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

2014 No. 9

Display Method:
Editorial
Improving understanding of liver immune function and enhancing research on cell therapy for liver diseases
Jia ZhanSheng, Lian JianQi
2014, 30(9): 839-841. DOI: 10.3969/j.issn.1001-5256.2014.09.001
Abstract:
As an important immune organ, the liver has a unique immune microenvironment, and is one of the important places for innate immunity and adaptive immunity. The liver is closely connected with the immune system through the gut- liver axis and is also the target organ of immune injury. However, the defensive role of the liver for Hepadnaviridae remains unclear. Cell therapy for liver diseases includes input of liver cells or stem cells for functional replacement, therapy by immune cells for antiviral and antitumor purposes, and genetic therapy for hereditary hepatopathy with cells as the carrier. The features of mesenchymal stem cells, multi- directional differentiation potential and immunomodulatory property, become the hot spots of cell therapy for liver diseases, and efficient in vitro amplification of cells makes it possible for the use of NK cells in the treatment of hepatocellular carcinoma.
Therapeutic guideline
World Gastroenterology Organisation global guidelines:nonalcoholic fatty liver disease and nonalcoholic steatohepatitis
Zhu Peng, Xu Zong, Wang YuMing
2014, 30(9): 842-845. DOI: 10.3969/j.issn.1001-5256.2014.09.002
Abstract:
Discussions by experts
Current status of research on liver innate immunity
Ye ChuanTao, Wei Xin, Zhang Ying
2014, 30(9): 846-850. DOI: 10.3969/j.issn.1001-5256.2014.09.003
Abstract:
Liver innate immunity plays an important role in the defense against pathogen invasion. The mechanisms of liver innate immunity for defending against pathogen invasion are reviewed, including the special anatomical and physiological characteristics of the liver, the features of innate immune cells in the liver ( liver- settled cells and cells raised from blood circulation) and their function and relationship with each other in pathogen invasion, the process of pathogen identification and effect of liver innate immune cells, and the mechanism of liver immune injury and immune tolerance. Given current research on innate immune cells and innate immune molecules in the liver, further studies should be conducted to understand the connection and difference between liver innate immunity and systemic immunity, thus promoting the diagnosis and treatment of liver diseases and deeper research.
Persistent hepatitis virus infection and immune homeostasis
Zhou Yun, Lian JianQi, Jia ZhanSheng
2014, 30(9): 851-854. DOI: 10.3969/j.issn.1001-5256.2014.09.004
Abstract:
Homeostasis between the host and viruses is naturally maintained. On the one hand, the immune system activates the immune response to kill or eliminate viruses; on the other hand, the immune system controls the immune response to maintain immune homeostasis.The cause of persistent infections with hepatitis viruses such as HBV and HCV is that viral molecules damage the immune system of the host and their variants escape immune clearance. Long- term coexistence of the host and viruses is the process involving various immune cells and molecules and is the result of homeostasis maintenance in antiviral immune response. The immune homeostasis maintained during persistent infections with hepatitis viruses is analyzed by the cellular and molecular mechanisms.
Immunoregulatory effect of multipotent stem cells in liver injury and repair
Cui LiNa, Han Ying
2014, 30(9): 855-859. DOI: 10.3969/j.issn.1001-5256.2014.09.005
Abstract:
Immunological imbalance is the foundation for the development of liver damage or fibrosis. Therefore, the treatment of liver diseases not only relies on regenerative medicine for cellular replacement, but also depends on immunoregulation. The immunological basis of liver injury and repair, the immunological basis of multipotent stem cells for allograft, and the research advances in the immunoregulatory effect of stem cells in the treatment of liver diseases demonstrated that multipotent stem cells, especially mesenchymal stem cells, have low immunogenicity and cause immunosuppression, with the immunological basis of allograft; in addition, they can improve the local immune microenvironment of the liver by immunoregulation to reduce the liver injury caused by immune response. It is suggested that multipotent stem cells, which meet the requirements of cellular replacement and immunoregulation in the liver, will become an ideal treatment of liver diseases.
Research advances in cellular immunotherapy for primary hepatocellular carcinoma
Zhang Ye, Zhang MingJie, Jia ZhanSheng
2014, 30(9): 860-864. DOI: 10.3969/j.issn.1001-5256.2014.09.006
Abstract:
The present therapy for primary hepatocellular carcinoma ( HCC) consists of surgery as well as local radiotherapy and chemotherapy. However, the majority of patients are susceptible to recurrence after comprehensive treatment, and the overall treatment outcome is not ideal due to the lack of effective drugs and strategies. Increasing evidence has demonstrated that the immune system is closely related to the development, progression, metastasis, and recurrence of HCC. Thus, immune therapy, especially cellular immunotherapy, could regulate immune function and induce specific antitumor immunity to achieve the goal of controlling HCC and reducing its recurrence and metastasis, which has become an essential part in the comprehensive treatment of HCC. The findings in preclinical and clinical studies on cellular immunotherapy for HCC data are reviewed, and the current problems are discussed.
Role of cancer- associated fibroblasts in growth and metastasis of hepatocellular carcinoma
Ma DeNing, Zhu XiaoDong, Tang ZhaoYou
2014, 30(9): 865-868. DOI: 10.3969/j.issn.1001-5256.2014.09.007
Abstract:
The development and progression of tumors are closely related to the tumor microenvironment. As one of the most important components in tumor microenvironment, cancer- associated fibroblasts ( CAFs) play an important role in carcinogenesis, angiogenesis, invasion, and metastasis of tumors. The role of CAFs in the development and progression of hepatocellular carcinoma ( HCC) is reviewed by discussing how CAFs are recruited and activated in the tumor microenvironment and how CAFs promote tumor angiogenesis and regulate tumor immunity. This review may provide new approaches for the treatment of HCC.
Original articles_Immunity and cell therapy of liver disease
Efficacy and safety of UCB- derived or autologous CIK cells combined with interferon therapy in patients with chronic hepatitis B
Liu Bo, Dong Jing, Zhang JunFei, Song HaiYan, Chen CongXin
2014, 30(9): 869-872. DOI: 10.3969/j.issn.1001-5256.2014.09.008
Abstract:

