The main goal of 2-stage liver transplant is to provide time to obtain a new liver source. We describe our experience of 3 patients with 3 different clinical conditions. A 57-year-old man was retransplanted successfully with this technique due to hepatic artery thrombosis. However, a 38-year-old woman with fulminant toxic hepatitis and a 5-year-old-boy with abdominal trauma had poor outcome. This technique could serve as a rescue therapy for liver transplant patients who have toxic liver syndrome or abdominal trauma. These patients required intensive support during long anhepatic states. The transplant team should decide early whether to use this technique before irreversible conditions develop.
Key words : Deceased donor, End-stage liver disease, Living donor, Retransplant, Toxic liver syndrome
Introduction
A 2-stage liver transplant involving total hepatectomy and temporary portacaval shunt requires intensive perioperative care, especially during prolonged anhepatic periods. The main goal of this technique is to enable more time to obtain a new liver source. This procedure was first performed in 1988 for a patient with multiorgan failure including graft failure.1 The main indications are acute conditions such as fulminant hepatic failure, primary graft failure, severe hepatic trauma, and spontaneous hepatic rupture secondary to HELLP syndrome (syndrome of hemolysis, elevated liver enzymes, and low platelet count) and preeclampsia.1,2
The most important indication for this technique is toxic liver syndrome, characterized by total hepatic necrosis that mimics systemic inflammatory response syndrome. Severe cardiorespiratory failure, neurologic dysfunction, and acute kidney injury accompany this syndrome.1,3 The necrotic liver is removed at the first stage and, when available, liver transplant is performed at the second stage.
We describe our experience with 3 patients who had 3 different clinical conditions. All patients were treated at Inonu University from 2011 to 2013.
Case Report
Case 1
A 57-year-old man underwent living-related donor liver transplant due to
hepatitis B virus and hepatocellular carcinoma. After successful liver
transplant, he was admitted to the transplant intensive care unit on mechanical
ventilation. The next day, he was evaluated by Doppler ultrasonography and had
hepatic artery thrombosis. He had reoperation with laparotomy on day 2, and we
decided retransplant. However, there was no additional liver source. His liver
was totally excised, and portacaval shunt was performed. After a 48-hour
anhepatic phase, he was retransplanted from a deceased donor. There was no need
for extracorporeal therapy because standard treatments were sufficient. He was
discharged from the hospital on day 15 after the second liver transplant and had
a good outcome.
Case 2
A 38-year-old woman was admitted to our center. A living-donor liver transplant
due to fulminant toxic hepatitis caused by ingestion of unknown amounts of wild
mushrooms was necessary, but a donor graft was not available. Perioperative
treatment included high-dose inotrope therapy for hypotension and continuous
venovenous hemofiltration (CVVHF) for acute kidney injury. We decided to perform
total hepatectomy and portacaval shunt due to her near-fatal status. The purpose
of this option was to attempt to prevent damage to the body by the nonfunctional
liver and immunologic reactions. The patient was acidotic, hypotensive, anuric,
and hypothermic during the operation. After the operation, extracorporeal liver
support was initiated (Molecular Adsorbent Recycling System [MARS], Gambro,
Baxter Corp, Stockholm, Sweden) and high-dose vasopressor therapy, fluid
therapy, and CVVHF were continued. However, she died 12 hours after surgery.
Case 3
A 5-year-old-boy underwent urgent deceased-donor liver transplant due to
abdominal trauma caused by a fall down stairs. He had been operated due to
severe liver laceration at another center 1 year earlier. After liver
transplant, he was discharged from the hospital with good outcome. After 11
months, he was admitted to the transplant intensive care unit. He had poor
health status and severe jaundice. Erythrocyte suspension, albumin infusion, and
plasma exchange were started. He was diagnosed with severe biliary stricture.
Percutaneous transluminal cholangiography was performed and a biliary drainage
catheter was inserted. Liver biopsy was performed and he was diagnosed with
rejection.
A living-related retransplant was performed. During the first postoperative week, hepatic artery thrombosis was diagnosed and he was reoperated. At reoperation, we observed that the total liver blood supply was interrupted. However, there was no additional liver source for retransplantation. The only available option was total hepatectomy and temporary portacaval shunt. In the intensive care unit, extracorporeal liver support (MARS, Gambro) therapy and CVVHF were performed. Urgent liver notification was performed, and he was successfully retransplanted with a deceased-donor graft 50 hours later. However, during the retransplant operation, he developed refractory lung edema. He was readmitted to the transplant intensive care unit. He was ventilated using the airway pressure release ventilation mode. Maximal doses of vasopressor therapy and CVVHF were continued. However, he died 6 hours after surgery due to severe cardiorespiratory collapse.
Discussion
We described our experience with two-stage liver transplant. All patients had different clinical scenarios. They had total hepatectomy and temporary portacaval shunt. Case 2 did not have a liver transplant because a donor was not available. Case 1 and case 3 had retransplant with deceased-donor grafts after total hepatectomy. Despite liver transplant in case 3, he died 6 hours after surgery. Case 1 was discharged from the hospital with a good prognosis.
