Hepatoportoenterostomy (Kasai procedure) is the primary surgical intervention for BA unless the initial presentation is beyond 3 months and there are signs of advanced liver disease at presentation including portal hypertension, defined by the presence of hypersplenism (thrombocytopenia, splenomegaly); a history of variceal bleed; ascites; growth failure; and synthetic liver dysfunction (INR ≥ 1.7, albumin ≤ 3.2 g/dL). In those who undergo the Kasai procedure, clinical evidence of failure may include persistent hyperbilirubinemia, portal hypertension with ascites or variceal bleeding, recurrent cholangitis, and other decompensations such as hypersplenism and hepatopulmonary syndrome. A significant portion of patients continue to have progressive liver disease (20%–40% over a 10-year period) and go on to require liver transplant. ^, The most significant decompensations of progressive liver disease include portal hypertension, malnutrition, and ascites.

Alagille’s syndrome is a cholestatic disease that may lead to end-stage liver disease requiring LT. This is an autosomal dominant disorder in which pathology demonstrates paucity of bile ducts and small caliber extrahepatic ducts. The majority are managed medically, often with the use of ursodiol to increase bile flow, medications to help treat jaundice-associated pruritis, and occasional partial external biliary diversion prior to liver transplant. Additionally, these children often have difficulties with absorption of fat-soluble vitamins, malnutrition, growth delay, delayed puberty, and failure to thrive.

Progressive familial intrahepatic cholestasis (PFIC) is an inherited cholestatic disorder in which bile salt, phospholipid, or cholesterol transport genes are mutated. The disease accounts for 15% of neonatal cholestatic disorders. Of the four subtypes, types 1 and 2 are more common. LT has been reported in types 1–3 with good outcomes.

LT can achieve phenotypic and functional cure for liver-based metabolic diseases. Some of the defects can cause metabolic crises leading to damage to other organ systems. Therefore, transplantation should be considered prior to the development of complications. The outcomes are usually excellent but certain metabolic conditions need continued medical treatment posttransplant due to long-term progression of the disease. There are many metabolic disorders that have indications for LT ( Box 44.1 ).

In acute liver failure (ALF), a specific diagnosis is not established in about half of affected children. Common causes of ALF include infection, previously undiagnosed metabolic disorders, immunological disorders, and drug-induced etiologies. Patients with ALF can potentially deteriorate rapidly and pose a diagnostic challenge. These patients are better served at a transplant center.

The Kings College Institute of Liver Studies has developed a scoring system for children with ALF to stratify their risk. Factors predictive of poor outcome include an international normalized prothrombin ratio (INR) > 4, serum bilirubin >13.8 mg/dL, age under 2 years, and white blood cell count (WBC) > 9 × 10 ⁹ /L. Patients with worsening encephalopathy have inferior outcomes, whereas survival is greatly improved when the candidates undergo transplantation prior to the development of irreversible neurological abnormalities. With development of encephalopathy, an early head computed tomography (CT) scan will establish a baseline. Placement of intracranial pressure monitoring devices have been described but pose a risk in coagulopathic patients. More recently, optic nerve sheath diameter assessment and trend monitoring has emerged as a safer noninvasive method. Liver support is often achieved based on availability of resources and include the Molecular Adsorbent Recirculating System (MARS, an extracorporeal support therapy), single-pass albumin dialysis (SPAD), therapeutic plasma exchange, and continuous renal replacement therapy (CRRT). The goal with any of these systems is to replicate the detoxifying function of the liver until the liver function recovers or a liver transplant becomes available.

Hepatoblastoma is the most common liver malignancy in children. Diagnosis is confirmed with a biopsy or surgical resection. Children with PRETEXT (PRE-Treatment EXTent of disease) III or IV in which tumor size or location prevents complete resection as well as those with metastatic disease should be referred to a transplant center for evaluation. Neoadjuvant therapy is extremely effective in converting initially unresectable tumors into tumors that can be safely resected. Complete tumor resection is crucial to achieving long-term survival. According to Children’s Oncology Group (COG) guidelines, any unresectable POSTEXT (POST-Treatment EXTent of disease) tumor warrants a liver transplant. Pulmonary metastases are not a contraindication if the lesions are cleared via chemotherapy or surgically. Attempts at incomplete liver resection are discouraged as survival rates after rescue transplantation are inferior.

