Circulating bacterial peptides and linked metabolomic signatures are indicative of early mortality in pediatric cirrhosis.

BACKGROUND: Patients with pediatric cirrhosis-sepsis (PC-S) attain early mortality. Plasma bacterial composition, the cognate metabolites, and their contribution to the deterioration of patients with PC-S to early mortality are unknown. We aimed to delineate the plasma metaproteome-metabolome landscape and identify molecular indicators capable of segregating patients with PC-S predisposed to early mortality in plasma, and we further validated the selected metabolite panel in paired 1-drop blood samples using untargeted metaproteomics-metabolomics by UHPLC-HRMS followed by validation using machine-learning algorithms. METHODS: We enrolled 160 patients with liver diseases (cirrhosis-sepsis/nonsepsis [n=110] and noncirrhosis [n=50]) and performed untargeted metaproteomics-metabolomics on a training cohort of 110 patients (Cirrhosis-Sepsis/Nonsepsis, n=70 and noncirrhosis, n=40). The candidate predictors were validated on 2 test cohorts-T1 (plasma test cohort) and T2 (1-drop blood test cohort). Both T1 and T2 had 120 patients each, of which 70 were from the training cohort. RESULTS: Increased levels of tryptophan metabolites and Salmonella enterica and Escherichia coli-associated peptides segregated patients with cirrhosis. Increased levels of deoxyribose-1-phosphate, N5-citryl-d-ornithine, and Herbinix hemicellulolytic and Leifsonia xyli segregated patients with PC-S. MMCN-based integration analysis of WMCNA-WMpCNA identified key microbial-metabolic modules linked to PC-S nonsurvivors. Increased Indican, Staphylobillin, glucose-6-phosphate, 2-octenoylcarnitine, palmitic acid, and guanidoacetic acid along with L. xyli, Mycoplasma genitalium, and Hungateiclostridium thermocellum segregated PC-S nonsurvivors and superseded the liver disease severity indices with high accuracy, sensitivity, and specificity for mortality prediction using random forest machine-learning algorithm. CONCLUSIONS: Our study reveals a novel metabolite signature panel capable of segregating patients with PC-S predisposed to early mortality using as low as 1-drop blood.

Wedged hepatic vein portovenography for assessment of Rex vein patency in children with extrahepatic portal venous obstruction.

BACKGROUND: Meso-Rex bypass is the surgical intervention of choice for children with extrahepatic portal vein obstruction (EHPVO). Patency of Rex vein, umbilical recessus of the portal vein, is a prerequisite for this surgery. Conventional diagnostic modalities poorly detect patency, while transjugular wedged hepatic vein portography (WHVP) accurately detects patency in 90%. OBJECTIVES: We aimed to assess Rex vein patency and portal vein branching pattern in children with EHPVO using transjugular WHVP and to identify factors associated with Rex vein patency. METHODS: Transjugular WHVP was performed in 31 children with EHPVO by selective cannulation of left and right hepatic veins. Rex vein patency, type of intrahepatic portal venous anatomy (Types A-E), and factors associated with patency of Rex vein were studied. RESULTS: The patency of Rex recess on transjugular WHVP was 29%. Complete obliteration of intrahepatic portal venous radicles was the commonest pattern (Type E, 38.7%) while Type A, the favorable anatomy for meso-Rex bypass, was seen in only 12.9%. Patency of the Rex vein, but not the anatomical pattern, was associated with younger age at evaluation (patent Rex: 6.6 ± 4.9 years vs. nonpatent Rex: 12.7 ± 3.9 years, p = 0.001). Under-5-year children had a 12 times greater chance of having a patent Rex vein (odds ratio: 12.22, 95% confidence interval: 1.65-90.40, p = 0.004). Patency or pattern was unrelated to local factors like umbilical vein catheterization, systemic thrombophilia, or disease severity. CONCLUSION: Less than one-third of our pediatric EHPVO patients have a patent Rex vein. Younger age at evaluation is significantly associated with Rex vein patency.

Relapse following withdrawal of D-penicillamine from combination (D-penicillamine + zinc) therapy in hepatic Wilson disease.

