Evaluation of impact of serial hepatitis B virus DNA levels on development of hepatocellular carcinoma

Abstract

We aimed to investigate the impact of hepatitis B virus (HBV) DNA on the development of hepatocellular carcinoma (HCC). We conducted a case/control study based on 506 chronic HBV patients followed up since 1997. Forty-one patients developed HCC, and each of them was age and gender matched with two simultaneously recruited controls without HCC. HBV DNA was measured at the initial visit, at yearly intervals, and at the last visit. Patient age at the time of HCC development was 55 +/- 9 years. Forty-nine (40%) patients experienced antiviral treatment. The median time from diagnosis to the development of HCC was 17 months, and the control patients were followed for 92 months. At the trough level (defined as lowest level among all studied visits), more (27 patients; 66%) HCC patients had HBV DNA levels of >10,000 copies/ml than the controls (17 patients; 21%). The area under the receiver operating characteristic curve of the trough log HBV DNA level for HCC was 0.79 (95% confidence interval [CI], 0.69 to 0.89). Trough log HBV DNA (odds ratio, 11.4; 95% CI, 3.6 to 37.6; P < 0.0001) and liver cirrhosis (odds ratio, 11.4; 95% CI, 3.6 to 36.2; P < 0.0001) levels were independently associated with HCC after an adjustment for age, gender, antiviral treatment, and HBV genotype. The difference in the trough HBV DNA level was more obvious among untreated patients (5.7 +/- 1.4 log copies/ml in HCC patients versus 3.2 +/- 1.3 log copies/ml in control patients; P < 0.0001) than among those who had received antiviral treatment (3.0 +/- 1.4 log copies/ml in HCC patients versus 2.5 +/- 0.9 log copies/ml in control patients; P = 0.38). A high trough HBV DNA level was associated with a higher risk of HCC. Whether antiviral treatment could prevent HCC was uncertain.

FIG. 1.

ROC curves of log HBV DNA at different time points for HCC. The area under the ROC curve for the first log HBV DNA (LogDNA_first) is 0.65 (95% CI, 0.50 to 0.71; P = 0.059). The area under the ROC curve for the last log HBV DNA (LogDNA_last) is 0.72 (95% CI, 0.62 to 0.81; P < 0.0001). The area under the ROC curve for the peak log HBV DNA (LogDNA_peak) is 0.51 (95% CI, 0.41 to 0.61; P = 0.88). The area under the ROC curve for the trough log HBV DNA (LogDNA_trough) is 0.79 (95% CI, 0.69 to 0.89; P < 0.0001).

FIG. 2.

ROC curves of ALT at different time points for HCC. The area under the ROC curve for the first ALT (ALT_first) is 0.59 (95% CI, 0.48 to 0.69; P = 0.13). The area under the ROC curve for the last ALT (ALT_last) is 0.67 (95% CI, 0.57 to 0.77; P = 0.002). The area under the ROC curve for the peak ALT (ALT_peak) is 0.60 (95% CI, 0.50 to 0.71; P = 0.063). The area under the ROC curve for the trough ALT (ALT_trough) is 0.66 (95% CI, 0.55 to 0.76; P = 0.005).