PREDICTIVE VALUE OF BIOCHEMICAL MARKERS AS COMPARED TO BIOPSY FOR ASSESSMENT OF CHRONIC LIVER DAMAGE IN HEPATITIS "C" INFECTION

ABSTRACT

Background: Several noninvasive markers are being used to assess the structural liver damage in patients with chronic hepatitis C (CHC). We evaluated predictive value of biochemical markers in comparison with Metavir staging and grading of liver biopsy for assessment of hepatic fibrosis in the CHC patients.

Patients and Methods: This validation was carried out in Department of Pathology, Army Medical College, Rawalpindi. One hundred thirty two CHC patients, naive for HCV treatment, underwent liver biopsy in tertiary care hospitals of district Rawalpindi-Pakistan. Liver biopsies were reviewed by Metavir scoring system. Standard liver functions tests were carried out  using Selectra-E, platelets were done on Syxmes KX-21 hematology autoanalyzer, serum alpha2 macroglobin (A2M) was analyzed by turbidimetric method, hylauronic acid (HA) was measured on ELISA micro plate reader. Hepascore and APRI were calculated using the published equations. A multivariate regression model was developed utilizing the variables significantly related to fibrosis i.e. gamma glutmyl transferase (GGT), hylauronic acid (HA); Alplha-2-macroglobin (A2M) and tissue inhibitor of metalloproteinase-I (TIMP-I). Patients with no/mild fibrosis (F0, F1) were differentiated from significant fibrosis (F2, F3, F4); advanced fibrosis (F3, F4) and F4 (cirrhosis). Similarly patients with mild activity (A0, A1) were differentiated from patients with significant activity (A2, A3).

Results: Most of the patients were males 83 (63%) with mean age 39 years. The CHC patients had raised levels of biochemical markers (mean± SD) for ALT 74±23 IU/l, AST, 69±25 IU/l, bilirubin, 10±3 µmol/l/, GGT, 80±30 IU/l, hylauronic acid, 65±35 ng/ml , TIMP-1, 397±78 ng/ml, Apo A1, 1.4±0.09 g/L, A2M, 2.82±0.16 g/L and haptoglobin 0.93±0.17 g/L. Liver biopsies revealed the frequency of significant fibrosis (≥F2) and advanced fibrosis (≥ F3) by Metavir scoring in 61 % and 31 % respectively. APRI with area under curve (AUC) of 0.81(95% CI: 0.74- 0.88) and Hepascore AUC of 0.86 (95% CI: 0.80-0.92) revealed lower diagnostic accuracy in our CHC patients as compared to their originally reported values. Hepascore correctly classified 108 (81%) patients of  significant fibrosis with AUC=0.86 (95%CI 0.76-0.87) at cutoff 0.55 with  negative predictive value (NPV), positive predictive value (PPV), sensitivity and specificity of 75%, 84%, 83% and 77% respectively. The new biomarker model had the highest AUC of 0.95 (95% CI: 0.92-1.00) for significant fibrosis and 0.97 for cirrhosis. Out of 132 patients n=110 (84 %) patients were accurately classified for significant fibrosis (≥F2) by the new biochemical regression model.

Conclusion: The combination of routine and specialized biomarkers of hepascore could correctly identify significant fibrosis, advanced fibrosis and cirrhosis as compared to liver biopsy with acceptable degree of diagnostic accuracy in CHC patients in our clinical practice. Liver biopsy should be done in only those cases who are left unclassified by these biochemical markers.