COVID-19 infection in patients on long-term home parenteral nutrition for chronic intestinal failure.

BACKGROUND AND AIMS: To investigate the incidence and the severity of COVID-19 infection in patients enrolled in the database for home parenteral nutrition (HPN) for chronic intestinal failure (CIF) of the European Society for Clinical Nutrition and Metabolism (ESPEN). METHODS: Period of observation: March 1st, 2020 March 1st, 2021. INCLUSION CRITERIA: patients included in the database since 2015 and still receiving HPN on March 1st, 2020 as well as new patients included in the database during the period of observation. Data related to the previous 12 months and recorded on March 1st 2021: 1) occurrence of COVID-19 infection since the beginning of the pandemic (yes, no, unknown); 2) infection severity (asymptomatic; mild, no-hospitalization; moderate, hospitalization no-ICU; severe, hospitalization in ICU); 3) vaccinated against COVID-19 (yes, no, unknown); 4) patient outcome on March 1st 2021: still on HPN, weaned off HPN, deceased, lost to follow up. RESULTS: Sixty-eight centres from 23 countries included 4680 patients. Data on COVID-19 were available for 55.1% of patients. The cumulative incidence of infection was 9.6% in the total group and ranged from 0% to 21.9% in the cohorts of individual countries. Infection severity was reported as: asymptomatic 26.7%, mild 32.0%, moderate 36.0%, severe 5.3%. Vaccination status was unknown in 62.0% of patients, non-vaccinated 25.2%, vaccinated 12.8%. Patient outcome was reported as: still on HPN 78.6%, weaned off HPN 10.6%, deceased 9.7%, lost to follow up 1.1%. A higher incidence of infection (p = 0.04), greater severity of infection (p < 0.001) and a lower vaccination percentage (p = 0.01) were observed in deceased patients. In COVID-19 infected patients, deaths due to infection accounted for 42.8% of total deaths. CONCLUSIONS: In patients on HPN for CIF, the incidence of COVID-19 infection differed greatly among countries. Although the majority of cases were reported to be asymptomatic or have mild symptoms only, COVID-19 was reported to be fatal in a significant proportion of infected patients. Lack of vaccination was associated with a higher risk of death.

Characterization of Colonoscopies in Preschool Children.

OBJECTIVES: The indications, diagnostic yield, complications, and cecal and ileal intubation rates (CIR and IIR) for colonoscopies in children aged <6 years, denoted preschoolers, is unclear since there is limited information for this group. We aimed to describe the above parameters in our cohort of preschoolers undergoing a colonoscopy. METHODS: Retrospective review of all colonoscopies in a tertiary pediatric hospital between December 1, 2014 to December 31, 2020 was undertaken. Demographic factors, indication for colonoscopy, extent of colonoscopy, CIR, IIR, and histologic findings were noted. Preschoolers were further subdivided into those aged <2 years, and those aged 2 to <6 years. RESULTS: One thousand six hundred seventy-one total colonoscopies were performed, of which 13% (n = 219) were in preschoolers with median age 3.9 (range 0.3-5.9) years. Most common indications in preschoolers were rectal bleeding 35% (n = 78), inflammatory bowel disease 24% (n = 53), diarrhea 13% (n = 30), iron-deficiency anemia 11% (n = 25), and abdominal pain 7% (n = 16). IIR and CIR were lower in preschoolers compared to older children, 81% vs 92% ( P = 0.0001), and 93% vs 96.4% ( P = 0.02), respectively, and even lower in those aged <2 years, 48.1% IIR ( P = 0.0001) and 85.1% CIR. Juvenile polyps, 31% (n = 27), were the most common positive finding in preschool children. CONCLUSION: Rectal bleeding was the most common indication and juvenile polyps the most common finding at colonoscopy in preschoolers. A high IIR is achievable in young children but rates are increasingly lower the younger the child.

Hepatocellular carcinoma requiring liver transplantation in hereditary tyrosinemia type 1 despite nitisinone therapy and α1-fetoprotein normalization.

