Alpha-interferon treatment of chronic hepatitis C after bone marrow transplantation for homozygous beta-thalassemia.
No experience has been reported to date in treating chronic hepatitis C virus (HCV) infection with interferon (IFN) therapy after BMT, mainly due to concerns related to the impact of an immunomodulatory drug in patients who are immunologic and haematologic chimeras. However, chronic inflammatory activity related to HCV infection results in a chronic fibrogenous mechanism potentially leading to liver cirrhosis and hepatocellular carcinoma. Moreover, patients transplanted for beta-thalassemia could be at greater risk because of concomitant iron overload and pre-existing fibrous liver damage. Eleven patients with serological, biochemical, histological and molecular biological evidence of HCV infection were included in the study and treated for 6-12 months with recombinant IFN 24-65 months following BMT. The serum alanine aminotransferase (ALT) was persistently elevated (range 85-1242 U/l; mean 416) for at least 1 year prior to IFN treatment. Ten patients completed the protocol; five were considered as responders to treatment. In these five patients the liver histology showed an overall reduction of inflammation and necrosis: histological inflammatory activity improved from chronic active hepatitis (CAH) to chronic persistent hepatitis (three patients) or minimal residual inflammatory activity (two patients). The Knodell total activity score varied from 5.4 (range 3-9) to 1.4 (range 1-2; P = 0.05). All responding patients revealed negativization of serum HCV-RNA, that has been persistent in four (follow-up 1-3 years). ALT level fell to 15-80 U/l (mean 52; P = 0.0027). No major complications occurred during the therapy and no influence on marrow engraftment parameters were noted. We conclude that IFN therapy does not adversely interfere with engraftment and that it is a feasible therapy for treatment of chronic hepatitis C virus after BMT.
Giardini
C
C
Divisione di Ematologia e Centro Trapianto di Midollo Osseo di Muraglia, Azienda Ospedale di Pesaro, Italy.
Galimberti
M
M
Lucarelli
G
G
Polchi
P
P
Angelucci
E
E
Baronciani
D
D
Erer
B
B
Gaziev
D
D
Piga
A
A
Di Gregorio
F
F
Romeo
M A
MA
Mangiagli
A
A
Petrelli
E
E
Muretto
P
P
D000293:Adolescent; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D001706:Biopsy; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D002648:Child; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000473:pathology; D006720:Homozygote; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008099:Liver / Q000473:pathology; D008297:Male; D017086:beta-Thalassemia / Q000150:complications / Q000628:therapy*
D000998:Antiviral Agents; D016898:Interferon-alpha