Liver Fibrosis Risk Profile With Hepatic Function Panel, Complete Blood Count (CBC) With Differential, FIB-4, and APRI

Assessments of stained smears are performed if results meet specific numeric and/or instrument flagging criteria. Smear review includes assessment of WBC cell populations, presence of WBC and/or RBC inclusions, RBC morphology, and platelet evaluation.

Presence of one or more of the following may be indication for further investigation: hemoglobin <10 g/dL, hemoglobin >18 g/dL, MCV >100 fl, MCV <80 fl, MCHC >37%, WBC >20,000/ mm3, WBC <2000/mm3, presence of sickle cells, spherocytes, Pappenheimer bodies, basophilic stippling, stomatocytes, schistocytes (fragmented RBCs), target cells, oval macrocytes, teardrop red blood cells, abnormal cell populations, nucleated red blood cells in other than the newborn, blood parasites (malarial or Babesia organisms or the possibility of parasitic organisms), hypersegmented neutrophils, agranular neutrophils, hyposegmented neutrophils (Pelger-Huet anomaly or pseudo-Pelger-Huet [pelgeroid] cells), mononuclear cells in which apparent nucleoli are prominent (blast-like cells), presence of metamyelocytes, myelocytes, promyelocytes, neutropenia, presence of plasma cells, peculiar atypical lymphocytes, significant increase or decrease in platelets or bizarre platelets.

A six-part differential reported in some lab locations includes IG % and IG absolute counts. IG (immature granulocytes) includes metamyelocytes and myelocytes. It does not include bands or blast cells.^1,2 Promyelocytes and blasts are reported separately to denote the degree of left shift. An elevated percentage of IG has not been found to be clinically significant as a sole clinical predictor of disease. IGs are associated with infections, a variety of inflammatory disorders, cytokine therapy; neoplasia, hemolysis, tissue damage, seizures, metabolic abnormalities, myeloproliferative neoplasms, and with the use of certain medications such as steroids.³

Pregnancy-associated leukocytosis may also show increased immature granulocytes without clinical significance. There is a significant increase of normoblastic erythropoiesis and, to a lesser extent, of granulopoiesis during pregnancy, which is associated with an increase in immature cells (shift to the left) of both erythropoietic and granulopoietic tissues. A possible physiologic explanation for the appearance of immature granulocytes in the peripheral blood of pregnant women, increased alkaline phosphate activity in granulocytes, and increased glycogen content of lymphocytes may be found in the excretion curves of hormones during pregnancy. There is a sharp rise in the fifth month then a decrease in the eighth month and a subsequent rise in the ninth month.⁴

AST to Platelet Ratio Index (APRI) is calculated using 2 parameters formula: APRI = [AST/AST(ULN)] / platelet count (109/L) x 100 Where AST(ULN) is upper limit of AST reference interval.⁵ The FIB-4 index value is calculated using the 4 parameters formula: FIB-4 = [Age(Years) x AST(IU/L)] / [Platelets(10E3/L) x ALT^.5 (IU/L)]⁶

The FIB-4 index was reported in a study of patients with HCV infection to correctly identify patients with severe fibrosis (METAVIR F3-F4) with area under the ROC curve of 0.85. A FIB-4 index of less than 1.45 had a negative predictive value of 94.7% to exclude extensive fibrosis (F3-F4) with a sensitivity of 74.3% and a specificity of 80.1%. A FIB-4 index of greater than 3.25 had a positive predictive value of 82.1% to confirm the existence of significant fibrosis (F3-F4) with a specificity of 98.2% and a sensitivity of 37.6%. In the same study, FIB-4 index was in agreement with FibroTest (known in the US as FibroSure) test results of 92.1% for exclusion of severe fibrosis (F3-F4) using a cutoff of less than 1.45, and agreement of 76.0% for detection of severe fibrosis (F3-F4) using a cutoff of greater than 3.25.

In more recent studies of patients with NAFLD, FIB-4 index was reported to have area under ROC curve of 0.802 for prediction of advanced fibrosis (F3-F4) using slightly different cutoffs of 1.30 and 2.67. A negative predictive value for the absence of advanced fibrosis at a cutoff of 1.30 was 83% and a positive predictive value for the presence of advanced fibrosis and hazard ratio for developing liver related events at a cutoff of 2.67 was 80% and 14.6 respectively. A liver biopsy had been appropriately avoided in 54% of cases.^5-14