Rate of non-response to ursodeoxycholic acid in a large real-world cohort of primary biliary cholangitis patients in Italy.

Background and aim: Response to ursodeoxycholic acid (UDCA) is crucial for the prediction of primary biliary cholangitis (PBC) prognosis, and different response criteria were validated and proposed by reference centers for PBC. To date, rates of non-response to UDCA from real-world series are lacking.Methods: Hepatology/Gastroenterology centers belonging to 'Club Epatologi Ospedalieri' (CLEO) and 'Associazione Italiana Gastroenterologi Ospedalieri' (AIGO) were invited to participate in the study, and asked to extract all patients followed for PBC, without any selection or exclusion, and fill in the database provided.Results: Thirty-four centers were enrolled throughout Italy, for a total of 713 patients. None of these centers, except one, had a hepatology outpatient clinic devoted to the care of patients with autoimmune liver diseases. After excluding 79 cases of PBC/autoimmune hepatitis overlaps, 634 patients were analyzed: mean age, 64.4 ± 12.0 years; 91.2% females; F/M 10.3/1. For patients with at least 1 year of UDCA treatment (583), rates of non-response to UDCA were evaluated according to the Paris-I/-II, Toronto and GLOBE criteria, and compared with those in the original cohorts: 27% vs 39% in Paris-I cohort; 39.6% vs 52% in Paris-II; 20.1% vs 43.5% in Toronto; 15.7% vs 30% in GLOBE (age-specific cutoffs). Mean alkaline phosphatase levels on UDCA treatment, and the age-adjusted prevalence of F3/F4 fibrosis, appeared lower in this PBC population than in reference cohorts.Conclusions: A mean ∼15% better response to UDCA is observed in a real-world PBC population, probably due to migration of some of most severe/advanced cases to PBC referral centers.

Outcomes of Double Balloon-Enteroscopy in Elderly vs. Adult Patients: A Retrospective 16-Year Single-Centre Study.

Background and Aim: Double-balloon enteroscopy (DBE) is a well-established procedure for direct visualisation of the entire small bowel mucosa, and, in contrast with other imaging techniques, allows to perform biopsies and therapeutic interventions. The aim of this study was to evaluate the indications, diagnostic yield, therapeutic yield, and complications of DBE in a cohort of consecutive patients according to patients' age. Methods: We conducted a retrospective study of consecutive patients who underwent DBE in our endoscopy unit between January 2006 and December 2021. Results: A total of 387 consecutive patients who underwent 460 DBE procedures were included. Mean age of the patients was 63 years. The overall diagnostic yield was 67.6%; vascular lesions were the predominant endoscopic findings (31.5%), followed by polyps or neoplastic masses (17.6%). Older patients (≥65 years) showed statistically higher rates of clinically relevant findings than adult patients (18-65 years) (p = 0.001). Crohn's disease and polyps or neoplastic masses were more frequent in the younger group (p = 0.009 and p = 0.066, respectively), while vascular lesions and non-specific inflammation were the most common findings in the older group (p < 0.001 and p < 0.001, respectively). The therapeutic intervention rate was 31.7%. Rates of endoscopic treatment were significantly higher in the older group (p < 0.001). Total complications occurred in five procedures (1.1%). Conclusion: In clinical practice, DBE is an efficient diagnostic and therapeutic tool with a high safety profile, particularly in the elderly population.

Clinical management and patient outcomes of acute lower gastrointestinal bleeding. A multicenter, prospective, cohort study.

BACKGROUND & AIM: Although acute lower GI bleeding (LGIB) represents a significant healthcare burden, prospective real-life data on management and outcomes are scanty. Present multicentre, prospective cohort study was aimed at evaluating mortality and associated risk factors and at describing patient management. METHODS: Adult outpatients acutely admitted for or developing LGIB during hospitalization were consecutively enrolled in 15 high-volume referral centers. Demographics, comorbidities, medications, interventions and outcomes were recorded. RESULTS: Overall 1,198 patients (1060 new admissions;138 inpatients) were included. Most patients were elderly (mean-age 74±15 years), 31% had a Charlson-Comorbidity-Index ≥3, 58% were on antithrombotic therapy. In-hospital mortality (primary outcome) was 3.4% (95%CI 2.5-4.6). At logistic regression analysis, independent predictors of mortality were increasing age, comorbidity, inpatient status, hemodynamic instability at presentation, and ICU-admission. Colonoscopy had a 78.8% diagnostic yield, with significantly higher hemostasis rate when performed within 24-hours than later (21.3% vs.10.8%, p = 0.027). Endoscopic hemostasis was associated with neither in-hospital mortality nor rebleeding. A definite or presumptive source of bleeding was disclosed in 90.4% of investigated patients. CONCLUSION: Mortality in LGIB patients is mainly related to age and comorbidities. Although early colonoscopy has a relevant diagnostic yield and is associated with higher therapeutic intervention rate, endoscopic hemostasis is not associated with improved clinical outcomes [ClinicalTrial.gov number: NCT04364412].

Real-world experience with obeticholic acid in patients with primary biliary cholangitis.

