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J Gastroenterol Hepatol. 2019 Jun 3. doi: 10.1111/jgh.14750. [Epub ahead of print]

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

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Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.



Clinical course of hepatitis B virus (HBV) related hepatocellular carcinoma (HCC) patients presenting with low-level viremia (LLV) is unclear.


A total of 565 HBV-related HCC patients with LLV (detectable but HBV DNA ≤ 2,000 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 group. Overall survival was compared between those three groups.


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 group (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, BCLC 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 to 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 AVT at LLV. Flare risk was significantly lower among patients who started AVT at LLV compared to those who did not (adjusted HR 0.26, 95% CI 0.17-0.38).


Among HBV-related HCC patients with LLV, flare was frequent during follow-up and was associated with poorer overall survival compared to MVR group. Prospective studies that address whether inducing MVR by early AVT improves patient outcome are warranted.


Antiviral therapy; hepatitis B virus; hepatocellular carcinoma; low-level viremia; overall survival


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