Hepatocellular carcinoma is the second most common hepatic malignancy, primarily affecting children older than 10 years with known liver disease and cirrhosis; however, most occur in noncirrhotic livers. Metastatic disease is an absolute contraindication to transplantation.

Other liver tumors that may lead to LT include nonmetastatic embryonal sarcoma, vascular malformations with complications such as high output cardiac failure and Kasabach-Merritt syndrome, and metastatic neuroendocrine tumors in selected cases.

During surgery, the native hepatectomy can be complicated by extensive portal hypertension, prior surgeries, spontaneous bacterial peritonitis, recurrent cholangitis, and previous transplants. The risk for bleeding is high due to coagulopathy. Malformations such as an interrupted IVC, malrotations, and portal vein abnormalities can be challenging. Reconstructive techniques are planned based on recipient and donor anatomy and vascular integrity. A transit time flow probe device (VeriQ, MediStim) is utilized to assess the flow in the native hepatic artery and portal vein. If the native recipient artery is too small in caliber or has inadequate flow (usually due to splenic steal in the setting of hypersplenism), an aortic conduit is planned. If there is native portal venous thrombosis, a superior mesenteric vein conduit is planned. With this preparation the recipient is ready to undergo the hepatectomy and move to the next phase.

This phase starts when the native liver is removed. Physiologic derangements stem from portal vein clamping and resultant changes in venous return. Reconstruction starts with hepatic vein outflow and the three types of reconstructions include bicaval, piggyback, and cavocavostomy. In bicaval reconstruction the native vena cava is replaced with the donor vena cava with supra- and infrahepatic anastomoses. In piggyback reconstruction, the donor suprahepatic vena cava is anastomosed to the native hepatic vein confluence. When a left lateral section is utilized, the donor left hepatic vein is reconstructed to the recipient vena cava. Cavocavostomy is a newer modification of the piggyback reconstruction where a long vertical cavotomy is made on both recipient and donor cava and the anastomosis performed from 12 o’clock to 6 o’clock. Following the outflow reconstruction, portal vein reconstruction usually follows. A primary reconstruction is performed when the recipient portal vein is open. In the setting of portal vein thrombosis or a recanalized portal vein, a superior mesenteric vein conduit is used (which is reconstructed in the preanhepatic phase).

Following hepatic vein outflow and inflow reconstruction, reperfusion occurs, during which physiologic derangements can be noted. Consistent communication with the anesthesia team is imperative for a safe reperfusion. Arrhythmias can occur from hyperkalemia and hypothermia. Myocardial protective measures through use of calcium and sodium bicarbonate attempt to prevent undue effects from congested portal blood flow and preservation solution washout. In the setting of a split liver from an ex vivo split or reduced grafts, there can be significant bleeding from the cut surface. Once the recipient is stabilized and hemostasis secured, further reconstructions are undertaken.

Frequent arterial blood gases are utilized to correct any base deficit or lactic acidosis. The central venous pressure is maintained in a reasonable range to avoid hypotension or cause graft congestion due to outflow issues. Once the recipient is stabilized and hemostasis secured, further reconstructions are undertaken.

The three arterial reconstructions utilized in liver transplant include primary anastomosis, donor celiac axis to aorta, and interposition graft when the size of the donor vessel is inadequate.

A primary anastomosis is performed (hepatic artery to hepatic artery) when the arterial caliber and flow is considered adequate. A primary running or interrupted anastomosis is performed with a monofilament suture. There is increased risk of hepatic artery thrombosis in this setting due to the smaller caliber of the vessel. Often, some form of anticoagulation or antiplatelet therapy is required postoperatively to minimize this risk. Dextran, dipyridamole, and aspirin are frequently used.

In smaller pediatric patients, sometimes donor celiac axis to recipient supraceliac or infrarenal aorta is utilized. This may occur with a left lateral section or a left lobe graft, where a large donor is used for an infant or small child. The length of the left hepatic artery in continuation with the celiac axis can be long enough to directly reach the infrarenal aorta. The hepatic flexure and duodenum are mobilized, the infrarenal aorta is exposed, a side biting clamp is placed, and an end-to-side anastomosis is performed with running polypropylene suture. This technique has been shown to have the lowest incidence of HAT.

