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The objective of the study was to evaluate the diagnostic and prognostic role of serum cystatin C, urinary neutrophil gelatinase-associated lipocalin (NGAL), and renal resistive index (RRI) in AKI among pediatric cirrhotics. The study included cirrhotic children under 18 years of age. AKI was diagnosed as per Kidney Diseases-Improving Global Outcomes (KDIGO) guidelines. All patients underwent measurement of serum cystatin C, urinary NGAL, and RRI at baseline, 3 months, and 6 months. eGFR was calculated using both creatinine- and cystatin-based equations. Of the 247 cirrhotics admitted during the study, 100 gave consent and were included. Forty-one fulfilled the KDIGO definition of AKI of whom 22 showed resolution. Two of these children had a repeat AKI at 2 and 4 months after initial AKI; both resolved with medical management. On logistic regression analysis, serum cystatin C (OR: 544.8, 95% CI: 24.4-12170, p < 0.0005) and urinary NGAL (OR: 1.006, 95% CI: 1001-1.012, p = 0.019) were found to be significantly associated with AKI. Cystatin C alone was the best biomarker for diagnosing AKI in children with decompensation (OR: 486.7, p < 0.0005) or spontaneous bacterial peritonitis (p = 0.02). eGFR calculated by serum cystatin C-based formulas was more reliable than that calculated by creatinine-based equations.Conclusion: Serum cystatin C is the best biomarker for diagnosis of AKI in pediatric cirrhotics, especially with decompensation and SBP. eGFR calculated on serum cystatin C-based equations is more reliable than creatinine-based ones. What is Known: • Acute kidney injury (AKI) is a common complication in cirrhotic adults. • Newer biomarkers have diagnostic and prognostic role in adult cirrhotics. What is New: • Serum cystatin C is a useful biomarker to identify acute kidney injury in cirrhotic children with decompensation. • Glomerular filtration rate calculation is more accurate by cystatin-based equations than creatinine-based equations.

The objectives were to evaluate the role of optic nerve sheath diameter (ONSD) to detect raised intracranial pressure (ICP) in pediatric acute liver failure (PALF), study the variations in ONSD with ICP-lowering measures and to evaluate its prognostic role. PALF with clinical evidence of raised ICP were enrolled as cases, while those without raised ICP were control group A. ONSD was measured at admission and repeated regularly. It was also measured at time of each new episode of raised ICP and 2 h after the management of such episode. 31 PALF with raised ICP were included as cases and 15 without as control group A. ONSD was significantly higher in cases: 5 mm (IQR: 4.7–5.4) as compared to control group A: 3.8 mm (IQR: 3.3–4). ONSD greater than 4.55 mm at baseline diagnosed clinically raised ICP with 87.5% sensitivity and 100% specificity. The mean ONSD was 5.44 ± 0.49 mm during a total of 90 events of acute raised ICP. Clinical responders had a decrease in ONSD by 0.59 ± 0.24 mm by 2 h, whereas non-responders showed a decrease of 0.18 ± 0.23 mm, p

Varicella-zoster virus (VZV) is a DNA virus belonging to the Herpesviridae family. Primary infection causes chickenpox followed by latency in the sensory ganglia, which can sometimes reactivate leading to herpes zoster. Chicken pox is generally a mild disease of childhood with a secondary attack rate of >85%, but disseminated VZV infection with visceral involvement and fatal outcome may occur in immunocompromised individuals. Indian Academy of Pediatrics recommends two doses of live-attenuated varicella vaccine in healthy unexposed children at 15-18 months and then at 4-6 years of age. The effectiveness of a single dose of vaccine is around 85% and with a two-dose schedule is as high as 92%. Despite the vaccine-induced protection, community-acquired VZV infections still remain a problem in immunocompromised population. We hereby report a case of a previously immunized pediatric liver-transplant recipient who acquired VZV infection. This case report clearly highlights the importance of strict environmental infection control practices, early suspicion, diagnosis, and management in such cases.

Objectives There is lack of clarity regarding the exact prevalence of hepatopulmonary syndrome (HPS) in pediatric liver diseases owing to lack of standardized diagnostic criteria. Thus, we aimed to do a comparative study of HPS with respect to its prevalence using the available diagnostic criteria. Methods All consecutive children with biliary atresia (BA) and other chronic liver diseases (CLDs) were studied. Prevalence of HPS was compared using the 2 available criteria: demonstration of intrapulmonary vascular dilatation along with either alveolar-arterial oxygen difference (P [A-a] O2) on arterial blood gas analysis of more than 15 mmHg (criteria 1), or higher than age-appropriate calculated value for P (A-a) O2 (criteria 2). Results A total of 42 children in BA group and 62 in the non-BA CLD group were included. Using the criteria 1, the prevalence of HPS was 42.3%: 57.1% in the BA group and 32.2% in the CLD group, whereas using criteria 2, the prevalence was 48.1%: 61.9% in the BA group and 38.7% in the CLD group. Criteria 2 diagnosed 6 additional patients with HPS compared to criteria 1 (P value 0.405). BA subjects had higher risk (2.9-3 folds) of developing HPS compared to other CLDs. Conclusion There is high prevalence of HPS in pediatric liver disease subjects. Age-appropriate formula for HPS diagnosis may be better applicable in pediatric population. BA subjects have a higher risk of developing HPS compared to other CLDs overall, irrespective of the severity of liver disease and/or portal hypertension.

There is limited literature on Gilbert’s syndrome (GS) in children with persistent unconjugated hyperbilirubinemia from Indian subcontinent. All patients (< 18 y of age) with genetically confirmed GS were included, and their profile was analysed. A total of 170 subjects were confirmed as having GS as per genetic analysis (133 with homozygous and 37 with heterozygous status). Majority were diagnosed in the adolescent age group (mean age 13.6 y). The median serum total bilirubin (TB) levels were around 3.3 mg/dl with maximum levels reaching upto 18 mg/dl. Around 15% subjects had an associated condition including hematological or hepatobiliary disease amongst others. GS is an important but under-recognised cause of unexplained unconjugated hyperbilirubinemia in Indian pediatric subjects. It may co-exist with other hematological and hepatobiliary disorders, and complicate the clinical/laboratory picture. Extent of hyperbilirubinemia may fluctuate to levels much higher than what is usually described in current world literature.

