AIM: To study host gene expression and numberof immune cells in liver tissues from patients with fulminant hepatitis E(FH-E).METHODS: Microarray-based expression profiling was done using Illumina Human WG-6_v3_Bead Ch...AIM: To study host gene expression and numberof immune cells in liver tissues from patients with fulminant hepatitis E(FH-E).METHODS: Microarray-based expression profiling was done using Illumina Human WG-6_v3_Bead Chip arrays on post-mortem liver tissue from 5 patients with FH-E,and compared with similar tissue from 6 patients with fulminant hepatitis B(FH-B; disease controls) and normal liver tissue from 6 persons.Differential expression was defined as ≥ 2.0-fold change with Benjamini-Hochberg false discovery rate below 0.05 using t-test in liver tissue from FH-B and FH-E,than healthy liver tissue.For some genes that showed differential expression in FH-E,microarray data were validated using quantitative reverse transcription PCR.Differentially expressed gene lists were then subjected to "Gene Ontology" analysis for biological processes,and pathway analysis using Bio Carta database on the DAVID server.In addition,tissue sections were stained for CD4+,CD8+ and CD56+ cells using indirect immunohistochemistry; cells staining positive for each of these markers were counted and compared between groups.RESULTS: Compared to normal livers,those from patients with FH-E and FH-B showed differential expression of 3377 entities(up-regulated 1703,downregulated 1674) and 2572 entities(up 1164,down 1408),respectively.This included 2142(up 896,down 1246) entities that were common between the two sets; most of these belonged to metabolic,hemostatic and complement pathways,which are active in normal livers.Gene expression data from livers of patients with FH-E but not those of FH-B showed activation of several immune response pathways,particularly those involving cytotoxic T cells.The fold-change values of m RNA for selected genes in livers from FH-E than in normal liver tissue determined using quantitative reverse transcription PCR showed excellent concordance with microarray analysis.At immunohistochemistry,CD8+ T cells showed an increase in liver biopsies from both FH-E [median 53.4 per arbitrary unit area(range 31.2-99.9)]展开更多
AIM： To determine the effects of the calcineurin inhibitors, cyclosporine and tacrolimus, on hepatitis C virus （HCV） replication and activity of recurrent hepatitis C in patients post liver transplantation. METHODS...AIM： To determine the effects of the calcineurin inhibitors, cyclosporine and tacrolimus, on hepatitis C virus （HCV） replication and activity of recurrent hepatitis C in patients post liver transplantation. METHODS： The data of a cohort of 107 patients who received liver transplantation for HCV-associated liver cirrhosis between 1999 and 2003 in our center were retrospectively analyzed. The level of serum HCV-RNA and the activity of recurrent hepatitis were compared between 47 patients who received either cyclosporine or tacrolimus as the primary immunosuppressive agent and an otherwise similar immunosuppressive regimen which did not lead to biliary complications within the first 12 mo after transplantation. RESULTS： HCV-RNA increased within 3 mo after transplantation but the differences between the cyclosporine group and the tacrolimus group were insignificant （P=0.49 at 12 too）. In addition, recurrent hepatitis as determined by serum transarninases and histological grading of portal inflammation and fibrosis showed no significant difference after 12 mo （P= 0.34）.CONCLUSION： Cyclosporine or tacrolimus as a primary immunosuppressive agent does not influence the induction or severity of recurrent hepatitis in HCV- infected patients after liver transplantation.展开更多
AIM: To identify the property of dendritic cells (DCs) of peripheral blood monocytes (PBMC) in patients with chronic HBV infection. METHODS: Twenty patients with persistent HBV infection were included in this study, 1...AIM: To identify the property of dendritic cells (DCs) of peripheral blood monocytes (PBMC) in patients with chronic HBV infection. METHODS: Twenty patients with persistent HBV infection were included in this study, 10 healthy subjects being used as a control group. The peripheral blood mononuclear cells (PBMC) of T cell-depleted populations were incubated and induced into mature dendritic cells in the RPMI-1640 medium in the presence of cytokines GM-CSF, IL-4, FLt-3,TNF-alpha and 100mL.L(-1 )of fetal calf serum