Galectin-3 in biliary atresia and other pediatric cholestatic liver diseases.

AIMS: Biliary atresia (BA) is characterized by intrahepatic inflammation and rapid progression of liver fibrosis. Galectin-3, a beta-galactoside binding protein, is a key regulator of inflammation and fibrosis. The aim of this study was to characterize circulating and hepatic Galectin-3 levels in children with BA. METHODS: Plasma and liver samples were obtained from children with early BA at time of Kasai hepatoportoenterostomy, late BA at time of transplant, early and late other cholestatic liver diseases (CLD), and controls. Plasma Galectin-3 was measured using standard enzyme-linked immunoassay. Liver tissue was analyzed with multiplex immunohistochemistry and quantified using whole slide analysis. Statistical comparisons were made using nonparametric testing. RESULTS: Plasma Galectin-3 in late BA was significantly higher than in early BA (20.82 [12.45-30.46] vs. 11.30 [8.74-16.83] ng/mL, p = 0.0096). Galectin-3 levels correlated with markers of disease severity and interleukin-6. There were significantly more Galectin-3+ M2 macrophages in late BA in comparison to late other CLD (162 [157-233] vs. 49 [33-59] cells/mm2, p = 0.03). The number of Galectin-3+ M2 macrophages correlated with the number of activated hepatic stellate cells and bile duct proliferation. CONCLUSIONS: Plasma Galectin-3 is higher in late BA at time of transplant in comparison to early BA at time of Kasai. The number of Galectin-3 expressing M2 macrophages in late BA is elevated relative to late other CLD and was associated with other prognostic histological findings. Galectin-3 targeted therapy may be beneficial in slowing disease progression to cirrhosis in children with BA.

Consensus document on acute-on-chronic liver failure (ACLF) established by the Mexican Association of Hepatology.

Acute-on chronic liver failure (ACLF) has been an intensively debated topic mainly due to the lack of a unified definition and diagnostic criteria. The growing number of publications describing the mechanisms of ACLF development, the progression of the disease, outcomes and treatment has contributed to a better understanding of the disease, however, it has also sparked the debate about this condition. As an attempt to provide medical professionals with a more uniform definition that could be applied to our population, the first Mexican consensus was performed by a panel of experts in the area of hepatology in Mexico. We used the most relevant and impactful publications along with the clinical and research experience of the consensus participants. The consensus was led by 4 coordinators who provided the most relevant bibliography by doing an exhaustive search on the topic. The entire bibliography was made available to the members of the consensus for consultation at any time during the process and six working groups were formed to develop the following sections: 1.- Generalities, definitions, and criteria, 2.- Pathophysiology of cirrhosis, 3.- Genetics in ACLF, 4.- Clinical manifestations, 5.- Liver transplantation in ACLF, 6.- Other treatments.

Increased Hepatic Expression of SARS-CoV-2 Entry Points and Proinflammatory Cytokines in Cirrhosis.

It has been recently reported that patients with cirrhosis have significantly higher mortality following severe acute respiratory syndrome coronavrisu 2 (SARS-CoV-2) infection compared with those without.1,2 Specifically, it was demonstrated that mortality was greater in those with advanced cirrhosis (Child-Pugh B and C), and that from cirrhotic patients experiencing SARS-CoV-2 infection, close to half suffer acute decompensation including acute-on-chronic liver failure (ACLF).2 Unfortunately, the presence of hepatic decompensation at baseline has been shown to be an independent predictor of all-cause mortality in patients with coronavirus disease 2019 (COVID-19).1 Patients with decompensated cirrhosis contracting COVID-19 have a poor outcome, with an overall reported mortality of over 30%.1.

Galectin-3 is overexpressed in advanced cirrhosis and predicts post-liver transplant infectious complications.

