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    Chinese Hepatolgy    2023, 28 (2): 148-151.  
    Abstract835)      PDF (723KB)(893)      
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    Establishment and investigation of carbon tetrachloride-induced acute liver injury model in mice
    FU Shuang-nan, GAO Da, GUO Jia-jia, MIAO Ming-san, ZHU Ping-sheng, GONG Man
    Chinese Hepatolgy    2022, 27 (9): 1036-1040.  
    Abstract1284)      PDF (1030KB)(891)      
    Objective To investigate the stable animal model of carbon tetrachloride (CCl4)-induced acute liver injury in mice, which is convenient for the research and application of new clinical drugs. Methods The Kunming (KM) mice were randomLy divided into blank group, model group, and bifendate group (5.625 mg/kg), and the acute liver injury of mice was replicated by intraperitoneal injection of 0.1% CCl4 solution. The aminotransferase level, liver index, and pathological changes of liver tissue at 3h, 6h, 12h, and 24h after modeling were detected to study the stability of the model. Results After exposure to the model group, alanine aminotransferase (ALT) increased slightly at 3 h [(45.21 ± 13.17) IU/L, P<0.01], and increased significantly at 12 h [(112.30 ± 30.54) IU/L] and 24 h [(121.98 ± 21.66) IU/L] (both P<0.01); AST increased at 3 h [(162.51 ± 28.57) IU/L], 6 h [(192.07 ± 31.05) IU/L], 12 h [(250.75 ± 90.82) IU/L] and 24 h [(274.27 ± 44.02) IU/L] (all P<0.01), but increased significantly at 12 and 24 h; liver index slightly increased at 3 h [(6.72 ± 1.90) g/100 g] and 6h [(6.72 ± 1.90) g/100 g] (both P<0.01). At 12 h [(12.41 ± 1.18) g/100 g] and 24 h [(14.90 ± 2.56) g/100 g] (both P<0.01), the liver pathological changes showed obvious hepatocyte swelling and inflammatory cell infiltration, and the injury degree was more significant at 24 h. Conclusion When the mouse acute liver injury model was prepared by intraperitoneal injection of 0.1% CCl4 solution, the modeling time between 12 h and 24 h was more appropriate.
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    Chinese Hepatolgy    2022, 27 (12): 1340-1343.  
    Abstract762)      PDF (795KB)(864)      
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    Metabolic changes of macrophages in LPS-induced liver failure
    GUO Jin, SHI Chun-xia, DENG Wei, ZHANG Lu-yi, CHEN Qian, WANG Yao, GONG Zuo-jiong
    Chinese Hepatolgy    2022, 27 (9): 973-977.  
    Abstract175)      PDF (651KB)(745)      
    Objective During the process of acute liver failure (ALF), endotoxin activated macrophages to release cytokines and induced changes in cellular metabolism. The aim of this study was to investigate the change of the substrates and products of malate dehydrogenase, and to analyze the metabolic changes of mice ANA-1 macrophages in response to lipopolysaccharide (LPS). Methods A total of 16 subjects were enrolled, including 8 ALF cases and 8 were healthy controls. Liquid Chromatograph Mass Spectrometer (LC-MS) was used to analyze the level of the substrates and related metabolite (malate and oxaloacetate). The Mice ANA-1 macrophages cultured in vitro were divided into normal control group and LPS group [treated by LPS (5μg/ml)]. The levels of tumor necrosis factor-α (TNF-α), malate dehydrogenase 1 (MDH1), lactic acid, glucose, adenosine-5'-triphosphate (ATP) were tested. Western-blot was used to detect the intracellular MDH1 protein content. Results Compared with the normal group, the malate increased and oxaloacetate decreased in ALF group (P<0.05). In LPS-induced mice ANA-1 macrophages, the level of TNF-α in supernatant increased [(1722.501 ± 76.261) pg/mL vs (255.010 ± 16.139) pg/mL], P<0.05, which indicates that LPS stimulated macrophages release cytokines. Compared with the control group (15.710 ± 0.302) ng/mL, the level of MDH1(11.831 ± 0.335) ng/mL and protein content in the LPS group were reduced (P<0.05). In addition, the levels of lactate and glucose in ANA-1 cells treated by LPS increased [(0.281 ± 0.016) mmol/L vs (0.081±0.012) mmol/L, (0.081 ± 0.006) μmol/mL vs (0.033 ± 0.004) μmol/mL], and the ATP levels decreased [(61.766 ± 11.982) μmol/gprot VS (130.786 ± 25.386) μmol/gprot], P<0.05. Conclusion During the process of ALF, LPS suppressed the activity of MDH1 in macrophages, induced mitochondrial-related metabolism disorders, resulted in the increase of lactate and glucose, and decrease of ATP production.
