Portal-sinusoidal vascular disorder (PSVD) is one of the important causes of non-sclerosing portal hypertension. Due to a lack of awareness of this disease among some clinicians, certain PSVD patients may be misdiagnosed as having cryptogenic or autoimmune cirrhosis. The etiology and underlying mechanisms of PSVD are still unclear, and only symptomatic treatment is available in clinical practice. So far, there are no standardized diagnostic and treatment guidelines. This article summarizes the research progress of PSVD at home and abroad in recent years, in order to improve the early diagnosis rate of the disease and the accuracy of intervention.
Drug-induced liver injury (DILI) caused by platinum-based chemotherapy drugs is characterized by elevated aminotransferase, while vascular injury is relatively rare as a special clinical phenotype of DILI. It has been reported that DILI caused by platinum-based chemotherapy drugs is more common with hepatic sinus obstruction syndrome, while porto-sinusoidal vascular disorder (PSVD) caused by platinum-based chemotherapy drugs is rarely reported. This report describes a case with prominent clinical manifestations of portal hypertension and normal or nearly normal liver function. Liver function impairment and portal hypertension were not parallel. Extrahepatic vascular diseases were excluded by imaging. Although imaging suggested cirrhosis, liver transient elastography (TE) did not support cirrhosis, and liver biopsy histopathology also excluded cirrhosis, revealing characteristic histopathological features of PSVD. The patient was diagnosed with PSVD induced by platinum-based chemotherapy drugs. After one year of follow-up, the patient's condition remained relatively stable.
Objective: The objective was to evaluate the clinical efficacy of Tongyang Qushi Fang in patients with nonalcoholic fatty liver disease (NAFLD). Methods: 130 patients with NAFLD were randomly divided into the control group (62 cases) and the treatment group (68 cases). The control group received simple weight control, while the treatment group was given Tongyang Qushi Fang in addition to the routine treatment provided to the control group. Results: After 24 weeks of treatment, both groups showed a significant reduction in TCM syndrome scores, liver-spleen CT ratio, body weight, and BMI (P<0.05) . The treatment group showed a better decrease in TCM syndrome scores compared to the control group (P<0.05).The liver-spleen CT ratio improved in both groups, with statistically significant differences (P<0.05) The improvement of biochemical indexes such as alanine aminotransferase (ALT) , aspartate aminotransferase (AST) , glutamyl transpeptidase (GGT) , alkaline phosphatase (Alp) , total cholesterol (TC) , triglyceride (TG) , high-density lipoprotein cholesterol (HDL-C) , low-density lipoprotein (LDL-C) and glycated hemoglobin (HbA1c) in the treatment group was superior to that in the control group(P<0.05). Conclusion: Tongyang Qushi Fang can improve the clinical efficacy in patients with cold-dampness-trapped spleen type NAFLD.
Objective: Exploring the diversity of the microbiota in patients with nonalcoholic fatty liver disease (NAFLD) and its correlation with liver fibrosis-related cytokines. Methods: A total of 137 patients with NAFLD treated in our hospital from January 2023 to December 2023 were selected as the NAFLD group, and 109 patients with healthy results in our hospital during the same period were selected as the control group. Stool samples were collected from all patients for analysis and comparison of intestinal flora, while fasting venous blood was collected for detection and comparison of liver fibrosis-related cytokines interleukin1β, 6, 12, 17, 21, 32 (IL-1β, IL-12, IL-17, IL-21, IL-32) and tumor necrosis factor α (TNF-α). Finally, the correlation between intestinal flora diversity and liver fibrosis related factors in NAFLD patients was analyzed. Results: IL-1β, IL-12, IL-17, IL-21, IL-32 and TNF-α in NAFLD group were significantly higher than those in control group, with statistical significance (P<0.05). Chao1 index, ACE index and Shannon index in NAFLD group were lower than those in control group, while Simpson index was higher than those in control group, with statistical significance (P<0.05). In the control group, Parabacteroides, Lactobacillus, Prevotella, Bifidobacterium, Flavobacterium and Oscillibacter had high abundance and were the main dominant bacteria. In the intestinal flora of NAFLD group, Bacteroides,Clostridiun_butyricum,Escherichia,Clostridiun_leptum,Enterobacteriaceae,Bacteroidetes,Eubacteriun,Streptococcus have a high abundance and are the main dominant bacteria. Parabacteroides, Lactobacillus, Prevotella, Bifidobacterium and Oscillibacter were negatively correlated with liver fibrosis-related cytokines. Bacteroides, Clostridiun_butyricum, Escherichia and Bacteroidetes were positively correlated with liver fibrosis related cytokines (P<0.05). Conclusion: Patients with NAFLD have significant abnormalities in the diversity of intestinal microflora and correlate with liver fibrosis-related cytokines.
