PubMed Health⌕ Search

Biomedical subjects

P M Battezzati

Publications and source records attributed to P M Battezzati.

At least 19 recordsLinked to original sources
PubMed2007

Inadequate dietary intake but not renal tubular acidosis is associated with bone demineralization in primary biliary cirrhosis.

BACKGROUND: Metabolic bone disease associated with primary biliary cirrhosis (PBC) is inadequately characterized. Renal tubular acidosis (RTA) may lead to bone loss through chronic mobilization of skeletal calcium salts to buffer increased acid load. AIM: To evaluate the prevalence of RTA in PBC and establish the relationships among bone mineral density (BMD), renal function and nutritional status. METHODS: We enrolled 69 female patients with compensated PBC and 35 control patients with chronic hepatitis C. RTA was searched in all patients, and 24-h dietary recalls were collected at enrolment. BMD was measured by dual-energy X-ray absorptiometry at the femur neck, lumbar spine and radius ultradistalis sites. RESULTS: No patients received a diagnosis of RTA. BMD values (Z-scores) showed only little deviation from normal population with no difference between PBC and controls. Osteopoenic PBC patients (T-score < 1) showed significantly lower daily phosphorus intake [median: 672 (288-1374) vs. 921 (253-1923) mg/day; P = 0.037], with a trend towards lower caloric intake than their nonosteopoenic counterparts. CONCLUSIONS: Renal tubular acidosis is uncommon in compensated PBC. Cholestasis is not associated with an increased risk of bone demineralization. Inadequate dietary intake may be a preventable factor contributing to bone loss in PBC.

Acidosis, Renal Tubular↗
PubMed2006

Hypercholesterolaemia is not associated with early atherosclerotic lesions in primary biliary cirrhosis.

BACKGROUND: Hypercholesterolaemia often occurs in primary biliary cirrhosis (PBC) as a result of chronic cholestasis, but whether these patients are exposed to greater cardiovascular risk is unknown. AIM: To establish whether hypercholesterolaemia is associated with subclinical atherosclerosis in PBC. PATIENTS: 103 consecutive patients with PBC (37 with total cholesterol > or =6.21 mmol/l) and 37 controls with hypercholesterolaemia, and 141 matched controls with normocholesterolaemia. METHODS: Ultrasound imaging of carotid artery to determine intima-media thickness (IMT) and stenosis. RESULTS: Controls with hypercholesterolaemia had higher IMT and prevalence of carotid stenosis compared with patients with hypercholesterolaemic PBC (mean (SD) 0.850 (0.292) mm v 0.616 (0.137) mm, p(c)<0.001; 43% v 19%, p(c) = 0.129) who, in turn, were similar to the 66 patients with normocholesterolaemic PBC (0.600 (0.136) mm; 5%). Compared with subjects with normocholesterolaemia, controls with hypercholesterolaemia, but not patients with hypercholesterolaemic PBC, had an increased risk of raised IMT (odds ratio (OR) 5.4, 95% confidence interval (CI) 2.5 to 11.9, p<0.001; and 0.7, 0.3 to 2.0, p = 0.543) or carotid stenosis (8.2, 3.4 to 20, p<0.001; and 2.5, 0.9 to 6.9, p = 0.075). In PBC, compared with younger patients without hypertension, the risk of increased IMT was OR (CI) 3.1 (0.6 to 17; p = 0.192) in patients with hypertension or old age, but not hypercholesterolaemia, and 4.6 (0.8 to 27; p = 0.096) in patients who also had hypercholesterolaemia. The corresponding figures for risk of stenosis were 3.6 (0.4 to 36; p = 0.277) and 15.8 (1.8 to 141; p = 0.014). CONCLUSIONS: Hypercholesterolaemia is not consistently associated with subclinical atherosclerosis in PBC, but should be treated if other risk factors for cardiovascular disease are also present. The search for factors that may protect patients with hypercholesterolaemic PBC against atherosclerosis should be encouraged.

