Hope-For-HepB Top10 February 2009

Antiviral therapy for adults with chronic hepatitis B: a systematic review for a National Institutes of Health Consensus Development Conference.

Shamliyan TA, MacDonald R, Shaukat A, Taylor BC, Yuan JM, Johnson JR, Tacklind J, Rutks I, Kane RL, Wilt TJ.

Ann Intern Med. 2009 Jan; 150(2):111-24. Epub 2009 Jan 5.

Rating & Commentary
** Methodological strict study including 16 RCT and 4431 patients indicating that evidence of antiviral therapy in chronic hepatitis B was insufficient to assess treatment effect on clinical outcomes!

Meta-analysis: Treatment of hepatitis B infection reduces risk of hepatocellular carcinoma.

Sung JJ, Tsoi KK, Wong VW, Li KC, Chan HL.

Aliment Pharmacol Ther. 2008 Nov; 28(9):1067-77. Epub 2008 Jul 24.

Rating & Commentary
* Meta-analysis of 12 studies including 2742 patients, that indicates a significant risk reduction of HCC in chronic hepatitis B by antiviral therapy of IFN or Nucleoside Analogues.

Modeling complex decay profiles of hepatitis B virus during antiviral therapy.

Dahari H, Shudo E, Ribeiro RM, Perelson AS.

Hepatology. 2009 Jan;49(1):32-8.

Rating & Commentary
** Hepatitis B virus usually decays under nucleoside analogue therapy in a biphasic manner. More complex decay profiles of HBV DNA can according to this study be explained by introduction of the factor: critical drug efficacy. If drug efficacy in the specific patient is higher than critical drug efficacy, than viral levels will continually decline on therapy; if not, complex patients will evolve.

Complex dynamics of hepatitis B virus resistance to adefovir.

Pallier C, Rodriguez C, Brillet R, Nordmann P, Hézode C, Pawlotsky JM.

Hepatology. 2009 Jan;49(1):50-9.

Rating & Commentary
* Study of patients included in a 240-week clinical trial of adefovir monotherapy who developed resistance to adefovir. Analysis of nearly 4,000 full-length RT sequences suggest that adefovir selects during therapy emerging viral populations with adefovir resistance. Lamivudine add-on restores antiviral efficacy, but adefovir-resistant variants remain predominant.

Susceptibility of hepatitis B virus to lamivudine restored by resistance to adefovir.

Zaaijer HL, Takkenberg RB, Weegink CJ, Rebers SP, Menting S, Reesink HW, Schinkel J, Molenkamp R.

J Med Virol. 2009 Mar;81(3):413-6.

Rating & Commentary
* Small study describing replacement of all HBV wild type virus by lamivudine resistant mutants, which were replaces subsequently by adefovir resistant mutants. When lamivudine was added-on, the adefovir resistant variants persisted in all clones and lamivudine-related mutations did not reappear.

A mechanism to explain the selection of the hepatitis e antigen-negative mutant during chronic hepatitis B virus infection.

Frelin L, Wahlström T, Tucker AE, Jones J, Hughes J, Lee BO, Billaud JN, Peters C, Whitacre D, Peterson D, Milich DR.

J Virol. 2009 Feb;83(3):1379-92. Epub 2008 Nov 12.

Rating & Commentary
* Study in transgenic mice, providing the concept that HBeAg-negative chronic hepatitis B represents a CTL-escape mutant.

Impact of chewing betel-nut (Areca catechu) on liver cirrhosis and hepatocellular carcinoma: a population-based study from an area with a high prevalence of hepatitis B and C infections.

Wu GH, Boucher BJ, Chiu YH, Liao CS, Chen TH.

Public Health Nutr. 2009 Jan;12(1):129-35. Epub 2008 Apr 15.

Rating & Commentary
* Population based study identifying chewing betel-nuts as a key carcinogenic for hepatocellular carcinoma and cirrhosis.

Spontaneous Increases in Alanine Aminotransferase Levels in Asymptomatic Chronic Hepatitis B Virus-Infected Patients.

Kumar M, Chauhan R, Gupta N, Hissar S, Sakhuja P, Sarin SK.

Gastroenterology. 2009 Jan 16. [Epub ahead of print]

Rating & Commentary
* Study in 217 asymptomatic inactive HBsAg carriers for 5 years, describing the quantitative risk of disease activity over time. Spontaneous ALT flares were observed at an annual rate of 4,3% with a cumulative probabilities of 11% at 5 years.

20 years into the Gambia Hepatitis Intervention Study: assessment of initial hypotheses and prospects for evaluation of protective effectiveness against liver cancer.

Viviani S, Carrieri P, Bah E, Hall AJ, Kirk GD, Mendy M, Montesano R, Plymoth A, Sam O, Van der Sande M, Whittle H, Hainaut P; Gambia Hepatitis Intervention Study.

Cancer Epidemiol Biomarkers Prev. 2008 Nov;17(11):3216-23.

Rating & Commentary
* Interim report of a 30 year study showing in sub-Saharan Africa perinatal infection to be of negligible importance, update of hepatitis B vaccine to be higher than expected, and protection against hepatitis B not dependent of the number of vaccine doses received. Therefore, sooner than expected the outcome of the overall study can be expected.

Sociocultural factors that potentially affect the institution of prevention and treatment strategies for prevention of hepatitis B in Chinese Canadians.

Wu H, Yim C, Chan A, Ho M, Heathcote J.

Can J Gastroenterol. 2009 Jan;23(1):31-6.

Rating & Commentary
* This study is an important reminder that awareness of risk of disease is the starting point of an effective public health strategy for controlling morbidity and mortality of chronic hepatitis B.