Ten-year follow-up of cavoportal hemitransposition in pediatric liver transplantation for complete portomesenteric venous thrombosis: A case report and literature review.

BACKGROUND: Portal vein thrombosis is a potentially devastating complication following pediatric liver transplantation. In rare instances of complete portomesenteric thrombosis, cavoportal hemitransposition may provide graft inflow. Here we describe long-term results following a case of pediatric cavoportal hemitransposition during liver transplantation and review the current pediatric literature. METHODS: A 9-month-old female with a history of biliary atresia and failed Kasai portoenterostomy underwent living donor liver transplantation, which was complicated by portomesenteric venous thrombosis. The patient underwent retransplantation with cavoportal hemitransposition on postoperative day 12. OUTCOME: The patient recovered without further complication, and 10 years later, she continues to do well, with normal graft function and no clinical sequelae of portal hypertension. CT scan with 3-D vascular reconstruction demonstrated recanalization of the splanchnic system, with systemic drainage to the inferior vena cava via an inferior mesenteric vein shunt. The cavoportal anastomosis remains patent with hepatopetal flow. Of the 12 previously reported cases of pediatric cavoportal hemitransposition as portal inflow in liver transplantation, this is the longest-known follow-up with a viable allograft. Notably, sequelae of portal hypertension were also rare in the 12 previously reported cases, with no cases of long-term renal dysfunction, lower extremity edema, or ascites. CONCLUSIONS: Long-term survival beyond 10 years with normal graft function is feasible following pediatric cavoportal hemitransposition. Complications related to portal hypertension were generally short-lived, likely due to the development of robust collateral circulation. Additional reports of long-term outcomes are necessary to facilitate informed decision making when considering pediatric cavoportal hemitransposition for liver graft inflow.

Rare genetic mutation triggering acute liver failure in a toddler requiring a liver transplant.

APS-1 is an extremely rare, autosomal recessive condition that often presents with candidiasis, adrenal insufficiency, and hypoparathyroidism. This condition is associated with autoimmune hepatitis in less than 20% of cases, and there have only been a few reports of children with the condition who developed ALF. We present a unique case of an infant with APS-1 who developed ALF and subsequently required liver transplantation.

Catheter-Associated Urinary Tract Infection Reduction in a Pediatric Safety Engagement Network.

BACKGROUND: Catheter-associated urinary tract infections (CAUTIs) are a leading cause of health care-associated infection. Catheter insertion bundles (IBs) and maintenance bundles (MBs) have been developed to prevent CAUTIs but have not been extensively validated for use in pediatric populations. We report the CAUTI prevention efforts of a large network of children's hospitals. METHODS: Children's hospitals joined the Children's Hospitals' Solutions for Patient Safety engagement network from 2011 to 2017, using an open start time engagement approach, and elected to participate in CAUTI prevention efforts, with 26 submitting data initially and 128 at the end. CAUTI prevention recommendations were first released in May 2012, and IBs and MBs were released in May 2014. Hospitals reported on CAUTIs, patient-days, and urinary catheter-line days and tracked reliability to each bundle. For the network, run charts or control charts were used to plot CAUTI rates, urinary catheter use, and reliability to each bundle component. RESULTS: After the introduction of the pediatric CAUTI IBs and MBs, CAUTI rates across the network decreased 61.6%, from 2.55 to 0.98 infections per 1000 catheter-line days. Centerline shifts occurred both before and after the 2015 Centers for Disease Control and Prevention CAUTI definition change. Urinary catheter use rates did not decline during the intervention period. Network reliability to the IBs and MBs increased to 95.4% and 86.9%, respectively. CONCLUSIONS: IBs and MBs aimed at preventing CAUTIs were introduced across a large network of children's hospitals. Across the network, the rate of urinary tract infections among hospitalized children with indwelling urinary catheters decreased 61.6%.

Pediatric cholestatic liver disease: Successful transition of care.

With recent medical advances, more patients with childhood-onset liver disease and more pediatric liver transplant recipients are surviving into adulthood, generating distinctive challenges to adult primary care providers. Young adults with pediatric liver disease are a unique cohort of patients with different evaluation and monitoring strategies, treatment, complications, and comorbidities. This creates a critical need for successful transition of these patients into adult care, with incorporation of a formal transitional model and multidisciplinary team.

Improved Survival Following Living Donor Liver Transplantation for Pediatric Acute Liver Failure: Analysis of 20 Years of US National Registry Data.

