中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R

2019 Vol. 35, No. 6

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Editorial
Research status and challenges of HBV cccDNA
Zhang JiMing
2019, 35(6): 1177-1180. DOI: 10.3969/j.issn.1001-5256.2019.06.001
Abstract:
Current antiviral treatment regimens seldom clear hepatitis B virus (HBV) infection and achieve complete cure, and therefore, many patients need long-term or even life-long antiviral therapy with nucleos (t) ide analogues. The root cause is the presence of covalently closed circular DNA (cccDNA) with transcriptional activity within hepatocytes. In order to help readers understand the research advances in HBV cccDNA, this issue invites leading experts in China to introduce the research advances from the following six aspects: anti-HBV treatment and functional cure of chronic hepatitis B, drugs and biotechniques targeting HBV cccDNA, transcriptional regulation of HBV cccDNA and prospects of anti-HBV treatment, in vitro cell models and experimental mouse models of HBV cccDNA, application of in situ hybridization in detection of HBV nucleic acid and cccDNA, and quantification of HBV cccDNA.
Discussions by experts
Influence of interferon and nucleos (t) ide analogues on HBV cccDNA and functional cure of chronic hepatitis B
Chen JieLiang, Yuan ZhengHong
2019, 35(6): 1181-1187. DOI: 10.3969/j.issn.1001-5256.2019.06.002
Abstract:
At present, interferon (IFN) and nucleos (t) ide analogues (NAs) remain the most important methods for the treatment of chronic hepatitis B in clinical practice, but neither of them can effectively eliminate the virus and cure hepatitis B. As the template for HBV transcription and replication, HBV covalently closed circular DNA (cccDNA) persistently exists in the nucleus in the form of minichromosome and is considered the most important reason for chronic and refractory HBV infection. Since it is hard to completely eliminate cccDNA, functional cure of chronic hepatitis B through sustained silencing of cccDNA has become a major goal of clinical and basic research in recent years. This article reviews the influence of current treatment methods on cccDNA, the factors regulating the amount and activity of cccDNA, and the key obstacles to eradication of cccDNA pool, with perspectives of cccDNA research towards a functional cure of chronic hepatitis B.
Advances in drugs and biotechnology targeting hepatitis B virus cccDNA
Chen Ran, Wang Jie, Lu FengMin
2019, 35(6): 1188-1191. DOI: 10.3969/j.issn.1001-5256.2019.06.003
Abstract:
Hepatitis B virus (HBV) infection is the main cause of chronic hepatitis B (CHB) , liver cirrhosis, and hepatocellular carcinoma. HBV covalently closed circular DNA (cccDNA) is the template for HBV replication and exists stably in hepatocytes, which is the main factor for persistent infection. However, existing antiviral drugs including nucleos (t) ide analogues and interferons do not directly target cccDNA, and thus it is difficult to achieve the clinical cure of CHB. With the progress in biotechnology and in-depth understanding of the features of HBV cccDNA, more and more studies have been conducted on antiviral therapies targeting cccDNA, but there is still a long way before clinical application. This article briefly reviews related research advances.
Epigenetic regulation of hepatitis B virus cccDNA and related prospects for antiviral therapy
Chen Juan, Huang AiLong
2019, 35(6): 1192-1196. DOI: 10.3969/j.issn.1001-5256.2019.06.004
Abstract:
Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) is stably maintained in hepatocytes in the form of minichromosome and is considered the most important cause of chronicity of HBV infection, presence of HBV after antiviral therapy, and recurrence of hepatitis after drug withdrawal. However, due to a lack of antiviral regimens targeting cccDNA itself or the formation and transcription of cccDNA, there is an urgent need for treatment strategies targeting cccDNA. With the gradual understanding of epigenetic modification of histones of the cccDNA minichromosome, epigenetic therapy is expected to become a potential therapy for HBV. This article reviews the current status and future directions of HBV DNA methylation and cccDNA-bound histone modification, in order to provide new thoughts for epigenetic therapy for HBV.
Application of in situ hybridization in the detection of hepatitis B virus nucleic acids and cccDNA
Xu Tong, Zhang XiaoNan, Yuan ZhengHong
2019, 35(6): 1197-1200. DOI: 10.3969/j.issn.1001-5256.2019.06.005
Abstract:
In situ hybridization (ISH) is a new technique which combines molecular biology, histochemistry, and cytology. It can quantify and locate specific nucleic acids at the cellular and chromosomal levels and is widely used in virological research. ISH is of great significance for the detection of hepatitis B virus (HBV) nucleic acids (RNA and replicative intermediate DNA) and covalently closed circular DNA.This article reviews the development of ISH and its application in HBV research.
Recent advances of quantitative detection methods for HBV cccDNA
Jiang PeiXue, Mao RiCheng, Zhang JiMing
2019, 35(6): 1201-1204. DOI: 10.3969/j.issn.1001-5256.2019.06.006
Abstract:
Elimination of HBV cccDNA from hepatocytes infected with chronic HBV virus is considered to be the key to eradicating HBV.Monitoring HBV cccDNA before, during, and after viral treatment is essential for routine treatment of patients with chronic hepatitis B. With the introduction of new anti-HBV treatment technologies and new drugs targeting HBV cccDNA, Accurate and sensitive HBV cccDNA assays are urgently needed to evaluate efficacy. In recent years, HBV cccDNA detection methods have achieved gratifying results in both traditional PCR methods and digital PCR methods popular in recent years. In this paper, the advances in HBV cccDNA quantitative detection by qPCR, Magnetic bead capture hybridization, rolling circle amplification combined with in situ PCR, digital PCR and digital PCR assay in single cells were reviewed.
In vitro cell model and mouse model of HBV cccDNA
Su Yu, Zhu YuanFei, Tian QingYou, Xie YouHua, Deng Qiang
2019, 35(6): 1205-1211. DOI: 10.3969/j.issn.1001-5256.2019.06.007
Abstract:
Chronic hepatitis B virus (HBV) infection remains a major public health threat worldwide. Current antiviral drugs can effectively inhibit the replication of HBV, but they fail to achieve a complete cure. As the original template for HBV replication, covalently closed circular DNA (cccDNA) is intrinsically stable in vivo and is regarded as the molecular basis for persistent HBV infection and the key target for the cure of HBV infection. Studies on biosynthesis, metabolism, and regulation of HBV cccDNA have been limited by the low copy number of cccDNA within cells and the lack of sensitive and reliable detection methods. Establishment of appropriate research models of cccDNA helps to understand related biological processes. This article reviews the latest research advances in cell models and mouse models of HBV cccDNA, in order to facilitate future studies on HBV virology and development of antiviral drugs against HBV.
Guidelines
An expert consensus for the adjustment of treatment strategies in patients with chronic hepatitis B treated with non-first-line nucleos (t) ide analogues
The Hepatitis Group, Chinese Society of Hepatology, Chinese Medical Association, Chinese Journal of Hepatology
2019, 35(6): 1212-1214. DOI: 10.3969/j.issn.1001-5256.2019.06.008
Abstract:

Oral nucleos (t) ide analogues (NAs) is one of the main and efficient way for the treatment of chronic hepatitis B (CHB) . Considering the antiviral potency and drug resistance of domestic and foreign guidelines, NAs are divided into first-line and non-first-line drugs. “An Expert Consensus for the Adjustment of Treatment Strategies in Patients with Chronic Hepatitis B Treated with Non-first-line Nucleos (t) ide Analogues, ”is mainly aimed at those patients who are currently using non-first-line NAs drugs. In addition, how to standardize the adjustment to first-line NAs drugs of choice, which can strengthen the effectiveness of initial antiviral treatment to obtain better antiviral efficacy, and improve patient compliance, coinciding with the avoidance of occurrence of serious drug adverse reactions in patients with CHB is presented.

