Search

Steatohepatitis is a common finding in chronic hepatitis C virus (HCV) infection. As in other forms of steatohepatitis, oxidative damage may play an outstanding role. However, there are conflicting results relative to the role of iron on hepatic lipogenesis. Proinflammatory cytokines up-regulate ferritin expression, probably reflecting a defensive mechanism against increased oxidative stress, capable to open haem ring and release reactive iron. On the contrary, some adipokines, such as adiponectin, are associated with low ferritin levels. The aim of this study is to analyse the relationships of the amount of liver steatosis with serum iron, transferrin and ferritin as well as with proinflammatory cytokines, such as tumour necrosis factor (TNF)-α and interleukin (IL)-6, and adiponectin levels. We included 82 HCV infected patients and assessed the amount of liver fat by histomorphometry and its relationships with serum iron, ferritin and transferrin, adiponectin and TNF-α and IL-6. Liver steatosis was observed in 67 patients out of 82; in the remaining 15 patients, no steatosis at all was found. Patients with steatosis showed significantly higher serum ferritin levels than patients without steatosis (Z = 2.14; p = 0.032). When patients were classified in quartiles according to the intensity of steatosis, we observed that both TNF-α (KW = 10.6; p = 0.014) and IL-6 (KW = 15.2; p = 0.002) were significantly different among the four groups. Patients with more intense steatosis (highest quartile) showed the highest TNF-α and IL-6 values. Patients with severe hepatitis had higher levels of serum iron than patients with mild to moderate hepatitis. Serum iron also showed a correlation with the proportion of fibrosis (ρ = 0.30; p = 0.007). Serum iron levels are related with biochemical and histological parameters derived from liver inflammation in HCV-associated liver disease. Serum ferritin is higher among those with intense steatosis and also shows a (non-significant) trend to be associated with the more severe forms of hepatitis.

Aims: The aims of this study were to assess bone mineral density (BMD) and content (BMC), osteocalcin, serum telopeptide, PTH and vitamin D in alcoholics, and to determine if a 6-month period of abstinence leads to changes in these parameters. Methods: Serum osteocalcin, insulin-like growth factor 1 (IGF-1), telopeptide (40 patients) and 1,25 dihydroxyvitamin D, were measured in 28 controls and 77 alcoholic patients, 48 of whom were evaluated again 6 months later. All patients underwent whole-body assessment of BMD by a Hologic QDR-2000 (Waltham, MA, USA) bone densitometer, at the beginning of the study and 6 months later. Results: Patients showed higher serum telopeptide levels (0.59 ± 0.40 versus 0.19 ± 0.10 nmol/100 ml, P < 0.001), lower IGF-1 [median = 49, interquartile range (IQR) = 31–121 ng/ml versus 135, IQR = 116–237 ng/ml, P < 0.001], vitamin D [26.5, IQR = 17.0–37.8 pg/ml versus 82.4 (IQR = 60.9–107.4 pg/ml, P < 0.001] and osteocalcin (2.1, IQR = 1.1–3.6 ng/ml versus 6.65, IQR = 4.9–8.8 ng/ml, P < 0.001) than those in controls. Patients also showed lower BMD values, Z - and T -scores at many levels of the skeleton and reduced total BMC. After 6 months, those who continued drinking showed a loss of bone mass, whereas those who abstained showed either no change or increase, differences being especially marked at pelvis, right arm and total BMD and BMC. Simultaneously, abstainers showed a significant increase in osteocalcin (versus a decrease among those who continued drinking). Serum telopeptide increased in both groups. Conclusion: Ethanol consumption leads to osteopenia, and decreased serum osteocalcin, which improve with abstinence, whereas those who continue drinking show a worsening of both parameters.