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    Chinese Hepatolgy    2022, 27 (6): 622-624.  
    Abstract536)      PDF (592KB)(502)      
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    Chinese Hepatolgy    2022, 27 (10): 1143-1145.  
    Abstract333)      PDF (629KB)(491)      
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    Early efficacy of tenofovir amibufenamide (TMF) in the treatment of patients with chronic hepatitis B: a real-word multicenter clinical study
    LI Ya-ping, CUI Dan-dan, GOU Guo-e, LIN Yong-mei, ZU Hong-mei, XU Guang-hua, GAO Xiao-hong, DANG Shuang-suo
    Chinese Hepatolgy    2023, 28 (1): 100-104.  
    Abstract1277)      PDF (762KB)(489)      
    Objective To evaluate the efficacy and safety of tenofovir amibufenamide (TMF) in the treatment of patients with chronic hepatitis B (CHB). Methods In this multicenter, prospective, real-world cohort study, we recruited 91 patients with CHB who attended the outpatient clinic of the Department of Infection of the 4 sites from August 2021 to August 2022 and were treated with TMF antiviral therapy. We collected clinical data, and compared the changes of HBV DNA, alanine transaminase (ALT), hepatitis B virus e antigen (HBeAg) and hepatitis B virus surface antigen (HBsAg) conversion, renal function and lipid metabolism at 12W and 24W. Results A total of 91 CHB patients were enrolled at 24W, 28 patients in treatment-naïve and 63 patients in previously treated. Complete virological response was achieved in 17.4% and 47.9% of treatment-naïve patients at 12W and 24W. The proportion of treated patients achieving complete virological response at 12W and 24W was 48.4% and 58.1%, respectively. HBV DNA [(4.88±0.54) lg IU/mL vs (2.69±0.35) lg IU/mL vs (2.40±0.39 lg IU/mL)] was significantly lower compared to baseline and 12W primary patients (F=24.51, P=0.000); HBV DNA in previously treated patients[(2.67±0.31) lg IU/mL vs (1.70±0.24) lg IU/mL vs (1.49±0.09) lg IU/mL decreased from before (F=5.83, P=0.009). The ALT recurrence rates based on laboratory criteria were 64% and 92% for 12W and 24W, respectively. And the ALT recurrence rates were 38.4% and 78.9% for 12W and 24W using AASLD 2018 criteria. After 24W of antiviral therapy 4.53% of patients had HBeAg conversion, 2.17% of patients had HBeAg seroconversion, 1.09% of patients had HBsAg conversion, no patients have yet had HBsAg seroconversion. In terms of safety, there was no significant change in blood Cr, eGFR and CysC at 24 weeks of antiviral therapy in CHB patients compared with baseline. 33 treated patients who had early kidney injury switched to TMF and continued antiviral therapy for 24W had a significant decrease in urinary α1-MG and urinary NAG and urinary β2-MG compared with baseline, with P values <0.05, which were statistically significant. Compared with baseline, there was a trend of decreasing TG and increasing TC, but the difference was not statistically significant.Conclusion TMF is effective and safe in the treatment of patients with CHB.
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    Chinese Hepatolgy    2023, 28 (2): 135-145.  
    Abstract355)      PDF (2000KB)(463)      
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    Efficacy of ascites ultrafiltration concentration and peritoneal reinfusion in the treatment of refractory cirrhotic ascites in 305 cases
    TANG Ru-jia, ZHOU Xia, YAO Hong-yu, HU Yan-ming, WANG Huan, WANG Kai-li, XING Han-qian, ZHAO Jun, LIU Hong-ling
    Chinese Hepatolgy    2022, 27 (12): 1268-1270.  
