Review Article
Open Access
Khat-associated Autoimmune Hepatitis: A Review with RUCAM Analysis
Rachael Hagen, George Y. Wu
Published online August 18, 2025
Journal of Clinical and Translational Hepatology.
doi:10.14218/JCTH.2025.00180
Abstract
Khat (Catha edulis) is a plant native to East Africa and the Arabian Peninsula, chewed for its stimulant effects by millions worldwide. Its sympathomimetic properties, primarily
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Khat (Catha edulis) is a plant native to East Africa and the Arabian Peninsula, chewed for its stimulant effects by millions worldwide. Its sympathomimetic properties, primarily due to cathinone and other pyrrolizidine alkaloids, resemble those of amphetamine. Emerging reports have linked khat use to the development of autoimmune hepatitis, supported by elevated autoimmune markers, characteristic liver biopsy findings, and clinical resolution following khat cessation or a prompt response to corticosteroid therapy without recurrence. In this review, we aimed to update knowledge on both acute and chronic forms of khat-associated AIH. We discuss cathinone metabolism, pharmacokinetics, and proposed mechanisms of khat hepatotoxicity. We also provide an updated synthesis of published cases of khat-associated autoimmune hepatitis, including our calculated Roussel-Uclaf Causality Assessment Method analysis and the simplified Hennes AIH score where data were available. Case presentations, diagnostic criteria, histopathological findings, and treatment approaches are summarized to help guide management.
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Original Article
Open Access
High-grade Serous Carcinomas Identified in Cervical Biopsies: A Clinicopathologic Study Supporting the Exclusion of Cervical Serous Carcinoma from World Health Organization Classification
Vijaya Kadam Maruthi, Tong Sun
Published online August 18, 2025
Journal of Clinical and Translational Pathology.
doi:10.14218/JCTP.2025.00023
Abstract
High-grade serous carcinoma is a rare diagnosis in cervical biopsies. Cervical serous carcinoma is no longer recognized as a primary cervical tumor in the 2020 World Health Organization
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High-grade serous carcinoma is a rare diagnosis in cervical biopsies. Cervical serous carcinoma is no longer recognized as a primary cervical tumor in the 2020 World Health Organization classification. This study aimed to characterize the clinicopathologic, immunohistochemical, and molecular features of high-grade serous carcinoma identified in cervical or endocervical biopsies, to assess tumor origin and ensure accurate classification.
Fifty-nine cases originally diagnosed as “serous carcinoma” or “high-grade serous carcinoma” in cervical or endocervical biopsies from 2013 to 2023 were retrospectively reviewed. Clinical data, radiologic findings, and follow-up information were analyzed. Histologic features and immunohistochemical profiles were re-evaluated. Targeted next-generation sequencing was performed on a subset of cases.
The majority of tumors (96%) were determined to originate from the endometrium (n = 47) or the tubo-ovarian region (n = 4), with only one case confirmed as a primary cervical carcinoma. Morphologic patterns varied and could mimic human papillomavirus-associated adenocarcinoma. All tumors showed aberrant p53 expression and diffuse p16 positivity. WT-1 was expressed in all tubo-ovarian tumors but in only 12% of endometrial cases. Estrogen receptor and progesterone receptor were frequently positive in endometrial tumors; human epidermal growth factor receptor 2 was positive in 31% of cases. Molecular analysis confirmed tumor protein p53 mutations and other alterations typical of uterine serous carcinoma.
High-grade serous carcinoma identified in cervical biopsies is overwhelmingly secondary to upper genital tract tumors, most commonly of endometrial origin. A small subset of endocervical adenocarcinomas may mimic serous carcinoma. These findings support the exclusion of primary cervical serous carcinoma from the current World Health Organization classification and emphasize the importance of accurate diagnosis for appropriate management.
