Technique advance to avoid hepatic venous outflow obstruction in pediatric living‐donor liver transplantation

HVOO represents a serious critical complication of pediatric living‐donor liver transplantation because open surgical repair is virtually impossible. Currently, despite several technical innovations and the introduction of triangulated anastomosis for hepatic vein reconstruction, the reported incidence of HVOO is still considerable. The aim of this study was to propose a new technique for hepatic venous reconstruction that avoids the original orifice of the recipient hepatic veins. Instead, anastomosis is performed in a newly created wide longitudinal orifice in the anterior wall of the recipient inferior vena cava. A total of 210 living related‐donor liver transplantations were performed using two methods for reconstruction of the hepatic vein. Group 1 included 69 patients subjected to direct anastomosis of the orifice of the graft hepatic vein and a wide orifice created in the recipient inferior vena cava by the confluence of the orifices of the right, left, and middle hepatic veins. Group 2 included 141 patients in whom the original orifices of the recipient hepatic veins were closed, the inferior vena cava was widely opened, and a long longitudinal anastomosis was performed using two lines of continuous sutures. Diagnosis of HVOO was suspected based on clinical findings and ultrasound studies and then confirmed by liver biopsy and interventional radiology examinations. Among the 69 recipients in group 1, 16 patients died due to graft problems during the postoperative period and eight of the survivors (15.1%) presented with HVOO. In group 2 (141 patients), 21 patients died, and there were no cases of HVOO. A comparison of the incidence of HVOO between groups revealed a significant difference (p = 0.01). Hepatic venous reconstruction during pediatric living‐donor liver transplantation should be performed using a wide longitudinal incision in the anterior wall of the recipient inferior vena cava because this technique eliminated anastomosis complications.     

Waiting list mortality for pediatric deceased donor liver transplantation in a Japanese living‐donor–dominant program

Living donor liver transplantation (LDLT) has become a major life‐saving procedure for children with end‐stage liver disease in Japan, whereas deceased donor liver transplantation (DDLT) has achieved only limited success. The annual number of pediatric liver transplantations is approximately 100‐120, with a patient 20‐year survival rate of 81.0%. In 2005, the liver transplantation program at the National Center for Child Health and Development in Tokyo, Japan, was initiated, with an overall number of 560 pediatric patients with end‐stage liver disease to date. In July 2010, our center was qualified as a pediatric DDLT center; a total of 132 patients were listed for DDLT up until February 2019. The indications for DDLT included acute liver failure (n = 46, 34.8%), metabolic liver disease (n = 26, 19.7%), graft failure after LDLT (n = 17, 12.9%), biliary atresia (n = 16, 12.1%), and primary sclerosing cholangitis (n = 10, 7.6%). Overall, 25.8% of the patients on the waiting list received a DDLT and 52.3% were transplanted from a living donor. The 5‐year patient and graft survivals were 90.5% and 88.8%, respectively, with an overall waiting list mortality of 3.0%. LDLT provides a better survival compared with DDLT among the recipients on the DDLT waiting list. LDLT is nevertheless of great importance in Japan; however, it cannot save all pediatric recipients. As the mortality of children on the waiting list has not yet been reduced to zero, both LDLT and DDLT should be implemented in pediatric liver transplantation programs.     

Management of late‐onset portal vein complications in pediatric living‐donor liver transplantation

The purpose of this study was to evaluate retrospectively the results of PTA for late‐onset PV complications after pediatric LDLT and to assess whether a meso‐Rex shunt is a viable option for treating restenosis of the PV after PTA in selected cases. Seventy‐five children who underwent adult‐to‐child LDLT were included in this study, and there were six late‐onset PV complications (8.0%). The initial therapeutic approach was PTA, with or without stent: PTA with balloon dilation for three children, PTA with stent placement for one child, and failure to cannulate the occluded PV for two children. A meso‐Rex shunt was performed in the two children after failed PTA: One suffered complete obstruction of the main PV, and the other, restenosis with total thrombosis after PTA with stent. The PTA was a technical and clinical success in four with PV stenosis of the six patients (66.7%), and successful application of a meso‐Rex shunt in the other two children resulted in restoration of PV flow. In conclusion, PTA is a safe and effective procedure for treating late‐onset PV stenosis after pediatric LDLT. However, in growing pediatric recipients with restenosis of the PV after PTA or chronic PV thrombosis, a meso‐Rex shunt may be a better choice for late‐onset PV complications.     