In alcoholic hepatitis, Kupffer cells are activated by intestinal gram-bacteria, leading to cytokine production and free radicals release, which, enhancing cytokine secretion, create a positive feedback loop which contributes to liver inflammation. Free radicals also damage the liver in chronic hepatitis C virus (HCV) infection, a condition frequently associated to alcohol consumption. In both situations, activity of antioxidant enzymes and of its cofactors zinc (Zn), selenium (Se), and copper (Cu) is important. This study was performed to assess the relative and combined effects of chronic alcoholism and HCV infection on serum Se, Zn, and Cu, and its relation with serum malondialdehyde (MDA) and tumor necrosis factor-α, interferon-γ, and interleukins (IL) 4, 6, and 8, in 19 HCV- alcoholic patients, 12 HCV+ alcoholic patients, nine HCV+ non-alcoholic patients, and 20 controls. Serum Zn and Se were lower in both HCV+ and HCV- alcoholic patients, whereas serum Cu was lower in HCV+ individuals. Serum Zn and Se were related to liver function derangement. MDA levels were higher in alcoholics, but no relation was observed between trace elements and MDA or cytokines, so that our results do not support a relevant role of the analyzed trace elements in the pathogenesis of chronic liver disease.

El objetivo del estudio es el analisis de la supervivencia en el cancer colorrectal metastasico tras la cirugia de rescate. Entre 1991 y 1998 se diagnosticaron 498 pacientes con cancer colorrectal. En 10 pacientes se realizo cirugia de rescate de metastasis metacronicas hepaticas o pulmonares. Se analizaron las caracteristicas clinicas, el tratamiento realizado y la supervivencia. Siete fueron hombres y 3 mujeres con edades comprendidas entre 36–75 anos (mediana: 61 anos). La localizacion mas frecuente fue recto seguida de sigma. Solo 3 pacientes tenian afectacion ganglionar. La localizacion mas frecuente de las metastasis fue hepatica, seguida de pulmonar. El nUmero de metastasis fue 3 en un paciente, 2 en 3 pacientes y en el resto fue Unica. El tamano oscilo entre 2 y 6,5 cm. La mediana del intervalo libre de enfermedad hasta el diagnostico de la metastasis fue de 17 meses (rango: 8–48). El intervalo libre de enfermedad tras metastasectomia fue de 15,5 meses de mediana (rango: 3–72). La mediana del tiempo de seguimiento fue 47 meses (rango: 19–97). La cirugia de rescate de las metastasis hepaticas y pulmonares del cancer colorrectal puede ofrecerun aumento de la supervivencia en pacientes seleccionados. The aim of this research is the analysis of the survival after metastatic colorectal cancer resection. From 1991 to 1998 a total of 498 patients with colorectal cancer were diagnosed. This study reviewed 10 patients who underwent resection of both hepatic and pulmonary metastases from colorectal cancer. The clinical characteristics, the treatment and the survival were analysed. Seven of these patients were men and three women between 36–75 years old (median: 61 years). Rectum followed by sigma was the most frequent location. Only three patients presented nodal afection. The hepatic site was the most frequent, followed by the pulmonary. The number of metastases were three in one patient, two in three patients and one for the rest. The size varied between 2 and 6.5 cm. The median of the disease free interval after metastasectomy was 15.5 months (range: 3–72 months). The median follow-up was 47 months (range: 19–97). Resection of pulmonary and hepatic metastases in colorectal cancer can offer an increase of survival in selected patients.

To identify patients with or without liver steatosis and its severity in treatment-naïve patients affected by hepatitis C virus (HCV) infection.We included 56 HCV infected patients, and assessed the amount of liver fat by histomorphometry, and its relationships with fat and lean mass at different parts of the body (by densitometry), hormones [insulin, homeostatic model assessment (HOMA)], adipokines (resistin, adiponectin, leptin), and cytokines (tumor necrosis factor α, interleukin-6).Although the intensity of liver steatosis is related to trunk fat mass and HOMA, 33% of patients showed no liver steatosis, and this finding was not related to body mass index or genotype. Besides trunk fat mass, no other factor was related to the presence or not of liver steatosis, or to the intensity of it, by multivariate analysis. Lean mass was not related to liver steatosis. Adiponectin levels were lower among patients. No differences were observed in leptin and resistin.Steatosis in HCV infection is common (67.2%), and closely related to trunk fat, and insulin resistance, but not with leg fat mass or adipokines.

