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Table of Content

    31 January 2019, Volume 24 Issue 1
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    Original Articles
    The chronic liver disease spectrum in 21 382 patients with liver biopsy
    FU Yi-ming, HAN Ping, JI Dong, SHAO Qing, LI Zhong-bin, WANG Chun-yan, CHEN Guo-feng
    2019, 24(1):  16-19. 
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    Objective To analyze the spectrum and trend of liver disease in our hospital, and to provide the evidence for chronic liver disease management.Methods The clinical data of inpatients with liver biopsy in our hospital from January 2007 to December 2016 were retrospectively analyzed. Results A total of 21382 patients with liver biopsy were enrolled and analyzed. In these cases, the top 5 etiologies were chronic hepatitis B (CHB), drug induced liver injury (DILI), chronic hepatitis C (CHC), cryptogenic liver disease (CLD), and autoimmune liver diseases (AILD). CHB mainly occurred in the young patients (62%). The majority of DILI was the young and middle-aged (47.7%, 36.4%). The proportions of the juvenile, young and middle-aged in CHC were similar (27.3%, 36.9%, 28.7%, respectively). The majority of CID was the juvenile and young (45.4%, 36.1%). AILD mainly occurred in the young and middle-aged (33.1%, 50.9%). In the past decade, the proportion of CHB in chronic liver disease decreased from 58.6% to 32.9%, while the proportion of DILI, CLD and AILD increased from 7.4% to 21.4%, 4.7% to 32.9% and 4.7% to 7.7%, respectively. The proportion of CHC increased from 7% to 22.4%, and then decreased to 2.2%. Moreover, the distributions differed in different gender and age groups. CHB mainly occurred in males, regardless of ages. However, DILI and AILD were more common in females, especially in middle age group. The constituent ratios of male and female in patients with CHC were similar. CLD mainly occurred in males and was more likely to occur in adolescents.Conclusion CHB and CHC are still the main causes of liver disease. However, the proportions of DILI, AILD and CID have increased rapidly, while the proportions of CHB and CHC have decreased significantly. Especially, the direct-acting antiviral therapy has achieved a great success in CHC.
    Transient elastography combined with alpha fetoprotein as an early-warning model for hepatocellular carcinoma
    CHEN Song-hai, JI Dong, HU Zhi-jun, LU Yin-ying, WANG Chun-yan, SHAO Qing, CHEN Guo-feng
    2019, 24(1):  20-23. 
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    Objective To establish a noninvasive early-warning model for hepatocellular carcinoma (HCC) and improve the diagnosis accuracy of high-risk individuals as early as possible.Methods Patients with hepatitis B virus related-cirrhosis or HCC, who were admitted to our hospital from 2008 to 2017, were enrolled. They were followed up at least 3 times with an interval of 3 to 6 months. Liver stiffness measurement (LSM) by transient elastography was performed on the day enrolled. Alpha-fetoprotein (AFP) and other serum parameters were detected at each visit. HCC was diagnosed using multiphase-dynamic-contrast-enhanced magnetic resonance imaging scan. The noninvasive predictors for HCC were identified using logistic regression, and an early-warning model named ALA was constructed with age, LSM and AFP. The receiver operating characteristic (ROC) curve analysis was applied to evaluate the early warning effectiveness of ALA on HCC. Results A total of 321 consecutive patients were included in the study, who were randomly divided into 2 groups at the ratio of 2∶1 (200 cases in training group and 121 cases in validation group). The clinical parameters (age, sex, Child-Pugh score, liver function, AFP, LSM) showed no differences between the 2 groups. The age, percentage of HCC patients, percentage of Child-A patients, median of AFP and median of LSM in training and validation group was 51.42±10.10 and 49.96±10.23 years old, 34% and 35.5%, 65% and 57%, 12 ng/ml and 6 ng/ml, 25 kPa and 27kPa, respectively. Multivariable logistic regression showed that age, LSM and AFP were the independent risk factors for HCC. The ALA model was calculated using 0.103×age (years) +0.116×LSM (kPa) +0.026×AFP (ng/ml). The area under ROC curve of ALA was 0.91 (95% confidence interval, 0.86-0.95) in the training group. Using ALA of 9.61 as the cut-off value, the accuracy was 84.3% in the validation group.Conclusion ALA, a noninvasive early-warning model consisting of age, LSM and AFP, is worthy of clinical application, which might improve the early diagnosis rate of HCC and provide early curative interventions for HCC patients.
    Risk factors for early portal venous system thrombosis after devascularization with splenectomy and portal hypertension in cirrhotic patients with portal hypertension and preventive effects of blood activating, anticoagulation and antiplatelet therapy
    ZHANG Zhen, WANG Meng-long, ZHANG Hai-tao, ZHANG Qi-kun, LIU Fu-quan
    2019, 24(1):  24-27. 