Objective The objective was to evaluate the efficacy and safety of sodium benzoate in the management of hyperammonemia and hepatic encephalopathy (HE) in decompensated chronic liver disease. Methods It was a prospective, interventional, double-blinded randomized controlled trial conducted from August 2017 to December 2018. Children with decompensated chronic liver disease and hyperammonemia were included in the study. Those with ammonia >400 μg/dL, already receiving sodium benzoate or with grade III ascites were excluded. Group A received sodium benzoate (400 mg/kg loading dose followed by 200 mg · kg · daymaintenance for 5 days) along with the standard medical therapy. Group B received standard medical therapy with placebo. Results A total of 108 episodes of hyperammonemia occurred in 86 patients of whom 16 were excluded. The final analysis included 46 episodes in each group. The median decrease in ammonia from baseline to day 5 was 52 μg/dL in group A versus 42 μg/dL in group B (P = 0.321). There was a significant decrease in ammonia on days 1 and 2 in group A as compared to group B, but not on subsequent days. There was no significant difference in the resolution of HE (57.1% vs 50%; P = 1), but there was higher, albeit insignificant increase in ascites in group A (15.9% vs 4.5%). Conclusions Addition of sodium benzoate significantly reduced the ammonia levels on the first 2 days of therapy but the effect was not sustained till day 5. The effect of sodium benzoate would probably be more sustained, if higher dosage (400 mg · kg · day) could be used under monitoring of benzoate levels. There was no effect on resolution of HE. Sodium benzoate caused an increasing trend of adverse events with no effect on short-term survival.

Limited pediatric literature is available regarding hepatopulmonary syndrome (HPS) especially in subjects with biliary atresia (BA) despite its proven prognostic significance. Thus, we aimed to study the natural history, risk factors, and outcome of HPS in BA and other chronic liver disease (CLD) subjects. All children (BA and other non-BA CLDs) older than 6 months of age were included in the study. HPS was diagnosed on the basis of standard international criteria. Also, fractional exhaled nitric oxide (FeNO) was measured at baseline. During the study period from January 2017 to December 2018, there were 42 children in BA and 62 in the CLD group. The overall prevalence of HPS was 42.3%: 57.1% in the BA group and 32.2% in the CLD group. Median age at HPS diagnosis was 14.4 months and 90 months in the BA and non-BA CLD groups, respectively. By the end of study period, the prevalence of HPS in the BA group further increased to 73.8% at 0.7% per month. Lower serum albumin (p

Ballismus is defined as rapid, forceful, shaking or throwing involuntary movement of the extremities, mainly proximal parts. When it affects half of the body (upper and lower limbs on one side), it is called hemiballismus. If it affects one limb, it could be labeled as focal or one limb ballismus. Any lesion (vascular, trauma, tumor, deposition, and demyelination) in the subthalamic nucleus of the basal ganglia results in ballismus. A rare entity such as copper deposition in Wilson's disease can manifest as ballismus. In this case report, we described a boy with Wilson's disease with focal ballismus of the right arm.

To study the Hepatitis A virus (HAV) infection-related pediatric liver disease burden. Hospital records of 431 children (age

The objectives of the study were to evaluate the indications, feasibility, complications and clinical implications of transjugular liver biopsy (TJLB) in children.Data of all TJLB performed in children18 years old was retrieved from the computerized hospital information system. TJLB was done using a 19 G quick-core needle biopsy system with 20 mm throw length. Hepatic venous pressure gradient was additionally measured in children with portal hypertension. A single pathologist reviewed all the biopsies again and provided structured information.A total of 102 children, including 5 with acute liver failure underwent TJLB with technical success in 101 (99%). A mean of 2.3 ± 0.9 passes (range: 1-5) was taken for the biopsy. The most common indications for TJLB in our cohort were elevated international normalized ratio1.5 (66, 64.7%), ascites (46, 45.1%) and thrombocytopenia (platelet count 60,000/mm3) (42, 41.2%). Mean size of the tissue received was 14.5 ± 5.6 mm with an average of 10.2 ± 4.7 portal tracts. Only one child developed major (category D) complication (hemobilia) and 12 (11.8%) developed minor complications post-procedure. Etiological diagnosis could be made in a total of 64 (63.9%) children undergoing TJLB, the most common diagnosis being autoimmune hepatitis (n = 31), non-cirrhotic portal fibrosis (n = 16) and drug-induced liver injury (n = 4).TJLB is well tolerated, feasible and helps make a diagnosis in close to 64% children allowing timely medical and/or surgical intervention. It is especially useful for diagnosis of autoimmune liver diseases, drug-induced liver injury and non-cirrhotic portal fibrosis.

The clinical course after liver transplantation (LT) in progressive familial intrahepatic cholestasis type 1 (PFIC1) is complicated by intractable diarrhoea, growth failure, graft steatosis and cirrhosis. Recent evidence from Japan suggests the role of genotype to predict outcome after LT. We report a case with pathogenic frameshift mutation who had failed partial external biliary diversion, underwent LT and his post-LT course has been complicated by intractable diarrhoea, growth failure, steatosis and fibrosis. This case highlights the fact that homozygous frameshift p.Gly197LeufsTer10 mutation in ATP8B1 is associated with poor outcome and genetic evaluation should be mandatory before subjecting the patient to LT.

Objectives: To report 2 children with acute hepatic myelopathy after hepatitis A infection who recovered completely after living donor liver transplantation. Methods: All the children admitted into liver intensive care unit (LICU) from November 1st 2018 to 31st October 2019, were evaluated for the neurological features. The data was collected from the admission register of the LICU unit in children below 15 years age. Medical records of these children were reviewed and data collected. Established clinical criteria were used to categorize the various grades of hepatic encephalopathy/myelopathy. Results: 37 children were seen over 1-year period between 6 months to 15 years age. There were 24 male(64.9%) and 13 females. Acute liver failure was seen in 19 (51.3%) and acute on chronic liver failure in 18 (48.7%). There were 10 cases of hepatitis A in acute liver failure group,10 of 19 cases (52.6%), while Wilson’s disease and undetermined etiology group formed the chronic group. 2 cases of hepatic myelopathy were seen in acute liver failure following hepatitis A infection. Both these children underwent live liver donor transplantation and recovered completely. Further in hepatitis A group,3 children had spontaneous recovery, 4 died and 1 child was discharged with end of life care. Overall out of all 37 children with liver failure,20 (54%) were discharged, 6 (16.2%) were advised end of life care and 11 (29.8%) died. Conclusion: Two cases (10.5%) of reversible hepatic myelopathy were seen in acute liver failure group of 19 cases. 18 out of 37 (48.6%) children had residual neurological features at discharge time.

