Short Communication
Treatment of Severe Hepatic Veno-Occlusive Disease after Bone Marrow Transplantation by Trans Jugular Intrahepatic Portosystemic Stent-Shunt (TIPS)
Hugo Rodrigues Gouveia*, João Marcello Araújo Neto and Leonardo Javier Arcure
National Cancer Institute, Servidores Federal Hospital, Brazil
*Corresponding author: Patrícia de Oliveira Costa, National Cancer Institute, Servidores Federal Hospital, Praça da Cruz Vermelha 23 Rio de Janeiro, Brazil
Published: 30 Jul, 2018
Cite this article as: Gouveia HR, Neto JMA, Arcure LJ.
Treatment of Severe Hepatic Veno-
Occlusive Disease after Bone Marrow
Transplantation by Trans Jugular
Intrahepatic Portosystemic Stent-Shunt
(TIPS). Ann Clin Case Rep. 2018; 3:
1538.
Abstract
Severe Veno-Occlusive Disease (VOD) of the liver is an important cause of mortality after bone
marrow transplantation. This paper reports the case of a child that underwent Transjugular
Intrahepatic Portosystemic Shunt (TIPS) for life-threatening VOD after following haploidentical
bone marrow transplantation for acute lymphatic leukemia. TIPS permitted regression of the
hepatic symptoms as decreased aminotransferase levels and resolution of ascites. TIPS were an
effective method for portal decompression.
Keywords: Veno-occlusive disease, Bone marrow transplantation, Treatment, Transjugular
intrahepatic portosystemic stent-shunt (TIPS)
Introduction
Hepatic Veno-Occlusive Disease (VOD) is a complication after Hematopoietic Stem Cell
Transplantation (HSCT). The development of VOD has been associated with high-dose and
combination cytoreductive therapy, particularly regimens that involve busulfan, cyclophosphamide,
carmustine, and etoposide, associated with total body irradiation, preexisting liver dysfunction,
advanced disease status at time of transplant, HLA-mismatched or unrelated donor transplant [1-4].
The hepatic histology of VOD is characterized by a non-thrombotic obstruction of hepatic
venules, sinusoidal congestion, sinusoidal fibrosis, and hepatocellular necrosis, which occurs
predominantly in the centrilobular zone of the liver acinus. Portal hypertension with ascites
frequently accompanies these histological changes and hallmarks the clinical manifestations of this
syndrome [5].
Despite treatments, severe VOD is frequently fatal. It is important always to consider portal
decompression in patients with life-threatening veno-occlusive disease [6].
Case Report
The 9-years-old boy was diagnosed with T acute lymphoblastic leukemia. He was treated with
ALL BRM 2009. He had various chemotherapy toxicity including aplasia marrow and perianal ulcer.
Cytomegalovirus and Fanconi Anemia research were negatives. He received conditioning regimen
to three. Haploidentical bone marrow with fludarabine and TBI total dose decreased from 1200 to
1000 cGy. Prophylaxis to graft-versus-host disease was made with cyclophosphamide, tacrolimus
and mycophenolate. He received ursodeoxycholic acid 600 mg/day in 2 divided doses to prophylaxis
of VOD.
Twenty-two days after marrow infusion, the child presented abdominal pain, increase of serum
aminotransferases, 23% weight gain, and impaired coagulation. Abdominal computed tomography
showed marked hepatomegaly. ALT peaked 539 U/l, AST 1872 U/l and GGT 88 U/l. When TIPS was
indicated total bilirubin was 1.55 mg/dl and he was anicteric. Hepatitis serologies were negatives.
He had kidney failure with volume overload and creatinine clearance 69 mL/min/1.73 m2 possibly
associated to increase abdominal pressure and/or renal hepatic syndrome. He required dialyze and
paracentesis to release abdominal pressure and alleviate respiratory distress before TIPS. But despite
the efforts, he needed mechanical ventilation support.
