2016 No. 12

Application of magnetic resonance imaging in hepatobiliary diseases and related challenges

Wang XiaoMing, Wang YueRen

2016, 32(12): 2231-2235. DOI: 10.3969/j.issn.1001-5256.2016.12.002

Abstract(1766)

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Abstract:
Hepatobiliary diseases are highly prevalent and diverse in China. Besides chronic viral hepatitis,the incidence of non- alcoholic fatty liver disease and alcohol liver disease has been increasing gradually year by year. In recent years,with the improvement of magnetic resonance software and hardware technology,individualized selection of parameters,transformation and combination of pulse sequences,and the use of new contrast agents,magnetic resonance imaging( MRI) has become an irreplaceable examination method for hepatobiliary diseases,but still faces great challenges. This article reviews the application of MRI in hepatobiliary diseases and related research difficulties and how to further increase clinical research level in future.

Role of endoscopic ultrasonography in treatment and prognostic evaluation of esophageal and gastric varices

Li Shuang, Lu Wei, Cui ShuBo, Li Jia, Hu DongSheng, Zhou YongHe, Yao ShengJuan

2016, 32(12): 2268-2272. DOI: 10.3969/j.issn.1001-5256.2016.12.008

Abstract(2367)

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Through a comprehensive evaluation of collateral circulation establishment in portal hypertension,endoscopic ultrasonography( EUS) not only helps to predict and evaluate the risks of first bleeding from esophageal and gastric varices and recurrence and rebleeding after treatment,but also guides and participates in the treatment of varices. This article introduces the unique advantages of EUS in the treatment and prognostic evaluation of esophageal and gastric varices and provides an important reference for individualized treatment of patients with liver cirrhosis complicated by esophageal and gastric varices. EUS also helps to improve treatment safety and response rate. EUS for the systematic treatment of portal hypertension has become a hot research topic in recent years.

Research advances in the application of specific molecular probes for positron emission tomography in diagnosis of early-stage liver fibrosis

Yang MengYi, Xu XiangXin, Xin Jun

2016, 32(12): 2273-2276. DOI: 10.3969/j.issn.1001-5256.2016.12.009

Abstract(2182)

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Abstract:
Liver fibrosis is a symbolic process of many chronic liver diseases,and liver biopsy is the gold standard for the diagnosis of liver fibrosis in clinical practice. At present,there is a lack of effective methods for the noninvasive diagnosis of early- stage liver fibrosis. The process of liver fibrosis is accompanied by complicated changes at the molecular level,which are associated with the progression of liver fibrosis. As an imaging examination which can provide the information at the molecular level such as tissue function and metabolism,positron emission tomography( PET) has the ability to monitor such quantitative information. This article mainly introduces the principles of specific molecular probes for PET used in the diagnosis of early- stage liver fibrosis,summarizes the value of these specific molecular probes in the diagnosis and staging of early- stage liver fibrosis,and points out that it is necessary to find more specific molecular probes for the diagnosis of early- stage liver fibrosis.

Role of functional magnetic resonance imaging in evaluating the therapeutic effect of transcatheter arterial chemoembolization in hepatocellular carcinoma

Luo YongHeng, Xiao EnHua

2016, 32(12): 2277-2281. DOI: 10.3969/j.issn.1001-5256.2016.12.010

Abstract(2134)

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Transcatheter arterial chemoembolization( TACE) is the first- line treatment for unresectable hepatocellular carcinoma( HCC).Postoperative follow- up helps to determine tumor survival and necrosis timely and accurately and plays an important role in evaluating therapeutic outcome,guiding future treatment,and reducing pain. This article introduces the application of functional magnetic resonance imaging,including magnetic resonance spectroscopy,magnetic resonance perfusion weighted imaging,diffusion weighted magnetic resonance imaging,intravoxel incoherent motion,and blood oxygen level- dependent magnetic resonance imaging,in observing the changes in metabolism,blood flow,energy,and blood oxygen in tumor cells and points out that functional magnetic resonance imaging has promising prospects in evaluating the therapeutic effect of TACE in HCC.

Imaging diagnosis of liver tumors in children

Sun XueFeng, Yuan XinYu

2016, 32(12): 2282-2288. DOI: 10.3969/j.issn.1001-5256.2016.12.011

Abstract(2233)

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Primary liver tumors in children are not rare,and the incidence of malignant liver tumors in children ranks third of all malignant abdominal tumors in children,with the features of a high rate of malignancy,a high incidence of congenital tumors,and a specific age of onset.Liver tumors in children often have no specific clinical manifestations,with an insidious onset,a large volume of tumor lesion,various pathological types,and complicated locations,which makes them more difficult to treat compared with liver tumors in adults. This article reviews the imaging diagnosis of liver tumors in children and points out that with the rapid development of imaging medicine,imaging examination provides an important reference for clarifying the location of liver tumors,identifying benign or malignant tumors,and determining tumor stage.

Imaging feature of rare liver neoplasms

Li XinMing, Quan XianYue, Tan ShuPing

2016, 32(12): 2289-2294. DOI: 10.3969/j.issn.1001-5256.2016.12.012

Abstract(2493)

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Various primary and secondary tumors are commonly seen in the liver and have different histological types,but some types of tumors are rare. Computed tomography( CT) and magnetic resonance imaging( MRI) can show the size,morphology,and density or signal of intrahepatic lesions,their association with surrounding tissues,and tumor blood supply. Meanwhile,MRI has a high resolution for soft tissue. This article summarizes the CT and MRI findings of rare liver tumors,in order to improve the diagnostic level of rare liver tumors and give full play to the role of imaging examination in the diagnosis and treatment of liver tumors.