Objective To investigate the efficacy and safety of umbilical cord blood ( UCB) - derived or autologous cytokine- induced killer ( CIK) cells combined with interferon therapy in patients with chronic hepatitis B ( CHB) . Methods Thirty CHB patients hospitalized in the Department of Infectious Diseases from October 2010 to June 2013 were included in the study. These patients were randomly and equally divided into first and second treatment groups and control group. The first or second treatment group underwent transplantation of UCB- derived or autologous CIK cells combined with interferon therapy; the control group received interferon therapy alone. At 4 and 12 weeks after treatment, alanine aminotransferase ( ALT) , serum hepatitis B virus ( HBV) marker, HBV DNA, and CD4+/CD8+ratio in peripheral blood were measured. Comparison of means was made by paired t test or independent- samples t test. Results At 12 weeks after transplantation of UCB- derived or autologous CIK cells, the first or second treatment group had ALT, HBeAg, and HBV DNA levels of ( 22. 6 ± 14. 4) or ( 32. 9 ± 15. 3) U /L, ( 12. 5 ± 5. 8) or ( 18. 4 ± 8. 8) PEIU /ml, and ( 3. 2 ± 0. 7) or ( 3. 7 ± 0. 6) log10 copies /ml, respectively, significantly lower than those for control group ( t = 2. 80 ~ 5. 45, P < 0. 05) . At 4 weeks after transplantation, the two treatment groups had significantly increased CD4+levels and CD4+/CD8+ratios compared with the control group ( t = 2. 21 ~ 2. 43, P < 0. 05) . No severe adverse reactions and transplantation- related severe complications were found in the two treatment groups. Conclusion For CHB patients, transplantation of UCB- derived or autologous CIK cells significantly inhibits virus replication rapidly, improves liver function, relieves clinical symptoms, improves cellular immunity, and has high safety.

In vitro proliferation capacity and killing efficacy of CIK cells from umbilical cord blood versus patients with chronic hepatitis B
Liu LiWei, Li JiaJia, Zhu LiXin, Liu Bo
2014, 30(9): 873-876. DOI: 10.3969/j.issn.1001-5256.2014.09.009
Abstract:

Objective To observe the in vitro proliferation capacity and killing efficacy of cytokine- induced killer ( CIK) cells from umbilical cord blood ( UCB) and versus chronic hepatitis B ( CHB) patients of different ages. Methods Five samples of UCB from healthy fetuses born in our hospital from January to December, 2012, as well as 20 samples of peripheral blood from CHB patients, were divided into group A ( 5 samples of UCB) , group B ( 12 samples of peripheral blood from CHB patients aged 20- 35 years) , and group C ( 8 samples of peripheral blood from CHB patients aged over 35 years) . Mononuclear cells were separated by Ficoll- Hypaque centrifugation. Peripheral blood mononuclear cells were induced into CIK cells in the presence of cytokines. The immunophenotypes of CIK cells were determined by flow cytometry. The killing efficacy of CIK cells against K562 cells was measured by MTT assay. Results On day 15, CIK cells from group B multiplied 589. 15 ± 237. 6 times, versus 600. 93 ± 249. 1 times for group A ( P > 0. 05) ; CIK cells from group C multiplied 370. 45 ±165. 2 times, which were significantly lower than those for groups A and B ( P < 0. 05) . The killing efficacy of CIK cells from groups A, B, and C against K562 cells was ( 77. 3 ± 5. 1) %, ( 54. 5 ± 3. 5) %, and ( 44. 1 ± 3. 4) %, respectively; there were significant differences in killing efficacy between group A and groups B and C ( P < 0. 01) . Conclusion UCB- derived CIK cells have high in vitro proliferation capacity and killing efficacy. The in vitro proliferation capacity of CIK cells declines in CHB patients aged over 35 years, so autologous transplantation of CIK cells is not suitable for this group of patients.

