The Complexities of Treating Chronic Hepatitis C (HCV)

“Dear Dr.,
I am a 57 year old female diagnosed with HCV 1B. In 2004, I got pneumonia for no reason. I have always lead a very active lifestyle: married to a chiropractor, I started as a teen lifting weights etc. At the time of I was also diagnosed with gallstones and had my gallbladder removed. I had high liver enzymes, the surgeon (on her game) did a liver biopsy while she was in there and found the HCV. I was then referred to a gastro and started peg/ribovarin. In the beginning of 2005, I had very high iron levels so testing was performed for hemochromatosis (negative). Treatment was started–no blood letting. I was very precise in every aspect of treatment down to the time of day medication was taken, but I did not reach the expected load decrease at twelve weeks. It was slight. I was kept on treatment for a total of 46 weeks. I had a very ill reaction to medication.

During this time, I had educated myself, fear was gone, I knew something was wrong. I went to see Dr. Gene Lesage, at the Texas Liver Center. He took me off treatment almost immediately and I have since learned I never should have been put on treatment. Biopsy had slight bridging fibrosis. I was labeled a slow responder. There is no available treatment for 1B. I have been sick for 6 years: severe fatigue, nausea, headaches, and severe, severe pain in lower extremities. I am just sick all the time. I was not before starting treatment except for getting the pneumonia…” — Karyn of Marble Falls, Texas

Dr. Michell Shiffman of Bon Secours' Liver Institute of Virginia

Dr. Michell Shiffman of Bon Secours' Liver Institute of Virginia

Karyn’s story is not unlike many with chronic HCV.  Chronic HCV is known to cause scarring or fibrosis in the liver and lead to cirrhosis.  Advnaced fibrosis is associated with severe fatigue.  HCV is know to interact with the immune system and cause diffuse muscle and joint pains.  It does so by forming complexes in the blood called cryoglobulins, which is the hepatitis C virus covered by numerous antibodies.  These complexes are deposited in small capillaries and damage nerves, joints and skin causing skin rashes, and pain.

Karyn is also like many other persons who tried peginterferon and ribavirin in the past but failed to respond and be cured of HCV with of this treatment.  We now know the reason why some patients with chronic HCV respond to treatment and others do not is based upon genetics.  We all have a gene, called IL28B, which modulates our response to interferon.  If the gene is “turned on” and makes us sensitive to interferon the cure rate for patients with HCV is about 70% when treated with peginterferon and riabvirin.  If the gene is “turned off” the cure rates are only about 20-25%.  I suspect Karyn is genetically not sensitive to interferon and that is why she did not respond well.  She can be tested for this gene, the test is commercially available and this will help Karyn know her chances of being cured of HCV with the new treatments.

Fortunately, the FDA has now approved 2 new potent anti-viral agents for HCV; telaprevir and boceprevir.  These drugs directly inhibit HCV and make the virus much more sensitive to interferon and ribavirin treatment.  When combined with peginterferon and ribavirin either one of these anti-viral agents significantly increase the number of patients who are cured of HCV.  The likelihood that a patient will be cured is related to the interferon sensitive gene, IL28B.  If the gene is in the “on position” the cure rate approaches 90%.  If the gene is in the off position the cure rate is about 50%.  IF the gene is in the middle position the cure rate is about 66%.

Karyn’s previous non-response to peginterferon and ribavirin also gives us information about her chance of being cured on re-treatment.  It is hard to tell from her story if she was a “Null responder” and had mess than a 100-fold (2 log) decline in the virus during her previous treatment.  She may have been a “Partial responder” and had a significant drop in the virus but just did not become negative.  Patients with prior null response have a 33% of cure when retreated with either of the anti-viral agents peginterferon and ribavirin.  In contrast, patients with prior partial response are more sensitive to interferon and therefore have a 66% chance of being cured on re-treatment.

At the Liver Institute of Virginia my staff and I take the time to explain all of these issues to our patients with chronic HCV.  Many anti-viral agents for HCV are currently being developed and studied and there is great hope and promise that all patients with chronic HCV like Karyn will one day be cured of HCV.  It just may take a bit more time to develop all the tools we need for all patients.

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About Dr.MLShiffman

Dr. Mitchell Shiffman is the Bon Secours expert on liver disease and liver treatments for Virginia. Prior to joining Bon Secours, Dr. Shiffman was a professor of Medicine at Virginia Commonwealth University (VCU) in Richmond, VA. He was the Chief of the Hepatology Section and Medical Director of the Liver Transplant Program at the VCU Medical Center from 1989 until 2009. During his 20 years at the VCU Medical Center Dr. Shiffman built and directed one of the most respected and productive hepatology programs in the United States. Dr. Shiffman is recognized as one of the world’s leaders in the field of Hepatology. His particular area of research is viral hepatitis. He has been involved with and/or directed numerous clinical trials to develop new and better treatments for viral hepatitis B and C. Dr. Shiffman is a regular speaker on the treatment of viral hepatitis, the management of various liver disorders, and issues related to liver transplantation at regional, national and international society meetings. He has published over 200 articles in medical journals related to the treatment of liver diseases and has edited two books on this topic. In addition, he has contributed to various HCV educational resources including an HCV educational kit. Dr. Shiffman is also a widely recognized expert consultant to pharmaceutical companies on the treatment of liver disease. Dr. Shiffman holds a Bachelor of Arts from State University of New York at Buffalo, a Master of Science in physiology from the University of New Mexico School of Medicine in Albuquerque, N.M. and his Doctor of Medicine from State University of New York Upstate Medical Center in Syracuse, N.Y. He completed his internship and residency in internal medicine and fellowship training in gastroenterology and hepatology at the Medical College of Virginia Hospitals in Richmond, VA. Dr. Shiffman is a member of many professional organizations including: the American College of Gastroenterology, American College of Physicians, the American Gastroenterological Association, American Society for the Study of Liver Diseases, American Society of Transplantation, European Association for the Study of the Liver, International Liver Transplantation Society, Richmond Academy of Medicine, Virginia Medical Society and the Virginia Gastrointestinal Society. He was a member of the Board of Trustees with the American College of Gastroenterology from 2003-2009.

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