Imaging evaluation of complications after liver transplantation

Wang MingYue, Lu ZhiYan

2016, 32(12): 2295-2299. DOI: 10.3969/j.issn.1001-5256.2016.12.013

Abstract(2001)

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Liver transplantation is an effective treatment for end- stage chronic liver diseases and acute liver failure. With the rapid development of surgical techniques,organ preservation technology,and pharmacotherapy,patients' survival rates are improved constantly. However,postoperative complications are still major influencing factors for postoperative incidence and mortality rates. Since clinical and laboratory examinations lack specificity and it is difficult to diagnose various postoperative complications,the application of imaging techniques effectively solves such problems. This article summarizes the imaging findings of common complications after liver transplantation,such as vascular complications,biliary complications,liver parenchyma lesions,and postoperative infection,and points out that imaging examinations have significant advantages and can be used for comprehensive evaluation of disease progression.

Clinical effect of brachytherapy with ~(125)I seed implantation in treatment of malignant hepatopancreatobiliary tumors

Jiang Xu, Yang JiJin, Li Hui

2016, 32(12): 2300-2304. DOI: 10.3969/j.issn.1001-5256.2016.12.014

Abstract(2290)

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Malignant hepatopancreatobiliary tumors are highly malignant and have poor prognosis.~(125)I seed implantation combined with other minimally invasive therapies for radical treatment of early liver cancer has achieved a good clinical effect in preventing early recurrence after liver cancer surgery. It is also used in the treatment of advanced liver cancer and portal vein tumor thrombosis.~(125)I seed has achieved a good local control rate in the treatment of tumors with a lack of blood supply,such as intrahepatic cholangiocellular carcinoma and metastatic liver cancer.~(125)I seed combined with biliary stenting can significantly relieve the symptoms of malignant biliary obstruction and extend the time to restenosis. Comprehensive interventional treatment based on~(125)I seed can significantly improve quality of life and extend survival time in patients with pancreatic cancer. Therefore,~(125)I seed implantation is safe and convenient in clinical practice and holds promise for clinical application.

Imaging diagnosis of pancreatic cancer and preoperative imaging evaluation of resectability and staging

Chen Lu, Yu RiSheng

2016, 32(12): 2305-2311. DOI: 10.3969/j.issn.1001-5256.2016.12.015

Abstract(2252)

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Pancreatic cancer is an invasive malignant tumor with a high mortality rate. As the preferred imaging method for pancreatic imaging,multi- slice CT angiography can evaluate the presence or absence,extent,and degree of invasion of peripancreatic major vessels to provide reliable evidence for tumor staging and surgical resectability evaluation. As an important supplementary method of CT,magnetic resonance imaging has an important guiding value in disease diagnosis,liver metastasis,and prognostic evaluation. Vascular invasion of pancreatic cancer is the main indicator for preoperative evaluation of respectability. Lymph node metastasis,distant metastasis,neural invasion of pancreatic cancer,and hepatic artery abnormalities are influencing factors for patients' prognosis. It is pointed out that preoperative imaging evaluation for patients with pancreatic cancer has guiding significance for the development of treatment regimens,selection of surgical procedures,and prognostic evaluation.

Preparation of human hepatitis B virus monoclonal antibodies using single cell RT-PCR

Li TeTe, Wu Jing, Lu: XinPing, Zhou Hao, Chen JingTao

2016, 32(12): 2312-2316. DOI: 10.3969/j.issn.1001-5256.2016.12.016

Abstract(1919)

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Objective To establish the system for the isolation of peripheral single antibody- secreting cells( ASCs) and single cell RT-PCR system,and to clone highly specific human hepatitis B monoclonal antibody efficiently and rapidly. Methods Three patients with HBV infection in the recovery stage were enrolled. Peripheral B cells were collected and activated by HBc Ag Peptide pool. Flow sorting was performed to obtain memory ASCs( CD19~+CD10~-IgG~+CD27~+),the limiting dilution method was used to obtain single cells,single cell RT-PCR was used to obtain cDNA,and nested PCR was used for the amplification of the fragment in the constant region of the heavy chain of antibody. PCR product was purified and cloned to pEASY~- T1 simple cloning vector for sequencing and identification. Results The results of ELISA showed that a high level of IgG was observed in all three patients with HBV infection in the recovery stage. There were significant differences in peripheral IgG level between patients and healthy volunteers( both P < 0. 05). The results of flow sorting showed that the proportion of B cells was higher than 94% and memory ASCs were isolated. A total of 24 ASCs containing at least one cell with normal morphology were selected,and after identification,14 were successfully amplified,with a size of about 200 bp,which was consistent with expected results. The analysis of the sequence of the heavy chain of antibody showed successful amplification of the fragment in the constant region of the antibody. Conclusion The system for the isolation of single ASCs and single cell RT- PCR system are successfully established and the sequence of the heavy chain of antibody is obtained,which lays a solid foundation for the high- throughput production of human hepatitis B monoclonal antibodies in future.

Change in peripheral blood CD4~+ regulatory T cells and its association with antiviral effect in patients with chronic hepatitis C

Guo FeiBo

2016, 32(12): 2317-2321. DOI: 10.3969/j.issn.1001-5256.2016.12.017

Abstract(233)

