Hope for liver patients

Thursday, March 31, 2011

UMASS SEEKS TO STOP TRANSPLANT RE-INFECTION

By Karen Nugent TELEGRAM & GAZETTE STAFF

WORCESTER — A new liver does not mean the end of hepatitis C.

The virus, which can go undetected for years, is the leading cause of liver failure in the United States, and for many patients, a transplant is the only life-saving treatment. But the hepatitis C virus circulates in the blood, and during transplant surgery, infected blood immediately gets into a donated liver.

“One-hundred percent (of transplanted livers) get re-infected,” said Dr. Donna M. Ambrosino, executive director of Massachusetts Biologic Laboratories, a division of the University of Massachusetts Medical School. “The virus stays in the blood for a couple of days, if not longer. You cannot be without your liver, and you can't put the new liver in without blood spilling on it and getting into it. So we're between a rock and a hard place.”

A re-infected liver, while giving patients perhaps five more years of life, she said, accelerates the course of the disease, and standard antiviral medications are not well-tolerated in transplant patients.

The medical school, along with five hospitals in Boston, New York and Connecticut, is entering the second phase of a clinical trial of a new treatment for the prevention of hepatitis C re-infection in liver transplant patients. The treatment, a monoclonal antibody, is different from the usual antiviral drugs in that it binds the virus and blocks its ability to get into the liver, Dr. Ambrosino said.

There are 10 patients currently in the study, with a target enrollment of 16 patients. Half are given the antibody, so far known only as MBL-HCV1, and half are given a placebo.

Dr. Ambrosino, who is also a professor of pediatrics at the medical school, said results will likely be available in the summer. If the virus is not found in patients 42 days after transplantation, it will be deemed a success. If the virus is found, a trial with a higher dose of antibody will begin.

The antibody — or the placebo — is administered to patients by infusion, in phases.

The first dose is given a few hours before transplant surgery, and another is given during surgery between when the diseased liver is removed and the donor liver is implanted. A third infusion is given just after surgery, followed by daily infusions during the first week of recovery. A final infusion is given on the 14th day after surgery.

A 2009 study of the antibody in 31 healthy volunteers showed no serious side effects.

Dr. Ambrosino said it generally takes 10 years of development and trials before a new medication becomes available.

According to the U.S. Centers for Disease Control and Prevention, hepatitis C virus infection is the most common chronic blood-borne infection in the United States, with approximately 3.2 million people chronically infected, and about 10,000 deaths per year. Of 6,000 or so liver transplants each year in the United States, half are the result of hepatitis C infection.

However, it is a slow-growing infection that may not show symptoms for 20 years — until liver failure becomes apparent, or abnormal laboratory tests are found.

Dr. Ambrosino said because the average age of a hepatitis C patient is 55 — smack in the middle of the baby boomer generation — they will probably make up the next wave of patients.

“So that's a large group, and there will be more people needing liver transplants,” she said.

While many boomers unknowingly carry the virus, Dr. Ambrosino said it is not entirely because of bad behavior such as drug use and multiple sex partners in the 1970s.

Hepatitis C can be transmitted through drug use via contaminated needles, and rarely through sexual contact, but she said the majority of cases were contracted through blood transfusions prior to the late 1970s when the virus was first identified. Since 1990, all donated blood has been tested for hepatitis C.

“It was not known in the '70s,” Dr. Ambrosino said.

The virus differs from hepatitis A, a largely food-borne illness, and hepatitis B, a more obvious illness, which is also transmitted through blood but was identified earlier and for which there is a vaccine.

The Massachusetts Biologic Institute was part of the state Department of Public Health until 1997, when it became aligned with UMass. Its main focus is public health — especially infectious diseases — and its major source of revenue is manufacturing tetanus-diphtheria vaccine and other medications. Monoclonal antibodies are the latest products, Dr. Ambrosino said.

Contact Karen Nugent via email at knugent@telegram.com

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