Best practices on immunomodulators and biologic agents for ulcerative colitis and Crohn's disease in Asia

The Asia-Pacific Working Group on inflammatory bowel disease (IBD) was established in Cebu, Philippines, under the auspices of the Asian Pacific Association of Gastroenterology with the goal of improving IBD care in Asia. This consensus is carried out in collaboration with Asian Organization for Crohn's and Colitis. With biologic agents and biosimilars becoming more established, it is necessary to conduct a review on existing literature and establish a consensus on when and how to introduce biologic agents and biosimilars in the conjunction with conventional treatments for ulcerative colitis (UC) and Crohn's disease (CD) in Asia. These statements also address how pharmacogenetics influence the treatments of UC and CD and provide guidance on response monitoring and strategies to restore loss of response. Finally, the review includes statements on how to manage treatment alongside possible hepatitis B and tuberculosis infections, both common in Asia. These statements have been prepared and voted upon by members of IBD workgroup employing the modified Delphi process. These statements do not intend to be all-encompassing and future revisions are likely as new data continue to emerge.

The 2017 M Balasegaram Memorial Lecture: The Changing Landscape of Liver Diseases in Malaysia—60 Years On!

@#The landscape of liver diseases in Malaysia has changed dramatically since the time of Professor Balasegaram Manickavasagar—an eminent surgeon in the 1960s. The most significant discoveries in hepatology have been that of hepatitis B virus in 1963 and hepatitis C virus in 1989, which have both been shown to be predominantly blood borne diseases. Hepatitis B and C infections result in long term carrier state and a high propensity to develop liver cirrhosis and cancer. Hepatitis B is the most common cause of liver cirrhosis and cancer in Malaysia. Blood bank screening and public health preventive measures have reduced the disease burden significantly and an effective vaccination for hepatitis B is now incorporated in our National Immunisation Programme. Although no vaccine is available for hepatitis C, highly effective eradication therapies were introduced in 2011. These agents will significantly change the disease scenario across the world. A “new” disease was described in 1980, by Ludwig et al.—non-alcoholic fatty liver (NAFLD) disease. With the global epidemic of obesity and diabetes mellitus, NAFLD is set to increase exponentially across the world including in Malaysia. It will be the most important liver disease in the future, replacing hepatitis B and C infections.

Hepatitis B virus infection among children of hepatitis B surface antigen positive mothers in a Malaysian hospital

transmission of hepatitis B virus (HBV) infection amongchildren of hepatitis B surface antigen (HBsAg) positivemothers in Malaysia. Methods: This is a cross-sectional study of all the childrenof HBsAg-positive mothers who delivered at the Universityof Malaya Medical Centre between 1993 and 2000. Results: A total of 60 HBsAg-positive mothers and their 154children participated in the study. HBsAg was detected infour children (2.6%) while IgG antibody to the hepatitis Bcore antigen (anti-HBc IgG) was detected in seventeenchildren (11.0%). The mother’s age at childbirth wassignificantly lower in the children with detectable HBsAg(22.5±6.1 years vs. 29.7±4.5 years, p=0.043) and anti-HBc IgG(26.6±6.1 years vs. 30.0±4.3 years, p=0.004). Children born inthe 1980s were significantly more likely to have detectableHBsAg (18.8% vs. 0.7%, p=0.004) and anti-HBc IgG (37.5%vs. 8.0%, p=0.000) compared with those born later. Allchildren with detectable HBsAg were born via spontaneousvaginal delivery, and hepatitis B immunoglobulin was eithernot given or the administration status was unknown. Themajority of mothers with chronic HBV infection (70.4%) werenot under any regular follow-up for their chronic HBVinfection and the main reason was the lack of awareness ofthe need to do so (47.4%). Conclusion: Transmission of HBV infection among childrenof HBsAg-positive mothers in Malaysia is low. However,attention needs to be given to the high rate of HBsAg-positive mothers who are not on any regular follow-up.

