Liver volume-based prediction model stratifies risks for hepatocellular carcinoma in chronic hepatitis B patients on surveillance

<div><p>Background and aim</p><p>The aim of this study was to determine whether dynamic computed tomography (CT)-measured liver volume predicts the risk of hepatocellular carcinoma (HCC) when the CT scans do not reveal evidence of HCC in chronic hepatitis B (CHB) patients on surveillance.</p><p>Methods</p><p>This retrospective multicentre cohort study included 1,246 patients who received entecavir and regular HCC surveillance in three tertiary referral centres in South Korea. Liver volumes were measured on portal venous phase CT images. A nomogram was developed based on Cox independent predictors and externally validated. Time-dependent receiver operating characteristic (ROC) analysis was performed for comparison with previous prediction models.</p><p>Results</p><p>Patients who received dynamic CT studies during surveillance had significantly higher risk for HCC compared to patients without CT studies (hazard ratio [HR] = 3.1; p < 0.001). Expected/measured liver volume ratio was an independent predictor of HCC (HR = 4.2; p = 0.002) in addition to age, sex and cirrhosis. The nomogram based on the four predictors discriminated risks for HCC (HR = 4.1 and 6.0 in derivation and validation cohort, respectively, for volume score > 150; p < 0.001). Time-dependent ROC analysis confirmed better performance of the volume score compared to HCC prediction models with conventional predictors (integrated area under curve = 0.758 vs. 0.661–0.712; p < 0.05).</p><p>Conclusions</p><p>CT-measured liver volume is an independent predictor of future HCC, and nomogram-based liver volume score may stratify the risks of HCC in CHB patients who showed negative CT findings for HCC during surveillance.</p></div

Kaplan-Meier analysis of HCC incidence in the derivation cohort.

<p>Kaplan-Meier analysis of HCC incidence in the derivation cohort.</p

Flow chart of the study population.

<p>*HCV or HIV coinfection, other malignancy or organ transplantation. ^†Dynamic imaging (+) subgroup received at least one dynamic CT study during surveillance which revealed no evidence of HCC: this subgroup served as the derivation dataset for liver volume analysis. No dynamic imaging subgroup did not receive dynamic CT studies during surveillance, except for the confirmative imaging tests in case of HCC. ETV, entecavir; HCC, hepatocellular carcinoma; NA, nucleos(t)ide analogue.</p

Predictors of HCC development by Cox proportional hazard model.

<p>Predictors of HCC development by Cox proportional hazard model.</p

Stratification of HCC probability by nomogram-based liver volume score.

<p>Kaplan-Meier probabilities of HCC incidence were plotted according to the liver volume score cut-off of 150 in the derivation and validation cohort.</p

Predictors of HCC by Cox proportional hazard model in derivation cohort.

<p>Predictors of HCC by Cox proportional hazard model in derivation cohort.</p

Comparisons of baseline characteristics in patients with and without subsequent development of hepatocellular carcinoma.

<p>Comparisons of baseline characteristics in patients with and without subsequent development of hepatocellular carcinoma.</p

Cumulative incidence of hepatocellular carcinoma in diabetic patients with DM-HCC risk scores.

<p>Cumulative incidence of hepatocellular carcinoma in diabetic patients with low (≤16) and high (>16) DM-HCC risk scores in the derivation cohort (A) and the validation cohort (B).</p

Study flow diagram.

<p>Diabetic patients without chronic viral hepatitis or alcoholic cirrhosis were identified and randomly allocated to derivation or validation cohort.</p

ROC analysis of the DM-HCC risk score in predicting development HCC in 10 years.

<p>At the cutoff value of 16, the area under ROC curve was 0.86 (95% CI, 0.85–0.88) in derivation cohort (A) and 0.86 (95% CI, 0.84–0.88) in validation cohort (B). The sensitivity, specificity positive predictive value and negative predictive value were shown with 95% confidence intervals in parentheses.</p