Cirrhosis is associated with cardiovascular abnormalities. Scanty information is available as to whether these include left ventricle diastolic dysfunction and wall thickness increase. To this aim in 27 cirrhotic patients with tense ascites, 17 cirrhotic patients with previous episodes of ascites (not actual), and 11 controls we investigated by echocardiography and echocolor Doppler left ventricle diastolic function (E wave, A wave, E/A ratio, deceleration time of E wave), systolic function (ejection fraction), and wall thickness (left ventricle posterior wall thickness + interventricular septum thickness) along with neurohumoral variables. All measurements (supine position) were repeated after total paracentesis (10.7 +/- 0.6 L of ascites) in ascitic patients. Both in patients with and without ascites E/A ratio was reduced as compared with controls (0.93 +/- 0.07 and 0.97 +/- 0.06 vs. 1.18 +/- 0.08, P < .05) while left ventricle wall thickness was increased (18.6 +/- 0.6 and 20.1 +/- 0.8 vs. 17.2 +/- 0.7, P < .05 and P < .01, respectively), irrespective of the postviral or alcoholic cause of liver disease. In all cirrhotics both right and left atrial and right ventricle diameters were significantly greater. Ejection fraction was slightly but significantly (P < .01) reduced in ascitic patients. Paracentesis induced a reduction of the highly increased basal plasma renin activity, aldosterone, norepinephrine (P < .01), and epinephrine (P < .05) and improved diastolic function (E/A, P < .05). Systolic function was unaffected. Thus, irrespective of ascites and cause, advanced cirrhosis is associated with left ventricle diastolic dysfunction and wall thickness increase. We can speculate that neurohumoral overactivity, known to stimulate cardiac tissue growth, may challenge the heart, promoting fibrosis and exerting a further hindrance to ventricular relaxation in patients with cirrhosis experiencing episodes of ascites.

Mild to moderate hepatic iron overload is frequent in patients with chronic viral hepatitis (CH). We evaluated the role of hemochromatosis (HFE) gene mutations and other acquired factors in the development of iron overload in these patients. We studied 110 patients with chronic B or C viral hepatitis (31 women, 79 men), including 20 with cirrhosis, and 139 controls. Hepatic iron was evaluated by semiquantitative analysis in all the patients, and hepatic iron concentration (HIC) was determined in 97 of them (26 women, 71 men). C282Y and H63D mutations were sought in all the subjects by a polymerase chain reactionrestriction assay. The frequency of HFE genotypes and alleles did not differ in patients and controls. No relation was detected between hepatic iron stores and HFE gene mutations in women. In men, all C282Y heterozygotes had iron overload, and the H63D mutation was significantly more frequent in patients with more marked hepatic siderosis than in those with mild or no siderosis (P ‫؍‬ .0039) and in controls (P ‫؍‬ .0008). Heavy alcohol intake and hepatic cirrhosis were also associated with increased hepatic iron stores in the men. In the 71 men in whom HIC was measured, multiple regression analysis showed that this variable was related independently only to alcohol intake and HFE gene mutations. We suggest that in patients with CH, iron accumulates in the liver as the result of an interplay between genetic and acquired factors, and that increased liver iron stores may influence progression toward liver fibrosis. (HEPATOLOGY 1998;28:1105-1109

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In the follow-up group, iron and metabolic indices did not change over time. Serum alanine aminotransferase, gamma-glutamyl transferase, cholesterol and triglycerides significantly decreased after iron depletion. Serum glucose, cholesterol, triglyceride, ferritin and liver function tests significantly decreased after dietary treatment. Transferrin saturation decreased below 20% during phlebotomy treatment in 52% of the patients. In conclusion, our results show that IR-HIO patients had relatively low amount of iron overload that seems not to increase even after a long follow-up period. Both venesections and diet improved iron, metabolic and hepatic indices. Data suggest a relationship between hepatic iron overload and insulin resistance, and a role for both iron overload and insulin resistance in hepatocellular damage. The behaviour of iron indices during venesections suggests an impaired iron release from hepatic cells.

