BACKGROUND AND OBJECTIVE

Patients with liver cirrhosis have an increased risk for poor postoperative outcomes after non-hepatic surgery, with liver dysfunction being the most important predictor of poor outcomes. This study aims to determine the association of the albumin-bilirubin (ALBI) grade, aspartate aminotransferase-platelet ratio index (APRI) score, and ALBI-APRI score with postoperative outcomes among cirrhotic patients who have undergone non-hepatic surgery.

This was a retrospective cohort study involving 34 patients. Age, ASA class, urgency of surgery, etiology of liver cirrhosis, preoperative Child-Turcotte-Pugh (CTP) score, Model for End-Stage Liver Disease (MELD) score, ALBI grade, APRI score, and ALBI-APRI score were documented. The outcomes analyzed were postoperative hepatic decompensation (POHD) and in-hospital mortality. Bivariate analysis using the Mann-Whitney U test and Fisher’s exact test was performed. Receiver operating characteristic (ROC) curve analysis was performed to compare the ability of the liver scoring systems to predict the occurrence of study outcomes. Binary logistic regression was performed to measure the odds ratio.

The ALBI grade and ALBI-APRI score were significantly associated with both POHD and in-hospital mortality. Both scores were non-inferior to the CTP and MELD scores in predicting study outcomes. Compared to CTP and MELD scores, the ALBI grade was more sensitive but less specific in predicting POHD and as sensitive but more specific in predicting in-hospital mortality. The ALBI-APRI score was less sensitive but more specific than the ALBI grade in predicting both POHD and in-hospital mortality.

The ALBI grade and ALBI-APRI score were both associated with postoperative hepatic decompensation and in-hospital mortality and were noninferior to the CTP score and MELD score in predicting short-term in-hospital outcomes among cirrhotic patients after non-hepatic surgery.

Liver fibrosis is a dynamic wound-healing response characterized by the agglutination of the extracellular matrix (ECM). Si-Wu-Tang (SWT), a traditional Chinese medicine (TCM) formula, is known for treating gynecological diseases and liver fibrosis. Our previous studies demonstrated that long non-coding RNA H19 (H19) was markedly upregulated in fibrotic livers while its deficiency markedly reversed fibrogenesis. However, the mechanisms by which SWT influences H19 remain unclear. Thus, we established a bile duct ligation (BDL)-induced liver fibrosis model to evaluate the hepatoprotective effects of SWT on various cells in the liver. Our results showed that SWT markedly improved ECM deposition and bile duct reactions in the liver. Notably, SWT relieved liver fibrosis by regulating the transcription of genes involved in the cytoskeleton remodeling, primarily in hepatic stellate cells (HSCs), and influencing cytoskeleton-related angiogenesis and hepatocellular injury. This modulation collectively led to reduced ECM deposition. Through extensive bioinformatics analyses, we determined that H19 acted as a miRNA sponge and mainly inhibited miR-200, miR-211, and let7b, thereby regulating the above cellular regulatory pathways. Meanwhile, SWT reversed H19-related miRNAs and signaling pathways, diminishing ECM deposition and liver fibrosis. However, these protective effects of SWT were diminished with the overexpression of H19 in vivo. In conclusion, our study elucidates the underlying mechanisms of SWT from the perspective of H19-related signal networks and proposes a potential SWT-based therapeutic strategy for the treatment of liver fibrosis.
Humans ; RNA, Long Noncoding/genetics* ; Liver Cirrhosis/genetics* ; Liver/metabolism* ; Hepatic Stellate Cells/pathology* ; MicroRNAs/metabolism* ; Extracellular Matrix/metabolism* ; Drugs, Chinese Herbal

