Incidence and prevalence of inflammatory bowel disease in Devon, UK.

BACKGROUND AND AIMS: We sought to define temporal changes in prevalence of inflammatory bowel disease (IBD) in East Devon, UK, in order to facilitate service planning over the next 5 years. METHODS: Multiple primary and secondary care databases were used to identify and verify cases. Point prevalence and incidence of IBD were reported in April 2017 and from 2008 to 2016, respectively. Future prevalence and healthcare activity requirements were estimated by linear regression. RESULTS: Prevalence of ulcerative colitis (UC), Crohn's disease (CD) and inflammatory bowel disease unclassified (IBDU) were 479.72, 265.94 and 35.34 per 100 000 persons, respectively. In 2016, the incidence rates of UC, CD and IBDU were 15.4, 10.7 and 1.4 per 100 000 persons per year, respectively. There were no significant changes in the incidence of CD (p=0.49, R=0.26) or UC (p=0.80, R=0.10). IBD prevalence has increased by 39.9% (95% CI 28.2 to 53.7) in the last 10 years without differences in the rate of change between UC and CD. Overall, 27% of patients were managed in primary care, a quarter of whom were eligible but not receiving endoscopic surveillance. Outpatient clinics, MRI and biologic use, but not helpline calls, admissions, or surgeries increased over and above the change in IBD prevalence. CONCLUSIONS: We report one of the highest prevalence and incidence rates of IBD from Northern Europe. Overall, IBD incidence is static, but prevalence is increasing. We estimate that 1% of our population will live with IBD between 2025 and 2030.

Root-cause analyses of missed opportunities for the diagnosis of colorectal cancer in patients with inflammatory bowel disease.

BACKGROUND: Colonoscopic surveillance in patients with inflammatory bowel disease (IBD) leads to earlier detection of colorectal cancer (CRC) and reduces CRC-associated mortality. However, it is limited by poor adherence in practice. AIM: To identify missed opportunities to detect IBD-associated CRC at our hospital METHODS: We undertook root-cause analyses to identify patients with missed opportunities to diagnose IBD-associated CRC. We matched patients with IBD-associated CRC to patients with CRC in the general population to identify differences in staging at diagnosis and clinical outcomes. RESULTS: Compared with the general population, patients with IBD were at increased risk of developing CRC (odds ratio 2.7 [95% CI 1.6-3.9], P < 0.001). The mean incidence of IBD-associated CRC between 1998 and 2019 was 165.4 (IQR 130.4-199.4) per 100 000 patients and has not changed over the last 20 years. Seventy-eight patients had IBD-associated CRC. Forty-two (54%) patients were eligible for CRC surveillance: 12% (5/42) and 10% (4/42) patients were diagnosed with CRC at an appropriately timed or overdue surveillance colonoscopy, respectively. Interval cancers occurred in 14% (6/42) of patients; 64% (27/42) of patients had a missed opportunity for colonoscopic surveillance where root-cause analyses demonstrated that 10/27 (37%) patients known to secondary care had not been offered surveillance. Four (15%) patients had a delayed diagnosis of CRC due to failure to account for previous colonoscopic findings. Seventeen (63%) patients were managed by primary care including seven patients discharged from secondary care without a surveillance plan. Matched case-control analysis did not show significant differences in cancer staging or 10-year survival outcomes. CONCLUSION: The incidence of IBD-associated CRC has remained static. Two-thirds of patients eligible for colonoscopic surveillance had missed opportunities to diagnose CRC. Surveillance programmes without comprehensive and fully integrated recall systems across primary and secondary care are set to fail.

Clinical Features and Genetic Risk of Demyelination Following Anti-TNF Treatment.

