Bikrant Bihari Lal

Pediatric Acute-on-chronic Liver Failure in a Specialized Liver Unit: Prevalence, Profile, Outcome, and Predictive Factors

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.

Profile and Outcome of first 109 cases of Pediatric Acute liver Failure at a Specialized Pediatric Liver Unit in India

The outcome of paediatric acute liver failure largely depends on age and aetiology. The aim of this work was to study the aetiological spectrum and outcome of the paediatric acute liver failure cases.

Metabolic liver diseases presenting as acute liver failure in children

ContextSuspecting metabolic liver disease in an infant or young child with acute liver failure, and a protocol-based workup for diagnosis is the need of the hour.Evidence acquisitionData over the last 15 years was searched through Pubmed using the keywords “Metabolic liver disease” and “Acute liver failure” with emphasis on Indian perspective. Those published in English language where full text was retrievable were included for this review.ResultsMetabolic liver diseases account for 13-43% cases of acute liver failure in infants and young children. Etiology remains indeterminate in very few cases of liver failure in studies where metabolic liver diseases were recognized in large proportion. Galactosemia, tyrosinemia and mitochondrial disorders in young children and Wilson’s disease in older children are commonly implicated. A high index of suspicion for metabolic liver diseases should be kept when there is strong family history of consanguinity, recurrent abortions or sibling deaths; and history of recurrent diarrhea, vomiting, failure to thrive or developmental delay. Simple dietary modifications and/or specific management can be life-saving if instituted promptly.ConclusionsA high index of suspicion in presence of red flag symptoms and signs, and a protocol-based approach helps in timely diagnosis and prompt administration of lifesaving therapy.

Cholemic or Bile Cast Nephropathy in a Child with Liver Failure

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.

Non-cirrhotic Portal Fibrosis in Pediatric Population.

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 <18 years) and diagnosed as NCPF was done and data were evaluated. Results: A total of 19 patients were diagnosed as NCPF with median age at onset of symptoms and diagnosis as 10 years and 13.8 years respectively. Majority presented with left upper quadrant discomfort or mass. Laboratory parameters showed hypersplenism in majority with preserved liver synthetic functions. Median values for hepatic venous pressure gradient and liver stiffness measurement were 13.5 mmHg and 10.6 kPa, respectively. Classical hepatic histopathological features seen were maintained lobular architecture, atretic portal tracts, approximation of portal-portal and portal-central areas, and aberrant peripheral portal channels. During follow-up, majority of the patients did not show disease progression. Conclusions: NCPF is not an uncommon entity in pediatric population with age of onset in early second decade. Hepatic histopathology must be used to exclude cirrhosis and to confirm the diagnosis. Hepatic venous pressure gradient and liver stiffness measurement values, in some cases, may overlap with those in patients with cirrhosis and may not be diagnostic in isolation. Any patient presenting with evidence of portal hypertension with preserved hepatic functions, irrespective of the age, should be evaluated for possible NCPF.

Profile, risk factors and outcome of acute kidney injury in paediatric acute-on-chronic liver failure

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.

Response to Profile and outcome of first 109 cases of paediatric acute liver failure at a specialized paediatric liver unit in India: Methodological issues

In the present study, we have considered both these points before preparing the multivariate model. We first listed all the variables with P<.2, but then considered the more significantly associated variables, that is those with smaller P values, for logistic reason. Being aware of limited sample size, we could not include more than nine variables. As for the multicollinearity, all the variables considered were relating to liver failure and indices were calculated from the same parameters, hence all variables are multicollinear. Despite multicollinearity, we have found the best model but by adding the variable one by one and/or doing exploratory analysis. In the exploratory analysis there was no improvement in the prediction of outcome from 87.3%.These details may have been deleted in trying to limit the manuscript in terms of length. We did not perform formal sample size calculation, but followed the rule of thumb which states that we should have at least 510 events2 per variable included in the multivariate model in our study we have not exceeded the minimum requirement. Our centre is unique by being the only public sector paediatric liver transplant centre in India, hence the single centre data report. But we feel this data is important and can be usefully used in a metaanalysis later. Finally we must thank Ayubi et al. for improving our knowledge about measures to be taken to handle sparse data. We need time to understand the concept before we can use it on any data.

Hepatic Dysfunction in a Child Post Bone Marrow Transplantation

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).

Regression of fibrosis in pediatric liver diseases

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.

Bile Duct Perforation due to Inspissated Bile Presenting as Refractory Ascites.

Non hepatic origin of refractory ascites is not a rarity. Hemolytic anemias are known to cause inspissated bile and biliary obstruction. Distal biliary obstruction can lead to biliary perforation. The authors report a case of hereditary spherocytosis leading to inspissated bile causing bile duct perforation and biliary ascites. A high index of suspicion for biliary ascites should be kept in a child with refractory ascites in the setting of progressive ascites with decreasing bilirubin. Ascitic fluid bilirubin analysis will clinch the diagnosis. Surgical repair is the optimal management.