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Background and aims the Barcelona Clinic Liver Cancer intermediate stage (BCLC-B) of hepatocellular carcinoma (HCC) includes extremely heterogeneous patients in terms of tumor burden and liver function. Transarterial-chemoembolization (TACE) is the first-line treatment for these patients although it may be risky/useless for someone, while others could undergo curative treatments. This study assesses the treatment type performed in a large cohort of BCLC-B patients and its outcome. Methods retrospective analysis of 485 consecutive BCLC-B patients from the ITA.LI.CA database diagnosed with naive HCC after 1999. Patients were stratified by treatment. Results 29 patients (6%) were lost to follow-up before receiving treatment. Treatment distribution was: TACE (233, 51.1%), curative treatments (145 patients, 31.8%), sorafenib (18, 3.9%), other (39, 8.5%), best supportive care (BSC) (21, 4.6%). Median survival (95% CI) was 45 months (37.4-52.7) for curative treatments, 30 (24.7-35.3) for TACE, 14 (10.5-17.5) for sorafenib, 14 (5.2-22.7) for other treatments and 10 (6.0-14.2) for BSC (p

Background and Aims: We evaluated the usefulness of Positon Emission Tomography (PET) with two tracers, 11C-Acetate and 18FFluorodeoxyglucose (FDG), for differentiating focal nodular hyperplasia (FNH), that is managed conservatively, from hepatic adenoma (HA) that needs to be resected. Methods: We prospectively enrolled 30 patients with known or suspected FNH or HA. The diagnostic work-up included Doppler ultrasonography (US), contrast enhanced computed tomography (CT) and/or magnetic resonance imaging (MRI). Fine needle biopsy (FNB) was performed if imaging study was inconclusive. All patients underwent double tracer PET with a single day protocol. The images were acquired with a PET-CT tomograph to obtain image fusion. The tracer uptake was evaluated using the maximum standardized uptake value (SUVmax). The target to background (T/B) ratio was also calculated. Lesions

In Intrahepatic Cholestasis of Pregnancy (ICP) an accumulation of bile acids (BA) in the fetal compartment occurs. It is known that a BA efflux is induced by UDCA administration but the molecular basis of this transplacental transport is only partially defined. Aim of the present study was to determine if placental BCRP, able to transport BA, is regulated by UDCA in ICP. Methods: 14 pregnant women with ICP (6 untreated, 37.5±1.33 years; 8 treated with UDCA − 25 mg/kg/day, 32.14±2.16 years) and 7 agematched healthy controls (34.2±1.2 years) have agreed to participate to the study (none had gallstone disease, abnormal liver tests, liver steatosis on ultrasonography). Placentas were obtained at delivery and processed for membrane extraction. Protein expression was evaluated by standard immunoblotting techniques using actin as an internal control. Statistical differences between groups were evaluated by one way ANOVA with Dunn’s Multiple Comparison test. Results: BCRP was expressed only on the apical membrane of the syncytiotrophoblast. A significant difference was observed between the three groups (ANOVA, p = 0.01). BCRP expression was similar in cont rols and in the untreated ICP group. The administration of UDCA induced a significant increase in placental BCRP expression compared to controls (254.5±58.46 vs 100±8.002% of control, p

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., Graphical abstract, Highlights • Under real-world conditions, OCA was effective in ~43% of patients who were non-responders to UDCA, according to Poise criteria. • Patients with cirrhosis showed lower efficacy (29.5%), mainly attributed to reduced tolerability and higher discontinuation rate. • Patients with overlap AIH-PBC showed a comparable efficacy to pure PBC, with a higher ALT reduction at 6 months. • Most patients with PBC are still in need of additional therapy if aiming to normalise liver biochemistry.

