Nine Abstracts on Hepatitis C Subjects

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

A multi-disciplinary approach to treating hepatitis C with interferon and

ribavirin in alcohol-dependent patients with ongoing abuse.

Lan CL, Guillygomarc'h A, ou H, Dréau GL, Lainé F, Védeilhié C,

Deugnier Y, Brissot P, Guyader D, Moirand R.

Source

CHU de Rennes, Unité d'Addictologie, F-35033 Rennes, France; CHU de Rennes,

Service des Maladies du Foie, F-35033 Rennes, France; INSERM, UMR-991, F-35000,

France.

Abstract

BACKGROUND & AIMS:

Guidelines recommend 6 months of alcohol abstinence before treating hepatitis C

(HCV). Abstinence is difficult for alcohol-dependent patients to achieve. This

study evaluated HCV treatment in alcoholic patients with ongoing consumption or

less than 6 months of abstinence.

METHODS:

A multidisciplinary management model was built by a liver unit and two centers

involved in the care of addict patients. Patients were included in a prospective

observational study of treatment with pegylated interferon and ribavirin if they

presented alcohol dependence with ongoing intoxication or abstinence of less

than 6 months. Pre-therapeutic evaluation and follow-up were multidisciplinary,

and addiction care was personalized to patient condition and willingness.

Alcohol abstinence or reduction was encouraged but not mandatory. The primary

end point was sustained virological response (SVR). Results were compared to a

control group of patients matched for genotype, viral load, fibrosis stage, sex,

and age.

RESULTS:

A total of 73 patients treated between 2002 and 2008 were included in the study.

Intent to treat analysis showed a SVR in 48% (35/73) of patients versus 49%

(36/73) of controls. Low viral load and the length of abstinence during

treatment were independently associated with SVR. During treatment, 20 (27%)

patients were abstinent, 23 (32%) had controlled consumption, and 24 (33%) had

excessive consumption. At the end of the follow-up, 22 (30%) patients were

durably abstinent.

CONCLUSION:

A multidisciplinary approach allowed HCV treatment in alcohol-dependent patients

with a satisfactory SVR rate and positive effects on addiction behavior.

Copyright © 2011. Published by Elsevier B.V.

PMID: 21756854 [PubMed - as supplied by publisher]

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

Hyporesponsiveness to pegifnα2b plus ribavirin in patients with hepatitis

C-related advanced fibrosis.

Prati GM, Aghemo A, Rumi MG, D'Ambrosio R, Nicola SD, Donato MF, Degasperi E,

Colombo M.

Source

A.M. Migliavacca Center for Liver Disease, 1st Division of Gastroenterology,

Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli

Studi di Milano, Milan.

Abstract

BACKGROUND & AIM:

The success of pegylated-interferon (PegIFN) / ribavirin (Rbv) therapy of

chronic hepatitis C is compromised by liver fibrosis. Whether fibrosis equally

affects the two PegIFNα-based therapies is unknown. To assess the response to

the two PegIFN regimens in patients with different degree of liver fibrosis.

METHODS:

A sub-analysis of the MIST study: 431 consecutive naïve patients randomly

assigned, based on HCV genotype, to receive either PegIFNα2a 180 μg/wk plus

daily Rbv 800-1200mg (A) or PegIFNα2b 1.5 μg/kg/week plus daily Rbv 800-1200mg

(, were stratified according to Ishak staging (S) into mild (S0-S2) or

moderate (S3,S4) fibrosis and cirrhosis (S5,S6).

RESULTS:

In A the sustained virological response (SVR) rates were not significantly

influenced by fibrosis stage (71% in S0-S2, 66% in S3,S4, 53% in S5,S6, p=0.12),

compared to B where the SVR rates differed according to fibrosis stage (65%, 46%

and 38%, p=0.004, respectively). This was even more so in HCV-1/4 patients

treated with PegIFNα2b where the SVR rates were twice as many in S0-S2 vs S⩾3

(44% vs 22%, p=0.02), while in A the SVR rates were similar between the two

fibrosis subgroups (S0-S2: 47% vs S⩾3: 48%, p=0.8). By logistic regression

analysis genotype 1/4 and lack of rapid virological response were independent

predictors of treatment failure in both treatment groups, while S⩾3 fibrosis

was associated to PegIFNα2b treatment failure, only (OR 2.83, 95%CI 1.4 - 5.68,

p=0.004).

