Hypovascular nodules in patients with chronic liver disease: risk factors for development of hypervascular hepatocellular carcinoma.
OBJECTIVE
To identify patient characteristics and magnetic resonance (MR) imaging findings associated with subsequent hypervascularization in hypovascular nodules that show hypointensity on hepatobiliary phase gadoxetic acid-enhanced MR images in patients with chronic liver diseases.


METHODS
Institutional review board approval was obtained, and informed consent was waived. At multiple follow-up gadoxetic acid-enhanced MR imaging examinations of 68 patients, 160 hypovascular nodules were retrospectively reviewed. A Cox regression model for hypervascularization was developed to explore the association of baseline characteristics, including patient factors (Child-Pugh classification, etiology of liver disease, history of local therapy for hepatocellular carcinoma [HCC], and coexistence of hypervascular HCC) and MR imaging findings (fat content, signal intensity on T2-weighted images, and nodule size). In addition, the growth rate was calculated as the reciprocal of tumor volume doubling time to investigate its relationship with subsequent hypervascularization by using receiver operating characteristic and Kaplan-Meier analyses.


RESULTS
The prevalence of subsequent hypervascularization was 31% (50 of 160 nodules). Independent Cox multivariable predictors of increased risk of hypervascularization were hyperintensity on T2-weighted images (hazard ratio [HR] = 8.7; 95% confidence interval [CI]: 3.6, 20.8), previous local therapy for hypervascular HCC (HR = 5.0; 95% CI: 1.8, 13.6), Child-Pugh B cirrhosis (HR = 3.6; 95% CI: 1.4, 9.5) and coexistence of hypervascular HCC (HR = 2.0; 95% CI: 1.0, 3.8). The mean growth rate was significantly higher in nodules that showed subsequent hypervascularization than in those without hypervascularization. Kaplan-Meier analysis based on the receiver operating characteristic cutoff level (1.8 × 10(-3)/day [tumor volume doubling time, 542 days]) showed that nodules with a higher growth rate had a significantly higher incidence of hypervascularization (P = 5.2 × 10(-8), log-rank test).


CONCLUSIONS
Hyperintensity on T2-weighted images is an independent and strong risk factor at baseline for subsequent hypervascularization in hypovascular nodules in patients with chronic liver disease. Tumor volume doubling time of less than 542 days was associated with a high rate of subsequent hypervascularization.
Department of Radiology and Internal Medicine, Kinki University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan.
Tomoko
T
Hyodo
Takamichi
T
Murakami
Yasuharu
Y
Imai
Masahiro
M
Okada
Masatoshi
M
Hori
Yuki
Y
Kagawa
Sachiyo
S
Kogita
Seishi
S
Kumano
Masatoshi
M
Kudo
Teruhito
T
Mochizuki
D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis*; D003287:Contrast Media; D018450:Disease Progression; D058625:End Stage Liver Disease / Q000150:complications*; D005260:Female; D019786:Gadolinium DTPA; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000175:diagnosis*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000175:diagnosis*; D016016:Proportional Hazards Models; D012372:ROC Curve; D012189:Retrospective Studies; D012307:Risk Factors; D012680:Sensitivity and Specificity
D003287:Contrast Media; C073590:gadolinium ethoxybenzyl DTPA; D019786:Gadolinium DTPA