BACKGROUND: Hereditary tyrosinemia type 1 is a rare metabolic condition associated with an increased risk of hepatocellular carcinoma. Nitisinone (2-[2-nitro-4-trifluoromethylbenzoyl]-1,3-cyclohexanedione, NTBC) treatment has reduced but not eliminated the risk. The delayed initiation of nitisinone treatment, and persistently abnormal α1-fetoprotein (AFP) levels are recognized to be risk factors for late-onset hepatocellular carcinoma. We report three children diagnosed and treated with nitisinone since infancy who developed hepatocellular carcinoma despite long-term normalization of AFP. METHODS: A retrospective review of all patients with tyrosinemia on nitisinone managed at our center was undertaken. Patient demographics, age at diagnosis, duration of therapy, timing of AFP normalization, and radiographic imaging findings were noted. RESULTS: Three patients at our center with tyrosinemia type 1 developed hepatocellular carcinoma 9-13 years after diagnosis despite long-term nitisinone therapy and normalization of AFP. Two patients developed new nodules on imaging with an elevation of AFP leading to the diagnosis and subsequent liver transplant. The third patient proceeded with liver transplant because of a very nodular liver and increasing splenomegaly despite normal AFP and no change in surveillance gadoxetate magnetic resonance imaging. Early hepatocellular carcinoma was found in her liver explant. All three patients were cirrhotic at diagnosis. CONCLUSIONS: Patients with hereditary tyrosinemia type 1, especially those already cirrhotic at diagnosis, remain at high risk of developing hepatocellular carcinoma despite long-term nitisinone therapy and AFP normalization, and warrant close monitoring and surveillance.

Chronic Intestinal Failure in Children: An International Multicenter Cross-Sectional Survey.

Background: The European Society for Clinical Nutrition and Metabolism database for chronic intestinal failure (CIF) was analyzed to investigate factors associated with nutritional status and the intravenous supplementation (IVS) dependency in children. Methods: Data collected: demographics, CIF mechanism, home parenteral nutrition program, z-scores of weight-for-age (WFA), length or height-for-age (LFA/HFA), and body mass index-for-age (BMI-FA). IVS dependency was calculated as the ratio of daily total IVS energy over estimated resting energy expenditure (%IVSE/REE). Results: Five hundred and fifty-eight patients were included, 57.2% of whom were male. CIF mechanisms at age 1−4 and 14−18 years, respectively: SBS 63.3%, 37.9%; dysmotility or mucosal disease: 36.7%, 62.1%. One-third had WFA and/or LFA/HFA z-scores < −2. One-third had %IVSE/REE > 125%. Multivariate analysis showed that mechanism of CIF was associated with WFA and/or LFA/HFA z-scores (negatively with mucosal disease) and %IVSE/REE (higher for dysmotility and lower in SBS with colon in continuity), while z-scores were negatively associated with %IVSE/REE. Conclusions: The main mechanism of CIF at young age was short bowel syndrome (SBS), whereas most patients facing adulthood had intestinal dysmotility or mucosal disease. One-third were underweight or stunted and had high IVS dependency. Considering that IVS dependency was associated with both CIF mechanisms and nutritional status, IVS dependency is suggested as a potential marker for CIF severity in children.

The effects of child anxiety and depression on concordance between parent-proxy and self-reported health-related quality of life for pediatric liver transplant patients.

BACKGROUND: HRQOL is a key outcome following pediatric LT. Parent-proxy reports may substitute for patients unable to report their own HRQOL. This study compared parent-proxy and self-reported HRQOL in children who have undergone LT. METHODS: Pediatric LT recipients between the ages of 8 and 18 years, and a parent, completed self and proxy versions of the PeLTQL questionnaire, PedsQL Generic and Transplant modules, and standardized measures of depression and anxiety. RESULTS: Data from 129 parent-patient dyads were included. Median parent age was 44 years, and most (89%) were mothers. Median patient age was 2.5 years at LT and 13.6 years at the time of study participation. Parents had significantly lower scores than patients on PedsQL total generic (70.8 ± 18.5 and 74.3 ± 19.0, p = .01), PeLTQL coping and adjustment (63.0 ± 15.6 and 67.3 ± 16.2, p < .01), and social-emotional (66.3 ± 14.9 and 71.9 ± 15.6, p < .001) domains. Higher patient anxiety and depression were related to larger absolute differences between parent-proxy and self-reported scores on all HRQOL measures (all p < .05). In this disparity, parents reported higher HRQOL scores than their child as self-reported anxiety and depression scores increased. CONCLUSIONS: Differences in concordance between parent-proxy and self-reported HRQOL scores can be more prominent when children have more symptoms of anxiety and depression. Children's mental health symptoms should be queried, if feasible, when interpreting differences in parent and child reports of HRQOL.

