Mild-to-moderate elevation of alanine aminotransferase may increase liver stiffness measurement by transient elastography in patients with chronic hepatitis B

Abstract

Background: Recent studies have shown that in acute severeflares of hepatitis, liver stiffness measurements can be increaseddramatically. In contrast to severe hepatitis flares, it is notknown currently whether lesser degrees of hepatitis alsoincrease liver stiffness measurements. In the present study weaimed to investigate the effect of mild-to-moderate elevations ofALT on liver stiffness in patients with chronic hepatitis B. Patientsand Methods: Patients with chronic hepatitis B and elevated ALTwere included. Those patients with ALT elevations of greaterthan 10x upper limit of normal (ULN), indicating severe flareswere not included. All patients underwent liver biopsy and liverstiffness measurement for assessment of liver fibrosis prior tostarting antiviral therapy. Oral antiviral therapy (adefovir n=14, clevudine n= 24) was commenced after liver biopsy andliver stiffness measurement was performed. Once ALT normal-ization was achieved, a repeat liver stiffness measurement wasperformed. Results Thirty-eight patients were included, of which21 were male, with a median age of 39 years (range, 18-63).All patients achieved normalization of ALT after commencement of antiviral therapy, and the median time between the first andsecond liver stiffness measurement was 3 months (range, 1-7).There was a significantly lower mean liver stiffness measure-ments after the commencement of antiviral therapy with the nor-malization of ALT levels, compared to pre-treatment levels in the38 patients (7.5 vs 10.5 kPa respectively, p<0.001). Themedian liver stiffness reduction observed in patients with pre-treatment ALT of 1-2x ULN, 2-5X ULN, and 5-10x ULN were0.9, 1.4, and 3.9 kPa respectively, with an overall reduction of2.0 kPa. The higher the pre-treatment ALT, the higher the liverstiffness reduction observed (p=0.027). The AUROC curve fordiagnosing F2 fibrosis in patients with elevated ALT was 0.68,compared with 0.73 for the same patients after ALT normaliza-tion. No patients had evidence of cirrhosis on liver histology.Using the cutoff value of 11.0 kPa for cirrhosis, 12 (32%)patients would have been misclassified as having cirrhosisusing liver stiffness measurements taken at the time of ALT ele-vation. In contrast, 6 (16%) patients would have been misclas-sified as having cirrhosis using liver stiffness measurements atthe time where ALT had normalized. Conclusion: Even mild tomoderate elevation in ALT levels may increase liver stiffnessmeasurements independent of underlying liver fibrosis. HigherALT levels were associated with higher discrepancies in liverstiffness.