The interposition graft is reconstructed to the recipient infrarenal aorta. In this technique, the donor iliac vessels procured during the donor operation are utilized. The infrarenal aorta is exposed in a similar fashion and conduit is reconstructed. This is usually performed before the native hepatectomy to save time later. A bulldog clamp is placed on the conduit and the clamp is removed from the aorta. During arterial reconstruction the donor celiac axis is reconstructed to this conduit in an end-to-end fashion. This appears to be the next best method to minimize HAT. In the setting of larger patients or retransplants a supraceliac conduit is sometimes used. For various reasons there appears to be a high incidence of stenosis or HAT in this method of reconstruction.

Biliary reconstruction varies based on recipient anatomy and institutional preference. Post-Kasai portoenterostomy patients have an existing roux limb that is utilized for a choledochojejunostomy. A primary duct-to-duct anastomosis is performed in most other cases ( Fig. 44.5 ). A choledochoduodenostomy is a comparable alternative to Roux-en-Y choledochojejunostomy when the duct-to-duct anastomosis is not possible. A fenestrated silastic stent is placed (when feasible), which usually passes through the GI tract.

Bile duct reconstruction is shown using the common hepatic duct in whole-organ transplants (left) and segmental hepatic ducts into a Roux-en-Y intestinal limb for reduced-size liver transplants (right). An internal multifenestrated stent is used in both situations.

From Ryckman F. Liver transplantation. In: Ziegler MM, Azizkhan RG, Weber T, eds, Operative Pediatric Surgery . McGraw-Hill; 2003:1275.

According to the OPTN, criteria for diagnosis of primary nonfunction (PNF) within 7 days of transplantation should include at least two of the following: (1) alanine aminotransferase (ALT) greater than or equal to 2000 U/L; (2) INR greater than or equal to 2.5; (3) total bilirubin greater than or equal to 10 mg/dL; and (4) acidosis, defined as one of the following: arterial pH less than or equal to 7.30, venous pH less than or equal to 7.25, or lactate greater than or equal to 4 mmol/L. Contributing factors are profound hypotension requiring massive pressor support, donor liver severe macro steatosis, acidosis, and prolonged ischemia time. Retransplantation might be necessary with no signs of improvement. MARS and CRRT with SPAD can be used postoperatively for liver dysfunction.

Hepatic artery thrombosis (HAT) can be a devastating vascular complication following LT, with an incidence of around 8% and a retransplant rate of about 60%. Contributing factors include recipient age, type of anastomosis, splenic steal, portal hyperperfusion, rejection, hemodynamic instability, and hypercoagulability. Doppler ultrasound is the primary and most reliable screening tool for HAT. Unexpected clinical changes or coagulopathy should prompt an urgent ultrasound. Most centers obtain daily ultrasounds until postoperative day 5 or more frequently when indicated. Features on Doppler waveforms such as delayed systolic upstroke, tardus parvus waveforms (delayed, reduced amplitude systolic pattern), absent diastolic flow, and persistently abnormal resistive indices are indicative of impending HAT. Early HAT can cause graft failure or biliary necrosis. When identified early, an attempt at revascularization is made. After thrombectomy, usually 1–2 mg tPA is instilled into the donor hepatic artery. If the primary anastomosis has failed, a conduit may be necessary from the aorta. In the setting of graft failure urgent relisting and retransplantation might be necessary. In the setting of HAT beyond 7 days, other endovascular techniques may be employed. Delayed HAT beyond 30 days is usually clinically silent and can cause progressive biliary injury, which can lead to biliary strictures and recurrent cholangitis.

Portal vein thrombosis (PVT) occurs in <10% of cases. Anatomic factors include hypoplastic portal vein (usually seen in BA), chronic portal venous thrombosis, and the need for venous reconstruction techniques. PVT may manifest with elevated liver enzymes, graft dysfunction, and coagulopathy. Doppler ultrasound is primarily utilized. When identified, thrombectomy is done with anastomotic revision followed by anticoagulation. If graft dysfunction does not improve, retransplantation may be necessary. Late PVT may lead to portal hypertension, thrombocytopenia, and GI bleeding. Percutaneous techniques are utilized to manage stenosis. Posttransplant shunt procedures such as meso-Rex bypass may be necessary.

