Showing papers in "Alimentary Pharmacology & Therapeutics in 2016"

Review article: the global emergence of Helicobacter pylori antibiotic resistance.

Abstract: Author(s): Thung, I; Aramin, H; Vavinskaya, V; Gupta, S; Park, JY; Crowe, SE; Valasek, MA | Abstract: BackgroundHelicobacter pylori is one of the most prevalent global pathogens and can lead to gastrointestinal disease including peptic ulcers, gastric marginal zone lymphoma and gastric carcinoma.AimTo review recent trends in H. pylori antibiotic resistance rates, and to discuss diagnostics and treatment paradigms.MethodsA PubMed literature search using the following keywords: Helicobacter pylori, antibiotic resistance, clarithromycin, levofloxacin, metronidazole, prevalence, susceptibility testing.ResultsThe prevalence of bacterial antibiotic resistance is regionally variable and appears to be markedly increasing with time in many countries. Concordantly, the antimicrobial eradication rate of H. pylori has been declining globally. In particular, clarithromycin resistance has been rapidly increasing in many countries over the past decade, with rates as high as approximately 30% in Japan and Italy, 50% in China and 40% in Turkey; whereas resistance rates are much lower in Sweden and Taiwan, at approximately 15%; there are limited data in the USA. Other antibiotics show similar trends, although less pronounced.ConclusionsSince the choice of empiric therapies should be predicated on accurate information regarding antibiotic resistance rates, there is a critical need for determination of current rates at a local scale, and perhaps in individual patients. Such information would not only guide selection of appropriate empiric antibiotic therapy but also inform the development of better methods to identify H. pylori antibiotic resistance at diagnosis. Patient-specific tailoring of effective antibiotic treatment strategies may lead to reduced treatment failures and less antibiotic resistance.

Review article: insights into colonic protein fermentation, its modulation and potential health implications

Abstract: SummaryBackground Beneficial effects of carbohydrate fermentation on gastrointestinal health are well established. Conversely, protein fermentation generates harmful metabolites but their relevance to gastrointestinal health is poorly understood. Aim To review the effects of increased protein fermentation on biomarkers of colonic health, factors influencing fermentative activity and potential for dietary modulation to minimise detrimental effects. Methods A literature search was performed in PubMed, Medline, EMBASE and Google scholar for clinical and pre-clinical studies using search terms – ‘dietary protein’, ‘fermentation’, ‘putrefaction’, ‘phenols’, ‘sulphide’, ‘branched-chain fatty acid’, ‘carbohydrate fermentation’, ‘gastrointestinal’. Results High protein, reduced carbohydrate diets alter the colonic microbiome, favouring a potentially pathogenic and pro-inflammatory microbiota profile, decreased short-chain fatty acid production and increased ammonia, phenols and hydrogen sulphide concentrations. These metabolites largely compromise the colonic epithelium structure, causing mucosal inflammation but may also directly modulate the enteric nervous system and intestinal motility. Increased protein fermentation as a result of a high-protein intake can be attenuated by addition of oligosaccharides, resistant starch and nonstarch polysaccharides and a reduction in total protein or specifically, aromatic and sulphur-containing amino acids. These factors may have clinical importance as novel therapeutic approaches to problems, in which protein fermentation may be implicated, such as malodorous flatus, irritable bowel syndrome, ulcerative colitis and prevention of colorectal cancer. Conclusions The direct clinical relevance of excessive protein fermentation in the pathogenesis of irritable bowel syndrome, malodorous flatus and ulcerative colitis are underexplored. Manipulating dietary carbohydrate and protein intake have potential therapeutic applications in such settings and warrant further clinical studies.

Systematic review with meta‐analysis: the incidence and prevalence of eosinophilic oesophagitis in children and adults in population‐based studies

Abstract: Summary Background The recognition of eosinophilic oesophagitis (EoE) has risen sharply, but its current epidemiology is still under debate. Aim To estimate accurately the prevalence and incidence rates of EoE, by a systematic review and meta-analysis. Methods MEDLINE, EMBASE and SCOPUS databases were searched for population-based studies on the epidemiology of EoE. Pooled incidence and prevalence rates, male:female and children:adult ratios, and geographical and temporal variations were calculated with random-effects models. Results The search yielded 1334 references; the final quantitative summary included 13 population-based studies from North America, Europe and Australia, with the results showing high heterogeneity. The pooled EoE incidence rate was 3.7/100 000 persons/year [95% confidence interval (CI): 1.7–6.5] and was higher for adults (7; 95% CI: 1–18.3) than for children (5.1; 95% CI: 1.5–10.9). The pooled prevalence of EoE was 22.7 cases/100 000 inhabitants (95% CI: 12.4–36), rising to 28.1 (95% CI: 13–49) when studies with a lower risk of bias were considered; prevalence was higher in adults than in children (43.4; 95% CI: 22.5–71.2 vs. 29.5; 95% CI: 17.5–44.7, respectively), and in American compared to European studies. A steady rise in EoE incidence and prevalence rates was observed upon comparison of studies conducted before and after 2008. No significant publication bias was found. Conclusions Eosinophilic oesophagitis is an increasingly common diagnosis in North America and Europe. The population-based incidence and prevalence of eosinophilic oesophagitis vary widely across individual studies, probably due to variations in diagnosis and risk of bias of research. More prospective, large-scale, multicenter studies are needed to evaluate reported data.

Review article: sarcopenia in cirrhosis – aetiology, implications and potential therapeutic interventions

Abstract: SummaryBackground Sarcopenia (loss of muscle mass) is common in cirrhosis and is associated with poor outcomes. Current teaching recommends the use of protein supplementation and exercise, however, this fails to address many other factors which contribute to muscle loss in this setting. Aims To summarise existing knowledge regarding the aetiology of sarcopenia in cirrhosis, diagnostic modalities and the clinical significance of this condition. In addition to discuss recent research findings that may allow the development of more effective treatments. Methods We conducted a Medline and PubMed search using the search terms ‘sarcopenia’, ‘muscle’, ‘body composition’, ‘cirrhosis’, ‘liver’ and ‘malnutrition’ from inception to October 2015. Results Cirrhotic patients with sarcopenia have reduced survival, experience increased rates of infection and have worse outcomes following liver transplantation. The aetiology of this condition is more complex than simple protein and calorie malnutrition. Cirrhosis also results in depleted glycogen stores and metabolic alterations that cause excessive protein catabolism, increased activation of the ubiquitin–proteasome pathway and inappropriate muscle autophagy. Satellite cell differentiation and proliferation is also reduced due to a combination of elevated myostatin levels, reduced IGF-1 and hypogonadism. Although there is some evidence supporting the use of late evening snacks, branched chain amino acid supplementation and high protein/high calorie diets, well designed clinical trials addressing the effects of treatment on body composition in cirrhosis are lacking. Conclusion Sarcopenia in cirrhosis has a complex pathogenesis and simple dietary interventions are insufficient. Improved understanding of the multiple mechanisms involved should allow the development of more effective therapies, which target the specific underlying metabolic derangements.

