Abstract
Background
Cure rates of hepatitis C virus (HCV) treatment with direct-acting antivirals (DAAs) for patients with active and inactive hepatocellular carcinoma (HCC) may differ, but ...well-controlled studies are limited. We aimed to evaluate DAA outcomes in a large East Asian HCV/HCC population compared with HCV/non-HCC patients.
Methods
Using data from the Real-World Evidence from the Asia Liver Consortium (REAL-C) registry (Hong Kong, Japan, South Korea, and Taiwan), we used propensity score matching (PSM) to match HCC and non-HCC (1:1) groups for age, sex, cirrhosis, prior treatment, HCV genotype, treatment regimen, baseline platelet count, HCV RNA, total bilirubin, alanine aminotransferase, and albumin levels to evaluate DAA treatment outcomes in a large population of HCV/HCC compared with HCV/non-HCC patients.
Results
We included 6081 patients (HCC, n = 465; non-HCC, n = 5 616) treated with interferon-free DAAs. PSM of the entire study population yielded 436 matched pairs with similar baseline characteristics. There was no statistically significant difference in the overall SVR rate of HCC (92.7%) and non-HCC (95.0%) groups. Rates of treatment discontinuation, adverse effects, and death were also similar between HCC and non-HCC groups. Among patients with HCC, those with active HCC had a lower SVR than inactive HCC cases (85.5% vs 93.7%; P = .03). On multivariable analysis, active HCC, but not inactive HCC, was significantly associated with lower SVR (OR, 0.28; P = .01) when compared with non-HCC.
Conclusions
Active HCC but not inactive HCC was independently associated with lower SVR compared with non-HCC patients undergoing DAA therapy, although cure rate was still relatively high (85%) in active HCC patients.
We found no significant difference in treatment tolerability or completion rate between DAA-treated patients with and without Hepatocellular Carcinoma (HCC). Non-HCC and inactive HCC patients had similar cure rate (95%) but not active HCC (85%), an independent risk factor for lower SVR.
Pancreatic ductal adenocarcinoma (PDAC) is the most lethal cancer, with a dismal 5-year survival rate of less than 10%. It is estimated that approximately 80% of pancreatic ductal carcinoma (PDAC) ...patients are diagnosed at an advanced or metastatic stage. Hence, most patients are not appropriate candidates for surgical resection and therefore require systemic chemotherapy. However, it has been reported that most patients develop chemoresistance within several months, partly because of antiapoptotic mechanisms. Hence, inducing alternative programmed cell death (PCD), including ferroptosis, necroptosis or pyroptosis, seems to be a promising strategy to overcome antiapoptosis-mediated chemoresistance. In this review, we shed light on the molecular mechanisms of ferroptosis, necroptosis and pyroptosis and suggest several potential strategies (e.g., compounds and nanoparticles NPs) that are capable of triggering nonapoptotic PCD to suppress PDAC progression. In conclusion, these strategies might serve as adjuvants in combination with clinical first-line chemotherapies to improve patient survival rates.
Introduction
Eight-week glecaprevir/pibrentasvir (GLE/PIB) is indicated for treatment-naïve (TN) patients with chronic hepatitis C (CHC), with or without compensated cirrhosis. Given that the ...Taiwanese government is committed to eliminating hepatitis C virus (HCV) by 2025, this study aimed to measure real-world evidence for TN patients using 8-week GLE/PIB in the Taiwan HCV Registry (TACR).
Methods
The data of patients with CHC treated with 8-week GLE/PIB were retrieved from TACR, a nationwide registry program organized by the Taiwan Association for the Study of the Liver (TASL). Treatment efficacy, defined as a sustained virologic response at posttreatment week 12 (SVR12), was assessed in the modified intention-to-treat (mITT) population, which excluded patients who were lost to follow-up or lacked SVR12 data. The safety profile of the ITT population was assessed.
