From November 10th to 14th, 2023, the Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2023) was grandly held in Boston, USA. Dr. Qin Ning’s team from Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, presented 2 posters of distinction and 6 posters on scientific research in the fields of liver injury, fatty liver, hepatitis B, end-stage liver disease, and complications. “Hepatology Digest” hereby reports on some of the research abstracts, providing you with a glimpse of the team’s achievements.
1
Intestinal IL-33-Hif-1α Axis Increases Gut Microbiota-Derived TMAO Synthesis, Mediating NAFLD Progression
2335-C | Intestinal IL-33-Hif-1α axis mediates NAFLD progression by increasing gut microbiota-derived TMAO synthesis
First Author: Suping Hai
Corresponding Author: Xiaojing Wang
Research Background
Non-alcoholic fatty liver disease (NAFLD) is a metabolic disease characterized by hepatic lipid deposition and has become the most common chronic liver disease worldwide. The gut microbiota and its metabolites play a crucial role in the development of NAFLD. IL-33, a member of the IL-1 family, is highly expressed in mucosal barriers and regulates various intestinal and extraintestinal diseases. However, the role of IL-33 in NASH is not fully understood. In this study, we investigated the regulatory role of the IL-33-Hif-1α axis in gut microbiota changes associated with NAFLD.
Research Methods
IL-33 knockout mice and control mice were fed a 60% high-fat diet for 24 weeks to establish the NAFLD model. DMB (3,3-dimethyl-1-butanol) was used to inhibit gut microbiota synthesis of TMAO. NAFLD mice were treated with antibiotics and received feces from IL-33 knockout mice and wild-type mice to clarify the direct role of IL-33-related gut microbiota in NAFLD. The gut microbiota was analyzed by 16S rRNA sequencing, and serum metabolites were analyzed by metabolomics. Naïve CD4+ T cells from mouse spleens and Caco-2 intestinal epithelial cell lines were used for in vitro studies.
Research Results
In NAFLD mice, intestinal IL-33 and its receptor ST2 expression increased, while liver levels remained unchanged. Knocking out IL-33 alleviated intestinal barrier leakage in NAFLD mice and reduced hepatic lipid deposition, inflammation, and fibrosis. On one hand, a high-fat diet stimulated intestinal epithelial cells to produce a large amount of IL-33, with increased IL-33 entering the cell nucleus and inhibiting the synthesis of Hif-1α and its downstream pathways, directly disrupting the intestinal barrier. On the other hand, IL-33 released from damaged intestinal epithelial cells promoted the expression of Hif-1α in intestinal lamina propria T lymphocytes, leading to pro-inflammatory Th1 differentiation and indirectly disrupting the intestinal barrier. The dual regulatory role of intestinal IL-33 resulted in dysbiosis of the gut microbiota, with upregulation of TMA and its synthesis by bacteria such as Lachnoclostridium, Providencia, Desulfovibrio, Blautia, and Prevotella. The increased TMA was oxidized to TMAO in the liver, causing oxidative stress damage and exacerbating NAFLD progression. Transplanting the gut microbiota from IL-33 knockout mice into wild-type mice reversed the NAFLD phenotype.
Research Conclusion
Intestinal IL-33 induces gut microbiota TMAO synthesis by dual regulation of intestinal epithelial cells and intestinal immune cell Hif-1α function, exacerbating NAFLD progression. Targeting intestinal IL-33 may provide a new strategy for the treatment of NAFLD.
Brief Introduction of the First Author
Doctoral student in infectious diseases, studying at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology.
2
FGL2-C3aR Axis Mediates Neutrophil Extracellular Traps, Promoting Intravascular Coagulation and Liver Fibrosis in NASH Progression
2314-C｜Fgl2-C3aR axis mediated neutrophil extracellular traps promote intravascular coagulation and liver fibrosis in NASH progression
First Author: Xitang Li
Corresponding Author: Xiaojing Wang
Research Background
The incidence of non-alcoholic fatty liver disease (NAFLD) is increasing year by year, including a spectrum of diseases such as simple fatty liver (NAFL), non-alcoholic steatohepatitis (NASH), liver fibrosis, and liver cancer. It is reported that about 10% of NASH patients develop metabolic liver fibrosis, which is a major cause of liver transplantation. Currently, there is no specific drug for treating liver fibrosis associated with fatty liver disease, making it imperative to further study the pathophysiological mechanisms of NAFLD and develop new therapeutic targets. Studies have suggested the existence of isolated coagulation abnormalities in NAFLD patients, and coagulation disorders have been observed to be positively correlated with the progression of NAFLD liver fibrosis. However, the role and mechanism of the coagulation system in NAFLD liver fibrosis are not clear. Recent studies have indicated that neutrophil extracellular traps (NETs) play a crucial role in promoting coagulation activation and immune thrombosis. This study aims to explore the role and potential mechanism of NETs-mediated coagulation in NASH fibrosis.
