Faculty Bibliography
Searched for:
in-biosketch:true
person:panc01
Total Results:
196
The clinical course and management of cervical cancer with splenic metastasis: Case report and review of the literature [Case Report]
Adenovirus-mediated herpes simplex virus thymidine kinase gene therapy (ADV-TK) in combination with interventional treatment could relieve the symptoms in patients with widespread splenic metastasis.
PMCID:7869355
PMID: 33598227
ISSN: 2050-0904
CID: 4802272
The case for simplifying and using absolute targets for viral hepatitis elimination goals
The 69th World Health Assembly endorsed the Global Health Sector Strategy for Viral Hepatitis, embracing a goal to eliminate hepatitis infection as a public health threat by 2030. This was followed by the World Health Organization's (WHO) global targets for the care and management of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. These announcements and targets were important in raising awareness and calling for action; however, tracking countries' progress towards these elimination goals has provided insights to the limitations of these targets. The existing targets compare a country's progress relative to its 2015 values, penalizing countries who started their programmes prior to 2015, countries with a young population, or countries with a low prevalence. We recommend that (1) WHO simplify the hepatitis elimination targets, (2) change to absolute targets and (3) allow countries to achieve these disease targets with their own service coverage initiatives that will have the maximum impact. The recommended targets are as follows: reduce HCV new chronic cases to ≤5 per 100 000, reduce HBV prevalence among 1-year-olds to ≤0.1%, reduce HBV and HCV mortality to ≤5 per 100 000, and demonstrate HBV and HCV year-to-year decrease in new HCV- and HBV-related HCC cases. The objective of our recommendations is not to lower expectations or diminish the hepatitis elimination standards, but to provide clearer targets that recognize the past and current elimination efforts by countries, help measure progress towards true elimination, and motivate other countries to follow suit.
PMID: 32979881
ISSN: 1365-2893
CID: 4679282
EFFICACY AND SAFETY OF SOFOSBUVIR-BASED REGIMENS IN HEPATITIS C PATIENTS WITH DECOMPENSATED CIRRHOSIS: A SYSTEM REVIEW AND META-ANALYSIS [Meeting Abstract]
ISI:000707188003034
ISSN: 0270-9139
CID: 5074112
The Characteristics of Natural Killer Cells in Chronic Hepatitis B Patients Who Received PEGylated-Interferon versus Entecavir Therapy
Background/UNASSIGNED:To explore the role of natural killer (NK) cells in the process of hepatitis B virus (HBV) clearance and whether their phenotype is related to antiviral treatment outcome in chronic hepatitis B (CHB) patients. Method/UNASSIGNED:NK cells and mean fluorescence intensity (MFI) of receptors NKp46 and IFNAR2 on the surface of NK cells were measured. Subgroup analyses were performed by comparing treatment responders versus nonresponders with aforementioned parameters in each group. Results/UNASSIGNED:NK frequency and IFNAR2 MFI significantly decreased at 12 and 24 weeks from baseline. Conclusions/UNASSIGNED:treatment significantly enhanced NK cell frequency and function when compared to entacavir. Positive treatment responses to either interferon or entecavir were associated with NK cell function improvement. This trial is registered with clinical trial registration no. NCT03208998.
PMCID:7857883
PMID: 33575322
ISSN: 2314-6141
CID: 4799822
Antiviral kinetics of tenofovir alafenamide and tenofovir disoproxil fumarate over 24 weeks in women of childbearing potential with chronic HBV
BACKGROUND/PURPOSE/OBJECTIVE:Use of tenofovir disoproxil fumarate (TDF) improves patient outcomes in preventing mother-to-child transmission (pMTCT) of the hepatitis B virus (HBV) in mothers with chronic HBV and high viral loads. Given the lack of data for tenofovir alafenamide (TAF) in pMTCT, rates of early viral suppression with TAF and TDF were evaluated in women of childbearing potential (WOCBP) participating in 2 randomized, double-blind, Phase 3 studies in chronic HBV. METHODS:In a patient subset meeting WOCBP criteria and with baseline HBV DNA >200,000 IU/mL, rates of viral suppression with TAF or TDF in achieving the target of HBV DNA <200,000 IU/mL at weeks 12 and 24 were assessed. Multivariate logistic regression was used to identify factors predictive of failure to suppress HBV DNA to the target level. RESULTS:In 275 of 1298 (21%) patients meeting WOCBP criteria with high viral load, 93% and 96% had HBV DNA <200,000 IU/mL at weeks 12 and 24, respectively. Results for TAF (n = 194) vs TDF (n = 81) treatment were similar at weeks 12 and 24 (94% vs. 90% and 97% vs. 93%), respectively. High baseline HBV DNA level, genotype D infection, and prior interferon (week 24 only) were predictive of failure to achieve the target level. Both treatments were well tolerated with TAF showing less impact on renal and bone parameters. CONCLUSIONS:In WOCBP with high VL, no differences were found between TAF and TDF in reducing HBV DNA to levels associated with lower transmission risk. These data support ongoing studies of TAF for pMTCT.
PMID: 33984038
ISSN: 1932-6203
CID: 4878452
Editorial: tenofovir alafenamide fumarate-a new bullet to prevent mother-to-child transmission of hepatitis B virus. Authors' reply [Editorial]
PMID: 33205865
ISSN: 1365-2036
CID: 4684462
The safety of antiviral therapy and drug withdrawal for the prevention of mother-to-child transmission of HBV during pregnancy
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.
PMID: 32410298
ISSN: 1096-9071
CID: 4438272
RIPK1 gene variants associate with obesity in humans and can be therapeutically silenced to reduce obesity in mice
Obesity is a major public health burden worldwide and is characterized by chronic low-grade inflammation driven by the cooperation of the innate immune system and dysregulated metabolism in adipose tissue and other metabolic organs. Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) is a central regulator of inflammatory cell function that coordinates inflammation, apoptosis and necroptosis in response to inflammatory stimuli. Here we show that genetic polymorphisms near the human RIPK1 locus associate with increased RIPK1 gene expression and obesity. We show that one of these single nucleotide polymorphisms is within a binding site for E4BP4 and increases RIPK1 promoter activity and RIPK1 gene expression in adipose tissue. Therapeutic silencing of RIPK1 in vivo in a mouse model of diet-induced obesity dramatically reduces fat mass, total body weight and improves insulin sensitivity, while simultaneously reducing macrophage and promoting invariant natural killer T cell accumulation in adipose tissue. These findings demonstrate that RIPK1 is genetically associated with obesity, and reducing RIPK1 expression is a potential therapeutic approach to target obesity and related diseases.
PMID: 32989316
ISSN: 2522-5812
CID: 4616622
Clinical Features of Hepatitis B Patients at Immune-tolerance Phase with Basal Core Promoter and/or Precore Mutations
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.
PMID: 32384194
ISSN: 1365-2893
CID: 4439212
Efficacy and safety of tenofovir alafenamide fumarate for preventing mother to child transmission of hepatitis B virus: a national cohort study
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.
PMID: 32852100
ISSN: 1365-2036
CID: 4617482