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Objective To investigate the change in peripheral blood CD4~+regulatory T( Treg) cells and its association with antiviral effect in patients with chronic hepatitis C( CHC). Methods A total of 85 CHC patients who completed standard antiviral therapy and follow- up in The First People's Hospital of Tianmen from January 2013 to January 2016 were enrolled as CHC group,and 40 healthy volunteers were enrolled as control group. Flow cytometry was used to measure peripheral blood CD4~+Treg cells,and the serum levels of HCV RNA,aspartate aminotransferase( AST),and alanine aminotransferase( ALT) were measured before treatment,at 12 and 48 weeks of treatment,and at24 weeks of follow- up. The t- test was used for comparison of continuous data between groups. Results Before treatment,the CHC group had significantly higher levels of HCV RNA,AST,ALT,and CD4~+Treg cells than the control group( all P < 0. 001). At 12 weeks of treatment,of all patients in the CHC group,36( 42. 35%) achieved early virological response( EVR)( EVR group) and 49( 57. 65%) did not achieve EVR( no- EVR group); the EVR group had significant reductions in the levels of HCV RNA and CD4~+Treg cells after treatment( t = 39. 241 and 8. 763,both P < 0. 001),and there were significant differences in the levels of HCV RNA and CD4~+Treg cells between the two groups( t = 76. 520 and 8. 227,both P < 0. 001). At 48 weeks of treatment,of all patients in the CHC group,49( 57. 65%)achieved end- of- treatment response( ETR)( ETR group) and 36( 42. 35%) did not achieve ETR( no- ETR group); the ETR group had significant reductions in the levels of AST,ALT,CD4~+Treg cells,and HCV RNA at 48 weeks of treatment( t = 46. 197,11. 806,15.368,and 9. 694,all P < 0. 001) and had significantly lower levels than the no- ETR group( t = 72. 612,9. 274,9. 682,and 7. 729,all P< 0. 001). At 24 weeks of follow- up,of all patients in the CHC group,39( 45. 88%) achieved sustained virological response( SVR)( SVR group),among whom 30 achieved EVR and 32 achieved ETR,and 46( 54. 12%) did not achieve SVR( no- SVR group); at 48 weeks of treatment and 24 weeks of follow- up,the SVR group had significantly lower levels of HCV RNA,AST,ALT,and CD4~+Treg cells than the no- SVR group( at 48 weeks of treatment: t = 117. 564,17. 113,10. 564,and 4. 452,all P < 0. 001; at 24 weeks of follow- up: t = 11. 196,20. 997,13. 384,and 7. 900,all P < 0. 001). Conclusion CHC patients have an increase in peripheral blood CD4~+Treg cells and antiviral therapy can effectively reduce the level of CD4~+Treg cells and alleviate liver injury. Measurement of peripheral blood CD4~+Treg cells can be used as an assessment index for the development of CHC and the effect of antiviral therapy.

Clinical value of FibroScan in diagnosis of moderate-to-severe liver fibrosis in patients with chronic hepatitis B

Wang Lin, Xue Fang, Shi YuXin

2016, 32(12): 2322-2325. DOI: 10.3969/j.issn.1001-5256.2016.12.018

Abstract(2312)

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Objective To investigate the clinical value of transient elastography( FibroScan) in the diagnosis of moderate- to- severe liver fibrosis in patients with chronic hepatitis B( CHB). Methods A total of 245 patients with pathologically confirmed CHB by liver biopsy who underwent FibroScan and serological examinations in Shanghai Public Health Clinical Center from 2012 to 2015 were enrolled and divided into mild liver fibrosis group( S1- S2,189 patients) and moderate- to- severe liver fibrosis group( S3- S3,56 patients). The FibroScan value,aspartate aminotransferase- to- platelet ratio index( APRI) [( aspartate aminotransferase/upper limit of normal × 100)/platelet count],and levels of hyaluronic acid( HA),aspartate aminotransferase( AST),and alanine aminotransferase( ALT) were measured. The t- test was used for comparison of normally distributed continuous data between groups,and the Mann- Whitney U rank sum test was used for comparison of non- normally distributed continuous data between groups. A logistic regression analysis was used for risk prediction. The receiver operating characteristic( ROC) curve,95% confidence interval( 95% CI),and area under the ROC curve( AUC) were used to investigate the accuracy of FibroScan in the diagnosis of moderate- to- severe liver fibrosis. The FibroScan value corresponding to the maximum of the sum of sensitivity and specificity was the optimal cut- off value for liver fibrosis. Results There were significant differences in age,the levels of ALT,AST,and HA,APRI,and FibroScan value between the two groups( all P < 0. 05). The univariate analysis showed that the severity of liver fibrosis was associated with the measured FibroScan value,HA level,and APRI( OR = 2. 56,1. 03,and31. 73,all P < 0. 001),and the multivariate analysis showed that only FibroScan value was associated with moderate- to- severe liver fibrosis( OR = 2. 25,P < 0. 001). The AUCs of FibroScan,HA,and APRI in the diagnosis of moderate- to- severe liver fibrosis were 0. 985( 95% CI: 0. 969- 1. 000),0. 842( 95% CI: 0. 774- 0. 911),and 0. 868( 95% CI: 0. 813- 0. 922),respectively,at cut- off values of11. 65,104. 4,and 0. 69,respectively. In the diagnosis of moderate- to- severe liver fibrosis,FibroScan,HA,and APRI had sensitivities of98. 9%,96. 3%,and 96. 3%,specificities of 85. 7%,55. 4%,and 48. 2%,positive predictive values of 95. 9%,87. 9%,and 86. 3%,and negative predictive values of 96. 0%,81. 6%,and 79. 4%. Conclusion FibroScan has a high clinical value in the diagnosis of moderate- to- severe liver fibrosis and plays an important role in early identification of liver fibrosis and accurate evaluation of fibrosis degree.

Association between portal vein pressure drop gradient after transjugular intrahepatic portosystemic shunt and clinical prognosis

Xu ZhengGuo, Zhao YongBing, Zheng YuanYu, Liu En, Yang ShiMing

2016, 32(12): 2326-2330. DOI: 10.3969/j.issn.1001-5256.2016.12.019

Abstract(1970)

