Fulminant Hepatic Failure From the Budd-Chiari Syndrome

The syndrome of portal hypertension and hepatomegaly as the result of hepatic venous outflow obstruction was first described by Budd in 1845 (1). The histologic findings associated with this syndrome were then characterized by Chiari in 1899 (2). Subsequently, the Budd-Chiari syndrome (BCS)* has been defined by Ludwig and coworkers as hepatic venous outflow obstruction and its clinical manifestations, which include right upper quadrant abdominal pain, hepatomegaly, ascites, and/or esophageal varices (3). Regardless of cause, the obstruction is located within the liver or the suprahepatic inferior vena cava (IVC). In Asia and Africa, membranous obstruction of the IVC is the responsible etiology in the majority of cases. In contrast, occlusion of the major hepatic veins by thrombosis and/or fibrosis is more common in the Western world (4). The presentation of BCS is often insidious, with vague upper abdominal pain, progressive ascites, mild jaundice, and minimal hepatic synthetic dysfunction. However, chronic hepatic venous outflow obstruction ultimately results in progressive liver failure and variceal hemorrhage. In rare instances, the first manifestation of the BCS is fulminant hepatic failure. In their series of 177 patients with BCS, Dilawari and colleagues found that 7% were first seen with fulminant hepatic failure (5). In this setting, despite the availability of mesocaval and mesoatrial shunt procedures, orthotopic liver transplantation (OLT) has been deemed by Bismuth and Sherlock to be the “only reasonable solution” (6). In fulminant hepatic failure, patient candidacy for OLT can be affected by associated conditions such as cerebral edema, systemic infection, acute renal failure, or multisystem organ dysfunction. These factors, in combination with the obligate waiting time for a suitable organ, are, in part, responsible for the 34% mortality on the waiting list for UNOS status 1 patients. In an effort to support the candidate with fulminant hepatic failure during the waiting period, a number of bridging techniques have been proposed, including bioartificial liver support devices, ex vivo xenograft perfusion, exchange transfusion, and heterotopic liver transplantation. We now report the use of a transjugular intrahepatic portosystemic shunt (TIPSS) as a bridge to OLT in a patient with fulminant hepatic failure secondary to BCS. The patient was a 51-year-old man who was evaluated at an outside hospital for a 3-day history of nausea, vomiting, diarrhea, and right upper quadrant abdominal discomfort. His past medical history was notable for an ongoing workup for polycythemia vera and occasional alcohol ingestion (1-2 pints) on the weekends. He took no medications, had no known allergies, and had had no prior surgery. Until the time of his illness, he was employed full time as an auto mechanic. On examination, the patient was conversant but lethargic, with grade 2 encephalopathy. His abdomen was tense, slightly protuberant, and tender to palpation in the right upper quadrant. The liver span was 18 cm and was palpable 4 cm below the costal margin. Initial laboratory values of note were white blood cell count 19,000/mm3, hematocrit 59.4%, prothrombin time 24.6 sec, serum HCO3 17 mmol/L, creatinine 3.0 mg/dl, alanine aminotransferase 80 IU/L, aspartate aminotransferase 128 IU/L, and total bilirubin 2.4 mg/dL. The toxicology screen was negative. Over the next 24 hr, the patient became increasingly somnolent, progressing to grade 3 encephalopathy, and was anuric; he was transferred to an intensive care unit. Hemodynamic assessment revealed a pulse of 115, blood pressure 140/89 mmHg, pulmonary capillary wedge pressure 13 mmHg, pulmonary artery pressure 11/3 mmHg, cardiac index 2.1 L/min/m2, and systemic vascular resistance 3957 dyne-sec/cm5. His prothrombin time was 24.3 sec after receiving four units of fresh frozen plasma. Additional laboratory values included creatinine 5.5 mg/dl, alanine aminotransferase 3185 IU/L, aspartate aminotransferase 8686 IU/L, and total bilirubin 2.9 mg/dl. Following infusion of 13 L of fluid and infusion of dobutamine (5 μg/kg/min), the patient's hemodynamic values were pulse 127, blood pressure 114/77 mmHg, pulmonary capillary wedge pressure 13 mmHg, pulmonary artery pressure 25/15 mmHg, cardiac index 2.3 L/min/m2, and systemic vascular resistance 2608 dyne-sec/cm5. He remained anuric, despite administration of intravenous furosemide (100 mg). A color Doppler ultrasound exam of the liver showed the presence of hepatosplenomegaly, moderate ascites, absent hepatic venous flow, and hepatofugal portal venous flow. On hospital day (HD) 3, the patient was transferred to the University of Maryland Hospital for OLT with the diagnosis of BCS. On transfer, the patient was found to be