Autoantibodies in Primary Biliary Cholangitis.

Primary biliary cholangitis (PBC) is a chronic immune-mediated liver disease characterized by a lymphocytic cholangitis, with subsequent cholestasis, progressive liver fibrosis, and ultimately complications arising from end-stage liver disease. Testing for autoantibodies is important in the diagnosis of PBC, as well as stratifying prognosis. This review focuses on the role of autoantibodies in the diagnosis of PBC, as well as the relationship between autoantibodies with pathophysiology and prognostication, along with a discussion regarding novel and other related disease autoantibodies.

Recurrent Primary Sclerosing Cholangitis: Current Understanding, Management, and Future Directions.

Patients with primary sclerosing cholangitis (PSC) constitute 5 to 15% of patients listed for liver transplantation worldwide. Although post-transplant outcomes are favorable, recurrent PSC (rPSC) occurs in an important subset of patients, with higher prevalence rates reported with increasing time from transplant. Given its association with poor graft outcomes and risk of retransplant, effort has been made to understand rPSC, its pathophysiology, and risk factors. This review covers these facets of rPSC and focuses on implicated risk factors including pretransplant recipient characteristics, inflammatory bowel-disease-related factors, and donor-specific and transplant-specific factors. Confirming a diagnosis of rPSC requires thoughtful consideration of alternative etiologies so as to ensure confidence in diagnosis, management, subsequent risk assessment, and counseling for patients. Unfortunately, no cure exists for rPSC; however, future large-scale efforts are underway to better characterize the natural history of rPSC and its associated risk factors with hopes of identifying potential key targets for novel therapies.

The Impact of Primary Liver Disease and Social Determinants in a Mixed Donor Liver Transplant Program: A Single-Center Analysis.

Organ allocation in liver transplantation (LT) remains imperfect. Periodic center reviews ensure programs transparently evaluate the impact of practice on access to transplantation, reflecting, in particular, patient (primary disease, social determinants) and program (deceased versus live donation) factors. Adult Ontario residents waitlisted for first LT at Toronto General Hospital from November 2012 to May 2019 were reviewed. Analyses were performed between distance to transplant center, income, education level, population density and primary liver disease, with LT, deceased donor liver transplant (DDLT), living donor liver transplant (LDLT), and delisting. Of 1735 listed patients, 549 were delisted (32%), while 1071 were transplanted (62%), with 819 DDLT recipients (76%) and 252 LDLT recipients (24%), while 115 (7%) remained actively listed at data census. On univariate analysis, DDLT recipients lived 30% closer (median 39.7 versus 60.6 km; P < 0.001), lived in more populous areas (median 8501.0 versus 6868.5 people in a 1-km radius; P < 0.001), and resided in households that annually earned 10% less (median $92,643.17 versus $102,820.89 Canadian dollars; P < 0.001) compared with LDLT recipients. These findings with population density and income differences between DDLT versus LDLT receival remained significant on multivariate modeling even when accounting for primary liver disease. Primary liver disease was a statistically significant factor on multivariate analyses in LT receival (P = 0.001) as well as DDLT versus LDLT receival (P < 0.001). Of patients listed for end-stage liver disease, more patients with autoimmune cholestatic liver diseases received LDLT (34%-41%) than DDLT (27%-30%); this contrasted with patients with noncholestatic diseases LDLT (8%-19%) versus DDLT (37%-59%) receival (P < 0.001). Review of transplant allocation in a large mixed-donor North American liver transplant program demonstrates how patient social determinants and primary liver disease etiology continue to be significantly associated with ultimate transplantation.

Gender differences in gastroenterology and hepatology authorship and editorial boards.

