Search Results (64)

Liver failure, both acute and chronic, represents a complex, life-threatening condition frequently requiring intensive care unit (ICU) admission. Nutritional management is a crucial component of supportive therapy, aiming to mitigate catabolism, preserve lean body mass, and support immune and organ function. In acute liver failure (ALF), early nutritional intervention within 24–48 h and individualized energy–protein prescriptions are essential, even in the presence of hepatic encephalopathy. Chronic liver failure (CLF) and acute-on-chronic liver failure (ACLF) are often associated with severe malnutrition, sarcopenia, and systemic inflammation, necessitating tailored nutritional strategies. Subjective Global Assessment (SGA) and Royal Free Hospital Global Assessment (RFH-GA) tools are instrumental in identifying nutritional risk. Enteral nutrition (EN) is preferred across all stages, with parenteral nutrition (PN) reserved for contraindications. Special considerations include micronutrient repletion, prevention of refeeding syndrome, and perioperative nutritional support in transplant candidates and recipients. This clinical overview summarizes current evidence and guidelines on ICU nutrition in liver failure, emphasizing a multidisciplinary approach to improve outcomes. Full article

Acute-on-chronic liver failure (ACLF) is a complex and severe condition marked by multiple organ failure and high short-term mortality. Coagulopathy, a key component of ACLF, is characterized by rebalanced hemostasis with both hypo- and hypercoagulable features, increasing the risk of bleeding and thrombosis. Conventional coagulation tests, including prothrombin time (PT) and platelet count, fail to fully capture the complexity of coagulation dysfunction in ACLF. Advanced diagnostic tools, like viscoelastic tests (VETs), offer a more comprehensive assessment, yet they remain limited in evaluating endothelial dysfunction and fail to account for reduced levels of anticoagulant factors. Emerging therapeutic strategies targeting coagulopathies in ACLF hold promise, but their clinical efficacy remains unclear. A more nuanced approach to diagnosing and managing coagulopathy in ACLF is needed, incorporating advanced hemostatic profiling to better inform prognosis and guide treatment decisions. Full article

ACLF is a severe stage of liver cirrhosis, characterized by multiple organ failure, systemic inflammation, and high short-term mortality. The intestinal microbiota (IM) influences its pathophysiology; however, there are currently no studies in Latin American populations. Therefore, we analyzed IM and its relationships with sepsis, organ failure, and mortality. In parallel, we quantified serum lipopolysaccharides as a marker of bacterial translocation. Fecal samples from 33 patients and 20 healthy controls (HCs) were obtained. The IMs were characterized by 16S-rRNA amplicon sequencing, the metagenomic functional predictive profiles were analyzed by PICRUSt2, and LPS quantification was performed by ELISA. Patients with ACLF showed significant alterations in alpha and beta diversity compared to the HCs. A strong dominance index accurately predicted 28-day and 90-day mortalities. The IMs showed a polarization toward Proteobacteria associated with increased LPS. The LPS correlated with clinical severity, organ dysfunction, and higher pathogenic taxa. The Klebsiella/Faecalibacterium ratio showed good performance in identifying sepsis (AUROC = 0.83). Furthermore, Morganella, Proteus, and Klebsiella were enriched in patients with multiorgan failure. Lactobacillus, Escherichia/Shigella, Veillonella, and Ruminococcus gnavus exhibited potential in predicting 28- and 90-day mortalities. The IM alterations in ACLF may be useful as clinical biomarkers of poor prognosis, primarily for mortality and sepsis. These findings are representative of western Mexico. Full article

Acute-on-chronic liver failure (ACLF) is a severe clinical syndrome characterized by high morbidity and mortality rates. Bacterial infection is a frequent precipitating factor and complication in ACLF patients, significantly worsening patient outcomes. Elucidating the mechanisms underlying bacterial infections and their impact on ACLF pathophysiology is crucial for developing effective therapies to reduce infection rates and mortality. Current research highlights that immune suppression in ACLF increases susceptibility to bacterial infections, which in turn exacerbate immune dysfunction. However, a comprehensive review summarizing the emerging mechanisms underlying this immunosuppression is currently lacking. This review aims to provide an overview of the latest research, focusing on alterations in the immune responses of innate immune cells—including monocytes, macrophages, and neutrophils—as well as adaptive immune cells such as T and B lymphocytes during the onset and progression of bacterial infections in ACLF. In addition, recent advances in immunomodulatory therapies, including stem cell-based interventions, will also be discussed. Full article

