Hepatitis C Virus( HCV) Infection affects approximately 170 million people globally,that causes chronic hepatitis C and has been associated with cirrhosis and hepatocellular carcinoma. In the past few years,significant advances have been made in development and clinical application of direct anti-viral agents( DAA) that have been demonstrated highly safe and effective with very high sustained virological response( SVR) rates. This article provides systemic review in this field,especially USA FDA approved DAA regimens for HCV treatment.

The research on prophylaxis and treatment of hepatitis C has been performed for more than 30 years,with outstanding achievements. The discovery and confirmation of hepatitis C virus( HCV) was a milestone for how humans discovered new life. Emphasis on HCV molecular biology,infection immunity,and pathogenesis is the basic rule for scientific research on infectious diseases. PEG-IFN combined with ribavirin as the standardized antiviral treatment has been a great success; this combination therapy achieves a sustained viral response more than 80% in Chinese people,which is a typical example for successful clinical application of cytokines. Direct-acting antiviral agent( DAA) or combined application has made it possible to cure all patients infected with hepatitis C,which is the most successful example for reference. Persistent viral infection and maintenance of immune homeostasis under certain conditions are the results of the interaction between the host and the virus,and the development of vaccines will be continued.

In recent years,direct-acting antiviral agent( DAA) that target specific enzymes in the life cycle of hepatitis C virus( HCV)have been developed rapidly. However,there are specific resistance-related mutation sites for DAA,which is associated with the gene types / subtypes of HCV. This article describes the resistance-related mutation sites for DAA and their impacts on the treatment regimen according to the mechanism of action of DAA. It is pointed out that some natural mutation sites lead to drug resistance in the treatment for patients with some HCV subtypes,so careful evaluation is needed before treatment to determine the appropriate regimen. For patients experiencing failure in the previous interferon therapy,the pre-existing drug resistance should be studied if DAA in combination with the therapy or interferon-free DAA therapies are to be used.

Patients with hepatitis C virus( HCV)-related cirrhosis are at a higher risk for the development of hepatic failure and hepatocellular carcinoma( HCC) compared with non-cirrhotic patients. Antiviral therapies for HCV-related cirrhosis may reduce the incidence of HCC and hepatic failure. This article introduces current antiviral therapies for HCV-related cirrhosis: P / R,DAA + P / R,and IFN-free regimens,and summarizes the present situation of antiviral therapies for HCV-related cirrhosis. It is thought that the advent of direct-acting antivirals has improved the rate of sustained virologic response and reduced the incidence of adverse events during the treatment of HCV-related cirrhosis. Interferon-free regimens have great advantage and potential in antiviral therapies for HCV-related cirrhosis.

Hepatitis C virus( HCV) is one of the major causes of acute and chronic hepatitis,liver cirrhosis,and hepatocellular carcinoma.Laboratory diagnosis is essential for the diagnosis of HCV infection. Laboratory etiological diagnosis of chronic HCV infection includes HCV antigen and antibody detection and quantitative detection of HCV RNA. Quantitative detection of serum HCV RNA is the only laboratory diagnosis index for current HCV infection and plays a very important role in determination of treatment time,selection of treatment regimens,and evaluation of therapeutic effect of antiviral treatment. This paper elaborates on the target population,detection methods,and clinical significance in laboratory screening for chronic HCV infection,so as to provide timely diagnosis and effective treatment of chronic HCV infection.

Hepatitis C virus( HCV) infection represents an important public health problem worldwide. Eradicating HCV can finally delay or prevent the progression of HCV infection to end-stage liver diseases such as liver cirrhosis and liver cancer. Chemokine( C-X-C motif) ligand 10( CXCL10) is a chemokine belonging to the CXC chemokine family,and it exerts its function through binding to chemokine( C-X-C motif) receptor 3( CXCR3),playing a critical role in eradication of HCV. This article reviews the relationship of CXCL10 with the pathogenesis of HCV and the effectiveness of antiviral treatment,as well as the CXCL10 measurements. Meanwhile,this article introduces the clinical value of CXCL10 in assessing the risk of liver fibrosis and liver cancer. Further studies are needed to investigate the association between CXCL10 and liver diseases,and CXCL10 may provide a new therapeutic strategy for HCV infection.

