BACKGROUND Effective treatment of osteoporosis is essential for improving morbidity and health-related quality of life in chronic liver disease(CLD)patients.Denosumab has been shown to increase bone mineral density(BM...BACKGROUND Effective treatment of osteoporosis is essential for improving morbidity and health-related quality of life in chronic liver disease(CLD)patients.Denosumab has been shown to increase bone mineral density(BMD)and decrease the risk of osteoporotic fracture in the general population.However,there are few reports evaluating the efficacy of denosumab in CLD patients.AIM To investigated the effects and safety of denosumab in CLD patients with osteoporosis.METHODS Sixty CLD patients with osteoporosis were subcutaneously administered denosumab once every 6 mo.The study period for evaluating efficacy and safety was 12 mo.Changes from baseline in BMD at the lumbar spine,femoral neck,and total hip were evaluated at 12 mo of denosumab treatment.Bone turnover and quality were assessed by measuring serum tartrate-resistant acid phosphatase-5b(bone resorption marker),serum total procollagen type I N-terminal propeptide(bone formation maker),and plasma pentosidine(bone quality marker).RESULTS Among the 405 CLD patients,138(34.1%)patients were diagnosed with osteoporosis;among these,78 patients met the exclusion criteria and thus 60 patients were finally included in the present study.The median percentage changes from baseline to 12 mo of denosumab treatment in BMD at the lumbar spine,femoral neck,and total hip were+4.44%,+3.71%,and+4.03%,respectively.Denosumab significantly improved BMD,regardless of sex,patient age,and presence of liver cirrhosis.Serum tartrate-resistant acid phosphatase-5b and procollagen type I N-terminal propeptide levels constantly and significantly declined after denosumab treatment(P<0.001).Plasma pentosidine levels were also significantly lower at 12 mo of treatment(P=0.010).No patients experienced fractures and moderate-to-severe adverse events,except for transient hypocalcemia.CONCLUSION Denosumab treatment was safe and increased BMD,suppressed bone turnover,and improved bone quality marker levels in CLD patients with osteoporosis,irrespective of differences in baseline characteristics.展开更多
AIM To evaluate the therapeutic effects of ursodeoxycholic acid(UDCA)on autoimmune hepatitis(AIH).METHODS A total 136 patients who were diagnosed with AIH were included in our study.All of the patients underwent a liv...AIM To evaluate the therapeutic effects of ursodeoxycholic acid(UDCA)on autoimmune hepatitis(AIH).METHODS A total 136 patients who were diagnosed with AIH were included in our study.All of the patients underwent a liver biopsy,and had at least a probable diagnosis on the basis of either the revised scoring system or the simplified scores.Initial treatment included UDCA monotherapy(Group U,n=48)and prednisolone(PSL)monotherapy(Group P,n=88).Group U was further classified into two subgroups according to the effect of UDCA:Patients who had achieved remission induction with UDCA monotherapy and showed no sign of relapse(Subgroup U1,n=34)and patients who additionally received PSL during follow-up(Subgroup U2,n=14).We compared the clinical and histological findings between each groups,and investigated factorscontributing to the response to UDCA monotherapy.RESULTS In Group U,34 patients(71%)achieved and maintained remission over 49(range:8-90)mo(Subgroup U1)and 14 patients(29%)additionally received PSL(Subgroup U2)during follow-up.Two patients in Subgroup U2 achieved remission induction once but additionally required PSL administration because of relapse(15 and 35 mo after the start of treatment).The remaining 12 patients in Subgroup U2 failed to achieve remission induction during follow-up,and PSL was added during 7(range:2-18)mo.Compared with Subgroup U2,Subgroup U1 had significantly lower alanine aminotransferase(ALT)levels at onset(124 IU/L vs 262 IU/L,P=0.023)and a significantly higher proportion of patients with mild inflammation(A1)on histological examination(70.6%vs 35.7%,P=0.025).When multivariate analysis was performed to identify factors contributing to the response to UDCA monotherapy,only a serum ALT level of 200 IU/L or lower was found to be associated with a significant difference(P=0.013).CONCLUSION To prevent adverse events related to corticosteroids,UDCA monotherapy for AIH needs to be considered in patients with a serum ALT level of 200 IU/L or lower.展开更多