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Original Article
Open Access
Seroprevalence 36 Months after a Single-dose Bivalent Human Papillomavirus Vaccination among Nine to Fifteen-year-old Girls in Dhaka, Bangladesh: A Cross-sectional Study
Ashrafun Nessa, Md Foyjul Islam, Shirin Akhter Begum, Jannatul Ferdouse, Fawzia Hossain, Noor-E-Ferdous, Saif Ullah Munshi, Shakila Jahan Shimu
Published online August 13, 2025
Cancer Screening and Prevention.
doi:10.14218/CSP.2025.00008
Abstract
Immunization against human papillomavirus (HPV), particularly with a single-dose vaccine, offers a cost-effective strategy for cervical cancer prevention. This study aimed to evaluate
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Immunization against human papillomavirus (HPV), particularly with a single-dose vaccine, offers a cost-effective strategy for cervical cancer prevention. This study aimed to evaluate the seroprevalence following a single-dose bivalent HPV vaccine among adolescent girls in Bangladesh and to examine its association with sociodemographic characteristics.
A cross-sectional study was conducted among 648 adolescent girls (aged nine to fifteen years) in Dhaka, Bangladesh, who received a single dose of the bivalent HPV vaccine in November 2019. Participants were recruited from ten local schools. At 36 months post-vaccination, blood samples were analyzed for HPV16/18 L1-specific immunoglobulin G using enzyme-linked immunosorbent assay. Sociodemographic data were collected and analyzed using logistic regression.
Most participants were aged nine to thirteen years (82.4%), with a mean age of 11.89 ± 1.59 years. The overall seroprevalence was 72.8% for HPV16 and 82.4% for HPV18. Seropositivity for HPV16 was significantly lower among participants aged 14–15 years [adjusted odds ratio (aOR) = 0.61; 95% confidence interval (CI): 0.39–0.95; p = 0.020] and those in grades nine to ten (aOR = 0.50; 95% CI: 0.28–0.89; p = 0.004). For HPV18, significantly reduced odds of seropositivity were observed among participants from households with monthly incomes up to Taka 10,000 (aOR for Taka 10,001–20,000 = 0.41; 95% CI: 0.26–0.67; p < 0.001; aOR for Taka 20,001–50,000 = 0.21; 95% CI: 0.11–0.40; p < 0.001).
A single-dose bivalent HPV vaccine induces sustained immunity in Bangladeshi adolescent girls, with lower HPV16 seropositivity among older girls and those in higher grades, and higher HPV18 seropositivity is linked to lower household income.
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Original Article
Open Access
Microarray Analysis of Differential Expression of Long Non-coding RNAs in Peripheral Blood Mononuclear Cells in Luminal A Breast Cancer
Varvara I. Minina, Ruslan A. Titov, Vladislav Yu. Buslaev, Renata R. Savchenko, Alexey A. Sleptcov, Natalia A. Gavrineva, Marina L. Bakanova, Yana A. Zakharova, Andrey N. Glushkov
Published online August 13, 2025
Abstract
In the post-genomic era, long non-coding RNAs (lncRNAs) have emerged as critical regulators in various cancers and hold potential as minimally invasive diagnostic biomarkers. This
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In the post-genomic era, long non-coding RNAs (lncRNAs) have emerged as critical regulators in various cancers and hold potential as minimally invasive diagnostic biomarkers. This study aimed to perform microarray analysis of the peripheral blood mononuclear cell (PBMC) transcriptome to evaluate differential lncRNA expression in women with luminal A breast cancer.
A one-color microarray analysis was conducted using SurePrint G3 Human Unrestricted 8×60K arrays and a SureScan Microarray Scanner (Agilent Technologies, USA). The study cohort comprised 16 participants: eight patients diagnosed with luminal A breast cancer and eight healthy controls. Bioinformatic analysis was performed using the “limma” and “tidyverse” packages in the R statistical environment. Functional enrichment analysis was conducted to identify significantly differentially expressed gene clusters. The false discovery rate-adjusted p-value (padj) was applied to ensure methodological rigor. Associations between lncRNAs and disease progression were explored using the LncRNADisease 2.0 database.
