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: 3.63). 01/2011; 26 Suppl 1(Suppl 1):138-43. DOI: 10.1111/j.1440-1746.2010.06545.x
Source: PubMed

ABSTRACT 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 Conventional interferon alpha (IFN-α), the only agent licensed in 1991, has been superseded by pegylated IFN-α.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: Niranthin is a lignan 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 niranthin using HepG2.2.15 cells and duck hepatitis B virus (DHBV) infected ducks as in vitro and in vivo models. Materials and methods: Niranthin 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 antihepatitis B virus activity was evaluated on the expression of HBV replication, HBsAg, HBeAg, ALT and AST on day 0, 7, 14, 17 after niranthin was dosed intragastricly (i.g.) once a day for 14 days at the dosages of 25, 50 and 100 mg/kg/day in the duck hepatitis B virus (DHBV) infected ducks. Results: In the human HBV-transfected liver cell line HepG2.2.15, the secretion of HBsAg and HBeAg were significantly decreased after treatment with niranthin for 144 h, with IC50 values for HBsAg of 15.6 mu M, IC50 values for HBeAg of 25.1 mu M. In DHBV-infected ducklings, niranthin significantly reduced the serum DHBV DNA, HBsAg, HBeAg, ALT and AST. Furthermore, analysis of the liver pathological changes confirmed the hepatoprotective effect of niranthin. Conclusion: The experimental data demonstrated that niranthin 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
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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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    • "About a quarter of the world’s population have been infected with hepatitis B virus (HBV), including 350 million patients with chronic hepatitis B (CHB); and about 15% to 25% of CHB patients would progress to life-threatening liver disease including cirrhosis and hepatocellular carcinoma [1]. Nucleos(t)ide analogues (NAs) as an important class of antiviral drugs have changed the treatment paradigm and prognosis of CHB [2]. However, the development of antiviral resistance has become a threat of NAs therapy [3,4], and an increasing number of patients experience multiple NAs treatment failures, especially when they are sequentially treated with NAs that have low genetic barrier and similar characteristics [5-7]. "
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    ABSTRACT: Aim To evaluate the efficacy and safety of Entecavir (ETV) plus adefovir (ADV) for chronic hepatitis B (CHB) patients after multiple nucleos(t)ide analogue (NAs) failure treatment. Methods Hepatitis B e antigen (HBeAg)-positive patients who had a suboptimal response or developed resistance to two or more previous NAs treatments were included, and all subjects were treated with ETV in combination with ADV for ≥ 24 months. Complete virologic response (CVR) was defined as an undetectability of serum hepatitis B virus (HBV) DNA level during treatment. Safety assessment was based on the increasing of serum creatinine and creatine kinase levels. Results A total of 45 eligible patients were included. Twenty-five patients had been treated with lamivudine (LAM) or telbivudine (LdT) and developed genotypic resistance. Resistance to ADV was present in 18 patients and 4 patients had a suboptimal response to ETV. Two patients had a resistance to both LAM and ADV. The cumulative probabilities of CVR at 12 and 24 months of ETV + ADV treatment were 88.9% (40/45) and 97.8% (44/45), respectively. Although one patient failed to achieve CVR, its serum HBV DNA level decreased by 3.3 log copies/mL after 24 months of combination therapy. The cumulative probability of HBeAg seroconversion was 15.6% (7/45) and 26.7% (12/45) at 12 and 24 months of treatment, respectively. History of prior exposure to specific NAs did not make a difference to ETV + ADV treatment outcome. There were no significant adverse events related to ETV + ADV therapy observed in the study subjects. Conclusion ETV + ADV can be used as an effective and safe rescue therapy in patients after multiple NA therapy failures, especially in the areas where tenofovir is not yet available.
    Virology Journal 05/2013; 10(1):162. DOI:10.1186/1743-422X-10-162 · 2.09 Impact Factor
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