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Article: Early Successes in an Open Access, Provincially Funded Hepatitis C Treatment Program in Prince Edward Island.

Francheville, Jordan W / Rankin, Robin / Beck, Jeremy / Hoare, Connie / Materniak, Stefanie / German, Greg / Barrett, Lisa / Bunimov-Wall, Natalie / Smyth, Daniel

Annals of hepatology

2019 Volume 17, Issue 2, Page(s) 223–231

Abstract: Introduction: The availability of curative hepatitis C therapies has created an opportunity ... design, all chronic hepatitis C referrals received from April 2015 to April 2016 were recorded ... of this multi-phase hepatitis C elimination strategy demonstrate improved access to treatment, and high rates ...

Abstract	Introduction: The availability of curative hepatitis C therapies has created an opportunity to improve treatment delivery and access. Local providers, government, industry, and community groups in Prince Edward Island developed an innovative province-wide care model. Our goal was to describe the first year of program implementation. Material and methods: Using a communitybased prospective observational study design, all chronic hepatitis C referrals received from April 2015 to April 2016 were recorded in a database. Primary analysis assessed the time from referral to assessment/treatment, as well as the number of referrals, assessments, and treatment initiations. Secondary objectives included: (1) treatment effectiveness using intention-to-treat analysis; and (2) patient treatment experience assessed using demographics, adverse events, and medication adherence. Results: During the study period 242 referrals were received, 123 patients were seen for intake assessments, and 93 initiated direct-acting antiviral therapy based on medical need. This is compared to 4 treatment initiations in the previous 2 years. The median time from assessment to treatment initiation was 3 weeks. Eighty-two of 84 (97.6%, 95% CI 91.7 - 99.7%) patients for whom outcome data were available achieved sustained virologic response at 12 weeks post-treatment; 1 was lost to follow-up and 1 died from an unrelated event. In the voluntary registry, 39.7% of patients reported missed treatment doses. Conclusion: In conclusion, results from the first 12 months of this multi-phase hepatitis C elimination strategy demonstrate improved access to treatment, and high rates of safe engagement and cure for patients living with chronic hepatitis C genotype 1 infections.
MeSH term(s)	Adult ; Aged ; Antiviral Agents/adverse effects ; Antiviral Agents/economics ; Antiviral Agents/therapeutic use ; Community Health Services/economics ; Databases, Factual ; Delivery of Health Care, Integrated/economics ; Drug Costs ; Female ; Genotype ; Health Services Accessibility/economics ; Hepacivirus/drug effects ; Hepacivirus/genetics ; Hepatitis C, Chronic/diagnosis ; Hepatitis C, Chronic/drug therapy ; Hepatitis C, Chronic/economics ; Hepatitis C, Chronic/epidemiology ; Humans ; Male ; Middle Aged ; Prince Edward Island/epidemiology ; Program Evaluation ; Prospective Studies ; Referral and Consultation/economics ; Time Factors ; Time-to-Treatment/economics ; Treatment Outcome ; Young Adult
Chemical Substances	Antiviral Agents
Language	English
Publishing date	2019-05-08
Publishing country	Mexico
Document type	Journal Article ; Observational Study ; Duplicate Publication
ZDB-ID	2188733-0
ISSN	1665-2681
ISSN	1665-2681
DOI	10.5604/01.3001.0010.8637
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Article ; Online: Persistence of Hepatitis C Virus Traces after Spontaneous Resolution of Hepatitis C.

Chen, Annie Y / Hoare, Matthew / Shankar, Arun N / Allison, Michael / Alexander, Graeme J M / Michalak, Tomasz I

PloS one

2015 Volume 10, Issue 10, Page(s) e0140312

Abstract: Hepatitis C virus (HCV) frequently causes chronic hepatitis, while spontaneous recovery ... from infection is infrequent. Persistence of HCV after self-limited (spontaneous) resolution of hepatitis C was ... self-resolved hepatitis C in individuals with normal liver enzymes and undetectable virus ...

