The goal of this project is to collect blood or skin tissues from subjects with liver disease to learn more about the factors that predispose individuals to their conditions. We are focusing our attention on subjects with two specific liver diseases: hepatitis C and non-alcoholic steatohepatitis (the latter is termed "NASH" or "fatty liver disease"). These are the two most common causes of liver disease in California. In the case of hepatitis C, research to date shows that factors such as race, genetic makeup and immunologic makeup influence individual responses to infection by the hepatitis C virus as well as responses to antiviral drug treatment. Our goal is to recruit individuals with diverse backgrounds and responses to hepatitis C infection and treatment, to enable scientists to identify the determinants of susceptibility or resistance to hepatitis C-related liver disease. In the case of fatty liver disease, we are recruiting subjects who have significant liver injury due to the accumulation of fat, proven on a liver biopsy (NASH). NASH is typically found in subjects who are overweight, and who often have additional health problems such as high blood pressure, high cholesterol and diabetes. We are also looking for subjects who are at risk for NASH and have prominent fat accumulation in the liver on a biopsy, but have no evidence of actual liver injury. As with hepatitis C, the goal with fatty liver disease is to accumulate a cohort of subjects with diverse backgrounds and a spectrum of disease severity, to enable scientists to determine the factors that predispose some individuals at risk to serious liver disease while sparing others.
Reporting Period:
Year 2
The goal of this project is to collect blood or skin tissues from subjects with liver disease to learn more about the factors that predispose individuals to their conditions. We are focusing our attention on subjects with two specific liver diseases: hepatitis C and non-alcoholic steatohepatitis (the latter is termed "NASH" or "fatty liver disease"). These are the two most common causes of liver disease in California. In the case of hepatitis C, research to date shows that factors such as race, genetic makeup and immunologic makeup influence individual responses to infection by the hepatitis C virus as well as responses to antiviral drug treatment. Our goal is to recruit individuals with diverse backgrounds and responses to hepatitis C infection and treatment, to enable scientists to identify the determinants of susceptibility or resistance to hepatitis C-related liver disease. In the case of fatty liver disease, we are recruiting subjects who have significant liver injury due to the accumulation of fat, proven on a liver biopsy (NASH). NASH is typically found in subjects who are overweight, and who often have additional health problems such as high blood pressure, high cholesterol and diabetes. We are also looking for subjects who are at risk for NASH and have prominent fat accumulation in the liver on a biopsy, but have no evidence of actual liver injury. As with hepatitis C, the goal with fatty liver disease is to accumulate a cohort of subjects with diverse backgrounds and a spectrum of disease severity, to enable scientists to determine the factors that predispose some individuals at risk to serious liver disease while sparing others.
Reporting Period:
Year 3/NCE
The goal of this project was to collect blood or skin tissue from subjects with liver diseases to learn more about the factors that provoke these illnesses. We focused our attention on two specific liver diseases: (a) hepatitis C and (b) non-alcoholic steatohepatitis, otherwise known as "NASH" or "fatty liver disease." Hepatitis C and fatty liver disease are the two most common liver diseases in the state of California.
In patients infected with the hepatitis C virus, factors such as race, genetic makeup and immunologic makeup can affect the severity of disease and can influence individual responses to antiviral drug treatment. Our goal was to recruit hepatitis C-infected individuals from diverse backgrounds, to enable scientists to use stem cells from these subjects to study how liver cells from different individuals respond to virus infection. We enrolled 117 adults with hepatitis C (62% white, 38% non-white).
In the case of fatty liver disease, we recruited subjects who had a proven diagnosis of this disease based on a liver biopsy. Fatty liver disease typically occurs in people who are overweight and have additional health problems such as high blood pressure, high cholesterol and diabetes. It is very common in people of Hispanic descent. We enrolled 48 adults with fatty liver disease into the study. Although the subjects were from diverse backgrounds, the majority (66%) were Hispanic. The long-term objective of the work is to permit scientists to use stem cells from these subjects to investigate genetic factors that cause fatty liver disease. Scientists can also study whether liver cells made from the stem cells are unusually sensitive to injury from fat accumulation.
Grant Application Details
Application Title:
iPSC-derived Hepatocytes as Platforms for Research in Viral Hepatitis and Non-alcoholic Steatohepatitis
Public Abstract:
Hepatitis C and fatty liver disease are the two most common liver diseases in California. Individuals from different backgrounds are susceptible to these liver diseases, but they have unique genetic profiles that may influence the severity of disease and the response to specific therapies. Technology now makes it possible to generate stem cells from a person’s own skin. These cells can subsequently be used to generate liver cells identical to those from the original donor. Using this approach, scientists can perform research directly on an individual’s own liver cells to identify features that make the cells susceptible or resistant to disease and drug therapy. In this project, the research team will collect blood and skin tissue from people with liver disease and from healthy control subjects. The donated tissues will be placed in a "bank" for the production of stem cells. The overall goal is for the donated cells to be made available to scientists who will convert them to liver cells, and then carefully study them to learn more about liver disease. Research such as this is extremely valuable because it allows patients and volunteers to make a very personal contribution to the understanding of liver disease. The materials donated to this tissue "bank" will be a resource to the scientific community for many years.
Statement of Benefit to California:
Hepatitis C and fatty liver disease are the two most common liver diseases affecting the citizens of California. Together they afflict one in every 12 people in the state and kill roughly 4,000 state residents each year. Researchers in California are actively seeking new information about the causes of and treatments for liver disease; their progress will be greatly accelerated by the opportunity to directly study the biology of diseased patients. The goal of this project is to build a "bank" of stem cells from local patients with liver disease. Patient donors will come from many different backgrounds, reflecting the great diversity of California. The bank, once established, will be a tremendous resource for medical research because the banked cells will be renewable and made available to the entire research community. Banked stem cells will enable researchers to study the genetics and biology of liver disease and to test new therapies. Importantly, they will give researchers an opportunity to study liver disease in its most important context - the affected patient. The research made possible through this effort will greatly enhance our understanding of liver disease; this will in turn reduce the negative impact of liver disease on the health and well-being of California residents.
