Famciclovir treatment of anti-HBE+ chronic hepatitis B: Results of a randomized, placebo-controlled study

Hepatitis B virus (HBV) infection is a serious global health problem, with 2 billion people infected worldwide, and 350 million suffering from chronic HBV infection. The 10th leading cause of death worldwide, HBV infections result in 500 000 to 1.2 million deaths per year caused by chronic hepatitis, cirrhosis, and hepatocellular carcinoma; the last accounts for 320 000 deaths per year. In Western countries, the disease is relatively rare and acquired primarily in adulthood, whereas in Asia and most of Africa, chronic HBV infection is common and usually acquired perinatally or in childhood. More efficacious treatments, mass immunization programs, and safe injection techniques are essential for eliminating HBV infection and reducing global HBV-related morbidity and mortality. Safe and effective vaccines against HBV infection have been available since 1982. The implementation of mass immunization programs, which have been recommended by the World Health Organization since 1991, have dramatically decreased the incidence of HBV infection among infants, children, and adolescents in many countries. However, not all countries have adopted these recommendations and there remains a large number of persons that were infected with HBV prior to the implementation of immunization programs. Antiviral treatment is the only way to reduce morbidity and mortality from chronic HBV infection. Conventional interferon alfa and lamivudine have been the primary treatments to date. Conventional interferon alfa produces a durable response in a moderate proportion of patients but has undesirable side-effects and must be administered subcutaneously three times per week. Lamivudine also produces a response in a modest proportion of patients and causes few side-effects. However, prolonged treatment is often necessary to prevent relapse on cessation of therapy, and continuous treatment can lead to the development of lamivudine resistance. Promising emerging new treatments include adefovir, entecavir and peginterferon alfa-2a (40 kDa).

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“…Nucleoside/nucleotide analogues suppress HBV replication through inhibition of HBV DNA polymerase [52][53][54].…”

Section: Nucleoside and Nucleotide Analogues In The Treatment Of Chromentioning

confidence: 99%

Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures

Lavanchy

2004

Journal of Viral Hepatitis

2,321

1,729

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“…Ganciclovir and famciclovir were found to be rather ineffective in phase II/III trials and have probably been abandoned. 55,56 Emtricitabine (the 5-fluorinated derivative of lamivudine), clevudine (a pyrimidine analogue), and L-nucleosides (natural nucleosides in ␤-Lconfiguration), particularly L-deoxythymidine, have given very promising results in preliminary phase I/II trials [57][58][59] and are also being evaluated for the treatment of CHB in phase III clinical trials. Initial data regarding the efficacy of immunomodulatory approaches, such as interleukin-2 or -12, interferon-␥, or vaccine-based therapies, have been relatively disappointing, and the results for thymosin are rather conflicting.…”

Section: Treatment Strategies In 2003 and Beyondmentioning

confidence: 99%

Treatment of HBeAg-Negative Chronic Hepatitis B

Hadziyannis¹,

Papatheodoridis²,

Vassilopoulos³

2003

Semin Liver Dis

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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.

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“…Famciclovir and its active form penciclovir have inhibitory activity against herpesviruses and hepadnaviruses [118,119]. In patients with chronic hepatitis B irrespective of HBeAg status, however, famciclovir, at a dose of 500 mg orally three times daily, was found to have a less potent antiviral effect than that observed with lamivudine therapy [120,121]. Viral resistance due to mutations in the B domain of the HBV polymerase gene remains a frequent problem with famciclovir, similar to that observed with lamivudine monotherapy [122].…”

Section: Management Of Pre‐core Mutant Hbv‐related Liver Diseasementioning

confidence: 99%

Diagnosis and management of pre‐core mutant chronic hepatitis B

Papatheodoridis

Hadziyannis

2001

Journal of Viral Hepatitis

102

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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.

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Famciclovir treatment of anti-HBE+ chronic hepatitis B: Results of a randomized, placebo-controlled study

Cited by 6 publications

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Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures

Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures

Treatment of HBeAg-Negative Chronic Hepatitis B

Diagnosis and management of pre‐core mutant chronic hepatitis B

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