BackgroundObeticholic acid (OCA) stands as the sole approved second-line treatment for primary biliary cholangitis (PBC) patients unresponsive to ursodeoxycholic acid (UDCA). Preliminary studies suggested OCA's efficacy in reducing PBC decompensation and increasing survival. However, these studies face limitations, either due to heterogeneous cohorts (OCA registrative trial Vs real-world controls) or reliance on administrative data.AimTo compare transplant-free and liver-related event (LRE)-free survival between two large real-world cohorts of OCA-treated and untreated PBC patients.MethodsThe Italian RECAPITULATE is a multicenter real-world cohort of OCA-treated PBC patients enrolled from across Italy. An external control cohort of OCA-untreated PBC patients was derived from the GLOBAL-PBC dataset. Controls met OCA prescription criteria in Italy (ALP≥1.5/ULN and/or 1<bilirubin<2 mg/dl after ≥1 year of UDCA treatment), and a random visit in which eligibility criteria were met represented the index date. LRE (ascites with-/-out spontaneous bacterial peritonitis, hepatic encephalopathy, and upper gastrointestinal bleeding), liver transplant and liver-related death were tracked during follow-up. Weighted Cox regression method (using propensity scores) was applied for the external control group, incorporating age, ALP, AST, bilirubin, UDCA duration, cirrhosis and age at OCA start as baseline confounders.ResultsThe study included 437 RECAPITULATE patients (female: 88%; cirrhotics: 34%; on UDCA: 98%), and 831 GLOBAL-PBC controls (female: 91%; cirrhotics: 15%; on UDCA: 74%). RECAPITULATE's median follow-up was 30 months, and time was censored accordingly in the control cohort. Liver transplant/liver-related death and LRE were 4 and 16 in the RECAPITULATE cohort, and 58 and 107 in GLOBAL-PBC controls, respectively. In the weighted Cox regression analyses, patients in the RECAPITULATE cohort showed reduced risk of liver transplant/liver-related death [HR 0.318 (0.153-0.660); p<0.0001] and LRE [HR 0.327 (0.196-0.543); p<0.001] with respect to GLOBAL-PBC controls (Figure 1).ConclusionIn the comparison between two real-world cohorts, OCA-treated PBC patients show a longer transplant-free and LRE-free survival with respect to propensity-matched untreated controls.

Introduction and aim: Primary biliary cholangitis (PBC) is a slowly progressive autoimmune cholangiopathy, mainly affecting women. Our aim was to describe clinical and epidemiological profile of PBC patients followed-up in three hub hepatological canters in Piedmont and Liguria.

Introduction and Aims: Autoimmune hepatitis have a variable occurrence, clinical phenotype and outcome, and the factors contributing to this variability are uncertain. The goal of this study is to evaluate, through a retrospective analysis, data of severe acute hepatitis (SAH) requiring hospital admission between 1/2017 and 6/2018 in a tertiary inpatient Hepatological Unit. Incidence, clinical impact and outcome of non-viral/autoimmune acute hepatitis (AAH) were analyzed. AAH diagnosis was made using AAH scoring: definite diagnosis when AAH score was >15 pre-treatment and >17 post-treatment, or probable diagnosis when it was <15 and <17 respectively. SAH and Acute-on-Chornic Liver Disease (ACLD) were defined as presence of joundice, hepatomegaly and/or coagulation alteration (showed by an increased INR) and presence of a previous chronic liver disease, respectively.

Conclusions: HSC express ActRIIB and respond to myostatin with increased chemotaxis, reduced proliferation, and increased expression of profibrogenic genes

