Researchers have used a modified virus to help repair damaged hepatocytes in mice with liver disease. If it proves to be similarly effective in humans, the technique could be a much-needed treatment option for thousands of patients diagnosed with liver disease.
In the US alone, over 35,000 people die of liver disease every year. The viral therapy works to reverse the continuous scarring of the liver, known as liver fibrosis, which eventually results in organ failure.
Liver disease is often caused by exposure of hepatocytes to alcohol, or stress caused by disease. As healthy hepatocytes are damaged and die, myofibroblasts take their place by generating collagen-based scar tissue. Once the liver reaches a critical number of hepatocytes, it is unable to perform its functions and goes into liver failure.
Dr. Holger Willenbring and his colleagues at the University of California, San Francisco, developed a new technique whereby myofibroblasts could be transformed into hepatocytes using viral therapy. The researchers used a modified adeno-associated virus to deliver liver transcription factors into the myofibroblast cells of liver-damaged mice. After infection with the genetically modified virus, the transcription factor genes are integrated into the host cell’s genome, inducing the cells to transform into hepatocytes.
The researchers found that the viral therapy reduced the collagen content of the mice livers by about one third, as well as increased the number of healthy liver cells. “We think the combination of making more hepatocytes and reducing collagen is the most promising approach to treating liver fibrosis,” said Willenbring.
According to Vanessa Hebditch, director of communications and policy at the British Liver Trust, the research could have exciting implications for the future treatment of liver disease. “The vector used in these studies is one that has already been used in the treatment of other human diseases so this is a promising approach.”
Adeno-associated viral therapy has been tested in multiple clinical trials for diseases like cystic fibrosis, hemophilia and retinal eye conditions. Willenbring expects that it will be five years or more before the viral therapy can be tested in human liver disease patients.