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Biomedical subjects

L Okolicsanyi

Publications and source records attributed to L Okolicsanyi.

At least 19 recordsLinked to original sources
PubMed2006

Hepatitis C virus infection in a resident elderly population: a 10-year follow-up study.

BACKGROUND: The natural history of hepatitis C virus infection in the elderly is poorly known. OBJECTIVE: To assess the mortality rate, the progression of liver disease, the hepatitis C virus carrier state and the co-morbidity in a cohort of 35 out of 1,063 anti-hepatitis C virus positive elderly people prospectively followed-up from 1992 to 2002. METHODS: Liver function tests, hepatitis C virus-RNA analysis, hepatitis C virus genotyping and abdominal ultrasonography were assessed at the beginning of the study, and then, liver function tests and ultrasonography were performed annually during the first 5 years of the follow-up. At the end of the 10-year period, causes of death were recorded, while surviving patients underwent again medical examination, liver function tests and abdominal ultrasonography. RESULTS: Out of 35 patients with a 10-year follow-up, 12 patients died: only 2 (5.7%) from liver-related disease (hepatocellular carcinoma and liver failure), whilst 10 (28.5%) from extrahepatic causes. Out of the two patients dying from liver-related causes, one was hepatitis C virus-RNA positive and one hepatitis C virus-RNA negative. Among the 23 living patients, 13 were hepatitis C virus-RNA positive (56.5%), the majority being infected with genotype 2 (69%); of them, 6 (46.1%) had persistently normal alanine aminotransferase levels. None of the hepatitis C virus-RNA positive individuals had excessive alcohol intake. CONCLUSION: Despite the presumably long duration of infection in our cohort, the liver-related mortality was five-fold lower than that from extrahepatic causes (five-fold higher). Lack of hepatic co-morbidity factors, such as alcohol consumption, seems to be relevant for the limited severity of liver disease.

Age Distribution↗
PubMed2003

Treatment of primary sclerosing cholangitis with low-dose ursodeoxycholic acid: results of a retrospective Italian multicentre survey.

BACKGROUND: 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. AIM: To evaluate the efficacy of low-dose ursodeoxycholic acid in the treatment of primary sclerosing cholangitis. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Adult↗
PubMed2003

Association of keratin 8 gene mutation with chronic pancreatitis.

BACKGROUND: Keratin 8 (K8) and 18 (K18) are the major components of the intermediate filament cytoskeleton of pancreatic acinar cells and play a relevant role in pancreatic exocrine homeostasis. Transgenic mice for K8 have shown to display progressive exocrine pancreas alterations, including dysplasia, loss of acinar architecture, redifferentiation of acinar to ductal cells, inflammation, fibrosis, and substitution of exocrine tissue by adipose tissue. AIM: To investigate whether mutations in the keratin 8 gene are associated with chronic pancreatitis. METHODS: Mutations in the keratin 8 gene were determined by polymerase chain reaction/restriction fragment length polymorphism in 67 chronic pancreatitis patients and 100 normal controls. Sequence analysis was performed when necessary. RESULTS: Glycine-to-cysteine mutations at position 61 (G61C) of the keratin 8 gene were found in six patients (8.9 vs. 0%, p(c) < 0.003, odds ratio = 21.24, confidence interval = 2.74-164.42); none of the controls presented the mutation. No tyrosine-to-histidine mutations at position 53 (Y53H) were detected in any subject. CONCLUSION: G61C mutation of the keratin 8 gene, together with other environmental factors and/or genetic factors, could predispose to chronic pancreatitis, by interfering with the normal organization of keratin filaments.

Chronic Disease↗
PubMed2003

Novel association of HLA-haplotypes with primary sclerosing cholangitis (PSC) in a southern European population.

AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Adult↗
PubMed2002

Gastroprotective effects of amtolmetin guacyl: a new non-steroidal anti-inflammatory drug that activates inducible gastric nitric oxide synthase.

