BACKGROUND:The first priority in treating fibrosis is to eliminate the causes that result in liver injury,e.g.,hepatitis B and C virus.However,in many liver diseases the cause is either unknown or untreatable.The pres...BACKGROUND:The first priority in treating fibrosis is to eliminate the causes that result in liver injury,e.g.,hepatitis B and C virus.However,in many liver diseases the cause is either unknown or untreatable.The present study was designed to investigate the long-term antifibrotic effect of interferon-gamma(IFN-γ)treatment in patients chronically infected with hepatitis B virus. METHODS:A total of 42 patients,30 treated with IFN-γand 12 controls,were enrolled from an original clinical trial(Clin Gastroenterol Hepatol 2005;3:819.).Three serial liver biopsies that were obtained at the initiation and end of IFN-γtreatment as well as 4 to 6 years after treatment discontinuation were assessed according to the modified Chevallier scoring system. RESULTS:Twenty-five out of 30 IFN-γ-treated patients were followed up until 4 to 6 years after the treatment was stopped. However,all controls were excluded from follow-up due to death,loss and elevated virus level within 2 years.Twenty-five IFN-γ-treated patients had stable serum liver function and liver fibrosis indices without any further antiviral or anti-fibrotic treatment.Improved inflammatory and fibrotic scores were found after nine months of IFN-γtreatment according to the modified Chevallier scoring system(inflammation:11.8±6.5 at the beginning of IFN-γtreatment vs.9.2±4.1 after 9 months, P<0.05;fibrosis:15.0±7.3 at baseline vs.12.6±6.8 after 9 months, P<0.05).Among them,14 patients accepted a third serial liver biopsy 4 to 6 years after treatment discontinuation,and the fibrotic score was increased(14.2±8.3 vs.11.9±7.6 after 9 months, P<0.05). CONCLUSIONS:Nine-month IFN-γtreatment significantly improves the fibrosis score in patients with chronic HBV infection.The majority of patients demonstrate stable serum biochemical indices and quality of life.However,they do not show a long-term benefit according to histological criteria. Given the limited sample size,long-term IFN-γtreatment regimens should be assessed in further clinical trials.展开更多
AIM: To analyse the influence of Smad7, antagonist of transforming growth factor (TGF)-β canonical signaling pathways on hepatic stellate cell (HSC) transdifferentia-tion in detail. METHODS: We systematically analyse...AIM: To analyse the influence of Smad7, antagonist of transforming growth factor (TGF)-β canonical signaling pathways on hepatic stellate cell (HSC) transdifferentia-tion in detail. METHODS: We systematically analysed genes regulated by TGF-β/Smad7 in activated HSCs by microarray analy-sis and validated the results using real time polymerase chain reaction and Western blotting analysis. RESULTS: We identif ied 100 known and unknown tar-gets underlying the regulation of Smad7 expression and delineated 8 gene ontology groups. Hk2, involved in glycolysis, was one of the most downregulated proteins, while BMP2, activator of the Smad1/5/8 pathway, was extremely upregulated by Smad7. However, BMP2 de-pendent Smad1 activation could be inhibited in vitro by Smad7 overexpression in HSCs. CONCLUSION: We conclude (1) the existence of a tight crosstalk of TGF-β and BMP2 pathways in HSCs and (2) a Smad7 dependently decreased sugar metabolism ameliorates HSC activation probably by energy with-drawal.展开更多
Fibroblast growth factor 23(FGF23)is an osteocyte-and osteoblast-derived hormone that primarily regulates phosphate and vitamin D metabolism.Circulatory FGF23 levels are abnormally increased in pathological conditions...Fibroblast growth factor 23(FGF23)is an osteocyte-and osteoblast-derived hormone that primarily regulates phosphate and vitamin D metabolism.Circulatory FGF23 levels are abnormally increased in pathological conditions like acute or chronic kidney injury,resulting in disease progression as well as increased rates of morbidity and mortality.^(1) However,FGF23 production in acute liver injury is not fully investigated.In this study.展开更多
基金supported by Else-Krner Fresenius(H.L.W.,S.D.)Returned Overseas Chinese Scholars,State Education Ministry(SRF for ROCS,SEM,J20050337491010-G50523),China(H.L.W)Zhejiang Administration of Traditional Chinese Medicine(2009CA053)
