Favourable Outcome of Hepatic Veno-Occlusive Disease in a Renal Transplant Patient Receiving Azathioprine, Treated by Portacaval Shunt

Eisenhauer, T.; Hartmann, Heinz; Rumpf, K. W.; Helmchen, Udo; Scheler, F.; Creutzfeldt, W.

doi:10.1159/000199104

Cited by 30 publications

(19 citation statements)

References 6 publications

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“…and nodular regenerative hyperplasia. [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] It has been speculated that all of these lesions are related to sinusoidal endothelial damage or disruption of the hepatic microcirculation. 10,[21][22][23][24] Azathioprine is extensively meAbbreviations: HVOD, hepatic venoocclusive disease; SEC, sinusoidal epithelial cells; GSH, glutathione; DMEM, Dulbecco's minimum essential metabolized in the small intestine and liver by GSH Sdium; MTT, [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium; ANOVA, transferase to 6-mercaptopurine.…”

Section: Prine Maintained Intracellular Gsh Levels Better Thanmentioning

confidence: 99%

Toxicity of azathioprine and monocrotaline in murine sinusoidal endothelial cells and hepatocytes: The role of glutathione and relevance to hepatic venoocclusive disease

DeLeve¹,

Wang²,

Kuhlenkamp³

et al. 1996

Hepatology

227

122

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The mechanisms leading to hepatic venoocclusive dis-Little is known about the causal mechanisms of heease (HVOD) remain largely unknown. Azathioprine and patic venoocclusive disease (HVOD). There has been monocrotaline were studied as part of a series of studies speculation as to whether hepatocytes or endothelial looking at a variety of toxins that induce HVOD to find cells might be the initial target, 1-4 but with little evicommon features that might be of pathogenic signifi-dence to support any of the contentions. Biopsy and cance. In a previous study, dacarbazine showed selective autopsy material demonstrate damage to both hepatoin vitro toxicity to sinusoidal endothelial cells (SEC) cytes or sinusoidal endothelial cells (SEC) early on. 1,2 compared with hepatocytes and a key role for SEC gluta-However morphology does not allow continuous monithione (GSH) was demonstrated. Murine SEC and hepatoring of changes and does not provide information on tocytes were isolated and studied in culture. Azathiosublethal damage that might lead to other events. Thus prine and monocrotaline were found to be selectively more toxic to SEC than to hepatocytes. The relative re-it is currently unknown why a variety of insults lead sistance of hepatocytes to azathioprine was due to en-to HVOD rather than to another manifestation of liver hanced GSH defense: hepatocytes exposed to azathio-toxicity. prine maintained intracellular GSH levels better thanOur approach to HVOD has been to study a number SEC, particularly when supplemental GSH precursors of chemically diverse compounds to search for common were added, and hepatocyte resistance was completely characteristics in an in vitro model. The first compound overcome by depletion of intracellular GSH. In contrast, studied, dacarbazine, demonstrated selective toxicity monocrotaline toxicity in hepatocytes was largely unaf-to SEC rather than to hepatocytes. 5 These studies also fected by depletion of GSH, which suggests that selectivdemonstrated that glutathione (GSH) plays a major ity of monocrotaline for SEC may be attributable to difrole in dacarbazine detoxification in the SEC. Based ferences in metabolic activation. Both compounds are on these findings, we have postulated that SEC GSH detoxified by GSH in SEC, as demonstrated by enhanced toxicity in the presence of buthionine sulfoximine (BSO) status may be a major determinant of susceptibility to and attenuation of toxicity with exogenous GSH. SEC this toxicity. In the current study, the characteristics of GSH levels were more than 70% to 80% depleted by mo-azathioprine and monocrotaline were studied in vitro. nocrotaline and azathioprine, respectively, before cell Azathioprine has been linked to multiple different death. Azathioprine and monocrotaline are selectively liver lesions in patients on long-term immunosupprestoxic to SEC; the mechanism of toxicity in the SEC may sion after kidney or liver transplantation: HVOD, sinube caused by profound GSH depletion. (HEPATOLOGY soidal dilatation, sinusoidal fibrosis, peliosis hepati...

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Section: Prine Maintained Intracellular Gsh Levels Better Thanmentioning

confidence: 99%

Toxicity of azathioprine and monocrotaline in murine sinusoidal endothelial cells and hepatocytes: The role of glutathione and relevance to hepatic venoocclusive disease

DeLeve¹,

Wang²,

Kuhlenkamp³

et al. 1996

Hepatology

227

122

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“…It has since been related to the use of cytotoxic drugs [6][7][8][9][10][11][12][13][14][15] and radiotherapy [16]. VOD has also been associated with various clinical situations: hereditary tyrosinemia [17], kidney transplants [8,[18][19][20][21], bone marrow allografts [6, 11-13, 15, 22-24], familial immunodeficiency [25], use of contraceptives [26], alcoholism [27], systemic lupus erythematosus [28,29], the Spanish toxic oil syndrome [30] and abetalipoproteinemia [31].…”

Section: Introductionmentioning

confidence: 99%

“…Despite the high rate of hepatic affectation in renal transplant patients mentioned in the literature [32][33][34][35][36][37][38][39][40][41][42] and the high number of patients undergoing transplants, VOD has only been reported in 12 kidney allograft recip ients [8,[18][19][20][21], This work reports 5 new cases of VOD in kidney transplant patients. It analyses the insidious presentation of the disease, its clinical outcome and some aspects probably related with etiology: the history of a previous hepatic viral infection and the use of azathioprine em ployed as immunosuppressive agent.…”

Section: Introductionmentioning

confidence: 99%

Veno-Occlusive Hepatic Disease of the Liver in Renal Transplantation: Is Azathioprine the Cause?