BACKGROUND & AIMS: Obeticholic acid (OCA) is the second-line treatment approved for patients with primary biliary cholangitis (PBC) and an inadequate response or intolerance to ursodeoxycholic acid. We aimed to evaluate the effectiveness and safety of OCA under real-world conditions. METHODS: Patients were recruited into the Italian PBC Registry, a multicentre, observational cohort study that monitors patients with PBC at national level. The primary endpoint was the biochemical response according to Poise criteria; the secondary endpoint was the biochemical response according to normal range criteria, defined as normal levels of bilirubin, alkaline phosphatase (ALP), and alanine aminotransferase (ALT) at 12 months. Safety and tolerability were also assessed. RESULTS: We analysed 191 patients until at least 12 months of follow-up. Median age was 57 years, 94% female, 61 (32%) had cirrhosis, 28 (15%) had histologically proven overlap with autoimmune hepatitis (PBC-AIH). At 12 months, significant median reductions of ALP (-32.3%), ALT (-31.4%), and bilirubin (-11.2%) were observed. Response rates were 42.9% according to Poise criteria, and 11% by normal range criteria. Patients with cirrhosis had lower response than patients without cirrhosis (29.5% vs. 49.2%, p = 0.01), owing to a higher rate of OCA discontinuation (30% vs. 12%, p = 0.004), although with similar ALP reduction (29.4% vs. 34%, p = 0.53). Overlap PBC-AIH had a similar response to pure PBC (46.4% vs. 42.3%, p = 0.68), with higher ALT reduction at 6 months (-38% vs. -29%, p = 0.04). Thirty-three patients (17%) prematurely discontinued OCA because of adverse events, of whom 11 experienced serious adverse events. Treatment-induced pruritus was the leading cause of OCA discontinuation (67%). CONCLUSIONS: Effectiveness and safety of OCA under real-world conditions mirror those in the Poise trial. Patients with cirrhosis had lower tolerability. Overlap PBC-AIH showed higher ALT reduction at 6 months compared with patients with pure PBC. LAY SUMMARY: Obeticholic acid (OCA) was shown to be effective in more than one-third of patients not responding to ursodeoxycholic acid in a real-world context in Italy. Patients with cirrhosis had more side effects with OCA, and this led to suspension of the drug in one-third of patients. OCA was also effective in patients who had overlap between autoimmune hepatitis and primary biliary cholangitis.

Proton pump inhibitors in cirrhosis: tradition or evidence based practice?

Proton pump inhibitors (PPI) are very effective in inhibiting acid secretion and are extensively used in many acid related diseases. They are also often used in patients with cirrhosis sometimes in the absence of a specific acid related disease, with the aim of preventing peptic complications in patients with variceal or hypertensive gastropathic bleeding receiving multidrug treatment. Contradicting reports support their use in cirrhosis and evidence of their efficacy in this condition is poor. Moreover there are convincing papers suggesting that acid secretion is reduced in patients with liver cirrhosis. With regard to Helicobacter pylori (H pylori) infection, its prevalence in patients with cirrhosis is largely variable among different studies, and it seems that H pylori eradication does not prevent gastro-duodenal ulcer formation and bleeding. With regard to the prevention and treatment of oesophageal complications after banding or sclerotherapy of oesophageal varices, there is little evidence for a protective role of PPI. Moreover, due to liver metabolism of PPI, the dose of most available PPIs should be reduced in cirrhotics. In conclusion, the use of this class of drugs seems more habit related than evidence-based eventually leading to an increase in health costs.

C-11 acetate does not enhance usefulness of F-18 FDG PET/CT in differentiating between focal nodular hyperplasia and hepatic adenoma.

PURPOSE OF THE REPORT: We assessed the usefulness of F-18 fluorodeoxyglucose positron emission tomography (FDG PET) and C-11 acetate PET (AC PET) in distinguishing hepatic lesions due to consequential disease (hepatocellular adenoma and malignant lesions) from focal nodular hyperplasia (FNH) in patients at low risk of malignancy. MATERIALS AND METHODS: Thirty-one patients with 43 lesions were prospectively enrolled. The diagnostic work-up included Doppler and contrast-enhanced ultrasonography, contrast-enhanced computed tomography, and/or magnetic resonance imaging. Fine needle biopsy was performed if the imaging study was inconclusive. The work-up revealed 36 FNH and 7 consequential lesions (5 hepatocellular adenoma, 1 hepatoma, and 1 metastasis). All patients underwent FDG and AC PET. FDG PET with target/background ratio (T/Br) greater than 1.2 and AC PET with T/Br of less than 1.2 were considered positive test for consequential disease. RESULTS: On FDG PET, we had 6 true-positive out of 7 lesions due to consequential diseases, with a sensitivity of 85.7%, and 33 true-negative out of 36 lesions with FNH, with a specificity of 91.7%. Using AC PET, there were 2 true-positive lesions out of 7 caused by neoplasms, with a sensitivity of 28.6%, and 34 true-negative lesions out of 36 FNH, with a specificity of 94.4%. CONCLUSIONS: When the goal is differentiating FNH from liver neoplasms, AC PET offered no additional diagnostic advantage over what is achieved with FDG PET.