Implications and Management of Cirrhosis-Associated Immune Dysfunction Before and After Liver Transplantation.
TL;DR: In this article, the authors summarize the detailed dynamic immunological perturbations associated with advanced chronic liver disease and highlight the importance of recognizing immune dysregulation as a sequela of cirrhosis.
About: This article is published in Liver Transplantation.The article was published on 2021-11-05 and is currently open access. It has received 3 citations till now. The article focuses on the topics: Chronic liver disease & Liver transplantation.
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TL;DR: In this article , the absolute count of immature neutrophils and LOX-1+ MDSC along with T lymphocyte count and checkpoint inhibitor expression were altered in cirrhotic patients before and after liver transplant.
Abstract: Background: Advanced stages of cirrhosis are characterized by the occurrence of progressive immune alterations known as CAID (Cirrhosis Associated Immune Dysfunction). In advanced cirrhosis, liver transplantation (LT) remains the only curative treatment. Sepsis, shares many similarities with decompensated cirrhosis in terms of immuno-inflammatory response. In both conditions, the neutrophil-lymphocyte ratio (NLR) is associated with poor outcomes. Based on alterations in sepsis, we hypothesized that we could observe in cirrhotic and LT patients more detailed neutrophil and lymphocyte phenotypes. To this end, along with leukocyte count, we assessed immature neutrophils, LOX-1+ MDSC and PD-1 and TIM-3 lymphocyte expressions in cirrhotic patients before transplantation in association with liver disease severity and during the first month after transplantation. Methods: We conducted a prospective monocentric study including cirrhotic patients registered on LT waiting-list. Blood samples were collected at enrolment before LT and for 1 month post-LT. In addition to NLR, we assessed by whole blood flow cytometry the absolute count of immature neutrophils and LOX-1+ MDSC as well as the expressions of immune checkpoint receptors PD-1 and TIM-3 on T lymphocytes. Results: We included 15 healthy volunteers (HV) and 28 patients. LT was performed for 13 patients. Pre-LT patients presented with a higher NLR compared to HV and NLR was associated with cirrhosis severity. Increased immature neutrophils and LOX-1+ MDSC counts were observed in the most severe patients. These alterations were mainly associated with acute decompensation of cirrhosis. PD-1 and TIM-3 expressions on T lymphocytes were not different between patients and HV. Post-LT immune alterations were dominated by a transitory but tremendous increase of NLR and immature neutrophils during the first days post-LT. Then, immune checkpoint receptors and LOX-1+ MDSC tended to be overexpressed by the second week after surgery. Conclusion: The present study showed that NLR, immature neutrophils and LOX-1+ MDSC counts along with T lymphocyte count and checkpoint inhibitor expression were altered in cirrhotic patients before and after LT. These data illustrate the potential interest of immune monitoring of cirrhotic patients in the context of LT in order to better define risk of sepsis. For this purpose, larger cohorts of patients are now necessary in order to move forward a more personalised care of LT patients.
TL;DR: In this article , a retrospective observational study identified infections in children with biliary atresia (BA) using predefined criteria, including VRI, bacteremia with and without central line (CL), bacterial peritonitis, positive stool pathogens, urinary tract infections, and cholangitis.
TL;DR: In this paper , the authors summarize the current literature in adults who experience these complications of cirrhotic portal hypertension beyond variceal hemorrhage and present the available literature in children, with a focus on diagnosis, management, and liver transplant decision making in children with cirrhosis who develop ascites, SBP, HRS, HE, and cardiopulmonary complications.
Abstract: Complications of cirrhotic portal hypertension (PHTN) in children are broad and include clinical manifestations ranging from variceal hemorrhage, hepatic encephalopathy (HE), ascites, spontaneous bacterial peritonitis (SBP), and hepatorenal syndrome (HRS) to less common conditions such as hepatopulmonary syndrome, portopulmonary hypertension, and cirrhotic cardiomyopathy. The approaches to the diagnosis and management of these complications have become standard of practice in adults with cirrhosis with many guidance statements available. However, there is limited literature on the diagnosis and management of these complications of PHTN in children with much of the current guidance available focused on variceal hemorrhage. The aim of this review is to summarize the current literature in adults who experience these complications of cirrhotic PHTN beyond variceal hemorrhage and present the available literature in children, with a focus on diagnosis, management, and liver transplant decision making in children with cirrhosis who develop ascites, SBP, HRS, HE, and cardiopulmonary complications.
References
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TL;DR: The potential exists for altering the bile acid pool by targeting key enzymes in the 7α/β-dehydroxylation pathway through the development of pharmaceuticals or sequestering bile acids biologically in probiotic bacteria, which may result in their effective removal from the host after excretion.
