Attilio Cecchetto

Iron storage, lipid peroxidation and glutathione turnover in chronic anti-HCV positive hepatitis

BACKGROUND/AIMS Little is known about the pathogenesis of liver damage related to hepatitis C virus. The presence of steatosis or increased ferritin levels, and preliminary data on the relevance of iron as a prognostic factor prompted us to ascertain whether hepatitis C virus-related liver damage might be mediated by iron accumulation. METHODS We evaluated the degree of hepatic inflammation and steatosis, serum ferritin, transferrin saturation and iron levels, tissue iron concentrations and iron index, liver glutathione and malondialdehyde in 33 males and 20 females with chronic hepatitis C virus- or hepatitis B virus-related hepatitis (42 + 11). We also considered six patients with both alcohol abuse and hepatitis C virus, four males with chronic alcoholic liver disease and four males with genetic hemochromatosis, giving a total of 67. All diagnoses were histologically confirmed. Patients with cirrhosis were excluded. RESULTS Our data show that: 1. Steatosis is more frequent in hepatitis C virus and hepatitis C virus+alcohol abuse patients; 2. In males, serum ferritin and tissue iron are significantly higher in hepatitis C virus- than in hepatitis B virus-positive patients (p < 0.01 and 0.05); transferrin saturation is higher (p < 0.05) in hepatitis C virus-positive than in hepatitis B virus-positive patients only when males and females are considered together; 3. Serum ferritin and transferrin saturation only correlate with liver iron (r = 0.833 and r = 0.695, respectively, p = 0.00001); tissue iron is significantly higher in hepatitis C virus- than in hepatitis B virus-positive patients (p < 0.05); 4. In patients with chronic hepatitis, serum ferritin is a better marker of liver iron storage than transferrin saturation, both in males and in females; 5. Hepatitis C virus-positive patients have higher malondialdehyde levels and activation of turnover of glutathione, probably in response to free-radical-mediated liver damage. Females have lower liver iron levels but similar trends. CONCLUSIONS These findings suggest that hepatitis C virus-related liver damage is characterized by increased iron storage (possibly induced by the virus) which elicits a free-radical-mediated peroxidation, with consequent steatosis and activation of glutathione turnover.

Histological features after liver transplantation in alcoholic cirrhotics

BACKGROUND/AIMS Though alcoholic cirrhosis is a common indication for liver transplantation, it carries the risk of alcohol recidivism and consequent graft failure. This study aims to evaluate the effect of alcohol recidivism on survival rates and histological parameters in patients transplanted for alcoholic cirrhosis, with and without hepatitis C virus (HCV) infection. METHODS Fifty-one out of 189 consecutive transplanted patients underwent psychosocial evaluation and liver biopsy at 6 and 12 months, then yearly after transplantation. RESULTS The cumulative 84 month survival rate was identical in patients transplanted for alcoholic (51%) and non-alcoholic cirrhosis (52%). No difference emerged between anti-HCV negative vs. positive alcoholic cirrhosis patients. Psycho-social evaluation revealed alcohol recidivism in 11/34 long-term survivors, but this did not affect overall survival rate in patients with or without HCV. In anti-HCV negative cases, fatty changes and pericellular fibrosis were significantly more common in heavy drinkers than in occasional drinkers and abstainers. When HCV status was considered regardless of alcohol intake, fibrosis was significantly more frequent in patients with HCV. CONCLUSION Alcohol recidivism after transplantation in alcoholic cirrhosis patients does not affect survival, irrespective of HCV status. Fatty changes and pericellular fibrosis are the most relevant histological signs of heavy alcohol intake.

Chondrosarcoma of the larynx: Review of the literature and report of three cases

Three patients with laryngeal chondrosarcoma were observed at the ENT Department of Padua University from 1966 to 1983. Including the present observations, about 150 of these neoplasms have been described in the literature. The male to female ratio was 3:1, and the age at diagnosis ranged from 33 to 91 years (median, 66 years). The rate of metastasis was 8 per cent, and histologically positive lymph nodes developed in only five patients. Surgery is the treatment of choice for laryngeal chondrosarcoma. Radical neck dissection does not appear to be indicated, unless results of clinical examination suggest metastatic lymph nodal involvement.