BACKGROUND & AIMS: Patients with advanced cirrhosis often have immune dysfunction and are more susceptible to infections. Galectin-3 is a ß-galactoside-binding lectin implicated in inflammation, immune regulation and liver fibrosis. We aim to investigate galectin-3 expression in advanced cirrhosis and its ability to predict post-transplant infectious complications. METHODS: We collected sera and liver samples from 129 cirrhotic patients at the time of liver transplantation and from an external cohort of 37 patients with alcoholic liver disease including alcoholic hepatitis (AH) at the time of diagnosis. Galectin-3 was assessed by ELISA, real-time PCR, immunohistochemistry and RNA-seq. Receiver operating characteristic curves and Cox proportional-hazards regression analysis were performed to assess the predictive power of galectin-3 for disease severity and post-transplant infections. RESULTS: Increased galectin-3 levels were found in advanced cirrhosis. Galectin-3 significantly correlated with disease severity parameters and inflammatory markers. Galectin-3 had significant discriminating power for compensated and advanced cirrhosis (AUC = 0.78/0.84, circulating/liver galectin-3; p < .01), and was even higher to discriminate severe AH (AUC = 0.95, p < .0001). Cox Proportional-hazard model showed that galectin-3, MELD-Na and the presence of SIRS predict the development of post-transplant infectious complications. Patients with circulating galectin-3 (>16.58 ng/ml) were at 2.19-fold 95% CI (1.12-4.29) increased risk, but when combined with MELD-Na > 20.0 and SIRS, the risk to develop post-transplant infectious complications, increased to 4.60, 95% CI (2.38-8.90). CONCLUSION: Galectin-3 is a novel biological marker of active inflammation and disease severity that could be clinically useful alone or in combination with other scores to discriminate advanced cirrhosis and predict post-transplant infectious complications.

Renal and brain failure predict mortality of patients with acute-on-chronic liver failure admitted to the intensive care unit.

INTRODUCTION AND OBJECTIVES: Acute on Chronic Liver Failure (ACLF) is characterized by organ failure and high 28-day mortality. Identifying clinical predictors associated with early mortality could have implications for the treatment of patients with ACLF. PATIENTS AND METHODS: Patients diagnosed with chronic liver failure that developed ACLF based on the EASL-CLIF Consortium definition admitted to the Intensive care unit of a tertiary hospital between 2012-2018 were included. Bivariate and multivariate Cox regression analyses were performed to identify factors associated with mortality. RESULTS: 148 patients (55% female) were diagnosed with ACLF of which 55% (n = 82) had ACLF grade 3, 28% (n = 41) grade 2 and 17% (n = 25) grade 1. The median age was 54 years (41-63). Hepatitis C virus (HCV) was the most frequent etiology in 29.8% (n = 44) of the patients with bacterial infection being the most predominant precipitant factor in 58.1% (n = 86). Ninety-day global cumulative survival was only 18%. When divided by grade, mortality reached to 10% in ACLF 3. Moreover, in the multivariate Cox regression analysis, renal failure (HR 3.26, 95% CI (2.13-4.99), brain failure (HR 1.37, 95% CI 1.09-2.04) and male sex (HR 1.62, 95% CI 1.10-2.40) were independent predictors of 28- and 90-day mortality. CONCLUSIONS: ACLF is a frequent syndrome among chronic liver disease patients. Brain and renal failure are significantly associated with higher mortality and are independent predictors of 28 and 90-day mortality.

Direct or Collateral Liver Damage in SARS-CoV-2-Infected Patients.

Liver injury can result from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with more than one-third of COVID-19 patients exhibiting elevated liver enzymes. Microvesicular steatosis, inflammation, vascular congestion, and thrombosis in the liver have been described in autopsy samples from COVID-19 patients. Several factors, including direct cytopathic effect of the virus, immune-mediated collateral damage, or an exacerbation of preexisting liver disease may contribute to liver pathology in COVID-19. Due to its immunological functions, the liver is an organ likely to participate in the viral response against SARS-CoV-2 and this may predispose it to injury. A better understanding of the mechanism contributing to liver injury is needed to develop and implement early measures to prevent serious liver damage in patients suffering from COVID-19. This review summarizes current reports of SARS-CoV-2 with an emphasis on how direct infection and subsequent severe inflammatory response may contribute to liver injury in patients with and without preexisting liver disease.