Research Methods
Two NAFLD models were induced by a 60% high-fat diet (HFD) or a methionine-choline-deficient (MCD) diet. Intraperitoneal injection of DNase 1 was used to deplete NETs. To investigate the effect of fibrinogen-like protein 2 (FGL2) on NETs generation, coagulation disorders, and NAFLD liver fibrosis, we constructed fgl2 knockout mice (fgl2-/-). WT neutrophils and fgl2-/- neutrophils were adoptively transferred into WT MCD mice to explore the effects of neutrophil-specific fgl2 on NETs generation, coagulation disorders, and disease progression. RNA sequencing and non-substantial cell transcriptome sequencing were used to analyze the major differential pathways and key molecules in the liver tissues of WT mice and fgl2-/- mice (dual models of MCD and HFD). To explore the role of C3aR in NASH fibrosis, MCD mice were treated with a C3aR antagonist (SB290157). In vitro, WT and fgl2-/- mouse bone marrow neutrophils were stimulated with palmitic acid (PA) and
LPS, and NETs-related molecular expression was detected. At the same time, the expression of FGL2, NETs, and C3aR in liver tissues of fatty liver patients was detected.
Research Results
Neutrophil infiltration and NETs release significantly increased in MCD and HFD liver fibrosis mice. Simultaneously, NETs and fibrinogen co-deposited, suggesting a potential association between NETs and local intravascular coagulation in liver tissue. Depleting NETs with DNase1 alleviated liver inflammation and fibrosis, and coagulation-related indicators such as TAT, complement-related component C3a, and liver fibrin deposition were significantly downregulated. After fgl2 knockout, NAFLD liver inflammation and fibrosis improved. Transcriptomic analysis suggested that fgl2 knockout inhibited NETs release and complement and coagulation activation pathways, which was further verified in vivo. Neutrophil adoptive transfer experiments indicated that neutrophil fgl2 could promote liver NETs release, activating the complement and coagulation systems. Transcriptomic analysis screened key genes in the complement and coagulation pathways, revealing that FGL2 might act through affecting the complement key molecule C3aR. In vitro experiments showed that under high-fat and LPS stimulation, neutrophil FGL2 could mediate NETs release and complement system activation by interacting with C3aR. In vivo experiments suggested that after C3aR inhibitor treatment, mouse liver damage was reduced, NETs release in the liver decreased, and complement and coagulation indicators were downregulated.
Research Conclusion
NETs can promote local intravascular coagulation in the liver, exacerbating NASH liver fibrosis development by activating the complement and coagulation systems. In NASH liver fibrosis, NETs generation is regulated by the FGL2-C3AR axis, and intervention with FGL2, C3aR, and NETs can alleviate disease progression.
First Author:
Medical Doctor, graduate of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology.
Corresponding Author:
Xiaojing Wang
Researcher, Ph.D. supervisor.
3
Fgl2 Targets PKM2 to Regulate Macrophage Glycolytic Reprogramming and Aggravates Alcoholic Liver Injury
Publication ID: 44296
First Author: Xue Hu
Corresponding Authors: Qin Ning, Hongwu Wang
Research Background:
Macrophage-mediated inflammatory responses play a crucial role in regulating the progression of alcoholic liver injury. The role of Fgl2, as an important inflammation-regulating molecule, in alcoholic liver injury is currently unclear. Therefore, this study aims to explore the regulatory mechanism of Fgl2 on macrophages, providing new insights for the diagnosis and treatment of alcoholic hepatitis.
Research Methods
– Collection of liver biopsy samples from patients with alcoholic hepatitis to observe the expression of Fgl2 on liver macrophages.
– Construction of NIAAA models using wild-type C57BL/6J mice and Fgl2 gene knockout mice to observe liver tissue damage indicators and macrophage phenotypic changes.
– In vitro culture of wild-type and Fgl2 gene knockout bone marrow-derived macrophages (BMDMs) and construction of Fgl2-overexpressing THP-1 cell lines.
– Implementation of immunoprecipitation and mass spectrometry analysis to determine target proteins, differential gene and pathway screening using next-generation sequencing.
