Acute Liver Failure Publications (16103)
Acute Liver Failure Publications
Hepatitis was induced in mice by independent injections of two different bacterial PAMPs: lipopolysaccharide (LPS) and unmethylated CpG oligodeoxynucleotide (CpG-DNA) motifs. The role of RIPK1 was evaluated by making use of mice specifically lacking RIPK1 in liver parenchymal cells (Ripk1(LPC-KO)). Administration of clodronate encapusated-liposome served to investigate the role of Kupffer cells in the establishment of the disease. Etanercept, a Tumor Necrosis Factor (TNF)-decoy receptor, was used to study the contribution of TNF-α during LPS-mediated liver injury.
Whereas RIPK1 deficiency in liver parenchymal cells did not trigger basal hepatolysis, it greatly sensitized hepatocyte to apoptosis and to liver damages following single injection of LPS or CpG-DNA. Importantly, hepatocyte death was prevented by previous macrophage depletion or by TNF inhibition.
Our data highlight the pivotal function of RIPK1 in maintaining liver homeostasis in conditions of macrophage-induced TNF burst in response to PAMPs sensing.
An excessive hepatocyte death is a characteristic of liver injury. A new programmed cell death pathway has been described involving upstream death ligands such as TNF and downstream kinases such as RIPK1. Here, we show that in the presence of LPS in liver induced hepatic injury due to secreted of TNF by liver macrophages and that RIPK1 is a powerful protector of hepatocyte death. This newly identified pathway in liver may therefore be helpful in the management of patients in the prediction of their risk to develop acute liver failure.
We collected data on the prevalence of HCV from the National Health and Nutrition Examination Survey (NHANES), from the 2010 and 2013-2014 cycles. We also collected data from the HealthCore Integrated Research Database on patients with cirrhosis and chronic liver failure (CLF) from 2006 through 2014, and data on patients who received transplant from the United Network for Organ Sharing (UNOS), from 2003 through 2015. We determined percentages of new waitlist members and transplant recipients with HCV infection, stratified by indication for transplant, modeling each calendar year as a continuous variable using the Spearman rank correlation, non-parametric test of trends, and linear regression models.
In an analysis of data from the NHANES (2013-2014), we found that the proportion of patients with a positive HCV antibody who had a positive HCV RNA was 0.5 (95% CI, 0.42-0.55); this value was significantly lower than in 2010 (0.64; 95% CI, 0.59-0.73) (P=.03). Data from the HealthCore databased revealed significant changes (P<.05 for all), over time, in percentages of patients with compensated cirrhosis (decreases in percentages of patients with cirrhosis from HCV or ALD, but increase in percentages of patients with cirrhosis from non-alcoholic steatohepatitis [NASH]), CLF (decreases in percentages of patients with CLF from HCV or ALD, with an almost 3-fold increase in percentage of patients with CLF from NASH), and hepatocellular carcinoma (HCC) (decreases in percentages of patients with HCC from HCV or ALD and a small increase in HCC among persons with NASH). Data from the UNOS revealed that among patients new to the liver transplant waitlist, or undergoing liver transplantation, for CLF, there was a significant decrease in the percentage with HCV infection and increases in percentages of patients with NAFLD or ALD. Among patients new to the liver transplant waitlist, or undergoing liver transplantation, for HCC, proportions of those with HCV infection, NAFLD, or ALD did not change between 2003 and 2015 CONCLUSIONS: In an analysis of 3 different databases (NHANES, HealthCore, and UNOS), we found the proportion of patients on the liver transplant waitlist or undergoing liver transplantation for chronic HCV infection to be decreasing, and fewer patients to have cirrhosis or CLF. However, the percentages of patients on the waitlist or receiving liver transplants for NASH or ALD are increasing, despite different relative burdens of disease among the entire population of patients with cirrhosis.
Of 986 participants, 110 had lactate and pyruvate levels collected on the same day. Of the 110, the etiology of PALF was a mitochondrial disorder in 8 (7%), indeterminate in 65 (59%), and an alternative diagnosis in 37 (34%). Lactate, pyruvate, and L:P were similar among the 3 etiologic groups. There was no significant association between the initial lactate or L:P and biochemical variables of clinical severity or clinical outcome at 21 days.
A serum lactate ≥ 2.5 mmol/L and/or elevated L:P was common in all causes of PALF, not limited to those with a mitochondrial etiology, and did not predict 21-day clinical outcome.
Thirty healthy subjects served as control group.
Patients with cirrhosis exhibited higher levels of cytokines as compared to controls. In stable cirrhosis, during a median follow-up of 17months, liver-related events occurred in 26 patients. Higher IL-10 levels and Child-Pugh B/C were independently associated with reduced event-free survival. In AD cohort, death after 90days of follow-up occurred in 39 patients and was independently associated with ascites, higher IL-6 and model for end-stage liver disease. IL-6 levels also showed higher AUROC than CRP for predicting bacterial infection in the AD cohort (0.831±0.043vs. 0.763±0.048, respectively). IL-17 decreased at third day of hospitalization only in patients who progressed to death. Higher IL-6 levels were observed in acute-on-chronic liver failure (ACLF) patients even in the absence of bacterial infection whereas IL-10 was higher only in subjects with infection-related ACLF. Higher IL-10 and IL-17 levels were associated with progression to death in ACLF.
The pattern of immune response seems to vary according to the phase of cirrhosis and is related to prognosis, from stable disease to ACLF.
