Tenofovir alafenamide or tenofovir disoproxil fumarate in pregnancy to prevent HBV transmission: Maternal ALT trajectory and infant outcomes.

BACKGROUND: The use of antiviral agents, specifically tenofovir disoproxil fumarate (TDF), in pregnant women to prevent mother-to-child HBV transmission is a key step towards hepatitis elimination. However, data on using tenofovir alafenamide (TAF) is insufficient. The frequent occurrence of postpartum ALT flares may impact the clinical implementation. METHODS: The maternal and infant outcomes were compared in multi-centre trials of high viral load HBsAg/HBeAg+ pregnant women receiving TAF or TDF from the third trimester until 2 weeks postpartum with intensive follow-ups. To explore the dynamic pre- and postpartum changes in ALT levels, we used a group-based trajectory model for analysing data of 332 women from three prospective studies. RESULTS: After treatment, the maternal HBV DNA levels significantly decreased from baseline to delivery: 7.87 ± 0.59 to 3.99 ± 1.07 Log10 IU/mL TAF (n = 78) and 8.30 ± 0.36 to 4.47 ± 0.86 Log10 IU/mL (TDF, n = 53), with viral load reductions of 3.87 versus 3.83 Log10 IU/mL. The HBsAg-positive rates among 12-month-old infants were 1.28% (1/78) versus 1.82% (1/55) respectively (p = 1.00). Of the TAF or TDF-treated mothers, 25.64% versus 16.98% experienced ALT > 2X ULN, and 11.54% versus 1.89% received extended antiviral treatment. Our model revealed four distinct ALT patterns: stable ALT (87.2%), moderate (8.0%) or marked (2.4%) postpartum flares, or prepartum elevations (2.4%). CONCLUSIONS: TAF effectively reduces mother-to-child HBV transmission, but prophylaxis failure still occurred in few cases. Postpartum ALT flares are common in women receiving TAF or TDF during pregnancy. Approximately 12.8% of mothers may require extended postpartum antiviral treatment. CLINICAL TRIAL NUMBER: NCT03695029 (ClinicalTrials.gov).

Temporal Trends of Inflammatory Bowel Diseases in Taiwan from 2016 to 2020: A Population-Based Study.

BACKGROUND: There are scanty population-based studies investigating the incidence and prevalence rates of inflammatory bowel disease (IBD) in Taiwan. AIMS: This study aimed to estimate the nationwide prevalence and incidence of IBD and identify its noticeable trends in Taiwan between 2016 and 2020. METHODS: A retrospective study by analyzing the data from the National Health Insurance Research Database of Taiwan. RESULTS: A total of 2595 patients with catastrophic IBD illness were registered from 2016 to 2020 in Taiwan (CD, 880; UC, 1715). The male-to-female ratio in the study sample was 1.83:1 for CD and 1.69:1 for UC. The median age of those registered with CD and UC was 37 and 47 years, respectively. The incidence rate of CD was 0.65 per 100,000 persons in 2016 and it was increased to 0.81 per 100,000 persons in 2020. The incidence rate of UC was 1.16 per 100,000 persons in 2016 and it was increased to 1.53 in 2020. Overall, the incidence of IBD was increase from 1.81 per 100,000 persons to 2.34 per 100,000 persons between 2016 and 2020. Overall, the prevalence rates of IBD was increase from 14.95 per 100,000 persons to 20.02 per 100,000 persons between 2016 and 2020. CONCLUSION: The epidemiological stages of IBD in Taiwan was considered in the acceleration in incidence stage, during which incidence rises and prevalence is relatively low. Understanding these geographical differences is important for the rising global burden of IBD.

The trends of pediatric duodenal ulcer and predictors of recurrence.

