First, there were 20 eligible studies included in the meta-analysis, but this number was too small for further subgroup analysis. This limitation was compounded by the fact that there were few studies with a large sample size and multiple centers. The second limitation was the significant heterogeneity of included studies. A considerable variation between the results of diagnostic studies is a common occurrence, possibly to a greater extent than is seen for therapeutic interventions. One of the potential sources of heterogeneity and a direct consequence of the fact that the importance of rigorous design has been less well appreciated for diagnostic studies than for therapeutic interventions, is poor adherence to methodological constraints. This is noticeable in many studies that we included, and can be considered as a general problem in many studies dealing with the diagnostic accuracy of liver fibrosis markers, as already noted by others. In our study, although disease spectrum, blindness and prevalence were found to be the factors causing heterogeneity, and further sensitivity analysis and/or subgroup analysis were performed in our study. Unfortunately, the eligible studies were too few to perform this. Finally, we only included published manuscripts, so bias in the selection of search channels may have influenced our results. Our meta-analysis has several implications for future research. For example, we WY 14643 believe that more studies on the diagnostic accuracy for liver fibrosis are needed in patient populations with CHB. In the future, authors of studies exploring the performance of the FIB-4 index in CHB patients should be encouraged to insist on a rigorous design and methodology. In this regard, QUADAS2 describes what is required for a rigorous study design and methodology, and is a good tool for guiding diagnostic study design. As common flaws in design and methodology found in our eligible studies, we emphasize two points: first, a study should ideally enroll all consecutive, or a random sample of, eligible patients with suspected disease – otherwise there is potential for bias. Second, selecting the test threshold to optimize sensitivity and/or specificity may lead to overoptimistic estimates of test performance, which is likely to be poorer in an independent sample of patients in whom the same threshold is used. As a result, if a threshold was used, it should be pre-specified. Implications for practice deriving from our results suggest that the FIB-4 index is of excellent utility for detecting cirrhosis in patients with CHB, and has moderate accuracy in detecting significant fibrosis. On the other hand, it has suboptimal performance in the exclusion of significant and severe fibrosis, and cirrhosis. Thus, it is necessary to further improve the test or combine it with other noninvasive modalities in order to improve its accuracy. DENV infection is often asymptomatic, but it can also lead to clinical manifestations ranging from a mild febrile illness to a severe and potential life-threatening disease. To differentiate the degree of disease severity, World Health Organization classifies dengue into dengue fever, dengue hemorrhagic fever and dengue shock syndrome.