To date,the infectious cell culture systems of hepatitis C virus( HCV) representative of genotypes 1-3 have been developed with the aid of adaptive mutations identified from JFH1-based chimera viruses or replicons. Nevertheless,JFH1 is still the unique clone capable of spontaneous replication in liver cell lines. It is an urgent need to develop a universal infectious cell culture system for any HCV clinical isolate. This article reviews the progress in HCV cell culture systems,existing infectious HCV clones,and permissive cell lines supporting HCV replication,as well as the application of HCV replication and infection model in drug development.

Objective To investigate the influencing factors for achieving sustained virological response( SVR) to pegylated interferon alpha-2a combined with ribavirin in Uygur and Han patients with chronic hepatitis C,and to provide a reference for predicting the treatment of chronic hepatitis C in Uygur and Han patients. Methods A retrospective analysis was performed on the clinical data of 160 patients( 80 cases of Uygur nationality and 80 cases of Han nationality) with chronic hepatitis C who received pegylated interferon alpha-2a combined with ribavirin in the Infectious Disease Hospital in Hetian from January 2012 to March 2014. All patients were followed up for 24 weeks after48 weeks of treatment. The two groups were compared in terms of the ratios of rapid virological response( RVR),early virological response( EVR),end treated virus response( ETVR),SVR,and no response( NR). The factors which might influence achieving SVR to interferon therapy in the two groups were subjected to univariate analysis and multivariate analysis( conditional logistic regression). For normally distributed continuous data,the comparison was made by t test,and Wilcoxon rank-sum test was made for abnormally distributed continuous data. The comparison of categorical data was made by chi-square test. And univariate analysis and multivariate analysis( conditional logistic regression) were carried out. Results There were no significant differences in the rates of RVR( 48. 8% vs 60. 0%,P > 0. 05),EVR( 53. 8% vs 63. 8%,P > 0. 05),ETVR( 72. 5% vs 78. 7%,P > 0. 05),SVR( 63. 8% vs 72. 5%,P > 0. 05),and NR( 27. 5% vs21. 3%,P > 0. 05) between Uygur group and Han group. The univariate analysis showed that age and age > 40 years were the influencing factors for all patients' SVR( P < 0. 05). Age > 40 years and HCV RNA level > 1 × 106 copies / ml were the influencing factors for Uygur patients' SVR( P < 0. 05). Male sex,age,and age > 50 years were the influencing factors for Han patients' SVR( P < 0. 05). Multivariate analysis showed that age > 40 years and HCV RNA level > 1 × 106 copies / ml were the influencing factors for Uygur patients. And age > 50 years and male sex were the influencing factors for Han patients. Conclusion There is no significant difference in clinical efficacy of pegylated interferon alpha-2a combined with ribavirin in the treatment of chronic hepatitis C between Uygur patients and Han patients. Age > 40 years and HCV RNA level > 1 × 106 copies / ml go against achieving SVR for Uygur patients. Age > 50 years and male sex go against achieving SVR for Han patients.

Objective To investigate the influence of concurrent human immunodeficiency virus( HIV) infection on antiviral therapy for hepatitis C virus( HCV) in patients with chronic hepatitis C. Methods Twenty-eight patients with hepatitis C and concurrent HIV infection( HCV / HIV group) and 28 patients with pure HCV infection( HCV group) treated in Ruzhou People's Hospital and the Sixth People's Hospital of Zhengzhou from 2013 to 2014 were selected and treated with common interferon combined with ribavirin as anti-HCV therapy.HCV RNA viral load and blood routine were measured at weeks 0,12,24,and 48 of therapy and 24 weeks after therapy,and other adverse effects were recorded in detail. The t-test was applied for comparison of continuous data between groups,and chi-square test was applied for comparison of categorical data between groups. Results HCV RNA viral load was gradually reduced after antiviral treatment in both groups,and the two groups showed significant differences in sustained virologic response and end-of-treatment virologic response( χ2=6. 744 vs 5. 622,P = 0. 013 vs 0. 024). As for adverse effects,the two groups showed decreases in leukocyte count,with significant differences between the two groups at weeks 12,24,and 48 of therapy( t = 3. 422,4. 443,and 2. 949,all P < 0. 01). The two groups showed no significant differences in platelet count,gastrointestinal symptoms,and flu-like symptoms( all P > 0. 05). Conclusion Concurrent HIV infection has varying degrees of influence on anti-HCV virologic response and adverse effects in patients with chronic hepatitis C.

