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

2016 No. 4

Display Method:
Editorial
A clinical analysis of strengthening integrated traditional Chinese and Western medicine therapy for prevention and treatment of liver cancer
Liu Ping
2016, 32(4): 615-618. DOI: 10.3969/j.issn.1001-5256.2016.04.001
Abstract:

Primary liver cancer has the second highest fatality among malignant tumors in China,and in our country,most cases of liver cancer occur on the basis of liver cirrhosis. In view of the clinical characteristics of primary liver cancer in China,we need to make full use of effective therapies in Western medicine,explore the advantages of traditional Chinese medicine,develop unique comprehensive regimens for the prevention and treatment of liver cancer,and effectively reduce the incidence and fatality of liver cancer.

Therapeutic guidelines
ACG clinical guideline(2016): liver disease and pregnancy
Yu YueCheng, Hou JinLin
2016, 32(4): 619-627. DOI: 10.3969/j.issn.1001-5256.2016.04.002
Abstract:
The role of endoscopy in the evaluation and management of patients with solid pancreatic neoplasia: 2015 ASGE guidelines
Zhang YongGuo, Guo XiaoZhong
2016, 32(4): 628-632. DOI: 10.3969/j.issn.1001-5256.2016.04.003
Abstract:
Recommendation about United Kingdom National guideline on the management of the viral hepatitides A, B and C 2015
Jiang Yong, Wang ZeYu, Han Tao
2016, 32(4): 633-638. DOI: 10.3969/j.issn.1001-5256.2016.04.004
Abstract:
Recommendations of JSH guidelines for the management of hepatitis C virus infection:  a 2016 update for genotype 1 and 2
Zhang NingYi, Luo ShengQiang
2016, 32(4): 639-643. DOI: 10.3969/j.issn.1001-5256.2016.04.005
Abstract:
Discussions by experts
Clinical application of traditional Chinese medicine constitution theory in diagnosis and treatment of chronic hepatitis B
Xun YunHao, Guo JianChun
2016, 32(4): 644-648. DOI: 10.3969/j.issn.1001-5256.2016.04.006
Abstract:

The traditional Chinese medicine( TCM) constitution theory is an important means to reveal the host's genetic characteristics from the perspective of TCM. The types of constitution can influence liver pathological changes and the prognosis of disease in patients with chronic hepatitis B virus infection,and to a certain degree,they are associated with the polymorphisms of genes involved in immunoregulation,for example,human leukocyte antigen( HLA) class Ⅱ gene. Yin- deficiency constitution is associated with various adverse clinical outcomes,as well as the genotypes of genes including HLA- DQA1 * 0501. Preliminary data also show that the chronic hepatitis B( CHB) patients with yin- deficiency constitution have a poor response to interferon therapy. This article reviews the current application of TCM constitution theory in the diagnosis and treatment of CHB,its potential value,and existing problems.

Neutrophil- lymphocyte ratio: a novel predictor of clinical outcome of patients with hepatocellular carcinoma
Wang XianBo, Gao FangYuan, Liu Yao
2016, 32(4): 649-652. DOI: 10.3969/j.issn.1001-5256.2016.04.007
Abstract:

Accumulating evidence has shown that neutrophil- lymphocyte ratio( NLR),as an assessment index for inflammatory response,is closely related to the prognosis of various malignant tumors. This article summarizes the research advances in the relationship of NLR with overall survival,disease- free survival,and pathological features of hepatocellular carcinoma and related mechanisms of action,and points out that NLR is a convenient,economic,and effective predictor for the prognosis of patients with hepatocellular carcinoma.

Original articles_Integrated traditional and western medicine on hepatopancteatobiliary disease
Efficacy of Baihe Xiaoyao powder in treatment of chronic hepatitis B with depression: a clinical analysis
Tang Ning, Zhang YongHua
2016, 32(4): 653-656. DOI: 10.3969/j.issn.1001-5256.2016.04.008
Abstract:

Objective To investigate the efficacy of Baihe Xiaoyao powder in patients with chronic hepatitis B( CHB) and depression,and to explore its mechanism of action from the perspectives of endocrine and immune function. Methods A total of 120 patients with CHB who visited the Outpatient Department of Zhejiang Hospital of Integrated Traditional Chinese and Western Medicine from September 2013 to February 2015 were enrolled,and according to the Hamilton Depression Scale( HAMD) scores,they were divided into CHB- depression group( 80 patients) and CHB group( 40 patients). The levels of cortisol( Cor) and interleukin- 2( IL- 2) and the proportion of natural killer( NK) cells were compared between the two groups. The 80 patients in the CHB- depression group were further divided into control group and treatment group,with 40 patients in each group. The patients in the control group were treated with entecavir for 12 weeks,and those in the treatment group were treated with entecavir and Baihe Xiaoyao powder for 12 weeks. The effects of Baihe Xiaoyao powder on liver function [alanine aminotransferase( ALT) and aspartate aminotransferase( AST) ],hepatitis B virus( HBV) DNA,HAMD score,Cor,and immune function( IL- 2 and NK cells) were observed in patients with CHB and depression. The t- test was used for comparison of continuous data,the chi- square test was used for categorical data,and correlation analysis was also performed. Results Compared with CHB patients without depression,those with depression had a significantly higher level of Cor,a significantly lower level of IL- 2,and a significantly lower proportion of NK cells( P < 0. 01),and Cor level was negatively correlated with IL- 2 level( r =- 0. 786,P < 0. 01) and the proportion of NK cells( r =- 0. 681,P < 0. 01). After the treatment with Baihe Xiaoyao powder for 12 weeks,compared with the control group,the treatment group had significantly lower HAMD score and levels of Cor,ALT,and AST( P < 0. 01) and significantly higher level of IL- 2,proportion of NK cells,and HBV DNA clearance rate( P < 0. 05). Conclusion The CHB patients with depression have endocrine disorders,an increased serum level of Cor,a reduced level of IL- 2,and a reduced proportion of NK cells. Baihe Xiaoyao powder can improve depressive emotion,reduce the level of Cor,improve the body's immune function and liver function,and increase HBV DNA clearance rate.A combination of Baihe Xiaoyao powder and antiviral therapy can improve the clinical outcome of CHB.

Effect of “treating liver by nourishing spleen”on gut microbiota in rats with liver fibrosis based on Xiaoyao powder and its separated recipe
Chen Bin, Xu JiaYu, Peng Jie, He Wan, Li Wu, Su XuChu, Sun KeWei
2016, 32(4): 657-662. DOI: 10.3969/j.issn.1001-5256.2016.04.009
Abstract:

Objective To investigate the possible mechanism of“treating liver by nourishing spleen”in the treatment of liver fibrosis with reference to the effect of Xiaoyao powder and its separated recipe on gut microbiota and the level of portal endotoxins. Methods A total of70 healthy Wistar rats were randomly divided into blank group( 10 rats),model group( 20 rats),experimental group( 20 rats),and control group( 20 rats),and tail vein injection of bovine serum albumin was performed for 8 weeks to establish a rat model of immune liver fibrosis.The rats in the experimental group were given Xiaoyao granules by gavage,and those in the control group were given Xiaoyao granules without the spleen- strengthening traditional Chinese medicines Atractylodes macrocephala Koidz.,Poria cocos,ginger,and Radix Glycyrrhizae Preparata by gavage. Serum aminotransferases,liver pathology,portal endotoxins,and the enterobacterial repetitive intergenic consensus( ERIC)- PCR fingerprint of gut microbiota were observed in each group. The analysis of variance was applied for comparison of continuous data with homogeneity of variance between multiple groups,and the least significant difference t- test was used for further comparison between any two groups; the Tamhane's method was applied for data with heterogeneity of variance; the Pearson correlation analysis was used for correlation analysis. Results Compared with the blank group,the model group showed changes in the diversity and structure of gut microbiota and an increase in the level of portal endotoxins( 0. 421 ± 0. 170 EU / ml vs 0. 784 ± 0. 180 EU / ml),which showed significant differences between these two groups( P < 0. 01),and the level of portal endotoxins was positively correlated with collagen area percentage in liver tissue( r = 0. 736,P < 0. 01). Compared with the model group,the experimental group had significantly reduced levels of alanine aminotransferase( ALT),aspartate aminotransferase( AST),and portal endotoxins( 73. 25 ± 10. 90 U / L vs 59. 84 ± 9. 60 U / L,135. 36 ±31. 41 U / L vs 107. 43 ± 17. 71 U / L,0. 784 ± 0. 180 EU / ml vs 0. 576 ± 0. 220 EU / ml,P < 0. 01 or P < 0. 05),and the rats in the experimental group had similar diversity and structure of gut microbiota as normal rats. The levels of ALT,AST,and portal endotoxins showed no significant differences between the experimental group and the control group( P > 0. 05). Conclusion The rats with liver fibrosis experience intestinal dysbacteriosis which causes the increase in portal endotoxins,and it is one of the mechanisms for the pathogenesis of “liver disease affecting spleen”during the pathological process of chronic liver injury. Xiaoyao powder can relieve liver fibrosis,partially restore the normal structure of gut microbiota,and reduce endotoxins,while the removal of the spleen- strengthening drugs will weaken the protective effect of Xiaoyao powder on the liver. This suggests that restoration of gut microbiota and reduction of portal endotoxins may be an important mechanism of “treating liver by nourishing spleen”in the treatment of liver fibrosis.

