Saeed Mohammad

Health Status in Young Adults Two Decades After Pediatric Liver Transplantation

We conducted a cross‐sectional study of patients who underwent pediatric liver transplant (LT) between 1988 and 1992 to evaluate long‐term health status. Survivors completed socio‐demographic, medical and Health‐Related Quality of Life (HRQOL) surveys by mail including the SF‐36v2, PedsQL™4.0 Generic Core Scale, PedsQL™ Cognitive Functioning Scale and PedsQL™3.0 Transplant Module. SF‐36 scores were converted to SF6D‐based utilities and risk factors for lower outcomes were assessed.

Approach to Optimizing Growth, Rehabilitation, and Neurodevelopmental Outcomes in Children After Solid-organ Transplantation

One of the most critical differences between the posttransplant care of children and adults is the requirement in children to maintain a state of health that supports normal physical and psychological growth and development. Most children with organ failure have some degree of growth failure and developmental delay, which is not quickly reversed after successful transplantation. The challenge for clinicians caring for these children is to use strategies that minimize these deficits before transplantation and provide maximal opportunity for recovery of normal developmental processes during posttransplant rehabilitation. The effect of chronic organ failure, frequently complicated by malnutrition, on growth potential and cognitive development is poorly understood. This review presents a summary of what is known regarding risk factors for suboptimal growth and development following solid-organ transplant and describe possible strategies to improve these outcomes.

Liver Transplantation Followed by Allogeneic Hematopoietic Stem Cell Transplantation for Atypical Mevalonic Aciduria

Mevalonic aciduria because of mutations of the gene for mevalonate kinase causes limited synthesis of isoprenoids, the effects of which are widespread. The outcome for affected children is poor. A child with severe multisystem manifestations underwent orthotopic liver transplantation at age 50 months for the indication of end‐stage liver disease. This procedure corrected liver function and eliminated portal hypertension, and the patient showed substantial improvement in neurological function. However, autoinflammatory episodes continued unabated until hematopoietic stem cell transplantation was performed at 80 months. Through this complex therapy, the patient now enjoys a high quality of life without significant disability.

Estimation of fish and ω-3 fatty acid intake in pediatric nonalcoholic fatty liver disease.

Aims: Fish and &ohgr;-3 fatty acids are reported to be beneficial in pediatric nonalcoholic fatty liver disease (NAFLD), but no studies have assessed their relation to histological severity. The objectives of this study were to evaluate the dietary intake of fish and &ohgr;-3 fatty acids in children with biopsy-proven NAFLD, and examine their association with serological and histological indicators of disease. Methods: This was a cross-sectional analysis of 223 children (6–18 years) who participated in the Treatment of Nonalcoholic Fatty Liver Disease in Children trial or the NAFLD Database study conducted by the Nonalcoholic Steatohepatitis Clinical Research Network. The distribution of fish and &ohgr;-3 fatty acid intake was determined from responses to the Block Brief 2000 Food Frequency Questionnaire, and analyzed for associations with serum alanine aminotransferase, histological features of fatty liver disease, and diagnosis of steatohepatitis after adjusting for demographic, anthropometric, and dietary variables. Results: The minority of subjects consumed the recommended 8 ounces of fish per week (22/223 [10%]) and 200 mg of long-chain &ohgr;-3 fatty acids per day (12/223 [5%]). Lack of fish and long-chain &ohgr;-3 fatty acid intake was associated with greater portal (P = 0.03 and P = 0.10, respectively) and lobular inflammation (P = 0.09 and P = 0.004, respectively) after controlling for potential confounders. Conclusions: Fish and &ohgr;-3 fatty acid intake was insufficient in children with NAFLD, which may increase susceptibility to hepatic inflammation. Patients with pediatric NAFLD should be encouraged to consume the recommended amount of fish per week.

Assessment of abdominal pain through global outcomes and recent FDA recommendations in children: are we ready for change?

Objectives: Irritable bowel syndrome is a multisymptom construct, with abdominal pain (AP) acting as the driving symptom of patient-reported severity. The Food and Drug Administration considers a >30% decrease in AP as satisfactory improvement, but this has not been validated in children. We investigated the correspondence of 2 measures for AP assessment, ≥30% improvement in AP and global assessment of improvement. Methods: Secondary analysis of data from 72 children who completed a randomized clinical trial for abdominal pain–associated functional gastrointestinal disorders. Children completed daily assessment of AP intensity, functional disability inventory (FDI), question regarding pains interference with activities, and 2 global assessment questions. We measured the extent to which ≥30% improvement of AP and global assessment questions correlated with each other and with disability. Results: The global questions correlated with each other (r = 0.74; P < 0.0001) and with a ≥30% improvement in AP (P < 0.01). Global outcomes were satisfaction with treatment was inversely related to the childs report of interference with activities (P < 0.01) and symptom relief was positively associated with ≥30% improvement in FDI scores (P < 0.009). A 30% change in FDI scores was associated with global questions of symptom relief (P = 0.009) but not with satisfaction with treatment (P = 0.07). The association of AP improvement with interference with activities (P = 0.14) or change in FDI scores (P = 0.27) did not reach significance. Conclusions: Currently used global assessments are significantly associated with decreased pain intensity, decreased interference with daily activities, and a ≥30% change in FDI scores, whereas recommended 30% improvement in pain intensity is not as comprehensive.

