Continuous clinical remission with biologics in ulcerative colitis: the 'AURORA' comparison study.

OBJECTIVES: Comparative trials among biological drugs for the treatment of ulcerative colitis (UC) provided conflicting results. After patent expire of infliximab originator, adalimumab, infliximab biosimilar, golimumab and vedolizumab have been approved in Italy.We compared the efficacy of these four biologics in UC according to the concept of continuous clinical remission (CCR). METHODS: In a retrospective, multicentre study, all UC patients treated with adalimumab, infliximab biosimilar, golimumab or vedolizumab between 2014 and 2019 were included. All drugs were compared to each other according to the 1-year CCR rate, defined as Mayo partial score ≤2, with bleeding subscore = 0, without any relapse or optimization with dose escalation, topical treatments or steroid use after first clinical remission. RESULTS: Four-hundred sixteen patients (adalimumab = 90, infliximab biosimilar = 105, golimumab = 79, vedolizumab = 142) were included. CCR was achieved in similar percentages among the groups (33%, 37%, 28%, 37%, respectively). All drugs were equivalent in biologic-naive patients, while vedolizumab was better than a second anti-TNFα in prior anti-TNFα agent failures. No differences were found according to type of adverse events or severe adverse events. CONCLUSIONS: Based on a strict definition of clinical remission, all biologics appear equally effective at 1 year. Changing to vedolizumab is more effective than switching to another anti-TNFα in TNFα failures.

Upper gastrointestinal bleeding in COVID-19 inpatients: Incidence and management in a multicenter experience from Northern Italy.

BACKGROUND: COVID-19 patients have an increased susceptibility to develop thrombotic complications, thus thromboprophylaxis is warranted which may increase risk of upper gastrointestinal bleeding (UGIB). Our aim was to evaluate incidence of UGIB and use of upper GI endoscopy in COVID-19 inpatients. METHODS: The medical and endoscopic management of UGIB in non-ICU COVID-19 patients has been retrospectively evaluated. Glasgow Blatchford score was calculated at onset of signs of GI bleeding. Timing between onset of signs of GI bleeding and execution, if performed, of upper GI endoscopy was evaluated. Endoscopic characteristics and outcome of patients were evaluated overall or according to the execution or not of an upper GI endoscopy before and after 24h. RESULTS: Out of 4871 COVID-19 positive patients, 23 presented signs of UGIB and were included in the study (incidence 0.47%). The majority (78%) were on anticoagulant therapy or thromboprophylaxis. In 11 patients (48%) upper GI endoscopy was performed within 24h, whereas it was not performed in 5. Peptic ulcer was the most common finding (8/18). Mortality rate was 21.7% for worsening of COVID-19 infection. Mortality and rebleeding were not different between patients having upper GI endoscopy before or after 24h/not performed. Glasgow Blatchford score was similar between the two groups (13;12-16 vs 12;9-15). CONCLUSION: Upper GI bleeding complicated hospital stay in almost 0.5% of COVID-19 patients and peptic ulcer disease is the most common finding. Conservative management could be an option in patients that are at high risk of respiratory complications.

Activities related to inflammatory bowel disease management during and after the coronavirus disease 2019 lockdown in Italy: How to maintain standards of care.

BACKGROUND AND AIMS: Restructuring activities have been necessary during the lockdown phase of the coronavirus disease 2019 (COVID-19) pandemic. Few data are available on the post-lockdown phase in terms of health-care procedures in inflammatory bowel disease (IBD) care, and no data are available specifically from IBD units. We aimed to investigate how IBD management was restructured during the lockdown phase, the impact of the restructuring on standards of care and how Italian IBD units have managed post-lockdown activities. METHODS: A web-based online survey was conducted in two phases (April and June 2020) among the Italian Group for IBD affiliated units within the entire country. We investigated preventive measures, the possibility of continuing scheduled visits/procedures/therapies because of COVID-19 and how units resumed activities in the post-lockdown phase. RESULTS: Forty-two referral centres participated from all over Italy. During the COVID-19 lockdown, 36% of first visits and 7% of follow-up visits were regularly done, while >70% of follow-up scheduled visits and 5% of first visits were done virtually. About 25% of scheduled endoscopies and bowel ultrasound scans were done. More than 80% of biological therapies were done as scheduled. Compared to the pre-lockdown situation, 95% of centres modified management of outpatient activity, 93% of endoscopies, 59% of gastrointestinal ultrasounds and 33% of biological therapies. Resumption of activities after the lockdown phase may take three to six months to normalize. Virtual clinics, implementation of IBD pathways and facilities seem to be the main factors to improve care in the future. CONCLUSION: Italian IBD unit restructuring allowed quality standards of care during the COVID-19 pandemic to be maintained. A return to normal appears to be feasible and achievable relatively quickly. Some approaches, such as virtual clinics and identified IBD pathways, represent a valid starting point to improve IBD care in the post-COVID-19 era.

