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Background & Aims: Obeticholic acid (OCA) has recently been restricted in patients with primary biliary cholangitis (PBC) with "advanced cirrhosis" because of its narrow therapeutic index. We aimed to better define the predicting factors of hepatic serious adverse events (SAEs) and non‐response in cirrhotic patients undergoing OCA therapy. Methods: Safety and efficacy of treatment were evaluated in a cohort of consecutive PBC cirrhotic patients started with OCA. OCA response was evaluated according to the Poise criteria. Risk factors for hepatic SAEs and non‐response were reported as risk ratios (RR) with 95% confidence intervals (CIs). Results: One hundred PBC cirrhotics were included, 97 Child‐Pugh class A and 3 class B. Thirty‐one had oesophageal varices and 5 had a history of ascites. Thirty‐three per cent and 32% of patients achieved a biochemical response at 6 and 12 months respectively. Male sex (adjusted‐RR 1.75, 95%CI 1.42–2.12), INR (1.37, 1.00–1.87), Child‐Pugh score (1.79, 1.28–2.50), MELD (1.17, 1.04–1.30) and bilirubin (1.83, 1.11–3.01) were independently associated with non‐response to OCA. Twenty‐two patients discontinued OCA within 12 months: 10 for pruritus, 9 for hepatic SAEs (5 for jaundice and/or ascitic decompensation; 4 for upper digestive bleeding). INR (adjusted‐RR 1.91, 95%CI 1.10–3.36), lower albumin levels (0.18, 0.06–0.51), Child‐Pugh score (2.43, 1.50–4.04), history of ascites (3.5, 1.85–6.5) and bilirubin (1.30, 1.05–1.56), were associated with hepatic SAEs. A total bilirubin≥1.4 mg/dl at baseline was the most accurate biochemical predictor of hepatic SAEs under OCA. Conclusions: An accurate baseline assessment is crucial to select cirrhotic patients who can benefit from OCA. Although OCA is effective in one third of cirrhotics, bilirubin level ≥1.4 mg/dl should discourage from its use. [ABSTRACT FROM AUTHOR]

Summary: Background: Inflammatory bowel disease (IBD) is a chronic inflammatory immune‐mediated disorder of the gut with frequent extra‐intestinal complications. Pancreatic involvement in IBD is not uncommon and comprises a heterogeneous group of conditions, including acute pancreatitis (AP), chronic pancreatitis (CP), autoimmune pancreatitis (AIP) and pancreatic exocrine insufficiency (PEI); however, data on such an association remain sparse and heterogeneous. Method: PubMed/MEDLINE and EMBASE databases were searched for studies investigating pancreatic involvement in patients with IBD. Results: Four thousand one hundred and twenty‐one records were identified and 547 screened; finally, 124 studies were included in the review. AP is the most frequent pancreatic manifestation in IBD; the majority of AP cases in IBD are due to gallstones and drugs but cases of idiopathic AP are increasingly reported. AIP is a rare disease, but a strong association with IBD has been demonstrated, especially for type 2 and ulcerative colitis. The pathogenetic link between IBD and AIP remains unclear, but an immune‐mediated pathway seems plausible. An association between CP and PEI with IBD has also been suggested, but data are to date scarce and conflicting. Conclusion: This is the first systematic review of the association between IBD and pancreatic diseases. Gallstones and drugs should be considered the most probable causes of AP in IBD, with type 2 AIP also being possible. [ABSTRACT FROM AUTHOR]

Background & Aims: Machine learning (ML) provides new approaches for prognostication through the identification of novel subgroups of patients. We explored whether ML could support disease sub‐phenotyping and risk stratification in primary biliary cholangitis (PBC). Methods: ML was applied to an international dataset of PBC patients. The dataset was split into a derivation cohort (training set) and a validation cohort (validation set), and key clinical features were analysed. The outcome was a composite of liver‐related death or liver transplantation. ML and standard survival analysis were performed. Results: The training set was composed of 11,819 subjects, while the validation set was composed of 1,069 subjects. ML identified four clusters of patients characterized by different phenotypes and long‐term prognosis. Cluster 1 (n = 3566) included patients with excellent prognosis, whereas Cluster 2 (n = 3966) consisted of individuals at worse prognosis differing from Cluster 1 only for albumin levels around the limit of normal. Cluster 3 (n = 2379) included young patients with florid cholestasis and Cluster 4 (n = 1908) comprised advanced cases. Further sub‐analyses on the dynamics of albumin within the normal range revealed that ursodeoxycholic acid‐induced increase of albumin >1.2 x lower limit of normal (LLN) is associated with improved transplant‐free survival. Conclusions: Unsupervised ML identified four novel groups of PBC patients with different phenotypes and prognosis and highlighted subtle variations of albumin within the normal range. Therapy‐induced increase of albumin >1.2 x LLN should be considered a treatment goal. [ABSTRACT FROM AUTHOR]

