Impaired Neurocognitive Performance in Children after Liver Transplantation.

OBJECTIVES: To assess longitudinal neurocognitive development after liver transplantation and evaluate factors associated with neurocognitive performance. STUDY DESIGN: Data from neurocognitive testing of 65 children (aged <18 years) who underwent liver transplantation at Oslo University Hospital between 1995 and 2018 were collected from the testing program after transplantation. The parent-reported version of the Behavior Rating Inventory of Executive Function was used to assess executive function. RESULTS: A total of 104 neurocognitive tests were conducted on 65 patients. At the first test, conducted at a median of 4.1 years (IQR, 1.5-5.3 years) after transplantation and at a median age of 6.7 years (IQR, 5.4-10.5 years), the mean full-scale IQ (FSIQ) was 91.7 ± 14, and the mean verbal comprehension index was 92.0 ± 14.5. In the 30 patients tested more than once, there was no significant difference in FSIQ between the first test at a median age of 5.8 years (IQR, 5.2-8.5 years) and the last test at a median age of 10.8 years (IQR, 9.8-12.9 years) (87.4 ± 12.9 vs 88.5 ± 13.2; P = .58). Compared with the patients who underwent transplantation a age >1 year (n = 35), those who did so at age <1 year (n = 30) had a lower FSIQ (87.1 ± 12.6 vs 96.6 ± 13.8; P = .005) and lower verbal comprehension index (87.3 ± 13.8 vs 95.4 ± 13.0; P = .020). Age at transplantation (P = .005; adjusted for cholestasis: P = .038) and transfusion of >80 mL/kg (P = .004; adjusted for age at transplantation: P = .046) were associated with FSIQ. CONCLUSIONS: Young age at transplantation and large blood transfusions during transplantation are risk factors for poor neurocognitive performance later in life. Children who undergo transplantation before 1 year of age have significantly lower neurocognitive performance compared with those who do so later in childhood. Cognitive performance did not improve over time after transplantation.

Mycophenolate mofetil use is associated with reduced incidence of food allergy in liver transplanted children.

OBJECTIVES: The incidence of food allergy in children following liver transplantation is high and the pathogenesis is still not known. We aimed to identify risk factors for development of food allergies in liver transplant children. METHODS: 107 children and adolescents who underwent liver transplantation from 1999 to 2019 were included. Data were retrospectively collected from medical records included total and specific IgE, eosinophil cationic protein and eosinophil count 12 months after transplantation and at yearly follow up (median follow-up). RESULTS: 24/107 (22%) patients reported clinical food reactions. Median time from transplantation to debut of food allergy was 1.6 (IQR 0.6-3.3) years. Mycophenolate mofetil (MMF) was discontinued in 24/78 patients (31%) due to side effects. Children treated with MMF in addition to tacrolimus one year after transplantation reported less food allergy (12.5% vs. 37.8%, p=0.003) and sensitization to food allergens one year after transplantation (8.9% vs. 17.8%, p=0.02) than those not receiving MMF. Tacrolimus trough levels did not differ between the patients treated with MMF and those who were not. Treatment with MMF two years after transplantation was associated with less food allergy (p=0.001) and food sensitization (p=0.002), also when adjusted for age at transplantation (p=0.006 and p=0.03, respectively) or for use of basilixmab (p=0.015 and p=0.018, respectively). Basiliximab was also associated with less food allergy. CONCLUSIONS: Use of MMF one and two years after transplantation was associated with less food allergy and sensitization against food allergens. The effect of MMF was not due to reduced trough levels of of tacrolimus. An infographic is available for this article at: https://links.lww.com/MPG/C821.

Cancer After Liver Transplantation in Children and Young Adults: A Population-Based Study From 4 Nordic Countries.

Cancer after liver transplantation (LT) constitutes a threat also for young recipients, but cancer risk factors are usually absent in children and large studies on the cancer risk profile in young LT recipients are scarce. Data of patients younger than 30 years who underwent LT during the period 1982-2013 in the Nordic countries were linked with respective national cancer registries to calculate standardized incidence ratios (SIRs). A total of 37 cancer cases were observed in 923 patients with 7846 person-years of follow-up. The SIR for all cancer types, compared with the matched general population, was 9.8 (12.4 for males and 7.8 for females). Cumulative incidence of cancer adjusted for the competing risk of death was 2% at 10 years, 6% at 20 years, and 22% at 25 years after LT. Non-Hodgkin lymphoma was the most common cancer type (n = 14) followed by colorectal (n = 4) and hepatocellular cancer (n = 4). Age was a significant risk factor for cancer, and the absolute risk of most cancers (except for lymphoma) increased considerably in young adults older than 20 years. The cancer risk pattern is different in pediatric and young LT patients compared with adult recipients. The striking increase in cancer incidence in young adulthood after the second decade of life deserves further consideration in transition programs.

Outcome for biliary atresia patients treated at a low-volume centre.