BACKGROUND: The novel non-steroidal anti-inflammatory drug amtolmetin guacyl has been shown to possess markedly reduced ulcerogenic effects and nitric oxide-mediated gastroprotective activity against the damage induced by ethanol in the rat. AIMS: To investigate, in the rat, the role of nitric oxide and of inducible nitric oxide synthase isoform in the protective effect of amtolmetin guacyl against the gastric damage induced by ethanol. METHODS: The effects of amtolmetin guacyl on gastric transmucosal potential difference and on gastric mucosal blood flow were investigated in the anaesthetised rat; myeloperoxidase activity, inducible and endothelial nitric oxide synthase protein content were determined in rat gastric mucosal homogenates. The anti-inflammatory drug tolmetin and the bacterial lipopolysaccharide from Escherichia coli were studied for comparison. RESULTS: In the anaesthetised rat, amtolmetin guacyl, but not tolmetin, reduced by approximately 50% the fall in gastric potential difference and, to a lesser extent, the macroscopic damage induced by ethanol. The effect of amtolmetin guacyl on transmucosal potential difference was prevented by the selective inducible nitric oxide synthase inhibitor 1400W. In amtolmetin guacyl-treated rats, 1400W decreased gastric mucosal blood flow, whereas it was inactive in vehicle- and tolmetin-treated animals. In gastric mucosal homogenates, both amtolmetin guacyl and lipopolysaccharide, but not tolmetin, increased inducible, but not endothelial, nitric oxide synthase protein content, as revealed by Western immunoblotting. CONCLUSIONS: These data confirm that amtolmetin guacyl is a non-steroidal anti-inflammatory agent devoid of gastrolesive properties, that can actually reduce the damaging effects of ethanol through the increase in nitric oxide production, via the inducible isoform of nitric oxide synthase.

Animals↗
PubMed2001

Long-acting octreotide is effective in controlling rebleeding angiodysplasia of the gastrointestinal tract.

BACKGROUND: Management of bleeding angiodysplasia of the gastrointestinal tract is often a major clinical problem. Lesions are frequently multiple, not detectable or missed during conventional endoscopy and patients are sometimes at high risk for complications because of advanced age and serious concomitant disorders. AIMS: To determine the efficacy of a new formulation of somatostatin analogue (octreotide long-acting) in management of recurrent bleeding angiodysplasia in patients resistant to endoscopic treatment and not suitable for surgery. PATIENTS AND METHODS: Three patients with recurrent bleeding angiodysplasia of gastrointestinal tract were treated with long-acting octreotide administered intramuscularly 20 mg monthly to each individual. The number of admissions for acute bleeding, hospital stay and number of blood units transfused before and after treatment (followup: 15-17 months) were regularly monitored. RESULTS: In each patient, a relevant decrease in number of hospital admissions, duration of hospital stay, number of administered blood units was seen and mean haemoglobin values significantly increased in all of them after introducing long-acting octreotide therapy. CONCLUSIONS: This is the first report on use of long-acting octreotide in bleeding angiodysplasia of gastrointestinal tract. Data suggest that long-acting octreotide is a safe drug and is successful in controlling recurrent gastrointestinal bleeding due to angiodysplasia in elderly patients not eligible for surgical or endoscopic therapy.

Aged↗
PubMed2001

Proinflammatory cytokines inhibit secretion in rat bile duct epithelium.

