Hepatitis C

Scope of Problem and Trends

Hepatitis C is caused by the hepatitis C virus (HCV), a blood borne infectious agent. The incidence of new HCV infections rose steadily through the 1960s and 1970s and peaked at ~200,000/yr in the late 1980s. In 1998 there were an estimated 28,000 new infections. More important is that 1.8 percent of the U.S. population are already persistently (chronically) infected with HCV. African-Americans and Hispanics are respectively three- and two-fold more likely to be HCV positive than whites. Currently hepatitis C causes 8,000 10,000 deaths each year and accounts for almost half of the ~4,000 liver transplantations done each year. Since death from HCV liver disease usually occurs 20 or more years after the initial infection, the HCV death rate is anticipated to triple in the next 15 to 20 years when sequelae peak.

Sequelae

HCV infects and damages the liver, an organ vital to energy production, detoxification, immune functions and digestion. HCV does its damage even without readily recognizable physical or clinical symptoms. Often they are mild and flu-like. Liver disease has discrete stages--fibrosis and its sub-stages, cirrhosis, decompensated cirrhosis (liver failure) and liver cancer. Patients appear to move linearly through these stages at slow, medium or fast rates. In fact, most are slow. Estimates are that over the first 20 years, about 20 percent progress to cirrhosis and one to five percent to cancer. Liver failure occurs in 25 percent of those with cirrhosis. Alcohol use, infection at an age >40, infection with other hepatitis viruses and being male are associated with more severe liver disease.

Treatment

There are four approved therapies whose effectiveness is measured by the sustained response rate. Three are interferon mono-therapies and the latest combines interferon with ribavirin. All have significant side effects. Interferon therapies produce an average 15 percent sustained response rate while the combination produces one of ~40 percent. Significantly poorer than average responses are seen in patients who have genotype 1 (most Americans) or are African-Americans, older than 40 or male, as well as those who with the later sub-stages of fibrosis. Viral replication cycle and fibrosis-based therapies as well as long-acting interferons and ribavirin-like drugs are being developed.

Cost

The CDC estimates that medical and work-loss costs for HCV are >$600 million annually. This excludes the costs for transplantation.

Challenges And Goals

Research and clinical management questions are numerous. Answers will come via:

Systematic, innovative and multi-disciplinary experiments to understand the mechanisms responsible for recovery, persistence, pathogenesis and progression.
Large patient based studies of the natural history of infection and disease as well as the impact of co-factors on it.
Development of better model systems , e.g., in vitro cell culture and small animals.

Risk Groups

Both past and present risk group identification is important since they differ somewhat. Ten to 15 years ago risk groups included: injection drug use (HCV is acquired faster than HIV or HBV.), multiple heterosexual partners, blood transfusions, use of blood products and hemodialysis. With the development of HCV tests for the blood supply and better procedures to inactivate viruses in blood products, risk groups changed and now are primarily injection drug use and multiple sexual partners. Still for about 10 percent of cases no risk factor is identified.

Research Priorities

Understand the mechanisms of recovery and persistence.
Define the viral replication and pathogenic processes.
Develop more effective and safer therapies as well as vaccines.

Useful Information Sites

ª Hepatitis Foundation International
ª American Liver Foundation

April 1999