Objective To study the efficacy and safety of high volume plasma exchange (HVPE) in Wilson disease presenting as acute liver failure (WD-ALF). Methods An analysis of prospectively collected data of consecutively admitted WD-ALF cases was done and patients were divided into two groups: (i) high volume plasma exchange (HVPE) group- who received HVPE + standard medical therapy (SMT), and (ii) SMT group- received only SMT. Outcome measure was transplant free survival (TFS) at 90 days post enrollment, change in biochemical, hemodynamic parameters & incidence of organ dysfunction in HVPE as compared to SMT group, and HVPE related complications. Results Out of the total 43 cases of WD-ALF reported in the study period, 37 were enrolled (median age 9 years, 62.2% males). All biochemical parameters and prognostic indices except blood ammonia and serum creatinine improved significantly at 72 to 96 hours after enrollment in the HVPE group. Overall, TFS at 90 days was present in 9/19 (47.3%) in HVPE group vs 3/18 (16.6%) in the SMT group (OR 2.84, 95% CI 0.91-8.8, P = .049). Kaplan Meier survival analysis revealed that HVPE group had significantly higher cumulative survival as per the Log Rank test (P = .027); median days of survival was 38 days (IQR 12-63) in HVPE group vs 14 (IQR 5-22) days in SMT group. Conclusions The present study indicates that in children with WD-ALF, HVPE not only acts as a bridging therapy to LT but may also improve proportion of the cases with TFS.

Clinical practice guidelines for Wilson's disease (WD) have been published by the American Association for the Study of Liver Diseases and European Association for the Study of the Liver in 2008 and 2012, respectively. Their focus was on the hepatic aspects of the disease. Recently, a position paper on pediatric WD was published by the European Society of Pediatric Gastroenterology Hepatology and Nutrition. A need was felt to harmonize guidelines for the hepatic, pediatric, and neurological aspects of the disease and contextualize them to the resource-constrained settings. Therefore, experts from national societies from India representing 3 disciplines, hepatology (Indian National Association for Study of the Liver), pediatric hepatology (Indian Society of Pediatric Gastroenterology, Hepatology and Nutrition), and neurology (Movement Disorders Society of India) got together to evolve fresh guidelines. A literature search on retrospective and prospective studies of WD using MEDLINE (PubMed) was performed. Members voted on each recommendation, using the nominal voting technique. The Grades of Recommendation, Assessment, Development and Evaluation system was used to determine the quality of evidence. Questions related to diagnostic tests, scoring system, and its modification to a version suitable for resource-constrained settings were posed. While ceruloplasmin and 24-h urine copper continue to be important, there is little role of serum copper and penicillamine challenge test in the diagnostic algorithm. A new scoring system – Modified Leipzig score has been suggested with extra points being added for family history and serum ceruloplasmin lower than 5 mg/dl. Liver dry copper estimation and penicillamine challenge test have been removed from the scoring system. Differences in pharmacological approach to neurological and hepatic disease and global monitoring scales have been included. Rising bilirubin and worsening encephalopathy are suggested as indicators predicting need for liver transplant but need to be validated. The clinical practice guidelines provide recommendations for a comprehensive management of WD which will be of value to all specialties.

Mevalonate kinase deficiency (MKD) is a rare autosomal recessive autoinflammatory disease caused by mutations in MVK. We report two siblings with MKD, presenting with recurrent febrile illnesses, detected to have compound heterozygous variants in MVK. MKD mimics common pediatric conditions and should be considered as a differential diagnosis.

The objectives of the study were to evaluate the prognostic value of APASL ACLF Research Consortium—Acute-on-chronic liver failure (AARC-ACLF) score against the current prognostic models in pediatric ACLF and to assess the role of pediatric modifications of AARC-ACLF score and chronic liver failure–sequential organ failure assessment (CLIF–SOFA) score. All children between 1 and 18 years of age satisfying the APASL definition of ACLF were included in the study. All the prognostic scores were calculated retrospectively from hospital records. Outcome was assessed at days 28 and 90. Pediatric modifications of AARC-ACLF and CLIF–SOFA scores were evaluated. Acute-on-chronic liver failure was seen in 86 (13.4%) of 640 children with chronic liver disease. Twenty-five (29.8%) children died, 7 (8.3%) underwent liver transplant and the remaining 52 (61.9%) survived with their native liver. Four prognostic models (AARC-ACLF, AARC-ACLF-Pediatric, CLIF–SOFA and CLIF–SOFA-Pediatric) had an AUROC greater than 0.9 for predicting poor outcome in pediatric ACLF. AARC-ACLF and CLIF–SOFA models were superior to other prognostic scores with a cutoff score of 11 or more predicting poor outcome. Pediatric modifications of AARC-ACLF and CLIF–SOFA scores were not superior to their original scores. Children with poor outcome had rising scores at day 4, whereas the scores were falling in those with good outcome. AARC-ACLF and CLIF–SOFA models are superior to other prognostic scores in pediatric ACLF. The scores are dynamic and a patient with either of these scores ≥ 11 at admission and/or a rising score at day 4 has high likelihood of death and needs to be urgently listed for liver transplantation.

OBJECTIVES There is limited literature on the spectrum of pediatric autoimmune liver disease (AILD, encompassing both autoimmune hepatitis/AIH and autoimmune sclerosing cholangitis [ASC]) in Asian populations and its diagnostic scores similarly require further validation. This work thus aimed to study the clinical characteristics, and to validate available diagnostic criteria in the local pediatric AILD cohort. METHODS A review of all pediatric AILD cases, presenting over a 6-year (2011-2017) period was done, along with comparison of the available diagnostic scores: original (1999), simplified (2008) score, and new proposed (2017) score. RESULTS A total of 85 subjects (AIH = 70 and ASC = 15) were diagnosed as having AILD. Majority of the cases in both groups presented with advanced hepatic disease (portal hypertension and/or hepatic decompensation). Overall 38 (44.7%) subjects had extrahepatic autoimmune disorders. Good outcome (survival with native liver with medically controllable disease), was seen in 80% AIH subjects, while poor outcome (death/need for liver transplantation or LT) was seen in 13% subjects, with similar results in the ASC cohort. All the 3 available scores had area under receiver operating characteristic (AUROC) curves exceeding 0.9 suggestive of excellent discrimination of AILD (to non-AILD patients), with no statistical difference between them (P >0.05). CONCLUSIONS In Indian subcontinent, pediatric AILD subjects usually present with advanced hepatic disease, but may have a good outcome if timely therapy can be instituted. Associated autoimmune disorders should be carefully screened. There is no difference in the predictive value of the available diagnostic scores for pediatric AILD.

