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Rapid Alanine Aminotransferase Normalization with Entecavir and Hepatocellular Carcinoma in Hepatitis B Virus-Associated Cirrhosis

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Abstract

Background

Sustained abnormal serum alanine aminotransferase (ALT) levels can increase the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B.

Aim

This study is aimed to confirm the impact of rapid ALT normalization (≤30 IU/L) on HCC risk in patients with hepatitis B virus (HBV)-associated cirrhosis after entecavir (ETV) commencement.

Methods

A total of 578 treatment-naïve patients with HBV-associated cirrhosis (mean age 51 ± 9 years, male sex 63.3%) were treated with ETV for more than 1 year. Serum ALT and HBV DNA levels were measured at three time points (baseline, 6, and 12 months after ETV commencement) and subjected to risk factor analysis.

Results

Median follow-up after ETV commencement was 43 (12–98) months. Cumulative incidences of HCC at 1, 3, 5, and 7 years were 0.3, 8.5, 19.5, and 30.6%, respectively. Univariate Cox regression analysis showed that older age, abnormal ALT at 6 months or 12 months, and lower platelet count were significant risk factors for HCC. However, gender, HBeAg positivity, abnormal ALT levels or HBV DNA levels at baseline, and detectable HBV DNA at 6 or 12 months were not risk factors. Multivariate analysis showed that older age (P < 0.001), abnormal ALT at 12 months (P = 0.006), and lower platelet count (P = 0.034) were the risk factors for HCC.

Conclusions

Abnormal serum ALT levels after ETV commencement are significant risk factor for HCC. Therefore, ALT should be rapidly normalized to minimize the risk of HCC development in patients with HBV-associated cirrhosis.

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Acknowledgments

The authors thank Dr. Hyeonsu Park and Hyun Jung Lee for coordination of this work.

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    Authors and Affiliations

    1. Division of Gastroenterology, Department of Internal Medicine, Gachon University Gil Medical Center, 21, Namdong-daero 774 beon-gil, Namdong-gu, Incheon, 21565, South Korea

      Eui Joo Kim, Oh Sang Kwon, Heon Nam Lee, Seung Kak Shin, Yun Soo Kim & Ju Hyun Kim

    2. Department of Internal Medicine, Korea University Medical College, Korea University Guro Hospital, 97 Gurodong-gil, Guro-gu, Seoul, 08308, South Korea

      Jong Eun Yeon, Seong Hee Kang & Kwan Soo Byun

    3. Department of Internal Medicine, Konkuk University School of Medicine, Konkuk University Medical Center, 120-1 Neungdong-ro, Hwayang-dong, Gwangjin-gu, Seoul, 05030, South Korea

      Jeong Han Kim & So Young Kwon

    4. Department of Internal Medicine, Korea University Medical College, Korea University Ansan Hospital, 123 Jeokgeum-ro, Danwon-Gu, Ansan-Si, Gyeonggi-Do, 15355, South Korea

      Sang Jun Suh & Hyung Joon Yim

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    1. Eui Joo Kim
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    Correspondence to Oh Sang Kwon.

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    Eui Joo Kim and Jong Eun Yeon contributed equally to the present study.

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    Kim, E.J., Yeon, J.E., Kwon, O.S. et al. Rapid Alanine Aminotransferase Normalization with Entecavir and Hepatocellular Carcinoma in Hepatitis B Virus-Associated Cirrhosis. Dig Dis Sci 62, 808–816 (2017). https://doi.org/10.1007/s10620-016-4431-8

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