CONCLUSION:

Liver fibrosis was an independent moderator of treatment outcome in patients

receiving PegIFNα2b, not in those receiving PegIFNα2a.

Copyright © 2011. Published by Elsevier B.V.

PMID: 21756847 [PubMed - as supplied by publisher]

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J Hepatol. 2011 Apr;54(4):640-9. Epub 2010 Dec 1.

Infection and systemic inflammation, not ammonia, are associated with Grade 3/4

hepatic encephalopathy, but not mortality in cirrhosis.

Shawcross DL, Sharifi Y, Canavan JB, Yeoman AD, Abeles RD, NJ, Auzinger

G, Bernal W, Wendon JA.

Source

Institute of Liver Studies, King's College London School of Medicine, London,

UK. debbie.shawcross@...

Abstract

BACKGROUND & AIMS:

Patients with cirrhosis are prone to infection which is a frequent precipitant

of hepatic encephalopathy (HE). Clinical studies have examined the importance of

inflammation and infection in modulating the manifestation of symptoms of HE in

acute liver failure and patients with cirrhosis and minimal/low grade HE. It

would be logical to presume that this relationship persists in patients who

develop severe HE in cirrhosis although this has not been examined to date.

METHODS:

We report the findings of a prospective audit of 100 consecutive patients with

cirrhosis admitted between Jan 2000 and March 2008 to a liver Intensive Care

Unit (ICU) where HE was the primary indication for admission (59% Grade 3; 41%

Grade 4). Haematological and microbiological data were collected at ICU

admission, and organ scores and outcomes were recorded.

RESULTS:

46% of patients had positive cultures taken within ± 48h from admission to ICU

[25% blood] and a further 22% were culture negative but had evidence of systemic

inflammation (SIRS). SIRS score (p=0.03) and SOFA score (p=0.006) were

significantly higher in those patients with Grade 4 HE, who were also less

likely to survive (p<0.001). HE grade/coma score did not correlate with ammonia,

biochemistry or MELD score. Fifty-two percent of patients survived their ICU

stay while the remainder developed progressive multiorgan failure and died; 38%

survived to discharge, and 16% were transplanted.

CONCLUSIONS:

These data support an association between infection/SIRS and not ammonia, in

patients with cirrhosis that develop severe HE. The presence or absence of

infection/SIRS did not determine survival.

Copyright © 2010 European Association for the Study of the Liver. Published by

Elsevier B.V. All rights reserved.

PMID: 21163546 [PubMed - indexed for MEDLINE]

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J Med Virol. 2011 Jul 13. doi: 10.1002/jmv.22153. [Epub ahead of print]

Killer cell immunoglobulin-like receptors and response to antiviral treatment in

Thai patients with chronic hepatitis C virus genotype 3a.

Vejbaesya S, Nonnoi Y, Tanwandee T, Srinak D.

Source

Department of Transfusion Medicine, Faculty of Medicine, Siriraj Hospital,

Mahidol University, Bangkok, Thailand. sisve@....

Abstract

Genetic factors of the host have been shown to influence the outcome of

treatment for hepatitis C virus (HCV) infection. Killer cell immunoglobulin-like

receptors (KIR) regulate natural killer (NK) cell activity by interaction with

specific human leukocyte antigen (HLA) class I. In this study, KIR gene

polymorphisms and their HLA ligands were investigated in 110 Thai patients with

chronic HCV genotype 3a. Seventy-six patients were sustained virological

responders and 34 patients were virological non-responders. KIR typing and HLA-C

typing were performed using PCR-SSP (polymerase chain reaction with sequence

specific primer). The frequency of HLA-C1C2 was significantly higher in

sustained responders than in non-responders (P = 0.04). However, the

frequencies of KIR2DL2/2DL3 genotype and KIR2DL2/2DL3-HLA-C1C1 genotype were

significantly higher in non-responders than in sustained responders

(P = 0.02, 0.004, respectively). In summary, this study showed the

association of KIR genes and ligands with the outcome of antiviral treatment in

chronic hepatic C virus genotype 3a infection. J. Med. Virol. © 2011

Wiley-Liss, Inc.

Copyright © 2011 Wiley-Liss, Inc.