Abstract	Hepatitis C virus (HCV) frequently causes chronic hepatitis, while spontaneous recovery from infection is infrequent. Persistence of HCV after self-limited (spontaneous) resolution of hepatitis C was rarely investigated. The current study aimed to assess incidence and robustness of HCV persistence after self-resolved hepatitis C in individuals with normal liver enzymes and undetectable virus by conventional tests. Applying high sensitivity HCV RNA detection approaches, we analyzed plasma and peripheral blood mononuclear cells (PBMC) from individuals with previous hepatitis C infection. Parallel plasma and PBMC from 24 such non-viraemic individuals followed for 0.3-14.4 (mean 6.4) years were examined. Additional samples from 9 of them were obtained 4.5-7.2 (mean 5.9) years later. RNA was extracted from 250 μl plasma and, if HCV negative, from ~5 ml after ultracentrifugation, and from ex vivo stimulated PBMC. PBMC with evidence of HCV replication from 4 individuals were treated with HCV protease inhibitor, telaprevir. HCV RNA was detected in 14/24 (58.3%) plasma and 11/23 (47.8%) PBMC obtained during the first collection. HCV RNA replicative strand was evident in 7/11 (63.6%) PBMC. Overall, 17/24 (70.8%) individuals carried HCV RNA at mean follow-up of 5.9 years. Samples collected 4.5-7.2 years later revealed HCV in 4/9 (44.4%) plasma and 5/9 (55.5%) PBMC, while 4 (80%) of these 5 PBMC demonstrated virus replicative strand. Overall, 6/9 (66.7%) individuals remained viraemic for up to 20.7 (mean 12.7) years. Telaprevir entirely eliminated HCV replication in the PBMC examined. In conclusion, our results indicate that HCV can persist long after spontaneous resolution of hepatitis C at levels undetectable by current testing. An apparently effective host immune response curtailing hepatitis appears insufficient to completely eliminate the virus. The long-term morbidity of asymptomatic HCV carriage should be examined even in individuals who achieve undetectable HCV by standard testing and their need for treatment should be assessed.
MeSH term(s)	Adult ; Aged ; Base Sequence ; Female ; Follow-Up Studies ; Hepacivirus/metabolism ; Hepatitis C, Chronic/blood ; Hepatitis C, Chronic/drug therapy ; Humans ; Leukocytes, Mononuclear/metabolism ; Leukocytes, Mononuclear/virology ; Male ; Middle Aged ; Molecular Sequence Data ; Oligopeptides/administration & dosage ; RNA, Viral/blood ; Remission, Spontaneous ; Time Factors
Chemical Substances	Oligopeptides ; RNA, Viral ; telaprevir (655M5O3W0U)
Language	English
Publishing date	2015
Publishing country	United States
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0140312
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Article: Early Successes in an Open Access, Provincially Funded Hepatitis C Treatment Program in Prince Edward Island.

Francheville, Jordan W / Rankin, Robin / Beck, Jeremy / Hoare, Connie / Materniak, Stefanie / German, Greg / Barrett, Lisa / Bunimov-Wall, Natalie / Smyth, Daniel

Annals of hepatology

2017 Volume 16, Issue 5, Page(s) 749–758

Abstract: Introduction: The availability of curative hepatitis C therapies has created an opportunity ... design, all chronic hepatitis C referrals received from April 2015 to April 2016 were recorded ... phase hepatitis C elimination strategy demonstrate improved access to treatment, and high rates of safe ...

