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Hepatitis
ViRgil Data – Real-life Study
Jurriën Reijnders (The Netherlands) presented results of an in the treatment-naïve group. Within the treatment-naïve group,
international multicentre cohort study as a member of the ViRgil HBeAg-negative patients had a higher response rate than HBeAg-
group. The study investigated the efficacy of entecavir in positive patients (92 versus 55%). Using a multivariate Cox analysis,
nucleos(t)ide analogue (NUC)-naïve and NUC-experienced patients, initial HBeAg negativity was a predictor of virological response, with
additionally identifying baseline factors that affect virological a hazard ratio of 0.51 (95% confidence interval [CI] 0.33–0.80;
response. A total of 161 chronic hepatitis B virus (HBV)-infected p=0.004); this was independent of viral load. Superior predictors of
patients were enrolled (104 were naïve) and monitored every three response were low HBV DNA at baseline, with a hazard ratio of 0.67
months for HBV DNA, alanine aminotransferase (ALT), creatinine (95% CI 0.59–0.77; p<0.001), and high ALT levels, with a hazard ratio
levels and hepatitis B ‘e’ antigen (HBeAg) status. Defined end-points of 1.06 (95% CI 1.03–1.09; p<0.001). For secondary outcomes, HBsAg
were virological response (<80IU/ml), HBeAg and HBsAg loss, loss did not occur, but 19% of the naïve patients had HBeAg loss
emergence of entecavir-related mutations and ALT normalisation. compared with 8% of previously treated patients. Furthermore, no
Patients previously treated with NUCs were more likely to be HBeAg- naïve patients developed genotypic resistance to entecavir, while 9%
positive than the naïve patients (p<0.001).* After 12 months of of the experienced patients did. The authors concluded that
treatment this group had a response rate of 55%, compared with 81% entecavir is highly efficacious in NUC-naïve patients.
87
n
*The majority of treatment-experienced patients had previously received lamivudine.
first three years of treatment. Consequently, the EASL clinical practice Summary and Conclusions
guidelines do not recommend the three older NUCs as first-line therapy The focus of the 44th International Liver Meeting was aimed at the new
in treatment-naïve patients. clinical practice guidelines and their application in clinical practice.
Discussion centred on the development of HBV resistance, avoidance
Compliance should be assessed in patients who experience a partial and control. The clinical practice guidelines and all speakers recommend
response. Patients adherent to medication should be treated with the new third-generation antiviral agents entecavir and tenofovir as first
second- or third-line therapies. Partial response with one of the third- line-therapy in treatment-naïve patients, particularly as they are
generation NUCs may be caused by drug resistance. The level of associated with a high genetic barrier to resistance. The use of less
viraemia and specific pattern of HBV DNA should be assessed for costly, older therapies such as lamivudine is more likely to cause longer-
each patient. term complications of resistance, and patients will consequently require
more expensive treatment regimens.
Sequential treatment with lamivudine followed by adefovir has been
used in clinical practice. However, it is, a time-consuming regimen: HBV Lamivudine has been widely used, however, and has proved to be a
DNA requires monitoring every three months and rescue treatment is safe and useful drug despite its early resistance development. The
required for viral breakthrough. With this strategy, 80% of patients will persistence of HBV in the liver as cccDNA inhibits complete
receive combination therapy within five years, said Lampertico. eradication of HBV with current therapies. There is evidence that
Lamivudine is inexpensive but in clinical practice may lead to the use of fibrosis, previously thought to be an established condition, can be
more expensive treatment regimens and at a cost to the patient. In reversed with effective long-term viral suppression with the most
Europe, in the case of lamivudine resistance the so-called ‘add on potent antiviral therapies available. n
strategy’ with adefovir given in addition to continuous therapy with
lamivudine has been used very successfully. Supported by Bristol-Myers Squibb.
1. World Health Organization, Hepatitis B. Fact sheet N°204. alone, lamivudine alone, and the two in combination in term therapy with adefovir dipivoxil for HBeAg-negative
Available at:
www.who.int/mediacentre/factsheets/fs204/ patients with HBeAg-negative chronic hepatitis B, N Engl J chronic hepatitis B for up to 5 years, Gastroenterology,
en/ (accessed 26 July 2009). Med, 2004;351:1206–17. 2006;131:1743–51.
2. Fattovich G, Natural history and prognosis of hepatitis B, 9. Wu IC, Shiffman ML, Tong MJ, et al., Sustained hepatitis B e 14. Heathcote EJ, Gane EJ, deMan RA, et al., Two year tenofovir
Semin Liver Dis, 2003;23:47–58. antigen seroconversion in patients with chronic hepatitis B disoproxil fumarate (TDF) treatment and adefovir dipivoxil
3. Fattovich G, Natural history of hepatitis B, J Hepatol, after adefovir dipivoxil treatment: analysis of precore and (ADV) switch data in HBeAg-positive patients with chronic
2003;39(Suppl. 1):S50–58. basal core promoter mutants, Clin Infect Dis, Hepatitis B (STUDY 103), preliminary analysis, Hepatology,
4. Hadziyannis SJ, Hepatitis B e antigen negative chronic 2008;47:1305–11. 2008;48(Suppl.):376A, abstract 158.
hepatitis B: from clinical recognition to pathogenesis and 10. Snow-Lampart A, Chappell BJ, Curtis M, et al., Week 96 15. Marcellin P, Maria Buti M, Krastev Z, et al., Two year
treatment, Viral Hepat Rev, 1995;1:7–36. resistance surveillance for HBeAg positive and negative tenofovir disoproxil fumarate (TDF) treatment and adefovir
5. Hadziyannis SJ and Papatheodoridis GV, Hepatitis B e subjects with chronic HBV infection randomized to receive dipivoxil (ADV) switch data in HBeAg-negative patients with
antigen-negative chronic hepatitis B: natural history and tenofovir DF 300 mg QD, Hepatology, 2008;48(Suppl.):745A, chronic Hepatitis B (STUDY 102), preliminary analysis,
treatment, Semin Liver Dis, 2006;26:130–41. abstract 977. Hepatology, 2008;48(Suppl.):370A, abstract 146.
6. Lampertico P, Partial virological response to nucleos(t)ide 11. Lai CL, Gane E, Liaw YF, et al., Telbivudine versus lamivudine 16. Seeger C, Zoulim F, Mason WS, Hepadnaviruses. In: Knipe
analogues in naive patients with chronic hepatitis B: From in patients with chronic hepatitis B, N Engl J Med, DM (ed.), Fields Virology, 5th ed, Philadelphia: Lippincott
guidelines to field practice, J Hepatol, 2009;50:644–7. 2007;357:2576–88. Williams & Wilkins, 2007;2977–3030.
7. European Association For The Study Of The Liver, EASL 12. Liaw YF, Gane E, Leung N, et al., 2-Year GLOBE trial results: 17. Heathcote EJ, Germanidis G, Dusheiko G, et al.,
Clinical Practice Guidelines: management of chronic telbivudine Is superior to lamivudine in patients with Characteristics of HBeAg-positive patients with HBsAg
hepatitis B, J Hepatol, 2009,50:227–42. chronic hepatitis B, Gastroenterology, 2009;136:486–95. loss/seroconversion following treatment with tenofovir
8. Marcellin P, Lau GK, Bonino F, et al., Peginterferon alfa-2a 13. Hadziyannis SJ, Tassopoulos NC, Heathcote EJ, et al., Long- disproxil fumarate (TDF), J Hepatol, 2009;50(Suppl. 1):S330,
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