Chronic hepatitis B: early viral suppression and long‐term outcomes of therapy with oral nucleos(t)ides

Abstract

Chronic hepatitis B is a serious health problem worldwide with a substantial minority of patients experiencing premature death due to end-stage liver disease and/or hepatocellular carcinoma. Antiviral therapy may help prevent complications of chronic hepatitis B, and seven agents are currently approved in many countries. Of these agents, five are nucleos(t)ide analogs that all have a risk of antiviral drug resistance with long-term use. Efforts have been made in the recent years to prevent or to reduce the risk of viral resistance in patients treated with oral nucleos(t)ides as the majority of these patients will require therapy for 3-5 years or longer. One approach is to identify patients who would most likely develop antiviral resistance on long-term therapy using predictors obtainable early in the course of treatment, when intervention with new or additional therapy can be instituted. The most important predictors of treatment outcomes are serum HBV DNA levels at baseline and during the first 6 months of therapy. The purpose of this synopsis is to review the recent literature regarding the importance of serum HBV DNA levels in association with treatment outcomes in chronic hepatitis B, particularly the association of complete viral suppression early in the course of oral therapy with long-term treatment outcomes, particularly the incidence of antiviral drug resistance.

Reviews on the Epidemiology, Quality of Life, and Management of Chronic Hepatitis B (CHB)

“…The response was sustained in 26% of patients 6 months after stopping LVD treatment . The main drawback of LVD is development of drug resistance (Jacobson, 2006;Y F Liaw et al, 2008;Nguyen & Keeffe, 2009;Yuen & Lai, 2001;Zoulim & Perrillo, 2008). According to a recent review, LVD drug resistance rates are approximately 50% after 3 years and 76% after 8 years (Ayoub & Keeffe, 2008;Fung et al, 2008;Leung, 2008;Nguyen & Keeffe, 2009;.…”

“…The main drawback of LVD is development of drug resistance (Jacobson, 2006;Y F Liaw et al, 2008;Nguyen & Keeffe, 2009;Yuen & Lai, 2001;Zoulim & Perrillo, 2008). According to a recent review, LVD drug resistance rates are approximately 50% after 3 years and 76% after 8 years (Ayoub & Keeffe, 2008;Fung et al, 2008;Leung, 2008;Nguyen & Keeffe, 2009;. The incidence of drug resistance increased with the duration of therapy (Ayoub & Keeffe, 2008;Fung et al, 2008;Jacobson, 2006;Leung, 2008).…”

“…After 2 years of ETV treatment, no virological breakthrough from ETV resistance has been found Lai & Yuen, 2008;Y F Liaw et al, 2008). The rate of resistance to ETV was very low at 1.2% in treatment-naïve patients after 5 years (Ayoub & Keeffe, 2008; European Association For the study of the liver, 2008; Lai & Yuen, 2008;Y F Liaw et al, 2008;Nguyen & Keeffe, 2009). ETV has demonstrated to be effective in LVD-resistant patients, but was associated with a lower response rate and a higher resistance rate of 39.5% after 4 years (Ayoub & Keeffe, 2008;Keeffe et al, 2008;Y F Liaw et al, 2008;Nguyen & Keeffe, 2009).…”

Hepatitis B virus pre-existing drug resistant mutation is related to the genotype and disease progression

“…The nucleos(t)ide analogues (NAs) are extensively used in clinical work. However, the efficacy of NAs like including lamivudine (LAM), adefovir (ADV), telbivudine (LDT) are challenged during the treatment by drug resistance [1][2][3]. The resistance rate of entecavir (ETV) is relatively low, five-years drug resistance rate is about 1.2% [4].…”

On-treatment monitoring of HBV DNA levels: predicting response and resistance to oral antiviral therapy at week 24 versus week 48

“…More recently, this strategy has been incorporated into regional clinical treatment guideline recommendations [1][2][3]. Despite these recommendations, the universal applicability of week 24 as the optimal time point for evaluating treatment response to all oral NAs remains unclear, particularly for agents with low genetic barriers to resistance [18][19][20].…”