Liver disease in the older child.

Liver disease in children tends to present either as: (i) an acute hepatitis with or without jaundice; (ii) incidental finding of abnormal liver function tests; or (iii) from a complication of portal hypertension with either haematemesis and/or incidental splenomegaly. Acute hepatitis may result from acute infection, prescribed or other drugs, ischaemia or vascular causes, autoimmune hepatitis, or idiopathic liver failure. Non-alcoholic fatty liver disease is now the most likely reason for abnormal liver function tests but medications, metabolic disease, cholangiopathy and non-liver causes should be considered. Autoimmune hepatitis and alpha-1-antitrypsin deficiency are the most likely causes of insidious liver disease. An international normalised ratio uncorrected by vitamin K reflects the severity of liver synthetic dysfunction, but not propensity to bleed. Creatine kinase helps to differentiate muscle from liver disease in patients with raised transaminases. Doppler ultrasound of hepatic vasculature is useful when assessing splenomegaly to differentiate extra-hepatic portal hypertension from inherent liver disease.

Outcomes for children after second liver transplantations are similar to those after first transplantations: a binational registry analysis.

OBJECTIVE: To assess long term graft and patient survival after donor liver retransplantation in children in Australia and New Zealand during 1986-2017; to determine the factors that influence survival. DESIGN: Retrospective cohort analysis (registry data). SETTING, PARTICIPANTS: Australia and New Zealand Liver Transplant Registry data for all liver retransplantations in children (under 18 years of age), 1986-2017, in all four paediatric and six adult liver transplantation centres in the two countries. MAIN OUTCOME MEASURES: Graft and patient survival at one, 5, 10 and 15 years. RESULTS: 142 liver retransplantations were undertaken in children (59 during 1986-2000, 83 during 2001-2017). Kaplan-Meier survival analysis indicated that survival was significantly greater during 2001-2017 than 1986-2000 (P < 0.001). During 2001-2017, graft survival one year after retransplantation was 84%, at 5 years 75%, at 10 years 70%, and at 15 years 54%; patient survival was 89% at one year, 87% at 5 years, 87% at 10 years, and 71% at 15 years. Median time between transplantations was 0.2 years (IQR, 0.03-1.4 years) during 1986-2000, and 1.8 years (IQR, 0.1-6.8 years) during 2001-2017 (P = 0.002). The proportion of graft failures that involved split grafts was larger during 2001-2017 (35 of 83, 42%) than 1986-2000 (10 of 59, 17%). Graft type, cause of graft failure, and number of transplants did not influence survival following retransplantation. CONCLUSION: Survival for children following retransplantation is excellent. Graft survival is similar for split and whole grafts. Children on the liver waiting list requiring retransplantation should have the same access to donor grafts as children requiring a first transplant.

Multidisciplinary approach to paediatric aerodigestive disorders: A single-centre longitudinal observational study.

