1.Hemodynamic characteristics of proper hepatic artery and portal vein in patients after splenectomy and devascularization
Xiaofei ZHAO ; Daobing ZENG ; Guangming LI ; Qingliang GUO ; Liang DI ; Jing DING
Journal of Clinical Hepatology 2023;39(1):104-109
		                        		
		                        			
		                        			 Objective To investigate the characteristics of hemodynamics of proper hepatic artery and portal vein after splenectomy and devascularization. Methods The clinical data of 103 patients with portal hypertension who underwent splenectomy and devascularization in the Capital Medical University-Affiliated You'an Hospital from April 2014 to February 2019 were retrospectively analyzed. Their hemodynamics of the proper hepatic artery and portal vein were recorded before and 1 week-, and 1-, 3-, 6-, 12-, and 24-months after surgery and then statistically analyzed. Continuous data with normal distribution were compared using paired-samples t test. Results Compared with the before surgery data, the portal vein diameter, portal vein flow, maximum velocity, and average velocity of the portal vein were all significantly decreased 1-week-, 1-, 3-, 6-, 12-, and 24-months after splenectomy and devascularization (all P < 0.05). The blood flow and velocity of the proper hepatic artery was significantly increased 1 week and 1 month after surgery (all P < 0.05); however, there was no statistically significant difference at 3-, 6-, 12-, and 24-months after surgery. Conclusion The diameter, flow, and flow velocity of the portal vein after splenectomy and devascularization were significantly lower than those before surgery, whereas the proper hepatic artery flow and flow velocity were increased within 1 month after surgery and then returned back to the pre-surgery levels 3 months after surgery. 
		                        		
		                        		
		                        		
		                        	
2.Association between the rs1800591 variation of the microsomal triglyceride transfer protein gene and the risk of nonalcoholic fatty liver disease in the elderly population
Jinhan ZHAO ; Jing ZHANG ; Yang ZHANG ; Xiaoyi XU ; Yusong GOU ; Hangfei XU ; Yan WAN ; Jian WU
Journal of Clinical Hepatology 2023;39(3):552-561
		                        		
		                        			
		                        			 Objective To investigate the association between the polymorphism of the microsomal triglyceride transport protein (MTTP) gene at rs1800591 locus and the risk of nonalcoholic fatty liver disease (NAFLD) in the elderly population. Methods The clinical cohort of this study was established in Menkuang Hospital, Beijing Jingmei Group General Hospital. A total of 1098 healthy elderly volunteers were recruited for physical examination in communities in Mentougou District of Beijing, China, from January 11, 2020 to September 30, 2021, among whom there were 614 patients with NAFLD and 484 individuals without NAFLD. Gene microarray was used to determine the genotypes of MTTP rs1800591; demographic data were collected, and blood biochemical parameters were measured. The independent samples t -test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data between groups. The chi-square test was used to investigate whether the distribution of genotype frequency was in accordance with Hardy-Weinberg equilibrium. The unconditional logistic regression model was used to calculate odds ratio ( OR ) and its 95% confidence interval ( CI ) to investigate the association of gene polymorphism with the risk of NAFLD and other comorbidities. Results There were significant differences in sex and age between the two groups ( P < 0.05). Compared with the non-NAFLD group, the NAFLD group had significantly higher levels of body mass index (BMI), waist-hip ratio, triglyceride, alanine aminotransferase, aspartate aminotransferase, controlled attenuation parameter (CAP), and liver stiffness measurement and a significantly lower level of high-density lipoprotein (HDL) (all P < 0.05). Compared with the non-NAFLD group, the NAFLD group had a significantly higher proportion of patients with hypertension, diabetes, obesity, and metabolic syndrome (all P < 0.05). The distribution of genotype frequency at MTTP rs1800591 locus was in accordance with Hardy-Weinberg equilibrium in the control group ( χ 2 =1.097, P =0.29). There were a significant differences in the genotype and the distribution of alleles at MTTP rs1800591 locus between the patients with NAFLD and the control group (all P < 0.001). In the total population, there was a significantly lower carrying rate of T allele (GT+TT, n =351) in male individuals, and the individuals carrying T allele had significantly higher BMI and CAP than those carrying GG allele ( n =747) ( P < 0.001). Compared with the individuals who did not carry T allele, the individuals carrying T allele (GT+TT, n =232) had a significantly higher proportion of patients with obesity and a significantly lower NFS score ( P < 0.05). As for the individuals with NAFLD, the individuals carrying T allele had a significantly lower proportion of male individuals, a significantly lower waist-hip ratio, and a significantly higher level of HDL compared with those who did not carry T allele (GG, n =382), and the GT+TT group had a significantly lower NFS score than the GG group (all P < 0.05). The non-conditional logistic regression analysis showed that after adjustment for the confounding factors of sex, age, and BMI, the GT+TT genotype at MTTP rs1800591 locus significantly increased the risk of NAFLD ( OR =1.643, 95% CI : 1.226-2.203, P =0.001), and carrying T allele also increased the risk of obesity in the total population ( OR =1.371, 95% CI : 1.051-1.788, P =0.02). Conclusion MTTP rs1800591 polymorphism is associated with the development of NAFLD in the elderly population, and carrying T allele may promote hepatic steatosis and increase the risk of obesity in NAFLD, while it may inhibit the progression of liver fibrosis. 
		                        		
