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Managing the Hepatitis C Virus
Medical Sciences Bulletin
Managing Hepatitis C Virus Infection
Drugs mentioned:
•recombinant interferon alpha-2b (Intron A/Schering)
•ribavirin (Virazole/ICN Pharmaceuticals)
•ursodeoxycholic acid (Actigall/Summit Pharmaceuticals)
Since the Hepatitis C agent was characterized in 1989, much has been learned
about this RNA virus and the disease it causes. Hepatitis C virus (HCV) is usually
acquired parenterally, although the route of transmission in sporadic cases
is still unknown. Compared with the Hepatitis B virus, human immunodeficiency
virus (HIV), and other sexually transmitted diseases, HCV appears to have a
low risk of sexual transmission. Heterosexual co-transmission of HCV along with
HIV has been described, however, and barrier contraception has been shown to
reduce the risk. After acute HCV infection, chronic hepatitis will develop in
more than half of patients. In most of these, the disease will be clinically
apparent (although a subclinical carrier state has been recognized). Healthy
blood donors with antibody to HCV show histologic evidence of chronic hepatitis,
despite good health status. According to hepatic virologists J. Lau and G. Davis
(University of Florida College of Medicine), chronic hepatitis may appear indolent,
but cirrhosis will develop in at least 20% of HCV-infected patients. Many of
these will progress to liver failure and some to hepatocellular carcinoma. Chronic
HCV infection accounts for many of the adults requiring liver transplantation.
Recombinant interferon alpha-2b (Intron A/Schering) has proved effective in
some cases of chronic Hepatitis C. In clinical studies, the drug returned serum
aminotransferase levels to normal in 27%, 33%, and 41.5% of patients receiving,
respectively, 1, 2, and 3 million units per week for 6 months, compared with
2.6% in untreated patients (study results pooled). However, relapse occurs in
at least half the responders after interferon alpha-2b treatment is discontinued.
The nucleotide analog ribavirin (Virazole/ICN Pharmaceuticals) reduces concentrations
of serum alanine aminotransferase and Hepatitis C viral RNA, although at a slower
rate than interferon alpha-2b. Currently, oral ribavirin is being evaluated
in large, multicenter, randomized trials. Patients with an autoimmune component
are difficult to treat because there is yet no way to determine whether hepatic
damage is caused by the virus or the autoimmune process. According to Lau and
Davis, interferon alpha-2b may exacerbate hepatocyte injury caused by autoimmune
chronic active hepatitis. Corticosteroids are used for autoimmune hepatic disease.
(Lau JYN, Davis GL. Br Med J. 1993; 306: 469-470.)
Recently Puoti et al. reported that the bile acid ursodeoxycholic acid (UDCA
or ursodiol, Actigall/Summit Pharmaceuticals) may improve serum liver enzyme
concentrations in chronic HCV infection. The investigators studied 91 patients
(47 males and 44 females) with immunologic, histologic, biochemical, and clinical
evidence of chronic HCV liver disease. Serum alanine-aminotransferase (ALT)
and gamma-glutamyltransferase (GGT) levels were at least twice the upper limit
of normal on three different occasions over the previous 12 months. Patients
were not positive for HIV or Hepatitis B, and had not taken interferon. They
were randomly assigned to receive UDCA 450 mg at bedtime for 6 months (44 patients)
or to no treatment (47 patients). No relevant side effects were reported. Compared
with the control group, the UDCA group demonstrated significant decreases in
liver enzyme concentrations (reductions of 36.7% for ALT and 47.6% for GGT).
It is not known how UDCA decreases enzymes in patients with chronic HCV hepatitis,
nor whether this decrease improves liver histology. The authors ask, "Might
UDCA be a possible alternative for patients who do not respond to interferon
or who relapse after discontinuation of interferon?" Perhaps investigating UDCA
will yield insights into the nature of chronic HCV infection. (Puoti C et al.
Lancet. 1993; 341:1413-1414.)
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Hepatitis Central
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