Acute Liver Injury In Patients Research Articles

Comparative Analysis of Machine Learning Models for Prediction of Acute Liver Injury in Sepsis Patients

Abstract Introduction: Acute liver injury (ALI) is a common complication of sepsis and is associated with adverse clinical outcomes. We aimed to develop a model to predict the risk of ALI in patients with sepsis after hospitalization. Methods: Medical records of 3196 septic patients treated at the Lishui Central Hospital in Zhejiang Province from January 2015 to May 2023 were selected. Cohort 1 was divided into ALI and non-ALI groups for model training and internal validation. The initial laboratory test results of the study subjects were used as features for machine learning (ML), and models built using nine different ML algorithms were compared to select the best algorithm and model. The predictive performance of model stacking methods was then explored. The best model was externally validated in Cohort 2. Results: In Cohort 1, LightGBM demonstrated good stability and predictive performance with an area under the curve (AUC) of 0.841. The top five most important variables in the model were diabetes, congestive heart failure, prothrombin time, heart rate, and platelet count. The LightGBM model showed stable and good ALI risk prediction ability in the external validation of Cohort 2 with an AUC of 0.815. Furthermore, an online prediction website was developed to assist healthcare professionals in applying this model more effectively. Conclusions: The Light GBM model can predict the risk of ALI in patients with sepsis after hospitalization.

Fibrinolysis-Mediated Pathways in Acute Liver Injury.

Acute liver injury (ALI), that is, the development of reduced liver function in patients without preexisting liver disease, can result from a wide range of causes, such as viral or bacterial infection, autoimmune disease, or adverse reaction to prescription and over-the-counter medications. ALI patients present with a complex coagulopathy, characterized by both hypercoagulable and hypocoagulable features. Similarly, ALI patients display a profound dysregulation of the fibrinolytic system with the vast majority of patients presenting with a hypofibrinolytic phenotype. Decades of research in experimental acute liver injury in mice suggest that fibrinolytic proteins, including plasmin(ogen), plasminogen activators, fibrinolysis inhibitors, and fibrin(ogen), can contribute to initial hepatotoxicity and/or stimulate liver repair. This review summarizes major experimental findings regarding the role of fibrinolytic factors in ALI from the last approximately 30 years and identifies unanswered questions, as well as highlighting areas for future research.

Hepatocytes-derived Prdx1 regulates macrophage phenotypes via TLR4 activation in acute liver injury

Acute liver injury (ALI) is a significant causative factor for multiple hepatic diseases. The excessive inflammatory response triggers proinflammatory immune cells recruitment, infiltration and differentiation, further contributing to inflammatory injuries in liver. As a proinflammatory factor, circulating Peroxiredoxin 1 (Prdx1) is elevated in ALI patients and mice. In this study, through carbon tetrachloride (CCl4) and cecal puncture and ligation (CLP)-induced liver injury mice model, we found hepatocytes-derived Prdx1 expression was increased in ALI. After AAV8-Prdx1-mediated Prdx1 knockdown, CCl4 and CLP-induced ALI was alleviated, along with the reduced proinflammatory cytokines, suppressed myeloid cells recruitment, decreased proportions of hepatic macrophages and neutrophils, restrained proinflammatory macrophage differentiation and infiltration. Mechanistically, hepatocyte-derived Prdx1 regulated macrophages through paracrine activation of the TLR4 signal. Our data support the immune and inflammatory regulatory role of Prdx1 in ALI pathological process to suggest its potential therapeutic application and clinical value.

S1417 Comparison of Logistic Regression Model With Machine Learning Models to Predict Acute Liver Injury in Patients Hospitalized With COVID-19

S1417 Comparison of Logistic Regression Model With Machine Learning Models to Predict Acute Liver Injury in Patients Hospitalized With COVID-19

Outcomes of Patients with Acute Hepatotoxicity Caused by Mushroom-Induced Poisoning.