PMID: 21755501 [PubMed - as supplied by publisher]

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J Med Virol. 2011 May;83(5):871-8. doi: 10.1002/jmv.22038. Epub 2011 Feb 25.

Association of IL28B variants with response to pegylated-interferon alpha plus

ribavirin combination therapy reveals intersubgenotypic differences between

genotypes 2a and 2b.

Sakamoto N, Nakagawa M, Tanaka Y, Sekine-Osajima Y, Ueyama M, Kurosaki M,

Nishida N, Tamori A, Yuki NS, Itsui Y, Azuma S, Kakinuma S, Hige S, Itoh Y,

Tanaka E, Hiasa Y, Izumi N, Tokunaga K, Mizokami M, Watanabe M; Ochanomizu-Liver

Conference Study Group.

Source

Department of Gastroenterology and Hepatology, Tokyo Medical and Dental

University, Tokyo, Japan. nsakamoto.gast@...

Abstract

Genetic polymorphisms of the interleukin 28B (IL28B) locus are associated

closely with outcomes of pegylated-interferon (PEG-IFN) plus ribavirin (RBV)

combination therapy. The aim of this study was to investigate the relationship

between IL28B polymorphism and responses to therapy in patients infected with

genotype 2. One hundred twenty-nine chronic hepatitis C patients infected with

genotype 2, 77 patients with genotype 2a and 52 patients with genotype 2b, were

analyzed. Clinical and laboratory parameters, including genetic variation near

the IL28B gene (rs8099917), were assessed. Drug adherence was monitored in each

patient. Univariate and multivariate statistical analyses of these parameters

and clinical responses were carried out. Univariate analyses showed that a

sustained virological response was correlated significantly with IL28B

polymorphism, as well as age, white blood cell and neutrophil counts, adherence

to RBV, and rapid virological response. Subgroup analysis revealed that patients

infected with genotype 2b achieved significantly lower rapid virological

response rates than those with genotype 2a. Patients with the IL28B-major allele

showed higher virus clearance rates at each time point than those with the

IL28B-minor allele, and the differences were more profound in patients infected

with genotype 2b than those with genotype 2a. Furthermore, both rapid and

sustained virological responses were associated significantly with IL28B alleles

in patients with genotype 2b. IL28B polymorphism was predictive of PEG-IFN plus

RBV combination treatment outcomes in patients infected with genotype 2 and,

especially, with genotype 2b. In conclusion, IL-28B polymorphism affects

responses to PEG-IFN-based treatment in difficult-to-treat HCV patients.

Copyright © 2011 Wiley-Liss, Inc.

PMID: 21360545 [PubMed - indexed for MEDLINE]

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JAMA. 2011 Jul 20;306(3):294-301.

Hepatitis C virus infection and coinfection with human immunodeficiency virus:

challenges and advancements in management.

Hadigan C, Kottilil S.

Source

Laboratory of Immunoregulation, National Institute of Allergy and Infectious

Diseases, National Institutes of Health, Bethesda, land 20892, USA.

hadiganc@...

Abstract

Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) both emerged in

the second half of the 20th century, and chronic infection with these agents is

among the greatest challenges facing health care in the United States and

worldwide. Despite tremendous advances in treatment and management of HIV and

HCV, individuals with HIV/HCV coinfection experience a more complicated disease

course and treatment. Recognition of the important role that host factors, such

as IL28B genotype, have in response to HCV therapy and the emergence of new

effective therapies for HCV are actively reshaping the standard of care. These

advances may translate into more effective treatment and management of patients

with chronic HCV and HIV coinfection in the years ahead.

PMID: 21771990 [PubMed - indexed for MEDLINE]

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Pediatr Infect Dis J. 2011 Mar 30. [Epub ahead of print]

IMPACT OF HUMAN IMMUNODEFICIENCY VIRUS COINFECTION ON THE PROGRESSION OF

MOTHER-TO-CHILD TRANSMITTED HEPATITIS C VIRUS INFECTION.

Claret-Teruel G, Noguera-n A, Esteva C, Muñoz-Almagro C, Sánchez E,

Jiménez R, Fortuny C.

Source

From the *Infectious Diseases Unit, Department of Pediatrics, Hospital Sant Joan

de Déu, Universitat de Barcelona, Barcelona, Spain; †Microbiology Department,

Hospital Sant Joan de Déu, Universitat de Barcelona, Barcelona, Spain; and

‡Blanquerna School of Health Science, Universitat Ramon Llull, Barcelona,

Spain.

