Seventh Annual Public Interest Organization Meeting

Dr. Harvey J. Alter, Chief, Infectious Diseases Section, Department of Transfusion Medicine, NIH Clinical Center, summarized the history of research on hepatitis viral infection. He focused on the seminal research findings that eventually led to elimination of post-transfusion infection of the liver from hepatitis C virus (HCV).

Hepatitis: Research and Results

The research that ultimately led to identification of HCV began in the 1960s in the laboratories of two NIH scientists—Dr. Alter, who worked on transfusion medicine in the NIH blood bank, and Dr. Baruch Blumberg, a geneticist who studied inherited differences in seroproteins from tissue samples collected from around the world. Together, they collaborated on studies of blood from an Australian aborigine that opened the door to understanding hepatitis.

Dr. Alter noted that, after years of futile research by many scientists, he and Dr. Blumberg pursued a previously unknown antigen that they discovered in the aborigine's blood. Their initial laboratory and clinical studies suggested that a person's ability to respond to the antigen is inherited. In subsequent studies of institutionalized children with Down syndrome, they proved that the antigen was an infectious agent that had been transmitted in the crowded living conditions. When a laboratory worker in Dr. Blumberg's laboratory became ill after a needle stick, the scientists were able to define the antigen as a new hepatitis agent, which they termed hepatitis B virus (HBV).

Dr. Alter noted that, in the late 1960s and 1970s, the NHLBI supported a series of prospective studies of transfusion-associated hepatitis in individuals undergoing open-heart surgery. These studies led to the determination that blood donors who were paid for their blood were at high risk of having, and therefore transmitting, hepatitis. As a result, blood centers stopped using paid-donor blood and by 1970 the United States had an all-volunteer blood donor system. At this time, the first-generation test for the hepatitis B antigen was introduced, which resulted in a dramatic decrease in post-transfusion hepatitis infection. By 1973, a third-generation test was available and, in the course of assaying stored samples of blood, scientists were able to identify another previously unknown hepatitis virus, which they termed "non-B." That virus was subsequently renamed "non-A, non-B" after scientists discovered the hepatitis A virus in 1974.

Scientists studied the non-A, non-B hepatitis virus for 15 years, from 1975 to 1990, to determine its structure, composition, and infectivity. The studies included viral inoculation of chimpanzees, which became infected but not ill, followup of an infected individual who recovered from acute hepatitis, liver biopsies, and testing of stored samples. In 1989, cloning studies by Chiron Corporation resulted in the detection of HCV as the cause of non-A, non-B hepatitis. With the development of increasingly more sensitive tests for HCV, scientists were able to reduce the rate of post-transfusion HCV infection to near zero by 1997.

HCV Infection

Currently, HCV causes approximately 15 percent of all cases of acute hepatitis. It is the main cause of chronic liver disease around the world, accounting for 42 percent of cases by itself and for 22 percent of cases in association with alcohol use. Dr. Alter noted that HCV is the leading indicator for liver transplantation because it causes persistent infection in 70-85 percent of affected individuals.

The three major patterns of transfusion-associated HCV are (i) acute, but resolving infection (in 15-20 percent of individuals infected); (ii) persistent, chronic, and progressive, though relatively asymptomatic, infection (in 45-65 percent); and (iii) rapid-developing chronic infection (in 20-30 percent, usually elderly persons). Dr. Alter noted that the outcomes for individuals infected with HCV largely depend on their age at the time of infection. HCV infection associated with other infections (e.g., HIV) or conditions (e.g., alcohol use) has a far worse prognosis than HCV infection in individuals with no co-morbidities.

Treatment for HCV

Dr. Alter noted that the availability of effective treatment for HCV infection is changing the picture of the disease. Use of interferon is especially promising, for 50-55 percent of the individuals treated can be completely cured of the infection. Dr. Alter elaborated on the prospects for individuals receiving treatment. He noted that 20 percent of individuals acutely infected with HCV will spontaneously recover, while 80 percent become carriers. Among carriers, 72 percent will have a favorable outcome, and treatment will be successful in approximately 50 percent. Dr. Alter noted that the prospects for individuals with HCV infection are therefore good and will become even better as treatment for HCV infection improves.

Still, HCV infection is a major problem. Globally, 1-3 percent of the world's population, which amounts to millions of people, are infected with HCV and lack effective treatment. Dr. Alter commented that medical personnel have different views of HCV disease—while a blood banker considers it a mild disease, a transplant surgeon considers it a severe complication.

Discussion

Liver Biopsy

Patient Studies

Tattoos