Analysis of TCM deficiency and excess attributes in patients with HBV- related acute- on- chronic liver failure based on phenotype of dendritic cells and function of T lymphocytes
Yin SiHan, Liu Peng, Zhang Tao, Sun KeWei
2016, 32(4): 663-668. DOI: 10.3969/j.issn.1001-5256.2016.04.010
Abstract:

Objective To summarize the traditional Chinese medicine( TCM) deficiency and excess attributes in patients with HBV- related acute- on- chronic liver failure( HBV- ACLF),and to analyze its association with the phenotype of dendritic cells( DCs) and T lymphocyte subsets. Methods The basic information,stages,and TCM syndromes of 30 patients who were diagnosed with HBV- ACLF in The First Affiliated Hospital of Hunan University of Chinese Medicine from March to November,2012 were collected,and according to their deficiency and excess attributes,they were divided into excess group and deficiency group. Ten healthy volunteers were enrolled as the control group. Flow cytometry was used to measure the percentage of CD3+,CD4+,and CD8+T lymphocytes in peripheral blood and the expression rate of CD4+CD25highCD127lowcells,as well as the expression rates of DCs with phenotypes of CD1α,HLA- DR,CD80,CD83,and CD86 which were isolated from peripheral blood mononucleated cells,induced,and cultured in vitro,and its association with TCM deficiency and excess attributes. The t- test was used for comparison of normally distributed continuous data between groups,the Wilcoxon rank sum test was used for comparison of continuous data which were not normally distributed between groups,and the chi- square test was used for comparison of categorical data between groups. Results Compared with the healthy control group,the HBV- ACLF patients showed significant reductions in the percentages of CD3+,CD4+,and CD8+T lymphocytes in peripheral blood and the expression rates of DCs with phenotypes of CD1α,HLA- DR,CD80,CD83,and CD86,as well as a significant increase in the expression rate of CD4+CD25highCD127lowcells( all P < 0. 01). Compared with the excess group,the deficiency group showed significant reductions in the percentages of CD3+and CD4+T lymphocytes and the expression rate of CD4+CD25highCD127lowcells( all P < 0. 05). Compared with the deficiency group,the excess group showed significant increases in the expression rates of DCs with phenotypes of CD1α,CD83,and CD86( all P < 0. 05). Conclusion The HBV- ACLF patients in deficiency and excess groups experience reduced functions of T lymphocyte subsets and insufficient activation function of DCs,which are more obvious in the deficiency group. The immune indices including phenotype of DCs and T lymphocyte subsets can be used as objective reference indices for determining TCM deficiency and excess attributes in HBV- ACLF patients.

Protective effect of Cordyceps militaris polypeptide against acute alcoholic liver injury in rats
Cai Qi, Yan WeiWei, Wang ShaoKun, Wu Yang
2016, 32(4): 669-672. DOI: 10.3969/j.issn.1001-5256.2016.04.011
Abstract:

Objective To investigate the protective effect of Cordyceps militaris polypeptide against acute alcoholic liver injury in rats and related mechanism. Methods A total of 60 Wistar rats were randomly divided into blank control group,model group,and low-,medium-,and high- dose Cordyceps militaris polypeptide groups. All rats except those in the blank control group were given 10 ml / kg 56° liquor by gavage once a day; the rats in the blank control group were given distilled water of the same dose by gavage once a day. At 1 hour after gavage with liquor,the rats in the model group and low-,medium-,and high- dose Cordyceps militaris polypeptide groups were given distilled water or Cordyceps militaris polypeptide solution( 6 ml / kg) by gavage. Blood samples were collected from the orbit 4 weeks later.The serum levels of alanine aminotransferase( ALT) and aspartate aminotransferase( AST) and the activity of superoxide dismutase( SOD)and level of malondialdehyde( MDA) in the liver were measured for each group,and the pathological changes in the liver were observed under a light microscope. Analysis of variance was applied for comparison between multiple groups,and the SNK- q test was applied for comparison between any two groups. Results Compared with the model group,the low-,medium-,and high- dose Cordyceps militaris polypeptide groups showed significant reductions in the serum levels of ALT and AST and the level of MDA in the liver( all P < 0. 05),as well as a significant increase in the activity of SOD in the liver( all P < 0. 05),while these indices showed significant differences between the low-,medium-,and high- dose Cordyceps militaris polypeptide groups( all P < 0. 05). The liver pathological sections from the low-,medium-,and high- dose Cordyceps militaris polypeptide groups showed alleviated hepatocyte fatty degeneration and necrosis induced by alcohol under a light microscope. Conclusion Cordyceps militaris polypeptide has a protective effect against acute liver injury induced by alcohol,and its mechanism of action may be related to its antioxidant effect.

Effect of ultrasound- guided percutaneous injection of cinobufotalin or anhydrous ethanol in treatment of portal vein tumor thrombus: a comparative analysis
Ji JianFeng, Xiao QiuJin, Deng XiaoLi
2016, 32(4): 673-677. DOI: 10.3969/j.issn.1001-5256.2016.04.012
Abstract:

To investigate the effect of ultrasound- guided percutaneous injection of cinobufotalin or anhydrous ethanol in the treatment of portal vein tumor thrombus( PVTT) through a comparative analysis. Methods A total of 56 patients with PVTT after liver cancer surgery,who were admitted to the 94 th Hospital of PLA from October 2009 to December 2011,were enrolled. Among these patients,27 underwent ultrasound-guided percutaneous injection of cinobufotalin( cinobufotalin group) and 29 underwent ultrasound- guided percutaneous injection of anhydrous ethanol( anhydrous ethanol group). The clinical outcome and survival time were compared between the two groups after treatment,and the levels of total bilirubin( TBil),alanine aminotransferase( ALT),and aspartate aminotransferase( AST) before and after treatment were compared. The t- test was used for comparison of continuous data between groups,the chi- square test was used for comparison of categorical data between groups,the rank sum test was used for comparison of ranked data,and the Kaplan- Meier method was used for survival analysis. Results The response rate showed no significant difference between the cinobufotalin group and the anhydrous ethanol group( 63. 0% vs 58. 6%,χ~2= 0. 111,P > 0. 05). After treatment,the cinobufotalin group had significantly lower levels of TBil,ALT,and AST than the anhydrous ethanol group( t = 2. 24,2. 40,and 2. 39,all P < 0. 05). The 6- month,1- year,and 2- year survival rates showed no significant differences between the cinobufotalin group and the anhydrous ethanol group( 81. 5% /63. 0% /29. 6% vs 82. 8% /58. 6% /31. 0%,χ~2= 0. 016,0. 111,and 0. 013,all P > 0. 05). Conclusion Ultrasound- guided percutaneous injection of cinobufagin or anhydrous ethanol has similar short-and long- term effects in the treatment of PVTT and can inhibit the growth of tumor thrombus and prolong survival time,but cinobufagin is superior to anhydrous ethanol in the aspect of protecting liver function.

Effects of early intervention with Huoxueqingjie decoction on hemorheological parameters and D- dimer,thromboxane A2,and prostaglandin I2 levels in patients with severe acute pancreatitis
Sha YingYing, Liang Chao, Zhu XiaoMing, Wang XiongDa, Zhu YuHua
2016, 32(4): 678-681. DOI: 10.3969/j.issn.1001-5256.2016.04.013
Abstract:

Objective To investigate the effects of early intervention with Huoxueqingjie decoction on hemorheological parameters and the levels of thromboxane A_2( TXA_2) and prostaglandin I_2( PGI_2) in patients with severe acute pancreatitis. Methods A total of 50 patients with severe acute pancreatitis( SAP) who were hospitalized in our hospital from January to December,2013 were randomly divided into treatment group and control group. The patients in the two groups were given symptomatic / supportive treatment,and those in the treatment group were given Huoxueqingjie decoction twice a day through a spiral nasointestinal tube,with a course of the treatment of 1 week. Blood amylase,hemorheological parameters,and the levels of D- dimer,TXA_2,and PGI_2 were measured before treatment and on the 7th day of treatment. Comparison of normally distributed continuous data between groups was performed by t test,and comparison of categorical data between groups was conducted by chi- square test. Results Compared with the control group,the treatment group had a significant increase in overall response rate on the 7th day of treatment( 64% vs 88%,χ~2= 3. 947,P = 0. 047). On the 7th day of treatment,both groups showed significant reductions in the serum levels of amylase,D- dimer,and TXA2 and TXA_2/ PGI_2ratio( all P < 0. 01),and the treatment group had significantly lower levels of these parameters than the control group( P < 0. 05 or P < 0. 01). On the 7th day of treatment,both groups showed a significant increase in PGI_2 level( both P < 0. 01),and the treatment group had a significantly higher PGI_2 level than the control group( P < 0. 01). On the 7th day of treatment,both groups showed significant reductions in all hemorheological parameters,high,middle,and low blood viscosity,plasma viscosity,whole blood reduced viscosity at high or low shear rate,hematocrit,erythrocyte rigidity index,erythrocyte aggregation index,equation K value of erythrocyte sedimentation rate,erythrocyte deformation index,and erythrocyte sedimentation rate( P < 0. 05 or P < 0. 01),and the treatment group had significantly lower hemorheological parameters than the control group( P < 0. 05 or P < 0. 01). Conclusion Traditional Chinese medicine Huoxueqingjie decoction can improve hemorheological parameters,inhibit the increase in D- dimer,maintain the balance between TXA2 and PGI2and therefore plays an important role in the treatment of SAP.