BACKGROUND: Anti-TNF exposure has been linked to demyelination events. We sought to describe the clinical features of demyelination events following anti-TNF treatment and to test whether affected patients were genetically predisposed to multiple sclerosis [MS]. METHODS: We conducted a case-control study to describe the clinical features of demyelination events following anti-TNF exposure. We compared genetic risk scores [GRS], calculated using carriage of 43 susceptibility loci for MS, in 48 cases with 1219 patients exposed to anti-TNF who did not develop demyelination. RESULTS: Overall, 39 [74%] cases were female. The median age [range] of patients at time of demyelination was 41.5 years [20.7-63.2]. The median duration of anti-TNF treatment was 21.3 months [0.5-99.4] and 19 [36%] patients were receiving concomitant immunomodulators. Most patients had central demyelination affecting the brain, spinal cord, or both. Complete recovery was reported in 12 [23%] patients after a median time of 6.8 months [0.1-28.7]. After 33.0 months of follow-up, partial recovery was observed in 29 [55%] patients, relapsing and remitting episodes in nine [17%], progressive symptoms in three [6%]: two [4%] patients were diagnosed with MS. There was no significant difference between MS GRS scores in cases (mean -3.5 × 10-4, standard deviation [SD] 0.0039) and controls [mean -1.1 × 10-3, SD 0.0042] [p = 0.23]. CONCLUSIONS: Patients who experienced demyelination events following anti-TNF exposure were more likely female, less frequently treated with an immunomodulator, and had a similar genetic risk to anti-TNF exposed controls who did not experience demyelination events. Large prospective studies with pre-treatment neuroimaging are required to identify genetic susceptibility loci.

Quality improvement project identifies factors associated with delay in IBD diagnosis.

BACKGROUND: Delay in the diagnosis of inflammatory bowel disease (IBD) is common and contemporary UK studies are lacking. AIM: To determine factors associated with, and the consequences of, a prolonged time to diagnosis in IBD. METHODS: This quality improvement study included 304 adults with a new IBD diagnosis made between January 2014 and December 2017 across 49 general practices (GP) and gastroenterology secondary care services. Outcome measures were demographic, clinical and laboratory factors associated with a delayed time, defined as greater than upper quartile, to: (a) patient presentation (b) GP referral (c) secondary care diagnosis, and factors associated with a complicated disease course (hospitalisation and/or surgery and/or biologic treatment) in the year after diagnosis. RESULTS: The median [IQR] diagnosis sub-intervals were: (a) patient = 2.1 months [0.9-5.1]; (b) GP = 0.3 months [0.0-0.9]; (c) secondary care = 1.1 months [0.5-2.1]. 50% of patients were diagnosed within 4 months and 92% were diagnosed within 2 years of symptom onset. Diagnostic delay was more common in Crohn's disease (7.6 months [3.1-15.0]) than ulcerative colitis (3.3 months [1.9-7.3]) (P < 0.001). Patients who presented as an emergency (P < 0.001) but not those with a delayed overall time to diagnosis (P = 0.35) were more likely to have a complicated disease course. CONCLUSION: Time to patient presentation is the largest component of time to IBD diagnosis. Emergency presentation is common and, unlike a delayed time to diagnosis, is associated with a complicated disease course.

Primary care faecal calprotectin testing in children with suspected inflammatory bowel disease: a diagnostic accuracy study.

OBJECTIVE: To determine the diagnostic accuracy of calprotectin to diagnose inflammatory bowel disease (IBD) in children in whom general practitioners (GPs) suspected IBD. DESIGN: Prospective observational cohort study of a new calprotectin-based primary care referral pathway. SETTING: 48 GP practices and gastroenterology secondary care services at the Royal Devon and Exeter NHS Foundation Trust in the South-West of England, UK. PATIENTS: 195 children aged between 4 and 18 years referred on the pathway between January 2014 and August 2017 for investigation of gastrointestinal symptoms were included. INTERVENTIONS: Primary-care-driven faecal calprotectin testing. Primary and secondary care records over 12 months from the point of calprotectin testing were used as the reference standard. MAIN OUTCOME MEASURES: Diagnostic accuracy of calprotectin testing to detect IBD. RESULTS: 7% (13/195) tested patients were diagnosed with IBD. Using our prespecified cut-off of 100 µg/g, calprotectin had a diagnostic accuracy of 91% (95% CI 86% to 95%) with a sensitivity for distinguishing IBD from non-IBD of 100% (95% CI 75% to 100%), a specificity of 91% (95% CI 85% to 94%), a positive predictive value of 43% (95% CI 25% to 63%) and a negative predictive value of 100% (95% CI 98% to 100%). Calprotectin testing had no effect on the time to diagnosis, but a negative test contributed to saved referrals and was associated with fewer diagnostic tests in secondary care. CONCLUSIONS: Calprotectin testing of children with suspected IBD in primary care accurately distinguishes IBD from a functional gut disorder, reduces secondary care referrals and associated diagnostic healthcare utilisation.

