M Karajeh

The role of high-magnification-chromoscopic colonoscopy in hereditary nonpolyposis colorectal cancer screening: a prospective "back-to-back" endoscopic study.

BACKGROUND:In hereditary nonpolyposis colorectal cancer flat and diminutive adenomas occur, particularly in the right colon. Such lesions may assume a high risk of malignant transformation. Interval cancers are known to occur in this group. Chromoscopic colonoscopy enhances detection in patients assuming a moderate to high lifetime risk of colorectal cancer.AIM:To prospectively assess the efficacy of high-magnification-chromoscopic colonoscopy for the detection of neoplastic lesions in patients undergoing hereditary nonpolyposis colorectal cancer screening.METHODS:Twenty-five asymptomatic patients fulfilling modified Amsterdam criteria underwent “back-to-back” colonoscopy. Conventional colonoscopy with targeted chromoscopy was performed initially followed by pan-colonic chromoscopic colonoscopy. Diagnostic extubation times and volumes of normal saline and indigo carmine (IC) were controlled.RESULTS:Using conventional colonoscopy and targeted chromoscopy 24 lesions were detected in 13 patients (20 exophytic/4 flat). Pan-colonic chromoscopy identified a further 52 lesions in 16 patients (17 exophytic/35 flat). Pan-chromoscopy identified significantly more adenomas than conventional colonoscopy (p = 0.001) and a significantly high number of flat adenomas (p = 0.004).CONCLUSIONS:Pan-colonic chromoscopic colonoscopy improves detection of significant neoplastic lesions in hereditary nonpolyposis colorectal cancer screening. Pan-chromoscopy may help better stratify colorectal cancer “risk” in this cohort and aid planning of surveillance colonoscopic follow-up.

Rectal aberrant crypt foci identified using high-magnification-chromoscopic colonoscopy: biomarkers for flat and depressed neoplasia.

BACKGROUND:Aberrant crypt foci may represent preneoplastic lesions in the human colon. The prevalence of aberrant crypt foci detected using magnification chromoscopic colonoscopy is known to follow a stepwise progression from normal subjects to those with exophytic adenomas and colon cancer. No studies have addressed the prevalence of rectal aberrant crypt foci in patients with flat and depressed colonic lesions that cluster within the right hemi-colon and may undergo de novo neoplastic transformation.METHODS:All patients underwent total colonoscopy by a single endoscopist using the Olympus CF240Z magnifying colonoscope. Flat and depressed lesions were diagnosed using targeted indigo carmine chromoscopy. Prior to extubation, pan high-magnification-chromoscopy using indigo carmine was applied to the rectum and the distal 10 cm of mucosa examined using forward and retroflexed views. Aberrant crypt foci were defined as two or more crypts with dilated or slit-like openings that were raised above the adjacent mucosa. Using high-magnification chromoscopic colonoscopy we assessed the prevalence and dysplastic features of aberrant crypt foci in three groups: endoscopically “normal” subjects, patients with flat/depressed adenoma, and flat/depressed cancer.RESULTS:Two thousand five hundred and fifty-nine patients underwent colonoscopy of which 1,000 were eligible for inclusion. The median number of aberrant crypt foci per patient in the endoscopically normal, adenoma, and cancer group was 1 (range: 0–5), 9 (range: 0–22), and 38 (range: 14–64), respectively. The estimated relative risk of dysplastic aberrant crypt foci when comparing the flat adenoma group with the endoscopically “normal” group was 4.68 (95% CI: 2.23–9.91) with the relative risk for flat cancer versus endoscopically normal group being 21.8 (95% CI: 10.9–23.8). Patients with >5 flat adenomas had higher crypt foci densities than those with <5 adenomas (r = 0.53; p < 0.001).CONCLUSIONS:The number of aberrant crypt foci in normal patients, patients with flat adenoma, and flat cancer follow a stepwise incremental change as previously observed for exophytic adenomas and cancer. Detection of aberrant crypt foci in the rectum may be a useful biomarker for proximal colonic flat neoplasia and could be used at index flexible sigmoidoscopic screening to stratify risk of proximal colonic neoplasia. Patients with dysplastic aberrant crypt foci of high density should receive total colonoscopy.