    Abstract288)      PDF (684KB)(435)      
    Objective To investigate the clinical efficacy of ascites ultrafiltration concentration and peritoneal reinfusion (referred to as ascites reinfusion) in the treatment for patients with refractory cirrhotic ascites.Methods A total of 305 patients with cirrhosis and refractory ascites admitted to our hospital from January 2019 to December 2020 were selected as the research objects. On the basis of conventional liver protection treatment and diuresis, ascites infusion therapy was performed. The clinical symptoms and signs (abdominal distention, anorexia, body weight, abdominal circumference, etc.) of the patients before and after treatment were observed. Laboratory indicators including serum creatinine (Scr), blood urea nitrogen (BUN), albumin, platelets, hemoglobin, and ascites routine were detected.Results After ascites reinfusion treatment, the clinical symptoms of 274 patients (89.8%) were improved, including weight loss, reduction in abdominal circumference, reduced bloating and dyspnea, and appetite improvement. Thirty-one patients (10.2%) had no obvious effect or progressed. During the treatment, 10 patients developed hypotension (3%), 4 patients muscle spasm (1.3%), and 2 patients mild abdominal pain (0.6%), all of which resolved spontaneously after operation and no serious complications occurred. After treatment, the Scr and BUN levels did not increase significantly, but the serum albumin level increased significantly (28.4 g/L vs. 29.6 g/L, P=0.000), and the platelet count decreased (93.34×109 vs. 90.39×109, P=0.006). There was no significant deference in serum sodium, international normalized ratio (INR), hemoglobin and other indicators before and after treatment.Conclusion Routine treatment combined with ascites reinfusion therapy can safely and effectively improve the clinical symptoms of patients with decompensated liver cirrhosis and refractory ascites.
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    Chinese Hepatolgy    2022, 27 (8): 940-940.  
    Abstract349)      PDF (640KB)(429)      
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    Chinese Hepatolgy    2022, 27 (6): 715-719.  
    Abstract345)      PDF (622KB)(420)      
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    Establishment of animal models of chronic liver disease and modeling methods
    ZHU Xue-jing, WANG Men-ting, YAN He-xin, HUANG Ren-jie
    Chinese Hepatolgy    2022, 27 (9): 1030-1035.  
    Abstract667)      PDF (1791KB)(419)      
    Objective To establish an ideal model of chronic liver injury and evaluate stability of the modeling methods. Methods In this study, the mouse model of non-alcoholic steatohepatitis (NASH), the mouse model of liver fibrosis and the rat model of cirrhosis were induced by the modified high-fat diet (HFD), carbon tetrachloride (CCl4) and thioacetamide (TAA), respectively. Pathological hematoxylin-eosin (HE), oil red O and sirius red (SR) staining were used to observe the structural changes, steatosis and fibrosis of animal liver. Serum alanine transaminase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), γ-glutamyltransferase (GGT),glycyl proline dipeptidyl aminopeptidase (GPDA), albumin (ALB), total cholesterol (TC) and triglyceride (TG) were detected by automatic biochemical instrument. Results Compared with traditional diet group (8 mice), the modified HFD group (64 mice) could increase the activities of ALT [(268.7 ± 69.8) vs (35.0 ± 21.9)], AST [(215.0 ± 91.0) vs (34.4 ± 9.4)] and LDH [(560.3 ± 158.5) vs (240.6 ± 101.3)] significantly (all P<0.05), and decrease the activities of TC [(1.5 ± 0.3) vs (2.2 ± 0.2)] and TG [(0.9 ± 0.1) vs (1.6 ± 0.2)] significantly (both P<0.05). In the pathological results, oil red O and HE staining were observed in pathology showed that the hepatic tissue of mice fed with the modified HFD were filled with lipid droplets. Compared with mice injected with olive oil (8 mice), levels of ALT [(8507.3 ± 1083.1) vs (41.8± 29.2)] and AST [(4911.2 ± 644.0) vs (104.0 ± 33.6)] increased significantly (P<0.05) in mice injected with 10% CCl4 (2mL/kg, tiw) for 12 weeks (52 mice). The pathological results of HE and SR staining showed that there was a large number of collagen fibers in the liver tissue of mice injected with CCl4. Compared with mice injected with