Bone disease in patients with cirrhosis of different etiology and severity; are Klotho protein and osteoprotegerin potential biomarkers?

BACKGROUND AND AIMS: Cirrhosis is associated with increased risk for osteoporosis and osteopenia. This study aims to further investigate this relationship by examining if etiology and severity of cirrhosis are independent predictors of bone mineral density (BMD) loss. Furthermore we examined the serum levels of osteoprotegerin (OPG) and Klotho proteins that have been involved in bone metabolism. METHODS: Seventy-four patients with cirrhosis of different etiology and 25 matched healthy controls were included in this study. Bone mineral densitometry at both lumbar spine and femoral neck was measured. Serum total OPG, Klotho protein and vitamin D levels were also determined. Comparisons were performed according to etiology and severity of cirrhosis. RESULTS: Decreased bone density was observed in cirrhotic patients compared to healthy controls with T = -1.46 and T = -1.37 in lumbar spine and femoral bone respectively compared to T = -0.396 and T = -0.672 in the control group. In the cirrhotic group, osteopenia was observed in 46% in lumbar spine and 51% in femoral bone whereas osteoporosis was observed in 20% in lumbar spine and 9% in femoral bone. Decreased bone density was confirmed, regardless of cirrhosis etiology or stage of liver function. Patients were found to have higher levels of OPG than the control group (136 pg/ml vs. 67 pg/ml, p < 0.001), but lower levels of Klotho protein (1051 pg/ml vs. 1842 pg/ml, p < 0.001) regardless etiology and severity of cirrhosis. High OPG levels were found to be associated with low femoral bone density. CONCLUSIONS: BMD is lower in cirrhotic patients regardless etiology and severity of liver disease with osteopenia and osteoporosis be present in 50% and 20%, respectively. Higher levels of OPG and lower levels of Klotho protein were observed in cirrhotic patients regardless etiology and severity in comparison to matched healthy group.

The burden and recent epidemiological changes of the main chronic liver diseases in a Greek referral tertiary centre.

OBJECTIVE: To investigate the burden and recent epidemiological changes of the main chronic liver diseases in a Greek referral tertiary centre. METHODS: We evaluated the main epidemiological characteristics of 1080 consecutive adult patients, seen at our outpatient liver clinic between 2002 and 2007, with chronic hepatitis B (HBV) and/or C (HCV) virus infection, alcoholic liver disease (ALD) or nonalcoholic fatty liver disease (NAFLD). Our patient population was divided into two groups in relation to the time of the first visit (period A: 2002-2004, period B: 2005-2007). RESULTS: Among our patient population, 86.1% had chronic HBV and/or HCV infection (chronic HCV alone: 44.9%), 9.2% NAFLD and 4.8% ALD. From period A to B, there was a decrease in chronic HBV cases (44.0 vs. 37.8%, P = 0.045) with immigrants being responsible for 35.5% of them and being more frequent in period B than A (39.7 vs. 30.5%, P = 0.046). In chronic hepatitis B, hepatitis B e antigen-positive patients, who were more frequent immigrants compared with hepatitis B e antigen-negative patients (65.5 vs. 29.5%, P = 0.001), increased from period A to B (8.0 vs. 17.6%, P = 0.045). Intravenous drug use was reported by 41.2% of HCV patients with its proportion increasing from period A to B (32.5 vs. 47.4%, P = 0.002). Decompensated cirrhosis was present in 67, 10, 11 and 3% of patients with ALD, HBV, HCV and NAFLD, respectively. CONCLUSION: At Greek tertiary centres, chronic viral hepatitis remains responsible for most chronic liver disease cases, but its epidemiology is changing owing to immigrants and intravenous drug users.

Adaptive immunity in hepatocellular carcinoma: prognostic and therapeutic implications.

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world and has a poor prognosis. Host immunity can either protect or promote tumor growth by the predominance and activation of certain subsets of immune cells. It has been established that antigens such as AFP, MAGE, glypican 3 and NY-ESO, which are highly expressed in HCC, are potential targets for T-cell responses. Several studies have come to the conclusion that cytotoxic T-cell infiltration of the tumors is indicative of a better survival, whereas the predominance of suppressor cells is associated with a worse outcome and lower survival rates. Finally, certain therapeutic strategies, including radiofrequency ablation and chemoembolization, can enhance the release and exposure of tumor antigens, which might help to overcome the immune tolerance towards the tumor. Therefore, such immune-stimulating therapeutic interventions in combination with immunotherapy strategies represent a promising future approach for HCC treatment.

Selective hepatic vascular exclusion versus Pringle maneuver in major liver resections: prospective study.

Selective hepatic vascular exclusion (SHVE) and the Pringle maneuver are two methods used to control bleeding during hepatectomy. They are compared in a prospective randomized study, where 110 patients undergoing major liver resection were randomly allocated to the SHVE group or the Pringle group. Data regarding the intraoperative and postoperative courses of the patients are analyzed. Intraoperative blood loss and transfusion requirements were significantly decreased in the SHVE group, and postoperative liver function was better in that group. Although there was no difference between the two groups regarding the postoperative complications rate, patients offered the Pringle maneuver had a significantly longer hospital stay. The application of SHVE did not prolong the warm ischemia time or the total operating time. It is evident from the present study that SHVE performed by experienced surgeons is as safe as the Pringle maneuver and is well tolerated by the patients. It is much more effective than the Pringle maneuver for controlling intraoperative bleeding, and it is associated with better postoperative liver function and shorter hospital stay.