2020 No. 10

Evolution and development of surgical treatment for liver cancer

Wang Jie, Chen QieWei, Zheng GuoRong, He ChuanChao, Xiao ZhiYu

2020, 36(10): 2161-2166. DOI: 10.3969/j.issn.1001-5256.2020.10.001

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The treatment of liver cancer involves multidisciplinary comprehensive treatment including internal medicine,surgical treatment,radiation,and interventional surgery,and surgical treatment based on surgery is currently the main treatment method for liver cancer. This article summarizes and analyzes the update in the concept of surgical treatment of liver cancer,the development of treatment methods,and the advances in surgical technology and discusses the advantages and limitations of related techniques and concepts in the surgical treatment of liver cancer,so as to provide a reference for further promoting the improvement in the surgical treatment of liver cancer.

Pathogenesis of hepatitis B virus-related hepatocellular carcinoma

Yan YongCong, Wen Kai, Mao Kai, Xiao ZhiYu, Wang Jie

2020, 36(10): 2167-2172. DOI: 10.3969/j.issn.1001-5256.2020.10.002

Abstract(1343)

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Hepatocellular carcinoma( HCC) is one of the major malignant tumors that lead to death,and chronic hepatitis B virus( HBV)infection is an important risk factor for HCC. This article introduces the detailed mechanisms of HBV-related HCC,including HBV X protein,immune imbalance,and integration of HBV DNA into the host genome,with a focus on the pathological role and related mechanisms of HBV X protein in HCC. HBV X protein enhances carcinogenesis by promoting tumor cell proliferation,invasion,and metastasis,affecting angiogenesis,promoting cell apoptosis,and interfering with cell metabolism. In-depth studies on the biological functions of HBV X protein,immune imbalance,and HBV DNA integration will help to clarify the pathogenesis of liver cancer and promote the development of novel therapeutic targets for HBV-related HCC.

Research advances in systemic therapy for hepatocellular carcinoma in the era of precision medicine

Zhu GuiQi, Tang Zheng, Shi YingHong, Fan Jia

2020, 36(10): 2173-2178. DOI: 10.3969/j.issn.1001-5256.2020.10.003

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Hepatocellular carcinoma( HCC) is one of the most common malignant tumors in clinical practice and has the features of high incidence rate,poor prognosis,and high mortality rate,and its incidence rate and mortality rate rank among the top malignant tumors in the world. High heterogeneity of HCC affects the evolution and therapeutic response of HCC. Since most HCC patients are in the advanced stage at the time of diagnosis,systemic treatment has become the main treatment option. In recent years,remarkable achievements have been made in molecular targeted therapy and immunotherapy for HCC,and the latest NCCN guidelines for the systemic treatment of HCC show that sorafenib,lenvatinib,and atezolizumab combined with bevacizumab are recommended as the first-line treatment of HCC,and regorafenib,cabozantinib,nivolumab,pembrolizumab,and ramucirumab are the second-line treatment options for HCC. In the era of precision medicine,how to select the optimal individualized systemic treatment regimen is the key problem in the systemic treatment of HCC. This article reviews the advances in the systemic treatment of HCC in the era of precision medicine and discusses the development direction of HCC treatment in the future.

Advances in multimodality therapy for hepatocellular carcinoma

Fu YiZhen, Xu Li

2020, 36(10): 2179-2183. DOI: 10.3969/j.issn.1001-5256.2020.10.004

Abstract(1108)

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Primary liver cancer is one of the most common malignances worldwide,among which hepatocellular carcinoma( HCC) accounts for about 90% of all cases. Multidisciplinary multimodality therapy involving surgery,ablation,interventional treatment,targeted therapy,and immunotherapy is an effective strategy for the treatment of liver cancer. In recent years,great achievements have been made in multimodality therapy for liver cancer,especially the advances in combination therapy for advanced liver cancer and drug research and development,which improves the overall prognosis of liver cancer patients,and the improvement in targeted drug therapy and immunotherapy is expected to change the pattern of multimodality therapy for liver cancer. This article systematically reviews the recent advances in multimodality therapy for liver cancer from the aspects of local treatment and systemic therapy.

Clinical significance of heterogeneity in multifocal hepatocellular carcinoma: A multi-omics study

Kuang Ming, Xu LiXia, Liu Xin, Zhang Ying, Shen ShunLi

2020, 36(10): 2184-2187. DOI: 10.3969/j.issn.1001-5256.2020.10.005

Abstract(1213)

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More than half of patients with hepatocellular carcinoma( HCC) have multiple lesions in the liver at the time when they attend the hospital,and there are limited treatment methods with poor efficacy for multifocal HCC in clinical practice. The high degree of tumor heterogeneity in multifocal HCC is the leading cause of treatment failure. More and more studies use multi-omics sequencing to explore the heterogeneity between different lesions at the genetic and transcriptional levels,including tumor clonal evolution,gene mutations,copy number variations,structural variations,RNA expression,and tumor immune microenvironment. Drug target distribution shaped by clonal evolution and the characteristics of immune microenvironment can accurately predict the response to targeted drugs and immunotherapy in patients with multifocal HCC. Therefore,a comprehensive and accurate assessment of the heterogeneity of multifocal HCC based on a multi-omics study is of vital importance in the implementation of precise treatment.

Clinical practice guidelines for the interventional treatment of advanced pancreatic carcinoma (on trial) (4th edition)

National Clinical Research Center for Radiology and Therapy; Committee of Interventional Medicine and Bioengineering, Chinese Society of Interventional Physicians; Committee of Interventional Medicine, Cancer Foundation of China

2020, 36(10): 2188-2196. DOI: 10.3969/j.issn.1001-5256.2020.10.006

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An excerpt of management of patients with liver derangement during the COVID-19 pandemic: An Asia-Pacific position statement

Zhu MengHua, He YingLi, Qi XingShun

2020, 36(10): 2197-2198. DOI: 10.3969/j.issn.1001-5256.2020.10.007

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Value of mean platelet volume in evaluating the prognosis of hepatitis B virus-associated acute-on-chronic liver failure

Xu Ying, Huang XiaoPing, Chen Li, Gu Jing, Wang Yan, Gan JianHe

2020, 36(10): 2199-2202. DOI: 10.3969/j.issn.1001-5256.2020.10.008

Abstract(1129)

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Objective To investigate the association between mean platelet volume( MPV) and prognosis of hepatitis B virus-associated acute-on-chronic liver failure( HBV-ACLF) and the value of MPV in prognostic evaluation. Methods A retrospective analysis was performed for the clinical data of 37 patients with hepatitis B cirrhosis,44 patients with HBV-ACLF,and 27 patients with chronic hepatitis B,who were admitted to Department of Infectious Diseases,The First Affiliated Hospital of Soochow University,from January 2015 to December 2019,as well as 24 individuals who underwent physical examination during the same period of time. Related clinical data included sex,age,total bilirubin( TBil),creatinine( Cr),blood urea nitrogen( BUN),albumin( Alb),blood ammonia( NH3),routine blood test results,Model for End-Stage Liver Disease( MELD) score,and blood coagulation parameters. According to prognosis,the patients with HBV-ACLF patients were divided into improvement group with 19 patients and non-improvement group with 25 patients,and the patients were followed up for 3 months. The Kruskal-Wallis H test was used for comparison between multiple groups,and the Wilcoxon rank sum test was used for comparison within each group,the Mann-Whitney U test was used for comparison between two groups; a binary logistic regression analysis was used to investigate the independent influencing factors for prognosis,and the receiver operating characteristic( ROC)curve was used to predict the accuracy of variables. Results There were significant differences in MPV,platelet count,prothrombin time( PT),international normalized ratio( INR),Alb,BUN,TBil,and MELD score between the liver cirrhosis group,the HBV-ACLF group,the chronic hepatitis group,and the healthy group( χ2= 39. 031,75. 837,59. 894,56. 033,22. 760,83. 353 and 70. 299,all P <0. 001). Further comparison of MPV between two groups showed that the HBV-ACLF group had a significantly higher MPV than the healthy group and the chronic hepatitis group( Z = 9. 076 and 4. 435,both corrected P < 0. 001),and the liver cirrhosis group had a significantly higher MPV than the healthy group( Z = 2. 646,corrected P = 0. 049). For the patients with HBV-ACLF,there were significant differences in MPV,age,PT,INR,and MELD score between the improvement group and the non-improvement group( Z =-3. 710,-2. 726,-2. 678,-2. 322 and-2. 610,all P < 0. 05),and further binary logistic regression analysis showed that MPV( odds ratio [OR]= 1. 175,95%confidence interval [CI]: 1. 067-2. 756,P = 0. 026) and MELD score( OR = 1. 643,95% CI: 1. 021-2. 644,P = 0. 041) were independent influencing factors for the prognosis of HBV-ACLF. MPV alone,MELD score alone,and MPV combined with MELD score had an area under the ROC curve of 0. 742,0. 731,and 0. 791,respectively,in predicting the prognosis of HBV-ACLF,and MPV combined with MELD score had relatively high sensitivity( 0. 72) and specificity( 0. 895). Conclusion MPV is an independent influencing factor for the prognosis of HBV-ACLF and has a good value in predicting prognosis. MPV combined with MELD score has advantages over MPV or MELD score alone in predicting the prognosis of HBV-ACLF.