Background: Adrenal dysfunction (AD) is an emerging issue in end-stage liver disease.In cirrhotics with severe sepsis and septic shock it was associated with poor prognosis.Its clinical relevance and impact on survival in nonseptic cirrhotic patients are almost unknown.Aims: To evaluate the impact of AD on survival in nonseptic cirrhotic patients with ascites.Patients and Methods: A corticotropin stimulation test (tetracosactide 250 mg i.v) was performed in a series of consecutive cirrhotic patients with ascites; all were haemodynamically stable and without clinical or laboratory signs of sepsis.AD was defined by a "delta cortisol" lower than 9 mg /dL and/or a "peak cortisol" lower than 18 mg /dL.Patients were followed-up until liver transplantation or death.Results: Eighty-five patients were included.Overall AD prevalence was 39% (33/85).Median follow-up was 198 days (range 3-1031).Sixteen patients died, 11 (group 1) among patients with AD (11/33, 33%; median survival: 170 days, range 9-1031) and 5 (group 2) among patients without AD (5/52, 10%; median survival: 212 days, range 3-949).The most common cause of death was liver failure (5/11 pts in group 1 vs 2/5 pts in group 2), followed by hepatorenal syndrome type 1 (1/11 pts in group 1 vs 3/5 pts in group 2), sepsis (3 pts, all in group 1) and portal hypertension related bleeding (2 pts, all in group 1).The proportions of the causes of death were not significantly different between the two groups (p = ns).At univariate analysis, MELD score (p = 0.003), AD (p = 0.02), Child-Pugh score (p = 0.04) and plasma renin activity (p = 0.04) were significantly associated with mortality.Even at multivariate analysis AD was significantly associated with reduced survival (p = 0.03), together with MELD score (p = 0.02) and plasma renin activity (p = 0.03).Conclusions: Adrenal dysfunction is common in nonseptic cirrhotic patients and, according to our preliminary results, its presence is independently associated with reduced survival.These findings highlight the clinical relevance of adrenal dysfunction in nonseptic cirrhotic patients with ascites.

AIM:Triple therapy consisting of a proton pump inhibitor (PPI) and two antibiotics is used as first choice in treating Helicobacter pylori (H. pylori) infection. Since in the North Italian population, metronidazole resistance is less than 40%, this antibiotic would be preferable as first approach. The aim of this randomized study was to assess the efficacy of a metronidazole-based versus a tinidazole-based treatment, in naïve patients with H. pylori infection.METHODS:Diagnosis and eradication of H. pylori infection were assessed by 13C-urea breath test, and by histology when an endoscopic examination was necessary. A total of 171 patients was treated: 91 (47 males, mean age 50+/-3 years) with metronidazole 250 mg q.i.d., amoxicilline 1 gr b.i.d. and PPI standard dose (MAO), and 80 (36 males, mean age 52+/-3.8 years) with tinidazole 500 mg b.i.d., amoxicilline 1 gr b.i.d. and PPI standard dose (TAO) regimen for 7, 10 or 14 days.RESULTS:Three patients suspended MAO treatment due to side effects. H. pylori eradication was obtained as follow indicated. After 7 days, in 23/30 (76.6%) patients in MAO versus 20/27 (74.0%) in TAO regimen. After 10 days, in 20/26 (76.9%) patients in MAO versus 20/26 (76.9%) in TAO regimen. After 14 days, in 25/32 subjects (78.1%) in MAO versus 21/27 (77.7%) in TAO treatment. The differences among durations or between metronidazole-versus tinidazole-based triple therapy were not statistically different.CONCLUSION:Treatment with metronidazole is as effective as that with tinidazole in terms of efficacy. Moreover, duration did not influence efficacy of treatment.

AIM:Given the demographic shifts and needs of cost rationalization, it is of high priority to organize health care on the basis of ambulatory outpatients models. The aim of this study was to examine activity at the gastro-hepatology outpatients clinic of the Molinette Hospital. In this facility, the management is based on a work team organization that follows cohorts of patients with specific pathologies. METHODS:All services, consultations and urea breath test (UBT) for the diagnosis of Helicobacter pylori infection, carried out from January 2003 to December 2006, were extrapolated from the computerized system. Consultations were divided into first examination and controls. Furthermore, the destination of the patients after each consultation was considered. RESULTS:During the year 2003, 8 842 consultations and 4 071 UBT were carried out, in the year 2004, 11 342 consultations and 2 409 UBT, in the year 2005, 12 474 consultations and 2 510 UBT, in the year 2006, 12 249 consultations and 2 357 UBT. No further specialistic management was required for 25% of patients, while 2% had been hospitalized in the bed unit, 3% in the short hospitalization unit or the day-hospital. The remaining 70% were included in work teams or monitored thereafter. The comparison with consultations from 1994 shows an increase due to both first examination (+300%) and controls (+83%). CONCLUSIONS:The burden of the requests from the population and primary care structures addressed to the outpatients clinic of gastro-hepatology is relevant. The activity of this facility leads to a low rate of hospitalization as well as of cost reduction.

