From the beginning of clinical transplantation, back in the 1950s, clinicians struggled to reconcile the contradictory interests in living-related donor transplantation. Murray and Merrill contributed to identifying the three basic principles to be promoted in the use of live donor organs: (1) a significant chance for a successful outcome for the recipient, (2) low risk to the donor, and (3) an informed consent from the donor to take part in the process. The ethical requirements of living donor liver transplantation (LDLT) have been thoroughly discussed by Siegler, Broelsch, and Whitington in Chicago at the end of the 1980s, with application of the general principles of utility, justice, and autonomy. LDLT using left hepatic segments from an adult LD to a child was introduced in 1989, and nowadays it constitutes a valid alternative to deceased donation to overcome the shortage of organs for children. In that context, easily available LDLT offers pediatric recipients a unique opportunity to escape the uncertainty of the unpredictable waiting time on the list for deceased donors. Data reported in the pre-LTLD era showed a higher mortality rate on the waiting list (15%) when compared with that after LDLT introduction (2%). Moreover, some other advantages have been suggested, including the ability to (1) anticipate LT, thereby avoiding late decompensation and clinical degradation; (2) improve clinical and nutritional status before LT; (3) assure the adequate quality of the graft; and (4) allow the best timing of LT for patients with liver malignancies. Furthermore, children for whom there is no LDLT possibility may benefit from a reduced “competition” for deceased donor grafts. The introduction of intrafamilial LDLT requires, however, a profound analysis of its ethical implications for the donor, the recipient, and their family. The medical and psychological selection process for potential LDs should be strictly defined and followed to minimize post-transplant morbidity.
Living Donor Selection and Workup
Liver LD evaluation must be standardized and follow a stepwise protocol with inclusion and exclusion criteria to be approved by the Institutional Ethical Committee ( Box 8.1 ). At Cliniques universitaires Saint-Luc, LD selection and workup are performed in three phases. In phase 1, potential LDs who volunteer for donation fill a prescreening paper sheet with their general medical information and with routine biochemistry. The nurse coordinator performs a preliminary selection, excluding those with obvious contraindications to donation (see Box 8.1 ). A member of the medical donor team then evaluates the potential LD candidate. Past medical history is carefully collected to rule out any contraindication to donation. Special attention is paid to chronic metabolic diseases such as diabetes, obesity, hypercholesterolemia, and/or hypertriglyceridemia, as well as past history of infectious diseases (viral hepatitis, tuberculosis, and human immunodeficiency disease, among others). LD candidates should be interrogated about endemic disease in their native countries (e.g., malaria, Chagas disease, dengue, and schistosomiasis). History of illicit drug addiction, mainly cocaine use, is also investigated because such consumption may be associated with hepatotoxicity and arterial spasms. Ingestion of a high amount of soft drinks may be associated with nonalcoholic fatty liver disease. Phase 1 laboratory investigation includes blood cell counts and coagulation tests, liver and renal function tests, thrombophilic screening (protein C, protein S, antithrombin III, and activated protein C resistance), lipid profile, and viral screening including hepatitis A, B, and C; Ebstein-Barr virus; and cytomegalovirus. Electrocardiogram, pulmonary function tests, and a chest x-ray are also performed. Liver ultrasonography with Doppler analysis is carried out to study the liver parenchyma (nodules, steatosis) and/or to identify any vascular or biliary variation. In phase 2, cholangiogram–magnetic resonance imaging (MRI) is performed to determine (1) the absence of liver parenchymal alteration, (2) the absence of suspect hepatic lesions, (3) vascular and biliary anatomy, and (4) the volume of liver lobes. Finally, all potential donors undergo an evaluation by a medical internist who does not belong to the transplant team and acts as a medical advocate to exclude any contraindication to the surgical donor procedure. Phase 2 is finalized by a psychologist or psychiatrist consultation to discuss any psychological disturbance or donor coercion. Phase 3 is reserved for potential LD candidates who require a liver biopsy to rule out any suspicion of liver steatosis or hepatic involvement and for the cases where a more accurate hepatic volume calculation is needed, mainly for adolescent recipients. In such cases, a hepatic computed tomography (CT) scan with contrast injection is performed, and images are used for liver volume calculation by the MeVis software (MeVis Medical Solutions AG, Bremen, Germany).
Age < 18 and > 55 years
BMI > 28 kg/m 2
History of complex upper abdominal surgery
HBV (including HBc Ab +), HCV, HIV infection
LD affected by some specific genetic/metabolic diseases (i.e., wild Alagille mutation, familial hypercholesterolemia, PFIC, etc.)
Any medical contraindication increasing operative risk
Right lobe portal vascularization coming from the left lobe
Presurgical Evaluation of Recipients
Pre-LT recipient workup includes clinical, growth, and nutritional assessment; liver and kidney function tests; metabolic profile; serological assays; eye fundus examination; electroencephalography; chest radiography; cardiac ultrasonography; and other investigations according to the etiology and presentation of liver disease (see Chapter 8). Particular attention must be paid to the nutritional status, the optimal management of which should be a major goal before transplant. Provided the clinical condition of the child permits waiting, nutrition is accepted to minimize perioperative morbidity and mortality.