BACKGROUND AND AIMS: Women are numerically under-represented in the field of gastroenterology and hepatology. This study aims to characterize the gender distribution of first and senior authors and editorial board members across high impact factor journals in gastroenterology and hepatology. METHODS: Publications from January 1, 2019 to December 31, 2019 were reviewed from 29 journals. Gender of editorial board leadership, editorial board members, first, and senior authors was identified using publicly available data. Spearman correlation coefficients were calculated to assess for a relationship among editorial board, first author, and senior author gender and impact factor. RESULTS: Of 29 journals (median impact factor 5.55) with 357 journal issues and 8036 articles, there were 3 of 39 female chief editors (7.7%), 601 of 3455 female editorial board members (17.4%), 2547 of 8036 female first authors (31.7%), and 1390 of 7335 female senior authors (19%). No statistically significant correlations existed between impact factor and chief editor gender with gender distribution of editorial boards, first authors, or senior authors. Positive correlations existed between male-dominated editorial boards and male first (+.52, P = .005) and senior authorship (+.56, P = .002), whereas negative correlations occurred between male-dominated editorial boards and female first (-.51, P = .006) and senior authorship (-.56, P = .002). Positive correlations also existed between publication of first and senior authors of the same gender (+.57, men [P = .001]; +.58, women [P = .001]). CONCLUSIONS: Although gender distribution of female first authorship approaches current distributions in the field of gastroenterology and hepatology, editor-in-chief positions, editorial board membership, and senior authorship continue to be primarily men. Future endeavors to improve proportionate gender representation include improved journal leadership selection transparency, targeted diversity statements, and enhanced mentorship.

Long-term outcomes of liver transplant recipients followed up in non-transplant centres: Care closer to home.

INTRODUCTION: Increasing rates of liver transplantation and improved outcomes have led to greater numbers of transplant recipients followed up in non-transplant centres. Our aim was to document long-term clinical outcomes of liver transplant recipients managed in this 'hub-and-spoke' healthcare model. METHODS: A retrospective analysis of all adult patients who underwent liver transplantation between 1987 and 2016, with post-transplant follow-up in two non-transplant centres in the UK (Nottingham) and Canada (Ottawa), was performed. RESULTS: The 1-, 5-, 10- and 20-year patient survival rates were 98%, 95%, 87% and 62%, and 100%, 96%, 88% and 62% in the Nottingham and Ottawa groups, respectively (p=0.87). There were no significant differences between the two centres in 1-, 5-, 10- and 20-year cumulative incidence of death-censored graft-survival (p=0.10), end-stage renal disease (p=0.29) or de novo cancer (p=0.22). Nottingham had a lower incidence of major cardiovascular events (p=0.008). CONCLUSION: Adopting a new model of healthcare provides a means of delivering post-transplant patient care close to home without compromising patient survival and long-term clinical outcomes.

The Risk of Adverse Neonatal Outcomes With Maternal Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.

BACKGROUND: Patients with inflammatory bowel disease (IBD) may be at increased risk of adverse neonatal outcomes. The aim of this study was to determine pooled incidences and risk factors for these outcomes. METHODS: Medline, Embase, and Cochrane Library were searched through May 2019 for studies reporting adverse neonatal outcomes in IBD. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. RESULTS: The pooled incidence of preterm birth, low birth weight, congenital anomalies, and infants transferred to the neonatal intensive care unit was 8.6% (95% CI, 7.0%-10.1%), 8.9% (95% CI, 7.3%-10.5%), 2.1% (95% CI, 1.6%-2.6%), and 4.9% (95% CI, 2.9%-6.9), respectively. Compared with healthy controls, patients with IBD were more likely to deliver infants with low birth weight (<2500 grams; OR, 2.78; 95% CI, 1.16-6.66) and infants admitted to the intensive care unit (OR, 3.33; 95% CI, 1.83-6.05). Patients with Crohn's disease had an increased incidence of congenital anomalies (OR, 3.03; 95% CI, 1.43-6.42). Among IBD patients, active disease was associated with increased incidence of preterm birth (OR, 2.06; 95% CI, 1.21-3.51), low birth weight (OR, 2.96; 95% CI, 1.54-5.70), and small for gestational age (OR, 2.62; 95% CI, 1.18-5.83). Antitumor necrosis factor (anti-TNF) use during pregnancy was associated with an increased incidence of neonatal intensive care unit admission (OR, 2.42; 95% CI, 1.31-4.45) and low birth weight (OR, 1.54; 95% CI, 1.01-2.35). CONCLUSIONS: Patients with IBD, particularly with active disease or requiring anti-TNF therapy, may be at increased risk of developing adverse neonatal outcomes.

Review article: pathophysiology and management of primary biliary cholangitis.