Development of transplantable B-cell lymphomas in the MHC-defined miniature swine model.

BACKGROUND: Establishment of transplantable tumors in clinically relevant large animals allows translational studies of novel cancer therapeutics. METHODS: Here we describe the establishment, characterization, and serial transplantation of a naturally occurring B-cell lymphoma derived from a unique, highly inbred sub-line of Massachusetts General Hospital (MGH) major histocompatibility complex (MHC)-defined miniature swine. RESULTS: The lymphoblastic cell line (LCL) originated from peripheral blood of a 2.5 year old female swine leukocyte antigen (SLA)dd-inbred miniature swine breeder demonstrating clinical signs of malignancy. Flow cytometric phenotypic analysis of subclones derived from the original cell line revealed surface markers commonly expressed in a B-cell lineage neoplasm. A subclone of the original LCL was transplanted into mildly-conditioned histocompatible miniature swine and immunocompromised NOD.Cg-Prkdc scid Il2rg tm1Wjl /SzJ (NSG) mice. Tissue and blood samples harvested 2 weeks following subcutaneous and intravenous injection in a highly inbred SLAdd pig were cultured for tumor growth and phenotypic analysis before serial transfer into NSG mice. Evidence of tumor growth in vivo was found in all tumor cell recipients. In vitro growth characteristics and surface phenotype were comparable between the original and serially transplanted tumor cell lines. CONCLUSIONS: These results indicate the feasibility of developing a large-animal transplantable tumor model using cells derived from spontaneously occurring hematologic malignancies within the highly inbred miniature swine herd.

The effects of galectin-3 depletion apheresis on induced skin inflammation in a porcine model.

Galectin-3 (Gal-3), a ß-galactoside-binding lectin that is expressed in mammalian cells, is known to modulate several biological functions such as cell-cell adhesion, macrophage activation, angiogenesis, metastasis, and fibrosis. The goal of this study was to evaluate the ability of Gal-3 depletion apheresis using an adsorption column with immobilized anti-Gal-3-antibody to reduce inflammation induced by Complete Freund's Adjuvant injection in a skin inflammation porcine model. Here, we report that plasma perfusion by apheresis through a Gal-3 binding immuno-affinity column reduces plasma Gal-3 levels to below limits of quantitative detection, and results in significant decrease in skin inflammation, including degree and duration of inflammatory lesions. Human plasma was tested ex vivo and found to be efficiently depleted using the anti-Gal-3 affinity column. This study demonstrates the potential of Gal-3 depletion apheresis as a therapeutic method for inflammation-mediated disease, supporting continued research in this area for clinical application.

Routine guidewire application facilitates cholangioscopy in the management of postoperative residual hepatolithiasis.

BACKGROUND AND AIM: Although postoperative cholangioscopy (POC) is considered to be an effective treatment for residual hepatolithiasis after surgery, its security and validity still need to be improved. This study compared wire-guided POC (WG-POC) versus traditional POC (T-POC) in the management of patients with residual hepatolithiasis. METHODS: This retrospective study included a total of 203 patients who suffered from hepatolithiasis and underwent hepatectomy as initial intervention from 1 January 2016 to 1 January 2017. After surgery, 110 patients were subjected to T-POC and 93 to WG-POC for eliminating residual hepatolithiasis. Perioperative course and follow-up outcomes were retrospectively analyzed. RESULTS: No significant differences in clinical characteristics or distribution of residual hepatolithiasis between the WG-POC and T-POC groups were observed (P > 0.05). However, overall POC interventional sessions (2.9 ± 0.85 vs 4.0 ± 1.21 times), average operating time (264.8 ± 103.61 vs 389.4 ± 136.26 min), overall complications rate (18.28% vs 32.73%), and overall T-tube retaining time (21.8 ± 6.20 vs 28.8 ± 8.09 days) were lower in the WG-POC group than in the T-POC group (P < 0.05). In addition, there were no significant differences between the two groups (WG-POC vs T-POC) in recurrence (4.30% vs 4.55%) and residual calculi (8.60% vs 6.36%) at half-a-year follow up (P > 0.05). CONCLUSIONS: Routine wire guidance may improve the outcome of cholangioscopy in managing complicated residual hepatolithiasis, being associated with clear advantages such as shorter operating time and number of POC interventions, reduced T-tube retaining time, and fewer postoperative complications.