Is there a link between periampullary diverticula and biliopancreatic disease? An EUS approach to answer the question.

BACKGROUND: Many studies, almost all in an Endoscopic Retrograde Cholangiopancreatography (ERCP) setting, have been conducted to establish if a link exists between periampullary diverticula (PADs) and biliopancreatic diseases but the issue is still debated. AIMS: The objective was to clarify the link between PADs and biliopancreatic disease, for the first time using Endoscopic Ultrasound (EUS). METHODS: We retrospectively reviewed our database seeking patients scheduled for EUS with an indication that entailed the exploration of the second duodenum. For each patient with a PAD enrolled in the study, 6 controls were randomly selected. RESULTS: 2475 patients met the inclusion criteria. Among them, 185 subjects with a PAD were found (prevalence 7.5%), 1110 subjects served as controls. Patients with a PAD had more frequently a history of cholangitis (8.1 vs 2.2%; OR 3.99, p < 0.001), a higher prevalence of common bile duct (CBD) dilation (44.3 vs 28.2%; OR 2, p < 0.0001) and a higher prevalence of CBD stones (34.1 vs 19.6%; OR 2.1, p < 0.0001). No differences were found about history of jaundice, acute/recurrent pancreatitis or EUS signs of chronic pancreatitis. CONCLUSION: Whereas PADs were linked with history of cholangitis, CBD stones and dilation, no association was found with pancreatic diseases.

Impact of viral eradication with sofosbuvir-based therapy on the outcome of post-transplant hepatitis C with severe fibrosis.

BACKGROUND & AIMS: Several studies have shown that new direct-acting antivirals maintain their efficacy in liver transplant (LT) recipients with severe hepatitis C virus (HCV) recurrence. We determined the clinical impact of sofosbuvir/ribavirin in LT through the changes in liver function and fibrosis state at 24 and 48 weeks after treatment. METHODS: Between June 2014 and July 2015, 126 patients (30 F3, 96 F4 Metavir stage) were enrolled to receive sofosbuvir + ribavirin (24 weeks, 118 patients) or sofosbuvir + simeprevir + ribavirin (12 weeks, 8 patients); treatment was initiated at a median time of 4.3 years from LT. Median follow-up after therapy completion was 461 days. RESULTS: All 30 F3 patients achieved a sustained virological response at week 24 after treatment (SVR24) and showed a distinct amelioration of the AST-to-platelet ratio index (APRI), FIB-4 and liver stiffness at elastography by week 24 post-therapy, which were maintained at week 48. Of the 96 F4 cirrhotic patients, 72 (75%) achieved SVR24 accompanied by significant improvement of liver function, which was maintained at week 48 (Child B-C 22% baseline, 11% week 24, 7% week 48); APRI, FIB-4 and liver stiffness further improved significantly between weeks 24 and 48 of follow-up. Among the 77 responders (27 F3, 50 F4) who underwent elastography at baseline and at the end of follow-up, 39 (50.6%; 18 F3, 21 F4) exhibited a regression in fibrosis stage. CONCLUSION: At about 1 year from the completion of successful sofosbuvir-based therapy, patients with post-LT HCV and severe fibrosis experienced a long-term liver function improvement accompanied by a regression of fibrosis stage in half of them.

Bone mineral density at diagnosis of celiac disease and after 1 year of gluten-free diet.