Original articles_Viral hepatitis
Influence of pegylated interferonα- 2a versus telbivudine on renal function in patients with chronic hepatitis B
Peng MeiJuan, Wang Wei, Yang XiaoFei, Hao ChunQiu, Bai XueFan, Jia ZhanSheng, Lian JianQi, Zhang Ye
2016, 32(4): 682-686. DOI: 10.3969/j.issn.1001-5256.2016.04.014
Abstract:

Objective To investigate the influence of pegylated interferonα- 2a( PEG- IFNα- 2a) versus telbivudine( Ld T) on renal function in patients with chronic hepatitis B( CHB). Methods The clinical data of 92 previously untreated HBe Ag- positive CHB patients who participated in the CHB IV clinical trial in Tangdu Hospital of Fourth Military Medical University from July 2007 to March 2013 were analyzed retrospectively,and among these patients,39 received subcutaneous injection of PEG- IFNα- 2a 180 μg / week( PEG- IFNα- 2a group) and 53 received antiviral therapy with Ld T 600 mg / d( Ld T group). The HBV DNA clearance rate,alanine aminotransferase( ALT)normalization rate,serum creatinine,urea nitrogen,and estimated glomerular filtration rate( e GFR) at baseline and weeks 24 and 48 of treatment were calculated and analyzed,and e GFR was calculated by Chronic Kidney Disease Epidemiology Collaboration( CKD- EPI) or Modification of Diet in Renal Disease( MDRD). The independent samples t- test was used for comparison of normally distributed continuous data between the two groups,and the Wilcoxon rank sum test was used for comparison of continuous data with non- normal distribution between the two groups; the repeated measures analysis of variance was used for comparison of data before and after treatment within one group,and Mauchly's test of sphericity was performed for data before the repeated measures analysis of variance; the chi- square test was used for comparison of categorical data between the two groups. Results In the PEG- IFNα- 2a group,serum creatinine decreased significantly at weeks 24 and 48 of treatment compared with the baseline value( 0. 68 ± 0. 11 mg / dl and 0. 67 ± 0. 11 mg / dl vs 0. 75 ± 0. 11 mg / dl,P<0. 000 1),and e GFR increased significantly at week 24 [128. 30 ± 10. 98 ml / min /1. 73 m2( CKD- EPI) or 143. 90 ± 25. 82 ml/min/1. 73m2( MDRD) ]and week 48 [128. 00 ± 10. 17 ml/min/1. 73 m2( CKD- EPI) or 144. 30 ± 24. 68 ml/min/1. 73 m2( MDRD) ] compared with the baseline value [123. 10 ± 9. 64 ml / min /1. 73 m2( CKD- EPI) or 127. 40 ± 20. 16 ml/min/1. 73 m2( MDRD) ]( P < 0. 000 1). In the Ld T group,serum creatinine( 0. 73 ± 0. 13 mg / dl) and e GFR [122. 30 ± 11. 22 ml / min /1. 73 m2( CKD- EPI) or 128. 10 ± 20. 67 ml/min /1. 73 m2( MDRD) ]at week 24 showed significant differences from those at baseline [serum creatinine: 0. 74 ± 0. 13 mg/dl; e GFR:121. 50 ± 11. 21 ml / min /1. 73 m2( CKD- EPI) or 126. 40 ± 20. 96 ml/min/1. 73 m2( MDRD) ]( P >0. 05); compared with the baseline values,serum creatinine at week 48( 0. 68 ± 0. 12 mg / dl) decreased significantly( P < 0. 000 1),while e GFR [125. 30 ± 11. 55 ml / min /1. 73 m2( CKD- EPI) or 138. 00 ± 25. 94 ml/min/1. 73 m2( MDRD) ]increased significantly( P < 0. 000 1). At week 48 of treatment,the Ld T group had significantly higher HBV DNA clearance rate and ALT normalization rate than the PEG- IFNα- 2a group( HBV DNA seroconversion rate: 60. 4% vs 38. 5%,χ~2= 6. 17,P = 0. 037; ALT normalization rate: 75. 5% vs 33. 3%; χ~2= 16. 34,P < 0. 000 1). Conclusion PEG- IFNα- 2a and Ld T do not influence renal function in CHB patients.

Efficacy of add- on adefovir dipivoxil at week 12 /24 in HBe Ag- positive chronic hepatitis B patients during PEG-IFNα therapy
You Jia, Chen Jing, Ye QiaoXia, Zheng Qi, Zhu YueYong, Dong Jing, Liu YuRui, Jiang JiaJi
2016, 32(4): 687-690. DOI: 10.3969/j.issn.1001-5256.2016.04.015
Abstract:

Objective To investigate the efficacy of add- on adefovir dipivoxil( ADV) at week 12 /24 in HBe Ag- positive chronic hepatitis B( CHB) patients with hepatitis B virus( HBV) DNA levels of ≥105copies / ml during pegylated interferonα( PEG- IFNα) therapy.Methods A retrospective analysis was performed on 74 HBe Ag- positive CHB patients,who had HBV DNA levels of ≥105copies / ml after12 weeks of PEG- IFNα treatment in The First Affiliated Hospital of Fujian Medical University from October 2009 to January 2014. These patients were divided into group A( n = 36),which was given ADV at week 12 of PEG- IFNα treatment,group B( n = 19),which was given ADV at week 24 of PEG- IFNα treatment,and group C( n = 19),which was not given ADV during the PEG- IFNα treatment. The combined response rate after 48 weeks of treatment was compared between the three groups,and the influencing factors for treatment outcome were investigated. Comparison of continuous data( mean ± SD) between the three groups was made by one- way analysis of variance,and comparison of categorical data was made by chi- square test. The receiver operating characteristic curve and multivariate Cox logistic analysis were used to evaluate the predictive values of these parameters. Results After 48 weeks of treatment,the combined response rate of group A( 27. 78%,10 /36) was significantly higher than those of group B( 5. 26%,1 /19) and group C( 5. 26%,1 /19)( both P =0. 045). The negative predictive values of HBe Ag decrease at week 12,HBe Ag decrease at week 24,and HBV DNA decrease at week 24 for combined response were 90. 0%,94. 44%,and 94. 55%,respectively. HBV DNA level at week 24 < 103 copies / ml and HBe Ag decrease at week 24 > 1. 06 log10 S / CO were independent predictive factors for combined response. Conclusion Add- on ADV therapy could increase the 48- week combined response rate of HBe Ag- positive CHB patients who have HBV DNA levels of ≥105copies / ml after 12 weeks of PEG- IFNα treatment. The HBV DNA and HBe Ag decreases at week 24 have high negative predictive values for combined response.

Efficacy of peginterferon α- 2a in treatment of chronic hepatitis B resistant to multiple nucleos( t) ide analogues
Yang Long, Yang Yang, Jiang XueHua, Chen ZhiYong
2016, 32(4): 691-694. DOI: 10.3969/j.issn.1001-5256.2016.04.016
Abstract:

Objective To investigate the efficacy of peginterferon alfa- 2a( PEG- IFN α- 2a) in the treatment of HBe Ag- positive chronic hepatitis B( CHB) resistant to multiple nucleos( t) ide analogues( NAs). Methods A total of 120 patients with HBe Ag- positive CHB resistant to multiple nucleos( t) ide analogues who were hospitalized or treated in the outpatient department in our hospital from August 2009 to February 2014 were randomly divided into two groups,with 60 patients in each group. The patients in the treatment group stopped NAs and were given PEG- IFNα- 2a for 48 weeks,and those in the control group received PEG- IFNα- 2a for 48 weeks in addition to the original therapeutic regimen with NAs. The changes in the serological markers of hepatitis B and HBV DNA were observed at weeks 24 and 48 of treatment and at 24 weeks after drug discontinuation. The chi- square test was used for comparison of categorical data between groups,while comporison of continuous data was mode by t test. Results The patients in both groups achieved a satisfactory outcome. The serum HBe Ag clearance rate,HBe Ag seroconversion rate,HBV DNA clearance rate,and HBs Ag clearance rate showed no significant differences between the two groups at weeks 24 and 48 of treatment and at 24 weeks after treatment( all P > 0. 05). The adverse events that occurred during PEG- IFNα- 2a treatment were pyrexia,headache,inflammation at the injection site,diarrhea,neutropenia,anemia,and depression,and the disease is not serious. Conclusion PEG- IFNα- 2a is safe and effective in the treatment of CHB resistant to multiple NAs,and the patients can convert to PEG- IFNα- 2a directly as their antiviral therapy.

