Molecular Adsorbent Recirculating System for Acute Liver Failure in a New Pediatric-Based Extracorporeal Liver Support Program.

IMPORTANCE: Acute liver failure (ALF) carries significant morbidity and mortality, for both pediatric and adult patients. Albumin dialysis via the molecular adsorbent recirculating system (MARS) is a form of extracorporeal liver support (ELS) that can reduce hepatic encephalopathy (HE), a main driver of mortality in ALF. However, data on MARS and its benefit on mortality have been inconsistent. OBJECTIVES: We sought to report our experiences and patient outcomes from the first 2 years of operation of a new ELS program, within an established pediatric liver transplantation center. DESIGN SETTING AND PARTICIPANTS: Retrospective review of outcomes in pediatric and adult patients treated with MARS therapy for ALF, from 2021 to 2022. MAIN OUTCOMES AND MEASURES: Outcomes included reduction in HE and biochemical markers of ALF after MARS therapy, survival, and transplant-free survival. Comparisons were made via Wilcoxon signed-rank test. RESULTS: Five pediatric and two adult patients underwent MARS for ALF. Ages ranged from 2 to 29 years. Overall, 21 MARS runs were performed (median 3 runs per patient, 12.4 hr per run [interquartile range, IQR 10.1-17]). Overall survival was 85.7%, and transplant-free survival was 71.4%. There was a statistically significant reduction in HE score with MARS therapy (median 3 [IQR 3-4] to 1 [IQR 0-1], p = 0.03), and in ALF biomarkers including ammonia (256 µL/dL [195-265] to 75 µL/dL [58-101], p = 0.02), aspartate aminotransferase (6,362 U/L [920-8,305] to 212 U/L [72-431], p = 0.02), alanine aminotransferase (8,362 U/L [3,866-9,189] to 953 U/L [437-1,351], p = 0.02), and international normalized ratio (4.5 [3.3-6.7] to 1.3 [1.2-1.4], p = 0.02). CONCLUSIONS AND RELEVANCE: MARS therapy for ALF was well tolerated by both pediatric and adult patients, and resulted in significant improvement in clinical and biochemical parameters. We demonstrated encouraging overall and transplant-free survival, suggesting that early initiation of MARS with relatively long and frequent cycle times may be of significant benefit to ALF patients, and is worthy of additional study in larger cohorts.

Longitudinal progression of clinical variables associated with graded liver injury in COVID-19 patients.

BACKGROUND: Hospital-acquired liver injury is associated with worse outcomes in COVID-19. This study investigated the temporal progression of clinical variables of in-hospital liver injury in COVID-19 patients. METHODS: COVID-19 patients (n = 1361) were divided into no, mild and severe liver injury (nLI, mLI and sLI) groups. Time courses of laboratory variables were time-locked to liver-injury onset defined by alanine aminotransferase level. Predictors of liver injury were identified using logistic regression. RESULTS: The prevalence of mLI was 39.4% and sLI was 9.2%. Patients with escalated care had higher prevalence of sLI (23.2% vs. 5.0%, p < 0.05). sLI developed 9.4 days after hospitalization. sLI group used more invasive ventilation, anticoagulants, steroids, and dialysis (p < 0.05). sLI, but not mLI, had higher adjusted mortality odds ratio (= 1.37 [95% CI 1.10, 1.70], p = 0.005). Time courses of the clinical variables of the sLI group differed from those of the nLI and mLI group. In the sLI group, alanine aminotransferase, procalcitonin, ferritin, and lactate dehydrogenase showed similar temporal profiles, whereas white-blood-cell count, D-dimer, C-reactive protein, respiration and heart rate were elevated early on, and lymphocyte and SpO2 were lower early on. The top predictors of sLI were alanine aminotransferase, lactate dehydrogenase, respiration rate, ferritin, and lymphocyte, yielding an AUC of 0.98, 0.92, 0.88 and 0.84 at 0, - 1, - 2 and - 3 days prior to onset, respectively. CONCLUSIONS: This study identified key clinical variables predictive of liver injury in COVID-19, which may prove useful for management of liver injury. Late onset of sLI and more aggressive care are suggestive of treatment-related hepatotoxicity.

Hepatic Predictors of Mortality in Severe Acute Respiratory Syndrome Coronavirus 2: Role of Initial Aspartate Aminotransferase/Alanine Aminotransferase and Preexisting Cirrhosis.

