Patients presenting with abdominal pain and diarrhea are often labelled as suffering from irritable bowel syndrome,and medications may be used often without success. Advances in the understanding of the causes of the ...Patients presenting with abdominal pain and diarrhea are often labelled as suffering from irritable bowel syndrome,and medications may be used often without success. Advances in the understanding of the causes of the symptoms(including pelvic floor weakness and incontinence,bile salt malabsorption and food intolerance) mean that effective,safe and well tolerated treatments are now available.展开更多
Primary sclerosing cholangitis(PSC)is an orphan,cholestatic liver disease that is characterized by inflammatory biliary strictures with variable progression to end-stage liver disease.Its pathophysiology is poorly und...Primary sclerosing cholangitis(PSC)is an orphan,cholestatic liver disease that is characterized by inflammatory biliary strictures with variable progression to end-stage liver disease.Its pathophysiology is poorly understood.Chronic biliary inflammation is likely driven by immune dysregulation,gut dysbiosis,and environmental exposures resulting in gutliver crosstalk and bile acid metabolism disturbances.There is no proven medical therapy that alters disease progression in PSC,with the commonly prescribed ursodeoxycholic acid being shown to improve liver biochemistry at low-moderate doses(15–23 mg/kg/day)but not alter transplant-free survival or liver-related outcomes.Liver transplantation is the only option for patients who develop end-stage liver disease or refractory complications of PSC.Immunosuppressive and antifibrotic agents have not proven to be effective,but there is promise for manipulation of the gut microbiome with fecal microbiota transplantation and antibiotics.Bile acid manipulation via alternate synthetic bile acids such as norursodeoxycholic acid,or interaction at a transcriptional level via nuclear receptor agonists and fibrates have shown potential in phase II trials in PSC with several leading to larger phase III trials.In view of the enhanced malignancy risk,statins,and aspirin show potential for reducing the risk of colorectal cancer and cholangiocarcinoma in PSC patients.For patients who develop clinically relevant strictures with cholestatic symptoms and worsening liver function,balloon dilatation is safer compared with biliary stent insertion with equivalent clinical efficacy.展开更多
文摘Patients presenting with abdominal pain and diarrhea are often labelled as suffering from irritable bowel syndrome,and medications may be used often without success. Advances in the understanding of the causes of the symptoms(including pelvic floor weakness and incontinence,bile salt malabsorption and food intolerance) mean that effective,safe and well tolerated treatments are now available.
基金supported by an Australian Government Research Training Program(RTP)Scholarship and a research grant from Dr Falk Pharma.
文摘Primary sclerosing cholangitis(PSC)is an orphan,cholestatic liver disease that is characterized by inflammatory biliary strictures with variable progression to end-stage liver disease.Its pathophysiology is poorly understood.Chronic biliary inflammation is likely driven by immune dysregulation,gut dysbiosis,and environmental exposures resulting in gutliver crosstalk and bile acid metabolism disturbances.There is no proven medical therapy that alters disease progression in PSC,with the commonly prescribed ursodeoxycholic acid being shown to improve liver biochemistry at low-moderate doses(15–23 mg/kg/day)but not alter transplant-free survival or liver-related outcomes.Liver transplantation is the only option for patients who develop end-stage liver disease or refractory complications of PSC.Immunosuppressive and antifibrotic agents have not proven to be effective,but there is promise for manipulation of the gut microbiome with fecal microbiota transplantation and antibiotics.Bile acid manipulation via alternate synthetic bile acids such as norursodeoxycholic acid,or interaction at a transcriptional level via nuclear receptor agonists and fibrates have shown potential in phase II trials in PSC with several leading to larger phase III trials.In view of the enhanced malignancy risk,statins,and aspirin show potential for reducing the risk of colorectal cancer and cholangiocarcinoma in PSC patients.For patients who develop clinically relevant strictures with cholestatic symptoms and worsening liver function,balloon dilatation is safer compared with biliary stent insertion with equivalent clinical efficacy.
