Although women with chronic hepatitis C virus (HCV) infection are at lower risk for developing cirrhosis, researchers who compared outcomes for men and women after having liver transplantation found that women have a significantly increased risk of overall graft loss and graft loss from recurrent HCV than men. “Given the higher rate of graft losses due to recurrent HCV and higher risk of developing advanced HCV, our results highlight the need for close monitoring of HCV disease progression after liver transplantation and the appropriate timing of interventions, such as HCV treatment,” said Jennifer Lai, MD, lead investigator for the study.

In this study to be presented at the annual meeting of the American Association for the Study of Liver Diseases, data were analyzed from four experienced liver transplant centers in the United States, which included 850 patients who underwent liver transplantation from March 2002 through December 2007 for HCV-related liver disease. Not only were women at greater risk of graft loss from all causes and recurrent HCV, but they experienced increased rates of advanced HCV-related liver disease compared with men.

These differences were not explained by differences in baseline recipient or donor characteristics, or rates of acute rejection after transplantation. “However,” said Dr. Lai, “understanding the factors contributing to this gender difference is critical to improving post-transplant outcomes for all patients with HCV.”

Based on this multicenter study, further studies are needed to evaluate modifiable donor factors and post-transplant therapeutics that influence outcomes. There may be a future role for gender-specific models to optimize post-transplant outcomes in women. “Whether we should have a more intensive approach to monitoring for and management of recurrent HCV would improve outcomes in women will need to be established in future studies,” said Dr. Lai.

In addition, Dr. Lai discussed future research on this topic, “We found recipient age to be a stronger predictor of outcome for women than for men, and we noted that women had higher rates of having a sex-mismatch donor liver than men. A more in depth analysis of the role of recipient-donor sex mismatch is planned. In addition, we found that women had significantly increased rates of acute rejection and although this factor did not account for differences in graft outcomes in our study, we believe sex differences in frequency of rejection and response to rejection treatment warrant further study.”

Abstract title:

Hepatitis C virus (HCV) infected females are at higher risk of graft loss after liver transplantation (LT): A multicenter cohort study

About the AASLD

AASLD is the leading medical society focused solely on advancing the science and practice of hepatology and represents more than 3,300 practitioners, researchers, and allied health professionals worldwide. Founded by physicians in 1950, AASLD has upheld the standards of the profession and fostered research that generates treatment options for the millions of patients with liver diseases.

This year’s Liver Meeting, held in Boston, Massachusetts, October 30 - November 3, will bring together more than 7,000 researchers from 55 countries. A pressroom will be available from October 31 at the annual meeting.

Source: AASLD

The Lymphoma Research Foundation (LRF) is pleased to announce that David Frank, MD, PhD of the Dana-Farber Cancer Institute and Thomas Kipps, MD, PhD, Moores Cancer Center, University of California, San Diego are the recipients of the second round of funding under the Foundation’s Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) Research Initiative.

Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL) are the same disease with slightly different manifestations. Where the cancerous cells gather determines whether it is called CLL or SLL. When the cancer cells are primarily found in the lymph nodes, lima bean shaped structures of the lymphatic system, an essential part of the body’s immune system, it is called SLL. When most of the cancer cells are in the bloodstream and the bone marrow, it is called CLL.

John Balan, founder of the CLL Information Group with membership of approximately 1000 patients and caregivers, expressed the group’s delight with these two awards. “We have a great deal of respect for the work that Drs. Kipps and Frank have been doing with CLL. These two awards will only augment what they have already done and add to the arsenal of treatments available to patients.”

The purpose of Dr. Frank’s, A Clinical Trial of STAT3 Inhibition in Patients with CLL, will be to evaluate the benefits of targeted therapy for CLL/SLL patients. Through prior research, Dr. Frank and his team found that CLL/SLL cells are characterized by an abnormality in a protein called STAT3, which regulates genes controlling the abnormal proliferation of lymphocytes in patients with this disease. They further identified a drug that inhibits STAT3, and, with the two-year $300,000 grant from LRF, Dr. Frank will carry out a clinical trial to test its safety and effectiveness in CLL/SLL patients. This is Dr. Frank’s second LRF grant supporting his efforts to discover more effective CLL/SLL therapeutics.

Dr. Kipps’ “Gene-Chemoimmunotherapy for Intractable Chronic Lymphocytic Leukemia” will focus on developing a treatment option for CLL/SLL patients with refractory disease who have limited treatment options. Dr. Kipps and his team have found that gene-immune therapy can render drug-resistant cells sensitive to chemotherapy. With this two-year $200,000 grant, Dr. Kipps will examine the mechanism(s) of drug-resistant disease and will pursue a clinical trial examining the use of gene-immune therapy to improve the capacity of patients with CLL/SLL refractory disease to respond to chemotherapy. Dr. Kipps is a member of the Foundation’s Scientific Advisory Board.

Source: Marion F. Swan

Lymphoma Research Foundation

The Salk Institute has been awarded a $10.8 million grant by the California Institute for Regenerative Medicine (CIRM) for translational research focusing on developing a novel stem-cell based therapy for Amyotrophic Lateral Sclerosis (ALS) - or Lou Gehrig’s Disease.

Sam Pfaff, Ph.D., a professor in the Salk’s Gene Expression Laboratory and an investigator for the Howard Hughes Medical Institute, will lead the group of researchers who will work on the four-year project announced as part of the $250 million CIRM Disease Team Award.

It marks the first CIRM funding explicitly expected to result in FDA approval for clinical trials. The grants were given to multidisciplinary teams of basic scientists, clinicians and industry in collaboration with two international partners, the Medical Research Council, UK, and the Cancer Stem Cell Consortium, Canada.

ALS is a progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord. When motor neurons die, the ability of the brain to initiate and control muscle movement is lost. The progressive degeneration of motor neurons in ALS eventually leads to paralysis and death.

The research team, which includes co-principal investigators Drs. Larry Goldstein and Don Cleveland, both of UCSD, will focus on astrocytes, the star-shaped support cells that provide nutrients for nearby motor neurons. Working with six different lines of human embryonic stem cells (hESC), Pfaff and the team of researchers will grow clinical-grade astrocyte precursor cells and identify the line that is best suited for implantation in laboratory models.

They hypothesize that the transplanted human astrocyte precursors (hAP) will mature into astrocytes in vivo and provide support for diseased spinal motor neurons. Astrocytes are also capable of clearing excess neurotoxic glutamate and could thereby slow or halt the progression of ALS by preventing motor neuron degeneration.

Once the astrocyte precursors are tested for efficacy and safety to minimize the possibility of tumorigenesis, the next step will be to move forward with human clinical trials after approval by the FDA, says Pfaff.

“This team grant is a natural fit for San Diego because it capitalizes on the strength of neuromuscular disease research from the local scientific community,” says Pfaff. “The standard has been set very high on this project because we are aiming to grow a safe population of astrocytes that can be introduced into patients. Our success will be measured by whether it will help extend the lives of patients suffering from ALS.”

CIRM President Alan Trounson said the pace of the Disease Team projects stands in contrast to the decade or more that’s usually required to reach clinical trials. “Scientists have talked for years about the need to find ways to speed the pace of discovery,” he said. “By encouraging applicants to form teams composed of the best researchers from around the world we think CIRM will set a new standard for how translational research should be funded.”

Source: Mauricio Minotta

Salk Institute