Objective To investigate the status of hepatitis C virus( HCV) infection among injecting drug users( IDUs) in Chenzhou,China. Methods Serum samples from 181 IDUs who were treated in methadone clinics in Chenzhou from August to September,2014 were collected. RT-PCR and ELISA were applied to detect HCV RNA and antibody,and sequencing was applied to determine the HCV genotype.Mann-Whitney U test was applied for comparison between groups. Results Among these 181 IDUs,160 were infected with HCV,with a positive rate of 88. 4%( 160 /181); 134 patients had positive antibody and RNA results( Ig G+RNA+: 74%),19 patients had positive antibody and negative RNA results( Ig G+RNA-: 10. 5%),and 7 patients had negative antibody and positive RNA results( Ig G-RNA+:3. 9%); 19 patients had co-infection with HCV and hepatitis B virus( HBV). The patients infected with HCV in Ig G+RNA+group had significantly higher levels of alanine aminotransferase( ALT) and aspartate aminotransferase( AST) levels than those in Ig G-RNA+and Ig G+RNA-groups( all P < 0. 01); ALT and AST levels did not differ significantly between patients with single infection with HCV or HBV and those with co-infection with HBV and HCV( all P > 0. 05). Among the 133 HCV RNA-positive samples,there were 81 samples of genotype 6a( 60. 9%) and 36 samples of genotype 3( 27. 1%). Conclusion IDUs have a high HCV infection rate,with main genotypes of 6a and 3,and co-infection with HCV and HBV does not aggravate liver injury.

Objective To analyze the distribution characteristics of hepatitis C virus( HCV) genotypes in Xingtai,China,and their relationship with disease progression and sustained virologic response( SVR),and to provide a basis for the prognostic judgment. Methods A retrospective analysis was performed among 231 patients with hepatitis C who lived in Xingtai and were newly diagnosed and treated in our hospital from December 2010 to December 2014. In those patients,general information was collected,and alanine aminotransferase,aspartate aminotransferase,white blood cell,genotype,and viral load were determined. Continuous data were analyzed using analysis of variance,and categorical data were analyzed using χ2test. Results In all patients,patients with 1b subtype accounted for the highest proportion( n =109,47. 2%),followed by patients with 2a subtype( n = 89,38. 5%). There was significant difference in gender distribution between patients with different genotypes( χ2= 13. 461,P = 0. 009). There was significant difference in HCV RNA load between patients with different genotypes( F = 13. 461,P = 0. 034). Particularly,patients with type 1 HCV had a significantly higher viral load than patients with type2 or 3 HCV. There was also significant difference in severity of liver disease between patients with different genotypes( P < 0. 001). Particularly,the incidence rate of cirrhosis or liver cancer in patients with type 1b HCV was higher than that in patients with other genotypes. The incidence of SVR was significantly higher in patients with type 2 HCV than type 1 HCV( 93. 1% vs 69. 4 %,χ2= 19. 850,P < 0. 001).In all patients,112( 48. 5%) had a rapid virologic response( RVR),and there was significant difference in the incidence of SVR between patients with and without a RVR( 96. 4% vs 64. 7%,χ2= 36. 407,P < 0. 001). In all patients,169 had a complete early virologic response( c EVR),and there was significant difference in the incidence of SVR between patients with and without a c EVR( 88. 8%vs 56. 5%,χ2= 29. 684,P < 0. 001). Conclusion In patients with HCV in Xingtai,1b subtype accounts for the highest proportion,followed by 2a subtype. There are significant differences in sex,RNA viral load,SVR,and severity of liver disease between patients with different genotypes. An analysis of genotype before treatment is important for the treatment,disease progression,and prognosis of patients with HCV. RVR and cEVR well predict the incidence of SVR: patients with these virologic responses are likely to achieve a SVR.