Recommendations for integrated traditional Chinese and Western medicine diagnosis and treatment of HBV-related acute-on-chronic liver failure
Infectious Disease Committee, China Society of Integrated Traditional Chinese and Western Medicine, Liver Disease Committee, China Society of Integrated Traditional Chinese and Western Medicine, Branch of Hepatobiliary Diseases, China Association of Chinese Medicine
2019, 35(6): 1215-1221. DOI: 10.3969/j.issn.1001-5256.2019.06.009
Abstract:
Clinical guidelines on nutrition in end-stage liver disease
Chinese Society of Hepatology, Chinese Medical Association, Chinese Society of Gastroenterology, Chinese Medical Association
2019, 35(6): 1222-1230. DOI: 10.3969/j.issn.1001-5256.2019.06.010
Abstract:

Malnutrition is common in patients with end-stage liver disease (ESLD) and is an independent risk factor for survival, therefore it should be treated as the same important complications as ascites and hepatic encephalopathy. However, up to now, there is no clinical nutrition guideline for patients with ESLD in China. In order to standardize the nutrition treatment, Chinese Society of Hepatology (CSH) and Chinese Society of Gastroenterology (CSGE) , Chinese Medical Association (CMA) co-organized and co-developed this guideline. Recommendations on nutritional screening and assessment as well as principles of intervention and management in patients with ESLD were provided to help clinicians make rational decisions on clinical malnutrition.

