Articles are available as citation abstract only
No abstract available
Articles are available as full text
Articles are available as citation plus
Click the icon to view the article
The latest thinking published in the leading Gastroenterology Journal. This randomized controlled double blind trial concludes that : 'treatment with adefovir dipivoxil for up to 240 weeks was well tolerated and produced significant, increasing improvement in hepatic fibrosis, durable suppression of HBV replication, normalization of liver enzymes, and delayed development of resistance' .
1 Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B for up to 5 years.
Hadziyannis SJ, Tassopoulos NC, Heathcote EJ, Chang TT, Kitis G, Rizzetto M, Marcellin P, Lim SG, Goodman Z, Ma J, Brosgart CL, Borroto-Esoda K, Arterburn S,
Chuck SL; Adefovir Dipivoxil 438 Study Group.
Gastroenterology. 2006 Dec;131(6):1743-51.
PMID: 17087951
There are now 6 approved therapies for hepatitis B virus (HBV) infection including 2 formulations of interferon, standard interferon α-2b (IFN-α-2b) and pegylated interferon α-2a (pegIFN-α-2a), and 4 nucleos(t)ide analogues, lamivudine (Epivir), adefovir (Hepsera), entecavir (Baraclude), and telbivudine (Tyzeka). Despite these advances, approved treatments for hepatitis B do not eradicate hepatitis B virus. Thus, clinical benefit is dependent on the ability to maintain sustained suppression of HBV replication. However, long-term treatment with nucleos(t)ide analogues is associated with increasing rates of drug resistance, and the safety and efficacy of these therapies beyond 1-5 years have not been established. This review aims to help the reader navigate the maze of hepatitis B treatments. And Anna Lok with her more than 160 publications on HBV - more than anyone else - is the best navigator to have on-board in these still largely uncharted waters.
2 Navigating the Maze of Hepatitis B Treatments.
Lok AS.
Gastroenterology. 2007 Feb 24; [Epub ahead of print] No abstract available.
PMID: 17408643 [PubMed - as supplied by publisher]
Again from Gastroenterology – but it is the top high impact GI journal - the ‘house journal' of the AGA published by Elsevier – the world’s largest medical publisher. Available via HINARI for non-western readers.
This phase III double blind trial concluded that in patients with lamivudine-refractory chronic hepatitis B, switching to entecavir provides superior histologic improvement, viral load reduction, and ALT normalization compared with continuing lamivudine, with a comparable adverse event profile'.
3 Entecavir for treatment of lamivudine-refractory, HBeAg-positive chronic hepatitis B.
Sherman M, Yurdaydin C, Sollano J, Silva M, Liaw YF, Cianciara J, Boron-Kaczmarska A, Martin P, Goodman Z, Colonno R, Cross A, Denisky G, Kreter B, Hindes R; AI463026 BEHoLD Study Group.
Gastroenterology. 2006 Jun;130(7):2039-49.
PMID: 16762627
This recent New England Journal of Medicine (NEJM) article is available full text after registration at the NEJM website. It’s good to see trials comparing drugs against each other rather than against placebo – even though ‘industry’ prefers control against placebo. This phase 3, double-blind trial randomly assigned 648 patients with HBeAg-negative chronic hepatitis B who had not previously been treated with a nucleoside analogue to receive 0.5 mg of entecavir or 100 mg of lamivudine once daily for a minimum of 52 weeks.
It concludes that among patients with HBeAg-negative chronic hepatitis B who had not previously been treated with a nucleoside analogue, the rates of histologic improvement, virologic response, and normalization of alanine aminotransferase levels were significantly higher at 48 weeks with entecavir than with lamivudine.
4 Entecavir versus lamivudine for patients with HBeAg-negative chronic hepatitis B.
Lai CL, Shouval D, Lok AS, Chang TT, Cheinquer H, Goodman Z, DeHertogh D, Wilber R, Zink RC, Cross A, Colonno R, Fernandes L; BEHoLD AI463027 Study Group.
N Engl J Med. 2006 Mar 9;354(10):1011-20. Erratum in: N Engl J Med. 2006 Apr 27;354(17):1863.
PMID: 16525138
This article , in the world’s highest ranking (by impact factor) medical journal concludes:
Among patients with HBeAg-positive chronic hepatitis B, the rates of histologic, virologic, and biochemical improvement are significantly higher with entecavir than with lamivudine.
Full text is available after registration.
5 A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B.
Chang TT, Gish RG, de Man R, Gadano A, Sollano J, Chao YC, Lok AS, Han KH, Goodman Z, Zhu J, Cross A, DeHertogh D, Wilber R, Colonno R, Apelian D; BEHoLD AI463022 Study Group.
N Engl J Med. 2006 Mar 9;354(10):1001-10.
PMID: 16525137
This offering form the Cochrane Hepato-Biliary Group in Copenhagen – a great source for systematic reviews - published in the BMJ , one of the serious advocates for evidence based publishing - looked at three outcomes: the relative risks of hepatitis B occurrence, antibody levels to hepatitis B surface antigen, and adverse events. They identified 29 randomised clinical trials, five of which were considered high quality .