Hepatic venous outflow obstruction (HVOO) is underdiagnosed and increasingly being evaluated. HVOO immediately postoperatively can be devastating. Early high-grade HVOO can cause PVT and hepatic artery thrombosis due to outflow obstruction and subsequent graft loss. Moderate to low-grade HVOO can cause refractory ascites and graft dysfunction. Risk factors include the need for reconstruction techniques, torsion in the setting of technical variant grafts, anastomotic stricture, and tight fascial closure leading to abdominal compartment syndrome. For HVOO due to torsion, repositioning of the graft or reattaching the falciform ligament might help. If HVOO has led to inflow thrombosis, the graft failure might be significant and retransplant may be warranted. Delayed HVOO can be managed by venoplasty and stents. Diagnosis can be made noninvasively using an echocardiogram and assessing the gradient between hepatic veins, inferior vena cava, and atrium. Dynamic magnetic resonance imaging (MRI) or 4D MRIs can be utilized to assess real-time flows through the hepatic veins and the vena cava and to assess for turbulence and obtain gradients.

The incidence of biliary complications is about 10%. Early complications include bile leak or stricture and can be related to technical factors or secondary to hepatic artery thrombosis. Small bile leaks can be managed nonoperatively. High-volume leaks will likely require operative revision. Primary anastomosis has a higher incidence of stricture compared to Roux-en-Y reconstruction. Endoscopic or interventional techniques can be employed to address delayed strictures.

Within 1 year of transplant, 22%–29% of pediatric liver transplant recipients (transplants done in 2021) had at least one episode of rejection. Anatomical causes should be ruled out with a Doppler ultrasound, and an infectious work up should also be done. Liver biopsy is usually required for definitive diagnosis. Important features of rejection include the presence of endotheliitis, infiltration of the portal triad by lymphocytes, and hepatocyte parenchymal damage. Most patients respond to pulse steroids, and in refractory cases, a T-cell depleting agent might be necessary. In the setting of elevated CNI levels and mild liver enzyme elevation, correction of the level should suffice.

Chronic rejection can be silent, causing progressive fibrosis and eventual cirrhosis. Risk factors include African American race, number of acute rejection episodes, history of posttransplant lymphoproliferative disease, and CMV and EBV infections. ^, Treatment can be challenging and usually consists of increasing immunosuppression levels or considering other agents. Chronic rejection has a significant effect on long-term graft survival.

Infection is one of the most common causes of death even in long-term follow-up. Early postoperative infections are mostly bacterial in nature and require broadspectrum antibiotics. Fungal infections are more common in the setting of bowel perforation, large-volume transfusion, or prolonged exposure to steroids in the pretransplant period. Viral infections are typically delayed and are due to cytomegalovirus (CMV), Epstein–Barr Virus (EBV), adenovirus, and herpes simplex virus (HSV). CMV is the most common, especially with positive donors for negative recipients. EBV can occur similarly, either by primary infection or reactivation, and increases the risk for posttransplant lymphoproliferative disorder. As the symptoms are nonspecific, high levels of suspicion are maintained with periodic viral load monitoring. Pneumocystis jiroveci infection is concerning in the first year and the prophylactic regimen includes thrice weekly oral trimethoprim-sulfamethoxazole for the first 6–12 months.

Posttransplant lymphoproliferative disorder (PTLD) is the most common malignancy in the pediatric recipient. By 5-year posttransplant, 4.1% of recipients developed posttransplant lymphoproliferative disorder. PTLD is usually a polyclonal expansion of B lymphocytes and can be associated with EBV infection. Treatment includes decreasing the intensity of immunosuppression and a biopsy of the lesions to determine the biology. In cases of CD20 expression, rituximab (anti-CD 20 monoclonal antibody) is administered. When some tumors of monoclonal origin do not respond, other chemotherapy agents such as cyclophosphamide and prednisone may be necessary.

Skin cancers are the second most common malignancy in the pediatric posttransplant patient. These include squamous cell carcinoma, basal cell carcinoma, and melanoma. As most of these malignancies are related to sun exposure, using sunblock (SPF > 50), surveillance, and education are important. These are treated with excisions with generally good outcomes. Lastly, there is reportedly an increase in the incidence of thyroid papillary cancer, Kaposi’s sarcoma, and ovarian tumors. ^,

The allograft is tailored to the individual patient’s needs with the exclusion or inclusion of multiple organs, which may include the stomach, pancreaticoduodenal complex, small intestine, colon, and liver. Multivisceral transplant is considered when intestinal failure has led to multiorgan dysfunction. Multivisceral transplantation is often used in the pediatric population for intestinal dysmotility syndromes but occasionally may also be used for other indications (e.g., advanced intraabdominal desmoid tumors of the mesentery following radical surgical resection). For multivisceral graft transplantation, arterial inflow is through the donor celiac and superior mesenteric arteries and venous outflow is from the multivisceral allograft via the transplanted liver placed in the standard orthotopic position. Occasionally the liver is reduced due to size constraints of the recipient. GI continuity is completed via a gastrogastric anastomosis proximally and an ileocolic or colonic anastomosis distally.