Helicobacter pylori Infection and Gastric Autoimmune Diseases: Is There a Link?

Background.  Helicobacter pylori is thought to be involved in atrophic body gastritis. We explored the prevalence of H. pylori infection in asymptomatic subjects with gastric parietal cell antibodies, as well as in patients with pernicious anemia, to evaluate a possible role of H. pylori gastric infection in gastric autoimmunity.

The mechanism of anion translocation and pH equilibration in erythrocytes

Abstract The process of anion translocation across the red cell membrane has been found to have the following properties: 1. 1. The half-time for the electrogenic Cl − translocation is of the order of 100 sec, about 500 times greater than that for the electroneutral Cl − exchange. 2. 2. The pH equilibration is the result of an exchange of Cl − against HCO 3 − or of Cl − against OH − , and does not involve the translocation of H + as such. 3. 3. The kinetics of Cl − translocation show phenomena of competition and saturation. The above properties are discussed from the point of view of the hypothesis that the translocation of anions across the red cell membrane is due to the operation of carriers.

Hepatocyte transplantation in the treatment of acute liver failure: microencapsulated hepatocytes versus hepatocytes attached to an autologous biomatrix.

A liver transplant is considered today to be the only effective therapeutic solution for many otherwise intractable hepatic disorders. However, liver transplantation is beset by shortage of donors. Over the years, many liver support systems have been developed to supply the liver functions, mostly as a bridge to transplantation. Transplantation of isolated hepatocytes (HcTx) instead of whole liver has constituted one of the most appealing possibilities to treat several diseases. We compared two different models of HcTx in a surgical model of acute liver failure in pigs, using microencapsulated hepatocytes (MHcTx) and hepatocytes attached to a porcine biomatrix (PBMHcTx), both transplanted into peritoneum. The collected data were survival, laboratory findings, hemodynamic parameters, light microscopy, histology, MTT, and glycogen content. The group with PBMHcTx has a better outcome than the group with MHcTx (p < 0.05). Histology showed normal morphology of the hepatocytes, high glycogen content, 75% viability, positive MTT, and 95% adhesion of the hepatocytes to the biomatrix. Our biomatrix (PBM) provides cell-to-cell contact and interaction with extracellular matrix, which have been shown to play major roles in hepatocyte survival and physiologic regulation of gene expression, and guarantee a prompt engraftment and an adequate neovascularization. PBMHcTx is a useful method to treat acute liver failure and it indicates a possible liver-direct gene therapy in the treatment of inherited and acquired disorders.

Imbalance between cytoproliferation and apoptosis in hepatitis C virus related chronic liver disease

An imbalance between cytoproliferation and apoptosis may be relevant in liver carcinogenesis. The aim of this study was to analyse these parameters in patients with chronic liver damage in relation to the aetiology of the disease. Forty‐eight patients were studied: 23 had hepatitis C virus (HCV)‐ and 11 had hepatitis B virus (HBV)‐related chronic hepatitis, seven had alcoholic liver disease, and seven had haemochromatosis. The biopsies were used for routine diagnosis, cytoproliferative indexing (MIB1, Ki67 monoclonal antibody), apoptosis (APO, in situ end labelling) and, in part, liver iron and malondialdehyde determination. Apoptosis was similar in all patient subgroups and correlated with hepatitis grading (P=0.002) and ALT levels (P=0.004); cytoproliferation (MIB1) levels were higher in HCV patients, both as a whole and in the periportal area (P=0.02 and P=0.03). MIB1 correlated with ALT levels (P=0.0001), hepatitis grading (P=0.02) and tissue iron (P=0.04). APO and MIB1 were higher in patients with than in those without cirrhosis (P=0.0006 and P=0.03, respectively). APO correlated with MIB1 (P=0.001), overall but not in HCV patients. The MIB1/APO ratio was significantly higher in HCV patients than in the other groups (P=0.02). In summary, cytoproliferation is more pronounced in chronic HCV‐related hepatitis, while APO is not significantly higher than in other types of liver damage, suggesting an imbalance between the two. APO and MIB1 are directly related to the extent of liver damage and, from a biochemical point of view, to tissue iron levels.

