AIM: To review the effectiveness of exercise as a therapy for nonalcoholic fatty liver disease(NAFLD) and potential benefits in treating insulin resistance and atherosclerosis.METHODS: Medline(EBSCOhost) and Pub Med w...AIM: To review the effectiveness of exercise as a therapy for nonalcoholic fatty liver disease(NAFLD) and potential benefits in treating insulin resistance and atherosclerosis.METHODS: Medline(EBSCOhost) and Pub Med were searched for English-language randomized controlled trials and prospective cohort studies in human adults aged ≥ 18 which investigated the various effects of exercise alone, a combination of exercise and diet, or exercise and diet coupled with behavioral modification on NAFLD from 2010 to Feburary 2015.RESULTS: Eighteen of 2298 available studies were chosen for critical review, which included 6925 patients. Nine(50%) studies were randomized controlled trials. Five(27.8%) studies utilized biopsy to examine the effects of physical activity on hepatic histology. The most commonly employed imaging modality to determine change in hepatic steatosis was hydrogen-magnetic resonance spectroscopy. Only two studies examined the effects of low impact physical activity for patients with significant mobility limitations and one compared the efficacy of aerobic and resistance exercise. No studies examined the exact duration of exercise required for hepatic and metabolic improvement in NAFLD.CONCLUSION: While exercise improved hepatic steatosis and underlying metabolic abnormalities in NAFLD, more studies are needed to define the most beneficial form and duration of exercise treatment.展开更多
In the recent decades, the incidence of hepatocellular carcinoma (HCC) has been found to be increasing in males in some countries. In China, HCC ranked second of cancer mortality since 1990s. Hepatitis B and C viruses...In the recent decades, the incidence of hepatocellular carcinoma (HCC) has been found to be increasing in males in some countries. In China, HCC ranked second of cancer mortality since 1990s. Hepatitis B and C viruses (HBV and HCV) and dietary aflatoxin intake remain the major causative factors of HCC. Surgery plays a major role in the treatment of HCC, particularly for small HCC. Downstaging unresectable huge HCC to smaller HCC and followed by resection will probably be a new approach for further study. Liver transplantation is indicated for small HCC, however, some issues remain to be solved.Different modes of 'regional cancer therapy for HCC' have been tried. Systemic chemotherapy has been disappointing in the past but the future can be promising.Biotherapy, such as cytokines, differentiation inducers,anti-angiogenic agents, gene therapy and tumor vaccine will probably play a role, particularly in the prevention of tumor recurrence. HCC invasiveness is currently the major target of study. Tremendous works have been done at the molecular level, which will provide clues for biomarker of HCC progressionas well as targets for intervention.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
The prognosis of hepatocellular carcinoma (HCC) still remains dismal, although many advances in its clinical study have been made. It is important for tumor control to identify the factors that predispose patients to ...The prognosis of hepatocellular carcinoma (HCC) still remains dismal, although many advances in its clinical study have been made. It is important for tumor control to identify the factors that predispose patients to death. With new discoveries in cancer biology, the pathological and biological prognostic factors of HCC have been studied quite extensively. Analyzing molecular markers (biomarkers) with prognostic significance is a complementary method. A large number of molecular factors have been shown to associate with the invasiveness of HCC, and have potential prognostic significance. One important aspect is the analysis of molecular markers for the cellular malignancy phenotype. These include alterations in DNA ploidy, cellular proliferation markers (PCNA, Ki-67, Mcm2, MIB1, MIA, and CSE1L/CAS protein), nuclear morphology, the p53 gene and its related molecule MD M2, other cell cycle regulators (cyclin A, cyclin D, cyclin E, cdc2, p27, p73), oncogenes and their receptors (such as ras, c-myc, c-fms, HGF, c-met, and erb-B receptor family members), apoptosis related factors (Fas and FasL), as well as telomerase activity. Another important