OBJECTIVES: The importance of case load for treatment of extrahepatic biliary atresia (BA) is debated. The aim of this study was to register results of BA treatment in a small volume centre. METHODS: Retrospective chart review study of patients with BA treated from 2000 to 2017. The institutional review board approved the study. RESULTS: Forty-five babies were identified of which 42 (93%) are alive. Forty-one patients had a Kasai portoenterostomy (PE), two had a hepaticojejunostomy and two had a primary liver transplantation. The age at PE/hepaticojejunostomy was median 63 (4-145 days). Seven surgeons performed the operations, and the median duration of the diagnostic work-up was 8 (3-24) days. Clearance of jaundice was achieved in 23/43 (53%) babies, and 3- and 5-year native liver survival was 47% and 40%, respectively. Clearance of jaundice post-PE/hepaticojejunostomy was a strong predictor of native liver survival (adjusted OR: 0.027; 95%; p = .009). Plasma level of conjugated bilirubin at time of referral was also a significant predictor of native liver survival (adjusted OR: 1.053; p = .017). CONCLUSION: A small volume centre may achieve satisfactory results for BA patients. The study has, however, identified factors that may further improve results; earlier referral, optimizing diagnostic work-up and establishing one dedicated surgical team.

No effect of treatment with intravenous ganciclovir on Epstein-Barr virus viremia demonstrated after pediatric liver transplantation.

EBV after pediatric LT is a risk factor for PTLD. We wanted to evaluate the effect of intravenous ganciclovir on EBV viremia and to identify risk factors for chronic EBV viremia. All pediatric patients who underwent LT in Norway from 2002 until 2015 were reviewed. Twenty-two of 38 patients with viremia were treated with intravenous ganciclovir for a median of 22 (21-38) days. Treated and untreated patients were not different with respect to EBV seroconversion prior to transplantation or age at transplantation, but treated patients had significantly earlier viremia after transplantation (P=.005). There was no difference in the proportion of patients with reduction in virus load in patients treated with ganciclovir compared to untreated patients at 8 weeks. After 1 year, five of 19 patients treated with ganciclovir and six of 14 untreated patients had reduced virus load compared to start of viremia (P=.27). In conclusion, treatment with intravenous ganciclovir did not change the proportion of patients with reduction in EBV load at 8 weeks and 1 year after viremia. Younger age at transplantation, short time from transplantation to viremia, and lack of EBV seroconversion prior to transplantation were significant predictors of chronic EBV viremia.

Effect of operator experience and frequency of procedure performance on complication rate after ultrasound-guided percutaneous liver biopsies.

OBJECTIVE: The aim of the present study was to assess whether the complication rate after ultrasound-guided percutaneous liver biopsies in children is affected by how frequently the procedure is performed by the operator. METHODS: Medical charts and ultrasound descriptions of 311 ultrasound-guided percutaneous liver biopsy procedures performed by 18 radiologists at a single center from 2000 to 2011 were reviewed. Postbiopsy ultrasound the following day was performed after 97% of the procedures. RESULTS: There were no differences in the procedure-associated rate of major bleeding incidents (2.2% vs 0.8%, P = 0.38), minor bleeding incidents (15.2% vs 10.2%, P = 0.31), or abdominal pain (13.0% vs 10.6%, P = 0.61) among operators who performed ≤10 procedures and those who performed >10 procedures during the study period. A higher rate of minor bleeding incidents were recorded after liver biopsy when operators had performed <10 biopsies compared with operators who had performed >20 pediatric liver biopsies during the study period (odds ratio 3.4 [1.3-9.1], P = 0.02). No association between the number of biopsies performed by the operator during the 2 years preceding the date of the biopsy and complications was found. CONCLUSIONS: Major complications are infrequent after pediatric liver biopsies and no relation between operator experience and major complications was found. We found a significant, but minor, effect of operator procedure frequency on the rate of minor bleeding incidents after ultrasound-guided pediatric liver biopsies.

Evaluation of risk factors for bleeding after liver biopsy in children.

OBJECTIVES: Acetylsalicylic acid is used in liver-transplanted children to prevent thrombosis of the hepatic artery. We evaluated whether acetylsalicylic acid and other risk factors were associated with bleeding after percutaneous liver biopsy. METHODS: Medical charts, laboratory results, imaging studies, and anesthesia charts of 275 ultrasound-guided liver biopsy procedures in 190 children were reviewed. A total of 178 biopsies were performed on native livers and 97 on transplanted livers. RESULTS: Three major and 28 minor bleeding incidents were found. The mortality rate was 0%. Acetylsalicylic acid had been given the last 5 days before 55 of the biopsy procedures and no increased risk of bleeding was found (odds ratio 0.96 [0.37-2.26]; P = 1.00). Low-molecular-weight heparin and biopsies from focal lesions were risk factors for bleeding complications. Acute liver failure was associated with increased risk for major complications (odds ratio 26.1 [3.3-205]; P = 0.01) and was a risk factor for major bleeding. Postbiopsy ultrasound the day after the procedure (n = 266 [96% of 275 biopsies]) revealed minor bleeding after 7.1% of the biopsies and after 2.6% of the ultrasounds revealed unsuspected bleeding, but none of these required intervention. CONCLUSIONS: Ultrasound-guided liver biopsy in children is a procedure with a low rate of major complications and a high rate of minor bleeding not requiring intervention. Treatment with low-dose acetylsalicylic acid did not increase bleeding incidence or total complication rate. Low-molecular-weight heparin and biopsies from focal lesions were risk factors for bleeding complications. Routine ultrasound the day after the procedure did not change handling of the patients.

