya S, Kruse-Jarres R, Sood S, Maahs J. Women leaders in hematology: Inspirations & insights. Am J Hematol 2016; 91 Suppl 1:S6-S34. [PMID: 26851875 DOI: 10.1002/ajh.24316] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Affiliation(s)
- Doris Quon
- Orthopaedic Institute for Children, Orthopaedic Hemophilia Treatment Center, Los Angeles, California
| | - Meera Chitlur
- Children's Hospital of Michigan, Division of Hematology/Oncology, Detroit, Michigan
| | | | - Mindy Simpson
- Rush University Medical Center, Department of Pediatrics, Chicago, Illinois
| | - Sarah O'Brien
- Nationwide Children's Hospital, Department of Hematology & Oncology, Columbus, Ohio
| | - Veronica Flood
- Medical College of Wisconsin, Department of Pediatrics, Milwaukee, Wisconsin
| | - Loan Hsieh
- Children's Hospital of Orange County, Hematology, Orange, California
| | - Suchitra Acharya
- Northwell Health, Pediatric Hematology/Oncology, New Hyde Park, New York
| | - Rebecca Kruse-Jarres
- Washington Center for Bleeding Disorders at Bloodworks Northwest, Seattle, Washington
| | - Suman Sood
- University of Michigan, Department of Hematology, Ann Arbor, Michigan
| | - Jennifer Maahs
- Indiana Hemophilia and Thrombosis Center, Indianapolis, Indiana
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15
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Singleton T, Cooper DL, Gunawardena S. Women leaders in hematology: Inspirations & insights. Am J Hematol 2016; 91 Suppl 1:S3-5. [PMID: 26852011 DOI: 10.1002/ajh.24317] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2016] [Accepted: 01/25/2016] [Indexed: 11/12/2022]
Affiliation(s)
- Tammuella Singleton
- Tulane University School of Medicine, Department of Pediatrics; New Orleans Louisiana
| | - David L. Cooper
- Clinical Development, Medical and Regulatory Affairs, Novo Nordisk Inc; Plainsboro New Jersey
| | - Sriya Gunawardena
- Clinical Development, Medical and Regulatory Affairs, Novo Nordisk Inc; Plainsboro New Jersey
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16
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Baranoski AS, Cotton D, Heeren T, Nunes D, Kubiak RW, Horsburgh CR. Clinical Liver Disease Progression Among Hepatitis C-Infected Drug Users With CD4 Cell Count Less Than 200 Cells/mm(3) Is More Pronounced Among Women Than Men. Open Forum Infect Dis 2015; 3:ofv214. [PMID: 26955643 PMCID: PMC4777902 DOI: 10.1093/ofid/ofv214] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2015] [Accepted: 12/24/2015] [Indexed: 12/13/2022] Open
Abstract
The rate of clinical liver disease progression in this cohort of HCV mono-infected and HIV/HCV co-infected individuals was higher than previously reported. Risk of clinical liver disease progression was associated with level of immune suppression, and was more pronounced in women. Background. Hepatitis C virus (HCV) infection is a leading cause of liver-related morbidity and mortality in the United States, and injection drug users are at particularly high risk. Methods. This prospective observational cohort study assessed the rate of, and risk factors for, clinical liver disease progression in a cohort of HCV monoinfected and human immunodeficiency virus (HIV)/HCV coinfected drug users using unadjusted and multivariate Cox proportional hazards regression analyses. Results. Of 564 subjects including 421 (75%) with HIV/HCV coinfection and 143 with HCV monoinfection, 55 (10%) had clinical liver disease progression during follow-up with a rate of 25.3 events per 1000 person-years. In unadjusted analysis, there was an interaction between sex and HIV status. In sex-stratified multivariate analysis, HIV/HCV-coinfected women with CD4 <200 cells/mm3 had 9.99 times the risk of liver disease progression as HCV-monoinfected women (confidence interval [CI], 1.84–54.31; P = .008), and white women had a trend towards increased risk of liver disease progression compared with non-white women (hazard ratio, 2.84; CI, .93–8.68; P = .07). Human immunodeficiency virus/HCV-coinfected men with CD4 <200 cells/mm3 had 2.86 times the risk of liver disease progression as HCV-monoinfected men (CI, 1.23-6.65; P = .01). Conclusions. Hepatitis C virus-monoinfected and HIV/HCV-coinfected drug users had high rates of clinical liver disease progression. In those with HIV infection, liver disease progression was associated with advanced immune suppression. This effect was strikingly more pronounced in women than in men.
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Affiliation(s)
- Amy S Baranoski
- Department of Medicine, Division of Infectious Diseases and HIV Medicine, Drexel University College of Medicine, Philadelphia, Pennsylvania; Department of Epidemiology; Department of Medicine, Section of Infectious Diseases
| | - Deborah Cotton
- Department of Epidemiology; Department of Medicine, Section of Infectious Diseases
| | - Timothy Heeren
- Department of Biostatistics , Boston University School of Public Health
| | - David Nunes
- Department of Medicine , Section of Gastroenterology , Boston University School of Medicine , Massachusetts
| | | | - C Robert Horsburgh
- Department of Epidemiology; Department of Medicine, Section of Infectious Diseases
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17
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Cenderello G, Artioli S, Viscoli C, Pasa A, Giacomini M, Giannini B, Dentone C, Nicolini LA, Cassola G, Di Biagio A. Budget impact analysis of sofosbuvir-based regimens for the treatment of HIV/HCV-coinfected patients in northern Italy: a multicenter regional simulation. CLINICOECONOMICS AND OUTCOMES RESEARCH 2015; 8:15-21. [PMID: 26770065 PMCID: PMC4706121 DOI: 10.2147/ceor.s93641] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023] Open
Abstract
Objectives Chronic hepatitis C virus (HCV) is a leading cause of hospitalization and death in populations coinfected with human immunodeficiency virus (HIV). Sofosbuvir (SOF) is a pan-genotypic drug that should be combined with other agents as an oral treatment for HCV. We performed a 5-year horizon budget impact analysis of SOF-based regimens for the management of HIV/HCV-coinfected patients. Methods A multicenter, prospective evaluation was conducted, involving four Italian Infectious Diseases Departments (Galliera, San Martino, Sanremo, and La Spezia). All 1,005 genotype-coinfected patients (30% cirrhotics) under observation were considered (patients in all disease-stages were considered: chronic hepatitis C, cirrhosis, transplant, hepatocellular carcinoma). Disease stage costs per patient were collected; the expected disease progression in the absence of treatment and sustained virological response (SVR) success rate for SOF-based regimens were calculated based on the literature and expert opinion. Drug prices were based on what the National Health Service paid for them. The comparison of “no treatment” disease progression costs versus the economic impact of SOF-based regimens was investigated. Results Over the following 5 years, the disease progression scenario resulted in direct costs of approximately €54 million. Assuming an SVR success rate of 90%, average SOF-based regimens cost up to €50,000 per person, resulting in a final cost of more than €56 million, so this option is not economically viable. At the average price of €12,000, SOF-based regimens, expense was €17 million, saving 68%. At this price level, the economic resources invested in treating mild to moderate fibrosis stage patients would be equal to the amount of direct costs of disease management in this stage, resulting in a valid return of investment in the short-term. Conclusion Given the high rates of SVR, in the Italian Healthcare System, SOF-based regimens, price is a determinant and a predictor of the overall cost for the Hepatitis C patient’s management. At the average price per therapy of €12,000 over the next 5 years, SOF-based regimens are becoming highly sustainable.