aspect is the analysis of molecular markers involved in the process of cancer invasion and metastasis. Adhesion molecules (E-cadherin, catenins, serum intercellular adhesion molecule-1, CD44 variants), proteinases involved in the degradation of extracellular matrix (MMP-2, MMP-9, uPA, uPAR, PAI), as well as other molecules have been regarded as biomarkers for the malignant phenotype of HCC, and are related to prognosis and therapeutic outcomes. Tumor angiogenesis is critical to both the growth and metastasis of cancers including HCC, and has drawn much attention in recent years. Many angiogenesis-related markers, such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet-derived endothelial cell growth factor (PD-ECGF), thrombospondin (TSP), angiogenin, pleiotrophin, and endostatin (ES) levels, as well as intratumor microvessel density (M展开更多
Objective: Liver cancer is one of the most common cancers and major cause of cancer deaths in China,which accounts for over 50% of new cases and deaths worldwide.The systematic liver cancer statistics including of pro...Objective: Liver cancer is one of the most common cancers and major cause of cancer deaths in China,which accounts for over 50% of new cases and deaths worldwide.The systematic liver cancer statistics including of projection through 2030 could provide valuable information for prevention and control strategies in China,and experience for other countries.Methods: The burden of liver cancer in China in 2014 was estimated using 339 cancer registries’ data selected from Chinese National Cancer Center(NCC).Incident cases of 22 cancer registries were applied for temporal trends from 2000 to 2014.The burden of liver cancer through 2030 was projected using age-period-cohort model.Results: About 364,800 new cases of liver cancer(268,900 males and 95,900 females) occurred in China,and about 318,800 liver cancer deaths(233,500 males and 85,300 females) in 2014.Western regions of China had the highest incidence and mortality rates.Incidence and mortality rates decreased by about 2.3% and 2.6% per year during the period of 2000-2014,respectively,and would decrease by more than 44% between 2014 and 2030 in China.The young generation,particularly for those aged under 40 years,showed a faster down trend.Conclusions: Based on the analysis,incidence and mortality rates of liver cancer are expected to decrease through 2030,but the burden of liver cancer is still serious in China,especially in rural and western areas.Most cases of liver cancer in China can be prevented through vaccination and more prevention efforts should be focused on high risk groups.展开更多
Liver fibrosis is a reversible wound-healing process aimed at maintaining organ integrity, and presents as the critical pre-stage of liver cirrhosis, which will eventually progress to hepatocellular carcinoma in the a...Liver fibrosis is a reversible wound-healing process aimed at maintaining organ integrity, and presents as the critical pre-stage of liver cirrhosis, which will eventually progress to hepatocellular carcinoma in the absence of liver transplantation. Fibrosis generally results from chronic hepatic injury caused by various factors, mainly viral infection, schistosomiasis, and alcoholism; however, the exact pathological mechanisms are still unknown. Although numerous drugs have been shown to have antifibrotic activity in vitro and in animal models, none of these drugs have been shown to be efficacious in the clinic. Importantly, hepatic stellate cells(HSCs) play a key role in the initiation, progression, and regression of liver fibrosis by secreting fibrogenic factors that encourage portal fibrocytes, fibroblasts, and bone marrow-derived myofibroblasts to produce collagen and thereby propagate fibrosis. These cells are subject to intricate cross-talk with adjacent cells, resulting in scarring and subsequent liver damage. Thus, an understanding of the molecular mechanisms of liver fibrosis and their relationships with HSCs is essential for the discovery of new therapeutic targets. This comprehensive review outlines the role of HSCs in liver fibrosis and details novel strategies to suppress HSC activity, thereby providing new insights into potential treatments for liver fibrosis.