The effectiveness of interferon therapy on occurrence of hepatocellular carcinoma in chronic hepatitis C.

Horiike, Norio; Fujisawa, Tomoki; Michitaka, Kojiro; Tada, Kouji; Masumoto, T.; Iuchi, Hidehito; Kojima, Naohiko; Onji, Morikazu

doi:10.3892/or.5.5.1171

Cited by 11 publications

(9 citation statements)

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“…Nishiguchi et al 8 demonstrated that IFN prevents the development of HCC even in cirrhotic patients who are nonresponders. Horiike et al 7 showed that the incidence rate of HCC is significantly lower in IFN-treated patients than in untreated patients. However, Kasahara et al 10 reported that the 5-year incidence rates of HCC in long term responders, transient responders, and nonresponders were 4.3%, 4.7%, and 21.4%, respectively.…”

Section: Discussionmentioning

confidence: 99%

“…Although the difference was not statistically significant, these findings may suggest that the incidence of HCC is related closely to the response to IFN therapy but not to IFN treatment by itself. In our IFN-treated patients, only 11 of 42 (26%) showed SR. Because it has been reported that, in 15%40% of IFN-treated patients, HCV was eradicated, 7,10,28,30 it remains to be established definitively whether IFN therapy by itself can diminish the risk of HCC. To determine the efficacy of IFN in the prevention of HCC, further follow-up study of IFN-treated patients is essential, given that the incidence rate of HCC in patients with chronic HCV increases with its progress over the time of follow-up.…”

Section: Discussionmentioning

confidence: 99%

“…5,6 It has been reported that IFN delays the progression to cirrhosis and reduces the incidence of HCC, even when HCV is not eradicated. [7][8][9] However, a recent study reported a high occurrence rate of HCC in nonresponders to IFN therapy whose serum alanine aminotransferase (ALT) level had not been normalized. 10 This finding may suggest that IFN therapy by itself does not reduce the risk of HCC but, rather, that the response to IFN therapy is the critical factor affecting the risk.…”

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confidence: 99%

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Analysis of factors affecting the appearance of hepatocellular carcinoma in patients with chronic hepatitis C

Aizawa

Takagi

et al. 2000

Cancer

105

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Analysis of factors affecting the appearance of hepatocellular carcinoma in patients with chronic hepatitis C

Aizawa

Takagi

et al. 2000

Cancer

105

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“…nterferons are currently used as a pivotal treatment regime in a variety of virus-infected and malignant diseases, among which the liver diseases, especially the viral hepatitis and hepatocellular carcinoma, were most extensively treated by IFNs (1)(2)(3)(4)(5). IFN monotherapy has been used in the treatment standard for chronic hepatitis C virus infection, and has been shown to reduce serum alanine aminotransferase levels and eliminate serum virus RNA in ϳ40% of patients (1)(2)(3).…”

mentioning

confidence: 99%

IL-1β Attenuates IFN-αβ-Induced Antiviral Activity and STAT1 Activation in the Liver: Involvement of Proteasome-Dependent Pathway

Tian

Shen

Hong

et al. 2000

The Journal of Immunology

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IFN-αβ is the only established treatment for viral hepatitis; however, more than 60% of patients are poorly responsive. Because viral hepatitis is associated with inflammation, we hypothesized that inflammation may attenuate the efficacy of IFN therapy. To test this hypothesis, the effect of IL-1β, one of the major proinflammatory cytokines, on IFN signaling pathway in the liver was examined. Administration of IL-1β in vivo attenuated IFN-αβ-induced STAT1 tyrosine phosphorylation in the liver but not in the spleen. The inhibitory action of IL-1β in vivo was not affected by depleting hepatic Kupffer cells, suggesting that IL-1β may directly target IFN-αβ signaling in hepatocytes. Indeed, pretreatment of human hepatocellular carcinoma HepG2 cells with IL-1β suppressed IFN-αβ-induced antiviral activity and antiviral protein MxA mRNA expression. Furthermore, IL-1β attenuated IFN-αβ-induced STAT1 binding and tyrosine phosphorylation without affecting the level of STAT1 protein. This inhibitory effect can be reversed by pretreatment with either proteasome inhibitors or transfection of dominant negative NF-κB inducing kinase mutants. Taken together, these findings suggest that IL-1β attenuates IFN-αβ-induced STAT1 activation by a proteasome-dependent mechanism. In view of high levels of IL-1β in the serum or within the liver of patients with chronic liver diseases, attenuation of IFN-αβ signaling in the liver by IL-1β could be one of the mechanisms underlying the resistance to IFN therapy in chronic hepatitis C, and IL-1β could be a potential therapeutic target for improving the efficacy of IFN therapy.

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“…We conducted a systematic review of the literature on 2 key questions: (1) What is the efficacy of using screening tests for HCC to improve clinical outcomes in patients with chronic hepatitis C and (2) what are the sensitivity and specificity of screening tests for HCC, especially resectable HCC, in patients with chronic hepatitis C? Sensitivity refers to the ability to detect HCC in those who have HCC, and specificity refers to the ability to rule out HCC when HCC is not present.…”

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Screening tests for hepatocellular carcinoma in patients with chronic hepatitis C: A systematic review

et al. 2002

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This systematic review addresses the following questions: (1) What is the efficacy of using screening tests for hepatocellular carcinoma (HCC) in improving outcomes in chronic hepatitis C, and (2) what are the sensitivity and specificity of screening tests for HCC in chronic hepatitis C? The search strategy involved searching Medline and other electronic databases between January 1985 and March 2002. Additional articles were identified by reviewing pertinent articles and journals and by querying experts. Articles were eligible for review if they reported original human data from studies of screening tests that used virological, histological, pathologic, or clinical outcome measures. Data collection involved paired reviewers who assessed the quality of each study and abstracted data. One nonrandomized prospective cohort study suggested that HCC was detected earlier and was more often resectable in patients who had twice yearly screening with serum alpha-fetoprotein (AFP) and hepatic ultrasound than in patients who had usual care. Twenty-four studies, which included patients with chronic hepatitis C or B or both, addressed the sensitivities and specificities of screening tests. They were relatively consistent in showing that the sensitivity of serum AFP for detecting HCC usually was moderately high at 45% to 100%, with a specificity of 70% to 95%, for a threshold of between 10 and 19 ng/mL. The few studies that evaluated screening with ultrasound reported high specificity, but variable sensitivity. In conclusion, screening of patients with chronic hepatitis C with AFP and ultrasound may improve detection of HCC, but studies are needed to determine whether screening improves clinical outcomes. (HEPATOLOGY 2002;36:S84-S92.)

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The effectiveness of interferon therapy on occurrence of hepatocellular carcinoma in chronic hepatitis C.

Cited by 11 publications

References 0 publications

Analysis of factors affecting the appearance of hepatocellular carcinoma in patients with chronic hepatitis C

Analysis of factors affecting the appearance of hepatocellular carcinoma in patients with chronic hepatitis C

IL-1β Attenuates IFN-αβ-Induced Antiviral Activity and STAT1 Activation in the Liver: Involvement of Proteasome-Dependent Pathway

Screening tests for hepatocellular carcinoma in patients with chronic hepatitis C: A systematic review

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