Development of type 1 diabetes mellitus during interferon alfa therapy for chronic HCV hepatitis.
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Biomedical subjects
Publications and source records attributed to A Floreani.
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To verify whether improvements in hygiene affect the risk of HBV infection, a seroepidemiological survey on HBV infection was carried out in a home for the elderly with continuous-care accommodation. HBV serum markers were tested in 315 subjects and the results of HBV infection were compared to those observed in two different types of nursing homes for the elderly from an earlier seroepidemiological study carried out in 1978. In addition, results from a cohort of a pre-geriatric population living in their own homes in the same geographical area surveyed in 1980 were compared to the present study. A statistically significant lower prevalence of HBV serum markers in the new home for the elderly compared to the two types studied in 1978 was observed. No difference was found between the new institutionalized study group and the cohort of a pre-geriatric population surveyed in 1980. These results reflect the improved sanitation in homes for the elderly and show that the elderly have very few opportunities to become infected, even in a close cohabitation system.
A seroepidemiological survey of anti-hepatitis C virus (anti-HCV) was carried out in 315 institutionalized elderly people. HBV serum markers were tested in the same sera. Clinical details were also studied in the anti-HCV-positive subjects. The overall prevalence of anti-HCV was 2.2%, while the prevalence of HBV serum markers was 36.8% (the HBsAg prevalence was 0.6%). In 1 subject anti-HCV was found in association with HBsAg positivity. Serum transaminase levels were found within the normal range in all 315 subjects (either anti-HCV+ve and anti-HCV-ve), except in the subject who was found to be HBsAg-positive and anti-HCV+ve. In conclusion we found in the institutionalized elderly people a similar prevalence of anti-HCV compared to blood donors of the same geographical area; homes for the aged appear to bring together subjects with previously acquired infections.
In many human tissues, fuel is stored for immediate use, as well as for energy exchange between different parts of the body. Fat and glycogen represent, together with proteins, the principal energy storage materials. During energy requirement, e.g. muscular exercise, glycogen as a local reserve, is used first to supply energy needs. Acetyl-carnitine, as an active molecular group, represents an intermediate substrate, usable directly in the working tissue. The present study investigates whether plasma acetyl-carnitine could be a useful biochemical measure for information on fuel exchange in the body, and whether it is a rapidly available energy source exchangeable among tissues with different metabolic functions, such as muscle and liver. The present study investigated control and hepatopathic subjects after maximal and submaximal muscular exercise. Hepatopathic patients may be a useful model, as liver carnitine metabolism is likely to be impaired. Plasma acetyl-carnitine before, during and after maximal exercise in hepatopathic subjects did not differ, while in normal subjects it increased. After submaximal exercise, acetyl-carnitine increased in patients, as well in controls. In the patients (n = 9) with liver metabolism disorders we observed that during maximal exercise plasma acetyl-carnitine varied from 3.26 +/- 2.18 mumol/l (time 0 min) to 4.30 +/- 2.02 mumol/l (time 20 min) and from 1.99 +/- 1.36 mumol/l to 4.83 +/- 2.60 mumol/l (p less than 0.05) in the controls (n = 7).(ABSTRACT TRUNCATED AT 250 WORDS)
Antigliadin antibody (AGA) subtypes (IgG and IgA class) were tested in sera from 67 patients with chronic liver disease of different aetiology (29 with primary biliary cirrhosis (PBC), 31 with chronic non-A non-B hepatitis, and 7 with autoimmune chronic active hepatitis (CAH) compared with 23 subjects with inflammatory bowel disease (IBD). Nineteen patients with coeliac disease served as positive controls. IgA-AGA alone were found in 3.4% of patients with primary biliary cirrhosis and in 3.2% of non-A, non-B CAH. IgG-AGA alone were found in 1.3% of patients with IBD, in 6.8% of primary biliary cirrhosis and in 14.2% of autoimmune CAH. IgA-AGA and IgG-AGA together were found in 6.8% of PBC and in 1 patient with autoimmune CAH. Jejunal biopsy, performed in 7 out of the 2 patients with both IgA and IgG-AGA, showed the characteristic features of coeliac disease in one subject with autoimmune CAH. The same patient had the highest titre of AGA. In conclusion, these results indicate that AGA (either IgG and IgA) can be present at low titre in chronic liver disease and their presence may be secondary to the liver damage per sè. High titres of AGA in chronic liver disease may suggest a real association with coeliac disease.