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Objective To investigate the association between portal vein pressure drop gradient in patients with cirrhotic portal hypertension treated by transjugular intrahepatic portosystemic shunt( TIPS) and clinical prognosis,as well as the ideal range of portal vein pressure drop. Methods A total of 58 patients who underwent TIPS in Xinqiao Hospital of Third Military Medical University from November 2013 to December 2015 were enrolled. All the patients underwent TIPS and embolization of the gastric coronary vein and the short gastric veins,and the change intervals of portal vein pressure gradient were monitored. The follow- up time ranged from 3 days to 2 years,and the association of portal vein pressure drop gradient with postoperative liver function,splenic function,rebleeding rate,hepatic encephalopathy,and portal hypertensive gastrointestinal diseases was analyzed. The paired t- test was used for comparison of parameters before and after treatment. Results The patients had a significant reduction in liver function on day 3 after surgery. At 2 month after surgery,the levels of TBil was rised and had significant changes[( 49. 81 ± 27. 82) μmol/L vs( 31. 64 ± 17. 67) μmol/L,t = 5. 372,P < 0. 001]. At 6 months after surgery,red blood cell count and platelet count had no significant changes,but,white blood cell count was reduced[( 3. 79 ± 1. 37) ×10~9/L vs( 4. 57 ±2. 24) ×10~9/L,t = 2. 835,P = 0. 006]. There was a 23% reduction in portal vein pressure after surgery( from 30. 62 ± 3. 56 mm Hg before surgery to 21. 21 ± 2. 90 mm Hg after surgery,t = 23. 318,P < 0. 001). All the patients had varying degrees of relief of gastrointestinal symptoms associated with portal vein hypertension,such as abdominal distension,poor appetite,and diarrhea. Of all patients,none experienced in- stent restenosis or occlusion and 13 experienced hepatic encephalopathy after surgery,which tended to occur at the time when postoperative portal vein pressure was reduced to 14. 7- 25. 7 mm Hg,i. e.,a 36%- 40% reduction in portal vein pressure. The results of splenic venography performed immediately after surgery showed that varicose veins almost disappeared and that there were no collateral varices. Gastroscopy was performed again within 1 month after surgery and 5 patients had no significant changes in esophageal varices. The other patients were followed up for 2 years,and the severity of esophageal and gastric varices gradually changed from severe varices with red color sign to moderate and mild varices and even disappeared. The proportion of patients with mild and disappeared varices increased from 22% on day 3after surgery to 52% in the second year after surgery. No patients experienced rebleeding within 1 month after surgery. Six patients each experienced rebleeding at 2,6,10,14,16,and 24 months after surgery,and in one patient,duodenal bulbar ulcer and bleeding was not excluded; the other 5 patients experienced gastric variceal bleeding again,with a median portal vein pressure of 36. 46 mm Hg before surgery and 24. 8 mm Hg after surgery,with a 32% reduction in portal vein pressure. Conclusion TIPS has a good clinical effect in hemostasis and prevention of rebleeding in patients with cirrhotic portal hypertension and can control the portal vein pressure below 21. 21 ± 2. 90 mm Hg,and the degree of reduction in portal vein pressure is below 36%- 40%. It can reduce the incidence of postoperative rebleeding and avoid the development of hepatic encephalopathy. TIPS can cause liver impairment within a short period of time after surgery,and liver function can return to normal within 1- 6 months after surgery,but splenic function does not recover significantly.

Mechanism of action of 1,25(OH)_2D_3 in influencing the expression of interleukin-17 and macrophage inflammatory protein-3α and inhibiting the formation of liver fibrosis in rats

Li XiaoTian, Yin Yan, Guo YongZe, Zhou LiYun, You ZiXuan

2016, 32(12): 2331-2336. DOI: 10.3969/j.issn.1001-5256.2016.12.020

Abstract(1873)

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Objective To investigate the changes in the expression of interleukin- 17( IL- 17) and macrophage inflammatory protein- 3α( MIP- 3α) in liver tissue and peripheral blood during the formation of liver fibrosis and the mechanism of action of 1,25( OH)2D3in influencing the IL- 17 pathway and inhibiting the formation of liver fibrosis. Methods A total of 48 Sprague- Dawley rats were randomly divided into normal group( olive oil),model group( CCl4 olive oil solution),drug control group( CCl4 olive oil solution + olive oil by gavage),and treatment group( CCl4 olive oil solution + 1,25( OH)2D3olive oil solution by gavage). Eight weeks later the liver tissue was collected for HE staining and Masson staining to determine the pathological staging of fibrosis. ELISA was used to measure the serum level of IL- 17 at different time points after intervention( weeks 4,6,and 8). Immunohistochemistry was used to measure the protein expression of IL- 17 and MIP- 3α in liver tissue at different time points( weeks 4,6,and 8),and real time- PCR was used to measure the mRNA expression of IL- 17 and MIP- 3α in liver tissue at week 8 after intervention. A one- way analysis of variance was used for comparison of continuous data between groups,and the LSD- t test was used for further pairwise comparison. The linear regression analysis was used for correlation analysis. Results At week 8 after intervention,the model group and the drug control group had significant liver fibrosis,and the treatment group had significant alleviation in liver fibrosis. There were significant differences in serum IL- 17 level between the four groups at weeks4,6,and 8( F = 6. 13,5. 79,and 7. 18,all P < 0. 05). The normal group had an extremely low serum level of IL- 17; at each time point,the model group and the drug control group had a significant increase in the serum level of IL- 17 compared with the normal group( all P < 0. 01). At each time point,the treamtent group had significant reductions in the serum level of IL- 17 compared with the model group and the drug control group( all P < 0. 05),and all the groups had the highest level at week 4. Immunohistochemistry and real time-PCR showed that there was almost no expression of IL- 17 and a very low expression level of MIP- 3α in liver tissue in the control group.With the progression of liver fibrosis,serum IL- 17 level decreased gradually,while the IL- 17 level in liver tissue increased gradually( r=- 0. 793,P < 0. 01). There were significant differences in the expression of IL- 17 and MIP- 3α in liver tissue between the four groups at weeks 4,6,and 8( IL- 17: F = 11. 02,9. 61,and 7. 45,all P < 0. 05; MIP- 3α: F = 9. 47,8. 93,and 6. 15,all P < 0. 05). The model group and the drug control group had significant increases in the protein expression of IL- 17 and MIP- 3α in liver tissue compared with the normal group at weeks 4,6,and 8( all P < 0. 01),and the treatment group had significant reductions compared with the drug control group at these time points( all P < 0. 05); all the groups had the highest expression at week 8. At week 8,the model group and the drug control group had significant increases in the mRNA expression of IL- 17 and MIP- 3α compared with the normal group,and the treatment group had significant reductions compared with the drug control group and the model group( FIL- 17= 7. 36,FMIP- 3α= 10. 15,both P < 0.05). Conclusion During the development and progression of liver fibrosis,serum IL- 17 level first increases and then decreases,while the expression of IL- 17 in liver tissue tends to increase gradually,suggesting that in the late stage of liver fibrosis,Th17 cells in serum tend to accumulate in the liver. The 1,25( OH)2D3treatment group had significant reductions in the protein and mRNA expression of IL- 17 and MIP- 3α in the liver compared with the model group and the drug control group,suggesting that the IL- 17 pathway may be one mechanism of action of 1,25( OH)2D3in inhibiting the development and progression of liver fibrosis.

