M Podda

Publications (87)547.39 Total impact

• Article: Genetic association of Fc receptor-like 3 polymorphisms with susceptibility to primary biliary cirrhosis: ethnic comparative study in Japanese and Italian patients.

  A Tanaka, H Ohira, K Kikuchi, S Nezu, A Shibuya, I Bianchi, M Podda, P Invernizzi, H Takikawa
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  ABSTRACT: A functional variant in the Fc receptor-like 3 (FCRL3) gene is associated with the susceptibility to several autoimmune diseases. In this study, we examined whether the FCRL3 is associated with susceptibility to primary biliary cirrhosis (PBC) by comparing the two different ethnic groups, Japanese and Italians. We enrolled 232 patients with PBC and 230 controls in Japanese, and 216 PBC and 180 controls in Italians. Minor allele frequency of fcrl3_3 (-169 T>C) in the patients with PBC and controls was 0.20 and 0.09 in Japanese and 0.24 and 0.21 in Italians, respectively. We found a significant association of fcrl3_3 with PBC only in Japanese (P = 9.64 × 10(-7) ). These findings support the presence of common FCRL3-related pathological pathways in several autoimmune diseases, especially in Asians.
  Tissue Antigens 03/2011; 77(3):239-43. · 2.59 Impact Factor
• Article: A short version of a HRQoL questionnaire for Italian and Japanese patients with Primary Biliary Cirrhosis.

  Lorenzo Montali, Atsushi Tanaka, Paolo Riva, Hiroki Takahashi, Claudio Cocchi, Yoshiyuki Ueno, Massimo Miglioretti, Hajime Takikawa, Luca Vecchio, Alessandra Frigerio, Ilaria Bianchi, Roberta Jorgensen, Keith D Lindor, Mauro Podda, Pietro Invernizzi
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  ABSTRACT: The available self-report questionnaire for the quality of life in patients with primary biliary cirrhosis (PBC-40) is currently validated only in the British population but it lacks an evaluation of its dimensionality. To validate the Italian and Japanese versions of PBC-40 and to assess the dimensionality of the original structure of PBC-40 by a confirmatory factor analysis. PBC-40 was translated to Italian and Japanese using the forward-backward method and then reviewed in focus groups in the framework of a large multicentric study. A sample of 290 patients with PBC (125 Italian and 165 Japanese) was administered two questionnaires previously validated for PBC-specific (PBC-40) and general quality of life (SF-36). The confirmatory model failed to fit adequately the original hypothesized structure. A principal component analysis led to a seven-factor structure, with exclusion of 13 items characterized by lower load; PBC-27 questionnaire was the final instrument. The validity of the PBC-27 was supported by its strong correlation with the SF-36 scores. We here propose an alternative structure of the quality of life questionnaire for PBC, namely PBC-27, which appears to be effective in detecting the impact of PBC on quality of life in Italian and Japanese patients.
  Digestive and Liver Disease 02/2010; 42(10):718-23. · 3.05 Impact Factor
• Article: Acute liver and renal failure during treatment with buprenorphine at therapeutic dose.

  M Zuin, A Giorgini, C Selmi, P M Battezzati, C A Cocchi, A Crosignani, A Benetti, P Invernizzi, M Podda
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  ABSTRACT: Buprenorphine is a semi-synthetic opioid derivative commonly used in the treatment of heroin addiction. Life-threatening complications have been described following overdoses while few cases of hepatotoxicity due to drug use at therapeutic doses have been recently described in hepatitis C virus carriers. In these cases, however, histological assessment was not exhaustive and no extra-hepatic organ failure was observed. We describe herein a case of acute liver and kidney failure in a patient with previously latent hepatitis C virus chronic infection following recommended doses of buprenorphine. Histology did not demonstrate any feature compatible with hepatitis C virus reactivation or liver cirrhosis and suspension of the treatment led to the resolution of both liver and kidney failure. Causality criteria fulfillment indicates a high probability of buprenorphine-induced liver toxicity. No signs of pre-existant kidney impairment or of pre- or post-renal causes were observed. Since buprenorphine is metabolized through cytochrome P450 3A4, we genotyped six genetic polymorphisms previously described in poor metabolizers but could not confirm these pharmacogenetic bases in this case. In conclusion, we surmise that buprenorphine at suggested doses can induce liver and kidney failure in susceptible individuals, possibly through direct mitochondrial toxicity.
  Digestive and Liver Disease 03/2008; 41(7):e8-e10. · 3.05 Impact Factor
• Article: Inadequate dietary intake but not renal tubular acidosis is associated with bone demineralization in primary biliary cirrhosis.

