Case Report
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 14, 2015; 21(26): 8203-8207
Published online Jul 14, 2015. doi: 10.3748/wjg.v21.i26.8203
Anti-inflammatory effect of recombinant thrombomodulin for fulminant hepatic failure
Kazutaka Kurokohchi, Osamu Imataki, Fumiyoshi Kubo
Kazutaka Kurokohchi, Osamu Imataki, Fumiyoshi Kubo, Department of Internal Medicine, Uchinomi Hospital, Kagawa 761-0793, Japan
Osamu Imataki, Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Kagawa University, Kagawa 761-0793, Japan
Author contributions: Kurokohchi K managed the patient’s case, contributed to the literature search, and wrote the manuscript; Kurokohchi K made substantial contributions to the concept and design of the report; Imataki O qualified the patient’s data, suggested important intellectual content, and reviewed the manuscript; Kurokohchi K and Imataki O contributed equally to this work; Kubo F was involved in the drafting and supervision of the manuscript and took part in critical discussions; all authors read and approved the final version of the manuscript.
Informed consent statement: All study participants, or their legal guardian, provided written informed consent prior to study enrollment.
Conflict-of-interest statement: The authors declare that they have no competing interests.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Osamu Imataki, Division of Hematology and Stem Cell Transplantation, Department of Internal Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan. oima@med.kagawa-u.ac.jp
Telephone: +81-878-912145 Fax: +81-878-912147
Received: November 16, 2014
Peer-review started: November 17, 2014
First decision: December 29, 2014
Revised: March 1, 2015
Accepted: March 18, 2015
Article in press: March 19, 2015
Published online: July 14, 2015
Processing time: 239 Days and 20.8 Hours
Abstract

Fulminant hepatic failure (FHF) is a critical illness that can be comorbid to primary liver damage. FHF shows a high mortality rate, and patients with FHF require intensive therapy, including plasma apheresis. However, intensive care at the present is not enough to restore the severe liver damage or promote hepatocellular reproduction, and a standard therapy for the treatment of FHF has not been established. An 86-year-old female with FHF was admitted to our hospital. Her manifestation demonstrated a clinical situation of systemic inflammatory response syndrome (SIRS) and disseminated intravascular coagulation. A diagnosis of fulminant hepatitis was made according to the definition given in the position paper of the American Association for the Study of Liver Diseases. Her serum hepatocyte growth factor (HGF) level had increased to 11.84 ng/mL. The HGF level indicated massive liver damage as seen in FHF. Recombinant thrombomodulin (rTM) was administered daily from the admission day for 1 wk at 380 U/kg. The patient’s white blood cells and C-reactive protein responded to the rTM treatment within a few days. The HGF level and PT recovered to the normal range. The levels of proinflammatory cytokines (tumor necrosis factor-α and interleukin-1β) were suppressed by the administration of rTM. The patient’s hepatic function (e.g., PT and albumin) completely recovered without plasma exchange. rTM may modulate the over-response of SIRS with the improvement of proinflammatory cytokines. The underlying mechanism is thought to be the inhibitory effect of rTM on high-mobility group box 1 (HMBG1). The pathogenesis of HMBG1 protein in fulminant hepatic failure has been already known. A novel favorable effect of rTM for SIRS would be promising for FHF, and the wide application of rTM for SIRS should be considered.

Keywords: Fulminant hepatic failure; Disseminated intravascular coagulation; Thrombomodulin; Hepatocyte growth factor; Systemic inflammatory response syndrome

Core tip: Fulminant hepatic failure (FHF) is a critical illness that can be comorbid to primary liver damage. However, no standard therapy for the treatment of FHF has been established. We experienced a fatal FHF case with systemic inflammatory response syndrome followed by disseminated intravascular coagulopathy (DIC). We administered recombinant thrombomodulin (rTM) for the treatment of DIC, which ameliorated all lethal conditions (coagulopathy and inflammation). Monitoring of proinflammatory cytokines, hepatocyte growth factor, and prothrombin time revealed the response of FHF to rTM. We hypothesized an anti-inflammatory effect of rTM-enhanced hepatocyte regeneration through inactivation of high-mobility group box 1.