Objective To investigate the association between different hepatitis C virus( HCV) genotypes and serum interleukin-17( IL-17),interleukin-6( IL-6),and vitamin D in patients with HCV-related cirrhosis. Methods Seventy-six patients with HCV-related cirrhosis,who were admitted to 302 Hospital of PLA from January to December,2012,were enrolled in the study,and they were divided into type 1b group( n = 47) and type 2a group( n = 29) according to the genotypes. The levels of serum IL-17,IL-6,and vitamin D were determined by enzyme-linked immunosorbent assay. Comparison between the two groups was made by t test,and Spearman correlation analysis was used to investigate the association between serum IL-17,IL-6,and vitamin D and genotypes. Results The findings in improved Child-Pugh classification showed that there were significant differences in the percentage of grade A patients between type 1b group and type 2a group( χ2= 4. 97,P < 0. 05); when compared with type 2a group,type 1b group showed significantly higher lentiviral titers of alpha-fetoprotein( AFP) and HCV RNA and levels of IL-17,IL-6,and tumor necrosis factor-α( TNFα)( t = 21. 56,16. 51,12. 31,10. 71,and 7. 23,respectively,all P < 0. 05),but significantly lower levels of interferon-γ( IFNγ),25( OH) D,and 1,25( OH)2D( t =3. 98,6. 32,and 4. 88,respectively; all P < 0. 05); Spearman correlation analysis showed that the lentiviral titers of AFP and HCV RNA and the levels of IL-17 and IL-6 were positively correlated with genotype 1b and genotype 2a( all P < 0. 05),while the levels of IFNγ,TNFα,and 25-OH-D were negatively correlated with genotype 1b and genotype 2a( all P < 0. 05). Conclusion Compared with those with genotype 2a,HCV-related cirrhosis patients with genotype 1b have higher serum levels of IL-17,IL-6,AFP,and HCV RNA,but a lower level of vitamin D; the results suggested that there are correlations between serum IL-17,IL-6,25-OH-D,AFP,and HCV RNA and genotype,but no significant correlation between 1,25( OH)2D and genotype.

Objective To investigate the serum interleukin-33( IL-33) level in patients with chronic hepatitis B,and to explore the correlation of serum IL-33 with hepatitis B virus( HBV) DNA load and alanine aminotransferase( ALT) level. Methods A total of 119 patients with chronic hepatitis B and 131 healthy controls were enrolled in this study. Serum levels of IL-33 were determined by enzyme-linked immunosorbent assay. For patients with chronic hepatitis B,HBV DNA loads were quantified by real-time quantitative PCR,while ALT levels were measured by continuous monitoring assays. The t test was applied in the comparison of continuous data. The Pearson correlation analysis was used to investigate the correlation of serum IL-33 level with HBV DNA load and ALT level. Results Serum levels of IL-33 were significantly higher in patients with chronic hepatitis B( 62. 7 ± 29. 3 ng / ml) than in healthy controls( 16. 4 ± 4. 5 ng / ml)( t =17. 02,P < 0. 01). Serum IL-33 level was negatively correlated with log10[HBV DNA]( r =-0. 703,P < 0. 01) but positively correlated with ALT( r = 0. 324,P < 0. 01) in patients with chronic hepatitis B. Conclusion This study suggests that IL-33,an immune stimulator,may play a role in inhibiting HBV replication in patients with chronic hepatitis B.

Objective To investigate the variation and clinical significance of T cell subsets( CD3+,CD4+,CD8+,and CD4+/ CD8+)and levels of cytokines,interleukin( IL)-15 and IL-16,in peripheral blood of patients with chronic hepatitis B virus( HBV) infection.Methods A total of 63 patients with chronic hepatitis B( CHB),112 asymptomatic carriers( ASC) of HBV,and 84 healthy controls who were treated in our hospital from July to December,2014,were assigned to CHB group,ASC group,and control group,respectively. In the three groups,the serum T cell subset populations were determined using flow cytometry; the expression of cytokines,IL-15 and IL-16,was measured by enzyme-linked immunosorbent assay; the HBV DNA load was measured by polymerase chain reaction. Comparison of data between multiple groups was made by analysis of variance. The data in each group were subjected to Pearson correlation analysis. Results Compared with the control group,the CHB and ASC groups had significantly lower CD3+,CD4+,and CD4+/ CD8+T cell proportions but a significantly higher CD8+T cell proportion( all P < 0. 05). The CHB and ASC groups also had significantly higher expression of IL-15 and IL-16 than the control group( all P < 0. 05). In the CHB group,patients with a high HBV DNA load had significantly lower CD3+,CD4+,and CD4+/ CD8+T cell proportions but a significantly higher CD8+T cell proportion than those with a low HBV DNA load( all P <0. 05). In the ASC group,patients with a high HBV DNA load had significantly lower CD4+and CD4+/ CD8+T cell proportions but a significantly higher CD8+T cell proportion than those with a low HBV DNA load( all P < 0. 05). In the peripheral blood of patients in the CHB group,the expression of CD4+was positively correlated with the expression of IL-15( r = 0. 516,P < 0. 05),while the expression of CD8+was positively correlated with the expression of IL-16( r = 0. 665,P < 0. 05). In the peripheral blood of patients in the ASC group,the expression of CD3+was positively correlated with the expression of IL-15( r = 0. 618,P < 0. 05). Conclusion Patients with HBV infection have abnormal proportions of T cell subsets. Cytokines,IL-15 and IL-16,may induce different degrees of cellular immune dysfunction and dysregulation.