HCV genotype and clinical features of patients with HIV/HCV coinfection in Guizhou,China: An analysis of 383 cases

Wang Mei, Xiong HuaGang, Yang ZhiGang, Long Hai, Wang Yi, Tan Li

2020, 36(10): 2203-2208. DOI: 10.3969/j.issn.1001-5256.2020.10.009

Abstract(1010)

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Objective To investigate the distribution of HCV genotypes in 383 patients with HIV/HCV coinfection in Guizhou,China and the effect of coinfection on HIV viral load,CD4+T lymphocytes,and platelet count( PLT),and to provide a basis for individualized treatment of patients with HIV/HCV coinfection. Methods Related clinical data were collected from 383 patients with HIV/HCV coinfection who were treated in Guiyang Public Health Clinical Center from March 2015 to December 2019,and HCV genotype,HIV viral load,CD4+T lymphocytes,and PLT were determined. A total of 1068 patients with HIV alone were enrolled as control. The Kruskal-Wallis H test was used for comparison between multiple groups,the Wilcoxon rank-sum test was used for comparison between two groups,and the Bonferroni method was used for further comparison between two groups; the chi-square test or the Fisher's exact test was used for comparison of categorical data between groups. Results Among the 4664 patients with HIV infection,383( 8. 21%) had HCV coinfection,and the main HCV genotypes were genotype 6 a( 35. 51%), genotype 3 b( 27. 42%), and genotype 1 b( 21. 41%), followed by genotypes3 a( 13. 32%),1 a( 1. 31%),2 a( 0. 52%),6 n( 0. 26%),and 6 xa( 0. 26%). The most common route of infection was intravenous drug addiction( 72. 59%),followed by sexual contact( 24. 80%). Compared with the patients with HIV infection alone,the patients with HIV/HCV coinfection had a significantly higher HIV RNA load and significantly lower CD4+T lymphocytes and PLT( Z = 6. 716,11. 813,and9. 192,all P < 0. 05). Among the patients with coinfection,the patients with HCV genotype 3 b had the highest HIV RNA load and the lowest CD4+T lymphocytes and PLT,while the patients with HCV genotype 1 a had the lowest HIV RNA load and the highest CD4+T lymphocytes( all P < 0. 05). Among the patients with different clinical stages,the patients with compensated cirrhosis had the highest HIV RNA load,the patients with chronic hepatitis C had the lowest HIV RNA load,the patients with end-stage liver disease had the lowest count of CD4+T lymphocytes,and the patients with chronic hepatitis C had the highest PLT( all P < 0. 05). Conclusion The distribution of HCV genotypes is diverse in the patients with HIV/HCV coinfection in Guizhou,and HCV strains with genotypes 6 a,3 b,and 1 b are the main epidemic strains. Intravenous drug addiction is the main route of infection. Coinfection may affect HIV replication and immune status,with a significantly marked effect on HCV genotype 3 b and liver cirrhosis or end-stage liver disease.

Clinical effect of elbasvir/grazoprevir in treatment of chronic hepatitis C in the real world

Liu Fang, Liang Jing, Han Tao, Zhang YaPing, Lu: HongMin, Cao YingYing, Shi LiLi

2020, 36(10): 2209-2213. DOI: 10.3969/j.issn.1001-5256.2020.10.010

Abstract(1156)

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Objective To investigate the clinical effect of elbasvir/grazoprevir in the treatment of patients with genotype 1 b chronic hepatitis C( CHC). Methods A total of 99 patients with genotype 1 b CHC and compensated cirrhosis who received elbasvir/grazoprevir treatment for 12 weeks and completed treatment and follow-up for 12 weeks after drug withdrawal in Tianjin Third Central Hospital from December2018 to October 2019 were enrolled. Related clinical data,serological markers,virological indices,and liver stiffness measurement were collected at baseline,at the end of treatment,and at week 12 after drug withdrawal,and virologic response was observed. The Friedman test and Wilcoxon signed rank sum test were used to observe virologic response rate and the changes in liver function and liver stiffness measurement at the end of treatment and at week 12 after drug withdrawal,and the safety of elbasvir/grazoprevir was evaluated. Results For the 99 patients treated with elbasvir/grazoprevir for 12 weeks,the proportion of patients with HCV RNA below the lower limit of detection was100% at the end of treatment and 99% at week 12 after drug withdrawal. There were significant reductions in alanine aminotransferase( ALT) and aspartate aminotransferase( AST) from baseline to the end of treatment( Z =-5. 857 and-5. 941,both P < 0. 05). Liver stiffness measurement decreased from 10. 5 kPa at baseline to 8. 0 kPa at week 12 after drug withdrawal( Z =-4. 036,P < 0. 05). Among the 99 patients,24 patients with compensatory cirrhosis reached a virologic response rate of 100% at the end of treatment and at week 12 after drug withdrawal,as well as significant reductions in ALT and AST from baseline( both P < 0. 05),and liver stiffness measurement decreased from 21. 1 kPa at baseline to 17. 5 k Pa at the end of treatment( Z =-1. 832,P = 0. 067) and 13. 6 k Pa at week 12 after drug withdrawal( Z =-3. 182,P = 0. 001). Compared with the non-liver cirrhosis group,the liver cirrhosis group had significantly greater reductions in liver stiffness measurement( P < 0. 05). The patients had good tolerance throughout the treatment,and 4 patients reported mild adverse events during the treatment. Conclusion Patients with genotype 1 b CHC have a high virologic response rate to elbasvir/grazoprevir in the real world,with significant improvements in liver function and liver stiffness measurement and good tolerance.

Construction and analysis of a predictive model for progressive liver fibrosis in nonalcoholic fatty liver disease based on LASSO regression

Feng Gong, Zhang Yan, Yan QinQin, Liu Jing, Liu ManLing, Fan LiPing, Lin SiCen, He Na, Mi Man

2020, 36(10): 2214-2218. DOI: 10.3969/j.issn.1001-5256.2020.10.011

Abstract(1103)

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Objective To construct a noninvasive LASSO regression model based on commonly used clinical and laboratory markers associated with NAFLD,and to investigate the value of this model in the prediction and diagnosis of progressive liver fibrosis in NAFLD. Methods A total of 258 NAFLD patients who were consecutively admitted to The First Affiliated Hospital of Xi'an Medical University from January 2018 to August 2019 were enrolled,and according to liver stiffness measurement measured by FibroScan,the patients were divided into non-progressive fibrosis group with 184 patients and progressive fibrosis group with 74 patients. General information and biochemical parameters were collected. The independent samples t-test was used for comparison of normally distributed continuous data between the two groups,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between the two groups. The chi-square test was used for comparison of categorical data between two groups. The LASSO regression algorithm was used to screen out the characteristic indicators with non-zero coefficients which were associated with progressive fibrosis,and a LASSO regression model was constructed. The area under the receiver operator characteristic curve( AUC),sensitivity,and specificity of this model were calculated,and the LASSO regression model was compared with known classic models. Results The LASSO regression analysis screened out the important variables of type Ⅳ collagen,body mass index,and aspartate aminotransferase,and a LASSO regression model was constructed based on these three indicators. The results showed that the LASSO regression model had an AUC of 0. 843( 95% confidence interval [CI]: 0. 790-0. 897),a sensitivity of 0. 851,and a specificity of 0. 810,with a significantly better AUC than APRI( AUC = 0. 791,95% CI: 0. 731-0. 850),FIB-4( AUC = 0. 426,95% CI:0. 345-0. 507),and NFS( AUC = 0. 540,95% CI: 0. 463-0. 617). Conclusion Compared with the existing noninvasive scoring system for progressive liver fibrosis in NAFLD,this regression model has better AUC,specificity,and sensitivity,with strong practicability and operability,and therefore,it can be used as a new noninvasive model for the diagnosis of liver fibrosis.