The 2-stage liver transplant procedure has been used since 1988. There are conflicting results reported with this procedure. Some studies showed that portacaval shunt may increase perioperative mortality. Other studies reported that survival is increased when liver transplant is available.2
In the previously described indications for this procedure, 2 indications are important: toxic liver syndrome and hepatic rupture with marked bleeding.4 Treatment of toxic liver syndrome mainly is supportive and includes mechanical ventilation, vasoactive agents, diuretics, and renal replacement therapy.5
Acute hepatic necrosis with multiorgan failure has a mortality rate of approximately 100%. The etiology of multiorgan failure is not explained clearly. The pathophysiologic mechanism is based on metabolites and endogenous vasoactive substances that are released from the toxic liver. Experimental studies have shown the effects of cardiosuppressor agents in ischemic and anoxic conditions. Toxic liver syndrome occurs in acute liver failure and decompensating chronic liver disease.1
Necrotic liver should be removed and transplant should be performed before irreversible changes occur from multiorgan failure.2,6 The main purpose of this strategy is hemodynamic and metabolic stabilization of the patient before transplant.5,7,8 A previous study described a 6-month-old baby with living-related transplant and recommended this procedure to provide additional time in treating emergency conditions.6
Various clinical studies have shown that total hepatectomy and portacaval shunt may provide hemodynamic and metabolic stabilization of patients by portal venous drainage. The most commonly used shunt is the transjugular intrahepatic portosystemic shunt. Varotti and coworkers reported an alternative temporary porto-middle hepatic vein shunt technique for 2-stage liver transplant.9
As a result of 2-stage liver transplant, there is longer anhepatic time. There is no consensus about the safest duration of the anhepatic period. A goal of two-stage liver transplant technique is to minimize the anhepatic period as much as possible. The reported anhepatic times vary between different case reports (Ringe and associates, 41 h; Bentdal and coworkers, 60 h; Patrono and associates, 6.58-72.5 h).3,6,7 Anhepatic times > 48 hours are associated with poor outcomes. Arora and coworkers reported anatomic anhepatic time 67 hours for a patient with primary nonfunction, and this is the longest anhepatic time in the literature.10 Anhepatic times < 30 hours are well tolerated.5
There are several problems during the anhepatic period, and patients require maximal intensive care. The common problems include hypoglycemia, hypothermia, hypocalcemia, oliguria, acute kidney injury, and coagulation disorders.5 Existing problems may contribute to worsening of the anhepatic state. Treatment options include intravenous glucose replacement for hypoglycemia and heating the patient with blankets and warm intravenous fluids and blood products for hypothermia.5
The risk of rapid development of acute kidney injury and oliguria is common in the first 24 hours. Early acute kidney injury predicts poor outcome and sepsis. Previous workers reported that urine output increased after total hepatectomy but decreased at 30 hours, and they recommended diuretic therapy and CVVHF.2,8 Therapy with CVVHF improves metabolic and fluid imbalance in these patients.1 All 3 patients in the present study received diuretic therapy, and 2 patients received CVVHF.
The citrate load due to administration of blood and blood products may cause hypocalcemia-induced coagulation disorders in long anhepatic states. Metabolic acidosis, anemia, hypomagnesemia, and hypothermia may contribute to coagulation defects.2 Laboratory evaluation of these disorders may reflect poor status, but these defects may be improved with fresh frozen plasma and fibrinogen replacement.2,5 Our team successfully treated coagulation defects in our patients.
Sepsis and multiorgan failure are the main causes of mortality from prolonged anhepatic periods. Sepsis is more fatal later in the course. Strict isolation techniques, routine surveillance cultures, and antibiotic prophylaxis for surgery are useful precautions against sepsis.2,5 The mortality rate of sepsis was 25% in the case series of Ringe and coworkers.3 Our patients had no sepsis, but case 2 died from multiorgan failure.
Extracorporeal support of the liver is another important option in 2-stage liver transplant. Nonbiologic systems (MARS, Gambro) may remove toxic substances, provide time to plan for liver transplant, and reduce intracranial pressure.2 We used this therapy in cases 2 and 3, but case 3 did not have enough time for this therapy due to refractory lung edema.
In summary, we described our limited experience with 2-stage liver transplant. This technique could serve as rescue therapy for liver transplant patients with toxic liver syndrome or abdominal trauma. These patients require intensive support in long anhepatic states. The transplant team should decide about using this technique in a timely manner before irreversible conditions develop.
References:
Volume : 13
Issue : 1
Pages : 286 - 289
DOI : 10.6002/ect.mesot2014.P135
From the 1Department of Anesthesiology and Reanimation, Baskent
University Faculty of Medicine, Ankara; 2Department of Anesthesiology
and Reanimation, Yeşilyurt State Hospital, Malatya; and the Departments of
3General Surgery and 4Anesthesiology and Reanimation, Inonu University
Faculty of Medicine, Malatya, Turkey
Acknowledgements: The authors have no conflicts of interest to declare.
No funding was received for this study.
Corresponding author: Ender Gedik, MD, Baskent University Faculty of
Medicine Department of Anesthesiology and Reanimation, 06490 Ankara, Turkey
Phone: +90 312 212 6868 ext. 4841
Fax: +90 312 223 7333
E-mail: gedikender@gmail.com