This study estimated the utility of technical variant grafts (TVGs), such as split/reduced liver transplantation (SRLT) and living donor liver transplantation (LDLT), in pediatric acute liver failure (PALF). PALF is a devastating condition portending a poor prognosis without liver transplantation (LT). Pediatric candidates have fewer suitable deceased donor liver transplantation (DDLT) donor organs, and the efficacy of TVG in this setting remains incompletely investigated. PALF patients from 1995 to 2015 (age <18 years) were identified using the Scientific Registry of Transplant Recipients (n = 2419). Cox proportional hazards model and Kaplan-Meier curves were used to assess outcomes. Although wait-list mortality decreased (19.1% to 9.7%) and successful transplantations increased (53.7% to 62.2%), patients <1 year of age had persistently higher wait-list mortality rates (>20%) compared with other age groups (P < 0.001). TVGs accounted for only 25.7% of LT for PALF. In the adjusted model for wait-list mortality, among other factors, increased age (subhazard ratio [SHR], 0.97 per year; P = 0.020) and access to TVG were associated with decreased risk (SHR, 0.37; P < 0.0001). LDLT recipients had shorter median waiting times compared with DDLT (LDLT versus DDLT versus SRLT, 3 versus 4 versus 5 days, respectively; P = 0.017). In the adjusted model for post-LT survival, LDLT was superior to DDLT using whole grafts (SHR, 0.41; P = 0.004). However, patient survival after SRLT was not statistically different from DDLT (SHR, 0.75; P = 0.165). In conclusion, despite clear advantages to reduce wait-list mortality, TVGs have been underutilized in PALF. Early access to TVG, especially from LDLT, should be sought to further improve outcomes.

Central Venous Line Associated Deep Vein Thrombosis in Hospitalized Children.

An increase in the incidence of deep vein thrombosis (DVT) has been reported in pediatric patients over the past decade. The presence of central venous line (CVL) is a major contributing risk factor with conflicting data on the relative risk of DVT with various types of central lines. We aimed to assess the incidence of and identify potential risk factors for DVT overall and with different types of CVL individually. A retrospective chart review of pediatric patients with a CVL placed at Cleveland Clinic Children's from 2011 to 2016 was conducted. Data collected included demographics, potential risk factors, CVL characteristics and related thrombotic events. The study cohort consisted of 376 CVLs in 325 patients between 0 and 26 years of age. There were 1.6 thrombi per 10,000 line-days (95% confidence interval: 1.0, 2.5), and the overall incidence of DVT was 5.1%. The incidence of DVT was highest with tunneled catheters (5/16=31%) versus with peripherally inserted central catheters (4/111=3.6%) or with ports (10/249=4%, P<0.001), and whereas there were overarching significant risk factors for CVL-associated thrombi, these risk factors differed in significance when analyzed by the CVL type. The study supports the need for continued improvement in pediatric hospital practices for early identification of patients at a higher thrombosis risk.

Outcomes of surgical management of familial intrahepatic cholestasis 1 and bile salt export protein deficiencies.

Progressive familial intrahepatic cholestasis (PFIC) with normal circulating gamma-glutamyl transpeptidase levels can result from mutations in the ATP8B1 gene (encoding familial intrahepatic cholestasis 1 [FIC1] deficiency) or the ABCB11 gene (bile salt export protein [BSEP] deficiency). We investigated the outcomes of partial external biliary diversion, ileal exclusion, and liver transplantation in these two conditions. We conducted a retrospective multicenter study of 42 patients with FIC1 deficiency (FIC1 patients) and 60 patients with BSEP deficiency (BSEP patients) who had undergone one or more surgical procedures (57 diversions, 6 exclusions, and 57 transplants). For surgeries performed prior to transplantation, BSEP patients were divided into two groups, BSEP-common (bearing common missense mutations D482G or E297G, with likely residual function) and BSEP-other. We evaluated clinical and biochemical outcomes in these patients. Overall, diversion improved biochemical parameters, pruritus, and growth, with substantial variation in individual response. BSEP-common or FIC1 patients survived longer after diversion without developing cirrhosis, being listed for or undergoing liver transplantation, or dying, compared to BSEP-other patients. Transplantation resolved cholestasis in all groups. However, FIC1 patients commonly developed hepatic steatosis, diarrhea, and/or pancreatic disease after transplant accompanied by biochemical abnormalities and often had continued poor growth. In BSEP patients with impaired growth, this generally improved after transplantation. Conclusion: Diversion can improve clinical and biochemical status in FIC1 and BSEP deficiencies, but outcomes differ depending on genetic etiology. For many patients, particularly BSEP-other, diversion is not a permanent solution and transplantation is required. Although transplantation resolves cholestasis in patients with FIC1 and BSEP deficiencies, the overall outcome remains unsatisfactory in many FIC1 patients; this is mainly due to extrahepatic manifestations. (Hepatology Communications 2018;2:515-528).