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Affiliation(s)
| | | | - Claudio Viscoli
- Infectious Diseases Unit, A San Martino, IST, Genoa University, Genoa, Italy
| | - Ambra Pasa
- IT Unit, Ospedali Galliera, Genoa, Italy
| | - Mauro Giacomini
- Department of Informatics, Bioengineering, Robotics and System Engineering (DIBRIS), University of Genoa, Genova, Italy
| | - Barbara Giannini
- Department of Informatics, Bioengineering, Robotics and System Engineering (DIBRIS), University of Genoa, Genova, Italy
| | - Chiara Dentone
- Infectious Diseases Unit, ASL-1 Imperiese, Sanremo, Imperia, Italy
| | | | | | - Antonio Di Biagio
- Infectious Diseases Unit, A San Martino, IST, Genoa University, Genoa, Italy
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18
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Fung J. Era of direct acting antivirals in chronic hepatitis C: Who will benefit? World J Hepatol 2015; 7:2543-2550. [PMID: 26523206 PMCID: PMC4621468 DOI: 10.4254/wjh.v7.i24.2543] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2015] [Revised: 09/07/2015] [Accepted: 10/13/2015] [Indexed: 02/06/2023] Open
Abstract
In the era of highly effective direct acting antiviral (DAA) drugs for the treatment of chronic hepatitis C (CHC) infection, where eradication is almost ensured with minimal side effects, all hepatitis C carriers should benefit theoretically. In the real world setting however, only a small proportion will benefit at this time point due to the multiple barriers to accessing therapy. Given that universal treatment is unlikely, treatment with DAAs will likely be restricted to those with the highest health benefits, and for those who can afford the high expense of a treatment course. Those with the highest unmet needs include those who have failed previous interferon-based therapy or who are interferon-ineligible with evidence of active disease, those with advance liver disease, and those with recurrence of hepatitis C after liver transplantation. In the future, the focus should be on increasing access to treatment for those infected with CHC.
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19
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Abstract
Coinfections of sexually transmitted infections are frequent due to the same transmission routes which may facilitate the transmission of other sexually transmitted infections. Sexually transmitted coinfections are associated with atypical and generally more severe clinical features, more complications, resistency to treatment, unfavourable outcome, and worse prognosis. Sexually transmitted infections may increase the likelihood of acquiring and transmission of HIV infection. The authors summarize the most important characteristics of sexually transmitted infections (such as HIV and hepatitis B virus, HIV and hepatitis C virus, HIV and syphilis, HIV and gonorrhoeae, HIV and chlamydia coinfections). These infections are more frequent in HIV infected patients than in the normal population. The shared transmission routes, impairment of the immune response, elevated cytokine levels and the associated inflammatory milieu produce local tissue damage, breaches in mucosal epithelium, which increases the risk of human immunodeficiency virus infection. Regular screening for sexually transmitted infections, use of more sensitive diagnostic methods, improved reporting and avoidance of unsafe sexual behaviour among certain subpopulations as well as education are essential in the prevention of sexually transmitted coinfections.
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Affiliation(s)
- Márta Marschalkó
- Semmelweis Egyetem, Általános Orvostudományi Kar Bőr-, Nemikórtani és Bőronkológiai Klinika Budapest Mária u. 41. 1085
| | - Katinka Pónyai
- Semmelweis Egyetem, Általános Orvostudományi Kar Bőr-, Nemikórtani és Bőronkológiai Klinika Budapest Mária u. 41. 1085
| | - Sarolta Kárpáti
- Semmelweis Egyetem, Általános Orvostudományi Kar Bőr-, Nemikórtani és Bőronkológiai Klinika Budapest Mária u. 41. 1085
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20
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Ascertainment and verification of end-stage renal disease and end-stage liver disease in the north american AIDS cohort collaboration on research and design. AIDS Res Treat 2015; 2015:923194. [PMID: 25789171 PMCID: PMC4350581 DOI: 10.1155/2015/923194] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2014] [Accepted: 01/16/2015] [Indexed: 02/08/2023] Open
Abstract
The burden of HIV disease has shifted from traditional AIDS-defining illnesses to serious non-AIDS-defining comorbid conditions. Research aimed at improving HIV-related comorbid disease outcomes requires well-defined, verified clinical endpoints. We developed methods to ascertain and verify end-stage renal disease (ESRD) and end-stage liver disease (ESLD) and validated screening algorithms within the largest HIV cohort collaboration in North America (NA-ACCORD). Individuals who screened positive among all participants in twelve cohorts enrolled between January 1996 and December 2009 underwent medical record review to verify incident ESRD or ESLD using standardized protocols. We randomly sampled 6% of contributing cohorts to determine the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of ESLD and ESRD screening algorithms in a validation subcohort. Among 43,433 patients screened for ESRD, 822 screened positive of which 620 met clinical criteria for ESRD. The algorithm had 100% sensitivity, 99% specificity, 82% PPV, and 100% NPV for ESRD. Among 41,463 patients screened for ESLD, 2,024 screened positive of which 645 met diagnostic criteria for ESLD. The algorithm had 100% sensitivity, 95% specificity, 27% PPV, and 100% NPV for ESLD. Our methods proved robust for ascertainment of ESRD and ESLD in persons infected with HIV.
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21
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Abstract
Liver transplantation has become the treatment of choice for nearly all causes of end-stage liver disease, fulminant liver failure, and selected primary hepatic malignancies. The demand for liver transplantation has persistently outmatched the availability of donor organs leading to the development of novel strategies to expand the donor pool. The authors review the process of liver transplant evaluation, methods used to address the donor shortage, and disease-specific outcomes and challenges and discuss posttransplant care.
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Affiliation(s)
- Ming-Ming Xu
- Division of Digestive and Liver Diseases, Department of Medicine, Columbia University College of Physicians & Surgeons, 622 West 168th Street, PH14, New York, NY 10032, USA
| | - Robert S Brown
- Division of Digestive and Liver Diseases, Department of Medicine, Columbia University College of Physicians & Surgeons, 622 West 168th Street, PH14, New York, NY 10032, USA.
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22
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Stemberger M, Seybold U, Eberle J, Denk G, Kolligs F, Kaspar M, Guba M, Pichler M, Spannagl M. Haemophilia-related outcome after liver transplantation and treatment with sofosbuvir/ribavirin in a HCV-HIV coinfected man with liver failure and hepatocellular carcinoma. Haemophilia 2015; 21:e131-e133. [PMID: 25622556 DOI: 10.1111/hae.12599] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/31/2014] [Indexed: 11/26/2022]
Affiliation(s)
- M Stemberger
- Haemostaseologie, Medizinische Klinik und Poliklinik IV, Klinikum der LMU, Munich, Germany
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23
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Hønge BL, Jespersen S, Medina C, da Silva Té D, da Silva ZJ, Lewin SR, Østergaard L, Laursen AL, Krarup H, Erikstrup C, Wejse C. Hepatitis C prevalence among HIV-infected patients in Guinea-Bissau: a descriptive cross-sectional study. Int J Infect Dis 2014; 28:35-40. [PMID: 25223805 DOI: 10.1016/j.ijid.2014.06.007] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2014] [Revised: 04/12/2014] [Accepted: 06/09/2014] [Indexed: 12/20/2022] Open
Abstract
OBJECTIVES To estimate the prevalence and determine the clinical presentation of risk factors of hepatitis C virus (HCV) among HIV-infected patients in Bissau, Guinea-Bissau. METHODS In this cross-sectional study, we included individuals who had a routine blood analysis performed during the period April 28 to September 30, 2011. Patient samples were tested for HCV antibodies (anti-HCV) with a chemiluminescence test (Architect, Abbott, USA) and INNO-LIA HCV Score (Innogenetics, Belgium). HCV viral load and genotype were analyzed using an in-house real-time PCR method. RESULTS In total, 576 patients were included (417 HIV-1, 104 HIV-2, and 55 HIV-1/2). Ten (1.7%) patients were anti-HCV-positive and eight (1.4%) patients had detectable HCV RNA; all were genotype 2. In a multivariable logistic regression analysis, age >50 years was associated with anti-HCV reactivity (p<0.01). No subjective symptoms or objective signs were more prevalent among patients with detectable HCV RNA compared to patients without detectable HCV RNA. Biochemically, detectable HCV RNA was associated with elevated amylase (83.3% vs. 38.6%, p=0.03), but not with the liver enzymes alanine aminotransferase and aspartate aminotransferase. CONCLUSIONS The prevalence of anti-HCV was low and comparable to similar settings, and genotype analysis confirmed the presence of genotype 2 in West Africa.
