Low-level viremia and cirrhotic complications in patients with chronic hepatitis B according to adherence to entecavir

Abstract

<jats:p>Background/Aims: Low-level viremia (LLV) after nucleos(t)ide analog treatment was presented as a possible cause of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). However, detailed information on patients’ adherence in the real world was lacking. This study aimed to evaluate the effects of LLV on HCC development, mortality, and cirrhotic complications among patients according to their adherence to entecavir (ETV) treatment.Methods: We performed a retrospective observational analysis of data from 894 consecutive adult patients with treatment-naïve CHB undergoing ETV treatment. LLV was defined according to either persistent or intermittent episodes of &lt;2,000 IU/mL detectable hepatitis B virus DNA during the follow-up period. Good adherence to medication was defined as a cumulative adherence ≥90% per study period.Results: Without considering adherence in the entire cohort (n=894), multivariate analysis of the HCC incidence showed that LLV was an independent prognostic factor in addition to other traditional risk factors in the entire cohort (&lt;i&gt;P&lt;/i&gt;=0.031). Good adherence group comprised 617 patients (69.0%). No significant difference was found between maintained virologic response and LLV groups in terms of the incidence of liver-related death or transplantation, HCC, and hepatic decompensation in good adherence group, according to multivariate analyses.Conclusions: In patients with treatment-naïve CHB and good adherence to ETV treatment in the real world, LLV during treatment is not a predictive factor for HCC and cirrhotic complications. It may be unnecessary to adjust their antiviral agent for patients with good adherence who experience LLV during ETV treatment.</jats:p>

Low-level viremia in patients undergoing antiviral therapy: Does it indicate time for a change?

“…11 Therefore, here is the question: Is LLV during high genetic barrier NA therapy a meaningful sign to change therapy? In this study, Lee et al 8 showed similar risks of liver-related death, transplantation, HCC, and hepatic decompensation between MVR and LLV groups in good adherent patients. However, the ultimate question is whether a change in therapy (switch to another NA or adding an additional NA) can decrease the risk of liver-related mortality or HCC among patients showing LLV.…”

“…However, the study design was an observational cohort study with inherent limitations. Lee et al 8 provide excellent discussion on the potential limitations and implications of their findings. In addition, some points need to be further discussed.…”

How does low-level viremia affect the prognosis of patients with chronic hepatitis B?

“…Second, the study by Shin et al 3 showed that poor adherence to ETV increased the risks of mortality, HCC and cirrhotic complications, particularly among patients with cirrhosis. In the study by Lee et al, 1 LLV increased the HCC risk compared to a maintained virological response (MVR), but there was no difference between LLV and MVR among patients with good adherence. Poor adherence to medication results in less viral suppression, which in patients with chronic hepatitis B (CHB) will affect long-term prognosis, including a higher risk of HCC or cirrhotic complications.…”

“…4 High genetic barrier antivirals such as ETV or tenofovir failed to achieve HBV DNA undetectability after 48 weeks in 10% and 30% of hepatitis B e antigen negative and positive patients with CHB. 5 According to Lee et al, 1 ETV therapy should be continued in patients with good ad-…”

“…Third, the definition of MVR vs. LLV is an important issue. In the study by Lee et al, 1 patients were categorized as MVR or LLV at the last follow-up. However, despite an update of the study period, the number of patients with good adherence was the same as in the study by Shin et al 3 How many HBV DNA measurements were made in each patient and how frequently?…”