Assessment of the Asian Neurogastroenterology and Motility Association Chronic Constipation Criteria: An Asian Multicenter Cross-sectional Study

BACKGROUND/AIMS: There is a need for a simple and practical tool adapted for the diagnosis of chronic constipation (CC) in the Asian population. This study compared the Asian Neurogastroenterology and Motility Association (ANMA) CC tool and Rome III criteria for the diagnosis of CC in Asian subjects. METHODS: This multicenter, cross-sectional study included subjects presenting at outpatient gastrointestinal clinics across Asia. Subjects with CC alert symptoms completed a combination Diagnosis Questionnaire to obtain a diagnosis based on 4 different diagnostic methods: self-defined, investigator's judgment, ANMA CC tool, and Rome III criteria. The primary endpoint was the level of agreement/disagreement between the ANMA CC diagnostic tool and Rome III criteria for the diagnosis of CC. RESULTS: The primary analysis comprised of 449 subjects, 414 of whom had a positive diagnosis according to the ANMA CC tool. Rome III positive/ANMA positive and Rome III negative/ANMA negative diagnoses were reported in 76.8% and 7.8% of subjects, respectively, resulting in an overall percentage agreement of 84.6% between the 2 diagnostic methods. The overall percentage disagreement between these 2 diagnostic methods was 15.4%. A higher level of agreement was seen between the ANMA CC tool and self-defined (374 subjects [90.3%]) or investigator’s judgment criteria (388 subjects [93.7%]) compared with the Rome III criteria. CONCLUSION: This study demonstrates that the ANMA CC tool can be a useful for Asian patients with CC.

Pharmacological and Safety Profile of Dexlansoprazole: A New Proton Pump Inhibitor - Implications for Treatment of Gastroesophageal Reflux Disease in the Asia Pacific Region

Although gastroesophageal reflux disease is not as common in Asia as in western countries, the prevalence has increased substantially during the past decade. Gastroesophageal reflux disease is associated with considerable reductions in subjective well-being and work productivity, as well as increased healthcare use. Proton pump inhibitors (PPIs) are currently the most effective treatment for gastroesophageal reflux disease. However, there are limitations associated with these drugs in terms of partial and non-response. Dexlansoprazole is the first PPI with a dual delayed release formulation designed to provide 2 separate releases of medication to extend the duration of effective plasma drug concentration. Dexlansoprazole has been shown to be effective for healing of erosive esophagitis, and to improve subjective well-being by controlling 24-hour symptoms. Dexlansoprazole has also been shown to achieve good plasma concentration regardless of administration with food, providing flexible dosing. Studies in healthy volunteers showed no clinically important effects on exposure to the active metabolite of clopidogrel or clopidogrel-induced platelet inhibition, with no dose adjustment of clopidogrel necessary when coprescribed. This review discusses the role of the new generation PPI, dexlansoprazole, in the treatment of gastroesophageal reflux disease in Asia.

24th Seah Cheng Siang Lecture: Seeing better, doing better--evolution and application of gastrointestinal (GI) endoscopy

Gastrointestinal (GI) endoscopy has evolved tremendously from the early days when candlelight was used to illuminate scopes to the extent that it has now become an integral part of the practice of modern gastroenterology. The first gastroscope was a rigid scope first introduced by Adolf Kussmaul in 1868. However this scope suffered from the 2 drawbacks of poor illumination and high risk of instrumental perforation. Rudolf Schindler improved on this by inventing the semiflexible gastroscope in 1932. But it was Basil Hirschowitz, using the principle of light conduction in fibreoptics, who allowed us to "see well" for the first time when he invented the flexible gastroscopy in 1958. With amazing speed and innovation, instrument companies, chiefly Japanese, had improved on the Hirschowitz gastroscope and invented a flexible colonoscope. Walter McCune introduced the technique of endoscopic retrograde cholangiopancreatography (ERCP) in 1968 which has now evolved into a sophisticated procedure. The advent of the digital age in the 1980s saw the invention of the videoendoscope. Videoendoscopes have allowed us to start seeing the gastrointestinal tract (GIT) "better" with high magnification and resolution and optical/digital enhancements. Fusing confocal and light microscopy with endoscopy has allowed us to perform an "optical biopsy" of the GI mucosa. Development of endoscopic ultrasonography has allowed us to see "beyond" the GIT lumen. Seeing better has allowed us to do better. Endoscopists have ventured into newer procedures such as the resection of mucosal and submucosal tumours and the field of therapeutic GI endoscopy sees no end in sight.

Preoperative Drainage for Malignant Biliary Strictures: Is It Time for Self-Expanding Metallic Stents?

Palliation of jaundice improves the general health of the patient and, therefore, surgical outcomes. Because of the complexity and location of strictures, especially proximally, drainage has been accompanied by increased morbidity due to sepsis. Another concern is the provocation of an inflammatory and fibrotic reaction around the area of stent placement. Preoperative biliary drainage with self-expanding metallic stent (SEMS) insertion can be achieved via a percutaneous method or through endoscopic retrograde cholangiopancreatography. A recently published multicenter randomized Dutch study has shown increased morbidity with preoperative biliary drainage. A Cochrane meta-analysis has also shown a significantly increased complication rate with preoperative drainage. However, few of these studies have used a SEMS, which allows better biliary drainage. No randomized controlled trials have compared preoperative deployment of SEMS versus conventional plastic stents. The outcomes of biliary drainage also depend on the location of the obstruction, namely the difficulty with proximal compared to distal strictures. Pathophysiologically, palliation of jaundice will benefit all patients awaiting surgery. However, preoperative drainage often results in increased morbidity because of procedure-related sepsis. The use of SEMS may change the outcome of preoperative biliary drainage dramatically.

