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  1. Verma N, Dhiman RK, Choudhury A, Taneja S, Duseja A, Singh V, et al.
    Hepatol Int, 2021 Aug;15(4):970-982.
    PMID: 34275111 DOI: 10.1007/s12072-021-10221-7
    BACKGROUND: We evaluated the dynamics of hepatic encephalopathy (HE) and ammonia estimation in acute-on-chronic liver failure (ACLF) patients due to a paucity of evidence.

    METHODS: ACLF patients recruited from the APASL-ACLF Research Consortium (AARC) were followed up till 30 days, death or transplantation, whichever earlier. Clinical details, including dynamic grades of HE and laboratory data, including ammonia levels, were serially noted.

    RESULTS: Of the 3009 ACLF patients, 1315 (43.7%) had HE at presentation; grades I-II in 981 (74.6%) and grades III-IV in 334 (25.4%) patients. The independent predictors of HE at baseline were higher age, systemic inflammatory response, elevated ammonia levels, serum protein, sepsis and MELD score (p 

  2. Choudhury A, Jindal A, Maiwall R, Sharma MK, Sharma BC, Pamecha V, et al.
    Hepatol Int, 2017 Sep;11(5):461-471.
    PMID: 28856540 DOI: 10.1007/s12072-017-9816-z
    BACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) is a progressive disease associated with rapid clinical worsening and high mortality. Early prediction of mortality and intervention can improve patient outcomes. We aimed to develop a dynamic prognostic model and compare it with the existing models.

    METHODS: A total of 1402 ACLF patients, enrolled in the APASL-ACLF Research Consortium (AARC) with 90-day follow-up, were analyzed. An ACLF score was developed in a derivation cohort (n = 480) and was validated (n = 922).

    RESULTS: The overall survival of ACLF patients at 28 days was 51.7%, with a median of 26.3 days. Five baseline variables, total bilirubin, creatinine, serum lactate, INR and hepatic encephalopathy, were found to be independent predictors of mortality, with AUROC in derivation and validation cohorts being 0.80 and 0.78, respectively. AARC-ACLF score (range 5-15) was found to be superior to MELD and CLIF SOFA scores in predicting mortality with an AUROC of 0.80. The point scores were categorized into grades of liver failure (Gr I: 5-7; II: 8-10; and III: 11-15 points) with 28-day cumulative mortalities of 12.7, 44.5 and 85.9%, respectively. The mortality risk could be dynamically calculated as, with each unit increase in AARC-ACLF score above 10, the risk increased by 20%. A score of ≥11 at baseline or persisting in the first week was often seen among nonsurvivors (p = 0.001).

    CONCLUSIONS: The AARC-ACLF score is easy to use, dynamic and reliable, and superior to the existing prediction models. It can reliably predict the need for interventions, such as liver transplant, within the first week.

