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Post-treatment fibrotic modifications overwhelm pretreatment liver fibrosis in predicting HCC in CHC patients with curative antivirals

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Abstract

Background/aims

Liver fibrosis determined hepatocellular carcinoma (HCC) occurrence in chronic hepatitis C patients with sustained virological response (SVR). We aimed to determine whether post-treatment fibrotic modification overwhelmed pretreatment fibrotic status in terms of long-term HCC prediction.

Methods

265 SVR patients with paired biopsies before and after antiviral therapy were enrolled for analysis of the association of fibrotic changes with HCC.

Results

Eighteen (6.8%) of the 265 patients developed HCC over 1931 person-years. Cox regression analysis without post-treatment fibrosis as a covariant revealed that factors predicted HCC included age (hazard ratio [HR]/confidence intervals [CI] 1.07/1.01–1.13, p = 0.01), male gender (HR/CI 4.57/1.45–14.36, p = 0.009), diabetes (HR/CI 3.60/1.32–9.85, p = 0.01) and pretreatment advanced fibrosis (HR/CI 2.73/1.05–7.07, p = 0.039). Advanced fibrosis in post-treatment status replaced pretreatment fibrosis as the most critical determinant of HCC when it was included for analysis (HR/CI 3.53/1.34–9.30, p = 0.01). The incidences of HCC among patients with fibrotic modification from F0–2 to F0–2, F34 to F0–2, F0–2 to F34 and F34 to F34 were 0.41%, 0.84%, 1.68%, and 3.05%, respectively (p = 0.004). Compared to patients whose fibrotic stage remained at F0–2 before and after treatment, the HCC risk decreased and did not differ among those whose fibrotic stage improved from F34 to F0–2. However, HCC risk increased significantly and gradually in patients whose fibrotic stages changed from F0–2 to F34 (HR/CI 4.13/1.11–15.36, p = 0.035) and whose fibrotic stages remained at F34 before and after treatment (HR/CI 7.47/2.37–23.55, p = 0.001) (trend p = 0.003).

Conclusions

Post-treatment fibrotic modifications overwhelmed pretreatment fibrotic statuses in predicting HCC.

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Abbreviations

ALT:

Alanine aminotransferase

AST:

Aspartate aminotransferase

CHC:

Chronic hepatitis C

DM:

Diabetes mellitus

HCV:

Hepatitis C virus

IL-28B:

Interleukin 28B

SVR:

Sustained virological response

SNP:

Single-nucleotide polymorphism

HCC:

Hepatocellular carcinoma

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Acknowledgements

This work was supported in part by grants from Kaohsiung Medical University (107CM-KMU-10, KMU-DK107004, MOST 106-2314-B-037-074) and Kaohsiung Medical University Hospital (KMUH106-6M02).

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Authors and Affiliations

  1. Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

    Chung-Feng Huang, Ming-Lun Yeh, Ching-I Huang, Po-Cheng Liang, Yi-Hung Lin, Zu-Yau Lin, Shinn-Cherng Chen, Jee-Fu Huang, Chia-Yen Dai, Wan-Long Chuang & Ming-Lung Yu

  2. Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Chung-Feng Huang, Ming-Lun Yeh, Zu-Yau Lin, Shinn-Cherng Chen, Jee-Fu Huang, Chia-Yen Dai, Wan-Long Chuang & Ming-Lung Yu

  3. Department of Occupational Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

    Chung-Feng Huang

  4. Department of Preventive Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

    Chia-Yen Dai

  5. Division of Gastroenterology and Hepatology, Chi-Mei Medical Center Liouying, Tainan, Taiwan

    Ming-Lung Yu

  6. Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan

    Ming-Lung Yu

  7. College of Biological Science and Technology, National Chiao Tung University, Hsin-Chu, Taiwan

    Ming-Lung Yu

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  1. Chung-Feng Huang
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Contributions

Conception and design: M-LY. Acquisition of data: C-FH, P-CL, Y-HL, C-IH, M-LY, J-FH, Z-YL, S-CC, C-YD, and W-LC. Data analysis and interpretation: C-FH and M-LY. Manuscript drafting and critical revision: C-FH and M-LY. Approval of the final version of the manuscript: M-LY.

Corresponding author

Correspondence to Ming-Lung Yu.

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Conflict of interest

Chung-Feng Huang, Ming-Lun Yeh, Ching-I Huang, Po-Cheng Liang, Yi-Hung Lin, Zu-Yau Lin, Shinn-Cherng Chen, Jee-Fu Huang, Chia-Yen Dai, Wan-Long Chuang, and Ming-Lung Yu declare that they have no conflict of interest.

Ethical approval

The study was conducted according to the Declaration of Helsinki. The institutional review board of the Kaohsiung Medical University Hospital approved the protocols that conformed to the guidelines of the International Conference on Harmonization for Good Clinical Practice. All patients provided written informed consent. All procedures followed the ethical standards of the responsible committee on human experimentation and the Helsinki Declaration of 1975, as revised in 2008.

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Supplementary material 1 (TIFF 94 kb) Patient flowchart.

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Huang, CF., Yeh, ML., Huang, CI. et al. Post-treatment fibrotic modifications overwhelm pretreatment liver fibrosis in predicting HCC in CHC patients with curative antivirals. Hepatol Int 12, 544–551 (2018). https://doi.org/10.1007/s12072-018-9908-4

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  • DOI: https://doi.org/10.1007/s12072-018-9908-4

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