Hepatitis B virus DNA levels and overall survival in hepatitis B-related hepatocellular carcinoma patients with low-level viremia

Background and Aim Clinical course of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients presenting with low-level viremia (LLV) is unclear. Methods A total of 565 HBV-related HCC patients with LLV (detectable but HBV DNA <= 2000 IU/mL) at the time of HCC diagnosis were analyzed. Based on patterns of HBV DNA levels during follow-up, patients were categorized into three groups: maintained virologic remission (MVR), LLV, and flare. Overall survival was compared between those three groups. Results During a median 4.5 years of follow-up, 33% showed MVR, 39% showed LLV, and 28% experienced flare. The overall survival differed between MVR, LLV, and flare groups (5-year overall survival: 74.3%, 67.3%, and 61.7%, respectively, 0.015). The patterns of HBV DNA levels were independent factors associated with overall survival, along with age, antiviral treatment, Barcelona clinic liver cancer stage, and initial treatment modality. Flare group showed increased risk of mortality (adjusted hazard ratio [HR] 1.71, 95% confidence interval [CI] 1.15-2.55) compared with MVR group, while the risk was statistically marginal for the LLV group (adjusted HR 1.39, 95% CI 0.95-2.04). During follow-up, 183 patients (32.4%) newly started antiviral therapy (AVT) at LLV. Flare risk was significantly lower among patients who started AVT at LLV compared with those who did not (adjusted HR 0.26, 95% CI 0.17-0.38). Conclusions Among HBV-related HCC patients with LLV, flare was frequent during follow-up and was associated with poorer overall survival compared with MVR group. Prospective studies that address whether inducing MVR by early AVT improves patient outcome are warranted.