Handgrip strength and lean mass are independently related to brain atrophy among alcoholics.

BACKGROUND: In neurodegenerative disorders or in normal aging humans a relationship between muscle mass and/or performance and brain volume was observed, that is not dependent on age or other confounding factors. The aim of the present study is to analyse the relationship between lean mass and handgrip strength in alcoholics, who frequently show brain and muscle atrophy. METHODS: It was included 101 male patients aged 58.35 ± 11.59 years, and 44 controls, all of them workers of our hospital, drinkers of less than 20 g ethanol/day, of similar age. Patients and controls underwent dominant handgrip assessment with a Collins' dynamometer, whole body composition analysis by densitometry, and brain computed tomography (CT) examination, with further calculation of several indices indicative of brain atrophy. MAIN RESULTS: 1) Brain atrophy is a very common finding among alcoholics, both among cirrhotics and non-cirrhotics. 2) Alcoholics show a marked reduction in handgrip strength, and also in lean mass, especially at the arms and legs -but not in the trunk, even if patients with ascites were excluded.3) There is a relationship between reduced lean mass and brain atrophy, and a close correlation between handgrip strength and brain atrophy, that is independent of age and liver function. 4) Total fat amount is not different among alcoholics and controls, but there are marked differences in fat distribution: alcoholics show less fat in arms, but more fat in trunk, so that if we calculate the peripheral fat/trunk fat index, marked differences were observed among alcoholics and controls. Neither total fat nor fat distribution were related to brain atrophy. CONCLUSION: among alcoholics, as in other neurodegenerative conditions, there is a relationship between reduced lean mass and brain atrophy, and a close correlation between handgrip strength and brain atrophy, that is independent of age, duration of ethanol consumption and liver function.

Soluble Klotho and Brain Atrophy in Alcoholism.

AIM: Fibroblast growth factor (FGF-23) and α-Klotho (Klotho) levels may be altered in inflammatory conditions, possibly as compensatory mechanisms. Klotho exerts a protective effect on neurodegeneration and improves learning and cognition. No data exist about the association of Klotho and FGF-23 levels with brain atrophy observed in alcoholics. The aim of this study is to explore these relationships. SHORT SUMMARY: FGF-23 and Klotho levels are altered in inflammation, possibly as compensatory mechanisms. Klotho enhances learning, but its role in ethanol-mediated brain atrophy is unknown. We found higher FGF-23 and lower Klotho levels in 131 alcoholics compared with 41 controls. Among cirrhotics, Klotho was higher and inversely related to brain atrophy. METHODS: The study was performed on 131 alcoholic patients (54 cirrhotics) and 41 age- and sex-matched controls, in whom a brain computed tomography (CT) was performed and several indices were calculated. RESULTS: Marked brain atrophy was observed among patients when compared with controls. Patients also showed higher FGF-23 and lower Klotho values. However, among cirrhotics, Klotho values were higher. Klotho was inversely related to brain atrophy (for instance, ventricular index (ρ = -0.23, P = 0.008)), especially in cirrhotics. Klotho was also directly related to tumor necrosis factor (TNF) alpha (ρ = 0.22; P = 0.026) and inversely to transforming growth factor (TGF)-ß (ρ = -0.34; P = 0.002), but not to C-reactive protein (CRP) or malondialdehyde levels. FGF-23 was also higher among cirrhotics but showed no association with CT indices. CONCLUSIONS: Klotho showed higher values among cirrhotics, and was inversely related to brain atrophy. FGF-23, although high among patients, especially cirrhotics, did not show any association with brain atrophy. Some inflammatory markers or cytokines, such as CRP or TGF-ß were related to brain atrophy.

Lipid profile and bone mineral density in heavy alcoholics.

