Hope-For-HepB Top10 February 2008

Limitations of conventionally derived chronic liver disease mortality rates: Results of a comprehensive assessment.

Manos MM, Leyden WA, Murphy RC, Terrault NA, Bell BP.

Hepatology. 2007 Dec 20; [Epub ahead of print].

Rating & Commentary
** Large study in 16,970 deaths among US health plan members documenting chronic liver diseases as the cause of death in 2,1% in 2000 and confirming that the number of hepatitis B virus (HBV) related deaths is underestimated. Only 48% of HBV associated deaths ascertained by medical record had that specific etiology mentioned on the death certificate.

96 Weeks combination of adefovir dipivoxil plus emtricitabine vs. adefovir dipivoxil monotherapy in the treatment of chronic hepatitis B.

Hui CK, Zhang HY, Bowden S, Locarnini S, Luk JM, Leung KW, Yueng YH, Wong A, Rousseau F, Yuen KY, Naoumov NN, Lau GK.

J Hepatol. 2007 Dec 31; [Epub ahead of print].

Rating & Commentary
** First randomized study comparing de-novo adefovir (ADV) and emtricitabine (FTC) combination therapy to adefovir monotherapy in 30 chronic hepatitis B virus infected patients. More patients in the combination group had normalization of serum ALT and HBV DNA <300 copies/ml at week 96 than with monotherapy. No ADV or FTC resistance was detected after 2 years.

The pharmacokinetics and safety of adefovir dipivoxil in children and adolescents with chronic hepatitis B virus infection.

Sokal EM, Kelly D, Wirth S, Mizerski J, Dhawan A, Frederick D.

J Clin Pharmacol. 2008 Feb 14; [Epub ahead of print].

Rating & Commentary
* First pharmacokinetic study in 45 children and adolescents showing that adefovir in a daily dose of 0.3mg/kg in children aged 2-6 and 10mg in adolescents resulted in exposures that were comparable to those seen previously in adults given adefovir 10 mg daily.

Acute hepatitis B 14 years after the implementation of universal vaccination in Italy: Areas of improvement and emerging challenges.

Mele A, Tosti ME, Mariano A, Pizzuti R, Ferro A, Borrini B, Zotti C, Lopalco P, Curtale F, Balocchini E, Spada E.

Clin Infect Dis. 2008;46(6):868-75.

Rating & Commentary
* Case-control study in Italy showing that from 1991 to 2005 the incidence of acute hepatitis B progressively decreased due to universal vaccination, particularly by reducing the risk of infection among persons aged 15-24 years.

Transmission routes of hepatitis B virus infection in chronic hepatitis B patients in The Netherlands.

Toy M, Veldhuijzen IK, Mostert MC, de Man RA, Richardus JH.

J Med Virol. 2008;80(3):399-404.

Rating & Commentary
* Large study in 464 newly diagnosed hepatitis B infected persons showing that the majority of persons were foreign-born (86%). Sexual transmission was the most frequently observed route of transmission in Dutch-born cases, while vertical transmission accounted for infection in most patients in the foreign-born group or those with a foreign mother.

HBeAg and hepatitis B virus DNA as outcome predictors during therapy with peginterferon alfa-2a for HBeAg-positive chronic hepatitis B.

Fried MW, Piratvisuth T, Lau GK, Marcellin P, Chow WC, Cooksley G, Luo KX, Paik SW, Liaw YF, Button P, Popescu M.

Hepatology. 2008;47(2):428-434.

Rating & Commentary
* Detailed analysis of peginterferon alfa-2a monotherapy in 271 chronic HBV infected patients showing that quantitative HBeAg level was a better predictor of HBeAg seroconversion than HBV DNA level; the negative predictive value of HBeAg ≥100 PEIU/mL at week 24 was 96%.

Virologic monitoring of hepatitis B virus therapy in clinical trials and practice: recommendations for a standardized approach.

Pawlotsky JM, Dusheiko G, Hatzakis A, Lau D, Lau G, Liang TJ, Locarnini S, Martin P, Richman DD, Zoulim F.

Gastroenterology. 2008;134(2):405-15.

Rating & Commentary
* Expert recommendations on the use of HBV virologic markers and tests in clinical trials and clinical practice.

Long-term lamivudine therapy reduces the risk of long-term complications of chronic hepatitis B infection even in patients without advanced disease.

Yuen MF, Seto WK, Chow DH, Tsui K, Wong DK, Ngai VW, Wong BC, Fung J, Yuen JC, Lai CL.

Antivir Ther. 2007;12(8):1295-303.

Rating & Commentary
* Large study suggesting that the cumulative rate of development of cirrhosis and/or HCC was significantly lower in 142 HBeAg positive patients on long-term lamivudine compared to 124 HBeAg positive controls (p = 0.005), even in those developing lamivudine resistance.

Cost effectiveness of entecavir versus lamivudine with adefovir salvage in HBeAg-positive chronic hepatitis B.

Veenstra DL, Sullivan SD, Clarke L, Iloeje UH, Tafesse E, Di Bisceglie A, Kowdley KV, Gish RG.

Pharmacoeconomics. 2007;25(11):963-77.

Rating & Commentary
* Cost-utility analysis using a Markov model showing that treatment with entecavir reduces the 10-year cumulative incidence of cirrhosis in a cost-effective manner compared to lamivudine with adefovir salvage or combination therapy.

Evaluation of the cost-effectiveness of entecavir versus lamivudine in hepatitis BeAg-positive chronic hepatitis B patients.

Yuan Y, Iloeje UH, Hay J, Saab S.

J Manag Care Pharm. 2008;14(1):21-33.

Rating & Commentary
* Cost-effective analysis in 709 HBeAg-positive patients suggesting that entecavir given for up to 10 years compared with lamivudine would avoid 79 cases of cirrhosis and 42 hepatocellular carcinoma (HCC) cases, which would be highly cost-effective ($3,230 per QALY gained).