Primary biliary cirrhosis( PBC) is an autoimmune liver disease characterized by the destruction of small intrahepatic bile ducts.Incomprehensible and complicated autoreactive responses participate in the development and progression of PBC,which involve various immune cells and inflammatory mediators. Based on the aspects of innate immunity and adaptive immunity,this article summarizes recent advances in the research on PBC pathogenesis at cellular and molecular levels and evaluates the clinical application of these studies. This article not only gives a feasible direction for researchers and clinicians in this study field,but also provides a theoretical basis for clinical diagnosis and novel therapeutic strategies.

Autoimmune hepatitis( AIH) is a progressive,chronic hepatitis of unknown cause. It is characterized by interface hepatitis,hypergammaglobulinaemia,circulating autoantibodies,and a favorable response to immunosuppression. This article summarizes the epidemiological and clinical characteristics of AIH and reviews recent advances in the diagnosis and treatment of AIH. Early diagnosis and proper treatment can improve the prognosis.

Primary biliary cirrhosis( PBC) is a chronic progressive cholestatic liver disease associated with immunity,with unknown etiology and pathogenesis. This article reviews the origin of its name,recent advances in research on PBC,and the prospect of treatment. Ursodeoxycholic acid is considered to be effective in improving cholestasis among PBC patients,but its naming and risk factors,as well as the response criteria and treatment,still need further research.

Primary biliary cirrhosis( PBC) is an autoimmune cholestatic liver disease. In this review,the epidemiology of PBC,which varies in different countries and regions,is comprehensively introduced. Furthermore,the natural history of PBC before and after the wide application of ursodeoxycholic acid is analyzed. Also,recent advances in the study field of PBC in China are summarized. However,we still lag far behind Western countries concerning the diagnosis and treatment of PBC. Therefore,we believe further improving the knowledge of PBC among primary care physicians and PBC patients,setting up the multi- center PBC study group in China,and probing into the pathogenesis of this disease would pave the way for effective treatment of PBC patients in China.

Sclerosing cholangitis can be divided into primary sclerosing cholangitis( PSC) and secondary sclerosing cholangitis according to the etiology and pathogenesis,and the pathogenesis of PSC may be associated with immunity. In recent years,a new type of sclerosing cholangitis has been found,which is characteristic of elevated levels of Ig G4 in serum and tissue and good response to steroid therapy. PSC and Ig G4- related sclerosing cholangitis can be collectively referred to as autoimmune sclerosing cholangitis. This article explores the similarities and differences between various diseases with manifestations of sclerosing cholangitis in the new concept,which will provide new ideas and directions for immune- related diseases.

Autoimmune liver disease overlap syndrome is a special type of autoimmune disease,and consensus has not been reached regarding the etiology and diagnosis and treatment. This paper reviews many aspects of overlap syndrome,such as etiology,pathogenesis,diagnosis and treatment,and its development process. In addition,the definition of this disease and the recent development of diagnosis and treatment are analyzed. It is pointed out that the pathogenesis of this disease is still not fully elucidated,and the standards for the diagnosis and treatment of this disease still need further discussion. Finally,the analysis showed that the clinical forms of AIH- PBC overlap syndrome can be varied,and early diagnosis and differentiation and reasonable treatment are the key points of current research.

Objective To evaluate the significance of combined analysis of different autoantibodies in the diagnosis of primary biliary cirrhosis( PBC). Methods Two- hundred and forty- five patients with liver diseases were randomly selected. According to the disease type,patients were divided into PBC group( n = 162),autoimmune hepatitis( AIH) group( n = 42),and liver disease control( LDC) group( n = 41). ELISA assay was used to detect serum anti- mitochondrial antibody( AMA- M2) and antibodies against SP100 and GP210.Western blot assay was employed to detect serum anti- SLA antibodies. Indirect immunofluorescence assay was performed to detect serum AMA. Comparison of antibody positive rates between groups was carried out using the chi- square test and Fisher' s test. Results Serum AMA,AMA- M2,and anti- GP210 positive rates of the PBC group were 93. 21%,87. 65%,and 19. 75%,respectively,significantly higher than those of the AIH group,i. e.,19. 05%,7. 14%,and 9. 52%,respectively( χ2= 97. 311,P = 0. 001; χ2= 98. 264,P =0. 001; χ2= 10. 312,P = 0. 012). The AMA,AMA- M2,and anti- GP210 positive rates of the PBC group were also significantly higher than those of the LDC group,i. e.,9. 76%,2. 44%,and 7. 32%,respectively( χ2= 142. 745,P = 0. 003; χ2= 112. 574,P = 0. 002; χ2= 15. 217,P = 0. 042). Conclusion Serum AMA has a remarkable meaning to PBC diagnosis,anti- SP100 gives a hint of PBC progression,and anti- GP210 plays a role in the diagnosis of AMA- negative PBC.