Toll- like receptor 2 drives Th17 cell activation in inflammatory response to hepatitis B virus infection
Zhao RongRong, Yang XiaoFei, Dong Jie, Huang ZhangXing, Zhang Ye, Lian JianQi
2014, 30(9): 877-881. DOI: 10.3969/j.issn.1001-5256.2014.09.010
Abstract:

Objective To investigate the relationship between Toll- like receptor 2 ( TLR2) in peripheral blood mononuclear cells ( PBMCs) and T helper 17 ( Th17) cells among hepatitis B patients and to provide a theoretical and experimental basis for the study on the mechanism of inflammatory response to hepatitis B virus ( HBV) infection. Methods Thirty- four previously untreated patients with hepatitis B ( 24 cases of chronic hepatitis B and 10 cases of acute hepatitis B) who visited or were hospitalized in the Center of Infectious Diseases, Tangdu Hospital, from July 2012 to July 2013, as well as ten healthy controls, were enrolled in this study. PBMCs were isolated and stimulated by HBV ( genotype C) envelope peptides ( specific) or propylene glycol monomethyl ether acetate ( PMA) plus ionomycin ( nonspecific) . Flow cytometry was performed to measure the expression of TLR2 and the percentage of Th17 cells. PBMCs were further stimulated by TLR2 agonist Pam3Csk4, and the changes in percentage of Th17 cells were evaluated. Comparison between groups was made by Kruskal-Wallis H test. Results When stimulated by PMA plus ionomycin, patients with chronic hepatitis B had a significantly higher percentage of Th17 cells than patients with acute hepatitis B and healthy controls [ ( 4. 08 ± 1. 78) % vs ( 1. 85 ± 1. 28) %, P = 0. 0009; ( 4. 08 ±1. 78) % vs ( 2. 09 ± 0. 53) %, P = 0. 0004], while the percentages of TLR2+and IL- 17A+TLR2+T cells in peripheral blood CD3+CD4+T cells showed no significant differences between patients with acute hepatitis B, patients with chronic hepatitis B, and healthy controls ( P > 0. 05 for all) . When stimulated by HBV envelope peptides, patients with chronic hepatitis B had significantly higher percentages of IL- 17A+T cells and TLR2+T cells than patients with acute hepatitis B [ ( 5. 45 ± 1. 61) % vs ( 3. 20 ± 1. 13) %, P = 0. 0006; ( 5. 19± 3. 18) % vs ( 1. 88 ± 1. 30) %, P = 0. 0006]. After the addition of Pam3Csk4, patients with chronic hepatitis B had a significantly increased percentage of Th17 cells, while patients with acute hepatitis B had a nonsignificantly increased percentage of Th17 cells. Conclusion TLR2 could directly influence Th17 cell responses, thereby playing a proinflammatory role in the immune response to HBV infection.

Changes in peripheral blood T cell subsets and TGFβ and their clinical significance among HBV infection patients with different viral loads
Li CaiDong, Wu Bin, Chen XiLian, Tian PengFei, Duan ZhengJun
2014, 30(9): 882-886. DOI: 10.3969/j.issn.1001-5256.2014.09.011
Abstract:

Objective To study the changes in peripheral blood T cell subsets among chronic hepatitis B ( CHB) patients and asymptomatic hepatitis B virus ( HBV) carriers ( ASC) , who have different viral loads, and to investigate the correlation of T cell subsets with transforming growth factor beta ( TGFβ) , alanine aminotransferase, and total bilirubin. Methods A total of 175 HBV infection patients admitted to our hospital from July to December, 2012 were recruited and divided into ASC group ( n = 112) and CHB group ( n = 63) ; 84 healthy controls who underwent physical examination in the same period were selected as control group. The percentages of T cell subsets in serum were determined by flow cytometry, and liver function parameters were measured. For normally distributed continuous data, comparison between groups was made by analysis of variance; for non- normally distributed continuous data, comparison between groups was made by Kruskal- Wallis H rank sum test. Results Among the 175 HBV infection patients, the percentages of CD3+, CD4+, and CD8+T cells and CD4+/CD8+ratio were72. 14%- 74. 07%, 38. 43%- 39. 47%, 30. 74%- 31. 42%, and 1. 31- 1. 34, respectively. Compared with the control group, the ASC group and CHB group had significantly increased TGFβ levels ( P < 0. 05 for both) , significantly reduced percentages of CD3+and CD4+T cells ( P < 0. 05 or P < 0. 01) , significantly reduced CD4+/CD8+ratios ( P < 0. 01) , and significantly increased percentages of CD8+T cells ( P<0.05 or P <0.01) .="" in="" the="" asc="" and="" chb="" both="" hbeag-="" positive="" negative="" patients="" had="" reduced="" percentages="" of="" t="" increased="" ratios.="" no="" correlation="" was="" found="" between="" hbv="" dna="" loads="" cell="" subsets="" two="" groups="" p="">0. 05) . Conclusion TGFβ may be involved in the pathogenesis of CHB, and its immunosuppressive effect may be exerted by inhibiting T cells and antigen- presenting cell maturation.

Effects of splenectomy on peripheral blood Th17 cells and immune function in patients with portal hypertension
Liu ChaoHui, Chen YiJie, Zhang ChengHua
2014, 30(9): 887-890. DOI: 10.3969/j.issn.1001-5256.2014.09.012
Abstract:

