Therapeutic plasma exchange in children with acute liver failure (ALF): is it time for incorporation into the ALF armamentarium?

Paediatric acute liver failure (PALF) is a rare but devastating condition with high mortality. An exaggerated inflammatory response is now recognised as pivotal in the pathogenesis and prognosis of ALF, with cytokine spill from the liver to systemic circulation implicated in development of multi-organ failure associated with ALF. With advances in medical management, especially critical care, there is an increasing trend towards spontaneous liver regeneration, averting the need for emergency liver transplantation or providing stability to the patient awaiting a graft. Hence, research is ongoing for therapies, including extracorporeal liver support devices, that can bridge patients to transplant or spontaneous liver recovery. Considering the immune-related pathogenesis and inflammatory phenotype of ALF, plasma exchange serves as an ideal liver assist device as it performs both the excretory and synthetic functions of the liver and, in addition, works as an immunomodulatory therapy by suppressing the early innate immune response in ALF. After a recent randomised controlled trial in adults demonstrated a beneficial effect of high-volume plasma exchange on clinical outcomes, this therapy was incorporated in European Association for the Study of Liver (EASL) recommendations for managing adult patients with ALF, but no guidelines exist for PALF. In this review, we discuss rationale, timing, practicalities, and existing evidence regarding the use of plasma exchange as an immunomodulatory treatment in PALF. We discuss controversies in delivery of this therapy as an extracorporeal device, and practicalities of use of plasma exchange as a ‘hybrid’ therapy alongside other extracorporeal liver assist devices, before finally reviewing outstanding research questions for the future.

The Use of Extracorporeal Liver Support Systems In Acute Decompensated Liver Failure

The aim of the study: to evaluate the efficacy of extracorporeal liver support systems in patients with acute liver failure of various etiologies.Material and methods. The study included 117 patients with acute liver failure of various etiologies. The main group consisted of 71 patients who received complex intensive therapy, including MARS-therapy and hemodiafiltration. The comparison group included 46 patients who received albumin dialysis (24 patients) and hemodiafiltration (22 patients) alone. The mean age of the patients was 34±5.6 years, the majority (56.4%) were men. Dynamic assessment of patients' severity was performed using Sequential Organ Failure Assessment (SOFA) and Model for End-Stage Liver Disease (MELD) scales.Results. A more significant reduction of SOFA and MELD scores was noted as early as by day 10 of intensive therapy in the main group with sequential use of extracorporeal liver detoxification methods — to 2.7±0.2 vs. 8.3±0.5 points (P=0.021) on SOFA and to 16.7±0.4 vs. 23.4±1.4 points (P=0.023) MELD scales. The use of a comprehensive approach to extracorporeal detoxification in acute decompensated liver failure increased the regression rate of multiple organ failure from 51.2 to 74.6% and reduced mortality from 47.8 to 25.4% (χ2=6.266; df=1; P=0.013). At the same time, the cumulative proportion of survivors depending on the type of complication within 30 days was 88.4% in the main group and 69.0% in the comparison group (χ2=4.164; df=1; P=0.042).Conclusion. A comprehensive approach to extracorporeal detoxification is highly effective, providing a more significant reduction of SOFA and MELD scores, increasing the proportion of regression of multiple organ dysfunction and reducing mortality.

Successful Bridging to Recovery Using the Prometheus® Liver Support in a Critical Ill COVID-19 Patient with Acute Liver Failure: A Case Report

Liver impairment is frequently reported in Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) infected patients and contributes to increased morbidity and mortality in critically ill Coronavirus disease-2019 (COVID-19) patients. We report of a 44-year-old male patient with hypoxic and cholestatic liver failure after an initially complicated course of COVID-19 pneumonia with moderate Acute Respiratory Distress Syndrome (ARDS), Acute Kidney Injury (AKI) stage 3 with Kidney Replacement Therapy (KRT), thromboembolic intestinal ischemia with subtotal colectomy and partial resection of the small intestine and septic shock. After considerable clinical improvement we initiated extracorporeal liver support due to progressive hyperbilirubinemia up to 25,3 mg/dl. Within 17 days we conducted 11 sessions of extracorporeal liver support by Fractionated Plasma Separation and Adsorption (FPSA; Prometheus®) until stabilization of liver function occurred. After 52 days of intensive care treatment and successful weaning from ventilation and KRT, the patient was transferred to an Intermediate Care (IMC) unit. To the best of our knowledge, this is the first report of a COVID-19 patient successfully treated with prolonged extracorporeal liver support. Extracorporeal procedures that support liver function should be considered as bridging to recovery in selected COVID-19 patients if liver failure presents a dominant organ dysfunction.