Validity and reliability of the Bristol Stool Form Scale in healthy adults and patients with diarrhoea-predominant irritable bowel syndrome.

Abstract: Background The Bristol Stool Form Scale (BSFS) is a 7-point scale used extensively in clinical practice and research for stool form measurement, which has undergone limited validity and reliability testing. Aim To determine the validity and reliability of the BSFS in measuring stool form in healthy adults and patients with diarrhoea-predominant irritable bowel syndrome (IBS-D). Methods One hundred and sixty-nine healthy volunteers provided a stool sample and used the BSFS to classify stool form, which was compared with measured stool water content and with values from 19 patients with IBS-D. Eighty-six volunteers used the BSFS to classify 26 stool models to determine accuracy and reliability. Results Volunteers' classifications of stool type correlated with stool water (Spearman's rho = 0.491, P Conclusions The BSFS demonstrated substantial validity and reliability, although difficulties arose around clinical decision points (Types 2, 3, 5, 6) that warrant investigation in larger clinical populations. Potential for improving validity and reliability through modifications to the BSFS or training in its use should be explored.

Systematic review with meta-analysis: mucosal healing is associated with improved long-term outcomes in Crohn's disease.

Abstract: SummaryBackground Clinical manifestations of Crohn's disease (CD) do not reliably correlate with endoscopic activity. While treating to achieve clinical remission (CR) has neither proven to improve CD outcomes nor alter the natural disease course, it is unclear whether targeting objective measures like mucosal healing (MH) is associated with improved long-term outcomes. Aim To perform a systematic review and meta-analysis comparing long-term outcomes in active CD patients who achieve MH compared to those who do not. Methods We performed a systematic literature search to identify studies with prospective cohorts of active CD patients that included outcomes of patients who achieved MH at first endoscopic assessment (MH1) compared to those who did not. The primary outcome was long-term (≥50 weeks) CR. Secondary outcomes included CD-related surgery-free rate, hospitalisation-free rate and long-term MH rate. Pooled odds ratio (OR) and 95% confidence intervals (CI) were calculated. Results Twelve studies with 673 patients met inclusion criteria. Patients achieving MH1 had a pooled OR of 2.80 (95%CI, 1.91–4.10) for achieving long-term CR, 2.22 (95%CI, 0.86–5.69) for CD-related surgery-free rate, and 14.30 (95%CI, 5.57–36.74) for long-term MH. Sensitivity analyses suggested no difference in outcomes if MH1 was achieved on biologics vs. non-biologics. No significant publication bias or heterogeneity was detected. Conclusions Achieving MH1 is associated with increased rates of long-term clinical remission, and maintenance of mucosal healing in active Crohn's disease and may therefore be a reasonable therapeutic target.

Systematic review: predicting and optimising response to anti-TNF therapy in Crohn's disease - algorithm for practical management.

Abstract: SummaryBackground Nonresponse and loss of response to anti-TNF therapies in Crohn's disease represent significant clinical problems for which clear management guidelines are lacking. Aim To review the incidence, mechanisms and predictors of primary nonresponse and secondary loss of response to formulate practical clinical algorithms to guide management. Methods Through a systematic literature review, 503 articles were identified which fit the inclusion criteria. Results Primary nonresponse to anti-TNF treatment affects 13–40% of patients. Secondary loss of response to anti-TNF occurs in 23–46% of patients when determined according to dose intensification, and 5–13% of patients when gauged by drug discontinuation rates. Recent evidence suggests that the mechanisms underlying primary nonresponse and secondary loss of response are multifactorial and include disease characteristics (phenotype, location, severity); drug (pharmacokinetic, pharmacodynamic or immunogenicity) and treatment strategy (dosing regimen) related factors. Clinical algorithms that employ therapeutic drug monitoring (using anti-TNF tough levels and anti-drug antibody levels) may be used to determine the underlying cause of primary nonresponse and secondary loss of response respectively and guide clinicians as to which patients are most likely to respond to anti-TNF therapy and help optimise drug therapy for those who are losing response to anti-TNF therapy. Conclusions Nonresponse or loss of response to anti-TNF occurs commonly in Crohn's disease. Clinical algorithms utilising therapeutic drug monitoring may establish the mechanisms for treatment failure and help guide the subsequent therapeutic approach.

Evidence that independent gut-to-brain and brain-to-gut pathways operate in the irritable bowel syndrome and functional dyspepsia : a 1-year population-based prospective study

Abstract: SummaryBackground Traditionally, functional gastrointestinal disorders (FGIDs) are conceptualised as originating in the brain via stress pathways (brain-to-gut). It is uncertain how many with irritable bowel syndrome (IBS) and functional dyspepsia (FD) have a gut origin of symptoms (gut-to-brain pathway). Aims To determine if there is a distinct brain-to-gut FGID (where psychological symptoms begin first) and separately a distinct gut-to-brain FGID (where gut symptoms start first). Methods A prospective random population sample from Newcastle, Australia who responded to a validated survey in 2012 and completed a 1-year follow-up survey (n = 1900). The surveys contained questions on Rome III IBS and FD and the Hospital Anxiety and Depression Scale. Results We found that higher levels of anxiety and depression at baseline were significant predictors of developing IBS (OR = 1.31; 95% CI 1.06–1.61, P = 0.01; OR = 1.54; 95% CI 1.29–1.83, P < 0.001) and FD (OR = 1.28; 95% CI 1.05–1.55, P = 0.01; OR = 1.55, 95% CI 1.32–1.83, P < 0.001), respectively, at the 1-year follow-up. Among those people who did not have elevated levels of anxiety and depression at baseline, subjects at baseline with documented IBS (mean difference 0.34; 95% CI 0.13–0.55, P = 0.002; 0.81; 95% CI 0.47–1.15, P < 0.001) and FD (0.38; 95% CI 0.14–0.63, P = 0.002; 0.92; 95% CI 0.57–1.27, P < 0.001), reported significantly higher levels of anxiety and depression at the 1-year follow-up. We calculated in one-third of individuals a mood disorder precedes FGID but in two-thirds an FGID precedes the mood disorder. Conclusion While brain–gut pathways are bidirectional, a major subset begin with gut symptoms first and only then psychological distress develops, implicating primary gut mechanisms as drivers of the gut and extra-intestinal features in many cases.

