TreatmentUpdate 68, Volume 8, No 4; May-June 1996
Sean Hosein

Discovered in 1989, the hepatitis C virus (HCV) infects the livers of more than 3 million people in North America. Although the initial infection does not immediately destroy the liver, HCV infection slowly spreads through that organ, as HCV-infected liver cells produce more and more viruses. This state of continual production of HCV is called chronic infection and occurs in at least 50% of infected people. Symptoms of HCV infection are mild, with "fatigue" being the most common.

A damaged liver

The immune system produces antibodies to attack HCV but these antibodies, like antibodies produced against HIV, do not stop the infection from spreading. Moreover, the immune response directed against HCV may cause further damage to the liver. About 20% of HCV-infected people develop severe liver damage after 20 years of chronic infection, requiring a new liver. Ten percent of these people will develop liver cancer.

Spreading the virus

Researchers are not sure how some people become infected with HCV. The virus is clearly spread through the use of infected blood or clotting factor that has not been treated to destroy viruses. HCV can also be spread by sharing unsterile injection equipment, and by unprotected sex but transmission is low: ~ 5% in one German study of 85 couples. In another study of 115 HCV-infected mothers, 7% transmitted the infection to their infants. The researchers could not detect HCV in samples of breast milk. HCV has been detected in tears but researchers do not know if contact with tears can infect other people. Living in the same household with an HCV-infected person does not appear to spread the infection.

Finding damage due to HCV

Since symptoms of HCV-infection may be mild, doctors rely on a number of lab tests and procedures to help them diagnose HCV-infection, including;

* checking for antibodies against HCV;

* measuring levels of the liver enzyme ALT;

* measuring levels of the amount of HCV in the blood;

* removing a small piece of liver for analysis.

Treatment options for HCV

- Corticosteroids

Corticosteroids do not cause HCV-infected people to recover.

- Ribavirin

The results of a recent 12-month double-blind, placebo-controlled study suggest that ribavirin 1200 mg/day is not effective therapy for HCV infection. Doses of ribavirin greater than 1200 mg/day causes bone marrow damage.

- Interferon-alpha

Treatment with a minimum of 3 million units of interferon-alpha three times weekly for "at least 6 months" will help between 50% and 60% of infected people recover. Once interferon-alpha therapy stops at least half of "recovered" patients relapse and levels of HCV in the blood rise. In HIV-infected subjects who also have HCV infection, doctors are testing longer courses of interferon-alpha, lasting for 12 months.

- Interferon-alpha and thymosin alpha1

Thymosin alpha1 is a hormone produced by the thymus gland which may improve the ability of T cells to fight certain infections. Reports on the use of thymosin alpha1 in HIV infection have appeared in TreatmentUpdate52. Results from one American study have not yet been released. In this study, some subjects received:

- thymosin alpha

11.6 mg injected under the skin twice weekly and 3 million units of interferon alpha twice weekly. Others received interferon-alpha alone. All drugs were given for 6 months.

Preliminary results suggest that the combination helped 39% of subjects by reducing levels of the liver enzyme ALT in their blood. In comparison, only 9% of subjects receiving interferon-alpha alone had decreased ALT levels.

- Interferon-alpha and ribavirin

In one study of 65 subjects who did not recover when treated with interferon-alpha alone, researchers assigned subjects to receive one of the following regimens for 6 months:

* fake drugs (placebo)

* ribavirin 1200 mg/day

* ribavirin 1200 mg/day and interferon-alpha "3 million units three times daily."

Preliminary results from 44 subjects indicate that 13 of 15 subjects receiving the combination had their ALT levels fall to normal. Also, HCV could not be detected in blood samples from 2 subjects.

- Interferon-alpha and bleeding

Some researchers have conducted a small study suggesting that some HCV-infected subjects who do not recover when given interferon-alpha may have high levels of iron in their blood. It is possible that reducing the amount of iron in their blood may improve their response to interferon-alpha. This can be achieved through weekly bleeding or by means of a low-iron diet that causes hemoglobin levels to fall below 11 grams.

- Interferon-beta and ribavirin

Researchers in Japan enrolled 27 subjects with chronic HCV infection. Subjects were randomly assigned to one of the following regimens for 6 months:

* ribavirin between 800 and 1,000 mg/day

* interferon-beta 3 million units thrice weekly

* a combination of both regimens

On average, liver enzyme levels fell by over 50% in all subjects compared to their pre-study levels. Use of interferon-beta caused significant reduction in levels of HCV in the blood. The decrease in production of HCV was greater among subjects in the combination group than in subjects on ribavirin alone. These differences were statistically significant. Use of ribavirin did not change levels of CD4+ or CD8+ cells. In three subjects receiving both drugs and two subjects receiving interferon-beta alone, levels of HCV fell and remained reduced after these subjects stopped using these agents. In all other subjects, levels of HCV and liver enzymes rose to their pre-study values once they stopped taking their drugs.

REFERENCES:

1. Report of a meeting of physicians and scientists, Royal Free Hospital and school of Medicine, London. Lancet 1995;345:562-566.

2. Koziel MJ. Immunology of viral hepatitis. American Journal of Medicine 1996;100:98-109.

3. Di Bisceglie AM, Conjeevaram HS, Fried MW, et al. Ribavirin as therapy for chronic hepatitis C: a randomized, double-blind, placebo-controlled trial. Annals of Internal Medicine 1995;123(12):897-903

4. James DG. Treatment options for chronic hepatitis C infection. Journal of Antimicrobial Chemotherapy 1995;36:591-593.

5. Anonymous. Zadaxinr thymosin alpha1, injection. 1995 Product information report, SciClone Pharmaceuticals, Inc.

6. Kakumu S, Yoshioka K, Wakita T, et al. A pilot study of ribavirin and interferon-beta for the treatment of chronic hepatitis C. Gastroenterology 1993;105:507-512.

7. Laufs R. Hepatitis C: increasing knowledge and unresolved questions. European Journal of Clinical Microbiology and Infectious Diseases 1996;15(2):105-106.

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Copyright © 1996 - TreatmentUpdate. Reproduced with permission. Reproduction of this article (other than one copy for personal reference) must be cleared through the Editor, The Canadian AIDS Treatment Information Exchange, 555 Richmond St. West, Suite 505, Box 1104, Toronto, ON, M5V 3B1 • Phone: 416-203-7122 • Toll Free: 1-800-263-1638 • Fax: 416-203-8284  http://www.catie.ca