Bacterial and Fungal Infections in Pediatric Acute Liver Failure and Their Impact on Clinical Outcomes.

Objectives: The current study aimed to explore the prevalence, predictors and outcomes of infections in pediatric acute liver failure (PALF).

Methods: Data were retrieved from a prospectively maintained database of patients admitted with PALF between January 2012 and June 2024. "Sepsis" was defined as the presence of systemic inflammatory response syndrome with suspected or proven infection.

Acute-on-chronic liver failure (ACLF): the 'Kyoto Consensus'-steps from Asia.

Acute-on-chronic liver failure (ACLF) is a condition associated with high mortality in the absence of liver transplantation. There have been various definitions proposed worldwide. The first consensus report of the working party of the Asian Pacific Association for the Study of the Liver (APASL) set in 2004 on ACLF was published in 2009, and the "APASL ACLF Research Consortium (AARC)" was formed in 2012.

Frailty in children with chronic liver disease: Prevalence and impact on outcomes.

Objectives: Frailty is a well-known complication of chronic liver disease and has been recognized as a poor prognostic factor in cirrhotic patients being associated with increased morbidity and mortality. There is limited available pediatric literature in this regard. The current study aimed to estimate the prevalence of frailty and analyze the predictive factors and their association with long-term outcomes in children with liver disease.

Portal hypertension in doublecortin domain-containing protein 2 (DCDC2)-related neonatal sclerosing cholangitis.

Mutations in doublecortin domain-containing protein 2 (DCDC2) lead to neonatal sclerosing cholangitis (NSC), and portal hypertension (PHTN). The objective of the study was to systematically evaluate PHTN, variceal bleeding, and outcomes of patients with DCDC2-related NSC. The study included children with homozygous or compound heterozygous variants in DCDC2.

Clinico-Pathological Spectrum of Hepatitis A Virus-Induced Autoimmune-Like Hepatitis in Children.

There is limited evidence that hepatitis A virus (HAV) infection can trigger hepatic autoimmunity, but this area remains largely unexplored. This study was thus planned with the aim to compare HAV-induced autoimmune-like hepatitis (HAV-ALH) with HAV-related liver dysfunction (HAV-acute viral hepatitis or HAV-AVH) and classical autoimmune hepatitis (AIH). This was a retrospective review of 46 patients with HAV infection who underwent liver biopsy (including 17 cases of HAV-ALH: diagnosis based on histopathology), and they were compared to 46 cases of age- and gender-matched classical AIH.

Natural course and outcomes of children with ubiquitin-specific protease 53 (USP53)-related genetic chronic cholestasis.

Ubiquitin-specific protease 53 (USP53) is essential for formation of cellular tight junctions and variations in this gene disrupt the tight junctions, resulting in cholestasis. We describe the clinical manifestations and outcomes of patients with USP53 mutations from the Indian progressive familial intrahepatic cholestasis registry. All 29 patients who harbored mutations in the USP53 gene either in the homozygous, compound heterozygous, or heterozygous state and presented with cholestasis were included.

Effect of Indo-Mediterranean diet versus calorie-restricted diet in children with non-alcoholic fatty liver disease: A pilot randomized control trial.

Background: Dietary interventions and increased physical activity are the cornerstones for management of the paediatric non-alcoholic fatty liver disease (NAFLD). Though, no specific diet has been proven superior, Indo-Mediterranean diet (IMD) has shown promise in adult literature. Thus, we aimed to compare the effect of IMD and a standard calorie-restricted diet (CRD) in Indian overweight children and adolescents with biopsy-proven NAFLD.

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.

Role of splenic hepatic elastography ratio in differentiating non-cirrhotic portal fibrosis and chronic liver disease in children and adolescents.

Background: Differentiation of Non-cirrhotic Portal Fibrosis (NCPF) from chronic liver disease (CLD) in children and adolescents with portal hypertension (PHT) is challenging especially in cases where liver stiffness measurement (LSM) and hepatic venous pressure gradient are higher. This objective of the current study was to evaluate the diagnostic accuracy of the splenic stiffness measurement (SSM)/LSM ratio in the diagnosis of NCPF.

Methods: From January 2019 to December 2023, consecutive children and adolescents of 6 months to 18 years of age with PHT (CLD and NCPF) were prospectively enrolled.

Therapeutic plasma exchange provides native liver survival benefit in children with acute liver failure: A propensity score-matched analysis.

Objectives: This study aimed to evaluate the safety and efficacy of therapeutic plasma exchange (TPE) in pediatric acute liver failure (PALF).

Methods: All children aged 2-18 years with PALF were included. The intervention cohort included a subset of PALF patients undergoing complete three sessions of TPE, whereas the matching controls were derived by propensity score matching from the patient cohort who did not receive any TPE.

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%.

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.

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.

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.

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.

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).

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.

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).

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.