A still simple but improved Index to exclude fibrosis in chronic hepatitis C: Higher sensitivity of the APRI- Score by adding Serum-Cholesterinesterase

Treatment decisions in chronic hepatitis C are based on the extent of fibrosis in the liver. Interferon-based therapies are recommended if at least stage-F2 is present. To avoid unnecessary liver biopsies, one would need a serum marker to exclude significant fibrosis with a PPV value for Ishak F0–2 of close to 100% to safely withhold antiviral therapy. A simple non-invasive fibrosis index considering AST levels and platelets was presented in 2003 (AST/ULN/platelets*100; APRI, Hepatology;38: 518). An APRI index of <0.5 predicted absence of cirrhosis correctly in 86% with a specificity of 91%. However, the sensitivity for Ishak F0–2 was rather low with 47% meaning that still more than half of the patients would require a liver biopsy although no significant fibrosis of ISHAK >F2 is present.

To examine the role of cholinesterase to improve the sensitivity of the APRI-score, we performed a retrospective analysis on a cohort of 140 patients infected with HCV who were admitted to our outpatient clinic. Liver biopsies were scored by one pathologist who was not aware of any biochemical parameter. None of the patients had Child B/C cirrhosis.

In this cohort, an APRI score of less than 0.5 proofed to predict the absence of cirrhosis with a PPV of 94% (specificity 97%). However, sensitivity was only 45%. A serum cholinesterase level 2 times above ULN excluded significant fibrosis with a PPV, specificity and sensitivity of 90%, 96% and 33%, respectively. Combing the APRI-index with serum cholinesterase (APRI/cholinesterase/2xcholinesterase-ULN*100, cut-off 3.5) maintained a high PPV and specificity for absence of significant fibrosis (PPV 95%, specificity 97%) but increased the sensitivity of this index to 66%. The usefulness of this new index was validated in a second independent cohort.

In conclusion, a combination of serum cholinesterase with AST and platelet counts accurately predicts the absence of significant fibrosis and might help to avoid liver biopsy in about two third of patients with chronic hepatitis C.