– Seahorse assay to measure extracellular acidification rate and oxygen consumption rate of macrophages.
– Validation of Fgl2 interaction with candidate proteins through pull-down experiments, immunofluorescence, and molecular docking. Subsequent functional recovery experiments were conducted.
Research Results:
– In alcoholic hepatitis patients, the expression of Fgl2 on liver macrophages increased compared to healthy controls.
– Fgl2 expression on liver macrophages was significantly upregulated in mice fed with an alcohol diet compared to the control diet group.
– After knocking out the Fgl2 gene, liver function indicators (ALT), and liver tissue levels of TC and TG were improved in alcohol-fed mice. Additionally, pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) and chemokine MCP-1 levels were downregulated, and oxidative stress marker MDA was significantly improved.
– Macrophages in the livers of alcohol-fed mice exhibited a pro-inflammatory phenotype compared to the control diet group. The phenotype of macrophages in Fgl2 knockout alcohol-fed mice was significantly improved, with a decrease in Ly6Chi IMs and iNOS+CD206- macrophages.
– After LPS stimulation combined with alcohol in BMDMs, Fgl2 knockout BMDMs showed a significant downregulation of the pro-inflammatory phenotype, accompanied by glycolytic reprogramming, downregulation of ECAR, key genes, and proteins involved in glycolysis, decreased lactate levels, and reduced mitochondrial ROS release. Molecular mechanism studies revealed that Fgl2 knockout BMDMs regulated the HIF-1 signaling pathway related to glycolysis.
– Fgl2 interacted with PKM2 in macrophages, promoting its nuclear translocation and facilitating macrophage activation. Overexpression of Fgl2 in THP-1 cells promoted the release of inflammatory factors, upregulated aerobic glycolysis, and promoted the transcription of glycolysis genes through the PKM2-HIF-1α axis. This phenomenon could be reversed by activating PKM2 tetramer formation using DASA-58.
Research Conclusion:
Intracellular Fgl2 in macrophages can bind to PKM2, promoting PKM2 nuclear translocation. Through the PKM2-HIF-1α axis, it induces macrophage glycolytic reprogramming, regulates pro-inflammatory activation of macrophages, promotes inflammatory responses, and ultimately accelerates the progression of alcoholic hepatitis.
First Author
Infectious Diseases Ph.D. candidate, currently enrolled at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology.
Corresponding Author:
Medical Doctor, Postdoctoral Researcher, Associate Chief Physician.
4
TAF Treatment for Efficacy and Safety in Treatment-Naïve and Nucleos(t)ide-Experienced CHB Patients—96-Week Data from a Real-World Study (TRUE)**
First Author:
Di Wu
Ph.D. candidate in Infectious Diseases, enrolled at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology.
Corresponding Author:
Qin Ning
Research Background:
Tenofovir alafenamide (TAF) is a first-line antiviral therapy recommended for chronic hepatitis B (CHB) in major guidelines. Phase III randomized controlled trials have shown that TAF is non-inferior to tenofovir disoproxil fumarate (TDF) in antiviral efficacy and has better renal and bone safety. However, real-world research data on the long-term efficacy and safety of TAF treatment in Chinese treatment-naïve (TN) and nucleos(t)ide-experienced (TE) CHB patients are limited. The TRUE study, a long-term multicenter prospective study, was conducted to assess the virological, biochemical response, and safety of TAF treatment.
A prospective real-world clinical study (TRUE study, NCT03752658) was conducted in six national hospitals. The study design is illustrated in Figure 4.
Patients included were adult males or non-pregnant and non-lactating females with chronic hepatitis B, HBeAg-positive or negative, TN or TE, who had not received TAF treatment, with or without cirrhosis. Exclusion criteria included evidence of decompensated liver disease, active hepatitis A, B, C, D, or E, and hepatocellular carcinoma. Patients received TAF monotherapy or TAF combined with entecavir (ETV) for 144 weeks, and the study evaluated virological, biochemical response, and bone and renal safety of TAF treatment.
Research Results:
The study included a total of 500 patients, with 404 completing 96 weeks of treatment (TN: 146; TE: 258). At baseline, 13.6% of patients had cirrhosis. All TN patients and 164 TE patients received TAF monotherapy, while 94 TE patients received TAF and ETV combination therapy. At week 96, 88.9% of TN patients achieved virological response (defined as HBV DNA <20 IU/mL), and 81.8% achieved ALT normalization (ALT <40 U/L). In TE patients switched to TAF, virological response rate significantly increased from 67.8% at baseline to 91.7% at week 96 (P < 0.05), and biochemical response rate increased from 79.7% at baseline to 92.1% at week 96. In TE patients receiving TAF+ETV combination therapy, virological response rate significantly increased from 42.0% at baseline to 91.3% at week 96 (P < 0.05), and biochemical response rate increased from 80.0% at baseline to 92.9% at week 96 (P < 0.05). Virological response rates are shown in Figure 5.
