ABSTRACT
Accurate monitoring of changes in fibrosis would be helpful in defining the need for intervention, and the response to treatment. In this case control study we aimed to evaluate the diagnostic utility of different serum markers and indices in detecting the stage of fibrosis in order to recommend the most accurate and efficient serum marker to be used in routine clinical practice to replace or minimize the use of liver biopsy. A written informed consent was collected from all patients and the study was approved by the ethical committee; thirty FICV infected patients admitted to Alexandria University hospital were enrolled together with fifteen healthy adults as controls. Initial liver biopsy was done to assess the degree of liver fibrosis. Laboratory work up included all routine liver tests, estimation of Hyaluronic acid level, Matrix metalloproteinase[MMP-1], Aminoterminal propeptide type III procollagen [PIIINP]. Marker Algorithms based on common laboratory tests included AST-to-platelet ratio [APRI score], AST-to-ALT ratio, Fibro test, Actitest. Forn's index, Shasta index and hepascore were calculated together with PIIINP/MMP-iscore. A statistically significant increase in ALT, AST, Hyaluronic acid and PIIINP, as well as APRI score, Hepascore and Shasta score was found among HCV patients compared to controls p<0.05; while MMP-1, Forn's score, fibrotest were not significantly different between both groups. Comparing serum markers with METAVIR fibrosis stage we found that PIIINP, APRI score, Forn's score and ALT/AST ratio were significantly correlated to Metavair fibrosis stage in groups with no or early fibrosis while MMP-l, Shasta score, 1-lepascore and Fibrotest were significantly correlated to late stages of fibrosis P<0.05. When using a calculated stepwise logistic regression analysis; a manual score equation for fibrosis has emerged; where F0F1 vs F2F3F4 score=-0.60 log MMP-l+ 0.936 log PIIINP and F0F1F2 vs. F3F4 score=-0.421 log MMP-l-0.272 log PHINP. These equations yielded different cut off scores which were applied in order to estimate two clinically relevant fibrosis stages in patients, FOFI versus F2F3F4 termed "significant fibrosis" and FOFIF2 versus F3F4 or "extensive fibrosis". A score below 0.2 observed in 23 patients [76.7%] excluded the presence of extensive fibrosis [F3F4] with negative predictive values of 99% and 86% respectively. A combination of markers as well as indices is an emerging tool for differentiating early from advanced fibrosis. PIIINP, APRI, Forn's score and ALT/AST ratio were significantly correlated to Metavair fibrosis stage in no or early fibrosis group. While Shasta score, HA, Hepascore, Fibrotest and MMP were significantly correlated to late stages. Fibrotest was of significant value for detecting early as well as significant fibrosis, but poor at predicting intermediate levels of fibrosis. Shasta score, APRI score and Forn's score showed AUC 1.0 with a sensitivity of 100% and specificity of 100% to exclude the presence of significant fibrosis. Liver biopsy may still be needed for chronic HCV cases to correctly stage liver fibrosis