Objective To establish a method for in vitro culture of plasmacytoid dendritic cell( pDC). Methods Umbilical cord blood( 40 ml) was collected from healthy parturients in the First Affiliated Hospital of Hunan University of Chinese Medicine,and cord blood mononuclear cell( CBMC) were isolated. The CBMC were cultured for 7 days with RPMI 1640 complete medium containing rh Flt3-ligand( Flt3-L)( 100 ng/ml) and rh interleukin( IL)-3( 10 ng/ml),and the medium was half changed every 2 days. On the eighth day,CpG ODN( 2 μg / ml) was added to the cells,and the attached cells and supernatant were collected 24 h later for flow cytometry and interferon( IFN) α measurement,respectively. On days 1,3,5,7,and 8 of cell culture,the morphological changes of pDC were observed. Results After 2 h of culture,the CBMC showed circular,flat morphology. Twenty-four hours later,the cells began to adhere to the wall,with extended cytoplasm and increased volumes,and they became round and translucent,with scattered small colonies. On days 3-4 of culture,the cell volume continued increasing; most cells were round,and some had small protrusions; few cells were spindle-,tadpole-,star-or irregularly shaped; the number and volumes of colonies increased substantially. On days 5-8 of culture,the number of colonies and the number of cells in colonies gradually decreased,and suspended cells that were round or had small protrusions gradually increased in the medium. The cells expressing CD123,BDCA-2,and BDCA-4,which were considered pDC,were detected by flow cytometry. Flow cytometry revealed that the proportion of pDC in CBMC increased during the culture: increasing from 1. 08% at the beginning of culture to 5. 32%on day 4,and finally reaching a peak of 19. 8% on day 8. On day 8,the level of IFNα in pDC culture supernatant was( 11 302. 61 ± 1745.31) pg / ml. Conclusion pDC can be successfully induced in vitro by rh Flt3-L combined with IL-3 from human umbilical CBMC.

Objective To investigate the application of percutaneous transhepatic variceal embolization( PTVE) in the treatment of rupture and rebleeding in esophageal and gastric varices after devascularization for liver cirrhosis,and to evaluate its therapeutic effect and advantages. Methods The clinical data of 34 patients with rupture and rebleeding in esophageal and gastric varices after devascularization for liver cirrhosis treated in Department of Gastroenterology,Xiangshui People's Hospital from January 2007 to June 2013 were collected,and all patients received PTVE. Regular gastroscopic reexaminations were performed after the surgery,and postoperative outcome,complications,and the condition of rebleeding were observed. Results Acute-stage hemostasis for 34 patients receiving PTVE was good,with a response rate of 97%( 33 /34); at 2 weeks after surgery,varices disappeared or were significantly relieved in 29 patients( 85. 3%),and after the 2-year follow-up,30 patients( 88. 2%) achieved improvement in or disappearance of esophageal and gastric varices; during the 2-year follow-up,6 patients( 17. 6%) experienced upper gastrointestinal bleeding. No severe complications were observed. Conclusion PTVE has a significant therapeutic effect in the treatment of variceal rebleeding after devascularization for liver cirrhosis,with minimal trauma and few complications,and can prevent the formation of new collateral vessels. Therefore,it is an effective method to treat rupture and rebleeding in esophageal and gastric varices after devascularization for liver cirrhosis.

