Maintaining Virologic Response Following HBV Treatment Reduces HCC Risk


The evidence regarding patients with entecavir-treated chronic hepatitis B without maintaining virological response is limited and uncertain.

Patients with chronic hepatitis B (CHB) treated with entecavir that did not maintain virologic response were at an increased risk of hepatocellular carcinoma (HCC), according to new research.

A team, led by Xiaomo Wang, Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences; School of Basic Medicine Peking Union Medical College, determined the relationship between patients who did not maintain virologic response and HCC risk for patients with chronic hepatitis B treated with entecavir.

Uncertain Evidence

There is uncertain evidence regarding patients with entecavir-treated chronic hepatitis B without maintaining virological response, defined as persistent HBV DNA less than 20 IU/mL during therapy.

The investigators examined 1447 patients with chronic hepatitis B treated with entecavir and conducted multivariate and propensity score-based inverse probability weighting (IPW) models to estimate the effect of maintaining virologic response on HCC.


There was a follow-up period of 5 years, during which 14.8% (n = 214) of patients did not maintain a virologic response. This patient population was associated with a higher risk of developing HCC after the investigators implemented the IPW model (HR, 3.59; 95% CI, 2.23-5.75) than patients who maintained virologic responses.

This was particularly true for patients with cirrhosis (HR, 4.60; 95% CI, 2.81-7.56) and the high HCC score by the Chinese University of Hong Kong (HR, 4.35; 95% CI, 2.58-7.32).

The investigators also found patients with chronic hepatitis B who maintained a virologic response with transient (HR, 4.72; 95% CI, 1.98-11.24) or persistent (HR, 12.16; 95% CI, 3.58-41.31) abnormal alanine transaminase (ALT) following virologic response had higher HCC hazard.

“Our study indicated an elevated HCC probability for entecavir-treated CHB patients with Non-MVR, especially for those with cirrhosis or a high predicted score at baseline,” the authors wrote. “For MVR patients, the trajectories in ALT after virologic response suggested different HCC risks.”

The Efficacy of Entecavir

Recently, investigators found both tenofovir alafenamide (TAF) and entecavir are safe and effective at treating hepatitis B virus reactivation.

HBV reactivation is classified as the reactivation of HBV DNA during cytotoxic or immunosuppressive therapy in patients who were previously treated for hepatitis B virus infections.

After HBV infects the host cells, the covalently closed circular DNA is stable in the infected cells and serves as a template for viral replication.

The reactivations can be asymptomatic but are commonly followed by a clinical flare characterized by a substantial increase in serum transaminase levels and histologic evidence of active inflammation, which could lead to fatal hepatic failure.

In the study, the investigators examined 77 patients treated with either entecavir (n = 66) and tenofovir alafenamide (n = 11) as a prophylaxis against or treatment of HBV reactivation during chemotherapy or immune suppression therapy between January 2010 and June 2020.

The team found at week 24 the antiviral effects on patients receiving either treatment were similar in terms of reduction of HBV DNA (−2.83 ± 1.45log IU/mL vs −3.05 ± 2.47log IU/mL; P = 0.857). There was also similar results of achieving undetectable levels of HBV DNA (78.8 vs 90.9%; P = 0.681) between the 2 cohorts.

Also, serum HBV DNA significantly decreased from week 0-24 in patients treated with entecavir (3.27 ± 1.72/0.43 ± 0.94 Log IU/mL, at week 0/24, respectively, P < 0.001) and tenofovir alafenamide (3.34 ± 2.98/0.29 ± 0.96 Log IU/mL at week 0/24, respectively, P = 0.005).

The study, “Virologic response maintenance and hepatocellular carcinoma in chronic hepatitis B patients treated with entecavir,” was published online in Expert Review of Gastroenterology & Hepatology.

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