Objective To evaluate the clinical efficacy of Biejiaruangan compound tablets in the treatment of primary biliary cirrhosis( PBC). Methods In a randomized,double- blind,placebo- controlled study,56 patients with PBC were collected and equally divided into treatment group and control group. The treatment group was given Biejiaruangan compound tablets( 4 pills per dose,3 doses per day,oral administration) combined with ursodeoxycholic acid( UDCA) tablets( 50 mg / pill,10- 15 mg per kg per day). The control group was given placebo( 4 pills per dose,3 doses per day,oral administration) combined with UDCA tablets( 50 mg / pill,10- 15 mg per kg per day). All patients were treated for 12 months. Clinical symptoms,PBC- 40 scales,liver function [alanine aminotransferase( ALT),aspartate aminotransferase( AST),alkaline phosphatase( ALP),γ- glutamyl transpeptidase( GGT),and total bilirubin( TBil) ],and liver stiffness values in the two groups were evaluated before and after treatment. Comparison of continuous data between the two groups was made by t test,and comparison of categorical data was made by chi- square test. Results The levels of ALT,AST,GGT,ALP,and TBil in the treatment group significantly decreased after 12 months of treatment( t = 3. 2019,P < 0. 01; t = 3. 0953,P < 0. 01; t = 3. 0279,P < 0. 01;t = 2. 4420,P < 0. 05; t = 2. 1621,P < 0. 05). In the control group,only the level of GGT significantly decreased after treatment( t =1. 9981,P < 0. 01). The levels of GGT and ALP were significantly lower in the treatment group than in the control group( t = 2. 0061,P <0. 05; t = 2. 3106,P < 0. 05). The liver stiffness value in the treatment group significantly decreased after treatment( 14. 37 ± 10. 58 vs10. 02 ± 5. 96 k Pa,t = 2. 1134,P < 0. 05). The PBC- 40 scales of skin itch,fatigue,and social dimension in the treatment group significantly decreased after treatment for 12 months( t = 2. 5158,P < 0. 05; t = 2. 1409,P < 0. 05; t = 3. 2441,P < 0. 05). There were significant differences in scales of fatigue and social dimension between the two groups after 12 months of treatment( t = 3. 1491,P < 0. 05; t =2. 6287,P < 0. 05). Conclusion Biejiaruangan compound tablets can significantly improve liver function,reduce the liver stiffness value,and improve PBC- 40 scales of skin itch and fatigue in patients with PBC. This therapy holds promise for widespread clinical application.

Objective To investigate the correlation between clinical data and pathological stage in patients with primary biliary cirrhosis( PBC) and to provide guidance for clinical diagnosis and treatment. Methods The clinical data of 54 PBC patients were collected for analyzing the correlation between the clinical data and pathological stage. The clinical data included biochemical parameters,immunological markers,and autoantibodies. Biopsy of the liver was used for the pathological staging of PBC. For the continuous data of normal distribution,analysis of variance was applied for comparisons between groups; for continuous data of skewed distribution,Wilcoxon rank sum test was used. For categorical data,chi- square test was used. Correlation analysis was performed by Pearson correlation and logistic regression. Results Among the 54 patients,the male- to- female ratio was 1∶ 5; the mean age was 48. 9 ± 9. 3 years; pathological stage Ⅰ was identified in 15 cases,stage Ⅱ in 18 cases,stage Ⅲ in 12 cases,and stage Ⅳ in 9 cases,and patients with stage Ⅳ disease were significantly older than the other patients( P < 0. 05). Total bilirubin( TBil),alkaline phosphatase,prothrombin time,Ig A,Ig G,and SP200 were positively correlated with pathological stage( r = 0. 592,0. 343,0. 281,0. 388,0. 274,and 0. 320,respectively,P < 0. 05),while a negative correlation was found between albumin and pathological stage( r =- 0. 569,P = 0. 000). Multivariate analysis revealed an independent correlation between TBil level and pathological stage( P = 0. 039). Patients with the same pathological stage might have different clinical stages,while those with the same clinical stage might have different pathological stages. Conclusions The same pathological stage may appear in different clinical stages. TBil level is an independent predictive factor for pathological stage in PBC patients.

Objective To investigate the incidence and risk factors for endoscopic retrograde cholangiopancreatography( ERCP)- related adverse events in patients with primary sclerosing cholangitis( PSC). Methods This study included 72 patients who were diagnosed with PSC by magnetic resonance cholangiopancreatography and underwent ERCP in the Third Hospital of Xingtai City from December 2009 to December 2013. The incidence of postoperative adverse events within 30 d after ERCP was monitored and recorded. Univariate and multivariate logistic regression analyses were used to analyze the risk factors for ERCP- related adverse events in PSC patients. Results The success rate of ERCP was 94. 4%( 68 /72). Among all adverse events,the incidence of pancreatitis and biliary tract infection were highest( 6. 94%and 4. 17%),while the incidence of perforation was lowest( 1. 38%). Univariate logistic regression analysis showed that the risk of adverse events was significantly higher in patients who underwent cholangiopancreatography and sphincterotomy than in those not undergoing these procedures( OR = 13. 642,P = 0. 017; OR = 7. 381,P = 0. 000); guide wire insertion and cholangiopancreatography also increased the incidence of adverse reactions( OR = 8. 042,P = 0. 000; OR = 2. 651,P = 0. 032). Multivariate logistic regression analysis showed that guide wire insertion( OR = 4. 547,95% CI: 1. 076- 12. 543) and biliary sphincterotomy( OR = 5. 023,95% CI: 2. 643- 18. 321) are associated with the incidence of ERCP- related adverse events. Conclusion Sphincterotomy and guide wire insertion can increase the risk of adverse events in PSC patients after ERCP.