in grade 4 hepatic encephalopathy and was electively intubated. An epidural intracranial pressure monitor was placed and exhibited normal pressures. He remained anuric. Laboratory values were remarkable for prothrombin time 21.2 sec, creatinine 8.3 mg/dl, alanine aminotransferase 2589 IU/L, aspartate aminotransferase 4435 IU/L, and total bilirubin 4.4 mg/dl. A magnetic resonance angiogram of the abdomen revealed the presence of ascites, a large liver with an enlarged caudate lobe, multiple paravertebral venous collaterals, and a patent portal vein with hepatofugal flow. The intrahepatic IVC was “slit-like.” The origin of the right hepatic vein was seen, but no flow was present in the right, middle, or left hepatic veins. The patient was listed for OLT with UNOS status 1 priority. On the day of transfer, a visceral angiogram and TIPSS procedure was performed. The right and left portal veins were patent and filled from the arterial rather than the mesenteric venous circulation. There was hepatofugal flow in the main portal vein with numerous portosystemic collaterals and an enlarged coronary vein. On hepatic venography, the intrahepatic IVC was narrowed but patent, without thrombus or membranous web. All three major hepatic veins were occluded. Contrast injection into the stump of the right hepatic vein opacified the hepatic parenchyma and demonstrated the presence of intrahepatic venous collaterals in the typical “spider web” pattern (Fig. 1). A TIPSS was performed with two Wall stents, 10 mm and 12 mm in diameter, from the occluded right hepatic vein to a branch of the right portal vein (Fig. 2). This resulted in brisk hepatopedal flow through the TIPSS. The following day, on HD 4, the patient was more hemodynamically stable and had converted to nonoliguric acute renal failure. A Doppler ultrasound exam of the liver demonstrated the TIPSS to the patent, with a peak velocity of 80 cm/sec. The patient continued to gradually improve, and on HD 8, his laboratory values were notable for prothrombin time 18.0 sec, creatinine 7.8 mg/dl, alanine aminotransferase 538 IU/L, aspartate aminotransferase 493 IU/L, and total bilirubin 6.7 mg/dl. Neurologically, he became more alert. The intracranial pressure monitor was removed on HD 10, and the patient was extubated on HD 12. In order to inhibit potential TIPSS thrombosis, a continuous heparin infusion was begun on HD 13, when the prothrombin time decreased below 18 sec. On HD 17, he was transferred from the intensive care unit; the patient was not encephalopathic, tolerated a regular diet, and had the following lab value: prothrombin time 16.6 sec, creatinine 3.0 mg/dl, alanine aminotransferase 176 IU/L, aspartate aminotransferase 200 IU/L, and total bilirubin 7.3 mg/dl. He was downgraded to UNOS status 2 priority. Over the next week, the patient continued to improve. On HD 21, a follow-up abdominal CT scan noted the presence of persistent ascites and hepatosplenomegaly, albeit decreased in comparison with previous studies. Improvement in renal function plateaued with a serum creatinine of 2.0-2.5 mg/dl. He began to complain of pruritus on HD 24. His laboratory values were notable for prothrombin time 16.9 sec, creatinine 2.4 mg/dl, alanine aminotransferase 88 IU/L, aspartate aminotransferase 104 IU/L, and total bilirubin 3.7 mg/dl. On HD 30, the patient underwent OLT and had an uncomplicated postoperative course. Pathological examination of the explanted liver revealed a heterogeneous histologic appearance with areas of necrosis, centrilobular congestion, and hemorrhagic lakes. Cirrhosis was present with fibrosis bridging the central veins typical of cardiac cirrhosis. The portal areas were preserved. The central veins exhibited organized thrombosis and recanalization. These histologic findings were present in the right, left, and caudate lobes. BCS is a rare disease characterized by hepatic venous outflow obstruction at the level of the hepatic veins or the IVC. The most common etiology for BCS is a myeloproliferative syndrome. This is often latent, and definitive diagnosis requires bone marrow biopsy or peripheral blood mononuclear cell cultures. Other causes include oral contraceptive use, chemotherapy, pregnancy, polycythemia vera tumor, paroxysmal nocturnal hemoglobinuria, and membranous vena caval webs. The natural history of this entity is typically progressive hepatic dysfunction with centrilobular congestion leading to fibrosis, and ultimately to cirrhosis. Medical therapy is quite limited in this illness and may involve treatment of the underlying hematologic disorder or management of ascites or variceal hemorrhage (6, 7). In a study by McCarthy and coworkers, 86% (12/14) of patients with BCS died within six months of diagnosis when managed without surgery (8). Surgical options include decompressive shunt