for a total of 10-12 days. The expressions of surface markers on DCs were evaluated using flow cytometric analysis. ELISA method was used to determine the cytokine levels of interleukin-12 (IL-12) and IL-10 in the supernatant produced by DCs. For detection of the stimulatory capacity of DCs to T cell proliferation, mytomycin C-treated DC were incubated with allogenic T cells. RESULTS: A typical morphology of mature DCs from healthy subjects and HBV-infected patients was induced in in vitro incubation, but the proliferation ability and cellular number of DCs from HBV-infected patients significantly decreased compared with healthy individuals. In particular, the expression levels of HLA-DR, CD80 (B7-1) and CD86 (B7-2) on DC surface from patients were also lower than that from healthy individuals (0.46 vs 0.92 for HLA-DR, 0.44 vs 0.88 for CD80 and 0.44 vs 0.84 for CD86,P【0.05). The stimulatory capacity and production of IL-12 of DCs from patients in allogenic mixed lymphocyte reaction (AMLR) significantly decreased, but the production level of nitric oxide (NO) by DCs simultaneously increased compared with healthy subjects (86 +/- 15 vs 170 +/- 22 micromol.L(-1), P 【0.05). CONCLUSION: The patients with chronic HBV infection have the defective function and immature phenotype of dendritic cells, which may be associated with the inability of efficient presentation of HBV antigens to host immune system for the clearance of HBV.展开更多
AIM: To establish clone cells with different metastatic potential for the study of metastasis-related mechanisms. METHODS: Cloning procedure was performed on parental hepatocellular carcinoma (HCC) cell line MHCC97, a...AIM: To establish clone cells with different metastatic potential for the study of metastasis-related mechanisms. METHODS: Cloning procedure was performed on parental hepatocellular carcinoma (HCC) cell line MHCC97, and biological characteristics of the target clones selected by in vivo screening were studied. RESULTS: Two clones with high (MHCC97-H) and low (MHCC97-L) metastatic potential were isolated from the parent cell line. Compared with MHCC97-L, MHCC97-H had smaller cell size (average cell diameter 43 microm vs 50 microm) and faster in vitro and in vivo growth rate (tumor cell doubling time was 34.2h vs 60.0h). The main ranges of chromosomes were 55-58 in MHCC97-H and 57-62 in MHCC97-L. Boyden chamber in vitro invasion assay demonstrated that the number of penetrating cells through the artificial basement membrane was (37.5 +/- 11.0) cells/field for MHCC97-H vs (17.7 +/- 6.3)/field for MHCC97-L. The proportions of cells in G0-G1 phase, S phase, and G2-M phase for MHCC97-H/MHCC97-L were 0.56/0.65, 0.28/0.25 and 0.16/0.10, respectively, as measured by flow cytometry. The serum AFP levels in nude mice 5wk after orthotopic implantation of tumor tissue were (246 +/- 66) microg.L(-1) for MHCC97-H and (91 +/- 66) microg.L(-1) for MHCC97-L. The pulmonary metastatic rate was 100% (10/10) vs 40% (4/10). CONCLUSION: Two clones of the same genetic background but with different biological behaviors were established, which could be valuable models for investigation on HCC metastasis.展开更多
AIM:To evaluate the covalently closed circle DNA (cccDNA) level of hepatitis B virus (HBV) in patients' liver and sera. METHODS:HBV DNA was isolated from patients' liver biopsies and sera.A sensitive real-time...AIM:To evaluate the covalently closed circle DNA (cccDNA) level of hepatitis B virus (HBV) in patients' liver and sera. METHODS:HBV DNA was isolated from patients' liver biopsies and sera.A sensitive real-time PCR method,which is capable of differentiation of HBV viral genomic DNA and cccDNA,was used to quantify the total HBV cccDNA.The total HBV viral DNA was quantitated by real-time PCR using a HBV diagnostic kit (PG Biotech,LTD,Shenzhen,China) described previously. RESULTS:For the first time,we measured the level of HBV DNA and cccDNA isolated from ten HBV patients' liver biopsies and sera.In the liver biopsies,cccDNA was detected from all the biopsy samples.The copy number of cccDNA ranged from from 0.03 to 173.1 per cell,the copy number of total HBV DNA ranged from 0.08 to 3 717 per cell.The ratio of total HBV DNA to cccDNA ranged from 1 to 3 406.In the sera, cccDNA was only detected from six samples whereas HBV viral DNA was detected from all ten samples.The ratio of cccDNA to total HBV DNA ranged from 0 to 1.77%.To further investigate the reason why cccDNA could only be detected in some patients' sera,we performed longitudinal studies.The cccDNA was detected from the patients' sera with HBV reactivation but not from the patients' sera without HBV reactivation.The level of cccDNA in the sera was correlated with ALT and viral load in the HBV reactivation patients. CONCLUSION:HBV cccDNA is actively transcribed and replicated in some patients' hepatoo/tes,which is reflected by a high ratio of HBV total DNA vs cccDNA.Detection of cccDNA in the liver biopsy will provide an end-point for the anti-HBV therapy.The occurrence of cccDNA in the sera is an early signal of liver damage,which may be another important clinical parameter.展开更多