BACKGROUND: Primary biliary cholangitis (PBC), an immune-mediated disease characterised by destruction of intrahepatic bile ducts, results in progressive damage to the biliary tree, cholestasis and ultimately advanced liver disease. In the last decade, advances in practice have improved clinical care, driven novel therapeutic options and improved risk stratification tools. AIMS: To provide an overview of the disease characteristics of PBC and review a patient-centred management approach for the clinical team caring for those with PBC. METHODS: We reviewed the current literature and guidelines on PBC with a focus on management and therapies. RESULTS: A confident diagnosis of PBC is usually made based on serum liver tests and immune serology. Management of PBC should focus on three main 'process' pillars: (a) treat and risk-stratify through use of biochemical and prognostic criteria; (b) manage concurrent symptoms and other associated diseases; and (c) stage disease, monitor progression and prevent complications. With ongoing complexities in management, including a newly licensed therapy (obeticholic acid) and alternative non-licensed treatments and ongoing clinical trials, discussion with PBC expert centres is encouraged. CONCLUSIONS: PBC is a dynamic disease wherein current treatment goals have become appropriately ambitious. Goals of care should prioritise prevention of end-stage liver disease and amelioration of patient symptom burden for all.

Absence of Day 3 Steroid Response Predicts Colitis-Related Complications and Colectomy in Hospitalized Ulcerative Colitis Patients.

BACKGROUND AND AIMS: Rates and predictors of complications among hospitalized ulcerative colitis (UC) patients requiring high-dose corticosteroids have not been well-characterized, especially in the era of biologics. METHODS: We retrospectively studied consecutive UC admitted for a colitis flare requiring high-dose corticosteroids between April 2006 and December 2016. We evaluated rates and determinants of serious in-hospital complications (colitis-related complications, systemic complications, peri-operative complications and death) and colectomy. We performed multivariable logistic regression analysis to assess the independent association between day 3 steroid response and the risk of incurring in-hospital complications and colectomy. RESULTS: Of 427 consecutive admissions, serious in-hospital complications occurred in 87 cases (20%), while colitis-related complications occurred in 47 cases (11%). There were significantly fewer colitis-related complications during the 2012 to 2016 period as compared to the 2006 to 2011 period (7% versus 16%, P < 0.01), but significantly more systemic complications (16% versus 5%, P = 0.001). In-hospital colectomy occurred in 50 hospitalizations (12%). Day 3 steroid response was achieved in 167 hospitalizations (39%). Day 3 steroid nonresponse was significantly associated with colitis-related complications among males (adjusted odds ratio [aOR] 8.22, 95% confidence interval [CI] 1.77 to 38.17), but not among females (aOR 1.39, 95% CI 0.54 to 3.60). Older age, C. difficile infection and admission to a non-gastroenterology service were also associated with a higher risk of in-hospital complications. Day 3 steroid nonresponse was significantly associated with in-hospital colectomy (aOR 10.10, 95% CI 3.56 to 28.57). CONCLUSION: In our series of UC hospitalizations for a colitis flare, absence of day 3 steroid response was associated with an increased risk of colitis-related complications among males and of in-hospital colectomy. Clinicians should recognize the importance of early steroid response as a marker to guide the need for treatment optimization.

Gastroduodenal Sarcoidosis With Concomitant Cytomegalovirus Gastritis.

Gastrointestinal sarcoidosis in the absence of pulmonary disease is rare. Likewise, cytomegalovirus (CMV) reactivation in the stomach is also rare. We present a 67-year-old woman with symptomatic CMV gastritis and gastroduodenal sarcoidosis who presented with epigastric pain, nausea, and vomiting. Initial gastric biopsies revealed CMV gastritis. Repeat assessment demonstrated worsening disease requiring antiviral treatment. After this, further investigations into ongoing epigastric pain demonstrated noncaseating granulomas on repeat gastrointestinal biopsies. A diagnosis of sarcoidosis was established and treated with prednisone to resolution.

Systematic review with meta-analysis: risk of adverse pregnancy-related outcomes in inflammatory bowel disease.

