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Low platelets: a new and simple prognostic marker for patients with hepatitis E virus-related acute liver failure

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Abstract

Background and aims

Hepatitis E virus-related acute liver failure (HEV-ALF) rapidly worsens and has a high mortality. However, no simple and specific parameters for predicting short-term mortality are available.

Methods

A derivation cohort including 97 patients with HEV-ALF and another validation cohort were enrolled. Laboratory and clinical parameters were recorded. Platelet count, model for end-stage liver disease (MELD), and King’s College criteria (KCC) were separately used for predicting mortality, and the levels of cytokines associated with systemic inflammation, platelet production, and platelet activation were measured.

Results

Platelet counts were significantly lower in patients with HEV-ALF, and nonsurvivors had lower platelet counts than survivors (p < 0.001). Platelet count was an independent risk factor for predicting 28- and 90-day mortality in patients with HEV-ALF. The AUROC of the baseline platelet count (cutoff, 131 × 109/L) for 28- and 90-day mortality was 0.786 and 0.764, respectively, which was superior to KCC score (p < 0.05) and comparable to MELD score. Furthermore, the platelet counts at 3 and 7 days after ALF diagnosis had similar predictive power for 28- and 90-day mortality. The value of platelet count was also confirmed in the validation cohort. Moreover, platelet-associated cytokines, including thrombopoietin, platelet factor 4, and P-selectin, were increased in patients with HEV-ALF.

Conclusions

Decreased platelet count is a simple and reliable indicator for predicting 28- and 90-day mortality in patients with HEV-ALF. Overactivation of platelets is an important risk for platelet counts decrease, and treatment aiming at platelet count recovery may be considered.

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Abbreviations

ALF:

Acute liver failure

HEV:

Hepatitis E virus

HE:

Hepatic encephalopathy

KCC:

King’s College criteria

MELD:

Model for end-stage liver disease

HEV-ALF:

Hepatitis E virus-related acute liver failure

HEV-AH:

Hepatitis E virus-related acute hepatitis

HC:

Healthy control

PT:

Prothrombin time

INR:

International normalized ratio

WBC:

White blood cell

Alb:

Albumin

TBil:

Total bilirubin

AST:

Aspartate aminotransferase

ALT:

Alanine aminotransferase

Cre:

Creatine

GI:

Gastrointestinal

AKI:

Acute kidney injury

TPO:

Thrombopoietin

PF-4:

Platelet factor 4

AUROC:

Area under the receiver operating characteristic curve

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Acknowledgements

The authors acknowledge the patients, study investigators, and coordinators for their contributions in this study.

Funding

This work was supported by the National Natural Innovation Fund (Project 81721002) and the Key R&D projects in Nanning (20193008-1).

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Author notes

  1. Xiuying Mu and Jun Zou contributed equally to this work.

Authors and Affiliations

  1. Peking University 302 Clinical Medical School, Beijing, China

    Xiuying Mu, Huajie Li & Fu-Sheng Wang

  2. Senior Department of Infectious Diseases, Fifth Medical Center of Chinese, PLA General Hospital, National Clinical Research Center for Infectious Diseases, 100 Xisihuan Road, Fengtai District, Beijing, 100039, China

    Xiuying Mu, Huajie Li, Tao Yang, Kai Liu, Wen-Jing Cao, Ming-Ju Zhou, Chao Zhang, Ji-Yuan Zhang, Yan-Mei Jiao, Jin-Wen Song, Xing Fan, Ming Shi, Ruonan Xu & Fu-Sheng Wang

  3. The Fourth People’s Hospital of Nanning, Guangxi, China

    Jun Zou & Lian Ma

  4. Senior Department of Liver Diseases, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China

    Jing Chen, Jingjing Tong, Peng Ning & Jinhua Hu

  5. The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China

    Zhiqian Feng

  6. Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, China

    Wen-Jing Cao

  7. Beijing Ditan Hospital, Capital Medical University, Beijing, China

    Ming-Ju Zhou

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  1. Xiuying Mu
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Contributions

XM, JZ, JC, JT, LM, PN, HL, ZF, TY, KL, WC, MJZ, CZ, JYZ, YMJ, JWS, XF, MS, and JH participated in the data acquisition and soluble cytokines analysis; XM, JZ, RX, and FSW designed the study; XM and JZ performed analyses and interpretation of data; XM and JZ wrote the first draft of the manuscript and incorporated revisions; XM, JZ, RX, and FSW prepared the final version; All authors approved the final manuscript to be published.

Corresponding authors

Correspondence to Ruonan Xu or Fu-Sheng Wang.

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Conflict of interest

Xiuying Mu, Jun Zou, Jing Chen, Jingjing Tong, Lian Ma, Peng Ning, Huajie Li, Zhiqian Feng, Tao Yang, Kai Liu, Wen‑Jing Cao, Ming‑Ju Zhou, Chao Zhang, Ji‑Yuan Zhang, Yan‑Mei Jiao, Jin‑Wen Song, Xing Fan, Ming Shi, Jinhua Hu, Ruonan Xu andFu‑Sheng Wang declare that they have no conflict of interest.

Ethical approval

Ethical approvals were obtained from the Fifth Medical Center of Chinese PLA General Hospital, and the study was performed in accordance with the 1975 Declaration of Helsinki.

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Mu, X., Zou, J., Chen, J. et al. Low platelets: a new and simple prognostic marker for patients with hepatitis E virus-related acute liver failure. Hepatol Int 16, 1116–1126 (2022). https://doi.org/10.1007/s12072-022-10302-1

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  • DOI: https://doi.org/10.1007/s12072-022-10302-1

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