About 30% of patients with cirrhosis have diabetes mellitus(DM).Nowadays,it is a matter for debate whether type 2 DM in the absence of obesity and hypertriglyceridemia may be a risk factor for chronic liver disease.DM...About 30% of patients with cirrhosis have diabetes mellitus(DM).Nowadays,it is a matter for debate whether type 2 DM in the absence of obesity and hypertriglyceridemia may be a risk factor for chronic liver disease.DM,which develops as a complication of cirrhosis,is known as "hepatogenous diabetes".Insulin resistance in muscular and adipose tissues and hyperinsulinemia seem to be the pathophysiologic bases of diabetes in liver disease.An impaired response of the islet β-cells of the pancreas and hepatic insulin resistance are also contributory factors.Non-alcoholic fatty liver disease,alcoholic cirrhosis,chronic hepatitis C(CHC) and hemochromatosis are more frequently associated with DM.Insulin resistance increases the failure of the response to treatment in patients with CHC and enhances progression of fibrosis.DM in cirrhotic patients may be subclinical.Hepatogenous diabetes is clinically different from that of type 2 DM,since it is less frequently associated with microangiopathy and patients more frequently suffer complications of cirrhosis.DM increases the mortality of cirrhotic patients.Treatment of the diabetes is complex due to liver damage and hepatotoxicity of oral hypoglycemic drugs.This manuscript will review evidence that exists in relation to:type 2 DM alone or as part of the metabolic syndrome in the development of liver disease;factors involved in the genesis of hepatogenous diabetes;the impact of DM on the clinical outcome of liver disease;the management of DM in cirrhotic patients and the role of DM as a risk factor for the occurrence and exacerbation of hepatocellular carcinoma.展开更多
AIM:To investigate the diagnostic accuracy of acoustic radiation force impulse (ARFI) imaging as a noninvasive method for the assessment of liver fibrosis in chronic hepatitis C (CHC) patients.METHODS:We performed a p...AIM:To investigate the diagnostic accuracy of acoustic radiation force impulse (ARFI) imaging as a noninvasive method for the assessment of liver fibrosis in chronic hepatitis C (CHC) patients.METHODS:We performed a prospective blind com-parison of ARFI elastography,APRI index and FibroMax in a consecutive series of patients who underwent liver biopsy for CHC in University Hospital Bucharest. His-topathological staging of liver fibrosis according to the METAVIR scoring system served as the reference. A to-tal of 74 patients underwent ARFI elastography,APRI index,FibroMax and successful liver biopsy. RESULTS:The noninvasive tests had a good correlation with the liver biopsy results. The most powerful test in predicting fibrosis was ARFI elastography. The diagnostic accuracy of ARFI elastography,expressedas area under receiver operating characteristic curve (AUROC) had a validity of 90.2% (95% CI AUROC = 0.831-0.972,P < 0.001) for the diagnosis of significant f ibrosis (F ≥ 2). ARFI sonoelastography predicted even better F3 or F4 fibrosis (AUROC = 0.993,95% CI = 0.979-1).CONCLUSION:ARFI elastography had very good accuracy for the assessment of liver fibrosis and was superior to other noninvasive methods (APRI Index,FibroMax) for staging liver fibrosis.展开更多