Objective To investigate the effects of splenectomy on peripheral immune cells including Th17 cells in patients with portal hypertension and to analyze the influence of splenectomy on their immune function. Methods Twenty- five portal hypertension patients treated with splenectomy in No. 180 Hospital of PLA from June 2012 to June 2014 were selected as observation group, and 25 healthy controls who underwent physical examination in the same period as control group. Flow cytometry was used to determine the percentages of CD3, CD4, and CD8 T lymphocytes, CD4 /CD8 ratio, and percentage of Th17 cells in the peripheral blood of portal hypertension patients ( 1 day before operation and at 7 days, 1 month, and 3 months after operation) and healthy controls. ELISA was used to evaluate the changes in serum interleukin- 6 ( IL- 6) , interleukin- 17 ( IL- 17) , and interleukin- 23 ( IL- 23) . Comparison between groups was made by one-way ANOVA and LSD- t test. Results Before splenectomy, the portal hypertension patients had significantly lower percentages of CD3, CD4, and CD8 T lymphocytes and CD4 /CD8 ratio ( P < 0. 01 for all) and significantly higher percentage of Th17 cells and levels of their associated inflammatory cytokines ( IL- 6, IL- 17, and IL- 23) ( P < 0. 01 for all) , as compared with the control group. At 7 days, 1month, and 3 months after operation, the percentages of CD3, CD4, and CD8 T cells and CD4 /CD8 ratio in portal hypertension patients first decreased and then increased, and these values were significantly lower at 7 days after operation than before operation ( P < 0. 01 for all) ; at3 months after operation, the patients showed no significant differences in the percentages of CD3, CD4, and CD8 T cells and CD4 /CD8 ratio compared with the control group ( P > 0. 05 for all) . At 7 days, 1 month, and 3 months after operation, the percentage of Th17 cells and levels of their associated inflammatory cytokines ( IL- 6, IL- 17, and IL- 23) in portal hypertension patients decreased gradually ( P <0. 05 for all) . Conclusion Th17 cells and their associated inflammatory cytokines ( IL- 6, IL- 17, and IL- 23) are reduced in portal hypertension patients treated with splenectomy, so their immune function can be improved.

Inhibitory effect of iAPA- DC /CTL on HepG2 xenograft in nude mice
Fu HaiFeng, Zhou WenBo, Ding YouMing, Wang Bin, Xu JunHui, Xu YanZhe
2014, 30(9): 891-894. DOI: 10.3969/j.issn.1001-5256.2014.09.013
Abstract:

Objective To investigate the inhibitory effect of inhibition of antigen presentation attenuators ( iAPA) - based dendritic cells ( DC) and cytotoxic T lymphocytes ( CTL) ( iAPA- DC/CTL) on HepG2 xenograft in nude mice. Methods Human hepatocarcinoma HepG2 cells were subcutaneously implanted into nude mice on nude mice to establish a HepG2 xenograft model transplanted tumor model of human HCC. Twelve nude mice were randomly and equally divided into two groups: normal saline control group ( C group) and iAPA- DC /CTL group ( DC group) . After four times of treatment with iAPA- DC /CTL ( once a week) , all mice were sacrificed. Tumor growth was evaluated by measuring the long and short diameters and delineating the tumor growth curve. The tumors were weighed, and the tumor inhibition rate was calculated. In addition, histopathological examination was performed. Comparison of means between the two groups was made by independent- samples t test. Results The HepG2 xenograft model was successfully established in 92. 31% of all mice. The tumor volume was 697. 69 ± 143. 99 mm3 in C group and 485. 64 ± 188. 75 mm3 in DC group; the tumor growth was significantly slower in DC group than in C group ( t = 2. 28, P < 0. 05) . The tumor weight was 0. 32 ± 0. 07 g in C group and 0. 22 ± 0. 08 g in DC group; DC group had a significantly lower tumor weight than C group ( t = 2. 31, P < 0. 05) , and the tumor inhibition rate was 30. 39%. After immunohistochemical staining, T lymphocyte count was 0 cell /high- power field ( HPF) in C group and 39. 74 ± 5. 11 cells /HPF in DC group; the number of T lymphocytes in DC group was significantly higher than that in C group ( t = 19. 05, P < 0. 05) . Conclusion iAPA- DC /CTL can effectively inhibit the growth of subcutaneous HepG2 xenograft in nude mice.

Original articles_Viral hepatitis
Analysis of predictors of liver injury stage in chronic HBV infection patients with ALT levels lower than 2 × ULN
Yang Rui, Zhang YaPing, Wang XinHong, Zhu Bin, Zhang GuangWen
2014, 30(9): 895-898. DOI: 10.3969/j.issn.1001-5256.2014.09.014
Abstract:
Objective To investigate the role of various clinical parameters in predicting liver injury stage in patients with chronic hepatitis B virus ( HBV) infection who had alanine aminotransferase ( ALT) levels lower than 2 times the upper limit of normal ( ULN) . Methods Ultrasound- guided liver biopsy was performed in chronic HBV infection patients with ALT levels lower than 2 × ULN. The activity of inflammation and degree of fibrosis in liver tissues were assessed. Meanwhile, liver function, serum HBV markers, and HBV DNA were measured. The role of these clinical parameters in predicting liver injury stage was evaluated by logistic regression analysis. Results Among 122 patients, 94 ( 77. 0%) had significant inflammation or fibrosis ( G≥2 or S≥2) , and 5 ( 4. 1%) had early cirrhosis. There was significant difference in HBV DNA between G ≥2 group and G < 2 group, but other parameters showed no significant differences between the two groups. There were significant differences in age, HBeAg, HBV DNA, AST, and platelet count between S≥2 group and S < 2 group. The logistic regression analysis showed that age, HBeAg, and AST were independent predictors of significant liver fibrosis ( S≥2) . Conclusion Liver biopsy is necessary for chronic HBV infection patients with serum ALT levels of < 2 × ULN, aged over 40 years, negative for HBeAg, or with serum AST levels of > 40 U /L.
Changing process and development trend of deaths ( mortality) in patients with viral hepatitis in China
He ShuPing, Liang Qin, Zhao Zhen
2014, 30(9): 899-902. DOI: 10.3969/j.issn.1001-5256.2014.09.-015
Abstract:
Objective To analyze the changing process and development trend of deaths ( mortality) in patients with viral hepatitis after the use of the Internet- based National Notifiable Infectious Disease Reporting System. Methods Descriptive statistical and moving average methods were employed to analyze the infectious disease reports released by the Chinese government during 1992- 2013, and the changing process and development trend of deaths ( mortality) in patients with viral hepatitis in China over the past 10 years were investigated. Results The annual deaths ( mortality) in patients with viral hepatitis showed a decreasing trend. The deaths ( mortality) from hepatitis B showed a slight declining trend, accounting for a great proportion ( over 70%) of the deaths ( mortality) from viral hepatitis; the deaths ( mortality) from hepatitis C had shown a slight downward trend since 2007; the deaths ( mortality) from hepatitis A and unclassified hepatitis decreased to different extents; the deaths ( mortality) from hepatitis E remained at a relatively low level. Conclusion The treatment of viral hepatitis has been gradually improved in China and the public awareness of viral hepatitis keeps increasing. However, much attention still needs to be given to the prevention and treatment of viral hepatitis, especially hepatitis B and C, by the government.
Original articles_Fatty liver
Risk factors for non- alcoholic fatty liver disease: a multivariate analysis
Pang XueQin, Chen WeiChang, Feng Huang, Tian WenYan
2014, 30(9): 903-905. DOI: 10.3969/j.issn.1001-5256.2014.09.016
Abstract:

Objective To investigate the risk factors for non- alcoholic fatty liver disease ( NAFLD) and to provide a basis for the prevention of NAFLD. Methods A total of 190 patients with NAFLD who visited the First Affiliated Hospital of Soochow University from January2011 to January 2013 were included in the study. The investigated factors included sex, age, height, weight, dietary habit, smoking and alcohol consumption, educational level, occupation, intensity and duration of physical exercise, bedtime, previous history, and family history. Univariate and multivariate analyses were performed using SPSS 18. 0 to determine the risk factors for NAFLD. Results The univariate analysis showed that sex, age, dietary habit, occupation, body mass index ( BMI) , and educational level were associated with NAFLD ( P <0. 05) . The logistic regression analysis showed that the risk factors for NAFLD were sex ( OR = 5. 692, P = 0. 029) , age ( OR = 0. 423, P =0. 041) , occupation ( OR = 0. 698, P = 0. 008) , BMI ( OR = 3. 939, P = 0. 003) , educational level ( OR = 5. 463, P = 0. 030) , and dietary habit ( OR = 9. 235, P = 0. 039) . Conclusion NAFLD may be related to many factors, and corresponding preventive measures may reduce the development of NAFLD.

Establishment and management of nonalcoholic fatty liver disease biobank
Chen LiZhen, Zhang HaiYing, Jiang Man, Niu TongHong, Wang Jian, Geng Ning, Liu HaoGang, Xin YongNing, Xuan ShiYing
2014, 30(9): 906-909. DOI: 10.3969/j.issn.1001-5256.2014.09.017
Abstract:

Objective To investigate the collection and preservation of blood specimens from patients with nonalcoholic fatty liver disease ( NAFLD) and the establishment and information management of biobank. Methods Whole blood samples were collected from 1226 patients who were diagnosed with NAFLD based on B- mode ultrasound and blood tests from October 2009 to October 2013. Biochemical parameters were measured. Plasma and whole- blood genomic DNA was extracted from the samples, and the purity and concentration of DNA were determined. Specimens were preserved in a refrigerator (- 80℃) . An information management system for NAFLD biobank was established. Results Specimens of 1226 NAFLD patients, including those of 83 twins and 100 families, were collected. The success rate was100% for extraction of plasma and whole- blood genomic DNA. One hundred DNA samples were randomly selected for testing, and the results showed that the collected specimens met the requirements of following experiments. Conclusion The NAFLD Biobank has been successfully established in this study. It has the standard information management system and enables the quality control and information management of specimens, laying a solid foundation for further research on NAFLD.

Original articles_Biliary diseases
Experience in perioperative management in difficult laparoscopic cholecystectomy
Tang ShiLong, Li JunJiu, Zhang XiaoBing, Chen ZhanHui, Li DongWei, Ceng YongFeng
2014, 30(9): 910-912. DOI: 10.3969/j.issn.1001-5256.2014.09.018
Abstract:
Objective To investigate perioperative management and the prevention of complications in difficult laparoscopic cholecystectomy. Methods A retrospective analysis was performed on the clinical data of 82 patients, who underwent difficult laparoscopic cholecystectomy due to acute cholecystitis, Mirizzi syndrome, a history of abdominal surgery with severe abdominal adhesion, atrophic cholecystitis, liver cirrhosis with gallstones, and other diseases in our hospital since 1999, to summarize the experiences and lessons. Results Among all patients, 6 ( 7. 31%) were converted to open laparotomy, and other patients were successfully treated by laparoscopic cholecystectomy.Postoperative biliary injury and biliary fistula occurred in 2 cases, and they were cured after reoperation. Postoperative bleeding occurred in4 cases, and they were cured with conservative treatment. Different degrees of biliary leak of unknown causes occurred in 10 cases, and they were cured after drainage. Conclusion For difficult laparoscopic cholecystectomy, surgical operation is characterized by high difficulty and high risk, but it can still be completed with proper perioperative management.
Original articles_Hepatopancreatobiliary tumor
Clinical effects of comprehensive treatment and liver transplantation for hepatocellular carcinoma exceeding Milan criteria: a comparative study
Liu JianYong, Cai QiuCheng, Jiang Yi
2014, 30(9): 913-916. DOI: 10.3969/j.issn.1001-5256.2014.09.019
Abstract:

Objective To analyze and compare the clinical effects of comprehensive treatment and liver transplantation for hepatocellular carcinomas ( HCC) exceeding Milan criteria. Methods A retrospective analysis was performed on the clinical data of 157 patients with HCC ( exceeding Milan criteria) who received comprehensive treatment ( 99 patients, including 48 cases meeting Shanghai criteria) and liver transplantation ( 58 patients, including 26 cases meeting Shanghai criteria) in our hospital from January 2006 to January 2010. The median survival times and 1-, 2-, and 3- year survival rates were calculated by the Kaplan- Meier method, and the log- rank test was used for survival difference analysis. Results For all patients, the median survival times of the comprehensive treatment group and liver transplantation group were 18. 00 ± 1. 15 and 23. 40 ± 4. 44 months, respectively, and their 3- year survival rates were ( 18. 2 ± 3. 9) % and ( 39. 7 ±6.4) %, respectively; the survival was significantly improved by the treatment of liver transplantation ( P =0.009) . For patients meeting Shanghai criteria, the median survival times of the comprehensive treatment group and liver transplantation group were 20. 00 ± 1. 17 and 36. 00 ± 0. 00 months, respectively, and their 3- year survival rates were ( 25. 0 ± 6. 3) % and ( 57. 7 ± 9. 7) %, respectively; there was significant survival difference between the two groups ( P = 0. 008) . For patients exceeding Shanghai criteria, the median survival times of the comprehensive treatment group and liver transplantation group were 16. 00 ± 1. 78 and 16. 00 ± 1. 69 months, respectively, and their 3- year survival rates were ( 11. 8 ± 4. 5) % and ( 25. 0 ± 7. 7) %, respectively; there was no significant survival difference between the two groups ( P = 0. 221) . Conclusion Compared with comprehensive treatment, liver transplantation leads to a significant higher long- term survival rate in HCC patients exceeding Milan criteria but meeting Shanghai criteria. However, the two therapies cause no significant survival difference in HCC patients exceeding Shanghai criteria.

Efficacy of transcatheter arterial chemoembolization in patients with hepatocellular carcinoma before hepatectomy:a meta-analysis
Gao Sheng, Liu JianYong, Zhang ZhiMing, Zhao YinNong, Yuan WeiPing, Wu FeiXiang, Xiang BangDe
2014, 30(9): 917-920. DOI: 10.3969/j.issn.1001-5256.2014.09.020
Abstract:

Objective To assess the efficacy of transcatheter arterial chemoembolization ( TACE) in patients with hepatocellular carcinoma ( HCC) before hepatectomy. Methods PubMed, Embase, the Cochrane Library, CNKI, VIP, and Wanfang Data were searched to identify randomized controlled trials ( RCTs) evaluating the efficacy of preoperative TACE plus hepatectomy ( study group) versus hepatectomy alone ( control group) in HCC patients published up to March 12, 2013. The quality of included studies was assessed, and relevant data were extracted. Statistical analysis was performed by RevMan 5. 2. Results A total of 4 RCTs involving 342 participants were included. Meta- analysis of data extracted from the included RCTs showed that there were no significant differences between the study group and control group in 1-, 3-, and 5- year disease- free survival ( DFS) , with relative risks ( RRs) ( 95% confidence intervals ( CIs) ) of 1. 07 ( 0. 92-1. 25) ( P = 0. 38) , 1. 05 ( 0. 79, 1. 41) ( P = 0. 72) , and 0. 95 ( 0. 64- 1. 42) ( P = 0. 81) , respectively, in 1-, 3-, and 5- year overall survival ( OS) , with RRs ( 95% CIs) of 1. 01 ( 0. 92- 1. 10) ( P = 0. 85) , 1. 14 ( 0. 97- 1. 34) ( P = 0. 11) , and 0. 95 ( 0. 75-1. 21) ( P = 0. 68) , respectively, and in rate of postoperative complications and mortality, with RRs ( 95% CIs) of 0. 89 ( 0. 45- 1. 75) ( P= 0. 73) and 0. 77 ( 0. 25- 2. 37) ( P = 0. 65) , respectively. Conclusion TACE before hepatectomy cannot increase DFS and OS and reduce complications and mortality in HCC patients. However, the numbers of studies and cases included in the analysis are small, and more high- quality, large- sample RCTs are needed to confirm the conclusion.