Barriers to access in pediatric living‐donor liver transplantation

Children receiving a LDLT have superior post‐transplant outcomes, but this procedure is only used for 10% of transplant recipients. Better understanding about barriers toward LDLT and the sociodemographic characteristics that influence these underlying mechanisms would help to inform strategies to increase its use. We conducted an online, anonymous survey of parents/caregivers for children awaiting, or have received, a liver transplant regarding their knowledge and attitudes about LDLT. The survey was completed by 217 respondents. While 97% of respondents understood an individual could donate a portion of their liver, only 72% knew the steps in evaluation, and 69% understood the donor surgery was covered by the recipient's insurance. Individuals with public insurance were less likely than those with private insurance to know the steps for LDLT evaluation (44% vs 82%; P < 0.001). Respondents with public insurance were less likely to know someone that had been a living donor (44% vs 56%; P = 0.005) as were individuals without a college degree (64% vs 85%; P = 0.007). Nearly all respondents generally trusted their healthcare team. Among respondents, 82% believed they were well‐informed about LDLT but individuals with public insurance were significantly less likely to feel well‐informed (67% vs 87%; P = 0.03) and to understand how donor surgery might impact donor work/time off (44% vs 81%; P = 0.001). Substantial gaps exist in parental understanding about LDLT, including its evaluation, potential benefits, and complications. Greater emphasis on addressing these barriers, especially to individuals with fewer resources, will be helpful to expand the use of LDLT.     

Diaphragmatic hernias after pediatric liver transplantation: Experience of a high‐volume transplant center

Diaphragmatic hernias (DHs) are rare complications after pediatric liver transplantation (PLT). It is now widely accepted that DHs after liver transplantation (LT) is a pediatric related condition. PLTs (under of age 18) performed between January 2013 and June 2019 at Malatya Inonu University Institute of Liver Transplantation were retrospectively scanned. Study group consisting DHs and a control group were compared. Among 280 PLTs, 8 of them were complicated with DHs (%2.9). Median age of the patients with DH was 3.0 (0.8‐9.5) years. Median graft recipient weight ratio was 2.5 (0.9‐4.4). Five patients were below 5th percentiles in terms of pediatric weight growth chart at the time of LT. Also, 6 patients were below 5th percentiles in terms of pediatric height growth chart. There was no statistical difference between study and control groups. There are many risk factors mentioned in literature that may be primarily responsible for DHs after PLT. These factors are left lobe and large‐for‐size grafts, malnutrition, trauma or diathermy of diaphragmatic nerve and vessels and immunosuppressants. In our study, we could not specify any reason that differs in DHs. In our aspect, narrow diaphragma and thorax are exposed to high intra‐abdominal pressure from abdomen. Large‐for‐size grafts, which are specific to children, also may contribute to this affect. Excessive diathermy and trauma to diaphragmatic collaterals may aggravate the risk of DH. More patients are needed to make an exact conclusion, in order to evaluate with comparable study on this aspect.     

Biliary reconstruction before clamp removal to avoid portal vein thrombosis in pediatric living‐donor liver transplantation using hyper‐reduced left lateral segment grafts: A novel technical strategy

LT has become the treatment of choice for children with end‐stage liver disease. The scarcity of donors and the considerable mortality on waiting lists have propelled the related living‐donor techniques, especially in small children. This population need smaller and good quality grafts and are usually candidates to receive a LLS from a related donor. Many times this grafts are still large and do not fit in the receptor's abdomen, so a further hyper‐reduction may be required. Despite all advances in LT field, vascular complications still occur in a considerable proportion remaining as a significant cause of morbidity, graft loss, and mortality. Technical issues currently play an essential role in its genesis. The widely spread technique for biliary and vascular reconstruction in living donor LT (LDLT) nowadays implies removal of the portal vein (PV) clamp after the venous anastomosis, then the arterial reconstruction is done, followed by the biliary reconstruction. However, due to the posterior location of the LLS bile duct, for its reconstruction, a rotation of the liver is required risking a potential transient PV occlusion leading to thrombosis afterward. We describe a new technique that involves performing biliary reconstruction after the PV anastomosis and before removing the vascular clamp, thus allowing to freely rotate the liver with less risk of PV occlusion and thrombosis.     

