Virological and histological responses to one year alpha-interferon-2a in hemodialyzed patients with chronic hepatitis C.
BACKGROUND
alpha-Interferon-2a (IFNalpha) alone is a therapy of limited proven benefit for non-uremic patients with chronic hepatitis C virus (HCV) infection. In dialyzed patients, such an effect is suggested on small short-term studies without sufficient clinical and virologic follow-up to document any sustained effect.


METHODS
Twelve chronically hemodialyzed patients with chronic hepatitis C and waiting for renal transplantation were included in a prospective open study of treatment with IFNalpha. We used, as did others, doses of 3 million units (MU), three times a week, but for a longer period of treatment of 12 months. Follow-up was continued for 6 months after the end of IFNalpha in order to document any sustained biochemical, virological and histological responses.


RESULTS
Aminotransferase levels returned to the normal range within 1-2 months of treatment in all patients in whom they had been elevated at baseline. At 1 month of treatment, serum HCV-RNA was not detected in 5 (41%) patients and in 9 (75%) at 12 months. A sustained virological response was documented in 4 (33%) patients 6 months after the end of treatment. Relapse occurred in 5 patients within 2 months after IFNalpha withdrawal. HCV genotype was not predictive of any sustained response. At inclusion, using the histologic Metavir scoring system, half of the patients had low-grade cytolytic activity and none had cirrhosis. After IFNalpha, liver biopsy specimens were available from 9 patients and showed histologic improvement in 3. IFNalpha tolerance was poor, inducing a 5% mean weight loss and the acute rejection of two nonfunctioning kidney grafts.


CONCLUSIONS
This study documents that administration of IFNalpha at 3 MU three times a week, for 12 months, in hemodialysis patients with chronic hepatitis C was efficient for clearing the serum of HCV-RNA in 75% of the patients. A sustained response was maintained in one third of these patients after cessation of IFNalpha, and was predicted by the early serum clearance of the virus within the first 2 months of treatment. We confirm that a 12-month treatment period carries a higher sustained response rate than shorter treatment periods. These encouraging results call for larger studies in uremic patients, using IFNalpha alone or in association with new antiviral drugs.
Hanrotel
C
C
Service de Néphrologie, Centre Hospitalier et Universitaire, Reims, France.
Toupance
O
O
Lavaud
S
S
Thiefin
G
G
Brodard
V
V
Ingrand
D
D
Diebold
M D
MD
Wynckel
A
A
Chanard
J
J
D000328:Adult; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001772:Blood Cell Count; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use*; D008099:Liver / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D006435:Renal Dialysis
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins