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Journal of Practical Hepatology

2021 Vol. 24, No. 5 Published:10 September 2021
Liver cirrhosis
Non-cirrhotic portal hypertension: current state
Zhao Jianbo, Tan Qing
2021, 24(5):  613-616.  doi:10.3969/j.issn.1672-5069.2021.05.002
Abstract ( 175 )   PDF (836KB) ( 292 )  
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Rivaroxaban as an oral anticoagulant in patients with Budd-Chiari syndrome after percutaneous endovascular intervention
Li Weizhi, Li Peijie, Ma Fuquan, et al
2021, 24(5):  621-624.  doi:10.3969/j.issn.1672-5069.2021.05.004
Abstract ( 244 )   PDF (1156KB) ( 362 )  
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Objective The aim of this study was to investigate the efficacy and safety of rivaroxaban as an oral anticoagulant in patients with Budd Chiari syndrome after percutaneous intravascular intervention (PII). Methods The clinical data of 103 patients with Budd Chiari syndrome who met the inclusion and exclusion criteria between December 2017 and April 2020 were retrospectively analyzed. All patients underwent PII, and were divided into two groups, taking rivaroxaban (n=49) or aspirin (n=54) as the anticoagulants after operation. The endpoint was mortality and/or massive bleeding. Results After operation, the average follow-up period in rivaroxaban- and aspirin-treated groups were 20.33±6.31 months and 19.43±6.34 months (P>0.05); at the end of 6 month, 12 month and 20 month, the stent patency rates in the rivaroxaban-treated groups were significantly higher than those in aspirin-treated group, e.g. 93.9% vs. 85.2%, 89.8% vs. 81.5% and 87.8% vs. 74.1%(all P=0.044); there were no significant differences as respect to massive bleeding free rates at 6 month, 12 month and 20 month in the two groups (95.9%, 91.8% and 87.8% vs. 88.9%, 87.0% and 19.6%, P>0.5); the survival rates at 6-month, 12-month and 20-month in rivaroxaban-treated group were 95.9%, 91.8% and 85.7%, not significantly different compared to 94.4%, 88.9% and 81.5% in aspirin-treated group (P=0.681); the endpoint mortality and/or massive bleeding free event in rivaroxaban-treated group were 95.9%, 89.8% and 83.7%, not significantly different compared to 88.9%, 87.0% and 81.5% in aspirin-treated group (P=0.675). Conclusion Compared with aspirin, rivaroxaban could improve stent patency in patients with Budd Chiari syndrome after PII, and might not increase massive bleeding, which is worthy of further clinical investigation.
Nocturnal snack in patients with liver cirrhosis: a Meta analysis
Tan Fenglei, Wu Liangliang, Deng Zerun, et al
2021, 24(5):  625-628.  doi:10.3969/j.issn.1672-5069.2021.05.005
Abstract ( 222 )   PDF (1216KB) ( 306 )  
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Objective The aim of this study was to evaluate the efficacy and safety of late evening snack (LES) in patients with liver cirrhosis (LC). Methods The systematic search was carried out in PubMed, EMbase, The Cochrane Library, China knowledge Network, Wanfang database and VIP database, and the articles published from January 2000 to August 2020 were retrieved systematically. RevMan5.3 was applied to conduct a statistical analysis. Results Fourteen trials involving 492 cases were included in this study; thirteen studies evaluated the changes of serum albumin levels after administration of LES, and the results showed that the high-quality proteins and amino acids-rich LES could increase serum albumin levels (MD =5.68,95%CI:1.78-9.59,P=0.004); eight clinical trials including 398 participants reported serum pre-albumin level was higher than the baseline (SMD=3.87,95%CI:2.14-5.61,P<0.0001); eight trials including a total of 366 participants reported that after a period of LES, serum CHE level was found to be higher than the baseline (SMD=0.95,95%CI:0.04-1.87,P=0.4); after LES intervention, HGB increased compared with baseline level (MD=4.41,95%CI:0.001-8.82,P=0.05) in 4 trials, and in 10 papers showed total serum bilirubin level decreased after LES intervention (MD=-22.62,95%CI:40.63--4.62,P=0.01); six studies reported an increase in RQ (MD=0.17,95%CI:-0.02-0.36,P=0.08) after taking LES for 1 to 12 weeks; there were 5 studies on fat, protein and carbohydrate oxidation rate, showed a downward trend in protein oxidation rate (MD=-4.07,95%CI:-7.22--0.91,P=0.01) , the utilization of carbohydrates increased significantly (MD=8.47,95%CI:7.51-9.43,P<0.00001), and fat oxidation decreased significantly (MD=-4.88,95%Cl:-7.73--2.02,P=0.0008) after LES. Conclusion LES could improve the malnutrition status of patients with LC.
Efficacy of esophageal variceal ligation and transjugular intrahepatic portosystemic shunt in treatment of patients with liver cirrhosis and esophageal varices bleeding
Li Wei, Song Weidong, Xie Batu Baiyin
2021, 24(5):  629-632.  doi:10.3969/j.issn.1672-5069.2021.05.006
Abstract ( 152 )   PDF (845KB) ( 156 )  
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Objective The aim of this study was to observe the efficacy of esophageal variceal ligation (EVL) and transjugular intrahepatic portosystemic shunt (TIPS) in treatment of patients with liver cirrhosis (LC) and esophageal varices bleeding (EVB). Methods 74 patients with LC complicated by EVB were admitted to our hospital between October 2016 and October 2018, and the EVL was carried out in 34 cases and the TIPS was performed in 40 patients. All patients were followed-up for 2 years. Results The EVL and TIPS were successfully completed in our patients after emergent hemostasis; at the end of two weeks, there was no significant difference as respect to liver function index or peripheral blood parameters in the two groups (P>0.05); the incidences of post-operational complications in EVL-treated patients was 88.2%, much higher than 40.0% in TIPS-intervened patients (P<0.05); during the two-year follow-up, the incidences of post-operational re-bleeding of esophageal varices were not significantly different between the two groups (41.2% vs. 35.0%, P>0.05); the fatality rate in EVL-treated patients was 20.6%, not significantly different compared to 10.0% in patients who received TIPS (P>0.05). Conclusion The efficacy of EVL and TIPS in dealing with patients with EVB is similar, while taking the post-operational complications into consideration, we recommend the latter for priority, which warrants further investigation.
Implication of peripheral blood leukocyte VCS parameters in patients with decompensated liver cirrhosis and sepsis
Wu Qiong, Sun Yang, Liu Na, et al
2021, 24(5):  633-636.  doi:10.3969/j.issn.1672-5069.2021.05.007
Abstract ( 168 )   PDF (920KB) ( 395 )  
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Objective The aim of this study was to explore the implication of peripheral blood leukocyte volume (V), conductivity (C) and scattering (C) parameters in patients with decompensated liver cirrhosis and sepsis. Methods 130 patients with decompensated liver cirrhosis including complicated sepsis in 39, other common infection in 46 and non-infected in 45, were admitted to our hospital between June 2017 and June 2020. The mean neutrophil volume (MNV), mean neutrophil conductivity (MNC)and mean neutrophil scattering (MNS), mean monocyte volume (MMV), mean monocyte conductivity (MMC) and mean monocyte scattering (MMS), and mean lymphocyte volume (MLV), mean lymphocyte conductivity (MLC) and mean lymphocyte scattering (MLS) were detected. The receiver’s operating characteristic (ROC) was applied to evaluate the diagnostic efficacy of these indicators for sepsis occurrence. Results The neutrophil MNV and MNC were (149.5±9.8) and(148.6±9.6), both significantly higher than in infected or in non-infected patients; theMMV was (179.6±11.3), significantly higher than in infected or in non-infected patients; the MLV was (90.1±5.1), much higher than in infected or in non-infected patients; theROC analysis showed than the AUC of MNV, MMV, MLV, APACHE II and SOFA in diagnosing sepsis in cirrhotics were 0.756, 0.768, 0.681, 0.796 and 0.794, while the combination of the five reached to 0.847, having the best diagnostic efficacy (P<0.05). Conclusion The peripheral blood leukocyte VCS parameters have a good diagnostic efficacy for sepsis in patients with decompensated liver cirrhosis, which warrants further clinical investigation.
Predicting value of serum ascites albumin gradient on esophageal variceal bleeding risk in patients with decompensated hepatitis B cirrhosis
Liu Yuling, Zhen Zengguo, Wang Huijuan, et al
2021, 24(5):  637-640.  doi:10.3969/j.issn.1672-5069.2021.05.008
Abstract ( 157 )   PDF (853KB) ( 178 )  
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Objective The aim of this study was to investigate the clinical predicting value of serum ascites albumin gradient (SAAG) on esophageal variceal bleeding (EVB) risk in patients with decompensated hepatitis B cirrhosis. Methods 84 patients with decompensated hepatitis B cirrhosis were admitted to our hospital between April 2017 and October 2019, and the SAAG and modified SAAG werecalculated. The Logistic multivariate analysis was used to analyze the independent impacting factors on EVB in patients with decompensatedhepatitis B cirrhosis. The receiver operating characteristic curve (ROC) was drawn and the area under the ROC (AUROC) was calculated to predict the EVB risk. Results 18 out of our series had, and 66 patients had not EVB during six-month followed-up period; the percentage of male cases older than 65 yr in patients with EBV was 72.2%,greatly older than in patients without EBV (43.9%,P<0.05); serum albumin level in patients with EVB was (35.8±2.7)g/L, significantly lower than , blood platelet count was (52.3±10.7)×109/L, significantly lower than , the APTT was (45.8±5.9)s, significantly longer than ,the SAAG was (18.7±5.1), significantly higher than , and the modified SAAG was (9.2±2.4), significantly higher than in patients without EVB; the spleen thickness was (5.2±1.3)cm, significantly higher than , and the portal vein blood flow velocity was (15.2±2.9) cm/s, significantly slower than in patients without EVB; the multivariate Logistic analysis showed that serum albumin level (OR=0.435, 95%CI=0.287-0.659), ascites albumin level(OR=1.845, 95%CI=1.063-3.202), the APTT(OR=1.469,95%CI=1.272-1.697), the MELD score (OR=3.285, 95%CI=1.697-6.359) and the modified SAAG(OR=2.917, 95%CI=1.337-6.364) were the independent impacting factors for EVB in patients with decompensated hepatitis B cirrhosis(P<0.05); the AUCs of modified SAAG and MELD score for predicting EVB were 0.827 and 0.791, respectively, and theirsensitivities were 0.889 and 0.787, and the specificities were 0.636 and 0.612, respectively. Conclusion The application of SAAG is helpful to predict the risk of EVB in patients with decompensated hepatitis B cirrhosis, and worth further clinical investigation.
Intestinal flora changes in patients with hepatitis B-induced liver cirrhosis after entecavir and glycyrrhizin combination treatment
Ji Minyou, Li Chao, Zhao Xingzhong, et al
2021, 24(5):  641-644.  doi:10.3969/j.issn.1672-5069.2021.05.009
Abstract ( 612 )   PDF (852KB) ( 186 )  
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Objective The aim of this study was to investigate the clinical predicting value of serum ascites albumin gradient (SAAG) on esophageal variceal bleeding (EVB) risk in patients with decompensated hepatitis B cirrhosis. Methods 84 patients with decompensated hepatitis B cirrhosis were admitted to our hospital between April 2017 and October 2019, and the SAAG and modified SAAG werecalculated. The Logistic multivariate analysis was used to analyze the independent impacting factors on EVB in patients with decompensatedhepatitis B cirrhosis. The receiver operating characteristic curve (ROC) was drawn and the area under the ROC (AUROC) was calculated to predict the EVB risk. Results 18 out of our series had, and 66 patients had not EVB during six-month followed-up period; the percentage of male cases older than 65 yr in patients with EBV was 72.2%,greatly older than in patients without EBV (43.9%,P<0.05); serum albumin level in patients with EVB was (35.8±2.7)g/L, significantly lower than , blood platelet count was (52.3±10.7)×109/L, significantly lower than , the APTT was (45.8±5.9)s, significantly longer than ,the SAAG was (18.7±5.1), significantly higher than , and the modified SAAG was (9.2±2.4), significantly higher than in patients without EVB; the spleen thickness was (5.2±1.3)cm, significantly higher than , and the portal vein blood flow velocity was (15.2±2.9) cm/s, significantly slower than in patients without EVB; the multivariate Logistic analysis showed that serum albumin level (OR=0.435, 95%CI=0.287-0.659), ascites albumin level(OR=1.845, 95%CI=1.063-3.202), the APTT(OR=1.469,95%CI=1.272-1.697), the MELD score (OR=3.285, 95%CI=1.697-6.359) and the modified SAAG(OR=2.917, 95%CI=1.337-6.364) were the independent impacting factors for EVB in patients with decompensated hepatitis B cirrhosis(P<0.05); the AUCs of modified SAAG and MELD score for predicting EVB were 0.827 and 0.791, respectively, and theirsensitivities were 0.889 and 0.787, and the specificities were 0.636 and 0.612, respectively. Conclusion The application of SAAG is helpful to predict the risk of EVB in patients with decompensated hepatitis B cirrhosis, and worth further clinical investigation.
Abdominal CT manifestations and CT quantitative parameters in patients with schistosomiasis cirrhosis
Ye Li, Wu Chenying, Song bin
2021, 24(5):  645-648.  doi:10.3969/j.issn.1672-5069.2021.05.010
Abstract ( 216 )   PDF (848KB) ( 407 )  
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Objective The purpose of this study was to investigate the abdominal computed tomography (CT) manifestations and CT quantitative parameters in patients with schistosomiasis liver cirrhosis (SLC). Methods A total of 72 patients with SLC and 25 healthy volunteers were enrolled in this study between May 2018 and May 2020. The patients with SLC included Child-Pugh class A in 26, Child-Pugh class B in 21, and Child-Pugh class C in 25. All the individuals underwent CT enhanced scan, and the blood volume (BV), blood flow (BF), mean transit time (MTT) , hepatic arterial fraction (HAF) and hepatic artery perfusion (HAP) were recorded. The laboratory indicators, such as total serum bilirubin, albumin, international standardized ratio of prothrombin time, white blood cell counts and platelet counts were detected. Results TheCT examination in 72 patients with SLC showed abnormal ratio of liver lobes, irregular contour and widening of liver fissure, a map-like, diffuse decrease of liver parenchyma density, high density schistosomia-like calcified nodules and portal vein dilatation in liver, portal vein and mesenteric vein, and the blood analysis demonstrated the injured liver function tests and hypersplenism; in healthy subjects,the abdominal CT perfusion parameters, e.g. the BV, BF, MTT, HAF and HAP levels were (47.3±8.2) ml/100g, (211.9±42.1) ml/min/100g, (12.9±3.1) s, (0.2±0.0) and (16.3±7.9) ml/min/100g, respectively, those in patients with SLC of Child-Pugh class A were (40.8±7.6) ml/100g, (183.1±37.2) ml/min/100g, (15.8±3.7) s, (0.3±0.0) and (19.1±8.8) ml/min/100g, in patients with Child-Pugh class B were (35.5±6.9) ml/100g, (124.7±33.2) ml/min/100g, (19.2±4.5) s, (0.3±0.0) and (24.5±9.9) ml/min/100g, and in patients with Child-Pugh class C were (24.8±8.4) ml/100g, (115.5±28.1) ml/min/100g, (24.6±5.5) s, (0.4±0.1) and (33.5±12.5) ml/min/100g, respectively, significantly different among them (P<0.05). Conclusion The CT examination of liver in patients with SLC could show the morphological changes, and the CT perfusion parameters obtained might help evaluate the severity of liver injuries.
Re-observation of splenectomy and esophagogastric devascularization in patients with hepatitis B cirrhosis and portal hypertension
Liu Gongwei, Wu Xue, Tang Dan, et al
2021, 24(5):  649-652.  doi:10.3969/j.issn.1672-5069.2021.05.011
Abstract ( 202 )   PDF (846KB) ( 446 )  
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Objective The aim of this study was to re-observe the clinical efficacy of splenectomy (SPL) and portal-azygous disconnection (PAD) in treating patients with hepatitis B cirrhosis and portal hypertension. Methods A total of 87 patients with hepatitis B cirrhosis and portal hypertension were enrolled in our hospital between Februar y 2017 and November 2019, and 45 patients out of them received SPL and esophagogastric devascularization (observation group) and 42 patients underwent percutaneous transhepatic variceal embolization ( PTVE) and partial splenic embolization. The body mass index (BMI), mid-upper arm circumference (MUAC) and riceps skinfold thickness (RST) were measured. The portal venous flow (PVF), superior mesenteric venous flow (SMVF) and splenic venous flow ( SVF) were measured by sonography. Results One month after operation, the BMI, MUAC and RST in the observation were (21.5±1.3)kg/m2, (22.1±1.0)cm and (10.3±1.0)mm, not significantly different as compared to in the control; the PVF and SMVF were (670.9±46.2)ml/min and (583.5±69.0)ml/min, significantly different compared to in the control; serum albumin levels was (34.0±1.4)g/L, significantly higher than in the control; the incidence of post-operational complications was 8.9%, much lower than 38.1%(P<0.05) in the control. Conclusion The classic splenectomy and esophagogastric devascularization combination is still an important choice of treatment for patients with hepatitis B cirrhosis and portal hypertension, which might reduce the portal pressure, improve liver function and liver blood perfusion with fewer complications.
Hepatitis in mice and in vitro
Notch family and lipid metabolism changes in LO2 cells with adipogenesis in vitro
Wu Weijie, Chen Yuanwen, Ding Wenjin, et al
2021, 24(5):  653-656.  doi:10.3969/j.issn.1672-5069.2021.05.012
Abstract ( 322 )   PDF (863KB) ( 419 )  
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Objective The aim of this experiment was to investigate Notch family and lipid metabolism changes in LO2 cells with adipogenesis in vitro. Methods Palmitic acid (PA) was used to intervene human hepatocytes (L02 cells) to construct an in vitro steatosis cell model. The L02 cells were cultured with different concentrations (0 mM, 0.1 mM, 0.25 mM and 0.5 mM) of PA and different concentrations 0μM, 1μM, 2μM, 5μM and 10 μM) of γ secretase inhibitors N--S-phenylycine t-butyl ester (DAPT ) in 0.25mM PA-intervened cells for 24 h. The cells at 0 mM PA culture was used as the control group and those with 0 μM DAPT culture was defined as the model group. The Notch family(Notch 1,2 and 3)and its downstream genes(Hes-1 and Hey-1) mRNA levels were detected by real-time quantitative PCR. The aspartate aminotransferase (AST) and alanine transaminase(ALT) levels in supernatants, the cell triglyceride(TG), cholesterol(TC) and free fatty acid (FFA) levels were measured by colorimetric method. Results In 0.25 mM and 0.5 mM PA-intervened cells, the Notch3 mRNA levels were (0.6±0.2) and (0.4±0.1), respectively, both significantly lower than in the controlled cells, and the Hes-1 mRNA levels were (1.7±0.2) and (1.5±0.1), significantly higher than in the control; the AST levels in the supernatants were (6.7±2.6) U/L and (12.4±1.6) U/L , significantly higher than in the control, and the ALT levels were (5.7±0.8) U/L and (10.3±0.7) U/L, significantly higher than[(2.2±0.3) U/L, P<0.01] in the control; the cell TG levels were (0.4±0.04) mmol/g and (0.4±0.04) mmol/g, significantly higher than in the control; the Notch1 mRNA, TC and FFA levels in cells at 0.5mM PA intervention were (1.9±0.1), (1.2±0.4) mmol/g and (0.07±0.004) mmol/g, significantly higher than in the control; after 24 hour treatment with 2 μM DAPT, the Hes-1 mRNA, Hey-1 mRNA, AST and TG levels were (0.5±0.1), (0.6±0.3), (6.4±2.9) U/L and (0.03±0.01) mmol/g, with 5 μM DAPT intervention were (0.4±0.2), (0.6±0.1), (7.3±1.3) U/L and (0.04±0.01) mmol/g, and with 10 μM DAPT culture were (0.3±0.2), (0.4±0.1), (4.9±0.7) U/L and (0.02±0.01) mmol/g, all significantly lower than in model cells; the cell TC level was (0.2±0.03) mmol/g in 10 μM DAPT intervention, significantly higher than in the model. Conclusion Inhibition of Notch signaling could effectively improve cell injures in adipogenic cells, suggesting that the Notch signaling pathway might be closely related to lipid metabolism in hepatocytes intro, which is worthy of further study.
Protective effects of L-ornithine L-aspartate on mice with nonalcoholic steatohepatitis and sarcopenic obesity
Wang Zixuan, Wang Mengyu, Li Jingwei, et al
2021, 24(5):  657-660.  doi:10.3969/j.issn.1672-5069.2021.05.013
Abstract ( 164 )   PDF (3110KB) ( 238 )  
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Objective The purpose of this study was to explore the intervening effect of L-ornithine L-aspartate (LOLA) on in mice with nonalcoholic steatohepatitis (NASH) and sarcopenic obesity. Methods 28 male C57BL/6 mice were randomly divided into control (n=11) and model group (n=17) and were fed with chow diet or high-fat diet, respectively. Five mice from each group were sacrificed to evaluate the establishment of NASH model after 12 weeks. The remaining mice fed with high fat diet were further randomized into the model control (n=6) and the intervention group (n=6) and were orally administrated with saline or LOLA solution once daily for 8 weeks. The pathological changes of liver and muscle were examined after execution. Results High-fat diet feeding for 12 weeks successfully established a NASH rodent model that presented with moderate-to-severe hepatic steatosis, lobular inflammatory cell infiltration, and hepatocyte ballooning; at the end of week 12, the grip strength of mice in model group was (100.2±1.8)g, significantly lower than in the control group; at the end of 20th week, the body fat mass and fat to body weight ratio of mice in the model control group were (8±0.7)g and (21.0±6.7)%, significantly higher than in the control group; the histopathological inflammatory severity of liver and muscle in the intervention group had significantly alleviated as compared to those in the model control group; the body fat mass and fat to body weight ratio in the intervention group were (3.7±0.3)g and (11.3±4.2)%, significantly lower than in the model control group (P<0.05); the lean body mass and grip strength in the intervention group were (75.2±2.7)% and (104.7±9.1)g, significantly higher than (64.7±3.2)% and (93.7±4.1)g in the model control group (P<0.05); in the intervention group, the muscle cells were normal with the diameter of muscle fibers increased, and the NAS score in liver tissues decreased, relieved NASH obtained in all mice. Conclusion s Twenty-week high-fat diet could establish a mouse model that simultaneously exhibits steatohepatitis and sarcopenic obesity, and the application of LOLA exerts some degree of protection to these two injuries.
Dynamic changes of blood glucose levels and gut microbiota in mice with high-fat diet-induced metabolic associated fatty liver diseases
Shou Diwen, Zhou Yongjian, Xu Haoming, et al
2021, 24(5):  661-664.  doi:10.3969/j.issn.1672-5069.2021.05.014
Abstract ( 289 )   PDF (1055KB) ( 240 )  
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Objective The purpose of this experiment was to investigate the dynamic changes of blood glucose levels and gut microbiota in mice with high-fat diet-induced metabolic associated fatty liver diseases (MAFLD). Methods Twelve C57BL/6 mice were fed with 60% fat-calorie high-fat diet for 24 weeks. AT 0 weeks, 8 weeks, 16 weeks and 24 weeks, the glucose tolerance test (GTT) and insulin resistance test (ITT) were performed to evaluate glucose metabolism and insulin sensitivity. The mice feces were collected for 16sRNA detection to analyze the changes of bacterial structure and diversity of gut microbiota. Results As the high-fat diet prolonged, the blood glucose by GTT and by ITT increased significantly (P <0.05); the chao1 index and ACE index increased, suggesting that the diversity of intestinal microflora increased as the high-fat diet continued; at the phylum levels, the percentages of Firmicutes and Proteobacteria at week 8, 16 and 24 were significantly increased compared with that at week 0 (P < 0.05), while the percentages of Bacteroidetes and Verrucomicrobia were significantly decreased (P <0.05); at the genus levels, the percentages of Akkermansia and Ruminococcaceae-UCG-014 were significantly decreased after high-fat diet at week 8, 16 and 24 (P<0.05), while percentage of Coriobacteriaceae-UCG_002 was significantly increased (P<0.05) compared with that at week 0; at week 24, the percentage of Dubosiella increased compared with that at week 0 (P<0.05). Conclusion With the prolongation of high-fat diet feeding, the blood glucose levels of mice gradually increase, the alpha diversity of the gut microbiota continues to increase, and the bacterial structure at the phylum and genus levels change, which warrants further investigation.
Effect of HIF-1α on development of nonalcoholic steatohepatitis in mice and in vitro
Li Yan, Lu Lungen, Cai Xiaobo
2021, 24(5):  665-668.  doi:10.3969/j.issn.1672-5069.2021.05.015
Abstract ( 193 )   PDF (2267KB) ( 489 )  
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Objective This paper aimed to investigate the effect of hypoxia-inducible factor 1α(HIF-1α) in the development of nonalcoholic steatohepatitis (NASH). Methods Thirty male 57BL/6J mice were randomly divided into control, high-fat diet and methionine-choline-deficient diet (MCD) group, and the NASH model was established. The liver tissues were obtained for histological examination and hypoxyprobe staining. The HIF-1α mRNA and protein expression were respectively detected by Real-time PCR and Western blotting. The hepatic stellate cells, JS-1, were obtained and divided into control, adenoviral vector-infected and HIF-1α ShRNA adenovirus-infected group. The MTT test was applied for cell living assay. The collagen type 1 (COL1) and type 3 (COL3), TNF-α, IL-1βand TGF-β1 mRNA levels were detected by Real-time PCR. Results The hypoxyprobe staining showed that the percentages of positive staining in the high-fat diet and MCD diet groups were85% and 78%, significantly higher than 7% in the control(P<0.05); the HIF-1α mRNA levels in the two groups were 2.1 fold and 1.6 fold higher than in the control (P<0.05), and the HIF-1α protein expression was also greatly intensified; the cell viability in the HIF-1α ShRNA adenovirus-infected group was only 37%(P<0.05) compared to in the control, and the COL1, COL3, TNF-α, IL-1β and TGF-β1 mRNA decreased greatly compared to in the control(P<0.05). Conclusion HIF-1α might facilitate development of NASH, while needs further investigation.
Effects of sirolimus on hepatic TLR4 expression and autophagy in mice with partial hepatic warm ischemia-reperfusion injury
Tang Shuangyi, Wang Xibin, Qiu Yue, et al
2021, 24(5):  669-672.  doi:10.3969/j.issn.1672-5069.2021.05.016
Abstract ( 141 )   PDF (2706KB) ( 135 )  
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Objective The aim of this study was to explore the effects of sirolimus on hepatic Toll-like receptor 4 (TLR4) expression and autophagy in mice with partial hepatic warm ischemia-reperfusion (I/R) injury. Methods Forty Balb/c mice were randomly divided into control, model, low-dose (1 mg.kg-1) and high-dose (3 mg.kg-1) of sirolimus group, with 10 mice in each group. The left and middle branches of Glison sheath were surgically clamped to construct partial hepatic warm I/R model. The mice in the intervention group were intraperitoneally injected with sirolimus 2 days before modeling. After 6 hours of reperfusion, serum tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) were detected by ELISA. The expression of TLR4, nuclear factor κB (P65), phosphorylated P65 (p-P65), microtubule-associated protein 1 light chain 3B-II (LC3B-II) and P62 protein in liver tissues was detected by Western blot. The autophagosomes were detected by fluoroscopic electron microscope. Results After 6 h of reperfusion, serum ALT, AST, TNF-α and IL-6 levels in the model group were (1,370.6±245.7) U/L, (1,584.3±321.5) U/L, (69.4±8.8) pg/ mL and (154.1±22.7) pg/mL, significantly higher than in the control group, while serum ALT and AST levels in low-dose and high-dose of sirolimus-intervened groups were significantly lower than those in the model group (P<0.05); the hepatic expression of TLR4 protein and p-p65/p65 ratio in the model group were significantly stronger than those in the control group (P<0.05), while the expression of TLR4 protein and p-p65/p65 ratio in the low-dose and high-dose of sirolimus-intervened groups were significantly weaker than those in the model group (P<0.05), the expression of LC3B-II and P62 proteins, and the number of autophagosomes were significantly stronger or higher than those in the model group (P<0.05). Conclusion Sirolimus might reduce inflammatory response by inhibiting the activation of TLR4/NF-κB signaling pathway, which could effectively protect partial hepatic warm I/R injury in mice by inducing autophagy of hepatocytes.
Viral hepatitis
Serum α1 acidic glycoprotein, α1-antitrypsin and haptoglobin levels could be applied to predict hepatic fibrosis in patients with chronic hepatitis B
Wang Ligong, Zhao Shan, Bai Kai, et al
2021, 24(5):  673-676.  doi:10.3969/j.issn.1672-5069.2021.05.017
Abstract ( 226 )   PDF (964KB) ( 255 )  
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Objective The aim of this study was to explore the probability to apply serum α1 acidic glycoprotein (AAG), α1-antitrypsin (AAT) and haptoglobin (HP) levels to diagnose the stages of liver fibrosis (LF) in patients with chronic hepatitis B (CHB). Methods 196 patients with CHB were recruited in our hospital between October 2017 and October 2019, and serum AAG, AAT and HP levels were detected by immunoturbidimetric method. All patients with CHB underwent liver biopsy. The diagnostic efficacy of serum AAG, AAT, HP levels and their combination for LF staging was assessed by the area under the receiver operating characteristic (ROC) curves (AUC). Results The pathological examination of liver tissues showed that in the 196 patients with CHB, there were 18 cases (9.2%) with liver fibrosis at S0 stage, 38 cases (19.4%) at S1 stage, and 140 cases (71.4%) at >S2 (significant LF); serum AAG and HP levels in patients with significant liver fibrosis were (0.5±0.2) g/L and (0.4±0.1) g/L, significantly lower than in patients with S1 or [(1.0±0.3) g/L and (1.3±0.4) g/L, P<0.05] in patients with S0, while serum AAT level was (59.7±7.2) μmol/L, significantly higher than in patients with S1 or in patients with S0; the ROC curves analysis showed that the cut-off values of serum AAG, AAT and HP in the diagnosis of significant liver fibrosis were 0.6 g/L, 50.2 μmol/L and 0.5 g/L, respectively, with the AUC of serum AAG, AAT and HP combination was 0.844 (0.769-0.902), significantly higher than that of AAG, AAT and HP alone , which had not significant difference compared with that of fibrosis 4 score (FIB-4) or aspartate aminotransferase to platelet index (APRI) . Conclusion The combination of serum AAG, AAT and HP levels shows a promising prospect in the diagnosis of significant LF in patients with CHB, which is worthy of further investigation.
Serum HBsAg clearance in sequential combination of peginterferon alpha-treated patients with chronic hepatitis B with low serum HBsAg levels after nucleos(t)ide analogs treatment
Wu Fengping, Lu Rui, Liu Yixin, et al
2021, 24(5):  677-680.  doi:10.3969/j.issn.1672-5069.2021.05.018
Abstract ( 177 )   PDF (859KB) ( 351 )  
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Objective The aim of this study was to analyze the efficacy and safety of sequential combination of nucleos(t)ide analogs (NAs) with peginterferon alpha (Peg-IFN-α) in the treatment of patients with chronic hepatitis B (CHB) with low serum HBsAg levels. Methods A total of 106 CHB patients with serum HBsAg levels less than 1500 IU/mL after NAs treatment were enrolled in our hospital between November 2015 and October 2018. 42 patients were given sequential combination therapy of NAs and Peg-IFNα-2a/2b for 48 weeks, and 64 patients were continuously treated with NAs who had always taken. All patients were followed-up to week 96 (48 weeks after discontinuation of Peg-IFN-α). Results Two patients in the sequential combination group and 4 patients in the NAs group were lost; the intention- to-treat (ITT) analysis showed that the baseline materials in the two groups were comparable; serum HBsAg clearance rate and anti-HBs seroconversion rate in the sequential combination group were 19.0% and 14.3% at the end of 48-week treatment, both significantly higher than 0.0% and 0.0%, respectively, in the NAs group (P <0.001); the rates of serum HBsAg clearance and anti-HBs seroconversion at the end of 48-week follow-up in the sequential combination group were 21.4% and 19.0%, both significantly higher than 1.6% and 1.6%,respectively (P <0.001)in the NAs group; the liver stiffness measurement (LSM) was (7.2±0.3) kPa, significantly lower than in the NAs group, Conclusion The sequential combination of NAs and Peg-IFN-α treatment ameliorate serum HBsAg clearance and seroconversion, which might improve liver fibrosis in CHB patients with low levels of HBsAg, and gain clinical recovery.
Re-treatment of chronic hepatitis B non-responders to pegylated interferon-α by tenofovir and entecavir
Zhou Bingqing, Yang Hanqing, Jiang Beili
2021, 24(5):  681-684.  doi:10.3969/j.issn.1672-5069.2021.05.019
Abstract ( 203 )   PDF (854KB) ( 125 )  
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Objective The aim of this study was to compare the efficacy of re-treatment of chronic hepatitis B (CHB) non-responders to pegylated interferon-α by tenofovir and entecavir. Methods 77 patients with CHB who were the non-responders to pegylated interferon-α were recruited in our hospital between June 2016 and March 2020, and divided into two groups, receiving tenofovir (n=41) or entecavir (n=36), respectively. Serum HBV DNA and HBsAg and HBeAg were assayed routinely, and peripheral blood lymphocyte subsets was detected by FCM. Results At the end of six and twelve month treatment, serum alanineaminotransferase normalization rates in tenofovir-treated patients were 80.5% and 90.2%, not significantly different as compared to 77.8% and 86.1% in entecavir-treated patients(P>0.05), serum HBV DNA loss were 65.9% and 95.1%, also not significantly different as compared to 63.9% and 88.9% (P>0.05) in entecavir-treated patients; the percentage of peripheral blood CD4+ cells in tenofovir-treated patients were(33.9±3.9)% and (38.6±5.6)%, significantly higher than , and the CD4+/CD8+ cell ratio were (1.2±0.1) and (1.5±0.1), significantly higher than [(1.0±0.0) and (1.3±0.1), respectively, P<0.05] in entecavir-treated patients; during the 12-month observation period, the resistance rate in tenofovir-treated patients was 4.9%, not significantly different compared to 2.8% in entecavir-treated patients (x2=0.013,P=0.908). Conclusion The administration of tenofovir and entecavir in the treatment of CHB patients who do not respond to polyethylene glycol interferon-α could obtain a good clinical efficacy, while the tenofovir could improve immune functions, which might improve serological response and warrants further investigation.
Quantitative evaluation of hepatic fibrosis in patients with chronic hepatitis B by enhanced MRI T1 mapping
Yang Yonghan, Lu Ping, Meng Qingning, et al
2021, 24(5):  685-688.  doi:10.3969/j.issn.1672-5069.2021.05.020
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Objective The purpose of this study was to evaluate the hepatic fibrosis in patients with chronic Hepatitis B (CHB) by gadolinium-ethoxybenzyl- diethylenetriamine-pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI T1 mapping. Methods A total of 74 patients with CHB were recruited between January 2018 and June 2020, and underwent Gd-EOB-DTPA enhanced MRI and liver biopsies. The hepatobiliary phase signal intensity (SI), hepatobiliary phase T1, relative enhancement (RE) and T1 changing rate of MRI were obtained. The ROC curve was drawn by MedCalc 15.1 statistical software, and the area under the curve (AUC) was calculated by Z test. The cut-off-value of each parameters were analyzed to evaluate the diagnostic efficacy. Results Out the 74 patients with CHB, the histopathological examination showed F0 liver fibrosis stage in 22 cases, F1 stage in 12, F2 stage in 15, F3 stage in 9 and F4 stage in 16; the SI of hepatobiliary phase, the T1 in hepatobiliary phase, the RE, and the T1 changing rate in 40 patients with significant liver fibrosis were(362.5±29.8), (418.5±41.2), (0.52±0.07) and (50.8±4.8)%, all significantly different compared to in 34 patents without significant liver fibrosis; the sensitivity and specificity of T1 changing rate in diagnosis of significant liver fibrosis were 77.6% and 93.2%, both significantly higher than by other three parameters. Conclusion The application of MRI T1 mapping technique in diagnosing liver fibrosis in patients with CHB is to some extent efficacious, which warrants further investigation.
Efficacy of 3D regimen in the treatment of patients with chronic hepatitis C with genotype 1b infection
Han Hongyan, Pan Juan, Jiang Wenping, et al
2021, 24(5):  689-692.  doi:10.3969/j.issn.1672-5069.2021.05.021
Abstract ( 165 )   PDF (856KB) ( 132 )  
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Objective The aim of this study was to analyze the efficacy of 3D regimen (paritaprevir/ritonavir/ombitasvir combined with dasabuvir sodium) in the treatment of patients with chronic hepatitis C (CHC) with genotype 1b infection and low serum viral load. Methods A total of 77 patients (naïve patients in 62 and re-treated in 15) with CHC with gene 1b infection and low serum viral load (less than 7.0 log10IU/ml) were recruited in our hospital between May 2019 and May 2020, and all received 3D regimen for 3 months and followed-up for 3 months. The early virological response (EVR), end treatment virologica response (ETVR) and sustained virologic response (SVR) were evaluated, and plasma interferon-γ (IFN-γ) and interferon-inducible protein 10 (IP-10) levels were detected by ELISA. Results The EVR, ETVR and SVR12 in naïve patients were 51.6%, 100.0% and 100%, and were 46.7%, 100.0% and 100% in re-treated patients (P>0.05); serum HCV RNA negativities in the 77 patients with CHC at the end of one month, two months, three months and three months after treatment were 93.5%, 98.7%, 100.0% and 100.0%, and serum HCV RNA loads were (1.1±0.1)log10IU/ml,(1.1±0.1)log10IU/ml,(1.1±0.1)log10IU/ml and (1.0±0.1)log10IU/ml, respectively, significantly lower than at presentation; serum alanine aminotrasaminase levels were (16.8±4.1)U/L, (15.3±3.9)U/L, (11.1±3.2)U/L and (12.0±3.4)U/L, all significantly lower than , and serum aspartate aminotransferase levels were(20.4±4.7)U/L,(17.9±4.4)U/L,(18.0±5.1)U/L and (14.7±4.8)U/L, all significantly lower than at presentation; plasma IFN-γ levels were (46.9±5.8)pg/ml, (50.2±6.3)pg/ml, (57.0±6.9)pg/ml and (51.3±4.6)pg/ml, significantly higher than , while plasma IP-10 level were (100.5±36.1)pg/ml, (72.1±22.8)pg/ml, (66.8±13.4)pg/ml and (68.7±12.5)pg/ml, significantly lower than at presentation. Conclusion 3D regimen could achieve a better short-term efficacy in the treatment of no matter naïve or re-treated patients with CHC with genetype 1b infection with low serum viral loads, and warrants further and long-term observation.
Meta-analysis on distribution of hepatitis C virus genotypes in China
He Yong, Zhang Zhenhua, Liu Zhongping, et al
2021, 24(5):  693-696.  doi:10.3969/j.issn.1672-5069.2021.05.022
Abstract ( 182 )   PDF (2191KB) ( 403 )  
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Objective The aim of this study was to investigate the distribution of hepatitis C virus (HCV) genotypes among people in different regions, ethnic groups and transmission risk factors in China. Methods Papers on the studies of HCV genotypes in China were searched in Wanfang and NCBI database, and the data was classified by different regions, ethnic groups, and transmission risk factors. The data was analyzed by meta-analysis to observe the distribution of genotypes. Results In China, the HCV genotype 1 was the most prevalent, the HCV genotypes were mainly genotype 1 (52.7%-79.7%) and genotype 2 (13.9-44.9%) in the northern region, the HCV genotypes were mainly genotype 1 (51.7%-79%) in the southeast region, and the genotype 6 was widely distributed in Hong Kong (31.3%), Guangdong (23.1%), Fujian (21.8%) and Macau (20.6%); the HCV genotypes were mainly genotype 1 (19.7%-73.4%) and genotype 3 (13.4%-58.5%) in the southwest region; the main genotypes distributed in the western region were genotype 1 (53.6%-66.8%), genotype 2 (15.8%-32.1%) and genotype 3 (12.8%-15.8%); the proportion of genotype 2 in Korean nationality was (22.4%, P<0.001), in Uyghur(13.1%, P<0.001) and in Kazakh (18.5%, P<0.05), and the proportion of genotype 3 in Uyghur was 16.6%,significantly higher than 9.4% of the Han nationality 42.2%, significantly higher than that in Han (P<0.001); the proportion of genotype 3 in persons with intravenous drug use was 31.1%, significantly higher than with blood transmission infected (4.5%, P<0.001) or sexual transmission infected (24.1%, P<0.05), and the proportion of genotype 6 infection in intravenous drug users was 26.7% , significantly higher than by blood transmission infection (4.1%, P<0.001) or by sexual transmission infection (15.1%, P<0.001); the proportion of type 3 and type 6 in individuals with HCV/HIV mixed infection were higher than that in with HCV infection alone (all P<0.001). Conclusion There are differences in the distribution of HCV genotypes among individuals in different regions, in different ethnic groups and with different transmission routs.
Non-alcoholic fatty liver diseases
Changes of serum miR-17, miR-20a and miR-20b levels in patients with non-alcoholic fatty liver disease and type 2 diabetes mellitus
Ge Haiyan, Kuang Xia, Zhou Ruijun
2021, 24(5):  697-700.  doi:10.3969/j.issn.1672-5069.2021.05.023
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Objective The aim of this study was to explore the implications of serum micro RNA (miR)-17, miR-20a and miR-20b in patients with non-alcoholic fatty liver disease and type 2 diabetes mellitus. Methods 46 patients with T2DM and 50 patients (mild in 19, moderate in 17 and severe in 14) with NAFLD and T2DM were admitted to our hospital between December 2018 and June 2020. Serum miR-17, miR-20a and miR-20b mRNA levels were detected by real-time fluorescent quantitative RT-PCR. Multivariate Logistic regression analysis was applied to analyze the independent risk factorsfor occurrence of T2DM with underlying NAFLD, and the area (AUC) under the receiver operating characteristic curve (ROC) was applied to analyze the diagnostic efficacy of each indicator for severe NAFLD. Results Serum miR-17, miR-20a and miR-20b mRNA levels in patients with NAFLD and T2DM were (5.6±1.3),(3.8±0.9) and (1.8±0.5), all significantly higher than in patients with T2DM; serum miR-17, miR-20a and miR-20b mRNA levels in patients with severe NAFLD were (6.0±1.1), (4.0±0.8) and (1.9±0.5), significantly higher than in patients with moderate NAFLD or in patients with mild NAFLD; multivariate Logistic regression analysis showed that the body mass index, serum LDL-C, miR-17, miR-20a and miR-20b levels were the independent risk factors for T2DM with underlying NAFLD (P<0.05); the ROC analysis demonstrated that the AUC were 0.75, 0.74 and 0.70 by serum miR-17, miR-20a and miR-20b in diagnosing severe NAFLD. Conclusion Serum miR-17, miR-20a and miR-20b levels in patients with NAFLD and T2DM significantly increase, which might be involved in the pathogenesis of NAFLD.
Short-term efficacy of Huazhuo Tongyu decoction in the treatment of patients with non-alcoholic fatty liver diseases
Xu Xiangtao, Qiao Fei, Che Junyong, et al
2021, 24(5):  701-704.  doi:10.3969/j.issn.1672-5069.2021.05.024
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Objective The aim of this study was to investigate the short-term efficacy of Huazhuo Tongyu decoction in the treatment of patients with non-alcoholic fatty liver diseases(NAFLD). Methods 100 patients with NAFLD were recruited in this clinical trial between January 2018 and January 2020, and were randomly divided into control group (n=50) and observation group (n=50), receiving silibinin capsules orally or Huazhuo Tongyu decoction, a decoction of herbal medicine, for three months. Blood biochemical parameters were measured by AU5800 automatic biochemical analyzer, fasting blood insulin was detected by Abbott Optium glucometer, serum leptin level was detected by double-antibodies ELISA, and the severity of fatty liver was assessed by ultrasonography (US). Results At the end of treatment, blood triglycerides (TG), total cholesterol (TC) and low density lipoprotein (LDL) in the observation group were(1.8±0.1)mmol/L, (5.1±0.3)mmol/L and (2.0±0.2)mmol/L, significantly lower than in the control group; the HOMA-IR and serum leptin level were (2.0±0.2) and (1.0±0.1)ng/mL, significantly lower than in the control, while there were no significant differences as respect to fasting plasma glucose level and HOMA-B between the two groups ; serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transpeptidase (GGT) and the US score were(41.5±4.2)U/L, (35.9±3.2)U/L, (63.6±4.0)U/L and (4.6±1.0), all significantly lower than in the control. Conclusion The administration of Huazhuo Tongyu decoction could effectively regulate blood lipids, alleviate insulin resistance and decrease serum leptin levels in patients with NAFLD, which needs further investigation.
Clinical feature and risk factors of elderly patients with nonalcoholic fatty liver diseases and concomitant coronary heart disease
Ma Shangji, Zheng Yang, Chen Xufeng, et al
2021, 24(5):  705-708.  doi:10.3969/j.issn.1672-5069.2021.05.025
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Objective The aim of this study was to investigate the clinical feature and risk factors of elderly patients with nonalcoholic fatty liver diseases (NAFLD) and concomitant coronary heart disease (CHD). Methods The clinical data of 186 elderly patients with NAFLD admitted to our hospital between May 2018 and June 2020 were retrospectively analyzed, and all patients underwent coronary angiography. The univariate and multivariate Logistic regression analysis was applied to reveal the influencing factors of CHD in elderly NAFLD patients. Results Among 186 elderly patients with NAFLD, 75 (40.3%) patients had concomitant CHD; the percentage of diabetes mellitus, hypertension, smoking and fasting blood glucose (FPG), total blood cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, and insulin resistance index (HOMA-IR) in patients with CHD were significantly different as compared to those in patients without CHD (all P <0.05); the multivariate Logistic regression analysis showed that the increased BMI, concomitant diabetes mellitus, high blood FPG, TC, TG, and LDL-C levels were the independent risk factors for CHD in elderly NAFLD patients (all P < 0.05). Conclusion The incidence of CHD in elderly patients with NAFLD is high, and the related risk factors should be early under surveillance and appropriately controlled to improve thequality of life in elderly patients with NAFLD.
