Sequential combination therapies for HBeAg-positive chronic hepatitis B: the search continues
Ankur Jindal & Manoj Kumar
Hepatology International volume 15, pages1–3(2021)Cite this article
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Total eradication of the hepatitis B virus (HBV) is still elusive, as even if HBsAg is lost, covalently closed circular DNA (cccDNA) often persists in the hepatocytes. The currently available drugs for treatment of chronic hepatitis B (CHB) are not able to give sustained off-treatment HBsAg loss (functional cure) in most of the patients, which is the ultimate goal of therapy of CHB and is closest to eradication. In the absence of functional cure, Hepatitis B e antigen (HBeAg) seroconversion and undetectable HBV DNA are taken as end-points of antiviral therapy in HBeAg-positive CHB.
At present, monotherapy with potent nucleot(s)ide analogues (NAs) (directly inhibit HBV DNA polymerase) or pegylated interferon alpha (Peg-IFN) (immune modulator) is recommended as the first-line therapy for HBeAg-positive CHB. Long-term potent NA treatment has excellent viral suppression (more than 95% at 5 years) [1], but relapse is common after stopping NAs. Therefore, prolongation of potent NAs therapy over long period maintains the initially high virological remission rates. The rationale for Peg-IFN use is to induce immunological control with a finite duration of therapy [2]. However, the response to Peg-IFN treatment is highly variable and it has more side effects as compared to NAs. Among HBeAg-positive CHB patients, Peg-IFN therapy leads to higher HBeAg seroconversion and HBsAg seroclearance rates as compared to NAs, but the sustained virologic response rates at 6 months following 12 months of Peg-IFNa therapy are ~ 20–30% [3]. Baseline predictors for good response to Peg-IFN treatment include lower HBV DNA levels (< 7 log10 IU/ml) and higher ALT levels (2–3 times ULN) [1].作者: StephenW 时间: 2021-2-18 18:14