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Displaying publications 41 - 44 of 44 in total

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Liver cirrhosis in Malaysia: peculiar epidemiology in a multiracial Asian country

Qua CS, Goh KL

J Gastroenterol Hepatol, 2011 Aug;26(8):1333-7.
PMID: 21443669 DOI: 10.1111/j.1440-1746.2011.06732.x

To determine the etiology of liver cirrhosis and risk factors for hepatocellular carcinoma (HCC) in a multiracial Asian population.

Matched MeSH terms: Hepatitis C, Chronic/ethnology
CD8+ T cells of chronic HCV-infected patients express multiple negative immune checkpoints following stimulation with HCV peptides

Barathan M, Mohamed R, Vadivelu J, Chang LY, Vignesh R, Krishnan J, et al.

Cell Immunol, 2017 03;313:1-9.
PMID: 28104239 DOI: 10.1016/j.cellimm.2016.12.002

Hepatitis C virus (HCV)-specific CD4+ and CD8+ T cells are key to successful viral clearance in HCV disease. Accumulation of exhausted HCV-specific T cells during chronic infection results in considerable loss of protective functional immune responses. The role of T-cell exhaustion in chronic HCV disease remains poorly understood. Here, we studied the frequency of HCV peptide-stimulated T cells expressing negative immune checkpoints (PD-1, CTLA-4, TRAIL, TIM-3 and BTLA) by flow cytometry, and measured the levels of Th1/Th2/Th17 cytokines secreted by T cells by a commercial Multi-Analyte ELISArray™ following in vitro stimulation of T cells using HCV peptides and phytohemagglutinin (PHA). HCV peptide-stimulated CD4+ and CD8+ T cells of chronic HCV (CHC) patients showed significant increase of CTLA-4. Furthermore, HCV peptide-stimulated CD4+ T cells of CHC patients also displayed relatively higher levels of PD-1 and TRAIL, whereas TIM-3 was up-regulated on HCV peptide-stimulated CD8+ T cells. Whereas the levels of IL-10 and TGF-β1 were significantly increased, the levels of pro-inflammatory cytokines IL-2, TNF-α, IL-17A and IL-6 were markedly decreased in the T cell cultures of CHC patients. Chronic HCV infection results in functional exhaustion of CD4+ and CD8+ T cells likely contributing to viral persistence.

Matched MeSH terms: Hepatitis C, Chronic/immunology*
Increased frequency of late-senescent T cells lacking CD127 in chronic hepatitis C disease

Barathan M, Mohamed R, Saeidi A, Vadivelu J, Chang LY, Gopal K, et al.

Eur J Clin Invest, 2015 May;45(5):466-74.
PMID: 25721991 DOI: 10.1111/eci.12429

Hepatitis C virus (HCV) causes persistent disease in ~85% of infected individuals, where the viral replication appears to be tightly controlled by HCV-specific CD8+ T cells. Accumulation of senescent T cells during infection results in considerable loss of functional HCV-specific immune responses.

Matched MeSH terms: Hepatitis C, Chronic/immunology*
Deriving the optimal limit of detection for an HCV point-of-care test for viraemic infection: analysis of a global dataset

Morgan Freiman J, Wang J, Easterbrook PJ, Robert Horsburgh C, Marinucci F, White LF, et al.

J Hepatol, 2019 Feb 20.
PMID: 30797050 DOI: 10.1016/j.jhep.2019.02.011

BACKGROUND & AIMS: Affordable point-of-care (POC) tests for hepatitis C (HCV) viraemia are needed to improve access to treatment in low and middle income countries (LMICs). Our aims were to determine the target limit of detection (LOD) necessary to diagnose the majority of persons with HCV eligible for treatment, and identify characteristics associated with low-level viraemia (LLV) (defined as the lowest 3% of the distribution of HCV RNA) to understand those at risk of being mis-diagnosed.
METHODS: We established a multi-country cross-sectional dataset of first available quantitative HCV RNA linked to demographic and clinical data. We excluded individuals on HCV treatment. We analyzed the distribution of HCV RNA and determined critical thresholds for detection of HCV viraemia. We then performed logistic regression to evaluate factors associated with LLV, and derived relative sensitivities for significant covariates.
RESULTS: The dataset included 66,640 individuals with HCV viraemia from Georgia (44.4%), Canada (40.9%), India (8.1%), Cambodia (2.6%), Egypt (1.6%), Pakistan (1.3%), Cameroon (0.4%), Indonesia (0.2%), Thailand (0.2%), Vietnam (0.1%), Malaysia (0.05%), and Mozambique (0.02%). The 97% LOD was 1,318 IU/mL (95% CI 1298.4, 1322.3). Factors associated with LLV were younger age 18-30 vs. 51-64 years (OR 2.56 95% CI 2.19, 2.99), female vs. male sex (OR 1.32, 95% CI 1.18, 1.49), and advanced fibrosis stage F4 vs. F0-1 (OR 1.44, 95%CI 1.21, 1.69). Only the younger age group had a decreased relative sensitivity below 95% at 93.3%.
CONCLUSIONS: In this global dataset, a test with an LOD of 1,318 IU/mL would identify 97% of viraemic HCV infections among almost all populations. This LOD will help guide manufacturers in the development of affordable POC diagnostics to expand HCV testing and linkage to care in LMICs.
LAY SUMMARY: We created and analyzed a dataset from 12 countries with 66,640 participants with chronic hepatitis C virus infection. We determined that about 97% of those with viraemic infection had 1300 International Units/mL or more of circulating virus at the time of diagnosis. While current diagnostic tests can detect as little as 12 International Units/mL of virus, our findings suggest that increasing the level of detection closer to 1300 would maintain good test accuracy and will likely allow for more affordable portable tests to be developed for use in low and middle income countries.

Matched MeSH terms: Hepatitis C, Chronic