BACKGROUND: Duodenal ulcer (DU) causes various symptoms in children. The prevalence of Helicobacter pylori (Hp)-associated DU has been reducing in some regions, yet the updated trend in Taiwan is unknown. Risk factors of DU recurrence have not been comprehensively investigated in children. METHODS: This retrospective study included children diagnosed with DU to evaluate the demographics, symptoms, diagnostics, treatment, and outcomes. Specific populations (infant, surgery required) were sorted for subgroup analysis. Predictors of DU recurrence was analyzed in patients who received endoscopic follow-ups. RESULTS: A total of 488 children were included. Most patients were male (72.5%), school-aged (11.3 ± 4.8 years old), and with varied underlying diseases in one-fifth. The annual incidences were around 3-5%, with a declining trend of case numbers and the Hp-positive proportion. Hp infection, concurrent gastric ulcer, perforation, and mortality were noted in 32.7%, 16%, 1.6%, and 1% of patients. Patients with or without Hp infection showed different clinical features but similar outcomes. The characteristics of subpopulations were depicted respectively. Male sex, lower Hb level, and perforation were independent risk factors associated with recurrence. CONCLUSIONS: Hp-positive DU seems to wane. Patients with male sex, lower Hb level, or perforation at diagnosis carried a higher risk of recurrence, which may warrant active surveillance and endoscopic follow-up.

An SNP Marker Predicts Colorectal Cancer Outcomes with 5-Fluorouracil-Based Adjuvant Chemotherapy Post-Resection.

Colorectal cancer (CRC) is a global health concern, necessitating adjuvant chemotherapy post-curative surgery to mitigate recurrence and enhance survival, particularly in intermediate-stage patients. However, existing therapeutic disparities highlight the need for biomarker-guided adjuvant chemotherapy to achieve better CRC inhibition. This study explores the molecular mechanisms underlying the inhibition of CRC through a genome-wide association study (GWAS) focused on 5-fluorouracil (5-FU)-based adjuvant therapy in intermediate-stage CRC patients, a domain previously unexplored. We retrospectively included 226 intermediate-stage CRC patients undergoing surgical resection followed by 5-FU-based adjuvant chemotherapy. The exploration cohort comprised 31 patients, and the validation cohort included 195 individuals. Genotyping was carried out using either Axiom Genome-Wide TWB 2.0 Array Plate-based or polymerase chain reaction-based methods on genomic DNA derived from collected tissue samples. Statistical analyses involved descriptive statistics, Kaplan-Meier analyses, and Cox proportional hazard analyses. From the GWAS, potential genetic predictors, GALNT14-rs62139523 and DNMBP-rs10786578 genotypes, of 5-FU-based adjuvant therapy following surgery in intermediate-stage CRC patients were identified. Validation in a larger cohort of 195 patients emphasized the predictive significance of GALNT14-rs62139523 genotypes, especially the "A/G" genotype, for improved overall and progression-free survival. This predictive association remained robust across various subgroups, with exceptions for specific demographic and clinical parameters such as age < 58 years old, CEA ≤ 2.5 ng/mL, tumor diameter > 44.0 mm, and tumor-free margin ≥ 50 mm. This study identifies that the GALNT14-rs62139523 "A/G" genotype modulates therapeutic outcomes, establishing it as a promising biomarker for predicting favorable responses to 5-FU-based adjuvant chemotherapy in intermediate-stage CRC patients, although further investigations are needed to detail these mechanisms.

Characterization of Hepatitis B Virus in Tenofovir-Treated and Untreated Chronically Infected Mothers and Their Immunoprophylaxis Failure Infants.

BACKGROUND: Maternal tenofovir disoproxil fumarate (TDF) therapy during late pregnancy can reduce mother-to-infant transmission of hepatitis B virus (HBV). We investigated HBV mutations associated with maternal TDF therapy and their role in infant immunonophylaxis failure (IPF). METHODS: Serum samples from untreated (n = 89) and TDF-treated (n = 68), highly viremic, chronically infected mothers and their infants were analyzed for HBV DNA by nested polymerase chain reaction (PCR) and direct sequencing. RESULTS: At delivery, compared with untreated mothers, TDF-treated mothers had a lower HBV DNA titer and a higher frequency of basal core promoter (BCP) gene mutations, but they had similar frequencies in pre-S/S and pre-core/core mutations. The 14 mothers harboring surface "a" determinant mutants did not transmit the mutants to their immunized infants. Such mutants were found in 3 of 13 IPF infants; the 13 mothers had wild-type hepatitis B surface antigen (HBsAg). In univariable analysis, maternal HBV DNA titer (odds ratio [OR]: 1.54; 95% confidence intervals [CI]: 1.02-2.33; P = .039), genotype C (OR: 4.18; 95% CI: 1.28-13.62; P = .018) and pre-S1 wild-type sequence (OR: 6.33; 95% CI: 1.85-21.68; P = .003) at delivery were associated with infant IPF. Multivariable analyses showed that maternal genotype C (OR: 3.71; 95% CI: 1.11-12.36; P = .033) and pre-S1 wild-type (OR: 6.34; 95% CI: 1.79-22.44; P = .004) were associated with infant IPF independently of maternal viremia. CONCLUSIONS: Along with high maternal HBV DNA titer at delivery, maternal genotype C and pre-S1 wild-type sequence were potential risk factors for infant IPF, although BCP mutations were not. The offspring of pregnant women harboring "a" determinant mutants as major strains seemed to be protected by immunoprophylaxis. CLINICAL TRIALS REGISTRATION: NCT01312012.