BACKGROUND & AIMS: Some studies have illustrated the association between serum lipid profile and bone mineral density (BMD) or fractures. None of these studies was performed among alcoholics, despite the fact that alcoholism may affect both bone mass and lipid metabolism. We here analyse the relationship of serum lipid profile with bone mass among a population of 280 heavy alcoholics (29 women). METHODS: patients underwent a densitometric assessment of BMD and determination of a serum lipid panel. Castelli index (Total cholesterol/HDL cholesterol) and the LDL/HDL cholesterol index were calculated. RESULTS: There was a direct correlation between both total cholesterol and LDL-cholesterol and femoral neck (r = 0.17 and r = 0.20, respectively) and lumbar spine (r = 0.16 and r = 0.20) T score, total BMD (r = 0.14 and r = 0.18) or pelvis BMD (r = 0.16 and r = 0.23; p < 0.025 in all cases). HDL-cholesterol showed no relationship with BMD. Serum triglycerides were also directly related to T score at the lumbar spine (ρ = 0.13; p = 0.032) and pelvis BMD (ρ = 0.13; p = 0.037). Pelvis BMD was significantly related to Castelli index (ρ = 0.15) and LDL/HDL index (ρ = 0.18; p < 0.015 in both cases). Multivariate analysis showed that the association between the serum lipid panel and BMD was independent of liver function and body mass index. CONCLUSIONS: Therefore, BMD was directly related to total cholesterol and LDL cholesterol in heavy alcoholism. This counter intuitive observation adds to others derived from several similar studies conducted in different population groups but not in alcoholics as of yet. The mechanisms that explain the association between serum lipids and bone metabolism need further investigation.

Alpha Klotho and Fibroblast Growth Factor-23 Among Alcoholics.

AIMS: Alcoholism may be a cardiovascular risk factor. Osteocyte derived molecules such as fibroblast growth factor 23 (FGF-23) and soluble α Klotho have recently been associated with cardiovascular disease, but their role in alcoholics is unknown. We here analyze the behavior of FGF23 and α Klotho in alcoholics. METHODS: Ninety-seven alcoholic patients were assessed for liver function, presence of hypertension, diabetes, atrial fibrillation, left ventricular hypertrophy (LVH), vascular calcifications (assessed by chest X-ray) and nutritional status (lean and fat mass measured by densitometry). We measured plasma levels of FGF-23 and serum soluble α Klotho, using ELISA in 97 patients and 20 age- and sex-matched controls. RESULTS: FGF-23 levels were higher in patients than in controls (Z = 3.50; P < 0.001). FGF-23 (Z = 5.03; P < 0.001) and soluble α Klotho (Z = 5.61; P < 0.001) were higher in cirrhotics, and both were related to liver function, independently of serum creatinine FGF-23 levels were higher among alcoholics with diabetes (Z = 2.55; P = 0.011) or hypertension (Z = 2.56; P = 0.01), and increased body fat (ρ = 0.28; P = 0.022 for trunk fat), whereas α Klotho levels were higher in patients with LVH (Z = 2.17; P = 0.03) or atrial fibrillation (Z = 2.34; P = 0.019). CONCLUSIONS: FGF-23 was higher in alcoholics than in controls, especially among cirrhotics, and soluble α Klotho levels were also higher among cirrhotics. Both were related to liver function impairment, independently of serum creatinine levels, and also showed significant associations with vascular risk factors, such as hypertension, diabetes or trunk fat amount in the case of FGF-23, or LVH or atrial fibrillation in the case of α Klotho. SHORT SUMMARY: We report increased values of fibroblast growth factor 23 (FGF-23) and soluble α Klotho in cirrhotic alcoholics. Both molecules are associated with liver function impairment, and with some cardiovascular risk factors such as diabetes, hypertension, increased body fat, left ventricular hypertrophy and atrial fibrillation independently of serum creatinine.

Metabolic syndrome and cardiovascular risk in diabetic population of El Hierro, Canary Islands / Síndrome metabólico y riesgo cardiovascular en la población diabética de El Hierro, Islas Canarias

Introduction: In the Canary Islands there is a high prevalence of vascular risk factors. Objective: To analyze the clinical characteristics of 300 patients with type 2 diabetes in El Hierro, in the Canary Islands. Methods: Patients were assessed at the Internal Medicine Unit of the hospital from 1982 to 2010, and followed up until December 2014 or until death. The sample is composed of 154 women and 156 men (52%). Results: mean age was 66.40 ± 11.60 years, with an average follow-up time of 11.04 ± 4.93 years, and 80.3% were diagnosed of metabolic syndrome, signifi cantly more frequent among women (86.43% vs74.67%, χ2 = 5.62, p = 0.018). During the follow-up period, 51 patients died and a signifi cant proportion developed new cardiovascular complications, such as heart failure (6.7%), ischemic heart disease (17.3%), atrial fi brillation (14.3%), stroke 7%), or peripheral arterial disease (6.9%). Cox regression analysis showed that, although advanced age was the major factor involved in the development of all these complications and in mortality, low cholesterol levels were related to the development of ischemic heart disease and mortality, results that were not dependent on the consumption of statins (as in other examples of inverse epidemiology). Ethanol consumption was related to the incidence of peripheral arterial disease. Conclusions: Old age was the main factor involved in the development of complications and mortality. In addition, low cholesterol levels were related to the development of ischemic heart disease and mortality.