Differential expression was observed for long intergenic non-coding (LINC), LOC, and antisense RNA genes. Notably, LINC RNA 974 (LINC00974) exhibited significant differential expression (log fold change > |1.5|, padj < 0.05) after multiple comparison correction. Analysis using the LncRNADisease 2.0 database revealed associations between LINC and antisense RNAs and other oncological disorders.
This study is the first to demonstrate differential lncRNA expression in PBMCs of patients with luminal A breast cancer. Despite the limited sample size, the study demonstrates statistically significant differences between groups, highlighting the potential of PBMC-derived lncRNAs as minimally invasive biomarkers. These findings enhance our understanding of the utility of PBMC-derived lncRNAs as biomarkers for breast cancer.
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Review Article
Open Access
Targeting Glypican-3 for Liver Cancer Therapy: Clinical Applications and Detection Methods
Jin Zhang, Rong Li, Xueqin Tan, Chuang Wang
Published online August 7, 2025
Journal of Clinical and Translational Hepatology.
doi:10.14218/JCTH.2025.00099
Abstract
Recent advancements in cancer immunotherapy have highlighted glypican-3 (GPC3) as a prominent target for treating hepatocellular carcinoma (HCC). However, approximately 10% to 30%
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Recent advancements in cancer immunotherapy have highlighted glypican-3 (GPC3) as a prominent target for treating hepatocellular carcinoma (HCC). However, approximately 10% to 30% of HCC patients exhibit low or absent GPC3 expression on the surface of tumor cells, which limits the feasibility of GPC3-targeted therapies. Consequently, it is essential for patients to undergo pre-diagnostic assessments of GPC3 expression in tumor cells to evaluate their suitability for GPC3-directed therapy. Although various methods have been developed to specifically detect GPC3 as a biomarker for treatment and prognosis, the diagnostic approaches currently employed in clinical studies remain relatively limited. Here, we provide a comprehensive overview of the clinical development of GPC3-targeted therapeutics, clinical trials in GPC3-positive HCC, and current methods for detecting GPC3 expression, highlighting their advantages and limitations. Furthermore, we explore the potential of integrating targeted therapy with various GPC3 detection modalities tailored to different pathological stages. This integration not only provides insights into the selection of effective methods for detecting GPC3 expression but also has the potential to significantly improve the clinical outcomes of patients with liver cancer. By simultaneously assessing the advantages and disadvantages of these methods, this review aims to establish a theoretical foundation for the clinical selection of appropriate GPC3 detection strategies for targeted therapy.
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Review Article
Open Access
Acute Liver Failure with Determinate rather than Indeterminate Etiology Facilitates Therapy and May Avoid Liver Transplantation: A Critical Analysis
Rolf Teschke, Axel Eickhoff
Published online August 7, 2025
Journal of Clinical and Translational Hepatology.
doi:10.14218/JCTH.2025.00203
Abstract
Acute liver failure (ALF) is a disorder with various etiologies. Although the causes leading to this disruptive condition are well documented in published ALF cohorts, there is
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Acute liver failure (ALF) is a disorder with various etiologies. Although the causes leading to this disruptive condition are well documented in published ALF cohorts, there is significant concern among patients who experience ALF with indeterminate causes, an issue requiring thorough analysis. This review aimed to analyze cohort studies on ALF with a focus on unknown causes leading to classification as indeterminate ALF. The analysis revealed that, among 67 worldwide adult and pediatric ALF cohorts, indeterminate causes of ALF ranged from 2% to 100%, with an average of 30%. Among the 13 pediatric ALF cohorts, the corresponding range was 22% to 100%, with an average of 47%, while among the 55 adult ALF cohorts, the range was 2% to 78%, with an average of 26%. The percentage values were higher in pediatric cohorts due to the higher incidence of rare genetic causes compared to adult patients. Notably, higher rates of indeterminate causes were found in cohorts studied before the availability of diagnostic serologic screening parameters and polymerase chain reaction techniques for various hepatitis virus infections. Patients with indeterminate ALF may not have received a specific treatment that, if effective, could have helped prevent liver transplantation. It is concluded that, in future cases, all efforts must be undertaken to clearly establish the cause of severe liver injury, enabling effective therapy when available and helping reduce the risk of progression to ALF and the need for liver transplantation.