Abstract	Introduction: The availability of curative hepatitis C therapies has created an opportunity to improve delivery and access. Local providers, government, industry, and community groups in Prince Edward Island developed an innovative province-wide care model. Our goal was to describe the first year of program implementation. Material and methods: Using a community based prospective observational study design, all chronic hepatitis C referrals received from April 2015 to April 2016 were recorded in a database. Primary analysis assessed the time from referral to assessment/treatment, as well as the number of referrals, assessments, and treatment initiations. Secondary objectives included: 1) Treatment effectiveness using intention-to-treat analysis; and 2) Patient treatment experience assessed using demographics, adverse events, and medication adherence. Results: During the study period 242 referrals were received, 123 patients were seen for intake assessments, and 93 initiated direct-acting antiviral therapy based on medical need. This is compared to 4 treatment initiations in the previous 2 years. The median time from assessment to treatment initiation was 3 weeks. Eighty-two of 84 (97.6%, 95% CI 91.7 - 99.7%) patients for whom outcome data were available achieved sustained virologic response at 12 weeks post-treatment; 1 was lost to follow-up and 1 died from an unrelated event. In the voluntary registry, 39.7% of patients reported missed treatment doses. Conclusion: In conclusion, results from the first 12 months of this multi-phase hepatitis C elimination strategy demonstrate improved access to treatment, and high rates of safe engagement and cure for patients living with chronic hepatitis C genotype 1 infections.
MeSH term(s)	Adult ; Aged ; Antiviral Agents/adverse effects ; Antiviral Agents/therapeutic use ; Cost-Benefit Analysis ; Databases, Factual ; Drug Costs ; Female ; Financing, Government ; Health Care Costs ; Health Services Accessibility ; Hepatitis C, Chronic/diagnosis ; Hepatitis C, Chronic/drug therapy ; Hepatitis C, Chronic/economics ; Hepatitis C, Chronic/virology ; Humans ; Intention to Treat Analysis ; Male ; Medication Adherence ; Middle Aged ; Prince Edward Island ; Program Evaluation ; Prospective Studies ; Sustained Virologic Response ; Time Factors ; Time-to-Treatment ; Treatment Outcome ; Young Adult
Chemical Substances	Antiviral Agents
Language	English
Publishing date	2017-09-27
Publishing country	Mexico
Document type	Journal Article ; Observational Study ; Duplicate Publication
ZDB-ID	2188733-0
ISSN	1665-2681
ISSN	1665-2681
DOI	10.5604/01.3001.0010.2757
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Article ; Online: Neuroimaging abnormalities in clade C HIV are independent of Tat genetic diversity.

Paul, Robert H / Phillips, Sarah / Hoare, Jacqueline / Laidlaw, David H / Cabeen, Ryan / Olbricht, Gayla R / Su, Yuqing / Stein, Dan J / Engelbrecht, Susan / Seedat, Soraya / Salminen, Lauren E / Baker, Laurie M / Heaps, Jodi / Joska, John

Journal of neurovirology

2017 Volume 23, Issue 2, Page(s) 319–328

Abstract: Controversy remains regarding the neurotoxicity of clade C human immunodeficiency virus (HIV-C ... When examined in preclinical studies, a cysteine to serine substitution in the C31 dicysteine motif of the HIV-C ... patient cohort studies identify significant neuropsychological impairment among HIV-C individuals ...

Abstract	Controversy remains regarding the neurotoxicity of clade C human immunodeficiency virus (HIV-C). When examined in preclinical studies, a cysteine to serine substitution in the C31 dicysteine motif of the HIV-C Tat protein (C31S) results in less severe brain injury compared to other viral clades. By contrast, patient cohort studies identify significant neuropsychological impairment among HIV-C individuals independent of Tat variability. The present study clarified this discrepancy by examining neuroimaging markers of brain integrity among HIV-C individuals with and without the Tat substitution. Thirty-seven HIV-C individuals with the Tat C31S substitution, 109 HIV-C individuals without the Tat substitution (C31C), and 34 HIV- controls underwent 3T structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). Volumes were determined for the caudate, putamen, thalamus, corpus callosum, total gray matter, and total white matter. DTI metrics included fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD). Tracts of interest included the anterior thalamic radiation (ATR), cingulum bundle (CING), uncinate fasciculus (UNC), and corpus callosum (CC). HIV+ individuals exhibited smaller volumes in subcortical gray matter, total gray matter and total white matter compared to HIV- controls. HIV+ individuals also exhibited DTI abnormalities across multiple tracts compared to HIV- controls. By contrast, neither volumetric nor diffusion indices differed significantly between the Tat C31S and C31C groups. Tat C31S status is not a sufficient biomarker of HIV-related brain integrity in patient populations. Clinical attention directed at brain health is warranted for all HIV+ individuals, independent of Tat C31S or clade C status.
Language	English
Publishing date	2017-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	1283265-0
ISSN	1538-2443 ; 1355-0284
ISSN (online)	1538-2443
ISSN	1355-0284
DOI	10.1007/s13365-016-0503-y
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Article ; Online: Persistence of Hepatitis C Virus Traces after Spontaneous Resolution of Hepatitis C.