Randomised clinical trial: vonoprazan, a novel potassium-competitive acid blocker, vs. lansoprazole for the healing of erosive oesophagitis

Abstract: SummaryBackground Vonoprazan is a novel potassium-competitive acid blocker which may provide clinical benefit in acid-related disorders. Aim To verify the non-inferiority of vonoprazan vs. lansoprazole in patients with erosive oesophagitis (EE), and to establish its long-term safety and efficacy as maintenance therapy. Methods In this multicentre, randomised, double-blind, parallel-group comparison study, patients with endoscopically confirmed EE (LA Classification Grades A–D) were randomly allocated to receive vonoprazan 20 mg or lansoprazole 30 mg once daily after breakfast. The primary endpoint was the proportion of patients with healed EE confirmed by endoscopy up to week 8. In addition, subjects who achieved healed EE in the comparison study were re-randomised into a long-term study to investigate the safety and efficacy of vonoprazan 10 or 20 mg as maintenance therapy for 52 weeks. Results Of the 409 eligible subjects randomised, 401 completed the comparison study, and 305 entered the long-term maintenance study. The proportion of patients with healed EE up to week 8 was 99.0% for vonoprazan (203/205) and 95.5% for lansoprazole (190/199), thus verifying the non-inferiority of vonoprazan (P < 0.0001). Vonoprazan was also effective in patients with more severe EE (LA Classification Grades C/D) and CYP2C19 extensive metabolisers. In the long-term maintenance study, there were few recurrences (<10%) of EE in patients treated with vonoprazan 10 or 20 mg. Overall, vonoprazan was well-tolerated. Conclusions The non-inferiority of vonoprazan to lansoprazole in EE was verified in the comparison study, and vonoprazan was well-tolerated and effective during the long-term maintenance study.

Non‐invasive screening of diabetics in primary care for NAFLD and advanced fibrosis by MRI and MRE

Abstract: SummaryBackground Current guidelines do not recommend screening for non-alcoholic fatty liver disease (NAFLD) or advanced fibrosis. Patients with type 2 diabetes mellitus (T2DM) are known to be at increased risk for NAFLD and advanced fibrosis. Aim To assess the feasibility in diabetics in a primary care setting of screening for NAFLD and advanced fibrosis, by using non-invasive magnetic resonance imaging (MRI) to estimate the hepatic proton density fat fraction (MRI-PDFF) and magnetic resonance elastography (MRE) to estimate hepatic stiffness. Methods We performed a cross-sectional analysis of a prospective study that included 100 (53% men) consecutively enrolled diabetics who did not have any other aetiology of liver disease. All patients underwent a standardised research visit, laboratory tests, MRI-PDFF, and MRE. Results Mean (±s.d.) age and body mass index (BMI) was 59.7 (±11.2) years and 30.8 (±6.5) kg/m2, respectively. The prevalence of NAFLD (defined as MRI-PDFF ≥5%) and advanced fibrosis (defined as MRE ≥3.6 kPa) was 65% and 7.1%, respectively. One patient with advanced fibrosis had definite hepatocellular carcinoma. When compared to those without NAFLD, patients with NAFLD were younger (P = 0.028) and had higher mean BMI (P = 0.0008), waist circumference (P < 0.0001) and prevalence of metabolic syndrome (84.6% vs. 40.0%, P < 0.0001). Only 26% of those with NAFLD had elevated alanine aminotransferase. Conclusions This proof-of-concept study demonstrates that T2DM has significant rates of both NAFLD and advanced fibrosis. Concomitant screening for NAFLD and advanced fibrosis by using MRI-proton density fat fraction and magnetic resonance elastography in T2DM is feasible and may be considered after validation in a larger cohort.

Vedolizumab induction therapy for inflammatory bowel disease in clinical practice--a nationwide consecutive German cohort study.

Abstract: Background Vedolizumab (VDZ) is a humanised monoclonal IgG1 antibody targeting alpha(4)beta(7) integrin. Aim To investigate the real-world efficacy of vedolizumab for the treatment of Crohn's disease (CD) and ulcerative colitis (UC). Methods A consecutive cohort of 212 adult IBD patients with active disease (HBI > 7/ partial Mayo > 4) newly receiving VDZ was prospectively recruited from 7 academic and 17 community centres. The primary endpoint was clinical remission (CRM) (CD HBI <= 4, UC pMayo < 1) in week 14. Secondary endpoints included steroid-free remission (SFCRM), clinical response (CRS) (HBI/pMayo score drop = 3), vedolizumab impact on CRP, calprotectin and haemoglobin. Results Data of 97 CD (71.1% female, HBI 11) and 115 UC (42.6% female, pMayo 6) patients were analysed. Only 5.2% CD and 24.3% UC were anti-TNF alpha naive. Most had extensive mucosal involvement (Montreal L3 69.1%/E3 53.9%). At week 14, 23.7% vs. 23.5% of CD vs. UC patients achieved CRM, 19.6% vs. 19.1% SFCRM and 60.8% vs. 57.4% CRS, respectively (all based on NRI). Week 14 CRM in CD was significantly associated with no history of extraintestinal manifestations (P = 0.019), no prior adalimumab use (P = 0.011), no hospitalisation in the past 12 months (P = 0.015) and low HBI score (P = 0.02) and in UC with active or previous smoking (P = 0.044/0.028) and no anti-TNFa (P = 0.023) use. Low HBI (P = 0.019) and no hospitalisation in the past 12 months (P = 0.01) predict CD CRM. The three most common AE were joint pain, acne and nasopharyngitis. Conclusion Vedolizumab is effective in routine use.