  M Allocca, A Crosignani, A Gritti, A Benetti, M Zuin, M Podda, P M Battezzati
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  ABSTRACT: 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. To evaluate the prevalence of RTA in PBC and establish the relationships among bone mineral density (BMD), renal function and nutritional status. 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. 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. 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.
  Alimentary Pharmacology & Therapeutics 02/2007; 25(2):219-27. · 3.77 Impact Factor
• Source

  Available from: Giorgio Ghilardi

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

  M Allocca, A Crosignani, A Gritti, G Ghilardi, D Gobatti, D Caruso, M Zuin, M Podda, P M Battezzati
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  ABSTRACT: 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. To establish whether hypercholesterolaemia is associated with subclinical atherosclerosis in PBC. 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. Ultrasound imaging of carotid artery to determine intima-media thickness (IMT) and stenosis. 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). 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.
  Gut 12/2006; 55(12):1795-800. · 10.11 Impact Factor
• Source

  Available from: bmj.com

  Article: Lack of serum antibodies to membrane bound carbonic anhydrase IV in patients with primary biliary cirrhosis.

  P Invernizzi, C Selmi, M Zuin, M Podda
  Gut 12/2005; 54(11):1665. · 10.11 Impact Factor
• Article: Genes and (auto)immunity in primary biliary cirrhosis.

  C Selmi, P Invernizzi, M Zuin, M Podda, M F Seldin, M E Gershwin
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  ABSTRACT: Primary biliary cirrhosis (PBC) is a chronic autoimmune cholestatic liver disease most commonly encountered in postmenopausal women; it is characterized by high-titer serum autoantibodies to mitochondrial antigens, elevated serum IgM, progressive destruction of intrahepatic bile ducts, and ultimately liver cirrhosis and failure. The cytopathic mechanisms leading to the selective destruction of intrahepatic cholangiocytes are still largely unknown. The current theory on the pathogenesis of PBC indicated that environmental factors might trigger autoimmunity in genetically susceptible individuals. In fact, genetic predisposition is critical to disease onset and progression, yet peculiar among autoimmune diseases, as indicated by the lack of a strong association with major histocompatibility complex haplotypes. Further, the recently reported concordance rate among monozygotic twins strengthens the importance of genetic factors, while also indicating that additional factors, possibly infectious agents or xenobiotics, intervene to trigger the disease. In this review, the available data regarding the genetic factors associated with PBC susceptibility and progression, as well as the available evidence regarding the immunomediated pathogenesis of PBC, will be critically illustrated and discussed.
  Genes and Immunity 11/2005; 6(7):543-56. · 3.87 Impact Factor
• Article: Ursodeoxycholic acid for liver disease associated with cystic fibrosis: A double‐blind multicenter trial

  C Colombo, P M Battezzati, M Podda, N Bettinardi, A Giunta
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  ABSTRACT: Liver disease is increasingly recognized as a major cause of morbidity in cystic fibrosis (CF). Preliminary data suggest that ursodeoxycholic acid (UDCA) may be beneficial for treatment of this manifestation. We performed a double-blind, multicenter trial in these patients to establish efficacy and safety of UDCA in terms of the improvement of clinical and nutritional indicators besides standard liver function tests. We also intended to establish whether taurine supplementation has a beneficial effect in patients receiving UDCA. From June to December 1990, we enrolled in 12 centers 55 CF patients with liver disease (39 male subjects; median age, 13.8 years). They were randomly assigned to receive for 1 year one of the following treatments: UDCA (15 mg/kg body weight daily) plus taurine (30 mg/kg body weight daily), UDCA plus placebo, placebo plus taurine, or double placebo. Clinical and laboratory evaluations were performed every 3 months. After 1 year, deterioration of overall clinical conditions, as indicated by the Shwachman-Kulczycki score (SKS), occurred in patients who received placebo but not in those who received UDCA (P = .025). Patients treated with UDCA also showed an improvement in γ-glutamyl transpeptidase (GGT) (P = .004) and 5′-nucleotidase (P = .006) levels. Treatment with taurine was followed by a significant increase in serum prealbumin levels (P = .053), a trend toward a reduction in fat malabsorption, and no effect on the biochemical profile. No severe side effects occurred with any treatment. Thus, we concluded that UDCA administration improves clinical and biochemical parameters in CF patients with liver disease. Taurine supplementation may be indicated in patients with severe pancreatic insufficiency and poor nutritional status.
  Hepatology 12/2003; 23(6):1484 - 1490. · 11.66 Impact Factor
• Source

  Available from: radiofrequency.it

  Article: Safety and efficacy of laparoscopic radiofrequency ablation of hepatocellular carcinoma in patients with liver cirrhosis.