Background and Objective: Patients with liver cirrhosis have an increased risk for poor postoperative outcomes after non-hepatic surgery, with liver dysfunction being the most important predictor of poor outcomes. This study aims to determine the association of the albumin-bilirubin (ALBI) grade, aspartate aminotransferase-platelet ratio index (APRI) score, and ALBI-APRI score with postoperative outcomes among cirrhotic patients who have undergone non-hepatic surgery. Methods: This was a retrospective cohort study involving 34 patients. Age, ASA class, urgency of surgery, etiology of liver cirrhosis, preoperative Child-Turcotte-Pugh (CTP) score, Model for End-Stage Liver Disease (MELD) score, ALBI grade, APRI score, and ALBI-APRI score were documented. The outcomes analyzed were postoperative hepatic decompensation (POHD) and in-hospital mortality. Bivariate analysis using the Mann-Whitney U test and Fisher’s exact test was performed. Receiver operating characteristic (ROC) curve analysis was performed to compare the ability of the liver scoring systems to predict the occurrence of study outcomes. Binary logistic regression was performed to measure the odds ratio. Results: The ALBI grade and ALBI-APRI score were significantly associated with both POHD and in-hospital mortality. Both scores were non-inferior to the CTP and MELD scores in predicting study outcomes. Compared to CTP and MELD scores, the ALBI grade was more sensitive but less specific in predicting POHD and as sensitive but more specific in predicting in-hospital mortality. The ALBI-APRI score was less sensitive but more specific than the ALBI grade in predicting both POHD and in-hospital mortality. Conclusions The ALBI grade and ALBI-APRI score were both associated with postoperative hepatic decompensation and in-hospital mortality and were noninferior to the CTP score and MELD score in predicting short-term in-hospital outcomes among cirrhotic patients after non-hepatic surgery.
liver cirrhosis ; in-hospital mortality ; hospital mortality

Humans ; Liver Cirrhosis ; Liver Diseases ; Liver Neoplasms ; Carcinoma, Hepatocellular

Objective: To investigate the efficacy of chitinase-3-like protein 1 (CHI3L1) and Golgi protein 73 (GP73) in the diagnosis of cirrhosis and the dynamic changes of CHI3L1 and GP73 after HCV clearance in patients with chronic hepatitis C (CHC) treated with direct-acting antiviral drugs (DAAs). The comparison of continuous variables of normal distribution were statistically analyzed by ANOVA and t-test. The comparison of continuous variables of non-normal distribution were statistically analyzed by rank sum test. The categorical variables were statistically analyzed by Fisher's exact test and χ(2) test. Correlation analysis was performed using Spearman correlation analysis. Methods: Data of 105 patients with CHC diagnosed from January 2017 to December 2019 were collected. The receiver operating characteristic curve (ROC curve) was plotted to study the efficacy of serum CHI3L1 and GP73 for the diagnosis of cirrhosis. Friedman test was used to compare CHI3L1 and GP73 change characteristics. Results: The areas under the ROC curve for CHI3L1 and GP73 in the diagnosis of cirrhosis at baseline were 0.939 and 0.839, respectively. Serum levels of CHI3L1 and GP73 in the DAAs group decreased significantly at the end of treatment compared with baseline [123.79 (60.25, 178.80) ng/ml vs. 118.20 (47.68, 151.36) ng/ml, P = 0.001; 105.73 (85.05, 130.69) ng/ml vs. 95.52 (69.52, 118.97) ng/ml, P = 0.001]. Serum CHI3L1 and GP73 in the pegylated interferon combined with ribavirin (PR) group were significantly lower at the end of 24 weeks of treatment than the baseline [89.15 (39.15, 149.74) ng/ml vs. 69.98 (20.52, 71.96) ng/ml, P < 0.05; 85.07 (60.07, 121) ng/ml vs. 54.17 (29.17, 78.65) ng/ml, P < 0.05]. Conclusion: CHI3L1 and GP73 are sensitive serological markers that can be used to monitor the fibrosis prognosis in CHC patients during treatment and after obtaining a sustained virological response. Serum CHI3L1 and GP73 levels in the DAAs group decreased earlier than those in the PR group, and the serum CHI3L1 levels in the untreated group increased compared with the baseline at about two years of follow-up.
Humans ; Hepatitis C, Chronic/drug therapy* ; Antiviral Agents/therapeutic use* ; Membrane Proteins/metabolism* ; Liver Cirrhosis/diagnosis* ; Fibrosis ; Biomarkers