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    Objective To investigate the risk factors for early portal venous system thrombosis (PVST) after devascularization with splenectomy in cirrhotic patients with portal hypertension and to explore the preventive effects of blood activating, anticoagulation and antiplatelet therapy.Methods A retrospective study was conducted on 320 patients with portal hypertension post liver cirrhosis in our hospital from January 2011 to December 2016. All patients were treated with splenectomy and devascularization, and followed up after operation. Clinical data were collected including the occurrence of PVST. The patients with PVST were treated with blood activating, anticoagulation and antiplatelet therapy (low molecular dextran + vitamin K1 + dipyridamole + warfarin), and the changes of blood coagulation indexes were recorded. Results There were 60 patients developing PVST after operation in the 320 patients with an incidence of 18.8%. Parameters including spleen size, splenic vein diameter, portal vein diameter, flow velocity of portal vein blood, blood transfusion volume, postoperative platelet count and postoperative D-dimer level in PVST group (n=60) were significantly different from those in non-PVST group (n=260) (P<0.05). Multivariate logistic regression analysis showed that the postoperative platelet count, postoperative D-dimer level and blood flow velocity of portal vein were the main independent risk factors for PVST (P<0.05). The area under the receiver-operating characteristic (AUROC) curve of D-dimer for the diagnosis of PVST was 0.794 with 95% confidence interval (CI) of 0.724-0.863 (P<0.05), and the diagnostic cut-off point was 3.55 mg/L. The AUROC curve of postoperative platelet count for the diagnosis of PVST was 0.754 with 95% CI of 0.672~0.836 (P<0.05), and the diagnostic cut-off point was 435.5×109/L. The prothrombin time and activated partial thromboplastin time at month 1 were significantly lower than those at day 1 after operation in PVST group, respectively (9.22±2.13 s vs. 11.67±1.84 s and 35.39±9.14 s vs. 41.94±10.92 s, both P<0.05).Conclusion The occurrence of PVST after devascularization with splenectomy in patients with portal hypertension post liver cirrhosis is common. The postoperative platelet count, postoperative D-dimer and blood flow velocity of portal vein are the main risk factors for the PVST. The blood activating, anticoagulation and antiplatelet therapy might effectively prevent the PVST.
    The effect of glucose and lipid metabolism disorders on silent information regulator 1 and AMP-activated protein kinase signaling pathway in HCV infected hepatocytes
    YU Jian-wu, Li Ming-rong, ZHANG Xiao-yu,SUN Li-jie, ZHAO Yong-hua, LIU Wei
    2019, 24(1):  28-30. 
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    Objective The aim of this study was to investigate the effect of different concentrations of glucose or oleic acid on expression and activity of silent information regulator 1 (SIRT1) and adenosine monophosphate-activated protein kinase (AMPK) in hepatitis C virus (HCV) infected hepatocytes.Methods Plasmid expressing HCV core protein was transfected into HepG2 cells, which were incubated for 24 hours in serum-free DMEM medium with different final concentrations of glucose or oleic acid. The activity and expression of SIRT1 and AMPK were detected using scintillation counting and western blot, respectively. Results With increasing glucose concentration(1 g/L, 2 g/L, 4.5 g/L), SIRT1 activity (1.0±0.2, 0.6±0.15, 0.2±0.05) and expression (0.9±0.2, 0.4±0.1, 0.1±0.05) were decreased, AMPK activity (1.0±0.2, 0.5±0.08, 0.22±0.05) and expression (0.9±0.2, 0.4±0.1, 0.2±0.05) were decreased. With the increase of oleic acid concentration(0, 300 μM/L, 500 μM/L), SIRT1 activity (1.0±0.2, 0.6±0.1, 0.2±0.05) and expression (0.9±0.2, 0.5±0.1, 0.2±0.05) were decreased, AMPK activity (1.0±0.2, 0.5±0.1, 0.1±0.05) and expression of p-AMPK (0.9±0.2, 0.5±0.1, 0.2±0.05) were decreased.Conclusion High glucose and high oleic acid may down-regulate the activity and expression of SIRT1-AMPK signaling pathway in HCV infected hepatocytes.
    The role of SUMO specific protease 3 in HBV replication
    Li Qing, Lai Rong-tao, Lu Jie, Li Zi-qiang, Xie Qing, Wang Hui, Guo Qing
    2019, 24(1):  31-34. 
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    Objective To investigate the role of small ubiquitin-related modifier (SUMO) specific protease 3 (SENP3) in hepatitis B virus (HBV) infection.Methods To explore the mechanism of SENP3, HepG2.2.15 cell and HBV transgenic mouse were applied for experiments in vivo and vitro using western blot, real-time polymerase chain reaction and immunohistochemistry. Results The HBV DNA of patients was negatively correlated with the content of SENP3 in peripheral blood mononuclear cells. The average protein concentration of SENP3 in healthy control group was 7.4 times higher than that in patient group (P<0.05). In the liver of HBV transgenic mice, the expression of SENP3 was significantly decreased and phosphorylation of protein kinase B (Akt) was 4.1 times higher than that of control group (P<0.01). In HepG2.2.15 cells transfected with HBV DNA whole-genome plasmid, the expression of SENP3 was significantly lower, while the phosphorylation of Akt was 5.2 times higher than that in HepG2 cells (P<0.01). Overexpression of SENP3 in HepG2.215 cells resulted in decreases of Akt phosphorylation and HBV DNA content. Moreover, SENP3 plasmid concentration was negatively correlated with HBV DNA content. When transfecting HepG2.2.15 cells with 100 ng and 500 ng SENP3 plasmids, the concentrations of HBV DNA were reduced from 7.983.03×106 IU/ml to 3.45×106 IU/ml and 1.92×106 IU/ml, respectively. While silencing SENP3 in HepG2.2.15 cells, phosphorylation of Akt was increased 5.6 times (P<0.01).Conclusion The expression of HBV DNA is negatively correlated with the expression of SENP3, which can reduce the level of HBV DNA by inhibiting the phosphorylation of Akt in hepatocytes.