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发表于 2004-2-28 06:47
| there are a lot of papers about review or treatment for heptitis B on medline.I would like to provide some of them
Aliment Pharmacol Ther. 2004 Jan 1;19(1):25-37.
Review article: current management of chronic hepatitis B.
Papatheodoridis GV, Hadziyannis SJ.
Academic Department of Medicine, Hippokration General Hospital, Athens, Greece.
Chronic hepatitis B can be diagnosed in patients with increased aminotransferases, hepatitis B virus viraemia and necroinflammation with fibrosis on liver biopsy. Although, ideally, all patients with chronic hepatitis B should be treated, therapeutic intervention is currently recommended for cases with a relatively satisfactory likelihood of response and/or advanced disease. A realistic therapeutic approach aims to sustain hepatitis B e antigen (HBeAg) loss and hepatitis B e antibody (anti-HBe) seroconversion in HBeAg-positive chronic hepatitis B and to sustain biochemical and virological remission in HBeAg-negative chronic hepatitis B. Currently, three drugs are licensed for chronic hepatitis B: interferon-alpha, lamivudine and adefovir dipivoxil. In patients with HBeAg-positive chronic hepatitis B, all of these drugs achieve HBeAg loss (24-33%) and anti-HBe seroconversion (12-30%) rates significantly superior to those observed in untreated placebo controls. In patients with HBeAg-negative chronic hepatitis B, the sustained off-therapy response rate is 20-25% after a > or =12-month course of interferon-alpha and minimal (<10%), if any, after a 12-month course of lamivudine or adefovir. Long-term lamivudine induces an initial response in 70-90% of patients, but only 30-40% of patients remain in remission after the third year due to progressively increasing viral resistance. Long-term adefovir achieves a response in approximately 70% of patients at 12 months, which is maintained at 24 months with rare (<2%) drug resistance. Adefovir is also effective against lamivudine-resistant strains. Many other anti-viral agents, immunomodulatory approaches and combination therapies are currently being evaluated in chronic hepatitis B.
Semin Liver Dis. 2003 Feb;23(1):81-8.
Treatment of HBeAg-negative chronic hepatitis B.
Hadziyannis SJ, Papatheodoridis GV, Vassilopoulos D.
Department of Medicine and Hepatology, Henry Dunant Hospital, Athens, Greece. [email protected]
The goals of therapy in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) are to abolish or efficiently suppress viral replication, which represents the main determinant of underlying liver necroinflammation and fibrosis. Currently available agents include interferon-alfa (IFN-alpha), lamivudine, and soon adefovir dipivoxil. A > or = 12-month course of IFN-alpha treatment or retreatment achieves sustained biochemical responses in 15 to 25% of patients with eventual hepatitis B surface antigen (HBsAg) loss and anti-HBs development in a proportion of them. Lamivudine induces initial virologic and biochemical responses in 70 to 90%, but breakthroughs due to lamivudine-resistant mutants accumulate with continuation of therapy and thus only one third of patients may remain in remission after the third year of therapy. Adefovir dipivoxil also achieves on-therapy responses in the majority of cases. Adefovir dipivoxil and entecavir appear to be effective against lamivudine-resistant strains. Many other antiviral agents and immunomodulatory approaches are currently evaluated for CHB, but, besides IFN-alpha, none has yet been convincingly shown to induce sustained off-therapy responses.
J Viral Hepat. 2001 Sep;8(5):311-21.
Diagnosis and management of pre-core mutant chronic hepatitis B.
Papatheodoridis GV, Hadziyannis SJ.
Academic Department of Medicine, Hippokration General Hospital, Athens, Greece.
Chronic hepatitis due to pre-core hepatitis B virus (HBV) mutants presents as hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB). HBeAg-negative CHB represents a late phase in the natural course of chronic HBV infection that develops after HBeAg loss and seroconversion to anti-HBe. It is usually associated with pre-core stop codon mutation at nucleotide 1896 (mainly selected in non-A HBV genotypes), but also with other pre-core changes or with mutations in the basic core promoter region (mainly in HBV genotype A). In chronic HBV infections, pre-core mutants can be detected both in patients with HBeAg-negative CHB and in inactive hepatitis B surface antigen (HBsAg) carriers. The diagnosis of HBeAg-negative CHB is based on HBsAg positivity, HBeAg negativity, and mainly on increased alanine aminotransferase (ALT) and serum HBV-DNA levels and exclusion of other causes of liver disease. The differential diagnosis between patients with CHB and inactive HBsAg carriers can be made only by close follow-up of aminotransferase activity and viraemia levels, although the cut-off level of serum HBV DNA has not been definitely determined. IgM anti-HBc levels have also been suggested as an index that increases the diagnostic accuracy for transient hepatitis flares, while liver biopsy confirms the diagnosis and evaluates the severity of the liver disease. Interferon-alpha (IFN-alpha) and lamivudine are the two drugs that have been tried, mainly in the management of HBeAg-negative CHB. A 12-month course of IFN-alpha achieves sustained biochemical remission in about 20% of patients, which has been associated with improvement in the long-term outcome of this subset. A 12-month course of lamivudine is rather ineffective, maintaining remission in less than 15% of patients after cessation of therapy. Long-term lamivudine is associated with progressively increasing rate of virological and subsequent biochemical breakthroughs due to YMDD mutants, with approximately 30% of patients remaining in remission in the third year of therapy. Several other antiviral agents are currently being evaluated in this setting with combined regimens being the most reasonable step for the near future.
