Recently, the combination of FibroTest with FibroScan has demonstrated high diagnostic accuracy for the detection of significant fibrosis and cirrhosis [30
]. However, the combination requires a complex instrument and is costly. Instead, the APRI is based on routinely performed, inexpensive laboratory parameters; it is potentially the ideal tool. The APRI has been derived and validated in HCV. In Wai and colleagues' original study [6
], the AUC for HCV-related significant fibrosis and cirrhosis in the training and validation cohorts were 0.80 to 0.88 and 0.89 to 0.94, respectively. Subsequently, many researches supported this view [31
]. A meta analysis researched by Abdel Aziz M et al. pointed out, in patients with chronic viral hepatitis C (CHC), the summary AUCs of the APRI for significant fibrosis and cirrhosis were 0.76 [95% CI: 0.74-0.79] and 0.82 [95%CI: 0.79-0.86], respectively; an APRI threshold of 0.5 was 81% sensitive and 50% specific, at a 40% prevalence of significant fibrosis, this threshold had a negative predictive value (NPV) of 80%. For cirrhosis, a threshold of 1.0 was 76% sensitive and 71% specific, at a 15% cirrhosis prevalence, the NPV of this threshold was 91%, the major strength of the APRI is the exclusion of significant HCV-related fibrosis [36
In contrast to HCV, Wai et al. [14
] evaluated the accuracy of models (ALT, AST and APRI) from HCV in 218 HBV patients, which indicated that non-invasive markers in predicting histology from CHC patients were unsuitable for CHB patients. Subsequent research demonstrated that in contrast to APRI, ASPRI was accurate in predicting cirrhosis and has the potential to reduce the number of liver biopsies in CHB patients when screening with ASPRI [27
]. However, W.G. Shin and colleagues' study indicated that of indirect markers, the APRI yielded the best area (0.86) under the receiver operating characteristic curve [95% CI: 0.82-0.91], the APRI may be the most accurate and simple marker for predicting significant fibrosis in chronic hepatitis B [24
]. Lin CS and colleagues' research supported this view [26
]. Thus, the present study conclusions are controversial. In our systematic review, we summarize the diagnostic accuracy of the APRI for the prediction of HBV-related fibrosis. In our systematic review, we calculated summary sensitivities and specificities at various thresholds to translate all point estimates into clinical practice. The summary AUROC of the APRI for the diagnosis of significant fibrosis was 0.79. Moreover, the 0.5 threshold was 84% sensitive and 41% specific. Assuming a 53.1% prevalence of significant fibrosis, this translates into estimated PPV and NPV of 64% and 68%, respectively. On the contrary, a cutoff of 1.5 was less sensitive (49%) and more specific (84%). Assuming a 53.1% prevalence of significant fibrosis, this translates into estimated 80%PPV and 57% NPV. With regard to cirrhosis, the summary AUROC was 0.75. Moreover, the1.0-1.5 threshold was 54% sensitive and 78% specific. Assuming a 13.5% prevalence of cirrhosis, this translates into estimated PPV and NPV of 39% and 86%, respectively. On the contrary, a cutoff of 2.0 was less sensitive (28%) and nearly specific (87%). Assuming a 13.5% prevalence of cirrhosis, this translates into estimated 36% PPV and 82% NPV. A diagnostic tool is considered as good if the AUROC is greater than 80%, excellent if the AUROC is greater than 90% and perfect if the AUROC is 100%. According to these results, the APRI may not be a good tool for predicting significant fibrosis and cirrhosis in hepatitis B-related fibrosis and can not reduce the number of liver biopsy.
A strength of our review is that meta-regression analyses have been used for exploring factors that may be responsible for heterogeneity. We analyzed carefully three indicators that might contribute to heterogeneity: (a) the interval between Biopsy & APRI (≤ 1 week or other); (b) blind biopsy (yes VS. no); (c) histological classification systems (METAVIR, Scheuer, Ishak, Batts and Ludwig). By meta-regression, we could see that for both significant fibrosis and cirrhosis, histological classification systems were found to provide heterogeneity to summary test results. Previous research has shown that the hypothesis of the liver biopsy is 80% - 90% accurate, the AUC of medical tests cannot reach 0.9, and more likely fluctuated from 0.75 to 0.9 [37
]. To solve the problem, one of the ways is improving the quality of liver biopsies.
Our study has several limitations. Firstly, only HBV-infected patients have been analyzed. Losing some patients with mix infections (HBV/HCV, HBV/HIV and HBV/NAFLD) suggest reduced accuracy. Secondly, some of the studies reported APRI thresholds not included in the original description (Table ). For example, W.G.Shin et al. proposed that the 1.4 cutoff appears promising (79% sensitive; 83% specific for significant fibrosis) [24
]. The number of studies is so small that we have not focused on these thresholds. Finally, we have chosen inclusions only by published manuscripts, so bias in the selection of search channels may influence the results to some extent.
In summary, our systematic review suggests that APRI show limited value in identifying hepatitis B-related significant fibrosis and cirrhosis. The APRI is not an appropriate choice for HBV patients to identify hepatitis B-related fibrosis in regions with limited health care resources. Future studies are necessary to identify high accuracy, cost-effectiveness and widely available measures.