Methods for the detection and serum depletion of porcine galectin-3.

BACKGROUND: Circulating galectin-3 (Gal-3) is elevated in systemic inflammatory disorders, fibrotic diseases, and in cancers. Gal-3 is a promising cancer target where it promotes tumorigenesis and metastasis, as well as in renal, pulmonary, hepatic, and cardiovascular diseases, because of its role as a driver of fibrotic remodeling. This reports goal was to establish methods for the detection and removal of porcine Gal-3 that will enable further studies of the therapeutic potential of Gal-3 depletion by apheresis in porcine disease models. The long-term aim is to develop a safe, effective method of removing Gal-3 via apheresis as a standalone therapeutic tool and as an adjuvant to other therapies. METHODS: Purified recombinant porcine Gal-3 was prepared and used as the standard for development of a porcine Gal-3 enzyme-linked immunosorbent assay (ELISA). Different affinity column matrices that incorporated either a rat IgG2a anti-Gal-3 monoclonal antibody or carbohydrate ligand were assessed for depletion of Gal-3 from porcine serum. RESULTS: A porcine Gal-3 ELISA with a linear range from 0.3 to 20 ng/mL was able to detect native porcine Gal-3 in both fetal (∼150-200 ng/mL) and juvenile (∼5-15 ng/mL) porcine serum samples. Use of an anti-Gal-3 monoclonal antibody affinity column depleted Gal-3 from porcine serum to at least 313 pg/mL, the limit of ELISA detection. CONCLUSIONS: Methods have been developed for the detection and depletion of porcine Gal-3. These methods will be used to study the specific effects of Gal-3 depletion via apheresis in porcine models of disease.

A reliable scoring system after major liver resection in mice.

BACKGROUND: Posthepatectomy liver failure and its transplant counterpart, small-for-size syndrome, remain significant limitations for liver resections and segmental liver transplantation. Partial hepatectomy in mice is one of the most commonly used models to study liver regeneration, but blood and tissue sampling necessary to collect data can affect outcomes or even require euthanasia. We therefore developed a quantitative observational system to predict death from hepatectomy during the first 24 postoperative hours. MATERIALS AND METHODS: A total of 100 female, 10 to 12-week-old C57BL/6 mice underwent two-thirds hepatectomy and were monitored for up to 7 d. Our scoring system was based on five categories, each assigned 0-2 points: activity level, body posture, fur condition, respiratory status, and eye appearance. Seventy-five mice were scored 6 h, 12 h, 24 h, 2 d, 3 d, 5 d, and 7 d after surgery. The remaining 25 mice were scored similarly, but underwent, in addition, blood sampling for serum alanine aminotransferase, total bilirubin, interleukin-6, tumor necrosis factor-alpha, or euthanasia with liver sampling for conventional hematoxylin-eosin and Ki-67 staining. RESULTS: Retrospective analysis indicated that body condition scores ≤5 on two consecutive time points within the first 24 postoperative hours accurately predicted eventual death. Animals in the low scoring group also had significantly higher serum alanine aminotransferase, total bilirubin, interleukin-6, tumor necrosis factor-alpha, more hepatocyte necrosis in hematoxylin-eosin, and fewer Ki-67 positive hepatocytes. CONCLUSIONS: Our scoring system accurately predicts survival, hepatocyte damage, liver regeneration, and systemic inflammation in a mouse hepatectomy model, within the first 24 hours of surgery. This could be useful in evaluating posthepatectomy interventions for their effect on survival and liver regeneration.

