Complete spontaneous liver graft disappearance after auxiliary liver transplantation
Authors: Safi Dokmak, Béatrice Aussilhou, François Durand, Valérie Paradis, Jacques Belghiti
Journal: Hepatology (2014)

A 59-year old female patient was admitted to the intensive care unit with acute liver failure (ALF) related to Aminata phalloides mushroom poisoning; mushrooms had been ingested 8 hours before symptoms developed. Treatment by N-acetyl cysteine (Flumicil) was begun. Four days after ingestion, a second increase in liver enzymes (transaminases level >1,000 UI/L) was observed with a marked decrease in coagulation factors (prothrombin time [PT] 6%; factor V 9%). Although there was no encephalopathy or altered renal function, the patient was scheduled for emergency liver transplantation because according to the literature and in our experience, rapid deterioration can occur with a fatal outcome if curative treatment is not undertaken.1, 2 Because of the absence of any underlying liver disease and the relative hemodynamic stability of the patient, auxiliary orthotopic liver transplantation (AOLT) was decided on. Frozen section histology of the native liver parenchyma showed hepatocyte necrosis of 70-80% without fibrosis, indicating that native liver regeneration was possible. A native liver right tri-sectionectomy was performed and segments IV to VIII were removed. A whole cadaveric liver graft was transplanted from a brain-dead donor and vascular anastomoses were performed to privilege the liver graft. The postoperative course was marked by rapid recovery of liver function tests (PT = 85%; bilirubin = 15 μmol/l) on postoperative day 5 and the patient was discharged on postoperative day 26. Immunosuppression included glucocorticoids (for 3 months), mycophenolate mofetil, and tacrolimus. Six months after AOLT, functional recovery of the native liver was confirmed by computed tomography (CT) scan volumetry (Fig. 1). There were signs of hypertrophy of the native liver, which was confirmed by liver biopsy showing normal liver architecture with a few inflammatory cells without necrosis. Eleven months after AOLT (Fig. 2), significant native liver hypertrophy was observed and was confirmed by another liver biopsy, which showed marked native liver regeneration with no acute or chronic inflammation. Immunosuppression was gradually tapered down according to our established protocol (0.5 mg × 2 of tacrolimus, twice weekly) at this time. The graft progressively atrophied as the native liver hypertrophied and immunosuppressive treatment was stopped completely 18 months after AOLT. The graft disappeared completely after 2 years (Fig. 1). The patient is now living a normal life without treatment. Although most cases of ALF recover rapidly with medical treatment, LT may be the only lifesaving treatment in certain critical patients in whom a spontaneous cure is unlikely.3, 4 Theoretically, AOLT is an excellent option. It provides temporary support of liver function until spontaneous recovery and regeneration of the native liver occurs, immunosuppressive treatment is withdrawn, and the graft atrophies and the patient can return to a normal life.4-7 In successful cases, graft atrophy occurs but in our experience complete graft disappearance is rare. Immunosuppressive therapy has numerous side effects, and adherence can also be difficult, especially in certain young patients with psychiatric disorders, for example, in cases of acetaminophen-induced ALF, which remains the main etiology of this disease.3 However, AOLT is a complex surgical procedure that remains challenging for many surgical teams because it requires partial native liver resection and complicated vascular anastomoses. Moreover, this procedure is usually performed in critically ill, hemodynamically unstable patients with coagulation disorders. Increased postoperative mortality and morbidity have been reported in many studies.4-6 Because withdrawal of immunosuppressants, which is the main objective of AOLT, is not always possible even in certain successful cases, the benefit and risk of long-term immunosuppressant withdrawal and a difficult surgical procedure must be considered. The indications for AOLT in ALF include the absence of underlying liver disease, young age, relative hemodynamic stability, excellent temporary liver graft, and a meticulous surgical technique. AOLT is also an excellent clinical model to study the regeneration of the injured native liver and recent research in this field has shown that regeneration is well regulated depending on the underlying etiology (acetaminophen toxicity versus others), the histological subtype (diffuse, map-like, or total loss) and the time of hepatectomy.6 On a molecular level, successful and failed liver regeneration was associated with different microRNA patterns.8 These new data can help select the subgroup of patients who can benefit from AOLT and the development of biomarkers to predict long-term prognosis.