Clinical effect of Fuhe Beihua prescription combined with transcatheter arterial chemoembolization in treatment of primary liver cancer patients with liver depression and spleen deficiency: An analysis of 218 cases

Jiang RuiYuan, Rong Zhen, Man TingTing, Tan YanChun, Liu QiuYue, Mo ChunMei

2020, 36(10): 2219-2225. DOI: 10.3969/j.issn.1001-5256.2020.10.012

Abstract(923)

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Objective To investigate the clinical effect of Fuhe Beihua prescription combined with transcatheter arterial chemoembolization( TACE) in the treatment of primary liver cancer patients with liver depression and spleen deficiency and its effect on T lymphocyte subsets.Methods A retrospective analysis was performed for the clinical data of stage Ⅲ primary liver cancer patients with liver depression and spleen deficiency who were treated in Department of Hepatology and Department of Oncology in The First Affiliated Hospital of Guangxi University of Chinese Medicine from January 2018 to January 2020. According to whether the traditional Chinese medicine Fuhe Beihua prescription was used,the patients were divided into treatment group( treated with routine TACE and oral administration of Fuhe Beihua prescription) and control group( treated with routine TACE alone),and the course of treatment was 16 weeks for both groups. The two groups were compared in terms of short-term response rate,quality-of-life score,serum alpha-fetoprotein( AFP) level,four indicators of liver fibrosis,coagulation function parameters,peripheral blood T lymphocyte subsets,and liver function parameters. The independent samples t-test was used for comparison of continuous data between two groups,and the chi-square test was used for comparison of categorical data between two groups. A repeated-measures analysis of variance was used for comparison of continuous data between different groups at different time points. Results A total of 218 patients were selected,with 118 in the control group and 100 in the treatment group. The treatment group had an objective response rate of 33% and a disease control rate of 66% at week 8 of treatment and an objective response rate of 34%and a disease control rate of 69% at week 16 of treatment,and the control group had an objective response rate of 26. 27% and a disease control rate of 68. 64% at week 8 of treatment and an objective response rate of 30. 51% and a disease control rate of 68. 64% at week 16 of treatment; there was a significant difference in objective response rate between the two groups at weeks 8 and 16 of treatment( P < 0. 05).Both groups had significant increases in Karnofsky Performance Scale( KPS) score,fibrinogen,and albumin( Alb) from before treatment to weeks 8 and 16 of treatment( all P < 0. 05),and there were significant differences in KPS score,fibrinogen,and Alb between the two groups at weeks 8 and 16 of treatment( all P < 0. 05). Both groups had significant reductions in AFP,the four indicators of liver fibrosis,alanine aminotransferase( ALT),aspartate aminotransferase( AST),prothrombin time( PT),and traditional Chinese medicine( TCM) syndrome score after treatment( all P < 0. 05),and at weeks 8 and 16 of treatment,there were significant differences between the two groups in AFP,the four indicators of liver fibrosis,ALT,AST,PT,and TCM syndrome score( all P < 0. 05). At weeks 8 and 16 of treatment,the treatment group had significant increases in the levels of CD3+,CD4+,and CD4+/CD8+( all P < 0. 05) and a significant reduction in the level of CD8+( P < 0. 05),and there were significant differences in the levels of T lymphocyte subsets between the two groups at weeks 8 and16 of treatment( all P < 0. 05). Conclusion Fuhe Beihua prescription combined with routine TACE has a better clinical effect than TACE alone in the treatment of primary liver cancer patients with liver depression and spleen deficiency,possibly by regulating the levels of T lymphocyte subsets.

Value of combined determination of hepatitis C virus genotype,AFP-L3,and P53 antibody in the diagnosis of hepatitis C virus-related hepatocellular carcinoma

Yang ZiLi, Zhang RenFei, He Xin, Zhang Jie, Wan Yi

2020, 36(10): 2226-2229. DOI: 10.3969/j.issn.1001-5256.2020.10.013

Abstract(940)

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Objective To investigate the value of combined determination of hepatitis C virus( HCV) genotype,the alpha-fetoprotein variant AFP-L3,and P53 antibody in HCV-related hepatocellular carcinoma( HCV-HCC). Methods A total of 84 patients with HCV-HCC who were diagnosed in our hospital from January 2016 to December 2019 were enrolled as HCV-HCC group,and 84 patients with benign liver diseases( hepatitis C and HCV liver cirrhosis) were enrolled as control group. The PCR-reverse dot blot hybridization technique was used to determine HCV genotype,ELISA was used to measure P53 antibody,and electrochemical luminescence was used to measure AFP-L3. The t-test and the Kruskal-Wallis H test were used for comparison between two groups; the chi-square test was used for comparison of categorical data between two groups. The logistic regression analysis and the receiver operating characteristic( ROC) curve were used to compare the value of each index in the diagnosis of HCV-HCC. Results Compared with the control group,the HCV-HCC group had a significantly higher proportion of patients with HCV 1 b genotype or AFP-L3 and a significantly higher level of P53 antibody( χ2=5. 714,Z =-9. 27,Z =-9. 92,all P < 0. 05). The logistic regression analysis showed that HCV genotype,AFP-L3,and P53 antibody had significant effects on HCV-HCC( all P < 0. 05). The above indices were fitted to establish a model of Logit( Y) =-3. 881 +0. 031 X(AFP-L3( %))+ 0. 043 XP53+ 1. 218 X(HCV genotype),in which Y was the positive probability value of combined determination. In the screening of HCV-HCC,Y had a significantly larger area under the ROC curve than HCV genotype( 0. 945 vs 0. 758,Z = 6. 17,P < 0. 001),AFP-L3( 0. 945 vs 0. 863,Z = 3. 97,P < 0. 001),and P53 antibody( 0. 945 vs 0. 887,Z = 3. 07,P = 0. 002). Y had higher AUC( 0.945),sensitivity( 90. 90%),specificity( 94. 00%),positive predictive value( 93. 80%),negative predictive value( 91. 16%),and diagnostic accuracy( 92. 44%) than each index alone. Conclusion HCV 1 b genotype,AFP-L3,and P53 antibody level are associated with the risk of HCV-HCC,and the combined determination of the three indices has important clinical significance in the early diagnosis of HCV-HCC.

Downregulation of miR-196b in regulating the growth and apoptosis of hepatoma cells by targeting nuclear apoptosis-inducing factor 1

Xiao ErHui, Ning HuiBin, Kang YueHua, Yin Hui, Ma Li, Mao ZhongShan, Zhao Yan, Shang Jia

2020, 36(10): 2230-2235. DOI: 10.3969/j.issn.1001-5256.2020.10.014

Abstract(859)