  R Santambrogio, M Podda, M Zuin, E Bertolini, S Bruno, G P Cornalba, M Costa, M Montorsi
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  ABSTRACT: The optimal treatment for hepatocellular carcinoma (HCC) is surgical resection. However, only a small percentage of patients are operative candidates. Percutaneous radiofrequency interstitial thermal ablation (RITA) has been shown to be efficacious in the treatment of unresectable HCC. Recent advances in laparoscopic ultrasound have greatly improved the accuracy in detecting intrahepatic HCC nodules, many of which were missed by computed tomography. Our objective was to introduce a novel operative combination of laparoscopic ultrasound with laparoscopic RITA in the treatment of HCC. Eighty-eight patients with HCC in liver cirrhosis were submitted to laparoscopic RITA under sonographic guide. Most patients were in Child's A class of liver function. Patients with large tumors (> 5 cm), portal vein thrombosis, or severe liver disease (Child's C class) were excluded. The laparoscopic RITA procedure was completed in 86 of 88 patients (98% feasibility rate). Laparoscopy with laparoscopic ultrasound identified 23 new malignant lesions (27%) in comparison with the results of preoperative imaging. A total of 127 lesions were treated by RITA. There was no operative mortality. Sixty-one patients had no complication (71%). After a mean follow-up of 14.3 +/- 11.6 months, a complete response with a 100% necrosis was achieved in 70 of 83 patients examined (86%). During follow-up, 9 patients (11%) locally recurred at the RITA site and 38 patients (46%) had new malignant nodules. Laparoscopic RITA of HCC proved to be a safe and effective technique in the short term. This technique may be indicated when the percutaneous approach to the lesion is very difficult or if the patient is too ill to undergo laparotomy.
  Surgical Endoscopy 11/2003; 17(11):1826-32. · 4.01 Impact Factor
• Article: Novel association of HLA-haplotypes with primary sclerosing cholangitis (PSC) in a southern European population.

  T M Neri, G M Cavestro, P Seghini, P F Zanelli, A Zanetti, M Savi, M Podda, M Zuin, M Colombo, A Floreani, F Rosina, G Bianchi Porro, M Strazzabosco, L Okolicsanyi
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  ABSTRACT: In patients with with primary sclerosing cholangitis we investigated the major histocompatibility complex (MHC) genes and mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. In 64 PSC patients and 183 normal controls of the same population (Northern Italy), allelic polymorphisms at the DNA level were investigated in MHC region genes: HLA-DRB1, HLA-DQB1 and HLA-B, tumour necrosis factor A (TNFA), and in CFTR gene, with polymerase chain reaction-based methodologies. Frequencies of DRB1*01, DQA1*0101, DQB1*0102 (14 vs. 8%, p<0.05), DRB1*16, DQA1*0102, DQB1*0502 (8 vs. 3%, p<0.025) and DRB1*04, DQA1*03, DQB1*0301 (10 vs. 4%, p<0.005) haplotypes were more elevated in PSC patients. The frequency of patients positive for HLA DRB1*01, *1601 or *04 related haplotypes was significantly increased (32 vs. 14%, p<0.00025). DRB1*07, DQA1*0201, DQB1*02 haplotype frequency was significantly decreased (4 vs. 15%, p<0.001). After removing HLA-DRB1*01, *1601, *04 related haplotype sharing patients, HLA-DRB1*03, DQA1*0501, DQB1*02 haplotype frequency was significantly increased (32 vs. 14%, p<0.01). TNFA2 allele frequency was significantly increased in PSC patients (23 vs. 14%, p<0.025), as well as the TNFA2 homozygous genotype (9 vs. 0.5%, p=0.0013). No mutations were found on the CFTR gene and the allelic frequency of the 5T polymorphism in intron 8 was not increased. These data suggest that the role of genes in the HLA region is relevant, but not necessarily disease-specific and it might be different in populations with divergent ancestries.
  Digestive and Liver Disease 08/2003; 35(8):571-6. · 3.05 Impact Factor
• Article: Treatment of primary sclerosing cholangitis with low-dose ursodeoxycholic acid: results of a retrospective Italian multicentre survey.

