Faculty Bibliography

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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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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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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OBJECTIVES/OBJECTIVE:Data on the virologic response and tolerability of direct-acting antivirals (DAAs) are lacking in older people because these individuals are underrepresented in clinical trials. This study aimed to assess the effectiveness and tolerability of DAA regimens in older individuals in a large cohort of real-life clinical practice. METHODS:In this retrospective study, patients with chronic hepatitis C infection between 2017 and 2018 were divided into patients aged 65 years and older and those younger than 65 years. We evaluated the sustained virologic response rates (SVRs) in both groups. Further subgroup analyses on the SVRs for patients aged 65 to 74, 75 to 84, and 85 years and older were performed. We also analyzed the predictors of treatment response in older individuals. RESULTS:Among 1151 eligible patients, 516 were in the older group and 635 were in the younger group. The overall treatment response in the entire cohort was 97.7%. A significantly higher percentage of patients presented with advanced stages of fibrosis in the older group (53.1% vs 39.5%; P = <.001). The SVR rates were similar between the two groups (98.3% vs 97.7%; P = .18). In multivariate models, age was not predictive of SVR after adjusting for confounders. Subgroup analyses in the age groups of 65 to 74, 75 to 84, and older than 85 years showed similar treatment response rates (97.4%, 97.2%, and 86.7, respectively; P = .06) and advanced fibrosis (50.8%, 61.5%, and 53.3%, respectively; P = .14). CONCLUSION/CONCLUSIONS:Although older people exhibit a significantly higher frequency of fibrosis, DAAs produce high rates of SVR in all age groups, and the age of the patient does not seem to have a significant impact on the efficacy of DAAs including patients in the oldest age category (≥75 y). Treatment should not be withheld in older individuals.

Mother-to-child transmission (MTCT) is responsible for the majority of chronic hepatitis B virus (HBV) infections worldwide. Despite timely HBV immunoprophylaxis of neonates, MTCT can occur in infants born to mothers with high levels of HBV viremia. We performed a retrospective cross-sectional analysis of Asian American women with chronic HBV evaluated with HBV DNA during prenatal care at two community health sites in New York City from 2007 to 2017. We described patient's demographic and clinical characteristics, categorized their HBV disease phase, and analyzed for variables associated with high MTCT risk (defined by HBV DNA level > 200,000 IU/mL) using multivariable logistic regression. A total of 1298 pregnancies among 1012 mostly China-born (97.6%) women with chronic HBV were included in the study. Of the 1241 pregnancies among women not on antiviral treatment, 22.4 % were considered high-risk for MTCT and of these, 255 (91.7%) were HBV e antigen (HBeAg)-positive and 19 (6.8%) were HBeAg-negative. HBeAg-positive status and ALT levels between 26 to 50 U/L were associated with higher likelihood for being high-risk for MTCT. Only 0.8% of pregnancies low-risk for MTCT were in the immune active phase while the majority (58.4%) were in the inactive chronic HBV phase of infection. Approximately one in five (22.4%) pregnancies among Asian American women with chronic HBV was considered high-risk for MTCT and met criteria for antiviral therapy. Full assessment of HBV pregnant women and early coordinated care is needed to deliver interventions to prevent MTCT during critical windows of time.

Felty's syndrome (FS) is a disorder wherein patients with rheumatoid arthritis develop splenomegaly, neutropenia, and in some cases, portal hypertension without underlying cirrhosis. Esophageal variceal bleeding is a complication of FS in patients with portal hypertension. In contrast to splenectomy, few reports exist on the management of variceal bleeding with endoscopic therapy. Moreover, the long-term outcome has not been reported. We present a patient with esophageal variceal bleeding due to portal hypertension secondary to Felty's syndrome. The patient was followed up for two years postendoscopy intervention. Literature review was performed and the histological features of portal hypertension in FS are discussed. The patient presented with a typical triad of rheumatoid arthritis (RA), splenomegaly, and neutropenia and was diagnosed as Felty's syndrome in 2012. She was admitted to our hospital in September 2017 for esophageal variceal bleeding. At the time of admission, her liver function test was normal. Abdominal CT showed no signs of cirrhosis and portal vein obstruction. Liver biopsy further excluded diagnosis of cirrhosis and supported the diagnosis of porto-sinusoidal vascular disease (PSVD), which was previously named as noncirrhotic idiopathic portal hypertension (NCIPH). An upper abdominal endoscopy revealed gastric and esophageal varices. A series of endoscopies was performed to ligate the esophageal varices. The patient was followed up for two years and did not show rebleeding. In conclusion, comorbid PSVD might be a cause of portal hypertension in FS patients. The present case had excellent outcome in two years, which supported the use of endoscopic therapy for the management of variceal bleeding in FS patients. Further large prospective study is needed to confirm the findings.