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Objective To investigate the mechanism of action of miR-196 b in regulating the growth and apoptosis of hepatoma cells by targeting nuclear apoptosis-inducing factor 1( NAIF1). Methods Real-time PCR was used to measure the expression of miR-196 b in hepatoma HuH-7,SNU-449,HepG2,and SMCC7721 cells versus normal human HL7702 hepatocytes. The hepatoma HepG2 cells were collected and divided into Control group( blank control),Anti-NC group( transfected with inhibitor control),Anti-miR-196 b group( transfected with miR-196 b inhibitor),si-NC group( transfected with siRNA control),si-NAIF1 group( transfected with NAIF1 siRNA),Anti-miR-196 b + si-NAIF1 group( co-transfected with miR-196 b inhibitor and NAIF1 siRNA),and Anti-miR-196 b + si-NC group( co-transfected with miR-196 b inhibitor and siRNA control). MTT assay was used to measure the change in proliferation,plate colony formation assay was used to measure colony formation ability,flow cytometry was used to measure cell apoptosis,and Western blot was used to measure the protein expression of Bax and C-caspase-3. Target gene prediction software predicted that NAIF1 might be a target gene of miR-196 b,and the luciferase reporting system was used to identify the targeting relationship. The t-test was used for comparison of continuous data between two groups; a one-way analysis of variance was used for comparison between multiple groups,and the SNK-q test was used for further comparison between two groups. Results There was a significant difference in the expression level of miR-196 b between hepatoma Hu H-7,SNU-449,Hep G2,and SMCC7721 cells and normal human HL7702 hepatocytes( 1. 85 ± 0. 16/1. 63 ±0. 12/2. 36 ± 0. 25/1. 92 ± 0. 13 vs 1. 00 ± 0. 09,F = 29. 05,P < 0. 001). Compared with the Anti-NC group,the Anti-miR-196 b group had significant reductions in the expression level of miR-196 b( 0. 42 ± 0. 03 vs 1. 02 ± 0. 10,P < 0. 05),cell proliferation( 0. 20 ±0. 02 vs 0. 30 ± 0. 05,P < 0. 05),and colony formation ability( 64. 35 ± 6. 97 vs 119. 54 ± 11. 82,P < 0. 05) and significant increases in apoptosis rate( 22. 30% ± 2. 09% vs 4. 26% ± 0. 35%,P < 0. 05) and relative protein expression of Bax( 0. 69 ± 0. 08 vs 0. 30 ± 0. 05,P < 0. 05) and C-caspase-3( 0. 63 ± 0. 05 vs 0. 21 ± 0. 04,P < 0. 05). Compared with the si-NC group,the si-NAIF1 group had significant increases in proliferation ability( 0. 46 ± 0. 05 vs 0. 31 ± 0. 04,P < 0. 05) and colony formation ability( 138. 92 ± 9. 66 vs 118. 47 ±8. 38,P < 0. 05) and significant reductions in apoptosis rate( 4. 12% ± 0. 40% vs 1. 23% ± 0. 12%,P < 0. 05),NAIF1( 0. 10 ± 0. 01 vs0. 17 ± 0. 02,P < 0. 05),and protein expression of Bax( 0. 18 ± 0. 02 vs 0. 29 ± 0. 03,P < 0. 05) and C-caspase-3( 0. 12 ± 0. 01 vs0. 20 ± 0. 03,P < 0. 05). Compared with the Anti-miR-196 b + si-NC group,the Anti-miR-196 b + si-NAIF1 group had significant increases in proliferation ability( 0. 28 ± 0. 02 vs 0. 21 ± 0. 03,P < 0. 05) and colony formation ability( 97. 12 ± 8. 23 vs 66. 35 ± 5. 20,P < 0. 05) and significant reductions in apoptosis rate( 9. 60% ± 1. 11% vs 21. 14% ± 1. 32%,P < 0. 05),NAIF1( 0. 30 ± 0. 04 vs 0. 52 ±0. 06,P < 0. 05),and protein expression of Bax( 0. 28 ± 0. 03 vs 0. 67 ± 0. 06,P < 0. 05) and C-caspase-3( 0. 22 ± 0. 05 vs 0. 60 ±0. 04,P < 0. 05). Conclusion Downregulation of miR-196 b can inhibit the growth and induce the apoptosis of hepatoma cells via negative regulation of NAIF1.

Correlation of miRNA-181c expression in peripheral blood mononuclear cells with interferon-γ,chemokine( C-X-C motif) ligand 10,and Toll-like receptor 4 in children with autoimmune hepatitis

Cui HaiXia, Jin ChunMei, Wu ZhengXie, Jin AiHua, Zhang MeiLan

2020, 36(10): 2236-2240. DOI: 10.3969/j.issn.1001-5256.2020.10.015

Abstract(946)

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Objective To investigate the correlation of miR-181 c expression in peripheral blood mononuclear cells( PBMCs) with interferon-γ( IFN-γ),chemokine( C-X-C motif) ligand 10( CXCL10),and Toll-like receptor 4( TLR4) in children with autoimmune hepatitis( AIH). Methods A total of 27 children with AIH who were admitted to The Affiliated Hospital of Yanbian University from March2015 to May 2019 were enrolled as AIH group,and 30 healthy children who underwent physical examination during the same period of were enrolled as control group. The expression of miR-181 c in PBMCs and the expression of IFN-γ,CXCL10,and TLR4 were measured for the two groups. The t-test was used for comparison of normally distributed continuous data between two groups,and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups. The Pearson correlation coefficient was used to investigate the correlation of miR-181 c expression with each index,and a logistic regression analysis was used to investigate the influence of each factor on AIH. Results Compared with the control group,the AIH group had significantly higher levels of the liver function parameters aspartate aminotransferase( AST),alanine aminotransferase( ALT),gamma-glutamyl transpeptidase( GGT),and total bilirubin( TBil)( t = 14. 445,20. 064,11. 728,13. 822,all P < 0. 001). The AIH group also had significantly higher levels of IgA,IgM,and IgG than the control group( t = 7. 772,5. 147,and6. 771,all P < 0. 05). The AIH group had significantly lower relative expression of miR-181 c in PBMCs than the control group( 0. 784 ±0. 173 vs 1. 106 ± 0. 224,t = 5. 819,P < 0. 05). Compared with the control group,the AIH group had significantly higher levels of IFN-γ and CXCL10 and mRNA expression of TLR4( t = 6. 949,12. 303,and 13. 835,all P < 0. 05). The correlation analysis showed that in the children with AIH,the expression of miR-181 c in PBMCs was negatively correlated with IFN-γ,CXCL10,TLR4,AST,ALT,GGT,TBil,and Ig G( r =-0. 316,-0. 348,-0. 322,-0. 427,-0. 442,-0. 408,-0. 396,and-0. 321,all P < 0. 05). The univariate logistic regression analysis showed that AST,ALT,GGT,TBil,IFN-γ,CXCL10,TLR4 mRNA,and miR-181 c were all included in the regression model( all P < 0. 05) and were the influencing factors for the onset of AIH. Conclusion Children with AIH have downregulated expression of miR-181 c in PBMCs,which is closely associated with IFN-γ,CXCL10,and TLR4,suggesting that miR-181 c may affect the development of AIH in children by regulating the immune system.

Efficacy and safety of sodium-glucose co-transporter 2 inhibitors in treatment of type 2 diabetes mellitus with nonalcoholic fatty liver disease: A meta-analysis

Li XiaoJing, Sun YuanLong, Zhang BinBin, Mei ZuBing, Feng Qin, Hu YiYang

2020, 36(10): 2241-2247. DOI: 10.3969/j.issn.1001-5256.2020.10.016

Abstract(398)

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Objective To systematically review the efficacy and safety of sodium-glucose co-transporter 2( SGLT2) inhibitors in the treatment of type 2 diabetes mellitus( T2 DM) with nonalcoholic fatty liver disease( NAFLD). Methods Foreign databases( PubMed,Cochrane Library,and Embase) and Chinese databases( CNKI,VIP,and Wanfang Data) were searched for articles published up to March2020. Keywords were used to screen out eligible studies,related scales were used to evaluate the quality of articles,and RevMan 5. 3 and Stata 15. 0 were used to perform the meta-analysis. Results A total of 9 cohort studies and 5 randomized controlled trials( RCTs) were included,with 605 patients in total. The meta-analysis of main observation indices showed that SGLT2 inhibitors significantly inhibited alanine aminotransferase( ALT)( mean difference [MD]=-24. 22,95% confidence interval [CI]:-29. 54 to-18. 89,P < 0. 001) and hemoglobin A1 c( Hb A1 c)( MD =-0. 53,95% CI:-0. 74 to-0. 32,P < 0. 001) in cohort studies,as well as ALT( MD =-12. 51,95% CI:-15. 61 to-9. 41,P < 0. 001) and HbA1 c( MD =-0. 54,95% CI:-0. 80 to-0. 27,P < 0. 001) in RCTs. The analysis of secondary observation indices showed that SGLT2 inhibitors significantly improved body mass index( P < 0. 001),fat mass( P < 0. 001),hepatic fat fraction( P < 0. 001),gamma-glutamyl transpeptidase( P < 0. 001),fasting blood glucose( P < 0. 001),serum ferritin( P <0. 001),and serum type Ⅳ collagen 7 S( P = 0. 02). There was a significant difference in the result of the meta-analysis of aspartate aminotransferase between RCTs( P = 0. 16) and cohort studies( P < 0. 001). After the administration of SGLT2 inhibitors,there were significant increases in the incidence rates of decreased body fluid volume( risk ratio [RR]= 7. 67,95% CI: 1. 45-40. 42,P = 0. 02),urinary tract infection( RR = 4. 27,95% CI: 1. 11-16. 43,P = 0. 03),and reproductive system infection( RR = 3. 76,95% CI: 1. 21-11. 69,P =0. 02). Conclusion Current evidence suggests that SGLT2 inhibitors can reduce body mass,blood glucose,liver enzymes,and liver fat content in patients with T2 DM and NAFLD and improve liver fibrosis to a certain degree,but they can increase the risk of fluid loss and reproductive system infection in patients. More studies are needed for further verification.

