Those with chronic liver disease can pray for the reversal of liver fibrosis, but new research gives hope for a more scientific approach.
The human liver is capable of recovering from an injury, but chronic liver disease repeatedly challenges this ability. Any continual threat to the liver’s well-being can progressively scar liver tissue, eventually rendering that tissue unable to function. The lack of effective pharmaceutical treatments capable of stopping or reversing liver damage means that liver health efforts primarily target liver injury prevention. However, a study led by researchers at the University of California at San Diego has revealed a potential solution for helping heal the liver, inspiring new hope in those with chronic liver disease.
Understanding Liver Scarring
Toxin exposure, oxidation and other occasional threats that can harm liver cells is part of our everyday experience. Normally, injured liver cells don’t present much of a problem because the liver is capable of regeneration. However, when the rate of liver cell injury outpaces the liver’s regenerative capacity, scars form. Known technically as liver fibrosis, scarring is the body’s attempt to keep the damage done to liver cells contained. However, repeated scarring can block blood flow through the liver and lead to damaged liver tissue that can no longer perform its duties.
Although there are a wide range of potential culprits, chronic liver disease is frequently due to fatty liver, chronic viral hepatitis or alcohol abuse. With chronic liver disease, normal liver regeneration may not occur because hepatic stellate cells become activated and launch an inflammatory and fibrotic cascade. This cascade eventually results in the buildup of collagen scar tissue in the liver. Once activated, hepatic stellate cells acquire characteristics of another cell type called myofibroblasts – cells that abundantly produce extracellular matrix proteins such as collagen. These proteins accumulate as scar tissue and cause organ dysfunction. When fibrosis has advanced to the point where the liver has hardened and shrunk, and can no longer function adequately, the scarring has progressed to cirrhosis – a hallmark of advanced liver disease.
Liver Scarring Reversal
The exact moment at which fibrosis becomes irreversible is unknown. Dense cirrhosis is generally considered to be permanent, but less severe scarring has demonstrated an amazing reversibility when the underlying cause of chronic liver disease is halted.
Although effective pharmacologic interventions that help liver scars heal have not yet materialized, researchers are in desperate pursuit. In the meantime, anti-fibrotic therapies are typically focused on suppressing inflammation in the liver. In addition to stopping the underlying liver disease cause and suppressing inflammation, treatment goals for fibrosis may include hepatic stellate cell destruction and breaking down collagenous liver scars. However, new research has just found another possible strategy for healing liver fibrosis.
Published in the May 7, 2012 online Early Edition of the Proceedings of the National Academy of Sciences, research led by the University of California, San Diego School of Medicine investigated myofibroblasts – the cells that produce the fibrous scarring in chronic liver injury.
As described earlier, the successful treatment or elimination of chronic liver disease can permit the liver to repair itself. Experts used to believe this repair was partially due to the activated hepatic stellate cells dying and being removed by other cells. However, according to Tatiana Kisseleva, MD, PhD, an assistant research scientist and first author of this study, that is not entirely accurate:
• The San Diego based research study found that even after a liver disease cause is removed, up to half of activated hepatic stellate cells (myofibroblasts) persist. These remaining myofibroblasts revert to an inactive state.
• After one month of myofibroblast inactivity, these cells stop producing collagen and return to their normal location.
• The inactive myofibroblasts are more vulnerable to repetitive injury than hepatic stellate cells that had never been activated.
Nonetheless, this breakthrough study gives scientists on the hunt for ways to reverse liver scarring an additional tool: reverting myofibroblasts to an inactive state.
Since liver fibrosis is the 12th leading cause of death in the United States, all efforts to help those affected warrant investigation. Preventing liver damage, devising better treatments for the causes of chronic liver disease, quelling liver inflammation, destroying activated hepatic stellate cells and metabolizing the fibrous matrix of liver scars has not yet revealed a successful formula for reversing liver fibrosis. However, finding a way to influence myofibroblasts to regress could be the missing piece needed to finally achieve the healing of liver scars.
http://health.ucsd.edu/news/releases/Pages/2012-05-07-scarring-cells-revert-as-liver-heals.aspx, Scarring Cells Revert To Inactive State As Liver Heals, Retrieved May 12, 2012, University of California, San Diego, 2012.
http://www.liverdisease.com/cirrhosis_hepatitis.html, What is Cirrhosis?, Retrieved May 13, 2012, Melissa Palmer, MD, 2012.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1899462/, The Myofibroblast, Boris Hinz, et al, Retrieved May 13, 2012, American Journal of Pathology, June 2007.
http://www.universityofcalifornia.edu/news/article/25240, Cholesterol Regulator key in liver, scarring, cirrhosis, Retrieved May 13, 2012, Regents of the University of California, 2012.
http://www.uptodate.com/contents/emerging-therapies-for-hepatic-fibrosis, Emerging Therapies for Hepatic Fibrosis, Retrieved May 13, 2012, UpToDate, Inc., 2012.