Age Factors↗
PubMed2002

Hyperlipidaemic state and cardiovascular risk in primary biliary cirrhosis.

BACKGROUND: Primary biliary cirrhosis (PBC), a chronic cholestatic liver disease, is frequently associated with severe hypercholesterolaemia but the clinical significance of this finding is unclear. AIMS: To characterise changes in serum lipid profile over time and to assess the risk of cardiovascular disease in PBC. SUBJECTS AND METHODS: We studied a cohort of 400 PBC patients for 6.2 years (range 4 months to 24 years) by serial determinations of serum lipid levels and registration of all cardiovascular events. Subjects included in an Italian prospective population based study served as controls. RESULTS: At presentation, 76% of patients had serum cholesterol levels >5.2 mmol/l. Hyperbilirubinaemic patients had higher total cholesterol and lower high density lipoprotein (HDL) cholesterol levels (p<0.001). With time, disease progression was associated with a reduction in total (p<0.001) and HDL (p<0.05) cholesterol. The incidence of cardiovascular events was similar to that of the general population (cerebrovascular events: standardised ratio 1.4; 95% confidence interval 0.5-3.7; coronary events: 2.2; 0.9-4.3). Hypertension was associated with an increased risk of cardiovascular events (3.8; 1.6-8.9). Association with moderate hypercholesterolaemia was of borderline significance (3.8; 0.9-17) whereas severe hypercholesterolaemia was not associated with increased risk (2.4, 0.5-11). CONCLUSIONS: In PBC, serum cholesterol levels markedly increase with worsening of cholestasis, and decrease in the late disease stages, despite a severe reduction in biliary secretion. Marked hypercholesterolaemia, typical of severe longstanding cholestasis, is not associated with an excess risk of cardiovascular disease while less advanced patients with moderate hypercholesterolaemia are exposed to an increased cardiovascular risk. Putative protective factors in PBC patients with severe hypercholesterolaemia should be assessed.

Adult↗
PubMed2001

Autoantibodies against nuclear pore complexes are associated with more active and severe liver disease in primary biliary cirrhosis.

BACKGROUND/AIMS: Antibodies against nuclear pore complexes (NPCs) have been detected in primary biliary cirrhosis (PBC), but their clinical relevance is still unsettled. METHODS: We tested sera from 171 consecutive PBC patients and 230 control subjects (149 with autoimmune or viral liver diseases, 28 with systemic lupus erythematosus, and 53 healthy) by immunoblotting for antibodies against purified human NPCs. RESULTS: Antibodies to NPCs were detected in 27% of the patients with PBC, were highly specific (97%), and were not associated with antimitochondrial antibodies. Their prevalence was higher in symptomatic patients (36 vs. 16%, P < 0.01) and was associated (P < 0.001) with more severe disease, as assessed by the presence of cirrhosis or its complications (13% prevalence in patients without cirrhosis, 31% in uncomplicated, and 54% in complicated cirrhosis), or by the application of the Mayo prognostic model (12% in the lowest, 21% in the median, 47% in the highest score tertile). Positive patients had higher levels of serum bilirubin (2.2 +/- 3.7 vs. 1.0 +/- 1.1 mg/dl, P < 0.01) and more marked inflammatory infiltrates on liver biopsy (P < 0.05). CONCLUSIONS: Autoantibodies to NPCs are more prevalent in PBC patients than in controls and are strongly associated with more active and severe disease.

Autoantibodies↗
PubMed2001

Long-term beneficial effects in sustained responders to interferon-alfa therapy for chronic hepatitis C.