OBJECTIVES: Long-term D-penicillamine (D-pen) therapy in Wilson disease (WD) has numerous adverse effects which advocates its withdrawal, but with an inherent risk of relapse. This prospective observational study was conducted with the objective of evaluating incidence of relapse following withdrawal of D-pen from combination (D-pen + zinc) therapy in maintenance phase of previously symptomatic hepatic WD. METHODS: Hepatic WD patients <18 years of age and on combination therapy for >2 years with 6 months of biochemical remission were included. Biochemical remission was defined as achievement of (i) aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤1.5 times upper limit of normal (ULN), (ii) serum albumin >3.5 g/dL, international normalized ratio (INR) <1.5 and (iii) 24-h urinary copper excretion (UCE) <500 mcg/day, nonceruloplasmin-bound-copper (NCC) <15 mcg/dL. After D-pen withdrawal, monthly liver function test (LFT) and INR and 3 monthly UCE and NCC were done till 1 year or relapse (elevation of AST/ALT/both >2 times ULN or total bilirubin >2 mg/dL), whichever occurred earlier. RESULTS: Forty-five patients enrolled with median combination therapy duration of 36 months. Sixty percent of them had their index presentation as decompensated cirrhosis. Fourteen patients (31.8%) relapsed (cumulative incidence: 4 at 3 months, 11 at 6 months, and 14 at 12 months after D-pen discontinuation). All relapsers had index presentation as decompensated cirrhosis. On Cox-regression, ALT at D-pen withdrawal was an independent predictor of relapse (hazard ratio [HR]: 1.077, 95% confidence interval [CI]: 1.014-1.145, p = 0.017) with area under the receiver operating characteristic (AUROC) of 0.860. ALT ≥40 U/L predicted risk of relapse with 85.7% sensitivity, 70.9% specificity. CONCLUSION: Incidence of relapse after withdrawal of D-pen from combination therapy is 31.8% in hepatic WD. ALT ≥40 U/L, at the time of D-pen stoppage, predicts future relapse.

Hepatitis A Liver Failure in Children: Native Liver Survival Despite Poor Prognosis.

Background: Hepatitis A virus (HAV) infection is the commonest cause of pediatric acute liver failure (PALF) in developing countries. Literature has shown good outcomes of HAV-induced PALF as compared to other etiologies. The advanced critical care and use of extracorporeal liver assist devices (ELAD) have improved the survival with native liver in PALF and overall outcomes. Various liver transplant listing criteria have been proposed in PALF, however none of them is specific enough to predict the outcome. The timing of liver transplant in living donor setting has never been straightforward. Dynamic clinical and biochemical monitoring of the ALF child is the key to decide for LT. Cases: Here we report three children with HAV-induced PALF presented with advanced hepatic encephalopathy (HE) and high international normalized ratio (INR > 10). These children survived with native liver despite fulfilling the liver transplant criteria. The first child is a 14-year-old male who had peak INR of more than 10.2 and grade 3-4 HE with cerebral edema and acute kidney injury. He responded to medical management and CRRT as liver assist device. The second one is a 7-year-old male child who also recovered well with native liver despite advanced HE and INR of more than 10. Third child is a 16-year-old male who had peak INR of 12.6 and grade 2 HE. He received ELAD (Therapeutic plasma exchange and CRRT) and survived with native liver. Conclusion: Children with HAV-induced PALF can recover with their native liver despite extremely poor prognostic markers like very high INR, ammonia and advanced HE.

Adequate Chelation and Cupriuresis in Hepatic Wilson Disease Patients Under Combination (Chelator + Zinc) Therapy at 2 Years of Follow-up.

