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.

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.

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.

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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BACKGROUND AND AIM/OBJECTIVE:The efficacy of prenatal antiviral therapy (AVT) for preventing the vertical transmission of hepatitis B virus (HBV) is well demonstrated. However, data are limited regarding the safety of postpartum cessation of AVT, which may induce alanine aminotransferase (ALT) elevation. We aimed to investigate the necessity of prolonging maternal AVT after delivery. METHODS:IU/ml were prospectively enrolled and received AVT during the third trimester until delivery. Patients were offered to discontinue AVT either at delivery or postpartum week (PPW) 6. In addition, mothers who deferred AVT during pregnancy served as the control group. All mothers were followed until postpartum week 52 for clinical and virological parameters of hepatitis flares. RESULTS:Among 118 mothers recruited, 91 received AVT with 53 (group A) and 24 (group B) discontinue their treatment at delivery and postpartum week 6, respectively. Twenty-seven mothers who deferred AVT during pregnancy were followed as the control (group C). Of 104/118 mothers who completed the study, 50% (52/104) had postpartum elevated ALT levels, which were mild and moderate except 6/104 (5.77%) of patients had levels > 5 times the upper limit of normal. 70% (36/52) of the ALT flares occurred within 12 weeks after delivery. In subgroup analyses, the freuquency of ALT elevation were similar among the groups A vs. B vs. C [50.9% (27/53) vs. 58.3% (14/24) vs 40.7% (11/27), respectively; P = 0.447], as well as the mean peak ALT level (108.4 / 74.1 / 126.7 U/L in groups A/B/C, respectively; P = 0.291). CONCLUSIONS:Although postpartum ALT flares were common for mothers with or without AVT during pregnancy, most cases of ALT elevation were mild to moderate. Our study observed that extending AVT to postpartum week 6 did not affect maternal outcomes and ATV should be discontinued at birth. Close monitoring is warrant as severe flares rarely occurred. ClinicalTrials.gov number: NCT03468907. This article is protected by copyright. All rights reserved.

Little data exists on basal core promoter/precore (BCP/PC) mutations in chronic hepatitis B (CHB) patients at the immune-tolerance (IT) phase. We studied consecutive treatment-naïve, CHBe-antigen (HBeAg) positive patients who had undergone liver biopsy and genotyping. Those in the IT phase or immune-clearance (IC) phase were enrolled for comparison of the frequency of BCP/PC mutations and their clinical presentations. Subgroup analyses for the IT group were also performed between patients with and without mutations, and IC patients between fibrosis stages≤2 vs fibrosis>2.Among 301 patients enrolled, 88/301 (29.24%) and 213/301 (70.76%) were at the IT and IC phase, respectively. The frequency of BCP/PC mutations in IT phase was significantly lower than those in IC phase (15.91% vs 64.79 %, P<0.001). The BCP mutation only was significantly more frequent than the PC mutation in both groups and also in all IC subgroups. IT patients with BCP/PC mutations had significantly higher quantitative anti-HBc levels compared with those of patients with wild-type virus (P<0.05). They also had significantly lower mean levels of alanine transaminase, aspartate transaminase, total bilirubin, and qAnti-HBc compared with those of IC patients (all P<0.05). Additionally, they were significantly younger in mean age; had higher platelet count, higher levels of HBV DNA and surface antigen, as well as higher frequency of genotype B than those of IC patients with fibrosis>2 (all P<0.05). BCP/PC mutations were found in IT patients with CHB. They had distinct clinical characteristics when compared with patients with wild-type or at IC phase. Further studies are needed to understand their natural history and treatment outcomes.