This study aimed to investigate the characteristics of severe hepatitis (SH), acute liver injury (ALI), and acute liver failure (ALF) in patients with mushroom-induced hepatotoxicity. Data of patients between 2010 and 2019 were retrospectively reviewed. Twenty-four patients with mushroom-induced hepatotoxicity were included and divided into 3 groups: SH, ALI, and ALF. SH was defined as transaminase level ≥10 times ULN, international normalized ratio (INR) ≤1.5, and the absence of hepatic encephalopathy (HE). ALI was defined as INR > 1.5, presumed acute illness onset, and the absence of HE. ALF was diagnosed based on the presence of HE of any degree, with INR > 1.5, presumed acute illness onset, and the absence of cirrhosis. The mean age of the patients was 51.6 years; 13 (54.2%) were female. At admission, 18 patients (75%) had SH, 5 (21%) had ALI, and 1 (4.1%) had ALF. During follow-up, 6 of the 18 SH (33%) patients progressed to ALI and 2 of the 5 ALI (40%) patients progressed to ALF. No progression to ALI or ALF was observed in the 8 SH cases with a baseline MELD score of <15. One patient with grade 4 HE died (4.1%). None underwent liver transplantation. The survival was 100% in the ALI and SH groups. A MELD score of <15 at admission may be used as a predictor of no progression to ALI or ALF in patients with SH. However, since 40% of ALI cases may progress to ALF, these cases should be followed up in a tertiary care center that is equipped to perform liver transplantation and advanced therapies.

[Analysis of clinical characteristics and risk factors of early heat stroke-related acute liver injury].

To analyze the clinical characteristics and risk factors of early acute liver injury in patients with heat stroke (HS), and to provide basis for early identification of HS-related liver injury and its pathogenesis in clinical practice. The clinical data of patients with HS admitted to the department of critical care medicine of Haian People's Hospital from June 2015 to August 2022 were retrospectively analyzed. The patients with HS were divided into early liver injury group and early non-liver injury group according to the occurrence of acute liver injury within 24 hours of admission. The differences of basic data, clinical data, laboratory indexes and clinical outcomes of the two groups were analyzed. Logistic regression was used to analyze the risk factors for early HS-related acute liver injury, and receiver operator characteristic (ROC) curves were drawn to evaluate their value in predicting the occurrence of early HS-related acute liver injury. A total of 76 patients with HS were enrolled, and 46 patients with acute liver injury, accounting for 60.53%. In the early liver injury group, 14 patients (30.43%) had elevated aminotransferase alone, 9 patients (19.57%) had elevated total bilirubin (TBil) alone, and 23 patients (50.00%) had elevated both aminotransferase and TBil. Among the patients with elevated aminotransferases, 24 patients (64.87%) had mild elevation, 5 patients (13.51%) had moderate elevation, 8 patients (21.62%) had severe elevation. Compared with the early non-liver injury group, acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA), arterial blood lactate (Lac), interleukin-6 (IL-6), procalcitonin (PCT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), TBil, γ-gamma glutamyl transferase (γ-GGT), lactate dehydrogenase (LDH), creatine kinase (CK), MB isoenzyme of creatine kinase (CK-MB), cardiac troponin I (cTnI), myoglobin (MYO), N-terminal B-type pro-brain natriuretic peptide (NT-proBNP), prothrombin time (PT), activated partial thromboplastin time (APTT), D-dimer in the early liver injury group were significantly increased, while platelet count (PLT) were significantly decreased within 24 hours after admission, the 28-day mortality was significantly increased [28.26% (13/46) vs. 6.67% (2/30)], and the differences were statistically significant (all P < 0.05). Univariate Logistic regression analysis showed that APACHE II score, SOFA score, PLT, Lac, IL-6, PCT, γ-GGT, LDH, CK, CK-MB, cTnI, MYO, PT, APTT, D-dimer were risk factors of early HS-related acute liver injury (all P < 0.05). Multivariate Logistic regression analysis showed that PLT, IL-6, and LDH were independent risk factors of early HS-related acute liver injury [odds ratio (OR) and 95% confidence interval (95%CI) were 0.986 (0.974-0.998), 1.027 (1.012-1.041), and 1.002 (1.000-1.004), all P < 0.05]. The ROC curve analysis showed that the area under the ROC curve (AUC) of PLT, IL-6 and LDH for predicting the occurrence of early HS-related acute liver injury was 0.672 (95%CI was 0.548-0.797), 0.897 (95%CI was 0.824-0.971) and 0.833 (95%CI was 0.739-0.927), respectively. IL-6 had the highest predictive value for early HS-related liver injury. When the optimal diagnostic threshold of IL-6 was 48.25 ng/L, the sensitivity was 95.7%, the specificity was 73.3%, and the predictive value of PLT was the lowest. The early HS-related liver injury is mainly manifested as the simultaneous elevation of aminotransferase and TBil, and most of cases are mild liver injury. PLT, IL-6 and LDH are independent risk factors of early HS-related acute liver injury.

