A significantly greater proportion of patients receiving TDF plus peginterferon for 48 weeks had HBsAg loss than those receiving TDF or peginterferon alone. ClinicalTrials.gov ID NCT01277601.

One major challenge in the treatment of chronic hepatitis B is to maintain long-term viral suppression without promoting the selection of drug-resistant mutations. We analyzed data from 347 hepatitis B e antigen-negative and 238 hepatitis B e antigenpositive patients receiving tenofovir disoproxil fumarate (TDF) in an open-label, longterm extension of two phase 3 studies. To date, resistance analyses have been completed for patients receiving up to 288 weeks (6 years) of TDF. Population sequencing of hepatitis B virus (HBV) polymerase/reverse transcriptase (pol/RT) was attempted for all patients at baseline, and any patient who remained viremic (HBV DNA 400 copies/ mL [69 IU/mL]) at week 288 or at the end of treatment with TDF (n 5 52) or emtricitabine (FTC)/TDF (n 5 7). Phenotypic analyses were performed in HepG2 cells using recombinant HBV containing patient pol/RT sequences. Approximately half of the patients on open-label treatment who qualified for genotyping had pol/RT sequence changes compared to baseline (23/52 [44%] on TDF, 4/7 [57%] on FTC/TDF). Most changes were at polymorphic sites and none were associated with TDF resistance. Virologic breakthrough occurred infrequently and was associated with nonadherence to study medication in the majority of cases (12/16, 75%). Per protocol, 57 patients (10%) were eligible to switch to FTC/TDF; the majority had HBV DNA <400 copies/mL at their last study visit regardless of whether they switched to FTC/TDF (n 5 34) or maintained TDF monotherapy (n 5 17). No patient exhibited persistent viremia (HBV DNA never <400 copies/mL) after week 240. Conclusion: TDF monotherapy maintains effective suppression of HBV DNA through 288 weeks of treatment with no evidence of TDF resistance. (HEPATOLOGY 2014;59:434-442) T he treatment goals for chronic hepatitis B (CHB)-infected patients are to improve quality of life and decrease the risk of life-threatening complications by potent and durable suppression of hepatitis B virus (HBV) replication. [1][2][3][4][5] As most patients with CHB will require long-term treatment with nucleos(t)ide analogs, one of the greatest challenges is to maintain effective viral suppression without the selection of resistance mutations. Long-term treatment with first-generation nucleos(t)ide analogs leads to relatively high cumulative resistance rates, 71% after up to 4 years of treatment with lamivudine (LAM), 6 and 29% in hepatitis B e antigen (HBeAg)-negative patients and 20% in HBeAg-positive patients after up to 5 years of treatment with adefovir (ADV). 7,8 Furthermore, 25% of HBeAg-positive patients and 11% of HBeAg-negative patients developed resistance after up to 2 years of treatment with telbivudine.9 Entecavir (ETV) has a markedly lower rate of resistance: 1.2% among treatment-na€ ıve patients treated for up to 5 years.10 However, ETV resistance develops rapidly in patients with prior resistance to LAM: the 5-year cumulative probability of developing ETV resistance is 51% in patients harboring LAM resistance.

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Tenofovir disoproxil fumarate (DF) is highly effective for the suppression of hepatitis B virus (HBV) in chronically infected adults. This study evaluated the safety and efficacy of tenofovir DF in adolescents with chronic hepatitis B (CHB). In this double-blind, placebo-controlled trial, adolescents 12 to <18 years of age with CHB were randomized to tenofovir DF 300 mg (n 5 52) or placebo (n 5 54) once daily for 72 weeks. The primary endpoint was virologic response (HBV DNA <400 copies/mL) at week 72. One hundred six patients were enrolled; 101 patients completed 72 weeks of treatment. At baseline, 91% of patients were hepatitis B e antigen-positive and 85% had prior exposure to HBV therapy. A virologic response was observed in 89% (46/52) of patients who received tenofovir DF and 0% (0/54) of patients who received placebo (P < 0.001). Treatment response was not affected by prior HBV treatment. Furthermore, no resistance to tenofovir DF developed through week 72. Among patients with an alanine aminotransferase (ALT) level greater than the upper limit of normal at baseline, normalization of ALT occurred in 74% of patients receiving tenofovir DF and 31% of patients receiving placebo (P < 0.001). The rate of grade 3/4 adverse events was higher among patients treated with placebo (24%) than patients treated with tenofovir DF (10%). No patients met the safety endpoint of a 6% decrease in spine bone mineral density at week 72. Conclusion: Tenofovir DF therapy in HBV-infected adolescents was well tolerated and highly effective at suppressing HBV DNA and normalizing ALT values in both treatment-naïve adolescents and those with prior exposure to HBV therapy. (HEPATOLOGY 2012;56:2018-2026 See Editorial on Page 2016 D espite the success of recent vaccination efforts, chronic hepatitis B (CHB) remains a serious global health care problem and is a major cause of serious liver disease. 1 It is estimated that approximately 350 million people live with CHB infection and approximately 600,000 die each year due to the acute or chronic consequences of hepatitis B. 1 Mathematical modeling suggests that over 80% of these deaths are from infections contracted during childhood. 2 This is most likely because approximately 90% of those infected as infants and 30%-50% of those infected from 1 to 4 years of age develop chronic infection. 1 These chronically infected children are at high risk of developing severe liver disease and dying from hepatitis B virus (HBV)-related sequelae. Approximately 25% of individuals who become chronically infected in childhood later develop cirrhosis or cancer of the liver. 1 Studies in adults with CHB have shown that the risk of developing liver complications is correlated with serum HBV DNA levels, which can be mitigated by effective viral suppression. 3,4 It is not yet known Abbreviations: ALT, alanine aminotransferase; BMD, bone mineral density; CHB, chronic hepatitis B; DF, disoproxil fumarate; HBeAg, hepatitis B e antigen; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; LLOQ, lower limit ...