AIM: To analyze the associations of pancreatic fat with other fat depots and β-cell function in pediatric nonalcoholic fatty liver disease(NAFLD).METHODS: We examined 158 overweight/obese children and adolescents, 80...AIM: To analyze the associations of pancreatic fat with other fat depots and β-cell function in pediatric nonalcoholic fatty liver disease(NAFLD).METHODS: We examined 158 overweight/obese children and adolescents, 80 with NAFLD [hepatic fat fraction(HFF) ≥ 5%] and 78 without fatty liver. Visceral adipose tissue(VAT), pancreatic fat fraction(PFF) and HFF were determined by magnetic resonance imaging. Estimates of insulin sensitivity were calculated using the homeostasis model assessment of insulin resistance(HOMA-IR), defined by fasting insulin and fasting glucose and whole-body insulin sensitivity index(WBISI), based on mean values of insulin and glucose obtained from oral glucose tolerance test and the corresponding fasting values. Patients were considered to have prediabetes if they had either:(1) impaired fasting glucose, defined as a fasting glucose level ≥ 100 mg/d L to < 126 mg/d L;(2) impaired glucose tolerance, defined as a 2 h glucose concentration between ≥ 140 mg/d L and < 200 mg/d L; or(3) hemoglobin A1 c value of ≥ 5.7% to < 6.5%.RESULTS: PFF was significantly higher in NAFLD patients compared with subjects without liver involvement. PFF was significantly associated with HFF and VAT, as well as fasting insulin, C peptide, HOMA-IR, and WBISI. The association between PFF and HFF was no longer significant after adjusting for age, gender, Tanner stage, body mass index(BMI)-SD score, and VAT. In multiple regression analysis withWBISI or HOMA-IR as the dependent variables, against the covariates age, gender, Tanner stage, BMI-SD score, VAT, PFF, and HFF, the only variable significantly associated with WBISI(standardized coefficient B,-0.398; P = 0.001) as well as HOMA-IR(0.353; P = 0.003) was HFF. Children with prediabetes had higher PFF and HFF than those without. PFF and HFF were significantly associated with prediabetes after adjustment for clinical variables. When all fat depots where included in the same model, only HFF remained significantly associated with prediabetes(OR = 3.38; 95%CI: 1.10-10.4; P = 0.034).CONCLUSION: In overweight/obese children with NAFLD, pancreatic fat is increased compared with those without liver involvement. However, only liver fat is independently related to prediabetes.展开更多
AIM To investigate the impact of telaprevir-basedtriple therapy on the serum alpha-fetoprotein （AFP）level of chronic hepatitis C patients.METHODS： A total of 210 patients with chronichepatitis C genotype 1 of high ...AIM To investigate the impact of telaprevir-basedtriple therapy on the serum alpha-fetoprotein （AFP）level of chronic hepatitis C patients.METHODS： A total of 210 patients with chronichepatitis C genotype 1 of high viral load （baselineserum hepatitis C virus RNA 〉 5.0 log10 IU/mL） weredivided into two groups by type of treatment： tripletherapy with telaprevir, pegylated-interferon-α （PEGIFNα）,and ribavirin （RBV） for 24 wk （n = 88）, or dualtherapy with PEG-IFNα and RBV for 48 wk （n = 122）.The relationship between virological response and thechange in the serum AFP level from baseline to 24 wkafter the end of treatment was examined.RESULTS： No significant difference in mean baselineAFP level was found between the triple and dualtherapy groups （8.8 ng/mL vs 7.8 ng/mL）. Tripletherapy produced significant declines in the AFP levelin sustained virological response （SVR） and non-SVRpatients （7.8 ng/mL at baseline to 3.5 ng/mL at 24 wkafter the end of treatment, P 〈 0.001 and 14.3 ng/mLto 9.5 ng/mL, P = 0.004, respectively）. In contrast,dual therapy resulted in a significant decline in AFPlevel only in SVR patients （4.7 ng/mL to 2.8 ng/mL, P AbstractAIM： To investigate the impact of telaprevir-basedtriple therapy on the serum alpha-fetoprotein （AFP）level of chronic hepatitis C patients.METHODS： A total of 210 patients with chronichepatitis C genotype 1 of high viral load （baselineserum hepatitis C virus RNA 〉 5.0 log10 IU/mL） weredivided into two groups by type of treatment： tripletherapy with telaprevir, pegylated-interferon-α （PEGIFNα）,and ribavirin （RBV） for 24 wk （n = 88）, or dualtherapy with PEG-IFNα and RBV for 48 wk （n = 122）.The relationship between virological response and thechange in the serum AFP level from baseline to 24 wkafter the end of treatment was examined.RESULTS： No significant difference in mean baselineAFP level was found between the triple and dualtherapy groups （8.8 ng/mL vs 7.8 ng/mL）. Tripletherapy produced significant declines in the AFP levelin sustained virological response （SVR） and non-SVRpatients （7.8 ng/mL at baseline to 3.5 ng/mL at 24 wkafter the end of treatment, P 〈 0.001 and 14.3 ng/mLto 9.5 ng/mL, P = 0.004, respectively）. In contrast,dual therapy resulted in a significant decline in AFPlevel only in SVR patients （4.7 ng/mL to 2.8 ng/mL,展开更多