Clinical features and changing trend of elderly patients with drug-induced liver injury in The Fifth Medical Center of Chinese PLA General Hospital from 2009 to 2019

Wang LiPing, He TingTing, Cui YanFei, Wang ZhongXia, Jing Jing, Wang LiFu, Zhu Yun, Sun YongQiang, Xu WenTao, Yu SiMiao, Sang XiuXiu, Tian Miao, Ren YueBo, Wang RuiLin

2020, 36(10): 2248-2252. DOI: 10.3969/j.issn.1001-5256.2020.10.017

Abstract(1115)

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Abstract:
Objective To investigate the features and changing trend of drug-induced liver injury( DILI) in the elderly from 2009 to2019,and to provide a reference for clinical prevention and treatment of DILI in the elderly. Methods A retrospective analysis was performed for the clinical data of 2107 elderly patients,aged ≥60 years,who were diagnosed with DILI in The Fifth Medical Center of Chinese PLA General Hospital from January 2009 to December 2019,and they were divided into groups according to age. Related clinical data were analyzed,including age,sex,clinical features,prognosis,and regional distribution. The Chi-square test was used for comparison of categorical data between groups. Results Among the 2107 patients with DILI,there were 802 male patients and 1305 female patients,with a male/female ratio of 1∶ 1. 63. Cholestasis type was the most common clinical type and was observed in 1439 patients( 68. 3%). There was the highest number of patients in the 60-64 years group( 942 patients,44. 7%),among whom 618( 65. 6%) were female,589( 62. 5%)had cholestasis type,471( 50. 0%) had chronic DILI,421( 44. 7%) had drug-induced liver cirrhosis,and 25( 2. 7%) had drug-induced liver failure. There were 187 patients in the 75-79 years group,among whom 110( 58. 8%) patients were male,137( 73. 3%) had cholestasis type,114( 60. 9%) had liver cirrhosis,4( 2. 1%) had drug-induced liver failure. The results showed that chronic DILI was more common in the 60-64 years group,and liver cirrhosis was more common in the 75-79 years group. As for prognosis,in the 60-64 years group,27 patients( 2. 9%) were cured,885( 93. 9%) were improved,30( 3. 2%) had no response or died; in the 65-69 years group,16( 2. 8%) were cured,528( 92. 0%) were improved,and 30( 5. 2%) had no response or died; in the 70-74 years group,9( 2. 8%) were cured,305( 94. 1%) were improved,and 10( 3. 6%) had no response or died. The results showed that there was no significant difference in mortality rate between the different age groups( P > 0. 05). The proportion of elderly DILI patients among hospitalized DILI patients increased from 15. 90% in 2009 to 22. 05% in 2013 and 27. 51% in 2019,with a 1. 73-fold increase in 11 years. As for regional distribution,the patients in North China accounted for the highest proportion of 47. 08%( the patients from Hebei,Shanxi,and Inner Mongolia accounted for 24. 92%,10. 96%,and 10. 25%,respectively),followed by those in Northeast China who accounted for 17. 85%.The patients in Beijing accounted for 11. 53%. Conclusion The proportion of elderly DILI patients among hospitalized DILI patients tends to increase in these years. Cholestasis type is the most common clinical type,and most of the patients with this clinical type progress to chronic DILI and drug-induced liver cirrhosis. Early diagnosis,early intervention,and standardized treatment of elderly DILI should be taken seriously.

Clinical features of DRESS,AOSD,HLH with liver injury: An analysis of 58 cases

Cheng Hao, Pan Jing, Yao TianTian, Wang GuiQiang, Wang Yan

2020, 36(10): 2253-2257. DOI: 10.3969/j.issn.1001-5256.2020.10.018

Abstract(989)

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Objective To investigate the clinical features of adult liver injury patients with drug reaction with eosinophilia and systemic symptoms( DRESS),adult-onset Still's disease( AOSD) or hemophagocytic lymphohistiocytosis( HLH) and the correlation of the degree of liver injury with inflammatory indices and immune indices. Methods Related clinical data were collected from 58 patients with liver injury caused by the above three systemic inflammatory diseases who were admitted to Peking University First Hospital from January 2008 to April2019,among whom 7 had DRESS,29 had AOSD,and 22 had HLH. General information,liver biochemical parameters,inflammatory indices,and immune indices were collected before treatment. The t-test was used for comparison of normally distributed continuous data between two groups; a one-way analysis of variance was used for comparison between multiple groups,and the least significant difference t-test was used for further comparison between two groups. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the Kruskal-Wallis H test was used for comparison between multiple groups,and the Bonferroni method was used for further comparison between two groups. Four inflammatory indices were compared between the groups with different alanine aminotransferase( ALT) levels( ≤200 U/L or > 200 U/L),and a Spearman correlation analysis was used to investigate the correlation of ferritin and immune indices with ALT level. Results The median age of the patients with DRESS or AOSD was 38 years,and the median age of the patients with HLH was 34 years. DRESS patients were mostly male( 5/7,71%),while most of AOSD patients( 20/29,69%)and HLH patients( 12/22,55%) were female. For liver injury indices,there were no significant differences between the three groups in ALT peak,aspartate aminotransferase level,and alkaline phosphatase level( all P > 0. 05). For the indices for the synthetic function of the liver,there were no significant differences in blood glucose,albumin,and prothrombin activity between the three groups( all P > 0. 05).For inflammatory indicators,there were significant differences between the three groups in erythrocyte sedimentation rate( ESR) and C-reactive protein( CRP)( all P < 0. 001),while there were no significant differences between the three groups in lactate dehydrogenase,ferritin,and procalcitonin( all P > 0. 05); the AOSD group had significantly higher median CRP and ESR than the other two groups( all P <0. 05). For the patients with the three diseases,there were no significant differences in the four inflammatory indices between any two the groups with different ALT levels( all P > 0. 05),and the level of ferritin was positively correlated with ALT level( R2= 0. 702 1,P < 0. 000 1).As for immune indices,there were no significant differences in Ig G,Ig A,C4,and the counts of NK and B cells between the three groups( P > 0. 05),and CD8+T cells were positively correlated with ALT level in HLH patients( R2= 0. 969 6,P < 0. 000 1). Conclusion Varying degrees of liver injury are observed in patients with DRESS,AOSD or HLH. Ferritin and CD8+T cells are well correlated with ALT level and can reflect liver injury,systemic inflammation,and immune status in patients with the three diseases,and therefore,they may become important indices for evaluating disease condition,guiding treatment,and judging treatment outcome and prognosis.