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Affiliation(s)
- Bo Langhoff Hønge
- Bandim Health Project, Indepth Network, Bissau, Guinea-Bissau; Department of Infectious Diseases, Aarhus University Hospital, Brendstrupgaardsvej 100, 8200 Aarhus, Denmark.
| | - Sanne Jespersen
- Bandim Health Project, Indepth Network, Bissau, Guinea-Bissau; Department of Infectious Diseases, Aarhus University Hospital, Brendstrupgaardsvej 100, 8200 Aarhus, Denmark
| | - Candida Medina
- National HIV Programme, Ministry of Health, Bissau, Guinea-Bissau
| | | | - Zacarias José da Silva
- Bandim Health Project, Indepth Network, Bissau, Guinea-Bissau; National Public Health Laboratory, Bissau, Guinea-Bissau
| | - Sharon R Lewin
- Department of Infectious Diseases, Alfred Hospital and Monash University, Australia; Centre for Biomedical Research, Burnet Institute, Melbourne, Australia
| | - Lars Østergaard
- Department of Infectious Diseases, Aarhus University Hospital, Brendstrupgaardsvej 100, 8200 Aarhus, Denmark
| | - Alex Lund Laursen
- Department of Infectious Diseases, Aarhus University Hospital, Brendstrupgaardsvej 100, 8200 Aarhus, Denmark
| | - Henrik Krarup
- Department of Clinical Biochemistry, Aalborg University Hospital, Denmark
| | | | - Christian Wejse
- Bandim Health Project, Indepth Network, Bissau, Guinea-Bissau; Department of Infectious Diseases, Aarhus University Hospital, Brendstrupgaardsvej 100, 8200 Aarhus, Denmark; GloHAU, Centre for Global Health, School of Public Health, Aarhus University, Denmark
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24
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Arain A, Robaeys G. Eligibility of persons who inject drugs for treatment of hepatitis C virus infection. World J Gastroenterol 2014; 20:12722-12733. [PMID: 25278674 PMCID: PMC4177459 DOI: 10.3748/wjg.v20.i36.12722] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2013] [Accepted: 05/19/2014] [Indexed: 02/06/2023] Open
Abstract
In this decade, an increase is expected in end-stage liver disease and hepatocellular carcinoma, most commonly caused by hepatitis C virus (HCV) infection. Although people who inject drugs (PWID) are the major source for HCV infection, they were excluded from antiviral treatments until recently. Nowadays there is incontrovertible evidence in favor of treating these patients, and substitution therapy and active substance use are no longer contraindications for antiviral treatment. The viral clearance in PWID after HCV antiviral treatment with interferon or pegylated interferon combined with ribavirin is comparable to the viral clearance in non-substance users. Furthermore, multidisciplinary approaches to delivering treatment to PWID are advised, and their treatment should be considered on an individualized basis. To prevent the spread of HCV in the PWID community, recent active PWID are eligible for treatment in combination with needle exchange programs and substitution therapy. As the rate of HCV reinfection is low after HCV antiviral treatment, there is no need to withhold HCV treatment due to concerns about reinfection alone. Despite the advances in treatment efficacies and data supporting their success, HCV assessment of PWID and initiation of antiviral treatment remains low. However, the proportion of PWID assessed and treated for HCV is increasing, which can be further enhanced by understanding the barriers to and facilitators of HCV care. Removing stigmatization and implementing peer support and group treatment strategies, in conjunction with greater involvement by nurse educators/practitioners, will promote greater treatment seeking and adherence by PWID. Moreover, screening can be facilitated by noninvasive methods for detecting HCV antibodies and assessing liver fibrosis stages. Recently, HCV clearance has become a major endpoint in the war against drugs for the Global Commission on Drug Policy. This review highlights the most recent evidence concerning HCV infection and treatment strategies in PWID.
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Clausen LN, Lundbo LF, Benfield T. Hepatitis C virus infection in the human immunodeficiency virus infected patient. World J Gastroenterol 2014; 20:12132-12143. [PMID: 25232248 PMCID: PMC4161799 DOI: 10.3748/wjg.v20.i34.12132] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2013] [Revised: 04/02/2014] [Accepted: 06/26/2014] [Indexed: 02/06/2023] Open
Abstract
Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) share the same transmission routes; therefore, coinfection is frequent. An estimated 5-10 million individuals alone in the western world are infected with both viruses. The majority of people acquire HCV by injection drug use and, to a lesser extent, through blood transfusion and blood products. Recently, there has been an increase in HCV infections among men who have sex with men. In the context of effective antiretroviral treatment, liver-related deaths are now more common than Acquired Immune Deficiency Syndrome-related deaths among HIV-HCV coinfected individuals. Morbidity and mortality rates from chronic HCV infection will increase because the infection incidence peaked in the mid-1980s and because liver disease progresses slowly and is clinically silent to cirrhosis and end-stage-liver disease over a 15-20 year time period for 15%-20% of chronically infected individuals. HCV treatment has rapidly changed with the development of new direct-acting antiviral agents; therefore, cure rates have greatly improved because the new treatment regimens target different parts of the HCV life cycle. In this review, we focus on the epidemiology, diagnosis and the natural course of HCV as well as current and future strategies for HCV therapy in the context of HIV-HCV coinfection in the western world.
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Althaf MM, Hussein MH, Abdelsalam MS, Amer SM. Acute kidney injury in a diabetic haemophiliac: one step at a time. BMJ Case Rep 2014; 2014:bcr-2014-203967. [PMID: 24811561 DOI: 10.1136/bcr-2014-203967] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Abstract
We present a young man with type 1 diabetes mellitus and haemophilia A; who presented with oliguric acute kidney injury (AKI). He is also known to have chronic hepatitis C virus infection. On presentation, he had an active urinary sediment warranting a renal biopsy for definitive diagnosis and management. Although he was at high risk for bleeding we elected for renal biopsy with appropriate factor VIII supplementation and monitoring. Ultrasound-guided percutaneous renal biopsy was successful with no immediate or long-term complications. Biopsy revealed advanced diabetic glomerulosclerosis with mild chronic interstitial inflammation.