Postnatal xenogeneic B-cell tolerance in swine following in utero intraportal antigen exposure.

BACKGROUND: The objective of this study was to investigate the humoral immune response to xenogeneic antigens administered during the fetal state utilizing a baboon-to-pig model. METHODS: Nine fetuses from an alpha-1,3-galactosyltransferase gene knockout (GalT-KO) MGH-miniature swine sow underwent transuterine ultrasound-guided intraportal injection of T-cell depleted baboon bone marrow (B-BM) at mid-gestation. Two juvenile GalT-KO swine undergoing direct B-BM intraportal injection were used as controls. RESULTS: Postnatal humoral tolerance was induced in the long-term surviving piglets as demonstrated by the absence of any antibody response to baboon donor cells. In addition, a second intraportal B-BM administration at 2.5 months post-birth led to no antibody formation despite re-exposure to xenogeneic antigens. This B-cell unresponsiveness was abrogated only when the animal was exposed subcutaneously to third-party xenogeneic and allogeneic antigens, suggesting that the previously achieved humoral non-responsiveness was donor specific. In comparison, the two juvenile GalT-KO control swine demonstrated increasing anti-baboon IgM and IgG levels following intraportal injection. CONCLUSIONS: In summary, xenogeneic B-cell tolerance was induced through in utero intraportal exposure to donor cells and this tolerance persisted following postnatal rechallenge with donor B-BM, but was lost on exposure to third-party antigen, possibly as a result of cross-reactive antibody formation.

Increased transfusion-free survival following auxiliary pig liver xenotransplantation.

BACKGROUND: Pig to baboon liver xenotransplantation typically results in severe thrombocytopenia and coagulation disturbances, culminating in death from hemorrhage within 9 days, in spite of continuous transfusions. We studied the contribution of anticoagulant production and clotting pathway deficiencies to fatal bleeding in baboon recipients of porcine livers. METHODS: By transplanting liver xenografts from α1,3-galactosyltransferase gene-knockout (GalT-KO) miniature swine donors into baboons as auxiliary organs, leaving the native liver in place, we provided the full spectrum of primate clotting factors and allowed in vivo mixing of porcine and primate coagulation systems. RESULTS: Recipients of auxiliary liver xenografts develop severe thrombocytopenia, comparable to recipients of conventional orthotopic liver xenografts and consistent with hepatic xenograft sequestration. However, baboons with both pig and native livers do not exhibit clinical signs of bleeding and maintain stable blood counts without transfusion for up to 8 consecutive days post-transplantation. Instead, recipients of auxiliary liver xenografts undergo graft failure or die of sepsis, associated with thrombotic microangiopathy in the xenograft, but not the native liver. CONCLUSION: Our data indicate that massive hemorrhage in the setting of liver xenotransplantation might be avoided by supplementation with primate clotting components. However, coagulation competent hepatic xenograft recipients may be predisposed to graft loss related to small vessel thrombosis and ischemic necrosis.

Optimizing nutrition in hepatic cirrhosis: A comprehensive assessment and care approach.

Cirrhosis is considered a growing cause of morbidity and mortality, which represents a significant public health problem. Currently, there is no effective treatment to reverse cirrhosis. Treatment primarily centers on addressing the underlying liver condition, monitoring, and managing portal hypertension-related complications, and evaluating the potential for liver transplantation in cases of decompensated cirrhosis, marked by rapid progression and the emergence of complications like variceal bleeding, hepatic encephalopathy, ascites, malnutrition, and more. Malnutrition, a prevalent complication across all disease stages, is often underdiagnosed in cirrhosis due to the complexities of nutritional assessment in patients with fluid retention and/or obesity, despite its crucial impact on prognosis. Increasing emphasis has been placed on the collaboration of nutritionists within hepatology and Liver transplant teams to deliver comprehensive care, a practice that has shown to improve outcomes. This review covers appropriate screening and assessment methods for evaluating the nutritional status of this population, diagnostic approaches for malnutrition, and context-specific nutrition treatments. It also discusses evidence-based recommendations for supplementation and physical exercise, both essential elements of the standard care provided to cirrhotic patients.