Abstract

Data on mother-to-child transmitted human immunodeficiency virus/hepatitis C

virus (HIV/HCV) coinfection are scarce. A prospective observational study with a

cohort of 70 HCV-infected children (13 of whom were HIV/HCV-coinfected; mean

follow-up: 7.3 years) is presented. In our series, surrogate markers of disease

progression (HCV viremia, maximum alanine aminotransferase values, and

spontaneous HCV infection clearance) suggest that the evolution of liver disease

in HIV/HCV-coinfected pediatric patients is more aggressive than it is in

HCV-only infected children.

PMID: 21772231 [PubMed - as supplied by publisher]

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Z Gastroenterol. 2011 Jul;49(7):836-44. Epub 2011 Jul 15.

[Molecular mechanisms of hepatitis C virus (HCV) replication - implications for

the development of antiviral drugs].

[Article in German]

Bühler S, Bartenschlager R.

Source

Department für Infektiologie, Molekulare Virologie, Universitätsklinikum

Heidelberg.

Abstract

More than 20 years after the discovery of the hepatitis C virus (HCV), chronic

hepatitis C still is a major medical problem. According to the World Health

Organisation 120 to 180 million people are chronically infected with HCV, with 5

million infected individuals living in Western Europe. These people have a high

risk to develop serious liver disease such as liver cirrhosis and hepatocellular

carcinoma (HCC). The standard-of-care therapy is not satisfying and there is no

vaccine in sight. Owing to intense research activities, most notably the

development of adequate cell culture systems, important insights into the viral

replication cycle have been gained and several strategies used by HCV to

overcome immune responses have been identified. Adequate cell culture systems

also provided the basis for the development of potent and selective antivirals

for treatment of chronic hepatitis C and it is expected that NS 3 / 4A protease

inhibitors will be approved for clinical use in 2011 / 2012. Nevertheless,

important questions are still unanswered and they will keep clinicians and basic

researchers busy for the coming years.

© Georg Thieme Verlag KG Stuttgart · New York.

PMID: 21766263 [PubMed - in process]

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J Viral Hepat. 2011 Aug;18(8):533-41. doi: 10.1111/j.1365-2893.2011.01128.x.

Epub 2011 Jun 22.

The impact of mode of acquisition on biological markers of paediatric hepatitis

C virus infection.

England K, Thorne C, H, Ramsay M, Newell ML.

Source

MRC Centre of Epidemiology for Child Health, UCL Institute of Child Health,

London, UK Immunisation Department, Centre for Infections, Health Protection

Agency, London, UK Africa Centre for Health and Population Studies, University

of KwaZulu Natal, Mtubatuba, South Africa.

Abstract

Summary.  Despite the introduction of blood donor screening, worldwide,

children continue to become infected with hepatitis C virus (HCV) via un-sterile

medical injections, receipt of unscreened blood and isolated hospital

contamination outbreaks. It is plausible that the natural history and disease

progression in these children might differ from that of their vertically

infected counterparts. Vertically and parenterally HCV-infected children were

prospectively followed within the European Paediatric HCV Network and the UK

National HCV Register, respectively. Biological profiles were compared.

Vertically and parenterally HCV-infected children differed in terms of some key

characteristics including the male to female ratio and the proportion of

children receiving therapy. Parenterally infected children were more likely to

have at least one hepatomegaly event during follow-up, 20%vs 10%. Parenteral

infection did not significantly affect the odds of being consistently viraemic

(AOR 1.14, P = 0.703) and there was no significant difference in the odds of

having consistently elevated ALT levels and mode of acquisition (AOR 0.83,

P = 0.748). The proportion of children with 2 or more markers of HCV

infection did not differ significantly by mode of acquisition (χ(2) 1.13,

P = 0.288). This analysis does not support substantial differences between

vertically and parenterally infected groups, but there are specific mechanisms

identified requiring further investigation. Given the continued parenteral

infection of children worldwide, it is vital that knowledge of disease

progression in this group is accurate and that the differences in comparison

with vertically infected children are clarified to inform more accurate and

individualized clinical management.

© 2011 Blackwell Publishing Ltd.

PMID: 21762285 [PubMed - in process]

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