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Affiliation(s)
- Mohammed Mahdi Althaf
- Department of Medicine, Section of Nephrology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
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27
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Blackard JT, Ma G, Sengupta S, Martin CM, Powell EA, Shata MT, Sherman KE. Evidence of distinct populations of hepatitis C virus in the liver and plasma of patients co-infected with HIV and HCV. J Med Virol 2014; 86:1332-41. [PMID: 24788693 DOI: 10.1002/jmv.23968] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/08/2014] [Indexed: 12/15/2022]
Abstract
Viral diversity is an important predictor of hepatitis C virus (HCV) treatment response and may influence viral pathogenesis. HIV influences HCV variability in the plasma; however, limited data on viral variability are available from distinct tissue/cell compartments in patients co-infected with HIV and HCV. Thus, this exploratory study evaluated diversity of the hypervariable region 1 (HVR1) of HCV in the plasma and liver for 14 patients co-infected with HIV and HCV. Median intra-patient genetic distances and entropy values were similar in the plasma and liver compartments. Positive immune selection pressure was observed in the plasma for five individuals and in the liver for three individuals. Statistical evidence supporting viral compartmentalization was found in five individuals. Linear regression identified ALT (P = 0.0104) and AST (P = 0.0130) as predictors of viral compartmentalization. A total of 12 signature amino acids that distinguish liver from plasma E1/HVR1 were identified. One signature amino acid was shared by at least two individuals. These findings suggest that HCV compartmentalization is relatively common among patients co-infected with HIV and HCV. These data also imply that evaluating viral diversity, including drug resistance patterns, in the serum/plasma only may not adequately represent viruses replicating with in the liver and, thus, deserves careful consideration in future studies.
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Affiliation(s)
- Jason T Blackard
- Division of Digestive Diseases, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio
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Zhang T, Tully DC, Zhou S, He N. Characteristics of HCV co-infection among HIV infected individuals from an area with high risk of blood-borne infections in central China. PLoS One 2014; 9:e94219. [PMID: 24709894 PMCID: PMC3978003 DOI: 10.1371/journal.pone.0094219] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2013] [Accepted: 03/14/2014] [Indexed: 12/17/2022] Open
Abstract
OBJECTIVE Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) co-infection has been proved to be a growing public health concern. The prevalence and genotypic pattern vary with geographic locations. Limited information is available to date with regard to HCV genotype and its clinical implications among those former commercial blood donor communities. The aims of this study were to genetically define the HCV genotype and associated clinical characteristics of HIV/HCV co-infected patients from a region with commercial blood donation history in central China. METHODS A cross sectional study, including 164 HIV infected subjects, was conducted in Shanxi province central China. Serum samples were collected and HCV antibody testing, AST and ALT testing were performed. Seropositive samples were further subjected to RT-PCR followed by direct sequence coupled with phylogenetic analysis of Core-E1 and NS5B regions performed in comparison with known reference genotypes. FINDINGS A total of 139 subjects were HCV antibody positive. Genotype could be determined for 88 isolates. Phylogenetic analysis revealed that the predominant circulating subtype was HCV 1b (65.9%), followed by HCV 2a (34.1%). The HCV viral load in the subjects infected with HIV1b was significantly higher than those infected with HCV 2a (P = 0.006). No significant difference for HCV RNA level was detected between ART status, CD4+ cell count level and HIV RNA level. Serum AST and ALT level were likely to increase with HCV RNA level, although no significance was observed. Those who had conducted commercial donation later than 1991 (OR 3.43, 95% CI: 1.12-10.48) and had a short duration of donation (OR 0.35, 95% CI: 0.13-0.96) were more likely to be infected with HCV 1b. CONCLUSION These results suggest that HCV subtype 1b predominates in this population, and the impact of HIV status and ART on HCV disease progression is not significantly correlated.
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Affiliation(s)
- Tiejun Zhang
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China and Key Laboratory of Public Health Safety (Fudan University), Ministry of Education, Shanghai, China
| | - Damien C Tully
- Ragon Institute of MGH, MIT and Harvard University, Harvard Medical School, Boston, Massachusetts, United States of America
| | - Sujuan Zhou
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China and Key Laboratory of Public Health Safety (Fudan University), Ministry of Education, Shanghai, China
| | - Na He
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China and Key Laboratory of Public Health Safety (Fudan University), Ministry of Education, Shanghai, China
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Takatsuki M, Soyama A, Eguchi S. Liver transplantation for HIV/hepatitis C virus co-infected patients. Hepatol Res 2014; 44:17-21. [PMID: 23607831 DOI: 10.1111/hepr.12132] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2013] [Revised: 04/07/2013] [Accepted: 04/07/2013] [Indexed: 12/26/2022]
Abstract
Since the introduction of antiretroviral therapy (ART) in the mid-1990s, AIDS-related death has been dramatically reduced, and hepatitis-C-virus (HCV)-related liver failure or hepatocellular carcinoma has currently become the leading cause of death in HIV/HCV co-infected patients. Liver transplantation may be one of the treatments of choices in such cases, but the indications for transplantation, perioperative management including both HIV and HCV treatments, immunosuppression and the prevention/treatment of infectious complications are all still topics of debate. With the improved understanding of the viral behaviors of both HIV and HCV and the development of novel strategies, especially to avoid drug interactions between ART and immunosuppression, liver transplantation has become a realistic treatment for HIV/HCV co-infected patients.
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Affiliation(s)
- Mitsuhisa Takatsuki
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
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Fransen van de Putte DE, Makris M, Fischer K, Yee TT, Kirk L, van Erpecum KJ, Patch D, Posthouwer D, Mauser-Bunschoten EP. Long-term follow-up of hepatitis C infection in a large cohort of patients with inherited bleeding disorders. J Hepatol 2014; 60:39-45. [PMID: 23978717 DOI: 10.1016/j.jhep.2013.08.010] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2013] [Revised: 08/04/2013] [Accepted: 08/06/2013] [Indexed: 01/16/2023]
Abstract
BACKGROUND & AIMS Patients with inherited bleeding disorders are an interesting group to study the long-term course of chronic hepatitis C virus (HCV) infection, because of their uniform mode of infection and reliable follow-up. Our aim was to assess the long-term occurrence of adverse liver-related events in these patients. METHODS The occurrence and determinants of end-stage liver disease (ESLD) were assessed using retrospective data of 863 HCV infected patients with inherited bleeding disorders from the Netherlands and the UK. RESULTS Median follow-up since HCV infection was 31 years, while 30% of patients had >35 follow-up years. Nineteen percent of patients spontaneously cleared the virus and 81% developed chronic HCV infection. Of the 700 patients with chronic HCV, 90 (13%) developed ESLD. Hepatocellular carcinoma (HCC) was diagnosed in 3% of patients with chronic HCV, 41% of which occurred in the last six years. Determinants of ESLD development were age at infection (hazard ratio (HR) 1.09 per year increase), HIV co-infection (HR 10.85), history of alcohol abuse (HR 4.34) and successful antiviral treatment (HR 0.14). Of the 487 patients who were still alive at the end of follow-up, 49% did not undergo optimal conventional antiviral treatment. CONCLUSIONS After over 30 years of HCV infection, ESLD occurred in a significant proportion of patients with inherited bleeding disorders. HCC appears to be an increasing problem. There is a significant potential for both conventional and new antiviral treatment regimens to try and limit ESLD occurrence in the future.