Objective To investigate the clinical efficacy of pegylated interferon α- 2a( PEG- IFNα- 2a) in the treatment of children with HBe Ag- positive chronic hepatitis B( CHB). Methods A total of 31 children with CHB aged from 2- 16 years were randomly enrolled in this study and divided into two groups based on the age: younger group( age 2- 6 years,n = 17) and older group( age 7- 16 years,n = 14). All patients were administered PEG- IFNα- 2a at the initial dose of 104 μg / m2/ week,which gradually increased to 135μg /week. The course of treatment ranged from 24 to 72 weeks. The indices including alanine aminotransferase( ALT),hepatitis B virus( HBV) DNA,HBV serological markers,and HBs Ag quantitative level were assayed at baseline and then regularly throughout the course of treatment. Treatment responses including biochemical,virological. and serological responses at different time points were compared between the two age groups. The safety of treatment and the relationship of treatment efficacy with age,course of treatment,and dynamics of HBs Ag quantitative level during treatment were analyzed. Normally distributed continuous data were analyzed by t test. Comparison of categorical data was made by χ2test. Results There were no significant differences in biochemical and virological responses at different time points between the two groups( all P > 0. 05). The HBs Ag clearance rate at week 24 of treatment was significantly higher in the younger group than in the older group( 41. 2% vs 7. 1%,χ2= 4. 644,P < 0. 05). The HBs Ag quantitative level declined more significantly in the younger group than in the older group at weeks 52 and 72 of treatment( both P < 0. 05). At week 52 of treatment,the HBV DNA clearance rate,HBe Ag clearance and seroconversion rates,and HBs Ag clearance and seroconversion rates in both groups increased,but no significant differences were found( all P > 0. 05). In patients whose treatment was extended to 72 weeks,the HBV DNA clearance rate and seroconversion rates of HBe Ag and HBs Ag were 100%,80%,and 60%,respectively. None of the 25 patients who finished the course of treatment experienced recurrence.Common adverse effects of interferon treatment were flu- like symptoms,changes in blood manifestation,and anorexia. No significant differences in body height and body weight were observed between the patients and normal children of the same age before and after the treatment.Conclusion PEG- IFNα- 2a is an appropriate treatment regimen for children with CHB. The treatment efficacy is related to the age of patients and the course of treatment. More prominent decrease in the HBs Ag quantitative level and higher HBs Ag clearance rate can be achieved in children of younger ages. Clinical efficacy can be improved with longer treatment. The change in HBs Ag quantitative levels has a predictive value for treatment outcomes. PEG- IFNα- 2a treatment is safe in children with CHB.

Objective To screen hepatitis B virus( HBV)- infected patients with normal alanine aminotransferase( ALT) using Fibro Scan( FS). Methods Liver biopsy was done for all the 125 patients who were admitted to our hospitals from November 2012 to November 2013,and FS was performed for the liver stiffness measurement( LSM). Using the pathological inflammation grade from liver biopsy as a classification standard and G1 group as a control,a receiver operating characteristic( ROC) curve was plotted and the cut- off value was determined.Comparison of continuous data between multiple groups was made by Kruskal- Wallis H test,and comparison between two groups was made by Bonferroni test. Results The LSM of HBV- infected patients with the same stage of liver fibrosis was found to increase with the progression of liver inflammation; there were significant differences in LSM between groups with different grades of inflammation in each stage of liver fibrosis( S0- S2)( P < 0. 05),but no such differences were found between patients with inflammation grades G0 and G1( P > 0. 05).For≥G2 liver inflammation,the area under the ROC curve of FS was 0. 784,and the cut- off value determined by the ROC curve was 8. 64 k Pa,with 78. 6% sensitivity and 69. 2% specificity. Conclusion For HBV- infected patients with normal ALT,FS should be performed to decide whether further examination and treatment are needed. For patients with LSM≥8. 64 k Pa,liver biopsy should be performed; while for those with LSM < 8. 64 k Pa,regular examination is recommended.

Objective To study the efficacy of thymosin α1 in the treatment of chronic hepatitis B virus( HBV) infection with low viral load. Method Seventy- six patients with low- viral load chronic HBV infection admitted to our hospital from June 2011 to June 2013 were randomly assigned to treatment group,and forty- one patients were assigned to control group. The treatment group received subcutaneous injection of 1. 6 mg thymosin α1 twice a week,and the treatment stopped at 3 months if the patients were negative for serum HBV DNA; otherwise,the treatment was extended to 6 months. The control group did not receive any treatment. The serum HBV DNA clearance rates at months 3 and 6 of treatment were measured in both groups. Comparison of continuous data between two groups was made by t test,and comparison of categorical data was made by χ2test. Results The treatment group showed significantly higher HBV DNA clearance rates than the control group at months 3 and 6 of treatment( χ2= 10. 61,P < 0. 01; χ2= 13. 09,P < 0. 01). At month 6 in the treatment group,the HBV DNA clearance rate in patients who had HBV DNA < 104 copies / ml and were positive for HBe Ag showed no significant difference from that in those who were negative for HBe Ag( χ2= 0. 02,P > 0. 05),but was significantly higher than that in patients with HBV DNA ≥104copies / ml( χ2= 7. 52,P < 0. 01). Conclusion Thymosin α1 significantly promotes HBV DNA clearance in patients with low- viral load chronic HBV infection. The clearance rate is negatively correlated with the DNA load,but shows no correlation with the HBe Ag status.

Objective To measure the expression of T- cell immunoglobulin- and mucin domain- 3- containing molecule 3( TIM- 3)on CD8+T cells in peripheral blood mononuclear cells( PBMCs) among patients with chronic hepatitis B( CHB) and to investigate the effect of common gamma- chain cytokines on the expression of TIM- 3 on CD8+T cells in these patients. Methods Fifteen previously untreated patients with CHB who visited the Department of Infectious Diseases,Tangdu Hospital,Fourth Military Medical University,from January to May,2014,as well as 8 healthy controls,were included in the study. Blood was collected from these subjects,and PBMCs were isolated from blood by Ficoll density gradient centrifugation. PBMCs were separately stimulated with gamma- chain cytokines,interleukin( IL) 2,IL- 7,IL- 15,and IL- 21,and anti- CD3 / CD28,and the untreated cells were used as a negative control. After four days of culture,PBMCs were stained with monoclonal antibody. Flow cytometry was used to measure the expression of TIM- 3 on CD8+T cells. Comparison of continuous data was made by independent- samples t test. Results Compared with the untreated group,the anti- CD3 / CD28,IL- 2,IL- 15,and IL- 7 groups had significantly increased expression of TIM- 3 on CD8+T cells( 9. 629% ± 9. 916%,P = 0. 000 1; 3. 817%± 2. 694%,P = 0. 000 6; 5. 772% ± 4. 732%,P = 0. 005 4; 3. 560% ± 2. 045%,P = 0. 030 2),while the IL- 21 group had nonsignificantly increased expression of TIM- 3 on CD8+T cells( 2. 503% ± 2. 117%,P = 0. 934 1). Conclusion Anti- CD3 / CD28 and gamma- chain cytokines IL- 2,IL- 7,and IL- 15 can effectively upregulate the expression of TIM- 3 on CD8+T cells in patients with CHB. It indicates that the inhibition of them can not only reduce the expression of TIM- 3,but also may enhance the killing function of CD8+T cells in patients with CHB.