Potent acid inhibition by vonoprazan in comparison with esomeprazole, with reference to CYP2C19 genotype

Abstract: SummaryBackground Acid inhibitory effects of proton pump inhibitors (PPIs) are influenced by CYP2C19 genotype. In contrast, the potent acid inhibition of vonoprazan is not influenced by CYP2C19 genotype. Aim To compare the acid inhibitory effects of vonoprazan and esomeprazole in relation to CYP2C19 genotype. Methods Twenty-eight healthy Japanese volunteers [7 CYP2C19 poor metabolisers (PMs), 11 intermediate metabolisers (IMs) and 10 rapid metabolisers (RMs)] received four different regimens in a randomised crossover manner: (i) vonoprazan 20 mg twice daily (b.d.), (ii) vonoprazan 20 mg daily, (iii) esomeprazole 20 mg b.d. and (iv) esomeprazole 20 mg daily. The timing of each dosing was 1 h before a meal. Twenty-four-hour intragastric pH monitoring was performed on day 7 on each regimen. Results In the overall genotype group, pH ≥4 holding time ratios (pH 4 HTRs) with vonoprazan b.d., vonoprazan daily, esomeprazole b.d. and esomeprazole daily were 100%, 95%, 91%, and 68% respectively. pH 5 HTRs were 99%, 91%, 84% and 54% respectively. Vonoprazan b.d. potently suppressed acid for 24 h, and was significantly superior to other regimens irrespective of CYP2C19 genotype. Vonoprazan daily was equivalent to esomeprazole b.d. in IMs and PMs, but superior in RMs. CYP2C19 genotype-dependent differences were observed in esomeprazole daily but not in vonoprazan b.d. or daily. Conclusion Vonoprazan 20 mg b.d. inhibits acid irrespective of CYP2C19 genotype, more potently than esomeprazole 20 mg b.d., pH 4 and 5 holding time ratios reached 100% and 99%, respectively.

Recurrent Clostridium difficile infection associates with distinct bile acid and microbiome profiles

Abstract: Summary Background The healthy microbiome protects against the development of Clostridium difficile infection (CDI), which typically develops following antibiotics. The microbiome metabolises primary to secondary bile acids, a process if disrupted by antibiotics, may be critical for the initiation of CDI. Aim To assess the levels of primary and secondary bile acids associated with CDI and associated microbial changes. Methods Stool and serum were collected from patients with (i) first CDI (fCDI), (ii) recurrent CDI (rCDI) and (iii) healthy controls. 16S rRNA sequencing and bile salt metabolomics were performed. Random forest regression models were constructed to predict disease status. PICRUSt analyses were used to test for associations between predicted bacterial bile salt hydrolase (BSH) gene abundances and bile acid levels. Results Sixty patients (20 fCDI, 19 rCDI and 21 controls) were enrolled. Secondary bile acids in stool were significantly elevated in controls compared to rCDI and fCDI (P < 0.0001 and P = 0.0007 respectively). Primary bile acids in stool were significantly elevated in rCDI compared to controls (P < 0.0001) and in rCDI compared to fCDI (P = 0.02). Using random forest regression, we distinguished rCDI and fCDI patients 84.2% of the time using bile acid ratios. Stool deoxycholate to glycoursodeoxycholate ratio was the single best predictor. PICRUSt analyses found significant differences in predicted abundances of bacterial BSH genes in stool samples across the groups. Conclusion Primary and secondary bile acid composition in stool was different in those with rCDI, fCDI and controls. The ratio of stool deoxycholate to glycoursodeoxycholate was the single best predictor of disease state and may be a potential biomarker for recurrence.

Systematic review: current concepts and challenges for the direct‐acting antiviral era in hepatitis C cirrhosis

Abstract: SummaryBackground The burden of HCV cirrhosis is high and projected to increase significantly over the next decade. While interferon therapy is problematic in HCV cirrhosis, the era of direct-acting anti-viral (DAA) therapy provides effective treatment for patients with cirrhosis. Aim To systematically review the results of DAA therapy to date in patients with HCV cirrhosis, and highlight the ongoing challenges for DAA therapy in this population. Methods A structured Medline search was conducted to obtain phase II and III HCV trials in patients with cirrhosis. Citations from review articles were cross-referenced and conference abstracts from EASL and AASLD liver meetings for the preceding 3 years were reviewed manually. Keywords used included hepatitis C, cirrhosis and the DAA's: sofosbuvir, ledipasvir, velpatasvir, grazoprevir, elbasvir, daclatasvir, beclabuvir, asunaprevir, simeprevir, paritaprevir, ombitasvir and dasabuvir. Results Successful direct-acting anti-viral treatment is now possible in patients with HCV-related cirrhosis including those with liver decompensation with several regimens now offering sustained virological response (SVR) of 90–95%. Overall success rates in GT1 cirrhosis are excellent while GT3-infected patients with cirrhosis remain hard to cure. The pangenotypic combination of sofosbuvir and velpatasvir holds promise for GT3 cirrhosis achieving SVR of ~90%. Conclusions Potent DAA therapies provide much needed, safe and highly effective treatment options for persons with HCV cirrhosis including those previously deemed unsuitable for treatment. Combination therapy with two or more classes of drug is essential to achieve high efficacy and minimise viral resistance, with the role of ribavirin still under evaluation. However, several challenges remain including the hard-to-cure groups of GT3 cirrhosis and direct-acting anti-viral failures, and managing drug–drug interactions.

Review article: safety and tolerability of direct‐acting anti‐viral agents in the new era of hepatitis C therapy

Abstract: SummaryBackground Direct-acting anti-virals (DAAs) licensed to treat chronic HCV infection have revolutionised treatment algorithms by drastically mitigating side effects while enhancing efficacy relative to interferon-based therapy. Aim To review adverse events (AEs) uniquely associated with DAA therapy across a broad spectrum of patient populations. Methods Searches of PubMed and FDA surveillance studies were undertaken to complete an exhaustive review. Search terms included ‘DAAs’, ‘safety’, and ‘tolerability’. Results While DAAs are remarkably well tolerated, they are accompanied by unique AEs. Simeprevir, an NS3/4A protease inhibitor, has been known, albeit infrequently, to cause mild hyperbilirubinemia and photosensitivity reactions; and paritaprevir boosted with ritonavir causes bilirubin and ALT elevations. Asunaprevir, another protease inhibitor, infrequently causes elevated transaminase levels. NS5A and NS5B inhibitors are well tolerated, although sofosbuvir is contraindicated in patients with severe renal impairment. Ribavirin co-administered in certain treatment regimens has been associated with cough, rash and haemolytic anaemia. Conclusions With the impending reality of a more tolerable interferon-sparing regimen, the future of DAA therapy offers shorter treatment duration, simplified disease management, and a patient-centred regimen. With advantages come drawbacks, including development of resistance to therapy and accessibility to this expensive treatment. DAA therapy continues to advance at a brisk pace with a promising trend for higher tolerability, even in difficult-to-treat subgroups such as those with cirrhosis, nonresponders to prior therapy, and transplant recipients. Subgroup-specific contraindications and safety-related limitations are active areas of research. Concerted research efforts and continuing advances lend hope to the goal of rendering HCV a routinely curable disease.

