Pediatric liver transplantation in severe hepatopulmonary syndrome and use of inhaled nitric oxide for post-transplant hypoxemia-a single center experience.

Data on pediatric patients with HPS undergoing LT are limited. Our aim was to study the spectrum and outcomes of pediatric patients with HPS undergoing LDLT. The role ofiNO for post-LDLT refractory hypoxemia was also assessed. Patients (aged < 18 years) undergoing LT were retrospectively studied. HPS was diagnosed based on European Respiratory Society Taskforce 2004 criteria. HPS was graded based on oxygenation criteria and contrast-enhanced echocardiogram. Post-operative course was studied. Refractory post-operative hypoxemia was treated with iNO by institutionally developed protocol. 23/150 pediatric patients undergoing LDLT had HPS. BA was the most common underlying cause (52.2%). By oxygenation criteria, 6 (26.1%) had VS-HPS. VS-HPS was associated with longer LOS (p = .031) and prolonged oxygen requirement (p = .001) compared with other HPS patients. 4/6 patients with VS-HPS had pO2 < 45 mm Hg. Among these, 2 developed ICH post-operatively and 1 died. 3 developed refractory post-operative hypoxemia, successfully treated with iNO. Mean duration of iNO was 26.3 days. In the group of patients with HPS, the incidence of HAT and portal vein thrombosis was 17.3% and 4.3%, respectively. One year post-LDLT survival of patients with HPS was similar to non-HPS patients (86.9% vs 94.4%; p = .88). We concluded that, pediatric patients with VS-HPS, especially those with pre-operative pO2 < 45 mm Hg, have long and difficult post-LT course. Refractory postoperative hypoxemia can be successfully overcome with strategic use of iNO. Vigilant monitoring and good intensive care support are essential.

Prompt diagnosis and management of Epstein-Barr virus-associated post-transplant lymphoproliferative disorder and hemophagocytosis: A dreaded complication in a post-liver transplant child.

EBV-associated PTLD is increasingly recognized as an important cause of morbidity and mortality in both solid organ and hematopoietic stem cell transplant recipients. Mortality rates due to PTLD and virus-induced HLH are reported to be quite high. We report a case of EBV-associated PTLD and HLH in a child after liver transplantation who was successfully managed due to timely intervention. This case highlights that measurement of EBV load by quantitative polymerase chain reaction assays is an important aid in the surveillance and diagnosis of PTLD and early detection of EBV-induced PTLD, and aggressive treatment with rituximab is a key to survival in patients who have undergone liver transplantation.

First living-related liver transplant to cure factor VII deficiency.

Congenital factor VII deficiency is an autosomal recessive serious disorder of blood coagulation with wide genotypic and phenotypic variations. The clinical presentation can vary from asymptomatic patients to patients with major bleedings in severe deficiency (factor VII <1%). Investigations show prolonged PT and low factor VII. Treatment modalities include FFP and repeated recombinant factor VII infusions. We hereby report the first successful LRLT for factor VII deficiency in an infant, the first-ever youngest baby reported worldwide. A six-month-old male child presented with easy bruisability, ecchymotic patches, hematuria, and convulsions. CT of the head showed subdural hemorrhage, which was treated conservatively. He had markedly increased PT (120 s) with normal platelets, and aPTT with factor VII level <1%. Despite the treatment by rFVIIa administration weekly, which was very expensive, he still had repeated life-threatening bleeding episodes. LRLT was performed with mother as the donor, whose factor VII level was 57%. A factor VII infusion plan for pre-, intra- and postoperative periods was formulated and TEG followed. Postoperatively, his factor VII started increasing from third day and was 38% on 24th day with PT <14 s. He had uneventful intraoperative and postoperative courses. LT is a safe and definite cure for factor VII deficiency.

Spectrum and trend of pediatric inflammatory bowel disease: A two-decade experience from northern India.

