Six Abstracts on Heatitis C Subjects

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Am J Gastroenterol. 2011 Jul 19. doi: 10.1038/ajg.2011.219. [Epub ahead of

print]

A Randomized Controlled Trial of an Integrated Care Intervention to Increase

Eligibility for Chronic Hepatitis C Treatment.

Evon DM, Simpson K, Kixmiller S, Galanko J, Dougherty K, Golin C, Fried MW.

Source

Division of Gastroenterology and Hepatology, UNC School of Medicine, University

of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.

Abstract

OBJECTIVES:

Mental health and substance abuse (MH/SA) comorbidities are the most oft-cited

reasons for deferral from peginterferon (PegIFN) therapy for chronic hepatitis C

virus (HCV). We sought to determine whether an integrated care intervention

(INT) for patients deferred from PegIFN owing to MH/SA could improve subsequent

treatment eligibility rates.

METHODS:

In this randomized controlled trial, 101 HCV patients who were evaluated at two

hepatology centers and deferred from antiviral therapy owing to MH/SA were

enrolled. Participants were randomized to an INT (N=50) or standard of care (SC;

N=51). The INT group received counseling and case management for up to 9 months.

All participants underwent 3-, 6-, and 9-month clinical follow-up visits, where

hepatologists, masked to group, re-evaluated patients for treatment eligibility.

Standardized mood and alcohol use instruments were administered to all

participants to aid clinicians in treatment decisions.

RESULTS:

Of 101 participants, the mean age was 48 years and 50% were men, 61% Caucasian,

and 77% genotype 1. Patients were initially deferred owing to psychiatric issues

(35%), alcohol abuse (31%), drug abuse (9%), or more than one of these reasons

(26%). In an intent-to-treat analysis, 42% (21/50) of INT participants became

eligible for therapy compared to 18% (9/51) of SC participants (P=0.009,

relative risk (RR)=2.38, 95% confidence interval (CI) (1.21, 4.68)). When

baseline predictors significant at P<0.10 in univariate models were entered into

multivariate models adjusted for treatment group, only baseline depression

remained significant (P=0.05, RR=0.98, 95% CI (0.96, 1.00)). With the exception

of a model adjusted for genotype, treatment group remained significant in all

models.

CONCLUSIONS:

This trial suggests that INTs can increase eligibility for HCV treatment and

expand treatment to the underserved population with MH/SA comorbidities.Am J

Gastroenterol advance online publication, 19 July 2011;

doi:10.1038/ajg.2011.219.

PMID: 21769136 [PubMed - as supplied by publisher]

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Dig Dis Sci. 2011 Jul 14. [Epub ahead of print]

Clinical Significance of Discordant Positive Hepatitis C Virus

Transcription-Mediated Amplification Following End of Treatment Response.

Thadani A, Harley J, Rubin J, Lebovics E.

Source

C. Upham Division of Gastroenterology and Hepatobiliary Diseases, New York

Medical College, Munger Pavilion, Suite 206, Valhalla, NY, 10595, USA.

Abstract

BACKGROUND:

Polymerase chain reaction (PCR) assays are the standard for detecting hepatitis

C virus viremia. The transcription-mediated amplification (TMA)-based assay is

more sensitive.

METHODS:

We retrospectively reviewed the charts of patients with a post-end of treatment

(EOT) PCR-/TMA+ result to assess the clinical significance of a positive TMA

result after a PCR negative EOT response or sustained viral response (SVR).

Patients were divided into Group 1: PCR-/TMA+ after EOT response but during 24

week follow-up (n = 4); and Group 2: PCR-/TMA+ after SVR (n = 11).

RESULTS:

All Group 1 patients achieved SVR. No Group 2 patients became PCR positive or

had a rise in ALT. The TMA subsequently became negative in 6/7 patients with

follow-up evaluation.

CONCLUSIONS:

A discordant positive TMA post-EOT response or SVR did not seem to be clinically

significant. This finding supports the possibility that patients with SVR have

an acquired immune surveillance that prevents low-level viremia from progressing

to clinical relapse.

PMID: 21755300 [PubMed - as supplied by publisher]

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Eur J Gastroenterol Hepatol. 2011 Jul 16. [Epub ahead of print]

Evaluation of a portable hemoglobinometer (HemoCue) to control anemia in

hepatitis C liver transplant recipients undergoing antiviral therapy.

Mariño Z, Carrión JA, Bedini JL, Crespo G, Martínez SM, Sánchez-Tapias JM,

Forns X, Navasa MA.

