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Hepatol Int. 2015 Apr;9(2):330-6. doi: 10.1007/s12072-015-9620-6. Epub 2015 Mar 3.

Natural history of large regenerative nodules and dysplastic nodules in liver cirrhosis: 28-year follow-up study.

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Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba City, Chiba, 260-8670, Japan,



Some follow-up studies of large regenerative nodules (LRNs) and dysplastic nodules (DNs) were reported previously. However, the pre-malignant potentiality of LRNs has remained controversial up to now. No LRNs showed malignant transformation in our previous study. We aimed to evaluate the pre-malignant potentiality of LRNs and DNs with a greater number of cases and longer follow-up periods.


From 1982 to 2005, 1,500 consecutive nodular lesions up to 2 cm in diameter were subjected to US guided thin-needle biopsy in cirrhotic patients at Chiba University Hospital. Of these lesions, 68 LRNs in 60 cases and 20 DNs in 22 cases were followed up for more than 6 months without any anti-cancer therapy. The last US examination was in 2010. The total study period was 28 years. We analyzed the histological findings and the clinical data of all cases retrospectively. The outcome of the lesions was examined.


The mean follow-up period was 38.9 (16-119) months in LRNs and 31.9 (6-101 months) in DNs. Rate of nodule enlargement was higher in DNs (8/24 nodules, 33%) than LRNs (11/68 nodules, 16 %), (p = 0.0743, not significant). Rate of malignant transformation was also higher in DNs (10/24 nodules, 42%) than LRNs (9/68 nodules, 13%), (p = 0.0040, significant). The rate of disappearance in images was similar between LRNs and DNs.


We should recognize LRN as low risk pre-malignant lesions whereas DNs as high risk lesions.

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