BACKGROUND: Pediatric inflammatory bowel disease (IBD) has been known to be a disease predominant in the west. There is scarcity of data on pediatric IBD (P-IBD) from northern India. The objective of our study was to analyze the clinical spectrum of P-IBD in northern India. METHODS: A retrospective analysis of 126 children (<18-year old) diagnosed with IBD from January 1999 to December 2019 was done on a pre-designed proforma. It was systematically entered in a MS Excel spreadsheet and analyzed using Statistical Package for the Social Sciences (SPSS) version 21.0. The descriptive phenotypes of Ulcerative colitis (UC) and Crohn's disease (CD) were revised according to the Paris classification. RESULTS: Of 126 children, UC was diagnosed in 76 (60.3%), CD in 44 (34.9%) and IBD-unclassified (IBD-U) in six (4.76%) patients. The mean age at diagnosis was 11.3 years; 38.8% were < 10 years with the male: female ratio of 1.6:1. Sixteen children (12.7%) had very early onset IBD (VEOBD). Overall, the median time to diagnosis in IBD was 12 months (interquartile range [IQR]: 3.25-24), which was as high as 52.5 months (IQR: 11-98) in CD. Pancolitis with bleeding per rectum and ileocolonic involvement with pain in abdomen were the commonest presentations in UC and CD, respectively. Stricturing disease was seen in 27% of CD cases. Relapses were seen in 46% (35/76) of U.C and 23% (10/44) of CD kids. Step-up treatment protocol was employed in them with the use of biologicals in 12% of cases. There was a 2.75-fold rise in the IBD cases in the last 10 years (2010-20). There was reduction in time to diagnosis (21 months vs. 90 months; p - 0.012) and empirical anti-tubercular therapy use (90% vs. 5.8%) in CD over two decades. CONCLUSION: From our experience in a tertiary care centre in northern India, P-IBD is on the rise. UC is more common than CD. Pancolitis and ileocolonic disease are the commonest disease sites in UC and CD, respectively There is a significant delay in the time to diagnosis in CD. Stricturing disease was seen in a quarter of children with CD.

Diagnosis and management of pediatric acute liver failure: consensus recommendations of the Indian Society of Pediatric Gastroenterology, Hepatology, and Nutrition (ISPGHAN).

Timely diagnosis and management of pediatric acute liver failure (PALF) is of paramount importance to improve survival. The Indian Society of Pediatric Gastroenterology, Hepatology, and Nutrition invited national and international experts to identify and review important management and research questions. These covered the definition, age appropriate stepwise workup for the etiology, non-invasive diagnosis and management of cerebral edema, prognostic scores, criteria for listing for liver transplantation (LT) and bridging therapies in PALF. Statements and recommendations based on evidences assessed using the modified Grading of Recommendations Assessment, Development and Evaluation (GRADE) system were developed, deliberated and critically reappraised by circulation. The final consensus recommendations along with relevant published background information are presented here. We expect that these recommendations would be followed by the pediatric and adult medical fraternity to improve the outcomes of PALF patients.

Indian Academy of Pediatrics Consensus Guidelines for Probiotic Use in Childhood Diarrhea.

JUSTIFICATION: Several probiotic species and strains, single or combined, have been evaluated in childhood diarrheal disorders, and recommendations have ever been changing as newer trials are published. Therefore, there is a need to develop a guideline for Indian children describing the current role of probiotics in clinical practice. OBJECTIVES: To develop a guideline for the use of probiotics in children with diarrhea. PROCESS: A national consultative group (NCG) was constituted by the Indian Academy of Pediatrics (IAP), consisting of subjects experts. Sub-topics were allotted to various experts as paired groups for detailed review. Members reviewed the international and Indian literature for existing guidelines, systematic reviews, meta-analyses and trials. Thereafter, two virtual structured meetings of the group were held on 2nd and 22nd August, 2020. The management guidelines were formulated by the group and circulated to the participants for comments. The final guidelines were approved by all experts, and adopted by the IAP executive board. RECOMMENDATIONS: The NCG suggests Lactobacillus GG as a conditional recommendation with low-to-moderate level evidence or Saccharomyces boulardii as a conditional recommendation with very low-to-low level evidence as adjuvant therapy in acute diarrhea. The NCG also recommends the use of combination probiotics in neonatal necrotizing enterocolitis (NEC), as these reduce the risk of NEC stage II and above, late-onset sepsis, mortality and also time to achieve full feeds. The NCG does not recommend the use of any kind of probiotics in the therapy of acute dysentery, persistent diarrhea, Clostridium difficile diarrhea and chronic diarrheal conditions such as celiac disease, diarrhea-predominant irritable bowel syndrome and inflammatory bowel disease in children. Risk of antibiotic-associated diarrhea (AAD) is high with some antibiotics and most of these cases present as mild diarrhea. The NCG recommends probiotics only in special situations of AAD. L. rhamnoses GG or S. boulardii may be used for the prevention of AAD. VSL#3, a combination probiotic, may be used as an adjuvant in active pouchitis, prevention of recurrences and maintenance of remission in pouchitis.

Erratum to 'Indian National Association for the Study of Liver Consensus Statement on Acute Liver Failure (Part-2): Management of Acute Liver Failure' [J Clin Exp Hepatol 10 (2020) 477-517].

[This corrects the article DOI: 10.1016/j.jceh.2020.04.011.].

Living donor liver transplantation for giant cavernous hemangioma of liver in a child.

