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BACKGROUND: Few data are available regarding the use of tenofovir disoproxil fumarate (TDF) during pregnancy for the prevention of mother-to-child transmission of hepatitis B virus (HBV). METHODS: In this trial, we included 200 mothers who were positive for hepatitis B e antigen (HBeAg) and who had an HBV DNA level higher than 200,000 IU per milliliter. Participants were randomly assigned, in a 1:1 ratio, to receive usual care without antiviral therapy or to receive TDF (at an oral dose of 300 mg per day) from 30 to 32 weeks of gestation until postpartum week 4; the participants were followed until postpartum week 28. All the infants received immunoprophylaxis. The primary outcomes were the rates of mother-to-child transmission and birth defects. The secondary outcomes were the safety of TDF, the percentage of mothers with an HBV DNA level of less than 200,000 IU per milliliter at delivery, and loss or seroconversion of HBeAg or hepatitis B surface antigen at postpartum week 28. RESULTS: At delivery, 68% of the mothers in the TDF group (66 of 97 women), as compared with 2% in the control group (2 of 100), had an HBV DNA level of less than 200,000 IU per milliliter (P<0.001). At postpartum week 28, the rate of mother-to-child transmission was significantly lower in the TDF group than in the control group, both in the intention-to-treat analysis (with transmission of virus to 5% of the infants [5 of 97] vs. 18% [18 of 100], P=0.007) and the per-protocol analysis (with transmission of virus to 0 vs. 7% [6 of 88], P=0.01). The maternal and infant safety profiles were similar in the TDF group and the control group, including birth-defect rates (2% [2 of 95 infants] and 1% [1 of 88], respectively; P=1.00), although more mothers in the TDF group had an increase in the creatine kinase level. After the discontinuation of TDF, alanine aminotransferase elevations above the normal range occurred more frequently in mothers in the TDF group than in those in the control group (45% [44 of 97 women] vs. 30% [30 of 100], P=0.03). The maternal HBV serologic outcomes did not differ significantly between the groups. CONCLUSIONS: In a cohort of HBeAg-positive mothers with an HBV DNA level of more than 200,000 IU per milliliter during the third trimester, the rate of mother-to-child transmission was lower among those who received TDF therapy than among those who received usual care without antiviral therapy. (Funded by Gilead Sciences; ClinicalTrials.gov number, NCT01488526.).

BACKGROUND: Entecavir (ETV) has been shown to be safe and efficacious in randomised controlled trials in highly selected patients with hepatitis B virus (HBV) infection. AIM: To determine the safety and effectiveness of ETV in 'real-world' HBV patients in the United States (US). METHODS: Treatment-naive HBV patients >/=18 years old who received ETV for >/=12 months between 2005 and 2013 were included in a retrospective, cohort study. Rates of ALT normalisation, undetectable HBV DNA, HBeAg and HBsAg loss/seroconversion, adverse events (AE) and clinical outcomes were evaluated. RESULTS: Of 841 patients, 658 [65% male, 83% Asian; median age 47 years] met the inclusion criteria. 36% were HBeAg+ and 9.3% cirrhotic. 89% had abnormal ALT. Baseline median HBV DNA was 5.8 log 10 IU/mL. Median duration of ETV treatment was 4 years. Rates of ALT normalisation at 1, 3 and 5 years were 37.2%, 48.7% and 56.2% in HBeAg+ and 39.6%, 46.8% and 55.6% in HBeAg- patients. HBV DNA was undetectable at 1, 3 and 5 years in 34.6%, 64.7% and 84.6% in HBeAg+ patients, and 81.9%, 90.3% and 96.2% in HBeAg patients. Five-year cumulative probability of HBeAg loss and seroconversion was 46% and 33.7% and HBsAg loss was 4.6%. ETV was discontinued due to adverse events in 1.2% of patients. Hepatic decompensation occurred in 0.8%, liver cancer in 2.7% and death in 0.6%. CONCLUSION: Entecavir treatment was safe in a large cohort of US patients, but ALT normalisation and hepatitis B virus DNA suppression rates were lower than previously reported in clinical trials.