Consensus on diagnosis and treatment of chronic cholecystitis and gallstones in China (2018)
He XiangYi, Shi Jian
2019, 35(6): 1231-1236. DOI: 10.3969/j.issn.1001-5256.2019.06.011
Abstract(1949) PDF (272KB)(2707)
Abstract:
Chinese consensus on the medical diagnosis and treatment of chronic cholecystitis and gallstones (2014) was issued for the first time in 2014 and effectively standardized the medical diagnosis and treatment of chronic cholecystitis and gallstones in China. Five years later, with the accumulation of new clinical data, the experts with various disciplines were invited to establish an expert committee and discuss the new version of the consensus. With reference to the newly developed evaluation criteria in Chinese clinical guidelines, the new version added the research data of the Chinese population, so as to provide guidance for the medical diagnosis and treatment of chronic cholecystitis and gallstones in the Chinese population.
An excerpt of endoscopic management of common bile duct stones: European Society of Gastrointestinal Endoscopy (ESGE) guideline (2019)
Zhou ChunHua, Zhou Wei, Meng YuTing, Zou DuoWu, Li ZhaoShen
2019, 35(6): 1237-1241. DOI: 10.3969/j.issn.1001-5256.2019.06.012
Abstract:
Guideline Interpretation
Key points and interpretation of EASL clinical practice guidelines: Drug-induced liver injury (2019)
Yu LeCheng, Lai RongTao, Chen ChengWei
2019, 35(6): 1242-1250. DOI: 10.3969/j.issn.1001-5256.2019.06.013
Abstract:
Original articles_Viral hepatitis
Clinical effect of nucleos (t) ide analogues in treatment of acute exacerbation of chronic hepatitis B
Ruan JianWen, Gao LiJuan, Su RuKai, Wang YaJiao, Yang Jing
2019, 35(6): 1251-1255. DOI: 10.3969/j.issn.1001-5256.2019.06.014
Abstract:
Objective To investigate the clinical effect of nucleos (t) ide analogues (NAs) in the treatment of acute exacerbation of chronic hepatitis B (CHB) for 48 weeks. Methods The CHB patients with positive or negative HBeAg who were diagnosed and treated in Haikou Hospital Affiliated to Xiangya School of Medicine, Central South University, from October 2014 to July 2018 were enrolled. Among these patients, 48 with an acute exacerbation of CHB and an alanine aminotransferase (ALT) level of > 10 × upper limit of normal (ULN) were enrolled as experimental group, and 51 with an ALT level of < 10 × ULN and a total bilirubin level of < 5 × ULN were enrolled as control group. Both groups were treated with entecavir and tenofovir disoproxil fumarate. The two groups were compared in terms of the clinical process and outcome of NA treatment, including baseline liver function, HBV DNA, HBsAg, anti-HBs, HBeAg, anti-HBe, and liver ultrasound findings, and follow-up was performed at weeks 12, 24, and 48 of treatment. The t-test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. The chi-square test or the Fisher's exact test was used for comparison of categorical data between two groups.Results There was a significant difference in ALT normalization rate at weeks 12, 24, and 48 of treatment between the experimental group and the control group (89. 58%/93. 75%/93. 75% vs 49. 02%/72. 55%/76. 47%, χ2= 18. 917, 7. 814, and 5. 743, all P < 0. 05) .There was a significant difference in the undetectable rate of HBV DNA at week 12 of treatment between the experimental group and the control group (83. 33% vs 60. 78%, χ2= 6. 198, P = 0. 013) , while there was no significant difference between the two groups at weeks 24 and48 of treatment (95. 83%/95. 83% vs 84. 31%/86. 27%, P > 0. 05) . There was a significant difference in HBeAg seroconversion rate between the experimental group and the control group at weeks 12, 24, and 48 of treatment (23. 26%/25. 58%/27. 91% vs 2. 22%/2. 22%/8. 89%, χ2= 8. 894, 10. 188, and 5. 346, all P < 0. 05) . Clearance or seroconversion of HBsAg was not observed in the experimental group or the control group. Conclusion NAs can achieve high ALT normalization rate, HBV DNA undetectable rate, and HBeAg seroconversion rate in the treatment of patients with acute exacerbation of CHB.
Clinical effect of interferon in treatment of genotype B or C chronic hepatitis B patients: A meta-analysis
Li Min, Dan Shan, Wu XiaoNing, Kong YuanYuan, Ou XiaoJuan, You Hong, Jia JiDong
2019, 35(6): 1256-1261. DOI: 10.3969/j.issn.1001-5256.2019.06.015
Abstract:
Objective To investigate the clinical effect of interferon (IFN) in the treatment of genotype B or C chronic hepatitis B (CHB) patients. Methods PubMed, Web of Science, The Cochrane Library, CNKI, Wanfang Data, and VIP were searched for articles on IFN in the treatment of genotype B or C CHB patients published up to November, 2018. Two researchers performed screening, data extraction, and quality assessment of the articles independently, and then a meta-analysis was performed. Results A total of 20 articles were included.The results of the meta-analysis showed that compared with the genotype C CHB patients, the genotype B CHB patients had significantly higher HBV DNA clearance rate (odds ratio [OR]= 2. 95, 95% confidence interval [CI]: 2. 22-3. 91, P < 0. 05) , HBeAg clearance rate (OR = 3. 16, 95% CI: 2. 38-4. 20, P < 0. 05) , HBeAg seroconversion rate (OR = 1. 83, 95% CI: 1. 44-2. 33, P < 0. 05) , HBsAg clearance rate (OR = 2. 59, 95% CI: 1. 05-6. 38, P < 0. 05) , and alanine aminotransferase normalization rate (OR = 2. 31, 95% CI: 1. 69-3. 16, P < 0. 05) . The subgroup analysis showed that the clinical effect of IFN in genotype B or C CHB patients was not affected by the type of IFN. Conclusion The antiviral effect of IFNs is affected by HBV genotype, and the patients with genotype B CHB have a better antiviral outcome than those with genotype C CHB. Therefore, HBV genotype is an important factor for predicting the clinical effect of IFN therapy.
Original articles_Liver fibrosis and liver cirrhosis
Value of liver stiffness measurement in the diagnosis of liver fibrosis degree in HBeAg-positive patients with chronic HBV infection
Liu Na, Li ChunXia, Dong Bing, Zhou LuLu, Zhang RuiQin, Zhao YingRen, He YingLi, Xu GuangHua
2019, 35(6): 1262-1265. DOI: 10.3969/j.issn.1001-5256.2019.06.016
Abstract:
To investigate the value of liver stiffness measurement (LSM) in the diagnosis of liver fibrosis degree in HBeAg-positive patients with chronic HBV infection. Methods A retrospective analysis was performed for the clinical data of 330 HBeAg-positive patients with chronic HBV infection who were hospitalized in Affiliated Hospital of Yan'an University from October 2013 to August 2018 and underwent liver biopsy, and according to liver pathological results, these patients were divided into mild liver fibrosis group (F0-F1) and significant liver fibrosis group (F2-F4) . The t-test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. Univariate and multivariate analyses were performed to screen out the indices for the diagnosis of significant liver fibrosis, and the receiver operating characteristic (ROC) curve was plotted for these indices to evaluate their value in the diagnosis of significant liver fibrosis. Results Of all 330 patients, 245 had mild liver fibrosis and 85 had significant liver fibrosis. There were significant differences between the two groups in HBV DNA, HBsAg, HBeAg, HBcAb, alanine aminotransferase, aspartate aminotransferase, total bilirubin, and LSM (all P < 0. 05) . The multivariate analysis showed that HBsAg and LSM were independent risk factors for significant liver fibrosis (both P < 0. 05) . The ROC curve analysis showed that only LSM had a diagnostic value, with an area under the ROC curve of 0. 744 (95% confidence interval: 0. 680-0. 808) . At the optimal cut-off value of6. 15 kPa, LSM had a sensitivity of 62. 4%, a specificity of 76. 3%, an accuracy of 72. 1%, a positive predictive value of 72. 5%, and a negative predictive value of 67. 0% in predicting significant liver fibrosis. Conclusion LSM has a good value in predicting significant liver fibrosis in HBeAg-positive patients with chronic HBV infection.
Value of heparin-binding protein in ascites and serum procalcitonin in diagnosis of spontaneous bacterial peritonitis
Yang LiXia, Zhang LunLi, Lai LingLing, Fang Ming
2019, 35(6): 1266-1269. DOI: 10.3969/j.issn.1001-5256.2019.06.017
Abstract:
Objective To investigate the value of heparin-binding protein (HBP) in ascites combined with serum procalcitonin (PCT) in the diagnosis of spontaneous bacterial peritonitis (SBP) . Methods A total of 120 patients with ascites who were hospitalized in our hospital from January 2016 to June 2018 were enrolled and divided into cirrhotic ascites + SBP group with 40 patients, leaky ascites group with 40 patients, malignant ascites group with 20 patients, and tuberculous ascites group with 20 patients. Bacterial culture of ascites was performed for all patients, and polymorphonuclear leukocyte (PMN) count in ascites, HBP in ascites, and serum PCT level were measured and analyzed.The independent samples t-test was used for comparison of normally distributed continuous data between two groups, and an analysis of variance was used for comparison between multiple groups; non-normally distributed continuous data were expressed as median [M (P25, P75) ], and the Kruskal-Wallis H test was used for comparison between multiple groups and the Nemenyi test was used for comparison between two groups. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficiency of HBP in ascites and serum PCT, and the Spearman correlation analysis was used to investigate the correlation between HBP in ascites and serum PCT. Results The cirrhotic ascites + SBP group had significant increases in the levels of HBP in ascites and serum PCT compared with the leaky ascites group, the malignant ascites group, and the tuberculous ascites group (P < 0. 05) . There was no significant difference in HBP level in ascites between patients with different bacteria determined by bacterial culture of ascites (P > 0. 05) , and there was also no significant difference in HBP level in ascites between patients with positive or negative results of bacterial culture of ascites (58. 59 ± 36. 23 ng/ml vs 63. 61 ±32. 54 ng/ml, t = 1. 763, P > 0. 05) . Serum PCT had an optimal cut-off value of 0. 62 ng/ml in the diagnosis of SBP, with an area under the ROC curve of 0. 831, a sensitivity of 86. 3%, and a specificity of 52. 8%. HBP in ascites had an optimal cut-off value of 23. 54 ng/ml in the diagnosis of SBP, with an area under the ROC curve of 0. 962, a sensitivity of 92. 3%, and a specificity of 65. 4%. Ascites HBP was highly correlated with serum PCT (r = 0. 776, P < 0. 05) . Conclusion The level of HBP in ascites has a high value in the diagnosis of SBP, and combined measurement of ascites HBP and serum PCT can improve the diagnostic efficiency of SBP.
Original articles_Liver neoplasms
Clinical effect of drug-eluting beads and conventional transcatheter arterial chemoembolization in treatment of unresectable liver cancer: A meta-analysis
Yin WeiLi, Lian Jia, Xiao ShiXiang, Xiang HuiLing, Liu Ying, Qian BaoXin, Wang Tao, Li Ying, Jin YuXia, Han Tao
2019, 35(6): 1270-1275. DOI: 10.3969/j.issn.1001-5256.2019.06.018
Abstract:
Objective To systematically review the clinical effect of transcatheter arterial chemoembolization with drug-eluting beads (DEB-TACE) versus conventional transcatheter arterial chemoembolization (cTACE) in the treatment of unresectable liver cancer. Methods PubMed, Embase, Cochrane, and CNKI were searched for articles on clinical control trials of DEB-TACE versus cTACE in the treatment of unresectable liver cancer. The articles were screened according to inclusion and exclusion criteria, and after valid data were extracted, Revman 5. 3 software was used for meta-analysis. The two groups were compared in terms of the number of patients with complete remission (CR) , partial remission (PR) , or stable disease (SD) and 6-and 12-month survival rates. Results A total of 12 articles were included, with 1177 patients in total, among whom 519 patients underwent DEB-TACE and 658 underwent cTACE. Compared with the cTACE group, the DEB-TACE group had a significantly higher number of patients with CR (risk ratio [RR]= 1. 42, 95% confidence interval [CI]: 1. 18-1. 72, P = 0. 0002) , and had a significantly higher 12-month survival rate (RR = 1. 09, 95% CI: 1. 01-1. 17, P =0. 03) . There were no significant differences between the two groups in the number of patients with PR (RR = 1. 13, 95% CI: 0. 97-1. 30, P = 0. 12) , the number of patients with SD (RR = 0. 82, 95% CI: 0. 64-1. 05, P = 0. 12) , 6-month survival rate (RR = 1. 05, 95% CI: 1. 00-1. 10, P = 0. 07) . Conclusion DEB-TACE has a better therapeutic effect than cTACE with iodinated oil.
Value of combined measurement of serum alpha-fetoprotein, Dickkopf-1, and cytoskeleton-associated protein 4 in diagnosis of hepatocellular carcinoma
Xi LiTing, Zhang HuiXian, Wu AiRong, Xu ChunFang, Zhu JinZhou
2019, 35(6): 1276-1279. DOI: 10.3969/j.issn.1001-5256.2019.06.019
Abstract:
Objective To investigate the value of combined measurement of serum alpha-fetoprotein (AFP) , Dickkopf-1 (DKK1) , and cytoskeleton-associated protein 4 (CKAP4) in the diagnosis of hepatocellular carcinoma (HCC) . Methods A total of 122 patients with HCC (76 patients in the early stage) , 152 patients with liver cirrhosis, and 105 patients with chronic hepatitis B, who were admitted to The First Affiliated Hospital of Soochow University from January 2013 to December 2017, were enrolled, and 101 individuals who underwent physical examination during the same period of time were enrolled as healthy control group. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups; the chi-square test was used for comparison of categorical data between multiple groups. A binary logistic regression analysis was used to obtain the new variable of predicted probability, and the receiver operating characteristic (ROC) curve analysis was performed for each index and predicted probability to investigate the area under the ROC curve (AUC) , sensitivity, and specificity of the three indices used alone or in combination. Results The HCC group had significantly higher serum levels of AFP, DKK1, and CKAP4 than the liver cirrhosis group, the chronic hepatitis B group, and the healthy control groups (F = 121. 618, 84. 559, and 91. 769, P < 0. 001) . The combination of AFP, DKK1, and CKAP4 had an AUC of 0. 967 (95% confidence interval [CI]: 0. 950-0. 984) , a sensitivity of 0. 869, and a specificity of 0. 980, which were significantly higher than the AUCs, sensitivities, and specificities of the three indices used alone (all P <0. 05) . The combination of the three indices had an AUC of 0. 965 (95% CI: 0. 942-0. 988) , a sensitivity of 0. 868, and a specificity of0. 980 in the diagnosis of early-stage HCC, which were significantly higher than the AUCs, sensitivities, and specificities of the three indices used alone (all P < 0. 05) . Conclusion Combined measurement of serum AFP, DKK1, and CKAP4 improves the accuracy, sensitivity, and specificity of HCC diagnosis and thus has an important clinical value in the screening for and early diagnosis of HCC.
Association of HOTAIR genetic variation and gene-environment interaction with clinical features of liver cancer
Liu GuiYan, Zhang JunGuo, Pi LuCheng, Ji XiaoHui, Liu Qing, Tan JianYi, Huang BaoYing, Liu Li, Gao YanHui
2019, 35(6): 1280-1285. DOI: 10.3969/j.issn.1001-5256.2019.06.020
Abstract:
Objective To investigate the association of the genetic variation of the long non-coding RNA HOX transcript antisense RNA (HOATIR) and gene-environment interaction with prognosis-related clinical features of liver cancer. Methods A total of 923 patients with primary liver cancer Shunde Hospital of Southern Medical University were admitted to a hospital from October 2010 to October 2016 were enrolled in this study. TaqMan quantitative PCR was used to detect HOTAIR rs17105613 T > C, rs12427129 C > T, and rs3816153 G> T genotypes. The chi-square test was used to analyze the difference in the distribution of clinical features of liver cancer, and the logistic regression model was used to analyze the influence of the genetic variation of HOTAIR on the TNM stage of liver cancer, portal vein tumor thrombus, and age of onset. Results After the adjustment for environmental factors, rs17105613 and rs3816153 were significantly associated with TNM stage in the recessive mode (P < 0. 05) , and there was a statistically significant multiplicative interaction between rs12427129 and smoking on the age of onset of liver cancer (P = 0. 029) , as well as an additive interaction with critical statistical significance (P = 0.092) . Conclusion HOTAIR rs17105613 and rs3816153 may be associated with TNM stage of liver cancer. The interaction between rs12427129 and smoking may influence the age of onset of liver cancer. Therefore, the genetic variation of HOTAIR may promote the invasion and metastasis of hepatoma cells.
Construction of PSCSI-GFP lentiviral vector for the endothelin-converting enzyme-like 1 gene
He Jian, Liao HongWu, Yang XueFeng
2019, 35(6): 1286-1292. DOI: 10.3969/j.issn.1001-5256.2019.06.021
Abstract:
Objective To design and construct the RNA interference (RNAi) lentiviral vector targeting the endothelin-converting enzyme-like 1 (ECEL1) gene. Methods The RNA interference target was designed with the ECEL1 gene as the template, and the short-hairpin RNA (shRNA) interference sequence was designed based on the selected target sequence. Enzyme cut sites for restriction endonuclease were added to both ends of this sequence to synthesize single-stranded DNA oligo, which was then paired in annealing buffer to form double-stranded DNA oligo. GV115 vectors were linearized by double digestion with Age I and EcoR I enzymes, and then they were connected with the DNA oligo; the grafted product transformed Escherichia coli receptor cells and was amplified, sequenced, and identified by PCR.The recombinant ECEL1 gene RNAi lentivirus was obtained by plasmid extraction, transfection, concentration, and purification, and HIV-1 p24 antigen ELISA was used to determine the titer of the recombinant RNAi lentivirus. Human hepatoma BEL-7404 cells were transfected with the qualified lentivirus, and a control group was set up. Fluorescence observation was performed to determine transfection rate. Real-time PCR and Western blot were used to measure the mRNA and protein expression of target gene after ECEL1 gene knockdown in human hepatoma BEL-7404 cells. The two-independent-samples t test was used for comparison between two groups. Results After the design with the ECEL1 gene as the template, the psc48784 fragment was selected as the target for RNAi; the double-stranded DNA oligo was prepared and the positive recons were identified and sequenced by PCR, and the results showed that psc48784 was the correct clone. The ECEL1 gene RNAi lentivirus was successfully constructed after plasmid extraction, transfection, concentration, and purification and was qualified for physical test and sterility test. HIV-1 p24 antigen ELISA showed that the ECEL1 gene RNAi lentivirus had a virus titer of 3 E+ 8 TU/ml, suggesting that the qualified ECEL1 gene RNAi lentivirus with a high titer was successfully constructed. After the human hepatoma BEL-7404 cells were transfected with the ECEL1 gene RNAi lentivirus, fluorescence observation showed a transfection efficiency of80% and a stable state of cells. Real-time PCR and Western blot showed significant reductions in the mRNA and protein expression of the ECEL1 gene in human hepatoma BEL-7404 cells in the experimental group (P < 0. 05) , and the knockdown efficiency reached 70. 5%.Conclusion The ECEL1 gene PSCSI-GFP lentiviral vector is successfully constructed, and stable virus samples with a high titer are obtained. The stable human hepatoma BEL-7404 cells with ECEL1 gene knockdown are also obtained.
Original articles_Biliary diseases
Necessity of magnetic resonance cholangiopancreatography in patients with initial diagnosis of gallstones on color Doppler ultrasound and an analysis of related indications
Zhu PeiYao, Yang Jun, Yang Yong, Han YaDong, Zhuang Lei, Han Yong
2019, 35(6): 1293-1298. DOI: 10.3969/j.issn.1001-5256.2019.06.022
Abstract:
Objective To investigate the necessity and indication of magnetic resonance cholangiopancreatography (MRCP) in patients with gallstones diagnosed by color Doppler ultrasound. Methods A retrospective case-control study was conducted. The clinical data of 1431 patients who were admitted to The Affiliated Hospital of Xuzhou Medical University from January 2013 to December 2017 with the initial diagnosis of gallstones were collected. On admission, abdominal ultrasound found gallstones alone, without other lesions. The patients who were diagnosed with gallstones alone after surgical treatment were enrolled as control group, and those who were diagnosed with gallstones and common bile duct stones were enrolled as experimental group. A logistic regression analysis was performed to establish a predictive model for gallstones with common bile duct stones. The receiver operating characteristic (ROC) curve was plotted for the predictive model and each index, and the area under the ROC curve was calculated. Results Four indices were finally screened out by the logistic regression analysis, i. e., bile duct dilation (χ1) , gallbladder enlargement (χ2) , direct bilirubin (DBIL) (χ3) , and gamma-glutamyl transpeptidase (GGT) (χ4) , and the logistic regression model was Logi (P) =-4. 153 + 3. 592χ1+ 1. 720χ2+ 1. 798χ3+ 1. 519χ4. In the diagnosis of common bile duct stones missed by color Doppler ultrasound, this model had a sensitivity of 53. 4%, a specificity of 99. 6%, an accuracy of92. 5%, and an area under the ROC curve of 0. 904, which was significantly better than each index alone. Conclusion MRCP is not necessary for patients diagnosed with simple gallstones by color Doppler ultrasound. However, enlarged gallbladder, a diameter of common bile duct of > 0. 8 cm, DBil > 7 μmol/L, and GGT > 40 U/L are independent risk factors for gallstones with common bile duct stones. The logistic regression model established in this study has high sensitivity and specificity and can provide a reference for to decision-making among clinicians.
Original articles_Others
Establishment and evaluation of short-term prognostic model for hepatitis B virus-related acute-on-chronic liver failure
Wang JiaXin, Cheng Na, Xiang TianXin, Li ShuYue, Xiao JinPing, Wu XiaoPing
2019, 35(6): 1299-1303. DOI: 10.3969/j.issn.1001-5256.2019.06.023
Abstract:

Objective To establish a new prognostic model, MACLF, for predicting the short-term prognosis of hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF) , and to investigate its value in predicting the short-term prognosis of HBV-ACLF.Methods A retrospective cohort study was performed for the clinical data of 270 patients with HBV-ACLF who were admitted to The First Affiliated Hospital of Nanchang University from January 2015 to November 2018. The patients were divided into survival group with 153 patients and death group with 117 patients according to their conditions after 3 months of treatment, and influencing factors for the short-term prognosis of HBV-ACLF were analyzed. The chi-square test was used for comparison of categorical data between two groups, A binary logistic regression analysis was performed for statistically significant indices determined by multivariate analysis and a model was established.and the Mann-Whitney U test was used for comparison of continuous data between two groups. A binary logistic regression analysis was used for multivariate analysis, a binary logistic regression analysis was performed for statistically significant indices determined by multivariate analysis and a model was established, and the receiver operating characteristic (ROC) curve was plotted to evaluate the value of MACLF in predicting the short-term prognosis of HBV-ACLF. Results The univariate analysis showed that there were significant differences between the survival group and the death group in free triiodothyronine (FT3) , thyroid stimulating hormone, international normalized ratio, neutrophil-lymphocyte ratio (NLR) , platelet count (PLT) , alanine aminotransferase, aspartate aminotransferase-alanine aminotransferase ratio, total bilirubin (TBil) , albumin, creatinine, total cholesterol, triglyceride, sodium, alpha-fetoprotein, serum ferritin, Child -Turcotte-Pugh (CTP) class, Model for End-Stage Liver Disease (MELD) score, and complications (hepatic encephalopathy, hepatorenal syndrome, spontaneous peritonitis, gastrointestinal bleeding, and pulmonary infection) (all P < 0. 05) . The multivariate analysis showed that TBil (odds ratio [OR]= 1. 007, P = 0. 001) , INR (OR = 5. 750, P < 0. 001) , FT3 (OR = 0. 084, P = 0. 003) , PLT (OR =0. 987, P = 0. 022) , hepatorenal syndrome (OR = 7. 146, P = 0. 045) , and pulmonary infection (OR = 3. 816, P = 0. 023) were independent influencing factors for the short-term prognosis of HBV-ACLF. Therefore, a new model of MACLF was established for the short-term prognosis of HBV-ACLF: Logit (P) = 0. 007 ×[TBil (umol/L) ]+ 2. 181 × INR-2. 762 × [FT3 (pg/mL) ]-0. 014 ×[PLT (×109/L) ]+ 1. 797 × [hepatorenal syndrome (with: 1; no: 0) ]+ 1. 339 × [pulmonary infection (with: 1; no: 0) ]-2. 291. The ROC curve analysis showed that MACLF had significantly higher area under the ROC curve (0. 934) and Youden index (0. 774) than CTP class, MELD, and MELD combined with serum sodium concentration. Conclusion The new model of MACLF has a good value in predicting the short-term prognosis of patients with HBV-ACLF after 3 months of treatment.