AIM: Aerodigestive clinics (ADCs) are multidisciplinary programmes for the care of children with complex congenital or acquired conditions affecting breathing, swallowing and growth. Our objective was to describe the demographic, clinical, etiological and investigational profile of children attending the inaugural ADC at a tertiary paediatric centre in Queensland. METHODS: Children referred to the ADC at Queensland Children's Hospital from August 2018 to December 2019 were included. Data on clinical, growth and lung function parameters, bronchoscopy and upper gastrointestinal endoscopy findings, thoracic imaging and comorbidities were retrospectively analysed. RESULTS: Fifty-six children (median (range) age 4 years (3 months-15 years); 18 female) attended the ADC during this 17-month period. Forty-six (82%) children had previous oesophageal atresia with tracheo-oesophageal fistula; 43 of these were type C. Previous isolated oesophageal atresia, congenital diaphragmatic hernia and congenital pulmonary malformation were the underlying disorder in three (5%) children each, with one child having a repaired laryngeal cleft. Vertebral Anal Tracheo Esophageal Renal Limb anomalies (VACTERL)/Vertebral Anal Tracheo Esophageal renal anomalies (VATER) association was seen in 21 (38%) children. Growth was adequate (median weight and body mass index z-score -0.63 and -0.48, respectively). Thirty-four (61%) children reported ongoing wet cough, with 12 (21%) requiring previous hospital admission for lower respiratory tract infection. Fourteen (25%) had bronchiectasis on computed tomography chest and 33 (59%) had clinical tracheomalacia, apparent on bronchoscopic examination in 21 patients. Dysphagia was reported in 15 (27%) children, 11 (20%) were gastrostomy feed-dependent and 5 (9%) had biopsy-proven eosinophilic oesophagitis. CONCLUSION: High proportion of children attending the ADC have ongoing respiratory symptoms resulting in chronic pulmonary suppuration and bronchiectasis. Potential benefits of this model of care need to be studied prospectively to better understand the outcomes.

Recurrent Abdominal Pain in Children: Is Colonoscopy Indicated?

Recurrent abdominal pain (RAP) in children is common, with most functional in origin. Colonoscopy has sometimes been performed to exclude pathology but its role is unclear. Our aim therefore was to assess the diagnostic yield and role of colonoscopy in these children. Retrospective review of consecutive colonoscopies in a tertiary pediatric hospital between November 2011 and October 2015 was undertaken. Only those with RAP as an indication for procedure were included. Chart review of patients with pain was undertaken to ensure they fulfilled Rome IV criteria. Patient demographics, indication for procedure, and adjunct preprocedure tests were noted. Statistical analyses were performed with SPSS software. A total of 652 colonoscopies were performed, of which 68 (10%) had abdominal pain as one of the indications, and was the sole indication in 15 (2%) patients. All 68 patients had preprocedure serum inflammatory markers measured and 53% (36/68) had stool calprotectin. Positive histology was found in 10% (7/68) including Crohn disease (n = 3), polyps (n = 2), and microscopic colitis (n = 2). The remaining 61 patients had normal colonoscopy and ileocolonic biopsies. Of the 36 patients 5 had raised fecal calprotectin, and all had abnormal histology. Serum inflammatory markers were raised in 4 patients and all also had abnormal calprotectin. No patient with isolated abdominal pain had positive histology. Rectal bleeding was the only associated indication to predict abnormal histology (P = 0.019). Colonoscopy is likely not warranted in children with RAP without bleeding, weight loss, or altered bowel habit. Fecal calprotectin is useful in helping predict positive findings.

Bone Mineral Density of Very Long-term Survivors After Childhood Liver Transplantation.

OBJECTIVES: Liver transplant patients are at risk of osteopenia and fractures but limited information is available in long-term survivors after childhood transplantation. This study aimed to assess bone mineral density (BMD) of very long-term, >5 years, survivors after liver transplantation in childhood. METHODS: Patients aged <18 years at transplant, having survived >5 years after transplant were potentially eligible but only those with ongoing review in our state were included. Dual-energy x-ray absorptiometry (DXA) was used to measure BMD. Patients aged <20 years had lumbar spine (LS) and total body (TB) measurements whereas those aged 20 years or more had LS and femoral neck but not TB. BMD z-scores for LS and TB, if available, were used in this study. BMD z-score ≤-2.0 was considered reduced. Pre-pubertal children had radiologic bone age assessment. RESULTS: Forty-two patients, 17 boys, participated of whom 64% had biliary atresia. Median age at transplant was 2.22 (range 0.38-14.25) years; time since transplant 10.10 (5.01-25.98) years; and age at DXA 14.64 (6.59-38.07) years. Mean BMD z-scores were LS -0.15 ±â€Š1.07, and TB -0.76 ±â€Š1.14, with no sex difference noted. Four (9.5%) patients had reduced LS BMD, and although ongoing steroid use was more frequent in these patients, other comorbidities were likely important. Age at transplant, time since transplant, height, weight, and body mass index at DXA did not predict LS BMD. Pathologic fractures occurred in 2 of 42 (5%) patients; all within 18 months of transplant. CONCLUSIONS: Very long-term survivors after childhood liver transplant have LS BMD within the normal range.

