Bennet Cecil, MD
About one in five American patients with HCV have cirrhosis. The average age of these cirrhotic patients is 50 years, but 6-10% of this subgroup dies each year. In other words, cirrhotic patients die at the speed of 80 year-old Americans. As the average age of patients with HCV increases each year, the percentage developing cirrhosis will increase. After twenty years of infection about 20% of patients develop cirrhosis and after fifty years of infection, about half develop cirrhosis. The Centers for Disease Control and Prevention has predicted that deaths from HCV will triple as Americans age.
Fortunately, most patients with hepatitis C have mild or moderate liver damage, and do not have an increased risk of death. Hepatitis C is almost always a slowly progressive disease, giving patients a long window of opportunity to cure their infection. If HCV is successfully eradicated, the liver improves each year instead of worsening. Only the liver and the bone marrow have this ability to regenerate. Over a period of years, the scar tissue in the liver will diminish after HCV is eradicated by successful antiviral therapy. Even biopsy proven cirrhosis has been shown to reverse in some patients. The risk of liver cancer or failure also falls, and with it the risk of premature death.
With few exceptions, hepatologists have not risen to the challenge of treating patients with advanced HCV cirrhosis with antiviral therapy. They have used the excuse that there is not enough data to recommend treatment. They have purposefully avoided starting clinical trials that enroll patients with advanced cirrhosis. Instead, more and more patients with HCV cirrhosis are added to the liver transplant list. About 18,000 patients are on the list with only 4-5,000 livers available. About 30% of them have genotype 2 or 3 strains of the virus, which have an excellent chance of responding to even low doses of interferon. Thousands of other patients are not on the liver transplant list because they are too old, too poor or are too sick with non-hepatic diseases.
Successful treatment of cirrhotic patients requires more than one year of treatment to prevent viral relapse once therapy is completed. Every single viral particle must be eliminated to prevent relapse, and the virus hides in scar tissue in cirrhotic patients. The worse the liver fibrosis, the longer treatment must last. In the HALT C study, which enrolled mostly patients with early cirrhosis, about a third of patients became undetectable for HCV-RNA on treatment. Unfortunately, half of them relapsed when therapy was stopped. In non-cirrhotic patients, only about 20% of treatment responders relapse.
Cirrhotic patients do not tolerate full doses of interferon and ribavirin very well. They tend to drop their white blood cell counts, become anemic and drop their platelet counts quickly. I start with a quarter dose of pegylated interferon or less in cirrhotic patients and raise the dose every week or two. If the pegylated interferon is working, the viral level falls by 90% or more each month. It the patient responds, I add ribavirin at 400-600 mg per day. The dose is increased by 200 mg each month up to 800-1,200 mg per day. Many cirrhotic patients need Procrit and/or Neupogen to keep the red blood cell and absolute neutrophil counts in an acceptable range. A few need Neumega to keep the platelet count above 30,000.
Treating advanced HCV cirrhosis with pegylated interferon plus ribavirin is an off label use and has not been approved by the FDA. Pharmaceutical companies cannot promote or advertise it. Patients and physicians can use drugs off label if they decide that the benefits exceed the risks. Liver transplant evaluation can be done concurrently and is necessary for interferon nonresponders. I hope that more physicians will offer this option to their patients with HCV cirrhosis, because I believe it will reduce the number of deaths from HCV cirrhosis.
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