They conclude that: “Hepatitis B vaccine, hepatitis B immunoglobulin, and vaccine plus immunoglobulin prevent hepatitis B occurrence in newborn infants of mothers positive for hepatitis B surface antigen.”
6 Effect of hepatitis B immunisation in newborn infants of mothers positive for hepatitis B surface antigen: systematic review and meta-analysis.
Lee C, Gong Y, Brok J, Boxall EH, Gluud C.
BMJ. 2006 Feb 11;332(7537):328-36. Epub 2006 Jan 27. Review.
PMID: 16443611
This review in GUT, one of the top 5 GI journals , is available full text for free. Its main conclusions: ALT is a poor predictor of outcome and therefore cannot be used as the sole indication for therapy. HBeAg positivity is associated with a higher risk of adverse outcomes than anti-HBe positivity. HBV DNA concentration at recruitment and during follow up is the best predictor of an adverse outcome.
The higher the HBV DNA concentration (above 104 copies/ml), the greater the mortality.
Treatment should be aimed at suppressing HBV DNA maximally, to below 104, and preferably to below.
7 Predicting survival in hepatitis B.
Sherman M.
Gut. 2005 Nov;54(11):1521-3. Review. No abstract available.
PMID: 16227355
This is a guideline representing the most recent thinking on Hepatitis B by the American Association for the study of the liver (AASLD). Interesting they call this a 'data-supported' approach rahter than an 'evidence-based' approach. Certainly searching Medline only and not adding searches in Embase and or the Cochrane Library is a little odd but on the other hand - the fact that they have scanned meeting abstracts is novel and a very good idea. With its 275 references and in view of who's writing this and where and when it is published I guess the guideline can be considered the definitive statement on where we are . Now who's going to break the mold!
8 Chronic hepatitis B.
Hepatology. 2007 Feb;45(2):507-39. No abstract available.
PMID: 17256718 [PubMed - indexed for MEDLINE]
Current treatments for hepatitis B are sub-optimal write this impressive line-up of key opinion leaders .So they compared the efficacy and safety of pegylated interferon alfa plus lamivudine, pegylated interferon alfa without lamivudine, and lamivudine alone for the treatment of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B.
They conclude that : ' In patients with HBeAg-positive chronic hepatitis B, peginterferon alfa-2a offers superior efficacy over lamivudine, on the basis of HBeAg seroconversion, HBV DNA suppression, and HBsAg seroconversion'.
It’s in the NEJM so it must be good!
9 Peginterferon Alfa-2a, lamivudine, and the combination for HBeAg-positive chronic hepatitis B.
NLau GK, Piratvisuth T, Luo KX, Marcellin P, Thongsawat S, Cooksley G, Gane E, Fried MW, Chow WC, Paik SW, Chang WY, Berg T, Flisiak R, McCloud P, Pluck N; Peginterferon Alfa-2a HBeAg-Positive Chronic Hepatitis B Study Group.
Engl J Med. 2005 Jun 30;352(26):2682-95.
PMID: 15987917
Treatment with adefovir dipivoxil for 48 weeks resulted in histologic, virologic, and biochemical improvement in patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B. The authors evaluated the effect of continued therapy as compared with cessation of therapy.
So, do you stop of do you go on? They conclude:
'In patients with HBeAg-negative chronic hepatitis B, the benefits achieved from 48 weeks of adefovir dipivoxil were lost when treatment was discontinued. In patients treated for 144 weeks, benefits were maintained, with infrequent emergence of viral resistance'.
Should we be wondering about 100 weeks? The article is available for free at the NEJM after registration.
10 Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B.
Hadziyannis SJ, Tassopoulos NC, Heathcote EJ, Chang TT, Kitis G, Rizzetto M, Marcellin P, Lim SG, Goodman Z, Ma J, Arterburn S, Xiong S, Currie G, Brosgart CL; Adefovir Dipivoxil 438 Study Group
N Engl J Med. 2005 Jun 30;352(26):2673-81.
PMID: 15987916
This comes from one of the leading WHO hepatologists and hepatitis experts.
Full text is available from 5 different electronic platforms (see the Pubmed ’link out’ feature) – all of them are commercial for profit platforms (Blackwell Publishing, EBSCO, Ingenta, Swets Information Services and OVID). It’s worth remembering you can often ‘bypass’ this system by asking authors to send you a copy – usually their email address is included.
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.
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.
Is there anything hopeful here? Lavanchy mentions: ‘promising emerging new treatments include adefovir, entecavir and peginterferon alfa-2a (40 kDa).
11 Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures.
Daniel Lavanchy
J Viral Hepat. 2004 Mar;11(2):97-107.
PMID: 14996343
This is all about HBV and genotype, natural history and phylogeny. An excellent article from the university of Cambridge, UK. Non western users can access this Elsevier journal via HINARI and all others need an ID and password or $ 30. - for 24 hr access.
Epidemiologically, the 7 identified genotypes are to a large extent related to geographical origin and they can contribute to the monitoring of infection of new virus strains in areas where the population is changing due to immigration for example. Different genotypes may have a different natural history and this in turn requires different screening strategies.
12 Epidemiology of Hepatitis B virus and genotype.
Jean-Pierre Allain.
J Clin Virol. 2006 May;36 Suppl 1:S12-7.
PMID: 16831687