In 75 TE patients with low viral load (defined as HBV DNA <2000 IU/mL) at baseline, 61 achieved virological response at week 96. In patients with estimated glomerular filtration rate (eGFR) below 90 mL/min/1.73 m² at baseline, eGFR significantly improved at week 96 (P < 0.05). Total cholesterol levels significantly increased at week 96 (P < 0.05). TAF-based treatment showed good tolerance and safety, with no treatment-related serious adverse events.
Research Conclusion:
TAF-based treatment is effective for both treatment-naïve and nucleos(t)ide-experienced CHB patients, including those with low viral load. For patients with mild renal impairment, renal function continued to improve after 96 weeks of TAF treatment.
Research Conclusions:
1. Study on TAF Treatment for CHB Patients in China:
Based on TAF treatment, it was found effective for both treatment-naive and treatment-experienced chronic hepatitis B (CHB) patients, as well as those with low-viremia. For patients with mild kidney impairment, after 96 weeks of TAF treatment, there was sustained improvement in glomerular function.
Author Introduction:
Associate Dr. and Deputy Chief Physician at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology.
05 Effectiveness and Safety of Treatment in Chronic Hepatitis B Patients: A Phase II Exploratory Randomized Controlled Trial (OCEAN cure05 Study)
OCEAN cure05 Study – Efficacy and safety of combination treatment of TLR7 agonist TQA3334 and anti-PD-L1 TQB2450 in virally suppressed chronic hepatitis B patients: a pilot RCT phase II study
First Author: Ting Wu
Corresponding Author: Qin Ning
Research Background:
The cure for chronic hepatitis B relies on the synergistic action of innate and adaptive immunity, along with sufficient suppression of viral replication. TQA3334, a selective TLR7 agonist, activates innate immunity, inducing cytokines like IFN-α and interferon-inducible protein-10 to inhibit HBV. TQB2450, an anti-PD-L1 antibody, inhibits the PD-1/PD-L1 axis, restoring adaptive immune response to HBV. This study evaluates the efficacy and safety of combination therapy with nucleos(t)ide analogs (NA) and TQA3334 with or without TQB2450 in chronic hepatitis B patients (OCEAN cure05 Study).
Research Methods:
The study included 24 virally suppressed chronic hepatitis B patients (250≤IU/ml HBsAg≤5000 IU/ml, HBV DNA <20 IU/ml). They were randomized into NA monotherapy group (n=6), NA combined with TQA3334 dual therapy group (n=9), and NA combined with TQA3334 and TQB2450 triple therapy group (n=9). The HBeAg-positive to negative ratio in each group was 1:2. TQA3334 (1.2 mg or 1.5 mg, once weekly) and TQB2450 (400 mg, once every 3 weeks) were administered for 24 weeks, and NA was administered for a total of 48 weeks.
Research Results:
One patient in the dual therapy group withdrew at week 6, leaving a total of 23 participants who completed the study. At the treatment endpoint, 66.67%, 62.5%, and 88.89% of patients in the monotherapy, dual therapy, and triple therapy groups, respectively, experienced a decrease in HBsAg compared to the baseline. Following the discontinuation of TQA3334 and TQB2450, 62.5% (5 individuals) in the dual therapy group and 66.6% (6 individuals) in the triple therapy group still maintained HBsAg levels below the treatment endpoint at the follow-up endpoint (Figure 6). Only patients in the triple therapy group achieved a reduction in HBsAg greater than 0.5 log10 IU/ml (n=3) and a decrease to below 100 IU/ml (n=2) at the treatment endpoint. In comparison to the monotherapy and dual therapy groups, the triple therapy group showed a larger average reduction in HBsAg at the treatment endpoint (0.04 ± 0.08, 0.04 ± 0.16, and 0.37 ± 0.50 log10 IU/ml, respectively). Within the triple therapy group, individuals receiving a high dose of TQA3334 exhibited a more significant reduction in HBsAg at the treatment endpoint (0.46 vs. 0.32 log10 IU/ml).
