HGH therapy/ the case for liver/HCV/diebetic benefit,

[merryBe]

1: J Interferon Cytokine Res. 2003 May;23(5):229-35. Links
TNF-alpha and growth hormone resistance in patients with chronic liver disease.Picardi A, Gentilucci UV, Zardi EM, Caccavo D, Petitti T, Manfrini S, Pozzilli P, Afeltra A.
Laboratory of Internal Medicine and Hepatology, Interdisciplinary Center for Biomedical Research (CIR), University Campus Bio-Medico, Rome, Italy. a.***@****

Liver cirrhosis is characterized by a severe impairment of the growth hormone/insulin-like growth factor-1 (GH-IGF-1) axis, that is, acquired GH resistance. The condition of the GH-IGF-1 axis in the phase of chronic liver disease (CLD) preceding cirrhosis, however, remains uncertain. The origin of GH resistance during CLD is multifactorial, and to date, the liver functional mass is considered to play a major role. Although proinflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and IL-1beta, were found to be elevated in patients with CLD and were shown to induce a state of GH resistance in other disease models, their involvement in the pathogenesis of GH resistance during CLD has never been investigated. We characterized the GH-IGF-1 axis by analyzing the individual components of the axis (GH, IGF-1, IGF-binding protein-3 [IGFBP-3], acid-labile subunit [ALS]) and the corresponding ratios (GH/IGF-1, GH/IGFBP-3, and GH/ALS) and verified the links with circulating proinflammatory cytokines (TNF-alpha, IL-1beta, and IL-6), in 34 patients with CLD and 12 healthy controls. Evolution of CLD from chronic hepatitis (CH, n = 17) to cirrhosis (CIR, n = 17) was associated with a progressive increase of GH resistance indices (e.g., GH/IGF-1 ratio: controls 0.5 +/- 0.9, CH 15.9 +/- 31.2, p < 0.01 vs. controls; CIR 188.4 +/- 282.7 mU/nmol, p < 0.001 vs. CH and controls), indicating its onset also in the early stages of CLD. The progressive increase in GH resistance indices matched the increase of circulatory TNF-alpha (e.g., TNF-alpha vs. GH/IGF-1, r = 0.54, p < 0.001). A similar trend was found for IL-6 without reaching statistical significance (r = 0.23, p = 0.13). We found undetectable levels of IL-1beta in our sample of patients and controls. We conclude that proinflammatory cytokines play an important role in the pathogenesis of GH resistance in CLD, but TNF-alpha is a major factor. In addition, GH resistance is present in CLD from the early stages. These results could begin new therapeutic lines of attack in the management of CLD.

[merryBe]

Diabetes in chronic liver disease: from old concepts to new evidence.
Picardi A, D'Avola D, Gentilucci UV, Galati G, Fiori E, Spataro S, Afeltra A.
Internal Medicine and Hepatology Laboratory, Center of Interdisciplinary Investigations CIR, University Campus Bio-Medico of Rome, Via E. Longoni 83, I-00155 Rome, Italy. a.***@****
The liver is one of the principal organs involved in glucose metabolism together with skeletal muscle and adipose tissue. A link between diabetes and chronic liver disease (CLD) was first observed in the early half of the last century, but to date several questions remain unsolved. Altered glucose tolerance has been well described in alcoholic CLD, non-alcoholic fatty liver disease, chronic hepatitis C and portal hypertension. Moreover, insulin resistance is assuming an ever-growing importance in CLD; chronic hepatitis C has recently been proposed as a metabolic disease and insulin sensitivity as a predictive factor for liver fibrosis.CLD is also complicated by acquired growth hormone (GH) resistance, characterized by low concentrations of insulin-like growth factor-1 (IGF-1) with respect to normal or elevated GH levels. GH resistance in CLD is determined by several factors, including malnutrition, impaired liver function and reduced expression of hepatic GH receptors. We recently described the possible role of tumour necrosis factor-alpha (TNF-alpha) in blunting the hepatic response to GH in patients with chronic hepatitis C. The role of GH in impaired glucose metabolism is well known, and recent evidence suggests a receptor and/or post-receptor modulation of insulin signalling. Moreover, as in other chronic inflammatory conditions, pro-inflammatory cytokines may directly modulate the signal cascade that follows insulin binding to its receptor in the course of CLD.In this review, the proposed links between impaired glucose tolerance and CLD are analysed, special emphasis being focussed on the most recent findings concerning the interplay of chronic inflammation, GH resistance and insulin resistance. Copyright (c) 2006 John Wiley & Sons, Ltd.