Correlation of GGT with AFP and diagnostic value of GGT for hepatocellular carcinoma
Gao Chun, Fang Long, Yao ShuKun
2014, 30(9): 921-925. DOI: 10.3969/j.issn.1001-5256.2014.09.021
Abstract:

Objective To analyze the correlation of gamma- glutamyl transpeptidase ( GGT) level with alpha- fetoprotein ( AFP) level and to re- evaluate the diagnostic value of GGT for hepatocellular carcinoma ( HCC) . Methods Four hundred and seventy- two patients with HCC or liver cirrhosis, who were hospitalized in China- Japan Friendship Hospital from January 2003 to June 2009, were included in the study. The correlation between GGT and AFP was analyzed by Spearman nonparametric test. The cut- off values for the two parameters were determined based on their receiver operating characteristics ( ROC) curves, areas under the ROC curve ( AUCs) , sensitivity, and specificity, and the diagnostic values were presented using their sensitivity, specificity, and correct index. Statistical analysis was performed using SPSS 17. 0. Normally distributed continuous data were analyzed by independent- samples t test, while non- normally distributed continuous data were analyzed by Mann- Whitney U test. Categorical data were analyzed by Pearson chi- square test, continuity- corrected chi-square test, or Fisher's exact test. Results Among 472 patients, 224 were diagnosed with HCC, and 248 with liver cirrhosis. Compared with cirrhotic patients, HCC patients had a significantly higher GGT level ( 113 ( 58- 254) U /L vs 38 ( 22- 72) U /L, Z =- 11. 037, P <0. 001) and a significantly higher AFP level ( 429. 5 ( 15. 7- 1210. 0) ng /ml vs 5. 7 ( 3. 4- 18. 2) ng /ml, Z =- 10. 157, P < 0. 001) . A significant correlation was found between GGT and AFP ( r = 0. 449, P < 0. 001) . The AUC was 0. 784 for GGT and 0. 788 for AFP. The cut- off value was 60 U /L for GGT and 20 ng /ml for AFP. The sensitivity was 74. 1% for GGT, 71. 8% for AFP, and 90. 7% for a combination of the two parameters, the specificity was 70. 2%, 77. 6%, and 58. 7%, respectively, and the correct index was 0. 443, 0. 494, and0. 494, respectively. Conclusion GGT may be regarded as one biomarker for HCC, and its level is significantly correlated with AFP level.The diagnostic value of AFP may not be improved when used in combination with GGT.

Relationship between classification of Doppler ultrasound blood flow signals and angiogenesis in primary hepatocellular carcinoma
Ma YanYan, Liu Ying, Zhang JingZhuo
2014, 30(9): 926-928. DOI: 10.3969/j.issn.1001-5256.2014.09.022
Abstract:

Objective To investigate the relationship of the classification of Doppler ultrasound blood flow signals with matrix metalloproteinase- 9 ( MMP- 9) expression and microvessel density ( MVD) in primary hepatocellular carcinoma ( PHC) . Methods Sixty patients with PHC, who underwent surgical resection in the Second Affiliated Hospital of Dalian Medical University from April 2008 to April 2013, were included in the study. These patients underwent ultrasound examination before operation. The classification of Doppler ultrasound blood flow signals in the focus was recorded. The expression of MMP- 9 and CD31 in carcinoma tissues was detected by immunohistochemistry, and MVD was calculated. Continuous data were analyzed by t test, while categorical data by chi- square test; the relationship was evaluated by Spearman correlation analysis. Results The classification of Doppler ultrasound blood flow signals was as follows: grade 0 ( 15 cases) ;grade 1 ( 20 cases) ; grade 2 ( 15 cases) ; grade 3 ( 10 cases) . The positive rate of MMP- 9 expression was 72. 3%. The MVD was 43. 2 ±5. 4. The classification of Doppler ultrasound blood flow signals in the focus was positively correlated with MMP- 9 expression and MVD ( r =0.56, P <0.05) . Conclusion The classification of Doppler ultrasound blood flow signals can reveal vascular changes in the focus, and it can be used in the clinical evaluation of angiogenesis in tumor tissues and the clinical diagnosis and treatment of PHC.