Value of HBsAg quantification in predicting the prognosis of patients with chronic severe hepatitis B
Gao Na, Wu RuiHong, Wang XiaoMei, Niu JunQi
2016, 32(4): 695-699. DOI: 10.3969/j.issn.1001-5256.2016.04.017
Abstract:

Objective To investigate the value of HBs Ag quantification in predicting the prognosis of patients with chronic severe hepatitis B. Methods The clinical data of 61 patients with chronic severe hepatitis B who were admitted to The First Hospital of Jilin University from January 2012 to August 2015 were analyzed retrospectively and were followed up for 90 days. Chemiluminescent microparticle immunoassay was used to measure the serum HBs Ag level. The receiver operating characteristic curves were used to determine the cut- off value of HBs Ag,and according to this value,the patients were divided into HBs Ag < 1. 63 log10 IU / ml group,1. 63- 2. 61 log10 IU / ml group,2. 61-3. 62 log10 IU / ml group,and HBs Ag > 3. 62 log10 IU / ml group. The Kruskal- Wallis test was used for comparison of continuous data between multiple groups,the Mann- Whitney U test was used for comparison of continuous data between two groups,and the Fisher' s exact test was used for comparison of categorical data between groups. The log- rank test was used for comparison of survival curves between multiple groups. The univariate and multivariate Cox regression analyses were used to analyze the factors related to the prognosis of chronic severe hepatitis B and obtain the hazards ratio( HR) of each variable. The Spearman correlation analysis was used for correlation analysis. Results The survival time showed a significant difference between the four groups( χ~2= 18. 261,P < 0. 001). The HBs Ag < 1. 63 log10 IU / ml group had a significantly lower 90- day survival rate than the 2. 61- 3. 62 log10 IU / ml group( χ~2= 10. 283,P = 0. 001) and the HBs Ag >3. 62 log10 IU / ml group( χ~2= 17. 236,P < 0. 001). The multivariate Cox regression analysis showed that HBs Ag( HR = 0. 562,95% CI:0. 364- 0. 870,P = 0. 010),blood urea nitrogen( HR = 1. 111,95% CI: 1. 042- 1. 185,P = 0. 001),hepatic encephalopathy( HR =4. 123,95% CI: 1. 729- 9. 830,P = 0. 001),and Model for End- Stage Liver Disease( MELD) score( HR = 1. 093,95% CI: 1. 024~(-1). 166,P = 0. 007) were independent risk factors for the 90- day survival rate of patients with chronic severe hepatitis B. HBs Ag showed a low correlation with HBV DNA( r = 0. 326,P = 0. 01). Conclusion Serum HBs Ag level is an important factor in predicting the prognosis of patients with chronic severe hepatitis B.

Prognostic risk factors in patients with hepatitis B virus- related acute- on- chronic liver failure
Shi XinXing, Zhang YanQiong, Zhu Peng, Yan GuoHua, Zhang ZhangJiang, Wang YuMing
2016, 32(4): 700-705. DOI: 10.3969/j.issn.1001-5256.2016.04.018
Abstract:

Objective To investigate the clinical characteristic and long- term prognosis risk factor of patients with hepatitis B virus- related acute- on- chronic liver failure( HBV- ACLF). Methods The clinical data of 1116 HBV- ACLF patients who were hospitalized in Southwest Hospital of Third Military Medical University from January 2010 to January 2015 were analyzed retrospectively. The risk factors for1- year survival time and prognosis were observed,and the Cox regression model was used to determine the independent risk factors for the prognosis of these patients. The t- test or t'- test was applied for comparison of continuous data between groups,and the chi- square test was applied for comparison of categorical data between groups. Results A total of 562 patients died within the 1- year follow- up period,and the fatality rate was 50. 4%. The comparison between the survival group and the death group showed that age,alanine aminotransferase,total bilirubin,urea nitrogen,serum creatinine,international normalized ratio,serum Na+,white blood cell( WBC),percentage of neutrophils,platelet( PLT),HBV DNA load,Model for End- Stage Liver Disease( MELD) score,ascites,spontaneous bacterial peritonitis,gastrointestinal bleeding,pulmonary infection,sepsis,electrolyte disturbance,hepatic encephalopathy,and acute kidney injury( AKI)were the risk factors for death within 1 year( all P < 0. 05). The Cox regression analysis showed that age,WBC,MELD score,hepatic encephalopathy,electrolyte disturbance,AKI,and PLT were the independent risk factors for the 1- year fatality in HBV- ACLF patients( all P < 0. 05). Conclusion Our findings show that HBV- ACLF has a high fatality rate and is often accompanied by serious complications.The major risk factors affecting the 1- year fatality in HBV- ACLF patients are age,WBC,MELD score,hepatic encephalopathy,electrolyte disturbance,AKI,and PLT.

Clinical features of acute hepatitis B and acute exacerbation of chronic hepatitis B: a comparative study
Li Qiang, Zhuo QiBin, Huang YuXian, Chen Liang
2016, 32(4): 706-710. DOI: 10.3969/j.issn.1001-5256.2016.04.019
Abstract:

Objective To investigate the clinical features of acute hepatitis B( AHB) and acute exacerbation of chronic hepatitis B( CHB)for differential diagnosis. Methods A retrospective analysis was performed on the clinical data of 96 AHB patients and 124 patients with acute exacerbation of CHB,who were admitted to the Public Health Clinical Center Affiliated to Fudan University from June to December,2014. Comparison of continuous data between the two groups was made by Mann Whitney U test,while comparison of categorical data was made by chi- square test. Results There were no significant differences in the age of onset and sex between the AHB group and the acute exacerbation of CHB group; the incidence was higher in males than in females. Sexual transmission and iatrogenic transmission were the main routes of transmission for AHB,while mother- to- child transmission was the main route of transmission for acute exacerbation of CHB. The sensitivity and specificity of alanine aminotransferase( ALT) level ≥1072 U / L for diagnosing AHB were 78. 6% and 79. 2%,respectively. The sensitivity and specificity of S / CO ≥13. 6 in the anti- HBc- Ig M test for diagnosing AHB were 94. 5% and 89. 3%,respectively. At week 2 after admission,the AHB group showed significantly greater decreases in levels of HBs Ag,HBe Ag,and hepatitis B virus( HBV) DNA than the acute exacerbation of CHB group( P < 0. 05). At week 8 after admission,the AHB group had significantly higher HBs Ag clearance rate,anti- HBs seroconversion rate,HBe Ag clearance rate,anti- HBe seroconversion rate,and HBV DNA clearance rate than the acute exacerbation of CHB group( P < 0. 05). Conclusion It is helpful for making the differential diagnosis between AHB and acute exacerbation of CHB to know the route of transmission,ALT level,anti- HBc- Ig M test result( S / CO value),HBV DNA clearance rate,and the seroconversion rates of HBV markers.

Natural resistance mutations to direct- acting antiviral agents in interferon / ribavirin treatment- experienced and treatment- nave patients with chronic hepatitis C in Beijing,China
Zhang Yu, Cao Ying, Zhang RenWen, Zhang XiaXia, Lu HaiYing, Wu ChiHong, Huo Na, Yu Min, Liu Dan, Xu XiaoYuan
2016, 32(4): 711-715. DOI: 10.3969/j.issn.1001-5256.2016.04.020
Abstract:

Objective To investigate the incidence of natural resistance mutations to direct- acting antiviral agents( DAAs) in patients with chronic hepatitis C( CHC) in Beijing,China,and to compare the natural resistance mutations to DAAs in interferon( IFN) / ribavirin( RBV) treatment- experienced and treatment- nave patients. Methods A total of 101 CHC patients with genotype 1b who visited Peking University First Hospital from July 2009 to November 2013 were enrolled,among whom 40 patients were once treated with IFN / RBV and 61 patients were not treated with IFN / RBV. The patients' HCV RNA was extracted,and polymerase chain reaction was applied for amplification. The genes in HCV NS3,NS5 A,and NS5 B regions were sequenced,sequence alignment and resistance analysis were performed,and the incidence of natural resistance was compared. The t- test was applied for comparison of normally distributed continuous data between groups,and the Mann- Whitney U rank sum test was applied for comparison of abnormally distributed continuous data between groups. The chi- square test or Fisher 's exact test was applied for comparison of categorical data between groups. Results The sequences of NS3,NS5 A,and NS5 B regions were obtained from 84( 83. 17%),92( 91. 09%),and 97( 96. 04%) patients,respectively. The natural resistance mutations to DAAs in NS3 region occurred in 7 patients( 8. 33%)( T54 S,n = 1,1. 19%; R117 H,n = 5,5. 95%; N174 F,n = 1,1. 19%),those in NS5 A region occurred in 19 patients( 20. 65%)( L28 M,n = 7,7. 61%; L31 M,n = 1,1. 09%; P58 S,n = 4,4. 35%; Y93 H,n = 7,7. 61%),and those in NS5 B region occurred in 95 patients( 97. 94%)( L159 F,n = 1,1. 03%; C316 N,n = 92,94. 85%; A421 V,n = 6,6. 18%; R422 K,n = 1,1. 03%; M426 L,n = 3,3. 09%; V499 A,n = 38,39. 18%). The incidence of resistance mutations to DAAs in NS3,NS5 A,and NS5 B regions showed no significant difference between the IFN / RBV treatment- experienced and treatment- nave patients( all P > 0. 05). Conclusion Natural resistance mutations to DAAs exist in the treatment- nave CHC patients with genotype 1b in Beijing. Most of these mutations are low resistance mutations,and their effects on the clinical efficacy of DAAs need further investigation. The association between IFN / RBV treatment and increased natural resistance mutations to DAAs was not observed in CHC patients.

