Association of Hepatitis B Virus DNA Level and Follow-up Interval With Hepatocellular Carcinoma Recurrence

IMPORTANCE: Antiviral treatment is important in hepatitis B virus (HBV)–related hepatocellular carcinoma (HCC) comprehensive therapy. A high HBV DNA level is an independent risk factor for HBV-related HCC, but no quantifiable clinical index is available to date. OBJECTIVE: To evaluate the feasibility and availability of the novel HBV DNA quantitation-time index (HDQTI), which includes HBV DNA quantitation and follow-up, to predict HBV-related HCC prognosis. DESIGN, SETTING, AND PARTICIPANTS: This retrospective prognostic study of patients with HCC from multiple centers in China was performed from January 1, 2002, to December 31, 2016. The median follow-up time was 18 months, and the longest follow-up time was 147 months. Data analysis was performed from January 1, 2017, to December 31, 2018. MAIN OUTCOMES AND MEASURES: Clinical characteristics, antitumor management, antiviral treatment, HDQTI scores, follow-up information, and overall survival were recorded and analyzed. A receiver operating characteristic curve and accompanying area under the curve were calculated for HDQTI. RESULTS: A total of 842 patients (mean [SD] age, 61.80 [9.85] years; 513 [60.9%] male) were included in the study. Of all included patients, 734 received no antiviral therapy before diagnosis (no previous diagnosis of HBV infection), 43 underwent nonstandard antiviral therapy, and 65 received regular antiviral therapy. Compared with the group without antiviral treatment, the Barcelona Clinic Liver Cancer (BCLC) stage was earlier (A:B:C, 73.8%:26.2%:0% to 5.7%:65.5%:28.8%, P < .001), the mean (SD) tumor size was smaller (2.89 [1.26] to 7.56 [3.28] cm, P < .001), the ratio of baseline HBV DNA level of more than 10(5) copies/mL was lower (10.8% to 40.6%, P < .001), and the ratio of the α(1)-fetoprotein level more than 400 ng/mL was less (21.5% to 78.2%, P < .001) in the standard antiviral treatment group, whereas the nonstandard treatment group was between the 2 groups. Recurrence occurred in 39 of 109 BCLC stage A cases. Patients with HDQTI scores higher than 34 had high risk of recurrence; at this cutoff level, the sensitivity of the HDQTI was 76.9% and the specificity was 92.9%, with an area under curve of 0.928. Patients in various BCLC stages had similar trends in overall survival and HDQTI scores (BCLC stage A: HDQTI score <34, not applicable; HDQTI score ≥34, 44.0 months; 95% CI, 38.3-49.7 months; BCLC stage B: HDQTI score <34, 35.0 months; 95% CI, 33.3-36.7 months; HDQTI score ≥34, 17.0 months; 95% CI, 14.5-19.5 months; P = .002; BCLC stage C: HDQTI score <34, 18.0 months; 95% CI, 16.5-19.6 months; HDQTI scores ≥34, 10.0 months; 95% CI, 8.5-11.5 months; P = .005). CONCLUSIONS AND RELEVANCE: The findings suggest that the HDQTI can be used as an independent prognostic indicator of recurrence in HBV-related HCC. Shorter follow-up intervals and accurate imaging evaluation are recommended in patients with HDQTI scores of 34 or higher.