Hepatitis B core-related antigen: A novel and promising surrogate biomarker to guide anti-hepatitis B virus therapy

The current requirement for biomarkers to detect hepatitis B virus (HBV) infection is polarized. One is a fully-automated and highly sensitive measurement system; the other is a simple system for point-of-care testing (POCT) in resource-limited areas. Hepatitis B core-related antigen (HBcrAg) reflects intrahepatic covalently closed circular DNA and serum HBV DNA. Even in patients with undetectable serum HBV DNA or HBsAg loss, HBcrAg may remain detectable. Decreased HBcrAg levels are associated with reduction of the occurrence of hepatocellular carcinoma (HCC) in chronic hepatitis B. Recently, a fully-automated, novel high-sensitivity HBcrAg assay (iTACT-HBcrAg, cut-off value: 2.1 logIU/mL) has been developed. This attractive assay has been released in Japan very recently. iTACT-HBcrAg can be useful for monitoring HBV reactivation and prediction of HCC occurrence, as an alternative to HBV DNA. Moreover, monitoring HBcrAg may be suitable for determining the therapeutic effectiveness of approved drugs and novel drugs under development. Presently, international guidelines recommend anti-HBV prophylaxis for pregnant women with high viral loads to prevent mother-to-child transmission of HBV. However, >95% of HBV-infected individuals live in countries where HBV DNA quantification is not available. Worldwide elimination of HBV needs the scaling-up of examination and medication services in resource-limited areas. Based on this situation, a rapid and easy HBcrAg assay as a POCT is valuable. This review provides the latest information regarding the clinical use of a new surrogate marker, HBcrAg, in HBV management, based on iTACT-HBcrAg or POCT, and introduces novel agents targeting HBV RNA/protein

ジュウイシ ノ セツメイ ギム イハン ニ カンスル サイバンレイ ニツイテ ノ ホウテキ コウサツ ジュウイリョウ ニオケル インフォームド コンセント ニ カンスル ヨビテキ ケンキュウ

P(論文)departmental bulletin pape

Balloon dilatation for congenital esophageal stenosis associated with esophageal atresia

The version of record of this article, first published in Pediatric Surgery International, is available online at Publisher’s website: https://doi.org/10.1007/s00383-024-05652-w.Purpose: Congenital esophageal stenosis (CES) associated with esophageal atresia (EA) is rare, and no standard treatment has been established. We reviewed cases of EA-associated CES to assess the clinical characteristics and treatment outcomes, especially the feasibility of endoscopic dilatation. Methods: We retrospectively examined patients with EA-associated CES. We also compared treatment outcomes of EA-associated CES with those of EA patients without CES who developed postoperative anastomotic stricture. Results: Among 44 patients with EA, ten had CES (23%). Postoperative complications were not significantly different between EA patients with CES and those without CES but with anastomotic stricture. All CES patients underwent balloon dilatation as initial treatment. Eight of nine patients (89%) were successfully treated by dilatation only, and one patient underwent surgical resection. The median number of balloon dilatations for CES was five (2–17), which was higher than that for anastomotic stricture in patients without CES (p = 0.012). Esophageal perforation occurred in five patients with CES (5/9, 56%) after dilatation, but all perforations were successfully managed conservatively with an uneventful post-dilatation course. Conclusions: Twenty-three percent of patients with EA had CES. Although balloon dilatation for EA-associated CES required multiple treatments and carried a risk of perforation, balloon dilatation showed an 89% success rate and all perforations could be managed conservatively

Prediction Models for BMI and NAFLD

Nonalcoholic fatty liver disease (NAFLD) is closely associated with obesity. Disulfide bond‐forming oxidoreductase A‐like protein (DsbA‐L) is known to be a key molecule in protection against obesity and obesity‐induced inflammation. In the present study, we used a modeling and simulation approach in an attempt to develop body mass index (BMI) and BMI‐based NAFLD prediction models incorporating the DsbA‐L polymorphism to predict the BMI and NAFLD in 341 elderly subjects. A nonlinear mixed‐effect model best represented the sigmoidal relationship between the BMI and the logit function of the probability of NAFLD prevalence. The final models for BMI and NAFLD showed that DsbA‐L rs1917760 polymorphism, age, and gender were associated with the BMI, whereas gender, patatin‐like phospholipase 3 rs738409 polymorphism, HbA1c, and high‐density and low‐density lipoprotein cholesterol levels were associated with the risk of NAFLD. This information may aid in the genetic‐based prevention of obesity and NAFLD in the general elderly population