Results
A total of 7246 (6897 without cirrhosis; 349 with cirrhosis) patients received at least one dose of GLE/PIB (ITT), 7204 of whom had SVR12 data available (mITT). The overall SVR12 rate was 98.9% (7122/7204) among all patients, 98.9% (6780/6856) and 98.3% (342/348) among patients without and with cirrhosis, respectively. For the selected subgroups, which included patients with genotype 3 infection, diabetes, chronic kidney disease, people who injected drugs, and those with human immunodeficiency virus coinfection, the SVR12 rates were 95.1% (272/286), 98.9% (1084/1096), 99.0% (1171/1183), 97.4% (566/581), and 96.1% (248/258), respectively. Overall, 14.1% (1021/7246) of the patients experienced adverse events (AEs). Twenty-two patients (0.3%) experienced serious AEs, and 15 events (0.2%) resulted in permanent drug discontinuation. Only one event was considered treatment drug related.
Conclusion
Eight-week GLE/PIB therapy was effective and well tolerated in all TN patients, regardless of cirrhosis status.
Understanding the barriers and tackling the hurdles of hepatitis C virus (HCV) care cascades is key to HCV elimination. The current study aimed to investigate the rates of disease awareness, ...link‐to‐care, and treatment uptake of HCV in a hyperendemic area in Taiwan. Tzukuan residents from 2000 to 2018 were invited to participate in the questionnaire‐based interviews for HCV. The rates of disease awareness, accessibility, and anti‐HCV therapy were evaluated in anti‐HCV‐seropositive participants. Among 10,348 residents, 1789 (17.3%) were anti‐HCV seropositive. Of these 1789 anti‐HCV‐seropositive participants, data of 594 participants from questionnaire‐based interviews in 2005–2018 were analyzed for HCV care cascades. Overall, 24.9% of anti‐HCV‐seropositive HCV participants had disease awareness, 53.9% of aware participants had accessibility, and 79.8% of assessed participants had received HCV treatment, with a community effectiveness of 10.7%. HCV prevalence decreased over time, from 21.2% in the early cohort to 9.3% in the recent cohort. Disease awareness increased over time, from 15.6% to 41.7%, with the community effectiveness increasing from 1.3% to 28.8%. Lower education levels and normal liver biochemistry were associated with a lower rate of disease awareness. Notably, 68% of participants with abnormal liver biochemistry and 69% of those with advanced fibrosis (FIB‐4 > 3.25) were unaware of their HCV disease. We demonstrated huge gaps in disease awareness, link‐to‐care, and treatment uptake in the HCV care cascade in an HCV‐hyperendemic area, even in the initial era of direct‐acting antiviral agents. There is an urgent need to overcome these hurdles to achieve HCV elimination.
Based on the oxidative stress theory, aging derives from the accumulation of oxidized proteins induced by reactive oxygen species (ROS) in the cytoplasm. Hydrogen peroxide (H
O
) elicits ROS that ...induces skin aging through oxidation of proteins, forming disulfide bridges with cysteine or methionine sulfhydryl groups. Decreased Ca
signaling is observed in aged cells, probably secondary to the formation of disulfide bonds among Ca
signaling-related proteins. Skin aging processes are modeled by treating keratinocytes with H
O
. In the present study, H
O
dose-dependently impaired the adenosine triphosphate (ATP)-induced Ca
response, which was partially protected via co-treatment with β-mercaptoethanol, resulting in reduced disulfide bond formation in inositol 1, 4, 5-trisphosphate receptors (IP
Rs). Molecular hydrogen (H
) was found to be more effectively protected H
O
-induced IP
R1 dysfunction by reducing disulfide bonds, rather than quenching ROS. In conclusion, skin aging processes may involve ROS-induced protein dysfunction due to disulfide bond formation, and H
can protect oxidation of this process.
Background
With the increase in the aging population, informal caregivers have become an essential pillar for the long-term care of older individuals. However, providing care can have a negative ...impact and increase the burden on caregivers, which is a cause for concern.
