Budd-Chiari Syndrome: Illustrated Review of Current Management

John D. Horton; Francisco L. San Miguel; Jorge A. Ortiz

Disclosures

Liver International. 2008;28(4):455-466. 

In This Article

Liver Transplantation

The first successful liver transplant for a patient with BCS was performed in 1974.[46] Since that time, several series and registry analyses of liver transplantation for BCS have been reported ( Table 1 ). Recently, two large series have been published documenting the European and U.S. experience.[47,48] For patients with BCS and acute fulminant liver failure or cirrhosis and decompensated disease with poor synthetic function, liver transplantation is the treatment of choice.[9] Evidence of poor hepatocyte synthetic function includes albumin <3g/dl, prothrombin time 3s greater than control, and conjugated bilirubin >3mg/dl.[23] When compared with patients who receive shunting procedures, transplanted patients maintain higher serum albumin levels and improved synthetic function.[25] In patients with certain synthetic deficiencies such as antithrombin III or protein C, liver transplantation offers the additional advantage of curing these genetic defects.[9,49,50] While liver transplantation has emerged as a safe therapeutic option for patients with BCS, its application should not be used liberally. Patients with BCS have multiple therapeutic options that may not be available to many patients on the transplant waiting list.

Calculating model for end-stage liver disease (MELD) scores in patients with chronic BCS may be problematic because many of these patients are on warfarin or some other form of anticoagulation. In this patient population, international normalized ratio (INR) is not an accurate indicator of hepatic synthetic function. It has recently been suggested that the INR be capped at 2.5 for patients on warfarin. Additionally, it has been proposed that patients with fulminant hepatic failure resulting from BCS should be listed as United Network for Organ Sharing (UNOS) status 1A.[51]

Several technical considerations make the transplantation procedure itself especially challenging in patients with BCS. Haemostasis can be particularly challenging, and above average blood loss is often reported.[39] Some centres employ venovenous bypass during all transplants in patients who have significant portal hypertension and prior shunt surgery. Caudate lobe enlargement (Fig. 1) may present problems during transplantation by making mobilization of the liver difficult and increasing the difficulty of the piggyback technique.[9] BCS may cause a diffuse fibrotic reaction in the retroperitoneum, which may increase the complexity of steps requiring control of the IVC.[9,38] Additionally, dense adhesions between the liver and diaphragm surrounding the suprahepatic IVC have been described.[38,52] The portal vein may be thickened, narrowed and even thrombosed.[39]

Segev published the largest series of transplantation for BCS.[48] This study included 510 patients who were divided into three time periods: historical (1987-1997), pre-MELD (1998-2002) and MELD (2002-2006). The analysis found that the demographic profile of patients receiving transplant changed through time. When compared with previous eras, the MELD era recipients were less likely to be female, hospitalized, on life support or have prior transplants. In the MELD era, a significant percentage of BCS patients (19%) received exception points, which caused an increase in the listing MELD compared with the calculated MELD (25.6 vs. 23.1 respectively). Graft and patient survival was significantly higher in the MELD era ( Table 1 ). The study also evaluated the impact of preoperative TIPS on outcomes of liver transplantation. The study found that TIPS did not adversely affect graft loss or death over all time periods. The final analysis found that only life support, prior transplantation and prolonged cold ischaemia time (>12h) were independent predictors of both graft loss and death. Taking into account the fact that MELD era patients were less likely to be on life support or have prior transplants, the improved patient survival over time may be a by-product of transplanting patients with less disease severity. The study did not calculate Child-Turcotte-Pugh (CTP) and MELD scores for the pre-MELD and historical groups, so direct comparison of disease severity between the groups is problematic. As opposed to the European experience, patients in the MELD era did not suffer inordinate early deaths or graft loss. Owing to the limitations of the UNOS database, the underlying aetiology of BCS in this cohort could not be captured.