Unlocking the Potential of Arginine Deprivation Therapy: Recent Breakthroughs and Promising Future for Cancer Treatment.

Arginine is a semi-essential amino acid that supports protein synthesis to maintain cellular functions. Recent studies suggest that arginine also promotes wound healing, cell division, ammonia metabolism, immune system regulation, and hormone biosynthesis-all of which are critical for tumor growth. These discoveries, coupled with the understanding of cancer cell metabolic reprogramming, have led to renewed interest in arginine deprivation as a new anticancer therapy. Several arginine deprivation strategies have been developed and entered clinical trials. The main principle behind these therapies is that arginine auxotrophic tumors rely on external arginine sources for growth because they carry reduced key arginine-synthesizing enzymes such as argininosuccinate synthase 1 (ASS1) in the intracellular arginine cycle. To obtain anticancer effects, modified arginine-degrading enzymes, such as PEGylated recombinant human arginase 1 (rhArg1-PEG) and arginine deiminase (ADI-PEG 20), have been developed and shown to be safe and effective in clinical trials. They have been tried as a monotherapy or in combination with other existing therapies. This review discusses recent advances in arginine deprivation therapy, including the molecular basis of extracellular arginine degradation leading to tumor cell death, and how this approach could be a valuable addition to the current anticancer arsenal.

Predictive Factors for Nasogastric Tube Removal in Post-Stroke Patients.

Background and Objectives: Stroke patients have different levels of functional impairment, and rehabilitation is essential to achieving functional recovery. Many post-stroke patients transition from acute treatment to post-acute care (PAC) with nasogastric tubes (NGTs) for rehabilitation. However, long-term NGT placement can lead to several complications, and its earlier removal can effectively reduce the incidence of mortality. This study aimed to use a PAC-cerebrovascular disease (CVD) program and physical functional evaluation scale tools to demonstrate the factors associated with NGT removal before post-stroke patient discharge. Materials and Methods: In this retrospective cohort study, data were collected between January 2017 and August 2022. We divided patients who had NGTs at admission into discharged with and without NGT groups to compare their baseline characteristics and physical functional status. Logistic regression analysis was used to detect the predictive factors for NGT removal. Results: There were 63 participants: 22 without NGT removal and 41 with NGT removal. The NGT removal rate was 65%. Age and scores for the activities of daily living by the Barthel index (BI), Functional Oral Intake Scale (FOIS), Mini-Mental State Examination, and Concise Chinese Aphasia Test were significantly different in terms of NGT removal status, but only the BI and FOIS were significantly correlated with NGT removal. Patients' BI scores indicating severe to moderate dependence (21-90) had a 4.55 times greater chance of NGT removal (odds ratio, 4.55; p < 0.05) than patients who had total dependence (<20). Every one-point increase in FOIS score indicated a 3.07 times greater chance of NGT removal (odds ratio, 3.07; p < 0.05). Conclusions: The BI and FOIS evaluations may indicate the probability of NGT removal in patients.

Absence of chronicity in infants born to immunized mothers with occult HBV infection in Taiwan.

