Ahmad Najib Azmi

Helicobacter pylori Eradication Causes Perturbation of the Human Gut Microbiome in Young Adults

Background Accumulating evidence shows that Helicobacter pylori protects against some metabolic and immunological diseases in which the development of these diseases coincide with temporal or permanent dysbiosis. The aim of this study was to assess the effect of H. pylori eradication on the human gut microbiome. Methods As part of the currently on-going ESSAY (Eradication Study in Stable Adults/Youths) study, we collected stool samples from 17 H. pylori-positive young adult (18–30 years-old) volunteers. The same cohort was followed up 6, 12 and 18 months-post H. pylori eradication. The impact of H. pylori on the human gut microbiome pre- and post-eradication was investigated using high throughput 16S rRNA gene (V3-V4 region) sequencing using the Illumina Miseq followed by data analysis using Qiime pipeline. Results We compared the composition and diversity of bacterial communities in the fecal microbiome of the H. pylori-positive volunteers, before and after H. pylori eradication therapy. The 16S rRNA gene was sequenced at an average of 150,000–170,000 reads/sample. The microbial diversity were similar pre- and post-H. pylori eradication with no significant differences in richness and evenness of bacterial species. Despite that the general profile of the gut microbiome was similar pre- and post-eradication, some changes in the bacterial communities at the phylum and genus levels were notable, particularly the decrease in relative abundance of Bacterioidetes and corresponding increase in Firmicutes after H. pylori eradication. The significant increase of short-chain fatty acids (SCFA)-producing bacteria genera could also be associated with increased risk of metabolic disorders. Conclusions Our preliminary stool metagenomics study shows that eradication of H. pylori caused perturbation of the gut microbiome and may indirectly affect the health of human. Clinicians should be aware of the effect of broad spectrum antibiotics used in H. pylori eradication regimen and be cautious in the clinical management of H. pylori infection, particularly in immunocompromised patients.

Hepatitis C and kidney disease: An overview and approach to management

Hepatitis C infection and chronic kidney disease are major health burden worldwide. Hepatitis C infection is associated with a wide range of extra-hepatic manifestations in various organs including the kidneys. A strong association between hepatitis C and chronic kidney disease has come to light. Hemodialysis in supporting the end stage renal disease patients unfortunately carries a risk for hepatitis C infection. Despite much improvement in the care of this group of patients, the prevalence of hepatitis C infection in hemodialysis patients is still higher than the general population. Hepatitis C infection has a negative effect on the survival of hemodialysis and renal transplant patients. Treatment of hepatitis C in end stage renal disease patients using conventional or pegylated interferon with or without ribavirin remains a clinical challenge with low response rate, high dropout rate due to poor tolerability and many unmet needs. The approval of new direct acting antiviral agents for hepatitis C may dramatically change the treatment approach in hepatitis C infected patients with mild to moderate renal impairment. However it remains to be confirmed if the newer Hepatitis C therapies are safe in individuals with severe renal impairment. This review article discusses the relationship between hepatitis C and chronic kidney disease, describe the various types of renal diseases associated with hepatitis C and the newer as well as the existing treatments for hepatitis C in the context of this subpopulation of hepatitis C patients.

Prevalence of Serum Celiac Antibodies in a Multiracial Asian Population-A First Study in the Young Asian Adult Population of Malaysia

