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The recovery of the PT-INR to less than 1.3 predicts survival in patients with severe acute liver injury

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
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Abstract

Background

Acute liver failure is a potentially fatal disease of various etiologies for which liver transplantation is the only known curative treatment. Although the decision-making on transplantation is largely dependent on the severity of liver injury (based on predicting a fatal outcome), a statistical analysis to predict “survival” has not been extensively conducted. In this study, we investigate the medical history of patients in two distinct areas of Japan with the aim of identifying the predictors of survival in patients with acute liver injury (ALI).

Methods

Datasets of 301 patients with ALI in two distinct areas (93 in southern Kyushu and 208 in northern Tohoku) of Japan, who were treated from 2004 to 2014, were included in the analysis.

Results

Among the enrolled 301 cases, 263 patients survived without transplantation. A PT-INR of ≥ 1.3 during the clinical course was found to be adequate for predicting a poor prognosis, because all of the fatal cases emerged from this population (hazard ratios: southern Kyushu, 0.2827; northern Tohoku, 0.1862). All surviving patients showed a reduction in their PT-INR during treatment, whereas the PT-INR did not decrease in the patients with a poor prognosis. A PT-INR of < 1.3 on days 7 and 8 efficiently predicted transplant-free survival (log-rank test: southern Kyushu, P = 0.0030; northern Tohoku, P = 0.0022).

Conclusions

A PT-INR of ≥ 1.3 during the clinical course might identify cases with a poor prognosis, while the recovery of the PT-INR to < 1.3 predicts transplant-free survival.

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Abbreviations

ALI:

Acute liver injury

ALF:

Acute liver failure

PT:

Prothrombin time

INR:

International normalized ratio

PT[%]:

Prothrombin index

ROC:

Receiver operating characteristic

AUROC:

Area under ROC

LOCF:

Last observation carried forward

NA:

Nucleos(t)ide analog

HGF:

Hepatocyte growth factor

rh-HGF:

Recombinant human HGF

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Acknowledgements

This research and development program was partially supported by the Medical Research and Development Programs Focused on Technology Transfer: Adaptable and Seamless Technology Transfer Program through Target-Driven Research and Development (A-STEP) of Japan Agency for Medical Research and Development.

Author information

Authors and Affiliations

  1. Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 8908544, Japan

    Seiichi Mawatari, Akihiro Moriuchi, Kohei Oda & Akio Ido

  2. R&D Planning Department, EA Pharma Co., Ltd., 2-1-1 Irifune, Chuo-ku, Tokyo, 1040042, Japan

    Fuminori Ohba

  3. KAN Research Institute, Inc, 6-8-2 Minatojima-Minamimachi, Chuo-Ku, Kobe, Hyogo, 6500047, Japan

    Tetsu Kawano

  4. Department of HGF Tissue Repair and Regenerative Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 8908544, Japan

    Kohei Oda, Akio Ido & Hirohito Tsubouchi

  5. Division of Hepatology, Department of Internal Medicine, School of Medicine, Iwate Medical University, 19-1 Uchimaru, Morioka, 0208505, Japan

    Yasuhiro Takikawa

  6. Department of Medicine, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-Ku, Tokyo, 1738606, Japan

    Hajime Takikawa

  7. Department of Gastroenterology and Hepatology, Kagoshima City Hospital, 37-1 Uearata-cho, Kagoshima, 8908760, Japan

    Hirohito Tsubouchi

Authors
  1. Seiichi Mawatari
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  2. Akihiro Moriuchi
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  3. Fuminori Ohba
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  4. Tetsu Kawano
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  5. Kohei Oda
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  6. Yasuhiro Takikawa
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  7. Hajime Takikawa
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  8. Akio Ido
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  9. Hirohito Tsubouchi
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Corresponding author

Correspondence to Seiichi Mawatari.

Electronic supplementary material

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535_2017_1421_MOESM1_ESM.docx

Supplemental Fig. 1. The outcomes of the whole study population stratified by PT-INR. (A) ROC curves for the PT(%) at the last observation (n = 301). (B) Kaplan–Meier curves for transplant-free survival to Day 30 in each group stratified by the two levels of PT-INR at the last observation (PT-INR < 1.3, PT-INR ≥ 1.3) (n = 301). Patients in the PT-INR < 1.3 group showed significantly higher rates of transplant-free survival than those in the PT-INR ≥ 1.3 group (Log-rank test: P = 0.0004, hazard ratio of PT-INR < 1.3 group/PT-INR ≥ 1.3 group: 0.2241 [95% CI: 0.09867–0.5091, Mantel–Haenszel]). (C) The outcomes by event and PT-INR < 1.3 recovery (n = 188). (D) Kaplan–Meier curves for each group stratified by PT-INR < 1.3 recovery at Day 8 or transplantation/death before Day 30 (n = 188). The patients in the PT < 1.3 recovery group showed significantly higher rates of transplant-free survival (Log-rank test: P < 0.0001, hazard ratio of PT-INR < 1.3 recovery group/no recovery group: 0.1593 [95% CI: 0.0734–0.3457, Mantel-Haenszel]). Supplemental Fig. 2. The patients outcomes stratified by PT(%). (A) ROC curves for the PT(%) at the last observation (n = 304). (B) Kaplan–Meier curves for transplant-free survival to Day 30 in each group stratified by the two levels of PT(%) at the last observation (PT(%) ≥ 60%, PT(%) < 60%) (n = 304). Patients in the PT(%) ≥ 60% group showed significantly higher rates of transplant-free survival than those in the PT(%) < 60% group (Log-rank test: P < 0.0001, hazard ratio of PT-INR < 1.3 group/PT-INR ≥ 1.3 group: 0.1919 [95% CI: 0.08761–0.4226, Mantel–Haenszel]). (C) The outcomes by event and PT(%) ≥ 60% recovery (n = 171). (D) Kaplan–Meier curves for each group stratified by PT(%) ≥ 60% recovery at Day 8 or transplantation/death before Day 30 (n = 171). Patients in the PT(%) ≥ 60% recovery group showed significantly higher rates of transplant-free survival (Log-rank test: P < 0.0001, hazard ratio of PT-INR < 1.3 group/PT-INR ≥ 1.3 group: 0.1293 [95% CI: 0.05977–0.2798, Mantel–Haenszel]). Supplemental Fig. 3. Correlation diagram between PT(%) and PT-INR. R2:decision coefficient (DOCX 3459 kb)

Supplementary material 2 (DOCX 34 kb)

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Mawatari, S., Moriuchi, A., Ohba, F. et al. The recovery of the PT-INR to less than 1.3 predicts survival in patients with severe acute liver injury. J Gastroenterol 53, 861–872 (2018). https://doi.org/10.1007/s00535-017-1421-3

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  • DOI: https://doi.org/10.1007/s00535-017-1421-3

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