High risk of drug-induced microscopic colitis with concomitant use of NSAIDs and proton pump inhibitors

Abstract: SummaryBackground Microscopic colitis (MC) is a chronic bowel disorder characterised by watery diarrhoea. Nonsteroidal anti-inflammatory drugs (NSAIDs), proton pump inhibitors (PPIs), selective serotonin reuptake inhibitors (SSRIs) and statins have been associated with MC. However, underlying mechanisms remain unclear. Aim To study the association between exposure to these drugs and MC, with attention to time of exposure, duration, dosage and combined exposure, and to test hypotheses on underlying pharmacological mechanisms. Methods A case–control study was conducted using the British Clinical Practice Research Datalink. MC cases (1992–2013) were matched to MC-naive controls on age, sex and GP practice. Drug exposure was stratified according to time of exposure, duration of exposure or dosage. Conditional logistic regression analysis was applied to calculate adjusted odds ratios (AORs). Results In total, 1211 cases with MC were matched to 6041 controls. Mean age was 63.4 years, with 73.2% being female. Current use of NSAIDs (AOR 1.86, 95% CI 1.39–2.49), PPIs (AOR 3.37, 95% CI 2.77–4.09) or SSRIs (AOR 2.03, 95% CI 1.58–2.61) was associated with MC compared to never or past use. Continuous use for 4–12 months further increased the risk of MC. Strongest associations (fivefold increased risk) were observed for concomitant use of PPIs and NSAIDs. Statins were not associated with MC. Conclusions Current exposure to NSAIDs, PPIs or SSRIs and prolonged use for 4–12 months increased the risk of MC. Concomitant use of NSAIDs and PPIs showed the highest risk of MC. Acid suppression related dysbiosis may contribute to the PPI effect, which may be exacerbated by NSAID-related side-effects.

Vedolizumab provides clinical benefit over 1 year in patients with active inflammatory bowel disease - a prospective multicenter observational study.

Abstract: SummaryBackground Vedolizumab, a monoclonal antibody targeting the α4β7-integrin, is effective in inducing and maintaining clinical remission in Crohn's disease and ulcerative colitis according to randomised clinical trials. Aim To determine the long-term effectiveness of vedolizumab in a real-world clinical setting. Methods This observational registry assessed the clinical outcome in patients treated with vedolizumab for clinically active Crohn's disease (n = 67) or ulcerative colitis (n = 60). Primary endpoint was clinical remission (HBI ≤ 4/pMayo ≤ 1) at week 54. Secondary endpoints included clinical response rates (HBI/pMayo score drop ≥3) and steroid-free clinical remission at weeks 30 and 54. Results Vedolizumab was stopped in 69/127 (56%) patients after a median time of 18 weeks (range 2–49) predominantly owing to lack or loss of response. Using nonresponder imputation analysis, clinical remission and steroid-free remission rates were 21% and 15% in Crohn's disease and 25% and 22% in ulcerative colitis, respectively. Lack of clinical remission was associated with prior treatment with anti-TNF or with steroids for more than 3 months in the last 6 months in ulcerative colitis. At week 14, the absence of remission in Crohn's disease or nonresponse in ulcerative colitis indicated a low likelihood of clinical remission at week 54 [2/31 (7%) in Crohn's disease, 4/41 (10%) in ulcerative colitis]. Accordingly, declining C-reactive protein in inflammatory bowel disease and/or lower faecal calprotectin in ulcerative colitis at week 14 predicted remission at week 54. Conclusion Among patients who started vedolizumab for active inflammatory bowel disease, clinical remission rates are 21–25% after 54 weeks.

Systematic review with meta-analysis: the adverse effects of tobacco smoking on the natural history of Crohn's disease.

Abstract: Background Tobacco smoking is a well-established risk factor for the development of Crohn's disease, and this may lead to a more complicated disease course. However, recent evidence suggests that many patients with Crohn's disease are unaware of this fact. Aim To perform a systematic review and meta-analysis of the effects of smoking on disease course in Crohn's disease. Methods A search of MEDLINE, EMBASE and EMBASE classic was carried out (up to July 2015) to identify observational studies reporting data on smoking and rates of surgery or flares of disease activity in patients with Crohn's disease. Dichotomous data were pooled to obtain odds ratios (ORs) for flares of disease activity or need for surgery, with 95% confidence intervals (CIs). Results The search identified 33 eligible studies. Compared with nonsmokers, smokers had increased odds of flare of disease activity (OR, 1.56; 95% CI, 1.21–2.01), flare after surgery (OR, 1.97; 95% CI, 1.36–2.85), need for first surgery (OR, 1.68; 95% CI, 1.33–2.12) and need for second surgery (OR, 2.17; 95% CI, 1.63–2.89). The odds of these outcomes among ex-smokers diminished upon smoking cessation, with ORs comparable to those among nonsmokers and, in the case of flare or second surgery, significantly lower than smokers. Conclusions Smokers with Crohn's disease have a more complicated disease course than nonsmokers, and quitting smoking may ameliorate this. Patients should be reminded of the detrimental effects of smoking on the course of their disease, and smoking cessation advice should be provided to reduce disease burden and costs in these patients.

Randomised clinical study: GR-MD-02, a galectin-3 inhibitor, vs. placebo in patients having non-alcoholic steatohepatitis with advanced fibrosis.

Abstract: SummaryBackground Non-alcoholic steatohepatitis (NASH) and resultant liver fibrosis is a major health problem without approved pharmacotherapy. Pre-clinical results of GR-MD-02, a galectin-3 inhibitor, suggested potential efficacy in NASH with advanced fibrosis/cirrhosis and prompted initiation of a clinical development programme in NASH with advanced fibrosis. Aim To evaluate the safety, pharmacokinetics and exploratory pharmacodynamic markers of GR-MD-02 in subjects having NASH with bridging fibrosis. Methods The GT-020 study was a first-in-human, sequential dose-ranging, placebo controlled, double-blinded study with the primary objective to assess the safety, tolerability and dose limiting toxicity of GR-MD-02, in subjects with biopsy-proven NASH with advanced fibrosis (Brunt stage 3). The secondary objectives were to characterise first-dose and multiple-dose pharmacokinetic profiles and to evaluate changes in potential serum biomarkers and liver stiffness as assessed by FibroScan. Results GR-MD-02 single and three weekly repeated of 2, 4 and 8 mg/kg revealed no meaningful clinical differences in treatment emergent adverse events, vital signs, electrocardiographic findings or laboratory tests. Pharmokinetic parameters showed a dose-dependent relationship with evidence of drug accumulation following 8 mg/kg (~twofold). Conclusions GR-MD-02 doses were in the upper range of the targeted therapeutic dose determined from pre-clinical data and were safe and well tolerated with evidence of a pharmacodynamic effect. These results provide support for a Phase 2 development programme in advanced fibrosis due to NASH.

