Randomized trial of interferon-alpha plus ursodeoxycholic acid versus interferon plus placebo in patients with chronic hepatitis C resistant to interferon.
BACKGROUND
Ursodeoxycholic acid (UDCA) could potentiate the effect of interferon (IFN) in patients with chronic hepatitis C resistant to IFN. We compared the efficacy of IFN with that of a combination of IFN and UDCA.


METHODS
Patients were randomized to receive UDCA (13-15 mg/kg/day) (n = 47) or placebo (n = 44) plus interferon (3 MU three times weekly) for 6 months and were then followed up for 6 additional months.


RESULTS
At entry 30% of patients had cirrhosis, and 70% had HCV genotype 1. Five and four patients withdrew from the combination and the monotherapy groups, respectively. At 6 months alanine aminotransferase (ALAT) and gamma-glutamyl transferase (GGT) activities were significantly lower (P < 0.001) in the combination group than in the monotherapy group; the differences were no longer significant at 1 year. At 6 months ALAT activities normalized in 10 and 8 patients in the combination and the monotherapy groups, respectively (P = 0.67). In 10 of them (5 in each group) HCV RNA levels became undetectable. At 1 year four versus one patient had a sustained normalization of ALAT, and in one patient the HCV RNA became negative. There was no difference in the histologic progression. In this setting, in contrast to chronic cholestasis, UDCA administration induced an increase in total serum bile acids and did not change primary bile acids.


CONCLUSIONS
An IFN plus UDCA combination is more effective than IFN alone in terms of ALAT but not in terms of the virologic response. These results favor the hypothesis that UDCA has an effect on the biochemical indices of cellular injury independent of a change in primary bile acids.
INSERM, Unit 370, Faculté de Médecine Necker, Paris France.
R E
RE
Poupon
A M
AM
Bonnand
P E
PE
Queneau
C
C
Trépo
Zarski JPí
D
D
Vetter
J J
JJ
Raabe
G
G
Thieffin
D
D
Larrey
J D
JD
Grangé
J P
JP
Capron
L
L
Serfaty
Y
Y
Chrétien
M F
MF
St Marc Girardin
H
H
Mathiex-Fortunet
E S
ES
Zafrani
J
J
Guéchot
U
U
Beuers
G
G
Paumgartner
R
R
Poupon
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage*; D002756:Cholagogues and Choleretics / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004352:Drug Resistance, Microbial; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage*; D007372:Interferons / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D018709:Statistics, Nonparametric; D016896:Treatment Outcome; D014580:Ursodeoxycholic Acid / Q000008:administration & dosage*
D000998:Antiviral Agents; D002756:Cholagogues and Choleretics; D016898:Interferon-alpha; D014580:Ursodeoxycholic Acid; D007372:Interferons