Objective To investigate the early diagnostic value of single or combined measurement of serum procalcitonin( PCT),peripheral white blood cells( WBC),and ratio of WBC to platelets( PLT)( WBC / PLT) for spontaneous bacterial peritonitis( SBP) in patients with liver cirrhosis. Methods The clinical data of 129 patients with liver cirrhosis who were admitted to our hospital from January 2011 to June2013 were retrospectively analyzed. One hundred and twelve patients who died of liver cirrhosis were divided into infection group,in which the cause of death was complicated infection( n = 94,including 61 SBP cases),and non- infection group( n = 18). Seventeen patients with compensated cirrhosis were assigned to control group. Before treatment with antibiotics,routine bacterial culture was made,and serum PCT,WBC,and WBC / PLT were measured. Mean comparison was made by t test and chi- square analysis. Ratio comparison was made by Pearson χ2test. The receiver operating characteristic( ROC) curve was plotted to calculate the sensitivity and specificity. Results There were 66 patients in the infection group whose bacterial culture was positive,and the positive rates for cultures from blood,ascites and other exudates were 25. 8%,30. 3%,and 43. 9%,respectively. In the infection group,lung infection,SBP,and unknown focus of infection accounted for 8. 5%,64. 9%,and 26. 6% of total cases,respectively. The level of serum PCT in the infection group was significantly higher than those in the non- infection group and the control group( F = 10. 98,P < 0. 05),but showed no significant difference in patients with different sites of infection. When PCT was ≥0. 5 ng / ml,the sensitivity and specificity for diagnosis of complicated infection were 92. 5%and 77. 1%,respectively,and the area under the ROC curve was 0. 89. When PCT was ≥2 ng / ml,the sensitivity was 62. 7% and the specificity was 94. 2%. When the peripheral WBC count was ≥10 × 109/ L and the WBC / PLT was ≥0. 25,the sensitivity was 47. 8% and39. 6%,respectively,and the specificity was 100%. When PCT was combined with WBC / PLT for diagnosis of complicated infection,the sensitivity was 76. 8% and the specificity was 94. 2%. For patients with SBP,the levels of PCT and WBC and WBC / PLT showed no significant differences between positive and negative ascites cultures. When PCT was combined with WBC / PLT for diagnosis of SBP,the sensitivity was 83. 6% and the specificity was 94. 2%. Conclusion PCT and WBC / PLT can be used as early diagnostic indicators for complicated infection in cirrhotic patients. PCT combined with WBC / PLT has a significant value for early diagnosis of SBP in cirrhotic patients.

Objective The administration of octreotide,as well as terlipressin,is a routine treatment for acute variceal bleeding in cirrhotic patients. This study aimed to evaluate the effects of octreotide,terlipressin,and their combination on hepatic venous pressure gradient( HVPG) in cirrhotic patients. Methods The study enrolled 49 cirrhotic patients with varicose veins who were hospitalized at the Department of Gastroenterology,Shandong Provincial Hospital Affiliated to Shandong University during January 2011 to April 2014. The patients were divided into three groups: group A( octreotide alone),group B( terlipressin alone),and group C( the combination). Group A: Octreotide was administered via intravenous injection of 1. 0 mg within 1 min followed by intravenous pumping at 25 μg / h,and HVPG was measured before drug administration and at 1,5,10,and 15 min after the start of octreotide injection. Group B: Terlipressin was administered by intravenous injection of 1 mg within 2 min,and HVPG was measured before drug administration and at 10,20,and 30 min after the start of terlipressin injection. Group C: First,octreotide was administered and HVPG was measured as performed for group A; then,terlipressin was given and HVPG was measured as performed for group B. Data were statistically analyzed using the t test,analysis of variance,and chi- square test. Results In group A,HVPG was significantly decreased at different time points after octreotide injection( t = 13. 173,P < 0. 001; t = 5. 364,P < 0. 001; t = 3. 894,P = 0. 001; t = 4. 160,P < 0. 001),but no significant differences were found between 5,10,and 15 min( all P > 0. 05). In group B,HVPG was significantly decreased at 20 min after terlipressin injection( t = 4. 062,P = 0. 002),with significant difference between 20 and 30 min( t = 4. 022,P = 0. 002). In group C,HVPG was further decreased at 20 min after terlipressin injection( t = 4. 926,P < 0. 001),with no significant difference between 20 and 30 min( t = 1. 733,P = 0. 101). A better effect was achieved in group C than in groups A and B( F = 10. 423,P < 0. 05). Conclusion Continuous octreotide injection rapidly reduces HVPG in cirrhotic patients with portal hypertension,but HVPG gradually increases to a stable level in a short period. Terlipressin injection also reduces HVPG but works more slowly than octreotide. Terlipressin injection after octreotide further reduces HVPG,indicating a better combined effect of the drugs than individual ones.