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 investigate the relationship between the economy and the adult prevalence of fatty liver disease(FLD) in China's Mainland. METHODS: Literature searches on the Pub Med and Chinese National Knowledge Infrast...AIM: To investigate the relationship between the economy and the adult prevalence of fatty liver disease(FLD) in China's Mainland. METHODS: Literature searches on the Pub Med and Chinese National Knowledge Infrastructure databases were performed to identify eligible studies published before July 2014. Records were limited to crosssectional surveys or baseline surveys of longitudinal studies that reported the adult prevalence of FLD and recruited subjects from the general population or community. The gross domestic product(GDP) per capita was chosen to assess the economic status. Multiple linear regression and Loess regression were chosen to fit the data and calculate the 95%CIs. Fitting and overfitting of the models were considered in choosing the appropriate models. RESULTS: There were 27 population-based surveys from 26 articles included in this study. The pooled mean prevalence of FLD in China was 16.73%(95%CI: 13.92%-19.53%). The prevalence of FLD was correlated with the GDP per capita and survey years in the country(adjusted R2 = 0.8736, P GDP per capita = 0.00426, P years = 0.0000394), as well as in coastal areas(R2 = 0.9196, P GDP per capita = 0.00241, P years = 0.00281). Furthermore, males [19.28%(95%CI: 15.68%-22.88%)] presented a higher prevalence than females [14.1%(95%CI: 11.42%-16.61%), P = 0.0071], especially in coastal areas [21.82(95%CI: 17.94%-25.71%) vs 17.01%(95%CI: 14.30%-19.89%), P = 0.0157]. Finally, the prevalence was predicted to reach 20.21% in 2020, increasing at a rate of 0.594% per year. CONCLUSION: This study reveals a correlation between the economy and the prevalence of FLD in China's Mainland.展开更多
AIM: To investigate the population-based prevalence of fatty liver disease (FLD) and its risk factors in Guangdong Province,China. METHODS: A cross-sectional survey with multiple-stage stratified cluster and random sa...AIM: To investigate the population-based prevalence of fatty liver disease (FLD) and its risk factors in Guangdong Province,China. METHODS: A cross-sectional survey with multiple-stage stratified cluster and random sampling of inhabitants over 7-year-old was performed in 6 urban and rural areas of Guangdong Province,China. Questionnaires,designed by co-working of epidemiologists and hepatologists,included demographic characteristics,current medication use,medical history and health-relevant behaviors,i.e. alcohol consumption,smoking habits,dietary habits and physical activities. Anthropometric measurements,biochemical tests and abdominal ultrasonography were carried out. RESULTS: Among the 3543 subjects,609 (17.2%) were diagnosed having FLD (18.0% males,16.7% females,P > 0.05). Among them,the prevalence of confirmed alcoholic liver disease (ALD),suspected ALD and nonalcoholic fatty liver disease (NAFLD) were 0.4%,1.8%,and 15.0%,respectively. The prevalence rate (23.0%) was significantly higher in urban areas than (12.9%) in rural areas. After adjustment for age,gender and residency,the standardized prevalence of FLD in adults was 14.5%. Among them,confirmed ALD,suspected ALD and NAFLD were 0.5%,2.3%,and 11.7%,respectively,in adults and 1.3% (all NAFLD) in children at the age of 7-18 years. The overall prevalence of FLD increased with age in both genders to the peak of 27.4% in the group of subjects at the age of 60-70 years. The prevalence rate was significantly higher in men than in women under the age of 50 years (22.4% vs 7.1%,P < 0.001). However,the opposite phenomenon was found over the age of 50 years (20.6% vs 27.6%,P < 0.05). Multivariate and logistic regression analysis indicated that male gender,urban residency,low education,high blood pressure,body mass index,waist circumference,waist to hip ratio,serum triglyceride and glucose levels were the risk factors for FLD. CONCLUSION: FLD,especially NAFLD,is prevalent in South China. There are many risk factors for FLD.展开更多
