Biologic exposure of short duration results in a marked reduction in cumulative surgical rates in Malaysian patients with inflammatory bowel disease

INTRODUCTION: Crohn disease (CD) is a chronic progressive disease that is associated with high surgical rates. In view of our recent practice is starting biologic therapy early, we sought to determine whether there were differences in surgical rates between patients who were exposed or not exposed to biologic therapy. METHODOLOGY: This was a retrospective, single-centre study conducted in a tertiary centre in Malaysia. The biologic- exposed group was defined as any patient with exposure for at least 6-8 weeks. Demographics, clinical characteristics and time to significant surgical intervention (ie bowel resection) were recorded and cumulative surgical rates were calculated. RESULT: A total of 158 patients were recruited: 85 from the biologic-exposed cohort and 73 from the non-biologic cohort. Baseline demography was as follows: Male 56.3% Female 43.7%; Malays 21.5% Chinese 33.5% Indians 43.0%. Median duration of disease was 11.9 years (1.4, 30.4). Differences seen in terms demographics, disease location and behavior at diagnosis between the two cohorts were not significant. For the biologic group, median time to commencing therapy was 26.4 months (0.0, 165.6) and median duration of therapy was 13 months (IQR 1.5,130.0). The biologic-exposed group had significantly lower cumulative surgical rates compared to the non-biologic group; 2.3% versus 21.9% at 1 year; 7.3% versus 31.5% at 5 years and 15.6% versus 39.7% at ten years. CONCLUSION: Surgical rates were significantly lower in CD patients who are biologic-exposed even for a short duration. This confirms that the role of biologic therapy in altering the disease progression of CD, even in a limited resource setting

Frequency of significant fibrosis in various chronic liver diseases: an evaluation with Transient Elastography (TE)

INTRODUCTION: Liver biopsy has long been the gold standard to evaluate liver fibrosis. TE was developed as a non- invasive method to assess liver fibrosis by measuring liver stiffness using shear wave velocity. Many studies have proven its’ effectiveness as a method for evaluating liver fibrosis.1-2 The use of TE in UMMC began in 2013. OBJECTIVE: To determine the frequency and aetiology of liver fibrosis and cirrhosis in our local population METHOD: This was a retrospective study conducted at UMMC. Inclusion criteria was all patients who had TE performed from 1 January 2013 to 31 December 2021. Their demographics, clinical characteristics and TE findings were charted. RESULTS: A total of 3066 patients were included, in which 51.7% were males and 48.3% were females. The median CAP value was 271 dB/m. The median E value was 6.5kPa. 11.2% and 11.3% of patients had significant fibrosis (10.1-14.9kPa) and cirrhosis(≥15kPa) respectively. Non-alcoholic fatty liver disease (NAFLD) was noted to be the most common aetiology for fibrosis (32.8%), followed by chronic hepatitis B (CHB) at 25.2%, chronic hepatitis C (CHC) at 6.7% and alcoholic liver disease (ALD) with 1.3%. This finding was also found to be similar in the cirrhosis group (NAFLD 32.5%, CHB 17.2%, CHC 11.9% and ALD 1.4%). 219 DISCUSSION: Our study shows that the most common cause for significant fibrosis and cirrhosis is NAFLD. This is in contrast with previous studies, that reported the most common aetiology being CHB.3-4 This is likely due to the availability of effective treatment for hepatitis B and C. This may also be attributed to the initiation of the national Hepatitis B vaccination program for newborns and the improvement in blood transfusion safety. CONCLUSION: NAFLD has the greatest frequency of fibrosis compared with other aetiologies of liver disease - mainly as there is no effective treatment, unlike viral hepatitis

Frequency of significant steatosis in various chronic liver diseases: an evaluation with Transient Elastography (TE)