Histopathological impact of SARS-CoV-2 on the liver: Cellular damage and long-term complications.

Coronavirus disease 2019 (COVID-19), caused by the highly pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), primarily impacts the respiratory tract and can lead to severe outcomes such as acute respiratory distress syndrome, multiple organ failure, and death. Despite extensive studies on the pathogenicity of SARS-CoV-2, its impact on the hepatobiliary system remains unclear. While liver injury is commonly indicated by reduced albumin and elevated bilirubin and transaminase levels, the exact source of this damage is not fully understood. Proposed mechanisms for injury include direct cytotoxicity, collateral damage from inflammation, drug-induced liver injury, and ischemia/hypoxia. However, evidence often relies on blood tests with liver enzyme abnormalities. In this comprehensive review, we focused solely on the different histopathological manifestations of liver injury in COVID-19 patients, drawing from liver biopsies, complete autopsies, and in vitro liver analyses. We present evidence of the direct impact of SARS-CoV-2 on the liver, substantiated by in vitro observations of viral entry mechanisms and the actual presence of viral particles in liver samples resulting in a variety of cellular changes, including mitochondrial swelling, endoplasmic reticulum dilatation, and hepatocyte apoptosis. Additionally, we describe the diverse liver pathology observed during COVID-19 infection, encompassing necrosis, steatosis, cholestasis, and lobular inflammation. We also discuss the emergence of long-term complications, notably COVID-19-related secondary sclerosing cholangitis. Recognizing the histopathological liver changes occurring during COVID-19 infection is pivotal for improving patient recovery and guiding decision-making.

The Influence of Interdisciplinary Work towards Advancing Knowledge on Human Liver Physiology.

The knowledge accumulated throughout the years about liver regeneration has allowed a better understanding of normal liver physiology, by reconstructing the sequence of steps that this organ follows when it must rebuild itself after being injured. The scientific community has used several interdisciplinary approaches searching to improve liver regeneration and, therefore, human health. Here, we provide a brief history of the milestones that have advanced liver surgery, and review some of the new insights offered by the interdisciplinary work using animals, in vitro models, tissue engineering, or mathematical models to help advance the knowledge on liver regeneration. We also present several of the main approaches currently available aiming at providing liver support and overcoming organ shortage and we conclude with some of the challenges found in clinical practice and the ethical issues that have concomitantly emerged with the use of those approaches.

Role of galectin-3 in the pathogenesis and progression of biliary atresia.

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Time-Dependent Changes of Laboratory Parameters as Independent Predictors of All-Cause Mortality in COVID-19 Patients.

Independent predictors of mortality for COVID-19 patients have been identified upon hospital admission; however, how they behave after hospitalization remains unknown. The aim of this study is to identify clinical and laboratory parameters from admission to discharge or death that distinguish survivors and non-survivors of COVID-19, including those with independent ability to predict mortality. In a cohort of 266 adult patients, clinical and laboratory data were analyzed from admission and throughout hospital stay until discharge or death. Upon admission, non-survivors had significantly increased C reactive protein (CRP), neutrophil count, neutrophil to lymphocyte ratio (NLR) (p < 0.0001, each), ferritin (p < 0.001), and AST (aspartate transaminase) (p = 0.009) compared to survivors. During the hospital stay, deceased patients maintained elevated CRP (21.7 mg/dL [admission] vs. 19.3 [hospitalization], p = 0.060), ferritin, neutrophil count and NLR. Conversely, survivors showed significant reductions in CRP (15.8 mg/dL [admission] vs. 9.3 [hospitalization], p < 0.0001], ferritin, neutrophil count and NLR during hospital stay. Upon admission, elevated CRP, ferritin, and diabetes were independent predictors of mortality, as were persistently high CRP, neutrophilia, and the requirement of invasive mechanical ventilation during hospital stay. Inflammatory and clinical parameters distinguishing survivors from non-survivors upon admission changed significantly during hospital stay. These markers warrant close evaluation to monitor and predict patients' outcome once hospitalized.