Introducción: en Canarias existe una elevada prevalencia de factores de riesgo vascular, superior a la del resto de España.Objetivo: analizar las características clínicas de 300 adultos diabéticos tipo II de El Hierro, en el Archipiélago Canario. Métodos: los pacientes fueron valorados en la Unidad de Medicina Interna del hospital entre 1982 a 2010, y seguidos hasta diciembre de 2014 o hasta su fallecimiento. La muestra se compone de 154 mujeres y 156 hombres (52%). Resultados: la edad media fue de 66.40 ± 11,60 años, con un tiempo medio de seguimiento de 11,04 ± 4,93 años, y el 80,3% fue diagnosticados de síndrome metabólico, significativamente más frecuente entre las mujeres (86,43% vs.74,67%; χ2 = 5,62, p = 0,018). Durante el periodo de seguimiento 51 pacientes murieron, y una proporción significativa desarrolló nuevas complicaciones cardiovasculares, como insuficiencia cardiaca (6,7%), cardiopatía isquémica (17,3%), fibrilación auricular (14,3%), ictus (4,7%), o enfermedad arterial periférica (6,9%). Mediante análisis de regresión de Cox observamos que, aunque la edad avanzada fue el factor principal implicado en el desarrollo de todas estas complicaciones y en la mortalidad, los niveles bajos de colesterol se relacionaron con el desarrollo de cardiopatía isquémica y de mortalidad, resultados que no eran dependientes del consumo de estatinas (como en otros ejemplos de epidemiología inversa). El consumo de etanol se relacionó con la incidencia de la enfermedad arterial periférica. Conclusiones: la edad avanzada fue el factor principal implicado en el desarrollo de complicaciones y mortalidad. Además, los niveles bajos de colesterol se relacionaron con el desarrollo de cardiopatía isquémica y mortalidad.

Síndrome metabólico y riesgo cardiovascular en la población diabética de El Hierro, Islas Canarias / Metabolic syndrome and cardiovascular risk in diabetic population of El Hierro, Canary Islands

Introducción: en Canarias existe una elevada prevalencia de factores de riesgo vascular, superior a la del resto de España. Objetivo: analizar las características clínicas de 300 adultos diabéticos tipo II de El Hierro, en el Archipiélago Canario. Métodos: los pacientes fueron valorados en la Unidad de Medicina Interna del hospital entre 1982 a 2010, y seguidos hasta diciembre de 2014 o hasta su fallecimiento. La muestra se compone de 154 mujeres y 156 hombres (52%). Resultados: la edad media fue de 66.40 ± 11,60 años, con un tiempo medio de seguimiento de 11,04 ± 4,93 años, y el 80,3% fue diagnosticados de síndrome metabólico, significativamente más frecuente entre las mujeres (86,43% vs. 74,67%; χ2 = 5,62, p = 0,018). Durante el periodo de seguimiento 51 pacientes murieron, y una proporción significativa desarrolló nuevas complicaciones cardiovasculares, como insuficiencia cardiaca (6,7%), cardiopatía isquémica (17,3%), fibrilación auricular (14,3%), ictus (4,7%), o enfermedad arterial periférica (6,9%). Mediante análisis de regresión de Cox observamos que, aunque la edad avanzada fue el factor principal implicado en el desarrollo de todas estas complicaciones y en la mortalidad, los niveles bajos de colesterol se relacionaron con el desarrollo de cardiopatía isquémica y de mortalidad, resultados que no eran dependientes del consumo de estatinas (como en otros ejemplos de epidemiología inversa). El consumo de etanol se relacionó con la incidencia de la enfermedad arterial periférica. Conclusiones: la edad avanzada fue el factor principal implicado en el desarrollo de complicaciones y mortalidad. Además, los niveles bajos de colesterol se relacionaron con el desarrollo de cardiopatía isquémica y mortalidad (AU)