		                        		
		                        		
		                        	
3.Value of combined baseline serum HBV markers in predicting HBeAg seroconversion in chronic hepatitis B patients treated by nucleos(t)ide analogues
Yang WANG ; Hao LIAO ; Zhongping DENG ; Jing ZHAO ; Dandan BIAN ; Yan REN ; Yingying JIANG ; Shuang LIU ; Yu CHEN ; Fengmin LU ; Zhongping DUAN ; Sujun ZHENG
Journal of Clinical Hepatology 2023;39(5):1070-1075
		                        		
		                        			
		                        			 Objective To investigate the ability of combined baseline serum markers, i.e., HBV DNA, HBV RNA, HBsAg, and HBcrAg, to predict HBeAg seroconversion in patients with HBeAg-positive chronic hepatitis B (CHB) treated by nucleos(t)ide analogues. Methods A retrospective analysis was performed for 83 HBeAg-positive patients selected as subjects from the prospective CHB follow-up cohort established by Difficult & Complicated Liver Diseases and Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, from June 2007 to July 2008, and the baseline serum levels of HBV DNA, HBV RNA, HBsAg, and HBcrAg were analyzed. The t -test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. The Spearman method was used for correlation analysis. A Cox regression model was established to calculate HBeAg seroconversion prediction score, and the time-dependent receiver operating characteristic curve was used to evaluate the ability of combined markers in predicting HBeAg seroconversion. The Kaplan-Meier method was used to calculate cumulative seroconversion rate in each group, and the Log-rank test was used for comparison between groups. Results For the 83 HBeAg-positive patients, the median follow-up time was 108 months, and 44.58%(37/83) of these patients achieved HBeAg seroconversion. Compared with the non-seroconversion group, the HBeAg seroconversion group had significantly lower baseline serum levels of HBV DNA [6.23(1.99-9.28) log 10 IU/mL vs 7.69(2.05-8.96) log 10 IU/mL, Z =-2.345, P =0.019] and HBV RNA [4.81(1.40-7.53) log 10 copies/mL vs 6.22(2.00-8.49) log 10 copies/mL, Z =-1.702, P =0.010], and there were no significant differences in the levels of HBsAg and HBcrAg between the two groups ( P > 0.05). The Cox regression equation constructed based on the above serum markers showed a median score of 0.95(range 0.37-3.45) for predicting HBeAg seroconversion. In the total population, the combined score was negatively correlated with HBsAg, HBV DNA, HBV RNA, and HBcrAg ( r =-0.697, -0.787, -0.990, and -0.819, all P < 0.001). Based on the median prediction score, the patients were divided into high HBeAg seroconversion group and low HBeAg seroconversion group; as for the prediction of HBeAg seroconversion rate at 36, 60, and 84 months, the high HBeAg seroconversion group had a seroconversion rate of 43.90%, 51.20%, and 63.10%, respectively, while the low HBeAg seroconversion group had a seroconversion rate of 9.60%, 17.00%, and 19.8%, respectively, and there was a significant difference between the two groups ( χ 2 =11.6, P < 0.001). Conclusion The combined prediction score based on baseline serum HBV markers can predict HBeAg seroconversion in CHB patients treated by nucleos(t)ide analogues. 
		                        		