文摘BACKGROUND:The first priority in treating fibrosis is to eliminate the causes that result in liver injury,e.g.,hepatitis B and C virus.However,in many liver diseases the cause is either unknown or untreatable.The present study was designed to investigate the long-term antifibrotic effect of interferon-gamma(IFN-γ)treatment in patients chronically infected with hepatitis B virus. METHODS:A total of 42 patients,30 treated with IFN-γand 12 controls,were enrolled from an original clinical trial(Clin Gastroenterol Hepatol 2005;3:819.).Three serial liver biopsies that were obtained at the initiation and end of IFN-γtreatment as well as 4 to 6 years after treatment discontinuation were assessed according to the modified Chevallier scoring system. RESULTS:Twenty-five out of 30 IFN-γ-treated patients were followed up until 4 to 6 years after the treatment was stopped. However,all controls were excluded from follow-up due to death,loss and elevated virus level within 2 years.Twenty-five IFN-γ-treated patients had stable serum liver function and liver fibrosis indices without any further antiviral or anti-fibrotic treatment.Improved inflammatory and fibrotic scores were found after nine months of IFN-γtreatment according to the modified Chevallier scoring system(inflammation:11.8±6.5 at the beginning of IFN-γtreatment vs.9.2±4.1 after 9 months, P<0.05;fibrosis:15.0±7.3 at baseline vs.12.6±6.8 after 9 months, P<0.05).Among them,14 patients accepted a third serial liver biopsy 4 to 6 years after treatment discontinuation,and the fibrotic score was increased(14.2±8.3 vs.11.9±7.6 after 9 months, P<0.05). CONCLUSIONS:Nine-month IFN-γtreatment significantly improves the fibrosis score in patients with chronic HBV infection.The majority of patients demonstrate stable serum biochemical indices and quality of life.However,they do not show a long-term benefit according to histological criteria. Given the limited sample size,long-term IFN-γtreatment regimens should be assessed in further clinical trials.
基金Supported by Deutsche Forschungsgemeinschaft DO373/6-1 and SFB TRR77,BMBF (HepatoSys), European Research Advisory Board and the Schlieben-Lange-Programm of the Ministerium für Wissenschaft, Forschung und Kunst of Baden-Württemberg and the Europflische Sozialfond
文摘AIM: To analyse the influence of Smad7, antagonist of transforming growth factor (TGF)-β canonical signaling pathways on hepatic stellate cell (HSC) transdifferentia-tion in detail. METHODS: We systematically analysed genes regulated by TGF-β/Smad7 in activated HSCs by microarray analy-sis and validated the results using real time polymerase chain reaction and Western blotting analysis. RESULTS: We identif ied 100 known and unknown tar-gets underlying the regulation of Smad7 expression and delineated 8 gene ontology groups. Hk2, involved in glycolysis, was one of the most downregulated proteins, while BMP2, activator of the Smad1/5/8 pathway, was extremely upregulated by Smad7. However, BMP2 de-pendent Smad1 activation could be inhibited in vitro by Smad7 overexpression in HSCs. CONCLUSION: We conclude (1) the existence of a tight crosstalk of TGF-β and BMP2 pathways in HSCs and (2) a Smad7 dependently decreased sugar metabolism ameliorates HSC activation probably by energy with-drawal.
基金supported by the National Research Foundation(NRF)basic science research program Korean government(Ministry of Science and ICT),Republic of Korea(No.2020R1A6A3A01096145,2020)(No.NRF-2019R1C1C1005319,2019)(No.NRF-2017R1A6A3A04006167,2017)(No.NRF-2020R1A2C3006952,2020)and(No.NRF-2021R1A2C3004923,2021)The Federal Ministry of Education and Research-Liver Systems Medicine Program of the Stiftung für Biomedizinische Alkoholforschung,Germany(No.PTJ-031L0043).
文摘Fibroblast growth factor 23(FGF23)is an osteocyte-and osteoblast-derived hormone that primarily regulates phosphate and vitamin D metabolism.Circulatory FGF23 levels are abnormally increased in pathological conditions like acute or chronic kidney injury,resulting in disease progression as well as increased rates of morbidity and mortality.^(1) However,FGF23 production in acute liver injury is not fully investigated.In this study.
