3 Colchicine Versus Peg-Interferon Alfa 2b Long Term Therapy: Results of the 4 Year Copilot Trial

Afdhal, Nezam H.; Levine, R; Brown, R.; Freilich, B.; O’Brien, Mark; Brass, Clifford A.

doi:10.1016/s0168-8278(08)60005-7

Cited by 78 publications

(60 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the CO-PILOT trial, 9 patients who were nonresponders to initial IFN-based antiviral therapy were randomized to receive either PEG-IFN alfa2b or colchicine for four years; while in the EPIC 3 trial, 38 nonresponders were randomized to receive either PEG-IFN alfa-2b or no treatment for up to three years. Data from the CO-PILOT and EPIC 3 trials demonstrated no overall benefit of maintenance IFN therapy on occurrence of clinical events (HCC, etc.…”

Section: Cancer Therapymentioning

confidence: 99%

“…[4][5][6][7] However, in those with advanced hepatitis C who did not achieve a sustained virologic response (SVR) to initial IFN-based antiviral therapy, maintenance peginterferon (PEG-IFN) treatment could not reduce overall HCC risk, as reported by the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) and Colchicine Versus Pegintron Long-term Therapy (CO-PILOT) trials recently. 8,9 Based on previous reports, several meta-analyses have been performed to evaluate the preventive effect of IFN on development of HCC in HCV-or HBV-infected patients. [10][11][12] However, in these meta-analyses, the authors pooled data mostly from the retrospective or nonrandomized studies, and they also included studies of different publication types (including full papers, abstracts, etc.)…”

mentioning

confidence: 99%

See 1 more Smart Citation

Effects of interferon treatment on development and progression of hepatocellular carcinoma in patients with chronic virus infection: A meta‐analysis of randomized controlled trials

Zhang

Jia

et al. 2011

Intl Journal of Cancer

View full text Add to dashboard Cite

Available literature on the effects of interferon (IFN) treatment on development and progression of hepatocellular carcinoma (HCC) in patients with chronic virus infection reports controversial results. The primary objective of this meta-analysis was to evaluate the effect of IFN on HCC risk in patients with chronic hepatitis C virus (HCV) or hepatitis B virus (HBV) infection; IFN's efficacy on local tumor progression and survival of advanced HCC patients was also assessed. All randomized controlled trials (RCTs) comparing IFN with no antiviral treatment were selected. Finally, we identified 11 RCTs including 1,772 patients, who met our inclusion criteria to perform this meta-analysis. Our analysis results showed that IFN significantly decreased the overall HCC incidence in HCV-infected patients [relative risk (RR) 5 0.39; 95% confidence interval (CI) 5 0.26-0.59; p 5 0.000], subgroup analysis indicated that IFN decreased HCC incidence in HCV-related cirrhotic patients evidently (RR 5 0.44; 95% CI 5 0.28-0.68; p 5 0.000); but HCC incidence in nonresponders to initial antiviral therapy did not reduce by maintenance IFN therapy (RR 5 0.96; 95% CI 5 0.59-1.56; p 5 0.864). Analysis results also demonstrated that IFN did not significantly affect the overall rate of HCC in HBV-infected patients although there was a trend favoring IFN therapy (RR 5 0.23; 95% CI 5 0.05-1.04; p 5 0.056). Besides, IFN did not improve one-year overall survival of advanced HCC patients significantly (RR 5 1.61; 95% CI 5 0.96-2.69; p 5 0.072); however, a quantitative analysis on local tumor progression could not be performed owing to lack of unified definitions among trials included in our study. By this meta-analysis, we conclude that IFN therapy is effective in reducing overall HCC risk in chronic HCV-infected patients; using it in this subpopulation seems promising, but its administration in other subpopulations still requires further exploration.Hepatocellular carcinoma (HCC) is one of the most common and aggressive malignant tumors and is the third most common cause of death from cancer in the world.1 Despite extensive efforts to improve its prognosis, the overall survival rate of HCC patients remains very low to date. Hepatitis C virus (HCV) and hepatitis B virus (HBV) infections are the most common etiologies of HCC, and they are estimated to be causally associated with 53 and 25% of HCC worldwide, respectively.2 Thus, HCC prevention and treatment have become an important issue in patients with chronic HCV or HBV infection.Studies show that interferon (IFN) can not only suppress the replication of HCV and HBV, but also has a tumoricidal effect on a number of tumors including HCC. 3 In the past few years, several clinical studies have reported the preventive effect of IFN treatment on HCC occurrence in patients with HCV or HBV infection, especially in sustained virologic responders. [4][5][6][7] However, in those with advanced hepatitis C who did not achieve a sustained virologic response (SVR) to initial IFN-based antiviral therapy, m...

show abstract

Section: Cancer Therapymentioning

confidence: 99%

mentioning

confidence: 99%

Effects of interferon treatment on development and progression of hepatocellular carcinoma in patients with chronic virus infection: A meta‐analysis of randomized controlled trials

Zhang

Jia

et al. 2011

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…[71][72][73] A subsequent report of the HALT-C Trial focusing on HCC development with a slightly longer duration of follow-up also showed no difference in the incidence of HCC between the patients that were randomized to the maintenance IFN or no treatment. [74] The same results were observed even when the duration of followup in these studies was more prolonged.…”

Section: Hcvmentioning

confidence: 98%

Role of antiviral therapy in patients with chronic hepatitis B or C virus in preventing the development of hepatocellular carcinoma