Original articles_Liver fibrosis and liver cirrhosis
Relationship between small intestinal bacterial overgrowth and severity of with hepatitis B cirrhosis
Wei XinPeng, Gao Xiao, Ma YingJie
2016, 32(4): 716-719. DOI: 10.3969/j.issn.1001-5256.2016.04.021
Abstract:

Objective To investigate the relationship between small intestinal bacterial overgrowth( SIBO) and the severity of hepatitis B cirrhosis. Methods Forty- seven patients with hepatitis B cirrhosis who visited Department of Gastroenterology,Zhengzhou People's Hospital,from June 2014 to June 2015 were selected as cirrhosis group; these patients consisted of 11 Child- Pugh class A cases,16 Child-Pugh class B cases,and 20 Child- Pugh class C cases. Fifteen healthy volunteers were selected as control group. The levels of procalcitonin,bilirubin,plasma albumin,and globulin were measured in all subjects. The lactulose hydrogen breath test( LHBT) was performed to measure small intestinal bacterial growth. Comparison of categorical data was made by chi- square test or Fisher's exact test. Comparison of normally distributed continuacs data between groups was performed by t test,The correlations of SIBO with procalcitonin,bilirubin,plasma albumin,and albumin / globulin ratio were investigated by Pearson correlation analysis. Results SIBO was found in 22( 46. 8%) of the 47 patients with liver cirrhosis,consisting of 2( 18. 1%) in the 11 Child- Pugh class A cases,7( 43. 7%) in the 16 Child- Pugh class B cases,and 13( 65. 0%) in the 20 Child- Pugh class C cases. The prevalence of SIBO showed a significant difference between the controls and all patients with hepatitis B cirrhosis,Child- Pugh class B cases,or Child- Pugh class C cases( P = 0. 005,0. 037,or 0. 001),but no significant difference between the controls and Child- Pugh class A cases( P = 0. 556); there was a significant difference in the prevalence of SIBO between Child- Pugh class A cases and Child- Pugh class B / C cases( χ~2= 4. 727,P = 0. 030). The levels of procalcitonin,bilirubin,plasma albumin,and globulin were significantly correlated with LHBT set- value( r = 0. 895,0. 907,- 0. 810,and 0. 755,respectively,all P < 0. 001). Conclusion The prevalence of SIBO increases with exacerbation of liver injury in patients with hepatitis B cirrhosis. The levels of procalcitonin,bilirubin,and globulin are positively correlated with SIBO,while plasma albumin level is negatively correlated with SIBO.

Effects of terlipressin and double- dose octreotide on hepatic venous pressure gradient in patients with liver cirrhosis:a comparative study
Feng QingLing, Feng ZeMin, Zhang ChunQing, Wang GuangChuan, Feng Hua
2016, 32(4): 720-723. DOI: 10.3969/j.issn.1001-5256.2016.04.022
Abstract:

Objective To investigate the efficacy of terlipressin and double- dose octreotide in reducing hepatic venous pressure gradient( HVPG) in patients with liver cirrhosis. Methods A total of 41 patients who were diagnosed with liver cirrhosis and esophageal and gastric varices in our hospital from June 2014 to March 2015 were randomly divided into terlipressin group( group A,22 patients) and octreotide group( group B,19 patients). The patients in group A were given intravenous injection of terlipressin 2 mg,and those in group B were given intravenous injection of octreotide 100 μg followed by intravenous infusion of the same drug at 50 μg / h. HVPG was measured before administration and at 10,20,and 30 min after administration,and the reduction in HVPG and changes in blood pressure and heart rate after administration were observed. The t- test was applied for comparison of continuous data between groups,and the chi- square test or Fisher's exact test was applied for comparison of categorical data between groups. Results In group A,HVPG before administration and at 10,20,and 30 min after administration was 18. 86 ± 5. 66,16. 75 ± 5. 54,16. 14 ± 5. 43,and 15. 25 ± 5. 93 mm Hg,respectively,while in group B,HVPG at the above time points was 19. 91 ± 6. 68,16. 58 ± 5. 86,17. 03 ± 6. 14,and 17. 66 ± 6. 09 mm Hg,respectively; each group showed a significant change in HPVG at each time point after administration compared with that before administration( t = 4. 010,6. 413,5. 134,5. 533,5. 741,and 4. 017,all P < 0. 05),while the reduction in HVPG after administration showed no significant differences across the two groups. The patients in both groups experienced varying degrees of reduction in heart rate and increase in blood pressure.Group A had a significantly larger reduction in heart rate compared with group B( 16. 13% ± 9. 28% vs 3. 35% ± 6. 34%; t =- 5. 062,P < 0. 001); group A had a significantly larger increase in blood pressure compared with group B( 17. 06 ± 8. 11% vs 11. 70 ± 7. 76%; t =2. 178,P = 0. 037). Conclusion Terlipressin and double- dose octreotide can effectively reduce HVPG in patients with liver cirrhosis and esophageal and gastric varices. Terlipressin can reduce HVPG more obviously over time,but terlipressin has a greater influence on heart rate and blood pressure.

Correlation of liver stiffness measured by Fibro Scan with sex and age in healthy adults undergoing physical examination
Zhao ChongShan, He WenYan, Wang NingFang, Geng Hua, An HongJie, Zhao BaoSheng, Gao MeiLi, Xu JinFeng
2016, 32(4): 724-727. DOI: 10.3969/j.issn.1001-5256.2016.04.023
Abstract:

Objective To determine the reference range of liver stiffness in healthy population,and to investigate the influence of age and sex on liver stiffness. Methods A total of 1794 healthy subjects who underwent physical examination in China National Petroleum Corporation Central Hospital from October 1,2012 to October 31,2014 were enrolled,and Fibro Scan was used to perform liver stiffness measurement( LSM). Since LSM value was not normally distributed,the Wilcoxon rank sum test was used to compare LSM value between male and female patients,the Kruskal- Wallis test was used to compare LSM value between different age groups,and the Spearman's rank correlation analysis was used to analyze the correlation between LSM value and age. The one- sided percentile method was used to determine the range of normal reference values in male and female subjects or in different age groups. Results LSM was successfully performed in 1590 patients,and the rate of successful measurement was 88. 63%. A total of 107 patients were excluded due to abnormal liver enzymes. The analysis showed that LSM value showed a significant difference between male and female subjects( Z =- 4. 980,P < 0. 001),as well as between different age groups( χ~2= 16. 983,P = 0. 001). Age was positively correlated with LSM value( r = 0. 087,P = 0. 001). The reference range was estimated to be ≤7. 1 k Pa in adults,≤7. 0 k Pa in females,and ≤7. 2 k Pa in males. From the perspective of age,the reference range was estimated to be ≤6. 8 k Pa in persons aged 20- 29 years,≤6. 7 k Pa in persons aged 30- 44 years,≤7. 8 k Pa in persons aged 45- 59 years,and ≤8. 8 k Pa in persons aged 60- 74 years. Conclusion Liver stiffness value is influenced by sex and age. Sex and age should be taken into account while performing liver stiffness measurement in healthy subjects.

Clinical features of drug- induced liver injury and primary biliary cirrhosis: a comparative analysis
Yang Jun, Yu YaLi, Zheng ZhangQing
2016, 32(4): 728-731. DOI: 10.3969/j.issn.1001-5256.2016.04.024
Abstract:

Objective To investigate and compare the clinical features of drug- induced liver injury( DILI) and primary biliary cirrhosis( PBC). Methods A total of 116 PBC patients and 124 DILI patients who were diagnosed in Shengjing Hospital of China Medical University from January 2005 to December 2013 were enrolled,and clinical features,laboratory indices,and the results of liver biopsy were compared between the two groups. The t- test or Nemenyi rank sum test was applied for comparison of continuous data between the two groups,and the chi- square test was applied for comparison of categorical data between the two groups. Results There were significant differences in age of onset and gender composition between the two groups( both P < 0. 05). The serological markers( except albumin),immunological indicators( Ig G,Ig M,and Ig A),and positive rate of autoantibodies( except SMA) showed significant differences between the two groups( all P < 0. 05). The histological appearances of PBC were hepatocyte edema( 30 patients),inflammatory cell infiltration around the bile duct( 29 patients),and atypical hyperplasia of the small bile duct( 28 patients),and those of DILI were hepatocyte steatosis( 15 patients)and spotty necrosis and loss of hepatocytes( 14 patients). Conclusion DILI and PBC are different in the aspects of laboratory tests and pathological examinations,which has a certain guiding significance in differential diagnosis in clinical practice.

Original articles_Liver neoplasms
Clinical and pathological features of cryptogenic liver cancer
Wang GuoHua, Cong LeLe, Zhao Zhao, Wang YueChao, Dai Jing, Zhao Ping
2016, 32(4): 732-734. DOI: 10.3969/j.issn.1001-5256.2016.04.025
Abstract:

Objective To investigate the clinical and pathological features of cryptogenic liver cancer,and to determine its etiology and pathogenesis. Methods A total of 22 patients with cryptogenic liver cancer who underwent surgical treatment in China- Japan Union Hospital of Jilin University from January 2010 to December 2015 were enrolled,and their clinical and pathological data were analyzed. Results The mean age of these patients was 57 years,and the male / female ratio was 1. 7 ∶ 1. Sixteen patients( 72. 7%) were complicated by fatty liver disease,and 13 patients( 59. 1%) had clinical symptoms such as abdominal pain and abdominal distension. The dominant abnormalities in biochemical examinations were increases in alkaline phosphatase and / or gamma- glutamyl transpeptidase,which occurred in 14 patients( 63. 6%). The results of pathological examination showed that 16 patients( 72. 7%) had cholangiocellular carcinoma,20( 90. 9%)had a single tumor,14( 63. 6%) had a tumor diameter of < 5 cm,4( 18. 2%) had local invasion,and 2( 9. 1%) had vessel invasion.The immunohistochemical results revealed 19 Ki67- positive patients,13 CK17- positive patients,and 16 CK19- positive patients. Conclusion The analyses of the clinical and pathological features of cryptogenic liver cancer confirm that nonalcoholic steatohepatitis( NASH)is one of the major pathogenic factors for cryptogenic liver cancer,and most liver cancer cases caused by NASH are single adenocarcinoma.