Comparing swallowing of capsule to endoscopic placement of capsule endoscopy in children.

BACKGROUND AND AIM: Capsule endoscopy (CE) offers a method of directly visualizing areas of the small bowel not accessible by conventional endoscopy. Some children are unable to swallow the capsule requiring endoscopic placement under general anesthesia. The aim of the present study was to identify any differences between children requiring endoscopic placement and those able to swallow the capsule. METHODS: Retrospective chart review of consecutive CE in a tertiary pediatric center was conducted. Patient demographics, outcomes, and complications between the two groups were noted. Paired t-test comparing continuous variables and Fisher exact test for categorical data were used. RESULTS: A total of 104 CEs were performed in 88 patients, median age 12.8 (range: 1.6-18.5) years. Almost half, 49% (51/104), swallowed the capsule. Children requiring endoscopic placement were significantly younger (9.8 vs 14.2 years; P < 0.001), lighter (34.5 vs 54.9 kg; P < 0.0001), and had longer small intestinal transit time (308 vs 229 min; P < 0.0001). Positive findings were more likely in those who swallowed the capsule (50% vs 30%, P = 0.017), likely a reflection of the indications for procedure. Poor views were found in 30% (16/53) of patients in the endoscopic placement group due to iatrogenic bleeding from biopsies taken from concurrent procedures but did not affect outcome or subsequent patient management. CONCLUSIONS: CE is safe and well tolerated in children. Children requiring endoscopic placement were significantly younger, lighter, had longer small intestine transit time, and less likely to have positive findings. Concurrent biopsies during capsule placement increase the likelihood of inadequate views but did not affect outcome or management.

Family Impact and Infant Emotional Outcomes Following Diagnosis of Serious Liver Disease or Transplantation in Infancy.

OBJECTIVES: Research is lacking into the emotional effects on families of serious chronic illness in infants. We examined the effect of the diagnosis of serious liver disease in infants upon parent psychological symptoms and family functioning. We hypothesized that parent psychological symptoms, family functioning, and father engagement will predict infant emotional outcomes. METHODS: Parents of infants recently diagnosed with serious liver disease completed validated questionnaires about parent stress, family function, impact of the illness on the family, and father engagement. The measures were repeated after 1 year, with the addition of the Child Behavior Checklist (CBCL). RESULTS: Parents of 37 infants participated. Parent stress and family functioning scores were not elevated. Parent psychological symptoms, family function, and father engagement did not predict infant outcome. For mothers, infant diagnosis other than biliary atresia, number of outpatient visits, and impact of the illness on the family explained 32% of the variation in CBCL (P = 0.001). For fathers, socioeconomic status, infant diagnosis other than biliary atresia, whether the infant had had a transplant, and impact of the illness on the family explained 44% of the variation in CBCL (P < 0.001). CONCLUSIONS: Parents and families appear to be resilient in coping with serious infant illness. Infant diagnosis other than biliary atresia and parental perceptions of high impact of the illness on the family are indicators of negative emotional outcomes for infants with serious liver disease. Psychosocial interventions for infants with chronic illness should target reducing the impact of illness on the family.

Family adjustment and parenting stress when an infant has serious liver disease: the Australian experience.