A 10-year-old female child, a known case of Beta-Thalassemia major with superimposed chronic Hepatitis C Viral (HCV) infection, underwent bone marrow transplantation and presented, 7 months later, with worsening hepatic functions and skin rash. Considering the wide variety of possible etiologies, she was evaluated and later confirmed as a case of hepatic dysfunction secondary to HCV related hepatic injury with concomitant chronic graft versus host disease (dermatological involvement only).

To find association of pediatric NAFLD with metabolic risk factors, and Patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene polymorphism. Cross-sectional study Pediatric Hepatology unit of a tertiary care hospital Overweight/obese children (

We studied the etiological spectrum, clinicolaboratory and histological profile, and outcome of infants and children under 18 years of age presenting between December 2010 and May 2016 with histological evidence of paucity of intralobular bile ducts (PILBD, bile ducts to portal tract ratio 0.6) Post-transplant PILBD was excluded. Of 632 pediatric liver biopsies screened, 70 had PILBD-44 were infants. PILBD was classified histologically into destructive (n = 50) and non-destructive PILBD (n = 20). Presentations were jaundice (98%), organomegaly (94%), pale stools (50%), and pruritus (43%). Infants had more cholestasis but less fibrosis on histology. Overall, 29 required liver transplantation (LT) for portal hypertension (n = 26), decompensation (n = 25), growth failure (n = 20), intractable pruritus (n = 5), and recurrent cholangitis (n = 2). Destructive PILBD has an odds for poor outcome (decompensation or need for LT within 1 year) of 1.53 (95% CI = 1.15-2.04). On binary logistic regression analysis, poor outcome was related to advanced fibrosis on liver biopsy [Exp (B) = 5.46, 95% CI = 1.56-19.04].PILBD was present in 11% of pediatric liver biopsies and has a varied etiological spectrum. Destructive PILBD has poor outcome. Need for LT is guided by the presence of advanced fibrosis. What is Known: • Natural history of syndromic ductal paucity (Alagille syndrome) is complex. • Duct loss is commonly seen with late presentation of biliary atresia. What is New: • The study classifies the etiological spectrum of ductal paucity histologically into destructive and non-destructive. • Destructive duct loss carries poor prognosis regardless of the etiology of liver disease with subsequent need for liver transplantation.

The concept of irreversibility of cirrhosis has been challenged in the recent past with literature in this regard, albeit still scarce, now being accumulated across all age groups, etiologies, and geographical regions. This small series of nine pediatric cases elegantly recapitulates the concept of regression of hepatic fibrosis/cirrhosis and paves way for further detailed studies to enable development of therapeutic anti-fibrotic modalities in future.

There are no evidence-based recommendations on the ideal dose and regimen for supplementation of vitamin D in children with chronic liver disease (CLD). This study aimed to compare the safety and efficacy of weekly and stoss regimens for treatment of vitamin D deficiency in these children. Children between the ages of 1 to 18 years with CLD and hypovitaminosis D defined by 25-OH vitamin D (25(OH)D)30µg/l were included. They were randomized to receive either stoss regimen (600,000 IU on day 1) or weekly (60,000 IU weekly) regimen of vitamin D. The 25(OH)D levels at 3 and 6 months were compared in the two groups. A total of 210 suspected cases of CLD were assessed for eligibility. Of a total of 67 children satisfying the inclusion criteria, 33 and 34 were randomized to receive stoss and weekly regimen, respectively. Final analysis included 28 children in each group. Clinical rickets was seen in 25.4% of children with hypovitaminosis D. The rise in levels of 25(OH)D at 3 months was higher with weekly regimen (34.3 ± 30.7 µg/l) as compared to stoss regimen (17.2 ± 11.5 µg/l) (p = 0.009). Rise at 6 months as compared to baseline was significantly higher with weekly regimen (30.7 ± 24µg/l) as compared to stoss regimen (11 ± 8.4 µg/l) (p0.001). Normal levels of 25(OH)D at 6 months were achieved in 24/28 (85.7%) of those receiving weekly regimen and 9/28 (32.1%) of those receiving stoss regimen (p0.001). With stoss therapy, 25(OH)D increased at 3 months as compared to baseline but thereafter dropped significantly at 6 months (p = 0.008).Weekly regimen of vitamin D supplementation is more effective than stoss regimen for treatment of hypovitaminosis D in children with CLD. Once normal levels are achieved, child should be shifted to 60,000 IU per month as maintenance dose. What is Known: • Vitamin D deficiency is more common and severe in children with chronic liver diseases. • Currently used doses fail to achieve normal vitamin D levels in these children. What is New? • Weekly regimen of 60,000 IU of vitamin D3 is the most effective regimen for treating vitamin D deficiency in children with CLD. • Children with CLD should further receive maintenance dose of 60,000 IU every month.