Total laparoscopic hepatectomy versus open hepatectomy in treatment of hepatocellular carcinoma in the left lateral lobe: a case- matched analysis
Xiong Yong, Wang HeBin, Liu DeQin, Chen JianXun, Liu JianPing, Sun ChangQin
2016, 32(4): 735-738. DOI: 10.3969/j.issn.1001-5256.2016.04.026
Abstract:

Objective To investigate the safety,feasibility,and efficacy of total laparoscopic hepatectomy in the treatment of hepatocellular carcinoma( HCC) in the left lateral lobe. Methods A case- matched analysis was performed between 25 patients with HCC in the left lateral lobe confirmed by postoperative pathological examination,who were admitted to Panzhihua Central Hospital and underwent total laparoscopic left lobe resection( LLLR) from April 2012 to April 2015,and 25 patients with HCC who underwent open left lobe resection( OLLR)during the same period. The t- test was used for comparison of continuous data between the two groups,and the chi- square test or Fisher's exact test was used for comparison of catagorical data between the two groups; the Kaplan- Meier method was used for survival analysis,and the log- rank test was used for comparison of survival curves. Results The time of operation,number of patients undergoing intraoperative blood transfusion,and number of patients with R0 resection margin showed no significant differences between the LLLR group and the OLLR group,but intraoperative blood loss( 216. 4 ± 15. 39 ml vs 273. 2 ± 16. 65 ml),mean hospital stay( 6. 92 ± 0. 29 min vs 10. 32 ±0. 52 min),and postoperative complications( 5 cases vs 12 cases) showed significant differences between the two groups( all P < 0. 05).The 1- and 3- year overall survival rates and progression- free survival showed no significant differences between the LLLR group and the OLLR group. Conclusion LLLR and OLLR have similar long- term efficacy in the treatment of HCC in the left lateral lobe,and LLLR has advantages in the aspects of intraoperative blood loss,postoperative complications,and length of hospital stay.

Expression of NOB1 in liver cancer tissues and its significance
Zhao LiJuan, Li ZhiFeng, Shi RongYa, Yang Ning, Liu JinZhong
2016, 32(4): 739-741. DOI: 10.3969/j.issn.1001-5256.2016.04.027
Abstract:

Objective To measure the expression of NOB1 in liver cancer tissues,and to investigate the relationship between NOB1 and clinicopathological features of liver cancer. Methods A total of 48 liver cancer samples were collected from the patients who underwent liver cancer surgery in our hospital from February 2011 to May 2015,and 22 samples of cirrhotic liver tissues and 22 samples of normal liver tissues were collected as controls. The immunohistochemical SP method was used to measure the expression of NOB1 in different tissues,and the relationship between the expression of NOB1 and clinicopathological features was analyzed. The chi- square test was applied for comparison of categorical data between groups. Results The expression of NOB1 in liver cancer tissues was significantly higher than that in cirrhotic liver tissues and normal liver tissues( 72. 9% vs 36. 4% /31. 8%; P = 0. 004 and 0. 001),while the expression of NOB1 showed no significant difference between cirrhotic liver tissues and normal liver tissues( P > 0. 05). The patients with a tumor diameter of > 5 cm had a significantly higher positive rate of NOB1 than those with a tumor diameter of ≤5 cm( χ~2= 4. 355,P = 0. 037),and the patients with Edmondson grade Ⅲ / Ⅳ tumor had a significantly higher positive rate of NOB1 than those with Edmondson grade Ⅰ / Ⅱ tumor( χ~2= 5. 127,P = 0. 024). The expression of NOB1 in liver cancer tissues was not correlated with age,sex,presence or absence of microvascular invasion,presence or absence of lymph node metastasis,and clinical TNM stage( all P > 0. 05). Conclusion NOB1 is highly expressed in liver cancer tissues. The expression of NOB1 is closely related to tumor size and Edmondson grade,and can be used as an important tumor marker for liver cancer.

Efficacy of raltitrexed combined with transcatheter arterial chemoembolization in treatment of advanced colorectal cancer with liver metastasis
Wang BaoXin, Zhang Rui, Hu XinHua, Qi XiuHeng, Xiao FangFang, Xing HongJian, Zou QingHua, Guo Qian, Wu ZhenMing
2016, 32(4): 742-745. DOI: 10.3969/j.issn.1001-5256.2016.04.028
Abstract:

Objective To investigate the efficacy of raltitrexed combined with transcatheter arterial chemoembolization( TACE) in the treatment of advanced colorectal cancer with liver metastasis. Methods A total of 80 patients with liver metastasis of advanced colorectal cancer who were admitted to Central Hospital of China National Petroleum Corporation and underwent surgery from January 2012 to June 2015 were enrolled and randomly divided into study group and control group,with 40 patients in each group. The patients in the study group underwent hepatic arterial infusion chemotherapy with raltitrexed combined with TACE,and those in the control group were treated with intravenous infusion of raltitrexed alone. The above treatment was performed once every 4 weeks for 3- 6 cycles. The response rate( RR),disease control rate( DCR),median time to disease progression,survival rate,and reductions in carcinoembryonic antigen( CEA),CA19- 9,aminotransferases,and bilirubin were observed in the two groups. The chi- square test was used for comparison of categorical data between groups.Results RR,DCR,and the median time to disease progression showed significant differences between the study group and the control group( 45. 0% vs 22. 5%,χ~2= 4. 528,P = 0. 033; 70. 0% vs 47. 5%,χ~2= 4. 178,P = 0. 041; 17. 9 months vs 10. 5 months,χ~2=24. 08,P < 0. 001). The study group had significantly higher 1- and 2- year survival rates than the control group( 80. 0% vs 57. 5%,χ~2= 4. 713,P = 0. 030; 55. 0% vs 32. 5%,χ~2= 4. 114,P = 0. 043). The study group had a significantly higher number of patients with more than 50% reductions in CA19- 9,CEA,aminotransferases,and bilirubin at 2 months after TACE than the control group( χ~2= 5. 333,4. 528,5. 051,and 5. 013,P = 0. 021,0. 033,0. 025,and 0. 025). Conclusion Raltitrexed combined with TACE is of good value in the treatment of advanced colorectal cancer with liver metastasis and holds promise for clinical application.

Original articles_Biliary diseases
Ultrasonographic signs as factors for recurrence of gallstones and polypoid lesions of the gallbladder after gallbladder-preserving surgery
Lu: ZhiHong, Yu Lei, Han EHui, Hong Wei, Hu XiaoJuan, Pei Fei
2016, 32(4): 746-749. DOI: 10.3969/j.issn.1001-5256.2016.04.029
Abstract:

Objective To investigate ultrasonographic signs as the factors for the recurrence of gallstones and polypoid lesion of the gallbla-dder in patients undergoing gallbladder- preserving surgery. Methods Related signs including gallbladder size,sound transmission of the gallbladder,gallbladder wall thickness,cholestasis,gallbladder contraction function,and common bile duct diameter measured by preoperative and postoperative ultrasonography,as well as the recurrence of gallstones and polypoid lesions of the gallbladder after surgery,were collected from 700 patients who underwent gallbladder- preserving surgery in Huangshi Central Hospital from January 2011 to February 2015.The Fisher's exact test and Cox proportional hazards regression model were applied for univariate and multivariate analysis of related factors for recurrence after gallbladder- preserving surgery. Results The shortest and longest follow- up time was 6 months and 48 months,respectively,and the mean follow- up time was 18 ± 12 months. Among the 700 patients,1 experienced recurrence of gallstones at 1 month after surgery,2 experienced recurrence of gallstones at 6 months after surgery,1 experienced recurrence of gallstones at 12 months after surgery,and 1 experienced recurrence of polypoid lesions of the gallbladder at 24 months after surgery. The mean time to recurrence of gallstones and polypoid lesions was 9. 8 months after surgery,and the recurrence rate was 0. 71%( 5 /700). The univariate analysis showed that gallbladder wall thickness ≥4 mm,gallbladder contraction function < 30%,and cholestasis were significantly associated with the recurrence of gallstones and polypoid lesions( all P < 0. 05). The multivariate analysis showed that gallbladder wall thickness ≥4 mm,cholestasis,and gallbladder contraction function < 30% were independent factors for recurrence after gallbladder- preserving surgery( P = 0. 000 3,0. 040 0,and 0. 040 0). Conclusion Ultrasonography shows that gallbladder wall thickness ≥4 mm,gallbladder contraction function < 30%,and cholestasis are closely associated with the recurrence of gallstones and polypoid lesions of the gallbladder.

Effects of laparoscopic retrograde cholecystectomy versus partial cholecystectomy in treatment of complex bile duct diseases: a comparative analysis
Ran JiangLin, Zhang ShaoMao, Wen Qiang
2016, 32(4): 750-753. DOI: 10.3969/j.issn.1001-5256.2016.04.030
Abstract:

Objective To compare the clinical effect between laparoscopic retrograde cholecystectomy and partial cholecystectomy in the treatment of patients with complex bile duct diseases. Methods The clinical data of 83 patients with bile duct diseases who were diagnosed and treated in Guangyuan Mental Health Center from June 2013 to March 2015 were collected. Among these patients,40 underwent laparoscopic retrograde cholecystectomy( group A),and 43 underwent partial cholecystectomy( group B). The surgical procedure and postoperative recovery were compared between the two groups. The independent samples t- test was applied for comparison of continuous data between groups,and the paired t- test was applied for comparison of continuous data within each group before and after treatment; the chi- square test was applied for comparison of categorical data between groups. Results Compared with group A,group B had a significantly shorter time of operation,a significantly less blood loss,a significantly lower volume of intraoperative fluid infusion,and a significantly lower volume of peritoneal drainage( t = 9. 245,2. 394,2. 529,and 3. 603,all P < 0. 05). The rate of conversion to laparotomy,time to functional recovery of the gastrointestinal tract,and length of hospital stay showed no significant differences between the two groups( all P > 0. 05). The body temperature and C- reactive protein on days 1- 3 after surgery showed no significant differences between the two groups( all P >0. 05),while in both groups,the body temperature and C- reactive protein were significantly lower on the 2nd and 3rd days than on the 1st day.( t = 3. 184,3. 402,3. 151,3. 390,3. 497,5. 184,3. 916,and 6. 024,all P < 0. 05). Group B had a significantly lower incidence of postoperative complications than group A( 2. 33% vs 20. 00%,χ~2= 6. 696,P = 0. 010). Conclusion Compared with laparoscopic retrograde cholecystectomy,partial cholecystectomy can shorten the time of operation and reduce intraoperative bleeding and postoperative complications,and holds promise for clinical application.