Clinical features of liver function and coagulation function in patients with Alongshan virus infection

Zhang Li, Lu: XiaoLong, Xu HongQin, Wang ZeDong, Wang Wei, Wang Bo, Wei Wei, Niu JunQi, Han ShuZhen, Liu Quan

2020, 36(10): 2258-2260. DOI: 10.3969/j.issn.1001-5256.2020.10.019

Abstract(969)

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Objective To investigate the clinical features of liver function and coagulation function in patients with Alongshan virus( ALSV) infection. Methods Clinical data were collected from 27 patients with ALSV infection who were admitted to Inner Mongolia General Forestry Hospital from May 2018 to September 2019,among whom there were 18 male patients and 9 female patients. Related data were extracted,and a database of relevant case reports was established. The descriptive epidemiological method was used to analyze the clinical features of liver function and coagulation markers,and the features of liver injury caused by ALSV infection were analyzed. Results For the27 patients,the abnormal rates of alanine aminotransferase( ALT),aspartate aminotransferase( AST),alkaline phosphatase( ALP),gamma-glutamyl transpeptidase( GGT),cholinesterase,and total bile acid were 25. 9%,33. 3%,25. 9%,40. 7%,8%,and 8%,respectively; among the 27 patients,4( 14. 8%) had an ALT level of > 2 × upper limit of normal( ULN),3( 11. 1%) had an AST level of >2 × ULN,1( 3. 7%) had an ALP level of > 2 × ULN,and 5( 18. 5%) had a GGT level of > 2 × ULN. Among the 27 patients,25( 17 male patients and 8 female patients) had the results of bilirubin test,among whom 1 had a reduction in total bilirubin( TBil)( 3. 30 μmol/L) and 3 had an increase in TBil( 23. 7 μmol/L,26. 2 μmol/L,and 32 μmol/L,respectively). The abnormal rates of the coagulation markers international normalized ratio,activated partial thromboplastin time,and fibrinogen were 3. 7%,11. 1%,and 22. 2%,respectively. Conclusion There is a certain degree of liver injury in patients with ALSV infection,generally with mild symptoms.

Clinical features of Caroli disease: An analysis of 41 cases

Cui YanFei, Yu SiMiao, Tian Miao, Sang XiuXiu, Wang LiFu, Sun YongQiang, Jing Jing, Wang ZhongXia, Wang LiPing, Xu WenTao, Wang RuiLin

2020, 36(10): 2261-2265. DOI: 10.3969/j.issn.1001-5256.2020.10.020

Abstract(868)

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Objective To investigate the clinical features of patients with Caroli disease. Methods The clinical data were collected from41 patients who were diagnosed with Caroli disease in The Fifth Medical Center of Chinese PLA General Hospital from April 2015 to January2020,and the patients were divided into type I group with 16 patients and type Ⅱ group with 25 patients. A retrospective analysis was performed for general information,laboratory markers,and clinical features. The independent samples t-test was used for comparison of normally distributed continuous data between groups,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data; a Spearman correlation analysis was also performed. Results The type Ⅰ group had a significantly higher level of albumin( Alb) than the type Ⅱ group( t = 0. 976,P = 0. 048),and the type Ⅱ group had a significantly higher prothrombin time( PT) than the type I group( Z = 3. 115,P = 0. 001). Compared with the type I group,the type Ⅱ group had significantly higher incidence rates of esophageal and gastric varices,upper gastrointestinal bleeding and/or tarry stool,and portal hypertension( χ2= 6. 077,5. 468,and 2. 403,P = 0. 002,0. 019,and 0. 028). In the patients with type Ⅱ Caroli disease,the level of cholinesterase was negatively correlated with the incidence rates of esophageal and gastric varices and portal hypertension( r =-0. 468 and-0. 436,P = 0. 018 and 0. 029); Alb level was negatively correlated with the incidence rate of esophageal and gastric varices( r =-0. 561,P = 0. 004); red blood cell count was negatively correlated with the incidence rates of esophageal and gastric varices,upper gastrointestinal bleeding and/or tarry stool,and portal hypertension( r =-0. 662,-0. 566,and-0. 436,P < 0. 001,P = 0. 003,and P = 0. 029); hemoglobin count was negatively correlated with the incidence rates of esophageal and gastric varices,upper gastrointestinal bleeding and/or tarry stool,and portal hypertension( r =-0. 605,-0. 590,and-0. 510,P = 0. 001,0. 002,and 0. 009); PT was positively correlated with the incidence rates of esophageal varices and portal hypertension( r = 0. 488 and 0. 520,P = 0. 013 and 0. 008).Conclusion Compared with the patients with type I Caroli disease,the patients with type Ⅱ Caroli disease have a higher incidence rates of esophageal and gastric varices,upper gastrointestinal bleeding and/or tarry stool,and portal hypertension,with the changes in clinical indicators such as the decrease of Alb level and the increase of PT level,and they tend to have poor prognosis.

Efficacy and safety of lenvatinib for unresectable,advanced hepatocellular carcinoma in a real-world setting

Li GuangXin, Zhang Yu, Yang YanMei, Wang Yi, Li Gong

2020, 36(10): 2266-2269. DOI: 10.3969/j.issn.1001-5256.2020.10.021

Abstract(951)

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Sarcomatoid carcinomas of the liver,gallbladder,and pancreas: A clinicopathological portrait and literature review

Cheng JieYao, Wang CangHai, Chen JianHong, Ding PengPeng, Du XueMei, Li Li, Wang YaDan, Wei Nan, Liu Hong

2020, 36(10): 2270-2273. DOI: 10.3969/j.issn.1001-5256.2020.10.022

Abstract(850)

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Clinical features of acquired hepatocerebral degeneration: An analysis of 6 cases

Tang TongDan, Zhu Lei, Liu YongHua

2020, 36(10): 2274-2275. DOI: 10.3969/j.issn.1001-5256.2020.10.023

Abstract(1026)

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Spontaneous rupture of small hepatic hemangioma: A case report

Zhao HongYu, Liang Wei, Wang YongFei, Du ZhiJian, Zhang MengYang, Han JingZhao

2020, 36(10): 2276-2278. DOI: 10.3969/j.issn.1001-5256.2020.10.024

Abstract(969)

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Liver abscess caused by Eikenella corrodens: A case report

Wang WenJun, Wu WenHua, Xue HongAn

2020, 36(10): 2279-2282. DOI: 10.3969/j.issn.1001-5256.2020.10.025

Abstract(906)

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A case of isolated hilar lymph node tuberculosis

Tang ChaoHui, Wang ShouQian, Li ChangXu, Liu YaHui, Wang YingChao

2020, 36(10): 2283-2284. DOI: 10.3969/j.issn.1001-5256.2020.10.026

Abstract(760)

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Multiple low-density foci in the liver with pulmonary embolism diagnosed as clonorchiasis: A case report

Jiang ShanMing, Huang JiKang, Liang QiDong, Liu Bin

2020, 36(10): 2285-2287. DOI: 10.3969/j.issn.1001-5256.2020.10.027

Abstract(866)

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Liver transplantation for idiopathic portal hypertension: A case report

Ma Bo, Zhang Yu, Zhang XiaoXue, Yang QianQian, Chen QingLing, Wen XiaoYu, Jin QingLong

2020, 36(10): 2288-2290. DOI: 10.3969/j.issn.1001-5256.2020.10.028

Abstract(805)

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A case of right-sided colon adenocarcinoma with gallbladder invasion and bilateral testicular metastasis

Lu XiangFeng, Jing Tao, Qin WeiNa, Zhang ShuXin, Dai Xin

2020, 36(10): 2291-2294. DOI: 10.3969/j.issn.1001-5256.2020.10.029

Abstract(713)

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Bouveret's syndrome: A case of surgical treatment and literature review

Dong ChaoQun, Chen YingGuo, Wu ShunLi, Wang HongBo

2020, 36(10): 2295-2297. DOI: 10.3969/j.issn.1001-5256.2020.10.030

Abstract(916)

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An overview of new antiviral drugs under research for chronic hepatitis B

He YinWu, Wang JianHua

2020, 36(10): 2298-2304. DOI: 10.3969/j.issn.1001-5256.2020.10.031

Abstract(720)

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Chronic hepatitis B caused by hepatitis B virus( HBV) infection remains a major public health problem worldwide,and functional cure and even complete cure of chronic hepatitis B are the goals pursued by drug researchers. At present,widely used nucleos( t) ide analogues and interferon therapy fail to achieve a high cure rate. This article reviews the anti-HBV drugs/therapies under research,including viral entry inhibitors,capsid inhibitors,HBsAg inhibitors,immune modulators,gene editing,and cell therapies,and summarizes related clinical research findings,so as to clarify the latest advances in this field and the new ideas in drug research and development.