Does High-Intensity Exercise Cause Acute Liver Injury in Patients with Fontan Circulation? A Prospective Pilot Study.

The Fontan procedure results in chronic hepatic congestion and Fontan-associated liver disease (FALD) characterized by progressive liver fibrosis and cirrhosis. Exercise is recommended in this population, but may accelerate the progression of FALD from abrupt elevations in central venous pressure. The aim of this study was to assess if acute liver injury occurs after high-intensity exercise in patients with Fontan physiology. Ten patients were enrolled. Nine had normal systolic ventricular function and one had an ejection fraction < 40%. During cardiopulmonary exercise testing, patients had near-infrared spectroscopy (NIRS) to measure oxygen saturation of multiple organs, including the liver, and underwent pre- and post-exercise testing with liver elastography, laboratory markers, and cytokines to assess liver injury. The hepatic and renal NIRS showed a statistically significant decrease in oxygenation during exercise, and the hepatic NIRS had the slowest recovery compared to renal, cerebral, and peripheral muscle NIRS. A clinically significant increase in shear wave velocity occurred after exercise testing only in the one patient with systolic dysfunction. There was a statistically significant, albeit trivial, increase in ALT and GGT after exercise. Fibrogenic cytokines traditionally associated with FALD did not increase significantly in our cohort; however, pro-inflammatory cytokines that predispose to fibrogenesis did significantly rise during exercise. Although patients with Fontan circulation demonstrated a significant reduction in hepatic tissue oxygenation based on NIRS saturations during exercise, there was no clinical evidence of acute increase in liver congestion or acute liver injury following high-intensity exercise.

Early-phase prothrombin time-international normalized ratio in acute liver injury indicates the timing of therapeutic intervention and predicts prognostic improvement.

We investigated whether an early-phase prothrombin time-international normalized ratio (PT-INR) is an interventional prognostic indicator for patients with acute liver injury, including acute liver failure. This was a multicenter retrospective observational study. We included 595 patients with alanine aminotransferase levels ≥300U/L due to acute liver injury who were admitted to Kagoshima University Hospital or other collaborative investigation organizations between January 1, 2010, and December 31, 2015. Patients with alanine aminotransferase levels ≥300U/L and no previous liver disease were defined as having an acute liver injury. Acute liver failure was defined by PT-INR ≥1.5 with or without hepatic encephalopathy in acute liver injury patients. Data were obtained retrospectively from case reports and analyzed. The PT-INR on day 1 was the most accurate independent prognosis predictor in patients with acute liver injury and acute liver failure. On day 1, the transplant-free survival rates were significantly lower in patients with PT-INR ≥1.3. The transplant-free survival rates were also significantly higher in patients with acute liver injury and acute liver failure, in whom the PT-INR had recovered from ≥1.3 on day 1 to <1.3 by day 8. Early-phase changes in the PT-INR can predict the prognosis of patients with acute liver injury and acute liver failure. Furthermore, PT-INR ≥1.3 could be an interventional marker, whereas PT-INR <1.3 after 1week could reflect prognostic improvement.

Clinical predictors of recovery of COVID-19 associated-abnormal liver function test 2 months after hospital discharge

This study investigated whether acute liver injury (ALI) persisted and identified predictors of ALI recovery [as indicated by alanine aminotransferase (ALT) level] at hospital discharge and 2 months post-discharge for 7595 hospitalized COVID-19 patients from the Montefiore Health System (03/11/2020–06/03/2021). Mild liver injury (mLI) was defined as ALT = 1.5–5 ULN, and severe livery injury (sLI) was ALT ≥ 5 ULN. Logistic regression was used to identify predictors of ALI onset and recovery. There were 4571 (60.2%), 2306 (30.4%), 718 (9.5%) patients with no liver injury (nLI), mLI and sLI, respectively. Males showed higher incidence of sLI and mLI (p < 0.05). Mortality odds ratio was 4.15 [95% CI 3.41, 5.05, p < 0.001] for sLI and 1.69 [95% CI 1.47, 1.96, p < 0.001] for mLI compared to nLI. The top predictors (ALT, lactate dehydrogenase, ferritin, lymphocytes) accurately predicted sLI onset up to three days prior. Only 33.5% of mLI and 17.1% of sLI patients (survivors) recovered completely at hospital discharge. Most ALI patients (76.7–82.4%) recovered completely ~ 2 months post-discharge. The top predictors accurately predicted recovery post discharge with 83.2 ± 2.2% accuracy. In conclusion, most COVID-19 patients with ALI recovered completely ~ 2 months post discharge. Early identification of patients at-risk of persistent ALI could help to prevent long-term liver complications.