Long-Term Prognostic Significance of Persisting Histological Activity Despite Biochemical Remission in Autoimmune Hepatitis.

Objectives:Biochemical remission is widely considered a satisfactory treatment end point in autoimmune hepatitis (AIH). The significance of persisting histological activity despite biochemical remission is unknown. We aimed to assess the frequency and prognostic significance of persisting histological inflammation in patients with AIH who had achieved biochemical remission with treatment.Methods:We studied 120 patients (median age at diagnosis 57 years; 81% female) with AIH by International Criteria (59% definite), who received immunosuppressive treatment and underwent a follow-up liver biopsy after at least 6 months of sustained biochemical remission (defined as normal serum ALT and globulin).Results:Fifty-five patients (46%) had persisting histological activity (Ishak histological activity index (HAI) ≥4). These patients had higher serum ALT (24 vs. 18 IU/l, P=0.003) and AST (27 vs. 23 IU/l, P=0.03) at the time of follow-up biopsy, compared with patients who achieved histological remission (HAI ≤3). They had less frequent regression of fibrosis on follow-up biopsy compared with those achieving histological remission (32 vs. 60%, P=0.004) and had excess mortality (standardized mortality ratio 1.4 vs. 0.7, P<0.05). The excess mortality was due to liver disease. On multivariate analysis, persisting histological activity was independently associated with all-cause death/transplantation (HR 3.1 (95% CI 1.2–8.1); P=0.02); an association with liver-related death/transplantation fell short of significance (HR 9.7 (95% CI 0.84–111.6; P=0.07).CONCLUSIONS:Persisting histological activity, despite biochemical remission, is frequent in patients with treated AIH and is associated with lower rates of fibrosis regression and reduced long-term survival.

Refractory bleeding from portal hypertensive gastropathy: a further novel role for thalidomide therapy?

Bleeding from portal hypertensive gastropathy (PHG) can pose a therapeutic challenge. Thalidomide, which selectively inhibits tumour necrosis factor-alpha production by enhancing messenger RNA degradation, has been shown to reduce portal venous pressure in cirrhotic and non-cirrhotic portal hypertension. Thalidomide is also a potent inhibitor of angiogenesis. We describe a case of intractable bleeding from PHG secondary to extrahepatic portal vein obstruction due to malignancy, which was managed successfully by thalidomide, thus obviating the need for major surgery. Although the use of thalidomide for treatment of severe intestinal bleeding has been described previously, this is the first case report, to our knowledge, describing its efficacy in bleeding secondary to PHG. We discuss the possible therapeutic mechanisms for thalidomide in PHG

Change in awareness of gluten-related disorders among chefs and the general public in the UK: a 10-year follow-up study.

Background and objectives In view of the increasing popularity of a gluten-free diet, we sought to determine whether there has been a change in awareness of gluten-related disorders (GRD) among the general public and chefs. Materials and methods A face-to-face questionnaire on coeliac disease (CD) and gluten sensitivity (GS) was performed on the general public and chefs based in Sheffield, UK. The assessment was first carried out in 2003 and repeated in 2013. Results In total, 513 public members in 2003 (mean age 49.2 years, 62% women) were compared with 575 public members in 2013 (mean age 37.8 years, 57% women). There was a significant increase in the public’s awareness of GRD from the years 2003 to 2013, CD [44.2% to 74.4%, adjusted odds ratio (AOR) 3.9; 95% confidence interval (CI) 3.0–5.19] and GS (58.3% to 89%, AOR 7.1; 95% CI 5.0–9.98; P<0.001). Also, 322 chefs in 2003 (mean age 37.6 years, 15% women) were compared with 265 chefs in 2013 (mean age 27.1 years, 38% women). There was a significant increase in chefs’ awareness of GRD from the years 2003 to 2013, CD (17.1% to 78.1%, AOR 12.5; 95% CI 7.9–19.6) and GS (9.3% to 87.5%, AOR 65.7; 95% CI 35.4–122; P<0.001). Whereas in 2003 the public were significantly more aware of GRD than chefs, by 2013, this had reached a similar prevalence in both groups. In addition, the correct recognition of the gluten-free symbol was 44% for the public and 40% for chefs (P=0.28). Gluten-free products were sold by 41% of restaurants and 27% of takeaways (P=0.07). Conclusion There has been a marked increase in both the public’s and chefs’ awareness of GRD. Such findings may ease the social phobia that individuals with GRD have traditionally been accustomed to.

