novel-treatment-for-complex-bile-leakage-after-liver-transplantation

Novel Treatment for Complex Bile Leakage After Liver Transplantation

Bile leakage is a common complication after liver transplantation that may usually be cured with endoscopic retrograde cholangiopancreatography (ERCP), ...

Sun Yat-sen University

Partial liver transplantation has recently been proposed to alleviate organ shortages. However, transplantation of a small-for-size graft is associated with an increased risk of posttransplant hepatic dysfunction, commonly referred to as small-for-size syndrome (SFSS). This review describes the etiology, pathological features, clinical manifestations, and diagnostic criteria of SFSS. Moreover, we summarize strategies to improve graft function, focusing on graft inflow modulation techniques. Finally, unmet needs and future perspectives are discussed.

Small-For-Size Syndrome and Graft Inflow Modulation Techniques in Liver Transplantation.

 Parvovirus B19 (B19V) infection is a rare cause of severe anemia in liver transplant recipients. However, few studies have systematically reviewed reported cases and summarized experience in managing this disease.  We described a retrospective case series of eight adult liver transplant recipients with B19V-associated severe anemia and performed a literature review of epidemiology, etiology, clinical courses, diagnosis, treatment options available, and outcomes of B19V-associated anemia in adult liver transplant recipients.  We systematically reviewed articles describing adult liver transplant recipients with B19V-associated anemia from PubMed and ScienceDirect databases from database inception to May 2022.  Eight articles containing 23 cases were identified in addition to eight cases from our center for a total of 31 patients (mean age, 45.7 ± 9.7 years; 74.2% male). Eighty-seven percent developed transfusion-dependent anemia within two months after liver transplantation (LT). Fever and progressive anemia are among the major manifestations. Intravenous immunoglobulin (IVIG)-based therapy was given to all patients and the treatment protocols varied among different centers. Except for two cases who died of comorbidities, 17 patients obtained long-term recovery from anemia after one course of treatment and six (19%) experienced relapses that were reversed by repeated courses of IVIG therapy. Two recipients presented with IVIG-associated side effects and two developed acute cellular rejection (ACR) after reduction of immunosuppression.  B19V infection should be suspected early as a cause of severe anemia of unknown etiology in adult liver transplant recipients. The clearance of B19V typically lags behind recovery of anemia, and inadequate clearance of virus after cessation of IVIG appears to be a potential risk of anemia recurrence. Moreover, more attention should be paid to the side effects of high-dose IVIG infusion and ACR because of reduction of immunosuppression.

Parvovirus B19-Associated Severe Anemia in Adult Liver Transplant Recipients: A Case Series and Review of the Literature.

The risk of alcoholic cirrhosis increases in a dose- and time-dependent manner with alcohol consumption and ethanol metabolism in the liver. Currently, no effective antifibrotic therapies are available. We aimed to obtain a better understanding of the cellular and molecular mechanisms involved in the pathogenesis of liver cirrhosis.

Dysregulation of innate cell types in the hepatic immune microenvironment of alcoholic liver cirrhosis.

Tumor cell density is a basic pathological feature of solid tumors. Chemotherapy, radiotherapy, and targeted therapy reduce tumor cell density, whereas unrestricted tumor cell proliferation promotes this feature. The impact of tumor cells on the microenvironment following changes in tumor cell density is still unclear. In this study, we focused on the response of key immune cell subsets to tumor cell density in hepatocellular carcinoma (HCC).

Tumor cell density dependent IL-8 secretion induces the fluctuation of tregs/CD8 + T cells infiltration in hepatocellular carcinoma: one prompt for the existence of density checkpoint.

Central to allograft rejection is the T cell-mediated adaptive immune response initiated by activated dendritic cells (DCs). Previous studies have shown that the DNA-dependent activator of IFN regulatory factors (DAI) is involved in the maturation and activation of DCs. Therefore, we hypothesized that inhibition of DAI could prevent DCs from maturation and prolong murine allograft survival.

Inhibition of DAI refrains dendritic cells from maturation and prolongs murine islet and skin allograft survival.