Acute-on-chronic liver failure (ACLF) and acute liver failure (ALF) are severe hepatitis that occur in patients with and without chronic liver diseases and/or cirrhosis, respectively, and both often result in death. Hepatitis A virus (HAV) and hepatitis E virus (HEV) infection can cause these severe conditions. We reviewed the role of HAV and HEV, which infect humans through the fecal–oral route, in ALF and ACLF in Asian countries. This narrative review was the derived from a traditional non-systematic review. Hepatitis A should be recognized as one of the sexually transmitted infections, especially among men who have sex with men. HAV genotype IIIA infection seems to present a more severe clinical manifestation. Acute HEV-1 infection is associated with ALF in pregnant women in India. HEV-4, rather than HEV-3, was found in severe hepatitis in Japan. HEV also plays a role as a cause of acute insult and/or chronic liver disease in immunocompromised patients with ACLF. Further studies are needed for the development of vaccines and antivirals against HAV and HEV infections. Despite the limitations of the recording of cases and the extent of specific vaccinations, multidisciplinary cooperation, involving hepatologists, virologists, experts in public health, etc., may improve the treatment of HAV and HEV infection. Full article

Acute-on-chronic liver failure (ACLF) is a clinical syndrome characterized by organ failure and high short-term mortality. Since its first definition in 2013, many international organizations have defined this syndrome and, till now, there has been no agreement regarding definitions and diagnostic criteria. Although the precise mechanism of ACLF is unknown, precipitant factors and the systemic inflammation response play a major role. Specific management of this high-mortality syndrome is still under development, but a general consensus in the diagnosis and management of ACLF is needed. Full article

Background: Acute-on-chronic liver failure (ACLF) is a severe, rapidly progressing syndrome in patients with liver cirrhosis, often triggered by bacterial infections. Piperacillin/Tazobactam is a key antibiotic in this setting, and therapeutic drug monitoring (TDM) helps optimize its dosing. This study evaluates the impact of an interprofessional TDM strategy for Piperacillin/Tazobactam in ACLF patients in the ICU. Methods: This retrospective ICU study evaluated an interprofessional TDM approach for optimizing Piperacillin/Tazobactam dosing in critically ill ACLF patients. The team, consisting of physicians, clinical pharmacists, and staff nurses, engaged in shared decision making, collaboratively interpreting TDM results and adjusting the dosing accordingly. This study included 26 patients with ACLF who underwent initial TDM and 7 who received follow-up TDM. Piperacillin/Tazobactam dosing was modified based on TDM recommendations, with serum concentrations measured weekly. Adherence to and the implementation of interprofessional dosing recommendations were systematically analyzed to assess the impact of this approach. Results: The initial TDM showed that 30.8% of patients had Piperacillin/Tazobactam levels within the target range, while 53.8% were above and 15.4% below. The interprofessional team recommended dose reductions in seven patients, increases in three, and no change in eleven, with five requiring antibiotic modifications. At the first follow-up TDM, 20.0% reached target levels, while 80.0% remained above, with no subtherapeutic cases. The team recommended one further dose reduction and maintained dosing in four patients. All recommendations were fully implemented, demonstrating strong adherence to the collaborative protocol. Conclusions: The interprofessional TDM strategy optimized Piperacillin/Tazobactam dosing in ACLF patients with full adherence to the recommendations. This collaborative approach improves outcomes and supports global efforts to curb antibiotic resistance. Full article

This study aimed to investigate the impact of IL-35 on the prognosis of patients with HBV-ACLF. We recruited 69 patients with HBV-ACLF, 20 patients with chronic hepatitis B (CHB), 17 patients with liver cirrhosis (LC), and 20 healthy controls (HCs) from a regional infectious disease treatment center in China. Plasma levels of IL-35 at baseline were detected using ELISA. Plasma IL-35 levels in the HBV-ACLF group were the highest among all four groups. Furthermore, survivors exhibited significantly higher IL-35 levels than non-survivors (p < 0.001). IL-35 levels correlated with MELD (r = −0.678, p < 0.001), COSSH-ACLF IIs (r = −0.581, p < 0.001), alpha-fetoprotein (AFP) (r = 0.433, p < 0.001), creatinine (Cr) (r =−0.396, p = 0.001), and lactate (r =−0.38, p =0.001). The combination of plasma IL-35 and MELD score had the highest mortality prediction efficiency, with an area under the curve (AUC) of 0.895 (95% CI: 0.812–0.978, p < 0.001), a sensitivity of 80.6%, and a specificity of 93.9%. Additionally, the Kaplan–Meier analysis revealed that lower levels of IL-35 (≤191.5pg/mL) were associated with poorer survival rates in HBV-ACLF patients (p < 0.001). Our results demonstrated that IL-35 could be an effective predictive marker for the prognosis of HBV-ACLF and improve the predictive performance when combined with the MELD score. Full article