In children with intestinal failure on long-term TPN, the development of compromised liver function secondary to prolonged parental nutrition is common. IFALD occurs with evolving cholestasis, portal hypertension, and loss of synthetic function. Considerations for combined intestinal-liver transplant include severe hepatosplenomegaly, hyperbilirubinemia (>10 mg/dL), or thrombocytopenia ( Fig. 44.8 ). A liver-small bowel composite allograft is a modification of the multivisceral allograft in which the stomach is removed during the procurement. The recipient’s liver and remaining small intestine are removed, and the native stomach, duodenum, pancreas, and spleen are left intact. A portocaval shunt from the native portal vein to the inferior vena cava is necessary to provide venous outflow from the recipient’s foregut organs ( Fig. 44.9 ). The donor celiac artery and superior mesenteric artery (SMA) are the source of arterial inflow to the transplanted organs and the donor portal vein and biliary tree remain intact, having not undergone dissection during the procurement. No portal vein or bile duct reconstruction is needed. The pancreas is also left intact to protect the peribiliary ductal vessels and to prevent the possibility of pancreatic leak from the divided surface. Venous outflow is provided by the donor liver placed in the standard orthotopic position. If the donor liver is larger than the recipient liver, an ex vivo hepatic lobectomy is performed ( Fig. 44.10 ). GI continuity is from the patient’s native stomach and duodenum to the newly transplanted small bowel via anastomosis of the native duodenum to the donor jejunum. Distal continuity is via ileocolonic or colonic anastomosis.

Schematic diagram of liver/intestine composite allograft .

From Abu-Elmagd K, Reyes J, Todo S, et al. Clinical intestinal transplantation: new perspectives and immunologic considerations. J Am Coll Surg . 1998; 186:512–527.

Schematic diagram of liver/intestine composite allograft with native portocaval shunt.

©Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, 2008.

Schematic diagram of reduced-size liver/intestine composite allograft.

From Reyes J, Mazariegos GV, Bond GMD, et al. Pediatric intestinal transplantation: historical notes, principles and controversies. Pediatr Transplant . 2002; 6:193–207.

Isolated intestinal transplant is considered when the total serum bilirubin concentration remains below 10 mg/dL, the patient has mild splenomegaly, and a platelet count that is in the low-to-normal range. ^, Isolated intestinal transplant should be performed only in patients who are likely to no longer need parenteral nutrition following restoration of normal liver function. If there is uncertainty about the severity of liver disease, based on clinical and laboratory data, a biopsy should be performed to discriminate mild from advanced and irreversible disease. Grade 3 bridging fibrosis would support intestinal and LT, while purely portal fibrosis (Grade 1) or portal plus mild bridging fibrosis (Grade 2) would favor isolated intestinal transplant. ^{, ,}

Transplantation of the small intestine alone entails procurement of only the jejunum and ileum; however, some centers also use the ascending and proximal transverse colon. During procurement, the SMA and superior mesenteric vein (SMV) are divided just below the third portion of the duodenum at the root of the mesentery, generating an allograft of jejunum, ileum, and proximal colon ( Fig. 44.11 ). Arterial inflow is provided by the anastomosis of the SMA to the recipient’s aorta. Venous drainage of the transplanted intestines is into the inferior vena cava or SMV. Sometimes an interposition graft using donor iliac vessels is required to allow for enough length on the vessels for the graft to lay appropriately within the abdomen without causing inflow/outflow vascular compromise. GI continuity is restored via anastomosis of the recipient’s native proximal bowel to the transplanted jejunum and distal native colon.

Schematic diagram of isolated small intestinal transplant. SMA, Superior mesenteric artery; SMV, superior mesenteric vein.

Adapted from Abu-Elmagd K, Fung J, Bueno J, et al. Logistics and technique for procurement of intestinal, pancreatic, and hepatic grafts from the same donor. Ann Surg . 2000; 232:680–687.

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