Faculty Bibliography

Background Treatment with sofosbuvir (SOF)-based regimens for HCV infection has resulted in sustained virologic response (SVR) rates of approximately 90% in pivotal trials, in which Asian patients were underrepresented. This study aims to assess the efficacy and safety of SOF-based therapy in the Asian-American patients. Methods Asian patients with HCV genotype 1-6 mono-infection, who received SOF-based therapy for 12 or 24 weeks, were retrospectively enrolled from multiple centers throughout the United States. The primary endpoint was SVR 12. Secondary endpoints were the safety and tolerability of SOF-based treatment regimens. Results Among the 80 patients enrolled, 45 were treated with SOF+ribavirin (RBV), 15 with SOF+simprevir (SIM), 10 with SOF+RBV+peginterferon, 8 with ledipasvir+SOF and 2 with SIM+SOF+RBV. Patient baseline values are shown in Table 1. By week 4, a rapid decrease in HCV RNA levels to <20 IU/mL was observed in 85% (68/80) of patients. SVR12 was achieved in 98.3% (60/61) patients who have reached the SVR12 assessment point. One genotype 4 patient, who was non-cirrhotic and treatment naive, experienced relapse after completing a 12 week SOF+RBV therapy. ALT normalization occurred in 91% (39/43) patients who had abnormal ALT at the baseline. At the time of abstract submission, 11 patients remain on therapy and 8 are <12-week post treatment follow-up; all were included in the safety analysis. No viral breakthrough occurred during therapy. Regimens were generally well tolerated with <15% patients reporting insomnia, nausea, rash, dyspnea and epigastric discomfort, however, fatigue was reported by 31.3% of patients. Of 57 patients on a RBV containing regimen, 6 required dose reduction and 2 discontinued RBV due to severe fatigue. Conclusions SOF-based therapies for Asian Americans with HCV were well tolerated. Their SVR12 rates were similar to the SVR12 rates of non-Asians in pivotal trials. No safety concerns were identified in this real life cohort. (Table Presented)

Background: Data on TDF use during pregnancy for preventing mother-to-child transmission (MTCT) of hepatitis B virus (HBV) are scarce. Methods: Hepatitis B E antigen (HBeAg)-positive mothers with HBV DNA levels >200,000 IU/mL were randomized 1:1 to receive either TDF from gestation week 30-32 to postpartum week 4 or no treatment, and were followed-up until postpartum week 28. All infants received immunoprophylaxis. The primary measurement was the MTCT rate, while endpoints included TDF safety, maternal HBV DNA reduction at delivery, and HBeAg or hepatitis B s antigen loss/seroconversion at postpartum week 28. Results: Among the 200 mothers enrolled in 5 regions of the country, 180 completed the study. At postpartum week 28, the MTCT rate was significantly lower in infants from TDF-treated mothers when compared to those from non-treated mothers, both on per-protocol analysis (0% vs. 6.82%, P = 0.013) and intention-to-treat analysis (5.16% vs. 18.0%, P = 0.007). The safety profile was similar between groups, with no difference in birth defect rates (2.11% with TDF exposure vs. 1.14% without exposure, P = 1.00). HBV DNA levels decreased to <200,000 IU/mL in 68% (66/97) of TDFtreated mothers before delivery compared to 2.0% (2/100) of non-treated mothers (P < 0.001). The HBV serologic outcome did not differ between groups. Conclusions: TDF therapy in late pregnancy for highly viremic mothers effectively reduced MTCT. The treatment was well tolerated, and no safety concerns were identified. TDF therapy should be strongly considered for mothers whose HBV DNA levels exceeded 200,000 IU/mL and started at gestation week 30-32. (Table Presented)

Entecavir (ETV) is a first-line antiviral therapy for treating chronic hepatitis B (CHB); however, some patients have suboptimal response to ETV. Currently, there are limited data on how to approach these patients. Therefore, our aim was to compare the effectiveness of two alternate therapies - tenofovir (TDF) monotherapy and combination therapy of ETV+T

