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ABSTRACT: The renin-angiotensin system (RAS) is involved in hepatic fibrosis. To date there is no known effective treatment for hepatic fibrosis. Modulation of the RAS with angiotensin converting enzyme inhibitors and angiotensin receptor blockers may be a promising therapeutic option for the treatment of hepatic fibrosis. This review provides an update about the role of RAS in hepatic fibrosis, and treatment of hepatic fibrosis in the light of different studies in animals and humans is also updated. RAS induces key steps involved in hepatic fibrosis, such as activation of hepatic stellate cells and expression of transforming growth factor β1. Treatment with angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers attenuate fibrosis progression in both animal and human studies. Further, controlled studies are required to evaluate the role of RAS inhibitors and angiotensin-converting enzyme 2 in patients with chronic liver diseases in whom the causative agent cannot be removed.
American journal of therapeutics 11/2011; 18(6):e202-8.
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ABSTRACT: Limited data are available regarding the serum lipids in primary sclerosing cholangitis.
To determine the lipid levels in patients with primary sclerosing cholangitis.
We monitored the serum lipid levels annually for up to 6 years in 157 patients included in three previous trials of ursodeoxycholic acid.
The baseline lipid values were: total cholesterol=207 mg/dL (127-433); high-density lipoprotein=56 mg/dL (26-132); low-density lipoprotein=129 mg/dL (48-334); triglycerides=102 mg/dL (41-698). Cirrhotic stage was associated with lower levels of total cholesterol (186 mg/dL vs. 217 mg/dL, p=.02). A significant correlation between the liver biochemistries and total and low-density lipoprotein cholesterol levels was observed. Ursodeoxycholic acid, as compared to placebo, significantly decreased total (-27 mg/dL vs. 22 mg/dL, p=.0004) and low-density lipoprotein cholesterol (-24 mg/dL vs. 17 mg/dL, p=.0001). After extended follow-up, small changes in the lipid levels were noticed. The incidence of coronary artery disease was 4%.
Our findings suggest that the lipid levels in primary sclerosing cholangitis are often above levels where treatment with lipid-lowering agents is recommended. However, primary sclerosing cholangitis patients seem to have no elevated risk for cardiovascular events. The correlation of total and low-density lipoprotein cholesterol with liver biochemistries implies that mechanisms linked to cholestasis may regulate cholesterol metabolism.
Digestive and Liver Disease 09/2011; 44(1):44-8. · 3.05 Impact Factor
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ABSTRACT: Primary biliary cirrhosis (PBC) is a chronic, autoimmune, cholestatic liver disease with a slowly progressive course. Without treatment, most patients eventually develop fibrosis of the liver and may need liver transplantation in the late stage of disease. Fatigue and pruritus are the most common symptoms of PBC, but the majority of patients are asymptomatic at first presentation. There is no specific treatment for fatigue in PBC, but modafinil has shown some potential beneficial effects, such as increased energy levels and decreased total sleep time. This Review article discusses the natural history and the measurement of fatigue in patients with PBC. The central and the peripheral mechanisms that have been suggested for the pathogenesis of fatigue in PBC are also discussed and treatment options are reviewed.
Nature Reviews Gastroenterology & Hepatology 06/2010; 7(6):313-9. · 8.10 Impact Factor
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ABSTRACT: Primary biliary cirrhosis is a cholestatic liver disease that at one time was the leading indication for liver transplantation. Treatment with ursodeoxycholic acid has clearly improved the natural history of primary biliary cirrhosis.
The treatment of primary biliary cirrhosis with a focus on ursodeoxycholic acid is covered. Papers related to treatment of primary biliary cirrhosis and associated conditions, using a variety of drugs but with a focus on ursodeoxycholic acid, are included. The papers reviewed date from 1984 - 2009.
The reader will gain an up-to-date understanding of current treatment strategies for primary biliary cirrhosis using ursodeoxycholic acid and an appreciation of what conditions are improved with this therapy and what associated conditions are not.
Ursodeoxycholic acid in a dose of 13 - 15 mg/kg/day should be considered in all patients with primary biliary cirrhosis who have abnormal liver enzymes.
Expert Opinion on Pharmacotherapy 02/2010; 11(3):387-92. · 3.20 Impact Factor
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ABSTRACT: INTRODUCTION: Cholangiocarcinoma (CCA) is an aggressive and nearly always fatal tumor of the biliary tract. PURPOSE: This review explores risk factors, epidemiology, current diagnostic approaches, and treatment of CCA arising in patients with primary sclerosing cholangitis (PSC). METHODS: We review latest recommendations about screening strategies to enable the early detection of CCA in PSC, using CA 19-9 and ultrasound imaging, as well as fluorescent in situ hybridization techniques to enhance the accuracy of biliary cytology. We also review the emerging role of liver transplantation.
Journal of Gastrointestinal Cancer 09/2009; 40(1-2):19-25.