  L Okolicsanyi, M Groppo, A Floreani, A M Morselli-Labate, A G Rusticali, A Battocchia, M Colombo, G Galatola, G Gasbarrini, M Podda, G Ricci, F Rosina, M Zuin
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  ABSTRACT: Data concerning the usefulness and type of drugs employed to treat patients with primary sclerosing cholangitis are controversial. Ursodeoxycholic acid has been shown to be a useful agent, however the drug dosage and its effect on the clinical course are still under debate. To evaluate the efficacy of low-dose ursodeoxycholic acid in the treatment of primary sclerosing cholangitis. We retrospectively analysed data from 86 patients with primary sclerosing cholangitis from eight centres in Italy between 1987 and 1997: 69 were treated with ursodeoxycholic acid (8-13 mg/kg/day), while 17 received symptomatic treatment and served as controls. The effect of therapy was evaluated by standard liver function tests and symptom analysis. Ursodeoxycholic acid treatment was associated with significant improvement in serum alkaline phosphatase (735+/-833 vs. 519+/-448 U/l, p<0.001), gamma-glutamyl transpeptidase (401+/-352 vs. 234+/-235 U/l, p<0.001), aspartate aminotransferase (87+/-70 vs. 56+/-42 U/l, p=0.001), alanine aminotransferase (146+/-139 vs. 76+/-73 U/l, p<0.001), and total bilirubin (1.88+/-2.44 vs. 1.76+/-4.12 U/l, p=0.01); there was also amelioration of fatigue (p=0.007), jaundice (p=0.002), and body weight loss (p=0.002). Ursodeoxycholic acid, at a dose of 8-13 mg/kg/day was beneficial for the general condition and liver biochemistry of patients with primary sclerosing cholangitis; high-dose ursodeoxycholic acid treatment requires further evaluation.
  Digestive and Liver Disease 06/2003; 35(5):325-31. · 3.05 Impact Factor
• Article: Hyperlipidaemic state and cardiovascular risk in primary biliary cirrhosis.

  M Longo, A Crosignani, P M Battezzati, C Squarcia Giussani, P Invernizzi, M Zuin, M Podda
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  ABSTRACT: Primary biliary cirrhosis (PBC), a chronic cholestatic liver disease, is frequently associated with severe hypercholesterolaemia but the clinical significance of this finding is unclear. To characterise changes in serum lipid profile over time and to assess the risk of cardiovascular disease in PBC. 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. 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). 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.
  Gut 09/2002; 51(2):265-9. · 10.11 Impact Factor
• Article: Ten-year combination treatment with colchicine and ursodeoxycholic acid for primary biliary cirrhosis: a double-blind, placebo-controlled trial on symptomatic patients.

  P M Battezzati, M Zuin, A Crosignani, M Allocca, P Invernizzi, C Selmi, E Villa, M Podda
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  ABSTRACT: Combined medical treatment may provide further benefit to primary biliary cirrhosis (PBC) patients administered ursodeoxycholic acid (UDCA). To evaluate the long-term effects of colchicine and UDCA in symptomatic PBC patients. 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. 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. In cirrhotic PBC patients, colchicine does not offer additional benefits to UDCA. In this population, UDCA does not obviate disease progression.
  Alimentary Pharmacology & Therapeutics 10/2001; 15(9):1427-34. · 3.77 Impact Factor
• Article: Long-term beneficial effects in sustained responders to interferon-alfa therapy for chronic hepatitis C.

  S Bruno, P M Battezzati, G Bellati, A Manzin, M Maggioni, A Crosignani, M Borzio, L Solforosi, A Morabito, G Ideo, M Podda
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  ABSTRACT: 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. 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. 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). 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.
  Journal of Hepatology 06/2001; 34(5):748-55. · 9.26 Impact Factor
• Article: Cholesterol metabolism in primary biliary cirrhosis during simvastatin and UDCA administration.