2,144 citations
TL;DR: This work shows that interleukin-22 (IL-22) has a crucial role in the early phase of host defense against C. rodentium and identifies a new innate immune function for IL-22 in regulating early defense mechanisms against A/E bacterial pathogens.
Abstract: Infections by attaching and effacing (A/E) bacterial pathogens, such as Escherichia coli O157:H7, pose a serious threat to public health. Using a mouse A/E pathogen, Citrobacter rodentium, we show that interleukin-22 (IL-22) has a crucial role in the early phase of host defense against C. rodentium. Infection of IL-22 knockout mice results in increased intestinal epithelial damage, systemic bacterial burden and mortality. We also find that IL-23 is required for the early induction of IL-22 during C. rodentium infection, and adaptive immunity is not essential for the protective role of IL-22 in this model. Instead, IL-22 is required for the direct induction of the Reg family of antimicrobial proteins, including RegIIIbeta and RegIIIgamma, in colonic epithelial cells. Exogenous mouse or human RegIIIgamma substantially improves survival of IL-22 knockout mice after C. rodentium infection. Together, our data identify a new innate immune function for IL-22 in regulating early defense mechanisms against A/E bacterial pathogens.
1,780 citations
TL;DR: The gut microbiome in liver cirrhosis is characterized by comparing 98 patients and 83 healthy control individuals and on the basis of only 15 biomarkers, a highly accurate patient discrimination index is created and validated on an independent cohort, suggesting microbiota-targeted biomarkers may be a powerful tool for diagnosis of different diseases.
Abstract: Liver cirrhosis occurs as a consequence of many chronic liver diseases that are prevalent worldwide. Here we characterize the gut microbiome in liver cirrhosis by comparing 98 patients and 83 healthy control individuals. We build a reference gene set for the cohort containing 2.69 million genes, 36.1% of which are novel. Quantitative metagenomics reveals 75,245 genes that differ in abundance between the patients and healthy individuals (false discovery rate < 0.0001) and can be grouped into 66 clusters representing cognate bacterial species; 28 are enriched in patients and 38 in control individuals. Most (54%) of the patient-enriched, taxonomically assigned species are of buccal origin, suggesting an invasion of the gut from the mouth in liver cirrhosis. Biomarkers specific to liver cirrhosis at gene and function levels are revealed by a comparison with those for type 2 diabetes and inflammatory bowel disease. On the basis of only 15 biomarkers, a highly accurate patient discrimination index is created and validated on an independent cohort. Thus microbiota-targeted biomarkers may be a powerful tool for diagnosis of different diseases. Invasion of the gut by oral bacteria in liver cirrhosis. Previous work has revealed an association between liver complications such as cirrhosis and the gut microbiome. Lanjuan Li and colleagues undertook a microbiome-wide association study of stool samples from 98 liver cirrhosis patients and 83 healthy controls. Quantitative metagenomics analysis revealed 75,245 genes that were significantly different in abundance between the two groups, many of which could be grouped into 66 clusters that represent cognate bacterial species. Of these, 28 species were enriched in liver cirrhosis patients and most were of buccal origin (mostly Veillonella and streptococci). The identified markers were unique liver cirrhosis-specific genes and the authors identify a set of just 15 of these genes that could form the basis of a highly accurate discrimination index that could be used as a diagnostic tool.
1,542 citations
TL;DR: The panel of experts, having emphasised the importance of initiating aetiologic treatment for any degree of hepatic disease at the earliest possible stage, extended its work to all the complications of cirrhosis which had not been covered by the European Association for the Study of the Liver guidelines.
1,534 citations
TL;DR: In patients with cirrhosis and spontaneous bacterial peritonitis, treatment with intravenous albumin in addition to an antibiotic reduces the incidence of renal impairment and death in comparison with treatment with an antibiotic alone.
Abstract: Background In patients with cirrhosis and spontaneous bacterial peritonitis, renal function frequently becomes impaired. This impairment is probably related to a reduction in effective arterial blood volume and is associated with a high mortality rate. We conducted a study to determine whether plasma volume expansion with intravenous albumin prevents renal impairment and reduces mortality in these patients. Methods We randomly assigned 126 patients with cirrhosis and spontaneous bacterial peritonitis to treatment with intravenous cefotaxime (63 patients) or cefotaxime and intravenous albumin (63 patients). Cefotaxime was given daily in doses that varied according to the serum creatinine level, and albumin was given at a dose of 1.5 g per kilogram of body weight at the time of diagnosis, followed by 1 g per kilogram on day 3. Renal impairment was defined as nonreversible deterioration of renal function during hospitalization. Results The infection resolved in 59 patients in the cefotaxime group (94 percent...
1,448 citations