Background & Aims Hospitalization is associated with inadequate colon cleansing before colonoscopy. We aimed to identify factors associated to inadequate colon cleansing among inpatients, and to derive and validate a model to identify inpatients with inadequate cleansing. Methods We performed a prospective observational study at 12 hospitals in Italy. Consecutive adult inpatients scheduled for colonoscopy for any indication were enrolled from February through May 2019 (derivation cohort, n = 1016) and from June through August 2019 (validation cohort, n = 508). Inadequate cleansing was defined as Boston bowel preparation scale scores below 2 in any colon segment. We performed multivariate logistic regression to identify factors associated with inadequate cleansing. Results In the combined cohorts, 1032 patients (68%) had adequate colon cleansing. Physicians’ meetings to optimize bowel preparation (odds ratio [OR], 0.42; 95% CI, 0.27–0.65), written and oral instructions to patients (OR, 0.48; 95% CI, 0.36–0.65), admission to gastroenterology unit (OR, 0.71; 95% CI, 0.51–0.98), split-dose regimens (OR, 0.27; 95% CI, 0.20–0.35), a 1-liter polyethylene glycol-based bowel purge (OR, 0.39; 95% CI, 0.23—0.65), and 75% or more intake of bowel preparation (OR, 0.09; 95% CI, 0.05–0.15) significantly reduced odds of inadequate colon cleansing. Alternatively, bedridden status (OR, 2.14; 95% CI, 1.55–2.98), constipation (OR, 2.16; 95% CI, 1.55–3.0), diabetes mellitus (OR, 1.61; 95% CI, 1.18–2.20), use of anti-psychotic drugs (OR, 3.26; 95% CI, 1.62–6.56), and 7 or more days of hospitalization (OR, 1.02; 95% CI, 1.00–1.04) increased risk of inadequate colon cleansing. We developed a model to identify patients with inadequate cleaning using data from patients in the derivation cohort and tested it in the validation cohort. Calibration values were P = .218 for the discrimination cohort and P = .232 for the validation cohort. Discrimination values were c-statistic, 0.78 (95% CI, 0.74–0.81) for the discrimination cohort and c-statistic, 0.73 (95% CI, 0.69–0.78) for the validation cohort. We developed app for use by clinicians. Conclusions In a prospective observational study, we identified setting-, patient- and preparation-related factors that affect colon cleansing among inpatients. We derived and validated a model to identify patients with inadequate preparation and developed an app for clinicians. ClinicalTrials.gov no: NCT03925506

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.

Background & Aims: Determining risk for recurrence or survival after curative resection or ablation in patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) is important for stratifying patients according to expected outcomes in future studies of adjuvant therapy in the era of direct-acting antivirals (DAAs). The aims of this meta-analysis were to estimate the recurrence and survival probabilities of HCV-related early HCC following complete response after potentially curative treatment and to identify predictors of recurrence and survival. Methods: Studies reporting time-dependent outcomes (HCC recurrence or death) after potentially curative treatment of HCV-related early HCC were identified in MEDLINE through May 2016. Data on patient populations and outcomes were extracted from each study by three independent observers and combined using a distribution-free summary survival curve. Primary outcomes were actuarial probabilities of recurrence and survival. Results: Eleven studies met the inclusion criteria. Pooled estimates of actuarial recurrence rates were 7.4% at 6months and 47.0% at 2years. Pooled estimates of actuarial survival rates were 79.8% at 3years and 58.6% at 5years. Heterogeneity among studies was highly significant for all outcomes. By univariate meta-regression analyses, lower serum albumin, randomized controlled trial study design and follow-up were independently associated with higher recurrence risk, whereas tumour size and alpha-foetoprotein levels were associated with higher mortality. Conclusions: This meta-analysis showed that recurrence risk and survival are extremely variable in patients with successfully treated HCV-related HCC, providing a useful benchmark for indirect comparisons of the benefits of DAAs and for a correct design of randomized controlled trials in the adjuvant setting.