Hepatitis B virus (HBV), a leading cause of cirrhosis and liver cancer, is a serious health threat, and prevention of HBV transmission is an important part of the strategy to alleviate infection and its outcomes. Hepatitis Bvirus can be vertically transmitted from mothers to fetuses during childbirth, and infants who are untreated can consequently develop chronic infection. This study aimed to assess the utility of tenofovir, a nucleotide analog and HBVpolymerase inhibitor, to prevent mother-to-child transmission ofHBV during pregnancy. A randomized controlled trial was designed to test the efficacy and safety of tenofovir therapy in mothers with HBV DNA levels greater than 200,000 IU/mL. Participants (HBeAg-positive) in a 1: 1 ratio were randomly assigned with or without an oral dose of 300 mg tenofovir daily starting from 30 to 32 weeks of gestation until postpartum week 4. The pregnant mothers and mother-infant dyads were evaluated every 4 weeks for any adverse events and at 4, 12, 24, and 28 weeks postpartum for laboratory results. The rates of mother-to-child transmission and birth defects with or without tenofovir exposure were the primary outcomes, whereas the secondary outcomes included the percentage of mothers with HBV DNA levels less than 200,000 IU/mL at delivery and the percentage of mothers with HBeAg or HBsAg loss or seroconversion at postpartum week 28. The median HBV DNA level was significantly lower at delivery in the tenofovir group compared with the control group (4.7 log10 IU/mL [interquartile range, 4.1-5.3] vs 8.0 log10 IU/mL [interquartile range, 7.5-8.3], P < 0.001). Also, 66 of 97 mothers in the tenofovir group (68%; 95% confidence interval, 59-77) had HBV DNA levels less than 200,000 IU/mL compared with 2 of 100 mothers in the control group (2%; 95% confidence interval, 0-6) at delivery (P < 0.001). In an intention-to-treat analysis, the rate of mother-to-child transmission was significantly lower in infants born tomothers in the tenofovir group (5%) than those in the control group (18%, P = 0.007). When only those women who complied with treatment were examined, the rates of vertical transmission were 0% in the tenofovir group versus 7% in the control group (P = 0.01). With regard to maternal adverse events, 2 significant differences were detected. A higher frequency of an elevation in the creatine kinase level among mothers in the tenofovir group than those in the control group (7% vs 0%, P = 0.006) and higher frequency of elevations in the alanine aminotransferase levels in the tenofovir group compared with the control group (45% vs 30%, P = 0.03) were observed. There were no significant differences between both groups with regard to congenital anomalies or infant growth. The study concluded that the rate of mother-to-child HBV transmission was lower among mothers who received tenofovir therapy than those who did not

The clinical course for chronic hepatitis B (CHB) patients with normal ALT and with or without minimal histologic activity remains unclear. We assessed frequency, amplitude, disease activities, and associated factors of ALT and/or AST flares in this subpopulation. Forty-seven consecutive treatment naive Asian patients with CHB were enrolled from two liver clinics between December 2003 and January 2013, who had normal baseline ALT by routine clinical biochemical testing performed 6 weeks before or after the liver biopsy. We defined a flare as elevation of ALT/AST above the upper limit of normal of ALT/AST. The mean follow-up was 37.6 (CI = 12, 88) months, and the mean age at entry into the study was 43.3 (CI = 19, 65); 22/47 (46.8%) were males; 15/45 (33.3%), HBeAg+; 68.1% had stage 0-1 fibrosis; 63.8% had grade 0-1 inflammation. During follow-up, 13/47 (27.7%) cases developed ALT flare at least once in a mean of 13.5 (CI = 2, 43) months after liver biopsy; ALT flare was not associated with baseline ALT level, fibrosis stage, inflammation grade, hepatitis B virus (HBV) DNA load, HBeAg status, HBV genotype, HBV precore and basal core promoter mutations. 11/13 (84/6%) of ALT flares resolved during follow-up. 13/13 (100%) of ALT flares met AASLD treatment criteria, but only 6/13 (46.2%) were on HBV treatment. Serum ALT and/or AST flares occur frequently in CHB carriers who initially presented with normal ALT during pretreatment period. Thus, regular follow-up is warranted despite status of ALT/AST. No clinical factors were found to be associated with ALT flares.

Background: Pre-core and/or basal core promoter mutations are frequently detected in HBeAg(-) CHB patients, but little is known about the clinical significance of their presence in HBeAg(+) patients. Methods We performed a 2 center cross-sectional study on treatment-naive CHB patients. Clinical characteristics were compared between HBeAg(+) and HBeAg(-) cohorts with mutation analysis. In addition, patients with and without PC/BCP mutations in HBeAg (+) cohort were compared. Results We enrolled 267 consecutive patients with obtainable mutation analysis in 2 centers. Of 177 HBeAg(+) patients, 6(3.39%) were genotype A, 65(36.72%) genotype B, 104(58.76%) genotype C, 1(0.57%) genotype B/C, and 1(0.57%) genotype C/D. Of 90 HBeAg(-) patients, 1(1.11%) were genotype A, 50(55.56%) genotype B, 37(41.11%) genotype C and 2(2.22%) genotype D. When compared to HBeAg(-) patients, HBeAg(+) patients were significantly younger in mean age (37.93 vs. 44.40; P<0.001), had higher levels of mean ALT (108.93+/-169.50 vs 59.41+/-90.29 U/mL; P0.001), higher levels of mean HBV DNA (7.50+/-1.48 vs 5.10+/-1.44 log₁₀ copies/mL; P0.001) and lower frequency of detectable PC/ BCP mutations (60.45% vs. 93.33%; P< 0.001), but had significantly higher percentage of cases with BCP when mutations were detected (37.85%, vs. 22.22%; P = 0.013). Among HBeAg(+) patients, 61% (107/177) had detectable PC/BCP and their clinical features are shown on Table 1. When compared to those with wild type, HBeAg(+) patients with PC/ BCP were significantly older in mean age, had higher mean ALT levels and lower mean HBV DNA levels. Conclusions In treatment-naive HBeAg(+) patients, up to 60% had PC/BCP mutants. These patients presented with distinct clinical characteristics when compared to HBeAg(+) cases with wild type or HBeAg(-) patients. Further studies are needed to substantiate the clinical significance of PC/BCP in HBeAg(+) patients as it may impact the natural history or treatment response in such patients. (Table Presented)

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.