Review of Liver Enzymes Abnormalities in Patients with SARS-CoV-2 Infection

Background: Liver function derangements have been reported in COVID-19, but reported rates are variable. Treatment in intensive care units (ICU) has become a major challenge; therefore, early recognition of severe and critical cases is absolutely essential for timely triaging of patients. Objectives: to review incidence of acute liver injury in patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Patients and methods: obtaining clinical records and laboratory results prospectively from one hundred patients with PCR-confirmed or radiography-confirmed COVID-19, who are admitted to the isolation wards and emergency departments of three different hospitals in Baghdad from 1st of December 2020 to 31st of March 2021. Results: The mean age group of study sample was (61.2±12.36) years, males formed 59%. GI manifestations were recorded in 47% of total cases, and were statistically correlated with disease severity (P value 0.001). Wide range of LFT abnormalities are found in patients with COVID-19, but none of which showed statistical significance in relation to disease severity. When LFT results were reviewed in relation to previous comorbidities, GGT was found to be statistically correlated with the underlying CLD (P value 0.001), and ALP with both underlying CLD and DM (P values &lt;0.001 and 0.029, respectively) and even in the absence of underlying comorbidity (P value 0.006). Conclusion: Liver enzyme derangements are increasingly reported in patients with COVID-19, but are not necessarily correlate with disease severity. Cholestatic picture of liver enzyme derangement is a more commonly recorded manifestation.

MALAT1-mediated EZH2 Recruitment to the GFER Promoter Region Curbs Normal Hepatocyte Proliferation in Acute Liver Injury.

The goal of this study was to investigate the mechanism by which the long noncoding RNA MALAT1 inhibited hepatocyte proliferation in acute liver injury (ALI). Lipopolysaccharide (LPS) was used to induce an ALI cellular model in HL7702 cells, in which lentivirus vectors containing MALAT1/EZH2/GFER overexpression or knockdown were introduced. A series of experiments were performed to determine their roles in liver injury, oxidative stress injury, and cell biological processes. The interaction of MALAT1 with EZH2 and enrichment of EZH2 and H3K27me3 in the GFER promoter region were identified. Rats were treated with MALAT1 knockdown or GFER overexpression before LPS induction to verify the results derived from the in vitro assay. MALAT1 levels were elevated and GFER levels were reduced in ALI patients and the LPS-induced cell model. MALAT1 knockdown or GFER overexpression suppressed cell apoptosis and oxidative stress injury induced cell proliferation, and reduced ALI. Functionally, MALAT1 interacted directly with EZH2 and increased the enrichment of EZH2 and H3K27me3 in the GFER promoter region to reduce GFER expression. Moreover, MALAT1/EZH2/GFER was activated the AMPK/mTOR signaling pathway. Our study highlighted the inhibitory role of reduced MALAT1 in ALI through the modulation of EZH2-mediated GFER.

Severe acute liver injury in patients with exertional heat stroke associated with poor short-term prognosis.

Severe acute liver injury in patients with exertional heat stroke associated with poor short-term prognosis.

Review of Liver Enzymes Abnormalities in Patients with SARS-CoV-2 Infection

<i>Background</i>: Liver function derangements have been reported in COVID-19, but reported rates are variable. Treatment in intensive care units (ICU) has become a major challenge; therefore, early recognition of severe and critical cases is absolutely essential for timely triaging of patients. Objectives: to review incidence of acute liver injury in patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). <i>Patients and methods</i>: obtaining clinical records and laboratory results prospectively from one hundred patients with PCR-confirmed or radiography-confirmed COVID-19, who are admitted to the isolation wards and emergency departments of three different hospitals in Baghdad from 1st of December 2020 to 31st of March 2021. <i>Results</i>: The mean age group of study sample was (61.2±12.36) years, males formed 59%. GI manifestations were recorded in 47% of total cases, and were statistically correlated with disease severity (P value 0.001). Wide range of LFT abnormalities are found in patients with COVID-19, but none of which showed statistical significance in relation to disease severity. When LFT results were reviewed in relation to previous comorbidities, GGT was found to be statistically correlated with the underlying CLD (P value 0.001), and ALP with both underlying CLD and DM (P values <0.001 and 0.029, respectively) and even in the absence of underlying comorbidity (P value 0.006). <i>Conclusion</i>: Liver enzyme derangements are increasingly reported in patients with COVID-19, but are not necessarily correlate with disease severity. Cholestatic picture of liver enzyme derangement is a more commonly recorded manifestation.