Association between blood ammonia and 90-day prognosis in patients with hepatitis B virus-related acute-on-chronic liver failure
Tong JingJing, Mu XiuYing, Xu Xiang, Chen Jing, Zhai XingRan, Wang Yu, Su HaiBin, Liu XiaoYan, Hu JinHua
2019, 35(6): 1304-1307. DOI: 10.3969/j.issn.1001-5256.2019.06.024
Abstract:

Objective To investigate the association between baseline blood ammonia (BLA) and 90-day prognosis in patients with hepatitis B virus (HBV) -related acute-on-chronic liver failure (HBV-ACLF) . Methods A retrospective analysis was performed for the clinical data of 789 patients with HBV-ACLF who were admitted to The Fifth Medical Center of Chinese PLA General Hospital from January2013 to December 2016, and the association between baseline BLA and 90-day prognosis was analyzed. The Cox regression risk model was used for multivariate analysis. The Kaplan-Meier survival curve was used to analyze the 90-day survival rate of patients with different levels of baseline BLA, and the log-rank test was used for comparison. Results The Cox multivariate regression analysis showed that BLA was independently and positively correlated with the risk of 90-day death in HBV-ACLF patients (Model 2: hazard ratio = 1. 007, 95%confidence interval: 1. 005-1. 010, P < 0. 00001) . The log-rank test indicated that in the patients without hepatic encephalopathy (HE) , the BLAhigh group had the highest 90-day cumulative mortality rate, followed by the BLAmid group and the BLAlow group (P = 0. 0023) ; among the patients with HE, the BLAhigh group had a significantly higher 90-day cumulative mortality rate than the other two groups (P= 0. 012) , while there was no significant difference in 90-day cumulative mortality rate between these two groups (P = 0. 18) . Conclusion Baseline BLA is independently and positively correlated with the risk of 90-day death in HBV-ACLF patients, and it may have a certain clinical value in treatment and prognostic evaluation.

Association of vitamin D-related gene polymorphisms with hepatitis B virus-related acute-on-chronic liver failure
Ou WeiJie, Lin YeHong, Zhou Qing, Shang TianYu, Lin Su, Zhu YueYong
2019, 35(6): 1308-1312. DOI: 10.3969/j.issn.1001-5256.2019.06.025
Abstract:

Objective To investigate the expression of single nucleotide polymorphisms (SNP) of vitamin D-related genes in patients with hepatitis B-related acute-on-chronic liver failure (HBV-ACLF) and its association with short-term prognosis of HBV-ACLF. Methods The patients with chronic hepatitis B who were admitted to Liver Diseases Research Center, The First Affiliated Hospital of Fujian Medical University, from July 2012 to March 2018 were enrolled, and according to the presence or absence of acute-on-chronic liver failure during the course of the disease (n = 400) , they were divided into HBV-ACLF group (n = 122) and non-ACLF group (n = 278) . The clinical data and laboratory examination results were collected; peripheral blood samples were collected, and imLDRTM multiple SNP typing kit was used to determine the genotypes of the SNPs of vitamin D receptor (VDR) rs1544410 and rs2228570 and vitamin D-binding protein (VDBP) rs2282679. The patients in the HBV-ACLF group were followed up for 3 months to observe their survival. The association of vitamin D-related gene SNP with HBV-ACLF susceptibility and prognosis was analyzed. Hardy-Weinberg equilibrium was used to evaluate the representativeness of gene samples. The t-test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. A logistic regression analysis was used to investigate the odds ratio of SNP in the development of HBV-ACLF. Results There were no significant differences in the genotype and allele frequencies of VDR rs1544410 and rs2228570 and VDBP rs2282679 between the HBV-ACLF group and the non-ACLF group (all P > 0. 05) . In addition, there were also no significant differences in the genotype and allele frequencies of VDR rs1544410 and rs2228570 and VDBP rs2282679 between the HBV-ACLF patients who survived and those who died (all P > 0. 05) . Conclusion SNPs of VDR rs1544410 and rs2228570 and VDBP rs2282679 are not associated with the development and short-term prognosis of HBV-ACLF.

Mechanism of HCV stimulation of human umbilical vein endothelial cells in the pathogenesis of atherosclerosis
Zhu ZiYi, Liu Yuan, Wang WenBo, Jiang ZhongYong, Chang Kai, Ye YuSheng, Xiong Jie
2019, 35(6): 1313-1317. DOI: 10.3969/j.issn.1001-5256.2019.06.026
Abstract:

Objective To investigate the mechanism of HCV infection in the pathogenesis of atherosclerosis with a model of human umbilical vein endothelial cells (HUVECs) stimulated by HCV in vitro. Methods HUVECs were stimulated with 1. 0 MOI HCVcc for 48 hours.CCK8 assay was used to measure cell proliferation; flow cytometry was used to measure cell apoptosis and cell cycle; wound healing assay and monocyte-endothelial adhesion assay were used to evaluate the influence of HCV on the migration and adhesion of HUVECs; quantitative real-time PCR and Western blot were used to measure the expression of inflammatory factors and endothelial injury factors in HUVECs stimulated by HCV. The two-independent-samples t test was used for comparison between two groups; an analysis of variance was used for comparison between multiple groups, and the LSD-t test was used for further comparison between two groups. Results Compared with the control group, the HCV group had no significant changes in the growth, apoptosis, and cell cycle of HUVECs (all P > 0. 05) . HCV stimulation inhibited the migration of HUVECs and enhanced their adhesion ability. Compared with the control group, the HCV group had significant increases in the mRNA and protein expression of the inflammatory factors interleukin-6 and interleukin-1β and the chemokines CXCL10 and monocyte chemotactic protein 1 (mRNA expression: t =-10. 155, -12. 048, -5. 025, and-20. 116, all P < 0. 05; protein expression: F = 2541. 739, 4806. 490, 477. 608, and 501. 38, all P < 0. 001) . HCV stimulation significantly upregulated the expression of the endothelial injury factors endothelin-1 and vascular endothelial growth factor and the adhesion molecules intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in HUVECs (t =-4. 530, -4. 497, -7. 692, and-7. 449, all P < 0. 05) . Conclusion HCV can cause inflammatory changes and dysfunction in endothelial cells and thus affect the development of atherosclerosis.