Objective To compare serum biochemical parameters,liver pathology,and fibronectin( FN) expression in Wister rats with hepatic fibrosis induced by bile duct ligation( BDL) and carbon tetrachloride( CCl4). Methods Ninety healthy male Wister rats were assigned to CCl4model( n = 44),CCl4control( n = 6),BDL model( n = 30),and BDL control groups( n = 10). Animal models of hepatic fibrosis were established by intraperitoneal injection of olive oil solution containing 50% CCl4 in the CCl4 model group and by BDL in the BDL group. General conditions of rats were examined. Expression of serum alanine aminotransferase( ALT),serum aspartate aminotransferase( AST),total bilirubin( TBil),and direct bilirubin( DBil) was measured by biochemical analysis. Expression of serum hyaluronic acid( HA) and laminin( LN) was measured by ELISA assay. Pathological changes in liver tissue were examined through hematoxylin- eosin and Masson staining. Expression of FN was assayed by immunohistochemistry. Comparison between groups was made by t test. Results Serum biochemical analysis showed that TBil and DBil levels in BDL model rats increased to and maintained at relatively high levels from day7 after surgery( P < 0. 05); these two parameters in CCl4 model rats increased gradually from week 2 and peaked at week 8 after injection( P < 0. 05). The indicators of hepatic fibrosis,i. e.,HA and LN levels,were significantly higher in the BDL model group than in the CCl4 model group. Pathologically,the CCl4 model group showed diffuse fatty degeneration of liver cells,with extremely significant fiber interval formation in the portal area- portal area or the portal area- central vein; the BDL model group showed coexistence of significant intrahepatic bile duct hyperplasia,inflammatory cell infiltration,and fiber interval formation. In the BDL model group,FN expression was dispersive and irregular with thin fibrous tissues; in the CCl4 model group,FN was mostly expressed in the interlobular septa,with thick fibrous tissues.Conclusion Both BDL and CCl4 can induce hepatic fibrosis in rats. The former induces early increases in the indicators of liver function and hepatic fibrosis and results in significant bile duct hyperplasia,whereas the latter mainly causes fatty degeneration. FN expression shows different distribution patterns in the two hepatic fibrosis models induced by BDL and CCl4.

Objective To assess the efficacy of intrahepatic arterial infusion of Endostar( rh- endostatin,YH- 16) combined with transcatheter arterial chemoembolization( TACE) for the treatment of advanced hepatocellular carcinoma( a HCC). Methods The study enrolled 76 a HCC patients who were admitted to and treated at the Petroleum Hospital Affiliated to Tianjin Medical University during September2009 to June 2011. Of these,44 patients were treated with TACE plus Endostar,and the other 32( the control group) with TACE alone.After treatment,all patients were subjected to non- scheduled re- examination by computed tomography( or magnetic resonance imaging),in order to check tumor recurrence( or metastasis) and angiogenesis. Count data were compared between groups using the χ2test. Survival curves were plotted using the Kaplan- Meier method,and postoperative survival differences were analyzed using the log- rank test. Results Compared with the control group,the experimental group treated with TACE plus Endostar had significantly increased response rate( 70. 45% vs. 43. 75%,χ2= 5. 47,P < 0. 05) and disease control rate( 84. 09% vs. 56. 25%,χ2= 7. 18,P < 0. 01). The median progression- free survival significantly differed between groups( 9. 00 vs. 5. 00 months,P = 0. 044),whereas the median overall survival showed no significant difference( 10. 64 vs. 8. 11 months,P = 0. 448). Conclusion TACE plus Endostar significantly improves the short- term outcome and progression- free survival but has little effect on the overall survival span in patients with a HCC.

Objective To investigate the relevant risk factors for early recurrence after microwave ablation for primary hepatocellular carcinoma( HCC),and to provide a reference for predicting and preventing tumor recurrence. Methods A retrospective analysis was conducted on the clinical data of 80 patients who had undergone microwave ablation for primary HCC at the Beijing You'an Hospital,Capital Medical University,Beijing,China( 2010- 2012). Factors possibly influencing early recurrence were selected for univariate analysis using logistic model. Risk factors for early recurrence of HCC after ablation were screened out for identifying the high- risk population and further guiding treatments against recurrence. Results There were 30 cases of recurrence in 6 months after ablation,accounting for a recurrence rate of37. 5%. Univariate analysis showed that no significant differences occurred between the recurrence and non- recurrence groups in age,gender,tumor location and size,family history of HCC,drinking history,HCC resection history,preoperative alpha- fetoprotein level,liver function Child- Pugh grade,MELD score,or HCC- related causes( P > 0. 05). In contrast,the number of tumors( ≥2) significantly differed between the two groups( P = 0. 008). Conclusion The number of tumors is an independent risk factor for early recurrence among patients after microwave ablation for HCC. High- risk population can be predicted according to the risk factors for early recurrence after microwave ablation for HCC. Targeted preventive measures should be taken for early detection and timely treatment of tumor recurrence.

Objective To explore the clinical value of three serum tumor markers,Golgi protein 73( GP73),alpha- fetoprotein( AFP),and AFP- L3,in the diagnosis of liver cancer and recurrence monitoring after radio frequency ablation. Methods A total of 174 patients who visited our hospital from July 2012 to October 2013 were included in the study,consisting of 86 patients with newly diagnosed liver cancer,39 with liver cirrhosis,29 with hepatitis,and 20 healthy controls. Among the patients with newly diagnosed liver cancer,37 were followed up for three months after the radiofrequency ablation. Serum levels of GP73,AFP,and AFP- L3 were measured by ELISA,electrochemiluminescence,and affinity adsorption chromatography,respectively. Nonparametric tests were performed on the results of serum samples from the four groups which showed skewed distribution and were represented by median( quartile interval) [M( P25- P75) ]. Overall comparison was made by Kruskal- Wallis H test,and comparison between groups was made by Mann- Whitney U test. Pair- matching rank- sum test was performed using Wilcoxon Signed Ranks,and categorical data were analyzed by χ2test. Results The levels of GP73,AFP,and AFP- L3 in the liver cancer group were significantly higher than those in other groups( all P < 0. 05). The positive rates of GP73 and AFP- L3 in the liver cancer group were significantly higher than those in other groups( all P < 0. 05),and the positive rates of the two markers were significantly higher than that of AFP among patients with liver cancer( P < 0. 05). Thirty- seven patients with newly diagnosed liver cancer were reexamined three months after radiofrequency ablation,and the preoperational AFP- L3 level in the patients who had recurrence was significantly higher than that in the patients without recurrence( P < 0. 05). Conclusion Serum GP73,AFP,and AFP- L3 show great values in the diagnosis of liver cancer. AFP- L3 can be used as an indicator for the identification of benign or malignant liver disease and risk of recurrence after radiofrequency ablation.