Introduction: In the Canary Islands there is a high prevalence of vascular risk factors. Objective: To analyze the clinical characteristics of 300 patients with type 2 diabetes in El Hierro, in the Canary Islands. Methods: Patients were assessed at the Internal Medicine Unit of the hospital from 1982 to 2010, and followed up until December 2014 or until death. The sample is composed of 154 women and 156 men (52%). Results: mean age was 66.40 ± 11.60 years, with an average follow-up time of 11.04 ± 4.93 years, and 80.3% were diagnosed of metabolic syndrome, significantly more frequent among women (86.43% vs 74.67%, χ2 = 5.62, p = 0.018). During the follow-up period, 51 patients died and a significant proportion developed new cardiovascular complications, such as heart failure (6.7%), ischemic heart disease (17.3%), atrial fibrillation (14.3%), stroke 7%), or peripheral arterial disease (6.9%). Cox regression analysis showed that, although advanced age was the major factor involved in the development of all these complications and in mortality, low cholesterol levels were related to the development of ischemic heart disease and mortality, results that were not dependent on the consumption of statins (as in other examples of inverse epidemiology). Ethanol consumption was related to the incidence of peripheral arterial disease. Conclusions: Old age was the main factor involved in the development of complications and mortality. In addition, low cholesterol levels were related to the development of ischemic heart disease and mortality (AU)

Malondialdehyde as a Prognostic Factor in Alcoholic Hepatitis.

AIMS: Alcoholic hepatitis is a severe complication of alcoholism, associated with high short-term mortality. Although pathogenesis remains obscure, it is generally accepted that lipopolysaccharide-induced cytokine secretion with further generation of reactive oxygen species (ROS) play outstanding roles. Prognosis is uncertain, and the usually employed prognostic scores do not include variables related to ROS generation. Therefore, this study was performed to assess short-term prognostic value of cytokines, nutritional status, different scores [Maddrey, model for end-stage liver disease (MELD), albumin, bilirubin, INR, creatinine index (ABIC), Lille, Glasgow, MELD-Na, Child-Pugh] and malondialdehyde (MDA, as an indicator of lipid peroxidation) at admission and after 1 week, among patients affected by severe acute alcoholic hepatitis (Maddrey index >32). METHODS: Sixty-two patients affected by severe acute alcoholic hepatitis, for whom we calculated Maddrey, MELD, ABIC, Lille, Glasgow, MELD-Na, Child-Pugh, and determined serum MDA and interleukin (IL)-6, IL-8, IL-4, tumor necrosis factor alpha and interferon gamma levels at admission and after 1 week. RESULTS: Twenty-four patients died during the follow-up period. MDA showed a better prognostic accuracy than the aforementioned scores, both at admission and after 1 week. CONCLUSION: Our study supports the importance of including MDA assessment in the prognostic evaluation of patients with alcoholic hepatitis. SHORT SUMMARY: Alcoholic hepatitis is associated with high short-term mortality. Although not included in prognostic scores, lipid peroxidation plays an outstanding role in its pathogenesis. We found that malondialdehyde levels showed a better prognostic accuracy than the usually employed scores. Therefore, it should be included in the prognostic evaluation of these patients.

Homocysteine, Liver Function Derangement and Brain Atrophy in Alcoholics.

AIMS: Hyperhomocysteinemia may be involved in the development of brain atrophy in alcoholics. Its pathogenesis is multifactorial. In the present study, we analyse the relationship between homocysteine levels and brain atrophy, and the relative weight of co-existing factors such as liver function impairment, the amount of ethanol consumed, serum vitamin B12, B6, and folic acid levels on homocysteine levels and brain alterations in alcoholic patients. METHODS: We included 59 patients admitted to this hospital for major withdrawal symptoms and 24 controls. The mini-mental state examination test and a brain computed tomography (CT) scan were performed and several indices were calculated. Serum levels of homocysteine, folic acid, vitamin B6 and vitamin B12 were determined. Liver function was assessed by Child-Pugh score. The daily consumption of ethanol in grams per day and years of addiction were recorded. RESULTS: A total of 83.6% and 80% of the patients showed cerebellar or frontal atrophy, respectively. Patients showed altered values of brain indices, higher levels of homocysteine and vitamin B12, but lower levels of folic acid, compared with controls. Homocysteine, B12 and liver function variables showed significant correlations with brain CT indices. Multivariate analyses disclosed that Pugh's score, albumin and bilirubin were independently related to cerebellar atrophy, frontal atrophy, cella index or ventricular index. Serum vitamin B12 was the only factor independently related to Evans index. It was also related to cella index, but after bilirubin. Homocysteine levels were independently related to ventricular index, but after bilirubin. CONCLUSION: Vitamin B12 and homocysteine levels are higher among alcoholics. Liver function derangement, vitamin B12 and homocysteine are all independently related to brain atrophy, although not to cognitive alterations. SHORT SUMMARY: Hyperhomocysteinemia has been described in alcoholics and may be related to brain atrophy, a reversible condition with an obscure pathogenesis. We studied 59 patients and found that liver function derangement, vitamin B12 and homocysteine levels are all independently related to brain atrophy assessed by computed tomography, although we found no association between these parameters and cognitive alterations.