BACKGROUND/AIMS: Assessment of chronic hepatitis C outcome in sustained responders to interferon requires prolonged observation and close monitoring. We prospectively studied the impact of sustained response on histology and clinically relevant outcomes. METHODS: The 47 sustained responders (ten with cirrhosis) from two interferon trials involving 235 chronic hepatitis C patients (81 with cirrhosis) were included. Hepatitis C virus (HCV) RNA was assessed every 6 months, liver histological changes from baseline, 6-12 and 48-72 months after treatment discontinuation. RESULTS: The mean follow-up was 102 +/- 19 months. HCV RNA became undetectable in 36/47 responders. Four responders, who had remained viremic, later relapsed. The histology progressively improved in non-viremic and viremic patients, with a more marked improvement in the former (P = 0.0089), normalizing in 53 vs. 0% (P = 0.0220). No patient progressed to cirrhosis. One non-viremic cirrhotic patient developed a hepatocellular carcinoma. Non-responders from the two original trials had worse histological outcomes and those with cirrhosis had a higher rate of clinically relevant events compared with cirrhotics showing a sustained biochemical response (4.5 vs. 1.2 cases/100 person-years; CI for the difference, 0.3-6.3). CONCLUSIONS: Most sustained, virological responders without cirrhosis normalize liver histology in the long-term and are cured of the disease. Sustained responders remaining viremic still show histological improvement, albeit to a lesser extent.

Adult↗
PubMed2001

Heart rate variability and early recurrence of atrial fibrillation after electrical cardioversion.

OBJECTIVES: The study evaluated the role of the autonomic nervous system in atrial fibrillation (AF) recurrence. BACKGROUND: Early recurrence of AF after cardioversion (CV) is attributed to electrical remodeling. The possibility that an abnormal autonomic modulation might contribute to this phenomenon has not yet been adequately tested. METHODS: We analyzed short-term heart rate variability (HRV) in 93 patients with persistent AF and on chronic amiodarone treatment, after restoration of sinus rhythm by electrical CV. RESULTS: Two weeks later, 25 patients presented with AF. Spectral analysis of HRV revealed that patients wi

Aged↗
PubMed2001

Ten-year combination treatment with colchicine and ursodeoxycholic acid for primary biliary cirrhosis: a double-blind, placebo-controlled trial on symptomatic patients.

BACKGROUND: Combined medical treatment may provide further benefit to primary biliary cirrhosis (PBC) patients administered ursodeoxycholic acid (UDCA). AIM: To evaluate the long-term effects of colchicine and UDCA in symptomatic PBC patients. PATIENTS/METHODS: We extended up to 10 years the double-blind treatment of 44 symptomatic PBC patients originally included in a 3-year multicentre study comparing UDCA and colchicine (U + C) versus UDCA and placebo (U + P). Outcome measures were death or liver transplantation; incidence of clinically relevant events; clinical and quantitative variables retaining prognostic information. RESULTS: Mean follow-up was 7 +/- 3 years. One patient was lost, three withdrew because of jaundice (U + P); two patients stopped colchicine but remained on UDCA. Eleven patients (two for liver-unrelated reasons, U + P) and six patients (U + C) died, three and two patients, respectively, were transplanted (incidence rate difference, five cases per 100 patient-years; 95% CI, -1 to 11). Hepatocellular carcinoma developed in one (U + P) and four (U + C) patients (difference, -2; CI, -5 to 1), portal hypertension complications in nine patients from each group (difference, 1; CI, -5 to 6). Trends of serum bilirubin, Mayo score, antipyrine clearance were similar among treatment groups. CONCLUSIONS: In cirrhotic PBC patients, colchicine does not offer additional benefits to UDCA. In this population, UDCA does not obviate disease progression.

Colchicine↗
PubMed2000

Blood fetal microchimerism in primary biliary cirrhosis.