Annie Y Chen / Matthew Hoare / Arun N Shankar / Michael Allison / Graeme J M Alexander / Tomasz I Michalak

PLoS ONE, Vol 10, Iss 10, p e

2015 Volume 0140312

Abstract	Hepatitis C virus (HCV) frequently causes chronic hepatitis, while spontaneous recovery from infection is infrequent. Persistence of HCV after self-limited (spontaneous) resolution of hepatitis C was rarely investigated. The current study aimed to assess incidence and robustness of HCV persistence after self-resolved hepatitis C in individuals with normal liver enzymes and undetectable virus by conventional tests. Applying high sensitivity HCV RNA detection approaches, we analyzed plasma and peripheral blood mononuclear cells (PBMC) from individuals with previous hepatitis C infection. Parallel plasma and PBMC from 24 such non-viraemic individuals followed for 0.3-14.4 (mean 6.4) years were examined. Additional samples from 9 of them were obtained 4.5-7.2 (mean 5.9) years later. RNA was extracted from 250 μl plasma and, if HCV negative, from ~5 ml after ultracentrifugation, and from ex vivo stimulated PBMC. PBMC with evidence of HCV replication from 4 individuals were treated with HCV protease inhibitor, telaprevir. HCV RNA was detected in 14/24 (58.3%) plasma and 11/23 (47.8%) PBMC obtained during the first collection. HCV RNA replicative strand was evident in 7/11 (63.6%) PBMC. Overall, 17/24 (70.8%) individuals carried HCV RNA at mean follow-up of 5.9 years. Samples collected 4.5-7.2 years later revealed HCV in 4/9 (44.4%) plasma and 5/9 (55.5%) PBMC, while 4 (80%) of these 5 PBMC demonstrated virus replicative strand. Overall, 6/9 (66.7%) individuals remained viraemic for up to 20.7 (mean 12.7) years. Telaprevir entirely eliminated HCV replication in the PBMC examined. In conclusion, our results indicate that HCV can persist long after spontaneous resolution of hepatitis C at levels undetectable by current testing. An apparently effective host immune response curtailing hepatitis appears insufficient to completely eliminate the virus. The long-term morbidity of asymptomatic HCV carriage should be examined even in individuals who achieve undetectable HCV by standard testing and their need for treatment should ...
Keywords	Medicine ; R ; Science ; Q
Subject code	360
Language	English
Publishing date	2015-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Book: Reflections on the work of C. A. R. Hoare

Hoare, C. A. R / Jones, Cliff B / Roscoe, A. W / Wood, Kenneth R

(History of computing)

2010

Author's details	Cliff B. Jones; A. W. Roscoe; A. W. Roscoe (eds.)
Series title	History of computing
Keywords	Computer science ; Electronic data processing
Language	English
Size	XII, 430 S., graph. Darst., 235 mm x 155 mm
Publisher	Springer
Publishing place	London u.a.
Document type	Book
Note	Literaturangaben
ISBN	9781848829114 ; 9781848829121 ; 1848829116 ; 1848829124
Database	Library catalogue of the German National Library of Science and Technology (TIB), Hannover

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Article ; Online: Impact of the HIV Tat C30C31S dicysteine substitution on neuropsychological function in patients with clade C disease.