Nonalcoholic fatty liver disease(NAFLD) has become the dominant form of chronic liver disease in children and adolescents with the increasing prevalence of obesity worldwide. NAFLD represents a wide spectrum of condit...Nonalcoholic fatty liver disease(NAFLD) has become the dominant form of chronic liver disease in children and adolescents with the increasing prevalence of obesity worldwide. NAFLD represents a wide spectrum of conditions, ranging from fatty liver-which generally follows a benign, non-progressive clinical course-to non-alcoholic steatohepatitis, a subset of NAFLD that may progress to cirrhosis and end-stage liver disease or liver carcinoma. The underlying pathophysiological mechanism of "pediatric" NAFLD remains unclear, although it is strongly associated with obesity and insulin resistance. In this review we provide a general overview on the current understanding of NAFLD in children and adolescents, which underpins practice, enabling early diagnosis and appropriate therapeutic intervention for this life-threatening liver disease.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
AIM: To characterize the anticancer function of cytokine-induced killer cells (CIK) and develop an adoptive immunotherapy for the patients with primary hepatocellular carcinoma (HCC), we evaluated the proliferation ra...AIM: To characterize the anticancer function of cytokine-induced killer cells (CIK) and develop an adoptive immunotherapy for the patients with primary hepatocellular carcinoma (HCC), we evaluated the proliferation rate, phenotype and the antitumor activity of human CIK cells from healthy donors and HCC patients in vitro and in vivo. METHODS: Peripheral blood mononuclear cells (PBMC) from healthy donors and patients with primary HCC were incubated in vitro and induced into CIK cells in the presence of various cytokines such as interferon-gamma (IFN-gamma), interleukin-1 (IL-1), IL-2 and monoclonal antibody (mAb) against CD3. The phenotype and characterization of CIK cells were identified by flow cytometric analysis. The cytotoxicity of CIK cells was determined by (51)Cr release assay. RESULTS: The CIK cells were shown to be a heterogeneous population with different cellular phenotypes. The percentage of CD3+/CD56+ positive cells, the dominant effector cells, in total CIK cells from healthy donors and HCC patients, significantly increased from 0.1-0.13% at day 0 to 19.0-20.5% at day 21 incubation, which suggested that the CD3+ CD56+ positive cells proliferated faster than other cell populations of CIK cells in the protocol used in this study. After 28 day in vitro incubation, the CIK cells from patients with HCC and healthy donors increased by more than 300-fold and 500-fold in proliferation cell number, respectively. CIK cells originated from HCC patients possessed a higher in vitro antitumor cytotoxic activity on autologous HCC cells than the autologous lymphokine-activated killer (LAK) cells and PBMC cells. In in vivo animal experiment, CIK cells had stronger effects on the inhibition of tumor growth in Balb/c nude mice bearing BEL-7402-producing tumor than LAK cells (mean inhibitory rate, 84.7% vs 52.8%, P【0.05) or PBMC (mean inhibitory rate, 84.7% vs 37.1%, P【0.01). CONCLUSION: Autologous CIK cells are of highly efficient cytotoxic effector cells against primary hepatocellular carcinoma cells and might 展开更多
基金Supported by The American Association for the Study of Liver Disease(AASLD) Foundation to Dr.VanWagner LB
文摘AIM: To review the effectiveness of exercise as a therapy for nonalcoholic fatty liver disease(NAFLD) and potential benefits in treating insulin resistance and atherosclerosis.METHODS: Medline(EBSCOhost) and Pub Med were searched for English-language randomized controlled trials and prospective cohort studies in human adults aged ≥ 18 which investigated the various effects of exercise alone, a combination of exercise and diet, or exercise and diet coupled with behavioral modification on NAFLD from 2010 to Feburary 2015.RESULTS: Eighteen of 2298 available studies were chosen for critical review, which included 6925 patients. Nine(50%) studies were randomized controlled trials. Five(27.8%) studies utilized biopsy to examine the effects of physical activity on hepatic histology. The most commonly employed imaging modality to determine change in hepatic steatosis was hydrogen-magnetic resonance spectroscopy. Only two studies examined the effects of low impact physical activity for patients with significant mobility limitations and one compared the efficacy of aerobic and resistance exercise. No studies examined the exact duration of exercise required for hepatic and metabolic improvement in NAFLD.CONCLUSION: While exercise improved hepatic steatosis and underlying metabolic abnormalities in NAFLD, more studies are needed to define the most beneficial form and duration of exercise treatment.
