Interferon and interferon plus ribavirine in hepatocellular carcinoma prevention: A prospective study on patients with HCV related cirrhosis

Azzaroli, Francesco; Mazzella, Giuseppe; Accogli, Esterita; Giovanelli, S.; Trerè, Davide; Mazzeo, Costanza; Nigro, Giovanni; Miracolo, A.; Lodato, Francesca; Colecchia, Antonio; Mwangemi, C.; Festi, Davide; Derenzini, Massimo; Roda, Enrico

doi:10.1016/s0016-5085(03)83553-9

Cited by 7 publications

(20 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Of the 147 studies, 137 did not fulfill the inclusion criteria (29 review articles, 9 case‐reports, 13 retrospective studies, 8 trials regarding preventive effect of IFN administration after treatment of primary tumors on HCC recurrence, 8 trials including patients treated with IFN for longer periods than 12 months, 6 trials including patients retreated with IFN during the follow‐up period, 29 trials without untreated control group, 34 concerning something other than preventive effect of IFN treatment on HCC development in chronic hepatitis C, 1 trial with the follow‐up period less than 1 year). Ten studies15–24 fulfilled the inclusion criteria. However, of the 10 studies, 221, 24 were reported by Testino and colleague.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Meta‐analysis: Reduced incidence of hepatocellular carcinoma in patients not responding to interferon therapy of chronic hepatitis C

Miyake

Iwasaki

Yamamoto

2010

Intl Journal of Cancer

View full text Add to dashboard Cite

Interferon treatment for chronic hepatitis C reduces the incidence of hepatocellular carcinoma (HCC) in sustained responders. However, estimation of the effect of interferon treatment on HCC development in nonresponders is yet to be fully implemented. We conducted a meta-analysis of 3 randomized controlled trials and 6 prospective cohort studies, including 3,246 patients (1,922 patients received interferon treatment) to estimate the effect of single-course interferon treatment on HCC development in patients with chronic hepatitis C. Single-course interferon treatment prevented HCC development (RR 0.45;). This preventive effect was shown even in nonresponders (RR 0.48; 95% CI 0.25-0.90). By subgroup analyses, single-course interferon treatment reduced HCC incidence in cirrhotic patients (RR 0.49; 95% CI 0.29-0.84), patients with annual HCC incidence less than 3% in control group (RR 0.42; 95% CI 0.26-0.66) and patients with annual HCC incidence of 3% or more in control group (RR 0.46; 95% CI 0.26-0.83). Furthermore, HCC incidence was reduced in 3 studies with follow-up period less than 5 years (RR 0.38; 95% CI 0.21-0.66) and in 6 studies with follow-up period of 5 years or more (RR 0.46; 95% CI 0.28-0.76). In conclusion, single-course interferon treatment was shown to prevent HCC development in chronic hepatitis C, even in nonresponders. This preventive effect may be speculated to be due to anti-inflammatory effect on persistent necro-inflammation and blocking progression of fibrosis in liver. Even if sustained virological response is not achieved, interferon may be worth administering in order to reduce HCC incidence in patients with chronic hepatitis C.In 2002, worldwide, primary liver cancer is the 6th most common cancer (626,000 cases and 5.7% of new cancer cases) and the 3rd most common cause of death from cancer (680,000 deaths). 1 Thereafter, incidence of primary liver cancer has been rising, especially in Oceania, Central Europe and North America. 2 In 2007, worldwide, 711,000 new cases with primary liver cancer are estimated. 3 Furthermore, as projected by the World Health Organization, deaths from primary liver cancer are projected to increase to 955,000 cases in 2030. 4 Hepatocellular carcinoma (HCC) accounts for $85-90% of primary liver cancer. 5 Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are estimated to be causally associated with 53 and 25%, respectively, of HCC in the world. 6 To reduce the incidence of primary liver cancer, prevention of HCC development in the population infected with HBV or HCV is required.Recently, in Asian patients with advanced chronic hepatitis B, antiviral treatment with the oral nucleoside analog lamivudine is reported to be effective in reducing HCC incidence. 7 Furthermore, by a meta-analysis, preventive effect of interferon (IFN) treatment on HCC development is suggested in populations with chronic HBV infection. 8 On the other hand, about 170 million people (3% of the world's population) are chronically infected with HCV and 3-4 million are newly ...

show abstract

Section: Resultsmentioning

confidence: 99%

“…So, one study21 was selected. Thus, 9 studies15–23 were selected after all. The characteristics of the 9 studies are shown in Table 1.…”

Section: Resultsmentioning

confidence: 99%

Meta‐analysis: Reduced incidence of hepatocellular carcinoma in patients not responding to interferon therapy of chronic hepatitis C

Miyake

Iwasaki

Yamamoto

2010

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…CNT2 is a high affinity transporter for ribavirin [44], although a comprehensive biochemical analysis of CNT2-ribavirin interactions is not available yet. This nucleoside-derivative is currently used along with IFN (interferon)-α in the treatment of hepatitis C infection [45][46][47][48]. 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.…”

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

View full text Add to dashboard Cite

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.

show abstract

“…The possible pharmacological relevance of CNT2 should also be discussed in the context of these findings. In fact, finding physiological agents that up-regulate CNT2 function in liver parenchymal cells is more important than basic physiological knowledge, since CNT2 is the highestaffinity transporter identified so far for ribavirin [50], a nucleoside-derived drug currently used in the treatment of hepatitis [51,52].…”

Section: Discussionmentioning

confidence: 99%

TGF-β transcriptionally activates the gene encoding the high-affinity adenosine transporter CNT2 in rat liver parenchymal cells

Valdés

Fernández‐Veledo

Aymerich

et al. 2006

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

The nucleoside transporter CNT2 is the highest-affinity adenosine transporter identified so far. Recent evidence suggests that CNT2 has functions other than salvage (i.e. modulation of purinergic responses). Here we identified TGF-beta1 as a potent inducer of CNT2 protein expression in liver parenchymal cells. By contrast, CNT1, which is a target of multifunctional cytokines involved in liver cell proliferation, does not respond to TGF-beta1 treatment. Cloning of a murine CNT2 gene sequence with promoter-like activity enabled us to demonstrate that this cytokine exerts this effect by transcriptionally activating the CNT2-encoding gene in a JNK-dependent manner. The evidence that CNT2 is not a target of multifunctional cytokines involved in hepatocyte proliferation, but instead, of a cytokine that plays major roles in differentiation and apoptosis, further supports the view that the main physiological role of this transporter protein is not nucleoside salvage.

show abstract

Interferon and interferon plus ribavirine in hepatocellular carcinoma prevention: A prospective study on patients with HCV related cirrhosis

Cited by 7 publications

References 0 publications

Meta‐analysis: Reduced incidence of hepatocellular carcinoma in patients not responding to interferon therapy of chronic hepatitis C

Meta‐analysis: Reduced incidence of hepatocellular carcinoma in patients not responding to interferon therapy of chronic hepatitis C

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

TGF-β transcriptionally activates the gene encoding the high-affinity adenosine transporter CNT2 in rat liver parenchymal cells

Contact Info

Product

Resources

About