Hepatocellular carcinoma(HCC) represents the fifth most common cancer in the world,and the third most frequent oncological cause of death.The incidence of HCC is on the increase.HCC typically develops in patients with...Hepatocellular carcinoma(HCC) represents the fifth most common cancer in the world,and the third most frequent oncological cause of death.The incidence of HCC is on the increase.HCC typically develops in patients with chronic liver diseases,and cirrhosis,usually with viral etiology,is the strongest predisposing factor.Nowadays HCC diagnosis is a multistage process including clinical,laboratory,imaging and pathological examinations.The prognosis of HCC is mostly poor,because of detection at an advanced,non-resectable stage.Potentially curative treatment(surgery) is limited and really possible only for cases with small HCC malignancies.For this reason,more effective surveillance strategies should be used to screen for early occurrence of HCC targeted to the population at risk.So far,the generally accepted serological marker is α-fetoprotein(AFP).Its diagnostic accuracy is unsatisfactory and questionable because of low sensitivity,therefore there is a strong demand by clinicians for new HCC-specific biomarkers.In this review,we will focus on other biomarkers that seem to improve HCC diagnosis,such as AFP-L3,des-γ-carboxyprothrombin,α-l-fucosidase,,γ-glutamyl transferase,glypican-3,squamous cell carcinoma antigen,a new generation of immunoglobulin M-immunocomplexes,and very promising geneexpression profiling.展开更多
基金Supported by National Institutes of Health,Bethesda,United States,No.5R01AI076192
文摘AIM: To study host gene expression and numberof immune cells in liver tissues from patients with fulminant hepatitis E(FH-E).METHODS: Microarray-based expression profiling was done using Illumina Human WG-6_v3_Bead Chip arrays on post-mortem liver tissue from 5 patients with FH-E,and compared with similar tissue from 6 patients with fulminant hepatitis B(FH-B; disease controls) and normal liver tissue from 6 persons.Differential expression was defined as ≥ 2.0-fold change with Benjamini-Hochberg false discovery rate below 0.05 using t-test in liver tissue from FH-B and FH-E,than healthy liver tissue.For some genes that showed differential expression in FH-E,microarray data were validated using quantitative reverse transcription PCR.Differentially expressed gene lists were then subjected to "Gene Ontology" analysis for biological processes,and pathway analysis using Bio Carta database on the DAVID server.In addition,tissue sections were stained for CD4+,CD8+ and CD56+ cells using indirect immunohistochemistry; cells staining positive for each of these markers were counted and compared between groups.RESULTS: Compared to normal livers,those from patients with FH-E and FH-B showed differential expression of 3377 entities(up-regulated 1703,downregulated 1674) and 2572 entities(up 1164,down 1408),respectively.This included 2142(up 896,down 1246) entities that were common between the two sets; most of these belonged to metabolic,hemostatic and complement pathways,which are active in normal livers.Gene expression data from livers of patients with FH-E but not those of FH-B showed activation of several immune response pathways,particularly those involving cytotoxic T cells.The fold-change values of m RNA for selected genes in livers from FH-E than in normal liver tissue determined using quantitative reverse transcription PCR showed excellent concordance with microarray analysis.At immunohistochemistry,CD8+ T cells showed an increase in liver biopsies from both FH-E [median 53.4 per arbitrary unit area(range 31.2-99.9)]
文摘AIM： To determine the effects of the calcineurin inhibitors, cyclosporine and tacrolimus, on hepatitis C virus （HCV） replication and activity of recurrent hepatitis C in patients post liver transplantation. METHODS： The data of a cohort of 107 patients who received liver transplantation for HCV-associated liver cirrhosis between 1999 and 2003 in our center were retrospectively analyzed. The level of serum HCV-RNA and the activity of recurrent hepatitis were compared between 47 patients who received either cyclosporine or tacrolimus as the primary immunosuppressive agent and an otherwise similar immunosuppressive regimen which did not lead to biliary complications within the first 12 mo after transplantation. RESULTS： HCV-RNA increased within 3 mo after transplantation but the differences between the cyclosporine group and the tacrolimus group were insignificant （P=0.49 at 12 too）. In addition, recurrent hepatitis as determined by serum transarninases and histological grading of portal inflammation and fibrosis showed no significant difference after 12 mo （P= 0.34）.CONCLUSION： Cyclosporine or tacrolimus as a primary immunosuppressive agent does not influence the induction or severity of recurrent hepatitis in HCV- infected patients after liver transplantation.
基金National Natural Science Foundation of China,No.39970831.