Endoscopic Ablation Therapy for Biliopancreatic Malignancies

Biliopancreatic malignancies such as cholangiocarcinoma (CCA) has notoriously been diagnosed late. As such most therapy have been palliative in nature. Cholangioscopy allows for an earlier diagnosis to be made. Brachytherapy with the insertion of catheter with iridium-132 seeds, percutaneously or through endoscopic retrograde cholangiopancreatography (ERCP) was the earliest ablative techniques used. It has been shown to have a beneficial effect only in prolonging survival. Photodynamic therapy (PDT) has also been used for several years. stenting with PDT versus stenting alone for unresectable CCA showed a marked survival benefit with the addition of PDT. However the most exciting endoscopic ablative modality appears to be intraductal radiofrequency ablation using the Habib catheter and device. Several case series have shown the effectiveness of this technique in ablating tumors. This technique is evolving and coupled with early diagnosis of CCA through cholangioscopy will allow for a curative therapy. The crux to the effective treatment of early cancerous lesions in the bile or pancreatic duct is the early diagnosis of such lesions. Effective endoscopic ablative therapy is now available with the advent of radiofrequency ablation probes that can be passed through the duodenoscope via ERCP.

Burden of Dyspepsia in Rural and Urban Asia: Author's Reply

No abstract available.

Economic Impact of Dyspepsia in Rural and Urban Malaysia: A Population-Based Study

BACKGROUND/AIMS: The economic impact of dyspepsia in regions with a diverse healthcare system remains uncertain. This study aimed to estimate the costs of dyspepsia in a rural and urban population in Malaysia. METHODS: Economic evaluation was performed based on the cost-of-illness method. Resource utilization and quality of life data over a specific time frame, were collected to determine direct, indirect and intangible costs related to dyspepsia. RESULTS: The prevalences of dyspepsia in the rural (n = 2,000) and urban (n = 2,039) populations were 14.6% and 24.3% respectively. Differences in socioeconomic status and healthcare utilisation between both populations were considerable. The cost of dyspepsia per 1,000 population per year was estimated at USD14,816.10 and USD59,282.20 in the rural and urban populations respectively. The cost per quality adjusted life year for dyspepsia in rural and urban adults was USD16.30 and USD69.75, respectively. CONCLUSIONS: The economic impact of dyspepsia is greater in an urban compared to a rural setting. Differences in socioeconomic status and healthcare utilisation between populations are thought to contribute to this difference.

Association of Ki67 with raised transaminases in hepatocellular carcinoma

Transaminase enzymes, alanine (ALT) and aspartate transaminase (AST), have been reported to be raised and implicated to have prognostic value in hepatocellular carcinoma (HCC). Ki67, a marker of cellular proliferative activity, has also been noted to be increased in HCC. A study was conducted at the Department of Pathology, Faculty of Medicine, University of Malaya, Kuala Lumpur to determine the possible association of proliferative activity, as determined by Ki67, with the transaminase enzymes. 31 cases of histologically diagnosed HCC who underwent tumour resection were retrieved from departmental archives. The patients' ages ranged between 40 to 79 years with a mean of 58.3 years. There was a male preponderance with M:F = 2.9:1. Ethnic Chinese formed 83.9% of the cases. 4 microm sections, cut from the formalin-fixed, paraffin-embedded tumour tissue block of each case, were immunohistochemically stained with Ki67 (DAKO monoclonal MIB-1) using the commercial DakoCytomation EnVision+System-HRP kit. The latest ALT and AST levels, assayed within 7 days prior to tumour resection, were retrieved from the patients' case records. 24 (77.4%) HCC demonstrated elevation of either ALT and/or AST. 27 (87.1%) HCC were immunopositive for Ki67. Ki67 immunoexpression was significantly correlated with raised transaminases (p<0.05). Hypothetically, the mechanism by which this phenomenon may occur may simply be release of transaminases due to destruction of hepatocytes by the cancer. Thus rising levels of the transaminases could signal a more rapid growth of the tumour and these routinely performed tests can be of prognostic value in management of HCC patients.