BACKGROUND AND AIMS: Cholestatic disorders often are associated with portal inflammation, but whether or how inflammation contributes to cholestasis is unknown. Thus we studied the effects of proinflammatory cytokines on bile duct epithelia secretory mechanisms. METHODS: Isolated bile duct units (IBDUs) were cultured with interleukin (IL)-6, interferon gamma, tumor necrosis factor (TNF)-alpha, and IL-1 alone or in combination. Ductular secretion was measured using video-optical planimetry. Bicarbonate and Cl(-) transport were assessed microfluorimetric measuring pH(i) (BCECF) and [Cl(-)](i) transients (MEQ). Expression of Cl(-)/HCO(3)(-) exchanger (AE-2), cystic fibrosis transmembrane conductance regulator (CFTR), and the secretin receptor (SR) were assessed by ribonuclease protection assay. Cellular cyclic adenosine monophosphate (cAMP) levels were studied by enzymatic immunoassay. Paracellular permeability was assessed using fluorescein-labeled dextrans (FD) in cholangiocyte monolayers (NRC-1). RESULTS: Although not effective when given alone, each combination of IL-6, interferon gamma, IL-1, and TNF-alpha inhibited secretion in IBDU. Cytokines inhibited cAMP formation, AE-2 activity, and cyclic AMP-dependent Cl(-) efflux, but not that induced by purinergic agonists. AE-2 gene expression was unaffected by proinflammatory cytokines, whereas CFTR and SR expression was increased. In addition, paracellular transit of FD across NRC-1 monolayers was increased. CONCLUSIONS: Inflammatory cytokines inhibit cAMP-dependent fluid secretion in cholangiocytes and impair the barrier functions of biliary epithelia. These changes may represent the molecular mechanisms by which inflammation leads to ductular cholestasis in vivo.

Animals↗
PubMed2000

Advances in familial and congenital cholestatic diseases. Clinical and diagnostic implications.

Recent progress in liver cell biology and molecular genetics revealed that a number of familial and congenital cholestatic disorders are caused by mutations in genes coding for hepatobiliary-transporter or for signalling proteins involved in morphogenesis. The status of the field is reviewed in the light of its impact on current diagnostic and clinical practice. The heterogeneous progressive familial intrahepatic cholestasis can now be separated into different genetic diseases. FIC1-defective progressive familial intrahepatic cholestasis (previously Byler disease) is determined by mutations in the FIC1 gene, coding for P-type ATPases of unknown physiological function, while a second form (bile salt export pump defective progressive familial intrahepatic cholestatis) is caused by a defective function of the canalicular bile salt export pump. Furthermore, a group of progressive familial intrahepatic cholestasis patients with high serum gamma glutamyltranspeptidase have mutations in the gene (PGY3) coding for the MDR3 protein, a canalicular ATP-dependent phopshatidylcholine translocator. Recurrent intrahepatic cholestasis (previously benign recurrent cholestasis), is also linked to specific mutations in the FIC1 gene. Finally, in Alagille syndrome, mutations in the JAG1 gene cause deficiency Jagged 1, a ligand for Notch 1, a receptor determining cell fate during early embryogenesis. Diagnosis of Alagille syndrome, a condition that should be suspected in all patients with unexplained cholestasis, will thus be confirmed by genetic analysis for mutations of JAG1. In children with cholestasis and low serum bile acid levels, an inborn error of bile acid synthesis should be excluded by urinary bile acid analysis by means of fast atom bombardment-ionization mass-spectrometry. In contrast, in children with cholestasis and high serum bile acid concentrations, a high serum gamma glutamyltranspeptidase value would indicate MDR3 deficiency, which should be excluded through biliary phospholipid determination and genetic analysis of PGY3 gene. Finally, in those children with cholestasis, high serum bile acids and low gamma glutamyltranspeptidase activity, analysis of mutation in FIC1 and bile salt export pump genes may lead to the diagnosis of progressive familial intrahepatic cholestasis either from bile salt export pump or FIC1 deficiency.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2000

Pathophysiology of the intrahepatic biliary epithelium.

The intrahepatic bile duct epithelium modulates the fluidity and alkalinity of the primary hepatocellular bile from which it reabsorbs fluids, amino acids, glucose and bile acids, while secreting water, electrolytes and immunoglobulin A. The transport function of the intrahepatic biliary epithelium is finely regulated by a number of gastrointestinal hormones, neuropeptides and neurotransmitters that promote either secretion or absorption. The intrahepatic biliary epithelium appears to be a primary target in a broad group of chronic cholestatic disorders that represent an important cause of morbidity and mortality. The spectrum of cholangiopathies ranges from conditions in which a normal epithelium is damaged by disordered autoimmunity, infectious agents, toxic compounds or ischaemia, to genetically determined disorders arising from an abnormal bile duct biology, such as cystic fibrosis or biliary atresia. Probably as a result of the known heterogeneity in cholangiocyte function, different portions of the biliary tree appear to be preferentially affected in specific cholangiopathies. From a pathophysiological point of view, cholangiopathies are characterized by the coexistence of cholangiocyte loss (by apoptotic or lytic cell death) with cholangiocyte proliferation and various degrees of portal inflammation, fibrosis and cholestasis. These basic disease mechanisms are discussed in detail. Better understanding of cholangiocyte pathophysiology, in particular the immune regulation of cholangiocyte function, will help in designing newer genetic or pharmacological approaches to treat cholangiopathies.