The aims of this study were to evaluate bone metabolism in primary biliary cirrhosis (PBC) and the effect of ADFR (activate, depress, free, repeat) therapy with vitamin D, calcium and calcitonin in preventing bone resorption. Sixty-nine female subjects entered the study: 38 PBC (AMA + ve) patients, 11 AMA-negative chronic liver disease patients and 20 age-matched healthy controls. Bone metabolism was evaluated by biochemical parameters and dual-photon absorptiometry of the lumbar spine at time 0, 6 and 18 months. Both PBC and chronic liver disease (CLD) patients showed low levels of serum 25-hydroxyvitamin D, osteocalcin and bone mineral content expressed as AAD (average area density) compared to healthy controls. Serum parathyroid hormone in PBC patients was at the lower limit of the normal range and was significantly lower than patients with chronic liver disease. At a 6-month interval, AAD significantly decreased in PBC patients (p less than 0.005). At the 6-month period PBC patients were allocated into two groups according to a cut-off AAD of 0.800 g/cm2: group A (no treatment, AAD greater than 0.800, n = 11), group B (treatment, AAD less than 0.800, n = 13). The latter group received a 4-week course with oral calcium carbonate (1500 mg daily) + oral 1,25-dihydroxyvitamin D (0.5 micrograms twice a day for 5 days) + carbocalcitonin (40 U MRC) i.m. thrice a week. The treatment was repeated with the same protocol at 2-month intervals for 12 months.(ABSTRACT TRUNCATED AT 250 WORDS)
Eosinophilic Gastroenteritis (EG) is a poorly understood disorder defined by eosinophilic infiltration of the bowel wall, eosinophilia and gastrointestinal symptoms. The disease's aetiology, course and treatment are not well known. We report two atypical cases of EG: one involving the mucosal layer and another involving the serosal and muscularis layer. The first shows how EG may present with a long history of episodes of intestinal obstruction and malabsorption and how the disease could take a severe course and may be unresponsive to treatment. The second case shows EG presenting as acute abdomen and which subsequently became asymptomatic without therapy, regardless of the fact that peripheral eosinophilia remained present. This case raises the problem of how to treat an asymptomatic patient, what parameters should be considered in order to assess the progress of the disease and the indications for treatment.
Sex hormones and sex hormone binding globulin (SHBG) have been studied in 32 female post-menopausal patients (16 with Primary Biliary Cirrhosis (PBC) and 16 with cryptogenic chronic liver disease (CLD). Dehydroepiandrosterone-sulfate (DHEA-S) serum levels were significantly higher in PBC compared to CLD subjects (p less than 0.005). In PBC DHEA-S concentration was higher in precirrhotic than in cirrhotic patients (p less than 0.02). SHBG was raised in both PBC and CLD patients but higher in CLD compared to PBC subjects (p less than 0.002). PBC reveals a sex hormone pattern similar to post-menopausal subjects with breast cancer. These results suggest that sex hormone alteration is present in females with different types of liver disease, but the metabolic pattern is not due to liver disease per se.
Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease with onset about menopause. To investigate its clinical features and the natural history in relation to age, we examined 86 consecutive patients with PBC (81 F, 5 M); 70 were less than 65 years (mean age 48 years) and 16 greater than 65 years (mean age 69 years). All patients were followed-up for 6 months-16 years (mean 4 years). Histological stage at presentation was comparable in the two groups, but among aged PBC subjects there was a significantly higher prevalence of asymptomatic patients (56% vs 24%, p less than 0.001). No significant differences were observed in the biochemical indices and immunological abnormalities. Survival curves showed no significant differences in PBC according to the age. Mortality was observed only in the group less than 65 years (15/70, 21.4%). In conclusion, the large proportion of asymptomatic subjects in the elderly PBC patients accounts for the similar survival in the two groups of patients.
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160 consecutive patients with primary biliary cirrhosis (PBC) (M:F, 13:147; total samples 286), 140 patients with other chronic liver disease (CLD) (M:F, 75:65; total samples 200), and 28 patients with primary Sjögren's syndrome (all F; total samples 37), were examined for bacteriuria over 6 months by midstream urine (MSU) examination. The overall prevalence of bacteriuria in PBC was 11.2% (7.5% on first MSU), in CLD 12.1% (10.7% on first MSU), 18.4% in the 65 female CLD patients, 10.7% in Sjögren's syndrome patients (3.5% on first MSU). The prevalence of bacteriuria was related to the age of the patient (P less than 0.02) in PBC and to the presence or absence of cirrhosis in both PBC and CLD (P less than 0.02). There was no difference in the prevalence of bacteriuria between PBC and CLD patients taken as a whole or among females alone, cirrhotic or non-cirrhotic groups. In a second prospective study of the cumulative incidence of bacteriuria in PBC versus CLD and Sjögren's no significant differences between groups was observed but among 29 PBC patients the cumulative proportion of positive tests for bacteriuria after 5 months (monthly testing) was 34%. We conclude that there is no specific association between PBC and bacteriuria compared with the prevalence of bacteriuria in other CLD.
