Impact of large regenerative, low grade and high grade dysplastic nodules in hepatocellular carcinoma development.
OBJECTIVE
The natural outcome of ultrasound-detected macronodules in cirrhosis is still poorly understood. In this study we assessed the incidence and predictors of malignant transformation in a prospective study of 90 consecutive ultrasound-detected macronodules in cirrhosis.


METHODS
Macronodules classification was based on recently proposed histological criteria. Extranodular large (LCC) and small cell changes were also evaluated. The follow-up included ultrasound and serum alfa-fetoprotein determination every 3 months. Independent predictors of hepatocellular carcinoma were evaluated by Cox proportional hazards regression analysis.


RESULTS
During a mean follow-up of 33 months, 28 (31%) nodules transformed into hepatocellular carcinoma. The incidence of hepatocellular carcinoma per 100 person-years of follow-up was 11.3%, with a malignant transformation rate of 3.5, 15.5, 31 and 48.5% at 1, 2, 3, and 5 years respectively. High-grade dysplastic nodules (HGDN) (hazard risk=2.4; CI 95%=1.1-5.0) and LCC (hazard risk=3.1; CI 95%=1.2-7.8) were independent predictors of malignant transformation. Eight additional hepatocellular carcinomas developed outside the original lesions raising the overall malignant transformation rate to 40% while 15 macronodules (17%) became undetectable at ultrasound (US).


CONCLUSIONS
Macronodules characterize a cirrhotic subpopulation with high risk of hepatocellular carcinoma. HGDN and LCC are strong predictors of malignant transformation; subjects with simultaneous presence of both these two conditions are at highest risk of cancer development. The management of cirrhotics with macronodules should be based on morphologic features detected on liver microsamples.
Borzio
Mauro
M
Department of Medicine, Gastroenterology Unit, Ospedale Fatebenefratelli, C.so Porta Nuova 23, 20121, Milan, Italy. maborzio@interfree.it
Fargion
Silvia
S
Borzio
Franco
F
Fracanzani
Anna Ludovica
AL
Croce
Anna Maria
AM
Stroffolini
Tommaso
T
Oldani
Silvia
S
Cotichini
Rodolfo
R
Roncalli
Massimo
M
D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000473:pathology*; D002471:Cell Transformation, Neoplastic; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008103:Liver Cirrhosis / Q000453:epidemiology / Q000473:pathology*; D008113:Liver Neoplasms / Q000453:epidemiology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012307:Risk Factors