A 10-yr-old girl presented with a seven-month history of upper abdominal discomfort and weight loss. Physical examination revealed an abdominal lump in the right hypochondrium and epigastrium. Ultrasound examination and a computerized tomographic scan showed a large lobulated mass arising from segments I, 1V, and VIII of liver with arteriovenous shunting and multiple small masses in segments VI and VII. An initial diagnosis of hemangioendothelioma with metastasis was made elsewhere following which she received chemotherapy. She had persistent abdominal discomfort because of which she became dependent on narcotics. The patient had fever because of tumor necrosis and also developed peripheral neuropathy. Finally, owing to progressively worsening of symptoms, she underwent left lobe living donor liver transplantation. Histopathological examination showed the mass to be a cavernous hemangioma, and the patient is now well.

Diagnosis and Management of Gastroesophageal Reflux Disease in Children: Recommendations of Pediatric Gastroenterology Chapter of Indian Academy of Pediatrics, Indian Society of Pediatric Gastroenterology, Hepatology and Nutrition (ISPGHAN).

JUSTIFICATION: Gastroesophageal reflux (GER) related symptoms are a major cause of parental concern and referrals at all ages. These guidelines have been framed to inform pediatricians regarding current diagnosis and management of gastro-esophageal reflux disease (GERD). PROCESS: A group of experts from the pediatric gastroenterology sub-specialty chapter of Indian Academy of Pediatrics (ISPGHAN) discussed various issues relating to the subject online on 25 October, 2020. A consensus was reached on most aspects and a writing committee was constituted. This committee had three meetings for a detailed discussion. The statement was sent to the entire group and their approval obtained. OBJECTIVE: To formulate a consensus statement to enable proper diagnosis and management of GERD in children. RECOMMENDATIONS: GER is physiological in most infants and it improves as age advances. The pathological form, called GERD causes distressing symptoms that affect daily activities and may result in complications. The presentation would vary from regurgitation to severe symptoms due to esophageal or respiratory tract disease. In older children, esophagitis is the commonest manifestation of GERD. A careful history and clinical examination are adequate to make a diagnosis in most patients, but judicious investigations are necessary in a few. Upper gastro intestinal tract endoscopy may be required in those with esophageal manifestations, dysphagia and hematemesis. In children with extra-esophageal symptoms, MII-pH monitoring and scintigraphy are necessary. Empirical treatment with a Proton pump inhibitor (PPI) has not been proven useful in infants, but a four-week trial is recommended in older children without complications. While positioning and feed thickening have limited benefit in infants, life-style modifications are important in older children.

Pediatric ABO-incompatible Living Related Donor Liver Transplantation: Experience from Indian Subcontinent.

We present our experience with pediatric ABO-incompatible liver transplantation in India. Data of patients <18 years of age undergoing ABO-incompatible liver transplantation our hospital between January, 2011 and November, 2018 were analyzed. Plasmapheresis was done pre-transplant till antibody titer was <16 units. Rituximab/Intravenous immunoglobulin was used for immunosuppression, in addition to standard drugs (mycophenolate mofetil, steroids, and tacrolimus). Out of 203 patients that underwent liver transplant during this period, 8 underwent ABO-incompatible liver transplantation; 4 (3 boys) had blood group O+ve. Median (range) age was 28 (7-91) mo, PELD score was 24.5 (14-42), and pre-transplant antibody titer range was 1:32-1024. Number of plasmapheresis sessions required ranged from 1-6. Post-operatively two patients had rise in antibody titer >64 requiring plasmapheresis. All 8 patients survived without rejection/biliary issues. Mean (range) of post-transplant hospital stay was 19.1 (13-22) d and follow-up period was 38.1 (7.1-84.4) mo. Pediatric ABO-incompatible liver transplantation can be successfully performed using plasmapheresis with optimal immune-suppression and vigilant post-op monitoring.

Specific Probiotics for the Treatment of Pediatric Acute Gastroenteritis in India: A Systematic Review and Meta-Analysis.

Pediatric acute gastroenteritis (PAGE) is a significant cause of morbidity, mortality and healthcare costs in many countries, but differences in PAGE vary from country-to-country; thus, we limited our analysis to 1 country. Probiotics have been recommended as an adjunct to standard treatment, but the choice of probiotic is unclear. PubMed, Google Scholar, and reviews were searched from inception to May 2020 for randomized controlled trials (RCTs) in India using probiotics for a treatment for PAGE. Meta-analyses using subgroups of identical probiotic types (≥2 RCT/type) were conducted for primary outcomes (duration of diarrhea, cured by day 3, rapidity of response, and length of hospital stay). Twenty-two RCTs were included in the systematic review (N = 4059 participants) including 5 single-strained probiotics and 3 multi-strained mixtures. For the meta-analyses, 17 RCT (20 treatment arms) were included. Saccharomyces boulardii CNCM I-745 had the strongest effect on shortening the duration of diarrhea (standardized mean difference, -1.86 d; 95% confidence interval, -2.8 to -0.9), while both Lactobacillus rhamnosus GG and a mixture of 4 Bacillus clausii strains (O/C, SIN, N/R, T) significantly reduced the duration of diarrhea (-1.7 and -1.4 d, respectively). S. boulardii and L. rhamnosus GG significantly reduced hospital stays (-1.8 and -1.1 d, respectively), while B. clausii had no effect. The frequency of stools/day was significantly reduced by day 4 for S. boulardii and by day 5 for L. rhamnosus GG. In India, 2 types of probiotics (S. boulardii CNCM I-745 and L. rhamnosus GG) significantly shortened both the duration of diarrhea and hospitalization stays in pediatric patients with PAGE. While these 2 probiotic strains were safe and effective for children in India, further research is needed to confirm if other probiotic strains or mixtures may be effective.

