STATEMENT OF

TERESA L. WRIGHT, MD
CHIEF, GASTROENTEROLOGY SECTION,
SAN FRANCISCO VETERANS ADMINISTRATION MEDICAL CENTER
BEFORE THE HOUSE VETERANS' AFFAIRS COMMITTEE
SUBCOMMITTEE ON BENEFITS

July 16, 1998

Mr. Chairman and Committee Members,

I am pleased to appear today to discuss the importance of Hepatitis C infection in the V.A. Healthcare system.

I am Chief of the Gastroenterology Section at the San Francisco VA and have been treating veterans at the liver clinic there for more than ten years. I am also an Associate Professor of Medicine at the University of California, San Francisco and currently hold research grants from the National Institutes of Health, the VA and from industry to study the epidemiology, pathogenesis and treatment of hepatitis C virus (HCV).

HCV affects 3.9 million Americans with a prevalence of 1.84% in the population as a whole, but with a higher prevalence in minority populations - 3.2% in blacks and 2.1% in Mexican Americans. The highest seroprevalence is in those between the ages of 30 and 39, and 40 and 49 years. In these groups, the prevalence is 3 fold greater than in the population as a whole, and it is these data, in conjunction with the long duration of infection before life threatening complications occur, that has led to the concern that mortality from HCV may triple in the coming decade. The natural history of infection is highly variable, with many being infected for 20-30 years without developing complications, yet some, albeit the minority, progressing to cirrhosis and even liver failure within 10-20 years. Nevertheless, HCV disease is linked to 10,000 deaths annually in the U.S. and the development of liver cancer. HCV disease is also the most common indication for liver transplantation in US transplant programs in general and VA transplant programs in particular.

There is limited information about factors which influence or accelerate the natural history of HCV disease, but three factors have been independently associated with progressive disease in one large epidemiological study were excess alcohol intake, male gender and age greater than 40 years at the time of acquisition of infection. The first two factors are directly relevant to our veterans. Other factors which are believed to contribute to progressive disease are HIV coinfection and immunosuppression following organ transplantation.

The prevalence of HCV infection in Veterans is unknown, but would be predicted to be higher than in the U.S. population as a whole because risk factors for infection are common in our Veteran population. HCV is transmitted by parenteral routes, i.e. through contact with blood. Injection drug use is the most common risk factor for HCV in the general population accounting for 40-60 per cent of all infections. Transfusion is also associated, but accounted for only 5 per cent of infections historically and many fewer today. HCV infection has also been associated with increasing number of sexual partners, and in minority populations with cocaine and marijuana use. In the largest epidemiological survey of HCV in the US, the NHANES III study, there was no association between HCV and education or military service for non-Hispanic whites. In Blacks and Mexican Americans with military service, the prevalence of infection was 3.3 and 1.9 per cent respectively. What complicates determination of the mode or time of acquisition of HCV in an individual is that initial infection is typically silent and duration of disease must be infered from presumed time of first exposure.

From our own experience at the San Francisco VA Medical Center, HCV disease is a common problem. In those who were tested as part of a city-wide needle-stick study, 10 per cent of hospitalized veterans were seropositive for HCV. This is substantially lower however than the experience at San Francisco General hospital where the seroprevalence is 30 per cent. Of 195 seropositive veterans attending the San Francisco VA liver clinic, 78% are between the ages of 40 and 59 years. In a limited survey of 48 seropositive veterans, 24% had served in Vietnam, 2% had served in Korea, 4% had served in World War II, but more than 60% had never been in combat. A history of injection drug use was obtained in almost half of these veterans, but many had started using drugs after their military service. A history of transfusion was obtained in almost 20%. However, in this limited survey, prior transfusion was also common in those without HCV infection. This study is too small in sample size to comment on the significance of these associations, and is currently being extended to a larger number of seropositive and seronegative individuals. The distribution of HCV genotypes in our veterans was similar to that in the U.S. population as a whole, a finding which supports prior observations by Dr. Leonard Seeff at the Washington DC VA. These results imply that HCV infection is being acquired in Veterans from U.S. rather than European or Asian sources. Our study was not designed to assess the prevalence of HCV infection in veterans as a whole nor in subpopulations of veterans such as those who served in Vietnam. These questions are being addressed in a study which is just getting underway at our VA and which is funded for the coming five years.

With the recently mandated 3look-back2 program in blood transfusion recipients, there has been much discussion about the importance or otherwise of infected individuals knowing their serological status. While initially skeptical about the benefits of such knowledge, I have been convinced over the past year from talking to many with infection that the vast majority want to know. Individuals with HCV should avoid alcohol, they should be immunized against other hepatitis viruses such as hepatitis A and B, they should be counseled regarding modes of transmission of this virus and they should be considered for treatment. At the San Francisco VA we have been involved in numerous studies of HCV therapies in the past decade. Interferon, a recombinant protein, remains the mainstay of treatment. There are three FDA-approved formulations of interferon which result in initial response rates of approximately 40 per cent but long-term response rates of only about 20 per cent. Interferon therapy is not appropriate in those

with significant psychiatric illness nor in those with ongoing substance abuse, problems which are frequently encountered in the patients we serve. Recently the FDA approved an oral antiviral agent, ribavirin, to be given in combination with interferon in HCV-infected patients who had previously responded to interferon but then had subsequently relapsed off therapy. This combination therapy is not yet approved in patients who are treatment naive, but results from Europe suggest that sustained viral clearance is achievable with treatment in almost 40 per cent. Results of large-scale U.S. studies will be available by the end of this calendar year.

I would like to thank the committee for allowing me to testify. Hepatitis C is a global public health problem which has only recently begun to get the attention it deserves. There are many reasons to believe that HCV infection is a greater problem in Veterans than in the U.S. population as a whole, although the prevalence of infection in Veterans is currently unknown. We should not lose sight however, of the fact that most individuals which HCV will never develop life-threatening complications from their infection. Nevertheless, this virus is an important cause of morbidity, and individuals with infection need to know their serological status. There is currently insufficient information to know whether HCV infection is linked to military service, but preliminary data would suggest that many veterans are acquiring infection by traditional, non-combat-related means.

References

Reichard O, Norkraus E, Fryden A, Braconier J-H, Sonnerberg A, Weiland O. Randomized, double-blind, placebo-controlled trial of interferon a-2b with and without ribavirin for chronic hepatitis C. Lancet 1998;351:83-87.

McQuillan GM, Alter MJ, Moyer LA, Lambert SB, Margolis HS. A population based serological study of hepatitis C virus infection in the United States.

Poynard TBedossa P, Opolon P et al. Natural history of liver fibrosis progression in chronic hepatitis C. Lancet 1997;349:825-32.