Faculty Bibliography

BACKGROUND:Data on tenofovir alafenamide fumarate (TAF) therapy for preventing mother to child transmission of hepatitis B virus (HBV) are lacking. AIMS/OBJECTIVE:To investigate the efficacy and safety of TAF therapy for preventing hepatitis B mother to child transmission. METHODS:Mothers with chronic HBV infection, positive for hepatitis B e-antigen and with HBV DNA >200 000 IU/mL received TAF for preventing mother to child transmission were enrolled retrospectively from multiple centres with data collection on mother-infant dyads up to postpartum week 24-28. Primary measurements were the mother to child transmission rate and infants' malformation rate. Secondary assessments included maternal HBV DNA reduction at delivery, and maternal or infant adverse events during follow up. RESULTS:Among 71 mothers enrolled, the mean (±SD) age was 30.3 (±2.2) years. TAF therapy was initiated during the second or third trimester and continued to delivery with a mean (±SD) duration of 12.8 (±4.0) weeks. At delivery, 85.9% (61/71) of the mothers achieved HBV DNA <200 000 IU/L. Seventy-three infants (two sets of twins) were born from mothers treated with TAF and none had congenital defects or malformations. All infants received HBV immunoglobulin and vaccine at birth with additional HBV vaccinations at one and six months. At age 24-28 weeks, all infants had negative hepatitis B surface antigen and undetectable levels of HBV DNA (<100 IU/mL). Body weight, height, and head circumferences were comparable to national standards for physical development. No severe adverse effects were reported in either mothers or infants. CONCLUSIONS:TAF for highly viraemic mothers effectively prevented mother to child transmission of hepatitis B. There were no safety concerns for either mothers or infants with 24-28 weeks of follow up.

OBJECTIVES/OBJECTIVE:Minority patients are under-screened for chronic hepatitis C (CHC) in the USA, and limited data exist for minority patients with advanced fibrosis. METHODS:In this cross-sectional study, CHC patients who were prescribed direct-acting antiviral agents were divided into White patients and minority patient groups. Primary measurements were the mean fibrosis scores and percentages of patients with stage III-IV fibrosis (late presenters) for the two groups. RESULTS:Among the 1421 patients with self-reported ethnicity, 697 were White patients, and 724 were minority patients (484 Hispanic, 175 Black, 65 Asians). Compared to the White, minority patients had significantly higher mean fibrosis score (p < 0.001) and a higher percentage of late presenters (p < 0.001). In subgroup analyses, the mean fibrosis scores for Hispanic, Black and Asian patients were 2.58 ± 1.38, 2.28 ± 1.41 and 2.28 ± 1.40, respectively. CONCLUSIONS:Minority populations with CHC in the USA experience disparities in access to treatment in the early stages of liver fibrosis. Public health strategies are necessitated to address the inequality, as late presenters are at risk of hepatocellular carcinoma.

BACKGROUND:A critical aspect of liver transplantation in hepatitis B patients is to prevent graft reinfection with hepatitis B virus. The use of hepatitis B immune globulin after transplant was a significant milestone, which allowed prolonged graft and patient survival by controlling hepatitis B reinfection in liver grafts. The development of anti-viral treatments with oral nucleos(t)ide analogues, led to a further reduction in graft reinfection and improvement in patient survival. The combination of the aforementioned two therapies has been widely used in hepatitis B-associated liver transplants. AIM/OBJECTIVE:To address the post-transplant management of hepatitis B and provide updates on preventing graft reinfection. METHODS:We performed a literature search on Ovid and PubMed for RCTs or cohort studies in English, which investigated the effectiveness of hepatitis B immune globulin and anti-viral therapy on hepatitis B-associated transplants (1/2000-1/2020). Studies that met pre-established criteria were reviewed. RESULTS:Based on currently available evidence, an algorithm for post-transplant management with anti-viral therapy is proposed. Also, the management of recipients who received grafts from hepatitis B core antibody-positive donors is discussed. CONCLUSIONS:The development of hepatitis B immune globulin and anti-viral treatments led to substantial improvement in graft and patient survival. The prevention of hepatitis B graft reinfection is complex and involves a broad interdisciplinary team.

Background and Aims: Recent studies demonstrate that the population with CHB is aging. Tenofovir alafenamide (TAF) is a first-line treatment for chronic hepatitis B virus infection (CHB), particularly in those at risk for TDF-associated bone and renal effects, including patients with advanced age. We reviewed our experience in the subset of geriatric CHB patients participating in ongoing TAF clinical trials.