The role of CD40 in ulcerative colitis: histochemical analysis and clinical correlation.

Objectives CD40 co-stimulator seems to be implicated in the loss of tolerance against self-antigens in many autoimmune diseases. The evidence suggests that in the pathogenesis of ulcerative colitis there is an activity state against self-antigens of the gut wall and flora. The aim of this study was to analyse the expression of CD40 in ulcerative colitis, comparing it with Crohns disease and nonspecific inflammation of the colon and to determine whether there is a relationship between its expression and the activity stage of the disease. Methods The expression of CD40 in the colonic samples of 51 patients (30 ulcerative colitis, 9 Crohns disease and 12 nonspecific inflammation) was analysed by immunohistochemistry. Twenty-four patients with ulcerative colitis were scored according to clinical, endoscopic and histological classification. Results The mean percentage of CD40+ cells per field in the colonic mucosa was: ulcerative colitis 21 ± 11%, Crohns disease 24 ± 9%, nonspecific inflammation 7 ± 7%. The ulcerative colitis patients were statistically significantly different compared to the patients with nonspecific inflammation (P < 0.005), even when comparing the patients in remission (P < 0.05). The expression in Crohns disease was similar to that in ulcerative colitis. The expression of CD40 in ulcerative colitis was directly proportional to the state of activity of the disease according to the clinical (P < 0.02), endoscopic (P < 0.01) and histological (P < 0.02) criteria. Conclusions The expression of CD40 in the colonic mucosae of patients with ulcerative colitis is significantly increased and is proportional to the state of activity. The results seem to confirm the hypothesis that a loss of tolerance could be involved in the pathogenesis of this disease.

Effect of zinc supplementation on trace elements and intestinal metallothionein concentrations in experimental colitis in the rat

BACKGROUND AND AIM Zinc enhances cell protection against infection and injury and the healing processes themselves. We evaluated the effect of zinc supplementation at different doses on a model of experimental colitis in the rat. METHODS Colitis, induced by intra-rectal instillation of dinitrobenzen-sulphonic acid, was assessed at 1 week by examining: general outcome and macroscopic damage, myeloperoxidase activity, mucosal zinc, iron and metallothionein concentrations. Rats received zinc sulphate, 2 mg/kg or 30 mg/kg, twice a day by gavage for 9 days, starting 3 days before the induction of colitis, or intrarectal instillation of zinc (20 mg/kg) once daily starting 8 hours after the induction of colitis and for 6 days thereafter RESULTS Zinc-treated rats had less diarrhoea, higher body weight and lower colonic weight than untreated rats but no effect was observed on macroscopic inflammation, adhesions, colonic distension and neutrophil infiltration of the colonic mucosa. Zinc supplementation did not affect mucosal iron and zinc concentrations or plasma zinc levels in colitic rats. Metallothionein synthesis was induced in control rats and to a lesser extent in colitic rats. CONCLUSION Zinc administration induces metallothionein synthesis but has little effect on the short-term course of experimental colitis.

HIV infection in the first heart transplantation in Italy: fatal outcome

A 46‐year‐old man with alcoholic dilated cardiomyopathy underwent heart transplantation on November 14, 1985. It was the first cardiac transplant in Italy and at that time no HIV antibody screening test was available in this country. The patient remained in good health for 6 years postoperatively, with only one episode of rejection (type 3A). In June 1992 he died of fulminant complications of AIDS and severe chronic rejection. Neither the patient nor the organ donor belonged to any of the known risk groups for HIV infection; a retrospective analysis revealed that perioperative blood transfusions had been the vectors of transmission.