Background & aims There are no studies on acute kidney injury in paediatric acute-on-chronic liver failure. This study was planned with aim to describe the clinical presentation and outcome of acute kidney injury among paediatric acute-on-chronic liver failure patients. Methods Data of all children 1-18 years of age presenting with acute chronic liver failure (Asia pacific association for the study of the liver definition) was reviewed. Acute kidney injury was defined as per Kidney Diseases-Improving Global Outcomes guidelines. Poor outcome was defined as death or need for liver transplant within 3 months of development of acute kidney injury. Results A total of 84 children with acute-on-chronic liver failure were presented to us in the study period. Acute kidney injury developed in 22.6% of patients with acute-on-chronic liver failure. The median duration from acute-on-chronic liver failure to development of acute kidney injury was 4 weeks (Range: 2-10 weeks). The causes of acute kidney injury were hepatorenal syndrome (31.6%), sepsis (31.6%), nephrotoxic drugs (21%), dehydration (10.5%) and bile pigment related acute tubular necrosis in one patient. On univariate analysis, higher baseline bilirubin, higher international normalized ratio, higher paediatric end stage liver disease, presence of systemic inflammatory response syndrome and presence of spontaneous bacterial peritonitis had significant association with presence of acute kidney injury. On logistic regression analysis, presence of systemic inflammatory response syndrome (adjusted OR: 8.659, 95% CI: 2.18-34.37, P = .002) and higher baseline bilirubin (adjusted OR: 1.07, 95% CI: 1.008-1.135, P = .025) were independently associated with presence of acute kidney injury. Of the patients with acute kidney injury, 5(26.3%) survived with native liver, 10(52.6%) died and 4 (21.1%) underwent liver transplantation. Conclusion Acute kidney injury developed in 22.6% of children with acute-on-chronic liver failure. Bilirubin more than 17.7 mg/dL and presence of systemic inflammatory response syndrome were high risk factors for acute kidney injury. Development of acute kidney injury in a child with acute-on-chronic liver failure suggests poor outcome and need for early intervention.

The first consensus report of the working party of the Asian Pacific Association for the Study of the Liver (APASL) set up in 2004 on acute-on-chronic liver failure (ACLF) was published in 2009. With international groups volunteering to join, the “APASL ACLF Research Consortium (AARC)” was formed in 2012, which continued to collect prospective ACLF patient data. Based on the prospective data analysis of nearly 1400 patients, the AARC consensus was published in 2014. In the past nearly four-and-a-half years, the AARC database has been enriched to about 5200 cases by major hepatology centers across Asia. The data published during the interim period were carefully analyzed and areas of contention and new developments in the field of ACLF were prioritized in a systematic manner. The AARC database was also approached for answering some of the issues where published data were limited, such as liver failure grading, its impact on the ‘Golden Therapeutic Window’, extrahepatic organ dysfunction and failure, development of sepsis, distinctive features of acute decompensation from ACLF and pediatric ACLF and the issues were analyzed. These initiatives concluded in a two-day meeting in October 2018 at New Delhi with finalization of the new AARC consensus. Only those statements, which were based on evidence using the Grade System and were unanimously recommended, were accepted. Finalized statements were again circulated to all the experts and subsequently presented at the AARC investigators meeting at the AASLD in November 2018. The suggestions from the experts were used to revise and finalize the consensus. After detailed deliberations and data analysis, the original definition of ACLF was found to withstand the test of time and be able to identify a homogenous group of patients presenting with liver failure. New management options including the algorithms for the management of coagulation disorders, renal replacement therapy, sepsis, variceal bleed, antivirals and criteria for liver transplantation for ACLF patients were proposed. The final consensus statements along with the relevant background information and areas requiring future studies are presented here., Article Highlights Updated on the basis of AARC data of >3300 cases enrolled into AARC registry prospectivelyACLF is distinct form Acute Decompensation of cirrhosisNewer sections on DILI-ACLF, AIH-ACLF, PVT/HVOTO–ACLFReversibility of Chronic Liver Disease in ACLFPortal and systemic hemodynamics and their relevance in ACLFAcute Portal Hypertension and Variceal progression in ACLFAARC score as a guide for treatment strategies in ACLFACLF in Children-first consensus on pediatric ACLF

Objectives Fatty acid oxidation defects (FAODs) may underlie or modify the course of acute liver failure (ALF). Overall significance of carnitine/acylcarnitine and amino acid profile in ALF is similarly undetermined. Thus, this study was undertaken to study the abnormalities in carnitine/acylcarnitine and amino acid profile in ALF. Methods A prospective study was performed including all patients with ALF, and detailed evaluation including metabolic testing was done. Results A total of 55 patients (33 pediatric and 22 adult patients) were included in the study. Three patients (a 1-year 6-month-old child, a 13-year-old adolescent, and a 21-year-old adult, ie, 5.5% of all) were identified for the study with underlying metabolic etiology, that is, carnitine palmitoyl transferase-1 deficiency, based on the abnormal carnitine/acylcarnitine profile. Almost three-fourths of patients (78%) had evidence of serum hyperaminoacidemia. Thirty-one patients (56%) had evidence of abnormal carnitine/acylcarnitine profile with predominant abnormality being low free carnitine (C0). Higher levels of serum tyrosine (P = 0.002) and lower levels of serum C0 (P = 0.032) in children and higher levels of serum phenyalanine (P = 0.047) in adults predicted poor outcome (death/liver transplant) on univariate analysis. Conclusions FAODs are not uncommon in ALF with a suggested prevalence of approximately 5.5%. FAODs can cause ALF or modify the natural course of ALF caused by other etiologies. Serum hyperaminoacidemia and low serum free carnitine may predict poor outcome in patients with acute liver failure.

Background and Aims The outcome of Pediatric acute liver failure largely depends on age and etiology. The aim of this work was to study the etiological spectrum and outcome of the pediatric acute liver failure cases. Methods This prospective observational study included all children (< 18 years age) fulfilling pediatric acute liver failure study group definition. Etiological evaluation was done and predictive factors for poor outcome (death or liver transplantation) were analyzed. Results There were 109 children in total. The commonest etiology was viral infections (50, 45.8%) followed by metabolic liver diseases (14, 13.2%) and drug induced liver injury (12, 11%). Viral, indeterminate and drug induced liver injury group were older in age, had higher international normalised ratio and alanine transaminases in comparison to metabolic liver diseases and other etiologies (p 7 days (Adjusted OR 9.16, 95% CI 1.55-53) and higher Pediatric/Model for End Stage Liver Disease scores at 72 hours (Adjusted OR 1.2, 95% CI 1.08-1.32) were associated with poor outcome. Conclusion Viral infections, indeterminate and drug induced liver injury related pediatric acute liver failure usually present in older children with higher international normalised ratio and alanine transaminases. Jaundice to encephalopathy interval > 7 days and Pediatric/Model for End Stage Liver Disease >24 at 72 hours are associated with poor outcome. This article is protected by copyright. All rights reserved.