Systematic review with meta‐analysis: long‐term outcomes of faecal microbiota transplantation for Clostridium difficile infection

Abstract: SummaryBackground Clostridium difficile infection is a major cause of nosocomial diarrhoea. Aim To evaluate long-term (≥90 days) efficacy and safety of faecal microbiota transplantation for C. difficile infection and explore the factors affecting the faecal microbiota transplantation outcomes. Methods MEDLINE, the Cochrane Library and EMBASE were searched and only observational studies that utilised faecal microbiota transplantation for C. difficile infection with long-term follow-up duration (≥90 days) were included. Primary cure rate, overall recurrence rate and early (<90 days) and late (≥90 days) recurrence rate were calculated. Results Eighteen observational studies with 611 patients were included. The primary cure rate was 91.2% (95% confidence interval, CI 86.7–94.8%). The overall recurrence rate was 5.5% (95% CI 2.2–10.3%). The early recurrence rate and late recurrence rate were 2.7% (95% CI 0.7–6.0%) and 1.7% (95% CI 0.4–4.2%) respectively. Most adverse events were expected, short-lived, self-limited and manageable. The association between faecal microbiota transplantation therapy and adverse events such as inflammatory bowel disease flare, infectious disease and autoimmune disease was a concern but remained insignificant. Old age (≥65 years) was identified as a risk factor for after faecal microbiota transplantation therapy. Upper gastrointestinal administration also results in less frequent primary cure. Conclusions Faecal microbiota transplantation seems to be a highly effective and robust therapy for recurrent C. difficile infection. However, more quality studies, such as randomised controlled trials and cohort studies with control groups, are needed to confirm its long-term efficacy and safety.

Miravirsen dosing in chronic hepatitis C patients results in decreased microRNA‐122 levels without affecting other microRNAs in plasma

Abstract: Summary Background MicroRNA-122 (miR-122) is an important host factor for hepatitis C virus replication. Administration of miravirsen, an anti-miR-122 oligonucleotide, resulted in a dose dependent and prolonged decrease in HCV RNA levels in chronic hepatitis C patients. Aim To assess the plasma level of various miRNAs in patients dosed with miravirsen. Methods We included 16 of 36 chronic hepatitis C patients who received five injections of either 3 mg/kg (n = 4), 5 mg/kg (n = 4), 7 mg/kg (n = 4) miravirsen or placebo (n = 4) over a 4-week period in a double-blind, randomised phase 2a study. Plasma levels of 179 miRNAs were determined by qPCR and compared between patients dosed with miravirsen or placebo. Results Median plasma miR-122 level at baseline in patients receiving miravirsen was 3.9 × 103 compared to 1.3 × 104 copies/4 μL in placebo-dosed patients (P = 0.68). At week 1, 4, 6 and 10/12, patients dosed with miravirsen had respectively a median 72-fold, 174-fold, 1109-fold and 552-fold lower expression of miR-122 than at baseline (P = 0.001, as compared to patients receiving placebo). At week 4 of dosing, miRNA-profiling demonstrated a significant lower expression of miR-210 and miR-532-5p compared to baseline (3.0 and 4.7-fold lower respectively). However, subsequent longitudinal analysis showed no significant differences in miR-210 and miR-532-5p plasma levels throughout the study period. Conclusions We demonstrated a substantial and prolonged decrease in plasma miR-122 levels in patients dosed with miravirsen. Plasma levels of other miRNAs were not significantly affected by antagonising miR-122.

A comparison of the gut microbiome between long-term users and non-users of proton pump inhibitors.

Abstract: Summary Background Proton pump inhibitor (PPI) use is associated with an increased risk of Clostridium difficile infection (CDI), though the mechanism is unclear. PPI induced alterations to the gut microbiome may facilitate the emergence of CDI, though the effects of PPIs on gut microbiota are not well characterised. [Correction added on 10 March 2016, after first online publication: microflora has been changed to microbiota throughout the article.] Aim To compare the faecal microbiomes of long-term PPI users to those with no history of PPI use. Methods We used a population-based database to identify individuals with ≥5 years of continuous PPI use along with non-PPI using controls. Stool samples were subjected to microbiological analysis, with hierarchical clustering at genus level, along with alpha and beta diversity measures comparing the two groups. Metadata was accounted for using quantile regression to eliminate potential confounding variables in taxonomic abundance comparisons. Results Sixty-one subjects (32 PPI, 29 controls) were analysed. While no significant differences in alpha diversity were found between the PPI users and controls, a moderate shift of the PPI users away from the non-PPI user cluster in the beta diversity was observed. After controlling for pertinent confounders, we discovered a decrease in Bacteroidetes and an increase in Firmicutes at the phylum level. We also performed species classifications and found Holdemania filiformis and Pseudoflavonifractor capillosus to be increased and decreased in the PPI cohort, respectively. Conclusions Long-term PPIs use has an effect on the gut microbiome. The alteration in the ratio of Firmicutes to Bacteroidetes may pre-dispose to the development of CDI.

Systematic review with meta-analysis: the diagnostic accuracy of transient elastography for the staging of liver fibrosis in patients with chronic hepatitis B

Abstract: Summary Background Transient elastography is a non-invasive method for staging liver fibrosis. The meta-analysis using the hierarchical models to evaluate the diagnostic accuracy of transient elastography for the staging of liver fibrosis in patients with chronic hepatitis B was rarely reported. Aim A meta-analysis using the hierarchical models was performed to assess transient elastography for diagnosing and stage liver fibrosis in patients with chronic hepatitis B. Methods Electronic databases were searched and studies were identified to assess the diagnostic accuracy of transient elastography in CHB patients for staging fibrosis F ≥ 2, F ≥ 3 and F = 4 with liver biopsy as a reference standard. The hierarchical summary receiver operating characteristic curve and the bivariate models were performed to evaluate the diagnostic accuracy of transient elastography, and meta-regression analyses were performed to explore the heterogeneity. The quality Assessment of Diagnostic Accuracy Studies-2 tool was used to assess the quality of studies. Results Twenty-seven studies with a total of 4386 patients were included in the meta-analysis. The summary sensitivity of transient elastography for staging fibrosis F ≥ 2, F ≥ 3 and F = 4 was 0.806 (95% CI, 0.756–0.847), 0.819 (95% CI, 0.748–0.874) and 0.863 (95% CI, 0.818–0.898), respectively, and the summary specificity was 0.824 (95% CI, 0.761–0.873), 0.866 (95% CI, 0.824–0.899) and 0.875 (95% CI, 0.840–0.903), respectively. The corresponding area under the summary receiver operating characteristic curve was 0.88 (95% CI, 0.85–0.91), 0.91 (95% CI, 0.88–0.93) and 0.93 (95% CI, 0.91–0.95), respectively. Meta-regression showed that patient age contributed to heterogeneity. Conclusions Transient elastography performs well to diagnose liver fibrosis in patients with chronic hepatitis B, which may reduce the use of liver biopsy.

