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A systematic review with meta-analysis: Efficacy and safety of potassium-competitive acid blocker compared with proton pump inhibitor in the maintenance of healed erosive esophagitis

Simadibrata DM, Lesmana E, Pratama MIA, Sugiharta AJ, Winarizal AS, Lee YY, et al.

JGH Open, 2024 Mar;8(3):e13053.
PMID: 38523708 DOI: 10.1002/jgh3.13053

INTRODUCTION: Proton pump inhibitor (PPI) is the mainstay therapy for the maintenance of healed erosive esophagitis (EE). It is unknown whether potassium-competitive acid blockers (PCABs) are more efficacious and safer than PPIs.
METHODS: Only randomized controlled trials (RCTs) comparing PCABs to PPIs in the maintenance of healing rates of endoscopically proven healed EE and indexed in MEDLINE, EMBASE, and CENTRAL until 3 February 2024, were included. A fixed-effects model meta-analysis was performed to pool primary efficacy outcome (maintenance of healing rates at week 24) and safety data (any treatment-emergent adverse event or TEAE). The risk of bias was assessed using Cochrane's Risk of Bias 2 (RoB2) tool.
RESULTS: Four RCTs with a total of 2554 patients were eligible for inclusion. All trials were of low risk of bias. Compared to lansoprazole 15 mg, the maintenance rates of healed EE at week 24 were significantly higher with vonoprazan 10 mg (RR 1.13; 95% CI 1.07-1.19) and vonoprazan 20 mg (RR 1.15; 95% CI 1.10-1.21). Likewise, compared to lansoprazole 15 mg, any TEAEs were significantly greater with vonoprazan 20 mg (RR 1.10; 95% CI 1.01-1.20) but not vonoprazan 10 mg.
CONCLUSION: Vonoprazan 10 and 20 mg were superior to lansoprazole 15 mg in the maintenance of the healing of EE. Any TEAEs were greater with vonoprazan 20 mg.
Fulltext Probiotics for Parkinson's disease: Current evidence and future directions

Tan AH, Hor JW, Chong CW, Lim SY

JGH Open, 2021 Apr;5(4):414-419.
PMID: 33860090 DOI: 10.1002/jgh3.12450

The gut-brain axis is a hot topic in Parkinson's disease (PD). It has been postulated that gut pathogens and dysbiosis can contribute to peripheral inflammatory states or trigger downstream metabolic effects that exacerbate the neurodegenerative process in PD. Several preclinical and clinical studies have demonstrated disrupted intestinal permeability, intestinal inflammation, altered gut microbiome, and reduced fecal short-chain fatty acids in PD. In this regard, microbial-directed therapies such as probiotics are emerging as potential therapeutic options. Probiotic supplementation is postulated to confer a variety of health benefits due to the diverse functions of these live microorganisms, including inhibition of pathogen colonization, modulation/"normalization" of the microbiome and/or its function, immunomodulatory effects (e.g. reducing inflammation), and improved host epithelial barrier function. Interestingly, several PD animal model studies have demonstrated the potential neuroprotective effects of probiotics in reducing dopaminergic neuronal degeneration. Notably, two randomized placebo-controlled trials have provided class I evidence for probiotics as a treatment for constipation in PD. However, the effects of probiotics on other PD aspects, such as motor disability and cognitive function, and its long-term efficacy (including effects on PD drug absorption in the gut) have not been investigated adequately. Further targeted animal and human studies are also warranted to understand the mechanisms of actions of probiotics in PD and to tailor probiotic therapy based on individual host profiles to improve patient outcomes in this disabling disorder.
Fulltext Association between non-alcoholic fatty liver disease evaluated by transient elastography with extracranial carotid atherosclerosis in a multiethnic Asian community