		                        		
		                        		
		                        	
4.Recompensation of complications in patients with hepatitis B virus-related decompensated cirrhosis treated with entecavir antiviral therapy.
Ting ZHANG ; You DENG ; Hai Yan KANG ; Hui Ling XIANG ; Yue Min NAN ; Jin Hua HU ; Qing Hua MENG ; Ji Lian FANG ; Jie XU ; Xiao Ming WANG ; Hong ZHAO ; Calvin Q PAN ; Ji Dong JIA ; Xiao Yuan XU ; Wen XIE
Chinese Journal of Hepatology 2023;31(7):692-697
		                        		
		                        			
		                        			Objective: To analyze the occurrence of recompensation conditions in patients with chronic hepatitis B virus-related decompensated cirrhosis after entecavir antiviral therapy. Methods: Patients with hepatitis B virus-related decompensated cirrhosis with ascites as the initial manifestation were prospectively enrolled. Patients who received entecavir treatment for 120 weeks and were followed up every 24 weeks (including clinical endpoint events, hematological and imaging indicators, and others) were calculated for recompensation rates according to the Baveno VII criteria. Measurement data were compared using the Student t-test or Mann-Whitney U test between groups. Categorical data were compared by the χ (2) test or Fisher's exact probability method between groups. Results: 283 of the 320 enrolled cases completed the 120-week follow-up, and 92.2% (261/283) achieved a virological response (HBV DNA 20 IU/ml). Child-Pugh and MELD scores were significantly improved after treatment (8.33 ± 1.90 vs. 5.77 ± 1.37, t = 12.70, P < 0.001; 13.37 ± 4.44 vs. 10.45 ± 4.58, t = 5.963, P < 0.001). During the 120-week follow-up period, 14 cases died, two received liver transplants, 19 developed hepatocellular cancer, 11 developed gastroesophageal variceal bleeding, and four developed hepatic encephalopathy. 60.4% (171/283) (no decompensation events occurred for 12 months) and 56.2% (159/283) (no decompensation events occurred for 12 months and improved liver function) of the patients had achieved clinical recompensation within 120 weeks. Patients with baseline MELD scores > 15 after active antiviral therapy achieved higher recompensation than patients with baseline MELD scores ≤15 [50/74 (67.6%) vs. 109/209 (52.2%), χ (2) = 5.275, P = 0.029]. Conclusion: Antiviral therapy can significantly improve the prognosis of patients with hepatitis B virus-related decompensated cirrhosis. The majority of patients (56.2%) had achieved recompensation. Patients with severe disease did not have a lower probability of recompensation at baseline than other patients.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Hepatitis B virus/genetics*
		                        			;
		                        		
		                        			Hepatitis B, Chronic/drug therapy*
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		                        			Antiviral Agents/adverse effects*
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		                        			Esophageal and Gastric Varices/complications*
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		                        			Liver Cirrhosis/complications*
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		                        			Treatment Outcome
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		                        			Gastrointestinal Hemorrhage/complications*
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		                        			Hepatitis B/drug therapy*
		                        			
		                        		
		                        	
5.Probing bundle-wise abnormalities in patients infected with human immunodeficiency virus using fixel-based analysis: new insights into neurocognitive impairments.
Jing ZHAO ; Bin JING ; Jiaojiao LIU ; Feng CHEN ; Ye WU ; Hongjun LI
Chinese Medical Journal 2023;136(18):2178-2186
		                        		
		                        			BACKGROUND:
		                        			Changes in white matter (WM) underlie the neurocognitive damages induced by a human immunodeficiency virus (HIV) infection. This study aimed to examine using a bundle-associated fixel-based analysis (FBA) pipeline for investigating the microstructural and macrostructural alterations in the WM of the brain of HIV patients.
		                        		