ZHANG Chun-mei, GAO Xiao-lian, WANG Jing-zhi, et al
Objective: This study, based on the theory of "soil impediment and wood stagnation," explores the value of body composition and liver function indicators in assessing traditional Chinese medicine(TCM) syndromes in metabolic associated fatty liver disease (MAFLD). Methods: 118 patients with MAFLD who first visited the Obesity Clinic at Hubei Provincial Hospital of Traditional Chinese Medicine between June and December 2022 were included in the study. The levels of body mass index (BMI), basal metabolic rate (BMR), visceral fat area (VFA), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), direct bilirubin (DBil), hypersensitive C reactive protein (hs-CRP) and controlled decay parameter (CAP)were compared in four syndrome types: liver-depression and spleen-deficiency, phlegm-turbidity internal obstruction, dampness-heat accumulation and phlegm-blood stasis interconnection. Multivariate disordered multiple Logistic regression was used to analyze the predictors of TCM syndrome types in MAFLD patients. Results: There were 40 cases (34.0%) in the liver-depression and spleen-deficiency group, 24 cases (20.3%) in the phlegm-turbidity internal obstruction group, 34 cases (28.8%) in the dampness-heat accumulation group, and 20 cases (16.9%) in the phlegm-blood stasis interconnection group. The levels of BMR, TBil and DBil were significantly different (P<0.05) in four groups. The results of disordered multiple Logistic regression showed that TBil was the predictor of phlegm turbidity obstruction syndrome (OR=1.27,95% CI:1.032-1.565,P=0.024), taking liver-stagnation and splee-deficiency syndrome as reference. The variables were not statistically significant in the phlegm-turbidity internal obstruction syndrome group, ddampness-heat accumulation syndrome group, and phlegm-blood stasis interconnection syndrome group as reference (P>0.05). Conclusion: MAFLD patients with different TCM syndromes exhibit differences in BMR, TBil, and DBil levels. TBil is higher in the phlegm-damp obstruction syndrome group compared to the liver-stagnation and splee-deficiency syndrome group. TBil is a promising predictive factor for TCM syndromes in MAFLD and warrants further research.
Objective: To observe the curative effect of pegylated interferon(Peg IFN) α-2b in the treatment of chronic hepatitis B patients with abnormal alanine aminotransferase(ALT) after nucleotide analogues(NAs) treatment, and to provide reference for clinical treatment. Methods: Chronic hepatitis B patients treated with NAs for more than 4 years and with abnormal ALT were included in the control group and the combination group from January 2021 to March 2022. According to China's "Chronic Hepatitis B Prevention and Treatment Guidelines (2022 edition)", the control group continued to receive NAs,the combined group was treated with Peg IFN α-2b. Other liver function indexes such as ALT, hepatitis B surface antigen content and hepatitis B DNA quantitative determination (take the qualitative result as a decision statistical value) were observed in the two groups, and adverse drug reactions were monitored. After 48 weeks of treatment, the combination group was switched to single NAs treatment regardless of outcome, and follow-up was conducted for 1 year. Results: A total of 86 patients were included, 31 patients in the control group and 55 patients in the combination group. There was no statistically significant difference in baseline levels between the two groups. After 24 weeks of treatment, the content of hepatitis B virus surface antigen and the normal rate of ALT in combination group were better than those in control group (P<0.05). After 48 weeks of treatment, the negative rate of hepatitis B virus surface antigen, the normal ALT, and the negative rate of hepatitis B virus DNA in combination group were better than those in control group (P<0.05). After 1 year of follow-up, the content of hepatitis B virus surface antigen, normal rate of ALT, negative rate of hepatitis B virus surface antigen, negative rate of hepatitis B virus DNA in combination group were better than those in control group (P<0.05). Five patients in the combination group had adverse drug reactions during combination therapy and were given Peg IFN α-2b intermittenously. Eleven patients persisted in treatment due to minor adverse drug reactions. Conclusion: Although there is a certain proportion of controllable adverse drug reactions, combined Peg INF α-2b therapy can improve the clinical efficacy of chronic hepatitis B patients with abnormal ALT after treatment with NAs.