Tan EC, Tai MS, Chan WK, Mahadeva S

JGH Open, 2019 Apr;3(2):117-125.
PMID: 31061886 DOI: 10.1002/jgh3.12114

Background and Aim: There is not much data on the association between non-alcoholic fatty liver disease (NAFLD) and advanced fibrosis assessed using Fibroscan with carotid intima-media thickness (CIMT) in the general population. The objective of this study was to evaluate the association between NAFLD and advanced fibrosis, as diagnosed by Fibroscan, with an increased CIMT in the Malaysian population.
Methods: A cross-sectional study of government officers and their family members attending a health screening at a public healthcare facility was conducted. All subjects underwent clinical evaluation, biochemical testing, anthropometry, ultrasound carotid Doppler, and Fibroscan examination.
Results: Data for 251 subjects were analyzed (mean age 47.1 ± 12.4 years, 74.1% male). Prevalence of NAFLD and advanced fibrosis were 57.4 and 17.5%, respectively. Independent factors associated with NAFLD were waist circumference (odds ratio [OR] = 1.077, 95% confidence interval [CI] 1.038-1.118, P < 0.001) and serum alanine aminotransferase (ALT) (OR = 1.039, 95% CI 1.005-1.074, P = 0.024). Independent factors associated with advanced fibrosis were male gender (OR = 4.847, 95% CI 1.369-17.155, P = 0.014) and serum aspartate aminotransferase (AST) (OR = 1.057, 95% CI 1.003-1.113, P = 0.036). Prevalence of increased CIMT was 29.0%. Independent factor associated with increased CIMT was older age (OR = 1.146, 95% CI 1.067-1.231, P < 0.001). Of the subjects, 34.5% with NAFLD had increased CIMT compared to 19.1% of the subjects without NAFLD (P = 0.063). Advanced fibrosis was not associated with increased CIMT.
Conclusions: Prevalence of NAFLD, advanced liver fibrosis, and increased CIMT were high. NAFLD and advanced liver fibrosis appeared not to be associated with increased CIMT. However, a larger sample size is needed to demonstrate whether there is any association.
Fulltext Kombiglyze (metformin and saxagliptin)-induced hepatotoxicity in a patient with non-alcoholic fatty liver disease

Thalha AM, Mahadeva S, Boon Tan AT, Mun KS

JGH Open, 2018 Oct;2(5):242-245.
PMID: 30483596 DOI: 10.1002/jgh3.12083

A 33-year-old man was referred with hyperosmotic symptoms of 4 weeks. Clinical examination showed palpable hepatomegaly and no stigmata of liver disease. Findings were random glucose 16.6 mmol/L, HbA1c 12.4%, triglyceride 6.2 mmol/L, normal LFTs and ultrasound liver: increased echogenicity. Management consisted of dietician referral and commencement of metformin 500 mg bd, diamicron MR 60 mg od, and fenofibrate 145 mg od. He was non-compliant, complaining of "heaviness of head" after consuming oral diabetic agents, without symptoms of hypoglycemia. Treatment was switched to Kombiglyze XR (saxaglipitin 5 mg + metformin 1000 mg) and empagliflozin 25 mg od. He presented 1 week later with generalised pruritus with ALT 307 IU/L and serum GGT 808 IU/L. Following this, a percutaneous liver biopsy was performed, revealing steatohepatitis and marked intra-hepatic cholestasis. Kombiglyze XR was withheld, with resolution of LFTs to baseline. Phenotypes of liver injury are categorised according to R value, defined as ratio ALT/ULN:ALP/ULN. R value of ≥5:hepatocellular injury, ≤2:cholestatic injury, 2-5:mixed-type injury. Here, R value points toward mixed type (R = 3.203). Hepatotoxicity in patients with NASH is difficult to diagnose, based on laboratory parameters. Liver histology was useful in indicating additional changes apart from NASH, causing liver derangement. The Rousal Uclaf Causality Assessment Method is a scoring method to determine the probability of drug induced liver injury. RUCAM score for this case was 6 (probable adverse drug reaction). Hepatotoxicity from saxagliptin not been reported prior. Clinicians need to be more vigilant, particularly in patients with NASH.
Epidemiology of non-alcoholic fatty liver disease-related hepatocellular carcinoma and its implications

