Long-Term Interferon Maintenance Therapy Improves Survival in Patients with HCV-Related Hepatocellular Carcinoma after Curative Radiofrequency Ablation

Kudo, Masatoshi; Sakaguchi, Yasuhiro; Chung, Hobyung; Hatanaka, Kinuyo; Hagiwara, Satoru; Ishikawa, Emi; Takahashi, Shunsuke; Kitai, Satoshi; Inoue, Takamitsu; Minami, Yasunori; Ueshima, Kazuomi

doi:10.1159/000111719

Cited by 62 publications

(77 citation statements)

References 44 publications

(30 reference statements)

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“…Therefore, patients with a high PIVKA-II level should be more carefully followed up and adjuvant therapy such as interferon therapy [41] or molecular-targeted agent such as sorafenib [42] should be considered for such patients after curative RFA treatment.…”

Section: Discussionmentioning

confidence: 99%

PIVKA-II Is the Best Prognostic Predictor in Patients with Hepatocellular Carcinoma after Radiofrequency Ablation Therapy

et al. 2008

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Objective: This study was undertaken to assess the prognostic predictor in patients with hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA). Methods: This study retrospectively evaluated clinical outcomes in a cohort of 179 Child-Pugh stage A cirrhotic patients who received curative RFA for naive HCC within Milan criteria. The median follow-up period was 40.5 months. Results: The cumulative survival rate was significantly lower in patients with prothrombin induced by vitamin K absence or antagonist II (PIVKA-II) ≥100 mAU/ml compared with PIVKA-II <100 mAU/ml (58.0 vs. 84.0% at 5 years; p < 0.001). The cumulative recurrence-free survival rates were significantly lower in patients with PIVKA-II ≥100 mAU/ml compared with PIVKA-II <100 mAU/ml (12.1 vs. 16.9% at 5 years; p < 0.032). The cumulative rate of maintaining period within Milan criteria was significantly lower in patients with PIVKA-II ≥100 mAU/ml compared with PIVKA-II <100 mAU/ml (34.1 vs. 55.6% at 5 years; p < 0.001). Cox regression analysis showed that low serum albumin (<3.5 g/dl; p = 0.002, RR 3.75, CI 1.64–8.56), a high level of PIVKA-II (≥100 mAU/ml; p = 0.04, RR 3.15, CI 1.45–6.87), and multiple nodules (p = 0.021, RR 2.61, CI 1.15–5.91) were independently significant mortality risk factors. Conclusion: In patients with Child-Pugh stage A HCC, the PIVKA-II level is the best prognostic predictor after curative RFA.

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Section: Discussionmentioning

confidence: 99%

PIVKA-II Is the Best Prognostic Predictor in Patients with Hepatocellular Carcinoma after Radiofrequency Ablation Therapy

et al. 2008

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“…As secondary prevention, IFN treatment to eradicate the virus following curative resection and ablation, and maintenance IFN treatment [36] are known to significantly reduce the cancer recurrence rate and to improve the prognosis [37]. The direct growth inhibitory action of IFN to the HCC cells has also been proved in vitro [38].…”

Section: Primary and Secondary Inhibition Of Hepatocarcinogenesismentioning

confidence: 99%

Hepatocellular Carcinoma 2009 and Beyond: from the Surveillance to Molecular Targeted Therapy