Evaluation of SOX9-Positive Hepatocytes in Human Liver Specimens and Mature Mouse Hepatocytes.

The liver has a remarkable regenerative capacity with different modes of regeneration according to the type and extent of an injury. It has been reported that mature hepatocytes could transdifferentiate into a cholangiocyte phenotype. Sry HMG box protein 9 (SOX9) is one of the earliest biliary markers that regulate bile duct development. We have found that SOX9-positive biphenotypic hepatocytes appear in severe acute liver injury patients' liver specimens accompanied by an elevation in plasma interleukin-8 levels. In vitro assays revealed that interleukin-8 homologs induce the expression of SOX9 in mature mouse hepatocytes. Here, we describe the methods used to detect SOX9-positive hepatocytes in human liver specimens and to induce SOX9-positive hepatocytes in mature mouse hepatocytes.

Octanoic acid-rich enteral nutrition prevented lipopolysaccharide-induced acute liver injury through c-Jun N-terminal kinase-dependent autophagy.

Acute liver injury (ALI) is an essential component of sepsis associated with poor outcomes. Octanoic acid (OA), a medium-chain fatty acid, has a protective effect on sepsis-induced organ damage, and autophagy is an adaptive response to sepsis. However, the underlying mechanism by which OA prevents ALI remains unknown. Therefore, we investigated whether OA-rich enteral nutrition (EN) prevented lipopolysaccharide (LPS)-induced ALI through the c-Jun N-terminal kinase (JNK)-dependent autophagy. Firstly, Sprague Dawley rats were randomly divided into four groups (sham, LPS, LPS + EN, and LPS + EN + OA) to detect the effect of OA-rich EN on LPS-induced ALI. Then, rats were randomly divided into five groups (sham, LPS, LPS + EN + OA, LPS + EN + OA + anisomycin (AN), and LPS + SP600125) to explore the mechanism by which OA-rich EN prevented ALI. EN and OA-rich EN were conducted through gastric tubes for 3 days. The liver protective effects were measured by liver histopathological changes, enzymes, inflammatory cytokines of serum and liver, the levels of autophagy, and JNK activity. OA-rich EN inhibited JNK activity, up-regulated autophagy and prevented LPS-induced ALI. Inhibition of JNK activity conferred by SP promoted autophagy and prevented LPS-induced ALI. Moreover, the protective effect of autophagy and inhibition of JNK activity conferred by OA-rich EN on ALI was counteracted by AN. OA-rich EN prevented LPS-induced ALI through JNK-dependent autophagy. This result suggested that OA-rich EN may be a therapeutic potential for ALI in patients with sepsis.

An Analytical Study on Acute Liver Injury in Patients Caused by Classic Heat stroke

Heat Stroke is a kind of medical emergency that can cause severe dehydration and neurological changes as a result multi-organ injuries or failure could be possible. Heat strokes occur when the body temperature exceeds 40 0C due to external heat and humidity. The liver is widely affected by heatstroke that’s why taking care of patients suffering from heatstroke is very important. Various studies have been reported in the literature regarding acute liver failure but none of the studies discussed acute liver failure during the hospital stay. Patients during their hospital stay will have a higher risk of mortality due to heatstroke. In this paper, an analytical study has been done on admitted patients to a government hospital in India. These patients are suffered from heatstroke from April 2007 to September 2011 and a second time period from July 2018 to September 2019. The sample includes 60 patients with 58 (97%) males having a totaled number of 12 fatalities. The observed International Normalized ratio (INR) parameter is greater than 1.6 and no increased mortality has been noticed, aspartate aminotransferase (AST), as well as alanine aminotransferase (ALT) levels, were not associated with an increased mortality rate.

Acute Liver Injury in Patients Hospitalized with COVID-19.

