HBL occurs at an incidence of one per one million children and accounts for approximately two-thirds of all liver tumors in the pediatric population [2]. Complete surgical removal of the tumor provides the best chance for cure, and resection has been recognized as the first-line treatment modality. For patients with unresectable HBL without metastatic disease, chemotherapy followed by total hepatectomy with LT has been advocated, and favorable long-term survival rates have been observed [3]. Most studies on outcomes following LT for HBL are small single-center series, and as such the true incidence of tumor recurrence remains poorly defined. Among 12 children who underwent LT for HBL after neoadjuvant chemotherapy , Reyes et al. reported that two patients (17 %) subsequently died as a result of disease recurrence [4]. Intrahepatic venous invasion, lymph node involvement, and contiguous spread were not associated with significant adverse effects on outcomes. In contrast, pretransplant distant metastases were suspected in both patients who succumbed to recurrent disease. Most deaths attributable to recurrent tumor occurred within 2 years posttransplant [5]. In a review of 15 pediatric patients who underwent LT for HBL, Beaunoyer et al. reported a 67 % recurrence-free survival after a 5-year follow-up [3]. In another single-center analysis, Malek et al. reported a disease recurrence rate of 4 % among 23 children with HBL and 2 children with HCC who underwent LT, which compares favorably with a recurrence rate of 17 % after liver resection [6]. A retrospective review of the Surveillance, Epidemiology, and End Results (SEER ) registry identified 318 children diagnosed with HBL between 1998 and 2009. Of all HBL patients, 83 % underwent resection and 17 %, transplantation [7]. Despite having more advanced disease at presentation, with higher incidences of vascular invasion and satellite nodules, transplant patients demonstrated equivalent disease-specific survival rates at 5 years compared with patients who underwent resection. More recently, a single-center retrospective review of 35 children diagnosed with HBL reported 1- and 5-year post-LT survival rates of 86 % and 66 %, respectively. Tumor recurrence was observed in nine cases, with a median time of 6.5 months to recurrence. Significant predictors of patient survival on multivariate analysis include intravascular tumor invasion, the presence of lung metastases, and rescue transplantation after failed resection attempts [8].

Although the incidence of HCC is <0.5 per two million children, it constitutes the second most common cause for primary liver tumors after HBL in the pediatric population [6]. Since HCC usually occurs in the setting of preexisting liver disease , and often lesions are quite large at the time of diagnosis; less than 25 % of lesions are amenable to surgical resection [9]. While outcomes following LT for HCC have been extensively studied in adults, less is known about outcomes in pediatric LT recipients with HCC. Reyes et al. reported a 5-year survival rate of 68 % after LT for HCC in children [4]. Six of 19 patients (32 %) died as a result of tumor recurrence, with most recurrences occurring within 3 months posttransplant. Vascular invasion, distant metastases, lymph node involvement, tumor size, and gender were all found to be significant risk factors for recurrence. However, the number of lesions was not associated with posttransplant outcomes in this study. Beaunoyer et al. reported a recurrence-free survival of 83 % at 5 years posttransplantation [3]. In contrast to the earlier study, the number of tumors, size, and gross vascular invasion were not associated with the risk of recurrence. In the SEER registry , a total of 80 children were diagnosed with HCC from 1998 to 2009 [7]. Of all HCC patients, 75 % underwent resection and 25 % received LT. Transplant patients again had more advanced disease as evidenced by a higher prevalence of vascular invasion and satellite lesions. Nevertheless, disease-specific survival at 5 years was superior for transplant patients (85 %) compared with resection patients (53 %). Venick et al. reported 1-, 5-, and 10-year survival rates of 86, 64, and 64 % for children undergoing LT for HCC [8]. Tumor recurrence was the cause of death in two patients, who were diagnosed with recurrence at 0.4 and 4 years post-LT, respectively.

