Therapeutic Plasma Exchange in Pediatric Acute Liver Failure

We aims to assess the efficacy and safety of therapeutic plasma exchange (TPE) in pediatric acute liver failure (PALF) and to examine possible risk factors for mortality. Similar data are limited in PALF. Thirty-three cases diagnosed with PALF who received TPE from June 2011 to June 2021 in the pediatric intensive care unit (PICU) of the First Hospital of Jilin University were included in this retrospective cohort analysis. Descriptive statistics were used for the clinical features of these patients and TPE related variables. The effect of TPE was measured by the difference tests before and after treatment. Survivors with native livers and nonsurvivors were also compared by the difference tests. In the TPE combined with continuous renal replacement therapy (CRRT) group (21/33, 63.6%), the patients were older, and more patients had multiple organ dysfunction syndrome (76.2% vs 25%, P =0.009) and a greater need for mechanical ventilation (86.2% vs 8.3%, P ＜0.001). TPE can significantly reduce alanine aminotransferase, total bilirubin, and international normalized ratio . The most common complication in the overall population was hypocalcemia (n=12, 36%), while the most common complication in children under 2 years of age was hypotension (n=3, 40%). The mortality of liver transplant-free patients was 10/30 (30%). The nonsurvivor group had significantly more failed organs, longer PICU stays and more patients requiring ventilatory support. ConclusionsTPE alone or combined with CRRT can effectively improve liver function and may reduce mortality. TPE can be performed relatively safely in critically ill children, including younger patients.

Prognostic Factors for Pediatric Acute Liver Failure: A Systematic Review and Meta-analysis of Prognostic Studies

Context: Pediatric acute liver failure (PALF) is a disease with high mortality, characterized by a multisystem disorder and acute liver dysfunction. Objectives: A systematic review and meta-analysis of prognostic studies is necessary to summarize the general prognostic factors for PALF. Also, these factors can contribute to the development of a new prognostic model. Methods: An electronic literature search was conducted systematically in PubMed, Embase and Cochrane databases to identify prognostic factors of pediatric acute liver failure and evaluate outcomes, including spontaneous survival, death without LT, and undergoing LT. Prospective or retrospective cohort designs were included. The methodological quality of studies was analyzed and scored, using the QUIPS tool. Also, a meta-analysis was performed to calculate the pooled odds ratio (OR) of the factors Results: 1465 citations were identified, 30 studies were reviewed, and 16 studies were included in the meta-analysis. The indicators extracted from the studies were divided into four categories: (1) general markers, (2) bio-markers, (3) scoring systems, and (4) treatments. Several prognostic factors were associated with the poor outcomes, including etiology (indeterminate disease and drugs), INR, ammonia, ALT levels, AST levels, bilirubin, albumin, severe HE (grade 3/4), sex (male), lactate. In addition, ammonia, bilirubin, albumin, AST levels, severe HE (grade 3/4) and etiology (indeterminate disease, drugs, metabolic disease) were associated with death (no LT). Conclusions: Etiology, ammonia, bilirubin, albumin, AST levels, severe HE (grade 3/4) were found associated with the poor outcomes or death (without LT) of PALF. Although these factors may contribute to the new prognostic model, they must be considered with caution. Further prognostic studies of PALF with larger cohorts are also needed.

Pediatric Acute Liver Failure in Sickle Cell Disease

<b><i>Introduction:</i></b> Sickle cell intrahepatic cholestasis (SCIC) is one of the rarest and the most severe acute hepatic manifestations of sickle cell disease (SCD) and it can rapidly progress to acute liver failure. It is associated with a high mortality rate, demanding prompt recognition and management. <b><i>Case Presentation:</i></b> We report a case of a 7-year-old boy with a history of homozygous HbS SCD who presented to the emergency department with fever, increasing abdominal pain, and jaundice. His course was complicated by acute liver injury (AST 9,472 IU/L, ALT 2,683 IU/L, total bilirubin 15.4 mg/dL; conjugated bilirubin 8.69 mg/dL, hypoalbuminemia 2.6 g/dL, and persistent hypoglycemia), with acute liver failure (coagulopathy not corrected by vitamin K administration with INR 3.26, decreased factors V 10% and VII 28%, and West Haven grade I hepatic encephalopathy associated with mild hyperammonemia of 71 µmol/L). After excluding other causes of acute liver failure, the patient was diagnosed as having SCIC and was successfully treated with manual exchange transfusion. <b><i>Conclusion:</i></b> This case reinforces that exchange transfusion is an effective treatment for SCIC and that it should be introduced promptly to prevent fulminant and potentially fatal liver failure.