Hepatitis A virus (HAV) is the commonest cause of pediatric acute liver failure (PALF) in developing countries. Our objective was to develop and validate a HAV-etiology specific prognostic model in PALF. All children with HAV induced PALF (IgM HAV reactive) were included. Outcome was defined at day 28. Only those with death or native liver survival were included. The model (Peds-HAV) was derived using the independent predictors of outcome and validated in a prospective independent cohort. Hepatitis A accounted for 131 (45.9%) of total 285 PALF. After excluding 11 children who underwent liver transplant, 120 children (74 survivors and 46 death) were included. The first 75 patients formed the derivation cohort and the next 45 patients formed the prospective validation cohort. In the derivation cohort, INR: OR 2.208, (95% CI 1.321–3.690), p = 0.003, grade of hepatic encephalopathy (HE): OR 3.078, (95% CI 1.017–9.312), p = 0.047 and jaundice-to-HE interval: OR 1.171, (95% CI 1.044–1.314), p = 0.007 were independent predictors of death. The final model comprised three criteria: (1) presence of grade 3–4 HE, (2) INR greater than 3.1, and (3) jaundice to HE interval more than 10 days. Presence of 2 or more of these criteria predicted death with 90% sensitivity, 81.4% specificity and 84.9% accuracy. Peds-HAV model was superior to existing prognostic models. In the validation cohort, Peds-HAV model predicted death with 83.3% sensitivity and 92.6% specificity. Peds-HAV model is a simple, bedside, dynamic, etiology (HAV) specific prognostic model based on 3 objective parameters with optimum sensitivity and specificity, hence should be used as liver transplant listing criteria in HAV induced PALF.

Clinical practice guidelines for Wilson's disease (WD) have been published by the American Association for the Study of Liver Diseases and European Association for the Study of the Liver in 2008 and 2012, respectively. Their focus was on the hepatic aspects of the disease. Recently, a position paper on pediatric WD was published by the European Society of Pediatric Gastroenterology Hepatology and Nutrition. A need was felt to harmonize guidelines for the hepatic, pediatric, and neurological aspects of the disease and contextualize them to the resource-constrained settings. Therefore, experts from national societies from India representing 3 disciplines, hepatology (Indian National Association for Study of the Liver), pediatric hepatology (Indian Society of Pediatric Gastroenterology, Hepatology and Nutrition), and neurology (Movement Disorders Society of India) got together to evolve fresh guidelines. A literature search on retrospective and prospective studies of WD using MEDLINE (PubMed) was performed. Members voted on each recommendation, using the nominal voting technique. The Grades of Recommendation, Assessment, Development and Evaluation system was used to determine the quality of evidence. Questions related to diagnostic tests, scoring system, and its modification to a version suitable for resource-constrained settings were posed. While ceruloplasmin and 24-h urine copper continue to be important, there is little role of serum copper and penicillamine challenge test in the diagnostic algorithm. A new scoring system - Modified Leipzig score has been suggested with extra points being added for family history and serum ceruloplasmin lower than 5 mg/dl. Liver dry copper estimation and penicillamine challenge test have been removed from the scoring system. Differences in pharmacological approach to neurological and hepatic disease and global monitoring scales have been included. Rising bilirubin and worsening encephalopathy are suggested as indicators predicting need for liver transplant but need to be validated. The clinical practice guidelines provide recommendations for a comprehensive management of WD which will be of value to all specialties.

Ductal plate malformations are a heterogenous group of congenital fibrocystic liver diseases resulting from insult to the ductal plate at various stages of embryogenesis. As a result various biliary malformations, cysts, hamartomas and congenital hepatic fibrosis may be seen. We present a radiological pictorial of ductal plate malformations, accurate diagnosis of which is important for clinical management.

Objectives The aim of the study was to assess the prevalence, profile, outcome, and predictive factors of pediatric acute-on-chronic liver failure (ACLF). Methods All children 3 months to 18 years satisfying the Asia Pacific Association for the Study of Liver Diseases definition of ACLF were included. Data were both extracted from records (January 2011 to December 2014) and prospectively collected (January to October 2015). Successful outcome was defined as survival with native liver at 90 days, whereas poor outcome included those who died or received liver transplantation. Results Of the 499 children with chronic liver disease (CLD), 56 (11.2%) presented as ACLF, with a mean age of 9.35 (±4.39) years. Wilson disease and autoimmune hepatitis were the commonest underlying CLDs accounting for 24 (42.8%) and 18 (32.1%) cases, respectively. The most frequent events precipitating ACLF were a flare up of the underlying disease in 27 (48.2%) and acute viral hepatitis in 17 (30%). Poor outcome occurred in 22 (39.3%) children: 17 (30.4%) died and 5 (8.9%) received liver transplantation. Poor outcome was associated with grades 3 to 4 hepatic encephalopathy, bilirubin ≥17.5, international normalized ratio ≥3.5, and presence of 2 or more organ failures. On multivariate analysis, a Chronic Liver Failure-Sequential Organ Failure Assessment score ≥10 best predicted mortality (odds ratio 20.45, 95% confidence interval 3.9-106.7). Conclusions ACLF is present in 11.2% of childhood CLD, with a 90-day native liver survival of 61%. A Chronic Liver Failure-Sequential Organ Failure Assessment score of ≥10 best predicts mortality at day 90.

Objective To study the clinical and laboratory profile of children with progressive familial intrahepatic cholestasis (PFIC) and evaluate their outcome. Methods The study is a retrospective review of all cases diagnosed with PFIC between January 2011 and July 2015. All children underwent histopathological examination and immunostaining. Management was done as per institute's protocol. Results There were a total of 24 PFIC cases (PFIC 1—2, PFIC 2—19, PFIC 3—3). Eleven presented as neonatal cholestasis, whereas 13 others presented after 6 months of life. Median age of presentation in PFIC 2 was 5.5 months with a time lag of 13 months in diagnosis. PFIC 1 and 2 presented in infancy, whereas PFIC 3 presented late. Familial clustering was seen in 12 of 24 cases. Pruritus resolved with medical management in two-thirds of cases, 3 cases required biliary diversion (BD) with dramatic improvement. One child improved after liver transplantation. Conclusions PFIC accounts for 8% of neonatal cholestasis and 34% of cholestasis in older children with PFIC 2 being the commonest subtype. Medical therapy is successful in majority. Partial internal BD should be offered to non-cirrhotic low gamma glutamyl transferase PFIC with intractable pruritus. Progression to cirrhosis may be prevented or delayed by early diagnosis and timely intervention.