  3. Ooi CJ, Makharia GK, Hilmi I, Gibson PR, Fock KM, Ahuja V, et al.
    J Gastroenterol Hepatol, 2016 Jan;31(1):45-55.
    PMID: 25819140 DOI: 10.1111/jgh.12956
    Inflammatory bowel disease (IBD) was previously thought to be rare in Asia, but emerging data indicate rising incidence and prevalence of IBD in the region. The Asia Pacific Working Group on Inflammatory Bowel Disease was established in Cebu, Philippines, at the Asia Pacific Digestive Week conference in 2006 under the auspices of the Asian Pacific Association of Gastroenterology with the goal of developing best management practices, coordinating research, and raising awareness of IBD in the region. The consensus group previously published recommendations for the diagnosis and management of ulcerative colitis with specific relevance to the Asia-Pacific region. The present consensus statements were developed following a similar process to address the epidemiology, diagnosis, and management of Crohn's disease. The goals of these statements are to pool the pertinent literature specifically highlighting relevant data and conditions in the Asia-Pacific region relating to the economy, health systems, background infectious diseases, differential diagnoses, and treatment availability. It does not intend to be all comprehensive and future revisions are likely to be required in this ever-changing field.
  4. Ooi CJ, Makharia GK, Hilmi I, Gibson PR, Fock KM, Ahuja V, et al.
    J Gastroenterol Hepatol, 2016 Jan;31(1):56-68.
    PMID: 25819311 DOI: 10.1111/jgh.12958
    The Asia Pacific Working Group on Inflammatory Bowel Disease was established in Cebu, Philippines, at the Asia Pacific Digestive Week conference in 2006 under the auspices of the Asian Pacific Association of Gastroenterology (APAGE) with the goal of developing best management practices, coordinating research and raising awareness of IBD in the region. The consensus group previously published recommendations for the diagnosis and management of ulcerative colitis (UC) with specific relevance to the Asia-Pacific region. The present consensus statements were developed following a similar process to address the epidemiology, diagnosis and management of Crohn's disease (CD). The goals of these statements are to pool the pertinent literature specifically highlighting relevant data and conditions in the Asia-Pacific region relating to the economy, health systems, background infectious diseases, differential diagnoses and treatment availability. It does not intend to be all-comprehensive and future revisions are likely to be required in this ever-changing field.
  5. Ooi CJ, Hilmi I, Banerjee R, Chuah SW, Ng SC, Wei SC, et al.
    Intest Res, 2019 Jul;17(3):285-310.
    PMID: 31146509 DOI: 10.5217/ir.2019.00026
    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.
  6. Koo JH, Leong RW, Ching J, Yeoh KG, Wu DC, Murdani A, et al.
    Gastrointest Endosc, 2012 Jul;76(1):126-35.
    PMID: 22726471 DOI: 10.1016/j.gie.2012.03.168
    BACKGROUND: The rapid increase in the incidence of colorectal cancer (CRC) in the Asia-Pacific region in the past decade has resulted in recommendations to implement mass CRC screening programs. However, the knowledge of screening and population screening behaviors between countries is largely lacking.
    OBJECTIVE: This multicenter, international study investigated the association of screening test participation with knowledge of, attitudes toward, and barriers to CRC and screening tests in different cultural and sociopolitical contexts.
    METHODS: Person-to-person interviews by using a standardized survey instrument were conducted with subjects from 14 Asia-Pacific countries/regions to assess the prevailing screening participation rates, knowledge of and attitudes toward and barriers to CRC and screening tests, intent to participate, and cues to action. Independent predictors of the primary endpoint, screening participation was determined from subanalyses performed for high-, medium-, and low-participation countries.
    RESULTS: A total of 7915 subjects (49% male, 37.8% aged 50 years and older) were recruited. Of the respondents aged 50 years and older, 809 (27%) had undergone previous CRC testing; the Philippines (69%), Australia (48%), and Japan (38%) had the highest participation rates, whereas India (1.5%), Malaysia (3%), Indonesia (3%), Pakistan (7.5%), and Brunei (13.7%) had the lowest rates. Physician recommendation and knowledge of screening tests were significant predictors of CRC test uptake. In countries with low-test participation, lower perceived access barriers and higher perceived severity were independent predictors of participation. Respondents from low-participation countries had the least knowledge of symptoms, risk factors, and tests and reported the lowest physician recommendation rates. "Intent to undergo screening" and "perceived need for screening" was positively correlated in most countries; however, this was offset by financial and access barriers.
    LIMITATIONS: Ethnic heterogeneity may exist in each country that was not addressed. In addition, the participation tests and physician recommendation recalls were self-reported.
    CONCLUSIONS: In the Asia-Pacific region, considerable differences were evident in the participation of CRC tests, physician recommendations, and knowledge of, attitudes toward, and barriers to CRC screening. Physician recommendation was the uniform predictor of screening behavior in all countries. Before implementing mass screening programs, improving awareness of CRC and promoting the physicians' role are necessary to increase the screening participation rates.
  7. Ooi CJ, Hilmi I, Banerjee R, Chuah SW, Ng SC, Wei SC, et al.
    J Gastroenterol Hepatol, 2019 Aug;34(8):1296-1315.
    PMID: 30848854 DOI: 10.1111/jgh.14648
    The Asia-Pacific Working Group on Inflammatory Bowel Disease was established in Cebu, Philippines, under the auspices of the Asia-Pacific Association of Gastroenterology with the goal of improving inflammatory bowel disease 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 conjunction with conventional treatments for ulcerative colitis and Crohn's disease in Asia. These statements also address how pharmacogenetics influences the treatments of ulcerative colitis and Crohn's disease and provides 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 inflammatory bowel disease 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.
  8. Fock KM, Talley N, Goh KL, Sugano K, Katelaris P, Holtmann G, et al.
    Gut, 2016 Sep;65(9):1402-15.
    PMID: 27261337 DOI: 10.1136/gutjnl-2016-311715
    OBJECTIVE: Since the publication of the Asia-Pacific consensus on gastro-oesophageal reflux disease in 2008, there has been further scientific advancement in this field. This updated consensus focuses on proton pump inhibitor-refractory reflux disease and Barrett's oesophagus.