Khat (Catha Edulis) as a possible cause of autoimmune hepatitis.

AIM To investigate the potential role of khat in triggering auto immune hepatitis. METHODS Patients with a history of khat use and acute hepatitis were identified using the computer database in the hepatology department at the Royal Hallamshire Hospital. They were then assessed for probability of having autoimmune hepatitis using the revised autoimmune hepatitis scoring criteria. RESULTS Six patients were identified. All of them had presented with acute hepatitis on a background of khat. All were male and five of these patients were of Somali origin, while one patient was from Yemen. The patients were given points on the modified autoimmune hepatitis score which is based on their liver enzymes, autoimmune screen, exclusion of viral hepatitis alcohol and drugs, immunoglobulin levels and liver histology. The patients were given a score of -4 for khat use due to its potential to cause drug induced liver injury. Five of these patients scored between 10 and 15 points, placing them in the probable group for having autoimmune hepatitis. All of these patients were treated with prednisolone and demonstrated a good response to immunosuppression. CONCLUSION One possibile cause of hepatotoxicity with khat could be via triggering of autoimmune hepatitis in a genetically susceptible individual. Further studies are needed for confirmation.

Neurological sequelae of Crohn's disease: opportunity to study common etiological pathways.

To the Editor, Focal neurological sequelae complicating Crohn’s disease (CD) are rare. We describe only the second reported case of an isolated sixth nerve palsy preceding the clinical diagnosis of CD and provide a possible unifying hypothesis of etiology. A 27-year-old female smoker presented with a 12-day history of diplopia on right lateral gaze associated with retro-orbital pain. No other neurological symptoms were evident, and there was no history of diabetes mellitus, hypertension or recent trauma. Systemic inquiry revealed history of diarrhea and abdominal pain, with significant weight loss in the preceding 6 months. Neurological examination revealed isolated right sixth nerve palsy with incomplete and slow abduction of the right eye. There were no other neurological deficits and fundoscopy was normal. Abdominal and rectal digital examination was unremarkable. Full blood count showed a relative thrombocytosis of 535 ¥ 10/L (reference range: 130–400). The erythrocyte sedimentation rate and C-reactive protein were elevated at 55 mm/h and 75 mg/L, respectively. Renal profile, random blood glucose, liver function tests, serum B12 and red cell folate were all within normal ranges. Abdominal and pelvic ultrasound scan, a chest radiograph and cerebral magnetic resonance imaging (MRI) were unremarkable. Cerebrospinal fluid (CSF) examination was also normal with no oligoclonal bands isolated. Antinuclear antibody, rheumatoid factor, extractable nuclear antigens, double stranded DNA antibodies, antiphospholipid antibodies, antineutrophil cytoplasmic antibodies, thyroid antibodies, antigliadin and antiendomysial showed no significant titres. A negative Tensilon test and absent acetylcholine antibodies excluded the diagnosis of myasthenia gravis. Colonoscopy showed segmental pancolitis with patchy erythema and apthous ulceration, confirmed histologically as CD with granuloma formation (Fig. 1). A small bowel barium study was normal. Clinical and laboratory parameters improved after commencing a 5ASA compound (mesalazine 4 g daily). The sixth nerve palsy resolved completely within 7 weeks of initial presentation, and has not recurred to date. Increased platelet activation, leading to multifocal microinfarction in mesenteric vasculature, has been postulated by some authors to be the primary event in the pathogenesis of CD, although this is controversial. The pathogenesis of neurological complications is, however, largely unknown and probably multifactorial. Neurological sequelae may be coincidental, secondary to complicating mononeuritis multiplex, or drug induced. Most patients have active CD at presentation. Cranial nerve palsies associated with CD have been previously reported, in addition to ischemic optic neuropathy and sensori-neural deafness. The Melkersson–Rosenthal syndrome, characterized by recurrent