Review article: prevention, diagnosis and management of COVID-19 in the IBD patient.

BACKGROUND: The current COVID-19 pandemic, caused by SARS-CoV-2, has emerged as a public health emergency. All nations are seriously challenged as the virus spreads rapidly across the globe with no regard for borders. The primary management of IBD involves treating uncontrolled inflammation with most patients requiring immune-based therapies. However, these therapies may weaken the immune system and potentially place IBD patients at increased risk of infections and infectious complications including those from COVID-19. AIM: To summarise the scale of the COVID-19 pandemic, review unique concerns regarding IBD management and infection risk during the pandemic and assess COVID-19 management options and drug interactions in the IBD population. METHODS: A literature review on IBD, SARS-CoV-2 and COVID-19 was undertaken and relevant literature was summarised and critically examined. RESULTS: IBD patients do not appear to be more susceptible to SARS-CoV-2 infection and there is no evidence of an association between IBD therapies and increased risk of COVID-19. IBD medication adherence should be encouraged to prevent disease flare but where possible high-dose systemic corticosteroids should be avoided. Patients should exercise social distancing, optimise co-morbidities and be up to date with influenza and pneumococcal vaccines. If a patient develops COVID-19, immune suppressing medications should be withheld until infection resolution and if trial medications for COVID-19 are being considered, potential drug interactions should be checked. CONCLUSIONS: IBD patient management presents a challenge in the current COVID-19 pandemic. The primary focus should remain on keeping bowel inflammation controlled and encouraging medication adherence.

Factors associated with depression in people with inflammatory bowel disease: The relationship between active disease and biases in neurocognitive processing.

BACKGROUND: Depression is common among people with inflammatory bowel disease (IBD), though the causes remain unclear. We conducted a cross-sectional study to investigate the role of emotional processing biases in contributing to depression among people with IBD. MATERIALS AND METHODS: One hundred and twenty outpatients with IBD were recruited and: (a) completed questionnaires to record: age, sex, social support, socioeconomic status, anxiety and depression (n = 104), (b) underwent assessments of biases in emotional recognition (n = 112), emotional memory and reinforcement learning (c) had recorded from clinical records: type of IBD, duration of IBD, IBD activity and (d) provided blood for high-sensitivity C-reactive protein levels (n = 99). KEY RESULTS: Sixty-eight participants had Crohn's disease and 49 had ulcerative colitis. Of these, 35 had active disease and 26 had depression. Those with depression were more likely to be female, lack social support, have active disease, be taking corticosteroids but not TNF-alpha inhibitors and exhibit less positive emotional recognition bias. On multivariable regression analysis, depression was associated independently with lack of social support (unstandardized regression coefficient (B) = -1.40, P = 0.02) and increased disease activity (B = 1.29, P = 0.03). Causal steps analysis was consistent with less positive emotional recognition bias partially mediating the effects of disease activity on depression. CONCLUSIONS AND INFERENCES: This is the first study to demonstrate links between disease activity and less positive biases in emotional recognition that could explain higher rates of depression among people with active IBD. Future prospective studies are required to confirm the effects of emotional processing biases in depression and allow stronger causal inferences to be drawn.

Predictors of anti-TNF treatment failure in anti-TNF-naive patients with active luminal Crohn's disease: a prospective, multicentre, cohort study.

