Telomerase activity of needle-biopsied liver samples: its usefulness for diagnosis and judgment of efficacy of treatment of small hepatocellular carcinoma

Background/Aims: High values for telomerase activity in malignant tumors have been reported. The clinical usefulness of measurements of telomerase activity as a diagnostic tool and to evaluate treatment efficacy in small hepatocellular carcinoma was investigated. Methods: We investigated 22 patients (26 nodules) with intrahepatic abnormal nodules 20 mm in size determined by abdominal ultrasound. All underwent needle biopsies of tumorous nodules and extranodular regions of the liver by ultrasound guidance for histopathological diagnosis and measurement of telomerase activity by the fluorescence-based telomeric repeat amplification protocol. Re-biopsy of the same nodule was performed 1 week after percutaneous ethanol injection therapy to measure telomerase activity in 10 patients (10 nodules) found to have hepatocellular carcinoma. Liver-biopsied samples from 30 patients with chronic hepatitis C were used as a control. Results: Telomerase activity increased with statistical significance stepwise: chronic hepatitis (n=30, mean: 0.00 U) extranodular regions (pre-cirrhosis or cirrhosis, n=22, mean: 1.80 U), atypical hyperplasia (borderline or premalignant lesions, n=15, mean: 7.02 U) and low-grade malignant hepatocellular carcinoma (n=11, mean: 31.96 U) (p<0.0001 by the Kruskal-Wallis test). Percutaneous ethanol injection therapy resulted in loss (0.00 U) of telomerase activity in 9 nodules and persistence in 1 nodule. Conclusions: Measurement of telomerase activity appeared useful for diagnosis of intrahepatic abnormal nodules and assessment of the efficacy of percutaneous ethanol injection therapy and may be used as an alternative diagnostic method, especially when pathohistological discrimination between atypical hyperplasia and well-differentiated hepatocellular carcinoma is difficult.