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Affiliation(s)
| | - Michael Makris
- Sheffield Haemophilia and Thrombosis Centre, Royal Hallamshire Hospital, Sheffield, United Kingdom
| | - Kathelijn Fischer
- Van Creveldkliniek, Department of Hematology, University Medical Center Utrecht, Utrecht, The Netherlands; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Thynn Thynn Yee
- Katharine Dormandy Haemophilia Centre and Thrombosis Unit, Royal Free London NHS Foundation Trust, London, United Kingdom
| | - Lisa Kirk
- Sheffield Haemophilia and Thrombosis Centre, Royal Hallamshire Hospital, Sheffield, United Kingdom
| | - Karel Johannes van Erpecum
- Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - David Patch
- Department of Hepatology, Royal Free London NHS Foundation Trust, London, United Kingdom
| | - Dirk Posthouwer
- Department of Internal Medicine, Maastricht University Medical Center, Maastricht, The Netherlands; Department of Medical Microbiology and Public Health Research Institute (CAPHRI), Maastricht University Medical Center, Maastricht, The Netherlands
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Sagnelli C, Uberti-Foppa C, Pasquale G, De Pascalis S, Coppola N, Albarello L, Doglioni C, Lazzarin A, Sagnelli E. Factors influencing liver fibrosis and necroinflammation in HIV/HCV coinfection and HCV monoinfection. Infection 2013; 41:959-967. [PMID: 23839212 DOI: 10.1007/s15010-013-0502-3] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2013] [Accepted: 06/25/2013] [Indexed: 02/06/2023]
Abstract
OBJECTIVES To define differences in liver histology between HIV/HCV coinfection and HCV monoinfection, and to investigate possible causative factors. METHODS Liver biopsies (LBs) from 440 consecutive HIV/HCV-coinfected patients (Group HIV/HCV) and 374 consecutive HCV-monoinfected patients (Group HCV) were evaluated for necroinflammation and fibrosis (Ishak) by a pathologist unaware of the clinical and laboratory data. All patients were HBsAg-negative, with no history of alcohol abuse and naïve to anti-HCV treatment. At LB, 78.4% of patients in Group HIV/HCV were on an antiretroviral regimen. RESULTS HIV/HCV-coinfected patients compared to the HCV-monoinfected patients were younger (p < 0.0001), more frequently males (p < 0.0001), and had HCV genotype 3 (p < 0.0001); they showed a good immunological condition (CD4+ cell count: 518 ± 166 cells/mm(3)). Patients in Group HIV/HCV more frequently showed a fibrosis score ≥4 (27.5 vs. 20.6%, p < 0.05) and a necroinflammation score ≥9 (25.9 vs. 13.4%; p < 0.0001). The prevalence of patients with fibrosis score ≥4 was significantly higher in older age classes in both Group HIV/HCV (p < 0.005) and Group HCV (p < 0.05). A necroinflammation score ≥9 was significantly higher in older age classes only in Group HIV/HCV (p < 0.05). A multivariate analysis for Group HIV/HCV revealed that the patient age and nadir of CD4+ cell count were independently associated to higher degrees of fibrosis, the patient age and antiretroviral treatment were associated to higher degrees of necroinflammation, and HCV genotype 3 was associated to higher degrees of steatosis. CONCLUSION The data suggest a need for early anti-HCV treatment in both HCV-monoinfected and HIV/HCV-coinfected patients.
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Affiliation(s)
- C Sagnelli
- Clinic of Infectious Diseases and Department of Pathology, Vita-Salute University, San Raffaele Scientific Institute, Milan, Italy,
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Eguchi S, Takatsuki M, Kuroki T. Liver transplantation for patients with human immunodeficiency virus and hepatitis C virus co-infection: update in 2013. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2013; 21:263-8. [PMID: 24027085 DOI: 10.1002/jhbp.31] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Because of the progress of anti-retroviral therapy (ART) for human immunodeficiency virus (HIV), mortality due to opportunistic infection resulting in AIDS has been remarkably reduced. However, meanwhile, half of those patients have died of end-stage liver cirrhosis due to hepatitis C virus (HCV) with liver cirrhosis and early occurrence of hepatocellular carcinoma. Recently, in 2013, non-cirrhotic portal hypertension due to ART drugs or still unknown mechanisms have become problematic with early progression of the disease in this patient population. Liver transplantation (LT) could be one treatment of choice in such cases, but the indications for LT perioperative management, including both HIV and HCV treatments and immunosuppression, are still challenging. In this review, we update the literature on HIV/HCV co-infection and LT as well as recent effort for modifying allocation system for those patients.
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Affiliation(s)
- Susumu Eguchi
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.
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Barcaui HS, Tavares GC, May SB, Brandão-Mello CE, Amendola Pires MM, Barroso PF. Low rates of sustained virologic response with peginterferon plus ribavirin for chronic hepatitis C virus infection in HIV infected patients in Rio de Janeiro, Brazil. PLoS One 2013; 8:e67734. [PMID: 23874441 PMCID: PMC3706550 DOI: 10.1371/journal.pone.0067734] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2013] [Accepted: 05/22/2013] [Indexed: 02/06/2023] Open
Abstract
Background The standard treatment for chronic hepatitis C virus (HCV) infection in HIV-infected subjects is the combination of alfapeginterferon (PEG-IFN) plus ribavirin. We designed this study to evaluate the rate of SVR and predictors of SVR in a public health setting in Rio de Janeiro, Brazil. Methods Retrospective cohort study of HCV/HIV co-infected patients treated with PEG-IFN plus ribavirin from 2004 to 2011 in 3 outpatient units in Rio de Janeiro. Exposure variables included age, sex, CD4+ cell count, HCV genotype, HCV and HIV viral loads, liver histology (METAVIR fibrosis scoring system) and previous treatment. The main outcome measurement was SVR. Results 100 patients were included in this analysis. Median age was 47 years and 68% were male. 80%, 4%, 14% and 2% were infected with HCV genotypes 1, 2, 3 and 4, respectively. At baseline, 77% had HCV viral load greater than 800,000 IU/ml, 99% had CD4+ greater than 200 cells/mm3 and 10% had a diagnosis of cirrhosis. The treatment was withdrawn in 9% of the subjects (5% with adverse effects and 4% dropped out). SVR was observed in 27 (27%) of the 100 patients included. 13 (13%) subjects were classified as null-responders, 33(33%) as non-responders, 9 (9%) as breakthrough and 9(9%) as relapsers. In the multivariate model only being infected with genotype 2 or 3 (p<0.01) and having low levels of gamma glutamyl transferase (GGT) at baseline (p = 0.04), were predictive of SVR. Conclusion SVR in HCV/HIV co-infected subjects in a public health setting is similar to that observed in clinical trials, albeit very low. A delay in therapy initiation should be considered until new therapies as direct acting antiviral drugs (DAA) become widely available and tested in coinfected subjects.
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Affiliation(s)
- Halime Silva Barcaui
- Infectious Diseases Service, Department of Preventive Medicine, Hospital Universitário Clementino Fraga Filho, School of Medicine, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
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Kuehlkamp VM, Schuelter-Trevisol F. Prevalence of human immunodeficiency virus/hepatitis C virus co-infection in Brazil and associated factors: a review. Braz J Infect Dis 2013; 17:455-63. [PMID: 23680064 PMCID: PMC9428044 DOI: 10.1016/j.bjid.2012.10.023] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2012] [Revised: 10/29/2012] [Accepted: 10/29/2012] [Indexed: 11/18/2022] Open
Abstract
The hepatitis C virus and human immunodeficiency virus share the same transmission routes, which makes co-infection an unfavorable condition for the natural history of both viral diseases. In this context, it should be highlighted that the knowledge of the extent of co-infection and associated risk factors is a vital tool for prevention and control over infectious diseases. The aim of this study was to review the literature, seeking to examine the prevalence of human immunodeficiency virus/hepatitis C virus co-infection reported in studies conducted in Brazil, and identify the main risk factors associated with co-infection. The electronic search was conducted in the Medline, Lilacs and SciELO databases. The following keywords were used: human immunodeficiency virus and Hepatitis C or hepatitis C virus and Brazil. The search led to 376 articles, of which 69 were selected for data extraction. We excluded animal studies, reports or case series, review articles, letters to the editor, other types of hepatitis and those studies in which co-infected patients were intentionally selected for comparison to single infected individuals. As a result, 40 articles were reviewed. The majority of the population in these studies was male (71%) and young adults, with a mean age of 26.7 years. The prevalence of hepatitis C virus co-infection among individuals living with human immunodeficiency virus in the studies conducted in Brazil ranged from 3.3% (serum samples) to 82.4% (drug users), with an average of 20.3%. The findings reveal that the prevalence of human immunodeficiency virus/hepatitis C virus co-infection is highly variable, depending on the characteristics of the study population. Risk factors associated with human immunodeficiency virus/hepatitis C virus co-infection were injection drug use and blood transfusion.