surgery or OLT. In most circumstances, OLT is reserved for patients with advanced fibrosis or cirrhosis on liver biopsy or severe hepatic synthetic dysfunction. Otherwise, patients should undergo mesoatrial or mesocaval shunt surgery. Mesocaval or side-to-side portocaval shunts are the preferred procedure except in the presence of a thrombosed or narrowed IVC or a significant pressure gradient (>20 mmHg) between the right atrium and infrahepatic IVC. In these instances, a mesoatrial shunt is performed (7). The results of shunt surgery in BCS has been reviewed by Bismuth et al. and Klein et al. (6, 7). Bismuth and Sherlock reported 22 patients with BCS who underwent portosystemic shunting with mesocaval, mesoatrial, or side-to-side portocaval procedures. Of 22 patients, 21 are alive and well, free from ascites, at a mean follow-up of 5.6 years (6). Klein and colleagues reviewed 21 patients with BCS who underwent mesocaval or mesoatrial shunt surgery; 31% of the patients died prior to discharge. During a median follow-up period of 43 months, the three- and five-year actuarial survival rates were 65% and 59%, respectively (7). Despite these encouraging results, in both reports, selected fatalities occurred in patients with fulminant hepatic failure (n=1 in Bismuth's series) or stage 4 hepatic encephalopathy (n=1 in Klein's series) (6, 7). As a result, Bismuth and Sherlock advocate OLT for those rare instances in which BCS occurs in the setting of fulminant hepatic failure (6). In a recent review of BCS, Tilanus states that OLT should be performed in preference to a surgical shunt in three settings: fulminant hepatic failure, end-stage chronic liver disease, and rapid deterioration following shunt surgery (4). With the emergence of OLT as accepted therapy for endstage liver disease, an additional therapeutic option for BCS is now available. In 1994, OLT for the indication of BCS comprised 0.4% of the total number of transplants in the UNOS Liver Transplant Registry (9). The five-year patient survival rate is 76%, and it includes those transplanted for fulminant hepatic failure and chronic hepatic dysfunction. However, when considering OLT for acute liver failure, recent studies indicate that 34% of candidates were not transplanted because of primary complications of liver disease such as renal failure and infection or because of death while waiting for an appropriate organ (10). Sepsis accounts for 20% of conditions that contraindicate OLT in fulminant hepatic failure (11). In patients with fulminant hepatic failure undergoing OLT, sepsis was responsible for 40% of the postoperative deaths. Furthermore, the requirement for hemodialysis following OLT has been associated with a mortality of 39% to 90% (12). In the subgroup of patients with acute renal failure preceding OLT, the in-hospital mortality was 40% in the series reported by Ishitani and coworkers (12). As a result, many transplant centers are reconsidering the propriety of OLT in the setting of fulminant hepatic failure with accompanying acute renal failure or sepsis. Any strategy that might ameliorate the degree of hepatic dysfunction, reverse accompanying organ dysfunction, and act as a bridge to OLT may increase the number of eligible patients. In addition, outcome following OLT might be improved as a result of improved perioperative renal or neurologic function and absence of sepsis. In this report, we detail the clinical course of a patient with fulminant hepatic failure from BCS. The most likely etiology was polycythemia rubra vera. He had the typical symptoms of nausea, abdominal distention, and right upper quadrant abdominal pain. His clinical course was remarkable for massive fluid sequestration in his splanchnic circulation, progressive hepatic encephalopathy, and an abrupt improvement following successful TIPSS placement. Although this patient falls within the category that heretofore has necessitated OLT, TIPSS placement has converted his disposition from one of UNOS status 1 with accompanying acute renal failure and hepatic coma to that of UNOS status 3 with acceptable renal function and the absence of hepatic encephalopathy. Although emergent OLT relieves the acute venous outflow obstruction, the presence of fulminant hepatic failure, acute renal failure, and stage 4 hepatic encephalopathy would certainly have placed the patient at increased risk. These considerations notwithstanding, in the specific case of fulminant hepatic failure as the result of BCS, TIPSS is a potential therapeutic option or bridge to OLT.Figure 1: Hepatic venography demonstrating recanalized right hepatic vein with intrahepatic collaterals in the typical “spider web” pattern.Figure 2: Completed transjugular intrahepatic portosystemic shunt placed through the occluded right hepatic vein to a branch to the right portal vein.