The autoimmune nature of primary biliary cirrhosis (PBC) is well established. We tested the hypothesis that fetal microchimerism indicated by the persistence of circulating fetal cells in women years after pregnancy might contribute to the aetiopathogenesis of PBC through a graft-versus-host-like response. We extracted DNA from the peripheral blood cells of 36 women carefully selected from 173 consecutive PBC patients, who were matched with 36 healthy women by age, age of last son, and number of children. Both patients and controls had to have male offspring, and no history of miscarriages or blood transfusions; they could not be twins. We tested all of the samples for the presence of two specific Y-chromosome sequences (SY154 and SRY) by amplifying DNA in a nested polymerase chain reaction. Y-chromosome-specific DNA was detected in the peripheral blood cell DNA of 13 (36%) of the 36 women with PBC and in 11 (31%) of the 36 healthy controls. The two groups of PBC patients with and without male DNA sequences were similar in terms of their clinical, biochemical, and serological features. Y-chromosome sequences were found in three of the four PBC women with associated systemic sclerosis. All of the 24 Y-positive samples contained SY154 sequences, but only three PBC patients and six controls showed the presence of both SY154 and SRY sequences. This discrepancy may suggest that not only fetal cells but also fragments of fetal DNA are present in maternal circulation. Overall, our data do not support the hypothesis that fetal microchimerism plays a significant role in the onset or progression of PBC.

Adult↗
PubMed1999

Differences in the metabolism and disposition of ursodeoxycholic acid and of its taurine-conjugated species in patients with primary biliary cirrhosis.

The clinical effectiveness of ursodeoxycholate in the treatment of liver disease may be limited by its poor absorption and extensive biotransformation. Because in vitro and in vivo studies suggest that the more hydrophilic bile acid tauroursodeoxycholate has greater beneficial effects than ursodeoxycholate, we have compared for the first time the absorption, metabolism, and clinical responses to these bile acids in patients with primary biliary cirrhosis (PBC). Twelve female patients with PBC were sequentially administered tauroursodeoxycholate and ursodeoxycholate (750 mg/d for 2 months) in a randomized, cross-over study. Bile acids were measured in serum, duodenal bile, urine, and feces by gas chromatography-mass spectrometry (GC-MS). Biliary ursodeoxycholate enrichment was higher during tauroursodeoxycholate administration (32.6% vs. 29.2% during ursodeoxycholate; P <.05). Lithocholic acid concentration was consistently higher in all biological fluids during ursodeoxycholate administration. Fecal bile acid excretion was the major route of elimination of both bile acids; ursodeoxycholate accounted for 8% and 23% of the total fecal bile acids during tauroursodeoxycholate and ursodeoxycholate administration, respectively (P <.05). Tauroursodeoxycholate was better absorbed than ursodeoxycholate, and, although it was partially deconjugated and reconjugated with glycine, it underwent reduced biotransformation to more hydrophobic metabolites. This comparative study suggests that tauroursodeoxycholate has significant advantages over ursodeoxycholate that may be of benefit for long-term therapy in PBC.

Absorption↗
PubMed1999

Delayed intestinal visualization at hepatobiliary scintigraphy is associated with response to long-term treatment with ursodeoxycholic acid in patients with cystic fibrosis-associated liver disease.

BACKGROUND/AIMS: Abnormalities of biliary drainage have been documented at hepatobiliary scintigraphy in many but not all patients studied with cystic fibrosis-associated liver disease. Ursodeoxycholic acid was shown to be beneficial in this disease, mainly by improving biliary secretion. Therefore, patients with impaired biliary drainage are expected to obtain the greatest benefit from this treatment. METHODS: We evaluated the effects of long-term treatment with ursodeoxycholic acid in 36 patients with cystic fibrosis-associated liver disease, and compared the response in patients presenting a normal (n=18) or delayed time of intestinal visualization (n=18) at baseline hepatobiliary scintigraphy. RESULTS: The mean treatment duration was 58+/-26 (S.D.) months and 63+/-29 months in the groups with normal or delayed time of intestinal visualization, respectively. The time of intestinal visualization decreased (57+/-23%, p<0.001) from baseline in patients with initially abnormal values and became normal in four (22%). Treatment failure, i.e. lack of sustained normalization of serum liver enzymes or the occurrence of a clinically relevant adverse event, was more frequently observed in patients with a normal time of intestinal visualization at baseline (OR, 5.50; 95% CI, 1.32-22.7). When only clinically relevant adverse events were considered, they occurred in six of the latter patients (liver transplantation in one case, development of ultrasographic or endoscopic signs of portal hypertension in six cases), but in only one patient (development of portal hypertension) in the group with delayed time of intestinal visualization (OR, 10.82; 95% CI, 1.17-100.4). CONCLUSIONS: Delayed intestinal visualization at hepatobiliary scintigraphy in patients with cystic fibrosis-associated liver disease seems to predict a better response to ursodeoxycholic acid.

