Rupert Leong

Background  Patients with inflammatory bowel disease (IBD) who are corticosteroid-dependent or -refractory are at higher risk of developing disease- and treatment-related complications.Aims  To identify retrospectively clinical factors present at diagnosis that predict the occurrence of corticosteroid dependency and refractoriness in Crohn’s disease (CD) and ulcerative colitis (UC) patients.Methods  A total of 310 IBD patients (134 CD, 176 UC) were observed for 2140 person years and their use of systemic corticosteroids was determined. Outcomes of corticosteroid dependency and refractoriness were recorded. Univariate and multivariate analyses were performed to determine the clinical factors associated with outcomes.Results  Seventy-seven (57.5%) CD and 95 (54.0%) UC patients had received corticosteroids during study period. In CD, thrombocytosis [Hazard ratio (HR):3.0] predicted, whereas colonic CD (HR:0.3) negatively predicted corticosteroid dependency. Stricturing phenotype (HR:4.5) predicted corticosteroid-refractory CD. For UC, thrombocytosis (HR:3.9) and extensive colitis (HR:1.7) predicted corticosteroid dependency. Presence of anaemia (HR:10.8) at diagnosis and initial requirement of total parenteral nutrition (TPN) (HR:18.8) predicted corticosteroid-refractory UC. The cumulative risks of surgery were 17.8% and 5.4% for CD and UC patients respectively at 1 year after starting corticosteroids.Conclusions  Thrombocytosis at diagnosis predicted corticosteroid-dependency in IBD. Stricturing phenotype of CD and the presence of anaemia in UC predicted subsequent course of corticosteroid refractoriness.

Helicobacter species, which may colonize the biliary tract, have been implicated as a possible cause of hepatobiliary diseases ranging from chronic cholecystitis and primary sclerosing cholangitis to gall-bladder carcinoma and primary hepatic carcinomas.Research in this area has been limited by the lack of a gold standard in the diagnosis of these organisms in bile. Most published data to date have been based on molecular techniques that detect the DNA of Helicobacter species in bile, rather than evidence of viable organisms in bile.Helicobacter species have not been shown to induce histological injury to the biliary epithelium or liver parenchyma. The strongest association of the presence of these organisms in bile is with cholestatic conditions. This article reviews the literature on this newly developing field as it has evolved historically, taking pertinent methodological issues into account.

Severe cytopenias in patients with autoimmune conditions treated with azathioprine are well-recognized. Thiopurine methyltransferase (TPMT) enzymatic activity is subject to individual and ethnic variability. Patients with low TPMT activity (poor metabolizers) are at high risk of developing severe and potentially fatal haematopoietic toxicity. Studies have shown that essentially all TPMT-deficient patients will develop haematopoietic toxicity on administration of conventional thiopurine dosages (6-mercaptopurine, azathioprine). Therefore, screening for TPMT polymorphisms in patients before prescribing thiopurine drugs has been proposed. However, despite normal in vitro enzymatic activity, cytopenia may still occur in vivo. This is the case report of an Asian patient with Crohn disease harbouring a rare TPMT mutation on DNA sequencing, who developed neutropenic sepsis and anaemia after a flare of Crohn disease. The report illustrates the importance of monitoring for cytopenia in the setting of active inflammatory disease despite prior normal phenotyping, the role of predictive pharmacogenetics and the limitations of TPMT phenotype assays that may result in misclassification of at-risk patients.

Background: Crohn's disease affects people world-wide, but the incidence in Asia is lower than in Western countries. This difference may be due to genetic and/or environmental factors. Three single nucleotide polymorphisms (SNPs) of the NOD2/CARD15 gene have been identified to be independently associated with the development of Crohn's disease in Caucasians. Whether these SNPs are involved in the pathogenesis of Crohn's disease in the Chinese population is unknown.Aim: To determine if NOD2/CARD15 gene polymorphisms are found in Chinese patients with Crohn's disease.Methods: Sixty-five consecutive Chinese Crohn's disease patients had genotyping performed using sequence-specific PCR directed against the wild-type and the Arg702Trp, Gly908Arg and 3020insC variants of the NOD2/CARD15 gene. Controls consisted of 63 patients with ulcerative colitis and 70 patients with dyspepsia.Results: None of the patients with Crohn's disease had heterozygous or homozygous SNP variants. Similarly none of the ulcerative colitis or dyspeptic controls had these SNPs.Conclusion: The three previously described SNPs associated with the development of Crohn's disease in Caucasians are not found in Chinese patients with Crohn's disease.

AbstractBackground: Cytomegalovirus (CMV) following orthotopic liver transplantation can result in significant morbidity and mortality. Prophylaxis with oral aciclovir (ACV) or ganciclovir (GCV) for all transplant recipients (universal prophylaxis) may be beneficial, but which agent is more cost-effective is unknown.Methods: A single centre, retrospective study of all patients who had OLT at the Western Australian Liver Transplantation Service was performed. Patients received ACV from 1992 to 1998, and GCV from 1999 to 2001. A comparative cost-effectiveness analysis for the two groups was performed based on the mean total cost of the number of cases of CMV infection and disease as the clinical end-point.Results: The ACV group comprised of 55 patients and there were 24 in the GCV group. The incidence of CMV disease was 7% and 4% for the ACV and GCV groups, respectively (P > 0.05). For CMV infection it was 16% and 8%, respectively (P > 0.05). GCV prevented more cases of CMV infection and disease than ACV but at an incremental cost of $A20 000 ($US10 172) per case prevented. Overall, ACV was more cost-effective than GCV by $A2200 ($US1119) per person. The cost benefit of ACV was derived principally through a reduced pharmaceutical cost. Both agents were well tolerated without development of antiviral resistance.Conclusions: Universal prophylaxis of CMV infection ­following liver transplantation with aciclovir is more cost-effective than with ganciclovir. (Intern Med J 2004; 34: 410−415)