Method(s): Included were patients age >=65 y treated with TAF in 3 large Phase 3 trials (pooled analysis of viremic patients naive to TAF in Studies 108 and 110, and suppressed patients switched from TDF to TAF [vs continued TDF] in Study 4018), and data from a single arm Phase 2 study in virally suppressed patients with renal and/or hepatic impairment switched to TAF from TDF and/or other antivirals (Study 4035). Efficacy (HBV DNA >9 or >0 IU/mL) and safety (adverse events [AEs], serious AEs, changes in hip and spine bone mineral density [BMD] and changes in creatinine clearance [eGFRCG]) were assessed for older (>=65 y) vs younger (>5 y) patients. In Studies 108, 110, and 4018, results for TDF in patients >=65 y were also determined for comparison.
Result(s): A total of 124 patients >=65 y were included, representing 6.5% of all enrolled patients. Other than age, decreases in renal/bone parameters, and increased comorbidities, the older and younger groups were generally similar. Efficacy and safety results are summarized in the Table. Rates of virologic suppression was comparable in geriatric vs non-geriatric patients treated with TAF. Overall, AEs and SAEs were similar between older vs younger patients; there were no Grade 3/4 AEs related to study drug in patients >=65 y. Compared with younger patients, declines in eGFRCGand hip/spine BMD were greater in viremic older patients; however, the decreases were less than in older patients on TDF. In suppressed patients, eGFRCGincreases were greater in younger vs older patients receiving TAF, while changes in hip and spine BMD were similar; TDF treatment resulted in declines in BMD and eGFRCG.
Conclusion(s): The efficacy and safety of TAF in geriatric CHB patients were generally similar to younger patients. Small improvements in renal and bone parameters can be seen in older patients switched from TDF to TAF.
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Background and Aims: Previously we reported increased HBV suppression, ALT normalization, and improved renal function with TAF treatment. However, certain patients that would potentially benefit from switching to TAF, e.g. with impaired renal function, remained on non-TAF therapies. Here we further examined variables associated with TAF adoption from approval (Nov 2016) to Dec 2018.
Method(s): Patients enrolled in the TRIO HBV registry from 6 academic and 4 community centers in the US were included in this study. TAF initiation was assessed using Kaplan-Meier methods with subsequent log-rank tests. Overall TAF initiation rates were compared using z-tests.
Result(s): Study population (n = 1037): predominantly male (599, 58%), Asian (887, 86%), <60 years old (700, 68%), from academic centers (611, 59%), with HBV DNA suppression (951/1035, 92%), and receiving tenofovir disoproxil fumarate (TDF [640, 62%]) at enrollment. A history of HCC (inactive) was present for 2% (25) patients, 4% (44) fatty liver, 10% (103) diabetes, 13% (131) hyperlipidemia, 23% (237) hypertension, and 8% (78) osteopenia/osteoporosis. At enrollment, 5% (48/965) had FIB4 >3.25, 6% (65/1030) had eGFR <60 ml/min, and 29% (304/1035) had elevated ALT (>25 U/L in females or >35 U/L in males). In the study window, 396 (38%) patients initiated TAF. Adoption was significantly higher in patients receiving TDF at enrollment (52% v. 12% non-TDF, p < 0.001), at community practices (56% v. 25% academic, p < 0.001), and without HCC history (39% v. 8%, p = 0.005), fatty liver (39% v. 8%, p < 0.001), or hyperlipidemia (39% v. 28%, p = 0.005). Adoption was not significantly different by age, insurance type, osteopenia/osteoporosis, eGFR, FIB4, or ALT. [Figure] Reasons for initiating TAF were provided for 365/396 patients: 66% (241/365) indicated safety/side effects, 27% (99/365) physician preference, and 6% (21/365) efficacy.
Conclusion(s): Safety/side effects was stated as a primary reason for initiating TAF, yet osteopenia/osteoporosis, suboptimal eGFR, ALT, or FIB4 were not associated with significantly higher TAF adoption. These data suggest that prevention, rather than observation of detrimental clinical measures, accounted for most TAF adoption. Most patients with renal or bone disease were not switched to TAF which may be due to access, an issue which will be further explored.