Semin Liver Dis. 2002;22 Suppl 1:33-6.
Advances in therapy for chronic hepatitis B.
Marcellin P.
Service d' Hepatologie and INSERM 0481, Hopital Beaujon, Clichy, France. [email protected]
Two agents are currently approved for the treatment of chronic hepatitis B: interferon alfa and lamivudine. Each agent has inherent limitations for use in the treatment of chronic hepatitis B. Interferon alfa is effective in a small number of patients and has serious side effects that limit its tolerability. The efficacy of lamivudine is limited by the emergence of drug-resistant hepatitis B virus (HBV) mutants, restricting its utility as a long-term therapy for chronic hepatitis B. As a result, a large proportion of chronic hepatitis B patients continue to be in need of a safe and efficacious therapy. This article provides an integrated analysis of the safety and efficacy of a new nucleotide analogue, adefovir dipivoxil, based on emerging data from recent studies. The study groups include patients with hepatitis B e antigen (HBeAg)-positive and HBeAg-negative chronic hepatitis B; lamivudine-resistant patients with compensated liver disease; lamivudine-resistant patients coinfected with the human immunodeficiency virus (HIV); and lamivudine-resistant pretransplant and posttransplant patients with decompensated liver disease. Adefovir dipivoxil 10 mg/d demonstrated potent anti-HBV activity consistently across this broad range of patient populations and was well-tolerated. Adefovir dipivoxil's effects include rapid and sustained virological, serological, histological, and biochemical responses, with minimal adverse effects. Significant histological improvement was seen in all patient subgroups at 48 weeks.
J Gastroenterol Hepatol. 2002 Apr;17(4):406-8.
Management of patients with chronic hepatitis B.
Liaw YF.
Liver Research Unit, Chang Gung University Memorial Hospital, 199 Tung Hwa North Road, Taipei, Taiwan. [email protected]
Better understanding of hepatitis B virus (HBV) replication and the natural history and immunopathogenesis of chronic hepatitis B, together with the introduction of effective agents with different mechanisms of action, is the basis for better therapeutic strategies against chronic hepatitis B. Substantial experience has now been accumulated in the use of some of these drugs, and an Asia-Pacific Consensus has been reached on indications for their use. The goals of therapy and aspects of general management will be reviewed here. Among currently available drugs, alpha-interferon therapy gives a response rate (hepatitis B e antigen (HBeAg) seroconversion) of 30-40% compared with 10-20% in matched controls, but patients with lower alanine aminotransferase (ALT), higher HBV-DNA, and immunosuppressed patients have a poorer response, and alpha-interferon can be dangerous in cirrhosis. Meta-analysis of four controlled trials also suggests that thymosin-alpha1 is effective, but more studies are needed. Lamivudine has been most extensively studied. It is effective in terms of HBV-DNA loss, ALT normalization, HBeAg seroconversion, and improvement in histology, as well as being well tolerated. After 1 year of treatment, HBeAg seroconversion rate increased with higher pretherapy ALT levels, suggesting that patients with stronger endogenous antiviral defenses to kill hepatocytes harboring covalently closed circular DNA have a better response to direct antiviral effects. Lamivudine is also beneficial in HBeAg negative chronic hepatitis B, and patients with decompensated cirrhosis and HBV replication. However, genotypic-resistant tyrosine-methionine-aspartate-aspartate (YMDD) mutations start to emerge after 9-10 months of lamivudine therapy, and their incidence increases more quickly than the HBeAg seroconversion rate durating prolonged therapy. Thus the benefits of long-term lamivudine must be balanced against concern about YMDD mutations, and the durability of treatment response. There are encouraging preliminary results for adefovir dipivoxil, entecavir, emtricitabine, clevudine and other nucleoside/nucleotide analogs in the early stages of appraisal; entecavir and adefovir dipivoxil appear effective in patients with YMDD mutants. Further development of new drugs and new strategies, such as combination or sequential therapy, may help to better achieve the goals of treatment for chronic hepatitis B in the new century. Copyright 2002 Blackwell Publishing Asia Pty Ltd
Intervirology. 2003;46(6):413-20.