文摘In the recent decades, the incidence of hepatocellular carcinoma (HCC) has been found to be increasing in males in some countries. In China, HCC ranked second of cancer mortality since 1990s. Hepatitis B and C viruses (HBV and HCV) and dietary aflatoxin intake remain the major causative factors of HCC. Surgery plays a major role in the treatment of HCC, particularly for small HCC. Downstaging unresectable huge HCC to smaller HCC and followed by resection will probably be a new approach for further study. Liver transplantation is indicated for small HCC, however, some issues remain to be solved.Different modes of 'regional cancer therapy for HCC' have been tried. Systemic chemotherapy has been disappointing in the past but the future can be promising.Biotherapy, such as cytokines, differentiation inducers,anti-angiogenic agents, gene therapy and tumor vaccine will probably play a role, particularly in the prevention of tumor recurrence. HCC invasiveness is currently the major target of study. Tremendous works have been done at the molecular level, which will provide clues for biomarker of HCC progressionas well as targets for intervention.
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.
文摘The prognosis of hepatocellular carcinoma (HCC) still remains dismal, although many advances in its clinical study have been made. It is important for tumor control to identify the factors that predispose patients to death. With new discoveries in cancer biology, the pathological and biological prognostic factors of HCC have been studied quite extensively. Analyzing molecular markers (biomarkers) with prognostic significance is a complementary method. A large number of molecular factors have been shown to associate with the invasiveness of HCC, and have potential prognostic significance. One important aspect is the analysis of molecular markers for the cellular malignancy phenotype. These include alterations in DNA ploidy, cellular proliferation markers (PCNA, Ki-67, Mcm2, MIB1, MIA, and CSE1L/CAS protein), nuclear morphology, the p53 gene and its related molecule MD M2, other cell cycle regulators (cyclin A, cyclin D, cyclin E, cdc2, p27, p73), oncogenes and their receptors (such as ras, c-myc, c-fms, HGF, c-met, and erb-B receptor family members), apoptosis related factors (Fas and FasL), as well as telomerase activity. Another important aspect is the analysis of molecular markers involved in the process of cancer invasion and metastasis. Adhesion molecules (E-cadherin, catenins, serum intercellular adhesion molecule-1, CD44 variants), proteinases involved in the degradation of extracellular matrix (MMP-2, MMP-9, uPA, uPAR, PAI), as well as other molecules have been regarded as biomarkers for the malignant phenotype of HCC, and are related to prognosis and therapeutic outcomes. Tumor angiogenesis is critical to both the growth and metastasis of cancers including HCC, and has drawn much attention in recent years. Many angiogenesis-related markers, such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet-derived endothelial cell growth factor (PD-ECGF), thrombospondin (TSP), angiogenin, pleiotrophin, and endostatin (ES) levels, as well as intratumor microvessel density (M
基金supported by National Natural Science Foundation of China(No.81602931)Ministry of Science and Technology(No.2014FY121100)State Key Projects Specialized on Infectious Diseases(No.2012ZX10002008)
文摘Objective: Liver cancer is one of the most common cancers and major cause of cancer deaths in China,which accounts for over 50% of new cases and deaths worldwide.The systematic liver cancer statistics including of projection through 2030 could provide valuable information for prevention and control strategies in China,and experience for other countries.Methods: The burden of liver cancer in China in 2014 was estimated using 339 cancer registries’ data selected from Chinese National Cancer Center(NCC).Incident cases of 22 cancer registries were applied for temporal trends from 2000 to 2014.The burden of liver cancer through 2030 was projected using age-period-cohort model.Results: About 364,800 new cases of liver cancer(268,900 males and 95,900 females) occurred in China,and about 318,800 liver cancer deaths(233,500 males and 85,300 females) in 2014.Western regions of China had the highest incidence and mortality rates.Incidence and mortality rates decreased by about 2.3% and 2.6% per year during the period of 2000-2014,respectively,and would decrease by more than 44% between 2014 and 2030 in China.The young generation,particularly for those aged under 40 years,showed a faster down trend.Conclusions: Based on the analysis,incidence and mortality rates of liver cancer are expected to decrease through 2030,but the burden of liver cancer is still serious in China,especially in rural and western areas.Most cases of liver cancer in China can be prevented through vaccination and more prevention efforts should be focused on high risk groups.