Thrombin activation and liver inflammation in advanced hepatitis C virus infection.

Hepatitis C virus (HCV) infection is associated with increased thrombotic risk. Several mechanisms are involved including direct endothelial damage by the HCV virus, with activation of tissue factor, altered fibrinolysis and increased platelet aggregation and activation. In advanced stages, chronic HCV infection may evolve to liver cirrhosis, a condition in which alterations in the portal microcirculation may also ultimately lead to thrombin activation, platelet aggregation, and clot formation. Therefore in advanced HCV liver disease there is an increased prevalence of thrombotic phenomena in portal vein radicles. Increased thrombin formation may activate hepatic stellate cells and promote liver fibrosis. In addition, ischemic changes derived from vascular occlusion by microthrombi favor the so called parenchymal extinction, a process that promotes collapse of hepatocytes and the formation of gross fibrous tracts. These reasons may explain why advanced HCV infection may evolve more rapidly to end-stage liver disease than other forms of cirrhosis.

Adipokines, cytokines and body fat stores in hepatitis C virus liver steatosis.

AIM: To identify patients with or without liver steatosis and its severity in treatment-naïve patients affected by hepatitis C virus (HCV) infection. METHODS: 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). RESULTS: 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. CONCLUSION: 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.

Liver steatosis in hepatitis C patients.

There is controversy regarding some aspects of hepatitis C virus (HCV) infection-associated liver steatosis, and their relationship with body fat stores. It has classically been found that HCV, especially genotype 3, exerts direct metabolic effects which lead to liver steatosis. This supports the existence of a so called viral steatosis and a metabolic steatosis, which would affect HCV patients who are also obese or diabetics. In fact, several genotypes exert metabolic effects which overlap with some of those observed in the metabolic syndrome. In this review we will analyse the pathogenic pathways involved in the development of steatosis in HCV patients. Several cytokines and adipokines also become activated and are involved in "pure" steatosic effects, in addition to inflammation. They are probably responsible for the evolution of simple steatosis to steatohepatitis, making it difficult to explain why such alterations only affect a proportion of steatosic patients.

Bone changes in alcoholic liver disease.

Alcoholism has been associated with growth impairment, osteomalacia, delayed fracture healing, and aseptic necrosis (primarily necrosis of the femoral head), but the main alterations observed in the bones of alcoholic patients are osteoporosis and an increased risk of fractures. Decreased bone mass is a hallmark of osteoporosis, and it may be due either to decreased bone synthesis and/or to increased bone breakdown. Ethanol may affect both mechanisms. It is generally accepted that ethanol decreases bone synthesis, and most authors have reported decreased osteocalcin levels (a "marker" of bone synthesis), but some controversy exists regarding the effect of alcohol on bone breakdown, and, indeed, disparate results have been reported for telopeptide and other biochemical markers of bone resorption. In addition to the direct effect of ethanol, systemic alterations such as malnutrition, malabsorption, liver disease, increased levels of proinflammatory cytokines, alcoholic myopathy and neuropathy, low testosterone levels, and an increased risk of trauma, play contributory roles. The treatment of alcoholic bone disease should be aimed towards increasing bone formation and decreasing bone degradation. In this sense, vitamin D and calcium supplementation, together with biphosphonates are essential, but alcohol abstinence and nutritional improvement are equally important. In this review we study the pathogenesis of bone changes in alcoholic liver disease and discuss potential therapies.

Vitamina D, riesgo vascular y mortalidad en pacientes alcohólicos / Vitamin D, vascular risk, and mortality in alcoholic patients

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Vitamin D, vascular calcification and mortality among alcoholics.

AIMS: To analyze the relationship between low vitamin D levels and mortality among alcoholics. METHODS: One hundred twenty-eight alcoholic patients admitted to our hospital were followed up as outpatients. Nutritional status was evaluated measuring percentages of fat and lean mass in different body compartments. RESULTS: Lower vitamin D levels were observed in patients with worse liver function. Vitamin D was lower in patients with lower total lean mass (Z = 2.8, P = 0.005), but it was not related to fat mass. There was a significant trend to higher long-term mortality among non-cirrhotics with vitamin D levels below 30 ng/ml, although Cox's regression model revealed that only Child score and age were independently related to mortality. CONCLUSION: Vitamin D deficiency is common among alcoholic patients and is associated with low lean mass and liver dysfunction. Among non-cirrhotics, serum vitamin D levels below 30 ng/ml are associated with a greater long-term mortality.