Absorption↗
PubMed1999

The monoethylglycinexylidide test for grading of liver cirrhosis.

BACKGROUND: Monoethylglycinexylidide (MEGX) formation following lignocaine injection has recently been proposed as a simple dynamic liver function test based on a single measurement of its serum concentration. AIM: To determine the optimal sampling time for MEGX determination. METHODS: A modelling analysis of lignocaine and MEGX kinetics was performed in seven normals and in four patients with compensated liver cirrhosis; a similar study was performed in 74 cirrhotic patients, divided into two groups according to disease severity (Pugh score). RESULTS: Only the MEGX fractional formation rate (kf) and formation delay (tau) were significantly altered in cirrhotic patients compared to normals: kf = 0.15 +/- 0.03 vs. 0.32 +/- 0.10 min-1 (mean +/- s.d.); tau = 7.7 +/- 2.0 vs. 3.9 +/- 2.9 min-1. A good correlation was found between kf and late (r = 0.82) but not early (r = 0.63) serum MEGX formation, suggesting that late measurements for the clinical MEGX test are preferred. In the second part of our investigation, by discriminant analysis of MEGX test data for 74 cirrhotic patients, the late MEGX concentrations gave the best discrimination between the two classes. In particular, the 60 min MEGX concentration showed the best diagnostic accuracy (81%), sensitivity (75%) and specificity (84%). The association of this with other MEGX parameters, either singly or derived from the whole curve measurements, did not improve the performance of the method. CONCLUSION: The MEGX test, based on a single determination 60 min after lignocaine injection, may be regarded as a simple and sensitive quantitative liver function test.

Adult↗
PubMed1999

Gallstone disease in an elderly population: the Silea study.

BACKGROUND: Little is known on gallbladder emptying and gallstone composition in the elderly. AIMS AND SUBJECTS: Cross-sectional survey on the prevalence of gallstone disease and associated factors, gallstone characteristics and gallbladder emptying in a population aged > or = 60 years. METHODS: Gallstone number and size as well as gallbladder motor function were assessed by ultrasound. Gallstone composition and pattern were evaluated by conventional radiology and computed tomography (CT) based on Hounsfield units (HU). RESULTS: Gallstones were found in 148/1,065 subjects (13.9%), while 136 subjects (12.8%) were cholecystectomized with an overall prevalence of gallstone disease of 26.7% (sex ratio: F > M). Multiple gallstones (62.7%) and small gallstones (52%, diameter < or = 15 mm) were seen; silent gallstones accounted for 93.9% of the total. Only diabetes mellitus in women was significantly associated with cholelithiasis. Gallbladder fasting volumes were larger in gallstone carriers than in controls (P < 0.01); residual and ejection volumes were also significantly greater in gallstone carriers, whereas ejection fractions were similar in the two groups (50.3% +/- 2.4 versus 54.9% +/- 3.0; not significant). Gallstone calcifications were detected in 29/91 gallstone carriers by X-ray and in another 20 by CT (HU > 90). Moreover, 35 gallstone carriers had a score < or = 50 HU and six had attenuation values between 50 and 90 HU. Six gallstone patterns were identified: hypo-isodense, homogeneously dense, rimmed, laminated, core-hyperdense, gas-containing. CONCLUSIONS: In the elderly, the prevalence of gallstone disease is very high, especially in women, but gallstone size, number and pattern and gallbladder emptying do not differ from those reported in the middle-aged gallstone population. Advanced age is associated with a high rate of calcified, probably pigment stones.

