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Insulin Resistance Inflames The Liver in HCV
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Reported by Jules Levin
EASL, April 2007, Barcelona, Spain
.....The present study showed that inflammatory activity in HCV-related chronic hepatitis is related to not only hepatic but also extra-hepatic, mainly skeletal muscle, IR. These data suggest that improvements in systemic IR by exercise and/or body fat reduction might lead to decreased inflammation in HCV-related hepatitis patients.....
"SYSTEMIC INSULIN RESISTANCE INFLUENCES HEPATIC INFLAMMATION IN PATIENTS WITH CHRONIC HEPATITIS C"
T. Mizuta 1, Y. Eguchi 1, T. Yasutake 1, K. Ario 1, S. Iwane 1, T.
Akiyama 1, Y. Ide 1, I. Ozaki 1, K. Fujimoto 1
1 Department Of Internal Medicine, Saga Medical School, Saga, Japan
Background/Aim: It is well recognized that hepatic inflammation facilitates the progression of hepatic fibrosis and the occurrence of hepatic cancer in HCV-infected patients, but little is known about the factors associated with hepatic inflammation. Recent studies have indicated that insulin resistance (IR) might be an important factor related to hepatic fibrogenesis and carcinogenesis. The purpose of this study was to determine whether hepatic or systemic IR influences
hepatic inflammation in patients with HCV-related chronic hepatitis.
Subjects/Method: One hundred and six HCV-positive chronic hepatitis patients (66 males, 40 females, mean age: 56.0±9.6, range: 26-73) who underwent liver biopsy and a 75g oral glucose tolerance test (OGTT) were included. Insulin resistance (or sensitivity) was evaluated with HOMA-IR, which indicates hepatic IR (HOMA-IR value=FPG (mg/dl) X FIRI (ľU/ml) /405), and the insulin sensitivity index (ISI) composite, which indicates whole-body, mainly skeletal muscle, insulin sensitivity (ISI composite value =10000/vFPG X FIRI X mean BS (0-120) X mean IRI (0-120)). Age, gender, glucose tolerance class, HOMA-IR, ISI composite, BMI, serum HCV core protein level, HCV genotype, serum adiponectin and leptin level, histological stage of fibrosis and grade of steatosis were analyzed for their association with serum ALT level using correlation coefficients, the Mann-Whitney U test and Kruskal-Wallis test.
Results:
Serum ALT level was correlated with HOMA-IR (r=0.375, p<0.0001) and ISI composite (r=-0.329, p=0.0005) and HCV core protein level (r=-0.274, p=0.047), but not age, BMI, and serum adiponectin or leptin level.
There was a significant difference in ALT levels according to grade of histological fibrosis (p=0.036) and steatosis (p=0.004), but not gender, glucose tolerance class, HCV genotype.
In cases with an HOMA-IR of <2, which indicates normal hepatic IR, there was a significant difference in ALT levels between cases with an ISI composite of <6 and >6 (67.3±36.4 vs. 45.2±21.0, respectively; p=0.046).
Conclusions: The present study showed that inflammatory activity in HCV-related chronic hepatitis is related to not only hepatic but also extra-hepatic, mainly skeletal muscle, IR. These data suggest that improvements in systemic IR by exercise and/or body fat reduction might lead to decreased inflammation in HCV-related hepatitis patients.
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