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  1. Azmi AN, Tan SS, Mohamed R
    World J Hepatol, 2015 Jan 27;7(1):78-92.
    PMID: 25624999 DOI: 10.4254/wjh.v7.i1.78
    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.
  2. Azmi AN, Tan SS, Mohamed R
    World J Gastroenterol, 2014 Sep 14;20(34):12045-55.
    PMID: 25232242 DOI: 10.3748/wjg.v20.i34.12045
    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.
  3. Wan Ibrahim NR, Chan HK, Soelar SA, Azmi AN, Mohd Said R, Abu Hassan MR
    Asian Pac J Cancer Prev, 2020 Apr 01;21(4):1057-1061.
    PMID: 32334470 DOI: 10.31557/APJCP.2020.21.4.1057
    BACKGROUND: While the world witnesses an increasing trend of young-onset colorectal cancer (CRC), the information regarding the impact of age on CRC is limited in Malaysia. This study aimed to compare the incidence, clinic-demographic profiles and survival rates of CRC between patients above and under 50 years of age in northern Malaysia.

    METHODS: This was a registry-based, cross-sectional study. All the CRC cases reported by 18 hospitals to the National Cancer Patient Registry - Colorectal Cancer (NCPR-CC) between January 2007 and December 2017 were included in the analysis. The patients were categorized by age into the above-50 and under-50 groups. The changes in the age-standardized incidence and mortality rates of both the age groups were determined using the time-series analysis, and the impact of age on the mortality risk was assessed using the Cox regression analysis.

    RESULTS: Of the 6,172 CRC patients enrolled in the NCPR-CC, 893 (14.5%) were in the under-50 group. As compared with their older counterparts, the patients in the under-50 group were more likely to be female, be of Malay ethnicity, be non-smokers, have a family history of CRC, and present late for treatment. The age-standardized incidence and mortality rates of CRC in the under-50 group remained stable over the years, while a decreasing trend was clearly seen in the mortality rates of CRC in the above-50 group (p=0.003). Nevertheless, the two age groups also did not differ in the mortality risk (adjusted hazards ratio: 1.10; 95% CI: 0.90, 1.36).

    CONCLUSION: Young-onset CRC constituted a considerable proportion of CRC cases in Malaysia. However, in contrast with the findings of most studies, it demonstrated neither an uptrend in age-standardized incidence rates nor a higher mortality risk. Our findings suggest the need to upscale and lower the recommended age for CRC screening in Malaysia.

  4. Leow AH, Azmi AN, Loke MF, Vadivelu J, Graham DY, Goh KL
    J Dig Dis, 2018 Nov;19(11):674-677.
    PMID: 30307122 DOI: 10.1111/1751-2980.12679
    OBJECTIVE: 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.

    METHODS: H. pylori-positive patients were assigned to Group A (7-day STT; rabeprazole 20 mg twice daily, amoxicillin 1 g twice daily, and clarithromycin 500 mg twice daily, for 7 days), Group B (7-day STT with bismuth; rabeprazole 20 mg twice daily, amoxicillin 1 g twice daily, clarithromycin 500 mg twice daily and bismuth subcitrate 240 mg twice daily, for 7 days) and Group C (14-day STT; rabeprazole 20 mg twice daily, amoxicillin 1 g twice daily, and clarithromycin 500 mg twice daily for 14 days). Eradication was tested using 13 C-UBT at least 4 weeks after the completion of therapy.

    RESULTS: A total of 364 patients were recruited. In the intention-to-treat analysis, eradication rates were 79.3% (96/121; 95% confidence interval [CI] 71.3-85.6%) for 7-day STT, 81.7% (98/120; 95% CI 73.8-87.6%) for 7-day STT with bismuth, and 88.6% (109/123; 95% CI 81.8-93.1%) for 14-day STT, respectively. Statistical significance was achieved between the 7-day and the 14-day STT treatment (P = 0.048).

    CONCLUSIONS: Adding bismuth to the 7-day STT did not result in an increase in the eradication rate. Extending the STT to 14 days, however, achieved a significantly higher eradication rate. Nevertheless, this did not achieve the targeted 90% eradication rate on intention-to-treat analysis.

  5. Yap TW, Chan WK, Leow AH, Azmi AN, Loke MF, Vadivelu J, et al.
    PLoS One, 2015;10(3):e0121908.
    PMID: 25799401 DOI: 10.1371/journal.pone.0121908
    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.

  6. Yap TW, Leow AH, Azmi AN, Callahan DL, Perez-Perez GI, Loke MF, et al.
    Front Microbiol, 2017;8:536.
    PMID: 28424674 DOI: 10.3389/fmicb.2017.00536
    Background:Helicobacter pylori colonizes the gastric mucosa of more than half of the world's 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.
  7. Yap TW, Leow AH, Azmi AN, Francois F, Perez-Perez GI, Blaser MJ, et al.
    PLoS One, 2015;10(8):e0135771.
    PMID: 26291794 DOI: 10.1371/journal.pone.0135771
    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.
  8. Yap TW, Gan HM, Lee YP, Leow AH, Azmi AN, Francois F, et al.
    PLoS One, 2016;11(3):e0151893.
    PMID: 26991500 DOI: 10.1371/journal.pone.0151893
    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.

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