Long-Term Linear Growth and Puberty in Pediatric Liver Transplant Recipients

OBJECTIVE To explore linear growth, puberty, and predictors of linear growth impairment among pubertal liver transplant recipients. STUDY DESIGN Review of data collected prospectively through the Studies of Pediatric Liver Transplantation registry. Thirty-one variables were tested as risk factors for linear growth impairment, and factors significant at P < .1 were included in a logistic regression model. Risk factor analysis was limited to 512 patients who had complete demographic and medical data. RESULTS A total of 892 patients surviving their first liver transplant by >1 year, with ≥ 1 height recorded, who were between 8 and 18 years old between the years 2005 and 2009 were included. Median follow-up was 70.2 ± 38.6 months, mean age was 12.9 ± 3.3 years, and mean height z-score (zH) was -0.5 ± 1.4 SD. Twenty percent had linear growth impairment at last follow-up. Of 353 subjects with Tanner stage data, 39% of girls and 42% of boys ages 16-18 years were not yet Tanner 5. Growth impairment rates were higher among boys than girls (30% vs 7%, P < .05) at Tanner stage 4, and occurred in 8/72 (11%) of Tanner 5 subjects. Among patients with parental height data, zH were lower than calculated mid-parental zH (P < .005). Independent predictors of growth impairment included linear growth impairment at transplant (OR 11.53, P ≤ .0001), re-transplantation (OR 4.37, P = .001), non-white race (P = .0026), and primary diagnosis other than biliary atresia (P = .0105). CONCLUSIONS Linear growth impairment and delayed puberty are common in pubertal liver transplant recipients, with pre-transplant growth impairment identified as a potentially modifiable risk factor. Catch-up growth by the end of puberty may be incomplete.

Withdrawal of immunosuppression following pediatric liver transplantation: A markov analysis

Objectives:Survivors of pediatric liver transplantation are at risk for developing complications related to posttransplant immunosuppressive medications. Withdrawal is possible in selected patients but carries the risk of graft rejection and loss. We modeled the effect of withdrawing immunosuppressive medications on survival, cost, and quality-adjusted life-years (QALYs) in a hypothetical cohort of pediatric patients who received transplantation for biliary atresia with stable liver enzymes and no recent episodes of rejection, and who were free from immunosuppression-related adverse effects. Methods:A decision analysis tree was developed, and Monte Carlo simulations were used to track patients through the model during a 10-year time course with 1-year cycles. Data from the literature were used to assign probabilities to major clinical events and preference-based utility scores to the values of health outcomes. One-way and probabilistic sensitivity analyses were used to evaluate the impact of uncertainty. Results:Patients following the withdrawal strategy had a 10-year survival rate of 95.8% and experienced 8.61 QALYs versus 88.6% survival and 8.01 QALYs for those taking immunosuppressive medications. Each additional QALY is attained at a cost of −

Infantile Cirrhosis, Growth Impairment, and Neurodevelopmental Anomalies Associated with Deficiency of PPP1R15B.

18,992.41 and was therefore cost saving. Conclusions:Patients in our model who had their immunosuppression withdrawn had improved survival and QALYs with lower costs. Although every effort was made to validate the model, it is limited by the accuracy of the underlying assumptions. Therefore, clinical trials are needed to determine predictors of successful immunosuppression withdrawal to allow for personalization of medication regimens.

Health-related Quality of Life in Infants With Chronic Liver Disease.

OBJECTIVE To assess the utility of whole-exome sequencing (WES) in a sibling pair with undetermined liver disease and describe the phenotype associated with mutations discovered therein. STUDY DESIGN Next-generation WES was performed on 2 siblings (S1 and S2) who were born to nonconsanguineous parents of European extraction. Both siblings developed cirrhosis of indeterminate etiology and required liver transplantation; S1 at 7 months and S2 at 22 months. RESULTS Sequencing of germline DNA identified compound heterozygous mutations in PPP1R15B resulting in increased levels of phosphorylated eukaryotic translation initiation factor 2α. CONCLUSIONS The first demonstration of PPP1R15B associated with liver disease expands the phenotypic spectrum of PPP1R15B related diseases. Our findings validate the application of WES in the diagnosis of children with undetermined liver disease. Understanding the genetic basis of liver disease may allow the development of targeted therapies for treatment and adequate counseling of families.

Exertional Heat Stroke in a Young Athlete Resulting in Acute Liver Failure.

Objective: The objective of the present study was to report on the health-related quality of life (HRQOL) of infants with chronic liver disease using the PedsQL (Pediatric Quality of Life Inventory) Infant Scales. Methods: The 36-item (ages 1–12 months) and 45-item (ages 13–24 months) PedsQL Infant Scales (physical functioning, physical symptoms, emotional functioning, social functioning, cognitive functioning) were completed by 50 parents of infants with chronic liver disease. Results: Infants ages 1 to 12 months had significantly lower HRQOL scores compared with a matched healthy sample. Infants 13 to 24 months trended to lower physical HRQOL scores that did not reach statistical significance. Recent hospitalizations had an impact on the majority of HRQOL subscales, as did ascites, and failure to thrive. Conclusions: Infants ages 1 to 12 months with chronic liver disease demonstrate lower HRQOL compared with healthy children with physical subscales being most severely affected. The PedsQL Infant Scales allow the definition of HRQOL during a critical period of an infants’ development that has been heretofore difficult to measure.