Objective To investigate the efficacy of hematopoietic stem cell(HSC) transplantation via the hepatic artery vs.the portal vein for end-stage liver disease(ESLD).Methods Patients with hepatic decompensation were prosp...Objective To investigate the efficacy of hematopoietic stem cell(HSC) transplantation via the hepatic artery vs.the portal vein for end-stage liver disease(ESLD).Methods Patients with hepatic decompensation were prospectively recruited from September 2010 to September 2012 to receive HSC transplantation via the hepatic artery or the portal vein.Liver function was examined at 3,6,and 12 months after transplantation.Liver biopsy results were analyzed using the Knodell score.Results Eighty patients(58 males and 22 females) were enrolled in the study.The Child-Pugh score was grade B in 69 cases,and grade C in the remaining 11 cases.HSC transplantation was performed via the portal vein in 36 patients and via the hepatic artery in 44 patients.ALT levels decreased while serum albumin levels increased significantly in both groups at 6 and 12 months after HSC transplantation(P<0.05 compared with pre-transplantation levels).Total bilirubin levels decreased significantly in both groups at 3,6,and 12 months after HSC transplantation(P<0.05 compared with pre-transplantation levels).Additionally,prothrombin time decreased in both groups at 12 months after HSC transplantation(P<0.05 compared with pre-transplantation level).There were no significant differences in ALT,total bilirubin and prothrombin time between the two groups either before or after transplantation.Moreover,Knodell score decreased significantly at 6 and 12 months.Histological examination showed that liver cell edema,degeneration,necrosis,and inflammation were significantly relieved at 3,6,and 12 months after transplantation.The incidence of portal vein thrombosis,upper gastrointestinal bleeding,and hepatic encephalopathy were 1.25%,3.75%,and 2.5% respectively.The one-year survival rate was 100%.Conclusions Autologous HSC transplantation improves liver function and histology in ESLD patients.The administration route of HSC has no significant impact on the efficacy of transplantation.展开更多
Chronic alcohol consumption is a major cause of liver disease.The term alcoholic liver disease(ALD)refers to a spectrum of mild to severe disorders including steatosis,steatohepatitis,cirrhosis,and hepatocellular carc...Chronic alcohol consumption is a major cause of liver disease.The term alcoholic liver disease(ALD)refers to a spectrum of mild to severe disorders including steatosis,steatohepatitis,cirrhosis,and hepatocellular carcinoma.With limited therapeutic options,stem cell therapy offers significant potential for these patients.In this article,we review the pathophysiologic features of ALD and the therapeutic mechanisms of multipotent mesenchymal stromal cells,also referred to as mesenchymal stem cells(MSCs),based on their potential to differentiate into hepatocytes,their immunomodulatory properties,their potential to promote residual hepatocyte regeneration,and their capacity to inhibit hepatic stellate cells.The perfect match between ALD pathogenesis and MSC therapeutic mechanisms,together with encouraging,available preclinical data,allow us to support the notion that MSC transplantation is a promising therapeutic strategy to manage ALD onset and progression.展开更多