Doubts have been raised about efficacy of New Wilson’s index (NWI) in predicting Liver Transplant (LT) or mortality in decompensated Wilson Disease (WD) patients. APASL ACLF Research Consortium (AARC) has introduced a new score (AARC-ACLF) which has not been studied in children. Data of all pediatric WD cases were prospectively collected and analyzed. Cox regression and Area Under Receiver Operative Curve (AUROC) analyses were used to identify best predictive score for mortality at 90 days. Sixty-six confirmed cases of decompensated WD, 39 (59%) improved on medical management and 27 (41%) either died (20) or were transplanted (7). Among those with NWI ≥ 11 (42/66 cases) 19 survived versus those with NWI

Objectives Kasai portoenterostomy (KPE) is the primary treatment for biliary atresia (BA) with subsequent liver transplantation in failed cases. The aim of this work was to study the outcome of KPE in children with BA and identify the factors predicting a successful KPE. Methods Children diagnosed with BA and undergoing KPE between January 2010 and January 2018 were included in the study. A successful KPE was defined as decrease in bilirubin to less than 2 mg/dL at 6 months after KPE. Factors affecting the outcome (successful KPE and survival with native liver [SNL] at 2 years) were evaluated by logistic regression. Results A total of 79 children with post-KPE BA were included. Successful KPE was achieved in 29 (36.7%) of 79 children undergoing KPE. The data for survival with native liver at 2 years were available for 61 children as 9 were lost to follow up before 2 years and another 9 were aged less than 2 years at the time of analysis. Twenty-seven (44.3%) of these 61 survived with their native liver at 2 years. On logistic regression analysis, lower age at KPE, use of postoperative steroids and absence of cholangitis were significant predictors of a successful KPE. A successful KPE at 6 months was the lone independent predictor of SNL at 2 years in these children. Conclusion Early age at KPE, use of postoperative steroid and prevention of cholangitis can result in successful KPE. Those with successful KPE are likely to survive with their native liver at 2 years.

Our aim was to evaluate the efficacy and safety of sequential therapy using pegylated interferon (Peg-IFN) and nucleos(t)ide analogue (NA) for treatment of children in immunoactive (IA) and immunotolerant (IT) phases of chronic hepatitis B. It was a prospective observational study where those willing for sequential therapy were allocated to group 1 (sequential therapy) and others to group 2 (standard therapy). Sequential therapy included 8 weeks of NA followed by 44 weeks of combination of NA and Peg-IFN. In group 2, IA children received NA monotherapy, and IT children received no therapy. HBe seroconversion, HBs seroconversion, and loss of HBV DNA were the major outcome measures. A total of 61 children (36 IA and 25 IT) were included in the analysis. Among the IA children, 17 received sequential therapy and 19 received standard therapy; whereas, among the IT children, 12 received sequential therapy and 13 did not receive any therapy. In IA phase, sequential therapy led to higher HBe seroconversion (64.7% vs. 21.05%, p = 0.017) and higher virological clearance (94.12% vs. 52.63%, p = 0.008). In IT children, there was no benefit of treatment with sequential therapy over observation alone. Baseline ALT > 100 IU/L predicted response to therapy with 100% sensitivity, 89.5% specificity, and LR+ of 9.52. Sequential therapy leads to higher HBe seroconversion and virological response in children in IA phase. Children with baseline ALT > 100 IU/mL are more likely to respond to sequential therapy. There appears to be no role of sequential therapy in children in IT phase.

Wilson disease and cholestatic liver diseases may present as a diagnostic dilemma if standard guidelines incorporating markers of copper overload are followed. We hereby present a series of four cases of sclerosing cholangitis masquerading as Wilson disease. True Wilson disease cases had significantly lower ceruloplasmin (6 vs. 16 mg/dL) and higher 24-hour urinary copper (322.3 vs. 74.5 μg/day) as compared to mimickers. Initial low serum ceruloplasmin levels normalized in mimickers on follow up, and this may used as a diagnostic indicator. Standard Wilson disease diagnostic criteria thus need further modification especially in developing countries to help avoid mismanagement.

Hepatitis B Virus (HBV) reactivation in patients receiving chemotherapy, biologicals, immunosupressants, or corticosteroids is emerging to be an important cause of morbidity and mortality in patients with current or prior exposure to HBV infection. These patients suffer a dual onslaught of illness: one from the primary disease for which they are receiving the culprit drug that led to HBV reactivation, and the other from HBV reactivation itself. The HBV reactivation not only leads to a compromised liver function, which may culminate into hepatic failure; it also adversely impacts the treatment outcome of the primary illness. Hence, identification of patients at risk of reactivation before starting these drugs, and starting treatment aimed at prevention of HBV reactivation is the best strategy of managing these patients. There are no Indian guidelines on management of HBV infection in patients receiving chemotherapy, biologicals, immunosupressants, or corticosteroids for the treatment of rheumatologic conditions, malignancies, inflammatory bowel disease, dermatologic conditions, or solid-organ or bone marrow transplantation. The Indian National Association for Study of the Liver (INASL) had set up a taskforce on HBV in 2016, with a mandate to develop consensus guidelines for management of various aspects of HBV infection, relevant to India. In 2017 the taskforce had published the first INASL guidelines on management of HBV infection in India. In the present guidelines, which are in continuation with the previous guidelines, the issues on management of HBV infection in patients receiving chemotherapy, biologicals, immunosupressants, or corticosteroids are addressed.