Objective: To explore the predictive value of serum eosinophil chemotactic factor (Eotaxin), neutrophil gelatinase-associated lipocalin (NGAL) and serum amyloid A (SAA) on adverse transfusion reactions in hepatitis B cirrhosis. Methods: A total of 80 hepatitis B cirrhosis patients who received blood transfusion treatment in our hospital from March 2021 to June 2023 were included. Of these, 39 patients who experienced adverse reactions were in the observation group, and 41 patients who did not experience adverse reactions were in the control group. Enzymelinked immunosorbent assay (ELISA) was used to detect serum levels of Eotaxin, NGAL, and SAA. Clinical data were collected, and multivariate logistic regression was applied to analyze factors influencing adverse transfusion reactions. Receiver Operating Characteristic (ROC) curve analysis was performed to assess the predictive value of serum Eotaxin, NGAL, and SAA in adverse transfusion reactions. Results: After blood transfusion, the serum levels of Eotaxin, NGAL and SAA in the observation group were higher than those in the control group (P<0.05). Clinical data comparison found that there were differences in the number of blood transfusions, time from onset to transfusion, history of previous blood transfusions, and history of allergies between the two groups (P<0.05), and the number of blood transfusions, time from onset to transfusion, previous transfusion history, allergy history, serum Eotaxin, NGAL and SAA levels were all factors that affected the occurrence of transfusion adverse reactions in hepatitis B cirrhosis (P<0.05). ROC curve analysis showed that the area under the curve (AUC) of serum Eotaxin, NGAL, SAA and their combination in predicting adverse transfusion reactions in hepatitis B cirrhosis was 0.891, 0.736, 0.877 and 0.969, respectively, the combined predictive value of these three factors was higher than that of single prediction (Z the combination-Eotaxin=2.264, Z the combination-NGAL=4.215, Z the combination-SAA=2.768, P<0.05). Conclusion: Serum Eotaxin, NGAL, and SAA levels are elevated in hepatitis B cirrhosis with adverse transfusion reactions, and the combination of these three factors has predictive value for adverse transfusion reactions.
XIE Jin-chi, MENG Jie, GOU Si-yuan, ZHANG Peng, et al
Objective: To explore the mechanism of Xuefuzhuyu Decoction in treating liver fibrosis through network pharmacology and animal experiments. Methods: The main components and potential targets of Xuefuzhuyu Decoction were obtained using TCMSP, ETCM, HERB, SwissTarget Prediction, and other databases. Liver fibrosis disease targets were retrieved from Genecard, OMIM, DRUGBANK, and TTD, and common targets between Xuefuzhuyu Decoction and liver fibrosis were identified. A protein interaction network was constructed to identify core targets. KEGG and GO enrichment analyses were conducted using Metascape to identify potential pathways. A mouse model of liver fibrosis was induced using CCl4, and liver tissue pathology, collagen type I and III expression, hepatic hydroxyproline (HYP) content, αSMA immunohistochemistry, and liver function changes were observed after Xuefuzhuyu Decoction intervention. RTqPCR was used to verify the changes in mRNA levels of key targets. Results: Xuefuzhuyu Decoction has 292 intersecting targets with liver fibrosis diseases, with core targets including AKT1, HIF-1α, mTOR, etc. KEGG enrichment analysis mainly involves cancer pathways, PI3K-AKT signaling pathway, HIF-1α signaling pathway, MAPK signaling pathway, etc. Animal experiments have shown that Xuefuzhuyu Decoction can improve liver fibrosis in mice, reduce the content of HYP and the expression of type Ⅰ and Ⅲ collagen in liver tissue, decrease the expression of α-SMA, alleviate liver inflammation, and downregulate the mRNA levels of PI3K, AKT1, mTOR, and HIF-1α in the liver. Conclusion: Xuefuzhuyu Decoction can improve liver fibrosis in mice, and its mechanism may be related to the regulation of the PI3K-AKT1-mTOR/HIF-1α pathway.