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Teira R. Hepatitis-B virus infection predicts mortality of HIV and hepatitis C virus coinfected patients. AIDS 2013; 27:845-8. [PMID: 23380966 DOI: 10.1097/qad.0b013e32835ecaf7] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
To study hepatitis B virus (HBV)-hepatitis C virus (HCV)-HIV triple coinfection in the Spanish VACH cohort, we selected HCV-antibody positive patients who had recorded results for HBV surface antigen (HBsAg) and classified them as HBsAg positive or not. We compared their characteristics and outcome (death by any cause). Six thousand three hundred and seventy-nine patients fulfilled the inclusion criteria. Three hundred and fifty-five (5.6%) were HBsAg positive, which showed an association with mortality (mortality rate ratio: 1.90; 95% confidence interval: 1.42-2.54). This association persisted after adjusting for other prognostic variables.
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Sorafenib for the treatment of unresectable hepatocellular carcinoma in HIV-positive patients. Anticancer Drugs 2013. [DOI: 10.1097/cad.0b013e32835c032f] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
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Comparison of the efficacy of ribavirin plus peginterferon alfa-2b for chronic hepatitis C infection in patients with and without coagulation disorders. J Med Virol 2012; 85:228-34. [DOI: 10.1002/jmv.23444] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/10/2012] [Indexed: 11/07/2022]
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Schwarze-Zander C, Blackard JT, Rockstroh JK. Role of GB virus C in modulating HIV disease. Expert Rev Anti Infect Ther 2012; 10:563-72. [PMID: 22702320 DOI: 10.1586/eri.12.37] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
GB virus C (GBV-C) is a member of the Flaviviridae family and the most closely related human virus to HCV. However, GBV-C does not replicate in hepatocytes, but rather in lymphocytes. GBV-C has a worldwide distribution and is transmitted sexually, parenterally and through mother-to-child transmission. Thus, co-infection with HCV and HIV is common. Until now, no human disease has been associated with GBV-C infection. However, there are several reports of a beneficial effect of GBV-C on HIV disease progression in vivo. Different mechanisms to explain these observations have been proposed, including modification of antiviral cytokine production, HIV co-receptor expression, direct inhibition of HIV-1 entry, T-cell activation and Fas-mediated apoptosis. Further understanding of these mechanisms may open new strategies for the treatment of HIV/AIDS.
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Maimaiti R, Zhang Y, Pan K, Wubuli M, Andersson R. Frequent coinfection with hepatitis among HIV-positive patients in Urumqi, China. J Int Assoc Provid AIDS Care 2012; 12:58-61. [PMID: 23087203 DOI: 10.1177/1545109712446176] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023] Open
Abstract
OBJECTIVE To analyze the epidemiology and outcome for patients with HIV coinfected with hepatitis in comparison with monoinfected patients. METHODS At the First Affiliated Hospital at Xinjiang Medical University in Urumqi, China, 395 patients were diagnosed with HIV between 2001 and 2010. The main routes of transmission were sexual (30%) and intravenous drug use (33%). The patient records were studied retrospectively. RESULTS A total of 135 patients had markers of viral hepatitis (34.2%). Abnormal liver function was seen among 48.9% of these patients. Hepatitis B surface antigen was positive in 24 patients (6.1%), with 15 (3.8%) being hepatitis B virus (HBV)-DNA positive, none on tenofovir treatment, because it is still not provided free in Xinjiang. Hepatitis C antibodies were found in 98 patients (24.8%), 46 (11.6%) were hepatitis C virus (HCV)-RNA positive. Only 1 patient had been treated with interferon and ribavirin. Both HBV and HCV were found in 13 (3.3%) of the patients. CONCLUSIONS Nearly half of the HIV patients in Urumqi had markers of hepatitis. Only antiretroviral treatment is provided free, and most of the patients cannot afford the hepatitis treatment they need, which has to be addressed in the treatment programs.
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Affiliation(s)
- Rena Maimaiti
- Department of Prevention and Care, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, China.
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40
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Gastaca M, Aguero F, Rimola A, Montejo M, Miralles P, Lozano R, Castells L, Abradelo M, Mata MDL, San Juan Rodríguez F, Cordero E, Campo SD, Manzardo C, de Urbina JO, Pérez I, Rosa GDL, Miro JM. Liver retransplantation in HIV-infected patients: a prospective cohort study. Am J Transplant 2012; 12:2465-76. [PMID: 22703615 DOI: 10.1111/j.1600-6143.2012.04142.x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Information regarding liver retransplantation in HIV-infected patients is scant. Data from 14 HIV-infected patients retransplanted between 2002 and 2011 in Spain (6% retransplantation rate) were analyzed and compared with those from 157 matched HIV-negative retransplanted patients. In HIV-infected patients, early (≤30 days) retransplantation was more frequently indicated (57% vs. 29%; p = 0.057), and retransplantation for HCV recurrence was less frequently indicated (7% vs. 37%; p = 0.036). Survival probability after retransplantation in HIV-positive patients was lower than in HIV-negative patients, 42% versus 64% at 3 years, although not significantly (p = 0.160). Among HIV-infected patients, those with undetectable HCV RNA at retransplantation and those with late (>30 days) retransplantation showed better 3-year survival probability (80% and 67%, respectively), similar to that in their respective HIV-negative counterparts (72% and 70%). In HIV-infected and HIV-negative patients, 3-year survival probability in those with positive HCV RNA at retransplantation was 22% versus 65% (p = 0.008); in those with early retransplantation, 3-year survival probability was 25% versus 56% (p = 0.282). HIV infection was controlled with antiretroviral therapy after retransplantation. In conclusion, HIV-infected patients taken as a whole have unsatisfactory survival after liver retransplantation, although patients with undetectable HCV RNA at retransplantation or undergoing late retransplantation show a more favorable outcome.
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Affiliation(s)
- M Gastaca
- Hospital Universitario de Cruces, University of the Basque Country, Bilbao, Spain
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41
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Clausen LN, Astvad K, Ladelund S, Larsen MV, Schønning K, Benfield T. Hepatitis C viral load, genotype 3 and interleukin-28B CC genotype predict mortality in HIV and hepatitis C-coinfected individuals. AIDS 2012; 26:1509-16. [PMID: 22555162 DOI: 10.1097/qad.0b013e3283553581] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE We hypothesized that hepatitis C virus (HCV) load and genotype may influence all-cause mortality in HIV-HCV-coinfected individuals. DESIGN AND METHODS Observational prospective cohort study. Mortality rates were compared in a time-updated multivariate Poisson regression analysis. RESULTS We included 264 consecutive HIV-HCV-coinfected individuals. During 1143 person years at risk (PYR) 118 individuals died [overall mortality rate 10 (95% confidence interval; 8, 12)/100 PYR]. In multivariate analysis, a 1 log increase in HCV viral load was associated with a 30% higher mortality risk [adjusted mortality rate ratio (aMRR): 1.30 (1.10,1.54)] when adjusted for sex, age, HIV exposure group, CD4 cell count, HIV RNA, HCV genotype and interleukin (IL)-28B genotype. Further, HCV genotype 3 vs. 1 [aMRR: 1.83 (1.12, 2.98)] and HIV RNA [aMRR: 3.14 (1.37,7.17) for undetectable vs. just detectable HIV RNA] were independent predictors of mortality, whereas a higher CD4 cell count was associated with a 41% reduction in mortality rate per 50 cell increase between 0 and 200 cells/μl [aMRR: 0.59 (0.48, 0.72)] and a 10% reduction for increases above 200 cells/μl [aMRR: 0.90 (0.82-0.98)]. IL28B) CC genotype was associated with 54% higher mortality risk [aMRR: 1.54 (0.89, 3.82] compared to TT genotype. CONCLUSION High-HCV viral load, HCV genotype 3 and IL28B genotype CC had a significant influence on the risk of all-cause mortality among individuals coinfected with HIV-1. This may have consequences for the management of HIV-HCV-coinfected individuals.