BACKGROUND: Anti-TNF drugs are effective treatments for the management of Crohn's disease but treatment failure is common. We aimed to identify clinical and pharmacokinetic factors that predict primary non-response at week 14 after starting treatment, non-remission at week 54, and adverse events leading to drug withdrawal. METHODS: The personalised anti-TNF therapy in Crohn's disease study (PANTS) is a prospective observational UK-wide study. We enrolled anti-TNF-naive patients (aged ≥6 years) with active luminal Crohn's disease at the time of first exposure to infliximab or adalimumab between March 7, 2013, and July 15, 2016. Patients were evaluated for 12 months or until drug withdrawal. Demographic data, smoking status, age at diagnosis, disease duration, location, and behaviour, previous medical and drug history, and previous Crohn's disease-related surgeries were recorded at baseline. At every visit, disease activity score, weight, therapy, and adverse events were recorded; drug and total anti-drug antibody concentrations were also measured. Treatment failure endpoints were primary non-response at week 14, non-remission at week 54, and adverse events leading to drug withdrawal. We used regression analyses to identify which factors were associated with treatment failure. FINDINGS: We enrolled 955 patients treated with infliximab (753 with originator; 202 with biosimilar) and 655 treated with adalimumab. Primary non-response occurred in 295 (23·8%, 95% CI 21·4-26·2) of 1241 patients who were assessable at week 14. Non-remission at week 54 occurred in 764 (63·1%, 60·3-65·8) of 1211 patients who were assessable, and adverse events curtailed treatment in 126 (7·8%, 6·6-9·2) of 1610 patients. In multivariable analysis, the only factor independently associated with primary non-response was low drug concentration at week 14 (infliximab: odds ratio 0·35 [95% CI 0·20-0·62], p=0·00038; adalimumab: 0·13 [0·06-0·28], p<0·0001); the optimal week 14 drug concentrations associated with remission at both week 14 and week 54 were 7 mg/L for infliximab and 12 mg/L for adalimumab. Continuing standard dosing regimens after primary non-response was rarely helpful; only 14 (12·4% [95% CI 6·9-19·9]) of 113 patients entered remission by week 54. Similarly, week 14 drug concentration was also independently associated with non-remission at week 54 (0·29 [0·16-0·52] for infliximab; 0·03 [0·01-0·12] for adalimumab; p<0·0001 for both). The proportion of patients who developed anti-drug antibodies (immunogenicity) was 62·8% (95% CI 59·0-66·3) for infliximab and 28·5% (24·0-32·7) for adalimumab. For both drugs, suboptimal week 14 drug concentrations predicted immunogenicity, and the development of anti-drug antibodies predicted subsequent low drug concentrations. Combination immunomodulator (thiopurine or methotrexate) therapy mitigated the risk of developing anti-drug antibodies (hazard ratio 0·39 [95% CI 0·32-0·46] for infliximab; 0·44 [0·31-0·64] for adalimumab; p<0·0001 for both). For infliximab, multivariable analysis of immunododulator use, and week 14 drug and anti-drug antibody concentrations showed an independent effect of immunomodulator use on week 54 non-remission (odds ratio 0·56 [95% CI 0·38-0·83], p=0·004). INTERPRETATION: Anti-TNF treatment failure is common and is predicted by low drug concentrations, mediated in part by immunogenicity. Clinical trials are required to investigate whether personalised induction regimens and treatment-to-target dose intensification improve outcomes. FUNDING: Guts UK, Crohn's and Colitis UK, Cure Crohn's Colitis, AbbVie, Merck Sharp and Dohme, Napp Pharmaceuticals, Pfizer, and Celltrion.

Association of Genetic Variants in NUDT15 With Thiopurine-Induced Myelosuppression in Patients With Inflammatory Bowel Disease.