Background Celiac disease (CD) is an immune-mediated disorder induced by the ingestion of gluten in genetically susceptible persons. The prevalence of CD in Malaysia is unknown. We aim to determine the seroprevalence of CD antibodies and also investigate the correlation between H. pylori infection and CD in the young and healthy multiracial Malaysian population. Methods Healthy young adult volunteers between the ages of 18–30 years were consecutively recruited from June 2012 to May 2014 at the University of Malaya Medical Centre (UMMC), Kuala Lumpur. Serum samples from all the participants were tested for anti-gliadin antibody immunoglobulin A/immunoglobulin G (IgA/IgG) and anti-tissue transglutaminase antibody (tTG) IgA/IgG. Samples positive for both anti-gliadin and anti-tTG were further validated for anti-human endomysial IgA antibodies (EmA). Serological diagnosis of CD was made when anti-gliadin, anti-tTG and anti-EmA were positive. Results 562 qualified participants with mean age 24 ± 2.4 years old were recruited into our study. CD was found in 7 participants where most of them were asymptomatic and unaware of their CD status. The median of anti-gliadin and anti-tTG IgA/IgG value was 38.2 U/ml (interquartile range, 28.3–60.4 U/ml) and 49.2 U/ml (interquartile range, 41.1–65.9 U/ml), respectively. Seroprevalence of CD antibodies was 1.9% (6 out of 324) in female while only 0.4% (1 out of 238) in male. Seroprevalence among Malay was 0.8% (2 of 236), Chinese was 1.7% (3 of 177) and Indian was 1.3% (2 of 149). Overall, seroprevalence of CD antibodies in healthy asymptomatic adults in the Malaysian population was 1.25% (95% CI, 0.78%-1.72%). No significant relationship was discovered between CD and H. pylori infection. Conclusions The seroprevalence of CD antibodies in healthy young adults in the Malaysian population was 1.25% (1 in 100). CD is underdiagnosed and it could be a much greater problem in Malaysia than previously thought.

Changes in Metabolic Hormones in Malaysian Young Adults following Helicobacter pylori Eradication

Background More than half of the world’s adults carry Helicobacter pylori. The eradication of H. pylori may affect the regulation of human metabolic hormones. The aim of this study was to evaluate the effect of H. pylori eradication on meal-associated changes in appetite-controlled insulinotropic and digestive hormones, and to assess post-eradication changes in body mass index as part of a currently on-going multicentre ESSAY (Eradication Study in Stable Adults/Youths) study. Methods We enrolled 29 H. pylori-positive young adult (18–30 year-old) volunteer subjects to evaluate the effect of H. pylori eradication on meal-associated changes on eight gastrointestinal hormones, using a multiplex bead assay. Changes in body mass index and anthropometric measurements were recorded, pre- and post-eradication therapy. Results Pre-prandial active amylin, total peptide YY (PYY) and pancreatic polypeptide (PP) levels were significantly elevated 12 months post-eradication compared with baseline (n = 18; Wilcoxons signed rank test, p<0.05). Four of the post-prandial gut metabolic hormones levels (GLP-1, total PYY, active amylin, PP) were significantly higher 12 months post-eradication compared to baseline (n = 18; p<0.05). Following H. pylori eradication, the BMI and anthropometric values did not significantly change. Conclusions Our study indicates that H. pylori eradication was associated with long-term disturbance in three hormones (active amylin, PP and total PYY) both pre- and post-prandially and one hormone (GLP-1) post-prandially. Longer post-eradication monitoring is needed to investigate the long-term impact of the observed hormonal changes on metabolic homeostasis.

Sustained complete remission of advanced hepatocellular carcinoma with sorafenib therapy

Hepatocellular carcinoma (HCC) is the fifth and seventh most commonly diagnosed carcinoma as well as the second and sixth most common cause of cancerrelated death in men and women, respectively, worldwide. It is also an important cancer in the Asia–Pacific region. In a recent report from our center in Malaysia, the late presentations in most of our patients with HCC were summerized. Curative therapies are limited and might be performed in selected patients only. Sorafenib (Nexavar, Bayer, Berlin, Germany) has been approved by the United States Food and Drug Administration (FDA) in November 2007 as the firstline treatment for advanced HCC. The landmark Sorafenib Hepatocellular Carcinoma Assessment Randomized Protocol (SHARP) trial showed that the median survival and time to radiological progression in patients treated with sorafenib were nearly 3 months longer than in those received placebo. Similar results were observed in another phase III randomized, double-blind, placebo-controlled trial carried out in the Asia–Pacific region. However, no patients achieved complete response of HCC in either study, although a complete response of advanced HCC to sorafenib has been reported in several case reports. In this study we reported a patient who achieved sustained complete remission after treated with sorafenib.

