Interferon and ursodeoxycholic acid combined therapy in the treatment of chronic viral C hepatitis: Results from a controlled randomized trial in 80 patients*1

Boucher, E.

doi:10.1016/0270-9139(95)90087-x

Cited by 20 publications

(16 citation statements)

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“…Interestingly, hepatitis C infection has also been treated with high doses of UDCA, leading to a decrease in the level of classical hepatotoxicity markers (i.e. alanine aminotransferase and γ -glutamyl transpeptidase) but without any evidence of anti-viral activity [49]. Whether UDCA improves responses to ribavirin therapy remains to be addressed.…”

Section: Discussionmentioning

confidence: 99%

Bile acids alter the subcellular localization of CNT2 (concentrative nucleoside cotransporter) and increase CNT2-related transport activity in liver parenchymal cells

Fernández-Veledo¹,

Huber-Ruano²,

Aymerich³

et al. 2014

Biochemical Journal

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CNT2 (concentrative nucleoside cotransporter) is a plasma membrane high-affinity Na + -coupled adenosine transporter, also localized in intracellular structures. This transporter protein may play additional roles other than nucleoside salvage, since it has recently been shown to be under purinergic control via K ATP channels, by a mechanism that does not seem to involve changes in its subcellular localization. In an attempt to identify the agents that promote CNT2 trafficking, bile acids were found to increase CNT2-related transport activity in a K ATP channel-independent manner in both Fao hepatoma and rat liver parenchymal cells. A maximum effect was recorded after treatment with hydrophilic anions such as TCA (taurocholate). However, this effect did not involve changes in the amount of CNT2 protein, it was instead associated with a subcellular redistribution of CNT2, resulting in an accumulation of the transporter at the plasma membrane. This was deduced from subcellular fractionation studies, biotinylation of plasma membrane proteins and subsequent CNT2 detection in streptavidin precipitates and in vivo confocal microscopic analysis of the distribution of a YFP (yellow fluorescent protein)-CNT2 construct. The induction of CNT2 translocation, triggered by TCA, was inhibited by wortmannin, dibutyryl-AMPc, PD98059 and colchicine, thus suggesting the involvement of the PI3K/ERK (phosphoinositide 3-kinase/extracellular-signal related kinase) pathway in microtubule-dependent activation of recombinant CNT2. These are novel effects of bile-acid physiology and provide the first evidence for short-term regulation of CNT2 translocation into and from the plasma membrane.

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Section: Discussionmentioning

confidence: 99%

Bile acids alter the subcellular localization of CNT2 (concentrative nucleoside cotransporter) and increase CNT2-related transport activity in liver parenchymal cells

Fernández-Veledo¹,

Huber-Ruano²,

Aymerich³

et al. 2014

Biochemical Journal

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“…17 Similarly, the use of ursodiol is associated with a decrease in transaminases. 18 None of these therapies, however, result in clearance of HCV RNA from serum. A recent study of prolonged therapy with IFN alone in nonresponders showed that even though viral clearance did not occur, serum transaminases were persistently lowered during therapy, and improvements in liver histopathology were seen as well.…”

Section: Discussionmentioning

confidence: 99%

Combination of interferon and ribavirin in chronic hepatitis C: Re-treatment of nonresponders to interferon