BACKGROUND & AIMS: In the Taiwanese population born in the universal vaccination era, HBsAg carrier rates have fallen below 2%, while approximately 5% develop occult hepatitis B infection (OBI). However, the potential for transmission from mothers with OBI to their infants has not been well studied. We aimed to investigate whether mothers with OBI could transmit HBV to their babies. METHODS: A total of 253 pregnant women who were born after July 1986 and had been fully vaccinated against HBV during infancy were recruited from a tertiary hospital in Northern Taiwan. HBV serology and DNA levels were determined. Babies born to mothers with OBI were followed-up until 1 year of age. The surface genes were sequenced. RESULTS: HBV infection was documented in 18 vaccinated mothers, 2 of whom were HBsAg-reactive (0.79 %). Seventeen were positive for HBV DNA, among whom 16 (6.32%) presented with OBI with a median DNA level of 145 IU/ml (interquartile range: 37.8-657.3 IU/ml). Eleven babies born to 10 mothers with OBI were recruited. Three babies were HBsAg-reactive, and 2 were positive for HBV DNA (17.0 and 212.0 IU/ml). Seven mothers with OBI carried multiple surface gene variants. Two transiently infected babies harbored variants originating from their mother's HBV quasi-species. All infants received complete hepatitis B vaccines. At 12 months of age, none of the babies were positive for HBsAg or HBV DNA. CONCLUSIONS: It was possible for mothers with OBI to transmit HBV to their babies, who consequently harbored surface gene variants originating from their mothers' minor variants. Viremia was cleared 1 year after completing the hepatitis B vaccination series. LAY SUMMARY: Since initiating the hepatitis B vaccination program in Taiwan, the rate of young individuals (i.e. born after 1986) carrying the HBV surface antigen has fallen below 2%, although around 5% of vaccinated individuals develop occult HBV infections. Herein, we show that pregnant mothers with occult HBV infections can transmit HBV to their offspring. However, no infant had sustained infection at 1 year of age having completed a full HBV vaccination series.

Primary endoscopic variceal ligation reduced acute variceal bleeding events but not long-term mortality in pediatric-onset portal hypertension.

BACKGROUND/PURPOSE: Esophageal variceal bleeding (EVB) is a medical emergency in patients with portal hypertension (PHT). However, studies on the long-term outcomes of prophylactic endoscopic variceal ligation (EVL) in pediatric-onset PHT are lacking. METHODS: Between 1999 and 2020, patients who received EVL in the Electronic Report System of the Pediatric Endoscopy Unit were included in this retrospective study. EVL was classified as primary prophylaxis when it was performed for esophageal varices (EVs) without previous bleeding. If it was implemented in acute EVB, the subsequent EVL was classified as secondary prophylaxis. RESULTS: Fifty-eight patients aged 10 months to 33 years with 31 males were included. Thirty-eight patients were classified as primary prophylaxis group, and twenty, secondary prophylaxis group. The primary prophylaxis group experienced fewer 5-year EVB events than the secondary prophylaxis group (cumulative risk: 14.4% versus 32.4%). Still, it didn't significantly affect overall survival and biliary atresia transplant-free survival. Long-term mortality was significantly associated with higher serum direct bilirubin levels (≥0.55 mg/dL) and lower albumin levels (≤2.54 mg/dL) at the first EVL. Aspartate aminotransferase-to-platelet ratio index (APRI) with a cut-off value of 1.24 helped to predict EV presence at the initial esophagogastroduodenoscopy (EGD) (AUROC = 0.762, sensitivity 75.0%, and specificity 66.7%). CONCLUSION: Primary prophylactic EVL, despite reducing acute EVB, may not change overall survival and biliary atresia transplant-free survival. APRI > 1.24 may predict EV presence at the first EGD and help to schedule a surveillance EGD. Higher direct bilirubin and lower albumin levels at the first EVL may relate to long-term mortality.

Occult Hepatitis B Virus Infection in Immunized Infants Born to Untreated and Tenofovir-Treated Highly Viremic Mothers.

Tenofovir disoproxil fumurate (TDF) therapy during late pregnancy in highly viremic mothers can reduce residual overt hepatitis B virus (HBV) infections of their infants that occur despite immunoprophylaxis.1,2 Occult HBV infection (OBI) has been defined as the presence of HBV DNA in liver or sera in subjects seronegative for hepatitis B surface antigen (HBsAg).3 OBI has been found in varying proportions of immunized infants born to HBsAg-positive mothers.4-6 We aimed to investigate the impact of maternal TDF therapy during pregnancy on vertically acquired OBI.

Detection of pediatric hepatic steatosis through ultrasound backscattering analysis.