Hepatitis B Virus Reactivation in Gastrointestinal Stromal Tumor Patients Treated With Imatinib

PurposeHepatitis B virus reactivation (HBVr) in patients with gastrointestinal stromal tumors (GISTs) have not been sufficiently characterized. This study aimed to review the possible mechanism of HBVr induced by imatinib and explore appropriate measures for patient management and monitoring.MethodsThe clinical data of GIST patients who experienced HBVr due to treatment with imatinib at Xiangya Hospital (Changsha, Hunan, China) were retrospectively analyzed. A literature review was also conducted.ResultsFive cases were analyzed, including 3 cases in this study. The average age of the patients was 61.8 y, with male preponderance (4 of 5 vs. 1 of 5). These patients received imatinib as adjuvant treatment (n=4) or as neoadjuvant treatment (n=1). Primary tumors were mostly located in the stomach (n=4) or rectum (n=1). High (n=3) or intermediate (n=1) recurrence risk was categorized using the postoperative pathological results (n=4). Imatinib was then started at 400 (n=4) or 200 mg (n=1) daily. Patients first reported abnormal liver function during the 2th (n=1),6th (n=3), or 10th (n=1) month of treatment with imatinib. Some patients (n=4) discontinued imatinib following HBVr; notably, 1 month after discontinuation, 1 patient experienced HBVr. Antivirals (entecavir n=4, tenofovir n=1), artificial extracorporeal liver support (n=1), and liver transplant (n=1) were effective approaches to treating HBVr. Most patients (n=3) showed favorable progress, 1 patient underwent treatment, and 1 patient died due to severe liver failure induced by HBVr.ConclusionsAlthough HBVr is a rare complication (6.12%), HBV screening should be conducted before starting treatment with imatinib in GIST patients. Prophylactic therapy for hepatitis B surface antigen positive patients, prompt antiviral treatment and cessation of imatinib are also necessary.

The use of a single pass albumin dialysis for the management of liver failure- a case series

Intoduction. A single pass albumin dialysis (SPAD) is a form of extracorporeal liver support system for the removal of albumin-bound toxins and water-soluble substances that accumulate in liver failure (LF). Case report. We present a retrospective case series of three patients hospitalized for LF and treated using the SPAD in the Clinical Center of Vojvodina, between 2018 and 2019. Of whom, two patients presenting with acute liver failure and one with acute-on-chronic liver failure. A total of 6 SPAD sessions were performed in each patient, resulting in decreased serum bilirubin and bile acid levels, and hepatic encephalopathy grade. On discharge from the hospital, liver function has been shown to improve in all the patients. Conclusion. SPAD removes the hepatotoxic substances without improvement of synthetic liver function, providing a supportive treatment for LF patients that do not respond to standard of care offering longer time for bridging to organ transplantation or spontaneous recovery of the liver function.

Impact of anion exchange adsorbents on regional citrate anticoagulation

Introduction: Heparin and citrate are commonly used anticoagulants in membrane/adsorption based extracorporeal liver support systems. However, anion exchange resins employed for the removal of negatively charged target molecules including bilirubin may also deplete these anticoagulants due to their negative charge. The aim of this study was to evaluate the adsorption of citrate by anion exchange resins and the impact on extracorporeal Ca2+ concentrations. Methods: Liver support treatments were simulated in vitro. Citrate and Ca2+ concentrations were measured pre and post albumin filter as well as pre and post adsorbents. In addition, batch experiments were performed to quantify citrate adsorption. Results: Pre albumin filter target Ca2+ concentrations were reached well with only minor deviations. Citrate was adsorbed by anion exchange resins, resulting in a higher Ca2+ concentration downstream of the adsorbent cartridges during the first hour of treatment. Conclusions: The anion exchange resin depletes citrate, leading to an increased Ca2+ concentration in the extracorporeal circuit, which may cause an increased risk of clotting during the first hour of treatment. An increase of citrate infusion during the first hour of treatment should therefore be considered to compensate for the adsorption of citrate.