Atypical or silent celiac disease may go undiagnosed for many years and can frequently lead to loss of bone mineral density, with evolution to osteopenia or osteoporosis. The prevalence of the latter conditions, in case of new diagnosis of celiac disease, has been evaluated in many studies but, due to the variability of epidemiologic data and patient features, the results are contradictory. The aim of this study was to evaluate bone mineral density by dual-energy X-ray absorptiometry in 175 consecutive celiac patients at time of diagnosis (169 per-protocol, 23 males, 146 females; average age 38.9 years). Dual-energy X-ray absorptiometry was repeated after 1 year of gluten-free diet in those with T-score value <-1 at diagnosis. Stratification of patients according to sex and age showed a higher prevalence of low bone mineral density in men older than 30 years and in women of all ages. A 1-year gluten-free diet led to a significant improvement in lumbar spine and femoral neck mean T-score value. We propose that dual-energy X-ray absorptiometry should be performed at diagnosis of celiac disease in all women and in male aged >30 years, taking into account each risk factor in single patients.

Prospective randomized trial: endoscopic follow up 3 vs 6 months after esophageal variceal eradication by band ligation in cirrhosis.

BACKGROUND AND OBJECTIVES: Endoscopic variceal ligation (EVL) is recommended to treat esophageal varices (EV) in cirrhosis and portal hypertension. A program of endoscopic surveillance is not clearly established. The aim of this prospective randomized trial was to assess the most effective timing of endoscopic monitoring after variceal eradication and its impact on the patient's outcome and on the costs. METHODS: A hundred and two cirrhotic patients with esophageal varices treated by EVL were evaluated. After variceal eradication patients were randomized to receive first endoscopic control at 3 (Group 1) and 6 (Group 2) months respectively. RESULTS: Variceal obliteration was achieved in all patients. Variceal recurrence was observed in 28 cases at the first control (29.1%) without difference between the two groups (32% vs 29% in group 1 and 2 respectively, p=0.75). The incidence of large varices is similar in the two groups (33% vs 38% respectively). Using a multivariate analysis, medical therapy with B blockers was the only independent predictor of lowest risk of variceal recurrence [OR 2.30, 95% CI (1.68-3.26)]. Bleeding related to recurrent varices occurred in 3.1% of cases and was associated with portal thrombosis. Child Pugh score ≥8 was the only predictor of mortality (p=0.0002). CONCLUSIONS: Recurrence of varices after banding ligation is not rare but it is associated with a low risk of variceal progression and bleeding. Accordingly, a first endoscopic control at 6 months after variceal eradication associated with a good risk stratification might be a cost-effective strategy of monitoring.

Extrahepatic aneurysm of the portal venous system and portal hypertension.

Portal venous aneurysm (PVA) is a rare condition characterized by dilatation of the portal venous system. PVA manifestation of symptoms is varied and depends on the aneurysm size, location and related-complications, such as thrombosis. While the majority of reported cases of PVA are attributed to portal hypertension, very little is known about the condition's pathophysiology and clinical management remains a challenge. Here, we describe a 67-year-old woman who presented with complaint of dyspepsia and without a significant medical history, for whom PVA was incidentally diagnosed. The initial upper abdominal ultrasound revealed marked dilatation of the main portal vein, and subsequent contrast-enhanced computed tomography with angiography revealed a large aneurysm arising from the extrahepatic troncus portion of the portal vein, as well as gastroesophageal varices. A conservative approach using beta-blocker therapy was chosen. The patient was followed-up for 60 mo, during which time the asymptomatic status was unaltered and the PVA remained stable.

Transcatheter arterial chemoembolization for hepatocellular carcinoma in cirrhosis: influence on portal hypertension.

BACKGROUND: Transcatheter arterial chemoembolization (TACE) is a routine treatment for hepatocellular carcinoma in cirrhotic patients. Whether TACE influences the degree of portal hypertension remains uncertain. AIM AND PATIENTS: We retrospectively analyzed the clinical course of 283 TACE to investigate the incidence of variceal bleeding and ascites after the procedure. We also prospectively evaluated portal pressure by hepatic venous portal gradient (HVPG) before and within 3 days by TACE in a group of 15 patients. RESULTS: Before TACE, esophageal varices were present in 125 patients. Variceal bleeding occurred in three (1.5%) and ascites in two (1%) patients during the follow-up post-TACE. Patients with variceal bleeding were significantly older (P=0.019). In 15 patients who underwent portal pressure measurement before and within 3 days by TACE, HVPG was unchanged (mean 13.1 vs. 12.8 mmHg, P>0.05). CONCLUSION: In our series portal hypertension-related complications after TACE were rare and did not result in higher mortality. As TACE did not influence HVPG, the preventive ligation of esophageal varices before TACE does not seem justified.