Development of hepatocellular carcinoma in patients with hepatitis C virus infection who achieved sustained virological response following interferon therapy: A large‐scale, long‐term cohort study

Nagaoki, Yuko; Aikata, Hiroshi; Nakano, Norihito; Shinohara, Fumi; Nakamura, Yuki; Hatooka, Masahiro; Morio, Kei; Kan, Hiromi; Fujino, Hatsue; Kobayashi, Tomoki; Fukuhara, Toru; Kitajima, Masaki; Ono, Atsushi; Nakahara, Takashi; Kawaoka, Tomokazu; Miki, Daiki; Tsuge, Masataka; Hiramatsu, Akira; Imamura, Michio; Takahashi, Shoichi; Kawakami, Yoshiiku; Ochi, Hidenori; Chayama, Kazuaki

doi:10.1111/jgh.13236

Cited by 54 publications

(49 citation statements)

References 31 publications

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“…The findings of our study were consistent with those of a Japanese cohort study, which showed that post-treatment serum α-fetoprotein levels achieved 80% predictability in detecting HCC by setting the cutoff value at 6 ng/mL 34 . Similarly, a recent study revealed that patients with α-fetoprotein levels higher than 10 ng/mL had an approximately 7.8-fold higher risk of developing HCC after achieving SVR 35 .…”

Section: Discussionmentioning

confidence: 85%

Clinical Efficacy and Post-Treatment Seromarkers Associated with the Risk of Hepatocellular Carcinoma among Chronic Hepatitis C Patients

Lee

Huang

Lai

et al. 2017

Sci Rep

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This follow-up study enrolled chronic hepatitis C patients to evaluate the treatment efficacy and to identify post-treatment seromarkers associated with risk of hepatocellular carcinoma (HCC) among patients with a sustained virological response (SVR) or nonsustained virological response (NSVR). A total of 4639 patients who received pegylated interferon and ribavirin during 2004–2013 were followed until December 2014. HCC was confirmed through health examinations and data linkage with a national database. A total of 233 HCC cases were reported after 26,163 person-years of follow-up, indicating an incidence of 8.9 per 1000 person-years: 6.9 for SVR and 21.6 for NSVR per 1000 person-years. The associated risk of HCC in patients with SVR was 0.37 (0.22–0.63) for those without cirrhosis and 0.54 (0.31–0.92) for those with cirrhosis compared with their respective counterparts with NSVR. Among patients with SVR, advanced age, male gender, cirrhosis, decreased platelet count, and increased aspartate aminotransferase and α-fetoprotein levels were associated with HCC (p < 0.001). The treatment of chronic hepatitis C patients before they developed cirrhosis showed a higher efficacy than did the treatment of those who had already developed cirrhosis. Patients with SVR may still have a risk of HCC and need to be regularly monitored.

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Section: Discussionmentioning

confidence: 85%

Clinical Efficacy and Post-Treatment Seromarkers Associated with the Risk of Hepatocellular Carcinoma among Chronic Hepatitis C Patients

Lee

Huang

Lai

et al. 2017

Sci Rep

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“…However, the risk of developing HCC remains high after SVR because liver fibrosis remains after eradication of HCV . The most important step after HCV eradication is follow‐up diagnostic imaging based on the risk for each patient . Thus, WFA + ‐M2BP represents an important monitoring marker for predicting tumor development after eradication of HCV.…”

Section: Discussionmentioning

confidence: 99%

Serum Wisteria floribunda agglutinin‐positive Mac‐2‐binding protein levels and liver fibrosis: A meta‐analysis

Ito

Murotani

Nakade

et al. 2017

J of Gastro and Hepatol

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“…One important risk factor in that study was a fibrosis stage > 2 [30]. In another Japanese study, the cumulative incidence of HCC among more than 1,000 patients with an SVR after IFN therapy was 3% a median follow-up time of 37 months after treatment [31]; again, advanced fibrosis (F > 3) was a significant risk factor for HCC development. Of note, HCC development may occur in patients without or with only mild fibrosis (F < 2).…”

Section: Discussionmentioning

confidence: 99%

Risk of de novo Hepatocellular Carcinoma after HCV Treatment with Direct-Acting Antivirals

et al. 2018

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Background and Aims: The aim of the study was to evaluate the risk of hepatocellular carcinoma (HCC) development after treatment with direct-acting antivirals (DAAs) and to compare HCC occurrence in these patients with that among patients treated with interferon (IFN)-based therapies. Methods: We analyzed a large cohort with chronic hepatitis C virus patients for the onset of new HCC after DAA treatment. A historical IFN-treated cohort was investigated for comparison. Results: A total of 819 patients were included in the DAA group. The median follow-up period was 263 days (0–1,001). Twenty-five patients (3.6 HCCs/100 person-years; 3.1%) were diagnosed with de novo HCC within the time of observation. No patient without cirrhosis had developed HCC. Patients with newly diagnosed HCC were mostly male, older, and treatment-experienced and had a lower 12-week sustained virologic response (SVR12) rate and higher levels of liver inflammation markers. The median time to HCC was 312 days (0–880). Investigation of the subcohort of 269 cirrhotic patients yielded an HCC rate of 8.9 HCCs/100 person-years. In this cohort, non-SVR12 was an independent risk factor for de novo HCC (HR 4.48; 95% CI 1.51–13.12; p = 0.007). Twenty-four patients (96%) with new HCC were Child-Pugh class A and 17 (68%) were diagnosed in early BCLC stage A. For the IFN-treated patients, we calculated an overall risk of HCC occurrence of 1.3/100 person-years (19 patients out of 351; 5.4%). The median time to diagnosis was 38.8 months (0–113). Conclusion: The de novo HCC rates did not differ between the DAA-treated patients and those who received IFN. Achievement of SVR is of utmost importance for HCC prevention.

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Development of hepatocellular carcinoma in patients with hepatitis C virus infection who achieved sustained virological response following interferon therapy: A large‐scale, long‐term cohort study

Abstract: Older age and male sex (host factors), advanced fibrosis stage (pre-IFN treatment factor), and higher alpha-fetoprotein values (post-treatment factor) were significantly associated with HCC development after HCV eradication.

Cited by 54 publications

References 31 publications

Clinical Efficacy and Post-Treatment Seromarkers Associated with the Risk of Hepatocellular Carcinoma among Chronic Hepatitis C Patients

Clinical Efficacy and Post-Treatment Seromarkers Associated with the Risk of Hepatocellular Carcinoma among Chronic Hepatitis C Patients

Serum Wisteria floribunda agglutinin‐positive Mac‐2‐binding protein levels and liver fibrosis: A meta‐analysis

Risk of de novo Hepatocellular Carcinoma after HCV Treatment with Direct-Acting Antivirals

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