BACKGROUND: The effect of inflammatory bowel disease (IBD) on pregnancy-related outcomes remains unknown. AIM: To determine the risk of adverse maternal, placental and obstetric outcomes in IBD METHODS: We searched Medline, Embase and Cochrane library through May 2019 for studies reporting adverse maternal, placental and obstetric outcomes in patients with IBD. Odds ratios (OR) with 95% confidence intervals (CI) were calculated for these outcomes in patients with IBD compared to healthy controls. RESULTS: Fifty-three studies were included (7917 IBD pregnancies and 3253 healthy control pregnancies). Caesarean delivery was more common in patients with IBD compared to healthy controls (OR 1.79, 95% CI, 1.16-2.77). This remained significant for UC (OR 1.80, 95% CI, 1.21-2.90) but not CD (OR 1.48, 95% CI, 0.94-2.34). Similarly, gestational diabetes occurred more commonly in IBD (OR 2.96, 95% CI, 1.47-5.98). The incidences of placental diseases were 2.0% (95% CI, 0.9%-3.1%) for pre-eclampsia, 3.3% (95% CI, 0%-7.2%) for placental abruption, 0.5% (95% CI, 0.2%-0.9%) for placenta previa and 0.3% (95% CI, 0%-0.5%) for chorioamnionitis. Patients with IBD were more likely to experience preterm prelabour rupture of membranes (OR 12.10, 95% CI, 2.15-67.98), but not early pregnancy loss (OR 1.63, 95% CI 0.49-5.43). Anti-tumour necrosis factor therapy was not associated with chorioamnionitis (OR 1.12, 95% CI, 0.16-7.67), early pregnancy loss (OR 1.49, 95% CI, 0.83-2.64) or placenta previa (OR 1.58, 95% CI, 0.30-8.47). CONCLUSIONS: Gestational diabetes and preterm prelabour rupture of membranes occurs more commonly in patients with IBD, although the incidence of placental diseases remains low.

Noninvasive Methods For Assessing Inflammatory Bowel Disease Activity in Pregnancy: A Systematic Review.

Active inflammatory bowel disease (IBD) may increase the risk of adverse outcomes during pregnancy. Our aim was to systematically review the role of noninvasive fecal tests, such as fecal calprotectin (FCP) and lactoferrin (FL), and laboratory tests including C-reactive protein (CRP), hemoglobin, and albumin in the assessment of IBD during pregnancy. A systematic search of electronic databases was performed through October 2018 for studies assessing the utility of fecal and laboratory tests in predicting IBD activity in pregnant patients. Active disease was defined based on routinely used clinical criteria such as the Harvey-Bradshaw Index or Mayo score for ulcerative colitis. Noninvasive test levels were stratified by the presence of active disease and by gestational period (preconception, first trimester, second trimester, and third trimester). Thirteen studies were included. Both FCP and FL levels were significantly higher in pregnant patients with IBD compared with those without IBD. FCP levels were also significantly higher in patients with active disease compared with those with the inactive disease during all gestational periods. Furthermore, 3 studies demonstrated no consistent correlation with serum CRP and active IBD during pregnancy. Similarly, serum albumin and hemoglobin levels did not correlate with disease activity in pregnant patients with IBD. Given the lack of high-quality evidence, only FCP appears to correlate with IBD activity in all gestational periods of pregnancy. The utility of the other noninvasive tests such as serum CRP, hemoglobin, and albumin remains to be determined in this population.

History of malignancy and relevant symptoms may predict a positive computed tomography enterography in obscure gastrointestinal bleeds.

BACKGROUND AND AIM: This study aimed to assess the clinical utility of computed tomography enterography (CTE) and identify factors associated with a diagnostic CTE for patients with obscure gastrointestinal bleeding (OGIB). METHODS: A retrospective observational study was performed at a Canadian tertiary care center from 2005 to 2015. A total of 138 patients underwent a CTE for OGIB. Univariate and multivariate logistic regressions were performed to determine factors associated with a diagnostic CTE. A highly sensitive clinical rule was then developed to help identify OGIB patients for whom a CTE may be beneficial in their clinical work-up. RESULTS: A possible bleeding source was identified in 30 (22%) cases. The presence of abdominal or constitutional symptoms as well as history of colorectal cancer was significantly associated with a positive CTE in univariate and multivariate analyses (P < 0.05). A positive CTE could be predicted based on the presence of abdominal or constitutional symptoms and history of colorectal cancer with 90% sensitivity (95% CI 74-98%) in our population. CONCLUSION: CTE identified a possible source of OGIB in one in five cases. In patients with the presence of abdominal or constitutional symptoms and a personal history of colorectal cancer, CTE may contribute to their diagnostic work-up.