none 48 no Background: In HCV-infected cirrhotic patients with successfully treated early hepatocellular carcinoma (HCC), the time to HCC recurrence and the effects of sustained viral eradication (SVR) by interferon (IFN)-based or IFN-free regimens on HCC recurrence remain unclear. Aim: To perform an indirect comparison of time to recurrence (TTR) in patients with successfully treated early HCC and active HCV infection with those of patients with SVR by IFN-based and by IFN-free regimens. Methods: We evaluated 443 patients with HCV-related cirrhosis and Barcelona Clinic Liver Cancer Stage A/0 HCC who had a complete radiological response after curative resection or ablation. Active HCV infection was present in 328, selected from the Italian Liver Cancer group cohort; 58 patients had SVR achieved by IFN-free regimens after HCC cure, and 57 patients had SVR achieved by IFN-based regimens after HCC cure. Individual data of patients in the last two groups were extracted from available publications. Results: TTR by Kaplan–Meier curve was significantly lower in patients with active HCV infection compared with those with SVR both by IFN-free (P = 0.02) and by IFN-based (P < 0.001) treatments. TTR was similar in patients with SVR by IFN-free or by IFN-based (P = 0.49) strategies. Conclusion: In HCV-infected, successfully treated patients with early HCC, SVR obtained by IFN-based or IFN-free regimens significantly reduce tumour recurrence without differences related to the anti-viral strategy used. Petta, S.; Cabibbo, G.; Barbara, M.; Attardo, S.; Bucci, L.; Farinati, F.; Giannini, E.G.; Tovoli, F.; Ciccarese, F.; Rapaccini, G.L.; Di Marco, M.; Caturelli, E.; Zoli, M.; Borzio, F.; Sacco, R.; Virdone, R.; Marra, F.; Felder, M.; Morisco, F.; Benvegnù, L.; Gasbarrini, A.; Svegliati-Baroni, G.; Foschi, F.G.; Olivani, A.; Masotto, A.; Nardone, G.; Colecchia, A.; Persico, M.; Boccaccio, V.; Craxì, A.; Bruno, S.; Trevisani, F.; Cammà, C; the Italian Liver Cancer (ITALICA) Group [ ; Maurizio Biselli; Paolo Caraceni; Alessandro Cucchetti; Marco Domenicali; Fabio Piscaglia; Annagiulia Gramenzi; Alessandro Granito; Donatella Magalotti; Carla Serra; Giulia Negrini; Lucia Napoli; Veronica Salvatore; Francesca Benevento;] Petta, S.; Cabibbo, G.; Barbara, M.; Attardo, S.; Bucci, L.; Farinati, F.; Giannini, E.G.; Tovoli, F.; Ciccarese, F.; Rapaccini, G.L.; Di Marco, M.; Caturelli, E.; Zoli, M.; Borzio, F.; Sacco, R.; Virdone, R.; Marra, F.; Felder, M.; Morisco, F.; Benvegnù, L.; Gasbarrini, A.; Svegliati-Baroni, G.; Foschi, F.G.; Olivani, A.; Masotto, A.; Nardone, G.; Colecchia, A.; Persico, M.; Boccaccio, V.; Craxì, A.; Bruno, S.; Trevisani, F.; Cammà, C; the Italian Liver Cancer (ITALICA) Group [ ; Maurizio Biselli; Paolo Caraceni; Alessandro Cucchetti; Marco Domenicali; Fabio Piscaglia; Annagiulia Gramenzi; Alessandro Granito; Donatella Magalotti; Carla Serra; Giulia Negrini; Lucia Napoli; Veronica Salvatore; Francesca Benevento;]

Summary Background Hepatocellular carcinoma (HCC) causes premature death and loss of life expectancy worldwide. Its primary and secondary prevention can result in a significant number of years of life saved. Aim To assess how many years of life are lost after HCC diagnosis. Methods Data from 5346 patients with first HCC diagnosis were used to estimate lifespan and number of years of life lost after tumour onset, using a semi-parametric extrapolation having as reference an age-, sex- and year-of-onset-matched population derived from national life tables. Results Between 1986 and 2014, HCC lead to an average of 11.5 years-of-life lost for each patient. The youngest age-quartile group (18–61 years) had the highest number of years-of-life lost, representing approximately 41% of the overall benefit obtainable from prevention. Advancements in HCC management have progressively reduced the number of years-of-life lost from 12.6 years in 1986–1999, to 10.7 in 2000–2006 and 7.4 years in 2007–2014. Currently, an HCC diagnosis when a single tumour

A 49-year old man was referred for colonoscopy due to positive fecal occult blood test. Laboratory tests and physical examination were unrevealing. A large pedunculated polyp was found in the sigmoid colon (Figures 1A-1B). Due to inadequate bowel cleansing, polypectomy was not performed at that time. Upon repeat colonoscopy, 120 days later, bowel cleansing was excellent. The exam was performed by an expert endoscopist, achieving a good vision with a good colonic distension and without blind angulations. However, despite every effort, he was unable to find the polyp. A second expert endoscopist was asked to repeat the exam in the same session. Although he had reached the cecum twice, he couldn’t detect the polyp as well. Interestingly, both endoscopists described a prolapsed normal mucosa with a scar on its edge, in the site previously described as the polyp location (Figure 3). On close inspection, no adenomatous tissue was visible. We hypothesized a case of polyp autoamputation, with the prolapsed mucosa being the remnant of the stalk of the missing polyp. Indeed, the patient reported having suffered of a passage of bright red material and clots per rectum a few weeks before, without relevant consequences. To our knowledge only 3 cases of polyp autoamputation have been reported in the colon - ; autoamputation has been described also in the stomach and in the duodenum. It has been linked mainly with pedunculated type of polyps, which are subject to higher mechanical traction and torsion of the stalk. This is the first case documented with endoscopic images both before and after the event. Autoamputation can be either asymptomatic or accompanied by abdominal pain and bleeding, eventually leading to hospitalization.4 No fatalities have been reported. Intrinsic limitations of colonoscopy usually represent the first cause of missed polyps. Nevertheless, in case of pedunculated polyps that are not found anymore in subsequent colonoscopies, autoamputation is a possibility that gastroenterologists should take into account.