Objective
This study aimed to comprehensively depict the concept of “informal caregiver burden” through bibliometric and content analyses.
Methods
We searched the Web of Science (WoS) database to obtain bibliometric data and included only papers published between 2013 and 2022. We used content analysis to extract and identify the core concepts within the text systematically.
Results
Altogether, 934 papers were included in the bibliometric analysis, from which we selected 19 highly impactful papers for content analysis. The results indicate that researchers have focused on exploring the factors that impact informal caregiver burden. Meanwhile, there has been a widespread discussion regarding the caregiver burden among those caring for recipients with specific illnesses, such as dementia, Alzheimer’s disease, and cancer, as these illnesses can contribute to varying levels of burden on informal caregivers. In addition, questionnaires and interviews emerged as the predominant methods for data collection in the realm of informal caregiver research. Furthermore, we identified 26 distinct assessment tools specifically tailored for evaluating burden, such as caregiver strain index (CSI).
Conclusion
For future studies, we suggest considering the intersectionality of factors contributing to the burden on informal caregivers. This approach could enhance the well-being of both caregivers and older care recipients.
Abstract
Free oligosaccharides are abundant macronutrients in milk and involved in prebiotic functions and antiadhesive binding of viruses and pathogenic bacteria to colonocytes. Despite the ...importance of these oligosaccharides, structural determination of oligosaccharides is challenging, and milk oligosaccharide biosynthetic pathways remain unclear. Oligosaccharide structures are conventionally determined using a combination of chemical reactions, exoglycosidase digestion, nuclear magnetic resonance spectroscopy, and mass spectrometry. Most reported free oligosaccharides are highly abundant and have lactose at the reducing end, and current oligosaccharide biosynthetic pathways in human milk are proposed based on these oligosaccharides. In this study, a new mass spectrometry technique, which can identify linkages, anomericities, and stereoisomers, was applied to determine the structures of free oligosaccharides in human, bovine, and caprine milk. Oligosaccharides that do not follow the current biosynthetic pathways and are not synthesized by any discovered enzymes were found, indicating the existence of undiscovered biosynthetic pathways and enzymes.
Although mRNA-based COVID-19 vaccines reduce the risk of severe disease, hospitalization and death, vaccine effectiveness (VE) against infection and disease from variants of concern (VOC) wanes over ...time. Neutralizing antibodies (NAb) are surrogates of protection and are enhanced by a booster dose, but their kinetics and durability remain understudied. Current recommendation of a booster dose does not consider the existing NAb in each individual. Here, we investigated 50% neutralization (NT
) titers against VOC among COVID-19-naive participants receiving the Moderna (
= 26) or Pfizer (
= 25) vaccine for up to 7 months following the second dose, and determined their half-lives. We found that the time it took for NT
titers to decline to 24, equivalent to 50% inhibitory dilution of 10 international units/mL, was longer in the Moderna (325/324/235/274 days for the D614G/alpha/beta/delta variants) group than in the Pfizer (253/252/174/226 days) group, which may account for the slower decline in VE of the Moderna vaccine observed in real-world settings and supports our hypothesis that measuring the NT
titers against VOC, together with information on NAb half-lives, can be used to dictate the time of booster vaccination. Our study provides a framework to determine the optimal time of a booster dose against VOC at the individual level. In response to future VOC with high morbidity and mortality, a quick evaluation of NAb half-lives using longitudinal serum samples from clinical trials or research programs of different primary-series vaccinations and/or one or two boosters could provide references for determining the time of booster in different individuals.