Objective To investigate the incidence rate and risk factors for the complications after laparoscopic splenectomy in patients with portal hypertension. Methods The clinical data of 83 patients with portal hypertension,who were admitted to our hospital and underwent laparoscopic splenectomy from June 2009 to December 2014,were analyzed retrospectively. The incidence rate of the complications was analyzed using the Clavien-Dindo classification system and the risk factors for the complications were analyzed using chi-square test and logistic regression method. Results The incidence rate of postoperative complications was 24. 10%( 20 /83). According to the Clavien-Dindo classification system,the numbers of patients with grade Ⅰ,Ⅱ,Ⅲ,Ⅳ,and Ⅴ complications were 5,3,10,2,and 0,respectively. The patients undergoing total laparoscopic splenectomy had a significantly higher incidence rate of postoperative complications than those undergoing hand-assisted laparoscopic splenectomy( 32. 59% vs 15. 00%,χ2= 3. 966,P = 0. 046). According to the univariate analysis,the Child-Pugh class,application of the hand-assisted device,gastroesophageal vein ligation,and American Society of Anesthesiologists( ASA) grade were all risks factors for the postoperative complications( all P < 0. 05). Further analysis using multiple logistic regression illustrated that Child-Pugh class B and ASA grade Ⅲ were independent risk factors for the postoperative complications( OR = 0. 328,95% CI: 0. 129 ~ 0. 834,P < 0. 05; OR = 0. 294,95% CI: 0. 150 ~ 0. 573,P < 0. 05). Conclusion Patients with portal hypertension undergoing laparoscopic splenectomy have a high incidence of postoperative complications and the occurrence of the complications is closely associated with the Child-Pugh class and the ASA grade.

Objective To explore the significance of plasma neutrophil gelatinase-associated lipocalin( pNGAL) and urine neutrophil gelatinase-associated lipocalin( u NGAL) in the diagnosis of acute kidney injury( AKI) in patients with cirrhosis. Methods A total of 78 patients with cirrhosis admitted to our hospital from January 2012 to December 2014 were selected and divided into groupA of 38 patients with cirrhosis and AKI and groupB of 40 patients with cirrhosis alone. The control group( groupC) included 40 healthy people undergoing the routine physical examination. The NGAL concentrations in serum and urine were measured by enzyme-linked immunosorbent assay.The levels of pNGAL,u NGAL,and serum creatinine,as well as glomerular filtration rate( GFR),were compared between different groups.The comparison between different groups was made by one-way ANOVA and simple linear correlation analysis was used to investigate the relationshipof GFR with pNGAL and u NGAL in groupA. Results The NGAL levels in serum and urine in groupA were significantly higher than those in groups B and C( all P < 0. 01). Staging of AKI was made according to the kidney injury criteria and the NGAL levels in serum and urine significantly increased with AKI stage( all P < 0. 01). In groupA,NGAL level was negatively correlated with GFR in both serum( r =-0. 757,P < 0. 05) and urine( r =-0. 547,P < 0. 05). Conclusion NGAL can be used as an indicator in the diagnosis of AKI in patients with cirrhosis. Early and continuous measurement of serum and urine NGAL levels in patients with cirrhosis and AKI has a great significance in monitoring the progression of renal damage in the patients and developing timely and appropriate intervention measures.

Objective To investigate the localization and therapeutic effect of allogeneic bone marrow hematopoietic stem cell( HSC) transplantation in the rat model of liver fibrosis induced by carbon tetrachloride( CCl4). Methods Bone marrow HSCs from allogeneic Sprague-Dawley( SD) rats were isolated and cultured in vitro and labeled with 5-bromo-2'-deoxyuridine( Brd U) before transplantation.Eighteen female SD rats were randomly and equally divided into groups A,B,and C. A female rat model of liver fibrosis was established using CCl4. The rats in group A were injected with HSC-containing suspension through the caudal vein in the fourth week after CCl4 injection,while the rats in groups B and C were injected with normal saline through the caudal vein. In the eighth week,blood samples were taken from all groups. Then all rats were sacrificed,and the liver,pancreatic,and stomach tissues were collected to examine the localization of HSC and evaluate the therapeutic effect of HSC on liver damage. The double-blind method was used to statistically analyze experimental results. Comparison of continuous data between these groups was made by analysis of variance,and pairwise comparison was made by SNK-q test; comparison of categorical data between these groups was made by Kruskal-Wallis H test,and pairwise comparison was made by Nemenyi test. Results Group A showed significantly improved histopathology compared with group B,while groups A and C showed approximately the same histological findings. There were significant differences in classification of liver fibrosis between groups A,B,and C( χ2= 13. 14,P = 0. 001),and groups A and C had significantly lower grades of liver fibrosis than group B( both P < 0. 05). In group A,Brd U-positive cells were detected in the liver tissues of all rats,but no positive cells were detected in the pancreatic and stomach tissues;no Brd U-positive cells were detected in groups B and C. Compared with group B,groups A and C had significantly lower alanine aminotransferase and aspartate aminotransferase levels but a significantly higher albumin level( all P < 0. 05). Conclusion Allogeneic HSC can be localized in the rat model of liver fibrosis and reverse the liver damage.