In this study, the maximum reduction in HBsAg was 1.4 log10 IU/ml. The baseline HBsAg for this patient was 2767 IU/ml, and the TQA3334 dosage was 1.5 mg. In the dual therapy and triple therapy groups, 5 individuals and 8 individuals, respectively, experienced treatment-related adverse events (TEAEs). The most common TEAE in the dual therapy group was fever. The triple therapy group had a higher incidence of TEAEs, with thyroiditis and elevated transaminases being the most common. Grade 1 thyroiditis was the most common immune-related adverse event associated with TQB2450. All TEAEs resolved before the follow-up endpoint. No serious adverse events (SAE) or deaths occurred.
Research Conclusion:
The combination therapy of nucleos(t)ide analogs, TQA3334, and TQB2450 leads to a more significant and persistent reduction in HBsAg in virally suppressed chronic hepatitis B patients, demonstrating good safety and tolerability. In the triple therapy group, a high dose of TQA3334 can further promote the reduction of HBsAg.
Author Information:
First Author:
– Doctor of Medicine
– Associate Chief Physician in the Department of Infectious Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology.
Corresponding Author:
– Chief of the Department of Infectious Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology.
06
Clinical Characteristics and Risk Factors of End-Stage Liver Disease Complicated by Bacterial or Fungal Infection: A Multi-Center Retrospective Study from Central China
Authors:
– Wei Liu (First Author)
– Corresponding Authors: Qin Ning, Tao Chen
Research Background
Bacterial or fungal infections are among the most common complications in patients with end-stage liver disease (ESLD). Currently, ESLD includes acute-on-chronic liver failure (ACLF), acute decompensation of liver cirrhosis (ADC), and chronic liver failure (CLF). In this multi-center retrospective study, we aimed to elucidate the epidemiology, clinical characteristics, and mortality risk associated with bacterial and fungal infections in different types of ESLD patients.
Research Methods:
Fourteen tertiary hospitals in the central China region participated in this retrospective cohort study. It included 1208 ESLD patients admitted for inpatient treatment between January 2012 and December 2018. The analysis involved demographic data, laboratory test results, and bacterial or fungal culture results.
Research Findings
– Among 1208 ESLD patients, 46.8% (565 cases) had bacterial infections, and 1.3% (16 cases) had fungal infections. The occurrence rates in ACLF, CLF, and ADC patients were 64.2%, 60.2%, and 37.4%, respectively.
– Spontaneous bacterial peritonitis was the most common infection type (51.5%), followed by pneumonia (43.7%), urinary tract infections (7.9%), septicemia (2.8%), and others (1.9%).
– The most common positive culture results were Gram-positive and Gram-negative bacteria (38.9% each) and fungi (22.2%).
– ESLD patients with bacterial or fungal infections showed significantly elevated white blood cell counts and procalcitonin (PCT) levels, severe impairment of liver and coagulation functions, and significantly higher rates of ascites, hepatorenal syndrome (HRS), hepatic encephalopathy (HE), upper gastrointestinal bleeding, and hepatopulmonary syndrome compared to patients without infections.
– Bacterial infection was identified as an independent risk factor for mortality in ESLD patients, while ACLF was an independent predictor of poor prognosis in ESLD patients with bacterial or fungal infections.
– Independent risk factors for ACLF patient mortality included elevated levels of total bilirubin and lactate dehydrogenase, and the occurrence of HRS. For CLF patients, independent risk factors for mortality were elevated neutrophil counts and the occurrence of HE. For ADC patients, an independent risk factor for mortality was an elevated PCT level.
Research Conclusion:
Bacterial infection is an independent risk factor for mortality in ESLD patients. Patients with different types of ESLD who are complicated by bacterial or fungal infections exhibit some homogeneity and heterogeneity in epidemiology, clinical characteristics, and mortality risk.
First Author: Wei Liu
Wei Liu is a doctoral candidate in Infectious Diseases, currently enrolled at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology.
7. A Quick and Accurate Tool Combining Number Connection Test A with Animal and Vegetable Naming Test to Identify Minimal Hepatic Encephalopathy in Hospitalized Patients
3059-A | First Author: Cheng Qiuyu | Corresponding Authors: Qin Ning, Chen Tao
Background:
Minimal Hepatic Encephalopathy (MHE) is often overlooked in hospitalized patients due to its subtle symptoms and time-consuming diagnosis. This study aims to establish a rapid and accurate tool for diagnosing MHE in hospitalized patients.