文摘AIM: To identify the property of dendritic cells (DCs) of peripheral blood monocytes (PBMC) in patients with chronic HBV infection. METHODS: Twenty patients with persistent HBV infection were included in this study, 10 healthy subjects being used as a control group. The peripheral blood mononuclear cells (PBMC) of T cell-depleted populations were incubated and induced into mature dendritic cells in the RPMI-1640 medium in the presence of cytokines GM-CSF, IL-4, FLt-3,TNF-alpha and 100mL.L(-1 )of fetal calf serum for a total of 10-12 days. The expressions of surface markers on DCs were evaluated using flow cytometric analysis. ELISA method was used to determine the cytokine levels of interleukin-12 (IL-12) and IL-10 in the supernatant produced by DCs. For detection of the stimulatory capacity of DCs to T cell proliferation, mytomycin C-treated DC were incubated with allogenic T cells. RESULTS: A typical morphology of mature DCs from healthy subjects and HBV-infected patients was induced in in vitro incubation, but the proliferation ability and cellular number of DCs from HBV-infected patients significantly decreased compared with healthy individuals. In particular, the expression levels of HLA-DR, CD80 (B7-1) and CD86 (B7-2) on DC surface from patients were also lower than that from healthy individuals (0.46 vs 0.92 for HLA-DR, 0.44 vs 0.88 for CD80 and 0.44 vs 0.84 for CD86,P【0.05). The stimulatory capacity and production of IL-12 of DCs from patients in allogenic mixed lymphocyte reaction (AMLR) significantly decreased, but the production level of nitric oxide (NO) by DCs simultaneously increased compared with healthy subjects (86 +/- 15 vs 170 +/- 22 micromol.L(-1), P 【0.05). CONCLUSION: The patients with chronic HBV infection have the defective function and immature phenotype of dendritic cells, which may be associated with the inability of efficient presentation of HBV antigens to host immune system for the clearance of HBV.
基金Supportod ty the State Key Basic Research Program Grant G1998051211 the Fund for Leading Specialty of Shanghai Metropolitan Bureau of Public Health.
文摘AIM: To establish clone cells with different metastatic potential for the study of metastasis-related mechanisms. METHODS: Cloning procedure was performed on parental hepatocellular carcinoma (HCC) cell line MHCC97, and biological characteristics of the target clones selected by in vivo screening were studied. RESULTS: Two clones with high (MHCC97-H) and low (MHCC97-L) metastatic potential were isolated from the parent cell line. Compared with MHCC97-L, MHCC97-H had smaller cell size (average cell diameter 43 microm vs 50 microm) and faster in vitro and in vivo growth rate (tumor cell doubling time was 34.2h vs 60.0h). The main ranges of chromosomes were 55-58 in MHCC97-H and 57-62 in MHCC97-L. Boyden chamber in vitro invasion assay demonstrated that the number of penetrating cells through the artificial basement membrane was (37.5 +/- 11.0) cells/field for MHCC97-H vs (17.7 +/- 6.3)/field for MHCC97-L. The proportions of cells in G0-G1 phase, S phase, and G2-M phase for MHCC97-H/MHCC97-L were 0.56/0.65, 0.28/0.25 and 0.16/0.10, respectively, as measured by flow cytometry. The serum AFP levels in nude mice 5wk after orthotopic implantation of tumor tissue were (246 +/- 66) microg.L(-1) for MHCC97-H and (91 +/- 66) microg.L(-1) for MHCC97-L. The pulmonary metastatic rate was 100% (10/10) vs 40% (4/10). CONCLUSION: Two clones of the same genetic background but with different biological behaviors were established, which could be valuable models for investigation on HCC metastasis.
基金SuppoSed by CRCG grant from the University of Hong KongCERG grant from University Grant Council of Hong Kong Research Fund from Science and Technology Commission of Shanghai,China
文摘AIM:To evaluate the covalently closed circle DNA (cccDNA) level of hepatitis B virus (HBV) in patients' liver and sera. METHODS:HBV DNA was isolated from patients' liver biopsies and sera.A sensitive real-time PCR method,which is capable of differentiation of HBV viral genomic DNA and cccDNA,was used to quantify the total HBV cccDNA.The total HBV viral DNA was quantitated by real-time PCR using a HBV diagnostic kit (PG Biotech,LTD,Shenzhen,China) described previously. RESULTS:For the first time,we measured the level of HBV DNA and cccDNA isolated from ten HBV patients' liver biopsies and sera.In the liver biopsies,cccDNA was detected from all the biopsy samples.The copy number of cccDNA ranged from from 0.03 to 173.1 per cell,the copy number of total HBV DNA ranged from 0.08 to 3 717 per cell.The ratio of total HBV DNA to cccDNA ranged from 1 to 3 406.In the sera, cccDNA was only detected from six samples whereas HBV viral DNA was detected from all ten samples.The ratio of cccDNA to total HBV DNA ranged from 0 to 1.77%.To further investigate the reason why cccDNA could only be detected in some patients' sera,we performed longitudinal studies.The cccDNA was detected from the patients' sera with HBV reactivation but not from the patients' sera without HBV reactivation.The level of cccDNA in the sera was correlated with ALT and viral load in the HBV reactivation patients. CONCLUSION:HBV cccDNA is actively transcribed and replicated in some patients' hepatoo/tes,which is reflected by a high ratio of HBV total DNA vs cccDNA.Detection of cccDNA in the liver biopsy will provide an end-point for the anti-HBV therapy.The occurrence of cccDNA in the sera is an early signal of liver damage,which may be another important clinical parameter.