Objective To measure the expression of divalent metal transporter 1( DMT1) in hepatocellular carcinoma( HCC) and to explore its clinical and pathological significance. Methods Fifty-seven liver cancer specimens collected from patients with HCC and preserved in paraffin in Second Affiliated Hospital of Shantou University Medical College from July 1999 to July 2011 were established as HCC tissue group,and 7 specimens of normal liver tissues from autopsy and 8 specimens of liver tissues from patients with intrahepatic bile duct stones and preserved in paraffin were established as normal control group. SP immunohistochemistry was applied to measure the expression of DMT1 in 15 specimens of normal liver tissues and 57 specimens of HCC tissues. One-way analysis of variance was applied to analyze the difference in expression of DMT1 in HCC tissues with varying degrees of differentiation,and χ2test was applied for the comparison of rates;the correlation between expression of DMT1 and tumor size was analyzed by Pearson correlation analysis. Results DMT1 in the liver tissues in normal control group was negative or weakly positive,with a positive rate of 20%( 3 /5); in HCC tissue group,the positive rate was78. 9%( 45 /57),with a strong positive rate of 15. 8%( 9 /57); the two groups showed a significant difference in positive rate( P < 0. 05).The expression of DMT1 varied significantly between patients with varying degrees of differentiation in HCC tissues( F = 4. 011,P < 0. 05),while the positive rate of DMT1 showed no significant differences between patients with different clinical stages and with or without blood vessel infiltration( all P > 0. 05). Correlation analysis did not find the correlation between expression of DMT1 and tumor size( r =-0. 047,P> 0. 05). Conclusion The positive expression rate of DMT1 increases significantly in HCC tissues and is closely related to the degree of tumor differentiation,which is potentially valuable for clinical and pathological grading of liver cancer.

Objective To investigate postoperative application of multidisciplinary treatment( MDT) in hepatobiliary and pancreatic malignancies based on the pathological results. Methods The clinical data of patients who were diagnosed as hepatobiliary and pancreatic malignancies who were diagnosed and treated with postoperative MDT in our hospital from Apirl 2014 to March 2015 were analyzed. MDT was performed by consultation for four to six patients once every other week. The postoperative comprehensive treatment strategy for each patient was discussed and determined by all experts in the consultation. The effect of postoperative treatment and prognosis was summarized. Results25 postoperative MDT consultations on hepatobiliary and pancreatic malignancies were held for 131 patients,including 53 patients with hepatocellular carcinoma,7 patients with intrahepatic cholangiocarcinoma,one patient with mixed-type liver cancer,3 patients with metastatic liver cancer,2 patients with liver sarcoma,29 patients with extrahepatic cholangiocarcinoma,22 patients with pancreatic cancer,5 patients with gallbladder cancer,and 9 patients with periampullary cancer. After surgery,38 patients received interventional treatment,19 systemic chemotherapy,15 radiotherapy,17 cell biotherapy,and 5 molecularly targeted therapy. The case fatality rate was 2. 29%( 3 /131). Conclusion Postoperative MDT provides scientific and rational personalized comprehensive treatment for patients with hepatobiliary and pancreatic malignancies,and improves medication compliance in patients,which holds promise for wide application.

Objective To evaluate the feasibility,safety,and follow-up results of endoscopic ligation with nylon snares for adenoma of the major duodenal papilla. Methods Twenty-three patients with adenoma of the major papilla who were treated in our hospital from January2012 to June 2014 were enrolled as subjects. All patients had biliary and pancreatic duct stents placed by endoscopic cholangiopancreatography,followed by complete ligation of tumors with nylon snares. Endoscopic follow-up evaluation of recurrence was performed regularly.Results All patients had biliary and pancreatic duct stents successfully placed and tumors successfully ligated with nylon snares in their first surgery. Endoscopic reexamination at two weeks after surgery showed that tumors were removed in all patients. Postoperative complications,cholangitis and pancreatitis,were found in one( 4. 3%) and two( 8. 7%) patients,respectively,and there were no bleeding,perforation,or death. A follow-up of more than one year in all patients showed that two patients had local recurrence of adenoma. Conclusion Endoscopic ligation with nylon snares is a safe and effective approach for treating adenoma of the major duodenal papilla.