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42
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Ragni MV, Devera ME, Roland ME, Wong M, Stosor V, Sherman KE, Hardy D, Blumberg E, Fung J, Barin B, Stablein D, Stock PG. Liver transplant outcomes in HIV+ haemophilic men. Haemophilia 2012; 19:134-40. [PMID: 22762561 DOI: 10.1111/j.1365-2516.2012.02905.x] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/21/2012] [Indexed: 12/14/2022]
Abstract
Hepatitis C virus infection is the major cause of end-stage liver disease and the major indication for transplantation (OLTX), including among HIV-HCV co-infected individuals. The age of HCV acquisition differs between haemophilic and non-haemophilic candidates, which may affect liver disease outcomes. The purpose of the study was to compare rates of pre- and post-OLTX mortality between co-infected haemophilic and non-haemophilic subjects without hepatocellular cancer participating in the Solid Organ Transplantation in HIV Study (HIV-TR). Clinical variables included age, gender, race, liver disease aetiology, BMI, antiretroviral therapy, MELD score, CD4 + cell count, HIV RNA PCR and HCV RNA PCR. Time to transplant, rejection and death were determined. Of 104 HIV-HCV positive subjects enrolled, 34 (32.7%) underwent liver transplantation, including 7 of 15 (46.7%) haemophilic and 27 of 89 (30.3%) non-haemophilic candidates. Although haemophilic subjects were younger, median 41 vs. 47 years, P = 0.01, they were more likely than non-haemophilic subjects to die pre-OLTX, 5 (33.3%) vs. 13 (14.6%), P = 0.03, and reached MELD = 25 marginally faster, 0.01 vs. 0.7 years, P = 0.06. The groups did not differ in baseline BMI, CD4, detectable HIV RNA, detectable HCV RNA, time to post-OLTX death (P = 0.64), graft loss (P = 0.80), or treated rejection (P = 0.77). The rate of rejection was 14% vs. 36% at 1-year and 36% vs. 43% at 3-year, haemophilic vs. non-haemophilic subjects, respectively, and post-OLTX survival, 71% vs. 66% at 1-year and 38% vs. 53% at 3-year. Despite similar transplant outcomes, pretransplant mortality is higher among co-infected haemophilic than non-haemophilic candidates.
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Affiliation(s)
- M V Ragni
- Department of Medicine and Surgery, University of Pittsburgh, Pittsburgh, PA 15213-4306, USA
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Harfouch S, Guiguet M, Valantin MA, Samri A, Ouazene Z, Slama L, Dominguez S, Simon A, Theodorou I, Thibault V, Autran B. Lack of TGF-β production by hepatitis C virus-specific T cells during HCV acute phase is associated with HCV clearance in HIV coinfection. J Hepatol 2012; 56:1259-68. [PMID: 22326469 DOI: 10.1016/j.jhep.2012.01.021] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2011] [Revised: 01/05/2012] [Accepted: 01/05/2012] [Indexed: 01/07/2023]
Abstract
BACKGROUND & AIMS Immunity and genetic factors govern the recovery from acute hepatitis C virus (HCV) infection. No predictive factors have been yet identified in patients coinfected with the human immunodeficiency virus (HIV). We investigated whether early T cell responses to HCV producing transforming-growth-factor beta (TGF-β) predict the outcome of acute HCV coinfection, independently of the IL-28B gene polymorphism. METHODS Intracellular cytokine staining assays against HCV-core, E1, NS2, and NS4 overlapping peptides were used for the analysis of peripheral HCV-specific TGF-β-producing T cells. Patients were genotyped for IL-28B polymorphisms. Healthy donors' samples were tested as controls. Twenty-four acute hepatitis C-HIV+ patients were followed-up for 15 months defining two groups: (A) Recovered (n=16, 5 spontaneous recoveries, 11 sustained virologic response after treatment), (B) Chronic HCV (n=8, 4 spontaneous chronic course, 4 therapeutic failures). RESULTS During the acute pretreatment phase, core/NS2-specific TGF-β-producing CD4+ and/or CD8+ T cells were detected in 8/24 (33%) patients. Lack of anti-HCV TGF-β+ cells was characteristic of healthy donors and Group A, except for 2 cases, with frequencies significantly lower than in Group B (p=0.04 and 0.01), and was associated with recovery in 14/16 cases. Presence of anti-HCV TGF-β+ cells was associated with persistent viremia in 6/8 cases (p=0.005). This profile remained stable over time. Such TGF-β production was independent of the rs129679860 SNP (p=1.0) which was not associated with recovery (p=1.0). CONCLUSIONS During acute hepatitis C, pre-therapeutic HCV-specific TGF-β-producing T cells are a new marker independent of the IL-28B gene polymorphism, predicting the lack of spontaneous or therapeutic HCV clearance.
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Affiliation(s)
- Sawsan Harfouch
- INSERM, UMRS-945, Laboratoire Immunité et Infection, Hôpital Pitié-Salpêtrière, F-75013 Paris, France
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44
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Klein MB, Rollet KC, Saeed S, Cox J, Potter M, Cohen J, Conway B, Cooper C, Côté P, Gill J, Haase D, Haider S, Hull M, Moodie E, Montaner J, Pick N, Rachlis A, Rouleau D, Sandre R, Tyndall M, Walmsley S. HIV and hepatitis C virus coinfection in Canada: challenges and opportunities for reducing preventable morbidity and mortality. HIV Med 2012; 14:10-20. [PMID: 22639840 DOI: 10.1111/j.1468-1293.2012.01028.x] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/10/2012] [Indexed: 12/21/2022]
Abstract
OBJECTIVES Hepatitis C virus (HCV) has emerged as an important health problem in the era of effective HIV treatment. However, very few data exist on the health status and disease burden of HIV/HCV-coinfected Canadians. METHODS HIV/HCV-coinfected patients were enrolled prospectively in a multicentre cohort from 16 centres across Canada between 2003 and 2010 and followed every 6 months. We determined rates of a first liver fibrosis or endstage liver disease (ESLD) event and all-cause mortality since cohort enrolment and calculated standardized mortality ratios compared with the general Canadian population. RESULTS A total of 955 participants were enrolled in the study and followed for a median of 1.4 (interquartile range 0.5-2.3) years. Most were male (73%) with a median age of 44.5 years; 13% self-identified as aboriginal. There were high levels of current injecting drug and alcohol use and poverty. Observed event rates [per 100 person-years; 95% confidence interval (CI)] were: significant fibrosis (10.21; 8.49, 12.19), ESLD (3.16; 2.32, 4.20) and death (3.72; 2.86, 4.77). The overall standardized mortality ratio was 17.08 (95% CI 12.83, 21.34); 12.80 (95% CI 9.10, 16.50) for male patients and 28.74 (95% CI 14.66, 42.83) for female patients. The primary causes of death were ESLD (29%) and overdose (24%). CONCLUSIONS We observed excessive morbidity and mortality in this HIV/HCV-coinfected population in care. Over 50% of observed deaths may have been preventable. Interventions aimed at improving social circumstances, reducing harm from drug and alcohol use and increasing the delivery of HCV treatment in particular will be necessary to reduce adverse health outcomes among HIV/HCV-coinfected persons.
