January 13, 2011

Articles in Press

Joseph Torresiab, Doug Johnsonab, Heiner Wedemeyerc

Received 31 May 2010; received in revised form 27 August 2010; accepted 7 September 2010. published online 12 January 2011.
Accepted Manuscript

Abstract

Hepatitis C virus (HCV) is a blood borne disease estimated to chronically infect 3% of the worlds’ population causing significant morbidity and mortality. Current medical therapy is curative in approximately 50% of patients. While recent treatment advances of genotype 1 infection using directly acting antiviral agents (DAAs) are encouraging, there is still a need to develop vaccine strategies capable of preventing infection. Moreover, vaccines may also be used in future in combination with DAAs enabling interferon-free treatment regimens.

Viral and host specific factors contribute to viral evasion and present important impediments to vaccine development. Both, innate and adaptive immune responses are of major important for the control of HCV infection. However, HCV has evolved ways of evading the host’s immune response in order to establish persistent infection. For example, HCV inhibits intracellular interferon signalling pathways, impairs the activation of dendritic cells, CD8+ and CD4+ T cell responses, induces a state of T-cell exhaustion and selects escape variants with mutations CD8+ T cell epitopes. An effective vaccine will need to produce strong and broadly cross-reactive CD4+, CD8+ T cell and neutralising antibody (NAb) responses to be successful in preventing or clearing HCV.

Vaccines in clinical trials now include recombinant proteins, synthetic peptides, virosome based vaccines, tarmogens, modified vaccinia Ankara based vaccines and DNA based vaccines. Several preclinical vaccine strategies are also under development and include recombinant adenoviral vaccines, virus like particles and synthetic peptide vaccines. This paper will review the vaccines strategies employed, their success to date and future directions of vaccine design.

Keywords: Hepatitis C, vaccines, preventative vaccines, therapeutic vaccines, hepatitis C immunology.

a Austin Centre for Infection Research, Department of Infectious Diseases Austin Hospital, Heidelberg, Victoria 3084, Australia
b Department of Medicine, Austin Hospital, University of Melbourne, Heidelberg, Victoria 3084, Australia
c Department of Gastroenterology and Hepatology, Medizinische Hochschule, 30625 Hannover, Germany

PII: S0168-8278(11)00018-3
doi:10.1016/j.jhep.2010.09.040
© 2011 Published by Elsevier Inc.

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Noncirrhotic portal hypertension in HIV infection

Curr Opin Infect Dis. 2011 Feb;24(1):12-8.

Vispo E, Morello J, Rodriguez-Novoa S, Soriano V.

Department of Infectious Diseases, Hospital Carlos III, Madrid, Spain.

Abstract

PURPOSE OF REVIEW: Liver disease in the HAART era is one of the leading causes of morbidity and mortality in HIV-infected individuals in Western countries. Even if the majority of cases rely on identifiable causes (viral hepatitis, steatohepatitis, alcohol abuse, drug toxicity, etc.), the cause of liver abnormalities remains unknown for a subset of patients, some of whom present with noncirrhotic portal hypertension (NCPH).

RECENT FINDINGS: In 2006, the first reports of NCPH in HIV-infected patients attracted special attention. Typically, individuals unaware of any underlying liver illness presented with variceal bleeding, occasionally fatal. Interestingly, severe portal hypertension occurred in the absence of liver function impairment in most cases. Liver biopsy revealed a distinctive histological feature characterized by massive absence of portal veins along with focal obliteration of small portal veins. After extensive ruling out of other causes, the role of antiretroviral toxicity (particularly didanosine exposure) emerged as the major contributor to this condition. Other potential factors could be an enhanced microbial translocation from the gut and prothrombotic conditions.

SUMMARY: NCPH is an uncommon condition, although increasingly being reported in HIV-infected individuals. It generally presents as a clinical episode of decompensated portal hypertension, generally with gastrointestinal bleeding. Long-lasting HIV infection and prolonged antiretroviral exposure are universally recognized in these patients. The involvement of didanosine has been highlighted in most series. Removal of this drug and prevention of variceal bleeding episodes are currently the most effective prophylactic and therapeutic interventions.

PMID: 21157331 [PubMed - in process]

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