Source

aLiver Unit, Institut de Malalties Digestives i Metabòliques, Hospital Clinic,

CIBERehd and IDIBAPS bService of Clinical Biochemistry, Hospital Clinic,

University of Barcelona, Barcelona, Spain.

Abstract

BACKGROUND:

Monitoring of anemia, the most frequent side-effect of antiviral therapy in

hepatitis C virus (HCV)-infected liver transplant recipients, requires frequent

blood tests and medical visits.

AIMS:

The primary aim of this study was to assess the usefulness and the accuracy of a

portable hemoglobinometer (HemoCue) in patients receiving antiviral therapy

after liver transplantation due to severe hepatitis C recurrence in the graft.

The secondary aim was to evaluate the usefulness of this device in terms of

cost-saving and time-saving benefits.

METHODS:

Multiple simultaneous hemoglobin measurements were obtained in venous blood by

the reference method (ADVIA 120) and in capillary blood using HemoCue in 16

patients receiving antiviral therapy after liver transplantation. In addition,

paired HemoCue measurements were taken to assess the reproducibility of this

method, and correlation coefficients (CC) were calculated between them. Time

requirements and cost of both procedures were recorded and compared.

RESULTS:

HemoCue showed an excellent reproducibility (CC 0.92) and very high correlation

with the standard method (CC 0.89). Its accuracy in detecting anemia (hemoglobin

≤10 mg/dl) was excellent as well (area under the receiver operator

characteristic curve, 0.96). The application of HemoCue in this cohort of

patients resulted in a significant reduction in the economical expense and labor

(i.e., time) per patient during follow-up.

CONCLUSION:

HemoCue is accurate and reproducible in measuring hemoglobin levels, and could

be effectively used in this cohort of patients to control anemia during

antiviral therapy. It could also help to reduce both overall costs and

displacements, thereby improving the quality of life of these patients.

PMID: 21772147 [PubMed - as supplied by publisher]

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Gastroenterology. 2011 Jul 13. [Epub ahead of print]

Inhibitory Molecules that Regulate Expansion and Restoration of HCV-Specific

CD4+ T Cells in Patients with Chronic Infection.

Raziorrouh B, Ulsenheimer A, Schraut W, Heeg M, Kurktschiev P, Zachoval R, Jung

MC, Thimme R, Neumann-Haefelin C, Horster S, Wächtler M, Spannagl M, Haas J,

Diepolder HM, Grüner NH.

Source

Medical Department II and Institute for Immunology,

Ludwig-Maximilians-University, Munich, Germany.

Abstract

BACKGROUND & AIMS:

Inhibitory receptors such as programmed death (PD)-1 and cytotoxic T

lymphocyte-associated antigen (CTLA)-4 mediate CD8+ T-cell exhaustion during

chronic viral infection, but little is known about roles in dysfunction of CD4+

T cells.

METHODS:

We investigated the functions of inhibitory molecules on hepatitis C virus

(HCV)-, influenza-, and Epstein-Barr-virus (EBV)-specific CD4+ T cells in

patients with chronic infections, compared with patients that resolve HCV

infection and healthy donors. Expression of PD-1, CTLA-4, CD305, and CD200R were

analyzed on HCV-specific CD4+ T cells, isolated from peripheral blood using MHC

class II tetramers. We investigated the effects of in vitro inhibition of

various inhibitory pathways on proliferation and cytokine production by CD4+ T

cells; we compared these effects with those from inhibition of interleukin

(IL)-10 and transforming growth factor (TGF)-β1.

RESULTS:

PD-1 and CTLA-4 were upregulated on virus-specific CD4+ T cells from patients

with chronic HCV infections. PD-1 expression was lower on influenza- than on

HCV-specific CD4+ T cells from subjects with chronic HCV infection, whereas

CTLA-4 was expressed at similar levels, independent of their specificity. CD305

and CD200R were upregulated in HCV resolvers. Blockade of PD-L1/2, IL-10, and

TGF-β1 increased expansion of CD4+ T cells in patients with chronic HCV,

whereas inhibition of IL-10 and TGF-β1 was most effective in restoring

HCV-specific production of interferon-γ, IL-2, and tumor necrosis factor-α.

CONCLUSION:

We characterized expression of inhibitory molecules on HCV-, influenza-, and

EBV-specific CD4+ T cells and the effects of in vitro blockade on CD4+ T-cell

expansion and cytokine production. Inhibition of PD-1, IL-10, and TGF-β1 is

most efficient in restoration of HCV-specific, CD4+ T cells.

Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

PMID: 21763239 [PubMed - as supplied by publisher]

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Hepatology. 2011 May;53(5):1468-75. doi: 10.1002/hep.24248.

Peginterferon with or without ribavirin has minimal effect on quality of life,

behavioral/emotional, and cognitive outcomes in children.

Rodrigue JR, Balistreri W, Haber B, Jonas MM, Mohan P, Molleston JP, Murray KF,

Narkewicz MR, Rosenthal P, LJ, Lobritto SJ, Schwarz KB, Robuck PR, Barton

B, González-Peralta RP.

Source

Beth Israel Deaconess Medical Center, Boston, MA. jrrodrig@...

Abstract

The aim of this study was to prospectively assess the quality of life (QOL),

behavioral/emotional functioning, and cognitive status of children undergoing

treatment for hepatitis C virus (HCV) infection. In all, 114 children (5 to 18

years old) enrolled in a multisite randomized clinical trial (Peds-C) to

evaluate peginterferon alpha 2a (PEG 2a) with ribavirin (RV) or with placebo

(PL) completed several standardized measures prior to treatment and at 24 weeks,

48 weeks, 6 months following treatment, and at two annual follow-up visits.

After 24 weeks of treatment, mean physical QOL scores declined significantly for

both groups from baseline to 24 weeks of treatment (F = 5.8, P = 0.004),

although scores remained in the average range. There were no significant time or

group effects for behavioral/emotional or cognitive functioning. Three children

(5%) in the PEG 2a + RV group and no children in the PEG 2a + PL group had a

clinically significant increase in depression symptoms. For those children who

received 48 weeks of treatment, there were no significant time or group effects

on any of the outcome measures (P > 0.05). A majority of children in both the

PEG 2a + RV and PEG 2a + PL groups experienced no clinically significant change

in physical QOL, behavioral adjustment, depression, or cognitive functioning

during or after treatment. CONCLUSION: Overall QOL and psychosocial functioning

are not deleteriously impacted by PEG 2a + RV or PL treatment of children with

HCV.

Copyright © 2011 American Association for the Study of Liver Diseases.

PMID: 21351116 [PubMed - indexed for MEDLINE] PMCID: PMC3082614 [Available on

2012/5/1]

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J Hepatol. 2011 Jul 11. [Epub ahead of print]

Gaps in the Achievement of Effectiveness of HCV Treatment in National VA

Practice.

Kramer JR, Kanwal F, P, Mei M, El-Serag H, Kramerer JR.

Source

Houston VA Health Services Research and Development Center of Excellence,

E. DeBakey VA Medical Center, Houston, TX; Section of Health Services

Research.

Abstract

BACKGROUND & AIMS:

Antiviral treatment for hepatitis C virus (HCV) has high efficacy rates for

achieving sustained viral response (SVR) in randomized controlled trials (RCTs)

(40% to 80%); however, it can be lower in community-based practice settings. We

wanted to determine the effectiveness of HCV treatment in Veterans

Administration (VA) hospitals nationwide.

METHODS:

Using the nationwide VA HCV Clinical Case Registry (CCR), we examined cohort of

veterans who had HCV viremia between 2000 and 2005 and identified patients who

received pegylated-interferon (PEG-INF) and ribavirin. The duration of treatment

and proportion of patients completing treatment was calculated. The

effectiveness of treatment was measured as the proportion of patients who

achieved SVR (negative viremia at least 12 weeks after the end of treatment) in

the entire cohort, and among patients who initiated and completed treatment.

RESULTS:

We identified 99,166 patients with HCV viremia. Of those, 11.6% received PEG-INF

with ribavirin and 6.4% completed treatment. Contraindications were present in

57.2% of the patients that did not receive treatment. SVR was documented in

39.9% and 58.3% of patients who completed treatment; 23.6% and 50.6% of patients

who initiated treatment; and 3.9% and 11.2% of the entire HCV cohort for

genotype 1 or 4 and 2 or 3, respectively. Overall, only 3.5% of the entire HCV

viremic cohort had documented SVR.

CONCLUSIONS:

Treatment effectiveness for HCV is low. In addition to fixed factors, such as

race and virus genotype, the drop in effectiveness is due to low rates of

antiviral treatment initiation and treatment completion.

Copyright © 2011. Published by Elsevier B.V.

PMID: 21756855 [PubMed - as supplied by publisher]

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