Liaño

Moreno

Matesanz

et al. 1989

Nephron

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Five male patients with veno-occlusive disease of the liver (VOD) were observed in 200 consecutive renal transplants (RT) treated with azathioprine and prednisone. Mild liver enzymatic increases not justified by other reasons were detected between 2 and 9 months after RT. All 5 patients developed portal hypertension and died between 18 and 79 months follwing RT. Diagnosis of VOD was histological; in 3 cases diagnosis was made while the patients were still alive. In our patients, 9 previous viral hepatotropic infections (5 during hemodialysis and 4 after TR) were demonstrated. Due to the reported low incidence of VOD in RT patients, when many of them have been treated with azathioprine, the etiological role of this drug must be questioned. However, the possible association of a previous hepatotropic viral infection and the use of an immunosuppressive agent should be considered as a probable cause of VOD in kidney grafts.

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“…[8][9][10] The easily recognizable central vein occlusion occurring in patients with this condition inspired the name hepatic veno-occlusive disease. Nonetheless, central vein involvement is not an essential feature because the disease process originates in the sinusoids.…”

mentioning

confidence: 99%

“…10 The incidence of clinical SOS in the largest series of LT recipients was 1.9%; this value contrasts with the 43% rate of silent reversible hepatic venular stenosis reported in another study. 9 In this setting, SOS is considered a part of the cellular rejection process with an endothelial predilection and is mainly related to azathioprine. There are no reports of a relationship between SOS and tacrolimus or any of the antiviral drugs used in our patient.…”

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confidence: 99%

Transjugular intrahepatic portosystemic shunt for the treatment of sinusoidal obstruction syndrome in a liver transplant recipient and review of the literature

et al. 2012

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Sinusoidal obstruction syndrome (SOS) is a rare, life-threatening clinical syndrome resulting from sinusoidal congestion, and it is characterized by hepatomegaly, ascites, weight gain, and jaundice. The frequency of this condition after liver transplantation (LT) is low, but when SOS is severe and refractory to medical therapy, the ultimate solution is retransplantation. We describe a patient with SOS after LT who was successfully treated by the placement of a transjugular intrahepatic portosystemic shunt (TIPS). Although information on this approach is scarce because of the low incidence of SOS in LT patients, we review the available literature on treating this condition with a TIPS. On the basis of the reported information and our patient's outcome, we suggest that prompt TIPS placement can be considered for SOS when medical treatment fails. Nonetheless, a formal assessment and prospective studies are needed to confidently indicate TIPS placement in this situation. In November 2008, a 54-year-old man underwent liver transplantation (LT) for end-stage liver disease due to a chronic hepatitis B virus (HBV) infection and alcohol abuse. The patient concurrently had a human immunodeficiency virus (HIV) infection; he had no history of opportunistic infections and a total CD4 þ cell count of 536 cells/mL. At the time of LT, he had an undetectable viral load and was receiving antiretroviral therapy (245 mg of tenofovir daily, 200 mg of emtricitabine daily, and 400 mg of raltegravir every 12 hours). His postoperative course was uneventful, and there was no evidence of rejection or infectious complications. His immunosuppressive regimen included tacrolimus and prednisone. For the prevention of recurrent HBV infections, he received tenofovir, emtricitabine, and long-term hepatitis B immune globulin following the standard hospital protocol.Two months after transplantation, the patient was admitted to the hospital because of ascites, peripheral edema (weight gain ¼ 16 kg or 21%), hepatomegaly, and impaired renal function. The serum creatinine concentration was 2.7 mg/dL, and the glomerular filtration rate, which was calculated with the Modification of Diet in Renal Disease formula, was 25.6 mL/ minute. He had no evidence of proteinuria or urinary

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Favourable Outcome of Hepatic Veno-Occlusive Disease in a Renal Transplant Patient Receiving Azathioprine, Treated by Portacaval Shunt

Cited by 30 publications

References 6 publications

Toxicity of azathioprine and monocrotaline in murine sinusoidal endothelial cells and hepatocytes: The role of glutathione and relevance to hepatic venoocclusive disease

Toxicity of azathioprine and monocrotaline in murine sinusoidal endothelial cells and hepatocytes: The role of glutathione and relevance to hepatic venoocclusive disease

Veno-Occlusive Hepatic Disease of the Liver in Renal Transplantation: Is Azathioprine the Cause?

Transjugular intrahepatic portosystemic shunt for the treatment of sinusoidal obstruction syndrome in a liver transplant recipient and review of the literature

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