AIM To establish a rat model for evaluating the maturity of liver regeneration derived from associating liver partition and portal vein ligation for staged hepatectomy(ALPPS).METHODS In the present study, ALPPS, parti...AIM To establish a rat model for evaluating the maturity of liver regeneration derived from associating liver partition and portal vein ligation for staged hepatectomy(ALPPS).METHODS In the present study, ALPPS, partial hepatecotmy(PHx), and sham rat models were established initially, which were validated by significant increase of proliferative markers including Ki-67, proliferating cell nuclear antigen, and cyclin D1. In the setting of accelerated proliferation in volume at the second and fifth day after ALPPS, the characteristics of newborn hepatocytes, as well as specific markers of progenitor hepatic cell, were identified. Afterwards, the detection of liver function followed by cluster analysis of functional gene expression were performed to evaluate the maturity.RESULTS Compared with PHx and sham groups, the proliferation of f LR was significantly higher in ALPPS group(P = 0.023 and 0.001 at second day, P = 0.034 and P < 0.001 at fifth day after stage I). Meanwhile, the increased expression of proliferative markers including Ki-67, proliferating cell nuclear antigen, and cyclin D1 verified the accelerated liver regeneration derived from ALPPS procedure. However, ALPPS-induced Sox9 positive hepatocytes significantly increased beyond the portal triad, which indicated the progenitor hepatic cell was potentially involved. And the characteristics of ALPPSinduced hepatocytes indicated the lower expression of hepatocyte nuclear factor 4 and anti-tryptase in early proliferative stage. Both suggested the immaturity of ALPPS-derived liver regeneration. Additionally, the detection of liver function and functional genes expression confirmed the immaturity of renascent hepatocytes derived in early stage of ALPPS-derived liver regeneration.CONCLUSION Our study revealed the immaturity of ALPPS-derived proliferation in early regenerative response, which indicated that the volumetric assessment overestimated the functional proliferation. This could be convincing evidence that the stage Ⅱ of ALPPS should be performed prudently in patients with marginally adequate f LR, as the ALPPS-derived proliferation in volume lags behind the functional regeneration.展开更多
基金Supported by Sapienza University of Rome(Progetti di Ricerca Universitaria 2011-2012)
文摘AIM: To analyze the associations of pancreatic fat with other fat depots and β-cell function in pediatric nonalcoholic fatty liver disease(NAFLD).METHODS: We examined 158 overweight/obese children and adolescents, 80 with NAFLD [hepatic fat fraction(HFF) ≥ 5%] and 78 without fatty liver. Visceral adipose tissue(VAT), pancreatic fat fraction(PFF) and HFF were determined by magnetic resonance imaging. Estimates of insulin sensitivity were calculated using the homeostasis model assessment of insulin resistance(HOMA-IR), defined by fasting insulin and fasting glucose and whole-body insulin sensitivity index(WBISI), based on mean values of insulin and glucose obtained from oral glucose tolerance test and the corresponding fasting values. Patients were considered to have prediabetes if they had either:(1) impaired fasting glucose, defined as a fasting glucose level ≥ 100 mg/d L to < 126 mg/d L;(2) impaired glucose tolerance, defined as a 2 h glucose concentration between ≥ 140 mg/d L and < 200 mg/d L; or(3) hemoglobin A1 c value of ≥ 5.7% to < 6.5%.RESULTS: PFF was significantly higher in NAFLD patients compared with subjects without liver involvement. PFF was significantly associated with HFF and VAT, as well as fasting insulin, C peptide, HOMA-IR, and WBISI. The association between PFF and HFF was no longer significant after adjusting for age, gender, Tanner stage, body mass index(BMI)-SD score, and VAT. In multiple regression analysis withWBISI or HOMA-IR as the dependent variables, against the covariates age, gender, Tanner stage, BMI-SD score, VAT, PFF, and HFF, the only variable significantly associated with WBISI(standardized coefficient B,-0.398; P = 0.001) as well as HOMA-IR(0.353; P = 0.003) was HFF. Children with prediabetes had higher PFF and HFF than those without. PFF and HFF were significantly associated with prediabetes after adjustment for clinical variables. When all fat depots where included in the same model, only HFF remained significantly associated with prediabetes(OR = 3.38; 95%CI: 1.10-10.4; P = 0.034).CONCLUSION: In overweight/obese children with NAFLD, pancreatic fat is increased compared with those without liver involvement. However, only liver fat is independently related to prediabetes.