		                        			METHODS:
		                        			This study collected 93 HIV infected patients and 45 age/education/handedness matched healthy controls (HCs) at the Beijing Youan Hospital between January 1, 2016 and December 30, 2016.All HIV patients underwent neurocognitive evaluation and laboratory testing followed by magnetic resonance imaging (MRI) scanning. In order to detect the bundle-wise WM abnormalities accurately, a specific WM bundle template with 56 tracts of interest was firstly generated by an automated fiber clustering method using a subset of subjects. Fixel-based analysis was used to investigate bundle-wise differences between HIV patients and HCs in three perspectives: fiber density (FD), fiber cross-section (FC), and fiber density and cross-section (FDC). The between-group differences were detected by a two-sample t -test with the false discovery rate (FDR) correction ( P <0.05). Furthermore, the covarying relationship in FD, FC and FDC between any pair of bundles was also accessed by the constructed covariance networks, which was subsequently compared between HIV and HCs via permutation t -tests. The correlations between abnormal WM metrics and the cognitive functions of HIV patients were explored via partial correlation analysis after controlling age and gender.
		                        		
		                        			RESULTS:
		                        			Among FD, FC and FDC, FD was the only metric that showed significant bundle-wise alterations in HIV patients compared to HCs. Increased FD values were observed in the bilateral fronto pontine tract, corona radiata frontal, left arcuate fasciculus, left corona radiata parietal, left superior longitudinal fasciculus III, and right superficial frontal parietal (SFP) (all FDR P <0.05). In bundle-wise covariance network, HIV patients displayed decreased FD and increased FC covarying patterns in comparison to HC ( P <0.05) , especially between associated pathways. Finally, the FCs of several tracts exhibited a significant correlation with language and attention-related functions.
		                        		
		                        			CONCLUSIONS
		                        			Our study demonstrated the utility of FBA on detecting the WM alterations related to HIV infection. The bundle-wise FBA method provides a new perspective for investigating HIV-induced microstructural and macrostructural WM-related changes, which may help to understand cognitive dysfunction in HIV patients thoroughly.
		                        		
		                        		
		                        		
		                        			Humans
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		                        			HIV
		                        			;
		                        		
		                        			HIV Infections
		                        			;
		                        		
		                        			Cognition
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		                        			Brain
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		                        			White Matter
		                        			
		                        		
		                        	
6.Chinese expert consensus on the overall management of liver function in conversion therapy for liver cancer (2022 edition).
Qinghua MENG ; Zhengqiang YANG ; Zhenyu ZHU ; Juan LI ; Xinyu BI ; Xiao CHEN ; Chunyi HAO ; Zhen HUANG ; Fei LI ; Xiao LI ; Guangming LI ; Yinmo YANG ; Yefan ZHANG ; Haitao ZHAO ; Hong ZHAO ; Xu ZHU ; Jiye ZHU ; Jianqiang CAI
Chinese Medical Journal 2023;136(24):2909-2911
7.Influence of intrahepatic cholestasis of pregnancy on adverse pregnancy outcomes of HBV-infected pregnant women
Xiali XIONG ; Yunxia ZHU ; Hong WEI ; Zhiqiang ZHAO ; Jun MENG ; Huaibin ZOU ; Zhongping DUAN
Journal of Clinical Hepatology 2022;38(8):1763-1767
		                        		