Objective: To investigate the effect and mechanism of Pachymaran on nonalcoholic fatty liver disease (NAFLD) induced by high-fat diet. Methods: Thirty C57BL/6 mice were divided into normal diet, NAFLD, high-,medium- and low-dose pachymaran groups, with 6 mice in each group. Except the normal diet group, the other groups were fed high-fat diet to induce NAFLD. Pachymaran groups irrigation to 1 time a day, eight weeks in a row. Then gather the liver, serum level of each index, and HE staining to observe the liver pathology. Western blotting test amp activated protein kinase (AMPK) expression, RT-qPCR detection of triglyceride metabolism enzyme mRNA level. Results: The body weight and body fat of the high Pachymaran dose group decreased significantly after treatment and serum lipid related indicators decreased significantly (P<0.05). Tissue staining showed hepatocyte hypertrophy accompanied by cystic steatosis and increased hepatocyte lipid droplets in NAFLD group, and the above conditions were significantly reduced after treatment (P<0.05). Western blotting revealed that AMPK phosphorylation level significantly increased after the treatment, and RT-qPCR results triglyceride synthetase significantly reduced, degrading enzymes rise significantly (P<0.05). Conclusion: Pachymaran inhibits fat accumulation, hepatocyte degeneration, and damage in NAFLD mice. Its mechanism may involve the regulation of the AMPK pathway and improvement in triglyceride metabolism, thus modulating the pathological progression of NAFLD.
WANG Fu-bing, ZHAO Pei-pei, FAN Hui, GU Xin-hong, et al
Objective: The study aimed to assess the therapeutic effects of Daning tablets and probiotics on non-alcoholic fatty liver disease (NAFLD) in rats, as well as their influence on the TLR4/NF-κBP65/MyD88/P38 signaling pathway in the liver. Methods: Forty male Sprague-Dawley rats were randomly assigned to a control group (n=10) fed a standard diet, and a NAFLD model group (n=30) fed a high-fat diet for 8 weeks to induce NAFLD. Following successful modeling, the NAFLD model group was subdivided into a model group (n=10), treatment 1 group (n=10, treated with Daning tablets), and treatment 2 group (n=10, treated with probiotics).Following an 8-week treatment period, the rats were euthanized and samples of peripheral blood and liver tissue were obtained. Subsequently, levels of endotoxin lipopolysaccharide (LPS), tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), total cholesterol (TC), triglycerides (TG), alanine aminotransferase (ALT), aspartate transaminase (AST), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), superoxide dismutase (SOD), and malondialdehyde (MDA) were quantified. HE staining was utilized for morphological analysis of liver tissues in each experimental group. Immunohistochemistry and Western blotting techniques were employed to assess the expression levels of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), nuclear factor κB P65 (NF-κB P65), P38 mitogen-activated protein kinase (P38 MAPK), phosphorylated P38 mitogen-activated protein kinase (P-P38), c-Jun N-terminal kinase (JNK), and caspase-1 in the liver tissues. Results: The TC, TG, ALT, AST,LDL-C, LPS, and MDA in the NAFLD model group were found to be significantly elevated compared to those in the control group. Conversely, HDL-C and SOD levels were significantly lower in the NAFLD model group. Additionally, the expression levels of TLR4, MyD88, NF-κB P65, P38 MAPK, P-P38, c-JUN, and Caspase-1 proteins in liver tissues were higher in the NAFLD model group compared to the control group. Treatment with groups 1 and 2 resulted in significantly decreased levels of TC, TG, ALT, AST, LDL-C, LPS, MDA, as well as reduced liver TC, TG, and free fatty acid (FFA) content compared to the model group. Conversely, SOD and HDL-C levels were significantly increased in the treatment groups. The levels of ALT, AST, LPS, and MDA in Treatment Group 2 were significantly lower than those in Treatment Group 1, while SOD and HDL-C levels were significantly increased. Liver TLR-4, MyD88, NF-kBP65, P38MAPK, P-P38, and Caspase 1 protein expression in Treatment Groups 1 and 2 were significantly lower than in the model group, with Treatment Group 2 showing lower levels compared to Treatment Group 1. Conclusion: The concurrent administration of Daning tablets and Bifidobacterium has been shown to effectively ameliorate hepatic function impairment in NAFLD rats by attenuating oxidative stress, reducing inflammatory cytokine levels, and potentially inhibiting TR4/NF-kBP65/My D88 activation, thereby exerting protective effects on the liver in NAFLD.