Excess risk of urinary tract cancers in patients receiving thiopurines for inflammatory bowel disease: a prospective observational cohort study.

Abstract: Background The risk of urinary tract cancers, including kidney and bladder cancers, was increased in transplant recipients receiving thiopurines. Aim To assess the risk of urinary tract cancers in patients with inflammatory bowel disease (IBD) receiving thiopurines in the CESAME observational cohort. Methods Between May 2004 and June 2005, 19 486 patients with IBD, 30.1% of whom were receiving thiopurines, were enrolled. Median follow-up was 35 months (IQR: 29-40). Results Ten and six patients developed respectively kidney and bladder cancer. The incidence rates of urinary tract cancer were 0.48/1000 patient-years in patients receiving thiopurines (95% CI: 0.21-0.95), 0.10/1000 patient-years in patients who discontinued thiopurines (95% CI: 0.00-0.56) and 0.30/1000 patient-years in patients never treated with thiopurines (95% CI: 0.12-0.62) at entry. The standardised incidence ratio of urinary tract cancer was 3.40 (95% CI: 1.47-6.71, P = 0.006) in patients receiving thiopurines, 0.64 (95% CI: 0.01-3.56, P = 0.92) in patients previously exposed to thiopurines and 1.17 (95% CI: 0.47-12.42, P = 0.78) in patients never treated with thiopurines. The multivariate-adjusted hazard ratio (HR) of urinary tract cancer between patients receiving thiopurines and those not receiving thiopurines was 2.82 (95% CI: 1.04-7.68, P = 0.04). Other significant risk factors were male gender (HR: 3.98, 95% CI: 1.12-14.10, P = 0.03) and increasing age (HR after 65 years (ref <50): 13.26, 95% CI: 3.52-50.03, P = 0.0001). Conclusion Patients with IBD receiving thiopurines have an increased risk of urinary tract cancers. Clinically relevant excess risk is observed in older men.

Serologic microbial associated markers can predict Crohn's disease behaviour years before disease diagnosis.

Abstract: SummaryBackground Patients with Crohn's disease (CD) have serologic responses to various microbial antigens. Serologic markers are associated with aggressive forms of disease and can be detected before onset of symptoms. Their utility in pre-clinical disease or prediction of complicated disease course before diagnosis is unclear. Aim To evaluate the pattern of serologic anti-microbial antibodies long prior to diagnosis and the subsequent risk of complicated Crohn's disease at diagnosis. Methods Sera from 100 US military personnel with Crohn's disease were obtained from the Department of Defense Serum Repository. For each patient, four samples were obtained at different time points before and around diagnosis, and were tested for 6 microbiota-directed antibodies (ASCA-IgA, ASCA-IgG, anti-OmpC, anti-CBir1, anti-A4-Fla2 and anti-FlaX). Associations between the presence and accumulation of Crohn's disease anti-microbial antibodies before diagnosis and with the later development of complications were evaluated. Results Overall, 65 patients were positive for at least one Crohn's disease associated anti-microbial antibody in the earliest available sample, at a median of 6 years before Crohn's disease diagnosis (interquartile range, 5.6–8.2). The number of positive anti-microbial antibodies increased up to the time of Crohn's disease diagnosis. Complicated disease developed around the time of diagnosis in 24 patients. The proportion of positive antimicrobial antibodies before diagnosis was higher in patients with complicated vs. noncomplicated Crohn's disease. There was an inverse relationship between the time to first complication and the magnitude of serologic response before diagnosis. Conclusion The presence and accumulation of circulating anti-microbial antibodies years before Crohn's disease diagnosis was associated with complicated Crohn's disease at or shortly after diagnosis.

The features of mucosa-associated microbiota in primary sclerosing cholangitis.

Abstract: Summary Background Little is known about the role of the microbiome in primary sclerosing cholangitis. Aim To explore the mucosa-associated microbiota in primary sclerosing cholangitis (PSC) patients across different locations in the gut, and to compare it with inflammatory bowel disease (IBD)-only patients and healthy controls. Methods Biopsies from the terminal ileum, right colon, and left colon were collected from patients and healthy controls undergoing colonoscopy. Microbiota profiling using bacterial 16S rRNA sequencing was performed on all biopsies. Results Forty-four patients were recruited: 20 with PSC (19 with PSC-IBD and one with PSC-only), 15 with IBD-only and nine healthy controls. The overall microbiome profile was similar throughout different locations in the gut. No differences in the global microbiome profile were found. However, we observed significant PSC-associated enrichment in Barnesiellaceae at the family level, and in Blautia and an unidentified Barnesiellaceae at the genus level. At the operational taxa unit level, most shifts in PSC were observed in Clostridiales and Bacteroidales orders, with approximately 86% of shifts occurring within the former order. Conclusions The overall microbiota profile was similar across multiple locations in the gut from the same individual regardless of disease status. In this study, the mucosa associated-microbiota of patients with primary sclerosing cholangitis was characterised by enrichment of Blautia and Barnesiellaceae and by major shifts in operational taxa units within Clostridiales order.

Randomised clinical trial: the efficacy of gut-directed hypnotherapy is similar to that of the low FODMAP diet for the treatment of irritable bowel syndrome.