基金Supported by Sapienza University of Rome(Progetti di Ricerca Universitaria 2011-2012)
文摘AIM To investigate the impact of telaprevir-basedtriple therapy on the serum alpha-fetoprotein （AFP）level of chronic hepatitis C patients.METHODS： A total of 210 patients with chronichepatitis C genotype 1 of high viral load （baselineserum hepatitis C virus RNA 〉 5.0 log10 IU/mL） weredivided into two groups by type of treatment： tripletherapy with telaprevir, pegylated-interferon-α （PEGIFNα）,and ribavirin （RBV） for 24 wk （n = 88）, or dualtherapy with PEG-IFNα and RBV for 48 wk （n = 122）.The relationship between virological response and thechange in the serum AFP level from baseline to 24 wkafter the end of treatment was examined.RESULTS： No significant difference in mean baselineAFP level was found between the triple and dualtherapy groups （8.8 ng/mL vs 7.8 ng/mL）. Tripletherapy produced significant declines in the AFP levelin sustained virological response （SVR） and non-SVRpatients （7.8 ng/mL at baseline to 3.5 ng/mL at 24 wkafter the end of treatment, P 〈 0.001 and 14.3 ng/mLto 9.5 ng/mL, P = 0.004, respectively）. In contrast,dual therapy resulted in a significant decline in AFPlevel only in SVR patients （4.7 ng/mL to 2.8 ng/mL, P AbstractAIM： To investigate the impact of telaprevir-basedtriple therapy on the serum alpha-fetoprotein （AFP）level of chronic hepatitis C patients.METHODS： A total of 210 patients with chronichepatitis C genotype 1 of high viral load （baselineserum hepatitis C virus RNA 〉 5.0 log10 IU/mL） weredivided into two groups by type of treatment： tripletherapy with telaprevir, pegylated-interferon-α （PEGIFNα）,and ribavirin （RBV） for 24 wk （n = 88）, or dualtherapy with PEG-IFNα and RBV for 48 wk （n = 122）.The relationship between virological response and thechange in the serum AFP level from baseline to 24 wkafter the end of treatment was examined.RESULTS： No significant difference in mean baselineAFP level was found between the triple and dualtherapy groups （8.8 ng/mL vs 7.8 ng/mL）. Tripletherapy produced significant declines in the AFP levelin sustained virological response （SVR） and non-SVRpatients （7.8 ng/mL at baseline to 3.5 ng/mL at 24 wkafter the end of treatment, P 〈 0.001 and 14.3 ng/mLto 9.5 ng/mL, P = 0.004, respectively）. In contrast,dual therapy resulted in a significant decline in AFPlevel only in SVR patients （4.7 ng/mL to 2.8 ng/mL,
基金Supported by the Science&Technology Department of Sichuan Province(2010FZ0098,2011HH0022)Chengdu Bureau of Science and Technology(10GGYB883SF)the Scientific Research Foundation of the Health Department of Sichuan Province(100487,100489)
文摘Objective To investigate the efficacy of hematopoietic stem cell(HSC) transplantation via the hepatic artery vs.the portal vein for end-stage liver disease(ESLD).Methods Patients with hepatic decompensation were prospectively recruited from September 2010 to September 2012 to receive HSC transplantation via the hepatic artery or the portal vein.Liver function was examined at 3,6,and 12 months after transplantation.Liver biopsy results were analyzed using the Knodell score.Results Eighty patients(58 males and 22 females) were enrolled in the study.The Child-Pugh score was grade B in 69 cases,and grade C in the remaining 11 cases.HSC transplantation was performed via the portal vein in 36 patients and via the hepatic artery in 44 patients.ALT levels decreased while serum albumin levels increased significantly in both groups at 6 and 12 months after HSC transplantation(P<0.05 compared with pre-transplantation levels).Total bilirubin levels decreased significantly in both groups at 3,6,and 12 months after HSC transplantation(P<0.05 compared with pre-transplantation levels).Additionally,prothrombin time decreased in both groups at 12 months after HSC transplantation(P<0.05 compared with pre-transplantation level).There were no significant differences in ALT,total bilirubin and prothrombin time between the two groups either before or after transplantation.Moreover,Knodell score decreased significantly at 6 and 12 months.Histological examination showed that liver cell edema,degeneration,necrosis,and inflammation were significantly relieved at 3,6,and 12 months after transplantation.The incidence of portal vein thrombosis,upper gastrointestinal bleeding,and hepatic encephalopathy were 1.25%,3.75%,and 2.5% respectively.The one-year survival rate was 100%.Conclusions Autologous HSC transplantation improves liver function and histology in ESLD patients.The administration route of HSC has no significant impact on the efficacy of transplantation.