Paul, Robert H / Joska, John A / Woods, Carol / Seedat, Soraya / Engelbrecht, Susan / Hoare, Jacqueline / Heaps, Jodi / Valcour, Victor / Ances, Beau / Baker, Laurie M / Salminen, Lauren E / Stein, Dan J

Journal of neurovirology

2014 Volume 20, Issue 6, Page(s) 627–635

Abstract: ... of the Tat protein that is associated with reduced neurovirulence in clade C human immunodeficiency virus ... HIV). However, clinical studies of patients infected with clade C HIV have reported significant levels ... of cognitive impairment. To date, no study has specifically examined cognitive function in clade C-infected ...

Abstract	Previous animal studies have identified a C31S residue substitution in the C30C31 dicysteine motif of the Tat protein that is associated with reduced neurovirulence in clade C human immunodeficiency virus (HIV). However, clinical studies of patients infected with clade C HIV have reported significant levels of cognitive impairment. To date, no study has specifically examined cognitive function in clade C-infected patients as a function of the presence or absence of the Tat C31 substitution. The present study investigated the impact of the Tat C30C31S genetic substitution among individuals residing in South Africa infected with clade C HIV that either exhibited the C30C31 motif (n = 128) or the C31S motif (n = 46). A control group of seronegative individuals was included to examine the overall impact of HIV on cognitive performance. All individuals completed a comprehensive neuropsychological battery consisting of tests sensitive to HIV. Results revealed that clade C-infected individuals performed significantly worse across cognitive tests compared to seronegative controls. However, there were no significant differences in cognitive performances between individuals with the C31S motif versus those without the C31S substitution. Proximal CD4 cell count and plasma viral load were unrelated to cognitive performances for either group. Results confirm that the C31S dicysteine motif substitution of the Tat protein does not appreciably moderate neuropsychological outcomes in clade C. Further, these findings highlight the importance of clinical management of cognitive symptoms among individuals infected with this viral clade worldwide.
MeSH term(s)	Adolescent ; Adult ; Amino Acid Substitution ; Animals ; Antiretroviral Therapy, Highly Active ; CD4 Lymphocyte Count ; Cognition ; Executive Function ; Female ; Genotype ; HIV Infections/drug therapy ; HIV Infections/physiopathology ; HIV Infections/virology ; HIV-1/genetics ; HIV-1/pathogenicity ; Humans ; Male ; Neuropsychological Tests ; Reaction Time ; South Africa ; Viral Load ; tat Gene Products, Human Immunodeficiency Virus/genetics
Chemical Substances	tat Gene Products, Human Immunodeficiency Virus
Language	English
Publishing date	2014-11-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1283265-0
ISSN	1538-2443 ; 1355-0284
ISSN (online)	1538-2443
ISSN	1355-0284
DOI	10.1007/s13365-014-0293-z
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Article ; Online: Resting-state functional magnetic resonance imaging in clade C HIV: within-group association with neurocognitive function.

du Plessis, Lindie / Paul, Robert H / Hoare, Jackie / Stein, Dan J / Taylor, Paul A / Meintjes, Ernesta M / Joska, John A

Journal of neurovirology

2017 Volume 23, Issue 6, Page(s) 875–885

Abstract: ... with clade C HIV, no study has examined functional connectivity (FC) using resting-state functional ... magnetic resonance imaging (rs-fMRI) in clade C HIV. In particular, we were interested to explore HIV-only effects ... on neurocognitive function using associations with rs-fMRI. In the present study, 56 treatment-naïve, clade C HIV ...

