title: Anti-inflammatory effect of recombinant thrombomodulin for fulminant hepatic failure.
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.
authors.affiliation: Kazutaka Kurokohchi, Osamu Imataki, Fumiyoshi Kubo, Department of Internal Medicine, Uchinomi Hospital, Kagawa 761-0793, Japan.
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Kurokohchi
authors.affiliation: Kazutaka Kurokohchi, Osamu Imataki, Fumiyoshi Kubo, Department of Internal Medicine, Uchinomi Hospital, Kagawa 761-0793, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Imataki
authors.affiliation: Kazutaka Kurokohchi, Osamu Imataki, Fumiyoshi Kubo, Department of Internal Medicine, Uchinomi Hospital, Kagawa 761-0793, Japan.
authors.forename: Fumiyoshi
authors.initials: F
authors.lastname: Kubo
mesh_terms: D000369:Aged, 80 and over; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D017114:Liver Failure, Acute / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D008111:Liver Function Tests; D011994:Recombinant Proteins / Q000627:therapeutic use; D018180:Thrombomodulin / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D018836:Inflammation Mediators; D011994:Recombinant Proteins; C546931:THBD protein, human; D018180:Thrombomodulin
keywords: Disseminated intravascular coagulation; Fulminant hepatic failure; Hepatocyte growth factor; Systemic inflammatory response syndrome; Thrombomodulin