Background & aim: Role of 24-h urinary copper excretion (UCE) in monitoring Wilson disease (WD) on combination (chelator + Zinc) therapy is not well studied, especially in the pediatric population. Hence, the present study is conducted with an aim to evaluate UCE and its role in deciding therapeutic adequacy in pediatric WD on long-term follow-up. Methods: All WD patients <18 years of age and on combination therapy with at least one UCE available after the first year of treatment were included. Liver biochemistries, UCE, and serum non-ceruloplasmin bound copper (NCC) were assessed at diagnosis and various follow-ups. For assessment of treatment efficacy, criteria for adequate chelation (CAC) were defined as fulfillment of both (i) AST & ALT ≤1.5 times upper limit of normal, serum albumin >35 gm/L, INR <1.5 and (ii) UCE <500 mcg/day. Results: Of the 74 included children, 70 (94.5%), 45 (60.8%), 28 (37.8%) and 21 (28.3%) completed 2-, 3-, 5-, and 7-year follow-up, respectively. Liver biochemistries improved significantly within 1 year of treatment. UCE (mcg/day) decreased significantly from baseline of 654.08 ± 803.78 to 308.23 ± 175.93 at 2 years with no further change at 3- and 5-years follow-up. UCE (mcg/day) at 2 years was <200 in 28.5%, 200-500 in 55.7%, and >500 in 15.7%. 61% achieved CAC in 2 years. On multivariate cox regression, treatment compliance was predictor for CAC achievement (Odds ratio: 3.48, 95%CI: 1.36-8.86. P = 0.009). Conclusion: UCE declines significantly from baseline to <500 mcg/day within 2 years. Majority of treatment-compliant patients achieve CAC within 2 years of combination therapy.

Genotype correlates with clinical course and outcome of children with tight junction protein 2 (TJP2) deficiency-related cholestasis.

BACKGROUND AND AIMS: The study aimed to describe the clinical course and outcomes, and analyze the genotype-phenotype correlation in patients with tight junction protein 2 (TJP2) deficiency. APPROACH AND RESULTS: Data from all children with chronic cholestasis and either homozygous or compound heterozygous mutations in TJP2 were extracted and analyzed. The patients were categorized into 3 genotypes: TJP2-A (missense mutations on both alleles), TJP2-B (missense mutation on one allele and a predicted protein-truncating mutation [PPTM] on the other), and TJP2-C (PPTMs on both alleles). A total of 278 cases of genetic intrahepatic cholestasis were studied, with TJP2 deficiency accounting for 44 cases (15.8%). Of these, 29 were homozygous and 15 were compound heterozygous variants of TJP2 . TJP2-A genotype was identified in 21 (47.7%), TJP2-B in 7 cases (15.9%), and TJP2-C in 16 cases (36.4%), respectively. Patients with the TJP2-C genotype were more likely to experience early infantile cholestasis (87.5% vs. 53.5%, p =0.033), less likely to clear jaundice (12.5% vs. 52.2%, p =0.037), more likely to develop ascites, and had higher serum bile acids. Patients with the TJP2-C genotype were more likely to die or require liver transplantation (native liver survival: 12.5% vs. 78.6%, p <0.001), with a median age at death/liver transplantation of 2.5 years. Cox regression analysis revealed that TJP2-C mutations ( p =0.003) and failure to resolve jaundice ( p =0.049) were independent predictors of poor outcomes. CONCLUSIONS: Patients with the TJP2-C genotype carrying PPTMs in both alleles had a rapidly progressive course, leading to early decompensation and death if they did not receive timely liver transplantation.

Prevalence and clinicopathological Spectrum of Auto-Immune Liver Diseases & Overlap syndrome.

