Altered BANKL/OPG system in hepatic osteodystrophy

The coexistence of liver disease and metabolic bone disease has been recognized for many years and is now the subject of increasing attention. Hepatic Osteodystrophy was established in patients with cholestatic liver disease, but new research suggests that it is prevalent in patients with other chronic liver diseases. Its etiology is complex and multifactorial. Receptor activator of nuclear factor Kb ligand [RANKL] plays a role in the differentiation and activation of bone resorbing osteoclasts by binding to its high affinity receptor [RANK] located on the surface of osteoclasts. This effect is counterbalanced by osteoprotegren [OPG], which acts as a decoy receptor competing with RANKL for RANK. To evaluate bone mineral density [BMD] and OPG/RANKL system in cirrhotic patients with backache. This study included 50 subjects suffering from backache, divided into 4 groups as follows: Group I: 10 subjects with normal BMD, Group II: 10 patients with pathological BMD but otherwise healthy considered as control, Group III: 15 patients with cirrhosis and normal BMD, Group IV: 15 patients with cirrhosis and pathological BMD. All patients underwent clinical examination, routine liver function tests, alkaline phosphatase, total calcium, serum OPG, serum RANKL, added to BMD. The lowest BMD values are estimated at the lumber spine, femoral neck, and lastly lower end of radius. There was a significant decrease in OPG in osteopenic/ osteoporotic non cirrhotic patients compared to control group, while it is significantly higher than control in both osteopenic/osteoporotic and patients with normal BMD of cirrhotic groups. RANKL, was significantly higher in non cirrhotic patients with pathological BMD compared to control group, but lower than control in cirrhotic groups both with normal and pathological BMD, with significant difference in cirrhotic with pathological BMD and non significant in those with normal BMD compared to controls. Serum OPG was negatively correlated to serum calcium, albumin, and International Normalized Ratio [INR], but positively correlated to bone alkaline phosphatase, and AST in cirrhotic patients of both groups. In cirrhotic patients, low BMD has tendency to affect axial bone early, which is similar to postmenopausal osteoporosis. On the contrary, higher OPG and lower RANKL levels are opposite to postmenopausal osteoporosis. This difference indicates that: OPG/RANKL system is activated in a different way in cirrhosis, suggesting a role for OPG/RANKL system in pathogenesis of hepatic osteodystrophy

Rankl/OPG system is altered in hepatic osteodystrophy

The coexistence of liver disease and metabolic bone disease has been recognized for many years and is now the subject of increasing attention. Hepatic Osteodystrophy has been established in patients with cholestatic liver disease, but new research suggests that it is prevalent in patients with other chronic liver diseases. Its etiology is complex and multifactorial. The Receptor activator of nuclear factor Kb ligand [RANKL] plays a role in the differentiation and activation of bone resorbing osteoclasts by binding to its high affinity receptor [RANK] located on the surface of osteoclasts. This effect is counterbalanced by osteoprotegren [OPG], which acts as a decoy receptor competing with RANKL for RANK. In this study we aim to evaluate OPG/RANKL system in cirrhotic patients with backache. This study includes 50 subjects suffering backache, divided into 4 groups as follows: Group I:10 subjects with normal bone mineral density [BMD] as control, Group II: 10 patients with pathological BMD but who are otherwise healthy, Group III: 15 patients with cirrhosis and normal BMD, Group IV: 15 patients with cirrhosis and pathological BMD. All patients underwent clinical examination, routine liver function tests, alkaline phosphatase, total calcium, serum OPG, serum RANKL, added to BMD estimation. The lowest BMD values were estimated at the lumber spine, then femoral neck, and lastly lower end of radius. There was a significant decrease in OPG in osteopenic non cirrhotic patients compared to the control group, while it was significantly higher than controls in both osteopenic and non osteopenic patients of the cirrhotic groups. SRANKL was significantly higher in non cirrhotic patients with pathological BMD compared to the control group, but lower than controls in cirrhotic groups both with normal and pathological BMD, with a significant difference in cirrhotics with pathological BMD, and a non significant difference in those with normal BMD compared to controls. Serum OPG was negatively correlated to serum calcium, albumin, and INR, but positively correlated to bone alkaline phosphatase, and AST in cirrhotic patients of both groups. OPG/RANKL system plays a role in the pathogenesis of hepatic Osteodystrophy. In cirrhotic patients, low BMD has a tendency to affect axial bone earlier, which is similar to postmenopausal osteoporosis. However in cirrhosis there are higher OPG and lower sRANKL levels which are opposite to postmenopausal osteoporosis. This difference indicates that: either OPG/RANKL system is working in a different way in cirrhosis, which might be due to an increased RANK/RANKL affinity which is not measurable, and consumes part of total RANKL leaving a smaller amount of measurable soluble RANKL to be assessed, which would explain its lower level in serum despite increased osteoporotic changes in bone, or there are other factors associated with this process to make their mechanism of action different than in postmenopausal osteoporosis

Hepcidin gene expression in chronic hepatitis C patients with and without cirrhosis

The liver is the main body site for iron stores and central in the regulation of iron homeostasis. Elevated serum ferritin and hepatic iron concentrations are frequently observed in chronic hepatitis C [CHC], and may be associated with more aggressive disease and decreased responsiveness to interferon therapy. It is now established that hepcidin, a peptide hormone made in the liver, is the principal regulator of systemic iron homeostasis. Because the role of hepcidin in CHC remains unclear, we aimed in this study to generate more information about it and its role in CHC and cirrhosis caused by CHC. This work was carried out on 20 chronic liver patients with HCV infection divided into two groups: Group 1: 10 patients with chronic hepatitis C [CHC], and Group 2: 10 patients with post hepatitis C liver cirrhosis A control group of 10 age and sex matched individuals undergoing emergency abdominal surgery was also included. Hepcidin mRNA from liver biopsy samples was extracted and quantified. Hepcidin mRNA levels were then correlated with haemoglobin, serum iron, ferritin, aspartate aminotransferase, alanine aminotransferase, prothrombin time, serum albumin, bilirubin, hepatic necroinflammatory activity and fibrosis. Liver Hepcidin mRNA expression correlated significantly with serum ferritin, serum albumin, prothrombin time, and liver fibrosis staging. However it did not correlate with haemoglobin, serum iron, transferrin receptor ALT, AST or hepatic necroinflammatory scoring. Hepcidin plays a unique role in hepatitis C infection. In CHC hepcidin gene expression shows no correlation with hepatic inflammatory activity contrary to other inflammatory conditions. Hepcidin gene expression correlates with serum albumin levels and hepatic fibrosis and could therefore be considered a marker for progression of fibrosis and hepatic dysfunction. Liver hepcidin gene expression correlates with ferritin levels indicating that its increase may be in response to increased iron stores with the purpose of down regulating iron absorption. Further studies could lead to improved understanding of the pathophysiology of systemic and hepatic iron disorders, and result in improved therapy for hepatitis C