To develop and validate a clinical risk score predictive of risk for colorectal advanced neoplasia for Asia. A prospective, cross-sectional and multicentre study was carried out in tertiary hospitals in 11 Asian cities. The subjects comprise 2752 asymptomatic patients undergoing screening colonoscopy. From a development set of 860 asymptomatic subjects undergoing screening colonoscopy, multiple logistic regression was applied to identify significant risk factors for advanced colorectal neoplasia defined as invasive carcinoma or advanced adenoma. The ORs for significant risk factors were utilised to develop a risk score ranging from 0 to 7 (Asia-Pacific Colorectal Screening (APCS) score). Three tiers of risk were arbitrarily defined: 0-1 'average risk' (AR); 2-3 'moderate risk' (MR); and 4-7…

The incidence of ulcerative colitis (UC) in Asia is increasing but reports on its long-term course are few. We set out determine the incidence, prevalence, and survival rate of UC in the Chinese population and phenotypic stability by longitudinal follow-up. A cohort of Chinese UC patients were followed up in a tertiary referral center in Hong Kong between 1985 and 2006. Clinical data were prospectively collected since 2001. Population statistics were obtained from the Census and Statistics Department of Hong Kong for the calculation of age-specific incidence, prevalence, and survival. The disease phenotypes at diagnosis and upon follow-up were documented. A total of 172 patients (51.7% men) with a median age at diagnosis of 37.0 years (range: 12.0-85.0) were included. The cohort was observed for a total of 1,393 person-years with a median follow-up duration of 7.0 years (range: 0.5-22.0). The age-standardized incidence and prevalence rates of UC per 100,000 were 2.1 (95% confidence interval, CI: 1.1-3.7) and 26.5 (95% CI: 22.6-30.9), respectively, in 2006. The 10-year cumulative rate of proximal extension was 23.8%. Only one patient developed colorectal cancer during the observation period. The cumulative colectomy rates were 2.4% and 7.6% at 1 and 10 years of follow-up. Overall survival was similar to that expected (P=0.07). The incidence of UC has increased sixfold in the past two decades in Hong Kong. The complication, colorectal cancer, and colectomy rates are low in Chinese patients but increase with duration of illness.

Tacrolimus is a calcineurin inhibitor that suppresses pro-inflammatory cytokine production and T-cell activation. These immunosuppressant effects have been used to treat inflammatory bowel disease, especially fistulising Crohn's disease and refractory ulcerative colitis. The more predictable oral bioavailability and better side-effect profile makes tacrolimus a more favourable choice as compared with ciclosporin. Dose-dependent side effects, such as nephrotoxicity, are reported but are mostly reversible with dose reduction or cessation of therapy. Topical tacrolimus has also been used to treat pyoderma gangrenosum, an extra-intestinal manifestation of inflammatory bowel disease. Tacrolimus is well-tolerated and should be considered as an alternative agent in the treatment of inflammatory bowel disease, especially those intolerant or refractory to the more conventional immunomodulators.

The incidence of Crohn's disease (CD) and ulcerative colitis (UC) is increasing, but differentiating between them is often extremely difficult. Pancreatic (PAB) and goblet cell autoantibodies (GAB) are specific for CD and UC, respectively, but with low sensitivity. In combination with anti-Saccharomyces cerevisiae (ASCA) and anti-neutrophil cytoplasmic antibodies (pANCA) testing, these antibodies may improve differentiation between the diseases. This study determined the sensitivity, specificity, and positive and negative predictive values (PPV and NPV) of PAB and GAB +/- ASCA and pANCA testing in Chinese and Caucasian IBD populations. Patients were recruited from Caucasian and Chinese populations (CD, n = 100; UC, n = 99; controls, n = 100). PAB was highly specific for CD, and detection was greater in patients less than 35 years old and in Chinese compared with Caucasian patients with CD (CD, 46% versus 22%, P = 0.018; UC, 2% versus 6%; controls, 0% versus 2%). GAB detection was poor in all groups (<2%). PAB showed a PPV of 93% to differentiate all patients with CD from patients with UC, but only 62% for those with isolated colonic disease. The PPV of PAB increased to 100%, specificity was 100%, and sensitivity was 21% for isolated colonic disease when combined with pANCA and ASCA. PAB expression was not associated with stricturing or perforating CD. This study identified that GAB was not useful in our patients with IBD. PAB expression was highly specific for CD and more sensitive in Chinese than Caucasian patients with CD. The combination of PAB, pANCA, and ASCA testing improved the differentiation between UC and CD, particularly in isolated colonic disease, compared with pANCA and ASCA testing alone.

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Page 1. J Gastroenterol 2001; 36:731–739 Review Helicobacter pylori and nonsteroidal anti-inflammatory drugs. Approaching the end of the controversy in the new millennium, or room for more debate? Rupert WL Leong, Francis KL Chan, and Joseph JY Sung ...