    METHODS: A steering committee identified three areas to address: (1) burden of disease and diagnosis of reflux disease; (2) proton pump inhibitor-refractory reflux disease; (3) Barrett's oesophagus. Three working groups formulated draft statements with supporting evidence. Discussions were done via email before a final face-to-face discussion. We used a Delphi consensus process, with a 70% agreement threshold, using Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria to categorise the quality of evidence and strength of recommendations.

    RESULTS: A total of 32 statements were proposed and 31 were accepted by consensus. A rise in the prevalence rates of gastro-oesophageal reflux disease in Asia was noted, with the majority being non-erosive reflux disease. Overweight and obesity contributed to the rise. Proton pump inhibitor-refractory reflux disease was recognised to be common. A distinction was made between refractory symptoms and refractory reflux disease, with clarification of the roles of endoscopy and functional testing summarised in two algorithms. The definition of Barrett's oesophagus was revised such that a minimum length of 1 cm was required and the presence of intestinal metaplasia no longer necessary. We recommended the use of standardised endoscopic reporting and advocated endoscopic therapy for confirmed dysplasia and early cancer.

    CONCLUSIONS: These guidelines standardise the management of patients with refractory gastro-oesophageal reflux disease and Barrett's oesophagus in the Asia-Pacific region.

  9. Gwee KA, Gonlachanvit S, Ghoshal UC, Chua ASB, Miwa H, Wu J, et al.
    J Neurogastroenterol Motil, 2019 Jul 01;25(3):343-362.
    PMID: 31327218 DOI: 10.5056/jnm19041
    Background/Aims: There has been major progress in our understanding of the irritable bowel syndrome (IBS), and novel treatment classes have emerged. The Rome IV guidelines were published in 2016 and together with the growing body of Asian data on IBS, we felt it is timely to update the Asian IBS Consensus.

    Methods: Key opinion leaders from Asian countries were organized into 4 teams to review 4 themes: symptoms and epidemiology, pathophysiology, diagnosis and investigations, and lifestyle modifications and treatments. The consensus development process was carried out by using a modified Delphi method.

    Results: Thirty-seven statements were developed. Asian data substantiate the current global viewpoint that IBS is a disorder of gut-brain interaction. Socio-cultural and environmental factors in Asia appear to influence the greater overlap between IBS and upper gastrointestinal symptoms. New classes of treatments comprising low fermentable oligo-, di-, monosacharides, and polyols diet, probiotics, non-absorbable antibiotics, and secretagogues have good evidence base for their efficacy.

    Conclusions: Our consensus is that all patients with functional gastrointestinal disorders should be evaluated comprehensively with a view to holistic management. Physicians should be encouraged to take a positive attitude to the treatment outcomes for IBS patients.

