Elsevier

Transplantation Proceedings

Volume 46, Issue 10, December 2014, Pages 3523-3535
Transplantation Proceedings

Frontiers in Transplantation
Liver transplantation
Severe Veno-occlusive Disease/Sinusoidal Obstruction Syndrome After Deceased-donor and Living-donor Liver Transplantation

https://doi.org/10.1016/j.transproceed.2014.09.110Get rights and content

Abstract

Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) occurring after liver transplantation is a relatively rare complication but it often takes a life-threatening course. However, the detailed etiology and mechanism of VOD/SOS after liver transplantation (LT) remains unclear. We report two cases with rapidly progressive VOD/SOS after ABO-identical LT resistant to various therapies. In case 1, in which the patient underwent deceased-donor LT, the first episode of acute allograft rejection was triggered VOD/SOS, and the presence of donor non-specific anti-HLA antibodies was confirmed. The recipient died with graft failure on day 46 after transplantation. Case 2, in which the patient underwent living-donor LT from the mother, had neither rejection nor mechanical venous obstruction, but condition of the patient rapidly worsened and he died on day 13 after transplantation. This recipient's direct cross-match test for the donor's B lymphocyte was strongly positive, but that for T lymphocyte was negative. In both cases, neither stenosis of hepatic vein outflow tract nor C4d deposition in post-transplantation liver biopsy specimens and autopsy specimen was found. On the other hand, in both cases, the patient was transfusion unresponsive thrombocytopenia and hyperbilirubinemia persisted postoperatively, and glycoprotein Ⅰ bα was strongly stained in the neighboring centrilobular area (zone 3), especially in the space of Disse, and platelet phagocytosis was observed in Kupffer cells and hepatocytes around zone 3 such as clinical xenotransplantation of the liver in post-transplantation liver biopsy specimens. From the viewpoint of graft injury, VOD/SOS was considered that sustained sinusoidal endothelial cells injury resulted in bleeding in the space of Disse and led to around centrilobular hemorrhagic necrosis, and the fundamental cause was damage around centrilobular area including sinusoid by acute cellular rejection, antibody-mediated rejection or ischemic reperfusion injury. The extrasinusoidal platelet activation, aggregation, and phagocytosis of platelets were some of the main reasons for VOD/SOS and transfusion-resistant thrombocytopenia.

Section snippets

Immunohistochemistry

Platelet activation and aggregation in the sinusoid space of Disse and parenchyma of the graft liver were evaluated by immunohistochemical staining for platelet surface receptor glycoprotein Ⅰ bα (GP Ⅰ bα: CD42b). The expressions of CD42b were examined immunohistochemically with respective primary antibodies using the EnVision+ System (DAKOk, Tokyo, Japan). De-waxed 4-μm sections were incubated with 1:50 with protein blocking serum for 10 minutes to block nonspecific binding; immunostaining was

Case 1

A 44-year-old woman underwent deceased-donor LT (DDLT) from an approximately 70-year-old donor with standard techniques including the piggyback technique (recipient middle and left hepatic two veins – graft inferior vena cava anastomosis) for end-stage liver disease because of autoimmune hepatitis. The patient's preoperative Model for End-stage Liver Disease (MELD) score was 29 points and the Child-Pugh score was 13 points with hepatic encephalopathy, massive ascites, and esophageal varices.

Discussion

Herein, we present two cases of VOD/SOS. The SOS was first described in a Jamaican child by Jelliffe et al in 1954 [19], replacing the previously named VOD. A considerable number of studies on VOD/SOS have since been conducted on recipients of hematopoietic stem cell transplantation. In the solid organ transplantation setting, SOS cases after kidney and liver transplantations were first reported as complications of azathioprine hepatotoxicity in 1982 [5] and 1991 [20], respectively. Only a few

References (63)

  • S.I. Bearman et al.

    Treatment of hepatic venoocclusive disease with recombinant human tissue plasminogen activator and heparin in 42 marrow transplant patients

    Blood

    (1997)
  • B. Rosado et al.

    Transjuglar intrahepatic portosystemic shunts: an update

    Liver Transpl

    (2003)
  • M.W. Fried et al.

    Transjuglar intrahepatic portosystemic shunt for the management of severe venoocclusive disease following bone marrow transplantation

    Hepatology

    (1996)
  • M. Taniguchi et al.

    Dipyridamole protects the liver against warm ischemia and reperfusion injury

    J Am Coll Surg

    (2004)
  • M. Kume et al.

    Dynamic changes of post-ischemic hepatic microcirculation improved by a pre-treatment of phosphodiesterase-3 inhibitor, milrinone

    J Surg Res

    (2006)
  • G. Bras et al.

    Veno-occlusive disease of liver with non portal type of cirrhosis, occurring in Jamaica

    Arch Pathol

    (1957)
  • H.M. Sculman et al.

    Veno-occlusive disease of the liver following marrow transplantation: histological correlates of clinical signs and symptoms

    Hepatology

    (1994)
  • R.J. Jones et al.

    Veno-occlusive disease of the liver following bone marrow transplantation

    Transplantation

    (1987)
  • H. Weitz et al.

    Veno-occlusive disease of the liver in patients receiving immunosuppressive therapy

    Virchows Arch A Pathol Anat Histol

    (1982)
  • T. Eisenhauer et al.

    Favourable outcome of hepatic veno-occlusive disease in a renal transplant patient receiving azathioprine, treated by portocaval shunt

    Digestion

    (1984)
  • A.E. Read et al.

    Hepatic veno-occlusive disease associated with renal transplantation and azathioprine therapy

    Ann Intern Med

    (1986)
  • F. Liano et al.

    Veno-occlusive disease of the liver in renal transplantation: is azathioprine the cause?

    Nephron

    (1989)
  • M. Sebagh et al.

    “Silent” presentation of veno-occlusive disease after liver transplantation as part of the process of cellular rejection with endothelial predilection

    Hepatology

    (1999)
  • M.H. Sanei et al.

    Acute cellular rejection resulting in sinusoidal obstruction syndrome and ascites postliver transplantation

    Transplantation

    (2011)
  • M. Sebagh et al.

    Significance of isolated hepatic veno-occlusive disease/sinusoidal obstruction syndrome after liver transplantation

    Liver Transpl

    (2011)
  • K. Kitajima et al.

    Intractable ascites without mechanical vascular obstruction after orthotopic liver transplantation: etiology and clinical outcome of sinusoidal obstruction syndrome

    Clin Transplant

    (2010)
  • Y. Nakazama et al.

    Life-threatening veno-occlusive disease after living-related liver transplantation

    Transplantation

    (2003)
  • T. Izaki et al.

    Early graft failure due to a veno-occlusive disease after a pediatric living donor liver transplantation

    Pediatr Transplant

    (2004)
  • D.B. Jelliffe et al.

    Veno-occlusive disease of the liver

    Pediatrics

    (1954)
  • M. Sterneck et al.

    Azathioprine hepatotoxicity after liver transplantation

    Hepatology

    (1991)
  • P. Parrilla et al.

    Analysis of the complications of the Piggy-back technique in 1,112 liver transplants

    Transplantation

    (1999)
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