Recent data on treatment of chronic hepatitis B with nucleos(t)ide analogues

Abstract

Forty years ago in 1967, Professor Blumberg discovered the Australian Antigen, later known as the hepatitis B surface antigen, and was awarded the Nobel Prize. This discovery enables the diagnosis of hepatitis B virus (HBV) infection and defines its epidemiology. Viral hepatitis B infection affects global health situation, and chronic hepatitis B (CHB) is particularly serious in the Asia-Pacific region. HBV vaccines created the first breakthrough in HBV prevention. Through universal HBV vaccination program for the newborns, promoted since the mid-1980s, the main route that perpetuates chronic infection from mother to child is curbed. Most children and young adults now have immunity against HBV infection. The next breakthrough comes with therapy for CHB. This prevents progression to cirrhosis and hepatocellular carcinoma. Standard interferon therapy with modest efficacy has been largely replaced by therapy with nuclos(t)ide analogues or pegylated interferons alfa-2a and -2b. Lamivudine was approved by the FDA USA in 1998, followed by adefovir dipivoxil in 2002, entecavir in 2005, and telbivudine in 2006. Clevudine, tenofovir, and many promising candidates are in different stages of development and clinical trial. This paper critically reviews recent data published or presented since the APASL Consensus and Guideline Update of 2005. Clinical efficacy mostly in patients with raised serum alanine aminotransferase will be analyzed.

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

“…It has an excellent safety profile (Ayoub & Keeffe, 2008;Fung et al, 2008;Jacobson, 2006;Leung, 2008;Y F Liaw et al, 2008) and is the least expensive of all nucleoside analogs approved for the treatment of CHB (Dan, Aung, & Lim, 2008;Zoulim & Perrillo, 2008). It is effective in suppressing HBV DNA, normalizing ALT and HBeAg seroconversion (Dienstag et al, 1999;Fung et al, 2008;Lai et al, 1998;Y F Liaw et al, 2008;.…”

“…It is effective in suppressing HBV DNA, normalizing ALT and HBeAg seroconversion (Dienstag et al, 1999;Fung et al, 2008;Lai et al, 1998;Y F Liaw et al, 2008;. Previous studies showed that LVD led to significant histological improvement and reduction in the progression of liver fibrosis (Ayoub & Keeffe, 2008;Dienstag et al, 1999;Lai et al, 1998;Leung, 2008). Long-term LVD therapy reduces the risk of developing cirrhosis and HCC in precirrhotic/cirrhotic and non-cirrohotic patients (Y. F. Liaw et al, 2004;.…”

“…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).…”

Chronic hepatitis B infection in a hepatology clinic at a university hospital in Jeddah

“…One of the yet unresolved CHB treatment issues is that the current recommendations and guidelines for CHB treatment exclude the groups of patients with lower HBV-DNA levels and patients with high HBV-DNA but normal ALT, who both still have a risk of progression to cirrhosis and HCC [18,[21][22][23]. In addition, most of the orally used nucleotide and nucleoside analogs for treatment of CHB carry variable risks of drug resistance [15,16,24]. Another issue of concern is the implementation of mass vaccination programs for HBV worldwide in children, which has resulted in the emergence of new HBsAg vaccine-escaped mutants of HBV [25].…”

Patterns of managing chronic hepatitis B treatment-related drug resistance: a survey of physicians in Mainland China, South Korea, Taiwan, and Thailand

“…It has been shown that the initial clinical benefit of NA therapy is lost among patients who develop NA resistance [5]. The emergence of NA-resistant mutations may lead subsequently to a loss of histologic improvement and, in some cases, severe exacerbations of liver diseases [6,7].…”