The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) is the causative agent of coronavirus disease 2019 (COVID-19). The presenting symptoms of this virus are variable, and there is an increasing body of literature on risk factors for mortality. The aim of this study was to evaluate the effect of initial aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and preexisting liver disease, including cirrhosis, in a cohort of patients admitted with COVID-19 infection at a tertiary care hospital network in the Bronx, New York. We reviewed 3,352 patients who had a positive SARS-CoV2 nasal swab, were over 18 years of age, and had an associated inpatient admission and discharge (or death) to the Montefiore Medical Center from February 28, 2020, to May 22, 2020. Of these, 39/86 (45%) patients died when the initial ALT was >5 times the upper limit of normal (ULN); 115/230 (50%) patients died when the initial AST was >3 times the ULN. The mortality of patients without preexisting liver disease was 26.6% compared to a mortality rate of 29.5% in patients with liver disease. Subgroup analysis showed a mortality of 36.1% in the patients with cirrhosis. Cirrhosis conferred a hazard ratio for mortality of 1.67 (95% confidence interval, 1.09, 2.55; P = 0.019). The baseline Model for End-Stage Liver Disease score was not prognostic in the cirrhosis cohort. There was no statistical difference between mortality in patients with a history of compensated or decompensated cirrhosis. The most common cause of death in the cirrhosis cohort was respiratory failure. Conclusion: COVID-19 hepatitis may lead to poor outcomes in patients who are hospitalized for the disease. Patients with cirrhosis are at a higher risk of COVID-19-related mortality.

The Inflammatory Relationship Between Hepatitis C Virus With Coronary and Carotid Atherosclerosis.

Hepatitis C virus (HCV), a global health concern, has been linked to various hepatic and extrahepatic deleterious manifestations. Several observational studies have either supported the increased likelihood of coronary and carotid atherosclerosis after infection with HCV or refuted it. To date, there has been no clear consensus to support either train of thought, as randomized, controlled clinical trials have not been completed. In this review, we first discuss articles that support the notion that HCV infection leads to increased plaque formation due to systemic inflammation and then focus on articles that refute this idea. From the literature, we do know that both inflammatory and lipid processes play a role in plaque formation, and thus both components are important in the successful treatment of atherosclerosis. Based on our review of the literature, we do believe that HCV-infected individuals are at an increased risk for more severe coronary artery disease than their healthy counterparts. Although there is no irrefutable evidence that links HCV infection with plaque formation and/or rupture, cardioprotective measures should be taken to reduce poor health outcomes, especially in those individuals who are already at risk of coronary disease.

Heart Transplantation for Hepatitis C Virus Non-Viremic Recipients From Hepatitis C Virus Viremic Donors.

Multiple strategies have been implemented to increase the donor pool to avoid transplant wait-list mortality. The approval of highly effective direct-acting antiviral regimens for the treatment of hepatitis C virus (HCV) has enabled expansion of the donor pool by allowing the transplantation of organs from HCV-viremic donors to HCV-negative recipients. Multiple centers have recently published data on outcomes of heart transplantation from HCV-viremic heart donors to HCV-negative recipients, with acceptable posttransplant outcomes. However, areas of uncertainty remain, particularly in the long-term risks of intentional HCV transmission, as well as the possibility that sustained virologic response may not be achieved. In this article, we review the literature illustrating both the risks and benefits of transplantation of organs from HCV-viremic donors to HCV-negative recipients. We also present the data collected at our institution regarding this special patient population.

Paramecium species ingest and kill the cells of the human pathogenic fungus Cryptococcus neoformans.

A fundamental question in the field of medical mycology is the origin of virulence in those fungal pathogens acquired directly from the environment. In recent years, it was proposed that the virulence of certain environmental animal-pathogenic microbes, such as Cryptococcus neoformans, originated from selection pressures caused by species-specific predation. In this study, we analyzed the interaction of C. neoformans with three Paramecium spp., all of which are ciliated mobile protists. In contrast to the interaction with amoebae, some Paramecium spp. rapidly ingested C. neoformans and killed the fungus. This study establishes yet another type of protist-fungal interaction supporting the notion that animal-pathogenic fungi in the environment are under constant selection by predation.