Abstract: Summary Background A low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet is effective in treating irritable bowel syndrome (IBS). Aim To compare the effects of gut-directed hypnotherapy to the low FODMAP diet on gastrointestinal symptoms and psychological indices, and assess additive effects. Methods Irritable bowel syndrome patients were randomised (computer-generated list), to receive hypnotherapy, diet or a combination. Primary end-point: change in overall gastrointestinal symptoms across the three groups from baseline to week 6. Secondary end-points: changes in psychological indices, and the durability of effects over 6 months. Results Of 74 participants, 25 received hypnotherapy, 24 diet and 25 combination. There were no demographic differences at baseline across groups. Improvements in overall symptoms were observed from baseline to week 6 for hypnotherapy [mean difference (95% CI): −33 (−41 to −25)], diet [−30 (−42 to −19)] and combination [−36 (−45 to −27)] with no difference across groups (P = 0.67). This represented ≥20 mm improvement on visual analogue scale in 72%, 71% and 72%, respectively. This improvement relative to baseline symptoms was maintained 6 months post-treatment in 74%, 82% and 54%. Individual gastrointestinal symptoms similarly improved. Hypnotherapy resulted in superior improvements on psychological indices with mean change from baseline to 6 months in State Trait Personality Inventory trait anxiety of −4(95% CI −6 to −2) P < 0.0001; −1(−3 to 0.3) P = ns; and 0.3(−2 to 2) P = ns, and in trait depression of −3(−5 to −0.7) P = 0.011; −0.8(−2 to 0.2) P = ns; and 0.6(−2 to 3) P = ns, respectively. Groups improved similarly for QOL (all p ≤ 0.001). Conclusions Durable effects of gut-directed hypnotherapy are similar to those of the low FODMAP diet for relief of gastrointestinal symptoms. Hypnotherapy has superior efficacy to the diet on psychological indices. No additive effects were observed.

Systematic review with meta-analysis: the risk of mother-to-child transmission of hepatitis B virus infection in sub-Saharan Africa.

Abstract: SummaryBackground The risk of mother-to-child transmission of hepatitis B virus (HBV) has been quoted as 70–90% among women positive for hepatitis B surface antigen (HBsAg) and e antigen (HBeAg), and 5–30% among HBsAg-positive HBeAg-negative women. These risks are derived from Asia; little is known about sub-Saharan Africa. Aim To determine the risk of mother-to-child transmission in sub-Saharan Africa, according to maternal HBeAg and type of prophylaxis. Methods We searched Medline, Global Health, Embase, African Journals Online and African Index Medicus. We included observational or interventional studies that enrolled infants of HBV-infected women, and that tested for HBsAg or HBV DNA between 3 and 12 months of age. Results Fifteen articles from 11 African countries were included. Among HBeAg-positive women, the pooled risk was 38.3% (95% CI: 7.0–74.4%) without prophylaxis, which was significantly lower than the lower bound of 70–90% risk in the literature (P = 0.007). Among HBeAg-negative women, the pooled risk was 4.8% (95% CI: 0.1–13.3%) without prophylaxis, which lays within the lower range of the 5–30% risk in Asia. By extrapolating the pooled transmission risks to the number of births to infectious mothers, an estimated 1% of newborns (n = 367 250) are annually infected with HBV at birth in sub-Saharan Africa. Conclusions Compared to Asia, the risk of mother-to-child transmission is low in sub-Saharan Africa. However, the annual number of infants perinatally infected with HBV is twice the number of incident paediatric HIV infections in sub-Saharan Africa (n = 190 000). This highlights the importance of preventing mother-to-child transmission of HBV in sub-Saharan Africa, which has been long neglected.

Distal mean nocturnal baseline impedance on pH-impedance monitoring predicts reflux burden and symptomatic outcome in gastro-oesophageal reflux disease.

Abstract: SUMMARYBackground Mean nocturnal baseline impedance (MNBI), a novel pH-impedance metric, may be a surrogate marker of reflux burden. Aim To assess the predictive value of MNBI on symptomatic outcomes after anti-reflux therapy. Methods In this prospective observational cohort study, pH-impedance studies performed over a 5-year period were reviewed. Baseline impedance was extracted from six channels at three stable nocturnal 10-min time periods, and averaged to yield MNBI. Distal and proximal oesophageal MNBI values were calculated by averaging MNBI values at 3, 5, 7 and 9 cm, and 15 and 17 cm respectively. Symptomatic outcomes were measured as changes in global symptom severity (GSS, rated on 100-mm visual analogue scales) on prospective follow-up after medical or surgical anti-reflux therapy. Univariate and multivariate analyses assessed the predictive value of MNBI on symptomatic outcomes. Results Of 266 patients, 135 (50.8%) were tested off proton pump inhibitor (PPI) therapy and formed the study cohort (52.1 ± 1.1 years, 63.7% F). The 59 with elevated acid exposure time (AET) had lower composite and distal MNBI values than those with physiological AET (P < 0.0001), but similar proximal MNBI (P = 0.62). Linear AET negatively correlated with distal MNBI, both individually and collectively (Pearson's r = −0.5, P < 0.001), but not proximal MNBI (Pearson's r = 0, P = 0.72). After prospective follow-up (94 patients were followed up for 3.1 ± 0.2 years), univariate and multivariate regression models showed that distal MNBI, but not proximal MNBI, was independently predictive of linear GSS improvement. Conclusions Distal oesophageal MNBI negatively correlates with AET and, when assessed off PPI therapy, is independently predictive of symptomatic improvement following anti-reflux therapy.

Systematic review: outcomes and post-operative complications following colectomy for ulcerative colitis.

Abstract: SummaryBackground Colectomy for ulcerative colitis is associated with short- and long-term complications. Estimates of the frequency of such complications are variable and may have changed since the introduction of biological therapy. Understanding the true burden of surgical complications is important to clinicians in assessing risks and benefits of colectomy vs. continued medical therapy. Aim To ascertain the outcomes of colectomy and ileal pouch surgery in patients with ulcerative colitis in the biologics era. Methods Embase, MEDLINE and The Cochrane Library were searched for studies (2002–2015) reporting the outcomes of colorectal procedures (total and subtotal colectomy, IPAA with J-, S-, W-pouch) in adults with ulcerative colitis. Conferences proceedings (2011–2015) were hand-searched. Results We identified 28 studies (20,801 patients) reporting outcomes from procedures conducted from 2002–2015. Early complications (≤30 days post-operatively), reported in 10 studies, occurred in 9–65% of patients with ulcerative colitis; late complications (>30 days post-operatively) occurred in 17–55% of patients. Most frequent short-term complications: infectious complications and ileus (mean incidence 20% and 18%). Most frequent long-term complications: pouchitis, faecal incontinence and small bowel obstruction (mean incidence 29%, 21% and 17%). Rates of early infection and late pouch failure decreased from 22% and 13% in 2002–2009 to 11% and 2% in 2010–2015. The mean incidence of post-operative mortality was 1.0% across 11 studies. Conclusions Early and late complications arise in about one-third of patients undergoing surgery for ulcerative colitis. While colorectal surgical procedures are recommended for a specific group of patients, the post-operative complications associated with these procedures should not be underestimated.