One Year of Preemptive Valganciclovir Administration in Children After Liver Transplantation

Ueno T., Kodama T., Noguchi Y., et al. One Year of Preemptive Valganciclovir Administration in Children After Liver Transplantation. Transplantation Proceedings 52, 1852 (2020); https://doi.org/10.1016/j.transproceed.2020.01.163.Objectives: Valganciclovir (VGCV) is used as prophylaxis against cytomegalovirus (CMV) infection after pediatric living donor liver transplantation (LDLT). The purpose of this study was to examine the efficacy of 1 year of preemptive VGCV administration compared with a shorter administration after pediatric LDLT. Methods: VGCV was administered to 56 children who underwent LDLT. CMV and Epstein-Barr virus (EBV) antibody status, pp65 antigenemia, and other laboratory data were assessed at 1 year after LDLT. Patients were divided into the 1-year group (n = 32) (patients who had 1 year of VGCV administration) and the <1-year group (n = 24) (patients who had less than 1 year of VGCV administration). Results: Study participants consisted of 34 females and 22 males, with a mean age of 4.2 years at transplant. Regarding pretransplant donor (D)/recipient (R) CMV antibody status, 13 were D positive (+)/R negative (-), 27 were D+/R+, 8 were D-/R+, and 8 were D-/R-. For EBV, 22 were D+/R+, 32 were D+/R-, and 2 were D-/R-. In the 1-year group, only 2 patients (6.5%) developed CMV infection, whereas 8 patients (33.3%) developed CMV infection in the <1-year group. The CMV pp65 antigenemia assay was positive in 2 patients. CMV IgM was positive in 7 patients. One year of preemptive VGCV administration was associated with a lower incidence of CMV infection (P = .008), but not EBV infection. No adverse effects were observed. Conclusions: One year of preemptive VGCV administration after LDLT is safe and suppresses CMV infection. It was useful after pediatric LDLT

Treatment and follow-up of late onset intra hepatic bile duct stones in congenital biliary dilatation

This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: https://doi.org/10.1007/s00383-022-05321-w.Purpose: The postoperative course after surgery for congenital biliary dilatation (CBD) has some complications. Intrahepatic bile duct (IHBD) stones were known as a late complication. We report on the treatment and long-term follow-up of postoperative IHBD stones in our department. Methods: Patients who underwent CBD surgery at age 15 years or younger in our department were identified. Those followed up for 5 years or more were enrolled. Annual blood chemistry tests and abdominal ultrasonography were performed. Each patient’s surgical procedure, IHBD stone diagnosis, treatments, and outcomes were retrospectively assessed. Results: Fifty-one patients were analyzed. The median age at the last visit was 24 years (range 7–45 years), and the median age at CBD surgery was 3 years. Eight patients (16%) developed late-onset IHBD stones. The median age at onset was 25 years, and the median duration after surgery was 20 years. The initial treatment was double-balloon enteroscopy (DBE) in 4 cases, which resulted in stone removal in 3 of the 4 patients (75%). Conclusion: Since CBD may cause late-onset IHBD stones, continuous follow-up is required even in adulthood. In this study, DBE was effective and minimally invasive, and it is recommended as the initial treatment

Early Use of Everolimus as a Third Immunosuppressive Agent for Intestinal Transplantation: A Report of 2 Cases

Ueno T., Toyama C., Deguchi K., et al. Early Use of Everolimus as a Third Immunosuppressive Agent for Intestinal Transplantation: A Report of 2 Cases. Transplantation Proceedings 54, 472 (2022); https://doi.org/10.1016/j.transproceed.2022.01.010.Background: In patients with intestinal transplantation (ITx), renal function is easily impaired because of long-term parenteral nutrition and side effects of tacrolimus. Everolimus was used in patients with renal insufficiency in our study. Methods: We administered everolimus as a third immunosuppressive agent in addition to tacrolimus and steroids for renal sparing in patients who received ITx. We assessed everolimus levels, complications, and renal function. Results: Two patients received everolimus after ITx. Patient 1 was a 13-year-old boy who underwent ITx for an allied disorder of Hirschsprung's disease. After induction therapy with rabbit antithymocyte globulin, maintenance therapy consisted of tacrolimus and steroids. Everolimus was introduced 3 months after ITx for renal sparing. Seven months later, the patient required partial intestinal graft resection owing to bowel obstruction. Everolimus was suspended for only 2 weeks. Four years after ITx, the trough level of tacrolimus was maintained at 3 to 5 ng/mL. The trough level of everolimus was maintained at 3 to 5 ng/mL. Patient 2 was a 32-year-old man who underwent deceased ITx for short gut syndrome. Induction and maintenance immunosuppression was the same as for patient 1. Everolimus was introduced 1 month after surgery. Two years after ITx, trough levels of tacrolimus and everolimus were the same as in patient 1. No rejection was observed in either patient, and renal function was well maintained. We observed no side effects caused by everolimus. Conclusions: Everolimus could be used safely and effectively after ITx. Early use of everolimus after ITx did not affect wound healing