Background A gluten-free diet (GFD) is the standard of care in the management of patients with celiac disease, but clinical and histological recovery are often delayed. In newly diagnosed patients, strict compliance to GFD is difficult to achieve; this is especially true in developing countries where gluten-free food is often difficult to obtain. Steroids, when used alone, can be effective in inducing recovery in patients with celiac disease. We performed a randomized controlled trial to study the effect of a short course of prednisolone combined with a GFD on the recovery of celiac disease. Materials and methods This study was a single-center, randomised, open-label trial. This investigation was done in a pediatric gastroenterology unit of a tertiary teaching hospital in north India.Twenty-eight newly diagnosed celiac disease patients were enrolled in the study. Prednisolone was given at 1 mg/kg for four weeks; duodenal biopsies and IgA anti-tissue transglutaminase (tTg) levels were assessed at eight weeks, six months, and 12 months from the start of the study. Outcome measures The primary outcome measures used to indicate clinical, histological, and immunological recovery of celiac disease were clinical improvement at eight weeks and the proportion of patients with improved histology by at least one grade and who were tissue transglutaminase (tTg) seronegative at eight weeks. The secondary measures were the proportion of patients showing normalization of histological features and the proportions of patients becoming seronegative at six months and one year of GFD. Results Patients were randomized into the GFD only (n = 14) or GFD with prednisolone (GFD+P) (n = 14) groups. No significant differences were detected in clinical recovery at eight weeks; none of the patients became seronegative at eight weeks, six months, or 12 months. The proportion of patients with improvement in histology by at least one grade was higher in the GFD+P group at eight weeks, and there was no difference in overall histological improvement at 12 months after starting treatment. Conclusion The addition of a short course of prednisolone to a GFD does not affect clinical and serological recovery but might result in rapid histological recovery compared to a GFD alone in patients newly diagnosed with celiac disease.

To study the etiological spectrum of acute liver failure in infants and young children and to identify clinical and biochemical markers for metabolic liver disease (MLD). This study was conducted at Department of Pediatric Hepatology, in a tertiary care specialized centre for liver diseases. All children less than 3 y of age, with liver dysfunction and INR ≥2 were included in the study. They were managed as per the departmental protocol. Included children were divided based on the etiology into 2 groups: MLD and non MLD group. Comparison analysis (MLD vs. non MLD) of the clinical and biochemical parameters was done. There were 30 children under 3 y of age with acute liver failure (ALF) with median age of 12.5 mo. Fifteen children were less than 12 mo. MLD (33 %) and hemophagocytic lymphohistiocytosis (HLH) (17 %) together accounted for half of the cases of ALF in children below 3 y of age. The other common etiologies were drug induced liver injury and acute viral hepatitis A. Etiology remained indeterminate in 3 cases (10 %). Comparative analysis of the clinical and biochemical parameters between MLD and non MLD group showed significant difference between the two groups in the median values of age (p = 0.014), bilirubin (p = 0.017), jaundice to encephalopathy (JE) interval (p = 0.039) and blood sugar (p = 0.001). Suggestive family history (OR 3.73, 95 %CI 1.67–8.30), developmental delay (OR 4.4 95 %CI 2.03–9.51), presence of diarrhea/vomiting (OR 3.28, 95 %CI 1.32–8.13) in the history and presence of urinary non glucose reducing substance (NGRS) (OR 15.5, 95 %CI 2.26–106.87) were also significantly associated with MLD group. Only 40 % children survived with native liver. MLD and HLH account for majority of ALF in infants. About 10 % of cases remain indeterminate. Viral hepatitis is more common in young children. Apart from clinical indicators, young age, high bilirubin, synthetic dysfunction, low sugar and NGRS in urine indicate MLD as a cause. Survival with native liver is low.

Limited literature is available in pediatric population regarding drug-induced liver injury (DILI) making it a diagnostic challenge. This study was thus planned to determine the clinical spectrum and the outcome of DILI in children. All patients with DILI under 18 y of age were retrospectively reviewed and details regarding clinical presentation, Roussel Uclaf Causality Assessment Method (RUCAM) scale, drugs implicated, biochemical abnormalities and outcome were noted. DILI constituted 3.7% of all children with liver disease. Cases were divided into the hepatocellular (18, 50%), cholestatic (10, 27.8%), and mixed pattern (8, 22.2%). Complementary and alternative medicines (CAM) and antitubercular (ATT) drugs accounted for three-fourth cases of total DILI (39% and 33% cases respectively). Overall, 4 (11%) patients died and 5 (14%) patients progressed to chronic DILI. Presence of ascites, non-hepatocellular injury pattern and high serum total IgG levels were significantly associated with unfavourable outcome (death or chronicity).

Cholemic or bile cast nephropathy is an under-reported entity characterized by acute renal dysfunction in patients with hepatic insult. Limited literature is available regarding its clinical presentation, pathogenesis and prognosis. We hereby present a pediatric case who presented with acute on chronic liver failure with renal dysfunction secondary to cholemic nephropathy.

OBJECTIVES Noncirrhotic portal fibrosis (NCPF) has been classically described as a disease of young to middle age with limited literature regarding its occurrence, onset, or clinical presentation in children. We hereby present a series of 19 patients diagnosed and managed as NCPF in pediatric age group. METHODS A retrospective review of all the patients presenting to the pediatric hepatology department (age

Perinatal and horizontal are the common modes of transmission of hepatitis-B virus in children. Two mother-child pairs with children having received multiple blood transfusions in past. Both the mothers developed acute hepatitis-B infection whereas children were demonstrated to be having chronic infection with hepatitis-B. One mother cleared her hepatitis-B in fection whereas it persisted in the other. Both children required anti-viral treatment. Hepatitis-B virus may rarely get transmitted from infected children to their mothers causing acute infection.

To study the effect of short term (2 wk) zinc supplementation on hemoglobin and iron status of children with acute diarrhea. This study was a prospective, open label, single arm interventional trial conducted from June 2008 through October 2009 in a teaching hospital of North India. Three to sixty months old children presenting with acute diarrhea participated in the study. Subjects were supplemented with recommended doses of oral zinc gluconate for 2 wk. Changes in levels of hemoglobin, serum iron, total iron binding capacity, and serum ferritin were the main outcome measures. Sixty-two patients completed the study successfully. The prevalence of anemia before and after 2 wk of zinc supplementation remained unchanged. However, a small decline (p > 0.05) was observed in mean hemoglobin (from 8.95 ± 1.4 to 8.73 ± 1.43 g/dL), serum iron (79.56 ± 45.81 to 78.61 ± 44.41 μg/dL) and ferritin (84.77 ± 45.35 to 83.55 ± 44.10 ng/mL) levels. Total iron binding capacity increased from 331.60 ± 109.72 to 341.30 ± 119.90 μg/dL post supplementation (p > 0.05). Even though statistically insignificant, the small change observed in the levels of hemoglobin, and indicators of iron status following short term zinc supplementation might assume significance in some settings in developing countries where children receive short courses of zinc repeatedly for frequent diarrheal episodes.