OBJECTIVES: Parenting stress, problems in family functioning, and lack of fathers' engagement in treatment are associated with poor quality of life in children with chronic illnesses. The aim of the present study was to examine these characteristics in families of infants with serious liver disease in Australia, to inform the provision of mental health care for these families. METHODS: From September 2009 to May 2013, 42 parents of infants recently diagnosed as having serious liver disease (defined as liver disease that may require transplantation in the future) completed questionnaires about family function, impact of the infant's illness on the family, parent stress symptoms, and fathers' engagement in the care of the child. Participants were recruited from 4 metropolitan children's hospitals in Australia. RESULTS: Parents reported psychological symptoms at similar rates to normative populations. Their reports of family functioning were significantly below mean scores in previously published populations with a medically ill family member (population mean 1.89; mothers mean 1.59; fathers mean 1.61, P < 0.001). Disruption to family roles was significantly correlated with psychological symptoms for mothers (r = 0.48, P < 0.01) and fathers (r = 0.31, P < 0.05). Greater helpfulness of fathers was correlated with lower depression in mothers (r = -0.35, P < 0.05), and fathers' anxiety was correlated with their increased engagement (r = 0.40, P < 0.01). CONCLUSIONS: When parents report the presence of psychological symptoms, symptoms are likely to be present in both parents and are associated with difficulties adjusting to disrupted family roles. Father engagement may be protective of mothers' mental health.

Development and validation of the pediatric liver transplantation quality of life: a disease-specific quality of life measure for pediatric liver transplant recipients.

OBJECTIVES: To develop and validate a Pediatric Liver Transplantation Quality of Life (PeLTQL) questionnaire via an international multicenter collaboration. STUDY DESIGN: Item generation with 146 child and/or parent interviews (92 pediatric liver transplantation [LT] recipients) and 3 focus groups generated over 300 items. An item reduction questionnaire with 76 questions was completed by 320 participants (212 pediatric LT recipients). RESULTS: Frequency-importance product ranking, questionnaire formatting, and pre-testing resulted in a 26-item PeLTQL questionnaire. Factor analysis identified 3 domains: future health, coping and adjustment, and social-emotional. The validation phase was completed by 133 (46% male) LT recipients (aged 8-18 years). Internal consistency (Cronbach α = 0.86) and test-retest reliability (intraclass correlation coefficient = 0.85) were excellent. Mean patient PeLTQL score was 69.54 ± 13.06. Construct validity with validated tools identified significant correlations between mean PeLTQL scores and (1) Pediatric Quality of Life Inventory generic (r = 0.64, P < .001); (2) Pediatric Quality of Life Inventory transplant (r = 0.73, P < .001); and (3) Screen for Child Anxiety Related Disorders (r = -0.57, P < .001) scores. Only 17/3458 (0.5%) questions were left blank. A Flesch-Kincaid grade level of 5.4 was calculated as a measure of the PeLTQL readability statistic. CONCLUSIONS: The PeLTQL is a valid and reliable novel 26-item disease-specific health related quality of life instrument for LT recipients aged 8-18 years. Low PeLTQL scores can identify patients at risk for childhood anxiety and depression. The tool is now ready for broad use in both clinical practice and clinical interventional trials.

Long-term effect of childhood liver transplantation on body cell mass.

Malnutrition is common in end-stage liver disease, but a correction after transplantation is expected. Body cell mass (BCM) assessment using total body potassium (TBK) measurements is considered the gold standard for assessing nutritional status. The aim of this study was to examine the BCM and, therefore, nutritional status of long-term survivors after childhood liver transplantation. This was a longitudinal nested cohort study of patients undergoing transplantation at <18 years of age and surviving >3 years with ongoing review at our center. TBK measurements were obtained before transplantation and during long-term follow-up. BCM was calculated from TBK and was adjusted for the height raised to power p, which depended on sex (BCM/height(p)). The effects of the age at transplant, linear growth impairment, a diagnosis of biliary atresia, and steroid use were assessed. Thirty-two patients (20 males) participated; 59% had biliary atresia. The median age at transplant was 2.11 years (range = 0.38-10.92 years). Posttransplant testing was performed at a median of 7.23 years (range = 3.28-14.99 years) when they were 10.12 years old (range = 4.56-20.77 years). This cohort attained mean z scores for height, weight, and body mass index of -0.41 ± 1.36, -0.26 ± 1.14, and 0.04 ± 0.99, respectively. BCM/height(p) was reduced before transplantation but was further reduced after transplantation (P < 0.001) despite the normalization of height and weight. Weight recovery, therefore, likely came from increased fat mass and not BCM. Linear growth impairment was associated with a greater reduction in posttransplant BCM/height(p) (P = 0.02). In multivariate analyses, only an older age at transplant predicted reduced posttransplant BCM/height(p) (P = 0.02). The age at transplant, sex, steroid use, and underlying diagnosis did not predict changes in BCM/height(p) after transplantation. In conclusion, weight recovery in long-term survivors of childhood liver transplantation is likely due to increased fat mass because BCM remains reduced. Nutritional compromise persists in long-term survivors of childhood liver transplantation.