Clinical effect of ultrasound-guided percutaneous drainage in treatment of liver abscess
Zhu QinLing, Xiang XiaoXing, Yuan LeYao, Xu QingCheng, Wang Su
2019, 35(6): 1318-1321. DOI: 10.3969/j.issn.1001-5256.2019.06.027
Abstract:

Objective To investigate the clinical value of ultrasound-guided percutaneous drainage in the treatment of liver abscess from the aspects of laboratory markers and size of abscess. Methods A total of 79 patients with liver abscess who underwent ultrasound-guided percutaneous drainage in Department of Gastroenterology in Northern Jiangsu People's Hospital from January 2013 to August 2018 were enrolled, among whom 36 patients who were lost or transferred, abandoned treatment, had an age pf < 18 years, or were not followed up in the outpatient service were excluded. A total of 43 patients were finally included in the retrospective study. The t-test was used for comparison of continuous data between groups, and the chi-square test was used for comparison of categorical data between groups. Results All 43 patients achieved a one-time success of puncture and placement of drainage tube. Of all 43 patients, 36 had fear of cold and pyrexia, among whom 31 (86. 1%) had a normal body temperature on day 3 after surgery, and there were significant changes in leukocyte count, percentage of neutrophils, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase after surgery (t = 6. 668, 6. 255, 2. 337, 3. 001, and 5. 198, all P < 0. 05) . There was a significant reduction in the diameter of abscess after surgery (74 ± 31 mm vs 31 ±28 mm, t = 18. 517, P < 0. 05) . The average length of hospital stay was 19. 84 ± 9. 37 days. Of all 43 patients, 19 (44. 2%) were cured and 24 (55. 8%) had response to treatment. Of all 43 patients, 38 had positive results of liver abscess culture, among whom 25 (65. 8%) had Klebsiella pneumoniae infection, suggesting that Klebsiella pneumoniae was the most common pathogenic bacteria. Conclusion Ultrasound-guided percutaneous drainage has a high success rate, few complications, and reliable clinical efficacy in the treatment of liver abscess. Therefore, it is recommended as the first choice for the clinical treatment of liver abscess.

Clinical effect of ursodeoxycholic acid combined with diammonium glycyrrhizinate in treatment of primary biliary cholangitis
Zhang YuGuo, Zhao SuXian, Li WenCong, Ren WeiGuang, Nan YueMin
2019, 35(6): 1322-1325. DOI: 10.3969/j.issn.1001-5256.2019.06.028
Abstract:

Objective To investigate the clinical effect of ursodeoxycholic acid (UDCA) alone or in combination with diammonium glycyrrhizinate on biochemical response and liver stiffness measurement (LSM) in the treatment of primary biliary cholangitis (PBC) . Methods A total of 66 patients with PBC who visited Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, from January 2014 to March 2016 were enrolled. The FibroTouch test was performed, and LSM was used to indicate the degree of liver fibrosis. The patients treated with UDCA and diammonium glycyrrhizinate (treatment group) and those treated with UDCA alone (control group) were compared in terms of liver biochemical response at 4, 12, 24, and 48 weeks of treatment and LSM at 24 and 48 weeks of treatment. The independent samples t-test was used for comparison of continuous data between two groups, and the paired t-test was used for comparison of biochemical parameters and LSM before and after treatment. Results Compared with the control group, the treatment group had a significantly lower level of aspartate aminotransferase at 4, 12, 24, and 48 weeks of treatment (4 weeks: 38. 4 ± 15. 4 U/L vs61. 6 ± 28. 8 U/L, t = 2. 684, P = 0. 012; 12 weeks: 36. 4 ± 12. 6 U/L vs 58. 1 ± 24. 8 U/L, t = 2. 953, P = 0. 006; 24 weeks: 37. 0 ± 8. 5 U/L vs 52. 9 ± 17. 2 U/L, t = 3. 134, P = 0. 004; 48 weeks: 34. 9 ± 7. 9 U/L vs 48. 6 ± 12. 7 U/L, t = 3. 463, P = 0. 002) , as well as a significantly lower level of alkaline phosphatase at 24 and 48 weeks of treatment (24 weeks: 91. 6 ± 15. 1 U/L vs 137. 3 ± 55. 6 U/L, t =2. 970, P = 0. 006; 48 weeks: 71. 3 ± 14. 7 U/L vs 128. 7 ± 45. 5 U/L, t = 4. 503, P < 0. 001) . There was a significant reduction in LSM at 24 and 48 weeks of treatment in the control group (24 weeks: 12. 9 ± 6. 8 kPa vs 13. 9 ± 7. 6 k Pa, t = 4. 814, P < 0. 001; 48 weeks:12. 6 ± 6. 4 kPa vs 13. 9 ± 7. 6 kPa, t = 3. 928, P = 0. 010) and the treatment group (24 weeks: 13. 4 ± 7. 0 kPa vs 15. 8 ± 9. 7 k Pa, t =3. 031, P = 0. 010; 48 weeks: 12. 0 ± 5. 7 kPa vs 15. 8 ± 9. 7 kPa, t = 3. 044, P = 0. 010) ; however, there was no significant difference in LSM between the control group and the treatment group at 24 and 48 weeks of treatment (all P > 0. 05) . Conclusion In patients with PBC, UDCA combined with diammonium glycyrrhizinate can improve serum biochemical response and has a better clinical effect than UDCA alone.Both groups have a significant reduction in LSM at 24 and 48 weeks of treatment, suggesting that UDCA combined with diammonium glycyrrhizinate can help to maintain disease stability.

Value of fumarate hydratase antibody in differential diagnosis of autoimmune hepatitis and drug-induced liver injury
Han Ying, Chen Jie, Dan Jing, Liu YanMin, Zhang XiaoDan, Ren MeiXin, Du XiaoFei, Bian XinQu, Liu Dan, Huang YunLi, Huang ChunYang, Liao HuiYu
2019, 35(6): 1326-1329. DOI: 10.3969/j.issn.1001-5256.2019.06.029
Abstract:

Objective To investigate the value of fumarate hydratase antibody (anti-FH) in the differential diagnosis of autoimmune hepatitis (AIH) and drug-induced liver injury (DILI) . Methods From March 2014 to December 2016, 105 patients with AIH who were hospitalized in Beijing You'an Hospital were enrolled as AIH group, and 92 patients with DILI were enrolled as DILI group. A total of 128 healthy individuals were enrolled as control group. ELISA was used to measure the serum level of anti-FH. The t-test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test or the Fisher's exact test was used for comparison of categorical data between groups. A consistency analysis of diagnostic compliance of anti-FH based on the Kappa test. The sensitivity, specificity, positive predictive value, and negative predictive value of anti-FH in the diagnosis of AIH were analyzed. Results Compared with the DILI group, the AIH group had significantly higher positive rate of anti-nuclear antibody (72. 4% vs 55. 4%, χ2=6. 147, P = 0. 013) and level of IgG ( (18. 3 ± 6. 1) g/L vs (15. 2 ± 5. 4) g/L, t =-2. 566, P = 0. 011) ) . The AIH group had a significantly higher positive rate of anti-FH than the DILI group and the control group (36. 2% (38/67) vs 6. 5% (6/92) and 2. 3% (3/128) , χ2= 59. 959, P < 0. 001) . In the diagnosis of AIH, anti-FH had a sensitivity of 36. 2%, a specificity of 93. 5%, a positive predictive value of 86. 4%, and a negative predictive value of 93. 5%. Conclusion Serum anti-FH has a certain reference value in the differential diagnosis of AIH and DILI.