OBJECTIVES: Hepatic steatosis has become a considerable concern in the pediatric population. The objective of this study was to evaluate the feasibility of using ultrasound Nakagami imaging to produce a parametric image for analyzing the echo amplitude distribution to assess pediatric hepatic steatosis. METHODS: A total of 68 pediatric participants were enrolled in healthy control (n = 26) and study groups (n = 42). Raw data from ultrasound imaging were acquired for each participant analysis using AmCAD-US, a software approved by the US Food and Drug Administration for ultrasound Nakagami imaging. The Nakagami parameters were compared with the hepatic steatosis index (HSI) and the steatosis grade (G0: HSI < 30; G1: 30 ≤ HSI < 36; G2: 36 ≤ HSI < 41.6; G3: 41.6 ≤ HSI < 43; G4: HSI ≥ 43) using correlation analysis, one-way analysis of variance (ANOVA), and receiver operating characteristic (ROC) curve analysis. RESULTS: The Nakagami parameter increased from 0.53 ± 0.13 to 0.82 ± 0.05 with increasing severity of hepatic steatosis from G0 to G4 and were significantly different between the different grades of hepatic steatosis (p < .05). The areas under the ROC curves were 0.96, 0.92, 0.85, and 0.82 for diagnosing hepatic steatosis ≥ G1, ≥ G2, ≥ G3, and ≥ G4, respectively. CONCLUSIONS: The Nakagami parameter value quantifies changes in the echo amplitude distribution of ultrasound backscattered signals caused by fatty infiltration, providing a novel, noninvasive, and effective data analysis technique to detect pediatric hepatic steatosis. KEY POINTS: • Ultrasound Nakagami imaging enabled quantification of the echo amplitude distribution for tissue characterization. • The Nakagami parameter increased with the increasing severity of pediatric hepatic steatosis. • The Nakagami parameter demonstrated promising diagnostic performance in evaluating pediatric hepatic steatosis.

Plasma interleukin-17 and alpha-fetoprotein combination effectively predicts imminent hepatocellular carcinoma occurrence in liver cirrhotic patients.

BACKGROUND: Predicting imminent hepatocellular carcinoma (HCC) in liver cirrhotic patients is an unmet medical need. We aimed to investigate circulatory biomarkers and their optimum combinations in a prospective study. METHODS: We investigated plasma interleukin 17 (IL-17) concentrations, quantified using enzyme-linked immunosorbent assay (ELISA), for the prediction of HCC in a large cohort of 404 HCC-naïve liver cirrhotic patients regularly followed after recruitment. Additionally, IL-17 in surgically resected tumor tissues were evaluated using immunohistochemistry staining. RESULTS: IL-17 was detected in HCC tissues. The IL-17 concentrations in the peripheral blood do not have correlation with an extensive list of 31 common demographic, metabolic and liver function variables in the cohort of liver cirrhotic patients. Furthermore, patients stratified by IL-17 and alpha-fetoprotein (AFP) showed distinctive cumulative incidence of HCC. Imminent HCC, defined here as HCC occurrence within 1 year, can be predicted by IL-17 alone with an area under the receiver operating characteristic curve [AUC] of 0.762 (P = 0.002). An multivariate analysis showed that age, hepatitis C viral infection, AFP and IL-17 were four independent factors associated with imminent HCC (adjusted P = 0.03, 0.041, 0.024 and 0.008 respectively). An explicit risk score (R) combining the concentrations of two plasma biomarkers, AFP and IL-17, achieved a high AUC of 0.933 (95% confidence interval 0.893-0.972, P < 0.001) in predicting imminent HCC, with 100% sensitivity and 79.9% specificity at the optimum cutoff. The score is defined as: [Formula: see text] CONCLUSIONS: The circulatory IL-17 concentration is a predictor of subsequent HCC occurrence in liver cirrhotic patients. The combination of AFP and IL-17 is highly effective in predicting imminent HCC within 1 year.

High initial bowel resection rate and very-early-onset inflammatory bowel disease - A challenge in a low-prevalence area.