Liver Transplantation as a Treatment for Severe Refractory Vitamin E Deficiency Related to Progressive Familial Intrahepatic Cholestasis Type 2 in a Pediatric Patient.

Refractory vitamin E deficiency is thought to have irreversible effects on neurologic function. We report an adolescent boy with severe refractory vitamin E deficiency due to progressive familial intrahepatic cholestasis (PFIC) type 2. His consequent neurologic dysfunction included severe ataxia, dysmetria, dysarthria, and cranial nerve VI palsy. He underwent liver transplantation at age 13 due to his neurologic dysfunction; and afterward, he had marked improvement in neurologic function. We demonstrate that in a patient with PFIC 2 and severe refractory vitamin E deficiency, liver transplant can improve vitamin E absorption, prevent further neurological sequelae, and reverse prior neurologic dysfunction.

Cardiovascular risk factors and cardiac disorders in long-term survivors of pediatric liver transplantation.

The MetS and cardiovascular disease are leading causes of late morbidity in adult liver transplantation recipients; however, limited data are available in pediatric liver transplantation. A single-center retrospective review was undertaken for patients who had a liver transplantation before 18 yr of age and were >5 yr post-transplantation, to study the prevalence of MetS, its components, and cardiac disorders. Fifty-eight patients were included in the study with a mean age at transplantation of 6.3 ± 6.1 yr and mean follow-up of 14.1 ± 6.0 yr. Of the study group, 41.4% were overweight or obese, with ongoing prednisone use and increased duration of follow-up being significant risk factors. Fifty-three patients had sufficient data for determining MetS, which was present in 17% of the patients. Although the prevalence of MetS is low in pediatric liver transplant recipients, it is associated with CKD and prednisone therapy (p < 0.05). Echocardiography data were available for 23 patients, of whom 43.4% had LVH and 13% had evidence of PH. The spectrum of cardiac disorders in this population is much wider than in adults.

Health-related quality of life in children with autoimmune liver disease.

BACKGROUND AND AIM: Health-related quality of life (HRQOL), a pivotal outcome indicator of health care interventions, has not been evaluated in children with autoimmune liver disease (AILD). The aim of this study was to determine HRQOL in children with AILD and the factors affecting it. METHODS: The Pediatric Quality Of Life Inventory, generic core scale, was used to collect HRQOL data on children with AILD. Specific liver disease-related questions were added. RESULTS: Survey responses were received from 30 of 40 patients. Patients' mean age at diagnosis was 11.6 ± 4.5 years, with M:F ratio of 1:1.3, and AILD for average of 4.6 ± 4.3 years. Seventy-three percent of patients had advanced liver disease. Mean overall health summary scores for the group per child and parent reports were 71.6 ± 19.0 and 71.3 ± 17.1, respectively, which were lower than healthy controls: 83.9 ± 12.5 and 82.3 ± 15.6 (P = 0.002). Frequent liver-related symptoms were associated with impaired physical and school functioning by child (P = 0.034 and 0.047) and parent reports (P = 0.051 and P = 0.018). Abdominal pain, fatigue, and psychological symptoms were found to adversely affect the HRQOL. Although it was difficult to estimate the effect of individual features of advanced liver disease such as cirrhosis, history of upper gastrointestinal bleed, and portal hypertension on the HRQOL, because of a relatively small sample size, the presence of ascites revealed lower social functioning score per parent report (P = 0.036). In an analysis of patients with any of the above complications versus those without, however, children reported lower social functioning scores (P = 0.018). There were no differences in HRQOL scores in children with autoimmune hepatitis versus primary sclerosing cholangitis versus autoimmune hepatitis/primary sclerosing cholangitis overlap syndrome. CONCLUSIONS: First study to date shows that AILD in children significantly affects HRQOL, especially with frequent liver disease-related symptoms, even in early stages of disease. Findings need to be validated in larger, multicenter studies and will help practitioners understand their patients better and optimize care.

Neurological complications following pediatric liver transplant.