Association of TRIB1 rs2954029 single nucleotide polymorphism with the risk of nonalcoholic fatty liver disease and coronary heart disease
Liu Qun, Luan GuiPing, Gao Hui, Zhao BenTian, Du ShuiXian, Liu ShouSheng, Xin YongNing
2019, 35(6): 1330-1336. DOI: 10.3969/j.issn.1001-5256.2019.06.030
Abstract:

Objective To investigate the association of TRIB1 rs2954029 single nucleotide polymorphism with nonalcoholic fatty liver disease (NAFLD) and coronary heart disease (CHD) and its influence on blood lipids in the Chinese Han population in Qingdao, China.Methods A total of 146 patients with NAFLD, 155 patients with CHD, and 156 patients with NAFLD and CHD, who were admitted to Qingdao Municipal Hospital from January to November, 2017, were enrolled as NAFLD group, CHD group, and NAFLD + CHD group, respectively, and 175 healthy individuals were enrolled as control group. Fasting venous blood samples were collected for biochemical analysis and TRIB1 rs2954029 genotyping. The chi-square test was used to analyze whether the distribution of genotypes was in accordance with the Hardy-Weinberg equilibrium. The chi-square test was used for comparison of categorical data between groups; the t-test and the Wilcoxon rank-sum test were used for comparison of continuous data between groups. The unconditioned logistic regression model was used to calculate odds ratio (OR) and its 95% confidence interval (CI) . Results There were no significant differences in rs2954029 genotype/allele frequency and distribution between the CHD group and the control group, as well as between the NAFLD + CHD group and the NAFLD group (all P > 0. 05) . In the CHD group and the control group, rs2954029 AT + AA carriers did not have an increased risk of CHD compared with rs2954029 TT carriers (OR = 1. 496, 95% CI: 0. 947-2. 363, P = 0. 084) ; in the NAFLD + CHD group and the NAFLD group, rs2954029 AT + AA carriers did not have an increased risk of CHD compared with rs2954029 TT carriers (OR = 1. 361, 95% CI: 0. 832-2. 227, P =0. 219) ; there were still no significant differences after adjustment for sex, age, and body mass index. In the whole population and the NAFLD group, there were no significant differences in biochemical parameters between the individuals carrying A allele and those not carrying this allele (P > 0. 05) ; in the CHD group and the NAFLD + CHD group, the individuals carrying A allele had a significantly higher level of triglyceride than those not carrying this allele (Z =-1. 986, -2. 521, all P < 0. 05) ; in the control group, the individuals carrying A allele had a significantly higher level of total cholesterol than those not carrying this allele (Z =-2. 653, P < 0. 05) . Conclusion In the Chinese Han population in Qingdao, TRIB1 rs2954029 single nucleotide polymorphism does not increase the risk of CHD in NAFLD patients.

