METHODS: This study aimed to conduct a 5-year budget impact analysis of the proposed stratified treatment cascade for HCV treatment in Malaysia. A disease progression model that was developed based on model-predicted HCV epidemiology data was used for the analysis, where all HCV patients in scenario A were treated with SOF/DAC for all disease stages while in scenario B, SOF/DAC was used only for non-cirrhotic patients and SOF/VEL was used for the cirrhotic patients. Healthcare costs associated with DAA therapy and disease stage monitoring were included to estimate the downstream cost implications.
RESULTS: The stratified treatment cascade with 109 in Scenario B was found to be cost-saving compared to Scenario A. The cumulative savings for the stratified treatment cascade was USD 1.4 million over 5 years.
DISCUSSION: A stratified treatment cascade with SOF/VEL was expected to be cost-saving and can result in a budget impact reduction in overall healthcare expenditure in Malaysia.
SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-023-03479-1.
AIMS: This review focuses on outlining the findings of studies that have been conducted to display the glycemic effect of Catha edulis, while trying to balance it with findings of the association of its chewing with the development of type 2 diabetes mellitus (DM).
MATERIALS AND METHODS: The search strategy adopted was based on a comprehensive research in Medline, PubMed, Web of Science, JSTOR, Scopus and Cochrane for articles, proceeding abstracts and theses to identify complete reports written in the English language about the glycemic effect of Catha edulis in humans and animals from 1976 to 2016. In addition, bibliographies were also reviewed to find additional reports not otherwise published. Thirty seven records were identified of which, 25 eligible studies were included in the meta-analysis using blood glucose as an outcome measurement. Studies were divided into four subgroups according to the experimental model, namely; non-diabetic animals, diabetic animals, non-diabetic humans and diabetic humans. The pooled mean difference (MD) of blood glucose between experimental and control were calculated using random effects model of the weighted mean difference of blood glucose with 95% confidence interval (CI). Heterogeneity between studies was tested using I(2) statistic and a value of P<0.05 was considered to indicate statistical significance.
RESULTS: The scientific reports in the literature prevailed that the glycemic effect of Catha edulis were greatly conflicting with the majority of studies indicating that Catha edulis has a mild hypoglycemic effect. However, the meta-analysis indicted that the overall result showed an insignificant reduction in blood glucose (MD=-9.70, 95% CI: -22.17 to 2.76, P=0.13, with high heterogeneity between subgroups, I(2)=88.2%, P<0.0001). In addition, pooled mean difference of blood glucose of non-diabetic animals, diabetic animals and non-diabetic humans showed an insignificant reduction in blood glucose (MD=-18.55, 95% CI: -39.55 to 2.50, P<0.08, MD=-52.13%, 95% CI: -108.24 to 3.99, P=0.07 and MD=-2.71%, 95% CI: -19.19 to -13.77, P=0.75) respectively. Conversely, a significant elevation in the pooled mean difference of blood glucose in diabetic humans was indicated (MD=67.18, 95% CI: 36.93-97.43, P<0.0001). The conflict shown in the glycemic effect of Catha edulis is thought to be cultivar-related, while demographic and epidemiological reports suggested that chewing Catha edulis might be a predisposing factor contributing to the development of type 2 DM.
CONCLUSION: It was difficult to draw a meaningful conclusion from both the systematic and the meta-analysis with respect to the glycemic effect of Catha edulis since the meta-analysis results were insignificant with high heterogeneity among subgroups and are greatly conflicting. The variation is most likely due to unadjusted experimental factors or is related to Catha edulis itself, such as the differences in the phytochemical composition. Therefore, it is highly recommended that further studies of the glycemic effect of the cultivar of Catha edulis being studied should come with the identification and quantification of phytochemical content so that a meaningful assessment can be made with regard to its hypoglycemic properties. In addition, well-controlled clinical studies should be conducted to confirm whether or not chewing Catha edulis is associated with the development of type 2 DM, since this would be a source of concern seeing that the plant is widely consumed in certain populations.
METHODS: The genotypes were assessed on 144 histologically confirmed NAFLD patients and 198 controls using a Sequenom MassARRAY platform.
RESULTS: The GCKR rs1260326 and rs780094 allele T were associated with susceptibility to NAFLD (OR 1.49, 95 % CI 1.09-2.05, p = 0.012; and OR 1.51, 95 % CI 1.09-2.09, p = 0.013, respectively), non-alcoholic steatohepatitis (NASH) (OR 1.55, 95 % CI 1.10-2.17, p = 0.013; and OR 1.56, 95 % CI 1.10-2.20, p = 0.012, respectively) and NASH with significant fibrosis (OR 1.50, 95 % CI 1.01-2.21, p = 0.044; and OR 1.52, 95 % CI 1.03-2.26, p = 0.038, respectively). Following stratification by ethnicity, significant association was seen in Indian patients between the two SNPs and susceptibility to NAFLD (OR 2.64, 95 % CI 1.28-5.43, p = 0.009; and OR 4.35, 95 % CI 1.93-9.81, p < 0.0001, respectively). The joint effect of GCKR with adiponutrin rs738409 indicated greatly increased the risk of NAFLD (OR 4.14, 95 % CI 1.41-12.18, p = 0.010). Histological data showed significant association of GCKR rs1260326 with high steatosis grade (OR 1.76, 95 % CI 1.08-2.85, p = 0.04).
CONCLUSION: This study suggests that risk allele T of the GCKR rs780094 and rs1260326 is associated with predisposition to NAFLD and NASH with significant fibrosis. The GCKR and PNPLA3 genes interact to result in increased susceptibility to NAFLD.
METHODS: Consecutive biopsy-proven NAFLD patients and controls without fatty liver were recruited for this study between 2009 and 2014. Genotyping for HSD17B13 variants was performed using rhAmp assays. A total of 165 patients with NAFLD were monitored up until August 2019. Clinical outcomes were recorded.
RESULTS: HSD17B13 rs72613567 TA allele and rs6834314 G allele were associated with lower odds of non-alcoholic steatohepatitis (NASH) in the overall cohort and among ethnic Chinese, but not among ethnic Malays or Indians (P<0.05). During a mean follow-up of 89 months, 32 patients (19.4%) experienced at least one clinical outcome (cardiovascular events, n=22; liver-related complications, n=6; extra-hepatic malignancy, n=5; and mortality, n=6). The rs72613567 homozygous TA allele and the rs6834314 homozygous G allele were independently associated with a lower incidence of liver-related complications (hazard ratio [HR], 0.004; 95% confidence interval [CI], 0.00-0.64; P=0.033 and HR, 0.01; 95% CI, 0.00-0.97; P=0.048, respectively) and were associated with lower grade of hepatocyte ballooning among the ethnic Chinese.
CONCLUSION: HSD17B13 rs72613567 and rs6834314 variants were inversely associated with NAFLD and NASH, and were associated with lower incidence of adverse liver outcomes in a cohort of multi-ethnic Asian patients with NAFLD.