Scribano¹,

Vanin²,

Gottardo³

et al. 2015

Hepatoma Res

View full text Add to dashboard Cite

Patients with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection are at significant risk for hepatocellular carcinoma (HCC). The most important risk factor associated with HCC is liver cirrhosis, which is again predominantly caused by chronic HBV or HCV infection. The most effective approach to avoid HCC development is to prevent HBV and HCV infection through vaccination. Indeed, HBV vaccine is the first vaccine demonstrated to prevent cancers. However, a vaccine for HCV is not available. Thus, the prevention of HCV-related HCC and to a large extent HBVrelated HCC (among persons who are already chronically infected) will rely on antiviral therapy to prevent progressive liver disease. The evidence that these patients can effectively be protected against HCC risk by the treatment with antiviral therapy is rather controversial, due to the lack of randomized controlled trials (RCTs) that are ideally needed to establish the effi cacy, but are logistically and ethically challenging. Although the strongest evidence to support that antiviral therapy can prevent HCC should be derived from RCTs with HCC as an endpoint, it should be emphasized that clinical trials showing the efficacy of antiviral therapy on virus suppression or eradication, and/or improvement in liver histology can be considered indirect evidence that antiviral therapy can prevent HCC because high virus levels (in the case of HBV infection) and cirrhosis (in both HBV and HCV infection) are the most important risk factors for HCC.

show abstract

“…Regarding liver decompensation and mortality, we have observed a significant association between virological response and the occurrence of liver events in both patients with and without EV, although the formers maintained a risk to develop liver decompensation and to die in consequence of liver events even after SVR achievement. Further evidences were provided from three randomized controlled trials -HALT-C [34], COPILOT [35] and EPIC-3 [36] -that investigated the effectiveness of a longterm maintenance therapy with pegylated-IFN in nonresponder HCV patients with advanced fibrosis or cirrhosis. The outcomes assessed were death, hepatic decompensation, HCC development and an increase in hepatic fibrosis for noncirrhotic patients: overall, a poor benefit of maintenance therapy on clinical outcomes -including HCC -was observed, despite the reduction of viral load and the improvement of inflammatory Cardoso et al…”

Section: Koreamentioning

confidence: 99%

Residual Risk of Hepatocellular Carcinoma After HCV Eradication: more than meets the eye

Macaluso

Calvaruso

2015

Future Microbiol.

View full text Add to dashboard Cite

Eradication of HCV in patients with advanced liver fibrosis or cirrhosis reduces, but does not altogether abolish, the risk of development of hepatocellular carcinoma. The reasons underlying this residual risk remain elusive. Even if HCV clearance eliminates its direct and indirect carcinogenic effects, the persistence of cirrhosis and the possible coexistence of metabolic factors (diabetes, obesity and insulin resistance) and of alcohol abuse can promote the development of hepatocellular carcinoma acting as autonomous, nonviral carcinogenic factors. Lessons learned in the IFN era may still assist in predicting the forthcoming scenario, when IFN-free regimens will obtain high rates of viral clearance even at the most advanced stages of liver disease. KeywordsHepatocellular carcinoma (HCC) is a challenging malignancy of global importance, being the second cause of cancer-related death worldwide [1]. The majority of HCCs occur in the context of chronic infection with HBV and HCV, and the cancer risk is directly related to the histological and clinical stage of the underlying liver disease [2]. In particular, HCV infection stands today as the leading risk factor for HCC in many industrialized countries [3], occurring at a rate between 3 and 8%, according to the geographic area, in patients with HCV-related cirrhosis [4]. On these assumptions, prevention of population exposure to HCV can be regarded as the most effective tool to reduce liver-related mortality from HCC due to chronic HCV infection. In the HCV scenario, where an effective vaccine is not currently available, antiviral treatments have stood as the real backbone of prophylaxis strategy in the prevention of HCC, of course together with all procedures implemented to prevent HCV transmission [5].However, the evidence that patients with chronic hepatitis C (CHC) are completely protected against occurrence of HCC by successful IFN-based treatments is controversial, mainly due to methodological limitations of available literature. All in all, HCC risk seems to be sharply attenuated, although not completely eliminated -especially in patients with advanced fibrosis -following eradication of HCV infection, and the causes for this residual HCC risk in patients who achieved a sustained virological response (SVR) remain receding. Moreover, the intrinsic limitations of the use of IFN to patients with less advanced liver disease have curtailed the potential benefit, due to the fact that HCC in HCV cirrhosis becomes more prevalent at the more advanced stages of liver disease.In this review, we discuss the available clinical evidence of the role of antiviral treatment against chronic HCV infection for the prevention of HCC, and the residual risk existing in patients successfully treated. In addition, we focus on the molecular mechanisms that might explain the pathophysiological rationale of the reduction, but not elimination, of HCC risk after HCV eradication. The lesson from the IFN era may be extremely useful to predict the near-future scenario, when For repri...

show abstract

3 Colchicine Versus Peg-Interferon Alfa 2b Long Term Therapy: Results of the 4 Year Copilot Trial

Cited by 78 publications

References 0 publications

Effects of interferon treatment on development and progression of hepatocellular carcinoma in patients with chronic virus infection: A meta‐analysis of randomized controlled trials

Effects of interferon treatment on development and progression of hepatocellular carcinoma in patients with chronic virus infection: A meta‐analysis of randomized controlled trials

Role of antiviral therapy in patients with chronic hepatitis B or C virus in preventing the development of hepatocellular carcinoma

Residual Risk of Hepatocellular Carcinoma After HCV Eradication: more than meets the eye

Contact Info

Product

Resources

About