Aims: Autoimmune liver diseases (AILD) represent a spectrum of related yet distinct immune-mediated disorders. The literature on the prevalence of these AILDs in Indian population is scarce. This study aims to assess the prevalence and clinicopathological spectrum of various AILDs especially the overlap syndrome. Materials and Methods: A 10-year (2011-2020) cross-sectional, retrospective observational study of histological proven cases of AILD was conducted. Clinical, demographic, and laboratory parameters were retrieved. Two pathologists independently reviewed the liver biopsies and reassessed 18 histopathological parameters. Results: During the study period, 17664 liver biopsies were received, out of which 1060 (6%) biopsies of AILD were identified. After exclusion, we had 721 cases which revealed a distribution of autoimmune hepatitis (AIH)-64.7%, primary biliary cholangitis (PBC)-14.8%, primary sclerosing cholangitis (PSC)-7.6%, overlap AIH-PBC 11%, and overlap AIH-PSC 1.7%. AIH patients had significantly higher prevalence for severe lobular inflammation (27%, P ≤ 0.001), several lobular plasma cells (37%, P ≤ 0.001), central perivenulitis (30%, P ≤ 0.001), hepatic rosettes (51%, P ≤ 0.001), and necrosis (35.5%, P ≤ 0.001), while PBC patients had significantly higher frequency of florid duct lesions (11.2%, P ≤ 0.001), duct loss (83.17%, P ≤ 0.001), bile duct damage (76.6%, P ≤ 0.001), and periportal copper deposits (19.6%, P ≤ 0.001). Overlap AIH-PBC group had the highest proportion of severe portal inflammation (27.5%, P ≤ 0.001), prominent portal plasma cells (75%, P ≤ 0.001), moderate interface activity (53.7%, P ≤ 0.001), Mallory-Denk bodies (27.5%, P ≤ 0.001), and periportal cholate stasis (25%, P ≤ 0.001). Conclusion: Prevalence of biopsy-proven AILDs in our study cohort is 6%. AIH (64.7%) is the most common AILD followed by PBC (14.8%). Overlap syndrome (AIH-PBC) showed prevalence of 11%.

Midodrine reduces new-onset acute kidney injury and hyponatremia in children with cirrhosis and ascites awaiting liver transplantation: Results from an open-label RCT.

OBJECTIVES: Midodrine, an oral α-1-adrenergic receptor agonist, counters arterial hypovolemia and reduces complications in adult patients with cirrhosis. This randomized controlled trial (RCT) aimed to assess the efficacy and safety of midodrine in preventing complications and improving survival in children with cirrhosis and ascites who are awaiting liver transplantation (LT). METHODS: This open-label RCT conducted from January 2022 to May 2023 included children under 18 years with cirrhosis and ascites. Patients were randomized to receive either midodrine plus standard medical therapies (SMTs) or SMT alone. The primary outcome measure was the incidence of cirrhosis-related complications within 6 months. RESULTS: Thirty-five subjects were enrolled and randomized. Patients in the midodrine arm had a lower incidence of new-onset acute kidney injury (AKI) compared with the SMT arm (11.1% vs. 41.2%). Patients in the midodrine arm showed a decline in serum creatinine and improvement in glomerular filtration rate, whereas no changes were observed in the SMT arm. There was a lower incidence of new-onset hyponatremia in the midodrine arm (20% vs. 56%). Midodrine led to reduction in plasma rennin activity (PRA) and improvement in systemic hemodynamics. There was no difference in the rate of resolution of ascites, recurrence of ascites, requirement of therapeutic paracentesis, cumulative albumin infusion requirement, episodes of spontaneous bacterial peritonitis, and hepatic encephalopathy between the two arms. CONCLUSION: Midodrine, when added to SMT, was effective in reducing the incidence of new-onset AKI and hyponatremia in pediatric cirrhotics awaiting LT. It also improved systemic hemodynamics and showed a trend towards reducing PRA.

Liver histology and hepatic progenitor cell activity in pediatric acute liver failure: Implications for clinical outcome.