BACKGROUND: Inflammatory bowel diseases (IBD) include ulcerative colitis (UC) and Crohn's disease (CD). The incidence in children and adolescents has risen since the 21st century globally, including Taiwan. The study aimed to disclose the characteristics and outcome of pediatric IBD (pIBD) patients in a tertiary center for the past two decades. METHODS: We retrospectively reviewed the charts of pIBD children from 2000 to 2018 in a tertiary center in Northern Taiwan. Demographics, presentations, diagnostic modalities, treatment, and outcomes were analyzed. RESULTS: A total of 38 cases were enrolled, including 27 CD and 11 UC patients. An almost 3-folds increase in incidence after 2010 was observed. Twelve cases (32%) were early-onset, and six of them (16%) were very-early-onset; four of them were detected with single-gene mutations [XIAP, TTC7A (2 siblings), and ZAP70]. Eleven CD patients (40.7%) received bowel resection at the onset, and another two (7.4%) had bowel resection years after the diagnosis. Initial bowel resection was associated with fibrostenotic/penetrating behavior, early-onset disease, and growth failure. CONCLUSION: This study demonstrated an increased incidence of pIBD in the past two decades in Taiwan, a low-prevalence region. The initial high bowel resection rate in CD was related to the fibrostenotic and/or penetrating behavior, younger age at diagnosis, and growth failure.

The Berg Balance Scale at Admission Can Predict Community Ambulation at Discharge in Patients with Stroke.

Background and Objectives: To regain the ability of community ambulation is a meaningful goal for stroke patients. Recent research recommended that the distance accomplished during the six-minute walk test (≥205 m in 6MWT) is the fittest for defining community ambulation. Until now, there are few studies that have used the updated definition to investigate the related predictors. The aim of this study was to investigate the association between the admission clinical parameters and community ambulation measured by the 6MWT at discharge. The other aim was to find the admission Berg Balance Scale (BBS) cut-off score to discriminate between household or community ambulators. Materials and Methods: This cohort study collected the data of patients who entered the post-acute Care Cerebrovascular Diseases program. Multivariate logistic regression was used to identify significant predictors measured at admission that are associated with community ambulation, and a receiver operating characteristic was adopted to calculate the cut-off value for admission status. There were 120 participants included in this study, and 25% (n = 30) of them regained the ability of community ambulation at discharge. The BBS on admission was identified as the only significant predictor for community ambulation (odds ratio 1.06). Results: The optimal cut-off score for the BBS at admission was 29, and the area under the curve for BBS scores on admission when discriminating between household and community ambulators at discharge was 0.74. Conclusions: The admission BBS scores could be used to predict household and community ambulators at discharge in stroke patients. The results of this study could help clinical physicians set appropriate discharge goals early.

Long-term growth and bone development in children of HBV-infected mothers with and without fetal exposure to tenofovir disoproxil fumarate.

BACKGROUND & AIMS: Tenofovir disoproxil fumarate (TDF) is the preferred treatment to prevent maternal transmission of HBV, owing to its efficacy and safety. However, data are lacking on the long-term safety outcomes in children following fetal exposure to TDF. METHODS: Children participating in a prospective, multisite trial of maternal TDF treatment during late pregnancy were recruited for follow-up visits once a year. Growth parameters, serum biochemistry, HBV serology, and bone mineral density (BMD) by dual-energy x-ray absorptiometery scan were measured. RESULTS: One hundred and twenty-eight children, 71 in the TDF and 57 in the control group, completed 255 follow-up visits at the age of 2 to 7 (median, 4.08) years. No differences in z-scores for weight-for-age (0.26 ± 0.90 vs. 0.22 ± 0.99, p = 0.481), z-scores for height-for-age (0.20 ± 1.02 vs. 0.25 ± 0.98, p = 0.812), and estimated glomerular filtration rate (169.12 ± 50.48 vs. 169.06 ± 34.46 ml/min/1.73m2, p = 0.479) were detected. After adjustment for age, sex and HBV status by multiple linear regression, children in the TDF and control group had comparable levels of serum calcium, phosphorus, bone-specific alkaline phosphatase, calcidiol and BMD of lumbar spines (0.55 ± 0.01 vs. 0.57 ± 0.01 g/cm2, p = 0.159) and left hip (0.56 ± 0.01 vs. 0.56 ± 0.01 g/cm2, p = 0.926). CONCLUSIONS: Children of HBV-infected mothers who did or did not receive tenofovir disoproxil fumarate treatment during late pregnancy had comparable long-term growth, renal function, and bone development up to 6-7 years after delivery. CLINICAL TRIAL NUMBER: NCT01312012 (ClinicalTrials.gov) LAY SUMMARY: Currently there are insufficient long-term safety data in children born to mothers who took antiviral agents during pregnancy to prevent mother-to-infant transmission of hepatitis B virus (HBV). In this study, we found that children of HBV-infected mothers who did or did not receive tenofovir disoproxil fumarate treatment during late pregnancy had comparable long-term growth, renal function, and bone development up to 6-7 years after delivery.