Importance: Use of thiopurines may be limited by myelosuppression. TPMT pharmacogenetic testing identifies only 25% of at-risk patients of European ancestry. Among patients of East Asian ancestry, NUDT15 variants are associated with thiopurine-induced myelosuppression (TIM). Objective: To identify genetic variants associated with TIM among patients of European ancestry with inflammatory bowel disease (IBD). Design, Setting, and Participants: Case-control study of 491 patients affected by TIM and 679 thiopurine-tolerant unaffected patients who were recruited from 89 international sites between March 2012 and November 2015. Genome-wide association studies (GWAS) and exome-wide association studies (EWAS) were conducted in patients of European ancestry. The replication cohort comprised 73 patients affected by TIM and 840 thiopurine-tolerant unaffected patients. Exposures: Genetic variants associated with TIM. Main Outcomes and Measures: Thiopurine-induced myelosuppression, defined as a decline in absolute white blood cell count to 2.5 × 109/L or less or a decline in absolute neutrophil cell count to 1.0 × 109/L or less leading to a dose reduction or drug withdrawal. Results: Among 1077 patients (398 affected and 679 unaffected; median age at IBD diagnosis, 31.0 years [interquartile range, 21.2 to 44.1 years]; 540 [50%] women; 602 [56%] diagnosed as having Crohn disease), 919 (311 affected and 608 unaffected) were included in the GWAS analysis and 961 (328 affected and 633 unaffected) in the EWAS analysis. The GWAS analysis confirmed association of TPMT (chromosome 6, rs11969064) with TIM (30.5% [95/311] affected vs 16.4% [100/608] unaffected patients; odds ratio [OR], 2.3 [95% CI, 1.7 to 3.1], P = 5.2 × 10-9). The EWAS analysis demonstrated an association with an in-frame deletion in NUDT15 (chromosome 13, rs746071566) and TIM (5.8% [19/328] affected vs 0.2% [1/633] unaffected patients; OR, 38.2 [95% CI, 5.1 to 286.1], P = 1.3 × 10-8), which was replicated in a different cohort (2.7% [2/73] affected vs 0.2% [2/840] unaffected patients; OR, 11.8 [95% CI, 1.6 to 85.0], P = .03). Carriage of any of 3 coding NUDT15 variants was associated with an increased risk (OR, 27.3 [95% CI, 9.3 to 116.7], P = 1.1 × 10-7) of TIM, independent of TPMT genotype and thiopurine dose. Conclusions and Relevance: Among patients of European ancestry with IBD, variants in NUDT15 were associated with increased risk of TIM. These findings suggest that NUDT15 genotyping may be considered prior to initiation of thiopurine therapy; however, further study including additional validation in independent cohorts is required.

Reversal of end-stage heart failure in juvenile hemochromatosis with iron chelation therapy: a case report.

BACKGROUND: Juvenile hemochromatosis is the most severe form of iron overloading phenotype. Although rare, it should be suspected in patients who present with hypogonadotropic hypogonadism, diabetes mellitus, or cardiomyopathy without a clear cause. CASE PRESENTATION: A young Serbian male presenting with end-stage heart failure was referred for extracorporeal membrane oxygenation. An endomyocardial biopsy revealed cytoplasmic iron deposits in myocytes. His condition was stabilized with biventricular assist devices and he was listed for heart transplantation. Iron chelation therapy was commenced and resulted in rapid removal of iron burden. Serial outpatient echocardiograms demonstrated myocardial recovery such that a successful biventricular assist device explant occurred 131 days after initial implant. Targeted gene sequencing revealed a loss-of-function mutation within the HJV gene, which is consistent with juvenile hemochromatosis. CONCLUSIONS: This rare case of a patient with juvenile hemochromatosis associated with a HJV mutation provides histologic evidence documenting the reversal of associated end-stage heart failure, requiring emergent mechanical circulatory support, with iron chelation therapy.

Could Adherence to Quality of Care Indicators for Hospitalized Patients With Cirrhosis-Related Ascites Improve Clinical Outcomes?