Impact of Monosegment Graft Use for Infants in Pediatric Living Donor Liver Transplantation

Ueno T., Toyama C., Deguchi K., et al. Impact of Monosegment Graft Use for Infants in Pediatric Living Donor Liver Transplantation. Transplantation Proceedings 54, 391 (2022); https://doi.org/10.1016/j.transproceed.2021.12.034.Background: Left lateral segment grafts are generally used for very young pediatric patients undergoing living donor liver transplantation (LDLT). Recently, graft reduction techniques were developed for LDLT. Monosegment grafting has been used in newborns. The aim of this study was to determine the usefulness of monosegment grafting for infants. Methods: Recipients <2 years of age who underwent LDLT with a monosegment graft between 2010 and 2020 were gathered. Parents comprised all LDLT donors. A segment 2 monosegment graft was resected as a graft from the donor. Standard liver volume (SLV) was estimated using Urata's equation. Graft type, graft weight (GW), and native liver weight were assessed. Results: Eight patients were included in the study. Original diseases consisted of biliary atresia (n = 6) and fulminant hepatitis (n = 2). Final graft type included monosegment (n = 5) and reduced monosegment (n = 3). Median final GW/body weight after reduction was 3% (range, 2%-3.4%). Median native liver weight/SLV was 134% except in patients with fulminant hepatitis. Median pre-reduction graft volume (GV)/estimated GV was 113% (range, 60%-208%). Median pre-reduction GV/SLV of monosegment grafts that required reduction (n = 3) was 109% (range, 106%-121%). Median final reduced graft GV/SLV was 80% (range, 74%-91%). Complications due to large-for-size grafts were not observed. One case of bile leakage due to graft reduction occurred as a complication. Grafts were functioning well with the exception of one graft loss due to antibody-mediated rejection. Conclusion: Estimated GV in infants varies widely. Monosegment grafting can be useful for infants as well as newborns

Long-Term Outcome of Portal Vein Stenting After Pediatric Living Donor Liver Transplantation

Ueno T., Toyama C., Deguchi K., et al. Long-Term Outcome of Portal Vein Stenting After Pediatric Living Donor Liver Transplantation. Transplantation Proceedings 54, 454 (2022); https://doi.org/10.1016/j.transproceed.2022.01.008.Background: Portal vein (PV) stenosis is sometimes seen in pediatric living donor liver transplantation (LDLT). PV stents have been attempted in adults with persistent stenosis. However, long-term usefulness of PV stenting is unknown because stents do not expand with growth. We investigated the effect and long-term outcome of PV stenting for stenosis after pediatric LDLT. Methods: We included patients aged <18 years who underwent LDLT from 1998 to 2020 and who underwent PV stenting for stenosis. We assessed age at procedure, stent complications, and long-term outcomes. Results: Five patients underwent PV stent placement. The median age at LDLT was 10 years (range, 0.8-18.1 years). The median interval between LDLT and stent placement was 25 months. The median age at stent placement was 16 years (range, 3-20 years). The median body weight was 38 kg (range, 13-63 kg). The median stent diameter was 8 mm. The median observation period after stent placement was 8 years. On average, body weight increased 1.6 times. One complication associated with stent placement was PV thrombosis, which resulted in stent failure, but we observed no portal hypertension. In the other 4 patients, the stent has remained functioning, and there was no clinical evidence of portal hypertension. Conclusions: PV stents are effective for intractable PV stenosis in children. PV stents were successfully placed in children as young as 3 years old and weighing 13 kg. Our data suggests that a stent placed in young children does not cause portal hypertension as patients grow