A GALNT14 rs9679162 genotype-guided therapeutic strategy for advanced hepatocellular carcinoma: systemic or hepatic arterial infusion chemotherapy.

Although targeted agents are recommended as the first-line treatments for advanced hepatocellular carcinoma (aHCC), systemic chemotherapy or hepatic arterial infusion chemotherapy (HAIC) are still being used in Asian countries. Beside economic considerations, it was found that targeted drugs could not significantly prolong overall survival in aHCC patients with distant metastasis. In addition, chemotherapy could achieve complete response in a small proportion of patients. Here, we aimed to investigate whether combination of three previously identified single nucleotide polymorphism (SNP) predictors (GALNT14-rs9679162, WWOX-rs13338697, and rs6025211) could guide our choice between systemic chemotherapy, HAIC, and targeted agents in aHCC patients. A cohort of 237 real-world aHCC patients (171 receiving systemic chemotherapy followed by various anticancer treatments including sorafenib; 66 receiving HAIC) were included for outcome analysis. By combining the three SNP markers with or without addition of two clinical criteria (tumor diameter <8 cm, neutrophils <80%), small groups of patients were found to harbor high complete response rates to systemic chemotherapy (35.3% if the 3-SNP signature alone matched; 60.0% if clinical criteria also matched). Subsequent sorafenib treatment for chemotherapy non-responders was associated with longer overall survival (P < 0.001). In HAIC-treated patients, GALNT14-rs9679162 genotype "GG" was associated with longer overall survival (P = 0.019, median survival > 10.5 months). In conclusion, pre-test for the 3-SNP signature in aHCC patients could identify potential systemic chemotherapy or HAIC responders. Chemotherapy non-responders still benefited from subsequent sorafenib treatment. Accordingly, we propose a roadmap for aHCC patients when chemotherapy or HAIC is to be used.

Decreasing seroprevalence of anti-hepatitis D virus antibodies in the antiviral era with inverse association with hepatitis B virus DNA, Taiwan, 2006 to 2019.

We examined the seroprevalence change of anti-hepatitis D virus (HDV) antibodies in Taiwan from 2006 to 2019. A total of 1147 patients who had chronic hepatitis B virus (HBV) infection were assessed. Of them, 51 (4.4%) were positive for anti-HDV antibodies. Comparison between anti-HDV-positive and negative groups was performed to examine clinical and virological factors related to anti-HDV positivity. It was found that the median HBV-DNA concentration was 1.6 × 105 IU/mL (range, <20-4.5 × 1010 IU/mL) and <20 IU/mL (range, <20-2.0 × 109 IU/mL) for patients with negative and positive anti-HDV antibodies, respectively (P < .001). In addition, a progressive year-to-year decrease of anti-HDV seroprevalence was unveiled. For patients who had HBV-DNA >15 000 IU/mL, the year-to-year (calculated every 2 years) seropositive rates of anti-HDV were 10.0%, 7.9%, 0.7%, 0.3%, 0%, 0%, and 0% (P < .001). For patients who had HBV-DNA <15 000 IU/mL, the year-to-year seropositive rates were 18.6%, 12.8%, 7.8%, 5.0%, 7.3%, 8.0%, and 3.7% (P < .001). In conclusion, seropositive of anti-HDV was inversely associated with HBV-DNA levels. A progressive decrease of anti-HDV seroprevalence was found with no anti-HDV-positive cases detected in high HBV-DNA patient group after 2014.

Hepatitis B Virus preS/S Truncation Mutant rtM204I/sW196* Increases Carcinogenesis through Deregulated HIF1A, MGST2, and TGFbi.