Kudo

2008

Oncology

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Hepatocellular carcinoma (HCC) is a malignant tumor which is becoming more prevalent worldwide. Patients at high risk of developing HCC, namely hepatitis B- and C-related liver cirrhosis patients, should be entered into surveillance programs, which should be performed using both ultrasonography and 3 tumor markers (AFP, PIVKA-II, AFP-L3). The surveillance interval needs to be shortened for patients at higher risk of HCC. Therefore, super-high-risk patients should be screened at 3- to 4-month intervals based on their risk of developing HCC. Sonazoid-enhanced US is extremely useful to characterize hepatic tumors when compared with multidetector-row computed tomography (MDCT). Moreover, Sonazoid-enhanced US with defect reperfusion imaging is a breakthrough approach in the treatment of HCC. This technique will markedly change the therapeutic strategy for liver cancer. Furthermore, diagnostic capability using the new imaging technique Gd-EOB-DTPA MRI is promising. A reduced uptake (low intensity) in the hepatobiliary phase of Gd-EOB-DTPA MRI strongly suggests HCC (including early-stage HCC) or a high-grade dysplastic nodule with high malignant potential. Empirically, intrahepatic arterial infusion chemotherapy using implanted reservoir port is known to be effective for advanced HCC with vascular invasion; however, no randomized study exists to prove its efficacy. Further controlled study is necessary to establish this treatment option as a standard of care in a treatment algorithm for HCC. In contrast, sorafenib was established as the first choice of treatment as a standard of care in advanced HCC patients with preserved liver function and vascular invasion/extrahepatic spread. Furthermore, global clinical trials are now ongoing using sorafenib as an adjuvant setting after resection, ablation or TACE. Efficacy of combined use of sorafenib with TACE or intra-arterial infusion chemotherapy is not clear. In order to clarify this issue a randomized clinical trial for intermediate and advanced HCC comparing sorafenib alone versus sorafenib combined with maintenance TACE/intra-arterial infusion chemotherapy and/or intra-arterial infusion chemotherapy is scheduled to be initiated in Japan in 2009. If positive results are obtained by these trials, its impact on treatment strategy for HCC will be drastically changed.

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“…In short, in cohort studies, maintenance IFN therapy using PEG-IFN for long periods seems to have more favorable results compared with other studies [57]. This implies that the longer IFN is administered, the longer is patient survival, through the continuous suppression of later recurrence.…”

Section: Impact Of Ifn Therapy After Curative Treatment Of Hcc: Resulmentioning

confidence: 99%

“…Sakaguchi et al [56] and Kudo et al [57] treated relatively large numbers of patients for relatively long periods of 1.8 and 4.7 years, respectively. In the Sakaguchi trial, both recurrence-free and overall survival were better in the IFN-treated group than in the control group.…”

Section: Impact Of Ifn Therapy After Curative Treatment Of Hcc: Resulmentioning

confidence: 99%

Impact of Interferon Therapy after Curative Treatment of Hepatocellular Carcinoma

Kudo¹

2008

Oncology

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Primary and secondary prevention of hepatocellular carcinoma (HCC) which has become endemic worldwide in recent years are the most important issues in reducing mortality of HCC patients. Among several compounds previously reported for secondary prevention, treatment with interferon (IFN) is widely applied and shows encouraging results. To date, there have been 8 published randomized control trials (RCTs) and 6 published non-RCTs on IFN therapy after curative treatment of HCCs. Positive results were shown in 6 of 8 RCTs and in all of 6 non-RCT cohort studies regarding either recurrence rate or patient survival. The impact of IFN therapy after curative treatment of HCC can be summarized as follows: (1) HCC incidence of recurrence is reduced through viral clearance or long-term IFN treatment, even though HCV is not cleared. (2) Low-dose, long-term IFN (maintenance) therapy may suppress HCC recurrence through direct action of IFN on tumor cells. (3) Patient survival is improved through growth inhibition of recurrent tumors, as well as preservation of liver function. (4) According to the above 3 points, there is more chance to receive curative treatment in the IFN than the non-IFN group. (5) Pegylated IFN (PEG-IFN) may be more beneficial than non-PEG-IFN products since IFN concentration is maintained in the body at a high level, which is favorable for its action as a direct anticancer agent. (6) It may be concluded that IFN treatment after curative treatment of HCC is beneficial at least in HCV-related HCC, since it lowers recurrence and improves survival.

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Long-Term Interferon Maintenance Therapy Improves Survival in Patients with HCV-Related Hepatocellular Carcinoma after Curative Radiofrequency Ablation

Cited by 62 publications

References 44 publications

PIVKA-II Is the Best Prognostic Predictor in Patients with Hepatocellular Carcinoma after Radiofrequency Ablation Therapy

PIVKA-II Is the Best Prognostic Predictor in Patients with Hepatocellular Carcinoma after Radiofrequency Ablation Therapy

Hepatocellular Carcinoma 2009 and Beyond: from the Surveillance to Molecular Targeted Therapy

Impact of Interferon Therapy after Curative Treatment of Hepatocellular Carcinoma

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