Brief reports
Dynamic changes in B7- H1 expression on peripheral blood mononuclear cells in chronic hepatitis B patients treated with entecavir
Wu LieXiu, Lin ShuMei, Zhang Xi, Zheng ShuQin, Ye Feng, Chen TianYan, Zhao YingRen, Zhang ShuLin
2014, 30(9): 929-931. DOI: 10.3969/j.issn.1001-5256.2014.09.023
Abstract:
Case reports
Abernethy malformation misdiagnosed as liver cirrhosis: a report of one case
Li Li, Gou ChunYan, Li JingYing, Li XiuHui
2014, 30(9): 932-934. DOI: 10.3969/j.issn.1001-5256.2014.09.024
Abstract:
Reviews
Research progress in TIM-3 and HBV infection
Dong Jie, Shen HuanJun, Yang XiaoFei, Zhao RongRong, Zhang Ye, Zhao YanYan, Huang ZhangXing, Lian JianQi
2014, 30(9): 935-938. DOI: 10.3969/j.issn.1001-5256.2014.09.025
Abstract:
Studies have found that T cell Ig- and mucin- domain- containing molecule- 3 ( TIM- 3) is associated with the development of many diseases. In hepatitis B virus ( HBV) infection, TIM- 3 acts as a negative immune regulatory molecule and its expression on CD8+T cells increases markedly. It indicates that TIM- 3 is closely related to the pathogenic mechanism of HBV infection. The latest research progress in TIM- 3 and HBV infection, including the biological characteristics of TIM- 3 and the outcomes and new therapeutic target of HBV infection, is reviewed and summarized. It is thought that TIM- 3 will become a new target in the treatment of HBV.
Research advances in role of myeloid- derived suppressor cells in tumorigenesis
Ji Bo, Liu YaHui
2014, 30(9): 939-943. DOI: 10.3969/j.issn.1001-5256.2014.09.026
Abstract:
The role of myeloid- derived suppressor cells ( MDSCs) in promoting inflammatory response and immune escape of tumor cells and the mechanism by which MDSCs promote the development and progression of tumors are reviewed. This could provide a new way for the investigation of immunological mechanism of liver fibrosis and liver cancer. Besides, MDSCs may be an effective therapeutic target for liver cirrhosis and liver cancer.
Current status and progress in research on helicobacter infection and chronic liver diseases
Chi ZhaoChun
2014, 30(9): 944-947. DOI: 10.3969/j.issn.1001-5256.2014.09.027
Abstract:
There has been increasing research on the association between Helicobacter infection and liver diseases, mostly the influence of Helicobacter on liver diseases. The prevalence and bacteriology of Helicobacter during the development of liver diseases, the mechanism by which Helicobacter causes liver diseases, and the diagnosis of liver diseases are reviewed. So far consensus has been reached that three species of Helicobacter are associated with human liver diseases, namely H. pylori, H. heilmanni, and H. cinaedi. H. pylori has been studied most extensively, but there is little research on the latter two. H. hepaticus is a new type of H. pylori. Studies have shown that further research should be conducted on the pathogenesis and prevention of chronic liver diseases.
Research advances in animal models of nonalcoholic fatty liver disease
Huang HaiYan, Xin YongNing, Jiang Man, Jin WenWen, Jiang XiangJun, Xuan ShiYing
2014, 30(9): 948-953. DOI: 10.3969/j.issn.1001-5256.2014.09.028
Abstract:
In recent years, the incidence of nonalcoholic fatty liver disease ( NAFLD) has increased gradually along with the rising prevalence of obesity, type 2 diabetes, and hyperlipidemia, and NAFLD has become one of the most common chronic liver diseases in the world and the second major liver disease after chronic viral hepatitis in China. However, its pathogenesis has not yet been clarified. Animal models are playing an important role in researches on NAFLD due to the facts that the development and progression of NAFLD require a long period of time, and ethical limitations exist in conducting drug trials in patients or collecting liver tissues from patients. The animal models with histopathology similar to that of NAFLD patients are reviewed, and their modeling principle, as well as the advantages and disadvantages, are compared. Animal models provide a powerful tool for further studies of NAFLD pathogenesis and drug screening for prevention and treatment of NAFLD.
Role of PI3K /Akt /mTOR signaling pathway in hepatocellular carcinoma
Yu Yuan, Chen XiaoRong
2014, 30(9): 954-957. DOI: 10.3969/j.issn.1001-5256.2014.09.029
Abstract:
Phosphatidylinositol 3- kinase, Akt, and the mammalian target of rapamycin ( PI3K/Akt/mTOR) signaling pathway is shown to play a key role in the tumorigenesis, proliferation, metastasis, apoptosis, and angiogenesis of hepatocellular carcinoma ( HCC) by regulating gene expression. The components and functions of PI3 K /Akt /mTOR signaling pathway are briefly described, and the research advances in the action mechanism of PI3 K /Akt /mTOR signaling pathway in the progression of HCC and related inhibitors are reviewed. It is disclosed that blocking the PI3 K /Akt /mTOR signaling pathway may become a new therapy for HCC.
Application of proteomics in study of hepatocellular carcinoma
Wang JianGang, Fei XinYing, Song Qing
2014, 30(9): 958-960. DOI: 10.3969/j.issn.1001-5256.2014.09.030
Abstract:
Hepatocellular carcinoma ( HCC) is one of the most fatal malignant tumors worldwide. As an important part of cutting- edge research fields, proteomics has been widely used in the studies of related diseases and has currently become a crucial experimental approach to research on HCC. Significantly expressed proteins can be identified as potential biomarkers for early diagnosis and targets for therapeutic drugs for HCC. Moreover, they can be used for prediction of the recurrence and prognosis of HCC, as well as for investigation of pathogenesis of the disease. The proteomic results from worldwide clinical studies of HCC are summarized, and it is suggested that the clinical application of results of basic research on HCC proteomics will bring great benefit to the diagnosis and treatment of HCC.
Progress in evaluation and treatment of hepatic iron overload
Ding Rui, Jia JiDong
2014, 30(9): 961-964. DOI: 10.3969/j.issn.1001-5256.2014.09.031
Abstract:
Iron overload is a metabolic disorder characterized by excessive iron deposition in the liver, pancreas, heart, endocrine organs, etc., resulting in structural damage and dysfunction. The liver is the primary organ for iron storage, and excessive iron deposition induces liver inflammation and fibrosis, which may progress to cirrhosis and even liver cancer, with a poor prognosis. Accurate evaluation and effective treatment can reduce liver injury caused by iron overload and improve patients' survival.
Research advances in circulating miRNAs for diagnosis of hepatobiliary diseases
Peng XiaoFang, Liu HaiYing
2014, 30(9): 965-968. DOI: 10.3969/j.issn.1001-5256.2014.09.032
Abstract:
MicroRNAs ( miRNAs) are involved in the pathological and physiological process of life activities, and some of them exist stably and abundantly in serum, plasma, and other body fluids. Previous studies have indicated that there are significant differences in the expression patterns of circulating miRNAs between patients with viral hepatitis, liver fibrosis, liver cirrhosis, hepatocellular carcinoma, drug- induced hepatitis, and other hepatobiliary diseases at different disease stages. Among these circulating miRNAs, some can act as novel noninvasive biomarkers for the early diagnosis, disease progression, and prognostic evaluation of related diseases. The latest research advances in circulating miRNAs for the diagnosis of hepatobiliary diseases are reviewed.