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.

SUMMARY: Beside substantial progress in treatment of chronic hepatitis C (CHC) particular patients (genotype 1/4, high viral load, previous nonresponse, cirrhosis) remain difficult to treat. The aim of our pilot randomized study was to compare efficacy and tolerability of standard doses of Peginterferon alpha-2b + ribavirin with higher doses of Peginterferon alpha-2b administered twice weekly + ribavirin. Sixty-five outpatients with CHC were subsequently enrolled. Group A (n = 22) received recommended doses of Peginterferon alpha-2b and group B (n = 43), received high doses twice weekly. Groups were comparable for baseline characteristics. All genotype 1/4 patients had high baseline viraemia. Sustained virological response (SVR) was significantly higher in group B among naïve patients (72%vs 25%, P = 0.024). A significantly higher rate of SVR was observed in group B both considering only genotype 1/4 patients, (46%vs 13%, P = 0.03) and grouping together genotype 1/4 naive and relapsers (57%vs 11%, P = 0.039). Discontinuation rate was 32% (7 of 22) in group A and 21% (9 [corrected] of 43) in group B. Our response rates are the highest reported for genotype 1/4 with high viraemia. Our pilot study supports the need of randomized studies to evaluate both viral kinetics and efficacy of high dose and twice weekly administration of Peginterferon alpha-2b in genotype 1/4 patients with high viraemia who may need personalized treatment schedules. SUMMARY: Beside substantial progress in treatment of chronic hepatitis C (CHC) particular patients (genotype 1/4, high viral load, previous nonresponse, cirrhosis) remain difficult to treat. The aim of our pilot randomized study was to compare efficacy and tolerability of standard doses of Peginterferon alpha-2b + ribavirin with higher doses of Peginterferon alpha-2b administered twice weekly + ribavirin. Sixty-five outpatients with CHC were subsequently enrolled. Group A (n = 22) received recommended doses of Peginterferon alpha-2b and group B (n = 43), received high doses twice weekly. Groups were comparable for baseline characteristics. All genotype 1/4 patients had high baseline viraemia. Sustained virological response (SVR) was significantly higher in group B among naive patients (72%vs 25%, P = 0.024). A significantly higher rate of SVR was observed in group B both considering only genotype 1/4 patients, (46%vs 13%, P = 0.03) and grouping together genotype 1/4 naive and relapsers (57%vs 11%, P = 0.039). Discontinuation rate was 32% (7 of 22) in group A and 19% (8 of 43) in group B. Our response rates are the highest reported for genotype 1/4 with high viraemia. Our pilot study supports the need of randomized studies to evaluate both viral kinetics and efficacy of high dose and twice weekly administration of Peginterferon alpha-2b in genotype 1/4 patients with high viraemia who may need personalized treatment schedules.

Background and Aim: Among the Endoscopic retrograde cholangiopancreatography (ERCP) adverse events, an increasingly arising problem is the transmission of Multi Drug Resistant (MDR) Bacteria through duodenoscopes. The aim of this survey was to evaluate the current clinical practice of management of ERCP associated infections in Emilia-Romagna, Italy., Methods: An online survey was developed including 12 questions on management of ERCP associated infections risk. The survey was proposed to all 12 endoscopy centers in Emilia Romagna that perform at least &gt; 200 ERCPs per year., Results: 11 centers completed the survey (92%). Among all risk factors of ERCP infections, hospitalization in intensive care units, immunosuppressant therapies, and previous MDR infections have achieved a 80 % minimum of concurrence by our respondents. The majority of them did not have a formalized document in their hospital describing categories and risk factors helpful in the detection of patients undergoing ERCP with an high-level infective risk (9/11, 82%). Most centers (8/11, 72%) do not perform screening in patients at risk of ERCP infections. Post procedural monitoring is performed by 6 of 11 centers (55%)., Conclusion: Our survey showed that, at least at regional level, there is a lack of procedures and protocols related to the management of patients at risk of ERCP infections.