BACKGROUND: Hepatic progenitor cell (HPC) activity and regenerative process that follows pediatric acute liver failure (PALF) is still not well understood. This clinicopathological study was thus conducted with an aim to study the correlation of liver histology and HPC activity with outcomes in PALF. METHODS: All PALF patients with available hepatic histological specimens were included and specimens were analyzed for hepatocyte loss, HPC activity [using cytokeratin (CK) 7, CK19, sex-determining region Y-related high mobility group box(SOX)9 and epithelial cell adhesion molecule (EpCAM)], hepatocyte proliferation (using Ki67), and hepatocyte senescence (using p53 and p21). RESULTS: Ninety-four children were included: 22 (23.4%) survived with native liver (SNL) (i.e., the good outcome group) while rest (i.e., the poor outcome group) either died [33%, 35.1%] or received liver transplant (LT) [39%, 41.5%]. When compared to subjects with poor outcomes, those in the SNL group exhibited significantly less severe hepatocyte loss, fewer HPC/hpf, more proliferating hepatocytes, and less senescent hepatocytes (p < .05). Increasing severity of hepatocyte loss (adjusted OR: 9.95, 95% CI: 4.22-23.45, p < .001) was identified as an independent predictor of poor outcome. Eighty percent children with >50% native hepatocyte loss had poor outcome within 10 days of hospitalization. CONCLUSION: In PALF, more severe hepatocyte loss, higher number of HPC activation, lesser number of proliferating hepatocytes, and greater number of senescent hepatocytes are associated with a poor outcome. Loss of >50% hepatocytes is an independent predictor of poor outcome in PALF.

Live donor liver transplantation for pediatric acute liver failure: challenges and outcomes.

OBJECTIVE: This study aimed at studying the challenges and outcomes of live-donor liver transplantation (LDLT) for pediatric acute liver failure (PALF). STUDY DESIGN: A total of 315 patients with PALF were treated over a period of 11 years. 42 underwent LT (41 LDLT and one DDLT), constituting 38% (41/110) of all pediatric transplants during this duration. The outcomes of LDLT for PALF were analyzed. RESULTS: All the 41 children who underwent LT met the Kings College criteria (KCC). The etiology was indeterminate in 46.3% (n = 19) children. 75.6% (n = 31) were on mechanical ventilation for grade 3/4 hepatic encephalopathy. There was presence of cerebral edema on a computed tomography scan of the brain in 50% of the children. One-third of our children required hemodynamic support with vasopressors. Systemic inflammatory response syndrome and sepsis were observed in 46.3% and 41.4% of patients, respectively. Post-LDLT 1- and 5-yr patient and graft survival were 75.6% and 70.9%, respectively. The survival in children satisfying KCC but did not undergo LT was 24% (38/161). Vascular and biliary complication rates were 2.4% and 4.8%, respectively. No graft loss occurred because of acute rejection. In multivariate analysis, pre-LT culture positivity and cerebral edema, persistence of brain edema after transplantation, and resultant pulmonary complications were significantly associated with post-LT death. Thirteen (32%) children who underwent plasmapheresis prior to LT had better post-LT neurological recovery, as evidenced by early extubation. CONCLUSION: LDLT for PALF is lifesaving and provides a unique opportunity to time transplantation. Good long-term survival can be achieved, despite the majority of patients presenting late for transplantation. Early referral and better selection can save more lives through timely transplantation.

Severe Acute Hepatitis of Unknown Etiology Presenting as Pediatric Acute Liver Failure: Analysis of Likely Etiology, Clinical Course and Outcome.

Adenovirus, adeno-associated virus, and severe acute respiratory syndrome-coronavirus-2 (SARS-COV2) have been recently implicated as probable causative agents of severe acute hepatitis of unknown etiology reported from most of Europe. High mortality and liver transplantation (LT) rates have been observed in those presenting with acute liver failure (ALF). Such cases have not been reported from the Indian subcontinent. We analyzed the etiologies, clinical course, and in-hospital outcomes of cases of severe acute hepatitis with ALF presenting to us between May and October 2022. A total of 178 children presented with severe acute hepatitis of known/unknown etiology including 28 presenting as ALF. Eight of them fulfilled the definition of severe acute hepatitis of unknown etiology presenting as ALF. Adenovirus was not associated with cases of ALF in these children. SARS-COV2 antibodies were detected in 6 (75%) of them. Children with severe acute hepatitis of unknown etiology presenting as ALF were young (median age 4 years), had hyper-acute presentation with a predominance of gastrointestinal symptoms, and a fulminant course with worse outcomes (native liver survival 25%). Expedited evaluation of these children for LT would be the key to management.

Association of HLA DRB1 Allele Profile with Pediatric Autoimmune Liver Disease in India.