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Original Article
Open Access
Urinary Arsenic Exposure and Metabolic Dysfunction-associated Steatotic Liver Disease: A NHANES Analysis
Silpa Choday, Anne Jarvis, William Graham, Paul Kang, Justin Reynolds
Published online August 1, 2025
Journal of Translational Gastroenterology.
doi:10.14218/JTG.2025.00019
Abstract
While metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with obesity, the cause of its rapidly rising prevalence is not well understood. In this study,
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While metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with obesity, the cause of its rapidly rising prevalence is not well understood. In this study, we aimed to examine the association between arsenic exposure and MASLD in humans.
Urinary inorganic arsenic data from the National Health and Nutrition Examination Survey, 2011–2020, were used. These were combined with death certificate data from the National Death Index of the National Center for Health Statistics to ascertain mortality rates. Weighted linear regression and chi-squared analysis were performed.
The analysis included 6,386 participants after exclusions. The mean urinary arsenic level was 5.92 µg/L in participants with MASLD versus 5.59 µg/L in those without. Alanine aminotransferase levels exhibited a statistically significant increasing trend across both continuous arsenic levels and arsenic quintiles. A statistically significant upward trend was observed for the income-to-poverty ratio and body mass index but not for education status. MASLD prevalence was highest among the white population, while an increasing trend was observed in the Hispanic population over the years (p < 0.001). The proportion of Mexican Americans increased to 12.6% in the MASLD group versus 8.09% in the non-MASLD cohort (p < 0.001). There was a statistically significant increase in the odds of MASLD across arsenic exposure levels, with individuals in the highest quintile having a 32% greater likelihood compared to those in the lowest quintile (p-trend = 0.002). The odds further increased to 55% in the highest quintile (odds ratio 1.55, 95% confidence interval: 1.19–2.03; p-trend < 0.001). MASLD was more prevalent in females than males (57.9% vs. 47.6%; p < 0.001), and the mean age increased from 46.9 years to 49.9 years (p = 0.016).
Our findings reveal a positive association between urinary arsenic exposure and MASLD, with increasing trends particularly observed among Hispanics and those with higher income-to-poverty ratios and body mass index.
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Original Article
Open Access
Hepatocellular Carcinoma Risk Stratification for Cirrhosis Patients: Integrating Radiomics and Deep Learning Computed Tomography Signatures of the Liver and Spleen into a Clinical Model
Rong Fan, Ya-Ru Shi, Lei Chen, Chuan-Xin Wang, Yun-Song Qian, Yan-Hang Gao, Chun-Ying Wang, Xiao-Tang Fan, Xiao-Long Liu, Hong-Lian Bai, Dan Zheng, Guo-Qing Jiang, Yan-Long Yu, Xie-Er Liang, Jin-Jun Chen, Wei-Fen Xie, Lu-Tao Du, Hua-Dong Yan, Yu-Jin Gao, Hao Wen, Jing-Feng Liu, Min-Feng Liang, Fei Kong, Jian Sun, Sheng-Hong Ju, Hong-Yang Wang, Jin-Lin Hou
Published online August 1, 2025
Journal of Clinical and Translational Hepatology.
doi:10.14218/JCTH.2025.00091
Abstract
Given the high burden of hepatocellular carcinoma (HCC), risk stratification in patients with cirrhosis is critical but remains inadequate. In this study, we aimed to develop and
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Given the high burden of hepatocellular carcinoma (HCC), risk stratification in patients with cirrhosis is critical but remains inadequate. In this study, we aimed to develop and validate an HCC prediction model by integrating radiomics and deep learning features from liver and spleen computed tomography (CT) images into the established age-male-ALBI-platelet (aMAP) clinical model.