Age Factors↗
PubMed1999

Hyperbilirubinemia: does it matter?

Serum bilirubin concentrations are increased in several hematological and hepatic disorders; however, hyperbilirubinemia, often of familial origin, may occur without overt signs of hemolysis or evident liver disease. The authors review briefly the main steps of hepatic bilirubin metabolism, then discuss the pathogenetic mechanisms of the different forms of familial hyperbilirubinemia. The knowledge of these conditions is increasingly important because orthotopic liver transplantation may be a therapeutic choice for some severe forms. Furthermore, early diagnosis is necessary to avoid unnecessary medical investigations for the otherwise relatively common, benign unconjugated hyperbilirubinemia. Finally, individuals with unmasked defective bilirubin handling may be potential liver donors; thus, unexplained jaundice occurring after orthotopic liver transplantation may be related to this disorder.

Humans↗
PubMed1998

Purinergic regulation of acid/base transport in human and rat biliary epithelial cell lines.

Biliary epithelial cells (cholangiocytes) are responsible for rapid regulation of bile volume and alkalinity. Secretin and other hormones raising intracellular cyclic adenosine monophosphate (cAMP) concentrations promote biliary HCO3 secretion by stimulating apical Cl- channels and Cl-/HCO3- exchange (AE2). Cholangiocyte ion transport may also be stimulated by locally acting mediators; for example, adenosine 5'-triphosphate (ATP), a secretagogue that can be released into the bile by hepatocytes and cholangiocytes, activates Cl- conductances and Na+/H+ exchange (NHE) in cholangiocyte cell lines. To further explore the role of extracellular ATP in the paracrine regulation of carrier mechanisms regulating cholangiocyte H+/HCO3- secretion, we investigated the effects of nucleotides on intracellular pH regulation (measured by microfluorimetry with 2'7'-bis(2-carboxyethyl)-5,6,carboxyfluorescein [BCECF]) in human (MZ-ChA-1) and rat (NRC-1) cholangiocyte cell lines. In MZ-ChA-1 cells, 10 mol/L ATP, uridine 5'-triphosphate (UTP), and ATPgammas significantly increased NHE activity. The pharmacological profile of agonists was consistent with that anticipated for receptors of the P2Y2 class. ATP did not increase AE2 activity, but, when given to cells pretreated with agents raising intracellular cAMP, had a synergistic stimulatory effect that was inhibited by amiloride. To assess the polarity of purinergic receptors, monolayers of NRC-1 cells were exposed to apical or basolateral nucleotides. Apical administration of purinergic agonists, but not adenosine, increased basolateral NHE activity (ATPgammaS > UTP > ATP). Basolateral administration of purinergic agonists induced a weaker activation of NHE, which was instead strongly stimulated by adenosine and by adenosine receptor agonists (NECA = R-PIA = S-PIA). In conclusion, this study demonstrates that, consistent with the proposed role for biliary ATP in paracrine and autocrine control of cholangiocyte ion secretion, extracellular ATP stimulates cholangiocyte basolateral NHE activity through P2Y2 receptors that are predominantly expressed at the apical cell membrane.

Adenosine↗
PubMed1998

Hepatitis C virus infection and related chronic liver disease in a resident elderly population: the Silea Study.

The prevalence of hepatitis C virus (HCV) infection increases with advancing age, but the disease has been poorly studied in the elderly. A population-based study was therefore carried out to investigate the prevalence of HCV infection and the severity of HCV-related chronic liver disease in the elderly. One thousand and sixty-three people (> or = 60 years of age) were screened for antibodies to HCV (anti-HCV) and for possible abnormalities of common liver function tests. Positive subjects and sex and age-matched anti-HCV-negative controls were recalled 12 months later for measurements of liver enzymes, confirmatory testing of anti-HCV, HCV RNA analysis and HCV genotyping. All subjects answered a specific questionnaire concerning medical history and possible risk factors. Forty-four subjects were positive for anit-HCV, the prevalence being 4.1%. Thirty-five positive subjects and 35 controls were investigated further. Risk factors for acquiring HCV were found to be: blood transfusion, surgical intervention and the use of non-disposable syringes. Abnormal alanine aminotransferase levels were found in 13 patients (37.1%). HCV RNA genotyping showed type 1b in three (15.8%), type 2a in 13 (68.4%) and not classified in three (15.8%) patients. There was no relationship between abnormalities of serum aminotransferase, the rate of HCV RNA positivity and HCV genotypes. Ultrasound abnormalities were present in 13 (37.1%) patients. In this elderly population the relatively high prevalence of HCV infection was thought to be caused by previous parenteral exposure. The low incidence of liver disease could be related to the prevalence of HCV genotype 2a in the majority of these patients, and hints at the possibility of an HCV carrier state in elderly individuals.