Intestinal and multivisceral transplantation in patients with chronic intestinal failure.

BACKGROUND: Patients with chronic intestinal failure are treated primarily with parenteral nutrition, often for many years. If serious complications arise for intravenous nutritional therapy, it is possible to perform intestinal or multi-organ transplantation in selected patients. We have established a collaboration with Professor Michael Olausson at Sahlgrenska University Hospital in Gothenburg and Professor Andreas Tzakis at the Jackson Memorial Hospital in Miami, USA, to provide an option for Norwegian patients with chronic intestinal failure. MATERIAL AND METHOD: Retrospective long-term study of seven patients (five in Gothenburg and two in Miami) with chronic intestinal failure who underwent intestinal or multi-organ transplantation (ventricle, duodenum, pancreas and small intestine) in the period 2001-2009. At the same time, liver and kidney transplantations were performed on six and two patients, respectively. RESULTS: Four of seven patients are alive and have a good quality of life 24-120 months after the transplantation. The graft function is satisfactory, so that the patients' food intake is mainly oral. Three patients died following a serious infection one, ten and 24 months, respectively, after transplantation took place. INTERPRETATION: Intestinal and multi-organ transplantation is a demanding and expensive treatment. Life-long multi-disciplinary follow-up of the patients is necessary after the transplantation in order to ensure early diagnosis of rejection and infections. Collaboration with international centres has given Norwegian patients with chronic intestinal failure an option of transplantation with satisfactory long-term results.

[Liver transplantation in Norway through 25 years]. / Levertransplantasjon i Norge gjennom 25 år.

BACKGROUND: In Norway, liver transplantation has been the treatment of choice for irreversible acute and chronic liver failure for 25 years. The aim of this article is to present a summary of the results obtained. MATERIAL AND METHODS: All liver transplants performed in Norway in the period 25.02.84-31.12.08 have been reviewed retrospectively with respect to patient and donor epidemiology, survival and recurrence. RESULTS: 651 transplants have been performed in this period. The annual number of transplants increased gradually up to the year 2000 (31), and more steeply afterwards - to 79 in 2008. Also the number of organ donations has increased and reached 98 (20 pr. million inh.) in 2008. 5-year patient survival was 53 % in the period 1984-1994. In the period 2001-2008, 1-year survival was 90 % and 5-year survival was 83 %. INTERPRETATION: The gradual improvement of results should be interpreted in light of improvements within transplant surgery, medicine and anaesthesiology and the increased local experience due to the increasing number of transplants performed. The transplant centre at Rikshospitalet has developed into being among the largest of its kind within the Nordic Countries and the results compare well with the best international data.

Comparative levels of psychological distress, stress symptoms, depression and anxiety after childbirth--a prospective population-based study of mothers and fathers.

OBJECTIVE: To compare maternal and paternal psychological responses following birth of a healthy baby; and to explore predictors of parental psychological distress. DESIGN: A prospective, longitudinal, population-based cohort study. SETTING: A Norwegian district general hospital. POPULATION: One hundred and twenty-seven mothers and 122 fathers were included. METHODS: Eligible consenting parents were enrolled. The assessments, which were performed zero to four days after birth, at six weeks and at six months, included General Health Questionnaire-28 (GHQ-28), State Anxiety Inventory and Impact of Event Scale. The response rates at the three occasions were 97%, 85% and 71%. MAIN OUTCOME MEASURES: Symptoms of intrusion, avoidance, arousal and psychological distress including anxiety, depression, social dysfunction and somatisation. RESULTS: Clinically important psychological distress was reported by 37% of the mothers and 13% of the fathers a few days after childbirth (P < 0.001). Severe intrusive stress symptoms were reported by 9% and 2% of mothers and fathers, respectively (P = 0.002). Level of intrusive stress was the outcome that differed most clearly between mothers and fathers at all three points of time. Being a single parent, multiparity and a previous traumatic birth were significant independent predictors of acute maternal psychological distress. After six weeks and six months, the level of psychological distress including symptoms of depression fell to levels found in the general population. CONCLUSIONS: Childbirth does not seem to trigger long term psychological distress in most parents. Clinically important psychological distress occurred more frequently in mothers than in fathers. Acute maternal psychological distress was predicted by being a single parent, being multiparous, and having a previous traumatic birth.