OBJECTIVES: The diagnosis of cirrhotic ascites is associated with significant morbidity, mortality, and reduced health-related quality of life. Adherence by health professionals to quality indicators (QIs) of care for ascites is low. We evaluated the effect of adherence to ascites QIs on clinical outcomes for patients hospitalized with new onset cirrhotic ascites. METHODS: The medical records of 302 patients admitted with new onset cirrhotic ascites were interrogated for demographic and clinical data and adherence to eight Delphi panel-derived QIs for ascites management. Associations between adherence to each QI and 30-day emergent readmission and 90-day mortality were analyzed. RESULTS: The majority of patients were males (68.9%) over 50 years of age (mean 57±12.83 years) with alcohol-related cirrhosis (59%). Twenty-nine percent were readmitted within 30 days. Patients who received an abdominal paracentesis within 30 days of ascites diagnosis (QI 1, relative risk (RR) 0.41, P=0.004) or during index hospitalization (QI 2, RR 0.57, P=0.006) were significantly less likely to experience a 30-day emergent readmission. Baseline serum bilirubin >2.5 mg/dl was associated with increased 30-day cirrhosis-related readmission (RR 1.51, P=0.03). A total of 18.5% of patients died within 90 days of index admission; median interval to death was 139 days (37-562 days). Pneumonia was the most frequent cause of death. Independent predictors of 90-day mortality included older age (odds ratio (OR) 1.03, P=0.03), increased Model for End-stage Liver Disease (MELD)-Na score (OR 1.06, P=0.05), primary SBP prophylaxis (QI 7, OR 2.30, P=0.04), and readmission within 30 days (OR 30.26, P<0.001). Discharge prescription of diuretics (QI 8, OR 0.28, P=0.01) was associated with reduced 90-day mortality. CONCLUSIONS: Early paracentesis in patients with new onset cirrhotic ascites lowers 30-day readmission rates, and early initiation of diuretic therapy lowers 90-day mortality.

Prevalence of eosinophilic oesophagitis in adults presenting with oesophageal food bolus obstruction.

AIM: To look at the relationship between eosinophilic oesophagitis (EO) and food bolus impaction in adults. METHODS: We retrospectively analysed medical records of 100 consecutive patients who presented to our hospital with oesophageal food bolus obstruction (FBO) between 2012 and 2014. In this cohort, 96 were adults (64% male), and 4 paediatric patients were excluded from the analysis as our centre did not have paediatric gastroenterologists. Eighty-five adult patients underwent emergency gastroscopy. The food bolus was either advanced into the stomach using the push technique or retrieved using a standard retrieval net. Biopsies were obtained in 51 patients from the proximal and distal parts of the oesophagus at initial gastroscopy. All biopsy specimens were assessed and reviewed by dedicated gastrointestinal pathologists at the Department of Pathology, University Hospital Geelong. The diagnosis of EO was defined and established by the presence of the following histological features: (1) peak eosinophil counts > 20/hpf; (2) eosinophil microabscess; (3) superficial layering of eosinophils; (4) extracellular eosinophil granules; (5) basal cell hyperplasia; (6) dilated intercellular spaces; and (7) subepithelial or lamina propria fibrosis. The histology results of the biopsy specimens were accessed from the pathology database of the hospital and recorded for analysis. RESULTS: Our cohort had a median age of 60. Seventeen/51 (33%) patients had evidence of EO on biopsy findings. The majority of patients with EO were male (71%). Classical endoscopic features of oesophageal rings, furrows or white plaques and exudates were found in 59% of patients with EO. Previous episodes of FBO were present in 12/17 patients and 41% had a history of eczema, hay fever or asthma. Reflux oesophagitis and benign strictures were found in 20/34 patients who did not have biopsies. CONCLUSION: EO is present in approximately one third of patients who are admitted with FBO. Biopsies should be performed routinely at index endoscopy in order to pursue this treatable cause of long term morbidity.

Prospective population-based cohort of inflammatory bowel disease in the biologics era: Disease course and predictors of severity.

