Among patients with chronic HBV infection, tenofovir DF at a daily dose of 300 mg had superior antiviral efficacy with a similar safety profile as compared with adefovir dipivoxil at a daily dose of 10 mg through week 48. (ClinicalTrials.gov numbers, NCT00116805 and NCT00117676.)

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Data are limited on the safety and effectiveness of oral antivirals other than lamivudine and adefovir dipivoxil for treatment of chronic hepatitis B (CHB) in patients with decompensated liver disease. This Phase 2, double-blind study randomized 112 patients with CHB and decompensated liver disease to receive either tenofovir disoproxil fumarate (TDF; n = 45), emtricitabine (FTC)/TDF (fixed-dose combination; n = 45), or entecavir (ETV; n = 22). The primary endpoint was safety; more specifically, tolerability failure (adverse events resulting in permanent treatment discontinuation) and confirmed serum creatinine increase ≥0.5 mg/dL from baseline or confirmed serum phosphorus <2 mg/dL. Patients with insufficient viral suppression (e.g., confirmed HBV DNA ≥400 copies/mL at week 8 or 24) could begin open-label FTC/TDF but were considered failures in this interim week 48 analysis for efficacy endpoints. Tolerability failure was infrequent across arms: 6.7% TDF, 4.4% FTC/TDF, and 9.1% ETV ( P = 0.622) as were confirmed renal parameters meeting threshold 8.9%, 6.7%, and 4.5% ( P = 1.000), respectively. Six patients died (none considered related to study drug) and six received liver transplants (none had HBV recurrence). The adverse event and laboratory profiles were consistent with advanced liver disease and complications, with no unexpected safety signals. At week 48, HBV DNA was <400 copies/mL (69 IU/mL) in 70.5% (TDF), 87.8% (FTC/TDF), and 72.7% (ETV) of patients. Proportions with normal alanine aminotransferase were: 57% (TDF), 76% (FTC/TDF), and 55% (ETV). Hepatitis B e antigen (HBeAg) loss/seroconversion occurred in 21%/21% (TDF), 27%/13% (FTC/TDF), and 0%/0% (ETV). Child-Turcotte-Pugh and Modification for End-stage Liver Disease scores improved in all groups. Conclusion: All treatments were well tolerated in patients with decompensated liver disease due to CHB with improvement in virologic, biochemical, and clinical parameters. (Hepatology 2011.)

Currently, compounds under evaluation for treatment of chronic hepatitis B virus (HBV) infection are evaluated with liver histology as the primary end point for efficacy. However, because of practical limitations in serial liver biopsies, there is a need for alternate markers to assess efficacy over shorter periods of time. Considering the direct correlation between viral replication and disease progression during human immunodeficiency virus and hepatitis C virus infection, we explored whether such a correlation exists for HBV infection. We reviewed the literature and conducted an analysis to investigate the relationship between absolute or treatment-induced changes in HBV DNA levels and other accepted markers of disease activity. A total of 26 prospective studies met our selection criteria, including 33 evaluable treatment arms. The study treatments consisted of nucleosides and/or interferon regimens and control arms. We found statistically significant and consistent correlations between viral load level or change and histologic grading and biochemical and serologic response. Our analysis suggests that a treatment-induced reduction in HBV DNA level can be used for assessing efficacy of treatment regimens. Further, we observed that quantitative HBV DNA has a broader dynamic range than histology, allowing demonstration of differences between 2 active treatments of unequal potency. The analysis showed stronger results in studies using nucleoside regimens and in hepatitis B e antigen (HBeAg)-positive patients. C hronic hepatitis B virus (HBV) infection often leads to severe complications and death after decades 1 ; therefore, the evaluation of therapeutic regimens is based on surrogate markers such as histology and hepatitis B e antigen (HBeAg) seroconversion. 2 Although the treatment of chronic HBV infection has advanced in the past decade through development of immune modulators and nucleoside/nucleotide analogues, there is a significant need for improving therapeutic responses.Currently, compounds under development are evaluated with liver histology as the primary end point for efficacy. Hepatic histology is invaluable for assessment of the etiology and staging of liver diseases. 3 However, serial liver biopsies are not part of the usual management of chronically HBV-infected patients because they are invasive, are associated with a certain level of complications, and may not be performed more frequently than yearly. 4 Thus, there is a need for alternate markers that are available in clinical practice and suitably reliable to assess the efficacy of therapeutic interventions over shorter periods of time.Considering the established direct correlation between viral replication and disease progression during human immunodeficiency virus and hepatitis C virus infection, we were interested in exploring whether such a correlation exists for chronic HBV infection. Both cirrhosis and cancer, which are sequelae of chronic HBV infection in humans, 5,6 are related to persistent and uncontrolled replication of the virus in ...