		                        			
		                        			 Objective To investigate the influence of intrahepatic cholestasis of pregnancy (ICP) on adverse pregnancy outcomes of hepatitis B virus (HBV)-infected pregnant women. Methods A retrospective analysis was performed for 232 pregnant women with chronic HBV infection who were admitted to Beijing YouAn Hospital, Capital Medical University, from March 2018 to March 2021. According to the presence or absence of ICP, the patients were divided into HBV infection group with 100 patients and HBV+ICP group with 132 patients; according to the severity of ICP, the patients in the HBV+ICP group were further divided into HBV+mild ICP group with 86 patients and HBV+severe ICP group with 46 patients. The above groups were compared in terms of the incidence rates of maternal complications during pregnancy, such as premature delivery, premature rupture of membranes, gestational diabetes mellitus, hypertensive disorder complicating pregnancy, and postpartum hemorrhage (PPH), as well as the adverse outcomes of fetus/neonate, such as intrauterine fetal death, neonatal asphyxia, amniotic fluid pollution degree Ⅲ(AFⅢ), neonatal respiratory distress syndrome, small-for-gestational-age (SGA), admission to the neonatal intensive care unit, pneumonia, and mother-to-child transmission (MTCT) of HBV. A one-way analysis of variance was used for comparison between multiple groups; the chi-square test, the chi-square test with continuity correction or the Fisher's exact test was used for comparison of categorical data between multiple groups. Results Compared with the HBV infection group in terms of maternal complications in late pregnancy, the HBV+ICP group had significantly higher incidence rates of premature delivery and PPH ( χ 2 =4.169 and 5.448, P =0.041 and 0.020), and in terms of the adverse outcomes of neonates, the HBV+ICP group had significantly higher incidence rates of neonatal asphyxia, AFⅢ, and SGA than the HBV infection group ( χ 2 =5.448, 16.567, and 11.053, P =0.020, P < 0.001, and P =0.002). In terms of the adverse outcomes of neonates, the HBV+severe ICP group had significantly higher incidence rates of AFⅢ and SGA than the HBV+mild ICP group ( χ 2 =4.200 and 4.511, P =0.040 and 0.034). Conclusion Compared with the pregnant women with HBV infection alone, the pregnant women with HBV infection and ICP have significantly higher incidence rates of adverse pregnancy outcomes in mothers and neonates, and the incidence rate of adverse outcomes in neonates increases with the increase in the severity of ICP. However, ICP has no influence on HBV MTCT. 
		                        		
		                        		
		                        		
		                        	
8.Features of anemia in patients with alcoholic liver cirrhosis
Xu YAN ; Wenjing WANG ; Dantong ZHAO
Journal of Clinical Hepatology 2022;38(8):1806-1812
		                        		