Global Fecal and Plasma Metabolic Dynamics Related to Helicobacter pylori Eradication

Background: Helicobacter pylori colonizes the gastric mucosa of more than half of the worlds population. There is increasing evidence H. pylori protects against the development of obesity and childhood asthma/allergies in which the development of these diseases coincide with transient dysbiosis. However, the mechanism underlying the association of H. pylori eradication with human metabolic and immunological disorders is not well-established. In this study, we aimed to investigate the local and systemic effects of H. pylori eradication through untargeted fecal lipidomics and plasma metabolomics approaches by liquid chromatography mass spectrometry (LC-MS). Results: Our study revealed that eradication of H. pylori eradication (i.e., loss of H. pylori and/or H. pylori eradication therapy) changed many global metabolite/lipid features, with the majority being down-regulated. Our findings primarily show that H. pylori eradication affects the host energy and lipid metabolism which may eventually lead to the development of metabolic disorders. Conclusion: These predictive metabolic signatures of metabolic and immunological disorders following H. pylori eradication can provide insights into dynamic local and systemic metabolism related to H. pylori eradication in modulating human health.

Practical approach in hepatitis B e antigen-negative individuals to identify treatment candidates.

The natural history of chronic hepatitis B is characterized by different phases of infection, and patients may evolve from one phase to another or may revert to a previous phase. The hepatitis B e antigen (HBeAg)-negative form is the predominant infection worldwide, which consists of individuals with a range of viral replication and liver disease severity. Although alanine transaminase (ALT) remains the most accessible test available to clinicians for monitoring the liver disease status, further evaluations are required for some patients to assess if treatment is warranted. Guidance from practice guidelines together with thorough investigations and classifications of patients ensure recognition of who needs which level of care. This article aims to assist physicians in the assessment of HBeAg-negative individuals using liver biopsy or non-invasive tools such as hepatitis B s antigen quantification and transient elastography in addition to ALT and hepatitis B virus DNA, to identify who will remain stable, who will reactivate or at risk of disease progression hence will benefit from timely initiation of anti-viral therapy.

Gastric Metastasis from Hepatocellular Carcinoma: A Rare Manifestation

Gastric involvement due to metastasis by primary hepatocellular carcinoma (HCC) is rare [1, 2]. It has usually been reported to occur as a consequence of direct invasion of the tumour [3] (from the left lobe of liver) or from contamination due to intraperitoneal surgical instrumentation. Metastasis via either lymphatic or haematogenous spread is not common [3]. We report a case of gastric involvement by HCC whereby no other mechanism could have caused it other than via metastasis.

Optimising first line seven day standard triple therapy for H.PYLORI Eradication: Prolonging treatment or adding bismuth- which is better?: Optimising therapy for H.pylori

The 7‐day standard triple therapy (STT) gives unacceptablly low eradication rates of Helicobacter pylori (H. pylori). We aimed to examine whether extending STT from 7 days to 14 days or adding a bismuth compound to a 7‐day STT would result in better eradication rates.

Endoscopic Submucosal Dissection Outcomes for Gastroesophageal Tumors in Low Volume Units: A Multicenter Survey

Background and Aims. Endoscopic submucosal dissection (ESD) outcomes have traditionally been reported from high volume centers in East Asia. Data from low volume centers in other parts of Asia remain sparse. Methods. A retrospective survey with a structured questionnaire of 5 tertiary centers in 3 countries in South East Asia was conducted. Details of training and clinical outcomes of ESD cases, with follow-up data from these centers, were analyzed. Results. Seven endoscopists from the 5 centers performed a total of 35 cases of ESD in the upper gastrointestinal tract (UGIT) over a 6-year duration. Details of the lesions excised were as follows: median size was 20 mm, morphologically 20 (68.6%) were flat/depressed and 6 (17.1%) were submucosal, and histologically 27 (77.1%) were neoplastic. The median duration of ESD procedures was 105 minutes, with an en-bloc resection rate of 91.4%. There was 1 (2.9%) case of delayed bleeding, but no perforation nor mortality in any of the cases. The recurrence rate after ESD was 5.7%. A prolonged ESD duration was influenced by a larger size of lesion (25 mm, p = 0.02) but not by factors related to the training experience of endoscopists. Conclusions. ESD in the UGIT is feasible and safe in low volume centers in Asia.