TITLE: Reappraisal of the Concept of Primary Virologic Response Defined by the Current Guidelines for the Management of Chronic Hepatitis B
AUTHORS (FIRST NAME, LAST NAME): Young Joo Yang1, Ju Hyun Shim2, Kang Mo Kim2, Young-Suk Lim2, Han Chu Lee2, Dong Jin . Suh2, 3
Institutional Author(s):
INSTITUTIONS (ALL): 1. Internal Medicine, Asan medical center, University of Ulsan College of Medicine, Seoul, Korea, Republic of.
2. Gastroenterology, Asan medical center, University of Ulsan College of Medicine, Seoul, Korea, Republic of.
3. Internal Medicine, Vievis Namuh Hospital, Seoul, Korea, Republic of.
ABSTRACT BODY: Background & Aims
Given the substantial evidence that early hepatitis B virus (HBV) DNA response after oral antiviral therapy can strongly predict prolonged virologic outcomes, treatment adaptation at an early phase is strongly recommended for chronic hepatitis B (CHB) patients with primary non-response during treatment. The purpose of this study is to assess whether the definition of primary virologic response to guide the CHB treatment algorithm suggested by the AASLD guidelines was optimal for treatment with entecavir, a newer and more potent antiviral agent.
Methods
This retrospective study included 1,262 treatment-naïve CHB patients receiving entecavir (0.5mg/day) monotherapy for over six months: median age 47 years, 63 % Male, 55% HBeAg-positive, and 42% cirrhosis. All patients had an HBV DNA level of at least 2,000 IU/mL at the start of their entecavir treatment. “Primary non-response” was defined as <2 log decrease in the serum HBV DNA level from the baseline after at least six months of therapy, according to the AASLD guidelines. The primary endpoint of this study was the virologic response, evidenced by achieving the serum HBV DNA to an undetectable level (<15 IU/mL) during the study period. The cumulative probability of a virologic response was evaluated and compared between the groups using Kaplan-Meier analysis and the log-rank test.
Results
In our study, the median duration of entecavir therapy was 31 months (range, 6 to 72 months). A total of 19 (1.5%) patients were categorized as primary non-responders. The cumulative rates for achieving a virologic response over time were 68.3%, 88%, 95%, and 95.7%, respectively, at 12, 24, 36, and 48 months, and which were significantly greater than the 29.4%, 64%, 88%, and 88%, respectively, seen in the primary non-responders (P=0.002). At 48 months, the proportion of virologic responders (95.6% vs 100%) and the mean reduction in the serum HBV DNA levels (-5.08 vs. -6.79 log10 IU/mL) were not associated with the presence of a primary response (P=NS for both). Entecavir resistance mutation emerged in 13 of the 36 patients who showed a virologic breakthrough during follow-up, and all of whom were classified as primary responders.
Conclusions
Our data indicate that long-term entecavir therapy leads to the ultimate virologic response in the vast majority of CHB patients, although the time required to achieve a virologic response was later in patients who did not show a primary response at six months. The current concept of primary non-response for early treatment adaptation should be refined on a drug-related basis in this current era of potent antivirals