The interest that surrounds the bacterium Helicobacter pylori (H. pylori) is due not only to its causal role in several gastroduodenal diseases, but also to its supposed involvement in the pathogenesis of extragastric manifestations. This review provides a literature update on the hypothetic correlation between H. pylori and headache. The authors examine three aspects of this potential association: epidemiology, intervention trials and pathogenesis. Regarding the first, apart in some subgroups, no difference in prevalence exists between patients and controls. Considering the intervention studies, it is documented that, at 6 and 12 months, bacterial eradication is associated to disappearance of symptoms in 23% and 28% of cases, and to a significant decrease of intensity, frequency and duration of acute attacks in the remaining patients. As to the pathogenetic aspect, if H. pylori has a role, it does not act through oxidative stress. In conclusion, the involvement of H. pylori infection in the pathogenesis of headache is unclear. Further investigations should focalize on particular subgroups of patients and, encouraged from data produced by intervention studies, evaluate the long-term benefit of eradication.

Background/Aims: Treatment of hepatorenal syndrome (HRS) is based on vasoconstrictors. Terlipressin is the one with the soundest evidence. Noradrenalin has been suggested as an effective alternative. The current study was aimed at assessing the efficacy and safety of noradrenalin vs terlipressin in patients with HRS.Methods: Twenty-two consecutive cirrhotic patients with HRS (9 with HRS type 1; 13 with HRS type 2) were included. Patients were randomly assigned to be treated with noradrenalin (0.1-0.7 mu g/kg/min) and albumin (10 patients) or with terlipressin (1-2 mg/4 h) and albumin (12 patients). Treatment was administered until HRS reversal or for a maximum of two weeks. Patients were followed-up until liver transplantation or death.Results: Reversal of HRS was observed in 7 of the 10 patients (70%) treated with noradrenalin and in 10 of the 12 patients (83%) treated with terlipressin, p = ns. Treatment led in both groups to a significant improvement in renal and circulatory function. No patient developed signs of myocardial ischemia.Conclusions: Data from this unblinded, pilot study suggest that noradrenalin is as effective and safe as terlipressin in patients with HRS. These results would support the use of noradrenalin, a cheap and widely available drug, in the management of these patients. (C) 2007 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

02B. Cirrhosis' and complications (b) Clinical aspects'indicate that even in the early stages of liver cirrhosis, structural changes are likely to account for the haemodynamic abnormalities.% 02B.Cirrhosis and complications-(b) Clinical aspects

Meckel's diverticulum is the most common developmental anomaly of the gastrointestinal tract, affecting 1-4% of the general population. It is usually an incidental finding during laparotomy for other causes; occasional complications are bleeding, obstruction, diverticulitis and perforation. Up to 60% of Meckel's diverticula harbor heterotopic mucosa (mostly gastric or pancreatic), neoplastic degeneration occurs in 1-5% of cases. We report herein a case of obscure gastrointestinal bleeding in a 25-years-old man, due to a double Meckel's diverticulum, both located into jejunum and ileum, harboring ectopic gastric mucosa, diagnosed by a small bowel double contrast enema and managed laparoscopically with a tangential resection. To the best of our knowledge this is an unfrequent case of such a variant of Meckel's diverticulum with ectopic gastric mucosa diagnosed by double contrast enema.

