Randomized Trial of Interferon-Alpha plus Ursodeoxycholic Acid versus Interferon plus Placebo in Patients with Chronic Hepatitis C Resistant to Interferon

Bonnand, Anne‐Marie; Queneau, P; Trépo, C.; Zarski, Jean Pierre; Vetter, D; Raabe, Jean–Jacques; Thieffin, G.; Larrey, Dominique; Grangé, Jean Didier; Capron, Jean‐Pierre; Serfaty, Lawrence; Chrétien, Yves; Girardin, Marie-Laure; Mathiex‐Fortunet, Hélène; Zafrani, Élie Serge; Guéchot, Jérôme; Beuers, Ulrich; Paumgartner, Gustav; Poupon, Raoul

doi:10.1080/003655200750023624

Cited by 20 publications

(8 citation statements)

References 14 publications

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“…Decreases serum ALT activity without affecting serum HCV RNA in chronic hepatitis C patients [98] Combination therapy with IFN did not lead to a significant increase in sustained responses compared with IFN alone [78,99] N-acetyl-l-cysteine (NAC) Glutathione (GSH) deficiency is associated with impaired T-cell function and impaired survival in some viral infections, such as HIV. NAC is used to replenish GSH [100] Patients with chronic hepatitis C are unlikely to benefit from the addition of NAC to conventional IFN [101] Ursodeoxycholic acid (UDCA) Serum liver enzymes improve in patients with HCV-related chronic liver disease during UDCA therapy [102] IFN/UDCA combination is more effective than IFN alone in terms of biochemical but not virological responses [103]…”

Section: Resultsmentioning

confidence: 99%

Therapeutic modalities in hepatitis C: challenges and development

Moreno–Otero

2005

Journal of Viral Hepatitis

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Our understanding of the pathogenicity of hepatitis C virus (HCV) is based on patients infected chronically for >20 years. The lack of a suitable animal model, the narrow host range of the virus, and the protracted onset of liver disease induced by HCV have hampered advances in treatment. In spite of these problems, we identified patient and viral characteristics that predict responses to current therapies, including HCV genotype, viral load, body weight, age, liver histology, co-infection with HIV and treatment adherence and tolerance. Interferon (IFN) alpha was the first therapy for chronic HCV infection. The combination of IFN plus ribavirin increases sustained virological response rates compared with IFN alone. Two pegylated IFNs have been developed and are widely approved for the treatment of chronic hepatitis C: peginterferon alpha-2a (40 KD), and pegylated IFN alpha-2b (12 KD). These products have reduced systemic clearance, prolonged half-lives and reduced antigenicity compared with conventional IFN. The reduced clearance results in sustained plasma levels of the drug and allows for once-weekly dosing. Pegylated IFN alpha-2b (12 KD) has a small, linear polyethylene glycol (PEG) moiety and has an intermediate duration of activity; peginterferon alpha-2a (40 KD) incorporates a large, branched-chain PEG moiety and has a longer half-life than both conventional IFN alpha and pegylated IFN alpha-2b (12 KD). The combination of a pegylated IFN plus ribavirin significantly increases sustained virological response rates compared with conventional IFN plus ribavirin in patients with chronic hepatitis C and is now recognized as the standard of care for these patients.

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Section: Resultsmentioning

confidence: 99%

Therapeutic modalities in hepatitis C: challenges and development

Moreno–Otero

2005

Journal of Viral Hepatitis

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“…2). The absence of lowering effect of UDCA on the endogenous bile acids has already been observed in patients with chronic hepatitis C. 22 Most importantly, a third explanation could be that the dosage regimen of UDCA was totally unadapted to the liver function of our patients. UDCA is exclusively metabolized and eliminated by the liver.…”

Section: Discussionmentioning

confidence: 99%

A randomized controlled trial of ursodeoxycholic acid in patients with alcohol-induced cirrhosis and jaundice

et al. 2003

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The aim of our multicenter study was to assess the efficacy of ursodeoxycholic acid (UDCA) on the survival of patients with alcohol-induced cirrhosis and jaundice. We included patients with histologically proven alcohol-induced cirrhosis and serum bilirubin >50 mol/L. After randomization, patients received either UDCA (13-15 mg/kg/d) or a placebo for 6 months. Two hundred twenty-six patients (113 in each group) were included in 24 centers. There were 139 men and 87 women, mean age of 50.3 years. Seventy-four percent had associated alcohol-induced hepatitis, and 24% received a corticosteroid therapy. At inclusion, the 2 groups were comparable for the main clinical and biologic parameters, but serum bilirubin was higher in the UDCA group than in the placebo group (163 mol/L vs. 145 mol/L, P < .03). The percentage of patients lost at follow-up or who resumed their alcoholism during the study was comparable in the 2 groups. During the study, 55 patients died, 35 in the UDCA group and 20 in the placebo group. In the intention to treat analysis, the probability of survival at 6 months (Kaplan-Meier method) was lower in the UDCA than in the P group (69% vs. 82%, respectively; P ‫؍‬ .04, log-rank test). After adjustment on the bilirubin level at entry (Cox model), the independent predictive value of the treatment group did not reach the statistical level (RR ‫؍‬ 1.64, CI 0.85-2.85; P ‫؍‬ .077). In conclusion, UDCA administered at the dose recommended in primary biliary cirrhosis has no beneficial effect on the 6-month survival of patients with severe alcohol-induced cirrhosis. An inappropriate dosage of UDCA cannot be excluded as an explanation for the lack of therapeutic benefit. (HEPATOLOGY 2003;37:887-892.)

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“…Data on the use of ursodeoxycholic acid in hepatitis C are limited to a small number of trials done in the early 1990s [47]. These data indicated that ursodeoxycholic acid used by itself or in combination with interferon improved aminotransferase levels but had no beneficial effect on histology or HCV RNA titers.…”

Section: Hepatoprotectantsmentioning

confidence: 93%