Relation between body fat and liver fat accumulation and cytokine pattern in non-alcoholic patients with chronic HCV infection.

BACKGROUND: Liver steatosis in chronic hepatitis C virus (HCV) infection is multifactorial. Therefore, there is not necessarily a relation between obesity and liver fat.On the other hand, body fat secretes cytokines, and cytokines and oxidative damage play important roles on progression of liver disease. METHODS: We analyzed the relationships between liver fat (assessed by histomorphometry) and trunk and subcutaneous fat (waist perimeter, triceps skinfold, BMI); the relationships between liver and body fat and cytokines (IL-6, TNF-alpha, IL-8, IFN-gamma, IL-4), adipokines (adiponectin and TIMP-1), and serum malondiladehyde and antioxidants (glutathione peroxidase and superoxide dismutase (SOD) activities); and the relationships of these data with histological changes in 40 HCV-infected non-alcoholic patients. RESULTS: Significant correlations were found between liver fat and waist perimeter and BMI, and between serum TIMP-1 and liver fat. Serum TIMP-1 was significantly related to body fat stores; serum IL-6 and IFN-gamma were related to histological inflammation. Patients with waist perimeter >102 cm (men) or 88 cm (women) showed increased liver fat. In 38.8% of non-obese patients, liver fat accumulation was intense. CONCLUSIONS: There is a relationship between visceral fat, serum TIMP-1 and liver steatosis. However, at least in some patients, factors different from mere adiposity play a role in liver steatosis.

Protein deficiency and muscle damage in carbon tetrachloride induced liver cirrhosis.

Protein undernutrition, alterations of hormones such as IGF-1, testosterone and cortisol, and increased lipid peroxidation-which may be related with deranged metabolism of some elements such as iron (Fe), zinc (Zn), manganese (Mn), selenium (Se) or copper (Cu)-may contribute to muscle damage in non alcoholic cirrhosis. Here, we analyse the effect of protein deficiency on muscle Cu, Fe, Zn, Mn and Se in carbon-tetrachloride (CCl(4)) induced liver cirrhosis. We also study the association between protein undernutrition and these trace elements with the activity of glutathione peroxidase (GPX), superoxide dismutase (SOD) and lipid peroxidation products, and how all these are related with muscle morphological changes in 40 male adult Sprague-Dawley rats. Liver cirrhosis was induced by intraperitoneal injection of CCl(4) to 10 rats fed a 2% protein diet, and to another 10 fed a 18% protein control diet. Two further groups included rats without cirrhosis fed the 2% protein and the 18% protein diets. After sacrifice (6 weeks later), we found type IIa fibre atrophy in the cirrhotic animals, especially in the low-protein fed ones and this was due to protein deficiency. Muscle Fe increased in low protein fed cirrhotic rats. No relationship was found between muscle changes and any of the hormones, enzymes and trace elements analysed, or with liver fibrosis. These results suggest that muscle atrophy observed in CCl(4)-induced cirrhosis is related with protein deficiency, but not with cirrhosis itself.

Relative and combined effects of propylthiouracil, ethanol and protein deficiency on liver histology and hepatic iron, zinc, manganese and copper contents.

The present study was performed in order to discern the effects of propylthiouracil (PTU) on ethanol and/or protein deficiency-mediated liver histological changes and liver Fe, Zn, Cu and Mn alterations in male adult Wistar rats. The study was performed on 64 animals divided into eight groups, fed with the Leiber-DeCarli control, 36% ethanol-2% protein- and 36% ethanol-2% protein-containing diets, without and with PTU, respectively. PTU was administered at a concentration of 0.05%, an amount which rendered the animals hypothyroid. Two further groups of 5 animals each, with and without PTU respectively, were allowed to consume the control diet ad libitum. Animals treated with PTU showed significantly less fibrosis, but more fat, than animals without PTU. Liver fibrosis was inversely correlated with liver zinc, liver content of this element being higher in the PTU-treated and the ethanol or protein deficiency groups. PTU also reversed ethanol-mediated hepatocyte ballooning and also led to a reduction in nuclear areas.