Alcoholic hepatitis
Comparative study on the clinical efficacy of lorazepam and oxazepam in treatment of patients with alcoholic liver diseases and alcohol withdrawal syndrome
Liu Lixia, Lin Yingyuan, Li Huamin, et al
2021, 24(5):  709-712.  doi:10.3969/j.issn.1672-5069.2021.05.026
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Objective This clinical trial aimed to compare the efficacy of lorazepam and oxazepam in treatment of patients with alcoholic liver diseases (ALD) and alcohol withdrawal syndrome (AWS). Methods A total of 127 patients with ALD and AWS were enrolled in our hospital between November 2017 and November 2020, and were randomly divided into control (n=63) and observation group (n=64), receiving lorazepam and oxazepam, respectively, for seven days. The scores of alcohol withdrawal syndrome scale (AWSS) and self-rating anxiety scale (SAS) score were evaluated. Serum hyaluronic acid (HA), laminin (LN), type III procollagen N-terminal peptide (PC-III) and type-IV collagen (IV-C) were detected by ELISA. Results At the end of 7 day treatment, the efficient rate in observation group was 96.9%, significantly higher than 81.0% in the control (P<0.05); at presentation, the AWSS and SAS, serum alanine transaminase (ALT), aspartate aminotransferase (AST), glutamyl transpeptidase (GGT),total bilirubin (TBIL) and alkaline phosphatase (ALP) as well as HA, LN, PC-Ⅲ and IV-C levels were not significantly different between the two groups(P>0.05); after treatment, the AWSS and SAS in observation were (9.5±2.4) and (30.8±6.4), significantly different as compared to in the control; serum ALT, AST, GGT, TBIL and ALP levels were (30.5±8.1)U/L, (71.6±15.3)U/L, (466.1±22.7)U/L, (23.5±6.5)μmol/L and (82.3±12.4)U/L, all much lower than in the control; serum HA, PC-Ⅲ and IV-C levels were (116.8±18.3)μg/L,(123.1±12.3)μg /L and (80.2±11.6)μg /L, significantly lower than in the control. Conclusion The clinical efficacy of oxazepam is good in treatment of ALD patients with complicated AWS, which could improve clinical symptom and anxiety relieving.
Drug-induced liver injuries
Clinical features and prognosis of patients with drug-induced liver injury
Guan Haiyan, Yang Wenbin
2021, 24(5):  713-716.  doi:10.3969/j.issn.1672-5069.2021.05.027
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Objective The purpose of this study was to summarize the clinical features and prognosis of patients with drug-induced liver injury (DILI). Methods The clinical materials in 164 patients with DILI between January 2015 and December 2019 were reviewed. The diagnosis of DILI was in accordance with the guidelines for the diagnosis and treatment of drug-induced liver injury reported by the Hepatology Branch of the Chinese Medical Association in 2015. Results Out of the 164 patients with DILI, the hepatocyte injury type was found in 97, the cholestasis type in 24, and the mixed type in 43; the average age in patients with hepatocyte injury was (47.2±13.3)yr, significantly younger than those in other two groups (P<0.05); serum ALT level in patients with hepatocyte injury was (652.5±350.6)U/L, in other two groups , significantly higher than those serum AST level was (451.8±418.1)U/L, much higher than in other two groups , while serum ALP level in patients with cholestasis type was (268.8±212.8)U/L, significantly higher than in other two groups , and serum bilirubin level was (66.8±13.5)μmol/L, also significantly higher than in other two groups ; the western medicine-, herbal medicine- and both-induced DILI accounted for 27.4%, 64.6% and 7.9%, respectively; the average age in 45 patients with western medicine-induced DILI was (44.2±13.5)yr, significantly younger than in other two groups (P<0.05), and male accounted for 42.2%, significantly higher than 33.0% in 106 patients with herbal medicine-induced DILI or 30.8% in 13 patients with western and herbal medicine-induced DILI; serum ALT level in western medicine-induced DILI was (510.2±361.8)U/L, significantly higher than , serum AST level was (360.8±251.5)U/L, significantly higher than in other two groups, while serum ALP level in herbal medicine-induced DILI was (174.7±113.6)U/L, much higher than in other two groups , and serum bilirubin level was (93.9±46.2)μmol/L, significantly higher than in other two groups ; 141 patients recovered and 23 not in our series; the male accounted for 52.2% in those unrecovered, significantly higher than 32.6%(P<0.05) in recovered, the hepatocyte injury accounted for 39.1%, significantly lower than 62.4%(P<0.05) in recovered, and herbal medicine-induced accounted for 78.2%, much higher than 62.4% (P<0.05) in recovered. Conclusion The clinical features of patients with DILI in our series are common with good prognosis, and the patients with herbal medicine-induced DILI tend to be with hyperbilirubinemia, whom should be taken more attention and dealt with appropriately.
Hepatic failure
Risk factors of infection and acute kidney injury in patients with acute-on-chronic hepatitis B liver failure
Chen Dandan, Long Zhida, Huang Shundong, et al
2021, 24(5):  717-720.  doi:10.3969/j.issn.1672-5069.2021.05.028
Abstract ( 151 )   PDF (850KB) ( 286 )  
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Objective The aim of this study was to explore the risk factors of infection and acute kidney injury (AKI) in patients with acute-on-chronic hepatitis B liver failure (HBV-ACLF). Methods A total of 102 patients with HBV-ACLF were admitted to our hospital between September 2017 and September 2019, and the infections occurred in 48 patients and the AKI occurred in 32 patients. The related risk impacting factors of infection and AKI were analyzed by multivariate Logistic regression analysis. Results The percentages of hospital stay longer than 15 days, invasive check-up, gastrointestinal bleeding, ascites, hepatic encephalopathy and diabetes mellitus in patients with infections were 56.3%, 37.5%, 43.8%, 52.1%, 25.0% and 16.7%, significantly higher than 24.1%, 13.0%, 16.7%, 22.2%, 5.6% and 3.7% (P<0.05), serum bilirubin level was (310.2±42.2)μmol/L, significantly higher than , the MELD score was (26.1±4.6), significantly higher than , while serum albumin level was (30.4±1.1)g/L, significantly lower than in patients without infection; the multivariate Logistic regression analysis showed that the long hospital stay , invasive manipulation , gastrointestinal bleeding and hepatic encephalopathy were the independent risk factors for the occurrence of infections in patients with HBV-ACLF; the multivariate Logistic regression analysis demonstrated that the hepatic diabetes and gastrointestinal bleeding were the impacting factors for the happening of AKI in patients with HBV-ACLF. Conclusion The patients with HBV-ACLF have some risk factors for complications such as infections and AKI, and the long hospitalization, invasive manipulation, upper gastrointestinal hemorrhage and hepatic encephalopathy are the causative elements, which should be dealt with appropriately to improve the prognosis.
Clinical significance of serum autophagy-related proteins in patients with hepatitis B virus-induced acute on chronic liver failure
Huang Shuangxiang, Yao Chaoguang, Lan Jing, et al
2021, 24(5):  721-724.  doi:10.3969/j.issn.1672-5069.2021.05.029
Abstract ( 161 )   PDF (929KB) ( 104 )  
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Objective The aim of this study was to explore the clinical significance of serum p62, microtubule-associated protein 1 light chain 3-II (LC3-II) and Beclin1 in patients with hepatitis B virus infection-induced acute-on-chronic liver failure (HBV-ACLF). Methods Sixty patients with HBV-ACLF and 65 subjects who underwent physical examination in our hospital during the same period were recruited in this study between September 2018 and September 2020. The scores of model for end-stage liver disease (MELD) were calculated. Serum 62, Beclin1 and LC3-II levels were detected by ELISA. The predictive efficacy of serum p62, Beclin1 and LC3-II as well as MELD for prognosis of patients with HBV-ACLF was evaluated by area under the receiver operating characteristic curves (AUROC). Results At admission, serum LC3-Ⅱ and Beclin1 levels in patients with HBV-ACLF were (66.8±13.5)ng/mL and (11.7±3.6)ng/mL, both significantly higher than [(35.8±6.2)ng/mL and (8.2±2.9)ng/mL, respectively, P<0.05], while serum p62 level was (2.5±0.9)ng/mL, significantly lower than [(4.5±1.6)ng/mL, P<0.05] in the control; at day 90, 18 patients(30.0%)died; serum LC3-Ⅱ, Beclin1 levels and MELD score in dead patients at presentation were (76.25±12.1)ng/mL, (10.9±3.2)ng/mL and (20.1±3.3), all significantly higher than [(62.8±10.2)ng/mL,(13.4±3.5)ng/mL and (16.7±4.6), respectively, P<0.05], while serum p62 level was (1.7±0.6)ng/mL, much lower than in the survivals; the ROC analysis showed that serum p62<2.2 ng/mL, LC3-Ⅱ>70.3 ng/mL and Beclin1>12.6 ng/mL were set as the cut-off-value, the AUC were 0.856, 0.820 and 0.765 in predicting the poor prognosis of patients with HBV-ACLF, and the AUC of the three combination was 0.910, similar to 0.917 by MELD score when greater than 18.3 of it was set as the cut-off-value. Conclusion Serum p62, LC3-II and Beclin1 levels might be monitored and applied to predict the prognosis of patients with HBV-ACLF.