A prognostic analysis of laparoscopic versus radical cholecystectomy for T1b unsuspected gallbladder carcinoma
Liu WenLong, Liang Bin, Tian YuanHu, Meng XiangFei, Yu Qiang, Chen JiYe, Pan YingWei, Liu Bo
2016, 32(4): 754-757. DOI: 10.3969/j.issn.1001-5256.2016.04.031
Abstract:

Objective To investigate the surgical treatment and prognosis of T1 b unsuspected gallbladder carcinoma( UGC). Methods Twenty- two patients with T1 b UGC admitted to our hospital were enrolled as subjects. The information on clinical pathology,radiological examination,laboratory tests,surgical treatment,and postoperative follow- up were analyzed in patients. The survival rate and recurrence were compared between patients treated with radical cholecystectomy and laparoscopic cholecystectomy. The Kaplan- Meier method was used to calculate survival rates,and the log- rank test was used for survival difference analysis. Comparison of categorical data was made by Fisher's exact test. Results The 1-,3-,and 5- year accumulative survival rates in all patients with T1 b UGC were 100%,89. 7%,and82. 8%,respectively; there was no significant difference in the 5- year accumulative survival rate between patients treated with laparoscopic cholecystectomy and radical cholecystectomy( 84. 6% vs 75. 0%,χ~2= 0. 000,P = 0. 991); two( 15. 4%) out of thirteen patients treated with laparoscopic cholecystectomy respectively; one( 12. 5%) out of eight patients treated with radical cholecystectomy had recurrence,there was no significant difference between the two groups( P > 0. 05). Conclusion Radical cholecystectomy is a superior therapy for T1 b UGC over laparoscopic cholecystectomy.

Gallbladder- preserving cholelithotomy by laparoscopy and cholangioscopy for cholecystolithiasis
Wang DaHai, Dai YongZe
2016, 32(4): 758-760. DOI: 10.3969/j.issn.1001-5256.2016.04.032
Abstract:

Objective To investigate the method and efficacy of cholelithotomy by laparoscopy and cholangioscopy,a controversial therapy for cholecystolithiasis. Methods Forty- eight patients with cholecystolithiasis who were admitted to our hospital and treated with gallbladder- preserving cholelithotomy by laparoscopy and cholangioscopy from March 2012 to June 2013 were enrolled as subjects. Results After surgery,all patients recovered without complications. One patient had relapse of cholecystolithiasis at six months after surgery. One patient had gallbladder atrophy at one year after surgery. Conclusion Gallbladder- preserving cholelithotomy by laparoscopy and cholangioscopy is a feasible and safe therapy for cholecystolithiasis. The therapy achieves satisfactory short- term outcomes. However,the long- term efficacy of this therapy needs further investigation.

Original articles_Others
Efficacy of three liver- protecting drugs commonly used in treatment of drug- induced liver injury: a comparative analysis
Wang Zhun, Gong TianBin
2016, 32(4): 761-763. DOI: 10.3969/j.issn.1001-5256.2016.04.033
Abstract:

Objective To compare the efficacy of three liver- protecting drugs commonly used in the treatment of drug- induced liver injury. Methods The clinical data of 90 patients with drug- induced liver injury who were treated in Yingcheng People's Hospital from November 2012 to April 2015 were analyzed retrospectively,and according to the drugs administered,they were divided into groups A,B,and C,with 30 patients in each group. The patients in groups A,B,and C were treated with reduced glutathione,polyene phosphatidylcholine injection,and tiopronin injection,respectively. The efficacy,drug cost,and incidence of adverse events were compared between the three groups. An analysis of variance was used for comparison of continuous data between multiple groups,and the LSD t- test was used for comparison of continuous data between any two groups; the chi- square test was used for comparison of categorical data between multiple groups.Results Group A had a significantly higher overall response rate than groups B and C( 90. 0% vs 73. 3% /76. 7%,χ~2= 2. 78 and 3. 75,both P < 0. 05). Group B had a significantly higher drug cost than groups A and C( 316. 12 ± 4. 05 RMB vs 235. 13 ± 2. 90 and 135. 21 ±7. 62 RMB,both P < 0. 01). The incidence of adverse events showed no significant differences between the three groups( P > 0. 05). Conclusion In the clinical treatment of drug- induced liver injury,reduced glutathione has better efficacy compared with polyene phosphatidylcholine and tiopronin,as well as a reasonable cost. Therefore,this drug is preferred in the treatment of this disease.

Clinical features of Klebsiella pneumoniae liver abscess
Chen Fan, Zhang YanTing, Qiao HuiJie, Ou YangKe, Zhou DongHui, Li Shuang
2016, 32(4): 764-768. DOI: 10.3969/j.issn.1001-5256.2016.04.034
Abstract:

Objective To analyze the clinical data of Klebsiella pneumoniae liver abscess( KPLA),and to provide a reference for early diagnosis and proper treatment. Methods The etiological features of 156 patients with bacterial liver abscess( BLA) and positive culture results who were hospitalized in The First Hospital Affiliated to Nanjing Medical University from March 2009 to July 2015 were analyzed retrospectively. According to the culture results,BLA patients were divided into KPLA group( 81 patients) and non- KPLA( NKPLA) group( 61 patients),and other positive strains including Escherichia coli were found in the other 14 patients with positive culture results for Klebsiella pneumoniae. The clinical,laboratory,and imaging data of KPLA and NKPLA were compared. The t- test was applied for comparison of normally distributed continuous data between groups,and the Mann- Whitney U test was applied for continuous data with skewed distribution between groups; the chi- square test or Fisher's exact test was applied for comparison of categorical data between groups. Results The most common pathogenic bacteria for BLA were Klebsiella pneumonia. In comparison with the NKPLA group,the KPLA group had a significantly higher proportion of male patients( χ~2= 4. 50,P = 0. 03),a significantly higher proportion of patients with diabetes( χ~2= 27. 28,P < 0. 001),and a significantly lower proportion of patients who complained of abdominal pain( χ~2= 5. 24,P = 0. 02). In the aspects of underlying diseases,the prevalence of biliary tract diseases,previous abdominal surgery,and a history of intraperitoneal tumors showed significant differences between the NKPLA group and the KPLA group( χ~2= 18. 38,20. 87,and 21. 68,all P < 0. 001). As for laboratory examination,the NKPLA group had a significantly greater reduction in hemoglobin compared with the KPLA group( t = 4. 903,P < 0. 001). In terms of imaging examination,most BLA patients showed a single lesion in the right lobe of the liver,but the KPLA group had a significantly higher proportion of patients with the formation of separation( χ~2= 4. 16,P = 0. 04). The patients in both groups experienced complications including pulmonary infection,pleural effusion,and perinephric infection. Most patients were treated with antibiotics combined with puncture,and the KPLA group had a significantly higher response rate than the NKPLA group( 93. 83% vs 80. 33%,χ~2= 6. 02,P = 0. 01).Conclusion The most common pathogenic bacteria for BLA are Gram- negative bacilli,especially Klebsiella pneumoniae. KPLA occurs more commonly in males,and most of the patients have diabetes. The clinical manifestations are not obvious,and the patients tend to develop the complications such as pleural effusion and pulmonary infection. Imaging examination should be performed as early as possible and proper treatment should be given in time.

Effect of PNPLA3 I148M mutation on expression of TGF- β1 in rat hepatic stellate cells
An BaiQuan, Xin YongNing, Lu LinLin, Xuan ShiYing
2016, 32(4): 769-771. DOI: 10.3969/j.issn.1001-5256.2016.04.035
Abstract:

Objective To investigate the mechanism of action of PNPLA3 I148 M mutation in the development and progression of non- alcoholic fatty liver fibrosis. Methods The lentiviral vectors carrying the mutant or wild- type PNPLA3 I148 M gene were constructed and transfected into rat hepatic stellate( HSC- T6) cells. Quantitative real- time PCR was applied to measure the mRNA expression of transforming growth factor β1( TGF β1). The t- test was applied for statistical analysis. Results The lentiviral vectors carrying the mutant or wild- type PNPLA3 I148 M gene were successfully constructed and transfected into HSC- T6 cells,and a HSC- T6 cell line with stable expression of the mutant or wild- type PNPLA3 gene was established. Compared with the cell line carrying the wild- type gene,the cell line carrying the mutant gene showed significantly higher mRNA expression of TGF β1( 1. 25 ± 0. 15 vs 0. 48 ± 0. 07; t = 11. 826,P < 0. 001).Conclusion PNPLA3 I148 M mutation can increase the expression of TGF β1 in HSC- T6 cells,which provides a new cell model and new research ideas for investigating the role of PNPLA3 I148 M mutation in non- alcoholic fatty liver fibrosis.