Patients were enrolled between 2018 and 2023 from a Chinese multicenter, prospective, observational cirrhosis cohort, all of whom underwent 3-phase contrast-enhanced abdominal CT scans at enrollment. The aMAP clinical score was calculated, and radiomic (PyRadiomics) and deep learning (ResNet-18) features were extracted from liver and spleen regions of interest. Feature selection was performed using the least absolute shrinkage and selection operator.
Among 2,411 patients (median follow-up: 42.7 months [IQR: 32.9–54.1]), 118 developed HCC (three-year cumulative incidence: 3.59%). Chronic hepatitis B virus infection was the main etiology, accounting for 91.5% of cases. The aMAP-CT model, which incorporates CT signatures, significantly outperformed existing models (area under the receiver-operating characteristic curve: 0.809–0.869 in three cohorts). It stratified patients into high-risk (three-year HCC incidence: 26.3%) and low-risk (1.7%) groups. Stepwise application (aMAP → aMAP-CT) further refined stratification (three-year incidences: 1.8% [93.0% of the cohort] vs. 27.2% [7.0%]).
The aMAP-CT model improves HCC risk prediction by integrating CT-based liver and spleen signatures, enabling precise identification of high-risk cirrhosis patients. This approach personalizes surveillance strategies, potentially facilitating earlier detection and improved outcomes.
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Review Article
Open Access
Pharmacological Insights into Scleromitrion diffusum (Willd.) Against Gastric Cancer: Active Components and Mechanistic Pathways
Yu-Xi Zhang, Jiang-Jiang Qin, Xiao-Qing Guan
Published online July 31, 2025
Oncology Advances.
doi:10.14218/OnA.2025.00011
Abstract
Gastric cancer remains a significant global health burden, with limited therapeutic options and poor clinical outcomes. Although conventional treatments such as surgery and chemotherapy
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Gastric cancer remains a significant global health burden, with limited therapeutic options and poor clinical outcomes. Although conventional treatments such as surgery and chemotherapy are widely used, their effectiveness is often hindered by adverse effects and high recurrence rates, highlighting the urgent need for safer and more effective alternatives. Scleromitrion diffusum (Willd.) (S. diffusum), a well-established anticancer herb in traditional Chinese medicine, has demonstrated promising clinical potential against gastric cancer. This review systematically examines the bioactive components of S. diffusum and their multi-target mechanisms of action against gastric cancer. Key active compounds, including flavonoids, anthraquinones, and terpenoids, have been identified as exerting synergistic anti-gastric cancer effects. These compounds collectively target critical pathways in gastric cancer pathogenesis, including apoptosis induction, suppression of proliferation and angiogenesis, and immune modulation. The mechanistic elucidation presented in this review not only validates the traditional use of S. diffusum in cancer management but also provides a molecular basis for its potential application in precision medicine strategies for gastric cancer. Beyond summarizing existing evidence, this work highlights critical gaps in current knowledge and proposes essential directions for future research, providing important references for integrating traditional medicine with modern oncology approaches.
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Mini Review
Open Access
The Artificial Intelligence-driven Revolution in Solid Tumor Drug Development
Yi-Han Li, Jiang-Jiang Qin
Published online July 31, 2025
Oncology Advances.
doi:10.14218/OnA.2025.00009
Abstract
Artificial intelligence (AI) is profoundly transforming the paradigm of solid tumor drug development. By integrating multi-omics data, spatial transcriptomics, and advanced computational
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Artificial intelligence (AI) is profoundly transforming the paradigm of solid tumor drug development. By integrating multi-omics data, spatial transcriptomics, and advanced computational models, AI has significantly accelerated the discovery and validation of new targets, compressing the traditional ten-year research and development cycle to two to three years. Generative AI platforms have optimized small molecule inhibitors, biologics, and messenger RNA vaccines, achieving breakthroughs in overcoming tumor heterogeneity, improving efficacy, and predicting drug resistance. However, clinical translation still faces challenges such as data bias, algorithm transparency, and the validation gap between models and real-world human experience. This review aims to systematically elaborate on the transformative role of AI in solid tumor drug development and to promote interdisciplinary cooperation as well as the construction of ethical frameworks to enable the full realization of precision oncology.
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