Objective To investigate the curative effect and prognostic impact of radical resection assisted by transcatheter arterial chemoembolization( TACE) in the treatment of intrahepatic cholangiocarcinoma( ICC). Methods The clinical data of 80 patients with ICC who were admitted to the Department of Hepatobiliary Surgery in our hospital from January 2008 to December 2010 were retrospectively analyzed.Thirty- five patients in the control group received radical resection,while forty- five patients in the observation group received adjuvant TACE therapy following radical resection. The curative effect and survival time were compared between the two groups. Comparison of continuous data between the two groups was made by t test,and comparison of categorical data was made by chi- square test. Results The observation group had significantly lower serum levels of alpha- fetoprotein,carcinoembryonic antigen,carbohydrate antigen 19- 9,and alanine aminotransferase than the observation group at 6 months after surgery( 47. 35 ± 13. 76 vs 83. 54 ± 24. 17 μg / L,t = 19. 58,P < 0. 05;309. 50 ± 125. 55 vs 375. 85 ± 136. 77 μg / L,t = 101. 33,P < 0. 05; 20. 86 ± 10. 38 vs 34. 18 ± 8. 55 ng / ml,t = 29. 46,P < 0. 05; 25. 44 ±8. 19 vs 58. 56 ± 22. 58 U / L,t = 32. 25,P < 0. 05). The 1- year,2- year,and 3- year survival rates in the observation group were significantly higher than those in the control group( χ2= 11. 43,P < 0. 05; χ2= 20. 15,P < 0. 05; χ2= 9. 87,P < 0. 05). The mean survival period was significantly longer in the observation group than in the control group( t = 15. 38,P < 0. 05). According to the analysis of factors influencing the survival period in patients with ICC,patients with a tumor size larger than 5. 0 cm,a low degree of differentiation,and metastasis had a significantly lower long- term survival rate and a significantly shorter mean survival period than other patients( P < 0. 05).Conclusion The adjuvant TACE therapy after radical resection is a safe and effective method in the treatment of ICC. The tumor size,degree of differentiation,portal vein tumor thrombus,and metastasis have a strong prognostic impact.

Objective To evaluate the relationship between estrogen receptor- α- 29( ERα- 29) gene polymorphisms and the development of HBV- related hepatocellular carcinoma( HCC) in Gansu Province,China,and to investigate the pathogenesis of HCC at the gene level. Methods Gene polymorphisms of ERα- 29 were analyzed in 106 HBV- related HCC patients and 98 healthy individuals as normal controls using the polymerase chain reaction- restriction fragment length polymorphism technique. Population allele frequencies were calculated using the gene counting method and then tested using the Hardy- Weinberg law of genetic equilibrium. Comparisons of genotype and allele frequencies between groups were performed using the χ2test. Results The frequencies of TT genotype and T allele of ERα- 29 gene in HBV- related HCC patients were significantly higher than those in the normal controls,i. e.,31. 1% and 53. 8% vs. 11. 2% and 32. 1%( χ2= 3. 449,P < 0. 05; χ2= 3. 840,P < 0. 05). In contrast,the frequencies of CC genotype and C allele of ERα- 29 gene in HBV- related HCC patients were significantly lower than those in the normal controls,i. e.,23. 6% and 46. 2% vs. 47. 0% and 67. 9%( χ2= 3. 488,P <0. 05; χ2= 3. 840,P < 0. 05). Compared with those carrying C allele,carriers of T allele had an increased risk( 2. 46- fold) of HBV- related HCC( OR = 2. 46,95% CI: 1. 64- 3. 69). Conclusion T allele of ERα- 29 gene can increase the risk of HBV- related HCC.

Objective To investigate the effect of NOTCH4 expression on vasculogenic mimicry( VM) formation in hepatocellular carcinoma( HCC). Methods Tumor tissues were collected from 85 patients diagnosed with HCC. The relationship between NOTCH4 expression and VM was examined using immunohistochemical staining and PAS / CD31 double staining. The influence of siRNA- mediated NOTCH4 silencing on VM network formation in HCC was observed in the 3D cell culture system in vitro. Experimental data were assessed with Mann-Whitney U test and one- way analysis of variance. Results NOTCH4 had significantly higher expression in VM- positive HCC tissues than in VM- negative HCC tissues( P = 0. 019). In siRNA- treated cells,NOTCH4 mRNA and protein expression was significantly down- regulated compared with those in mock- treated cells( P = 0. 007; P = 0. 003) and untreated cells( P = 0. 000; P = 0. 000). VM network formation was impaired by inhibition of NOTCH4 expression in the 3D cell culture system. Conclusion NOTCH4 plays an important role in VM formation in HCC and may provide a novel molecular target for anti- angiogenesis therapy for HCC.