The published reports presented above demonstrate that childhood HCC is a more aggressive disease than HBL, associated with worse survival and a higher risk for recurrence. Furthermore, children with HCC who undergo surgical resection may develop recurrences more frequently than patients who receive LT. The number of lesions, and perhaps tumor size, are not consistently associated with posttransplant outcomes. As such, the Milan criteria, which has been used to assign Model for End-Stage Liver Disease (MELD ) exception points to adult transplant candidates with HCC, are not applicable in the pediatric population [10]. Taken together, the favorable outcomes following LT, even in patients with advanced tumors, suggest that this treatment modality can be used more liberally in children diagnosed with HCC.

Giant cell hepatitis (GCH) is a rare form of rapidly progressive liver disease seen mostly in the neonatal period. The presence of giant multinucleated cells is thought to result from the response of immature hepatocytes to stress [20]. An autoimmune process or immune dysregulation is implicated in the pathophysiology of GCH. GCH often presents with an aggressive and fulminant course requiring intense immunosuppression, bone marrow transplantation, and/or LT. Most LT recipients will show a good initial response to immunosuppressive therapy but followed with frequent relapses.

The association of GCH with autoimmune hemolytic anemia (GCH-AIHA) is a distinct entity and has only been reported in 45 patients in the English literature [20, 21]. In a review of 24 GCH-AIHA cases, five children ultimately went on to require LT [22]. Outcomes following LT were poor, with two deaths secondary to posttransplant lymphoproliferative disease (PTLD) and sepsis; 4 out of the 5 LT recipients also developed recurrent disease. In another single-center report, two of 16 children with GCH-AIHA underwent LT, of which one patient is alive after 9 years of follow-up with normal serum alanine aminotransferase levels. Histologic examination of the liver graft, however, shows the occasional presence of giant multinucleated cells. The other patient died of multiple organ system failure within a few days of transplantation [20]. With these disappointing results and the high risk for recurrence, bone marrow transplantation may be the preferable treatment in children with GCH-AIHA. Nevertheless, in the face of liver failure during a relapse refractory to medical treatment, LT may be the only lifesaving treatment option and may be considered.

PSC is a chronic and progressive liver disease characterized by insidious inflammation and the obliteration of intrahepatic and extrahepatic bile ducts. This condition has a distinctive appearance on liver biopsy and on cholangiography and is accompanied by the presence of anti-neutrophil cytoplasm antibodies (p-ANCA). PSC is often associated with inflammatory bowel disease (IBD ) and can lead to end-stage liver disease and predispose to the development of cholangiocarcinoma. Currently available medical treatments for PSC address the symptoms related to complications but do not necessarily alter the natural history of the disease, and LT may offer the only chance for cure. Recurrence of PSC has been reported in up to one-third of adult patients who undergo LT [23]. Non-anastomotic biliary strictures are more common in PSC patients and are found to be present in 25 % of adult recipients within 3–5 years posttransplant [24].

In children, the incidence of PSC has been estimated at 0.23 per 100,000 person-years, which is only 20 % of the incidence reported for adults. Recurrence rates following LT are similar in children and adults, with reported rates of 0–33 % in the published series. In a single-center review of 12 pediatric LTs for PSC, four patients (33 %) developed disease recurrence after a median duration of 52 months [25]. A review of the UNOS registry reveals a higher proportion of children with PSC requiring retransplantation relative to those transplanted for biliary atresia. The median time to retransplantation for PSC patients was 4.1 years [25]. Analysis of the SPLIT database demonstrates a recurrence rate of 9.8 % at a mean duration of 18.7 months post-LT [26]. PSC patients were more likely to develop intrahepatic strictures by 6 months posttransplant, and experience more cholangitis episodes in the early posttransplant period compared with patients undergoing LT for other indications. Children with concurrent IBD were at a higher risk for PSC recurrence and posttransplant mortality. In adult recipients with IBD, pretransplant colectomy appeared to be protective against recurrent PSC, but it is unclear whether this association also applies to the pediatric population. Data from both the UNOS and SPLIT registries suggest superior survival for PSC patients in the early posttransplant period, but their long-term allograft survival may be worse than patients undergoing LT for other disease etiologies [26].