基金Supported by No.Fondef Ca13i10088 and No.Fondecyt 1150589
文摘Chronic alcohol consumption is a major cause of liver disease.The term alcoholic liver disease(ALD)refers to a spectrum of mild to severe disorders including steatosis,steatohepatitis,cirrhosis,and hepatocellular carcinoma.With limited therapeutic options,stem cell therapy offers significant potential for these patients.In this article,we review the pathophysiologic features of ALD and the therapeutic mechanisms of multipotent mesenchymal stromal cells,also referred to as mesenchymal stem cells(MSCs),based on their potential to differentiate into hepatocytes,their immunomodulatory properties,their potential to promote residual hepatocyte regeneration,and their capacity to inhibit hepatic stellate cells.The perfect match between ALD pathogenesis and MSC therapeutic mechanisms,together with encouraging,available preclinical data,allow us to support the notion that MSC transplantation is a promising therapeutic strategy to manage ALD onset and progression.
基金Supported by the Major Scientific and Technological Project of Zhejiang Province,China,No.2015C03026
文摘AIM To establish a rat model for evaluating the maturity of liver regeneration derived from associating liver partition and portal vein ligation for staged hepatectomy(ALPPS).METHODS In the present study, ALPPS, partial hepatecotmy(PHx), and sham rat models were established initially, which were validated by significant increase of proliferative markers including Ki-67, proliferating cell nuclear antigen, and cyclin D1. In the setting of accelerated proliferation in volume at the second and fifth day after ALPPS, the characteristics of newborn hepatocytes, as well as specific markers of progenitor hepatic cell, were identified. Afterwards, the detection of liver function followed by cluster analysis of functional gene expression were performed to evaluate the maturity.RESULTS Compared with PHx and sham groups, the proliferation of f LR was significantly higher in ALPPS group(P = 0.023 and 0.001 at second day, P = 0.034 and P < 0.001 at fifth day after stage I). Meanwhile, the increased expression of proliferative markers including Ki-67, proliferating cell nuclear antigen, and cyclin D1 verified the accelerated liver regeneration derived from ALPPS procedure. However, ALPPS-induced Sox9 positive hepatocytes significantly increased beyond the portal triad, which indicated the progenitor hepatic cell was potentially involved. And the characteristics of ALPPSinduced hepatocytes indicated the lower expression of hepatocyte nuclear factor 4 and anti-tryptase in early proliferative stage. Both suggested the immaturity of ALPPS-derived liver regeneration. Additionally, the detection of liver function and functional genes expression confirmed the immaturity of renascent hepatocytes derived in early stage of ALPPS-derived liver regeneration.CONCLUSION Our study revealed the immaturity of ALPPS-derived proliferation in early regenerative response, which indicated that the volumetric assessment overestimated the functional proliferation. This could be convincing evidence that the stage Ⅱ of ALPPS should be performed prudently in patients with marginally adequate f LR, as the ALPPS-derived proliferation in volume lags behind the functional regeneration.