Objectives: The aim of this study is to study the association of human leukocyte antigen (HLA) DRB1 alleles with treatment response in Indian children with autoimmune liver disease (AILD). Methods: HLA DRB1 alleles of 71 Indian children with pediatric AILD (pAILD) were analyzed along with 25 genetically confirmed patients with Wilson disease as controls. After 1 year of therapy, all those who failed to normalize aspartate & alanine transferase (AST/ ALT) (below 1.5 times of upper limit of normal) and/or failed to normalize IgG levels, or who had >2 relapses (AST/ALT levels >1.5 times of upper limit of normal) while on treatment, were labeled as difficult to treat (DTT). Results: HLA DRB1∗3 was found to be significantly associated with AIH type 1 (46.2% vs. 4% in controls; P corrected = 0.011). Majority of the patients [55 (77.5%)] had chronic liver disease at presentation, with 42 (59.2%) having portal hypertension and 17 (23.9%) having ascites. Out of the 71 with pAILD, 19 (26.8%) were DTT. HLA DRB1∗14 was found to be independently associated with DTT cases (36.8% vs. 9.6%, OR 5.87, 95% CI 1.07-32.09, P = 0.041). Other factors independently associated with DTT were presence of autoimmune sclerosing cholangitis (OR 8.57, P = 0.008) and high-risk varices (OR 7.55, P = 0.016), improving the correctness of classification of the model from 73.2% to 84.5%. Conclusion: HLA DRB1∗14 is independently associated with treatment response in pAILD and HLA DRB1∗3 is associated with AIH type 1. HLA DRB1 alleles may thus provide supportive information for diagnosis and prognosis of AILD.

Treatment of intractable cholangitis in children with biliary atresia: Impact on outcome.

OBJECTIVES: To evaluate the response and outcome with prolonged intravenous antibiotics including home-based intravenous antibiotics in children with intractable cholangitis (IC) after Kasai portoenterostomy (KPE) for biliary atresia (BA). METHODS: A retrospective review of treatment and outcome of children with IC post KPE (no resolution after four weeks of antibiotics) was done between 2014 and 2020. A protocol-based antibiotic regimen was used based on sensitivity and hospital antibiogram. Children afebrile for more than three days were discharged on home intravenous antibiotics (HIVA). RESULTS: Twenty children with IC were managed with prolonged antibiotic regimen, including HIVA. All patients were initially listed for liver transplantation (LT) with indication being IC (n = 20) with portal hypertension (n = 12). Seven patients had bile lakes of which four underwent percutaneous transhepatic biliary drainage. Bile culture grew Klebsiella in four and Escherichia coli and Pseudomonas one each. There were eight children with IC who had positive blood culture with most of these organisms being gram-negative (Escherichia coli: 5, Klebsiella pneumoniae: 2, Enterococcus: 1). Median duration of antibiotics was 58 days (interquartile range [IQR] 56-84). Median follow-up period post cholangitis was three years (IQR 2-4). Following treatment, 14 patients were successfully delisted from LT waitlist and are presently jaundice-free. Two of the five patients undergoing LT died of sepsis. One patient died awaiting LT. CONCLUSION: Timely and aggressive step-up antibiotic regimen may successfully treat IC and prevent/delay LT. HIVA provides a cost-effective and comfortable environment for a child which might improve compliance with intravenous antibiotics.

Liver transplantation for alpha 1 antitrypsin deficiency (A1ATD) using a heterozygous donor: Outcomes and review of the literature.

INTRODUCTION: Alpha 1 antitrypsin deficiency (A1ATD) accounts for 21% of all pediatric liver transplants due to metabolic disease in the western world. Donor heterozygosity has been evaluated in adults but not to a recipient with A1ATD. METHODS: The data of patient were retrospectively analyzed and a literature review performed. RESULTS: We present a unique case of living related donation from a A1ATD heterozygote female to a child for decompensated cirrhosis due to A1ATD. In the immediate postoperative period, the child had low-alpha 1 antitrypsin levels, but these normalized by 3 months posttransplant. He is currently 19 months post-transplant with no evidence of recurrent disease. CONCLUSION: Our case provides initial evidence that A1ATD heterozygote donors may be safely used for pediatric patients with A1ATD, thus expanding the donor pool.