Case reports
Cutaneous metastasis of chest wall from primary hepatocellular carcinoma: a report of one case
Ma ChaoYang, Guo XiaoLin, Ji HuiFan, Liu YuanYuan
2016, 32(4): 772-773. DOI: 10.3969/j.issn.1001-5256.2016.04.036
Abstract:
Elevated serum GGT level in recovery phase of cholestatic liver disease reveals good prognosis: a case report 
Zhang XuQian, Zhao ChunShan, Liu WenTian, Wang BangMao, Zhou Lu
2016, 32(4): 774-775. DOI: 10.3969/j.issn.1001-5256.2016.04.037
Abstract:
Type II Crigler-Najjar syndrome: a report of one case
Wu YuNan, Peng JianPing, Huang YuHong, Yang Hang, Sun KeWei
2016, 32(4): 776-778. DOI: 10.3969/j.issn.1001-5256.2016.04.038
Abstract:
Perforation due to congenital choledochocyst misdiagnosed as acute appendicitis in a child
Zhao ZhengWei, Shi XiaoJu, Wang GuangYi, Sun XiaoDong, Lu: GuoYue
2016, 32(4): 779-780. DOI: 10.3969/j.issn.1001-5256.2016.04.039
Abstract:
Reviews
Application of external treatment of traditional Chinese medicine in cirrhotic ascites
Yu Yuan, Zhang JianLiang, Lu YunFei, Chen XiaoRong
2016, 32(4): 781-784. DOI: 10.3969/j.issn.1001-5256.2016.04.040
Abstract:

In recent years,great progress has been made in the external treatment of traditional Chinese medicine( TCM) for cirrhotic ascites,including TCM umbilical compress therapy,TCM enema,acupuncture,moxibustion,and light therapy. The external treatment has similar effects as oral administration of TCM in relieving the clinical symptoms of cirrhotic ascites,and does not have gastrointestinal adverse reactions. This article reviews the research advances in external treatment of TCM for cirrhotic ascites,and the new research directions in the future are to establish an unified research protocol and expand the scope of application of external treatment of TCM.

Action of mechanism of traditional Chinese medicine in prevention and treatment of nonalcoholic fatty liver disease
Hou YiXin, Wang XianBo, Yang YuYing, Jiang YuYong
2016, 32(4): 785-789. DOI: 10.3969/j.issn.1001-5256.2016.04.041
Abstract:
In recent years,extensive studies have been conducted on the pathogenesis of nonalcoholic fatty liver disease( NAFLD),and the action of mechanism of traditional Chinese medicine( TCM) in NAFLD has become a new research topic. TCM has achieved good clinical efficacy in the treatment of NAFLD,with the advantages of specific,flexible,multilevel,and multi- target treatment. This article introduces the role of TCM in improving insulin,regulating lipid metabolism,preventing lipid peroxidation,regulating cytokines,regulating and maintaining the dynamic balance of factors involved in lipid metabolism,and maintaining the balance of intestinal microflora,and analyzes the major problems in TCM research.
A brief analysis of “the liver being an evil of Zang- organ”
Ge Shuai, Sun LiXia
2016, 32(4): 790-792. DOI: 10.3969/j.issn.1001-5256.2016.04.042
Abstract:
The liver being an“evil”of Zang- organ has been mentioned repeatedly in ancient medical books and is thought- provoking.The author believes that the ”evil”nature of the liver lies in the diversity,complexity,and latency of diseases caused by liver disorders,which is closely related to the physiological characteristics and pathological changes of the liver. This article discusses the liver itself and its relationship with other organs,meridians and collaterals,and qi- blood and body fluid and elaborates on the three pathogenic characters of the liver being an“evil”of Zang- organ. A correct understanding of the ”evil”nature of the liver plays an important role in guiding clinical diagnosis and treatment.
Research advances in pharmacological effects of Ophiacordyceps sinensis in treatment of liver diseases
Hu XianDa, Yue Ying, Wu Peng, Zhou Fei, Luo YuanDai
2016, 32(4): 793-797. DOI: 10.3969/j.issn.1001-5256.2016.04.043
Abstract:

Ophiacordyceps sinensis has been used as a traditional natural drug for at least 600 years. It has various pharmacological activities and has been widely used in clinical practice. This article summarizes the research on the pharmacological effects of Ophiacordyceps sinensis in liver diseases and points out that Ophiacordyceps sinensis has definite therapeutic effects in liver diseases including liver injury of various causes,liver fibrosis,and liver tumors. The bioactive components of Ophiacordyceps sinensis,such as cordyceps polysaccharides,cordycepin,cordycepic acid,and ergosterol,may play vital roles in the pharmacological activities of Ophiacordyceps sinensis.

Research advances in sofosbuvir for treatment of chronic hepatitis C
Peng HuanYan, Yang ErNa, Sun DianXing
2016, 32(4): 798-801. DOI: 10.3969/j.issn.1001-5256.2016.04.044
Abstract:

In recent years,new changes have occurred in the treatment of chronic hepatitis C. Direct- acting antiviral agents have shown powerful efficacy in the treatment of active hepatitis C,and even refractory hepatitis C shows a high continuous virologic response. Among these direct- acting antiviral agents,sofosbuvir( SOF) has the advantages of short course of antiviral treatment and high response rate,and some patients with certain hepatitis C genotypes have no need to receive interferon therapy. This article introduces the mechanism of action,current status of clinical application,and major adverse effects of SOF,and points out its promising future in patients with refractory hepatitis C.

Research advances in diagnosis and treatment of primary biliary cirrhosis
Ning HuiMing, Ou Qiang
2016, 32(4): 802-805. DOI: 10.3969/j.issn.1001-5256.2016.04.045
Abstract:

Primary biliary cirrhosis( PBC) is a chronic cholestatic liver disease,characterized by progressive non- pyogenic inflammation in the small intrahepatic bile ducts,and can cause hepatic fibrosis and liver cirrhosis. The etiology and pathogenesis of PBC remain unknown. The development and progression of PBC are caused by various factors,and the major factor is environmental factors acting on patients with genetic susceptibility. Ursodesoxycholic acid is thought to be the only effective drug,but the complete response rate remains low.This article reviews the diagnosis and treatment of PBC with reference to the literature in the world.

Role of pyruvate kinase muscle isozyme 2 in pathogenesis and diagnosis of liver cancer
Ci DanWangJiu, Zhao XiangXuan, Wang XiaoMing
2016, 32(4): 806-810. DOI: 10.3969/j.issn.1001-5256.2016.04.046
Abstract:

In recent years,studies have shown that the expression of pyruvate kinase muscle isozyme 2( PKM2) is increased significantly in various tumor cells. PKM2 acts like a signal molecule in tumor cells and participates in the expression and regulation of genes related to tumor cell proliferation,cell autophagy,and cell cycle progression. This article summarizes the expression of PKM2 in liver cancer tissues and cell lines,elaborates on the role of PKM2 in the proliferation,differentiation,and metastasis of liver cancer cells and prognostic evaluation,and points out that PKM2 can be used in the clinical diagnosis,treatment,and prognostic evaluation of liver cancer.

Research advances in tumor markers of hepatocellular carcinoma
Yang XiaoXiao, Ma Hong
2016, 32(4): 811-815. DOI: 10.3969/j.issn.1001-5256.2016.04.047
Abstract:
At present,tumor marker measurement is one of the most important methods for the diagnosis and monitoring of hepatocellular carcinoma( HCC) and prognostic evaluation. This review summarizes the value of tumor markers in the diagnosis of HCC,prediction of biological characteristics,and prognostic evaluation,as well as the diagnostic value of a combination of various tumor markers. With new tumor markers being discovered,the rate of early diagnosis and prognostic evaluation of HCC will be improved.
Research advances in sorafenib- induced apoptotic signaling pathways in liver cancer cells
Zhang ChaoYa, Zhao XiangXuan, Lu ZaiMing, Guo QiYong
2016, 32(4): 816-820. DOI: 10.3969/j.issn.1001-5256.2016.04.048
Abstract:

Currently,sorafenib is the multi- target inhibitor for the treatment of advanced primary liver cancer,and can effectively prolong the progression- free survival and overall survival in patients with advanced primary liver cancer. The application of sorafenib in the targeted therapy for liver cancer has become a hot topic. Major targets or signaling pathways include Raf / Mek / Erk,Jak / Stat,PI3 K / Akt / m TOR,VEGFR and PDGFR,STAT,microRNA,Wnt / β- catenin,autolysosome,and tumor- related proteins,and sorafenib can regulate the proliferation,differentiation,metastasis,and apoptosis of liver cancer cells through these targets. This article reviews the current research on the action of sorafenib on these targets or signaling pathways to provide useful references for further clinical research on sorafenib.

Research advances in drug- induced liver injury in the elderly
Wang YueZhi, Zhang Yu
2016, 32(4): 821-824. DOI: 10.3969/j.issn.1001-5256.2016.04.049
Abstract:
Nowadays,drug- induced liver injury( DILI) is attracting more and more attention during clinical medication and drug research and development. This article introduces the characteristics of DILI in the elderly from the aspects of epidemiology,predisposing factors,clinical features,common drugs inducing DILI,and prognosis,and points out that the health education for the elderly should be enhanced and the elderly should be instructed to use drugs rationally. When adverse events occur,treatment should be given in time and treatment regimen should be adjusted.