Objective: To compare the differences to determine resting energy expenditure (REE) measured with indirect calorimetry and REE predicted by formula method and body composition analyzer in patients with decompensated hepatitis B cirrhosis, so as to provide theoretical guidance for the implementation of precision nutrition intervention. Methods: Patients with decompensated hepatitis B cirrhosis who were admitted to Henan Provincial People's Hospital from April 2020 to December 2020 were collected. REE was determined by the body composition analyzer and the H-B formula method. Results: were analyzed and compared to REE measured by the metabolic cart. Results A total of 57 cases with liver cirrhosis were included in this study. Among them, 42 were male, aged (47.93 ± 8.62) years, and 15 were female aged (57.20 ± 11.34) years. REE measured value in males was (1 808.14 ± 201.47) kcal/d, compared with the results calculated by the H-B formula method and the measured result of body composition, and the difference was statistically significant (P = 0.002 and 0.003, respectively). REE measured value in females was (1 496.60 ± 131.28) kcal/d, compared with the results calculated by the H-B formula method and the measured result of body composition, and the difference was statistically significant (P = 0.016 and 0.004, respectively). REE measured with the metabolic cart had correlation with age and area of visceral fat in men (P = 0.021) and women (P = 0.037). Conclusion: Metabolic cart use will be more accurate to obtain resting energy expenditure in patients with decompensated hepatitis B cirrhosis. Body composition analyzer and formula method may underestimate REE predictions. Simultaneously, it is suggested that the effect of age on REE in H-B formula should be fully considered for male patients, while the area of visceral fat may have a certain impact on the interpretation of REE in female patients.
Humans ; Male ; Female ; Energy Metabolism ; Liver Cirrhosis/metabolism* ; Calorimetry, Indirect/methods* ; Hospitalization

Objective: To investigate the changes of intestinal wall barrier function and its correlation with infection occurrence in patients with cirrhotic portal hypertension. Methods: 263 patients with cirrhotic portal hypertension were split into: the clinically evident portal hypertension (CEPH) combined with infection group (n = 74); CEPH group (n = 104); and Non-CEPH group (n = 85). Among them, 20 CEPH patients and 12 non-CEPH patients in non-infection status were subjected to sigmoidoscopy. Immunohistochemical staining was used to detect the expression of trigger receptor-1 (TREM-1), CD68, CD14, the inducible nitric oxide synthase molecule, and Escherichia coli (E.coli) in the medullary cells of the colon mucosa. An enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of soluble myeloid cell trigger receptor-1 (sTREM-1), soluble leukocyte differentiation antigen-14 subtype (sCD14-ST) and intestinal wall permeability index enteric fatty acid binding protein (I-FABP). Fisher's exact probability method, one-way ANOVA, Kruskal-Wallis-H test, Bonferroni method, and Spearman correlation analysis were used for statistical analysis. Results: The serum sTREM-1 and I-FABP levels were higher in CEPH patients than those of non-CEPH patients in the non-infectious state (P < 0.05), but the difference in blood sCD14-ST levels was not statistically significant (P > 0.05). Serum levels of sTREM-1, sCD14-ST, and I-FABP in infected patients were higher than those in patients without a concurrent infection (P < 0.05). Serum sCD14-ST levels were positively correlated with serum sTREM-1, C-reactive protein (CRP), and procalcitonin (PCT), and sTREM-1 levels were also positively correlated with CRP and PCT (r > 0.5, P < 0.001). The rates of CD68, inducible nitric oxide synthase, CD14-positive cells, and E.coli-positive glands were higher in the intestinal mucosa of the CEPH group than those of the control group (P < 0.05). Spearman's correlation analysis showed that the rate of E.coli-positive glands in CEPH patients was positively correlated with the expression of molecular markers CD68 and CD14 in the lamina propria macrophages. Conclusion: Patients with cirrhotic portal hypertension have increased intestinal permeability and inflammatory cells, accompanied by bacterial translocation. Serum sCD14-ST and sTREM-1 can be used as indicators to predict and evaluate the occurrence of infection in patients with cirrhotic portal hypertension.
Humans ; Nitric Oxide Synthase Type II ; Lipopolysaccharide Receptors ; Prospective Studies ; Biomarkers ; C-Reactive Protein/analysis* ; Liver Cirrhosis/complications* ; Hypertension, Portal