Objective To preliminarily investigate the relationship of Peg10 with focal adhesion kinase( FAK)- mediated cell adhesion-mediated drug resistance( CAM- DR) in hepatocellular carcinoma( HCC),and to explore the underlying molecular mechanism. Methods The effects of 5- fluorouracil( 5- Fu) and adriamycin( ADR) on the proliferation of LO2 cells,ADR- resistant human HCC cells BEL- 7404 / ADR( 7404 / ADR),and Peg10- silenced cells siRNA- BEL- 7404 / ADR( siRNA- 7404 / ADR) were examined by MTT assay.To build a tumor- bearing nude mouse model,48 rats were randomly divided into six groups( n = 8 each) : groups A,C,and D were injected with 7404 / ADR cells; groups B,E,and F were injected with siRNA- 7404 / ADR cells. For experimental treatments,groups A and B revived saline by intravenous injection through the tail vein; groups C and E were given 5- Fu; groups D and F received ADR by intravenous injection through the tail vein; tumor mass volume was measured after injection. Peg10 mRNA expression was assayed by RT- PCR,and PEG10,p- FAK,p- JNK,p- ERK,and p- P38 protein expression was assayed by Western blotting. Results The 24- h IC50 values of ADR and 5- Fu on SiRNA- 7404 / ADR were both significantly reduced compared with those on 7404 / ADR( t = 7. 641 and 7. 560,respectively; both P < 0. 01). Significantly smaller tumor mass volume was observed in groups B,C,and D than in group A( P < 0. 05),and in groups E and F than in group B( P < 0. 01). Additionally,tumor mass volume was significantly different between groups E and C as well as between groups F and D( P < 0. 05). PEG10 mRNA was rarely expressed in groups B,E,and F. Compared with that in group A,PEG10 mRNA expression in groups C and D was relatively reduced. PEG10 protein was rarely expressed in group B and its expression level significantly differed from that in group A( P < 0. 01). Additionally,there were statistically significant differences in p- FAK,p- JNK,p-ERK,and p38 MAPK protein expression between groups B and A( P < 0. 05). In groups C and D,PEG10,p- FAK,p- JNK,p- ERK,and p38 MAPK protein expression was significantly reduced compared with that in group A( P < 0. 05). Significant differences in p- FAK,p- JNK,p- ERK,and p38 MAPK protein expression also occurred in groups E and F compared with group B( P < 0. 01). Moreover,there were significant differences in PEG10,p- FAK p- JNK,p- ERK,and p38 MAPK protein expression between groups C and E as well as between groups D and F( P < 0. 01). Conclusion The inactivation of PEG10 can increase the sensitivity of ARD- resistant cell line BEL- 7404 to 5- Fu and ARD. The underlying mechanism is possibly related to down- regulation of p- FAK,p- JNK,p- ERK,and p38 MAPK expression.

Objective To evaluate the value of thromboelastography( TEG) in guiding the proper use of blood components in patients after liver transplantation. Methods The blood samples from 35 patients after liver transplantation who visited our hospital from November 2013 to April 2014 were collected,in which TEG and conventional coagulation test were performed. The TEG parameters,such as reaction time of coagulation( R),clot formation time( K),Angle,and the maximum amplitude( MA),and coagulation parameters were subjected to bivariate linear regression analysis. The use of blood components and amount of blood transfusion following TEG's instruction were compared with the clinical application. Comparison of continuous data was made by paired t test. Results Activated partial thromboplastin time and prothrombin time were positively correlated with R( r = 0. 69 and 0. 41,P = 0. 001 and 0. 030,respectively). Fibrinogen was negatively correlated with K( r =- 0. 03,P = 0. 008). Platelet was positively correlated with Angle and MA( r = 0. 46 and 0. 68,P = 0. 029 and 0. 000,respectively). Fibrinogen was positively correlated with MA( r = 0. 33,P = 0. 040). There was a significant difference in R value of TEG before and after the heparanase neutralization( P = 0. 027). Conclusion TEG has a clinical value in guiding the proper use of blood components in patients after liver transplantation.

Objective To assess the relationship between alcoholic fatty liver disease( AFLD) and carotid intima- media thickness( CIMT) and the influencing factors for CIMT. Methods A cross- sectional study was conducted in 147 males who were inpatients or had physical examination at the Taishan Hospital in Shandong Province during January 2012 to December 2013. The participants,including 136 drinking cases and 11 non- drinking cases,were divided into mild AFLD group( A,45 cases),moderate to severe AFLD group( B,58 cases),and non- AFLD group( C,44 cases). Comparison of mean values between groups was performed using one- way ANOVA,and pairwise comparisons were performed using the LSD test( for homogeneity of variance) or Tamhane's test( for heterogeneity of variance). Results( 1) CIMT was significantly higher in group B than in group C( P = 0. 001).( 2) BMI was significantly higher in group A than in group C( P = 0. 029). Total cholesterol,triglyceride,very- low- density lipoprotein,apolipoprotein B,and uric acid levels significantly rose in groups A and B compared with group C( P < 0. 05).( 3) Gamma- glutamyl transpeptidase( GGT) level was significantly higher in group A than in group C( P = 0. 001),whereas alanine transaminase,aspartate aminotransferase,and GGT levels were significantly higher in group B than in group C( P = 0. 023,0. 003,and 0. 000,respectively).( 4) Serum creatinine level was significantly lower in groups A and B than in group C( P = 0. 007 and 0. 005,respectively). Conclusion AFLD can cause the increase in CIMT,resulting in metabolic syndrome- like changes and liver / kidney dysfunction. With increasing severity of AFLD,CIMT increase becomes more significant. Thus,AFLD can be used as an indicator for predicting CIMT increase in human population.