Biliary complications of living related pediatric liver transplant patients

Patients who undergo living related left lateral segment liver transplants have been reported to have a high incidence of biliary complications and some studies suggest that most patients will ultimately need operative revision. We reviewed our experience with living related transplantation in pediatric recipients to examine the occurrence of biliary complications and the utility of percutaneous biliary procedures in their management. Over a 10-yr period, 48 living donor transplants were performed in 47 patients. Sixteen patients (33%) had biliary complications. Complications included 10 leaks (20%) and eight strictures (17%). Although leaks were treated predominantly with operation, other biliary complications were treated almost exclusively non-operatively. Self limited leaks that lead to biloma accumulation were most often treated via percutaneous catheter drainage and all strictures were treated using percutaneous transhepatic biliary cholangioplasty and stenting. Sixty-seven percent of biliary complications underwent non-operative biliary intervention. Most strictures were focal anastomotic strictures and were successfully treated with cholangioplasty although multiple interventions were necessary and patients required stenting for an average of 13 months. Three of eight strictures were diffuse in nature and these included the only patient who required retransplantation. Graft survival with respect to biliary complications was 94%; 1 yr, 5 yr and overall patient survival for those with biliary complications was 88, 88 and 81%, and for the entire living related group was 84, 81 and 77%, respectively. Although biliary complications are frequent in pediatric living related transplantation, they are not associated with decreased patient survival. Excepting significant bile leaks, the majority can be treated non-operatively via biliary cholangioplasty and stenting. Strictures are especially amenable to this technique which, in our experience, has been successful at decreasing or postponing the need for retransplantation.     

Pneumatosis intestinalis following pediatric live‐related liver transplant: A case report and successful conservative approach

PI has been rarely reported following pediatric live‐related liver transplantation. Such a disorder is characterized by accumulation of gas in the bowel wall. The cause of PI has not been yet established; however, it has been strongly linked with steroid therapy. In this report, we present a case of PI following pediatric live‐related liver transplantation that has been successfully managed conservatively.     

From living related to in-situ split liver transplantation: how to reduce waiting-list mortality

The insufficient number of suitable cadaveric organs for pediatric recipients is the cause of high pretransplant mortality rates and long waiting times. With the introduction of split and living related liver transplantation, the waiting list mortality rate has dropped from greater than 15% to less than 5% and children are transplanted more rapidly. A 5-year patient and graft survival rate of greater than 80% has been obtained in those centers where split and living related liver transplantations are routinely performed. The data analyzed in this paper show that the only current solution to cadaveric organ shortage is a 'multimodal' approach, where whole liver cadaveric transplantation is associated with split and living related liver transplantation.     

Long‐term outcomes of living‐related small intestinal transplantation in children: A single‐center experience

Pediatric patients with irreversible intestinal failure present a significant challenge to meet the nutritional needs that promote growth. From 2002 to 2013, 13 living‐related small intestinal transplantations were performed in 10 children, with a median age of 18 months. Grafts included isolated living‐related intestinal transplantation (n=7), and living‐related liver and small intestine (n=6). The immunosuppression protocol consisted of induction with thymoglobulin and maintenance therapy with tacrolimus and steroids. Seven of 10 children are currently alive with a functioning graft and good quality of life. Six of the seven children who are alive have a follow‐up longer than 10 years. The average time to initiation of oral diet was 32 days (range, 13‐202 days). The median day for ileostomy takedown was 77 (range, 18‐224 days). Seven children are on an oral diet, and one of them is on supplements at night through a g‐tube. We observed an improvement in growth during the first 3 years post‐transplant and progressive weight gain throughout the first year post‐transplantation. Growth catch‐up and weight gain plateaued after these time periods. We concluded that living donor intestinal transplantation potentially offers a feasible, alternative strategy for long‐term treatment of irreversible intestinal failure in children.     

Outcomes of pediatric identical living‐donor liver and hematopoietic stem cell transplantation

Chronic IS is associated with significant morbidity in transplant recipients. Moreover, IS does not prevent chronic graft failure frequently. Allograft immune tolerance in LT can be induced by complete donor chimerism through allogenic HSCT combined with identical LDLT. This approach may exempt patients from chronic lifelong IS. However, it is unclear whether its benefits justify its risks. Here, we present three cases from our institution and analyze seven additional reports of children treated with HSCT/LDLT, all receiving HSCT due to hemato‐oncological indications. In eight of 10 cases, donor macrochimerism resulted in allograft tolerance. Nine patients survived. One patient died due to fulminant ADV infection. Further complications were GvHD (n = 3) and bone marrow failure (n = 2). In conclusion, donor‐specific allograft tolerance can be achieved by identical‐donor HSCT/LDLT. However, at present, this approach should generally be limited to selected indications due to a potentially unfavorable risk–benefit ratio. Novel toxicity‐reduced conditioning protocols for HSCT/LDLT in the absence of malignant or non‐hepatic disease may prove to be a sufficiently safe approach for inducing graft tolerance in children receiving a LDLT in the future. This concept may reduce the burden of lifelong IS.     