XIN Ying-ying, MEI Dong-xue, HAN Chao, ZHANG Guo-shun, et al
Objective: To investigate the effects of LINC00662 on the proliferation, migration, and invasion of hepatocellular carcinoma (HCC) cells by regulating the miR-144-3p/SRSF9 axis. Methods: HepG2 cells were divided into various groups: NC (non-transfected), si-NC, si-LINC00662, miR-NC, miR-144-3p mimic, si-LINC00662+inhibitor NC, si-LINC00662+miR-144-3p inhibitor, miR-144-3p mimics+pc-DNA, and miR-144-3p mimics+SRSF9. qRT-PCR was used to measure the expression levels of LINC00662, miR-144-3p, and SRSF9 mRNA in HCC tissue, different cells, and different HepG2 cell groups. EDU, scratch, and Transwell assays were used to assess HepG2 cell proliferation, migration, and invasion, respectively. A dual luciferase assay was used to verify the interaction between miR-144-3p, LINC00662, and SRSF9. Results: LINC00662 and SRSF9 mRNA expression was higher in HCC tissue compared to adjacent tissue, while miR-144-3p expression was lower (P<0.05). In HepG2 cells, LINC00662 and SRSF9 mRNA were elevated (P<0.05), and miR-144-3p was decreased (P<0.05). Inhibition of LINC00662 expression or overexpression of miR-144-3p could reduce the EDU positive cell rate, scratch healing rate, and invasive cell count in HepG2 cells (P<0.05). Inhibiting the expression of miR-144-3p and LINC00662 could increase the EDU positive rate, scratch healing rate and the number of invasive cells in HepG2 cells (P<0.05), and upregulation of SRSF9 and miR-144-3p expression could increase the EDU positive rate, scratch healing rate and the number of invasive cells in HepG2 cells (P<0.05). Dual luciferase reporter gene experiment showed a targeted regulatory relationship between miR-144-3p, LINC00662, and SRSF9 (P<0.05). Conclusion: LINC00662 is upregulated in HCC tissues and cells, and inhibition of LINC00662 expression can inhibit HCC cell proliferation, migration, and invasion by regulating the miR-144-3p/SRSF9 axis.
Objective: To investigate the application value of multimodal Magnetic Resonance Imaging(MRI) in the volume structure and functional connectivity changes of brain subregions in patients with mild and microhepatic encephalopathy. Methods: A total of 145 patients with cirrhosis admitted to our hospital from January 2022 to June 2024 were divided into MHE (n=74) and non-MHE (n=71) groups. After 1:1 propensity score matching, 50 patients from each group were compared for baseline characteristics and biochemical indices. All patients underwent head DWI, DTI, and rs-fMRI scans. We compared the volume structure of brain subregions, functional connectivity in different brain regions, and cognitive function scores between the groups. Multivariate logistic regression was used to analyze the correlation between brain subregion volume structure, functional connectivity, and MHE. Pearson correlation analysis was used to examine the relationships between changes in functional connectivity, cognitive dysfunction, and brain subregion volume structure. Results: When patients were matched based on propensity score matching, there was no statistically significant difference in baseline data between the two groups after matching (P>0.05).There were significant differences in biochemical indices (Alb, TBil, AMM, ALT) and PHES scores between the two groups (P<0.05).There were significant differences in ADC values between the MHE group and the non-MHE group in the white matter regions of the frontal and occipital lobes, the knee and pressure parts of the corpus callosum, the forelimb and hindlimb of the internal capsule, and the head of the caudate nucleus, and this result was statistically significant (P<0.05). The FA value in MHE group was significantly lower than that in non-MHE group (P<0.05).Compared with the non-MHE group, the functional connectivity of the right medial frontal gyrus, the left medial frontal gyrus and the right inferior temporal gyrus in the MHE group was significantly improved, while the functional connectivity of the right posterior central gyrus, the right superior marginal gyrus and the right posterior cingulate gyrus was significantly decreased.The multivariate