A major cause of liver cirrhosis and hepatocarcinoma is chronic infection by hepatitis C virus. Ethanol consumption is the most significant environmental factor that exacerbates the progression of chronic hepatitis C to liver cirrhosis and hepatocarcinoma, perhaps due to increased cytokine secretion together with increased lipid peroxidation. In this study, we compare the intensity of lipid peroxidation (estimated as malondialdehyde (MDA) serum levels), the antioxidant status, (measured as glutathione peroxidase (GPX) and superoxide dismutase (SOD) activities in red blood cells), and levels of cytokines derived from Th1 cells (such as interferon gamma (IFNG)), Th2 cells (such as interleukin (IL)-4), Th3 cells (such as transforming growth factor beta (TGF-beta)), and IL-6, IL-8, and tumor necrosis factor (TNF)-alpha in patients affected by chronic hepatitis C virus infection, 26 drinkers of alcohol and 40 nondrinkers of alcohol. Patients showed significantly higher TNF-alpha (Z = 4.92, P0.001), IL-8 (Z = 4.95, P0.001), IFNG (Z = 2.81, P = 0.005), TGF-beta (t = 2.12, P = 0.037), MDA (Z = 5, P0.001), but lower IL-6 (Z = 3.61, P0.001) and GPX (F = 4.30, P0.05) than controls, whereas no differences were observed regarding IL-4 (Z = 0.35, P = 0.72), GPX and SOD activities. Alcoholics showed significantly higher TNF-alpha, but lower IL-4, MDA, and GPX, than nonalcoholics. TNF-alpha was significantly related to albumin and prothrombin activity, whereas TGF-beta was significantly related to MDA levels. Thus, cytokine secretion is altered in HCV infection. This alteration mainly consists of a stimulation of Th1 cytokines and an inhibition--or at least, no stimulation--of Th2 cytokines; these changes are especially marked among alcoholics with HCV infection, and are accompanied by raised TGF-beta.

Background: Sclerostin inhibits osteoblast functions, differentiations, and survival rates. As an endogenous inhibitor of the Wnt/β-catenin pathway, the sclerostin should be related to decreased bone masses, although several studies indicate opposite results. In addition, it may be related to insulin resistances and carbohydrate metabolisms, a relation shared with other markers of bone metabolisms, such as osteocalcin. Hepatitis C virus (HCV) infected patients may present osteoporosis, and frequently show liver steatosis, which is a consequence of insulin resistance. The behaviour of sclerostin in these patients is yet unknown. The aim of this work is to analyse the relationships between serum sclerostin and osteocalcin levels and bone mineral density (BMD), liver functions, the intensity of liver steatosis and biochemical markers of bone homeostasis and insulin resistance in HCV-infected patients. Methods: Forty HCV patients with 20 years of age and gender-matching controls were included in this study and underwent bone densitometry. Serum sclerostin, osteocalcin, collagen telopeptide, adiponectin, leptin, insulin, resistin, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 were determined. Liver fat was histomorphometrically assessed. Results: Sclerostin levels were slightly higher in patients than in controls, and were directly related to BMD at different parts of the skeleton, also to the serum telopeptide, and to the liver steatosis and TNF-α. On the contrary, osteocalcin showed a significant direct relationship with serum adiponectin, and an inverse one with IL-6. Conclusions: Serum sclerostin levels were within the normal range in HCV patients, and correlated directly with BMD and serum telopeptide. In addition, the relationships of sclerostin and osteocalcin with variables associated with insulin resistance suggested the role of bones for intermediary metabolisms.