Advances in economic analysis and screening strategies for hepatitis C screening

Ren TianQi, Li LaMei, Yang QianQian, Zhang Xia, Luo LiTing, Niu JunQi

2020, 36(10): 2305-2309. DOI: 10.3969/j.issn.1001-5256.2020.10.032

Abstract(590)

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With the appearance of direct-acting antivirals( DAAs),breakthroughs have been achieved in the antiviral therapy for hepatitis C and hepatitis C patients can be cured completely. Due to the insidious onset of hepatitis C,most patients do not know their own conditions,and thus expanding diagnosis and treatment through screening is the key to the elimination of hepatitis C. However,hepatitis C virus is distributed widely and unevenly in the world,which results in difficulties in the screening and diagnosis of hepatitis C. This article introduces the current economic research on hepatitis C screening,analyzes the factors affecting the cost-effectiveness of hepatitis C screening,and shares the strategies and advances for hepatitis C elimination in other countries,so as to provide a reference for eliminating hepatitis C in China.

Application of ultrasound elastography in evaluating portal hypertension

Lin JingQi, Tian Bing, Deng BaoCheng

2020, 36(10): 2310-2314. DOI: 10.3969/j.issn.1001-5256.2020.10.033

Abstract(452)

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Portal hypertension( PH) is a common clinical syndrome,and the main risk factor for death is esophageal variceal bleeding.Therefore,the early and accurate diagnosis of PH can reduce the incidence rate of serious complications and mortality rate. Hepatic venous pressure gradient,as a main method for the diagnosis of PH,has certain limitations in clinical application,and thus it is necessary to explore new noninvasive diagnostic techniques. Up to now,ultrasound elastography has become one of the important methods for the noninvasive assessment of PH. This article elaborates on its current application and prospects in the assessment of PH.

Research advances in the risk prediction models for chronic hepatitis B-related hepatocellular carcinoma

Shi Ke, Zhang Qun, Li YuXin, Wang XianBo

2020, 36(10): 2315-2319. DOI: 10.3969/j.issn.1001-5256.2020.10.034

Abstract(589)

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Hepatocellular carcinoma is the third common cause of cancer-related death,and early diagnosis of hepatocellular carcinoma has great influence on the prognosis of patients. This article summarizes the risk prediction models for chronic hepatitis B-related hepatocellular carcinoma in the recent 5 years,and the analysis shows that the prediction models for hepatocellular carcinoma have important clinical significance in risk stratification and individualized monitoring strategy for patients.

Advances in targeted therapy and immunotherapy for hepatocelluar carcinoma

Wei JianYing, Sun Wei, Liu XiaoMin, Chen JingLong

2020, 36(10): 2320-2324. DOI: 10.3969/j.issn.1001-5256.2020.10.035

Abstract(602)

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There are still high incidence and mortality rates of hepatocellular carcinoma at present,and systemic treatment plays an important role in the treatment of advanced hepatocellular carcinoma. This article describes the application of molecular-targeted drugs and immune checkpoint inhibitors in hepatocellular carcinoma and points out that dual-targeted therapy,dual immunotherapy,and targeted therapy combined with immunotherapy are the current research hotspots in the treatment of hepatocellular carcinoma.

Research advances in apatinib combined with transcatheter arterial embolization in the treatment of hepatocellular carcinoma

Zhu ZeMin, Zhao ZhiJian, Tang CaiXi

2020, 36(10): 2325-2328. DOI: 10.3969/j.issn.1001-5256.2020.10.036

Abstract(458)

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Hepatocellular carcinoma( HCC) is a common malignant tumor that threatens the health of all mankind,and its incidence and mortality rates keep increasing in recent years. Most patients are in the advanced stage at the time of confirmed diagnosis and are unable to undergo potential therapeutic surgery. Transcatheter arterial chemoembolization( TACE) and the anti-angiogenic drug apatinib are two palliative treatments for HCC. At present,apatinib combined with TACE is still a new treatment method for HCC in clinical practice,and there are still controversies over its efficacy and safety,which needs further studies. This article reviews the research advances in apatinib combined with TACE in the treatment of HCC.

Association between diabetes and nonalcoholic fatty liver disease-related hepatocellular carcinoma

Zhang YongChao, Li Wei

2020, 36(10): 2329-2332. DOI: 10.3969/j.issn.1001-5256.2020.10.037

Abstract(466)

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Hepatocellular carcinoma( HCC) is one of the most common malignant tumors. With the development of antiviral therapy and the changes in lifestyle,the main pathogenic factor of HCC gradually changes from viral hepatitis to nonalcoholic fatty liver disease. Diabetes mellitus is a common chronic disease,and at present,there is an increasing number of patients with both nonalcoholic fatty liver disease and diabetes. Nonalcoholic fatty liver disease and diabetes share some common mechanisms,and diabetes may promote the progression of nonalcoholic fatty liver disease and increase the risk of HCC. This article reviews the association of diabetes and nonalcoholic fatty liver disease with HCC.

Role of exosomes in hepatocellular carcinoma

Yao YunTing, Zhou YuanZhong, Liu Jun

2020, 36(10): 2333-2339. DOI: 10.3969/j.issn.1001-5256.2020.10.038

Abstract(479)

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Exosomes are vesicles with a diameter of about 50-150 nm released by a variety of cells and contain miRNA,mRNA,and protein,with the potential to regulate the signal transduction pathways in receptor cells. Exosomes provide nucleic acids and proteins to coordinate cell-cell communication and microenvironment regulation. This article summarizes the latest research advances in the role of exosomes in hepatocellular carcinoma( HCC) and analyzes the effect of exosomes on the development and progression of HCC,including chemotherapy resistance,epithelial-mesenchymal transition,angiogenesis,metastasis,and immune response. The analysis shows that exosomes have a promising future in the treatment of HCC.

Mechanism of action of circular RNAs in hepatocellular carcinoma

Guo Xuan, Tan Wei, Wang ChangJun

2020, 36(10): 2340-2343. DOI: 10.3969/j.issn.1001-5256.2020.10.039

Abstract(495)

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Hepatocellular carcinoma( HCC) is one of the leading causes of cancer-related death worldwide and has high mortality and recurrence rates and low survival rates. Circular RNAs( circRNAs) are a class of single-stranded closed circular RNA molecules with tissue-and development-specific expression and play a regulatory role in organisms. These circRNAs regulate the progression of HCC by acting as miRNA sponges and targeted protein-coding genes,but the basic mechanism is still unclear. This article summarizes the formation mechanism and biological functions of circRNAs,reviews the research advances in the role of circRNAs in the pathogenesis of HCC,and points out their potential value as diagnostic markers and therapeutic targets for HCC.

Mechanism of liver regeneration after associating liver partition and portal vein ligation for staged hepatectomy

Ceng TaoFei, Chen GuangLei, Liu CaiGang, Dai ChaoLiu, Xu Feng

2020, 36(10): 2344-2348. DOI: 10.3969/j.issn.1001-5256.2020.10.040

Abstract(746)

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Insufficient volume of future liver remnant( FLR) often leads to the complications including liver failure and even death and thus remains a bottleneck for liver surgery. Associating liver partition and portal vein ligation for staged hepatectomy( ALPPS) is a newly developed two-stage hepatectomy procedure which can promote rapid regeneration of FLR,but the related mechanism has not yet been elucidated. With reference to the recent research advances in China and foreign countries,this article reviews the hemodynamic and humoral factors for ALPPS in promoting liver regeneration,the effect of ALPPS on liver parenchymal cells,and the role of non-parenchymal liver cells( including hepatic stellate cells,natural killer cells,macrophages,and liver progenitor/stem cells) in regulating liver regeneration. It is pointed out that the interaction between non-parenchymal liver cells and parenchymal cells is a hotspot in the research on the mechanism of liver regeneration after ALPPS.

Role of liver X receptor in nonalcoholic fatty liver disease

Li WenMi, Wang Nan, Bian Qian, Huang Qian, Li JingTao, Wei HaiLiang, Yan ShuGuang

2020, 36(10): 2349-2352. DOI: 10.3969/j.issn.1001-5256.2020.10.041

Abstract(620)

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Excessive lipid deposition,liver injury,and insulin resistance are hallmarks in the development and progression of nonalcoholic fatty liver disease( NAFLD). Liver X receptor( LXR) is a transcriptional regulator,and its two cell subtypes,LXRα and LXRβ,play a key role in regulating cholesterol metabolism,inducing anti-inflammation,and reducing insulin resistance. This article reviews the structure and function of LXR and its association with the pathogenesis of NAFLD,in order to provide new ideas and methods for the prevention and treatment of NAFLD.