  M Del Puppo, M Galli Kienle, A Crosignani, M L Petroni, B Amati, M Zuin, M Podda
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  ABSTRACT: Little is known about the effects of cholesterol-lowering agents in hypercholesterolemic patients with primary biliary cirrhosis (PBC). The aim of this study was to compare the changes induced by simvastatin and ursodeoxycholic acid (UDCA) on cholesterol metabolism in patients with PBC and preserved liver function. Six patients with PBC were administered simvastatin (40 mg/day) for 30 days and, after a washout period of 30 days, ursodeoxycholic acid (600 mg/day) for 30 days. Serum levels of lathosterol, campesterol, 7 alpha-hydroxycholesterol, and 27-hydroxycholesterol were measured by gas chromatography-mass spectrometry. During simvastatin administration, reduction of cholesterol levels (34% in 30 days) was paralleled by the decrease of lathosterol (55%), whereas concentrations of campesterol and of the two hydroxysterols were not substantially modified. During ursodeoxycholic acid administration, a trend toward a decrease of serum cholesterol concentrations was observed after only one year of treatment, and these changes were paralleled by the decrease of campesterol serum levels. Both simvastatin and UDCA were well tolerated, and a reduction of serum liver enzyme levels occurred with the latter. Simvastatin proved to be safe and effective in reducing serum cholesterol levels in patients with PBC by an inhibitory effect on cholesterol synthesis occurring within 24 h. --Del Puppo, M., M. Galli Kienle, A. Crosignani, M. L. Petroni, B. Amati, M. Zuin, and M. Podda. Cholesterol metabolism in primary biliary cirrhosis during simvastatin and UDCA administration. J. Lipid Res. 2001. 42: 437--441.
  The Journal of Lipid Research 04/2001; 42(3):437-41. · 5.56 Impact Factor
• Article: Autoantibodies against nuclear pore complexes are associated with more active and severe liver disease in primary biliary cirrhosis.

  P Invernizzi, M Podda, P M Battezzati, A Crosignani, M Zuin, E Hitchman, M Maggioni, P L Meroni, E Penner, J Wesierska-Gadek
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  ABSTRACT: Antibodies against nuclear pore complexes (NPCs) have been detected in primary biliary cirrhosis (PBC), but their clinical relevance is still unsettled. 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. 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). Autoantibodies to NPCs are more prevalent in PBC patients than in controls and are strongly associated with more active and severe disease.
  Journal of Hepatology 03/2001; 34(3):366-72. · 9.26 Impact Factor
• Article: Radiofrequency interstitial thermal ablation of hepatocellular carcinoma in liver cirrhosis. Role of the laparoscopic approach.

  M Montorsi, R Santambrogio, P Bianchi, E Opocher, M Zuin, E Bertolini, S Bruno, M Podda
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  ABSTRACT: The laparoscopic approach to radiofrequency interstitial thermal ablation (RITA) of hepatocellular carcinoma (HCC) with intraoperative ultrasound guidance has been proposed with the aim of obtaining additional information for a better neoplastic staging and a complete and effective treatment of the liver lesions in patients with a difficult percutaneous approach. In this pilot study, 29 patients with HCC in liver cirrhosis were submitted to laparoscopic RITA under sonographic guide. Most of these patients were in Child's A class of liver function. Patients with large tumors (> 5 cm), portal vein thrombosis, or severe liver disease (Child's C class) were excluded from the study. The laparoscopic RITA procedure was completed in 27 of 29 patients (93% feasibility rate). The laparoscopic ultrasound examination identified new malignant liver nodules in five patients (18.5%). A total of 44 lesions were treated. The mean operative time was 75.8 +/- 20.5 min (range, 45-120 min), and the mean RITA time was 18 +/- 10 min (range, 10-56 min). There was no operative mortality, and postoperative morbidity was low (four cases) without any mortality. A complete tumor necrosis was observed in 90% of the patients via spiral computed tomography (CT) 1 month after treatment. Laparoscopic RITA of hepatocellular carcinoma proved to be a safe and effective technique, at least in the short term. Its role in the treatment of HCC needs to be defined in larger series.
  Surgical Endoscopy 02/2001; 15(2):141-5. · 4.01 Impact Factor
• Article: Ursodeoxycholic acid alone or with chenodeoxycholic acid for dissolution of cholesterol gallstones: a randomized multicentre trial. The British-Italian Gallstone Study group.