  10. Sarin SK, Kumar M, Lau GK, Abbas Z, Chan HL, Chen CJ, et al.
    Hepatol Int, 2016 Jan;10(1):1-98.
    PMID: 26563120 DOI: 10.1007/s12072-015-9675-4
    Worldwide, some 240 million people have chronic hepatitis B virus (HBV), with the highest rates of infection in Africa and Asia. Our understanding of the natural history of HBV infection and the potential for therapy of the resultant disease is continuously improving. New data have become available since the previous APASL guidelines for management of HBV infection were published in 2012. The objective of this manuscript is to update the recommendations for the optimal management of chronic HBV infection. The 2015 guidelines were developed by a panel of Asian experts chosen by the APASL. The clinical practice guidelines are based on evidence from existing publications or, if evidence was unavailable, on the experts' personal experience and opinion after deliberations. Manuscripts and abstracts of important meetings published through January 2015 have been evaluated. This guideline covers the full spectrum of care of patients infected with hepatitis B, including new terminology, natural history, screening, vaccination, counseling, diagnosis, assessment of the stage of liver disease, the indications, timing, choice and duration of single or combination of antiviral drugs, screening for HCC, management in special situations like childhood, pregnancy, coinfections, renal impairment and pre- and post-liver transplant, and policy guidelines. However, areas of uncertainty still exist, and clinicians, patients, and public health authorities must therefore continue to make choices on the basis of the evolving evidence. The final clinical practice guidelines and recommendations are presented here, along with the relevant background information.
  11. Ling KL, Hilmi I, Raja Ali RA, Leong RWL, Leung WK, Ng SC, et al.
    JGH Open, 2020 Jun;4(3):320-323.
    PMID: 32514431 DOI: 10.1002/jgh3.12362
    The COVID-19 pandemic, secondary to SARS-CoV-2, has resulted in high mortality and morbidity worldwide. As inflammatory bowel disease (IBD) is a chronic disease, and most patients are on long-term immunosuppressive agents, there is understandable concern, particularly in terms of therapy. In view of this, experts in IBD across the Asia Pacific region were invited to put together recommendations based on their experience and the currently available data. In general, most IBD therapies (with a few exceptions) can be continued safely, and the general consensus is that maintaining disease control should remain the main principle of management. In addition, social distancing measures and the appropriate use of personal protective equipment should be strictly adhered to. During the current pandemic, face-to-face clinic follow ups and non-urgent procedures should be kept to a minimum.
  12. Ran Z, Wu K, Matsuoka K, Jeen YT, Wei SC, Ahuja V, et al.
    J Gastroenterol Hepatol, 2021 Mar;36(3):637-645.
    PMID: 32672839 DOI: 10.1111/jgh.15185
    Inflammatory bowel disease (IBD) has increased in incidence and prevalence in Asian countries since the end of the 20th century. Moreover, differences in the cause, phenotypes, and natural history of IBD between the East and West have been recognized. Therefore, the Asian Organization for Crohn's and Colitis and the Asia Pacific Association of Gastroenterology have established recommendations on medical management of IBD in Asia. Initially, the committee members drafted 40 recommendations, which were then assessed according to Grading of Recommendations Assessment, Development and Evaluation. Eight statements were rejected as this indicated that consensus had not been reached. The recommendations encompass pretreatment evaluation; medical management of active IBD; medical management of IBD in remission; management of IBD during the periconception period and pregnancy; surveillance strategies for colitis-associated cancer; monitoring side effects of thiopurines and methotrexate; and infections in IBD.
  13. Lee HH, Park JJ, Lee BI, Hilmi I, Sollano J, Ran ZH
    Intest Res, 2023 Jul;21(3):328-338.
    PMID: 37533264 DOI: 10.5217/ir.2023.00012
    BACKGROUND/AIMS: Inflammatory bowel disease (IBD) is no longer a rare disease in Asia, thus it needs to prepare recommendations relevant to Asian patients. This study aimed to identify disparities in the process of the diagnosis of IBD in Asian countries/regions.