Doppler ultrasound (US) examination of the abdomen provides the following information: (1) presence of nodules in the hepatic parenchyma, (2) diameter of portal vein (PV) and superior mesenteric vein (SMV), (3) direction and velocity of portal flow, (4) hepatic artery (HA) resistance index, and (5) spleen longitudinal measurement and presence of ascites. Abdominal CT, MRI, or positron emission tomography scans are generally not mandatory in a routine manner, but they could be useful in select cases, particularly for hepatic nodules workup. At the end of patient evaluation, particular attention must be paid to the possible presence of contraindications, including some medical conditions that may significantly increase the surgical risks (i.e., major cardiac abnormalities, multiorgan failure, or some concomitant viral infections, like active adenovirus or type I herpes virus). In the case of neurological impairment, consider the impact of transplantation on quality of life, weighing it against the risk of LDLT. In our center, such difficult situations may need a full multidisciplinary discussion and ethical committee approval before confirming the liver transplantation.
LDLT can be considered even in case of ABO mismatch, when no other ABO-compatible donor is available, particularly in children younger than 1 year old. In this situation, anti-donor isoagglutinins (ADI) levels must be assayed before LT. In the case of an ADI level of 1/16 or less, patients can undergo LT without any special management and with post-LT conventional immunosuppression. When ADI levels are above 1/16, patients must be prepared for ADI reduction using: (1) anti-CD20 monoclonal antibody (375 mg/m 2 , Rituximab, MacThera; Roche), starting 2–3 weeks before LT; (2) plasmapheresis, starting 6 days before LT in the case of elevated ADI levels; and (3) intravenous immunoglobulin 1 day before LT to prevent resynthesis of ADI. Steroids might be added to conventional immunosuppression in case of ABO incompatibility. ADI levels must be checked systematically after LT, considering plasmapheresis and/or anti-CD20 antibody in the event of an increase in ADI level above 1/16.
Our technique has been already described and updated over time as it improved. Currently, the procedure is performed through a supraumbilical median laparotomy. The falciform ligament is divided, and then the hepatic vein’s anatomy, particularly that of the median hepatic vein, is checked by an intraoperative USS. The left triangular ligament is divided to access to the left aspect of the suprahepatic and transdiaphragmatic inferior vena cava (IVC). The left inferior phrenic vein is tied and divided. The Arantius ligament is dissected and divided close to the left hepatic vein for later use during the hanging maneuver at the time of left bile duct (BD) section. The occurrence of a replaced left HA is checked during the division of the gastrohepatic ligament. The hilar dissection is limited to its left aspect, with dissection of the left HA down to the bifurcation of the proper HA. The left HA is wrapped with a Surgicel swab wetted with papaverine. The cystic duct is catheterized at the end of anterograde cholecystectomy. The parenchymal transection is started 0.5 cm on the right side of the falciform ligament in the case of left lobectomy or just above the middle hepatic vein (as located by intraoperative USS Doppler) in the case of a full left hepatectomy, which includes the middle hepatic vein. Parenchymotomy is performed using ultrasonic dissection (CUSA-CV720-472-000; Valleylab, Inc., Boulder, CO, USA), with hemostasis and biliostasis by monopolar diathermy, bipolar diathermy, argon beam gas surface coagulator (ConMed system 7500; Utica, NY, USA), nonabsorbable ligatures, and suturing with nonabsorbable monofilament stitches. Once the parenchymal transection is completed with exposition the hilar plate, a sling is passed from the site of the Arantius ligament to the plane of the parenchymotomy to hang the pedicle of the left lobe. A small clamp positioned in the anterior border of the hilar plate is used to identify the transection site of the left BD by intraoperative cholangiography ( Fig. 8.1 ). Once the left BD is sectioned, the donor side is oversewn with a running 6/0 PDS suture (J&J Medical). The left PV is prepared for cannulation; at this point, 1000 IU of heparin is administered via the central line. The left PV is clamped and catheterized for subsequent in situ cooling perfusion. The left HA is clipped and transected on the donor side, keeping the graft side open to avoid intimal injury. The left HV is clamped and sectioned, with immediate start of in situ perfusion using 500 mL of Hartmann solution at 4° C with 1000 IU heparin. Then the left lobectomy or hepatectomy is completed, and ex situ graft perfusion is continued on the back table with 1 L of IGL-1 (Institute Gomez Lopez, Lyon, France). In the middle of the perfusion, the left HV is digitally clamped to perform the arterial vascular bed retro-perfusion ( Fig. 8.2 ). At the back table, the left BD is also rinsed with cooled saline solution to avoid biliary epithelial injury caused by bile acid precipitation provoked by preservation solutions. The hemostasis on the liver cut surface is completed by using the argon coagulator and by the apposition of a Tachosil swab on the inferior part of the liver cut surface covering the hilar plate and the suture stumps of portal and left hepatic veins. When a portoplasty and/or an arterial graft interposition is required for liver graft implantation, we procure a segment of 5–7 cm donor inferior mesenteric vein (IMV) and/or a segment of donor right gastroepiploic artery, respectively.