Objective: To explore the pathogenic mechanism of the miR-340/high mobility group box 1 (HMGB1) axis in the formation of liver fibrosis. Methods: A rat liver fibrosis model was established by injecting CCl(4) intraperitoneally. miRNAs targeting and validating HMGB1 were selected with gene microarrays after screening the differentially expressed miRNAs in rats with normal and hepatic fibrosis. The effect of miRNA expressional changes on HMGB1 levels was detected by qPCR. Dual luciferase gene reporter assays (LUC) was used to verify the targeting relationship between miR-340 and HMGB1. The proliferative activity of the hepatic stellate cell line HSC-T6 was detected by thiazolyl blue tetrazolium bromide (MTT) assay after co-transfection of miRNA mimics and HMGB1 overexpression vector, and the expression of extracellular matrix (ECM) proteins type I collagen and α-smooth muscle actin (SMA) was detected by western blot. Statistical analysis was performed by analysis of variance and the LSD-t test. Results: Hematoxylin-eosin and Masson staining results showed that the rat model of liver fibrosis was successfully established. Gene microarray analysis and bioinformatics prediction had detected eight miRNAs possibly targeting HMGB1, and animal model validation had detected miR-340. qPCR detection results showed that miR-340 had inhibited the expression of HMGB1, and a luciferase complementation assay suggested that miR-340 had targeted HMGB1. Functional experiments results showed that HMGB1 overexpression had enhanced cell proliferation activity and the expression of type I collagen and α-SMA, while miR-340 mimics had not only inhibited cell proliferation activity and the expression of HMGB1, type I collagen, and α-SMA, but also partially reversed the promoting effect of HMGB1 on cell proliferation and ECM synthesis. Conclusion: miR-340 targets HMGB1 to inhibit the proliferation and ECM deposition in hepatic stellate cells and plays a protective role during the process of liver fibrosis.
Animals ; Rats ; Cell Proliferation ; Collagen Type I/metabolism* ; Fibrosis ; Hepatic Stellate Cells ; HMGB1 Protein/genetics* ; Liver Cirrhosis/pathology* ; MicroRNAs/metabolism*

Fontan-associated liver disease (FALD) is one of the main complications after the Fontan procedure, manifesting mostly as liver fibrosis and even cirrhosis, with a high incidence rate and a lack of typical clinical symptoms that seriously affect patient prognosis. The specific cause is unknown, although it is considered to be associated with long-term elevated central venous pressure, impaired hepatic artery blood flow, and other relevant factors. The absence of association between laboratory tests, imaging data, and the severity of liver fibrosis makes clinical diagnosis and monitoring difficult. A liver biopsy is the gold standard for diagnosing and staging liver fibrosis. The most important risk factor for FALD is time following the Fontan procedure; therefore, it is recommended to do a liver biopsy 10 years after the Fontan procedure and to be cautious for the presence of hepatocellular carcinoma. Combined heart-liver transplantation is a recommended choice with favorable outcomes for patients with Fontan circulatory failure and severe hepatic fibrosis.
Humans ; Liver Diseases/pathology* ; Liver Cirrhosis/pathology* ; Liver/pathology* ; Carcinoma, Hepatocellular/pathology* ; Liver Transplantation/adverse effects* ; Fontan Procedure/adverse effects* ; Postoperative Complications/pathology* ; Liver Neoplasms/pathology*

An effective therapeutic regimen for hepatic fibrosis requires a deep understanding of the pathogenesis mechanism. Hepatic fibrosis is characterized by activated hepatic stellate cells (aHSCs) with an excessive production of extracellular matrix. Although promoted activation of HSCs by M2 macrophages has been demonstrated, the molecular mechanism involved remains ambiguous. Herein, we propose that the vitamin D receptor (VDR) involved in macrophage polarization may regulate the communication between macrophages and HSCs by changing the functions of exosomes. We confirm that activating the VDR can inhibit the effect of M2 macrophages on HSC activation. The exosomes derived from M2 macrophages can promote HSC activation, while stimulating VDR alters the protein profiles and reverses their roles in M2 macrophage exosomes. Smooth muscle cell-associated protein 5 (SMAP-5) was found to be the key effector protein in promoting HSC activation by regulating autophagy flux. Building on these results, we show that a combined treatment of a VDR agonist and a macrophage-targeted exosomal secretion inhibitor achieves an excellent anti-hepatic fibrosis effect. In this study, we aim to elucidate the association between VDR and macrophages in HSC activation. The results contribute to our understanding of the pathogenesis mechanism of hepatic fibrosis, and provide potential therapeutic targets for its treatment.
Humans ; Hepatic Stellate Cells/pathology* ; Receptors, Calcitriol ; Liver Cirrhosis/pathology* ; Macrophages/metabolism*