IntroductionThe prevalence and significance of acute liver injury in patients with COVID-19 are poorly characterized.MethodsPatients with confirmed COVID-19 who were hospitalized in geographically diverse medical centers in North America were included. Demographics, symptoms, laboratory data results, and outcomes were recorded. Linear and logistic regression identified factors associated with liver injury, in-hospital mortality, and length of stay (LOS).ResultsAmong 1555 patients in the cohort, most (74%) had an elevated alanine aminotransferase (ALT) during hospitalization, which was very severe (> 20 × upper limit of normal [ULN]) in 3%. Severe acute liver injury (ALI) was uncommon, occurring in 0.1% on admission and 2% during hospitalization. No patient developed acute liver failure (ALF). Higher ALT was associated with leukocytosis (per mL3) (β 10.0, 95% confidence interval (CI) 6.7–12.6, p < 0.001) and vasopressors use (β 80.2, 95%CI 21.5–138.8, p = 0.007). In-hospital mortality was associated with ALT > 20 × ULN (unadjusted OR 6.0, 95%CI 3.1–11.5, p < 0.001), ALP > 3 × ULN (unadjusted OR 4.4, 95%CI 2.5–7.7, p < 0.001), and severe ALI (unadjusted OR 6.8, 95%CI 3.0–15.3, p < 0.001) but lost significance after adjusting for covariates related to severe COVID-19 and hemodynamic instability. Elevated ALP and ALT were associated with longer LOS, admission to intensive care, mechanical ventilation, vasopressor use, and extracorporeal membrane oxygenation use (p < 0.001).ConclusionsTransaminase elevation is common in hospitalized patients with COVID-19. Severe ALI is rare, and ALF may not be a complication of COVID-19. Extreme elevations in liver enzymes appear to be associated with mortality and longer LOS due to more severe systemic disease rather than SARS-CoV-2-related hepatitis.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10620-021-07230-9.

Protease inhibitor-based direct-acting antivirals are associated with increased risk of aminotransferase elevations but not hepatic dysfunction or decompensation

Cases of acute liver injury (ALI) have been reported among chronic HCV-infected patients receiving protease inhibitor (PI)-based direct-acting antiviral (DAA) regimens, but no analyses have compared the risk of ALI in patients receiving PI- vs. non-PI-based DAAs. Thus, we compared the risk of 3 ALI outcomes between patients (by baseline Fibrosis-4 [FIB-4] group) receiving PI-based or non-PI-based DAAs. We conducted a cohort study of 18,498 patients receiving PI-based DAA therapy (paritaprevir/ritonavir/ombitasvir±dasabuvir, elbasvir/grazoprevir, glecaprevir/pibrentasvir) matched 1:1 on propensity score to those receiving non-PI-based DAAs (sofosbuvir/ledipasvir, sofosbuvir/velpatasvir) in the 1945-1965 Veterans Birth Cohort (2014-2019). During exposure to DAA therapy, we determined development of: i) alanine aminotransferase (ALT) >200 U/L, ii) severe hepatic dysfunction (coagulopathy with hyperbilirubinemia), and iii) hepatic decompensation. We used Cox regression to determine hazard ratios (HRs) with 95% CIs for each ALI outcome within groups defined by baseline FIB-4 (≤3.25; >3.25). Among patients with baseline FIB-4 ≤3.25, those receiving PIs had a higher risk of ALT >200 U/L (HR 3.98; 95% CI 2.37-6.68), but not severe hepatic dysfunction (HR 0.67; 95% CI 0.19-2.39) or hepatic decompensation (HR 1.01; 95% CI 0.29-3.49), compared to those receiving non-PI-based regimens. For those with baseline FIB-4 >3.25, those receiving PIs had a higher risk of ALT >200 U/L (HR, 2.15; 95% CI 1.09-4.26), but not severe hepatic dysfunction (HR, 1.23 [0.64-2.38]) or hepatic decompensation (HR, 0.87; 95% CI 0.41-1.87), compared to those receiving non-PI-based regimens CONCLUSION: While risk of incident ALT elevations was increased in those receiving PI-based DAAs in both FIB-4 groups, the risk of severe hepatic dysfunction and hepatic decompensation did not differ between patients receiving PI- or non-PI-based DAAs in either FIB-4 group. Cases of liver injury have been reported among patients treated with protease inhibitor-based direct-acting antivirals for hepatitis C infection, but it is not clear if the risk of liver injury among people starting these drugs is increased compared to those starting non-protease inhibitor-based therapy. In this study, patients receiving protease inhibitor-based treatment had a higher risk of liver inflammation than those receiving a non-protease inhibitor-based treatment, regardless of the presence of pre-treatment advanced liver fibrosis/cirrhosis. However, the risk of severe liver dysfunction and decompensation were not higher for patients treated with protease inhibitor-based regimens.