文摘About 30% of patients with cirrhosis have diabetes mellitus(DM).Nowadays,it is a matter for debate whether type 2 DM in the absence of obesity and hypertriglyceridemia may be a risk factor for chronic liver disease.DM,which develops as a complication of cirrhosis,is known as "hepatogenous diabetes".Insulin resistance in muscular and adipose tissues and hyperinsulinemia seem to be the pathophysiologic bases of diabetes in liver disease.An impaired response of the islet β-cells of the pancreas and hepatic insulin resistance are also contributory factors.Non-alcoholic fatty liver disease,alcoholic cirrhosis,chronic hepatitis C(CHC) and hemochromatosis are more frequently associated with DM.Insulin resistance increases the failure of the response to treatment in patients with CHC and enhances progression of fibrosis.DM in cirrhotic patients may be subclinical.Hepatogenous diabetes is clinically different from that of type 2 DM,since it is less frequently associated with microangiopathy and patients more frequently suffer complications of cirrhosis.DM increases the mortality of cirrhotic patients.Treatment of the diabetes is complex due to liver damage and hepatotoxicity of oral hypoglycemic drugs.This manuscript will review evidence that exists in relation to:type 2 DM alone or as part of the metabolic syndrome in the development of liver disease;factors involved in the genesis of hepatogenous diabetes;the impact of DM on the clinical outcome of liver disease;the management of DM in cirrhotic patients and the role of DM as a risk factor for the occurrence and exacerbation of hepatocellular carcinoma.
基金Supported by Grant 41066/2007, financed by the Ministry of Education and Research
文摘AIM:To investigate the diagnostic accuracy of acoustic radiation force impulse (ARFI) imaging as a noninvasive method for the assessment of liver fibrosis in chronic hepatitis C (CHC) patients.METHODS:We performed a prospective blind com-parison of ARFI elastography,APRI index and FibroMax in a consecutive series of patients who underwent liver biopsy for CHC in University Hospital Bucharest. His-topathological staging of liver fibrosis according to the METAVIR scoring system served as the reference. A to-tal of 74 patients underwent ARFI elastography,APRI index,FibroMax and successful liver biopsy. RESULTS:The noninvasive tests had a good correlation with the liver biopsy results. The most powerful test in predicting fibrosis was ARFI elastography. The diagnostic accuracy of ARFI elastography,expressedas area under receiver operating characteristic curve (AUROC) had a validity of 90.2% (95% CI AUROC = 0.831-0.972,P < 0.001) for the diagnosis of significant f ibrosis (F ≥ 2). ARFI sonoelastography predicted even better F3 or F4 fibrosis (AUROC = 0.993,95% CI = 0.979-1).CONCLUSION:ARFI elastography had very good accuracy for the assessment of liver fibrosis and was superior to other noninvasive methods (APRI Index,FibroMax) for staging liver fibrosis.
文摘Hepatocellular carcinoma(HCC) represents the fifth most common cancer in the world,and the third most frequent oncological cause of death.The incidence of HCC is on the increase.HCC typically develops in patients with chronic liver diseases,and cirrhosis,usually with viral etiology,is the strongest predisposing factor.Nowadays HCC diagnosis is a multistage process including clinical,laboratory,imaging and pathological examinations.The prognosis of HCC is mostly poor,because of detection at an advanced,non-resectable stage.Potentially curative treatment(surgery) is limited and really possible only for cases with small HCC malignancies.For this reason,more effective surveillance strategies should be used to screen for early occurrence of HCC targeted to the population at risk.So far,the generally accepted serological marker is α-fetoprotein(AFP).Its diagnostic accuracy is unsatisfactory and questionable because of low sensitivity,therefore there is a strong demand by clinicians for new HCC-specific biomarkers.In this review,we will focus on other biomarkers that seem to improve HCC diagnosis,such as AFP-L3,des-γ-carboxyprothrombin,α-l-fucosidase,,γ-glutamyl transferase,glypican-3,squamous cell carcinoma antigen,a new generation of immunoglobulin M-immunocomplexes,and very promising geneexpression profiling.