Adolescent↗
PubMed1998

Complement system is not activated in primary biliary cirrhosis.

There is controversial evidence suggesting that the classical pathway of complement system is chronically activated in primary biliary cirrhosis (PBC) and that complement activation may be important in development of bile duct injury. We have reevaluated this issue by measuring by-products of complement activation such as C4a, C3a, Bb, and terminal complement complexes (SC5b-9) in plasma of 44 PBC patients with sensitive methods not previously used to detect complement activation in this disease. Age-matched healthy women and patients with chronic hepatitis of different etiology were studied as controls. We found that PBC patients have normal C4a concentrations. This finding argues strongly against chronic classical pathway activation. Although a minor increase of C3a levels was observed in a minority of PBC patients, the C3a/C3 ratio, an index used to evaluate the extent of native protein conversion, was remarkably similar in all groups. Potentially lytic terminal complement complexes were not increased. PBC patients had normal Bb plasma levels, indicating that the alternative pathway is also not activated. C3 concentration was higher in PBC patients than in healthy subjects and in chronic hepatitis patients, particularly in the early stages of the disease. C3 and C4 concentrations became lower in PBC and chronic hepatitis with the progression of the disease. The increase of C3 concentration in PBC does not reflect liver inflammation, since serum levels of C-reactive protein are normal. We found high serum C3 levels in patients with rare chronic cholestatic syndromes without superimposed infections and observed that serum C3 levels paralleled those of bilirubin in a patient with benign recurrent intrahepatic cholestasis. In conclusion, our data indicate that complement is not activated in PBC and that the increase of serum C3 levels is related to cholestasis.

Adult↗
PubMed1998

Antibody to carbonic anhydrase II is present in primary biliary cirrhosis (PBC) irrespective of antimitochondrial antibody status.

Antibody to carbonic anhydrase II, an enzyme abundantly present in biliary epithelium, has been proposed as a diagnostic marker for antimitochondrial antibody-negative PBC. In this study we determine its prevalence and clinical significance in a large series of patients with antimitochondrial antibody-positive and -negative PBC. Reactivity to carbonic anhydrase II was sought by Western immunoblotting in sera from 215 consecutive patients with PBC (26 antimitochondrial antibody-negative), 13 with autoimmune hepatitis, 25 with primary Sjögren's syndrome (pSS), 12 with systemic sclerosis, 19 with systemic lupus erythematosus and 73 healthy subjects. The prevalence of antibody to carbonic anhydrase II (titre 1:100) in PBC was 8%. No specific reactivity to carbonic anhydrase II was found in antimitochondrial antibody-negative PBC (7% versus 8% in antimitochondrial antibody-positive PBC). Ascites (P = 0.006) and Sjögren's syndrome (SS) (P = 0.022) in PBC were significantly associated with presence of the antibody. In patients with SS associated with PBC, the prevalence (19%) was similar to that observed in pSS (16%). At a serum dilution of 1:40, the prevalence of positive sera in PBC rose to 27% but disease specificity was reduced. Our findings in a large population of PBC patients rule out a relation between presence of antibody to carbonic anhydrase II and lack of antimitochondrial antibody. The higher prevalence of ascites found in positive patients warrants further evaluation.

Adult↗
PubMed1998

Liver and biliary problems in cystic fibrosis.