The aim of the study was to investigate the relationship between systemic immune-inflammation index (SII) and early allograft dysfunction (EAD) and 90-day mortality after liver transplantation (LT) in acute-on-chronic liver failure (ACLF).

High Systemic Immune-Inflammation Index, Predicting Early Allograft Dysfunction, Indicates High 90-Day Mortality for Acute-On-Chronic Liver Failure after Liver Transplantation.

The mature state of dendritic cells (DCs) determines their ability to regulate immune responses. Retinoic acid-inducible gene-1 (RIG-1) plays a critical role in DC activation and maturation. RIG-1 activation triggers mitogen-activated protein kinase and nuclear factor-kappa B signal transduction. In this study, we aimed to investigate the effects of inhibiting RIG-1 expression in DCs and its potential in inducing immune tolerance.

Retinoic acid-inducible gene-1 knockdown induces immature properties in dendritic cells and prolongs the survival time of allograft mice.

Dendritic cells (DCs) play a pivotal role in maintaining immune tolerance. Using recombinant adenovirus (rAd) to deliver vectors to immature dendritic cells (imDCs) is an important method for studying the tolerogenic function of DCs. We found that using RPMI medium and a higher MOI during transduction increased the expression of CD80, CD86, and MHC-II on the surface of imDCs. Our data reveal a significant increase in the secretion of the pro-inflammatory cytokine IL-6 in the group showing the most pronounced phenotypic changes. In the mouse heart transplant model, imDCs with unstable phenotype and function due to adenoviral transduction resulted in an increased proportion of Th1 and Th17 cells in recipients. However, these effects can be managed, and our proposed optimized transduction strategy significantly minimizes these adverse effects. Our study holds significant implications for the development and optimization of immunotherapy utilizing tolerogenic dendritic cells.

Optimal conditions for adenoviral transduction of immature dendritic cells without affecting the tolerogenic activity of DC-based immunotherapy.

Hepatitis B virus (HBV)-related liver diseases, including hepatitis, cirrhosis, and liver failure, seriously threaten human lives and health worldwide. Innate and adaptive immune cells are all thought to participate in HBV-related diseases. However, there is a lack of information on the comprehensive landscape of the immune microenvironment.

Article	Year
Small-For-Size Syndrome and Graft Inflow Modulation Techniques in Liver Transplantation. Digestive diseases (Basel, Switzerland)\| PubMed ID: 35753308	2023
Parvovirus B19-Associated Severe Anemia in Adult Liver Transplant Recipients: A Case Series and Review of the Literature. Surgical infections\| PubMed ID: 36269593	2022
Dysregulation of innate cell types in the hepatic immune microenvironment of alcoholic liver cirrhosis. Frontiers in immunology\| PubMed ID: 36845083	2023
Tumor cell density dependent IL-8 secretion induces the fluctuation of tregs/CD8 + T cells infiltration in hepatocellular carcinoma: one prompt for the existence of density checkpoint. Journal of translational medicine\| PubMed ID: 36932390	2023
Inhibition of DAI refrains dendritic cells from maturation and prolongs murine islet and skin allograft survival. Frontiers in immunology\| PubMed ID: 37197662	2023
High Systemic Immune-Inflammation Index, Predicting Early Allograft Dysfunction, Indicates High 90-Day Mortality for Acute-On-Chronic Liver Failure after Liver Transplantation. Digestive diseases (Basel, Switzerland)\| PubMed ID: 37494918	2023
Retinoic acid-inducible gene-1 knockdown induces immature properties in dendritic cells and prolongs the survival time of allograft mice. Gene\| PubMed ID: 38043832	2024
Optimal conditions for adenoviral transduction of immature dendritic cells without affecting the tolerogenic activity of DC-based immunotherapy. Journal of virological methods\| PubMed ID: 38552881	2024
Macrophage Evolution during Progression of Hepatitis Virus B-Related Acute-on-Chronic Liver Failure. Journal of innate immunity\| PubMed ID: 39637841	2025

Zongli Fu

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