基金Supported by the National Natural Science Foundation of China,No.81300251
文摘Liver fibrosis is a reversible wound-healing process aimed at maintaining organ integrity, and presents as the critical pre-stage of liver cirrhosis, which will eventually progress to hepatocellular carcinoma in the absence of liver transplantation. Fibrosis generally results from chronic hepatic injury caused by various factors, mainly viral infection, schistosomiasis, and alcoholism; however, the exact pathological mechanisms are still unknown. Although numerous drugs have been shown to have antifibrotic activity in vitro and in animal models, none of these drugs have been shown to be efficacious in the clinic. Importantly, hepatic stellate cells(HSCs) play a key role in the initiation, progression, and regression of liver fibrosis by secreting fibrogenic factors that encourage portal fibrocytes, fibroblasts, and bone marrow-derived myofibroblasts to produce collagen and thereby propagate fibrosis. These cells are subject to intricate cross-talk with adjacent cells, resulting in scarring and subsequent liver damage. Thus, an understanding of the molecular mechanisms of liver fibrosis and their relationships with HSCs is essential for the discovery of new therapeutic targets. This comprehensive review outlines the role of HSCs in liver fibrosis and details novel strategies to suppress HSC activity, thereby providing new insights into potential treatments for liver fibrosis.
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.
文摘AIM: To investigate the relationship between the economy and the adult prevalence of fatty liver disease(FLD) in China's Mainland. METHODS: Literature searches on the Pub Med and Chinese National Knowledge Infrastructure databases were performed to identify eligible studies published before July 2014. Records were limited to crosssectional surveys or baseline surveys of longitudinal studies that reported the adult prevalence of FLD and recruited subjects from the general population or community. The gross domestic product(GDP) per capita was chosen to assess the economic status. Multiple linear regression and Loess regression were chosen to fit the data and calculate the 95%CIs. Fitting and overfitting of the models were considered in choosing the appropriate models. RESULTS: There were 27 population-based surveys from 26 articles included in this study. The pooled mean prevalence of FLD in China was 16.73%(95%CI: 13.92%-19.53%). The prevalence of FLD was correlated with the GDP per capita and survey years in the country(adjusted R2 = 0.8736, P GDP per capita = 0.00426, P years = 0.0000394), as well as in coastal areas(R2 = 0.9196, P GDP per capita = 0.00241, P years = 0.00281). Furthermore, males [19.28%(95%CI: 15.68%-22.88%)] presented a higher prevalence than females [14.1%(95%CI: 11.42%-16.61%), P = 0.0071], especially in coastal areas [21.82(95%CI: 17.94%-25.71%) vs 17.01%(95%CI: 14.30%-19.89%), P = 0.0157]. Finally, the prevalence was predicted to reach 20.21% in 2020, increasing at a rate of 0.594% per year. CONCLUSION: This study reveals a correlation between the economy and the prevalence of FLD in China's Mainland.