Methods:
A prospective inclusion of 123 healthy volunteers and 252 hospitalized patients with cirrhosis or slow-onset acute-on-chronic liver failure (ACLF) meeting Asia-Pacific criteria, without overt hepatic encephalopathy (OHE). The patients underwent hepatic encephalopathy psychological measurement scores (PHES), Animal Naming Test (ANT), Vegetable Naming Test (VNT), and Animal and Vegetable Naming Test (AVNT). Patient serum ammonia concentrations were measured, and the occurrence of new-onset OHE during hospitalization was observed.
Results:
An AVNA diagnostic chart combining AVNT and Number Connection Test A (NCT-A) was established. In the development cohort (n=152), the AUC was 0.98 (sensitivity 97.1%, specificity 93.2%, accuracy 94.1%), and in the validation cohort (n=100), the AUC was 0.91 (sensitivity 87.9%, specificity 79.1%, accuracy 82.0%). Patients diagnosed with MHE by AVNA had a higher risk of developing OHE within 30 days compared to those diagnosed as non-MHE by AVNA (P<0.001). The average time for AVNA testing was significantly shorter than PHES testing (151±77 seconds vs. 398±192 seconds, P<0.001).
Conclusion:
A rapid and accurate AVNA testing method for hospitalized patients with cirrhosis or ACLF was established, combining AVNT and NCT-A, enabling quick diagnosis of MHE in routine clinical practice.
Note: P<0.001
Research Conclusion
A rapid and accurate AVNA testing method for patients with liver cirrhosis or ACLF, combining AVNT and NCT-A, has been established. This method enables the rapid diagnosis of Minimal Hepatic Encephalopathy (MHE) in routine clinical practice.
8
Elevated levels of plasma neurofilament light chain and glial fibrillary acidic protein are associated with the occurrence of mild hepatic encephalopathy.
3072-A | Elevated Plasma Neurofilament Light Chain and Glial Fibrillary Acidic Protein Levels Associated with Presence of Minimal Hepatic Encephalopathy
First Author: Qiuyu Cheng
Corresponding Authors: Qin Ning, Tao Chen
Background
Dysfunction of astrocytes and neurons is involved in the development of hepatic encephalopathy (HE). The purpose of this study is to investigate the relationship between plasma neurodegenerative biomarkers and Minimal Hepatic Encephalopathy (MHE) and overt hepatic encephalopathy (OHE).
Methods
This study included 124 patients with liver cirrhosis. Hepatic encephalopathy psychometric measurement scores were used to diagnose MHE. Single-molecule array was employed to detect levels of plasma neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), tau protein, and ubiquitin carboxy-terminal hydrolase L1 (UCHL1).
Results
Among 109 patients without a history of OHE, 46 were diagnosed with MHE. NfL and GFAP levels in MHE patients were significantly higher than those in patients without MHE (P<0.05). In multivariate logistic regression analysis, NfL levels were independently associated with MHE (odds ratio 1.013, 95% confidence interval 1.001-1.025; P<0.05). In patients with and without viral hepatitis-related cirrhosis, there were no differences in NfL, GFAP, tau, and UCHL1 levels. NfL and GFAP levels were correlated with IL-6 levels (Spearman’s=0.3 and 0.255, P<0.05). Tau levels were correlated with MELD scores (Spearman’s=0.236, P<0.05), and plasma UCHL1 levels were correlated with serum albumin and ascites (Spearman’s=-0.219 and 0.281, P<0.05). However, IL-6 levels, not neurodegenerative biomarkers, significantly influenced the development of OHE.
Note: The concentrations of plasma neurodegenerative biomarkers in patients with liver cirrhosis between the MHE and non-MHE groups. Data are presented as box plots with median, interquartile range (IQR), and range. The Mann-Whitney U test was used to assess the differences in neurodegenerative biomarker levels between MHE and non-MHE patients. P<0.05, ** P<0.001. Abbreviations: MHE – Minimal Hepatic Encephalopathy; NfL – Neurofilament Light Chain; GFAP – Glial Fibrillary Acidic Protein; UCHL1 – Ubiquitin Carboxy-terminal Hydrolase L1.
Research Conclusion
As candidate blood biomarkers, plasma NfL and GFAP levels are significantly elevated in patients with Minimal Hepatic Encephalopathy (MHE).
Brief Introduction of the First Author
Doctoral candidate at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology.
Brief Introduction of the Corresponding Author
Doctor of Medicine, Associate Dr., Associate Chief Physician, Master’s Supervisor. Deputy Director of the Department of Infectious Diseases at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology.