Liver transplantation is beneficial regardless of cirrhosis stage or acute-on-chronic liver failure grade: A single-center experience.

BACKGROUND: Liver transplantation for the most critically ill remains controversial; however, it is currently the only curative treatment option. AIM: To assess immediate posttransplant outcomes and compare the short (1 year) and long-term (6 years) posttransplant survival among cirrhotic patients stratified by disease severity. METHODS: We included cirrhotic patients undergoing liver transplantation between 2015 and 2019 and categorized them into compensated cirrhosis (CC), decompensated cirrhosis (DC), and acute-on-chronic liver failure (ACLF). ACLF was further divided into severity grades. Our primary outcomes of interest were total days of intensive care unit (ICU) and hospital stay, development of complications and posttransplant survival at 1 and 6 years. RESULTS: 235 patients underwent liver transplantation (CC = 11, DC = 129 and ACLF = 95). Patients with ACLF had a significantly longer hospital stay [8.0 (6.0-13.0) vs CC, 6.0 (3.0-7.0), and DC 7.0 (4.5-10.0); P = 0.01] and developed more infection-related complications [47 (49.5%), vs CC, 1 (9.1%) and DC, 38 (29.5%); P < 0.01]. Posttransplant survival at 1- and 6-years was similar among groups (P = 0.60 and P = 0.90, respectively). ACLF patients stratified according to ACLF grade [ACLF-1 n = 40 (42.1%), ACLF-2 n = 33 (34.7%) and ACLF-3 n = 22 (23.2%)], had similar ICU and hospital stay length (P = 0.68, P = 0.54), as well as comparable frequencies of overall and infectious post-transplant complications (P = 0.58, P = 0.80). There was no survival difference between ACLF grades at 1 year and 6 years (P = 0.40 and P = 0.15). CONCLUSION: Patients may benefit from liver transplantation regardless of the cirrhosis stage. ACLF patients have a longer hospital stay and frequency of infectious complications; however, excellent, and comparable 1 and 6-year survival rates support their enlisting and transplantation including those with ACLF-3.

Galectin-3 as a potential prognostic biomarker of severe COVID-19 in SARS-CoV-2 infected patients.

Severe COVID-19 is associated with a systemic hyperinflammatory response leading to acute respiratory distress syndrome (ARDS), multi-organ failure, and death. Galectin-3 is a ß-galactoside binding lectin known to drive neutrophil infiltration and the release of pro-inflammatory cytokines contributing to airway inflammation. Thus, we aimed to investigate the potential of galectin-3 as a biomarker of severe COVID-19 outcomes. We prospectively included 156 patients with RT-PCR confirmed COVID-19. A severe outcome was defined as the requirement of invasive mechanical ventilation (IMV) and/or in-hospital death. A non-severe outcome was defined as discharge without IMV requirement. We used receiver operating characteristic (ROC) and multivariable logistic regression analysis to determine the prognostic ability of serum galectin-3 for a severe outcome. Galectin-3 levels discriminated well between severe and non-severe outcomes and correlated with markers of COVID-19 severity, (CRP, NLR, D-dimer, and neutrophil count). Using a forward-stepwise logistic regression analysis we identified galectin-3 [odds ratio (OR) 3.68 (95% CI 1.47-9.20), p < 0.01] to be an independent predictor of severe outcome. Furthermore, galectin-3 in combination with CRP, albumin and CT pulmonary affection > 50%, had significantly improved ability to predict severe outcomes [AUC 0.85 (95% CI 0.79-0.91, p < 0.0001)]. Based on the evidence presented here, we recommend clinicians measure galectin-3 levels upon admission to facilitate allocation of appropriate resources in a timely manner to COVID-19 patients at highest risk of severe outcome.