NIH Consensus on Management of Hepatitis C
By Alan Tice, MD, FACP
In march, the national institutes of health (NIH) held a consensus conference in Bethesda, MD, on the diagnosis and treatment of hepatitis C. The conference schedule included two days reviewing the history, pathology, laboratory aspects, treatment outcomes, and their inter-relationships by a set of national and international experts (copies of their abstracts can be obtained from the NIH). A panel of experts then queried the experts and came up with a consensus during the night of the second day. The consensus statement draft was presented the next day for review and then finalized after comments from the conference attendees. The revised draft of March 27, 1997, is now available on the Internet. The final report will not be out in print for a few months.
Among the conclusions of the panel were that nearly 4 million Americans are infected with the hepatitis C virus that accounts for about 8000 deaths per year and is the primary reason for liver transplantation. There are about 30,000 new cases diagnosed each year now, but the epidemic has been in decline since 1989 when the blood test became available to test for the antibody and commercial blood donors were prohibited.
The virus is an RNA virus of the Flaviviradae family with a heterogeneous population of quasispecies reminiscent of the retroviruses. The significance of the different species is still in question, although some believe the 1b genotype is more refractory to therapy with interferon.
The primary means of transmission is parenteraleither from blood transfusions (which reached an incidence of up to 10% of patients who received multiple transfusion in some areas before the antibody screening test was available) or parenteral drug abuse (especially after the epidemic in the 1960s and 1970s). Intranasal cocaine use is also associated with spread of the infection. Sexual transmission is clearly possible and associated with multiple sexual partners and likely venereal disease, but the incidence in monogamous relationships is felt to be so low that condoms are not recommended. Hepatitis C is also not thought to be enough of a risk of transmission to babies to discourage pregnancy or breast feeding.
Acute symptomatic infections with hepatitis C are unusual, but records from transfusions suggest an incubation period of 1-3 weeks before the virus can be detected in the blood and about two months before liver injury is apparent. Antibodies to HCV can be detected in about half of patients when they become symptomatic, but it may take three months for 90% to become positive. Chronic hepatitis develops in about 85% of those infected with the virus as evidenced by elevated alanine aminotransferase (ALT) or polymerase chain reaction for HCV RNA or inflammatory changes on liver biopsy.
Once chronic hepatitis is established, it may be asymptomatic or accompanied by a variety of constitutional symptoms including fatigue, malaise, weakness, and anorexia. The rate of fibrosis and septal changes in the liver varies, but about 20% of patients are thought to progress to cirrhosis in 20 years, with about 1-5% developing a hepatoma. Alcohol is clearly a contributing factor to progressive disease. A variety of extrahepatic manifestations of hepatitis C are also known, including cryoglobulinemia, glomerulonephritis, and forms of arthritis.
Laboratory testing for hepatitis C virus is difficult. Although the antibody test by the second generation enzyme immunoassay (EIA-2) has a sensitivity of 92-95%, its specificity is not as good. In low-risk populations, it should be confirmed with a recombinant immunoblot assay (RIBA-2) and even then should not be considered certain. An assay for viral load by PCR may be helpful, but there is a great deal of laboratory-to-laboratory variation. The technology is so difficult that test kits are not even close to marketing. A liver biopsy may be helpful in clarifying the cause of hepatitis as well, especially if there is not a problem with alcohol excess.
Treatment of hepatitis C is an area of considerable frustration. The standard treatment regimen has been 3 million units of interferon three times a week for six months, although it has just been extended to 12 months or more by the FDA. Interferon-alpha 2b is clearly helpful for some, but there is a virologic response rate at the end of six months of therapy of only 30-40% and an additional relapse rate of about half of those six months later.
Other types of interferon evaluated to date are no better for hepatitis C. An additional six months of therapy may double the response rate. If oral ribavirin is added to interferon, the response rate may be even better. Phlebotomy in conjunction with interferon is presently under study. It appears that those who do not clear their blood of virus by PCR after 12 weeks of interferon will not respond and hence can be stopped early or placed on a different regimen that may include ribavirin. Abstinence from alcohol and drug abuse are essential to recovery.
It is curious how similar this virus is to HIV. It is an RNA virus with a high rate of mutation and viremia, a great potential for resistance to antivirals, and a significant percentage of Americans are affected.
As the panel suggests, we must now go beyond their statements and search for more epidemiologic information about the spread of hepatitis C. We also need better therapiesor at least clearer indications of the best dosing and duration of therapy with interferon. A vaccine, such as we have for hepatitis A and B, would certainly be helpful, but it is a few years off at least. Before then, we will be presented with an increasing number of patients with progressive liver disease.
It will be important for physicians and other health care workers to think of this infection when there are risk factors such as IVDA, transfusions before 1990, multiple sex partners, and intranasal cocaine use. Treating those with evidence of ongoing inflammation will reduce the rate of progression in many and allow the time necessary to find better forms of single or multiple drug therapy.
To obtain a copy of the consensus statement, contact the National Institutes of Health at NIH Consensus Program Information Center, P.O. Box 2577, Kensington, MD, 20891; call 1-888-644-2667; or e-mail at:
http://consensus.nih.gov (www),
ftp://public.nlm.nih.gov/hstat/nihcdcs (ftp), or
gopher://gopher.nih.gov/Health and Clinical Information (gopher).
You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content