Patients with chronic kidney disease( CKD) are susceptible to hepatitis C virus( HCV) infection due to hemodialysis and kidney transplantation. Despite the progress in treatment and new medicines for hepatitis C,the efficacy,tolerability,and safety of medicines in CKD patients remain unclear. This article reviews the current situation of HCV infection in CKD patients,methods for evaluating liver condition in HCV-CKD patients,and the latest progress in HCV-CKD treatment. More clinical practice is needed to verify the selection and dosage of medicines for HCV-CKD.

Hepatitis B virus( HBV) infection seriously threatens human health. Viral,environmental,and host factors can influence the progression,outcome,and prognosis of HBV infection. Accumulating evidence has shown that the host interleukin 28 B gene polymorphism is,to a certain degree,associated with host immunity,anti-HBV efficacy of interferon,and HBV infection outcome. However,at present a consistent conclusion has not been reached yet. IL28 B may influence the efficacy of interferon therapy and virus spontaneous clearance in patients with chronic hepatitis B( CHB) by affecting the host's immune status. Examining the immune status for CHB patients before the experimental study may help researchers to draw a more consistent conclusion.

Transjugular intrahepatic portosystemic shunt( TIPS) is widely used in the treatment of cirrhotic portal hypertension and its associated complications. However,postoperative shunt dysfunction has been an important factor restricting the clinical application of TIPS. This article summarizes the use of shunt,the incidence of shunt dysfunction after TIPS,preventive measures and diagnostic methods for shunt dysfunction,and indications and techniques of shunt recanalization,in order to enhance our knowledge of shunt dysfunction and recanalization,which could further improve the efficacy of TIPS for cirrhotic portal hypertension.

Hypersplenism is a common complication of post-hepatitis cirrhosis,and may not need to be treated. The treatment of hypersplenism is not considered if it is not proven clinically beneficial to patients. However,there are still some patients with hypersplenism who should be treated for some reasons. This article reviews the latest progress in the therapies for hypersplenism,including splenectomy,splenic artery embolization,splenic radiofrequency ablation,liver transplantation,medication,and transjugular intrahepatic portosystemic shunt. It is demonstrated that all the above treatments have advantages and disadvantages. Minimally invasive methods,through currently preferred for hypersplenism,have not yet been clinically applied for a long period,and remain to be technically improved and supported by relevant evidence for standardization.

Phosphoinositide 3-kinase( PI3K) / protein kinase-B( Ak T) / mammalian target of rapamycin( m TOR) /70-k Da ribosomal protein S6 kinase( p70S6K),PI3K/Akt/m TOR/p70S6 K,is an important signaling pathway in the life activities of cells,and it plays an important role in promoting the growth,proliferation,invasion,and anti-apoptosis of cells and promoting angiogenesis. It was clarified that the PI3 K / Akt / m TOR / p70S6 Ksignaling pathway is involved in regulating the activities of hepatic stellate cell( HSC),thus influencing the development and progression of hepatic fibrosis. Analysis demonstrated that blocking any target of the PI3 K / Akt / m TOR / p70S6 Ksignaling pathway can inhibit the activation and proliferation of HSC,promote the apoptosis of HSC,inhibit the extracellular matrix secretion from HSC,and delay the progression of hepatic fibrosis. Blocking the pathway is expected to be a treatment strategy for hepatic fibrosis.

Liver cancer is a malignant tumor. The current operation or chemoradiotherapy cannot achieve a satisfactory effect,and relapse and metastasis are always big problems in the treatment of liver cancer. According to the recent theory of liver cancer stem cells,the genesis,development,relapse,metastasis,and prognosis of liver cancer are all related to liver cancer stem cells. If the liver cancer stem cells are treated by targeted therapy,which would reduce the number of or destroy the stem cells,the relapse,metastasis,and drug resistance after tumor resection may be reduced or eliminated. The progress in targeted therapy for liver cancer stem cells is reviewed here. Although there are many types of targeted therapies for liver cancer stem cells,it is still a key problem that the targeting is not strong enough,which needs to be solved urgently. Whether the dual-or multi-targeting would solve this problem still needs to be confirmed by further experimental studies.