Abstract	Neuroimaging abnormalities are common in chronically infected HIV-positive individuals. The majority of studies have focused on structural or functional brain outcomes in samples infected with clade B HIV. While preliminary work reveals a similar structural imaging phenotype in patients infected with clade C HIV, no study has examined functional connectivity (FC) using resting-state functional magnetic resonance imaging (rs-fMRI) in clade C HIV. In particular, we were interested to explore HIV-only effects on neurocognitive function using associations with rs-fMRI. In the present study, 56 treatment-naïve, clade C HIV-infected participants (age 32.27 ± 5.53 years, education 10.02 ± 1.72 years, 46 female) underwent rs-fMRI and cognitive testing. Individual resting-state networks were correlated with global deficit scores (GDS) in order to explore associations between them within an HIV-positive sample. Results revealed ten regions in six resting-state networks where FC inversely correlated with GDS scores (worse performance). The networks affected included three independent attention networks: the default mode network (DMN), sensorimotor network, and basal ganglia. Connectivity in these regions did not correlate with plasma viral load or CD4 cell count. The design of this study is unique and has not been previously reported in clade B. The abnormalities related to neurocognitive performance reported in this study of clade C may reflect late disease stage and/or unique host/viral dynamics. Longitudinal studies will help to clarify the clinical significance of resting-state alterations in clade C HIV.
MeSH term(s)	Adolescent ; Adult ; Brain/diagnostic imaging ; Brain/physiopathology ; Brain/virology ; CD4 Lymphocyte Count ; Cognitive Dysfunction/complications ; Cognitive Dysfunction/diagnostic imaging ; Cognitive Dysfunction/physiopathology ; Cognitive Dysfunction/virology ; Connectome ; Female ; Genotype ; HIV Infections/complications ; HIV Infections/diagnostic imaging ; HIV Infections/physiopathology ; HIV Infections/virology ; HIV-1/classification ; HIV-1/genetics ; HIV-1/pathogenicity ; Humans ; Magnetic Resonance Imaging ; Male ; Nerve Net/diagnostic imaging ; Nerve Net/physiopathology ; Nerve Net/virology ; Neural Pathways/diagnostic imaging ; Neural Pathways/physiopathology ; Neural Pathways/virology ; Neuroimaging ; Neuropsychological Tests ; Viral Load
Language	English
Publishing date	2017-10-02
Publishing country	United States
Document type	Journal Article ; Multicenter Study
ZDB-ID	1283265-0
ISSN	1538-2443 ; 1355-0284
ISSN (online)	1538-2443
ISSN	1355-0284
DOI	10.1007/s13365-017-0581-5
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Article ; Online: Early Successes in an Open Access, Provincially Funded Hepatitis C Treatment Program in Prince Edward Island

Jordan W. Francheville / Robin Rankin / Jeremy Beck / Connie Hoare / Stefanie Materniak / Greg German / Lisa Barrett / Natalie Bunimov-Wall / Daniel Smyth

Annals of Hepatology, Vol 17, Iss 2, Pp 223-

2018 Volume 231

Abstract: Introduction. The availability of curative hepatitis C therapies has created an opportunity ... all chronic hepatitis C referrals received from April 2015 to April 2016 were recorded in a database. Primary ... hepatitis C elimination strategy demonstrate improved access to treatment, and high rates of safe engagement ...

Abstract	Introduction. The availability of curative hepatitis C therapies has created an opportunity to improve treatment delivery and access. Local providers, government, industry, and community groups in Prince Edward Island developed an innovative province-wide care model. Our goal was to describe the first year of program implementation.Material and methods. Using a communitybased prospective observational study design, all chronic hepatitis C referrals received from April 2015 to April 2016 were recorded in a database. Primary analysis assessed the time from referral to assessment/treatment, as well as the number of referrals, assessments, and treatment initiations. Secondary objectives included: (1) treatment effectiveness using intention-to-treat analysis; and (2) patient treatment experience assessed using demographics, adverse events, and medication adherence.Results. During the study period 242 referrals were received, 123 patients were seen for intake assessments, and 93 initiated direct-acting antiviral therapy based on medical need. This is compared to 4 treatment initiations in the previous 2 years. The median time from assessment to treatment initiation was 3 weeks. Eighty-two of 84 (97.6%, 95% CI 91.7 - 99.7%) patients for whom outcome data were available achieved sustained virologic response at 12 weeks post-treatment; 1 was lost to follow-up and 1 died from an unrelated event. In the voluntary registry, 39.7% of patients reported missed treatment doses.Conclusion. In conclusion, results from the first 12 months of this multi-phase hepatitis C elimination strategy demonstrate improved access to treatment, and high rates of safe engagement and cure for patients living with chronic hepatitis C genotype 1 infections.
Keywords	Hepatitis C virus ; Direct-acting antivirals ; Real-world ; Sustained virologic response ; Health plan implementation ; Specialties of internal medicine ; RC581-951
Subject code	610
Language	English
Publishing date	2018-03-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
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Article ; Online: A retrospective 15-year review: survival advantage after switching to sirolimus in hepatitis C virus infected liver graft recipients.