Long-term growth and anthropometry after childhood liver transplantation.

OBJECTIVES: To describe longitudinal height, weight, and body mass index changes up to 15 years after childhood liver transplantation. STUDY DESIGN: Retrospective chart review of patients who underwent liver transplant from 1985-2004 was performed. Subjects were age <18 years at transplant, survived ≥5 years, with at least 2 recorded measurements, of which one was ≥5 years post-transplant. Measurements were recorded pre-transplant, 1, 5, 10, and 15 years later. RESULTS: Height and weight data were available in 98 and 104 patients, respectively; 47% were age <2 years at transplant; 58% were Australian, and the rest were from Japan. Height recovery continued for at least 10 years to reach the 26th percentile (Z-score -0.67) 15 years after transplant. Australians had better growth recovery and attained 47th percentile (Z-score -0.06) at 15 years. Weight recovery was most marked in the first year and continued for 15 years even in well-nourished children. Growth impaired and malnourished children at transplant exhibited the best growth, but remained significantly shorter and lighter even 15 years later. No effect of sex or age at transplant was noted on height or weight recovery. Post-transplant factors significantly impact growth recovery and likely caused the dichotomous growth recovery between Australian and Japanese children; 9% (9/98) of patients were overweight on body mass index calculations at 10-15 years but none were obese. CONCLUSIONS: After liver transplant, children can expect ongoing height and weight recovery for at least 10-15 years. Growth impairment at transplant and post-transplant care significantly impact long-term growth recovery.

Heterogeneity of fibrosis patterns in non-alcoholic fatty liver disease supports the presence of multiple fibrogenic pathways.

BACKGROUND: Adult non-alcoholic fatty liver disease (NAFLD) involves lobular necroinflammatory activity and fibrosis is typically centrilobular, whereas paediatric NAFLD has predominantly portal fibrosis. The reasons for these differences are unclear. We aimed to determine (a) how centrilobular and portal fibrosis in children relate to histological parameters; and (b) whether atypical fibrosis patterns exist in adults that are unexplained by current fibrogenesis models. METHODS: Histological features of paediatric (n = 38) and adult (n = 56) NAFLD were assessed using conventional scoring systems. Keratin-7 immunostaining was used to assess hepatic progenitor cell numbers and the ductular reaction. Centrilobular and portal components of fibrosis were independently scored and fibrosis patterns were classified according to accepted types. Post-treatment (rosiglitazone/gastric banding) biopsies were also examined in adults. RESULTS: Twenty-six children (68.4%) had portal-predominant fibrosis, although the typical "adult" pattern was seen in 11 (28.9%). Portal fibrosis was associated with a ductular reaction (P = 0.021) and hepatic progenitor cell expansion (P < 0.001), whereas centrilobular fibrosis was associated with lobular inflammation (P = 0.026) and ballooning (P = 0.001). Before intervention, six adults (10.7%) had atypical fibrosis including 3 (5.4%) with a previously unrecognized pattern of very fine, non-zonal sinusoidal fibrosis. Despite improvements in steatosis and inflammation, more patients developed this unusual pattern after intervention with most having had surgery (9 of 10 adults; P < 0.001). CONCLUSION: Differing associations with portal and centrilobular fibrosis in children and atypical fibrosis patterns in adults suggest that multiple fibrogenic pathways exist in NAFLD. This has implications for therapy and understanding pathogenesis.