Masumi Fujimoto

Association Between Liver Fibrosis and Insulin Sensitivity in Chronic Hepatitis C Patients

BACKGROUND:Several clinical studies have suggested a possible link between chronic hepatitis caused by hepatitis C virus (HCV) and the development of diabetes mellitus. We investigated the association between liver fibrosis and glucose intolerance in HCV-infected patients by measuring insulin sensitivity and β-cell function.METHOD:A total of 83 chronic HCV-infected patients were recruited into this study. We evaluated insulin sensitivity and β-cell function of all patients in a fasting state (homeostasis model assessment of insulin resistance [HOMA-R] and homeostasis model assessment of β-cell function [HOMA-β]) and after an oral load of 75 g glucose (whole-body insulin sensitivity index [WBISI] and Δ-insulin/Δ-glucose 30).RESULTS:In a multivariate analysis, severe fibrosis was the only independent factor associated with insulin resistance. There were significant differences in both HOMA-R (P = 0.0063) and WBISI (P = 0.0159) between patients with mild fibrosis (N = 34) and those with severe fibrosis (N = 49). Although HOMA-β was increased significantly in the subjects with severe fibrosis compared with those with mild fibrosis (P = 0.0169), Δ-insulin/Δ-glucose 30 showed no significant difference in stage of liver fibrosis, suggesting an uncertain association between liver fibrosis and β-cell function.CONCLUSION:Our findings suggest that the development of liver fibrosis is associated with insulin resistance in HCV-infected patients.

Long-term increase in liver volume after Denver peritoneovenous shunt: report of two cases

To the Editor: The Denver peritoneovenous shunt is inserted in patients with refractory ascites (1–3). The clinical efficacy of the Denver shunt has not yet been established (4–6). Whether this approach will improve survival remains controversial. We report herein the findings of a long-term observation after the Denver shunt was placed in two patients in whom liver volume increased and liver function improved. Patient 1 was a 56-year-old man diagnosed with myelodysplastic syndrome and chronic hepatitis C in 1990. Cirrhosis was diagnosed in 2003. In 2006, he presented with massive ascites. Despite a sodium-restricted diet and high doses of diuretics, ascites was not well controlled and he was therefore hospitalised in August 2006. Soon after insertion of the Denver shunt, ascites started to decrease rapidly. Six months after insertion, body weight decreased from 81 to 57 kg, serum albumin level increased from 2.5 to 3.2 g/dl and cholinesterase level incraesed from 28 to 100 IU/L. Liver volume determined by computed tomography scanning increased from a pretreatment volume of 1156 to 1238 ml (6.9%). Patient 2 was a 67-year-old man diagnosed with hepatitis C virus cirrhosis in 1991. Despite a 90 mEq sodium-restricted diet, high doses of diuretics and repeated large-volume paracentesis, ascites was not well controlled. He was hospitalised for control of ascites in February 2002. A Denver shunt was inserted in April 2002. Six months after insertion of the Denver shunt, body weight decreased from 62 to 45 kg, serum albumin level increased from 2.4 to 3.3 g/dl and cholinesterase level increased from 27 to 60 IU/ L. Twelve months after shunt insertion, liver volume increased from 1036 to 1324 ml (27%) (Fig. 1). However, 42 months after shunt insertion, he died of hepatocellular carcinoma. These two cases had decompensated cirrhosis. However, after insertion of Denver shunt, liver function improved from Child–Pugh grade C to grade A. The mechanism by which the peritoneovenous shunt improves liver function may involve haemodynamic changes. After shunt insertion, rapid mobilisation of ascitic fluid into the circulating blood volume occurs. This results in an increased plasma volume and portal vein flow, factors that may contribute to the improvement of liver function. In both cases, liver volume was increased 1 year after insertion of Denver shunt. To our knowledge, liver volume increase has not previously been reported after insertion of a peritoneovenous shunt. The mechanism remains unclear but we believe that the increase in plasma volume and portal flow may also have triggered or stimulated liver regeneration. Previous studies have reported that hepatocyte growth factor (HGF) is secreted in ascites in patients with cirrhosis (7). Thus we speculate that ascitic fluid containing HGF diverted into the venous system through the peritoneovenous shunt stimulated liver regeneration, resulting in increased liver volume. In conclusion, the Denver shunt is well tolerated and prevents re-accumulation of ascites. These findings suggest that the mechanism by