Wong SW, Ting YW, Chan WK

JGH Open, 2018 Oct;2(5):235-241.
PMID: 30483595 DOI: 10.1002/jgh3.12070

Hepatocellular carcinoma (HCC) is the fifth most common cancer and the second leading cause of cancer-related mortality worldwide. Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver pathology that is characterized by the excessive accumulation of fat in the liver attributable to overnutrition and is strongly associated with the metabolic syndrome. Non-alcoholic steatohepatitis is the more severe form of NAFLD that is defined histologically by the presence of lobular inflammation and hepatocyte ballooning. Non-alcoholic steatohepatitis patients have a greater tendency to develop advanced liver fibrosis, cirrhosis, and HCC. This review focuses on the epidemiology of NAFLD-related HCC and its implications. NAFLD has been estimated to contribute to 10-12% of HCC cases in Western populations and 1-6% of HCC cases in Asian populations. NAFLD-related HCC is expected to increase in Asian populations, in line with the increased prevalence of NALFD similar to that of Western populations in recent years. The increasing burden of NAFLD-related HCC over time has been demonstrated in studies from both Western and Asian populations. Certain factors such as ethnicity, obesity, and diabetes mellitus appear to have an incremental effect on the risk of developing HCC among NAFLD patients. The difficulty in identifying NAFLD patients with cirrhosis and the possibility of HCC developing in noncirrhotic NAFLD patients are challenges that need to be addressed. Further understanding of these gaps may contribute to better surveillance strategies for the early detection of HCC in NAFLD patients to reduce the mortality and improve the survival of these patients.
Early experience with a low FODMAP diet in Asian patients with irritable bowel syndrome

Wong Z, Mok CZ, Majid HA, Mahadeva S

JGH Open, 2018 Oct;2(5):178-181.
PMID: 30483586 DOI: 10.1002/jgh3.12069

Background: The efficacy and acceptance of a low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet in Asian adults with irritable bowel syndrome (IBS) remain uncertain. We aimed to describe our early experience in a single center with a dedicated gastroenterology dietetic service.

Methods: Consecutive patients with IBS referred to our dedicated Dietetic Gastroenterology Clinic between February 2016 and May 2016 were screened. A low FODMAP diet was instituted as per standard protocol. Data on demographic and clinical variables were obtained from patients' records and prospective telephone interviews.

Results: A total of 16 patients, with a median age of 67 ± 13.57 years; female gender n = 10 (62.5%); ethnicity: Chinese n = 8 (50%), Indian n = 5 (31.25%), and Malay n = 3 (18.75%) with IBS, were included in the study. Compliance with the low FODMAP diet was complete in 8 of 16 (50%) patients, partial in 4 of 16 (25%), and 4 of 16 (25%) could not comply with the diet at all. Improvement in symptoms were reported in 11 of 16 (68.8%) patients. Among patients who complied (complete/partial) with the low FODMAP diet, predominant symptom improvement was reported as follows: abdominal pain 3 of 5 (60%), abdominal bloating/distension 7 of 10 (70%), and flatulence 7 of 8 (87.5%). Patients with the IBS-D subtype appeared to have the greatest improvement in stool consistency (87.5% IBS-D vs 12.5% non-IBS-D, P = 0.009).

Conclusion: Based on our pilot observational study of a relatively small sample of Asian IBS patients, compliance with a low FODMAP diet appears to be low. Further larger studies are required to verify our observation.

Study site: Universiti Malaya Medical Centre (UMMC)
Fulltext A case of urgent colonoscopic hemostasis of a cecal hemorrhagic ulceration in a patient receiving heparin for COVID-19 coagulopathy

Yoshida N, Hirose R, Watanabe M, Yamazaki M, Hashimoto S, Matsubara S, et al.

JGH Open, 2021 Jan;5(1):160-162.
PMID: 33490630 DOI: 10.1002/jgh3.12435

COVID-19 rarely causes lower gastrointestinal bleeding even though its RNA has been detected in patient's stool. Urgent colonoscopy in a COVID-19 patient with massive bloody stool requires various procedural and equipment considerations. Here, we present a case of colonoscopic hemostasis of a cecal hemorrhagic ulceration in a patient on heparin for COVID-19 coagulopathy. We also share various management methods for the prevention of COVID-19 contamination. A 71-year-old man was diagnosed with COVID-19 pneumonia and subsequently underwent hemodiafiltration. Heparin was initiated for COVID-19 coagulopathy. At day 42, the patient experienced 2000 mL of bloody stool. An operator performed urgent colonoscopy with three assistants in a negative-pressure room with full personal protective equipment. A hemorrhagic ulceration was detected at the cecum, and endoscopic hemostasis was performed. Immunohistochemistry was positive for cytomegalovirus. Postprocedure, the endoscopic systems were thoroughly cleaned, and specific measures for endoscope reprocessing and disinfection were performed to prevent contamination with COVID-19.
Fulltext Use of simple scoring systems for a public health approach in the management of non-alcoholic fatty liver disease patients

Zain SM, Tan HL, Mohamed Z, Chan WK, Mahadeva S, Basu RC, et al.