INTRODUCTION: TE was developed as a non-invasive method to assess liver fibrosis and steatosis using shear wave velocity. Many studies have proven its’ effectiveness as a method for evaluating liver fibrosis and steatosis.1-2 OBJECTIVE: To determine the prevalence and aetiology of steatosis in our local population. METHOD: This study was conducted as a retrospective review on all patients who had TE performed at UMMC from 1 January 2013 to 31 December 2021. Their demographics, clinical characteristics and TE findings were charted. RESULTS: A total of 3066 patients were included. 51.7% were males and 48.3% were females. The median CAP value was 271 dB/m. The median E value was 6.5kPa. 61.2% of patients had steatosis, with a staggering number of of these patients having significant steatosis (51.8%). 6.3% of patients had S2 steatosis whereas 45.5% of patients had severe (S3) steatosis. Interestingly, in those with S2 steatosis, 34.7% had chronic hepatitis B (CHB), 31.5% had non-alcoholic fatty liver disease (NAFLD), 5.2% with chronic hepatitis C (CHC) and 1% had alcoholic liver disease (ALD). In the S3 steatosis group, 66.7% had NAFLD, followed by ALD (36.6%), CHB (30.1%) and CHC (27.7%). 221 DISCUSSION: It is important to highlight that a large proportion of our patients has significant steatosis. This is likely in keeping with the global rise of obesity and sedentary lifestyle.3 NAFLD is a 4-decades old nomenclature that does not appropriately address the heterogenous pathogenicity of fatty liver disease. Our study reflects this heterogeneity, as it shows that steatosis often co-exists with other diverse aetiologies. CONCLUSION: Whilst NAFLD clearly has the greatest frequency of severe steatosis, it is also present in other aetiologies. These findings support the new terminology of metabolic associated fatty liver disease (MAFLD), which reflects the fact that NAFLD commonly co-exists with other aetiologies

Biologic exposure of short duration results in a marked reduction in cumulative surgical rates in Malaysian patients with inflammatory bowel disease

Background and Aim: Crohn’s disease (CD) is a chronic progressive dis- ease that is associated with high surgical rates. In view of our recent prac- tice is starting biologic therapy early, we sought to determine whether there were differences in surgical rates between patients who were exposed or not exposed to biologic therapy. Methods: This was a retrospective, single-centre study conducted in a tertiary centre in Malaysia. The biologic-exposed group was defined as any patient with exposure for at least 6–8 weeks. Demographics, clinical characteristics and time to significant surgical intervention (i.e. bowel resection) were recorded. and cumulative surgical rates were calculated. Results: A total of 158 patients were recruited: 85 from the biologic-exposed cohort and 73 from the non-biologic cohort. Baseline demography was as follows: male 56.3%, Journal of Gastroenterology and Hepatology 36 (Suppl. 2) (2021) 74–283 Editorial material and organization © 2021 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd. Copyright of individual abstracts remains with the authors. female 43.7%; Malays 21.5%, Chinese 33.5%, Indians 43.0%. Median duration of disease was 11.9 years (1.4, 30.4). Differences seen in terms demographics, disease location and behaviour at diagnosis between the two cohorts were not significant. For the biologic group, median time to commencing therapy was 26.4 months (0.0, 165.6), and median duration of therapy was 13 months (IQR 1.5, 130.0). The biologic-exposed group had significantly lower cumulative surgical rates compared to the non-biologic group: 2.3% versus 21.9% at 1 year, 7.3% versus 31.5% at 5 years and 15.6% versus 39.7% at 10 years. Conclusion: Surgical rates were significantly lower in CD patients who are biologic-exposed even for a short duration. This confirms that the role of biologic therapy in altering the disease progression of CD, even in a limited resource setting

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): A State-of-the-Art Review

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the latest term for steatotic liver disease associated with metabolic syndrome. MASLD is the most common cause of chronic liver disease and is the leading cause of liver-related morbidity and mortality. It is important that all stakeholders be involved in tackling the public health threat of obesity and obesity-related diseases, including MASLD. A simple and clear assessment and referral pathway using non-invasive tests is essential to ensure that patients with severe MASLD are identified and referred to specialist care, while patients with less severe disease remain in primary care, where they are best managed. While lifestyle intervention is the cornerstone of the management of patients with MASLD, cardiovascular disease risk must be properly assessed and managed because cardiovascular disease is the leading cause of mortality. No pharmacological agent has been approved for the treatment of MASLD, but novel anti-hyperglycemic drugs appear to have benefit. Medications used for the treatment of diabetes and other metabolic conditions may need to be adjusted as liver disease progresses to cirrhosis, especially decompensated cirrhosis. Based on non-invasive tests, the concepts of compensated advanced chronic liver disease and clinically significant portal hypertension provide a practical approach to stratifying patients according to the risk of liver-related complications and can help manage such patients. Finally, prevention and management of sarcopenia should be considered in the management of patients with MASLD

Community participation in general health initiatives in high and upper-middle income countries: A systematic review exploring the nature of participation, use of theories, contextual drivers and power relations in community participation.

