Primary biliary cholangitis (PBC) is a chronic progressive autoimmune disorder characterized by small non-purulent intrahepatic bile duct destruction (ductopenia) and cholestasis. While the etiology of PBC remains unclear, it is believed to involve genetic-environmental interactions. Emerging evidence highlights gut microbiota dysbiosis in PBC patients, with increased symbiotic bacteria and decreased pathogenic bacteria. Microbial alterations potentially influence disease pathogenesis through multiple mechanisms, including immune dysregulation, intestinal barrier damage, BA metabolic dysregulation, and cholestasis. These findings suggest that the gut microbiota can serve not only as a non-invasive biomarker for diagnosis and prognosis evaluation but also as a therapeutic target for the disease. In this review, we summarize changes in PBC patients’ gut microbiota, explain how these changes affect disease occurrence and development, and discuss treatment methods with potential clinical value that intervene in gut microbiota.

Regular exercise is fundamental for people with metabolic dysfunction-associated steatotic liver disease (MASLD), yet exercise maintenance is generally poor. This generative co-design process aimed to embed the voices and opinions of people with lived experience of MASLD and their care stakeholders to (i) frame barriers and enablers to exercise maintenance and (ii) highlight priorities for exercise-focused research agendas in MASLD.

A generative co-design framework was applied. Two virtual co-design sessions were undertaken: Session 1 – Framing the issue, where initial discovery was conducted with people with lived experience of MASLD; and Session 2 – Generative design and sharing ideas with lived experience partners and healthcare stakeholders. Sessions were audio-recorded and transcribed, and key determinants and considerations were discerned by two independent researchers.

Lived experience partners (n = 5, 53 ± 16 years, 40% male) ranked five equally important barriers to exercise maintenance: musculoskeletal and pain issues, lack of access to exercise equipment/facilities, cost, competing priorities, and low energy levels, which influenced core positive and negative determinants. Alongside lived experience partners, healthcare stakeholders (hepatologists [n = 3], exercise professionals [n = 3], 67% male) identified three core needs with eight considerations. Some disconnects in priorities were observed. Lived experience partners emphasized affordability, accessibility, and considerations for comorbidities, while healthcare partners advocated for research on natural history, prevention, behavior change, cost-effectiveness, and health system change.

This co-design methodology highlights unique consumer-informed research questions. Exercise interventions and their associated implementation trials will benefit from being co-designed with both people with MASLD and care stakeholders.

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.

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.

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.

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.

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.

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.