Restructuring Living-Donor Liver Transplantation at a High-Volume Center During the COVID-19 Pandemic.

BACKGROUND: Coronavirus disease 2019 (COVID-19) pandemic has led to deferral of elective transplants and proactive pretransplant testing of the donor/recipient. The impact of these on living-donor liver transplantation (LDLT) activity and outcome is not known. We performed LDLT only for sick patients or patients with advanced hepatocellular carcinoma in this period, with special COVID protocols. METHODS: Patients undergoing LDLT counseling, evaluation, and transplant in the period March to June 2020 (group A) under COVID-19 restrictions and special protocols were included. LDLT activity and outcomes among these patients were compared with those in the same period in 2019 (group B). RESULTS: In the period March 15-June 10, we performed 39 and 23 (59%) LDLTs in 2019 and 2020, respectively. The adult patients with cirrhosis in group A (n = 20) had a significantly higher MELD score, 19.8 ± 7.0 versus 16.1 ± 5.6 in group B (n = 36), p = 0.034. Early recipient mortality was similar in 2019 (2/39) and 2020 (2/23). One of 23 post-transplant recipients, 3/71 recipients and donors during evaluation, and 8/125 healthcare workers (HCWs) developed COVID-19, all of whom recovered uneventfully. CONCLUSION: LDLT activity substantially reduced during the COVID era. The incidence and outcome of COVID-19 among the waiting or transplanted patients and HCWs were similar to those of the general population. The outcome after LDLT in the COVID era was similar to that in non-COVID times. These data suggest that LDLT may be extended to more stable patients with strict protocols.

Langerhans cell histiocytosis with digestive tract involvement.

Gastrointestinal tract (GIT) involvement in Langerhans cell histiocytosis (LCH) is not commonly described. We present two children presenting with GIT involvement with LCH, one successfully treated on standard protocol and other being treated on a protocol for relapsed disease. A review of literature showed almost 95% children were less than 2 years of age and 62% were females. Vomiting, abdominal pain, constipation, intractable diarrhea, malabsorption, bloody stools, protein-losing enteropathy, and even intestinal perforation are some of the reported symptoms. More than 50% patients died within 18 months from diagnosis.

Chronic hepatitis C virus infection in children.

The importance of hepatitis C viral infection in the health care of children has grown in recent decades. More is now known about the epidemiology of this infection in children and the progression of disease in the pediatric age group, and the treatment options are increasing. In this review, we update readers on the state of our understanding of hepatitis C infection in children, provide the current recommendations for monitoring and treatment, and discuss emerging therapies.

Therapeutic Enteral Formulas in Children.

PURPOSE: A variety of enteral formulas for various diseases have become available in India in the last few years. Awareness among pediatricians about the availability and indications for these therapeutic formulas is low. METHODS: A literature search was conducted in PUBMED and relevant data collected from all English language publications available. Data on the commercial preparations was sourced from the individual companies, the Diet 4 life initiative as well as FSSAI (Food safety and standards authority of India). CONCLUSIONS: Therapeutic enteral formulas, which are indicated in various disease states belong to four categories - lactose modified, hydrolyzed, MCT based and metabolic disease specific formulas. Lactose modified formulas which are used in temporary or permanent lactose intolerance and Galactosemia are either casein or soy protein based. Hydrolyzed formulas could be partially hydrolyzed, extensively hydrolyzed or amino acid based. Only extensively hydrolyzed formula should be recommended in milk protein allergy. Amino acid (elemental) formulas are mainly indicated in patients with diffuse intestinal mucosal disease. MCT formulas are used in chronic liver disease with cholestasis, and have 30 to 80% MCT. Formulas for inborn errors of metabolism are free of specific carbohydrate, amino acid or fatty acid. Proprietary formulas presently available in India with their specifications have been listed.

Corrigendum to "Wilson's Disease: Clinical Practice Guidelines of the Indian National Association for the Study of Liver (INASL), The Indian Society of Pediatric Gastroenterology, Hepatology and Nutrition (ISPGHAN) and the Movement Disorders Society of India (MDSI)" [J Clin Exp Hepatol 9 (2019) 74-98].

[This corrects the article DOI: 10.1016/j.jceh.2018.08.009.].