基金Supported by a Grant from Guangzhou Health Bureau Project, No. 2004-Z001
文摘AIM: To investigate the population-based prevalence of fatty liver disease (FLD) and its risk factors in Guangdong Province,China. METHODS: A cross-sectional survey with multiple-stage stratified cluster and random sampling of inhabitants over 7-year-old was performed in 6 urban and rural areas of Guangdong Province,China. Questionnaires,designed by co-working of epidemiologists and hepatologists,included demographic characteristics,current medication use,medical history and health-relevant behaviors,i.e. alcohol consumption,smoking habits,dietary habits and physical activities. Anthropometric measurements,biochemical tests and abdominal ultrasonography were carried out. RESULTS: Among the 3543 subjects,609 (17.2%) were diagnosed having FLD (18.0% males,16.7% females,P > 0.05). Among them,the prevalence of confirmed alcoholic liver disease (ALD),suspected ALD and nonalcoholic fatty liver disease (NAFLD) were 0.4%,1.8%,and 15.0%,respectively. The prevalence rate (23.0%) was significantly higher in urban areas than (12.9%) in rural areas. After adjustment for age,gender and residency,the standardized prevalence of FLD in adults was 14.5%. Among them,confirmed ALD,suspected ALD and NAFLD were 0.5%,2.3%,and 11.7%,respectively,in adults and 1.3% (all NAFLD) in children at the age of 7-18 years. The overall prevalence of FLD increased with age in both genders to the peak of 27.4% in the group of subjects at the age of 60-70 years. The prevalence rate was significantly higher in men than in women under the age of 50 years (22.4% vs 7.1%,P < 0.001). However,the opposite phenomenon was found over the age of 50 years (20.6% vs 27.6%,P < 0.05). Multivariate and logistic regression analysis indicated that male gender,urban residency,low education,high blood pressure,body mass index,waist circumference,waist to hip ratio,serum triglyceride and glucose levels were the risk factors for FLD. CONCLUSION: FLD,especially NAFLD,is prevalent in South China. There are many risk factors for FLD.
基金Supported by The National Key Research and Development Program of China,No.2016YFC1305301
文摘Nonalcoholic fatty liver disease(NAFLD) has become the dominant form of chronic liver disease in children and adolescents with the increasing prevalence of obesity worldwide. NAFLD represents a wide spectrum of conditions, ranging from fatty liver-which generally follows a benign, non-progressive clinical course-to non-alcoholic steatohepatitis, a subset of NAFLD that may progress to cirrhosis and end-stage liver disease or liver carcinoma. The underlying pathophysiological mechanism of "pediatric" NAFLD remains unclear, although it is strongly associated with obesity and insulin resistance. In this review we provide a general overview on the current understanding of NAFLD in children and adolescents, which underpins practice, enabling early diagnosis and appropriate therapeutic intervention for this life-threatening liver disease.
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.
基金Science and Technology Development Foundation of Beijing Institute of Infectious Diseases,No.01 Z094
文摘AIM: To characterize the anticancer function of cytokine-induced killer cells (CIK) and develop an adoptive immunotherapy for the patients with primary hepatocellular carcinoma (HCC), we evaluated the proliferation rate, phenotype and the antitumor activity of human CIK cells from healthy donors and HCC patients in vitro and in vivo. METHODS: Peripheral blood mononuclear cells (PBMC) from healthy donors and patients with primary HCC were incubated in vitro and induced into CIK cells in the presence of various cytokines such as interferon-gamma (IFN-gamma), interleukin-1 (IL-1), IL-2 and monoclonal antibody (mAb) against CD3. The phenotype and characterization of CIK cells were identified by flow cytometric analysis. The cytotoxicity of CIK cells was determined by (51)Cr release assay. RESULTS: The CIK cells were shown to be a heterogeneous population with different cellular phenotypes. The percentage of CD3+/CD56+ positive cells, the dominant effector cells, in total CIK cells from healthy donors and HCC patients, significantly increased from 0.1-0.13% at day 0 to 19.0-20.5% at day 21 incubation, which suggested that the CD3+ CD56+ positive cells proliferated faster than other cell populations of CIK cells in the protocol used in this study. After 28 day in vitro incubation, the CIK cells from patients with HCC and healthy donors increased by more than 300-fold and 500-fold in proliferation cell number, respectively. CIK cells originated from HCC patients possessed a higher in vitro antitumor cytotoxic activity on autologous HCC cells than the autologous lymphokine-activated killer (LAK) cells and PBMC cells. In in vivo animal experiment, CIK cells had stronger effects on the inhibition of tumor growth in Balb/c nude mice bearing BEL-7402-producing tumor than LAK cells (mean inhibitory rate, 84.7% vs 52.8%, P【0.05) or PBMC (mean inhibitory rate, 84.7% vs 37.1%, P【0.01). CONCLUSION: Autologous CIK cells are of highly efficient cytotoxic effector cells against primary hepatocellular carcinoma cells and might