Community participation is commonly regarded as pivotal in enabling the success of many health initiatives. However, the theoretical constructs, and evidence about the contextual drivers and relational issues that shape participation is lacking. The aim of this systematic review was to examine the evidence for published academic literature on community participation in relation to general, non-disease specific health initiatives, including the use of theories to inform community participation, and the study of contextual drivers and relational issues that influence community participation, with a focus on high and upper-middle income countries. We searched multiple databases including Medline, Embase, Scopus, LILACs and Global Health from January 2000 to September 2016. We screened papers for inclusion, then conducted data extraction and a narrative synthesis of the data. Only papers that focused on general health were included. Disease-specific literature was excluded. 27,232 records were identified, with 23,468 after duplicate removal. 79 papers met our final inclusion criteria. Overall, our findings show that strategies to encourage community participation in health initiatives can be categorized along a continuum that varies from less to more participation and control among the community. Our analysis of reported outcomes demonstrates that community participation in general health initiatives can contribute to positive process, social and health outcomes. Social outcomes are more often associated with increasing community participation in our selection of papers. Overall, our findings reaffirm the understanding that community participation is a complex process that is strongly influenced by the context in which it occurs, and that social factors such as power relations must be carefully considered. There is a need for more robustly designed studies to improve the theorization of community participation, and to draw out a better understanding of how tangible and intangible elements such as power, influence community participation and its outcomes

Validation of the blood test MACK-3 for the noninvasive diagnosis of fibrotic NASH: an international study with 1,924 patients.

BACKGROUND AND AIMS Drug development in NASH is hampered by a high screening failure rate that reaches 60-80% in therapeutic trials, mainly because of the absence of fibrotic NASH on baseline liver histology. MACK-3, a blood test including three biomarkers (aspartate aminotransferase, homeostasis model assessment and cytokeratin 18), was recently developed for the noninvasive diagnosis of fibrotic NASH. We aimed to validate the diagnostic accuracy of this noninvasive test in an international multicenter study. METHODS 1,924 patients with biopsy-proven NAFLD from 10 centers in Asia, Australia, and Europe were included. The blood test MACK-3 was calculated for all patients. FAST, an elastography-based test for fibrotic NASH, was also available in a subset of 655 patients. Fibrotic NASH was defined as the presence of NASH on liver biopsy with NAFLD Activity Score ≥4 and fibrosis stage F≥2 according to the NASH CRN scoring system. RESULTS AUROC of MACK-3 for fibrotic NASH was 0.791 [0.768-0.814]. Sensitivity at the previously published MACK-3 threshold of 0.549 threshold was 85%. The MACK-3 AUROC was not affected by age, sex, diabetes, or BMI. MACK-3 and FAST results were well correlated (Rs=0.781, P < .001). Except an 8% higher rate of patients included in the grey zone, MACK-3 provided similar accuracy to that of FAST. Both tests included 27% of patients in their rule-in zone, with 85% specificity and 35% false positives (screen failure rate). CONCLUSION The blood test MACK-3 is an accurate tool to improve patient selection in NASH therapeutic trials

Validation of the blood test MACK-3 for the noninvasive diagnosis of fibrotic nonalcoholic steatohepatitis : an international study with 1924 patients

Abstract: BACKGROUND & AIMS: Drug development in nonalcoholic steatohepatitis (NASH) is hampered by a high screening failure rate that reaches 60% to 80% in therapeutic trials, mainly because of the absence of fibrotic NASH on baseline liver histology. MACK-3, a blood test including 3 biomarkers (aspartate aminotransferase, homeostasis model assessment, and cytokeratin 18), recently was developed for the noninvasive diagnosis of fibrotic NASH. We aimed to validate the diagnostic accuracy of this noninvasive test in an international multicenter study.METHODS: A total of 1924 patients with biopsy-proven nonalcoholic fatty liver disease from 10 centers in Asia, Australia, and Europe were included. The blood test MACK-3 was calculated for all pa-tients. FibroScan-aspartate aminotransferase score (FAST), an elastography-based test for fibrotic NASH, also was available in a subset of 655 patients. Fibrotic NASH was defined as the presence of NASH on liver biopsy with a Nonalcoholic Fatty Liver Disease Activity Score of 4 or higher and fibrosis stage of F2 or higher according to the NASH Clinical Research Network scoring system.RESULTS: The area under the receiver operating characteristic of MACK-3 for fibrotic NASH was 0.791 (95% CI 0.768-0.814). Sensitivity at the previously published MACK-3 threshold of less than 0.135 was 91% and specificity at a greater than 0.549 threshold was 85%. The MACK-3 area under the receiver operating characteristic was not affected by age, sex, diabetes, or body mass index. MACK-3 and FAST results were well correlated (Spearman correlation coefficient, 0.781; P < .001). Except for an 8% higher rate of patients included in the grey zone, MACK-3 provided similar accuracy to that of FAST. Both tests included 27% of patients in their rule-in zone, with 85% specificity and 35% false positives (screen failure rate).CONCLUSIONS: The blood test MACK-3 is an accurate tool to improve patient selection in NASH therapeutic trials