Twenty-six days after marrow infusion, TIPS was performed. Mean hepatic venous
pressure gradient decreased from 14 mmHg to 2 mmHg after TIPS insertion. Following TIPS, aminotransferases decreased. However, bilirubin increased. Six days
after TIPS, he was extubated.
Table 1
Discussion
In our patient, the risk factors for VOD were: unrelated donor
transplant and cyclophosphamide associated with total body
irradiation. The patient presented various systemic toxins during
induction chemotherapy and after conditioning treatment to HSCT.
It was interpreted as an indication that the cells are defective in the
repair mechanism to tolerate the cross-links produced [4] in his
DNA. Because of it, total dose of TBI was reduced. Nevertheless, he
had toxicity with severe VOD and pneumonitis.
EBMT diagnostic criteria for hepatic VOD were used in this
patient. It is the presence of two or more of the following: unexplained
consumptive and transfusion refractory thrombocytopenia; otherwise
unexplained weight gain on three consecutive days despite the use of
diuretics or a weight gain 45% above baseline value; hepatomegaly
(best if confirmed by imaging) above baseline value, ascites (best if
confirmed by imaging) above baseline value; rising bilirubin from a
baseline value on 3 consecutive days or bilirubin ≥ 2 mg/dL within 72
hrs. This patient had four criteria: otherwise unexplained weight gain
on three consecutive days despite the use of diuretics; hepatomegaly
confirmed by imaging, ascites; rising bilirubin from a baseline value
on 3 consecutive days (Table 1). He was icteric after TIPS.
This patient had many severity criteria to severe VOD: renal
failure, impaired coagulation, necessity invasive pulmonary
ventilation, increase of ALT and AST bigger than fivefold and need
for paracentesis. However, Bilirubin was 1.55 mg/dl when TIPS was
indicated. An icteric VOD was observed in 32% of patients in pediatric
prevention trial, including those experiencing severe disease. An
icteric VOD seems to be particularly prevalent in child. For this reason,
pediatric European Society for Blood and Marrow Transplantation
(EBMT) criteria recognize an icteric VOD as a frequent entity and
consider hyperbilirubinemia as a non-mandatory criterion. Instead
of a predefined level of hyperbilirubinemia in children, the EBMT
criteria require the bilirubin level to rise from an individual baseline
on 3 consecutive days, after the exclusion of competing causes
[5,7,8]. Doppler ultrasound gives unspecific information by showing
hepatomegaly, ascites, splenomegaly, periportal edema. It also helps
ruling out biliary obstruction, infiltrative tumors or infectious lesions
such as liver abscess, and detecting hepatic or portal vein obstruction.
However, observer dependent factors may affect the result of
Doppler Ultrasound. When clinical and imaging information is not
sufficient to make a diagnosis of VOD in patients with moderate or
severe disease, a liver biopsy is recommended. In patients with low
platelets or severe ascites, a transjugular route is usually preferred.
Complication and mortality rates related to this procedure have been
7% to 18% and 0% to 3%, respectively. We decided not to perform
liver biopsy due to the risks of the procedure and the high probability
of VOD.
A hepatic venous gradient (GHPV >10 mmHg) is highly specific
for SOS in a context of exposure to myeloablative therapy [9]. The
Hepatic venous pressure gradient value of this patient was 14 mmHg
and decreased to 2 mmHg after TIPS.
VOD shares with the Budd-Chiari syndrome the same rationale
for porta-caval decompression using the portal vein as an outflow
tract. Compared to surgical porta-caval shunts, TIPS may be
performed without laparotomy which is associated with the risks of
infection in an immunocompromised patient and bleeding due to the
coagulopathy. In addition, TIPS reduces the operative stress and the
tissue trauma to a minimum [6].
In this case, TIPS showed hepatic benefits. The patient improved
from ascites and hepatomegaly [6]. Data from literature favors precoce
TIPS insertion in VOD patients. Nevertheless, after TIPS insertion
the patient survived 10 weeks. This can lead us to hypothesize that
TIPS insertion brought benefits to this specific patient.
Conclusion
TIPS may be an option of treatment of severe VOD.
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