Inevitable long-term therapy with nucleos(t)ide analogs in patients with chronic hepatitis B virus (HBV) infection has selected reverse-transcriptase (rt) mutants in a substantial proportion of patients. Some of these mutants introduce premature stop codons in the overlapping surface (s) gene, including rtA181T/sW172*, which has been shown to enhance oncogenicity. The oncogenicity of another drug-resistant mutant, rtM204I/sW196*, has not been studied. We constructed plasmids harboring rtM204I/sW196* and assessed the in vitro cell transformation, endoplasmic reticulum (ER) stress response, and xenograft tumorigenesis of the transformants. Cellular gene expression was analyzed by cDNA microarray and was validated. The rtM204I/sW196* transformants, compared with the control or wild type, showed enhanced transactivation activities for c-fos, increased cell proliferation, decreased apoptosis, more anchorage-independent growth, and enhanced tumor growth in mouse xenografts. X box-binding protein-1 (XBP1) splicing analysis showed no ER stress response. Altered gene expressions, including up-regulated MGST2 and HIF1A, and downregulated transforming growth factor beta-induced (TGFbi), were unveiled by cDNA microarray and validated by RT-qPCR. The TGFbi alteration occurred in transformants with wild type or mutated HBV. The altered MGST2 and HIF1A were found only with mutated HBV. The rtM204I/sW196* preS/S truncation may endorse the cell transformation and tumorigenesis ability via altered host gene expressions, including MGST2, HIF1A, and TGFbi. Downregulated TGFbi may be a common mechanism for oncogenicity in HBV surface truncation mutants.

Is there a sex difference in postoperative prognosis of hepatocellular carcinoma?

BACKGROUND: Although men carry a higher risk of hepatocellular carcinoma (HCC) than women, it is still controversial whether men also have a poorer postoperative prognosis. A retrospective study was conducted to evaluate the postoperative prognostic predictors of HCC focusing on sex differences. METHODS: We enrolled 516 consecutive adult patients with HCC (118 women, 398 men), who received surgical resection between January 2000 and December 2007, and were followed-up for >10 years. Clinical and laboratory data together with postoperative outcomes were reviewed. RESULTS: At baseline, female patients had a higher anti-hepatitis C virus antibody prevalence (P = 0.002); lower hepatitis B virus surface antigen prevalence (P = 0.006); less microvascular invasion (P = 0.019); and lower alpha-fetoprotein (P = 0.023), bilirubin (P = 0.002), and alanine transaminase (P = 0.001) levels. Overall, there were no significant sex differences in terms of intrahepatic recurrence-free survival (RFS), distant metastasis-free survival (MFS), and overall survival (OS). However, subgroup analysis showed that women had favorable RFS (P = 0.019) and MFS (P = 0.034) in patients with alpha-fetoprotein ≤ 35 ng/mL, independent of other clinical variables (adjusted P = 0.008 and 0.043, respectively). Additionally, men had favorable OS in patients with prothrombin time (international normalized ratio [INR]) <1.1 (P = 0.033), independent of other clinical variables (adjusted P = 0.042). CONCLUSIONS: Female sex is independently associated with favorable postoperative RFS and MFS in patients with alpha-fetoprotein ≤35 ng/mL, while male sex is independently associated with favorable OS in patients with prothrombin time INR <1.1.

Double-balloon enteroscopy for pediatric patients: Application and feasibility evaluation in a medical center in northern Taiwan.

BACKGROUND/PURPOSE: The diagnostic and therapeutic benefits of double-balloon enteroscopy (DBE) in adults are established, but few data are available on pediatric patients. The aim of this study was to evaluate the clinical efficacy and safety of DBE in pediatric patients in Taiwan. METHODS: From April 2005 to September 2015, DBE procedures performed for diagnosis or therapy of small-bowel disease in children less than 18 years of age at Linkou Chang Gung Memorial Hospital, Taiwan were evaluated. The clinical decision to perform DBE via the oral or anal approach was based on the patient's primary clinical presentation. Data on indications, endoscopic findings, treatment outcome, and complications associated with the procedure were collected and reviewed retrospectively. RESULT: In total, 20 pediatric patients underwent a total of 29 DBEs due to suspicion of small-bowel disease. Among them, nine patients were evaluated for suspected small-bowel bleeding, six for Peutz-Jeghers syndrome, two for chronic abdominal pain, two for chronic diarrhea, and one for suspected protein-losing enteropathy. After excluding the six Peutz-Jeghers syndrome patients, 9 of the 14 patients (64%) got a positive endoscopic finding and diagnosis in 8 of the 14 patients (57%). DBE resulted in a further therapeutic intervention (endoscopic or surgical) in 50% of the patients (10/20) without serious complications. CONCLUSION: DBE has a high diagnostic yield and leads to therapeutic interventions in pediatric patients and shows promise for assessment and treating small-intestinal diseases in children in Taiwan.