Aged↗
PubMed1997

Factors associated with gallstone disease in the MICOL experience. Multicenter Italian Study on Epidemiology of Cholelithiasis.

The epidemiological associations of gallstone disease were evaluated in a general population sample of 29,584 individuals (15,910 men and 13,674 women; age range, 30-39 years) belonging to 14 cohorts examined between December 1984 and April 1987. Subjects were screened for the presence of gallstones by gallbladder ultrasonography, completed a questionnaire, and underwent a physical examination and blood chemistry tests. Participants were considered to have gallstone disease if they had already had cholecystectomy or gallstones. Statistical associations were established by univariate analysis of the age-standardized data and by stepwise multiple logistic regression. Increasing age and body mass index and a maternal family history of gallstone disease were the most consistent associations (both at univariate and multivariate analysis and in both sexes) found in this study. Personal history of dieting was associated with gallstone disease in men, and at univariate analysis, in women. Decreasing serum total cholesterol levels and increasing serum triglycerides were associated with gallstone disease in both sexes in the multivariate analysis. In women, associations were also found with a number of pregnancies and paternal family history of gallstone disease. A slight but negative association with contraceptive pill use was identified only at multivariate analysis. Associations (investigated at univariate analysis) were also found with diabetes, cirrhosis, angina or myocardial infarction, and peptic ulcer. There was no association with smoking habits and use of aspirin or antirheumatic drugs.

Adult↗
PubMed1996

Primary sclerosing cholangitis: clinical presentation, natural history and prognostic variables: an Italian multicentre study. The Italian PSC Study Group.

OBJECTIVE: Because large-scale reports of PSC in the Mediterranean area we are still lacking, in this study we evaluated by Kaplan-Meyer analysis the natural history of primary sclerosing cholangitis (PSC) in Italy and by means of other statistical methods we identified the variables most useful in predicting survival of such patients. DESIGN: Retrospective multicentre study of unselected patients with PSC. Several variables involving sex, age, associated diseases, clinical features, laboratory, cholangiographic and histological findings at presentation and clinical outcome at data recording were collected by means of a detailed questionnaire. SETTING: 16 Italian university and regional hospitals all over the country, thus giving a geographically representative population. PATIENTS: A total of 117 PSC patients (73 men and 44 women); median age 35 years. METHODS: Survival analysis was performed by the Kaplan-Meyer method; the prognostic influence on survival of collected data was evaluated by univariate chi(2) analysis with Wilcoxon and log-rank tests. The same prognostic variables were also evaluated by multivariate analysis (Cox model), using a stepwise regression procedure. All statistical analyses were performed using the SAS statistical software. RESULTS: At presentation 70% of patients were symptomatic; symptoms did not relate to liver histology. Both intra- and extrahepatic bile duct lesions were detected in 46% of patients at cholangiography. Inflammatory bowel disease was found in 54% of symptomatic patients, ulcerative colitis was 36% of total. Clinical outcome (91/117): 15 underwent liver transplantation or died from liver disease (cholangiocarcinoma). Survival at 10 years was 74%. Features of poor prognosis were cholesterol, aspartate aminotransferase (AST), haemoglobin and albumin. CONCLUSION: PSC in Italy mainly follows a benign course and among clinical features recorded at presentation, serum cholesterol, AST, haemoglobin and albumin may provide some objective criteria to assess disease severity.

Adult↗