Risk factors for the development of hepatocellular carcinoma among patients with chronic hepatitis C who achieved a sustained virological response to interferon therapy

Tokita, Hajime; Fukui, Hirokazu; Tanaka, Akihisa; Kamitsukasa, Hiroshi; Yagura, Michiyasu; Harada, Hideharu; Okamoto, Hiroaki

doi:10.1111/j.1440-1746.2005.03800.x

Cited by 89 publications

(89 citation statements)

References 40 publications

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“…Previous studies showed that interferon-based treatment for HCV patients could reduce the risk of hepatocellular carcinoma [17,18,19,20], but that risk factors for hepatocarcinogenesis after elimination of HCV RNA were severe fibrosis, male sex, and older age at the start of interferon treatment [20,21,22,23,24,25]. The present study based on 958 patients with HCV genotype 1 infection is the first to show that severe fibrosis and obesity are important predictors of hepatocarcinogenesis following eradication of HCV RNA by direct-acting antivirals.…”

Section: Discussionmentioning

confidence: 99%

Liver Fibrosis and Body Mass Index Predict Hepatocarcinogenesis following Eradication of Hepatitis C Virus RNA by Direct-Acting Antivirals

Akuta¹,

Kobayashi²,

Suzuki³

et al. 2016

Oncology

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Background and Aims: Predictive factors for hepatocarcinogenesis following eradication of hepatitis C virus (HCV) RNA by antiviral therapy with direct-acting antivirals are unknown. Especially the impact of treatment with or without interferon on hepatocarcinogenesis is not clear. Methods: A total of 958 patients with HCV genotype 1-related chronic liver disease and a sustained virological response defined as negative HCV RNA 24 weeks after cessation of antiviral therapy with direct-acting antivirals (triple therapy of NS3/4A protease inhibitor/peginterferon/ribavirin or all-oral combination therapy with NS3/4A protease inhibitor plus NS5A inhibitor) were included in a retrospective study. None of the patients had hepatocellular carcinoma before and during antiviral therapy. Results: In all, 14 patients developed hepatocellular carcinoma during follow-up, and the development rate per 1,000 person-years was 7.35. The cumulative hepatocarcinogenesis rates were 4.2 and 4.2% at the end of 5 and 7 years, respectively. Multivariate analysis identified fibrosis 4 (FIB4) index (≥2.7) and body mass index (≥23.0) as determinants of hepatocarcinogenesis, but they did not identify the treatment regimen. In patients with a FIB4 index ≥2.7, the hepatocarcinogenesis rates with the interferon regimen were not different from those for the regimen without interferon, regardless of gender. Conclusion: Liver fibrosis and body mass index, but not treatment regimen, are important predictors of hepatocarcinogenesis following eradication of HCV RNA by direct-acting antivirals.

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Section: Discussionmentioning

confidence: 99%

Liver Fibrosis and Body Mass Index Predict Hepatocarcinogenesis following Eradication of Hepatitis C Virus RNA by Direct-Acting Antivirals

Akuta¹,

Kobayashi²,

Suzuki³

et al. 2016

Oncology

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“…However, the reported HCC annual rate after eradication of HCV RNA by antiviral therapy is Յ1% (9,12,13). Based on the results of the present study, we recommend measurement of the core aa70 mutant level of HCV-1b before the start of antiviral therapy for eradication of HCV RNA.…”

mentioning

confidence: 90%

“…P revious reports indicated that amino acid (aa) substitutions at position 70 in the hepatitis C virus (HCV) core region in patients infected with HCV genotype 1b (HCV-1b) are pretreatment predictors of poor virological response to antiviral therapy (1,2) and also affect hepatocarcinogenesis, regardless of treatment response (3-7). In particular, hepatocellular carcinoma (HCC) still occurs even after eradication of HCV RNA by antiviral therapy (8)(9)(10)(11)(12), and substitutions of aa70 at the start of antiviral therapy also affect hepatocarcinogenesis following eradication of HCV RNA (13).…”

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confidence: 99%

Impact of Mutations at Amino Acid 70 in Hepatitis C Virus (HCV) Genotype 1b Core Region on Hepatocarcinogenesis following Eradication of HCV RNA