BACKGROUND AND AIM: We have previously found high incidence of inflammatory bowel disease (IBD) in Australia. A population-based registry was established to assess disease severity, frequency of complications, and prognostic factors. METHODS: Incident cases were prospectively identified over 4 years. Early disease severity was assessed according to need for hospitalization and resective surgery and medication use. RESULTS: We report on the early outcomes (median 18 months, range 12-60 months) for 252 patients comprising 146 with Crohn's disease (CD), 96 with ulcerative colitis (UC), and 10 IBD undifferentiated. Eighty-seven percent of CD patients had inflammatory disease at diagnosis, and this reduced to 73% at 5 years (n = 38). Immunomodulators were prescribed in 57% of CD patients and 19% with UC. A third of all CD patients were hospitalized, the majority (77%) in the first 12 months. Risk factors for hospitalization included penetrating, perianal, and ileocolonic disease (P < 0.05). Twenty-four percent of UC patients were hospitalized, most within the first 12 months. Intestinal resection rates were 13% at 1 year in CD and 26% at 5 years. Risk factors include penetrating and stricturing disease (P < 0.001) and ileal involvement (P < 0.05). Colectomy rates in UC were 2% and 13% at 1 and 5 years. High C-reactive protein (CRP) at diagnosis was associated with colectomy. CONCLUSIONS: A high rate of inflammatory disease, frequent immunomodulator use in CD, and a low rate of surgery in both CD and UC were identified. In CD, ileal involvement and complex disease behavior are associated with a more severe disease course, while in UC a high CRP predicted this outcome.

Abdominal pain post endoscopic mucosal resection: Treat the patient not the CT scan.

An 85-year-old female, with hereditary nonpolyposis colorectal cancer syndrome, underwent a colonoscopy and endoscopic mucosal resection (EMR) of a 25-mm proximal ascending colon polyp (Paris classification 0-Is). Post-procedure, the patient developed abdominal pain in the right iliac fossa which settled 1 h later. An urgent computed tomography (CT) scan of her abdomen was organised which happened 6 h post onset of abdominal pain. She had radiological evidence of perforation on the CT scan but clinically remained well and was managed conservatively. The exact aetiology of this patient's symptoms is not known. We suspect the radiological findings are probably due to a combination of injectate within the colonic wall and leakage of insufflated air or CO2 following transmural passage of the EMR needle. As EMR is becoming an increasingly effective treatment modality in the management of large sessile polyps, clinicians need to be aware of potential complications of treatment. It is also important to recognise that radiological features of perforation can be seen post EMR in the absence of an EMR associated perforation.

IL28B genotype is not useful for predicting treatment outcome in Asian chronic hepatitis B patients treated with pegylated interferon-α.

BACKGROUND AND AIM: IL28B genotype predicts response to pegylated interferon (peg-IFN)-based therapy in chronic hepatitis C. However, the utility of IL28B genotyping in chronic hepatitis B (CHB) cohorts treated with peg-IFN is unclear. It was investigated whether IL28B genotype is associated with peg-IFN treatment outcomes in a predominantly Asian CHB cohort. METHODS: This was a retrospective analysis of CHB patients treated with 48 weeks of peg-IFN monotherapy. IL28B genotype (rs12979860) was determined (TaqMan allelic discrimination kit). Baseline hepatitis B virus (HBV)-DNA, alanine aminotransferase, and liver histology were available. The primary end-points were HBV e antigen (HBeAg) seroconversion with HBV-DNA < 2000 IU/mL 24 weeks post-therapy (HBeAg-positive patients) and HBV-DNA < 2000 IU/mL 24 weeks after peg-IFN (HBeAg-negative patients). The association between IL28B genotype and peg-IFN outcomes was analyzed. RESULTS: IL28B genotype was determined for 96 patients. Eighty-eight percent were Asian, 62% were HBeAg positive, and 13% were METAVIR stage F3-4. Median follow-up time was 39.3 months. The majority of patients carried the CC IL28B genotype (84%). IL28B genotype did not differ according to HBeAg status. The primary end-points were achieved in 27% of HBeAg-positive and 61% of HBeAg-negative patients. There was no association between IL28B genotype and the primary end-point in either group. Furthermore, there was no difference in HBeAg loss alone, HBV surface antigen, alanine aminotransferase normalization, or on-treatment HBV-DNA levels according to IL28B genotype. CONCLUSIONS: In the context of a small possible effect size and high frequency in Asian populations, IL28B genotyping is likely to have, at best, limited clinical utility for predicting peg-IFN treatment outcome for CHB patients in the Asia-Pacific region.