PTU-085 Decompensated Alcoholic Liver Disease (ALD): High Long-Term Mortality Despite Initial Survival

Introduction Whilst early management and outcome of decompensated ALD has been extensively studied, there are few published data on long-term outcome. We have previously (McFarlane, Gut 2006; 55:A2 and 55:A36) reported on early and 4-yr mortality in 249 patients (163 men, age (mean(range)) 50(27–77) yr) admitted consecutively to our unit between 1/4/1998 and 31/12/2005 with first presentation of decompensated ALD (Child grade B or C).Here we aimed to assess long-term mortality and its associations in this cohort. Methods We reviewed available hospital records, and death certificates and contacted surviving patients and general practitioners to assess who had died, the causes of death and the patients’ overall alcohol drinking behaviour subsequent to the index hospital episode (classified as: abstinent, continued drinking but reduced, and did not reduce). Results 37 patients died during the index hospital episode, all because of liver disease. The other 212 patients (including one transplanted during the index episode) were followed up for 4.3 (0.03–13.0) years. Only one other patient was transplanted. 154 patients have subsequently died. Cause of death is known in 134 (87%) and was due to liver disease in 95 (71%) of these. Only 4 patients died of hepatocellular carcinoma. Overall 5- and 10- year total mortality rates were 52+(SEM)4% and 75+3% respectively; corresponding rates from causes known to be liver related were 41+5% and 51+4%. Patients who were abstinent (n = 52) had lower total and known liver-related mortality (61+9% and 20+6% after 10 yr) compared to those who continued but reduced (n = 105; 73+5% p = 0.122 and 53+6% p = 0.013) and to those who did not reduce (n = 53; 91+4% p < 0.001 and 71+7% p < 0.001). In Cox regression analysis, both total and known liver-related mortality were independent of age, gender and severity of liver dysfunction at index presentation (Child, MELD, Glasgow and Maddrey scores) but were strongly associated with subsequent drinking behaviour (both p < 0.001) and inversely associated with serum albumin at discharge following index hospital episode (p = 0.001 and 0.019). Conclusion Patients with decompensated ALD who survive their first hospital episode have high long-term mortality, mainly due to liver disease, which is reduced but not prevented by abstinence. Disclosure of Interest None Declared

Treatment of autoimmune hepatitis: what is the optimal end point on follow-up biopsy?