Clinical effect and safety of percutaneous radiofrequency ablation following transcatheter arterial chemoembolization in treatment of primary liver cancer in high-risk locations

Sun Wei, Ding XiaoYan, Chen JingLong

2016, 32(12): 2337-2341. DOI: 10.3969/j.issn.1001-5256.2016.12.021

Abstract(1968)

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Objective To investigate the clinical effect and safety of percutaneous radiofrequency ablation( RFA) following transcatheter arterial chemoembolization( TACE) in the treatment of primary liver cancer in high- risk locations. Methods The patients with primary liver cancer in high- risk locations who were diagnosed and treated from January 2011 to December 2015 were enrolled. All the patients underwent TACE followed by CT- guided RFA 3- 5 days later. The treatment outcome and adverse events were observed. Results A total of64 patients with 76 lesions were enrolled and all of them completed TACE and RFA. At one month after surgery,the complete tumor ablation rate was 81. 5%( 62/76). The patients were followed up for 6 to 64 months after surgery; at the end of follow- up,the local tumor progression rate was 28. 9%( 22/76),and the 1-,2-,and 3- year survival rates were 90. 6%,78. 1%,and 64. 1%,respectively. The incidence rate of severe surgical complications during follow- up was 3. 1%( one patient each experienced liver abscess and hematobilia),and the patients achieved remission after medical treatment and interventional treatment without any sequel. Conclusion CT- guided RFA after TACE is a safe and feasible regimen for primary liver cancer in high- risk locations.

Influence of serum levels of alkaline phosphatase and gamma-glutamyl transpeptidase on the prognosis of patients with primary liver cancer undergoing radiofrequency ablation

Zhu Ge, Zhao LingLing, Qian Lei, Dong YaBing, Zhao HengJun, Cui JiuWei, Wang NanYa

2016, 32(12): 2342-2346. DOI: 10.3969/j.issn.1001-5256.2016.12.022

Abstract(1897)

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Objective To investigate the influence of serum levels of alkaline phosphatase( ALP) and gamma- glutamyltransferase( GGT)before treatment on the prognosis of patients with primary liver cancer undergoing radiofrequency ablation. Methods A total of 165 patients with pathologically or clinically confirmed primary liver cancer who were admitted to Cancer Center of The First Hospital of Jilin University from October 2010 to June 2015 and treated with radiofrequency ablation were enrolled,and their preoperative clinical data were collected.The chi- square test was used for comparison of categorical data between groups,and the Kaplan- Meier method and Cox regression analysis were used to analyze the association of serum ALP and GGT levels before treatment with overall survival,progression- free survival,and clinical features. Results There were significant differences in the 1-,2-,and 5- year survival rates between the patients with normal( ≤135 U/L) or abnormal( > 135 U/L) serum ALP before treatment( 91%/90%/35% vs 79%/68%/18%,P = 0. 01). There were also significant differences in the 1-,2-,and 5- year survival rates between the patients with normal( ≤45 U/L) or abnormal( > 45 U/L)serum GGT before treatment( 95%/85%/37% vs 87%/71%/21%,P < 0. 001). The serum levels of ALP( HR = 1. 766,95% CI: 1. 068- 2. 921,P = 0. 027) and GGT( HR = 2. 312,95% CI: 1. 367- 3. 912,P = 0. 002) before treatment were closely associated with the overall survival of patients with primary liver cancer after radiofrequency ablation and were independent prognostic factors. There were significant differences in the 1-,2-,and 5- year progression- free survival rates between the patients with normal( ≤135 U/L) or abnormal( >135 U/L) serum ALP before treatment( 72%/52%/14% vs 50%/21%/3%,P < 0. 001); there were also significant differences in the 1-,2-,and 5- year progression- free survival rates between the patients with normal( ≤45 U/L) or abnormal( > 45 U/L) serum GGT before treatment( 81%/62%/18% vs 56%/35%/7%,P < 0. 001). The serum levels of ALP( HR = 1. 653,95% CI: 1. 001- 2. 729,P =0. 049) and GGT( HR = 1. 949,95% CI: 1. 296- 2. 930,P = 0. 001) before treatment were closely associated with the progression- free survival of patients with primary liver cancer after radiofrequency ablation. There were more male patients with abnormal ALP than the female patients,and the patients with abnormal ALP had high incidence rates of poor Child- Pugh classification and ascites. In the patients with abnormal GGT( > 45 U/L),there was a high proportion of patients with poor Child- Pugh classification,late tumor stages,and a tumor size of ≥5 cm and a high incidence rate of hepatic encephalopathy. Conclusion The serum levels of ALP and GGT before treatment can be used to predict the prognosis of patients with primary liver cancer after radiofrequency ablation and have certain guiding significance for the long- term survival of patients with primary liver cancer after radiofrequency ablation.

Synergistic effect of intervention of glypican-3 gene transcription combined with antitumor drugs in inhibiting hepatoma cell proliferation

Yang Jie, Yao Min, Wang Li, Dong ZhiZhen, Gu JuanJuan, Qiu LiWei, Zhang Wei, Yao DengFu

2016, 32(12): 2347-2352. DOI: 10.3969/j.issn.1001-5256.2016.12.023

Abstract(1925)