Background/Objectives: Alcohol can directly damage the liver, causing steatosis, steatohepatitis, cirrhosis, and hepatocellular cancer. The aim of this study was to examine 28-day survival in hospitalized patients with alcohol-related liver disease (ALD) cirrhosis, as well as to develop and validate a new survival prediction model. Methods: A total of 145 patients with ALD cirrhosis were included; 107 were diagnosed with acute decompensation (AD) and 38 with acute-on-chronic liver failure (ACLF). The new liver mortality inpatients (LIV-IN) score was calculated using the following variables: hepatic encephalopathy (HE), hepatorenal syndrome (HRS), ascites, systemic inflammatory response syndrome (SIRS), community-acquired infection (CAI), and fibrinogen. The diagnostic accuracy of the LIV-IN score was tested, along with the model for end-stage liver disease (MELD), model for end-stage liver disease-sodium (MELD-Na), albumin-bilirubin (ALBI), neutrophil-to-lymphocyte ratio (NLR), chronic liver failure consortium-C acute decompensation (CLIF-C AD), and chronic liver failure consortium-acute-on-chronic liver failure (CLIF-C ACLF). Results: Lethal outcome occurred in 46 (31.7%) patients. The mortality rate was higher in the ACLF group (n = 22, 57.9%) compared to the AD group (n = 24, 22.4%) (p < 0.01). The highest predictive power for short-term mortality was observed for the LIV-IN score (AUC 73.4%, p < 0.01). In patients with AD, the diagnostic accuracy of the CLIF-C AD score was better than for the LIV-IN score (AUC 0.699; p = 0.004, AUC 0.686; p = 0.007, respectively). In patients with ACLF, only the LIV-IN score had statistically significant discriminative power in predicting 28-day survival. Conclusions: The liver mortality inpatients prognostic score is a new, reliable prognostic model in predicting 28-day mortality. Full article

Inflammasome is linked to many inflammatory diseases, including COVID-19 and autoimmune liver diseases. While severe COVID-19 was reported to exacerbate liver failure, we report a fatal acute-on-chronic liver failure (ACLF) in a stable primary biliary cholangitis-autoimmune hepatitis overlap syndrome patient triggered by a mild COVID-19 infection. Postmortem liver biopsy showed sparse SARS-CoV-2-infected macrophages with extensive ASC (apoptosis-associated speck-like protein containing a CARD) speck-positive hepatocytes, correlating with elevated circulating ASC specks and inflammatory cytokines, and depleted blood monocyte subsets, indicating widespread liver inflammasome activation. This first report of a fatal inflammatory cascade in an autoimmune liver disease triggered by a mild remote viral infection hopes to elucidate a less-described pathophysiology of ACLF that could prompt consideration of new diagnostic and therapeutic options. Full article

Background/Objectives: Bacterial infections (BI) are a major cause of mortality in patients with alcohol-associated hepatitis (AH); however, only a few studies have investigated BI in AH in the last decade. Therefore, we aimed to assess the features and outcomes of BI in patients with AH. Methods: This observational descriptive study included patients with AH admitted to a tertiary academic hospital between 2016 and 2021. Clinical and complete microbiological data were recorded and complications, including acute-on-chronic liver failure (ACLF), and mortality over 90-days were compared between infected and noninfected patients. Results: Overall, 115 patients with AH were recruited and 75 had severe AH; among them, 66 started corticosteroid treatment. We identified 69 cases of BI in 44 patients; the incidence of BI upon hospital discharge was 32.2%, which reached 38.2% at 90 days. The predominant infection site was the chest (35%). Among the identified bacteria (52.1%), half were gram positive and half gram negative. A low rate of multidrug-resistant bacteria (14%) was also noted. Infected patients during hospitalization (n = 37) exhibited higher rates of hepatic decompensation and ACLF (p = 0.001) and lower survival (81.8% vs. 95.8%, p = 0.015) than did noninfected patients (n = 78). In-hospital infected patients (n = 22) exhibited worse survival (72.7%) than did those infected upon admission (93.3%) or noninfected patients (94.9%) (p = 0.009). Corticosteroid-treated patients displayed a nonsignificant increase in the total number of BI; however, without greater mortality. Conclusions: BI were common in our cohort of patients with AH. Patients with in-hospital infections commonly experienced serious complications, including high ACLF and death rates. Infections diagnosed upon admission were treated without affecting survival. Full article