Shah, M / Shankar, A / Gee, I / Nash, K / Hoare, M / Gibbs, P / Davies, S / Alexander, G J M

Alimentary pharmacology & therapeutics

2015 Volume 41, Issue 4, Page(s) 379–392

Abstract: ... in hepatitis C virus (HCV)-infected recipients, remains contentious. There is some evidence that sirolimus retards ...

Abstract	Background: The use of sirolimus-based immune suppression in liver transplantation, particularly in hepatitis C virus (HCV)-infected recipients, remains contentious. There is some evidence that sirolimus retards hepatic fibrosis, is renal sparing and may be of benefit in preventing hepatocellular carcinoma (HCC) recurrence. Sirolimus has not been adopted by many transplant centres because of persistent concerns regarding an increased risk of hepatic artery thrombosis, graft loss and death with de novo sirolimus. Aim: To review the impact of switching to sirolimus monotherapy in HCV-infected liver recipients with respect to survival, graft loss and hepatic fibrosis. Methods: A retrospective review of 190 patients from a single centre undergoing first liver transplantation for HCV over 15 years. 113 patients were switched from calcineurin inhibitor (CNI)-based therapy to low-dose sirolimus monotherapy at a median of 15 months after transplantation for HCV-related fibrosis (72%), renal impairment (14%) or high-risk HCC (5%). Results: Patients switched to sirolimus had improved survival (P < 0.001) and slower progression to cirrhosis (P = 0.001). In patients with HCC (n = 91), sirolimus duration rather than strategy was an independent predictor of survival (P = 0.001) and extended time to HCC recurrence (33 vs. 16 months). Patients switched for renal dysfunction showed improvement in serum creatinine (140-108 μmol/L, P = 0.001). Those remaining on CNI-therapy were more likely to develop post-transplant diabetes (P = 0.03). Conclusion: These data suggest selective switching to low-dose sirolimus monotherapy in HCV-positive liver recipients improves clinical outcome.
MeSH term(s)	Adult ; Aged ; Calcineurin Inhibitors/therapeutic use ; Carcinoma, Hepatocellular/prevention & control ; Comorbidity ; Disease Progression ; Female ; Hepacivirus ; Humans ; Immunosuppressive Agents/administration & dosage ; Immunosuppressive Agents/adverse effects ; Immunosuppressive Agents/therapeutic use ; Liver Cirrhosis/prevention & control ; Liver Neoplasms/prevention & control ; Liver Transplantation/methods ; Liver Transplantation/mortality ; Male ; Middle Aged ; Renal Insufficiency/chemically induced ; Retrospective Studies ; Sirolimus/administration & dosage ; Sirolimus/adverse effects ; Sirolimus/therapeutic use
Chemical Substances	Calcineurin Inhibitors ; Immunosuppressive Agents ; Sirolimus (W36ZG6FT64)
Language	English
Publishing date	2015-02
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	639012-2
ISSN	1365-2036 ; 0269-2813 ; 0953-0673
ISSN (online)	1365-2036
ISSN	0269-2813 ; 0953-0673
DOI	10.1111/apt.13049
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Inter-library loan at ZB MED

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In stock of ZB MED Cologne/Königswinter

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