Introduction The authors have reported1 that following immunosuppressive treatment of Autoimmune Hepatitis (AIH), many patients fail to achieve histological remission (necro-inflammatory score (NIS) ≥3), despite attaining biochemical remission (normal serum ALT). A recent report2 suggests that, following treatment, a NIS≥5 is not associated with fibrosis progression and hence, may be an acceptable treatment outcome.2 The authors therefore aimed to assess the associations of NIS on follow-up biopsy within the range 0–5, with change in fibrosis and survival. Methods The authors studied 114 patients with AIH by IAIHG criteria (81 definite, 94 female, mean age 48.7±1.7 years), treated initially with reducing dose prednisolone and 1 mg/kg azathioprine, who had achieved normal serum ALT and a NIS between 0 and 5 on follow-up biopsy (performed at median (range) 2.16 (0.65–13.67) years) after diagnosis (paired diagnostic and follow-up biopsies available in 93 patients). Biopsies were graded using the Ishak system. Results Fibrosis score between baseline and follow-up biopsy decreased in patients with follow-up NIS 0–3 (mean 3.4±0.24 to 2.7±0.21, n=59 p=0.001) but was unchanged in those with follow-up NIS of 4 or 5 (3.5±0.3 to 3.4±0.3, n=34 p=0.846). Fibrosis score on follow-up biopsy was higher in patients with NIS 4–5 (n=40) than with NIS 0–3 (n=72) (mean 3.3±0.3 vs 2.4±0.2, p=0.014). Regression of fibrosis was independently associated with lower NIS (p=0.014) and less portal inflammation (p=0.006) on follow-up biopsy, and with longer interval between the two biopsies (p=0.001). All cause death/transplantation rate was higher in those with NIS of 4–5 than in those with NIS 0–3 (18% vs 6% and 64% vs 24% after 10 and 20 years respectively; p<0.001) and this categorisation was independently associated with survival (p=0.001). A similar trend for liver death/transplantation just failed to reach significance (p=0.07). Conclusion In patients with AIH treated with immunosupression, even mild histological activity (NIS 4 or 5) on follow-up biopsy is associated with more fibrosis and with reduced survival and hence may not be an optimal end point of treatment.

PWE-122 Autoimmune hepatitis (aih): assessment of usefulness of diagnosic liver biopsy and of “simplified” diagnostic scoring system

Introduction Although recommended in published guidelines, only 62% of UK Gastroenterologists routinely recommend diagnostic liver biopsy in patients with suspected AIH (Dhaliwal Gut 2012:62). Also, the relative usefulness of the International AIH Group diagnostic criteria (full 1999 or simplified 2008) is not established. Our aim was to assess the relationships between histological and immunological diagnostic features and response to treatment in patients meeting the 1999 IAIHG criteria, which we also assessed against the 2008 simplified criteria. Method 90 patients were identified; 79% women, with median age 61 yrs (14–85) presenting since 2006 with suspected AIH and underwent diagnostic liver biopsy. Histology was assessed using the Ishak system by one liver Histopathologist (AKD) without reference to other results. Results Interface hepatitis was found in 87(97%) of biopsies, mainly plasma cell infiltrate in 74(83%), rosettes in 68(76%) and emperipolesis in 100% (of 48 patients assessed). Biliary changes were seen in 14% and mild steatosis in 24%. Prior to biopsy, patients had 13(7–19) diagnostic points by IAIHG criteria, with 11 of the 90 patients not having the required 10 points. Biopsy contributed an additional 5(0–6) points and all patients then met the 1999 IAIHG criteria (61 definite, 29 probable) with 17(12–22) points. In 49 patients, with a pre biopsy score of >13, biopsy contributed 4(0–5) points and was not needed for diagnosis of AIH but detected biliary changes in 10 patients (3 AMA -ve,1 weak +ve subsequently diagnosed as PBC and started on treatment, 2 PSC overlap and 4 not overlap) and also detected cirrhosis in 9. Histological features did not differ between: patients with (n = 68) and without (n = 22) serum autoantibodies (nuclear, smooth muscle or LKM-1); between those with (n = 72) and without (n = 10) raised serum IgG; or between treated patients who did (n = 75) and did not (n = 8) achieve normal serum ALT within 6 months. Eighteen patients (20%) did not meet the 2008 simplified diagnostic criteria for AIH (6 points). In these, necro-inflammatory score was 9(2–15), fibrosis score was 3(0–5) and 13 of 14 treated patients achieved normal serum ALT by 6 months. Conclusion Liver biopsy is important for diagnosis of AIH in those with lower, but less so in those with higher pre-biopsy IAIHG (1999) diagnostic scores. It may also detect cirrhosis or indicate additional unsuspected biliary disease. Histological features are not associated with immunological features or response to treatment. The 2008 simplified diagnostic criteria will “miss” 20% of patients with AIH by 1999 criteria. Most of these patients have significant disease and respond to treatment. Disclosure of interest None Declared.