  M L Petroni, R P Jazrawi, P Pazzi, A Lanzini, M Zuin, M G Pigozzi, M Fracchia, G Galatola, V Alvisi, K W Heaton, M Podda, T C Northfield
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  ABSTRACT: Combination therapy using ursodeoxycholic acid plus chenodeoxycholic acid has been advocated for dissolution of cholesterol gallstones because the two bile acids have complementary effects on biliary lipid metabolism and cholesterol solubilization. To compare the clinical efficacy of combination therapy with ursodeoxycholic acid monotherapy. A total of 154 symptomatic patients with radiolucent stones (< or = 15 mm) in functioning gallbladders were enrolled from six centres in England and Italy. They were randomized to either a combination of chenodeoxycholic acid plus ursodeoxycholic acid (5 mg.day/kg each) or to ursodeoxycholic acid alone (10 mg.day/kg). Dissolution was assessed by 6-monthly oral cholecystography and ultrasonography for up to 24 months. Both regimens reduced the frequency of biliary pain and there was no significant difference between them in terms of side-effects or dropout rate. Complete gallstone dissolution on an intention-to-treat basis was similar at all time intervals. At 24 months this was 28% with ursodeoxycholic acid alone and 30% with combination therapy. The mean dissolution rates at 6 and 12 months were 47% and 59% with ursodeoxycholic acid, and 44% and 59% with combination therapy, respectively. There is no substantial difference in the efficacy of combined ursodeoxycholic acid and chenodeoxycholic acid and that of ursodeoxycholic acid alone in terms of gallstone dissolution rate, complete gallstone dissolution, or relief of biliary pain.
  Alimentary Pharmacology & Therapeutics 02/2001; 15(1):123-8. · 3.77 Impact Factor
• Source

  Available from: Silvia M Sirchia

  Article: Blood fetal microchimerism in primary biliary cirrhosis.

  P Invernizzi, C De Andreis, S M Sirchia, P M Battezzati, M Zuin, F Rossella, F Perego, M Bignotto, G Simoni, M Podda
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  ABSTRACT: 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.
  Clinical & Experimental Immunology 01/2001; 122(3):418-22. · 3.36 Impact Factor
• Article: Multicentre randomized placebo-controlled trial of ursodeoxycholic acid with or without colchicine in symptomatic primary biliary cirrhosis.

  P L Almasio, A Floreani, M Chiaramonte, G Provenzano, P Battezzati, A Crosignani, M Podda, L Todros, F Rosina, G Saccoccio, F Manenti, G Ballardini, F P Bianchi, P J Scheuer, S E Davies, A Craxì
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  ABSTRACT: To establish the efficacy of combination therapy with ursodeoxycholic acid (UDCA) and colchicine in patients with symptomatic primary biliary cirrhosis (PBC), defined by the presence of liver cirrhosis, pruritus or bilirubin exceeding 2 mg/mL. A total of 90 patients were randomly assigned to ursodeoxycholic acid 500 mg/daily plus placebo (UDCA group, n=44), or ursodeoxycholic acid at the same dosage plus colchicine, 1 mg/daily (UDCA/C group, n=46). The two groups were comparable for age, sex, stage of disease, severity of pruritus, bilirubin, and Mayo score. All patients underwent clinical, ultrasonographic, and biochemical examinations at entry and then every 6 months up to 3 years of follow-up. Patients with cirrhosis underwent endoscopy every 12 months. In a sub-group of patients without cirrhosis, who consented, liver biopsy was repeated at the end of the study. The number of treatment failures (i.e. dead, orthotopic liver transplantation (OLT), complications of cirrhosis, doubling of bilirubin, untreatable pruritus) was 11 (25%) in the UDCA group and four (9%) in the UDCA/C group (P < 0.05). No significant differences were observed in terms of improvement of liver enzymes related to cholestasis and cytolysis and of amelioration of pruritus. The Mayo score values increased less above the baseline values at 24 and 36 month-intervals in the UDCA/C group than in the UDCA group. Histological evaluation at baseline and at the end of the study was available for 15 patients with pre-cirrhotic stage. A significant reduction in histological grading score was observed in patients from the UDCA/C group, whereas no changes in these histological scores were observed in the UDCA group. The addition of colchicine to ursodeoxycholic acid in patients with symptomatic primary biliary cirrhosis results in a small but significant reduction of disease progress.
  Alimentary Pharmacology & Therapeutics 12/2000; 14(12):1645-52. · 3.77 Impact Factor