Treatment of chronic hepatitis B: Evolution over two decades

Department of Medicine, the University of Hong Kong, Queen Mary Hospital, China.
Journal of Gastroenterology and Hepatology (Impact Factor: 3.5). 01/2011; 26 Suppl 1(Suppl 1):138-43. DOI: 10.1111/j.1440-1746.2010.06545.x
Source: PubMed


There has been a recent paradigm shift in the indications and endpoints of treatment for chronic hepatitis B (CHB). Hepatitis B e antigen (HBeAg)-negative disease is being increasingly recognized. Antiviral treatment for both HBeAg-positive and HBeAg-negative patients should aim at long-term suppression of HBV DNA, with the ultimate ideal endpoint of hepatitis B surface antigen (HBsAg) seroconversion. Conventional interferon alpha (IFN-α), the only agent licensed in 1991, has been superseded by pegylated IFN-α. HBeAg seroconversion using pegylated IFN-α is 33%, with only 25% of HBeAg-positive patients achieving undetectable HBV DNA by polymerase chain reaction (PCR) assay. Five nucleoside/nucleotide analogues have been licensed since 1998. Lamivudine, an L-nucleoside, is limited by the development of resistance in 76% of patients after 5 years of therapy. Telbivudine, another L-nucleoside, is more potent than lamivudine but resistance still develops in 25% of HBeAg-positive and 11% HBeAg-negative patients after 2 years. Adefovir, an acyclic phosphonate, is relatively weak, but is effective against lamivudine- and telbivudine- resistant mutations, for which it should be used in combination (add-on therapy) rather than substituted. Resistance to adefovir develops slowly, rising to 29% for HBeAg-negative patients by year 5, but more rapidly when used alone for lamivudine-resistant HBV. Currently the two first line nucleoside/nucleotides are entecavir and tenofovir. Entecavir, a cyclopentane (D-nucleoside), is very potent, with 94% of patients having undetectable HBV DNA after 5 years. Resistance develops in only 1.2% of treatment-naïve patients. Tenofovir, another acyclic nucleotide, is more potent with less renal toxicity compared to adefovir. It is effective against lamivudine-resistant mutations when used alone. No resistance to tenofovir has been described after its use for 3 years or longer, often for patients with human immunodeficiency virus/HBV co-infection. With these current, potent antiviral agents associated with very low rates of resistance, long-term HBV DNA suppression and possibly even reversal of cirrhosis can now be achieved in a proportion of patients. In addition, long-term treatment with these antiviral agents is associated with a reduced risk of development of hepatocellular carcinoma.