the expression of the disease is affected by genetic factors. 3,4 We evaluate the relation between genotype and phenoHaplotype analysis in Australian patients of Irish or Scottish type in 47 Italian male patients with homozygous genetic origin provides evidence of a common ancestral haplotype hemochromatosis (GH). Phenotype evaluation was characterized by the combination of D6S265-1, HLA-A3, based on the ratio of amount of iron removed (IR) by D6S105-8 alleles. is associated with a common mutation. Besides the HLApresent in 13 of 52 (25%) chromosomes in class I and A3 linked haplotype, a further haplotype restricted to GH in 24 of 42 (57%) chromosomes in class II (P Å .0027).chromosomes, which possesses HLA-A11 and the allele 2 of Homozygotes and heterozygotes for the ancestral haplo-HLA-F (restriction fragment length polymorphism), has been type had higher iron indices than patients carrying two described. 10 It is likely that this haplotype harbors a second haplotypes other than the ancestral one. Seven of the independent mutation different from the ancestral one. Seveight patients homozygous for the ancestral haplotype eral other haplotypes have been found in GH 5,6,8 suggesting were in class II, heterozygotes were equally distributed the possibility of heterogeneous molecular defects in contrast between the two classes, whereas 14 of 18 carriers of to the original hypothesis of a unique ancestral mutation as other haplotype combinations were in class I. Our reresponsible for all GH cases in white population. Both clinical presentation and body iron stores differ in three different clinical centers in northern Italy. They were aged 25 patients with genetic hemochromatosis (GH). Women usually to 68 years (mean { SD: 44.5 { 11). Inclusion criteria were: (1) no develop symptoms and signs of the disease later in their life known causes of secondary iron overload; (2) hepatocellular hemosidbecause of menstrual blood losses and pregnancy. Age, di-erin deposits of IIIЊ-IVЊ; (3) HII greater than 2 and/or a total amount of iron removed (IR) by phlebotomy to achieve iron depletion higher etary habits, and factors such as blood donations and blood than 5 g; and (4) availability of relatives to perform molecular studies losses can modify hepatic iron stores. Heavy alcohol intake and unambiguously assign haplotypes linked to the GH gene. Excluand chronic viral hepatitis facilitate the development of liver sion criteria were: (1) female sex; (2) history of chronic blood losses damage in patients with GH. 1,2 Phenotypic concordance beor blood donations; and (3) history of blood transfusions or parenteral tween siblings with homozygous GH provides evidence that iron administration.The presence of fibrosis or cirrhosis was determined at liver biopsy. Cardiopathy was based on physical signs of heart failure and/or left ventricular dilatation with low left ventricular ejection fraction and luteinizing hormone levels were considered affected by pituitary hy-

These data provide evidence that aldosterone blockade by long-term K-Canrenoate administration improves hepatic hemodynamics by lowering HVPG and ameliorates cardiac structure and function by favoring a reduction in LVWT and LVEDV as well. They also show, however, that this therapeutic intervention neither improves left ventricular diastolic dysfunction nor exerts sympathoinhibitory effects.

We studied 81 patients with chronic hepatitis C to investigate the relationship between iron and α‐interferon response. Sixty‐one patients (group A) were given α‐interferon irrespective of iron status, whereas 20 (group B) with iron overload, were iron depleted before α‐interferon therapy. In group A, 21 patients responded to α‐interferon and 40 were non‐responders. Increased iron indices were significantly more frequent in non‐responders than responders. Multivariate analysis showed that among the independent variables evaluated, only γ‐GT and liver iron concentration predicted therapy outcome. After phlebotomy treatment, serum alanine aminotransferase fell significantly both in patients of group B (196±122 IU/1 vs 82±37 IU/1, p<10‐6) and in 12 non‐responders of group A (198±89 IU/1 vs 107±81 IU/1, p<10‐6). In 16 iron depleted patients, eight from each group, subsequent treatment with α‐interferon produced a response in only one patient. These results suggest that increased liver iron is a negative prognostic factor for a‐interferon response in chronic hepatitis C. Iron depletion had a beneficial effect on serum alanine aminotransferase in all the patients treated, but did not improve the response to α‐interferon.

BackgroundGait variability can be considered an indirect measure of gait stability, in particular regarding temporal or spatial variability assessment. Physical activity, such as walking, is advised for the elderly and can be improved by gait stability. The aim of this study was to investigate the associations between gait stability and physical activity in women of different age ranges.MethodsForty-two healthy women of different age ranges (18-40 yrs. and 65-75 yrs.) were recruited in the study. To assess physical activity, the subjects wore a multi-sensor activity monitor for a whole week, inferring the time spent in moderate to vigorous physical activity (MVPA). MVPA were analysed in bouts of at least 10 subsequent minutes (MVPAbouts) and in overall minutes (MVPAtot). A kinematic analysis was performed with an optoelectronic system to calculate gait variability - expressed as standard deviation (SD) and coefficient of variability (CV) of step width, stride length, stance and swing time (during treadmill walking at different speeds).ResultsElderly women, with high walking speed (5 km/h), and moderate step width variability (CV = 8–27%), met the recommended levels of physical activity (MVPAtot and MVPAbouts). Furthermore, gait variability, adjusted for age and number of falls, was significantly and negatively associated with MVPAtot only at 3.5 km/h, and with MVPAbouts only at 4 km/h.ConclusionsIn a population of healthy elderly women, gait variability was significantly and negatively associated with the level of physical activity. Healthy elderly women, with moderate gait variability (step width variability), and high preferred walking speed, seem to be able to meet the recommended levels of physical activity.