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Pre-S Mutation Is a Significant Risk Factor for Hepatocellular Carcinoma Development: A Long-Term Retrospective Cohort Study

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Abstract

Background

Several cross-sectional studies have shown an association between pre-S mutation and hepatocellular carcinoma (HCC).

Aims

We aim to verify whether pre-S mutation represents a risk for HCC development in a longitudinal way.

Methods

A total of 195 patients with chronic HBV infection [age: 43.7 ± 10.8 years, males: 141 (72.3 %), genotype C: 195 (100 %), hepatitis B e antigen (HBeAg) positive: 109 (55.9 %), cirrhosis: 79 (40.5 %), and pre-S mutation positive: 44 (22.6 %)] were followed up for a median of 7.2 years (range 1.0–7.8 years).

Results

HCC developed in 24 patients during follow-up. The 1-, 3-, and 5-year cumulative incidences of HCC were 0.5, 4.9, and 10.4 %, respectively. Patients with pre-S mutation had significantly higher 5-year cumulative incidences of HCC than those without (26.5 vs. 5.7 %, p < 0.001) and showed higher hazard ratio for HCC [3.04 (95 % CI 1.24–7.42), p = 0.015, adjusted for age, gender, HBeAg, cirrhosis and baseline HBV DNA level]. Notably, in patients aged ≥50 years, the 5-year cumulative incidences of HCC in patients with pre-S mutation were considerably high (58.3 %), compared to those without (16.1 %, p < 0.001).

Conclusions

Patients with pre-S mutations had higher incidence of HCC during follow-up, especially in aged patients. Patients with pre-S mutations, especially older ones, may require careful attention to HCC development.

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Abbreviations

HBV:

Hepatitis B virus

HBsAg:

Hepatitis B surface antigen

HCC:

Hepatocellular carcinoma

PCR:

Polymerase chain reaction

AFP:

Alpha-fetoprotein

ROC:

Receiver operator curve

OR:

Odd ratios

ER:

Endoplasmic reticulum

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Authors and Affiliations

  1. Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, 135-710, South Korea

    Dong Hyun Sinn, Moon Seok Choi, Geum-Youn Gwak, Yong-Han Paik, Joon Hyeok Lee, Kwang Cheol Koh, Seung Woon Paik & Byung Chul Yoo

  2. Department of Medicine, Sanggye Paik Hospital, Inje University School of Medicine, Seoul, South Korea

    Dong Hyun Sinn

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  1. Dong Hyun Sinn
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  2. Moon Seok Choi
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Correspondence to Moon Seok Choi.

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Sinn, D.H., Choi, M.S., Gwak, GY. et al. Pre-S Mutation Is a Significant Risk Factor for Hepatocellular Carcinoma Development: A Long-Term Retrospective Cohort Study. Dig Dis Sci 58, 751–758 (2013). https://doi.org/10.1007/s10620-012-2408-9

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  • DOI: https://doi.org/10.1007/s10620-012-2408-9

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