AIMThe trend towards increasing prevalence of Helicobacter pylori (H. pylori) antibiotic resistance may jeopardize the efficacy of most regimens. Culture of the bacterium, the useful method able to address therapy, is influenced by various factors. Thus, validation of the procedure is fundamental. Most studies have been carried out in microbiological settings, while only few have been conducted in clinical frames. We evaluated the accuracy of culture for detection of H. pylori in a clinical dedicated laboratory.METHODSForty-six patients (28 females, 18 males, mean age 56+/-4.7 years) were included. Thirty experienced failure to H. pylori eradication after at least 3 courses of treatment. The control group included 16 subjects suffering from gastroesophageal reflux disease and negativity for H. pylori infection. Diagnostic strategy was based on histology, culture testing, serology and 13C-urea breath test. A patient was considered infected if 2 tests were positive. A commercial culture medium in microaerophilic atmosphere was utilized.RESULTSOut of 30 positive specimens, culture correctly identified 29. In 1 case, no growth of micro-organisms occurred. In the control group, bacterial culture accurately identified all negative samples. One of them indicated growth but neither aspect nor confirmation tests identified H. pylori. Sensitivity was 96.7%, specificity 100%, and accuracy 97.8%. Positive and negative predictive values were 100% and 94.1%, respectively.CONCLUSIONSCulture of H. pylori is a feasible method and provides a good level of diagnostic accuracy even in a clinical setting by following international guidelines combined with training of specialized personnel.

Background: The potential role of digestive endoscopy as a mode for transmission of hepatitis C virus (HCV) is controversial.Objective: To evaluate the role of digestive endoscopy in transmitting HCV by comparing the incidence of HCV infection in a cohort of patients undergoing endoscopy and in a cohort of blood donors.Design: Prospective cohort study.Setting: 3 endoscopic units and 2 blood banks in northwestern Italy.Patients: The potentially exposed cohort consisted of 9188 outpatients consecutively recruited from 3 endoscopic units. Of 9008 patients negative for antibody to HCV (anti-HCV), 8260 (92%) were retested for anti-HCV 6 months after endoscopy. The unexposed cohort consisted of 51 230 healthy, anti-HCV-negative persons who donated blood at 2 blood banks in the same area and during the same time period; 38 280 of them (75%) were tested again for anti-HCV 6 to 48 months after the first blood donation (95 317 person-years of observation).Measurements: Differences in the anti-HCV seroconversion rate between the exposed cohort (patients undergoing endoscopy) and the unexposed cohort (blood donors). Seroconversion was evaluated by a third-generation enzyme immunoassay for anti-HCV; persons positive for anti-HCV were tested for HCV RNA by polymerase chain reaction.Results: All 8260 persons undergoing endoscopy remained negative for anti-HCV 6 months after the procedure (risk per 1000 persons, 0 [95% Cl, 0 to 0.465]); in particular, none of the 912 patients who underwent endoscopy with the same instrument previously used on HCV carriers showed anti-HCV seroconversion (risk per 1000 persons, 0 [Cl, 0 to 4.195]). Four blood donors became positive for anti-HCV and HCV RNA (mean follow-up, 2.49 years; 0.042 case per 1000 person-years [Cl, 0.011 to 0.107 case per 1000 person-years]); each had undergone minor surgery before the second test.Limitations: In the endoscopy cohort, 8.3% of patients were lost to follow-up.Conclusions: These findings support the hypothesis that properly performed digestive endoscopy is not a major risk factor for the transmission of HCV.

We report a case of ticlopidine-induced cholestasis in a 62-year-old man with no previous hepatobiliary disease, who presented with jaundice and pruritus 4 weeks after starting ticlopidine therapy. Other drugs taken by the patient were not considered probable causes. The diagnostic evaluation showed no biliary obstruction and other possible causes of intra-hepatic cholestasis were excluded. The liver biopsy showed a cholestatic hepatitis with centrolobular steatosis and aggression of interlobular bile ducts. Steroid therapy was started but it was discontinued for reactivation of cytomegalovirus (CMV) infection that needed anti-viral therapy for 15 days. The disease ran a severe and protracted course, with anicteric cholestasis elevated 17 months after drug withdrawal. No rechallenge was attempted and ticlopidine was replaced with another anti-platelet drug.Cholestatic hepatitis has been reported infrequently in relation to several drugs, mainly chlorpromazine, and only once with ticlopidine. lts pathogenesis is still unknown, although some clinical findings and experimental results suggest that the drug may act through atoxic mechanism. (C) 2003 Elsevier B.V. All rights reserved.