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Objective To investigate the inhibitory effect of intervention of glypican- 3( GPC3) gene transcription combined with antitumor drugs on hepatoma cell proliferation. Methods Four types of GPC3- shRNA plasmids were established and transfected into HepG2 hepatoma cells. Quantitative real- time PCR and Western blot were used to measure the mRNA and protein expression of GPC3 to analyze its association with hepatoma cell proliferation and apoptosis. The independent samples t- test was used for comparison of continuous data between any two groups,and a one- way analysis of variance was used for comparison between multiple groups. Results Among these four plasmids,shRNA1 had a transfection efficiency of > 85% in the transfection of HepG2 cells and a silence efficiency of 89. 3% at the mRNA level,and the protein expression of GPC3 was significantly inhibited( P < 0. 01). At 72 hours,the GPC3- shRNA1 co- intervention group had an HepG2 cell inhibition rate of 71. 1%,significantly different from that in the negative group( t = 18. 092,P < 0. 001),an inhibition rate of migration of 89. 1%,significantly lower than that in the negative group( t = 8. 326,P < 0. 001),and inhibition rates of HepG2 cell movement and invasion of 53. 6% and 60. 1%,which were significantly different from those in the negative group( t = 52. 400 and 48. 245,both P < 0. 001). The GPC3- shRNA1 co- intervention group had a β- catenin mRNA inhibition rate of 46. 9% and a Gli1 mRNA upregulation rate of 7. 4%,significantly different from those in the negative group( t = 30. 108 and- 3. 551,P < 0. 001 and P = 0. 009). At 24 hours,10 μmol/L sorafenib combined with shRNA1 had an inhibition rate of tumor cells of 52. 6% and 100 μmol/L sorafenib combined with shRNA1 had an inhibition rate of tumor cells of 79. 5%,which were significantly different from that in the control group( t = 23. 314 and50. 352,both P < 0. 001). The half- maximal inhibitory concentrations of sorafenib,rapamycin,and erlotinib for HepG2 were 4. 67 ± 1. 20μmol/L,7. 85 ± 2. 00 nmol/L,and 18. 36 ± 0. 56 μmol/L,respectively,and their combination with shRNA1 had an HepG2 cell inhibition rate of 95. 11%. Conclusion Intervention of GPC3 gene transcription with specific shRNA can inhibit hepatoma cell proliferation,migration and movement,and invasion ability,induce hepatoma cell apoptosis,and inhibit hepatoma cell proliferation when combined with antitumor drugs in a synergistic manner. This suggests that GPC3 may be an effective therapeutic target for liver cancer and that combined targeted therapy can provide better strategies for the treatment of liver cancer.

Application of endoscopic retrograde cholangiopancreatography in treatment of extrahepatic biliary adenoma

Zhou HaiXiang, Dong XiaoYun, Bu Ping, Xiang XiaoXing, Xu XiaoLing, Chen ChaoWu

2016, 32(12): 2353-2355. DOI: 10.3969/j.issn.1001-5256.2016.12.024

Abstract(1407)

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Objective To investigate the clinical features of extrahepatic biliary adenoma and the role of endoscopic retrograde cholangiopancreatography( ERCP) in the diagnosis and treatment of extrahepatic biliary adenoma. Methods A retrospective analysis was performed for the clinical manifestations,imaging findings,ERCP treatment,and follow- up data of 7 patients with extrahepatic biliary adenoma who were admitted to Department of Gastroenterology in The People's Hospital of Northern Jiangsu from January 2010 to June 2016. Results Selective ERCP was performed for 7 patients after the exclusion of surgical contraindications. Intraoperative cholangiography showed interruption of different parts of the bile duct,and brush cytology under the guidance of guide wire and bile duct biopsy with ultrafine biopsy forceps were performed for all patients. The pathological examination showed bile duct adenoma. Among these patients,6 were treated with ERCP and 1 was treated with Roux- en- Y choledochojejunostomy after ERCP. Conclusion As a minimally invasive examination,ERCP helps to determine the cause of the disease and evaluate patients' condition. When patients have surgical contraindications or are not willing to choose surgery,ERCP can be used as palliative therapy to relieve their clinical symptoms.

Li YunQian, Chen Fan, Liu Yang, Yu HongQuan, Jin RiHua, Wu XinMin

2016, 32(12): 2364-2366. DOI: 10.3969/j.issn.1001-5256.2016.12.027

Abstract(2021)

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Ma PanPan, Jiang XiaoMing, Han DongFeng, Lin JieYu, Liu Fang, Liu XiaoLiang

2016, 32(12): 2367-2368. DOI: 10.3969/j.issn.1001-5256.2016.12.028

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Cong TingTing, Liu SiQi, Jia ShengNan, Pan LiuLan

2016, 32(12): 2369-2370. DOI: 10.3969/j.issn.1001-5256.2016.12.029

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Wang Long, Zheng PengFei, An HuiMeng, Peng Wei, Cao HongTai, Cheng ZhiBin

2016, 32(12): 2371-2372. DOI: 10.3969/j.issn.1001-5256.2016.12.030

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PD-1/PD-L signaling pathway in chronic hepatitis B

Tao LiLin, Lai Xin, Wei Jia

2016, 32(12): 2373-2378. DOI: 10.3969/j.issn.1001-5256.2016.12.031

Abstract(1555)

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Hepatitis B is one of the major diseases that affect the health of Chinese people,and chronic hepatitis B virus( HBV) infection can lead to disease progression. Programmed death- 1( PD- 1) discovered in recent years is an important coordinated stimulus molecule which belongs to the B7/CD28 family. After its binding with programmed death ligand( PD- L),it can regulate the activation,differentiation,and proliferation of T lymphocytes. PD- 1 and its ligand are differently expressed in different stages of chronic HBV infection. The interaction between PD- 1 and its ligand in different immune cells induces immune tolerance in human body and finally leads to the chronicity of HBV infection. Blocking the PD- 1/PD- L signaling pathway through different ways can improve T cell exhaustion,suggesting that this might be one of the directions of antiviral therapy in future.

Ultrasound elastography for evaluation of classification of liver fibrosis

Ge Na, He Qian

2016, 32(12): 2379-2382. DOI: 10.3969/j.issn.1001-5256.2016.12.032

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Liver fibrosis is the important stage of most liver diseases,and early and accurate diagnosis of classification of liver fibrosis plays an important role in developing individualized treatment regimens and reducing mortality rates. Ultrasound elastography has become popular in clinical physicians due to its unique advantages. This article compares the accuracy,sensitivity,and specificity of transient elastography,acoustic radiation force impulse elastography,real- time shear wave elastography,and real- time tissue elastography in the diagnosis of classification of liver fibrosis and helps to enhance clinical physicians' knowledge of advantages and shortcomings of various ultrasound elastography methods in the diagnosis of classification of liver fibrosis.