Despite improved understanding of the biology of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the evolutionary trajectory of the virus is uncertain, and the concern of future antigenically distinct variants remains. Current recommendations for a COVID-19 vaccine booster dose are primarily based on neutralization capacity, effectiveness against circulating variants of concern (VOC), and other host factors. We hypothesized that measuring neutralizing antibody titers against SARS-CoV-2 VOC together with half-life information can be used to dictate the time of booster vaccination. Through detailed analysis of neutralizing antibodies against VOC among COVID-19-naive vaccinees receiving either of two mRNA vaccines, we found that the time it took for 50% neutralization titers to decline to a reference level of protection was longer in the Moderna than in the Pfizer group, which supports our hypothesis. In response to future VOC with potentially high morbidity and mortality, our proof-of-concept study provides a framework to determine the optimal time of a booster dose at the individual level.
Gynura divaricata subsp. formosana is a widely used traditional herbal medicine for treating liver disorders such as hepatitis and liver cancer in Taiwan.
This study was aimed to evaluate the ...anti-cancer and cancer stabilization effect of water extract of the aerial part of G. divaricata (GD extract) both in vitro and in vivo.
Cytotoxicity and anti-proliferative effects of GD extract alone and in combination with cisplatin were determined by alamarBlue and clonogenic assay. Cancer stem cell (CSC) inhibition and the expression of CSC markers were revealed by sphere formation assay and real-time PCR (qPCR). The in vivo anti-cancer effect of GD extract was evaluated in Huh7 xenograft mice model and Ki-67 expression were also measured. The activity of Wnt signalling and the expression level of Wnt target genes and β-catenin were determined by luciferase reporter assay, qPCR, immunoblotting and IHC.
Moderate cytotoxicity of GD extract in liver cancer cells was observed. GD extract sensitized Huh7 cells to cisplatin treatment. Interestingly, GD extract inhibited cancer sphere formation and reduced the expression of CSC markers. Importantly, GD extract suppressed Huh7 tumor growth, Ki-67 expression and prolonged the anti-liver cancer effect of cisplatin in vivo. Treatment of GD extract resulted in reductions of Wnt reporter activity and the expression of Wnt target genes. Moreover, suppression of β-catenin were observed in both GD extract treated Huh7 spheres and xenograft tumors.
Accordingly, our findings suggest that G. divaricata may target liver CSC by suppressing the Wnt pathway and the combination of G. divaricata and cisplatin could be a candidate regimen for treating HCC.
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Background
Patients with Barcelona Clinic Liver Cancer Stage C (BCLC-C) hepatocellular carcinoma (HCC) can be markedly heterogeneous with varying prognosis. This study aims to establish a new ...subclassification system for BCLC-C HCC to better predict overall survival (OS) and to tailor therapy.
Methods
We retrospectively studied 1856 BCLC-C HCC patients between 2006 and 2017 from E-Da Hospital, Taiwan (
n
= 622, training cohort), Kaohsiung Medical University Hospital, Taiwan (
n
= 774, Taiwan validation cohort), and Stanford University Medical Center and Mayo Clinic (United States), Hanyang University Hospital (South Korea), and Ogaki Municipal Hospital (Japan) to make up the international validation cohort (
n
= 460).
Results
In the training cohort, significant factors associated with OS were largest tumor size ≥ 10 cm, extrahepatic spread, macrovascular invasion, and Child–Pugh class, which provided the basis, together with aged ≥ 75 years, for the substaging, through C0 to C4, of BCLC-C HCC patients. The median OS for substages C0, C1, C2, C3, and C4 were 43.8 months (95% confidence interval CI 32.2–53.7), 20.6 months (CI 14.1–25.9), 11.5 months (CI 8.02–14.1), 5.7 months (CI 4.02–5.98), and 3.2 months (CI 2.41–3.59), respectively, (
p
< 0.05). OS remained distinct among the proposed substages in the Taiwan validation cohort as well as the international validation cohort. The distinction between the substages persisted in subgroup analysis by substage combined with treatment modality. In substage C0–C3, patients receiving HCC curative therapy had a significantly better median OS than those receiving sorafenib or palliative therapy.
Conclusion
Our new substaging system provides more precise prognosis to better tailor therapy for BCLC-C HCC patients.
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