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Affiliation(s)
- M B Klein
- Department of Medicine, Divisions of Infectious Diseases/Immunodeficiency, Royal Victoria Hospital, McGill University Health Centre, Montreal, QC, Canada.
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45
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Konkle BA. The aging patient with hemophilia. Am J Hematol 2012; 87 Suppl 1:S27-32. [PMID: 22430948 DOI: 10.1002/ajh.23161] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2012] [Revised: 02/06/2012] [Accepted: 02/08/2012] [Indexed: 12/23/2022]
Abstract
The prospects for many boys born with hemophilia today include a normal life expectancy and minimal to no joint disease. However, despite the availability of safe replacement clotting factor concentrates and effective antiviral treatment, the aging patient with hemophilia today faces many challenges. These include management of their hemophilia as well as the same age-related health issues as experienced in the general population. While increasing, data on the prevalence of comorbidities and their management in the hemophilia population remain limited. This review will focus on issues related to management of hemophilia and complications of cardiovascular, musculoskeletal, hepatic, and renal disease. Available research is summarized and potential approaches to management are discussed.
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Affiliation(s)
- Barbara A Konkle
- Puget Sound Blood Center, University of Washington School of Medicine, Seattle, Washington 98104, USA.
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46
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Sherman KE, Thomas DL, Chung RT. Human immunodeficiency virus and liver disease forum 2010: conference proceedings. Hepatology 2011; 54:2245-53. [PMID: 21898501 PMCID: PMC3795389 DOI: 10.1002/hep.24651] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
Liver disease continues to represent a critical mediator of morbidity and mortality in those with human immunodeficiency virus (HIV) infection. The frequent presence and overlap of concomitant injurious processes, including hepatitis C virus and hepatitis B virus infections, hepatoxicity associated with antiretroviral therapeutic agents, alcohol, and other toxins, in the setting of immunosuppression lead to rapid fibrotic progression and early development of end-stage liver disease. This conference summary describes the proceedings of a state-of-the-art gathering of international experts designed to highlight the status of current research in epidemiology, natural history, pathogenesis, and treatment of HIV and liver disease.
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Affiliation(s)
- Kenneth E. Sherman
- Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, OH
| | - David L. Thomas
- Division of Infectious Diseases, Johns Hopkins University Medical Center, Baltimore, MD
| | - Raymond T. Chung
- Harvard Medical School and Massachusetts General Hospital, Boston, MA
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Sánchez-Conde M, Miralles P, Bellón JM, Rincón D, Ramírez M, Gutiérrez I, Ripoll C, López JC, Cosín J, Clemente G, Lo Iacono O, Bañares R, Berenguer J. Use of transient elastography (FibroScan®) for the noninvasive assessment of portal hypertension in HIV/HCV-coinfected patients. J Viral Hepat 2011; 18:685-91. [PMID: 21914085 DOI: 10.1111/j.1365-2893.2010.01371.x] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The hepatic venous pressure gradient (HVPG) is the gold standard for assessing portal pressure and correlates with the occurrence of portal hypertension (PH)-related complications. Transient elastography (TE) is a new, highly accurate noninvasive technique, which enables us to evaluate hepatic fibrosis to detect advanced fibrosis and cirrhosis. We performed a hepatic haemodynamic study and TE in 38 HIV/HCV-coinfected patients. The association between HVPG and liver stiffness was assessed by linear regression. The diagnostic value of TE was assessed by receiver operating characteristic (ROC) curves. We considered clinically significant PH as an HVPG ≥ 10 mmHg and severe PH as an HVPG ≥ 12 mmHg. A total of 38 HIV/HCV-coinfected patients were included. Twenty-eight patients (73.7%) had clinically significant PH (HVPG ≥ 10 mmHg), and 23 (60.5%) of these had severe PH (HVPG ≥ 12 mmHg). We found a statistically significant association between liver stiffness (kPa) and HVPG (r(2) = 0.46, P < 0.001, straight line equation HVPG=7.4 + 0.204*TE). The areas under the ROC curves were 0.80 [95% confidence interval (CI), 0.64-0.97] and 0.80 (95% CI, 0.66-0.94) for the prediction of HVPG ≥ 10 and ≥ 12 mmHg, respectively. Our data suggest that TE can predict the presence of clinically significant and severe PH in HIV/HCV-coinfected patients.
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Affiliation(s)
- M Sánchez-Conde
- Infectious Diseases and HIV Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
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Abstract
Chronic liver injuries of different etiologies eventually lead to fibrosis, a scarring process associated with increased and altered deposition of extracellular matrix in the liver. Progression of fibrosis has a major worldwide clinical impact due to the high number of patients affected by chronic liver disease which can lead to severe complications, expensive treatment, a possible need for liver transplantation, and death. Liver fibrogenesis is characterized by activation of hepatic stellate cells and other extracellular matrix producing cells. Liver fibrosis may regress following specific therapeutic interventions. Other than removing agents causing chronic liver damage, no antifibrotic drug is currently available in clinical practice. The extent of liver fibrosis is variable between individuals, even after controlling for exogenous factors. Thus, host genetic factors are considered to play an important role in the process of liver scarring. Until recently it was believed that this process was irreversible. However, emerging experimental and clinical evidence is starting to show that even cirrhosis in its early stages is potentially reversible.
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Affiliation(s)
- Mona H Ismail
- Department of Internal Medicine, Division of Gastroenterology, King Fahad University Hospital, Al-Khobar, Saudi Arabia
| | - Massimo Pinzani
- Dipartimento di Medicina Interna Center for Research, High Education and Transfer, Università degli Studi di Firenze, Florence, Italy
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50
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Ismail MH, Pinzani M. Reversal of hepatic fibrosis: pathophysiological basis of antifibrotic therapies. HEPATIC MEDICINE : EVIDENCE AND RESEARCH 2011. [PMID: 24367223 DOI: 10.2147/hmer.s905] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
Chronic liver injuries of different etiologies eventually lead to fibrosis, a scarring process associated with increased and altered deposition of extracellular matrix in the liver. Progression of fibrosis has a major worldwide clinical impact due to the high number of patients affected by chronic liver disease which can lead to severe complications, expensive treatment, a possible need for liver transplantation, and death. Liver fibrogenesis is characterized by activation of hepatic stellate cells and other extracellular matrix producing cells. Liver fibrosis may regress following specific therapeutic interventions. Other than removing agents causing chronic liver damage, no antifibrotic drug is currently available in clinical practice. The extent of liver fibrosis is variable between individuals, even after controlling for exogenous factors. Thus, host genetic factors are considered to play an important role in the process of liver scarring. Until recently it was believed that this process was irreversible. However, emerging experimental and clinical evidence is starting to show that even cirrhosis in its early stages is potentially reversible.
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Affiliation(s)
- Mona H Ismail
- Department of Internal Medicine, Division of Gastroenterology, King Fahad University Hospital, Al-Khobar, Saudi Arabia
| | - Massimo Pinzani
- Dipartimento di Medicina Interna Center for Research, High Education and Transfer, Università degli Studi di Firenze, Florence, Italy
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