OBJECTIVE: We studied neurological complications (NCs) after liver transplantation (LT) in children. METHODS: We performed an institutional review board-approved retrospective review of patients with LT ≤21 years during a period of 30 years (1980-2010). NCs were classified as early (within 3 months post-LT) and delayed (beyond 3 months post-LT). RESULTS: Of 65 children with LT, 20 (30.7%) had NCs; 16 were girls. Mean age was 11.8±5.9 years. Early NCs were found in 13.8% (9/65) of the patients: seizures in 7 and encephalopathy in 2. Abnormal neuroimaging findings were posterior reversible leukoencephalopathy syndrome (1), intracranial hemorrhage (1), mild cerebral edema (1), and bilateral basal ganglia T1W hyperintensities in magnetic resonance imaging (1). On follow-up, there were 3 deaths (unrelated to NCs). One with intracranial hemorrhage had residual hemiparesis and was taking a long-term antiepileptic drug. Late NCs are found in 16.9% (11/65) of the patients: seizures in 4, headache in 4, encephalopathy in 3 (1 had seizures in addition), and paresthesias caused by possible small-fiber neuropathy in 1. Abnormal neuroimaging findings were hypoxic-ischemic encephalopathy (1), encephalomalacia caused by old hemorrhage (1), and hyperintensity of the posterior periventricular white matter in magnetic resonance imaging (1). On follow-up, all of the patients survived; 1 had papilledema with secondary optic atrophy requiring optic nerve sheath fenestration and 1 needed long-term antiepileptic drug. CONCLUSIONS: NCs are common in children after LT, seizures being the most common. In contrary to the previous studies, we found delayed complications more often than early complications. Early detection and appropriate management of NCs is important.

Deep hypothermia with circulatory arrest to aid in the management of suprahepatic vena cava stenosis after liver transplantation.

Liver transplantation is the treatment of choice for many liver diseases in the pediatric population. Complications involving late suprahepatic vena cava obstructions after liver transplantation are not common, but they tend to be more frequently seen in pediatric recipients. When such complications have occurred, approaches involving direct abdominal surgery or interventional radiology guidance have been used with satisfactory results. We present a case report of an alternative approach to a suprahepatic vena cava complication. An 18-year-old man who underwent pediatric liver transplantation for biliary atresia presented with a symptomatic total occlusion of the suprahepatic caval anastomosis that could not be crossed with a wire. We used a right atrial approach and hypothermic circulatory (cardiac) arrest. The anastomotic stricture was easily identified and excised. The postoperative course was uneventful with a rapid resolution of the symptoms. Because the occlusion was not amenable to angioplasty or stenting, a direct surgical approach was necessary. The right atrial approach with hypothermic cardiac arrest gave us direct access to the obliterated cavoatrial anastomosis through a virgin area and allowed us to avoid the difficulties and dangers of the large collaterals in the abdomen.

Differences in presentation and progression between severe FIC1 and BSEP deficiencies.

BACKGROUND & AIMS: Progressive familial intrahepatic cholestasis (PFIC) with normal serum levels of gamma-glutamyltranspeptidase can result from mutations in ATP8B1 (encoding familial intrahepatic cholestasis 1 [FIC1]) or ABCB11 (encoding bile salt export pump [BSEP]). We evaluated clinical and laboratory features of disease in patients diagnosed with PFIC, who carried mutations in ATP8B1 (FIC1 deficiency) or ABCB11 (BSEP deficiency). Our goal was to identify features that distinguish presentation and course of these two disorders, thus facilitating diagnosis and elucidating the differing consequences of ATP8B1 and ABCB11 mutations. METHODS: A retrospective multi-center study was conducted, using questionnaires and chart review. Available clinical and biochemical data from 145 PFIC patients with mutations in either ATP8B1 (61 "FIC1 patients") or ABCB11 (84 "BSEP patients") were evaluated. RESULTS: At presentation, serum aminotransferase and bile salt levels were higher in BSEP patients; serum alkaline phosphatase values were higher, and serum albumin values were lower, in FIC1 patients. Elevated white blood cell counts, and giant or multinucleate cells at liver biopsy, were more common in BSEP patients. BSEP patients more often had gallstones and portal hypertension. Diarrhea, pancreatic disease, rickets, pneumonia, abnormal sweat tests, hearing impairment, and poor growth were more common in FIC1 patients. Among BSEP patients, the course of disease was less rapidly progressive in patients bearing the D482G mutation. CONCLUSIONS: Severe forms of FIC1 and BSEP deficiency differed. BSEP patients manifested more severe hepatobiliary disease, while FIC1 patients showed greater evidence of extrahepatic disease.