Splenic Stiffness Is the Best Predictor of Clinically Significant Varices in Children With Portal Hypertension.

BACKGROUND AND AIMS: We studied splenic stiffness measurement (SSM) by transient elastography (TE) and portal hemodynamics parameters (PHDp) on Doppler as predictors of clinically significant varices (CSV) in children. METHODS: All children of 6 months to 18 years of age with portal hypertension (PHT) (chronic liver disease, CLD and non-cirrhotic portal hypertension, NCPH) were enrolled. TE for spleen (SSM) and liver (liver stiffness measurement, LSM) and PHDp by Doppler ultrasonography were measured. Noninvasive indices for PHT were calculated. CSV were defined as esophageal varices ≥grade 2 and/or gastric varix. Binary logistic regression analysis (LRA) and receiver operating characteristic statistics were applied. RESULTS: A total of 150 (120 CLD and 30 NCPH) children formed the study cohort. Prevalence of CSV was higher in NCPH than CLD [73.3% vs 53.3%, Odd's ratio (OR) 2.369, P = 0.04]. On LRA, SSM was found to be the only independent predictor of CSV in children with CLD [OR 1.19 (95% Confidence Interval (CI) 1.018-1.16), P = 0.000] as well as in NCPH [OR 1.088 (95% CI 1.018-1.16), P = 0.013]. This model improved prediction of CSV in CLD from 52.5% to 83.9% and in NCPH from 73.3% to 86.7%. In children with CLD, SSM at a cut-off ≥27.6 kPa and in NCPH, SSM at a cut-off ≥29.5 kPa predicted CSV. In children with CLD, SSM correlated with LSM ( R = 0.610, P <0.001) and with noninvasive PHT indices except aspartate aminotransferase-to-platelet ratio index. CONCLUSION: SSM is the best noninvasive predictor of CSV in childhood CLD and NCPH and can be used as screening test for endoscopy in children with PHT.

Study of Adherence to Medication in Pediatric Liver Diseases ("SAMPLD" Study) in Indian Children.

Background/objectives: Adherence to medication(s) is an essential component of holistic management in any chronic disease including in post liver transplant (LT) patients. Thus, this study aimed to assess adherence to medications in Indian pediatric liver disease patients (including post LT recipients) and to identify variables affecting its occurrence. Methods: A cross-sectional study was conducted among pediatric (<18 years of age) subjects with Wilson disease (WD) and autoimmune liver disease (AILD) along with post LT recipients from May 2021 to October 2021. Structured tools using prevalidated questionnaires (Medication adherence measure and the Child & Adolescent Adherence to Medication Questionnaire) were used to collect data related to nonadherence prevalence (based on missed and late doses) and factors influencing the adherence. Results: A total of 152 children were included in the study (WD 39.5%, AILD 32.9%, and post LT 27.6%). Prevalence of missed and late dose nonadherence (at a cut-off of ≥20%) was 12.5% and 16.4%, respectively. Older age (odd's ratio/O.R 1.185), stay in a rural area (O.R 5.08), and barriers like bad taste of medication (O.R 4.728) and hard to remember the medication (O.R 7.180) were independently associated with nonadherence (P < 0.05). Conclusions: Overall, nonadherence was seen in 12-16%, i.e., around one-sixth of the patients, with least nonadherence seen in post LT recipients (0-2.4%). Older age of the patient, rural place of stay and personal barriers like hard to remember/forgetfulness and bad medication taste were identified as factors independently leading to nonadherence.

Operational Tolerance after Liver Transplantation: First Report from India.

Operational tolerance after liver transplantation is an ideal goal to avoid long-term morbidities associated with chronic immunosuppressive medication use. It is achievable in a highly selected group of post-transplant recipients but requires long-term follow-up and strict monitoring. We hereby report a post-transplant case who achieved spontaneous operational tolerance after inadvertent immunosuppression withdrawal.