Aberrant MHC Class II antigen expression and the nature of the infiltrating lymphoid cells were studied by immunohistochemical techniques in liver biopsies from 37 patients with Primary biliary cirrhosis (PBC) (11 histological stage I, 13 stage II-III, 13 stage IV) and 15 patients with chronic non autoimmune liver disease. Bile duct epithelial cells expressed HLA-DR, DP and DQ antigens in biopsies from patients with early (Stage I) PBC and less frequently in the late cirrhotic phases of the disease (Stage IV); these observations support the hypothesis that induction of Class II antigens on epithelial cells may be involved in initiating autoimmune responses towards bile duct components. The presence of cytotoxic/suppressor T cells around the bile ducts in Stage I suggests a role for cell mediated destruction of the ducts at this early stage. The nature of the chronic inflammatory cell infiltrate in the portal tracts, periportal areas and lobular parenchyma does not establish the mechanism(s) involved in disease progression. However, the lack of Class II antigen expression on hepatocytes is compatible with the hypothesis that hepatocellular damage is non-specific and may be secondary to the initial bile duct injury.
Only a single case of Graves' disease has been reported so far in Primary Biliary Cirrhosis (PBC), whereas hypothyroidism is a rather common association. We report two cases of hyperthyroidism associated with PBC. A common pathogenic mechanism involving HLA II class antigens is suggested.
Hepatitis B infection in the aged can be underestimated as the clinical and serological pictures can be rather peculiar in these subjects. Institutions for the elderly carry an increased risk of HBV spread as do many other closed communities. People from lower socioeconomic class and from countries with a high HBV prevalence are less susceptible to infection as they are already immunized by previous infections. However, epidemics have been described in homes for the aged, mostly from those for wealthy people or from those in low prevalence countries. When infected the elderly tend to develop a subclinical hepatitis detected only by serum analysis. These infections are frequently followed by asymptomatic chronic carriage of HBsAg. This phenomenon may be due to alterations of the immune system in the aged, which is also suggested by the finding of very poor antibody responses to hepatitis B vaccines in the aged. Overt acute hepatitis is infrequent. It usually have a benign course, even if occasionally cholestatic. Very active type B chronic hepatitis is very rare, while most elderly patients with HBsAg-positive chronic liver disease have cirrhosis as the end stage of chronic hepatitis acquired previously.
An antinuclear antibody specific for nuclear membrane (ANMA) was observed by the immunofluorescence method in sera from patients with primary biliary cirrhosis (PBC). ANMA was present in 18 of 63 PBC sera (28.5) and in 1 of 431 control sera (0.2%). Its reaction appeared as a thin fluorescent ring confined to the nuclear envelope and was more evident when the sera were highly diluted and the fluorescence, due to frequently associated antimitochondrial antibody, faded. The ANMA fluorescent pattern was confirmed by indirect immunoperoxidase staining. ANMA was seen on both tissue cryostat sections and HEp-2 cells. It was a poorly or non-complement-fixing IgG, specific for an antigen resistant to DNase I, RNase, and trypsin. The significance of its presence in PBC in unknown at present. Identification of its antigen with one of the centromeric antigens is suggested.
We studied the behavior of some biochemical markers of fibrosis, the aminoterminal propeptide of type III procollagen (P-III-P), laminin, hyaluronate and fibronectin, in the sera of patients with primary biliary cirrhosis (PBC). Significant increases were found in serum laminin, hyaluronate and P-III-P and, more important, a significant correlation was found between the histological stage of the disease and serum hyaluronate. This parameter seems to distinguish between early PBC (I and II stages) and advanced disease with fibrosis. Moreover, a correlation between the histological stage and serum levels of both laminin and P-III-P was observed. Serum laminin, however, increases particularly in advanced disease, whereas high levels of sP-III-P are already present in the early stage. Finally, no significant differences were found between the plasma fibronectin levels of patients with primary biliary cirrhosis and those of controls.