The mice received an intraperitoneal hepatotoxic dose of APAP (300[Formula: see text]mg/kg) and after 30[Formula: see text]min, were treated with BA at concentrations of 0, 15, 30, or 60[Formula: see text]mg/kg. After 16[Formula: see text]h of treatment, the mice were sacrificed for further analysis. APAP administration significantly elevated the serum alanine transferase (ALT) enzyme levels and hepatic myeloperoxidase (MPO) activity when compared with control animals. Baicalin treatment significantly attenuated the elevation of liver ALT levels, as well as hepatic MPO activity in a dose- dependent manner (15-60[Formula: see text]mg/kg) in APAP-treated mice. The strongest beneficial effects of BA were seen at a dose of 30[Formula: see text]mg/kg. BA treatment at 30[Formula: see text]mg/kg after APAP overdose reduced elevated hepatic cytokine (TNF-[Formula: see text] and IL-6) levels, and macrophage recruitment around the area of hepatotoxicity in immunohistochemical staining. Significantly, BA treatment can also decrease hepatic phosphorylated extracellular signal-regulated kinase (ERK) expression, which is induced by APAP overdose. Our data suggests that baicalin treatment can effectively attenuate APAP-induced liver injury by down-regulating the ERK signaling pathway and its downstream effectors of inflammatory responses. These results support that baicalin is a potential hepatoprotective agent.
A C>T mutation in SNP rs7308855 and a T>A mutation in SNP rs7298346 showed an association with the presence of coagulation failure in the entire population (n=61, P=0.024 and 0.060, respectively) and in the subgroup of patients with ACLF (n=44, P=0.081 and 0.056, respectively).
Genetic variation in the vasopressin 1a receptor was found not to be associated with circulatory or renal failure, but with the presence of coagulation failure in patients with acute decompensation of liver cirrhosis and ACLF.
This bioreactor is consequently connected extracorporeally to a rat model of acute liver failure for 3 h and major biochemical parameters studied. Bilirubin and aspartate transaminase showed a percentage decrease of 20-60% in the integrated bioreactor as opposed to 5-15% in the conventional setup. Urea and ammonia levels which showed negligible change in the conventional setup increase (40%) and decrease (18%), respectively in the integrated system. Also, an overall increase of 5% in human albumin in rat plasma indicated bioreactor functionality in terms of synthetic functions. These results were corroborated by offline evaluation of patient plasma. Hence, integrating the plasmapheresis and adsorbent units with the bioreactor module in one compact design improves the efficacy of the bioartificial liver device.
In addition, superoxide, nitric oxide, peroxynitrite and ammonia levels in the NTS or RVLM were elevated, alongside swelling of astroctytes. A scavenger of peroxynitrite, but not an antioxidant, delivered intracisternally reversed all these events. We conclude that nitrosative stress because of augmented peroxynitrite related to accumulation of ammonia and swelling of astrocytes in the NTS or RVLM, leading to cytotoxic edema in the brain stem and severance of the NTS-RVLM connectivity, underpins the defunct baroreflex-mediated sympathetic vasomotor tone that accounts for the high mortality associated with HE.
The baseline characteristics, clinical outcomes, and laboratory data of 512 acute HEV infection cases were analysed using logistic regression models.
All patients exhibited autochthonous sporadic HEV infections, and most were elderly. Their symptoms varied from asymptomatic to severe liver diseases. In all, 215 patients (42.0%) had liver failure and/or decompensation, and 45 (8.2%) patients died within 3 months. Nearly 60% of patients had underlying chronic liver diseases (CLDs), 20% were cirrhotic, and various extrahepatic underlying comorbidities were common. The logistic regression analysis revealed that underlying CLDs, especially cirrhosis, were closely associated with disease severity (OR = 8.78, P < 0.001) but not with mortality in patients with severe liver diseases. In addition to the known factors, including an old age, the male gender and CLDs, we identified pre-existing extrahepatic tumours, diabetes, and chronic respiratory and renal diseases as novel independent predictors for adverse clinical outcomes. Importantly, patients without these four extrahepatic comorbidities showed a much lower mortality rate (4.2%, P < 0.001) than patients with one (18.5%) or more comorbidities (34.5%).
Previous comorbidities, including tumours, diabetes, and chronic liver, lung and kidney diseases, were independent risk factors for adverse outcomes, especially mortality, in acute HEV infections. This study provides valuable data for improving the prevention and control of HEV infection.
We evaluated 44 patients with ALF on high-dose corticosteroid therapy before hepatic coma development. The predictive performance for coma development was assessed using the receiver operator curve method in both PT and JHEPM probability the day before administering high-dose corticosteroid therapy.
Among these patients, nine developed hepatic coma after the therapy. Selection bias was adjusted using propensity score method. High-dose corticosteroid therapy tended to decrease the risk of coma development although there was no statistical significance. The cut-off value of 53%, 1.95, and 39% in JHEPM probability, PT-international normalized ratio (PT-INR), and PT activity, respectively, showed high sensitivity and specificity.
We propose the appropriate timing to start high-dose corticosteroid therapy in patients with ALI/ALF; 40% of JHEPM probability, 1.53 of PT-INR, and 52% of PT because these values were theoretically discriminated at 98% coverage to the patients with coma. Because the study contained selection bias, the appropriate timing for therapy should be confirmed in a future prospective study.