Autoimmune hepatitis in children--impact of cirrhosis at presentation on natural history and long-term outcome.

UNLABELLED: Little is known regarding the natural history of autoimmune hepatitis in children. The aims of this longitudinal cohort study were to determine the long-term prognosis of children with autoimmune hepatitis and to determine the effect of cirrhosis at presentation on survival. METHODS: Thirty-three children with autoimmune hepatitis who were seen at our institution over a 25-year period were studied retrospectively. RESULTS: The median age of diagnosis was 12.9 years (2.7-18.1) with a female predominance of 3:1. Liver biopsies showed cirrhosis in 18 (55%) patients at time of diagnosis. Patients with cirrhosis at baseline had a similar 10-year survival 85% (70-100%) to those without cirrhosis 75% (49-100%) (p=0.97). The overall survival was significantly lower than the expected in the age- and gender-matched U.S. population (log-rank test; p<0.001). In Cox regression models, weight loss (p=0.037), baseline elevated bilirubin (p=0.028), prolonged International Normalized Ratio (INR) (p=0.013), and positive LKM-1 antibodies (p=0.007) were associated with shorter survival. CONCLUSION: AIH in children is associated with a significant shorter survival rate than the expected in the general population. Cirrhosis on initial liver biopsy does not seem to impact long-term survival in children with AIH.

Use and safety of rifaximin in children with inflammatory bowel disease.

BACKGROUND: Rifaximin, Food and Drug Administration approved for traveler's diarrhea, has been used in adult patients with active inflammatory bowel disease (IBD). This retrospective review was undertaken to determine its role in the treatment of pediatric IBD. METHODS: A review of children with IBD, who were treated with rifaximin from 2005 to 2007 at our institution, was performed. Collected data included diagnosis, age, medication history, recent therapy, symptom, and interval to improvement. Response was rated as none, moderate, or optimum relief for each symptom. RESULTS: Twenty-three patients were identified, 12 with Crohn disease and 11 with ulcerative colitis (UC) with a median age of 13 years. The most common complaints were diarrhea in 20 patients (87%), abdominal pain in 17 (74%), and bloody stools in 15 (65%). Rifaximin was given at doses ranging between 10 and 30 mg/kg (Table 1). Of the 20 patients who presented with diarrhea 5 (25%) had relief of diarrhea within 1 week of starting rifaximin and total of 12 patients (60%) experienced relief within 4 weeks. Abdominal pain resolved in 3 of 17 patients (17.6%) within 1 week and in 12 of 17 (70.6%) within 4 weeks. Visible bleeding resolved in 10 of 15 patients (66.7%) within 4 weeks of therapy (Table 2). Analysis of concurrent medications showed 61% experienced relief of symptoms when addition of rifaximin was the only meaningful treatment change. CONCLUSIONS: Rifaximin was well-tolerated and showed favorable results. Larger doses of rifaximin were statistically better for abdominal pain. Further studies are needed to evaluate efficacy and optimal dosing of rifaximin in this population.

A nonsense mutation of PEPD in four Amish children with prolidase deficiency.

Encoded by the peptidase D (PEPD) gene located at 19q12-q13.11, prolidase is a ubiquitous cytosolic enzyme that catalyzes hydrolysis of oligopeptides with a C-terminal proline or hydroxyproline. We describe here four Amish children with a severe phenotype of prolidase deficiency in the Geauga settlements of Ohio as the first report of prolidase deficiency in the Amish population as well as in the United States. The patients presented with infection, hepatosplenomegaly, or thrombocytopenia, in contrast to most cases previously reported in the literature, presenting with skin ulcers. All four patients had typical facial features, classic skin ulcers, and multisystem involvement. Recurrent infections, asthma-like chronic reactive airway disease, hyperimmunoglobulins, hepatosplenomegaly with mildly elevated aspartate transaminase (AST), anemia, and thrombocytopenia were common and massive imidodipeptiduria was universal. Prolidase activity in our patients is nearly undetectable. Direct sequencing of PCR-amplified genomic DNA for all of the exons from the four patients revealed the same homozygous single nucleotide mutation c.793 T > C in exon 11, resulting in a premature stop-codon at amino acid residue 265 (p.R265X). It is speculated that the severe phenotype in these patients might be associated with the type of the PEPD gene mutation.