normal saline (8 rats), levels of ALT [(197.3 ± 131.1) vs (34.0 ± 6.0)], AST [(590.3 ± 457.7) vs (57.5 ± 12.3)], GGT [(10.0 ± 8.4) vs (3.6 ± 3.3)] and GPDA [(290.5 ± 134.4) vs (63.3 ± 14.7)] increased significantly (all P<0.05) and level of ALB [(37.3 ± 1.9) vs (40.9 ± 1.3)] decreased significantly (P<0.05) in rat injected with TAA (200mg/kg, biw) for 16 weeks (37 rats). The pathological analysis of HE and SR staining showed that the liver tissue of rats injected with TAA presented with hepatic fibrosis, proliferation of hepatic fibroblasts and formed pseudo lobules with different sizes. Conclusion Mice were fed with the modified HFD for 2 weeks, the success rate of NASH model was 100%. The model was further aggravated after feeding for 4 weeks. In terms of mice that were injected with 10% CCl4 (2 mL/kg, tiw) for 12 weeks, the success rate of liver fibrosis model was 100%, and the model could be maintained for at least 2 weeks after drug withdrawal. Rats were injected with TAA (200mg/kg, biw) for 16 weeks, the success rate of liver cirrhosis model was 100%, and the model could last for at least 4 weeks after drug withdrawal.
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    Chinese Hepatolgy    2022, 27 (7): 725-729.  
    Abstract889)      PDF (699KB)(408)      
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    Chinese Hepatolgy    2023, 28 (1): 1-10.  
    Abstract346)      PDF (1293KB)(401)      
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    Chinese Hepatolgy    2022, 27 (10): 1055-1058.  
    Abstract281)      PDF (717KB)(391)      
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    Chinese Hepatolgy    2022, 27 (10): 1059-1061.  
    Abstract395)      PDF (621KB)(391)      
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    Chinese Hepatolgy    2022, 27 (12): 1258-1263.  
    Abstract299)      PDF (705KB)(388)      
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    Chinese Hepatolgy    2023, 28 (1): 13-16.  
    Abstract181)      PDF (800KB)(375)      
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    The therapeutic effect of carrelizumab or sintilimab combined with lenvatinib in the treatment of liver cancer and the influence on tumor markers
    YANG Jian-qi, CAO Wen-miao, WU Yin-xia, YIN Ting, XING En-ming
    Chinese Hepatolgy    2022, 27 (10): 1080-1083.  
    Abstract554)      PDF (647KB)(364)      
    Objective To investigate the therapeutic effect of carrelizumab or sintilimab combined with lenvatinib in the treatment of liver cancer and its influence on tumor markers. Methods Ninety-five patients with primary liver cancer admitted to our hospital from June 2018 to June 2021 were selected as the research objects. According to the treatment method, the patients were divided into lenvatinib group (lenvatinib, 33 cases), carrelizumab group (carrelizumab combined with lenvatinib, 30 cases), and sintilimab group (sintilimab combined with lenvatinib, 32 cases). The clinical therapeutic efficacy, side effects, liver function [alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil)] and tumor markers [alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), α-L-fucosidase (AFU), carbohydrate antigen 199 (CA199)] among the 3 groups after treatment were compared. Results The clinical efficacy of carrelizumab group and sintilimab group were significantly higher than lenvatinib group (P<0.05). The levels of ALT, AST and TBil in the 3 groups were all significantly decreased after treatment, the liver function of carrelizumab group and sintilimab group were significantly lower than lenvatinib group (P<0.05). The levels of AFP, CEA, AFU, and CA199 in the 3 groups were significantly decreased after treatment, the tumor markers levels of carrelizumab group and sintilimab group were significantly lower than lenvatinib group (P<0.05). There was no significant difference in side effects among the 3 groups (P>0.05). Conclusion Carrelizumab or sintilimab combined with lenvatinib in the treatment of liver cancer can effectively improve the therapeutic efficacy and liver function, reduce the levels of tumor markers, with good safety.
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    Chinese Hepatolgy    2022, 27 (7): 729-732.  
    Abstract462)      PDF (678KB)(360)      
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