Bisceglie¹,

Thompson²,

Smith-Wilkaitis³

et al. 2001

Hepatology

100

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Chronic infection with hepatitis C virus (HCV) may result in cirrhosis, liver failure, and hepatocellular carcinoma. A minority of patients have a sustained response to antiviral therapy, and nonresponders remain at risk of developing progressive liver disease. We conducted a randomized, controlled trial of therapy with the combination of interferon (IFN) and ribavirin in patients with chronic hepatitis C who had not responded to an initial course of therapy with IFN alone. A total of 124 patients were randomized to receive the combination of IFN and ribavirin for either 24 or 48 weeks and followed for an additional 24 weeks after stopping therapy. Thirty-eight treated patients (30.6%) achieved a sustained virologic response (undetectable HCV RNA at the 24-week follow-up point). This was associated with significant improvement in necroinflammatory activity noted on liver biopsy. Interestingly, there was not a statistically significant difference in response rates based on the duration of treatment; HCV genotype was the strongest predictor of a sustained response. Sustained responses were noted even in patients with poor predictive factors, including those with advanced hepatic fibrosis or cirrhosis, high levels of HCV RNA in serum, and those infected with HCV genotype 1. Considerable advances have recently been made in the therapy of chronic hepatitis C. While rates of sustained virologic response to interferon (IFN) alone have averaged between 10% and 15%, they have increased to 35% to 40% with the combination 1,2 of IFN and ribavirin. This combination has replaced the use of IFN alone as the first-line therapy in patients with chronic hepatitis C. One category of patients who seem to respond very well to IFN and ribavirin is the group that had an initial response to IFN, but then had a relapse of the hepatitis C viral infection after the IFN was stopped. Retreatment of these "relapsers" results in sustained virologic response rates approaching 70%. 3 However, similar benefit has not been observed in re-treating those patients who did not respond to their initial course of IFN, i.e., "nonresponders." They have persistence of hepatitis C virus (HCV) RNA with or without elevations in serum transaminases, even after a full course of IFN therapy. These patients often have more advanced hepatic fibrosis than those who responded to therapy and are more often infected with HCV genotype 1. 4 Thus, they remain at considerable risk of progression of their liver disease to cirrhosis, liver failure, and perhaps even hepatocellular carcinoma.Preliminary data on re-treatment of small numbers of nonresponders with the combination of IFN and ribavirin do not indicate a clear pattern of response. We therefore conducted a randomized, controlled trial of re-treatment with this combination in nonresponders to IFN, comparing the benefits of 24 versus 48 weeks of therapy in a large number of patients. PATIENTS AND METHODSPatients were offered participation in this study if they had chronic hepatitis C and had received at least 12 we...

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“…UDCA alone or in combination with interferon was evaluated in a number of controlled trials for the treatment of chronic hepatitis C. Although some biochemical improvement of serum transaminases was achieved, UDCA failed to improve either the virological response rate or histological features 182 –184 . Thus, UDCA (alone or in combination with interferon) cannot be generally recommended for the treatment of chronic hepatitis C, 185 although a subset of patients with high serum γ‐GT levels (increased to more than threefold) might benefit from UDCA 186 …”

Section: Treatment Of Non‐cholestatic Liver Diseasesmentioning

confidence: 99%

Review article: mechanisms of action and therapeutic applications of ursodeoxycholic acid in chronic liver diseases

Trauner

Graziadei

1999

Aliment Pharmacol Ther

140

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Ursodeoxycholic acid (ursodiol) is a non‐toxic, hydrophilic bile acid used to treat predominantly cholestatic liver disorders. Better understanding of the cellular and molecular mechanisms of action of ursodeoxycholic acid has helped to elucidate its cytoprotective, anti‐apoptotic, immunomodulatory and choleretic effects. Ursodeoxycholic acid prolongs survival in primary biliary cirrhosis and it improves biochemical parameters of cholestasis in various other cholestatic disorders including primary sclerosing cholangitis, intrahepatic cholestasis of pregnancy, cystic fibrosis and total parenteral nutrition‐induced cholestasis. However, a positive effect on survival remains to be established in these diseases. Ursodeoxycholic acid is of unproven efficacy in non‐cholestatic disorders such as acute rejection after liver transplantation, non‐alcoholic steatohepatitis, alcoholic liver disease and chronic viral hepatitis. This review outlines the present knowledge of the modes of action of ursodeoxycholic acid, and presents data from clinical trials on its use in chronic liver diseases.

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Interferon and ursodeoxycholic acid combined therapy in the treatment of chronic viral C hepatitis: Results from a controlled randomized trial in 80 patients*1

Cited by 20 publications

References 0 publications

Bile acids alter the subcellular localization of CNT2 (concentrative nucleoside cotransporter) and increase CNT2-related transport activity in liver parenchymal cells

Bile acids alter the subcellular localization of CNT2 (concentrative nucleoside cotransporter) and increase CNT2-related transport activity in liver parenchymal cells

Combination of interferon and ribavirin in chronic hepatitis C: Re-treatment of nonresponders to interferon

Review article: mechanisms of action and therapeutic applications of ursodeoxycholic acid in chronic liver diseases

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