Effect of splenectomy on liver cirrhosis and related surgical issues

Kong DeGang, Lu ShiChun

2016, 32(12): 2383-2386. DOI: 10.3969/j.issn.1001-5256.2016.12.033

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Patients with liver fibrosis and cirrhosis experience certain changes in spleen morphology and function,and there is always a controversy over whether to perform splenectomy in patients with liver cirrhosis. As a surgical treatment of recurrent portal hypertension complicated by esophagogastric variceal bleeding,splenectomy can reduce portal venous pressure,reduce the possibility of gastrointestinal bleeding,and correct the reduced white blood cell count and platelet count. It can also protect the liver by improving liver function,promoting regeneration of hepatocytes,and inhibiting the progression of liver fibrosis. With reference to available clinical and laboratory data,this article reviews the effect of splenectomy on the cirrhotic liver and related issues such as selection of surgical procedures and prevention and treatment of postoperative complications,in order to promote splenectomy in patients with liver cirrhosis.

Current status of research on microRNA associated with colorectal cancer liver metastasis

Wang DongXu, Huo TingTing, Tian YaoWen, Zhao Lei

2016, 32(12): 2387-2390. DOI: 10.3969/j.issn.1001-5256.2016.12.034

Abstract(2025)

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Tumor metastasis is a complicated process with multiple steps,and liver metastasis is the most common metastatic mode of colorectal cancer. Deep understanding and study of metastatic mechanism helps to find solutions for colorectal cancer liver metastasis. Recent studies have shown that microRNA are involved in tumor metastasis and recurrence,and studies on microRNA associated with colorectal cancer liver metastasis can provide new thoughts for the development and progression,diagnosis and treatment,and prognosis of the disease.This article summarizes the research advances in microRNA associated with colorectal cancer liver metastasis and reviews the biological function and molecular mechanism of microRNA,which suggests that microRNA have a vital significance in the field of tumor metastasis,especially colorectal cancer liver metastasis.

Role of intestinal mucosal barrier in the development and progression of nonalcoholic fatty liver disease

Zhang YuanYuan, Li Jing, Chi YuJing, Su Lin, Liu YuLan

2016, 32(12): 2391-2394. DOI: 10.3969/j.issn.1001-5256.2016.12.035

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The incidence of non- alcoholic fatty liver disease( NAFLD) has been increasing year by year in China. Intestinal mucosa is the largest organ for bacterial storage,and intestinal mucosal barrier includes biological barrier,mechanical barrier,immunological barrier,and chemical barrier. This article investigates the important role of intestinal mucosal barrier function in the pathogenesis of NAFLD. As for the intestinal biological barrier,abnormalities in gut microbiota occur earlier than obesity and other metabolic disorders; small intestinal bacterial overgrowth may affect energy metabolism,promote insulin resistance,and get involved in the pathogenesis of NAFLD; regulation of gut microbiota has a certain clinical effect in the treatment of NAFLD. Intestinal mechanical barrier impairment increases the mucosal permeability and is associated with intestinal dysbacteriosis. The changes in intestinal immunological barrier may be associated with obesity,metabolic disorders,and liver inflammation. The changes in intestinal chemical barrier can inhibit the synthesis and secretion of very low- density lipoprotein and low- density lipoprotein in hepatocytes and may result in triglyceride deposition in the liver. It is pointed out that the research on intestinal mucosal barrier function provides promising prospects for the prevention and treatment of NAFLD.

Role of the Mac-2 binding protein glycosylation isomer in diagnosis of chronic liver diseases

Yang YiLiang, Cui YuanYuan, Hu Yue, Xu HongQin, Pan Yu

2016, 32(12): 2395-2398. DOI: 10.3969/j.issn.1001-5256.2016.12.036

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Mac- 2 binding protein is a type of glycoprotein which exits in cytoplasm,interstitial fluid,and plasma and is secreted by a variety of tissues and organs. Mac- 2 binding protein glycosylation isomer( M2BPGi) is synthesized by hepatic stellate cells. This article briefly introduces the research advances in the role of M2 BPGi in chronic liver diseases and finds out that the serum level of M2 BPGi helps to increase the specificity and sensitivity of the diagnosis and monitoring of liver diseases,has certain advantages over other noninvasive methods,and may become a new biological marker for the diagnosis of liver diseases.

Research advances in signaling pathways involved in liver regeneration mediated by oval cells

Zhong XiaoMao, Han BaoSheng

2016, 32(12): 2399-2402. DOI: 10.3969/j.issn.1001-5256.2016.12.037

Abstract(2141)

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The apoptosis,necrosis,and senescence of hepatocytes are closely associated with the activation and proliferation of oval cells,and in addition,liver regeneration mediated by oval cells is an important part of regeneration after liver injury. Currently,studies have shown that a variety of cytokines,hormones,and neurotransmitters are involved in this process. This article reviews recent research findings,introduces the research advances in the association between various signaling pathways( TWEAK/Fn14,Hedgehog,and thyroid hormone) and liver regeneration mediated by oval cells,elaborates on the role of each pathway in the regeneration of hepatocytes,and investigates related mechanisms in liver regeneration.

Application and role of fibrates in treatment of primary biliary cholangitis and related mechanisms

Wu LiHong, Han Ying

2016, 32(12): 2403-2406. DOI: 10.3969/j.issn.1001-5256.2016.12.038

Abstract(2304)

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Primary biliary cholangitis( PBC) is an autoimmune chronic cholestatic liver disease. Ursodeoxycholic acid( UDCA) is the only safe and effective drug for PBC approved by FDA. To date,there is no unified therapeutic regimen for patients with suboptimal response to UDCA. Fibrates are a class of synthesized ligands of peroxisome proliferator- activated receptors,and recent studies have shown that fibrates may have anticholestatic,anti- inflammatory,and antifibrotic effects. The article reviews the application of fibrates in the treatment of PBC and possible mechanisms.