Hepatoma
Computed tomography and magnetic resonance imaging in the diagnosis of patients with hepatocellular carcinoma based on liver imaging report data system v2018
Liang Xu, Liu Yuanyuan, Yang Xuegang, et al
2021, 24(5):  725-728.  doi:10.3969/j.issn.1672-5069.2021.05.030
Abstract ( 160 )   PDF (1679KB) ( 143 )  
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Objective This study aimed to compare the efficacy of computed tomography (CT) and magnetic resonance imaging (MRI) in the diagnosis of patients with hepatocellular carcinoma (HCC) based on liver imaging report data system (LI-RADS) v2018. Methods We performed a retrospective study in 72 patients with high risk of HCC (proven pathologically HCC in 53, non-HCC malignant tumors in 10 and benign lesions in 9), and all patients underwent CT and MRI scan between September 2017 and July 2020. Two independent radiologists assigned a LI-RADS category for all hepatic foci in consensus. The intraclass agreement for the LI-RADS category between CT and MRI was evaluated by using Kappa statistic. The area under receiver operating characteristic curve (AUC) was analyzed for diagnostic accuracy of LI-RADS v2018. Results The intraclass agreement for the LI-RADS category between CT and MRI was substantial, and the kappa value was 0.693 (95% CI: 0.545-0.841), P<0.001]; the AUCs of the two modalities were 0.827 (95% CI: 0.708-0.946) and 0.856 (95% CI: 0.761-0.952), respectively, without significant difference(P>0.05); the sensitivities of CT and MRI in diagnosing HCC based on the LR-5 were significantly different, while the specificities of CT and MRI were comparable; among the major features defined by LI-RADS, the display rate of enhanced capsule of tumors by MRI was 40.3%, significantly higher than 5.5% by CT (P <0.001). Conclusion Based on the LI-RADS v2018, the CT and MRI show a considerable efficacy in diagnosing patients with HCC, and the sensitivity of MRI is high with obvious presentation of enhanced capsule of tumors.
UCK2, PRIM1 and DNTM1 levels in cancerous tissues of patients with hepatocellular carcinoma based on TCGA database
Zhao Yi, Lu Bingjiu
2021, 24(5):  729-732.  doi:10.3969/j.issn.1672-5069.2021.05.031
Abstract ( 361 )   PDF (1622KB) ( 423 )  
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Objective To search for differential genes in cancerous tissues of patients with hepatocellular carcinoma (HCC) based on TCGA database. Methods We search the differential genes in patients with HCC from TCGA database, and draw the survival curve according to the levels of differential genes by using fdr=0.05 and lgFC=1 as the screening basis. Results We successfully got the clinical and pathological materials of 374 cancerous tissues and 50 adjacent non-cancerous tissues from the TCGA-LIHC database; the total survival in patients with high risk was significantly lower than that in patients with low risk; we found the significant higher levels DNTM1, PRIM1 and UCK2 genes to screen and verify in TCGA database, and the results showed that many abundant signaling pathway, suggesting that DNTM1, PRIM1 and UCK2 were related to the survival of patients with HCC. Conclusion The UCK2, PRIM1 and DNTM1 genes are up-regulated and CYP2C9 gene is down-regulated in liver cancerous tissues by through TCGA database screening and verification, which might help the clinicians to deal with them in clinical practice.
Impacting efficacy factors of apatinib maintaining treatment after transcatheter hepatic artery chemoembolization in patients with advanced hepatocellular carcinoma
Zhang Ying, Zhang Lei, Ding Haitao
2021, 24(5):  733-736.  doi:10.3969/j.issn.1672-5069.2021.05.032
Abstract ( 147 )   PDF (847KB) ( 417 )  
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Objective This study aimed to investigate the impacting efficacy factors of apatinib maintaining treatment after transcatheter hepatic artery chemoembolization (TACE) in patients with advanced hepatocellular carcinoma (HCC). Methods 138 patients with advanced HCC were recruited in our hospital between January 2018 and December 2019, and all patients received apatinib maintenance therapy after TACE for 2 to 3 courses of treatment. Serum alpha fetoprotein (AFP) level was detected by chemiluminescence immunoassay and plasma level of heat shock protein 90 α (Hsp90 α) was measured by ELISA. The impacting efficacy factors were analyzed by multivariate Logistic regression analysis. Results At the end of the treatment, 10 patients (7.2%) obtained complete response, 56 patients (40.6%) obtained partial response, 42 patients (30.4%) got stable disease, and 30 patients (21.7%) got progressive disease; the proportions of age older than 60 years, Child-Pugh class B, BCLC stage C, tumor diameter greater than 5 cm, serum AFP level greater than 400.0 U/L and HSP90 level greater than 460.0 ng/mL in patients with progressive disease were 57.4%, 55.2%, 53.2%, 55.3%, 62.5% and 65.7%, allsignificantly higher than 42.6%, 44.8%, 46.8%, 44.7%, 37.5% and 34.3% in the disease controlled group (P<0.05); the multivariate Logistic regression analysis showed that Child-Pugh classification, BCLC stage, serum AFP and HSP90 were the independent factors influencing the clinical efficacy of apatinib after TACE in patients with advanced HCC (P<0.05). Conclusion The apatinib maintenance therapy after TACE in the treatment of patients with advanced HCC has to some extent short-term efficacy, however, the clinicians should take some influencing efficacy factors into consideration, and select the eligible patients for treatment.
Image quality of adaptive statistical iterative reconstruction under low tube voltage of CT scan in diagnosis of patients with primary liver cancer
Peng Guangming, Ge Shang, Jin Guiyin
2021, 24(5):  737-740.  doi:10.3969/j.issn.1672-5069.2021.05.033
Abstract ( 131 )   PDF (1201KB) ( 454 )  
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Objective The aim of this study was to investigate the image quality ofadaptive statistical iterative reconstruction (ASIR) under low tube voltage of CT scan in diagnosis of patients with primary liver cancer (PLC) . Methods 84 patients with PLC were encountered in our hospital between May 2018and May 2020, and all patients underwent CT examination, with ASIR under 100 kV scan in 38 patients (observation group) and filtered back projection (FBP) under normal 120kV scan in 46 patients (control group). The subjective indicators, such as noise, artifact, small structure, lesion display score, the Objective indicators, such as noise, signal to noise ratio and contrast signal to noise ratio in arterial phase, portal venous phase and delayed phase, and the CT dose index of volume (CTDIvol) and effective dose (ED) were recorded. Results The noise levels in arterial phase, portal vein phase and delayed phase in the observation group were (9.4±1.5) HU, (9.5±2.0) HU and (9.8±1.8) HU, significantly lower than in the control group, the signal-to-noise ratio in arterial phase and in delayed phase in the observation group were (9.1±1.6) and (10.6±2.1), significantly higher than in the control group, and the contrast signal to noise ratio in arterial phase and in delayed phase in the observation group were (3.1±0.9) and (4.6±1.5), significantly higher than in the control group; the scores of noise, fine structure, lesion display and artifact in arterial phase in the observation group were (1.4±0.6), (1.6±0.7),(1.2±0.6) and (1.2±0.5), significantly lower than in the control group; the score of noise, fine structure, lesion display and artifact in the delay phase in the observation group were (1.5±0.7),(1.7±0.8),(1.6±0.6) and (1.4±0.6), significantly lower than in the control group; the CTDIvol in the observation group was (6.4±1.7) mGy, significantly lower than and the ED was (2.3±0.7) mSv, significantly lower than in the control group. Conclusion The application of ASIR under low tube voltage fulfills the diagnostic requirement with good CT image quality and less radiation inpatients with PLC, which might need further clinical investigations.
Clinical implication of serum CXCL9 and IFN-γ levels in patients with intrahepatic cholangiocarcinoma
Song Xue, Xi Zihan, Li Ting, et al
2021, 24(5):  741-744.  doi:10.3969/j.issn.1672-5069.2021.05.034
Abstract ( 182 )   PDF (855KB) ( 146 )  
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Objective The purpose of this study was to investigate the clinical implication of serum C-X-C chemokine ligand 9 (CXCL9) and interferon-γ (IFN-γ) levels in patients with intrahepatic cholangiocarcinoma (ICC). Methods A total of 63 patients with ICC and 63 healthy persons were enrolled in our hospital between January 2012 and January 2017, and all patients underwent radical tumor removal and followed-up for 36 months. Serum levels of CXCL9 and IFN-γ were detected by enzyme-linked immunosorbent assay. The Kaplan-Meier survival curve was applied to analyze serum CXCL9 and IFN-γ levels in predicting the prognosis of patients with ICC after operation. Results Serum CXCL9 and IFN-γ levels in patients with ICC were (820.7±185.6)pg/mL and (18.7±7.2)ng/L, significantly different as compared to or in healthy persons; there were significant differences as respect to serum CXCL9 and IFN-γ levels between ICC patients with TNM stage Ⅰ/Ⅱ vs. stage Ⅲ/Ⅳ, with or without lymph node metastasis, and poorly vs. moderately/highly differentiated tumors(P<0.05); at the end of 36 month follow-up, 42 (66.7%) patients with ICC died and 21 (33.3%)patients survived in our series; 30 patients with ICC had low and 33 had high serum CXCL9 levels when 820.7 pg/mL was set as the cut-off-value, and the Kaplan-Meier analysis showed that the 36mon survival in patients with low serum CXCL9 levels was 53.3%, significantly higher than 15.2%(x2=12.448, P<0.001)in patients with high serumCXCL9 levels; 34 ICC patients had low and 29 patients had high serum IFN-γ levels when 18.7 ng/L was set as the cut-off-value, and the 36mon survival in patients with low serum IFN-γ levels was 14.7%, significantly lower than 55.2%(x2=10.554,P=0.001) in patients with high serum IFN-γ levels. Conclusion Serum CXCL9 levels increase and serum IFN-γ levels decrease in patients with ICC, and serum CXCL9 and IFN-γ levels are correlated with the prognosis of ICC patients after radical operation. The surveillance of serum CXCL9 and IFN-γ levels in this setting is helpful to evaluate the prognosis of patients with ICC.