    METHODS: In line with the 2020 Asian Organization for Crohn's and Colitis annual meeting, a multinational web-based survey about Asian physicians' perspectives on IBD was conducted.

    RESULTS: A total of 384 Asian physicians (99 in China, 93 in Japan, 110 in Korea, and 82 in other Asian countries/regions) treating IBD patients from 24 countries/regions responded to the survey. Most respondents were gastroenterologists working in an academic teaching hospital. About half of them had more than 10 years of clinical experience in caring for patients with IBD. The European Crohn's Colitis Organisation guideline was used most commonly for the diagnosis of IBD except for Japanese physicians who preferred their own national guideline. The Mayo score and Crohn's Disease Activity Index were the most commonly used activity scoring systems for ulcerative colitis and Crohn's disease, respectively. Endoscopy, not surprisingly, was the main investigation in assessing the extent and activity of IBD. On the other hand, there were disparities across countries/regions with regard to the favored modalities of small bowel and perianal evaluation of Crohn's disease, as well as the use of serologic markers.

    CONCLUSIONS: Results of the present survey revealed practical behaviors of Asian physicians in the diagnosis of IBD. Investigating the reasons for different diagnostic approaches among countries/regions might help us develop Asian guidelines further.

  14. Wait S, Kell E, Hamid S, Muljono DH, Sollano J, Mohamed R, et al.
    Lancet Gastroenterol Hepatol, 2016 11;1(3):248-255.
    PMID: 28404097 DOI: 10.1016/S2468-1253(16)30031-0
    In 2015, the Coalition to Eradicate Viral Hepatitis in Asia Pacific gathered leading hepatitis experts from Bangladesh, India, Indonesia, Malaysia, Pakistan, the Philippines, and Thailand to discuss common challenges to the burden posed by hepatitis B virus (HBV) and hepatitis C virus (HCV), to learn from each other's experience, and identify sustainable approaches. In this report, we summarise these discussions. Countries differ in their policy responses to HBV and HCV; however, substantial systemic, cultural, and financial barriers to achievement of elimination of these infections persist in all countries. Common challenges to elimination include limited availability of reliable epidemiological data; insufficient public awareness of risk factors and modes of transmission, leading to underdiagnosis; high rates of transmission through infected blood products, including in medical settings; limited access to care for people who inject drugs; prevailing stigma and discrimination against people infected with viral hepatitis; and financial barriers to treatment and care. Despite these challenges, promising examples of effective programmes, public-private initiatives, and other innovative approaches are evident in all countries we studied in Asia Pacific. The draft WHO Global Health Sector Strategy on Viral Hepatitis 2016-21 provides a solid framework upon which governments can build their local strategies towards viral hepatitis. However, greater recognition by national governments and the international community of the urgency to comprehensively tackle both HBV and HCV are still needed. In all countries, strategic plans and policy goals need to be translated into resources and concrete actions, with national governments at the helm, to enable a sustainable response to the rising burden of hepatitis B and C in all countries.
  15. Mohamed R, Desmond P, Suh DJ, Amarapurkar D, Gane E, Guangbi Y, et al.
    J Gastroenterol Hepatol, 2004 Sep;19(9):958-69.
    PMID: 15304110
    The Asia-Pacific Expert Committee on Hepatitis B Management recently reviewed the impact of hepatitis B in the region and assessed the differences and similarities observed in the practical management of the disease in individual Asia-Pacific countries. Hepatitis B is a major health concern in the Asia-Pacific region, and of all chronically infected carriers worldwide, approximately 75% are found in Asia. The disease poses a considerable burden on healthcare systems, and is likely to remain a cause of substantial morbidity and mortality for several decades. Disease prevention activities, including screening and vaccination programs, have been implemented successfully in some Asia-Pacific countries and similar measures are being established in other parts of the region. The management of hepatitis B in the Asia-Pacific varies throughout the region, with each country confronting different