Lower Protein Activity After Hepatitis C Treatment May Point to Healing Path for Scarred Liver | MUSK

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MUSC researchers report in Journal of Viral Hepatitis1 that the activity levels of proteins involved in scarring the liver, or cirrhosis, begin to decline immediately after treatment for hepatitis C virus (HCV), suggesting the possibility of early recovery. Understanding these changes could shed light on whether treatment, which is curative for HCV, puts the body on a path to reverse the damage caused by long-term infection. It could also inform new therapeutic interventions for cirrhosis caused by hepatitis C.

Hepatitis C is a viral infection of the liver which over time can cause scarring, increasing the risk of organ failure and cancer. Fortunately, a cure is already available.

“The good news about HCV treatment these days is that almost everyone who knows they have a hepatitis C infection and seeks treatment is cured,” said Eric Meissner, MD, Ph.D., senior author of the Journal of Viral Hepatitis article and associate professor in the Division of Infectious Diseases at MUSC. “The cure rates for current therapies are between 95% and 98%. It is one of the most successful stories in the field of infectious diseases. It really was just revolutionary when it came to drug discovery. “

“Most people don’t know that every adult is recommended to get tested for hepatitis C at least once, whether or not they have obvious risk factors. Hepatitis C is easy to cure. The earlier it is treated, the less scarring you will develop in your liver. – Dr Eric Meissner

Although the treatment is curative, in the sense that it rids the body of the virus, it is not well understood how well the body can reverse existing damage caused by long-term infection and how this process can differ from a person. to the other.

Some patients are unaware they are infected and harbor the virus for many years, making them vulnerable to cirrhosis caused by long-term infection and inflammation.

“Hepatitis C is a common infection, but not everyone knows they have it,” Meissner explained. “Most people don’t know that every adult is recommended to get tested for hepatitis C at least once, whether or not they have obvious risk factors. Hepatitis C is easy to cure. The earlier it is treated, the less scarring you will develop in your liver.

Although extensive testing and earlier treatment of HCV infection may prevent scarring of the liver and its harmful consequences in many people, Meissner’s team wanted to examine, in this study, how treatment affected the liver. already scarred liver.

“The aim of this investigation was to better understand the fate of the liver after the elimination of hepatitis C”, explained Meissner.

“We believe that eliminating the virus puts the liver and its proteins on the road to recovery.” – Dr Eric Meissner

Meissner teamed up with Lauren Ball, Ph.D., director of the Mass spectrometry facility to MUSC Proteomics Center, to design and interpret an in-depth analysis of proteins in liver biopsy samples from eight HCV patients collected before and after their curative treatments. Due to the small amount of tissue available for the study, the samples were analyzed using advanced phosphoproteomics technology developed at Harvard Medical School to measure changes in protein modification.

“Analysis of changes in protein abundance and modification after therapy revealed a robust antiviral response to treatment,” Ball said.

Dr Don Rockey, Director of DDRCC.

This research has been greatly facilitated by the new Digestive Diseases Research Center (DDRCC), funded by the National Institute of Diabetes and Digestive and Kidney Diseases, which supports researchers doing research on digestive and liver disease. The center also contributes funding to the MUSC Proteomics Center, which was instrumental in carrying out this research and is now providing this technology to MUSC for researchers.

“This work is extremely important as we are working to improve the non-invasive assessment of not only liver fibrosis, but also those at risk of having fibrosis reversal after HCV eradication,” said Don Rockey, MD, director of the DDRCC.

As expected, the activity of the proteins involved in fighting the virus and the inflammation of the liver decreased when the virus was treated. This expected discovery gave the team confidence in their analysis and gave credit to an unforeseen discovery: while the levels of proteins involved in the cirrhotic pathways have not changed, their activity levels as reflected by the cirrhotic pathways. protein changes were reduced.

“This work is extremely important as we are working to improve the non-invasive assessment of not only liver fibrosis, but also those at risk of having fibrosis reversal after HCV eradication.” – Dr Don Rockey, Director of DDRCC

“This decrease in activity could be an early sign or a window into how the liver might recover after the virus is cleared,” Meissner said. “We believe that eliminating the virus puts the liver and its proteins on the road to recovery.”

Meissner thinks it may take longer to see changes in protein levels.

“We haven’t seen any changes in the actual proteins that make up the scarred or damaged liver, but these changes in the proteins may take longer to manifest,” Meissner said.

Although these results are preliminary, Meissner is intrigued by what they suggest about the impact of HCV treatment on liver scar tissue.

“While the decrease in fibrotic protein activity that we have observed needs to be further investigated to fully understand any link with liver healing, it may offer new insight into how the liver’s healing process might work. unwind, “Meissner speculated. “Seeing these changes so soon after treatment for hepatitis suggests that the healing process could begin as soon as the treatments are finished and the virus is cleared. This finding underscores the importance for every HCV infected patient to receive curative treatment as soon as possible. “

Reference

1. Ball LE, Agana B, Count-Walters S, Rockey DC, Masur H, Kottilil S, Meissner EG. Treatment of hepatitis C virus with direct-acting antivirals induces rapid changes in the hepatic proteome. J Viral hepat. November 2021; 28 (11): 1614-1623. doi: 10.1111 / jvh.13593.


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