As the incidence of hepatocellular carcinoma(HCC) caused by infection with the hepatotropic viruses hepatitis B and hepatitis C decreases, greater attention has become focused on HCC caused by nonalcoholic steatohepat...As the incidence of hepatocellular carcinoma(HCC) caused by infection with the hepatotropic viruses hepatitis B and hepatitis C decreases, greater attention has become focused on HCC caused by nonalcoholic steatohepatitis(NASH), an advanced form of nonalcoholic fatty liver disease which has shown increasing prevalence in correspondence with the overall increase in metabolic syndrome over the recent decades. Several clinical population studies have shown a positive relationship between NASH and HCC, while also providing initial insights into the underlying mechanisms of HCC development from NASH. Research into the pathological progression of NASH to HCC has advanced by use of several beneficial rodent models. In this review, we summarize the established mouse models for preclinical research of NASH-associated HCC and discuss the underlying hepatic mechanisms of NASH-related tumorigenesis identified to date that could lead to new targets for treatment and prevention.展开更多
Because delayed diagnosis is one of the causes of poor prognosis in pancreatic ductal adenocarcinoma(PDAC), early detection is a key for overall improvement of prognosis. Towards this end, periodic screening is recomm...Because delayed diagnosis is one of the causes of poor prognosis in pancreatic ductal adenocarcinoma(PDAC), early detection is a key for overall improvement of prognosis. Towards this end, periodic screening is recommended for individuals considered high-risk for PDAC. Advances in diagnostic imaging modalities have increased the frequency of incidental findings of pancreatic cysts,including the intraductal papillary mucinous neoplasm(IPMN)-a major risk factor of PDAC, having 1% annual prevalence of concomitance with IPMN.Proper retainment of patients with IPMN and regular follow-up by routine imaging examination will likely improve early detection and better prognosis of PDAC. Unfortunately, current guidelines only address management of PDAC derived from IPMN and overlook PDAC concomitant with IPMN. Screening of patients with IPMN, by endoscopic ultrasonography(currently the most reliable modality for detecting small PDAC), may facilitate early detection of both IPMNderived and-concomitant PDAC. Prospective studies to evaluate the usefulness of endoscopic ultrasonography in screening of IPMN-concomitant PDAC will also help in determining the optimal surveillance strategy for more widespread applications.展开更多
文摘BACKGROUND Effective treatment of osteoporosis is essential for improving morbidity and health-related quality of life in chronic liver disease(CLD)patients.Denosumab has been shown to increase bone mineral density(BMD)and decrease the risk of osteoporotic fracture in the general population.However,there are few reports evaluating the efficacy of denosumab in CLD patients.AIM To investigated the effects and safety of denosumab in CLD patients with osteoporosis.METHODS Sixty CLD patients with osteoporosis were subcutaneously administered denosumab once every 6 mo.The study period for evaluating efficacy and safety was 12 mo.Changes from baseline in BMD at the lumbar spine,femoral neck,and total hip were evaluated at 12 mo of denosumab treatment.Bone turnover and quality were assessed by measuring serum tartrate-resistant acid phosphatase-5b(bone resorption marker),serum total procollagen type I N-terminal propeptide(bone formation maker),and plasma pentosidine(bone quality marker).RESULTS Among the 405 CLD patients,138(34.1%)patients were diagnosed with osteoporosis;among these,78 patients met the exclusion criteria and thus 60 patients were finally included in the present study.The median percentage changes from baseline to 12 mo of denosumab treatment in BMD at the lumbar spine,femoral neck,and total hip were+4.44%,+3.71%,and+4.03%,respectively.Denosumab significantly improved BMD,regardless of sex,patient age,and presence of liver cirrhosis.Serum tartrate-resistant acid phosphatase-5b and procollagen type I N-terminal propeptide levels constantly and significantly declined after denosumab treatment(P<0.001).Plasma pentosidine levels were also significantly lower at 12 mo of treatment(P=0.010).No patients experienced fractures and moderate-to-severe adverse events,except for transient hypocalcemia.CONCLUSION Denosumab treatment was safe and increased BMD,suppressed bone turnover,and improved bone quality marker levels in CLD patients with osteoporosis,irrespective of differences in baseline characteristics.