issues related to treatment options, disease monitoring and duration of therapy. The influence of cost, availability of diagnostic equipment, and patient awareness and compliance are of additional concern. Although guidelines such as those developed by the Asian Pacific Association for the Study of the Liver have been created to address problems encountered in the management of hepatitis B, many physicians in the region still find it difficult to make satisfactory management decisions because of the treatment choices available. This article examines the different approaches to hepatitis B management in a number of Asia-Pacific countries, and highlights the difficulties that can arise when adhering to treatment guidelines and disease prevention solutions that have proved to be successful in the region.
  16. Merican I, Guan R, Amarapuka D, Alexander MJ, Chutaputti A, Chien RN, et al.
    J Gastroenterol Hepatol, 2000 Dec;15(12):1356-61.
    PMID: 11197043
    Of the estimated 50 million new cases of hepatitis B virus (HBV) infection diagnosed annually, 5-10% of adults and up to 90% of infants will become chronically infected, 75% of these in Asia where hepatitis B is the leading cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC). In Indonesia, 4.6% of the population was positive for HBsAg in 1994 and of these, 21% were positive for HBeAg and 73% for anti-HBe; 44% and 45% of Indonesian patients with cirrhosis and HCC, respectively, were HBsAg positive. In the Philippines, there appear to be two types of age-specific HBsAg prevalence, suggesting different modes of transmission. In Thailand, 8-10% of males and 6-8% of females are HBsAg positive, with HBsAg also found in 30% of patients with cirrhosis and 50-75% of those with HCC. In Taiwan, 75-80% of patients with chronic liver disease are HBsAg positive, and HBsAg is found in 34% and 72% of patients with cirrhosis and HCC, respectively. In China, 73% of patients with chronic hepatitis and 78% and 71% of those with cirrhosis and HCC, respectively, are HBsAg positive. In Singapore, the prevalence of HBsAg has dropped since the introduction of HBV vaccination and the HBsAg seroprevalence of unvaccinated individuals over 5 years of age is 4.5%. In Malaysia, 5.24% of healthy volunteers, with a mean age of 34 years, were positive for HBsAg in 1997. In the highly endemic countries in Asia, the majority of infections are contracted postnatally or perinatally. Three phases of chronic HBV infection are recognized: phase 1 patients are HBeAg positive with high levels of virus in the serum and minimal hepatic inflammation; phase 2 patients have intermittent or continuous hepatitis of varying degrees of severity; phase 3 is the inactive phase during which viral concentrations are low and there is minimal inflammatory activity in the liver. In general, patients who clear HBeAg have a better prognosis than patients who remain HBeAg-positive for prolonged periods of time. The outcome after anti-HBe seroconversion depends on the degree of pre-existing liver damage and any subsequent HBV reactivation. Without pre-existing cirrhosis, there may be only slight fibrosis or mild chronic hepatitis, but with pre-existing cirrhosis, further complications may ensue. HBsAg-negative chronic hepatitis B is a phase of chronic HBV infection during which a mutation arises resulting in the inability of the virus to produce HBeAg. Such patients tend to have more severe liver disease and run a more rapidly progressive course. The annual probability of developing cirrhosis varies from 0.1 to 1.0% depending on the duration of HBV replication, the severity of disease and the presence of concomitant infections or drugs. The annual incidence of hepatic decompensation in HBV-related cirrhosis varies from 2 to 10% and in these patients the 5-year survival rate drops dramatically to 14-35%. The annual risk of developing HCC in patients with cirrhosis varies between 1 and 6%; the overall reported annual detection rate of HCC in surveillance studies, which included individuals with chronic hepatitis B and cirrhosis, is 0.8-4.1%. Chronic hepatitis B is not a static disease and the natural history of the disease is affected by both viral and host factors. The prognosis is poor with decompensated cirrhosis and effective treatment options are limited. Prevention of HBV infection thorough vaccination is still, therefore, the best strategy for decreasing the incidence of hepatitis B-associated cirrhosis and HCC.
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