WCTF.org Transplant News

MILAN, April 26/PRNewswire/ --

- Advances in Virology Translate Into New Promising Drugs to Combat
Hepatitis C

- Clarification of Oncogenic Pathways Aids Liver Cancer Research

- Stem Cells of Potential Benefit in Liver Transplantation

- Systems Biology Helps to Solve Complex Liver Diseases

At today's sessions of the 43rd Annual Meeting of the European
Association for the Study of the Liver (EASL), experts reported advances in
basic research that have important implications for the eventual treatment of
people with chronic liver diseases.

The goal of basic or "fundamental" biomedical science is to
gain knowledge and understanding for its own sake, without reference to a
particular practical problem. "Translational" science transforms basic
knowledge into practical terms. "Applied" research, such as "clinical
trials," takes the discoveries of basic research even further and uses them
to solve specific, clearly defined medical problems. Basic, translational,
and applied research are each necessary to progress in medicine, including
Hepatology.

In virology, for example, notable progress has been made in
clarifying the structure of the Hepatitis C virus (HCV), leading to the
development of new experimental drugs such as protease inhibitors and
polymerase inhibitors, drugs that inhibit virus production. Some of these
drugs have been extensively tested and some are currently in phase II trials.
Based on results to date, it is clear that these drugs can be highly
effective in combination with pegylated Interferon and Ribavirin. Phase III
trials are planned.

Important basic science advances in genetics and systems
biology have also been reported, offering potential progress for strategies
to treat hepatocellular carcinoma (HCC). Using genomics and microarrays to
determine gene expression, scientists have discovered that there are
different biological pathways - called "oncogenic pathways" -- that result in
HCC. This discovery corrects a past, widely held but mistaken assumption that
all cases of HCC arise from a single type of disease process. On the basis of
the new discovery, researchers can now classify and explore differing
subtypes of HCC, as well as designing and experimentally testing targeted
treatments for patients based on their respective cancer subtype. According
to Professor Michael Trauner, Professor of Medicine and Molecular Hepatology
at the Medical University, Graz, Austria, "It is extremely interesting to
look at different gene expression profiles of patients with the same disease
and realize that there are different clusters which may be associated with
differentially aggressive disease. For example, in the field of cancer,
varying gene expression profiles are linked to better and worse prognoses for
hepatocellular carcinoma." In addition to genetic signatures, new protein and
metabolic markers are also being developed to detect cancer at an early stage
among patients considered at risk. Most importantly, new drugs are now
available that are able to target signal transduction cascades which, under
pathological conditions, help tumor cells to grow and proliferate. These
novel drugs include multikinase inhibitors such as Sorafenib, which has
recently been shown to delay progression of HCC. Additional small molecules
targeting tumor cell proliferation will be available for clinical trials in
the near future.

A third area in which basic science offers the potential for
clinical progress in hepatology is in the use of embryonic stem cells for
liver repair. One of the major limitations for the development of liver cell
therapy programs is the shortage of human hepatocytes. Many laboratories have
therefore focussed on stem cells as a renewable source of hepatocytes
(although extensive liver tissue formation/replacement has not yet been
achieved with either adult or embryonic stem cells). Immortalized hepatocytes
could engraft, proliferate and correct a disease phenotype of a recipient
liver, but safety issues (e.g. tumor formation) still remain a concern. To
date, in the laboratory, stem cells have been found to differentiate into
hepatocyte-like cells and other liver cell types and used to restore liver
function in mice with liver failure. For some researchers, this is a
potential treatment that, if successfully applied to humans, will allow
correction of inborn errors of metabolism or allow patients to live long
enough for a donated organ to become available. Some scientists believe that
stem cells might even enable the liver to completely heal itself so a
transplant is no longer needed. In Professor Trauner's view, although the
latter application is interesting, its success may be limited due to severe
disturbances of liver architecture in advanced liver diseases such as
cirrhosis, which limits the function of newly transplanted cells. However, in
the future, stem cells perhaps could also be used to reverse fibrous scars in
liver cirrhosis.

A fourth promising area is the application of systems biology
-- which focuses on interactions in biological systems -- to clinical
problems in hepatology. As such, the systematic exploration of RNA, protein
and metabolic profiles in hepatitis, fatty liver and cancer may help to
identify patients at particular risk for developing severe forms of these
diseases, help to predict prognoses, and may unravel potential therapeutic
targets in individual patients. This approach brings us a major step toward
personalized, individualized medicine with better prediction of individual
prognosis and better selection of the best therapy for each individual
patient.

About EASL

The European Association for the Study of the Liver (EASL)
aims to promote investigation into liver disease and improve the treatments
that currently exist for these conditions. The association, through its
annual meetings, seeks to inform and educate both the scientific community as
well as society in general about the increasing occurrence of liver diseases
along with the importance of understanding these conditions in order to treat
and prevent them. Since its creation in 1966, the EASL congress has been
hosted in 20 different European countries. Currently the association has over
1400 members and the annual congress attracts over 6000 delegates from over
65 countries each year.

Source: EASL - European Association for the Study of the Liver

For more information: Carolina Annand / Karine Elkobbi /Melisa Corrigan, Carolina.annand@eurorscg.com / karine.elkobbi@eurorscg.com / melisa.corrigan@eurorscg.com, Tel. +33-617-43-03-38 / +33-6-61-17-44-77 / +39-328-411-01-38, Euro RSCG Life

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