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    • "HBV infection, responsible for over 1.2 million deaths annually, has produced a serious health problem, particularly in sub-Saharan Africa, China and South-East Asia (Parkin et al., 1999; Wong and Lok, 2006). Although several anti-viral drugs, including interferon-α and nucleoside analogs, have been approved for the treatment of hepatitis B, unresolved critical issues remain, including moderate to low efficacy, dose-dependent side effects, and the newly developed drug resistance (Perrillo, 2005; Yuen and Lai, 2011). Therefore, there exists a significant unmet medical need for safe and efficacious new anti-HBV drugs. "
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    ABSTRACT: Ethnopharmacological relevance: Nirtetralin B, a new lignan first reported by our team, is isolated from Phyllanthus niruri L. This plant has long been used in folk medicine for liver protection and antihepatitis B in many Asian countries. This study was designed to evaluate the anti-hepatitis B virus activity of nirtetralin B using HepG2.2.15 cells and duck hepatitis B virus (DHBV) infected ducks as in vitro and in vivo models. Materials and methods: Nirtetralin B was isolated from Phyllanthus niruri L. (Euphorbiaceae) by extraction and chromatographic procedures and the anti-hepatitis B virus activity was evaluated both in vitro and in vivo. The human HBV-transfected liver cell line HepG2.2.15 was used in vitro assay. And the in vivo anti-hepatitis B virus activity was evaluated on the expression of HBV replication, HBsAg, HBeAg, ALT and AST on day 0, 7, 14, 17 after nirtetralin B was dosed intragastricly (i.g.) once a day for 14 days at the dosages of 25, 50 and 100mg/kg/day in the duck hepatitis B virus (DHBV) infected ducks. Results: In the human HBV-transfected liver cell line HepG2.2.15, nirtetralin B effectively suppressed the secretion of the HBV antigens in a dose-dependent manner with IC50 values for HBsAg of 17.4μM, IC50 values for HBeAg of 63.9μM. In DHBV-infected ducklings, nirtetralin B significantly reduced the serum DHBV DNA, HBsAg, HBeAg, ALT and AST. And analysis of the liver pathological changes confirmed the hepatoprotective effect of nirtetralin B. Conclusion: The experimental data demonstrated that nirtetralin B exhibits anti-hepatitis B virus activity both in vitro and in vivo.
    Journal of Ethnopharmacology 07/2014; 155(2). DOI:10.1016/j.jep.2014.05.064 · 3.00 Impact Factor
    • "In both conditions, hepatitis B surface antigen (HBsAg), a glycoprotein of the envelope of HBV itself, initially referred to as Australia Antigen (Au Ag) (Blumberg, Alter, & Visnich, 1965), is positive in serum (Blumberg, Sutnick, & London 1969; Hadziyannis, 2011a). It has also been realized that in chronic HBV infection, the liver usually exhibits number of patients with chronic HBV infection, mostly children and young adults, were HBeAg-positive and had very high HBV DNA levels, but serum aminotransferases and liver histology were nearly normal (Chu et al., 1985; Yuen & Lai, 2011). This was considered to be an immune tolerant state, and then the natural history of chronic HBV infection consisting of three phases was proposed (Chu et al., 1985). "
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    ABSTRACT: Chronic infection with the hepatitis B virus (HBV) runs a long natural course during which underlying changes in liver histology can progress to cirrhosis and hepatic decompensation, as well as to hepatocellular carcinoma. Therapeutic intervention is currently aiming at suppression of HBV replication by applying a number of pharmacological agents. For an optimum use of available therapies, good knowledge of the natural course of chronic infection, as well as of the role played by several viral, host, and environmental factors, is mandatory. The larger part of this chapter deals with how to treat the various subsets of patients with chronic hepatitis B (CHB), using mainly three first-line drugs: pegylated interferon-α2a, entecavir, and tenofovir, administered either in finite courses or indefinitely. The frequency of virological, serological, biochemical, and histological responses in the various subsets of patients, both during and after stopping treatment, is reviewed. It is stressed that the application of the highly potent antivirals entecavir and tenofovir, with acceptable safety records and with a high barrier to HBV resistance, represents major progress in the treatment of CHB. Despite the hitherto important developments in the treatment of viral hepatitis B, clinical cure of chronic HBV infection with HBsAg loss is achievable only in a few treated patients while eradication of HBV infection appears unrealistic. Development of new pharmacological agents acting at multiple targets of the replicative cycle of HBV may achieve higher efficacy and even cure of CHB.
    Advances in pharmacology (San Diego, Calif.) 12/2013; 67:247-91. DOI:10.1016/B978-0-12-405880-4.00007-X
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    • "As a result of these factors, cases of hepatic diseases have also been on the rise [9]. Studies show that HIV co infection adversely impacts on the natural history of HBV and HCV [7] by accelerating progression to chronic live disease due to drug-related hepatotoxicity and hepatitis reactivation [10-12]. At this stage, most patients are likely to die due to liver-related diseases compared to those without HIV infection [13]. "
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    ABSTRACT: Hepatitis B virus (HBV) and Hepatitis C virus (HCV) co-infections among HIV-1 infected individuals are growing worldwide health problems characterized by lack of effective vaccines, need for expensive treatment, chronicity of morbidity and associated mortality. Their prevalence and distribution patterns continue to vary across geographical locations with high prevalence being detected among high risk populations. To determine the prevalence of HBV and HCV among HIV-1 infected individuals, blood samples were collected from consenting study subjects visiting comprehensive HIV clinics in Nairobi during the period between October and December 2009. Blood samples from volunteers were screened with ELISA tests for detecting HIV, HBV surface antigen (HBsAg) and anti-HCV antibodies. In a total of three (300) hundred infected individuals consisting of 129 (43%) males and 171 (57%) females 15.3% (46/300) were HIV-1 co-infected with either HBV or HCV or both, 10.3% (31/300) with HIV-1 and HCV and 6% (18/300) with HIV-1 and HBV infections. However, only three individuals (1%) were coinfected with the three viruses (HIV/HBV/HCV). Though, low levels of co-infection with all three viruses were reported, there could be higher prevalence rates than reported here especially among high risk populations.
    BMC Research Notes 09/2013; 6(1):363. DOI:10.1186/1756-0500-6-363
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