Wang MingMing

2016, 32(12): 2230-2230. DOI: 肝胆病杂志 2016,32(12),2230

Abstract(878)

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Zhang Ying, Zhang FuKui

2016, 32(12): 2248-2257. DOI: 10.3969/j.issn.1001-5256.2016.12.005

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Interpretation and analysis of EASL recommendations on treatment of hepatitis C 2016

Shen ShanShan, Dai MingJia, Yan XueBing

2016, 32(12): 2258-2262. DOI: 10.3969/j.issn.1001-5256.2016.12.006

Abstract(1998)

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Jin Lei, Li JingJing, Gao YuFeng

2016, 32(12): 2263-2267. DOI: 10.3969/j.issn.1001-5256.2016.12.007

Abstract(112)

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Clinical types and features of chronicity of drug-induced liver injury

Liang Shan, Fan ZuoPeng, Nie Wei, Chou LiXia, Chen Jie, Lin Wei, Liu YiRong, Zhang Jing, Hu ZhongJie

2016, 32(12): 2356-2359. DOI: 10.3969/j.issn.1001-5256.2016.12.025

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Objective To investigate the clinical types and features of chronicity of drug- induced liver injury( DILI). Methods The patients who were diagnosed with DILI in Beijing You An Hospital,Capital Medical University from January 2011 to December 2013 were screened,and a retrospective analysis was performed for 84 patients with chronic DILI. The case report form was filled out for each patient,and the data were entered into a database,including demographic features,underlying diseases,types of drugs,cardinal symptoms and signs,and laboratory examinations. Results Of all patients,63( 75. 0%) were female. The chronicity of DILI could be divided into six clinical types according to disease progression and recovery of liver function; of all patients,64( 76. 2%) had a recurrent type,4( 4. 8%)had a delayed recovery type,4( 4. 8%) had a recurrent fluctuation type,6( 7. 1%) had a chronic cholestasis type,5( 6. 0%) had a type of rapid progression to liver cirrhosis,and 1( 1. 2%) had a type of drug- induced autoimmune hepatitis. Among all the 84 patients,56( 66. 7%) had underlying diseases; 51( 60. 7%) had DILI induced by a single drug,mainly traditional Chinese medicine( 47. 0%),antipyretics and analgesics( 10. 6%),and antitubercular agents( 9. 1%); as for the type of liver injury,52( 61. 9%) had hepatocyte injury,8( 9. 5%) had cholestasis,and 5( 6. 0%) had a mixed type. Liver biochemistries showed abnormal results in 19 patients( 22. 6%). Conclusion The chronicity of DILI can be divided into six clinical types,of which the most common type is the recurrent type,and the other clinical types include delayed recovery type,recurrent fluctuation type,chronic cholestasis type,rapid progression to liver cirrhosis,and drug- induced autoimmune hepatitis.

Changes in serum markers of iron metabolism and their clinical significance in patients with nonalcoholic fatty liver disease

Ou Qiang, Wang Yang, Xu YanHua, Ning HuiMing, Huang Ling, Tang Qun

2016, 32(12): 2360-2363. DOI: 10.3969/j.issn.1001-5256.2016.12.026

Abstract(299)

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Objective To investigate the changes in the serum markers of iron metabolism and their clinical significance in patients with nonalcoholic fatty liver disease( NAFLD). Methods A total of 68 NAFLD patients who were admitted to The Eighth People' s Hospital of Shanghai from July 2014 to April 2016 were enrolled as NAFLD group,and 70 healthy persons who underwent physical examination were enrolled as healthy control group. Among the 68 patients in the NAFLD group,24 had NAFLD alone and 44 were complicated by abnormal alanine aminotransferase( ALT) level. The levels of aspartate aminotransferase( AST),ALT,total cholesterol( TC),triglyceride( TG),and serum markers of iron metabolism [serum iron( SI),serum ferritin( SF),and serum hepcidin( HEPC) ] were measured for all patients,and the correlations between abnormal ALT level and serum markers of iron metabolism were analyzed. The independent samples t- test was used for comparison of continuous data between groups,the chi- square test was used for comparison of categorical data between groups,and the Pearson correlation coefficient was used to investigate the correlation between two variables. Results The NAFLD group had significantly higher body mass index and serum levels of ALT,AST,TC,and TG than the healthy control group( t = 9. 8,8. 6,8. 5,9. 2,and 2. 7,all P < 0. 05). Compared with the healthy control group,the NAFLD group had significantly higher levels of SI( 21. 7 ± 7. 1 μmol/L vs18. 7 ± 6. 9 μmol/L,t = 2. 3,P = 0. 02) and SF( 340. 2 ± 257. 6 μg/L vs 119. 1 ± 81. 2 μg/L,t = 6. 7,P < 0. 01) and a significantly lower level of HEPC( 12. 2 ± 5. 3 μg/L vs 22. 2 ± 6. 5 μg/L,t = 9. 9,P < 0. 01). Compared with those with NAFLD alone,the patients complicated by abnormal ALT level had significantly higher serum levels of ALT( 89 ± 58 U/L vs 26 ± 8 U/L,t = 7. 1,P < 0. 01),SI( 23. 4 ± 6. 2 μmol/L vs 19. 6 ± 7. 9 μmol/L,t = 2. 2,P = 0. 03),and SF( 406. 2 ± 290. 0 μg/L vs 219. 4 ± 112. 0 μg/L,t = 3. 7,P <0. 01),as well as a significantly lower serum level of HEPC( 7. 4 ± 4. 9 μg/L vs 16. 1 ± 7. 8 μg/L,t = 4. 7,P < 0. 01). The Pearson correlation analysis showed that SF was significantly positively correlated with ALT and AST( r = 0. 28 and 0. 34,P = 0. 02 and P < 0. 01).Conclusion NAFLD patients have significant iron overload,especially in NAFLD patients complicated by abnormal ALT level. SF is significantly positively correlated with ALT and AST. To a certain degree,SF can reflect the severity of liver injury in NAFLD patients.

2016, 32(12): 2407-2418. DOI: 肝胆病杂志 2016,32(12),2407-2418

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2016 No. 12

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2016 No. 12

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