Objective To investigate the effects of niacin on the lipid metabolism in rat model of non- alcoholic fatty liver disease( NAFLD). Methods Forty Sprague- Dawley rats were randomly divided into control group,model group,intervention group 1( 0. 5%niacin),and intervention group 2( 1% niacin). Rats were fed with high- fat diet for 8 weeks to induce an NAFLD model. The serum levels of alanine aminotransferase( ALT) and aspartate aminotransferase,levels of total cholesterol( TC),triglyceride,and free fatty acid in serum and liver tissue,and level of malondialdehyde( MDA) in liver tissue were measured using assay kits. The morphological and histopathological changes in the liver were observed under a microscope. Comparison of data between groups was made by univariate analysis of variance using SPSS software; moreover,least significant difference test( equal variance assumed) and Tamhane's T2 test( equal variance not assumed) were used for pairwise comparison. Results Compared with the model group,every intervention group had significantly lower levels of ALT,TC,AST,TG,and FFA( all P < 0. 05) in serum and level of MDA in liver tissue( P < 0. 05),and had significantly increased expression of PPARα mRNA( P < 0. 05),DGAT2 mRNA( P < 0. 05),and SREBP1 c mRNA( P < 0. 05). Intervention group 2had significantly reduced expression of DGAT2 mRNA and SREBP1 c mRNA compared with intervention group 1( P < 0. 05). Compared with the model group,the intervention groups had relieved fatty degeneration of hepatocytes and alleviated inflammatory cell infiltration in the centrilobular portion of the liver. Conclusion Niacin regulates lipid metabolism in NAFLD animal models,reduces lipid oxidative stress,and significantly reduces liver steatosis and fibrosis by regulating the expression of PPARα mRNA,DGAT2 mRNA,and SREBP1 c mRNA,so as to realize the protective effect against NAFLD.

Liver steatosis is a frequent histological feature in patients with chronic hepatitis C( CHC),and it is associated with the progression of CHC and antiviral efficacy. This paper reviews recent research advances in the viral and host factors involved in the pathogenesis of steatosis among CHC patients and the prognostic impact of steatosis. The pathogenesis of liver steatosis in CHC patients needs further studies.

Since the liver is the major iron storage organ in human body,iron metabolism disorder is closely related to chronic hepatitis. So far,the mechanisms underlying iron overload in chronic hepatitis C( CHC) have not been fully elucidated. Highly complex regulation of hepcidin relies on a number of variables,including hepatic inflammatory conditions of different stages,transferrin- bound iron circulation,and intracellular iron storage. All these factors are associated with variations in hepatic iron concentrations among patients with hepatitis C virus( HCV)- related chronic liver disease. This paper discusses the regulation of systemic iron homeostasis,the relationship between CHC and iron metabolism disorder,and the mechanism of inducing iron overload. In- depth understanding about iron homeostasis and the relationship between relevant signaling pathways will contribute to the control and therapy of HCV- related diseases.

Early diagnosis of liver fibrosis and dynamic monitoring of relevant changes have great implications for the treatment and prognosis improvement of chronic liver diseases. So far,liver biopsy remains the“golden standard”for the diagnosis and staging of liver fibrosis. However,due to its inherent limitations,a great effort has been made to develop more accurate non- invasive diagnostic methods,including serum fibrosis markers and mathematical models,ultrasound,contrast- enhanced ultrasonography,ultrasonic elastography,computed tomography,magnetic resonance imaging,and nuclear medicine. The advantages and disadvantages of relevant methods are discussed. Furthermore,proper selection of the non- invasive diagnostic methods for clinical application and the means for mutual verification are analyzed. As for the future direction,it is expected to employ the above methods for combined analysis and comprehensive assessment,in order to enhance the clinical value of non- invasive liver fibrosis diagnosis.

Hedgehog( Hh) signaling pathway is present in many animals and plays an important role in regulating embryonic development and differentiation. Aberrant activation of Hh signaling contributes to the pathogenesis of many malignancies. Recent studies have shown that dysregulated Hh signaling pathway participates in the tumorigenesis,tumor invasion,and metastasis of hepatocellular carcinoma( HCC). Investigation of the relationship between Hh signaling pathway and HCC will help elucidate the molecular mechanism of pathogenesis of HCC and provide a new insight into the development of novel anticancer therapy and therapeutic target.

Adult hepatoblastoma is extremely rare in clinical practice,and its pathogenesis is unknown. At present,there is a lack of understanding of this disease,and therefore clinical misdiagnosis is common. This review introduces the pathogenesis,clinical manifestations,and radiological and pathological characteristics of hepatoblastoma,focuses on the choice of treatment for adult hepatoblastoma,and explains briefly the latest research progress in biological therapy. Comparison of different treatments suggests that comprehensive treatment based on radical resection is still the best choice. However,the curative effect is poor since the disease is highly malignant and its treatment experience is insufficient. The newly reported target for biological therapy may represent a breakthrough for the treatment of the disease,but its clinical efficacy remains to be evaluated. The pathogenesis of the disease in adults and children has not been confirmed as the same,and the review indicates that further clinical research is still needed.

Budd- Chiari syndrome( BCS) is characterized by the hepatic outflow obstruction from the small hepatic vein to the superior hepatic inferior vena cava. Portal vein thrombosis( PVT) refers to the development of thrombosis in the main portal vein,with or without thrombosis in the superior mesenteric or splenic vein. A large number of studies have shown that prothrombin( factor II,F2) G20210 A mutation is related to BCS and PVT. F2 and its G20210 A mutation are introduced,the effect of F2 G20210 A mutation on thrombosis is reviewed,and the prevalence of F2 G20210 A mutation in China is analyzed. An attempt is made to focus on the association of F2 G20210 A mutation with PVT and BCS. It is believed that F2 G20210 A mutation to some extent increases the risk for PVT and BCS. However,the prevalence of F2 G20210 A mutation is extremely low in the Chinese population. Thus,this mutation may not be regarded as the cause of PVT and BCS in China.

Silymarin is a traditional hepatoprotective herb for the adjuvant therapy of liver diseases,which shows marked pharmacological activities such as antioxidant and anti- inflammatory properties. This paper introduces the action mechanism of silymarin in regulating liver function,ameliorating hepatic fibrosis,protecting pancreatic cells,suppressing the growth of tumor cells,and inhibiting the replication of hepatitis C virus. Silymarin is considered to be a natural medicine with little toxic or side effect at a high dose. It holds promise for anti-tumor,antioxidant,anti- inflammatory,and antiviral application.