Hepatic cyst
Short-term curative efficacy of ultrasound-guided cyst puncture, laparoscopic fenestration and laparotomic fenestration drainage in patients with hepatic cysts
Liu Hong, Wang Yao, Hu Yufeng, et al
2021, 24(5):  745-748.  doi:10.3969/j.issn.1672-5069.2021.05.035
Abstract ( 218 )   PDF (845KB) ( 286 )  
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Objective The aim of this study was to compare the curative efficacy of ultrasound-guided cyst aspiration, laparoscopic fenestration and laparotomic fenestration drainage in patients with simple hepatic cysts. Methods A total of 117 patients with simple hepatic cysts were admitted to our hospital between April 2017 and November 2019, and out of them, 45 cases underwent ultrasound-guided cyst puncture drainage and sclerified, 42 cases underwent laparoscopic fenestration drainage and 30 cases underwent laparotomic fenestration drainage. Results The disappearance and effective rates in puncture drainage-treated patients were 71.1% and 22.2%, 66.7% and 23.8% in laparoscopic fenestration drainage-treated patients and 66.7% and 26.7% in laparotomic fenestration drainage-treated patients (P>0.05); after treatment, serum ALT, AST and bilirubin levels were (28.6±4.3)U/L, (28.6±3.9)U/L and (16.4±2.8)μmol/L,(29.4±3.9)U/L,(29.8±4.0)U/L and (16.8±3.2)μmol/L, and (29.7±3.4)U/L, (28.4±3.7)U/L and (16.2±3.1)μmol/L, respectively, in the three groups (P>0.05); the incidences of post-operational complications, such as nausea and vomiting, abdominal pain, fever and unformed stool were 15.6%, 6.7%, 13.3% and 4.4%, 21.4%, 14.3%, 19.0% and 7.1%, and 23.3%, 23.3%, 26.7% and 6.7%, no significant differences in the three groups (P>0.05). Conclusion The clinical efficacy of the three surgical approaches are similar for patients with simple liver cysts. However, the ultrasound-guided puncture drainage and sclerotherapy is easy and simple way in this setting.
Hepatic hemangioma
Improved CT diagnosis of patients with hepatic hemangioma by automatic tube current modulation and adaptive statistical iterative reconstruction
Zhang Wuhua, Li Hailong, Qin Qibin
2021, 24(5):  749-752.  doi:10.3969/j.issn.1672-5069.2021.05.036
Abstract ( 134 )   PDF (1605KB) ( 157 )  
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Objective The aim of this study was to explore the application of automatic tube current modulation (ATCM) and adaptive statistical iterative reconstruction (ASIR) in multilayer spiral computed tomography (CT) examination of patients with hepatic hemangioma (HH). Methods 144 patients with HH were encountered in our hospital between April 2017 and April 2020, andall underwent CT scan with different noise index (NI), e.g. in group A the NI was set to 9 in flat scan, in group B the NI was set to 9 in arterial phase, in group C the NI was set to 11 in venous phase, and in group D the NI was set to 13 in delayed phase and the ASIR was set to 50% in all scans. The image noise, image quality scores, image dose length product (DLP) and effective dose (ED) were calculated and compared. Results The image quality of CT scan met the needs of diagnosis and all obtain the final diagnosis in our series; the image quality score in group A was(4.9±0.3), significantly higher than (4.4±0.4) in group C or (3.8±0.4) in group D (P<0.05), and the image noise was(9.5±0.9)HU, significantly lower than (12.4±1.0)HU in group B, or (14.1±1.1)HU in group C or (16.3±1.1)HU in group D (P<0.05); the image quality score in group B was (4.8±0.3), significantly higher than in group C or in group D(P<0.05), and the image noise was (12.4±1.0)HU, significantly lower than ingroup C or in group D(P<0.05); the DLP and ED ingroup A were (253.2±100.8)mGy-cm and (3.8±1.6)mSv, significantly higher than(174.5±80.2)mGy-cm and (2.6±1.1)mSv in group C (P<0.05) or (128.50±60.4)mGy-cm and (1.9±0.9)mSv in group D (P<0.05); the DLP and ED in group B were (246.2±93.1)mGy-cm and (3.7±1.3)mSv, significantly higher than in group C or in group D(P<0.05). Conclusion The application of ATCM and ASIR with the NI equal to 9 in multislice spiral CT examination in patients with HH could reduce the radiation dose and meet the requirement of diagnosis.
Cholelithiasis
Outcomes of laparoscopic cholecystectomy and endoscopic retrograde cholangiopancreatography with endoscopic sphincterotomy in treatment of patients with gallbladder and extrahepatic bile duct stones
Liu Xiaofei, Zhang Dawei, Luo Hongyu, et al
2021, 24(5):  753-756.  doi:10.3969/j.issn.1672-5069.2021.05.037
Abstract ( 155 )   PDF (849KB) ( 212 )  
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Objective The aim of this study was to investigate the outcomes of laparoscopic cholecystectomy (LC) and endoscopic retrograde cholangiopancreatography (ERCP) with endoscopic sphincterotomy (EST) in treatment of patients with gallbladder and extrahepatic bile duct stones. Methods A total of 88 patients with gallbladder stones and extrahepatic bile duct stones were admitted to our hospital between January 2018 and October 2020, and were divided into observation group receiving LC and EST combination surgery in 47 cases and control group receiving open cholecystectomy and laparoscopic common bile duct exploration. The visual analogue scales (VAS ) was applied to evaluate the post-operational pain. Results The one-time radical stone removals in the two groups were 93.6% vs. 95.1% (P>0.05); in the observation group, the intraoperative blood loss was (28.1±6.2)ml, significantly less than ,and the operation time, postoperative fasting time and hospital stay were(105.7±25.5)min, (2.2±0.4)d and (7.6±1.0)d, all significantly shorter than in the control; at 48 and 72 hours, the VAS scores in the observation group were (3.7±0.6) and (2.5±0.5), both significantly lower than in the control; 7 days after operation, serum ALT and AST levels in the observation were (46.1±5.6)U/L and (42.5±5.2)U/L, both significantly lower than , while blood lipase level was (808.2±105.7)U/L, significantly higher than in the control; the incidence of post-operational complications in observation group was much lower than that in the control group (4.3% vs. 14.1%, P<0.05). Conclusion The combination of LC and EST under ERCP might have a good outcomes in patients with gallbladder stones and extrahepatic bile duct stones, which could promote postoperative recovery, and less postoperative complications.
Gallbladder carcinoma
MRI features of patients with wall-thickening gallbladder carcinoma
Xu Yan, Li Xiaotian, Liu Hui, et al
2021, 24(5):  757-760.  doi:10.3969/j.issn.1672-5069.2021.05.038
Abstract ( 295 )   PDF (1066KB) ( 173 )  
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Objective The aim of this study was to summarize the magnetic resonance imaging (MRI) characteristics of patients with wall-thickening gallbladder carcinoma. Methods A total of 60 patients with gallbladder diseases were admitted to our hospital between January 2019 and December 2020, and all patients underwent MR scan and surgical cholecystectomy or radical cholecystectomy. Results The gallbladder width and gallbladder wall thickness in 21 patients with wall-thickening gallbladder carcinoma were (3.5±0.4)cm and (1.5±0.2)cm, significantly larger than in 39 patients with chronic cholecystitis, and the incidences of blurred interface with adjacent tissues, biliary obstruction, gallbladder wall stiffness, irregular gallbladder morphology and incomplete gallbladder mucosal line in patients with thick-thickening gallbladder carcinoma were 61.9%, 76.2%, 71.4%, 85.7% and 95.2%, all significantly higher than 0.0%, 10.3%, 2.6%, 25.6% and 0.0%, respectively, in patients with chronic cholecystitis (P<0.05). Conclusion MRI is high valuable in diagnosis and differentiation of patients with wall-thickening gallbladder carcinoma, which has some characteristic features for clinicians to make medical plan early for them.
Models of nonalcoholic fatty liver disease
Zhang Yizhi, Zhang Xiaohui, Chen Yu
2021, 24(5):  761-764.  doi:10.3969/j.issn.1672-5069.2021.05.039
Abstract ( 441 )   PDF (860KB) ( 866 )  
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Objective The incidence rate of nonalcoholic fatty liver disease (NAFLD) is increasing. It might progress to the end-stage liver disease. However, there is still no specific treatment for this entity. Therefore, the establishment of representative animal models reflecting disease characteristics has become especially important. Although there are many different disease models, there is still a lack of NAFLD model which could cover the whole spectrum of this entity in human. In this paper, we reviewed the current progress on NAFLD model, focusing on animal model, 2D cell model, 3D liver model and their advantages and disadvantages.