From 1968 to 2001, the European Liver Transplant Registry (ELTR) recorded 391 patients who received transplantation for BCS with a 1-, 5- and 10-year patient survival of 73%, 68% and 63% respectively. Overall 1-, 5- and 10-year patient survival for all indications during this time period was 83%, 71% and 63% respectively.[53] The cohort of patients with BCS represented 1% or all transplants during that time period. The important observation here is that short-term survival in patients with BCS is lower while long-term survival is equivalent.

Mentha presented a cohort of patients, 256, undergoing transplantation for BCS in Europe. Multivariate analysis found the only pretransplant predictors of mortality to be impaired renal function (RR=3) and a history of a surgical shunt/TIPS (RR=2.2). However, the authors warned against interpreting this result to mean that surgical shunts or TIPS should be abandoned because, by definition, this cohort only included patients whose shunts had failed. The need for emergency transplant was not associated with increased mortality. Eighty-seven per cent of deaths occurred during the first year and the authors concluded that the slow course of myeloproliferative disorders was not significantly affected by transplantation.[47] However, two other series report cases of polycythaemia vera transforming into acute leukaemia several years after transplant.[49,54] The life expectancy for patients with polycythaemia who have developed myelofibrosis is approximately 3 years. Thus, transplantation does not offer a survival advantage in patients with myelofibrosis.[54] Based on Murad's classification system of patients with BCS, patients in class III from Mentha's cohort had improved survival with transplantation compared with Murad's cohort treated without transplant (5-year survival 71% vs. 42%).[44,47]

Yamada presented nine patients with BCS treated with living donor liver transplantation. This series reported an 88% 1-year and 71% 3-year survival, with two patients suffering recurrence of BCS.[55]

Liver transplants complicated by postoperative BCS may not always be amenable to minimally invasive interventions.[34] In a review of 1112 patients who underwent liver transplantation with the piggyback technique, nine patients suffered from early postoperative BCS. Retransplantation was performed in seven of these patients, and four of the nine died within 2 months of their operation.[7] Other large series have reported a 24% mortality rate for this complication.[6] Other than retransplantation and percutaneous interventions, alternate management strategies include surgical shunts,[56] simple rotation of the graft, caval thrombectomy, anastomosis reconstruction or diaphragmatic placement of the graft.[6]

Budd-Chiari syndrome following liver transplantation with the piggyback technique is a well-described complication with a reported incidence of 1-7%.[8] Venous outflow obstruction is often considered more common after the piggyback technique.[33] However, two recent retrospective studies were unable to detect a difference in the rate of BCS between the piggyback technique and the standard technique.[57,58] Furthermore, there is little difference in postoperative BCS when comparing large case series utilizing either the standard or piggyback technique, 1.7% vs. 1.1-1.5% respectively.[6,7,59] This complication usually presents in the early postoperative period. However, approximately 25% of cases may present after the first postoperative week.[7] Technical factors that have been associated with this complication are inadequate graft size and use of two hepatic veins for the venous anastomosis.[6,7] The rate of BCS after construction of the venous anastomosis with two veins is 2.3% while the use of three veins decreases the rate to 0.7%.[7] Compared with the conventional piggyback technique, the side-to-side variation of the piggyback technique has been associated with a decreased incidence of BCS, 2.4% vs. 0.7% respectively (P=0.014).[6]

As recurrent BCS after transplantation has been reported, lifelong anticoagulation is recommended.[4] Recurrence of BCS after transplantation has been reported to be as high as 27% and may require retransplantation.[49] Patients are often started on heparin postoperatively (total daily dose 7500-30000U intravenously) and converted to coumadin a week later.[23,54,60] In patients with myeloproliferative disorders, coumadin does not address their underlying pathophysiology. In these patients, administration of hydroxyurea and aspirin can be given instead of traditional anticoagulation to treat the aetiology of BCS. The newer drug, anagrelide, has replaced hydroxyurea in some centres.[23] Post-transplant anticoagulation may not be necessary in patients who possessed synthetic defects such as protein C deficiency corrected by transplantation.[23,50] While life-long anticoagulation after transplantation is routine for most patients, it does come with a price. Campbell [47]and Mentha [52]reported clinically significant haemorrhage in many patients, 44% and 11% respectively.

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