Case reports
Alcoholic hepatitis with multiple myeloma misdiagnosed as alcoholic cirrhosis: A case report
Liu ZhanTao, Cai YanJun, Qi Yue, Li WanYu
2019, 35(6): 1337-1339. DOI: 10.3969/j.issn.1001-5256.2019.06.031
Abstract:
A case of sarcomatoid combined hepatocellular-cholangiocarcinoma
Ceng YongChao, Dai ChaoLiu, Zhao Yang, Chang XiaoYing, Su Yang
2019, 35(6): 1340-1341. DOI: 10.3969/j.issn.1001-5256.2019.06.032
Abstract:
Transcatheter arterial chemoembolization combined with apatinib for the treatment of hepatic epithelioid hemangioendothelioma: A case report
Zhang Lu, Wang ZhongFeng, Song LiSha, Xin GuiJie
2019, 35(6): 1342-1343. DOI: 10.3969/j.issn.1001-5256.2019.06.033
Abstract:
Hilar cholangiocarcinoma with bladder metastasis: A case report
Zhou MingMing, Chai WenGang, Sun Lu, Zhao WenChao, Zhang Ping
2019, 35(6): 1344-1345. DOI: 10.3969/j.issn.1001-5256.2019.06.034
Abstract:
Gas-forming pyogenic liver abscess: A case report
Cai YiWei, Xiao Xin, Li Jing, Liu HuiNa, Liu Jun, Wu GuangLi
2019, 35(6): 1346-1348. DOI: 10.3969/j.issn.1001-5256.2019.06.035
Abstract:
Liver injury induced by recombinant human type Ⅱ tumor necrosis factor receptor-antibody fusion protein for injection
Pan GaoFeng, Fu MaoYing, Gao YuFeng
2019, 35(6): 1349-1350. DOI: 10.3969/j.issn.1001-5256.2019.06.036
Abstract:
Ultrasound diagnosis of hereditary hemorrhagic telangiectasia: A case report
Li Jie, Li Tong, Sun XiaoFeng
2019, 35(6): 1351-1352. DOI: 10.3969/j.issn.1001-5256.2019.06.037
Abstract:
Reviews
Characteristics and mechanism of virological and liver function changes in pregnant women with chronic hepatitis B virus infection during pregnancy and after delivery
Zhao MengYu, Zou HuaiBin, Chen Yu, Zheng SuJun, Duan ZhongPing
2019, 35(6): 1353-1357. DOI: 10.3969/j.issn.1001-5256.2019.06.038
Abstract:
In pregnant women with hepatitis B virus (HBV) infection, body changes (hormone levels and immune status) during pregnancy or drug withdrawal after antiviral therapy may lead to virological changes, abnormal liver function, and even adverse outcomes in severe cases. Therefore, strengthening the monitoring of virological indicators and liver function in pregnant women with chronic HBV infection during pregnancy and after delivery can help to find body changes in time and thus prevent the adverse outcomes such as hepatitis and liver failure.This article reviews the articles on the characteristics and mechanisms of virological and liver function changes in pregnant women with chronic HBV infection during pregnancy and after delivery, in order to provide theoretical support for clinicians on the management of pregnant women with chronic HBV infection during pregnancy and after delivery.
Clinical application of PIR classification in the evaluation of liver fibrosis regression
Zhang MengYang, Sun YaMeng, Zhao XinYan, You Hong
2019, 35(6): 1358-1360. DOI: 10.3969/j.issn.1001-5256.2019.06.039
Abstract:
Liver biopsy has been regarded as the gold standard for the assessment of liver fibrosis regression. In 2017, Liver Research Center, Beijing Friendship Hospital, proposed a new classification called PIR classification for the evaluation of liver fibrosis regression in patients with chronic hepatitis B after antiviral therapy, which was also called“Beijing classification”. This classification is new breakthrough based on conventional staging and grading systems, quantitative assessment methods for liver fibrosis, and the concept of liver biopsy. This article discusses the prospects and shortcomings of PIR classification.
The biological characteristics of GP73 and its value in the diagnosis of liver fibrosis and cirrhosis
Li JiaNa, Zheng RuiQi, Li Na, Hu YuLin
2019, 35(6): 1361-1364. DOI: 10.3969/j.issn.1001-5256.2019.06.040
Abstract:
Liver fibrosis is a necessary stage in the development of chronic liver diseases to liver cirrhosis. Liver cirrhosis is the end-stage change of various chronic liver diseases, and early diagnosis of liver fibrosis has an important value in timely treatment and prognosis. At present, liver biopsy, ultrasound, computed tomography, and magnetic resonance imaging are the main diagnostic methods for liver fibrosis and cirrhosis. Liver biopsy is the gold standard for the diagnosis of liver fibrosis and cirrhosis, but its clinical application is limited by invasiveness and sample error. Conventional noninvasive methods cannot meet the requirements for the diagnosis of liver fibrosis and cirrhosis.Therefore, searching for new serological markers for liver fibrosis and cirrhosis has become a research hotspot. Related studies have shown that serum Golgi protein 73 (GP73) can be used as a serum marker for the diagnosis of liver fibrosis and cirrhosis and has high clinical value. This article reviews the commonly used methods for the diagnosis of liver fibrosis and cirrhosis and elaborates on the biological characteristics of GP73 and its value in the diagnosis of liver fibrosis and cirrhosis.
Endoscopic therapy for liver cirrhosis with esophageal variceal bleeding
Jiang ZhangWen, Wang AnJiang, Zhang JinLian, Ruan FangMing, Li BiMin
2019, 35(6): 1365-1368. DOI: 10.3969/j.issn.1001-5256.2019.06.041
Abstract:
Esophageal variceal bleeding is a serious complication of liver cirrhosis. Endoscopic therapy is a main method for the prevention and treatment of esophageal variceal bleeding, which includes endoscopic variceal ligation, sclerosing agent injection, endoscopic ultrasound-guided injection of sclerosing agent, tissue adhesive injection, self-expandable covered metallic stent, and combination treatment. This article reviews the indications, clinical effect, and complications of these endoscopic therapies.
Influence of ischemia-reperfusion injury on liver cancer and related mechanism
Zheng JianHao, Dai ChaoLiu
2019, 35(6): 1369-1373. DOI: 10.3969/j.issn.1001-5256.2019.06.042
Abstract:
In the process of the surgical treatment of liver cancer, blood flow occlusion at the porta hepatis is an important method to reduce intraoperative bleeding, and ischemia-reperfusion injury (IRI) resulting from such occlusion has an important effect on tumor cell. IRI can not only lead to tumor recurrence and metastasis, but also exert an inhibitory effect on tumor. Such influence is associated with various factors including free radicals, nitric oxide, inflammatory cytokines, and enzymes. An understanding of such effect and related mechanisms is of great importance to the research on the association between IRI and liver cancer and the selection of treatment methods for liver cancer.
Effect of long non-coding RNAs on glycolytic pathway in primary liver cancer and related mechanisms
Duan YiFei, Zhao QingXi, Jing Xue
2019, 35(6): 1374-1376. DOI: 10.3969/j.issn.1001-5256.2019.06.043
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Primary liver cancer is a common malignant tumor with complex pathogeneses and has the features of insidious onset, high degree of malignancy, and poor prognosis. The change in glycolytic pathway is one of the most important differences between tumor cells and normal cells, and tumor cells prefer to generate energy from glycolysis. Aerobic glycolysis is often associated with the progression and poor prognosis of primary liver cancer. Long non-coding RNAs (lncRNAs) can influence the glycolysis pathway in many tumors by regulating glucose uptake and the expression and activation of glycolytic enzymes and thus play an important role in the development and progression of primary liver cancer, which suggests that lncRNAs can be used as a therapeutic target for liver cancer. This article summarizes the influence of lncRNAs on primary liver cancer and glucose metabolism and related mechanisms, so as to find potential and effective targeted therapies for primary liver cancer.
Independent association between sarcopenia and nonalcoholic fatty liver disease
Zhao LiQiong, Li LiangPing
2019, 35(6): 1377-1379. DOI: 10.3969/j.issn.1001-5256.2019.06.044
Abstract:
Nonalcoholic fatty liver disease (NAFLD) is a metabolic disease which can progress to liver fibrosis, liver cirrhosis, and liver cancer. Sarcopenia is an age-related disease and metabolic factors play an important role in its pathogenesis. NAFLD and sarcopenia share a variety of metabolic pathophysiological mechanisms. Further studies are needed to determine whether there is an association between NAFLD and sarcopenia and whether they are predisposing factors or risk factors for disease progression for each other, in order to help with better prevention, treatment, and prognostic evaluation of the two diseases in clinical practice. This article reviews the independent association between NAFLD and sarcopenia.
The role of the NOD-like receptor family, pyrin domain-containing protein 3 inflammasome in nonalcoholic steatohepatitis
Zhou QingLi, Xu ZhenYuan, Zhang SuYan, Shi AnHua, Zhang ShunZhen
2019, 35(6): 1380-1383. DOI: 10.3969/j.issn.1001-5256.2019.06.045
Abstract:
Nonalcoholic steatohepatitis (NASH) is an important pathological stage of nonalcoholic fatty liver disease characterized by hepatocyte fatty degeneration, liver injury, and liver inflammation and can further develop into liver cirrhosis and hepatocellular carcinoma. The NOD-like receptor family, pyrin domain-containing protein 3 (NLRP3) inflammasome is a multi-protein complex in cells and can induce cell apoptosis and expand inflammatory response by activating caspase-1 and releasing mature inflammatory factors such as interleukin-1β and interleukin-18. Recent studies have found that NLRP3 inflammasome may participate in the development and progression of NASH. Therefore, this article summarizes the role of NLRP3 inflammasome in NASH, so as to provide a theoretical basis for future research and treatment.
Research advances in diagnostic criteria for acute-on-chronic liver failure and models for prognostic evaluation
Liu Juan, Bai FeiYun, Zhang Jing
2019, 35(6): 1384-1387. DOI: 10.3969/j.issn.1001-5256.2019.06.046
Abstract:
Acute-on-chronic liver failure is a serious acute liver function decompensation based on chronic liver diseases. It has an extremely high short-term mortality rate and has always been a research hotspot in the field of liver disease. In recent years, China, Asian Pacific Association for the Study of the Liver, and European Association for the Study of the Liver have issued or updated the diagnostic criteria for acute-on-chronic liver failure, but the diagnostic criteria vary greatly due to different etiologies and pathogeneses in the East and the West. Prognostic models have also been constantly updated based on different diagnostic criteria. This article compares the above diagnostic criteria and introduces the new prognostic models in detail, in order to improve the understanding and diagnosis/treatment of this disease among clinicians.
Role of silent information regulator 1 in hepatic ischemia-reperfusion injury
Wang JingYuan, Li ShengWei, Gong JianPing, Jiang DeQuan
2019, 35(6): 1388-1391. DOI: 10.3969/j.issn.1001-5256.2019.06.047
Abstract:
Hepatic ischemia-reperfusion injury has always been a difficult problem in liver transplantation and liver tumor resection. The involvement of multiple mechanisms makes it particularly complex, among which energy expenditure during ischemia and oxidative stress induced by reperfusion are the main mechanisms leading to hepatic ischemia-reperfusion injury and may cause cell death and even liver failure. Silent information regulators are a class of nicotinamide adenine dinucleotide-dependent deacetylases which can lead to deacetylation of transcription factors including histones and nonhistones, and they are playing an important regulatory role in cell apoptosis, inflammatory response, energy balance, and oxidative stress. There are 7 types of silent information regulators in mammals, i. e., Sirt1-Sirt7, among which Sirt1 can reduce hepatocyte stress, regulate cell metabolic pathways, and thus alleviate the degree of hepatic ischemia-reperfusion injury through various signaling pathways. This article reviews the role of Sirt1-related signaling pathways in hepatic ischemia-reperfusion injury.
Autoimmune hepatitis-related autoantibodies and their clinical significance
Xue Mei, Shen Yi, Shen MengYi, Fan XiaoLi, Men RuoTing, Yang Li
2019, 35(6): 1392-1396. DOI: 10.3969/j.issn.1001-5256.2019.06.048
Abstract:
Autoimmune hepatitis (AIH) is an autoimmune response-mediated liver parenchymal inflammation targeting hepatocytes, with the features of autoantibodies in serum, a high serum level of immunoglobulin G, and/or hypergammaglobulinemia. Most AIH patients have one or more autoantibodies in serum, and these antibodies are important features of AIH and the basis for the diagnosis of AIH. Some antibodies are also associated with the clinical manifestations, disease activity, therapeutic response, and prognosis of AIH. This article reviews AIH-related autoantibodies and their clinical significance.
Role of cell apoptosis in the pathogenesis of primary biliary cholangitis
Qu Yao, Zhang Wei
2019, 35(6): 1397-1400. DOI: 10.3969/j.issn.1001-5256.2019.06.049
Abstract:
Cell apoptosis plays an important role in the development and progression of liver diseases and the maintenance of liver homeostasis. In primary biliary cholangitis, biliary epithelial cells can lead to the specific immune response of mitochondrial autoantigens. The signals such as the activation of death receptor, oxidative stress, infection, and toxin may cause selective damage of biliary epithelial cells by immune attack during cell apoptosis. Abnormal survival regulation of cells may result in a gradual loss of small bile ducts mainly in the way of cell apoptosis and may eventually lead to the development of primary biliary cholangitis.
Pathogenesis of immunoglobulin G4-related hepatobiliary and pancreatic diseases
Zhang DeHua, Zhao Jie
2019, 35(6): 1401-1405. DOI: 10.3969/j.issn.1001-5256.2019.06.050
Abstract:
Immunoglobulin G4 (IgG4) -related disease is a chronic progressive autoimmune disease involving multiple systems throughout the body. IgG4-related hepatobiliary and pancreatic diseases are the manifestation of IgG4-related disease involving the hepatobiliary and pancreatic systems, with the main features of an increased serum IgG4 level and IgG4-positive lymphoplasmacytic infiltration. IgG4-related hepatobiliary and pancreatic diseases can mimic various inflammations and tumor diseases, which may lead to missed diagnosis and misdiagnosis in clinical practice. This article elaborates on the pathogenesis of IgG4-related hepatobiliary and pancreatic diseases from the perspectives of genetic inheritance, infection and molecular mimicry, and immune factors, so as to improve the understanding of such diseases.