Risk factors and severity of acute liver injury in non-chronic liver disease and chronic liver disease patients

Objectives To study factors related to acute liver injury and compare the severity and risk of those factors in patients with and without chronic liver disease. Methods This cross-sectional study of 323 patients admitted to Somdejphrajaotaksin Maharaj Hospital between 1 January and 30 September 2019, analyzing data collected on the clinical background, signs and symptoms, and laboratory results of those patients. Results Of the 323 patients in the study, 188 did not have chronic liver disease (58.2%) and 135 had chronic liver disease (41.8%). Risk factors for acute liver injury in the chronic liver disease group included bacterial infection (33.3%) and spontaneous bacterial peritonitis (4.4%), much significantly higher than the rates in the no chronic disease group. However, the risk factors excessive consumption of alcohol (30.3%) and dengue infection (11.2%) in the no chronic liver disease group were significantly higher than in the chronic disease group. Both groups had a high incidence of disease severity as well as a high incidence of complications and mortality, although the mortality rate was higher in the chronic liver disease group (15.0% vs. 6.9%). Conclusions The types and frequencies of risk factors for acute liver injury in patients with chronic liver disease and those with no chronic liver disease groups are different. The incidence of bacterial infection and spontaneous bacterial peritonitis is higher in patients with chronic liver disease. The incidence of excessive alcohol consumption and dengue infection is much higher in patients without chronic liver disease. Both groups have high levels of disease severity, complications and mortality. Sepsis is the major cause of mortality, especially in patients with chronic liver disease.

CHI3L1 alleviate acute liver injury by inhibiting Th1 cells differentiation through STAT3 signaling pathway.

Acute liver injury (ALI) is a severe liver disease. Chitinase 3-like-1 (CHI3L1), a protein belonging to the glycosyl hydrolase family 18, is involved in many diseases, such as inflammatory diseases, bacterial infections, and various malignant tumors; however, the function of CHI3L1 in ALI remains unclear. The objective of this study was to evaluate the protective functions of CHI3L1 against thioacetamide (TAA)-induced ALI in mice and explore its potential mechanisms. Data from 20 patients with ALI and 10 healthy subjects was collected. Serum CHI3L1, serum aspartate transaminase (AST), and serum alanine aminotransferase (ALT) were measured. To establish ALI mouse models, thioacetamide was intraperitoneally injected into groups of the CHI3L1-knockout (CHI3L1-KO) and wild-type (WT) mice (80 and 150 mg/kg). Recombinant CHI3L1 protein (rCHI3L1) (5 µg/kg), IFN-γ (500 ng), and WP1033 (an inhibitor of P-STAT3, 0.2 mL) were injected before TAA treatment, after which the effects were estimated. Splenic CD4+CD62L+ naive T cells were isolated from CHI3L1-KO mice and stimulated to differentiate into regulatory T (Treg) cells, T-helper 1 (Th1) cells, T-helper 2 (Th2) cells, and T-helper 17 (Th17) cells. Increased serum CHI3L1 levels were seen both in healthy subjects and post-therapy patients compared with ALI patients. CHI3L1 levels were negatively correlated with serum ALT and AST levels in ALI patients. CHI3L1-KO group showed higher serum ALT and AST levels than the WT group following TAA treatment, while tail vein injection of rCHI3L1 reduced liver tissue injury and improved Treg cell differentiation in vivo. In vitro experiment showed that knockout of CHI3L1 improved IFN-γ+ Th1 cell differentiation. Furthermore, intraperitoneal administration of IFN-γ produced more severe hepatocellular necrosis compared with rCHI3L1 injection alone. Mechanism study showed that T-box expressed in T cells (T-bet), and signal transducer and activator of transcription 3 (STAT3), play a critical role in adversely mediating the effect of CHI3L1, which is consistent with the finding that treatment with WP1033 down-regulated the differentiation of the Th1 cells in vitro and reduced severity of liver injury in vivo. CHI3L1 reduced the production of IFN-γ and inhibited Th1 cell differentiation through the STAT3 signaling pathway, which could be a potential therapeutic strategy for treating ALI.