		                        			
		                        			 Objective To investigate the laboratory and clinical features of anemia in patients with alcoholic liver cirrhosis. Methods A retrospective analysis was performed for the patients who were hospitalized in Beijing YouAn Hospital, Capital Medical University, from December 2020 to May 2021 and were found to have anemia based on reticulocyte hemoglobin (Hb) content (Ret-He) and whole blood cell analysis, and 106 patients with the discharge diagnosis of alcoholic liver cirrhosis who had no history of upper gastrointestinal bleeding or blood transfusion were screened out as subjects. Clinical features and related influencing factors were retrospectively analyzed based on the severity of anemia, the cytomorphological classification of anemia, and Ret-He. The independent samples t -test was used for comparison of normally distributed continuous data between two groups; a one-way analysis of variance was used for comparison between multiple groups, and the SNK- q test and the least significant difference t -test were used for further comparison between two groups. The Mann-Whitney U test was used for comparison of continuous data with skewed distribution between two groups, and the Kruskal-Wallis H test was used for comparison between multiple groups. The chi-square test was used for comparison of categorical data between groups. A Spearman correlation analysis was performed to investigate the correlation of different classification criteria for anemia with laboratory markers and clinical features. Results Among the 106 patients, there were 103 male patients (97.2%), with a mean age of 55.07±10.18 years and a mean Hb level of 87.16±18.55 g/L; there were 49 patients (46.2%) with mild anemia, 49 (46.2%) with moderate anemia, and 8(7.5%) with severe anemia; mean Ret-He was 33.65(13.3-46.4) pg, and there were 33 patients (31.1%) with ≤29 pg and 73 patients (68.9%) with Ret-He > 29 pg; among these patients, 46(43.4%) had macrocytic anemia, 34(32.1%) had normocytic anemia, 2(1.9%) had simple microcytic anemia, and 24 (22.6%) had microcytic hypochromic anemia; among these patients, 87(82.1%) had ascites and/or intra-abdominal infection, 82(77.4%) had splenomegaly and/or hypersplenism, 65(61.3%) had esophageal and gastric varices, and 31(29.2%) had hepatic encephalopathy. Compared with the control group (moderate/severe anemia), the mild anemia group had significantly higher Ret-He, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular-hemoglobin concentration (MCHC), serum iron (SI), and transferrin saturation (TS) (all P < 0.05), a significantly higher proportion of patients with Ret-He > 29 pg (83.7% vs 56.1%, P =0.002) or normocytic anemia (44.9% vs 21.1%, P =0.009), a significantly lower unsaturated iron-binding capacity (UIBC) ( P < 0.05), and a significantly lower proportion of patients with microcytic hypochromic anemia (6.1% vs 36.8%, P < 0.05). Compared with the microcytic anemia group, the macrocytic anemia group had significantly higher alanine aminotransferase (ALT), Hb, and proportion of patients with ascites and/or intra-abdominal infection (91.3% vs 65.4%, P c < 0.05) and a significantly lower proportion of patients with severe anemia (2.2% vs 19.2 %, P c < 0.05) or esophageal and gastric varices (52.2% vs 84.6%, P c < 0.05); the macrocytic anemia group had significantly higher aspartate aminotransferase (AST) and AST/ALT ratio than the microcytic anemia group and the normocytic anemia group (all P c < 0.05); the microcytic anemia group had a significantly lower proportion of patients with mild anemia than the macrocytic anemia group and the normocytic anemia group, as well as a significantly higher proportion of patients with moderate anemia than the normocytic anemia group (all P c < 0.05); compared with the other two groups, the macrocytic anemia group had significantly higher Ret-He, MCV, MCH, MCHC, SI, and TS (all P c < 0.05) and significantly lower total iron-binding capacity (TIBC) and UIBC (all P c < 0.05). Compared with the Ret-He > 29 pg group, the Ret-He ≤29 pg group had significantly lower Hb, MCV, MCH, MCHC, SI, TS, and proportion of patients with mild anemia or ascites and/or intra-abdominal infection (all P < 0.05), a significantly higher UIBC ( P < 0.05), and a significantly higher proportion of patients with microcytic hypochromic anemia or esophageal and gastric varices ( P < 0.05). Hb, Ret-He, MCV, MCH, MCHC, UIBC, SI, and TS were correlated with the severity of anemia, the cytomorphological classification of anemia, and iron deficiency (all P < 0.05), and esophageal and gastric varices and ascites and/or abdominal infection were correlated with the cytomorphological classification of anemia and iron deficiency (all P < 0.05). Conclusion The degree of anemia is mostly mild and moderate in the decompensated stage of alcoholic liver cirrhosis, and macrocytic anemia and normocytic anemia are more common. The incidence rate of iron deficiency increases with the severity of anemia, and esophageal and gastric varices and ascites and/or intra-abdominal infection are correlated with the cytomorphological classification of anemia and iron deficiency; therefore, it is necessary to enhance the monitoring of iron deficiency anemia in such patients in clinical practice. 
		                        		