Liver disease associated with cystic fibrosis has been increasingly diagnosed during recent years probably due to the combined effect of systematic hepatic assessment and reduced death from extra-hepatic causes of CF patients. In a group of 173 CF patients regularly followed at our Center, cumulative incidence of liver disease was 17% over a mean period of 10 years. Although it generally runs a mild course, it is considered a major complication of CF which may limit survival and quality of life of affected patients. CF-associated liver disease should be considered as the first inherited liver disorder in which the primary defect affects cholangiocyte transport systems. Although data assessing the effects of defective CFTR on cholangiocyte pathobiology are not yet available, the impaired secretory function of the biliary epithelium is considered responsible for reduced biliary fluidity and alkalinity and for subsequent bile duct damage by cytotoxic compounds or infectious agents. No clear association with specific CFTR mutations has been observed. Treatment with ursodeoxycholic acid, aimed at improving biliary secretion in terms of bile viscosity and bile acid composition, is currently the most useful therapeutic approach in CF-associated liver disease. Beneficial effects on liver biochemistry, hepatic excretory function, liver histology, and essential fatty acid status have been reported, but no long-term data exist on its effectiveness on clinically relevant outcomes, such as death or need for transplantation. The effectiveness of bile acid therapy may be higher if started in patients with early stage liver disease, before symptoms have become clinically evident. Early diagnosis and identification of CF patients who are more liable to develop liver disease should be actively pursued.

Child↗
PubMed1998

Clinical significance of hepatic HCV RNA in patients with chronic hepatitis C demonstrating long-term sustained response to interferon-alpha therapy.

Whether sustained biochemical response and absence of serum HCV RNA in the 6-12 months following suspension of interferon-alpha (IFN-alpha) therapy reflect definitive viral clearance in patients with chronic hepatitis C virus (HCV) infection is controversial. To obtain more information on this topic, HCV RNA was sought in both liver and serum samples of 25 long-term responders who were followed for a median period of 39 months (range 21-79) after discontinuation of IFN-alpha. Liver biopsy was undertaken before and 6 to 12 months after IFN-alpha withdrawal. Liver and serum HCV RNA were tested by a nested polymerase chain reaction. Twenty-two patients (88%) tested negative for both liver and serum HCV RNA, two patients had detectable HCV RNA in both liver and serum, and one patient showed persistent HCV RNA only in the liver. Post-treatment liver histology improved markedly in all patients, including those with viral persistence. During further follow-up, biochemical remission was maintained in all patients except one in whom both serum and liver specimens remained HCV RNA positive. The data indicate that the large majority of long-term responders test negative for HCV RNA in the liver, which suggests definitive eradication of HCV RNA infection.

Adolescent↗
PubMed1997

Comparison of the clinical features and clinical course of antimitochondrial antibody-positive and -negative primary biliary cirrhosis.

Reports from North America and Northern Europe have suggested that antimitochondrial antibody (AMA) negative primary biliary cirrhosis (PBC) is a distinct chronic cholestatic liver disease with high prevalence of serum non-organ-specific autoantibodies other than AMA. To evaluate if such a peculiar serum immunoreactivity is associated with clinically relevant characteristics, we reviewed our experience with 297 Italian patients who have had a clinical and histological diagnosis of PBC and were regularly followed-up at our Center from June 1974 to June 1994. AMA-negative and AMA-positive patients were compared in terms of biochemical and clinical features, and clinical outcome of the disease. At presentation, 30 of 297 patients (10%) tested negative for AMA by indirect immunofluorescence. Six of them tested positive for antimitochondrial M2 antibodies (AMA-M2) by immunoblotting analysis, therefore, diagnosis of AMA-negative PBC was made in 24 patients (8%). At the initial visit, AMA-negative and AMA-positive patients were similar in terms of biochemical and clinical features. Antinuclear and anti-smooth-muscle antibodies (ANA and ASMA) were more frequently positive in the AMA-negative patients (71% vs. 31%, and 37% vs. 9%; both P = .0002). Incidence of complications of cirrhosis and development of liver failure resulting in death or referral for liver transplantation did not differ significantly between the two populations. In conclusion, data from this historical cohort study suggest that the distinct serological features of AMA-negative PBC are not associated with substantial differences in the clinical spectrum or course of the disease.

Adult↗