Comparing various cut-offs of aspartate aminotransferase-to-platelet ratio index (APRI) in liver cirrhosis diagnosis among hepatitis C patients in Malaysia.

INTRODUCTION: A major challenge in providing hepatitis C virus (HCV) treatment at primary healthcare clinics is the lack of radiological facilities to guide the decision making of liver cirrhosis (LC). This study aimed to compare the performance of three commonly used cut-offs of the aspartate aminotransferase-to-platelet ratio index (APRI) in diagnosing LC among hepatitis C patients in Malaysia. METHODS: This cross-sectional study was based on the data collected from the Hepatitis C Elimination through Access to Diagnostics (HEAD-Start) study in 25 primary healthcare clinics across three regions of Malaysia. The findings of biochemical tests were used to calculate the APRI for each study participant. Transient elastography was used as a standard reference for the diagnosis of cirrhosis. The area under the receiver operating curve (AUROC) was used to determine the discriminative ability of APRI in both HCV mono-infected and HCV/HIV co-infected patients. The diagnostic performance of APRI at three different cutoffs (>1.0, ≥1.5 and >2.0) were also evaluated. RESULTS: This study included 867 HCV-RNA-positive patients, 158 (16.1%) were co-infected with HIV. For the HCV mono-infected patients, the sensitivity, specificity, positive predictive value (PPV) and negative predictive values (NPV) for the cut-off of >1.0 were 61.8%, 88.7%, 73.8% and 81.9%, and for the cut-off of ≥1.5, 45.6%, 97.0%, 88.7% and 77.6%, respectively. A much lower sensitivity (29.9%) was observed for the cut-off of >2.0. The diagnostic accuracy of APRI at the cut-off of ≥1.5 in the HCV/HIV co-infected patients was relatively suboptimal. CONCLUSION: APRI, with a cut-off of ≥1.5, can more accurately predict LC among hepatitis C patients in Malaysia. However, additional physical examination and laboratory assessment are likely to be required to support the diagnosis, especially in those with HCV/HIV co-infection.

The CD14(+/low)CD16(+) monocyte subset is more susceptible to spontaneous and oxidant-induced apoptosis than the CD14(+)CD16(-) subset.

Human monocytes can be classified into two subsets with distinctive characteristics. In this study, we report a difference in apoptotic potential between these two subsets with CD14(+/low)CD16(+) monocytes being more susceptible than CD14(+)CD16(-) monocytes to undergo spontaneous apoptosis and apoptosis induced by reactive oxygen species (ROS). By global transcriptomic and proteomic approaches, we observed that CD14(+/low)CD16(+) monocytes expressed higher levels of pro-apoptotic genes and proteins such as TNFα, caspase 3, Bax and cytochrome c and showed more caspases 3 and 7 activities. They also exhibited greater aerobic respiration resulting in a higher production of ROS from the mitochondria. CD14(+)CD16(-) monocytes, in contrast, showed higher expression of glutathione (GSH)-metabolizing genes such as GSH peroxidase and microsomal GSH S-transferase and were more resistant to oxidative stress than CD14(+/low)CD16(+) monocytes. The apoptosis of CD14(+/low)CD16(+) monocytes was ROS dependent as reducing ROS levels significantly reduced cell death. This is the first report of a differential apoptotic propensity of human monocyte subsets, and gaining a better understanding of this process may help to provide a better understanding of the roles of these subsets during homeostasis and under pathological conditions, particularly in situations in which high levels of oxidants are present.