et al. 2015

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bThe impact of the HCV genotype 1b core amino acid (aa) 70 mutant on the cumulative rate of hepatocellular carcinoma following eradication of HCV RNA by antiviral therapy was investigated with the Q-Invader assay. Multivariate analysis based on 649 patients indicated that a core aa70 Q-Invader mutant level >20% is a predictor of hepatocellular carcinoma. P revious reports indicated that amino acid (aa) substitutions at position 70 in the hepatitis C virus (HCV) core region in patients infected with HCV genotype 1b (HCV-1b) are pretreatment predictors of poor virological response to antiviral therapy (1, 2) and also affect hepatocarcinogenesis, regardless of treatment response (3-7). In particular, hepatocellular carcinoma (HCC) still occurs even after eradication of HCV RNA by antiviral therapy (8-12), and substitutions of aa70 at the start of antiviral therapy also affect hepatocarcinogenesis following eradication of HCV RNA (13).Recently, Tadokoro et al. (14) reported the results of a comparative quantitative analysis of aa70 substitution in the HCV-1b core region by the real-time PCR monitoring Invader reaction (Q-Invader assay; BML, Inc., Saitama, Japan). This highly sensitive assay (based on the Q-Invader technology using mutant-specific primers) was developed to determine the relative ratio of the aa70 mutant (glutamine/histidine) to the aa70 wild-type (arginine) virus. The assay in that study (14) detected a minor type plasmid that constituted only 1% of a mixture of plasmids containing wild-type and mutant sequences. In this study, we evaluated the associations between core aa70 Q-Invader mutant levels at the start of antiviral therapy and HCC following eradication of HCV RNA.Among 5,023 consecutive patients infected with HCV in whom antiviral therapy (interferon monotherapy, interferon plus ribavirin combination therapy, or triple therapy of NS3/4A protease inhibitor plus peginterferon plus ribavirin) was initiated between February 1987 and June 2013 at Toranomon Hospital, 2,121 patients infected with a single genotype of HCV-1b, -2a, or -2b were selected for this retrospective study. All patients achieved sustained virological response, defined as negative HCV RNA at 24 weeks after cessation of antiviral therapy, based on HCV RNA qualitative analysis (Amplicor; Roche Diagnostics, Manheim, Germany) or by the Cobas TaqMan HCV test (Roche Diagnostics, Tokyo, Japan), and they were free of HCC before and during interferon therapy. The cumulative rate of HCC was calculated using the Kaplan-Meier technique; differences between the HCC rate curves were tested using the log-rank test. The period between the end of antiviral therapy and the diagnosis of HCC was used for group-based statistical analysis of HCC. Stepwise Cox regression analysis (multivariate analysis) was used to determine independent factors associated with HCC. This study protocol was in compliance with the Good Clinical Practice guidelines and the 1975 Declaration of Helsinki, and it was approved by the institutional review board at Toranomon ...

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“…For patients with severe fibrosis (F3 or F4) in the liver before treatment (p = 0.007), patients with alcohol intake of greater than 27 g/day (p = 0.015) and patients older than 65 years (p = 0.026), there was a significant independent association of HCC development even if eradication of virus was achieved by effective antiviral therapy [41]. The annual incidence of HCC development in cirrhotic patients with an SVR remained as high as 2.67% per person-year [40].…”

Section: Ifn-based Therapy In Preventing Hcc Developmentmentioning

confidence: 99%

Long-Term Effects of Interferon-Based Therapy for Chronic Hepatitis C

Huang

et al. 2007

Oncology

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Hepatitis C virus infection frequently causes chronic liver disease leading to cirrhosis and hepatocellular carcinoma (HCC) and has become the main indication for liver transplantation. Interferon (IFN)-based therapy has been used in the treatment of chronic hepatitis C (CHC) for viral clearance. Several earlier studies showed long-term beneficial effects of IFN monotherapy in reducing the progression of cirrhosis, hindering HCC development, and prolonging survival among both sustained virological responders and nonresponders. However, the benefits of preventing disease progression in CHC patients without sustained virological response (SVR) no longer existed over a longer observation period. Both IFN monotherapy and IFN-ribavirin combination therapy were shown to reduce significantly the complications of liver disease, in terms of development of cirrhosis, HCC and liver-related mortality. The significance disappeared after response to antiviral treatment was taken into account. The benefits were obtained mainly from successful antiviral treatment but were not related to the antiviral regimens, suggesting that the magnitude of this preventive effect could increase through the significant improvement of SVR rate by using a more effective regimen, such as interferon-ribavirin or peginterferon-ribavirin combination therapy. Nevertheless, about one-third of patients remain resistant to the current recommended antiviral regimens. More effective treatment is needed for the population.

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Risk factors for the development of hepatocellular carcinoma among patients with chronic hepatitis C who achieved a sustained virological response to interferon therapy

Abstract: Patients with CHC who had severe fibrosis, who had regularly taken moderate amounts of alcohol, or who were > or = 65 years at the start of IFN treatment should be carefully followed to detect small and controllable HCC, even after eradication of HCV.

Cited by 89 publications

References 40 publications

Liver Fibrosis and Body Mass Index Predict Hepatocarcinogenesis following Eradication of Hepatitis C Virus RNA by Direct-Acting Antivirals

Liver Fibrosis and Body Mass Index Predict Hepatocarcinogenesis following Eradication of Hepatitis C Virus RNA by Direct-Acting Antivirals

Impact of Mutations at Amino Acid 70 in Hepatitis C Virus (HCV) Genotype 1b Core Region on Hepatocarcinogenesis following Eradication of HCV RNA

Long-Term Effects of Interferon-Based Therapy for Chronic Hepatitis C

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