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Probability-Based Interpretation of Liver Stiffness Measurement in Untreated Chronic Hepatitis B Patients

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Abstract

Background

Liver stiffness measurement (LSM) by transient elastography is a popular noninvasive test of fibrosis. Traditional LSM cutoffs dichotomize patients and do not clearly indicate the confidence of diagnosis.

Aim

We derived and validated probability functions of fibrosis and cirrhosis based on LSM and determined the effect of alanine aminotransferase (ALT) on the scores.

Methods

Consecutive chronic hepatitis B patients who underwent liver function tests, LSM, and liver biopsies at six European and Asian centers (2/3 in the training cohort and 1/3 in the validation cohort) were recruited. Binary logistic regression was performed to predict the probabilities of different fibrosis stages based on LSM and/or ALT.

Results

A total of 1,051 patients were included in the final analysis (53 % with ALT ≥ 60 IU/L, 32 % F2, 20 % F3, and 24 % F4). The probability functions (LiFA-HBV score) with and without ALT adjustment closely mirrored the proportion with different fibrosis stages in both the training and validation cohorts. For a range of up to 300 IU/L, ALT maintained a weak linear relationship with LSM for each fibrosis stage (r 2 = 0.018–0.13). Based on relative integrated discrimination improvement, the addition of ALT to the LiFA-HBV score increased the correct reclassification of F3–4 and F4 by 5 and 17 %, respectively.

Conclusions

ALT increases LSM in a linear fashion in chronic hepatitis B patients at any fibrosis stage. The LiFA-HBV score accurately predicts the probability of fibrosis. ALT adjustment increases the rate of reclassification modestly and is not essential.

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Abbreviations

ALT:

Alanine aminotransferase

AUROC curve:

Area under the receiver operating characteristic curve

BMI:

Body mass index

CI:

Confidence interval

HBeAg:

Hepatitis B e antigen

HBV:

Hepatitis B virus

IDI:

Integrated discrimination improvement

IQR:

Interquartile range

LSM:

Liver stiffness measurement

NRI:

Net reclassification improvement

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Acknowledgments

This study was partly funded by the National Science and Technology Major Project to Jinlin Hou (2012ZX10002003) and the Direct Grant from The Chinese University of Hong Kong to Vincent Wong (2013.1.040).

Conflict of interest

Vincent Wong, Victor de Lédinghen, and Henry Chan have served as speakers for Echosens. Henry Chan is a consultant of Inner Mongolia Furui Medical Science Co Ltd.

Author information

Authors and Affiliations

  1. Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China

    Vincent Wai-Sun Wong & Henry Lik-Yuen Chan

  2. State Key Laboratory of Gastroenterology, The Chinese University of Hong Kong, Hong Kong, China

    Vincent Wai-Sun Wong & Henry Lik-Yuen Chan

  3. “A.M. e A. Migliavacca” Center for the Study of Liver Disease, 1st Division of Gastroenterology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy

    Pietro Lampertico & Giampaolo Mangia

  4. Centre d’investigation de la Fibrose Hepatique, Hopital Haut-Leveque, Pessac, France

    Victor de Lédinghen & Juliette Foucher

  5. INSERM U1053, Universite Bordeaux, Bordeaux, France

    Victor de Lédinghen

  6. Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore, Singapore

    Pik Eu Chang & Wan Cheng Chow

  7. Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemoon-gu, Seoul, 120-749, South Korea

    Seung Up Kim & Sang Hoon Ahn

  8. Liver Cirrhosis Research Center, Seoul, South Korea

    Seung Up Kim & Sang Hoon Ahn

  9. Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China

    Yongpeng Chen & Jinlin Hou

Authors
  1. Vincent Wai-Sun Wong
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  2. Pietro Lampertico
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  3. Victor de Lédinghen
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  4. Pik Eu Chang
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  5. Seung Up Kim
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  6. Yongpeng Chen
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  7. Henry Lik-Yuen Chan
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  8. Giampaolo Mangia
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  9. Juliette Foucher
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  10. Wan Cheng Chow
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  11. Sang Hoon Ahn
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  12. Jinlin Hou
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Corresponding authors

Correspondence to Sang Hoon Ahn or Jinlin Hou.

Additional information

For the LiFA Investigators.

Please refer “Appendix” section for the Liver Fibrosis Assessment (LiFA) Study.

Electronic supplementary material

Appendix: list of Investigators

Appendix: list of Investigators

The members of the Liver Fibrosis Assessment (LiFA) Study Group are as follows: Singapore General Hospital (Pik Eu Chang, Wan Cheng Chow, Zhongxian Poh), Southern Medical University (Yongpeng Chen, Jinlin Hou, Jian Sun), The Chinese University of Hong Kong (Henry Lik-Yuen Chan, Angel Mei-Ling Chim, Kwong Sak Leung, Peter Lo, Yee-Kit Tse, Grace Lai-Hung Wong, Vincent Wai-Sun Wong), Università degli Studi di Milano (Massimo Colombo, Mirella Fraquelli, Federica Invernizzi, Pietro Lampertico, Giampaolo Mangia, Mauro Viganò), Universite Bordeaux (Faiza Chermak, Juliette Foucher, Jean-Baptiste Hirart, Victor de Lédinghen, Wassil Merrouche, Julien Vergniol), and Yonsei University College of Medicine (Sang Hoon Ahn, Kwang-Hyub Han, Beom Kyung Kim, Do Young Kim, Seung Up Kim, Jun Yong Park).

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Wong, V.WS., Lampertico, P., de Lédinghen, V. et al. Probability-Based Interpretation of Liver Stiffness Measurement in Untreated Chronic Hepatitis B Patients. Dig Dis Sci 60, 1448–1456 (2015). https://doi.org/10.1007/s10620-014-3488-5

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  • DOI: https://doi.org/10.1007/s10620-014-3488-5

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