Dynamics of Systemic Inflammation as a Function of Developmental Stage in Pediatric Acute Liver Failure

The Pediatric Acute Liver Failure (PALF) study is a multicenter, observational cohort study of infants and children diagnosed with this complex clinical syndrome. Outcomes in PALF reflect interactions among the child’s clinical condition, response to supportive care, disease severity, potential for recovery, and, if needed, availability of a suitable organ for liver transplantation (LTx). Previously, we used computational analyses of immune/inflammatory mediators that identified three distinct dynamic network patterns of systemic inflammation in PALF associated with spontaneous survivors, non-survivors (NS), and LTx recipients. To date, there are no data exploring age-specific immune/inflammatory responses in PALF. Accordingly, we measured a number of clinical characteristics and PALF-associated systemic inflammatory mediators in daily serum samples collected over the first 7 days following enrollment from five distinct PALF cohorts (all spontaneous survivors without LTx): infants (INF, &lt;1 year), toddlers (TOD, 1–2 years.), young children (YCH, 2–4 years), older children (OCH, 4–13 years) and adolescents (ADO, 13–18 years). Among those groups, we observed significant (P&lt;0.05) differences in ALT, creatinine, Eotaxin, IFN-γ, IL-1RA, IL-1β, IL-2, sIL-2Rα, IL-4, IL-6, IL-12p40, IL-12p70, IL-13, IL-15, MCP-1, MIP-1α, MIP-1β, TNF-α, and NO2−/NO3−. Dynamic Bayesian Network inference identified a common network motif with HMGB1 as a central node in all sub-groups, with MIG/CXCL9 being a central node in all groups except INF. Dynamic Network Analysis (DyNA) inferred different dynamic patterns and overall dynamic inflammatory network complexity as follows: OCH&gt;INF&gt;TOD&gt;ADO&gt;YCH. Hypothesizing that systemically elevated but sparsely connected inflammatory mediators represent pathological inflammation, we calculated the AuCon score (area under the curve derived from multiple measures over time divided by DyNA connectivity) for each mediator, and identified HMGB1, MIG, IP-10/CXCl10, sIL-2Rα, and MCP-1/CCL2 as potential correlates of PALF pathophysiology, largely in agreement with the results of Partial Least Squares Discriminant Analysis. Since NS were in the INF age group, we compared NS to INF and found greater inflammatory coordination and dynamic network connectivity in NS vs. INF. HMGB1 was the sole central node in both INF and NS, though NS had more downstream nodes. Thus, multiple machine learning approaches were used to gain both basic and potentially translational insights into a complex inflammatory disease.

Early Detection and Rescue of an Unusual Case of Pediatric Acute Liver Failure Associated with Secondary Hemophagocytic Lymphophagocytosis: Case Report from a Liver Transplant Center in India

Hemophagocytic lymphohistiocytosis (HLH) is a rare, multisystem, potentially fatal clinicopathologic syndrome. HLH presenting predominantly as pediatric acute liver failure (PALF) has been rarely reported. Early recognition is imperative to initiate life-saving treatment but is often hampered due to the rarity of this syndrome, variable clinical presentations, and nonspecific clinical and laboratory findings. In this article, we reported a case of secondary HLH (H1N1 and RSV positive) presenting as PALF from India. A previously healthy 22-month-old boy presented with fever, vomiting, and altered sensorium for 10 days. He had coagulopathy and deranged liver functions. He was evaluated for underlying etiology and managed on lines of PALF. Due to persistent bicytopenia and excessively high ferritin levels, HLH was strongly suspected though he did not fulfill all clinical criteria for the diagnosis of HLH. Presence of seizures and cerebrospinal fluid analysis was suggestive of central nervous system involvement. There was no evidence of primary HLH on genetic evaluation. Real-time polymerase chain reaction amplifications were positive for RSV and influenza A H1N1, confirming the causative triggers. After the administration of immunosuppressants and oseltamivir, the patient's symptoms improved dramatically and he recovered completely. To the best of our knowledge, this is the fourth case reported worldwide till date of successful rescue of ALF in a child associated with HLH completely without resorting to liver transplantation. Clinical vigilance is crucial for possible presence of HLH with varied initial presentations in PALF despite incomplete diagnostic criteria, with detailed etiological workup for commencing life-saving therapy in time.