Unusual spontaneous porto‐systemic shunt: The importance of diagnosing non‐anatomical porto‐systemic shunts to improve portal flow in pediatric living–related liver transplantation. Case report

Collateral circulation secondary to liver cirrhosis may cause the development of large PSSs that may steal flow from the main portal circulation. It is important to identify these shunts prior to, or during the transplant surgery because they might cause an insufficient portal flow to the implanted graft. There are few reports of “steal flow syndrome” cases in pediatrics, even in biliary atresia patients that may have portal hypoplasia as an associated malformation. We present a 12‐month‐old female who received an uneventful LDLT from her mother, and the GRWR was 4.8. During the early post‐operative period, she became hemodynamically unstable, developed ascites, and altered LFT. The post‐operative ultrasound identified reversed portal flow, finding a non‐anatomical PSS. A 3D CT scan confirmed the presence of a mesocaval shunt through the territory of the right gonadal vein, draining into the right iliac vein, with no portal inflow into the liver. The patient was re‐operated, and the shunt was ligated. An intraoperative Doppler ultrasound showed adequate portal inflow after the procedure; the patient evolved satisfactorily and was discharged home on day number 49. The aim was to report a case of post‐operative steal syndrome in a pediatric recipient due to a mesocaval shunt not diagnosed during the pretransplant evaluation.     

A case of pediatric live‐donor liver transplantation with a left lateral segment reduction by a linear stapler after reperfusion

In pediatric LDLT, graft reduction is sometimes required because of the graft size mismatch. Dividing the portal triad and hepatic veins with a linear stapler is a rapid and safe method of reduction. We herein present a case with a left lateral segment reduction achieved using a linear stapler after reperfusion in pediatric LDLT. The patient was a male who had previously undergone Kasai procedure for biliary atresia. We performed the LDLT with his father's lateral segment. According to the pre‐operative volumetry, the GV/SLV ratio was 102.5%. As the patient's PV was narrow, sclerotic and thick, we decided to put an interposition with the IMV graft of the donor between the confluence and the graft PV. The graft PV was anastomosed to the IMV graft. The warm ischemic time was 34 min, and the cold ischemic time was 82 min. The ratio of the graft size to the recipient weight (G/R ratio) was 4.2%. After reperfusion, we found that the graft had poor perfusion and decided to reduce the graft size. We noted good perfusion in the residual area after the lateral edge was clamped with an intestinal clamp. The liver tissue was sufficiently fractured with an intestinal clamp and then was divided with a linear stapler. The final G/R ratio was 3.6%. The total length of the operation was 12 h and 20 min. The amount of blood lost was 430 mL. No surgical complications, including post‐operative hemorrhage and bile leakage, were encountered. We believe that using the linear stapler decreased the duration of the operation and was an acceptable technique for reducing the graft after reperfusion.     

Living-donor liver transplantation for propionic acidemia

Propionic acidemia is a rare autosomal recessive disorder affecting the catabolism of branched-chain amino acids because of a genetic defect in PCC. Despite the improvements in medical treatment with protein restriction, sufficient caloric intake, supplementation of l-carnitine, and metronidazole, patients with the severe form of propionic acidemia have life-threatening metabolic acidosis, hyperammonemia, and cardiomyopathy, which results in serious neurologic sequelae and sometimes death. This study retrospectively reviewed three children with neonatal-onset propionic acidemia who received LDLT. Between November 2005 and December 2010, 148 children underwent LDLT, with an overall patient survival of 90.5%, in our center. Three patients were indicated for transplantation because of propionic acidemia. All recipients achieved a resolution of metabolic derangement and better quality of life with protein restriction and medication, although urine methylcitrate and serum propionylcarnitine levels did not decrease markedly. LT can reduce the magnitude of progressive cardiac/neurologic disability as a result of poor metabolic control. Further evaluation is therefore required to determine the long-term suitability of this treatment modality.     

Lifesaving liver transplantation for multi‐organ failure caused by Bacillus cereus food poisoning

Bacillus cereus is a spore‐forming, gram‐positive bacterium that causes food poisoning presenting with either emesis or diarrhea. Diarrhea is caused by proteinaceous enterotoxin complexes, mainly hemolysin BL, non‐hemolytic enterotoxin (NHE), and cytotoxin K. In contrast, emesis is caused by the ingestion of the depsipeptide toxin cereulide, which is produced in B. cereus contaminated food, particularly in pasta or rice. In general, the illness is mild and self‐limiting. However, due to cereulide intoxication, nine severe cases with rhabdomyolysis and/or liver failure, five of them lethal, are reported in literature. Here we report the first case of life‐threatening liver failure and severe rhabdomyolysis in this context that could not be survived without emergency hepatectomy and consecutive liver transplantation.     