Alcoholism: a systemic proinflammatory condition.

Excessive ethanol consumption affects virtually any organ, both by indirect and direct mechanisms. Considerable research in the last two decades has widened the knowledge about the paramount importance of proinflammatory cytokines and oxidative damage in the pathogenesis of many of the systemic manifestations of alcoholism. These cytokines derive primarily from activated Kupffer cells exposed to Gram-negative intestinal bacteria, which reach the liver in supra-physiological amounts due to ethanol-mediated increased gut permeability. Reactive oxygen species (ROS) that enhance the inflammatory response are generated both by activation of Kupffer cells and by the direct metabolic effects of ethanol. The effects of this increased cytokine secretion and ROS generation lie far beyond liver damage. In addition to the classic consequences of endotoxemia associated with liver cirrhosis that were described several decades ago, important research in the last ten years has shown that cytokines may also induce damage in remote organs such as brain, bone, muscle, heart, lung, gonads, peripheral nerve, and pancreas. These effects are even seen in alcoholics without significant liver disease. Therefore, alcoholism can be viewed as an inflammatory condition, a concept which opens the possibility of using new therapeutic weapons to treat some of the complications of this devastating and frequent disease. In this review we examine some of the most outstanding consequences of the altered cytokine regulation that occurs in alcoholics in organs other than the liver.

Antioxidant vitamins and brain dysfunction in alcoholics.

AIMS: Alcohol induces cytokine secretion by Kupffer cells, which may exert also deleterious effects on distant organs, mediated in part by cytokine-derived increased production of reactive oxygen species (ROS). It is therefore important to assess antioxidant levels. The objective of this study is to analyse the relation of antioxidant vitamins with brain atrophy and cognitive dysfunction. METHODS: In 77 alcoholic patients admitted for withdrawal syndrome, subjected to brain computed tomography (CT), and 19 controls, we determined antioxidant vitamin levels and analysed their relationships with data of brain atrophy and dysfunction. Searching for causes of altered vitamin levels, we also assessed liver function, nutritional status, eating habits, alcohol intake, proinflammatory cytokine (TNF-α, IL-6, IL-8) levels and malondialdehyde (MDA) levels. RESULTS: Both retinol (vitamin A) and tocopherol (vitamin E) levels were decreased in alcoholics, the former in relation with liver failure, and the latter in relation with triglyceride levels and fat mass. Both were related to data of brain atrophy and cerebellar shrinkage (to which also IL-6 was significantly related). CONCLUSION: Among alcoholics, liver function impairment leads to altered serum vitamin A levels, which are related to brain alterations. Vitamin E levels are also decreased, but although in relation with liver function impairment, its decrease seems to be more dependent on nutritional status and irregular eating habits. Both vitamins are lower in patients with cerebellar atrophy and other features related to brain atrophy.

Iron and proinflammatory cytokines in chronic hepatitis C virus infection.

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.

Bone alterations in hepatitis C virus infected patients.

BACKGROUND AND AIMS: Most studies have shown that patients with chronic hepatitis C virus (HCV) infection are affected by osteoporosis. However, liver function impairment and deranged nutrition may both play a role in the bone alterations observed. In some works no osteoporosis was found, and some cases of osteosclerosis have been reported. The aim of the study is to assess bone alterations in treatment-naïve, well-nourished HCV patients, in order to discern whether or not HCV infection causes osteoporosis. METHODS: Whole-body bone densitometry and assessment of T-score at lumbar spine and hip were performed to 40 patients and 40 age- and sex-matched controls, with a Lunar Prodigy Advance (General Electric, Piscataway, NJ, USA). All the patients underwent liver biopsy. Nutritional evaluation was performed by subjective nutritional assessment, body mass index (BMI), and densitometric assessment of total lean mass and total fat mass. Serum osteocalcin, osteoprotegerin, RANKL, PTH, crosslaps, vitamin D3, testosterone, IGF-1, and estradiol were determined. RESULTS: Patients did not show differences in total bone mineral density (BMD) or T-score with controls. On the contrary, about a third of them showed positive T scores. Patients showed lower IGF-1, vitamin D3 and testosterone, but higher telopeptide levels, and a trend to higher osteoprotegerin levels. Multivariate analyses disclosed that age, sex, and total lean mass were the only parameters independently related with BMD. CONCLUSIONS: Therefore, chronic HCV infection in well nourished patients with preserved liver function does not cause osteoporosis.