Antivirals for the treatment of chronic hepatitis B: current and future options.
Humphries JC, Dixon JS.
GlaxoSmithKline KK, 6-15, Sendagya 4-chrome, Shibuya-ku, Tokyo 151-8566, Japan. [email protected]
Despite effective vaccination programmes, new hepatitis B virus (HBV) infections remain common and there are many millions of individuals already infected. Therapeutic agents are needed to reverse existing liver disease and prevent future disease progression. This article reviews recently published clinical data on the two currently available antivirals for the treatment of chronic hepatitis B infection, lamivudine and adefovir dipivoxil. Lamivudine, a nucleoside analogue, is currently the only licensed antiviral for the treatment of chronic hepatitis B in Asia. Extensive clinical trials have shown that lamivudine is effective and well tolerated in a wide range of patients. YMDD variants have been identified in some patients with reduced sensitivity to lamivudine after extended therapy. Adefovir dipivoxil, a nucleotide analogue, will soon be commercially available in Asia. Adefovir dipivoxil 10 mg is well tolerated and is as effective as lamivudine in reducing serum HBV DNA and alanine aminotransaminase levels and increasing seroconversion in patients with hepatitis B e antigen. No adefovir-resistant mutants have been reported during 48-week clinical trials. The addition of adefovir dipivoxil to ongoing lamivudine therapy, in patients with YMDD variants and a reduced response to lamivudine, leads to significant inhibition of viral replication and improvement in liver function after 1 year of therapy. Copyright 2003 S. Karger AG, Basel
Korean J Gastroenterol. 2003 Nov;42(5):357-62.
[Application and efficacy of adefovir dipivoxil in hepatitis B virus-associated [correction of assoicated] chronic liver diseases]
Cho YK, Kim BI.
Department of Internal Medicine, Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Pyeong-dong, Jongno-gu, Seoul 110-746, Korea. [email protected]
In therapy of chronic hepatitis B, there are new and exciting developments in antivirals such as nucleotide analogues. Adefovir dipivoxil is an oral prodrug of adefovir, a nucleotide analogue of adenosine monophosphate. This agent has a potent in vitro and in vivo effect against herpes virus, retroviruses, and hepadnaviruses. In the hepatitis B virus (HBV) setting, adefovir dipivoxil inhibits both the wild type and lamivudine-resistant HBV strains. The safety profile of adefovir dipivoxil 10 mg is excellent, but higher doses can produce renal tubular damage, particularly when the drug is used for prolonged therapy. Adefovir dipivoxil is an important new addition to the current first-line treatments for HBeAg positive and negative chronic hepatitis B, as well as being rescue therapy for lamivudine-resistant HBV strains. It is also licensed for use in adults with decompensated liver disease, as well as compensated liver disease where there is evidence of active viral replication, persistently elevated serum alanine aminotransferase levels and active liver inflammation and fibrosis. However, a longer follow-up is needed to establish the long term safety and efficacy of adefovir dipivoxil in patients with chronic HBV infection.
Forum (Genova). 2001 Apr-Jun;11(2):137-50.
Hepatitis B: therapeutic perspectives.
Rizzetto M, Lagget M.
Dipartimento di Gastroenterologia, Universita di Torino, Azienda Ospedaliera S. Giovanni Battista, Torino, Italy.
Therapy with interferon (IFN), an immunomodulant with anti-viral activities, is efficacious only in a minority of chronic hepatitis B (CHB); it is more efficacious in the hepatitis B e antigen (HBeAg)-positive variety sustained by the wild type hepatitis B virus (HBV) than in the HBeAg-negative variety sustained by mutant forms of the virus. Several other therapeutic approaches were attempted in recent years. The most promising is therapy with synthetic nucleosides as anti-virals capable of blocking the replicative activity of the HBV. Lamivudine (LAM) is the first of this class of compounds that has entered clinical use. It is well tolerated and highly effective in inhibiting HBV and abate HBV-related inflammation both in the HBeAg positive and negative variety of CHB. In the HBeAg positive variety it induces sero-conversion to anti-HBe at a rate that linearly increases over the years, reaching 40% at the third year. In the HBeAg-negative variety maintenance of viral repression requires continuative therapy. A major drawback of continued LAM therapy is the risk of the emergence of mutants in the tyrosine-methionine-aspartate-aspartate locus of the polymerase gene. These mutants are no longer responsive to LAM and may rekindle disease; wild type HBV and related disease often return after suspension of therapy. Other anti-viral drugs, the prototype of which is adefovir, are currently under clinical investigation in CHB as monotherapy or complementary therapy to LAM.
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