Health‐related quality of life and sleep among Chinese children after living donor liver transplantation

LDLT is a well‐established treatment for most terminal liver diseases in children. Survival rates have improved, yet few studies have considered HRQoL or sleep problems in LDLT recipients. In this cross‐sectional study, we enrolled 51 children who had undergone LDLT in Renji Hospital. PedsQL^? 4.0 Generic Core Scales, PedsQL^? 3.0 Transplant Module, and Pediatric Sleep Questionnaire were used to assess outcomes. Of all participants, 11.8% (6/51) reported low total HRQoL scores. Participants’ scores on most HRQoL subscales were comparable to the scores of healthy children. However, compared with solid organ transplant recipients, LDLT recipients scored significantly lower in About My Medicines II (t = 3.092, p = 0.002) and Worry (t = 2.760, p = 0.006). Sleep problems (41.2%) were common among participants. Hierarchical regression analyses showed that SRBD accounted for significant variance in HRQoL on total generic HRQoL (R² = 0.446, p < 0.001), psychosocial health (R² = 0.372, p = 0.001), physical health (R² = 0.345, p = 0.003), total transplant‐specific HRQoL (R² = 0.514, p < 0.001), About My Medicines I (R² = 0.365, p = 0.013), My Transplant and Others (R² = 0.334, p = 0.005), Pain and Hurt (R² = 0.544, p < 0.001), Worry (R² = 0.401, p = 0.001), Treatment Anxiety (R² = 0.526, p < 0.001), How I Look (R² = 0.221, p = 0.040), and Communication (R² = 0.343, p = 0.012). In conclusion, sleep problems are non‐negligible in children after LDLT and predicted significant variance on HRQoL.     

Trends in pediatric liver transplant donors and deceased donor circumstance of death in the United States, 2002‐2015

While much of the discussion regarding expanding the donor pool for pediatric liver transplantation has surrounded the use of technical variant grafts, little attention has been directed toward changes in the deceased donor population. The aim of this study was to investigate trends in the circumstance of the death of deceased donors used for pediatric liver transplantation. All pediatric liver transplant recipients transplanted between 2002 and 2015 were identified in the UNOS database and were categorized based on the donor circumstance of death. There was no significant correlation between year of transplantation and number of pediatric liver transplants performed, pediatric donors, split livers, or living donors. There was a significant downward trend in donors from motor vehicle fatalities and an upward trend in suicide, non‐MVA, and death due to natural causes. There was also an upward trend in drowning, one of the most common mechanisms of death among non‐MVA in 2015. While the number of donors who died in MVA has fallen, the number of deceased donors who died from suicide, natural causes, and non‐MVA, especially drowning, has increased, maintaining the overall number of pediatric deceased donor livers transplanted.     

Centrilobular necrosis as a manifestation of venous outflow block in pediatric malnourished liver transplant recipients – case reports

Gibelli NEM, Tannuri ACA, Andrade WC, Ricardi LRS, Tannuri U. Centrilobular necrosis as a manifestation of venous outflow block in pediatric malnourished liver transplant recipients – case reports. Abstract: CLN is a frequent histological finding in biopsies after pediatric: LT, and its pathogenesis has not yet been fully clarified and has different causes. Among the vascular causes, VOB is sometimes difficult to diagnose, especially when technical variants such as split‐liver, reduced‐liver, or living‐related LT are utilized. Three liver‐transplanted malnourished children (ages 12, 20, and 28 months) developed altered LFTs and post‐operative ascites with right pleural effusion (two cases) and jaundice (one case). Doppler ultrasound examinations were normal and liver biopsies showed CLN interpreted as severe ACR. There were no responses to the medical treatment. Additional investigation with CT angiography suggested obstructed hepatic vein drainage, which was confirmed by interventional radiology and angioplasty of the anastomosis between the hepatic vein and the inferior vena cava, with clinical and histological resolution. It is concluded that in malnourished children undergoing LT with technical variations, in which the occurrence of severe ACR is usually less common because of the severity of the patient condition, the finding of CLN should raise the possibility of VOB, so that excessive immunosuppression and its consequences can be avoided.