JGH Open, 2020 Dec;4(6):1155-1161.
PMID: 33319051 DOI: 10.1002/jgh3.12414

Background and Aim: Advanced fibrosis is the most important predictor of liver-related mortality in non-alcoholic fatty liver disease (NAFLD). The aim of this study was to compare the diagnostic performance of noninvasive scoring systems in identifying advanced fibrosis in a Malaysian NAFLD cohort and propose a simplified strategy for the management of NAFLD in a primary care setting.
Methods: We enrolled and reviewed 122 biopsy-proven NAFLD patients. Advanced fibrosis was defined as fibrosis stages 3-4. Noninvasive assessments included aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio, AST-to-platelet ratio index (APRI), AST/ALT ratio, diabetes (BARD) score, fibrosis-4 (FIB-4) score, and NAFLD fibrosis score.
Results: FIB-4 score had the highest area under the receiver operating characteristic curve (AUROC) and negative predictive value (NPV) of 0.86 and 94.3%, respectively, for the diagnosis of advanced fibrosis. FIB-4 score
Actual and estimated adenoma detection rates: a 2-year monocentric colonoscopic screening outcome in Shenzhen, China

Zeng L, Chua EG, Xiong Y, Ding S, Ai H, Hou Z, et al.

JGH Open, 2020 Aug;4(4):707-712.
PMID: 32782960 DOI: 10.1002/jgh3.12322

Background and Aim: While adenoma detection rate (ADR) is an important quality metric for screening colonoscopy, it remains difficult to be accessed due to the lack of integrated endoscopy and pathology databases. Hence, the use of an adenoma-to-polyp detection rate quotient and polyp detection rate (PDR) has been proposed to predict ADR. This study aimed to examine the usefulness of estimated ADR across different colonic segments in two age groups for Shenzhen people in China.
Methods: We retrospectively analyzed 7329 colonoscopy procedures performed by 12 endoscopists between January 2012 and February 2014. The PDR, actual ADR, and estimated ADR of the entire, proximal, and distal colon, and within each colonic segment, in two patient age groups: <50 and ≥50 years, were calculated for each endoscopist.
Results: The overall polyp and adenoma prevalence rates were 19.1 and 9.3%, respectively. The average age of adenoma-positive patients was significantly higher than that of adenoma-negative patients (54 ± 12.6 years vs 42.9 ± 13.2 years, respectively). A total of 1739 polyps were removed, among which 826 were adenomas. More adenomatous polyps were found in the proximal colon (60.4%, 341/565) than in the distal colon (40.9%, 472/1154). Overall, both actual and estimated ADR correlated strongly at the entire colon level and within most colonic segments, except for the cecum and rectum. In both age groups, these parameters correlated strongly within the traverse colon and descending colon.
Conclusion: Caution should be exercised when predicting ADR within the sigmoid colon and rectum.
Fulltext Low fermentable oligosaccharides, disaccharides, monosaccharides, and polypols diet and irritable bowel syndrome in Asia

Zhang Y, Ma ZF, Zhang H, Pan B, Li Y, Majid HA, et al.

JGH Open, 2019 Apr;3(2):173-178.
PMID: 31061894 DOI: 10.1002/jgh3.12125

Functional bowel disorders, including irritable bowel syndrome (IBS), are a chronic condition that can significantly reduce patients' quality of life. Therefore, this paper will review the roles of a low fermentable oligosaccharides, disaccharides, monosaccharides, and polypols (FODMAP) diet in treating IBS, particularly in an Asian setting. About 20% of the general population is diagnosed with IBS. However, there are limited effective medical therapies available for treating IBS. Therefore, IBS presents a major challenge to the health-care providers. Recently, there is an increasing interest in the use of a diet low in FODMAP for the treatment of IBS. A low FODMAP diet can decrease the delivery of readily fermentable substrates to the small intestine and colon, thereby improving functional gastrointestinal symptoms.

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