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Background and Aims: TAF provides similar efficacy to tenofovir disoproxil fumarate (TDF) but with an improved safety profile particularly for bone loss and renal injury. However, continued benefit with longer-term TAF has not been sufficiently studied. Here we evaluate virologic suppression rates, eGFR, fibrosis, and ALT at 48+ weeks of TAF therapy in US clinical practice.
Method(s): TRIO has developed a national HBV network consisting of 6 academic and 4 community-based centers serving 17 US States to understand real-world HBV treatment. Of the 1037 patients enrolled from Jan 2017,270 patients initiated TAF and remained on therapy for 48+ weeks as of Jan 2019. Lab measurement data at baseline and at or after (but nearest) 48 weeks of TAF therapy were collected. Elevated ALT was defined as >35 U/L for males and?>25 U/L for females, HBV suppression was assigned for HBV DNA measures <=2000 IU/ml. Comparisons between baseline and 48-week measures were made using McNemar's test (for dichotomous variables), Bowker's test (for multi-level variables) or t-test (for continuous variables). To identify variables associated with elevated ALT, eGFR >0 ml/min, or FIB4 >1.45 at 48 weeks, logistic regressions were conducted with adjustments for multicollinearity of variables.
Result(s): The study population (n = 270) was mostly male (59%), Asian (89%), and under or normal weight (60%) with a mean age of 53 years. Prior to initiating TAF, 81% of the patients received TDF, 8% entecavir, 6% were treatment naive, 2% TDF/emtricitabine, 1% lamivudine, and 1% adefovir dipivoxil. As of Jan 2019, mean (median) TAF duration was 508 (512) days and ranged from 338 to 803 days. In paired analyses (Table), statistically significant changes were reduced mean ALT and increased DNA suppression; changes in FIB4 and eGFR were not significantly different between baseline and 48 weeks. Variables associated with elevated ALT and eGFR >0 ml/min at 48 weeks were baseline elevated ALT (p < 0.001) and baseline eGFR >0 ml/min (p < 0.001), respectively. For FIB4?>1.45 at 48 weeks, significantly associated variables were baseline FIB4 >1.45 (p < 0.001) and Medicare as primary coverage (p = 0.010, collinear with Age >=50).
Conclusion(s): This study of HBV-infected individuals receiving TAF for 48+ weeks found that statistically significant improvements occurred in ALTand HBV DNA suppression. Continued monitoring is ongoing to understand changes in these and other measures with longer term TAF.
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Objectives: Here, we describe changes in HBV treatment in the 24 months after TAF approval as observed in a US network of 10 HBV-care centers.
Method(s): Data were retrospectively obtained from patient records through an electronic registry at enrollment (Nov 2016) with further collection at each patient visit. Of 1037 enrolled patients, 725 patients with 24-month follow up were included in this study.
Result(s): 7% (50/725) patients were untreated at enrollment and throughout the observation period (Nov 2016 to Dec 2018). Reasons for non-treatment: 82% (41/50) low HBV DNA, 54% (27/50) normal liver function, 8% (4/50) patient decision, 6% (3/50) HBeAg negative, 2% (1/50) does not meet guidelines, and 2% (1/50) unspecified. In Jan 2017 (end of enrollment), 58% (418/725) patients received tenofovir disoproxil fumarate (TDF), 23% (168/725) entecavir (ETV), and 2% (14/725) TAF. In Dec 2018 (end of the observation period), 30% (218/725) received TDF, 21% (152/725) ETV, and 35% (254/725) TAF. 37% (271/725) patients switched therapies for reasons of safety/side effects (58%, 156/271), physician preference (25%, 69/271), efficacy (8%, 23/271), or insurance/cost (6%, 17/271). Most switches were to TAF (91%, 246/271) from TDF (88%, 217/246). Rate of switching differed by site of care; compared to community practices, academic sites had a lower switch rate (26% [114/441] vs 55% [157/284]). Treatment switches in both academic (81%, 92/114) and community (98%, 154/157) sites were mainly to TAF, but the therapies prior to TAF were more varied in the academic sites.
Conclusion(s): In this study, 7% of patients were untreated while 37% received >1 regimen during the observation window. Reasons for non-treatment were mainly low HBV DNA and normal liver function. For the population receiving treatment, initial regimens were mostly TDF and ETV. Switches away from initial therapy was mainly due to safety/side effects concerns and were predominately to TAF.
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