文摘AIM To evaluate the therapeutic effects of ursodeoxycholic acid(UDCA)on autoimmune hepatitis(AIH).METHODS A total 136 patients who were diagnosed with AIH were included in our study.All of the patients underwent a liver biopsy,and had at least a probable diagnosis on the basis of either the revised scoring system or the simplified scores.Initial treatment included UDCA monotherapy(Group U,n=48)and prednisolone(PSL)monotherapy(Group P,n=88).Group U was further classified into two subgroups according to the effect of UDCA:Patients who had achieved remission induction with UDCA monotherapy and showed no sign of relapse(Subgroup U1,n=34)and patients who additionally received PSL during follow-up(Subgroup U2,n=14).We compared the clinical and histological findings between each groups,and investigated factorscontributing to the response to UDCA monotherapy.RESULTS In Group U,34 patients(71%)achieved and maintained remission over 49(range:8-90)mo(Subgroup U1)and 14 patients(29%)additionally received PSL(Subgroup U2)during follow-up.Two patients in Subgroup U2 achieved remission induction once but additionally required PSL administration because of relapse(15 and 35 mo after the start of treatment).The remaining 12 patients in Subgroup U2 failed to achieve remission induction during follow-up,and PSL was added during 7(range:2-18)mo.Compared with Subgroup U2,Subgroup U1 had significantly lower alanine aminotransferase(ALT)levels at onset(124 IU/L vs 262 IU/L,P=0.023)and a significantly higher proportion of patients with mild inflammation(A1)on histological examination(70.6%vs 35.7%,P=0.025).When multivariate analysis was performed to identify factors contributing to the response to UDCA monotherapy,only a serum ALT level of 200 IU/L or lower was found to be associated with a significant difference(P=0.013).CONCLUSION To prevent adverse events related to corticosteroids,UDCA monotherapy for AIH needs to be considered in patients with a serum ALT level of 200 IU/L or lower.
文摘As the incidence of hepatocellular carcinoma(HCC) caused by infection with the hepatotropic viruses hepatitis B and hepatitis C decreases, greater attention has become focused on HCC caused by nonalcoholic steatohepatitis(NASH), an advanced form of nonalcoholic fatty liver disease which has shown increasing prevalence in correspondence with the overall increase in metabolic syndrome over the recent decades. Several clinical population studies have shown a positive relationship between NASH and HCC, while also providing initial insights into the underlying mechanisms of HCC development from NASH. Research into the pathological progression of NASH to HCC has advanced by use of several beneficial rodent models. In this review, we summarize the established mouse models for preclinical research of NASH-associated HCC and discuss the underlying hepatic mechanisms of NASH-related tumorigenesis identified to date that could lead to new targets for treatment and prevention.
文摘Because delayed diagnosis is one of the causes of poor prognosis in pancreatic ductal adenocarcinoma(PDAC), early detection is a key for overall improvement of prognosis. Towards this end, periodic screening is recommended for individuals considered high-risk for PDAC. Advances in diagnostic imaging modalities have increased the frequency of incidental findings of pancreatic cysts,including the intraductal papillary mucinous neoplasm(IPMN)-a major risk factor of PDAC, having 1% annual prevalence of concomitance with IPMN.Proper retainment of patients with IPMN and regular follow-up by routine imaging examination will likely improve early detection and better prognosis of PDAC. Unfortunately, current guidelines only address management of PDAC derived from IPMN and overlook PDAC concomitant with IPMN. Screening of patients with IPMN, by endoscopic ultrasonography(currently the most reliable modality for detecting small PDAC), may facilitate early detection of both IPMNderived and-concomitant PDAC. Prospective studies to evaluate the usefulness of endoscopic ultrasonography in screening of IPMN-concomitant PDAC will also help in determining the optimal surveillance strategy for more widespread applications.
