Kwang Cheol Koh

Low‐level viremia and the increased risk of hepatocellular carcinoma in patients receiving entecavir treatment

The long‐term clinical impact of low‐level viremia (LLV; <2,000 IU/mL) is not well understood. As a result, it is unclear whether the development of LLV during entecavir monotherapy requires a change in therapy. A retrospective cohort of 875 treatment‐naive chronic hepatitis B virus (HBV) monoinfected patients (mean age 47.7 years, male = 564 [65.5%], cirrhosis = 443 [50.6%]) who received entecavir monotherapy were analyzed for the development of hepatocellular carcinoma (HCC). The HCC risk was compared between patients who maintained virological response (MVR), defined by persistently undetectable HBV DNA (<12 IU/mL), and patients who experienced LLV, defined by either persistent or intermittent episodes of <2,000 IU/mL detectable HBV DNA. During a median 4.5 years of follow‐up (range 1.0‐8.7 years), HCC was diagnosed in 85 patients (9.7%). HCC developed more frequently in patients who experienced LLV than MVR (14.3% versus 7.5% at 5 years, P = 0.015). The hazard ratio comparing those with LLV to MVR was 1.98 (95% confidence interval = 1.28‐3.06, P = 0.002, adjusted for age, sex, hepatitis B e antigen, baseline HBV DNA levels, and cirrhosis). Among patients with cirrhosis, those with LLV exhibited a significantly higher HCC risk than those with MVR (HCC incidence rate at 5 years 23.4% versus 10.3%, adjusted hazard ratio = 2.20, 95% confidence interval 1.34‐3.60; P = 0.002). However, for patients without cirrhosis, there was no significant difference in the HCC risk between LLV and MVR. Conclusion: LLV observed during entecavir monotherapy was associated with a higher risk of HCC, especially for those with cirrhosis, indicating that LLV during potent antiviral therapy is consequential. (Hepatology 2017;66:335–343).

A low viral load predicts a higher initial virologic response to adefovir in patients with Lamivudine-resistant chronic hepatitis B.

BACKGROUND/AIMSnAdefovir (ADV) is the preferred drug for treating lamivudine (LAM)-resistant hepatitis B. However, not all patients who face virologic breakthrough during LAM treatment respond to ADV. The aim of this study was to determine the factors associated with efficacy of ADV in LAM-resistant hepatitis B patients.nnnMETHODSnThe medical records of 231 patients who received ADV due to LAM-resistance were reviewed. Efficacy was assessed by the initial virologic response (IVR), defined as hepatitis B virus (HBV) DNA not being undetectable by real-time PCR at 6 months of ADV treatment.nnnRESULTSnSeventy patients (30%) achieved IVR. While add-on modality, hepatitis B e antigen (HBeAg) negativity, and low baseline HBV DNA levels were associated with IVR in univariate analysis, multivariate analysis revealed HBeAg status and the DNA level to be the significant factors. The probability of IVR achievement increased sharply per each log(10) copies/mL decrement in the baseline viral load, which was 133 times in patients who had HBV DNA <10(5) copies/mL compared with those who had ≥10(8) copies/mL.nnnCONCLUSIONSnFactors associated with the IVR were HBeAg negativity and a low baseline viral load. Therefore, when virologic breakthrough with genotypic resistance emerges during LAM therapy, ADV treatment should be considered immediately before further increases in viral load. Additional long-term follow-up data are warranted.