logistic regression analysis revealed that the ADC values of the occipital and frontal white matter, the head of the caudate nucleus, and the knee and pressor part of the corpus callosum, as well as functional connection changes in the middle frontal gyrus, right posterior central gyrus, and right inferior temporal gyrus were all identified as significant risk factors for MHE onset (P<0.05). Additionally, the FA value in the knee of corpus callosum was found to be a protective factor for MHE (P<0.05).Patients in the MHE group demonstrated higher scores on the NCT-A test compared to those in the non-MHE group, while exhibiting lower scores on the DST and MoCA assessments.The scores of NCT-A were positively correlated with the FC changes in the right medial frontal gyrus (P<0.05). MoCA score was negatively correlated with FC changes in the right medial frontal gyrus, and positively correlated with the right superior marginal gyrus and right inferior temporal gyrus (P<0.05).ADC values in white matter of frontal and occipital brain, knee of corpus callosum and head of caudate nucleus were positively correlated with NCT-A (P<0.05). The white matter of frontal and occipital parts, knee of corpus callosum and head of caudate nucleus were negatively correlated with DST score (P<0.05). There was a negative correlation between FA value and NCT-A score in the knee of corpus callosum, and a positive correlation with DST score (P<0.05). Conclusion: Combining DWI, DTI, and rsfMRI techniques, we can reveal underlying abnormal changes in the structure and functional connectivity of brain subregions in MHE patients. These techniques provide a powerful tool for clinical MHE diagnosis and show great application potential.
LUO Tian-ge, CHANG Zhan-jie, YAN Rui-juan, LIU Yong-gang, et al
Metabolic dysfunction associated fatty liver disease (MAFLD) is a kind of diseases associated with metabolic dysfunction. The occurrence of MAFLD tends to be younger and the burden of treatment continues to increase with the changes of lifestyle. Traditional Chinese medicine has good therapeutic effects on MAFLD. Xuanfu is the running channel of Qi-blood-body fluid. Xuanfu close and Qi-fluid disorder will lead to dysfunction of liver and spleen, producing pathological products, including stagnation, dampness, turbidity, phlegm and biood stasis. That is the demonstration of the disease progression from mild case to sthenia syndrome. Therefore, the core pathogenesis of MAFLD lies in Qi-fluid dysfunction in Xuanfu, and the key to treatment is "dispersing herbs eliminating sthenia." This paper will discuss the application value of this method in combination with Xuanfu theory in MAFLD, distinguishing and treating MAFLD from "six light to open Xuanfu". The authors desire to shed light on the treatment of MAFLD, the development of Xuanfu theory and the "dispersing herbs eliminating sthenia" theory.
LIU Xiao-yan, CHEN Hui, LEI Di-hui, RAN Si-miao, HU Shi-wei
Insomnia is a common clinical condition, often referred to in Traditional Chinese Medicine (TCM) as "unable to close the eyes", "unable to sleep", or "unable to lie down". According to the TCM theory of "the liver stores blood, and blood houses the soul" and "the soul moves with the spirit", this paper explores the relationship between insomnia, the movement of the soul, and the liver's role in storing blood. The main cause of liver-related insomnia, characterized by "the liver not housing the soul", is primarily due to the stagnation of liver Qi and the deficiency of liver blood. Treatment should focus on regulating liver Qi to ease stagnation, nourishing blood, and calming the soul, using comprehensive TCM approaches to ensure smooth liver Qi and sufficient liver blood, ultimately restoring the liver's ability to house the soul.
Started in 1991, Monthly Superintendent: Department of Education of Hubei Province Sponsored by: Chinese Association of Integrative Medicine
Hubei University of Chinese Medicine Published: Editorial office of Chinese Journal of Integrated Traditional and Western Medicine on Liver Diseases Editor-in-Chief: SHENG Guo-guang ISSN 1005-0264 CN 42-1322/R