		                        		
		                        		
		                        	
10.Effect of exosomes from adult human liver-derived stem cells on concanavalin A-induced acute liver injury in mice
Luxiang HAN ; Huixin TANG ; Zhenfeng ZHAO ; Shanshan LI ; Quanyi WANG ; Lingbin KONG ; Huiying BI ; Zhenfeng SHU ; Zhongping DUAN ; Yu CHEN ; Feng HONG
Journal of Clinical Hepatology 2022;38(5):1101-1105
		                        		
		                        			
		                        			 Objective To investigate the protective effect of adult human liver-derived stem cell exosomes (HLSC-exo) intravenously injected at different time points against acute liver injury induced by concanavalin A (ConA) in mice. Methods HLSC-exo was extracted by differential centrifugation. Western blot was used to measure the expression of the marker proteins CD9 and CD63, and nanoparticle tracking analysis was used to investigate particle size distribution. A total of 56 male C57BL/6 mice were randomly divided into blank control group, ConA model group, and HLSC-exo treatment group. The ConA model group and the HLSC-exo treatment group were further divided into 3-, 6-, and 12-hour subgroups according to the interval between phosphate buffer or HLSC-exo injection and ConA injection. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-α (TNF-α), and interleukin-10 (IL-10) were measured, and the gross morphology and histopathology of the liver were compared between groups. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t -test was used for further comparison between two groups. Results HLSC-exo was a membranous vesicle with a diameter of 90-110 nm, with a clear saucer-like structure under an electron microscope and marked expression of its specific marker proteins CD9 and CD63. In the blank control group, the levels of ALT and AST were 31.81±6.74 U/L and 69.75±8.30 U/L, respectively. Compared with the blank control group, the 3-, 6-, and 12-hour ConA model groups had significant increases in the levels of ALT and AST (all P < 0.001); compared with the 3-and 6-hour ConA model groups, the 3-and 6-hour HLSC-exo treatment groups had significant reductions in the levels of ALT and AST (225.58±115.59 U/L vs 1989.32±347.67 U/L, 1174.71±203.30 U/L vs 2208.33±349.96 U/L, 303.53±126.68 U/L vs 2534.27±644.72 U/L, 1340.70±262.56 U/L vs 2437.13±288.13 U/L, all P < 0.001); compared with the 6-hour HLSC-exo treatment group, the 3-hour HLSC-exo treatment group had significantly greater reductions ( P < 0.001). In the blank group, the levels of IL-10 and TNF-α were 313.51±10.97 pg/ml and 476.05±7.31 pg/ml, respectively. Compared with the blank control group, the 3-, 6-, and 12-hour ConA model groups had a significant reduction in the level of IL-10 (all P < 0.001); compared with the 3-and 6-hour ConA model groups, the 3-and 6-hour HLSC-exo treatment groups had a significant increase in the level of IL-10(331.61±10.46 pg/ml vs 266.20±8.15 pg/ml, 288.13±10.74 pg/ml vs 264.41±9.12 pg/ml, both P < 0.001); compared with the 6-hour HLSC-exo treatment group, the 3-hour HLSC-exo treatment group had a significantly greater increase ( P < 0.001). Compared with the blank control group, the 3-, 6-, and 12-hour ConA model groups had a significant increase in the level of TNF-α (all P < 0.001); compared with the 3-and 6-hour ConA model groups, the 3-and 6-hour HLSC-exo treatment groups had a significant reduction in the level of TNF-α (478.26±12.99 pg/ml vs 551.31±17.70 pg/ml, 515.58±7.18 pg/ml vs 556.21±11.15 pg/ml, both P < 0.001); compared with the 6-hour HLSC-exo treatment group, the 3-hour HLSC-exo treatment group had a significantly greater reduction ( P < 0.001). Compared with the 3-and 6-hour ConA model groups in terms of the gross morphology and histopathology of the liver, the 3-and 6-hour HLSC-exo treatment groups had a significant reduction in the degree of hepatocyte necrosis, and the 3-hour HLSC-exo treatment group had a basically complete lobular structure, with sporadic spotty necrosis; the 12-hour HLSC-exo treatment group had no significant improvement in hepatocyte necrosis compared with the 12-hour ConA model group. Conclusion Intravenous injection of adult HLSC-exo can alleviate acute liver injury induced by ConA in mice, and injection at 3 hours in advance has the most significant protective effect. Regulation of cytokines is one of the important mechanisms for HLSC-exo to alleviate liver injury. 
		                        		
		                        		
		                        		
		                        	
            
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