AIM: To compare the efficacy and safety of tenofovir disoproxil fumarate (TDF) in Asian and non-Asian chronic hepatitis B (CHB) patients. METHODS: The efficacy and safety of the initial 48 wk of treatment with TDF was compared in a post-hoc analysis of combined data from 217 Asians and 299 non-Asians included in Studies 102 and 103 and a post-approval, open-label trial (Study 123). Patient groups were compared according to baseline hepatitis B e antigen (HBeAg) status and viral load. The main outcome measures included the proportion of patients who achieved a hepatitis B virus (HBV) DNA level < 400 copies/mL at Week 48 of treatment. Secondary measures included: HBV DNA and alanine aminotransaminase (ALT) levels over time; proportion of patients with normal ALT levels; proportion of patients with HBeAg loss/seroconversion and proportion of patients with hepatitis B surface antigen loss/seroconversion; changes in liver histology. Safety and tolerability were evaluated by the occurrence of adverse events (AEs), serious AEs, laboratory abnormalities, discontinuation of the study drug due to AEs, or death. The primary efficacy and safety analysis set included all patients who were randomly assigned to treatment and received at least one dose of study drug. RESULTS: At week 48, similar proportions of Asians and non-Asians reached HBV DNA < 400 copies/mL (96% of Asian and 97% of non-Asian patients with HBeAg-negative CHB and 83% of Asian and 79% of non-Asian patients with HBeAg-positive CHB had HBV DNA) and normal ALT (78% of Asian and 81% of non-Asian patients with HBeAg-negative CHB and 71% of Asian and 74% of non-Asian patients with HBeAg-positive CHB had normal ALT). On-treatment HBV DNA decline rates were similar between Asians and non-Asians regardless of baseline HBeAg status and viral load. HBV DNA decline during the first four weeks was 2.9 log10 copies/mL in HBeAg-negative Asians and non-Asians, and in HBeAg-positive non-Asians, and 3.1 log10 copies/mL in HBeAg-positive Asians. HBeAg loss and seroconversion was achieved in 14% of Asians vs 26% and 24%, respectively, in non-Asians. Liver histology improved in 77.2% of Asians and 71.5% of non-Asians. No resistance to TDF developed. No renal safety signals were observed. CONCLUSION: TDF demonstrated similar viral suppression, normalization of ALT, improvements in liver fibrosis, and no detectable resistance in Asian and non-Asian patients regardless of baseline HBeAg status.

Aim: The impact of tenofovir disoproxil fumarate (TDF) on lipid profile in chronic hepatitisB(CHB) patients is unknown. Data from GSUS- 174-0149, a clinical trial evaluating pegylated interferon alfa-2a (PEG) +/- TDF combination therapy in non-cirrhotic CHB patients, were analyzed for impact of antiviral treatment on fasting lipid profile. Methods: 570 subjects with fasting baseline and week 24 total cholesterol, LDL, HDL, and triglyceride were included. Regression analyses of on-treatment changes in lipid profile were examined, adjusted for baseline lipid values, age, sex, race, and BMI. Results: Comparing baseline and week 24 results, TDF monotherapy was significantly associated with reductions in total cholesterol, LDL, and HDL (-25.6 mg/dL, -16.4 mg/dL, and, -9.6 mg/dL, respectively, P<0.05) with no significant change in triglyceride or total cholesterol/HDL ratio (p-values > 0.05). Moreover, TDF + PEG x 48 weeks combination therapy was significantly associated with an even greater reductions in total cholesterol, LDL, and HDL, and a moderate triglyceride increase (-42.5 mg/dL, -29.0 mg/dL, and -18.1 mg/dL, +18.8 mg/dL, respectively, p-values<0.05) compared to baseline. The changes were also significant relative to either monotherapy. In patients, who were on (TDF + PEG) x 16 weeks then continuing on TDF, the lipid impact of PEG lessened after its discontinuation. Only minor cardiovascular events, mostly palpitations, occurred up to Week 72. Conclusion: TDF monotherapy was associated with significant improvements in total cholesterol and LDL in CHB patients. PEG + TDF x 48 weeks was associated with greater changes in lipid profile than either monotherapy

Pregnant women with chronic hepatitis B (CHB) who receive antiviral treatment prior to or during pregnancy for the active disease can develop antiviral-resistance. Antiviral therapy may be required during pregnancy to control maternal disease or to prevent vertical transmission at the third trimester. We prospectively study the efficacy and safety of TDF in managing these patients. METHODS Treatment experienced HBeAg+ mothers who required antiviral treatment during pregnancy were screened. Those with antiviral resistance were prospectively enrolled and treated with TDF until 52 weeks postpartum. Primary endpoints were HBV DNA < 5log10 copies/mL at delivery and the percentage of patients with HBV DNA undetectable at postpartum week 52. Secondary endpoints were safety, tolerability, serological and biochemical responses. RESULTS During 3/2012-3/2013, 29 consecutive treatment experience mothers were screened, but only 14 were found to have genotypic resistance and enrolled. Maternal baseline values are shown in table 1. All subjects received TDF 300 mg daily with a mean (range) duration of 17.1 (9-39) weeks prior to delivery. At delivery, a significant reduction of HBV DNA was observed when compared to those at the baseline (2.8 vs. 7.1 log10 copies/mL, p<0.001), all mothers achieved HBV DNA reduction to the levels below 5log10 copies/mL. The treatment was well tolerated with no viral breakthrough. At postpartum week 4, four patients self-discontinued TDF without severe ALT flares. At postpartum week 52, 57% of mothers had undectable HBV DNA levels. In addition, 7.1% percent of patients (1/14) had HBeAg loss/seroconversion; 64.3% of patients (9/14) achieved normalization of alanine aminotransferase; no patients had HBsAg loss. The adverse events were mild in severity (

EMBASE:71640580

ISSN: 0270-9139

CID: 1363082