Mechanism of mitochondrial dysfunction in the development of nonalcoholic fatty liver disease

Xu ZiXin, Luo ShengZheng, Xu MingYi

2020, 36(10): 2353-2355. DOI: 10.3969/j.issn.1001-5256.2020.10.042

Abstract(693)

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Nonalcoholic fatty liver disease( NAFLD) includes a series of diseases affected by various complex factors. Mitochondrial dysfunction often occurs in NAFLD and may lead to the progression of hepatitis and liver fibrosis. This article reviews the important role of mitochondrial oxidative stress,respiration,energy metabolism,quality control,and mitochondrial DNA in NAFLD and summarizes the current status of mitochondria-targeted therapy for NAFLD,hoping to provide a new direction for the research and clinical treatment of NAFLD.

Reexamination of the diagnosis of fatty liver disease under the background of disease spectrum progression

Niu ChunYan, Liu Qin, Luo XiaoChun

2020, 36(10): 2356-2359. DOI: 10.3969/j.issn.1001-5256.2020.10.043

Abstract(497)

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Recent studies have shown that metabolic syndrome( MetS),e. g.,obesity,diabetes mellitus,insulin resistance,and nonalcoholic fatty liver disease( NAFLD),and drinking coexist in a considerable number of individuals,suggesting the overlap of alcoholic liver disease( ALD) and NAFLD promotes the development and progression of fatty liver disease and aggravates the adverse outcome of fatty liver disease in a synergistic and interactive way. The evolution of the disease spectrum of fatty liver disease challenges the exclusive diagnosis system which divides fatty liver disease into ALD and NAFLD. This article summarizes the research advances in recent years and introduce the latest international consensus on the renaming of NAFLD,aiming to pay attention to the influence of drinking and MetS on NAFLD,put forward our insights into the diagnosis of fatty liver disease,and thus provide a new basis for reexamination the diagnosis and individualized treatment of fatty liver disease.

Mechanism of action and clinical application of 17β-hydroxysteroid dehydrogenase 13 in alcohol-related liver diseases

Li Li, Chen HaiZhen, Huang Jing

2020, 36(10): 2360-2363. DOI: 10.3969/j.issn.1001-5256.2020.10.044

Abstract(775)

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As a new hepatocyte-specific lipid droplet-related protein,17β-hydroxysteroid dehydrogenase 13( HSD17 B13) is involved in hepatocyte lipid synthesis. Recent studies have shown that an insertion-deletion variant of the HSD17 B13 gene is associated with a reduced risk of chronic liver diseases; however,the specific biological function of HSD17 B13 and its involvement in the pathogenesis of liver diseases remain unclear. This article elaborates on the biological function of HSD17 B13,its mechanism of action in alcohol-related liver,and the research advances in clinical application.

Role of matrix metalloproteinases-2 and matrix metalloproteinases-9 in the development and progression of chronic liver diseases

Yang ShangQing, Yang DongLiang, Liu Jia

2020, 36(10): 2364-2369. DOI: 10.3969/j.issn.1001-5256.2020.10.045

Abstract(466)

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The degradation and remodelling of extracellular matrix are important pathophysiological phenomena during the progression of various chronic liver diseases. With the expanded research on matrix metalloproteinases( MMPs) in recent years,it has been found that MMPs can affect the degradation and remodelling of extracellular matrix,participate in the regulation of inflammation and immune responses through various mechanisms,and thus participate in the progression of liver diseases. This article reviews the basic characteristics of matrix metalloproteinase-2 and matrix metalloproteinase-9,their regulatory mechanisms,and their role in the development and progression of chronic liver diseases,so as to provide a basis for exploring new therapeutic strategies for chronic liver diseases.

Research advances in liver dysfunction in patients with type 2 diabetes

Pan XiuZhen, Qi Yun, Yang Yang

2020, 36(10): 2370-2374. DOI: 10.3969/j.issn.1001-5256.2020.10.046

Abstract(708)

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Abstract:
Diabetes mellitus is an endocrine and metabolic disease characterized by chronic hyperglycemia. Type 2 diabetes is not only the most common type of diabetes,but also the one with the most complications. Studies have shown that besides cerebrovascular and cardiovascular diseases,eye diseases,renal diseases,and nervous system disease,type 2 diabetes also has the complications of hypertension,abnormal blood lipid levels,and abnormal liver function,which can bring serious damage to the body. This article reviews the association between type 2 diabetes and liver dysfunction and related features of these diseases,in order to deepen the understanding of patients with liver dysfunction and type 2 diabetes and provide a reference for clinical diagnosis and treatment.

Mechanism of action of intestinal flora in hepatic encephalopathy and related treatment methods

Ceng ShengLan, Lu: Chao, Xiao WeiSong, Tan XiaoBin, Wu Cong, Mao DeWen

2020, 36(10): 2375-2379. DOI: 10.3969/j.issn.1001-5256.2020.10.047

Abstract(664)

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Abstract:
At present,hepatic encephalopathy has a relatively high mortality and thus greatly affects patients' quality of life. This article describes the changes of intestinal flora in patients with hepatic encephalopathy and analyzes the mechanism of action of intestinal flora in hepatic encephalopathy and related treatment methods. It is pointed out that the development of hepatic encephalopathy is closely associated with intestinal flora,and clinical treatment by regulating intestinal flora has achieved a marked effect in patients with hepatic encephalopathy. In the future,the research on intestinal flora in patients with hepatic encephalopathy can be deepened to provide better regimens for the treatment of hepatic encephalopathy.

Diagnosis and treatment of intrahepatic cholangiocarcinoma: Current status and thoughts

Xia Long, Xia YiJun, Zhang Lei, Zhu ShuGuang, Wu HuiJun, Li Hua, Chen GuiHua

2020, 36(10): 2380-2385. DOI: 10.3969/j.issn.1001-5256.2020.10.048

Abstract(738)

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Abstract:
Intrahepatic cholangiocarcinoma( ICC) is a primary liver cancer with malignant biological behaviors and ranks only second to hepatocellular carcinoma in incidence rate,and in recent years,the incidence and mortality rates of ICC have been increasing significantly.Since ICC has significant different biological characteristics from hepatocellular carcinoma and extrahepatic cholangiocarcinoma,ICC lacks characteristic clinical symptoms and specific tumor markers and has strong invasion,a low surgical resection rate,and a tendency of recurrence and metastasis after surgery,which results in poor overall prognosis. With the development of molecular biology techniques and the accumulation of diagnosis and treatment experience,there is a gradually deepened understanding of the biological characteristics and clinical outcomes of ICC,and the corresponding surgical diagnosis and treatment strategies and technical means are undergoing profound transformation. At present,multidisciplinary comprehensive treatment,mainly surgery,is the mainstream paradigm for the treatment of ICC,and emphasis on R0 resection and regional lymph node dissection helps to improve clinical outcome and prognosis. However,there are still some problems for consideration on the way to the early diagnosis and the precise,standardized,and individualized treatment of ICC.

Advances in the diagnosis and treatment of biliary sludge

Wang XueCai, Zhang QiFang

2020, 36(10): 2386-2390. DOI: 10.3969/j.issn.1001-5256.2020.10.049

Abstract(1043)

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Abstract:
Cholelithiasis is a major health burden and is classified into two types of gallstones and bile duct stones. Biliary sludge is a special type of cholelithiasis and is often known as microlithiasis,microcrystal disease,and bile sand. It has complex clinical manifestations,with no symptoms or various clinical symptoms,and may also lead to serious complications. At present,major diagnostic methods for this disease include ultrasound,computed tomography,magnetic resonance,endoscopic retrograde cholangiopancreatography,intraductal ultrasound,and endoscopic ultrasound,and major treatment methods include traditional Chinese and Western medicine therapy,medical treatment,surgery,and minimally invasive treatment. This article reviews the advances in clinical diagnosis and treatment.

Take responsibility, set sail again-The 13th National Clinical Academic Conference of Liver Diseases & The 3rd Annual Meeting of Huaxia Hepatology Alliance held in Guangzhou, China

Ren Hong, Niu JunQi, Chen ChengWei

2020, 36(10): 2391-2392. DOI: 10.3969/j.issn.1001-5256.2020.10.050

Abstract(208)

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Abstract:

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