Background: Adiponectin, an adipokine with anti-inflammatory properties, has been implicated in various liver diseases. This study aimed to elucidate the prognostic value of serum adiponectin levels in critically ill patients with liver disease. Methods: This observational study included 161 critically ill patients admitted to the medical ICU of RWTH Aachen University Hospital due to acute liver failure or decompensated advanced chronic liver disease. Serum adiponectin levels were measured at ICU admission and after 48 h. Clinical parameters and outcomes, including transplant-free survival, were analyzed. Results: Serum adiponectin concentrations were significantly elevated compared to healthy controls (p < 0.001). Levels were particularly high in patients with sepsis compared to those with gastrointestinal bleeding as the precipitating factor of acute decompensation (p = 0.045) and were higher in female patients (p = 0.023). Adiponectin concentrations correlated with the Model of End-Stage Liver Disease (MELD) score and Child–Pugh score. Multivariate analysis confirmed a significant correlation with total bilirubin (r = 0.292, p < 0.001) and serum sodium (r = −0.265, p = 0.028). Higher adiponectin concentrations were associated with a trend towards poorer 30- and 180-day survival. Cox regression analysis identified a significant association between increased adiponectin concentration and reduced transplant-free survival (p = 0.037), supported by a Kaplan–Meier analysis using a cutoff of 119 ng/mL (log-rank 5.145, p = 0.023). Conclusions: Elevated serum adiponectin concentrations are associated with liver dysfunction and poor outcomes in critically ill patients. Higher adiponectin levels at ICU admission may predict poorer transplant-free survival. Further research in larger, multicenter cohorts is warranted to validate these findings and explore the underlying mechanisms. Full article

Hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) is associated with pronounced systemic inflammation, and neutrophil extracellular traps (NETs) are key components of this response. The primary objective of this study was to establish an NET-related scoring system for patients with HBV-ACLF. A prospective training cohort of 81 patients from the Beijing Ditan Hospital was included. The concentrations of NET markers (cell-free DNA, myeloperoxidase DNA [MPO-DNA], and citrullinated histone H3) in peripheral blood were quantified. Random survival forest, LASSO regression, and multivariate Cox regression analyses were used to identify prognostic factors associated with 90-day mortality in ACLF patients and develop a nomogram for visualization, which was followed by evaluation in a validation cohort (n = 40). NET-related marker levels were significantly higher in the non-survival group than in the survival group (p < 0.05). The NET score was constructed by combining MPO-DNA, neutrophil-to-lymphocyte ratio, and age data. The score’s diagnostic effectiveness, assessed by the area under the curve, yielded values of 0.83 and 0.77 in the training and validation sets, respectively, markedly surpassing those of other established models (p < 0.05). In both groups, the 90-day mortality rates were 88.8% and 75.0%, respectively, for patients categorized as high risk and 18.0% and 12.5%, respectively, for those classified as low risk. Full article

Liver failure profoundly affects the immune system, leading to dysregulation of innate and adaptive immune response. This review explores the intricate relationship between liver function and immune homeostasis. The role of the liver as a central hub in immune response initiation is elucidated, emphasizing its involvement in hepatic inflammation induction and subsequent systemic inflammation. Cytokines, chemokines, growth factors, and lipid mediators orchestrate these immune processes, serving as both prognostic biomarkers and potential therapeutic targets in liver failure-associated immune dysregulation, which might result from acute-on-chronic liver failure (ACLF) and cirrhosis. Furthermore, the review delves into the mechanisms underlying immunosuppression in liver failure, encompassing alterations in innate immune cell functions such as neutrophils, macrophages, and natural killer cells (NK cells), as well as perturbations in adaptive immune responses mediated by B and T cells. Conclusion: Understanding the immunological consequences of liver failure is crucial for developing targeted therapeutic interventions and improving patient outcomes in liver disease management. Full article

Background: We aim to investigate the characteristics of invasive pulmonary aspergillosis (IPA) in patients with HBV-related acute on chronic liver failure (HBV-ACLF). Methods: A total of 44 patients with probable IPA were selected as the case group, and another 88 patients without lung infections were chosen as the control group. Results: HBV-ACLF patients with probable IPA had more significant 90-day mortality (38.6% vs. 15.9%, p = 0.0022) than those without. The white blood cell (WBC) count was the independent factor attributed to the IPA development [odds ratio (OR) 1.468, p = 0.027]. Respiratory failure was associated with the mortality of HBV-ACLF patients with IPA [OR 26, p = 0.000]. Twenty-seven patients received voriconazole or voriconazole plus as an antifungal treatment. Plasma voriconazole concentration measurements were performed as therapeutic drug monitoring in 55.6% (15/27) of the patients. The drug concentrations exceeded the safe range with a reduced dosage. Conclusions: The WBC count might be used to monitor patients’ progress with HBV-ACLF and IPA. The presence of IPA increases the 90-day mortality of HBV-ACLF patients mainly due to respiratory failure. An optimal voriconazole regimen is needed for such critical patients, and voriconazole should be assessed by closely monitoring blood levels. Full article