Background: We investigated associations between baseline use of immunosuppressive drugs and severity of Coronavirus Disease 2019 (COVID‐19) in autoimmune hepatitis (AIH). Patients and methods: Data of AIH patients with laboratory confirmed COVID‐19 were retrospectively collected from 15 countries. The outcomes of AIH patients who were on immunosuppression at the time of COVID‐19 were compared to patients who were not on AIH medication. The clinical courses of COVID‐19 were classified as (i)‐no hospitalization, (ii)‐hospitalization without oxygen supplementation, (iii)‐hospitalization with oxygen supplementation by nasal cannula or mask, (iv)‐intensive care unit (ICU) admission with non‐invasive mechanical ventilation, (v)‐ICU admission with invasive mechanical ventilation or (vi)‐death and analysed using ordinal logistic regression. Results: We included 254 AIH patients (79.5%, female) with a median age of 50 (range, 17‐85) years. At the onset of COVID‐19, 234 patients (92.1%) were on treatment with glucocorticoids (n = 156), thiopurines (n = 151), mycophenolate mofetil (n = 22) or tacrolimus (n = 16), alone or in combinations. Overall, 94 (37%) patients were hospitalized and 18 (7.1%) patients died. Use of systemic glucocorticoids (adjusted odds ratio [aOR] 4.73, 95% CI 1.12‐25.89) and thiopurines (aOR 4.78, 95% CI 1.33‐23.50) for AIH was associated with worse COVID‐19 severity, after adjusting for age‐sex, comorbidities and presence of cirrhosis. Baseline treatment with mycophenolate mofetil (aOR 3.56, 95% CI 0.76‐20.56) and tacrolimus (aOR 4.09, 95% CI 0.69‐27.00) were also associated with more severe COVID‐19 courses in a smaller subset of treated patients. Conclusion: Baseline treatment with systemic glucocorticoids or thiopurines prior to the onset of COVID‐19 was significantly associated with COVID‐19 severity in patients with AIH. [ABSTRACT FROM AUTHOR]

The cover image is based on the Editorial Anti‐gp210 and other anti‐nuclear pore complex autoantibodies in primary biliary cholangitis: What we know and what we should know by Laura Cristoferi, Alessio Gerussi, and Pietro Invernizzi., https://doi.org/10.1111/liv.14791. [ABSTRACT FROM AUTHOR]

Autoantibodies are essential tools for primary biliary cholangitis (PBC) diagnosis, and they seem to play an important role in risk stratification too. Anti-gp210 and other anti-nuclear pore complex autoantibodies in primary biliary cholangitis: What we know and what we should know Patients non-responders to ursodeoxycholic acid (UDCA) were more frequently reactive to anti-gp210 antibodies (39% vs 17%) and their transplant-free survival was lower compared to non-responders without anti-gp210 autoantibodies (log-rank I P i = .003). [Extracted from the article]

For many years the one‐size‐fits‐all approach has been the only one available to manage patients affected by primary biliary cholangitis. The introduction of obeticholic acid in 2016 as a second‐line treatment, together with the creation and validation of several biochemically based scores to stratify the risk of progressive disease, has opened up the need to redefine clinical practice by changing the actual paradigm. The precision medicine initiative is a model of patient‐centered health care that aims to improve medicine based on genotypic and molecular characteristics that correlate to specific phenotypic, individual characteristics. In summary, the aim of the precision medicine is to define the right treatment for the right person at the right time. The availability of a second‐line disease‐modifying drug and new molecules in phase 2 or 3 trials makes this an exciting time for the precision medicine initiative in primary biliary cholangitis. In this review we describe the current risk stratification tools and we track a possible path towards the application of precision medicine in clinical daily life. [ABSTRACT FROM AUTHOR]

Background and Aim Upper gastrointestinal endoscopic findings, such as esophagitis, Barrett's esophagus, peptic ulcer, and malignancy, represent a public health problem. This systematic review aimed to evaluate the prevalence of upper gastrointestinal endoscopic findings in the community. Methods A systematic search was conducted in PUBMED and EMBASE to May 2015. Studies were eligible if they reported the prevalence of upper gastrointestinal endoscopic findings in unselected samples of the community. Results Twelve articles were eligible, nine reported data from three endoscopic surveys ( n = 3063 subjects), and three from national screening programs ( n = 84 153). The overall prevalence of upper gastrointestinal endoscopic findings in the community was 30% in the Kalixanda study (Sweden), 24.9% in the Loiano-Monghidoro study (Italy), and 68.9% in the Systematic Investigation of Gastrointestinal Diseases study (China). The pooled prevalence of esophagitis, endoscopically suspected esophageal metaplasia (ESEM), peptic ulcer, and gastric cancer in all studies was 11.2, 5.1, 6.8, and 0.33%, respectively. The most frequent finding was esophagitis in Europe, with a prevalence of 15.5% in Sweden and 11.8% in Italy, and peptic ulcer in China (17.1%), both in asymptomatic and symptomatic individuals. The prevalence of Helicobacter pylori was positively associated with the prevalence of peptic ulcer ( r = 0.91) but negatively associated with the prevalence of both esophagitis ( r = −0.99) and ESEM ( r = −0.95). Conclusions Upper gastrointestinal endoscopic findings are present in at least a quarter of subjects in the community with different patterns in Western and Eastern countries, both in asymptomatic and symptomatic subjects. H. pylori prevalence negatively impacts on the prevalence of reflux-related esophageal findings. [ABSTRACT FROM AUTHOR]