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Original Article Open Access
Hydronidone for the Treatment of Liver Fibrosis Associated with Chronic Hepatitis B: Protocol for a Phase 3 Randomized Trial
Xiaobo Cai, Yin Qu, Wen Xie, Yanbin Wang, Mengyu Zhao, Ling Zhang, Ying Luo, Ping Yin, Jun Cheng, Lungen Lu
Published online March 10, 2025
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00472
Abstract
Liver fibrosis is a key process in the progression of chronic liver diseases. However, there are currently no drugs specifically designed to treat liver fibrosis. Our Phase 2 trial [...] Read more.

Liver fibrosis is a key process in the progression of chronic liver diseases. However, there are currently no drugs specifically designed to treat liver fibrosis. Our Phase 2 trial of hydronidone for the treatment of chronic hepatitis B (CHB)-associated liver fibrosis showed that adding hydronidone to entecavir resulted in significant reversal of liver fibrosis. To further evaluate the efficacy of a 270 mg/day dose of hydronidone for treating liver fibrosis associated with CHB, we conducted this Phase 3 trial.

This is a 52-week, randomized (1:1), double-blind, placebo-controlled, multicenter, entecavir-based Phase 3 clinical study conducted at 44 study centers across China. Adult patients aged 18 to 65 years with significant liver fibrosis (defined as an Ishak score ≥ 3 on liver biopsy) associated with CHB were included.

The primary endpoint of the trial is to demonstrate the efficacy of fibrosis reversal, defined as a decrease in the Ishak stage score of liver fibrosis by ≥1 after 52 weeks of treatment, compared to baseline.

The results of this trial are expected to further support the antifibrotic indication for this novel drug.

Full article
Case Report Open Access
Pancreatic Cystic Neoplasms: Diagnostic Challenges and Management Pathways Through Case-based Insights
Chisom Enwere, Vivien Wong, Jonathan Rieber
Published online April 23, 2025
Journal of Translational Gastroenterology. doi:10.14218/JTG.2024.00046
Abstract
Mucinous cystic neoplasms (MCNs) are rare pancreatic lesions that often go undiagnosed due to their asymptomatic nature. Though typically benign, they can harbor malignant potential, [...] Read more.

Mucinous cystic neoplasms (MCNs) are rare pancreatic lesions that often go undiagnosed due to their asymptomatic nature. Though typically benign, they can harbor malignant potential, making early detection and treatment essential. This case report presents a 32-year-old female with intermittent epigastric pain, who was found to have a cystic lesion in the pancreatic tail, diagnosed as an MCN through endoscopic ultrasound and fine-needle aspiration. The patient underwent a spleen-sparing distal pancreatectomy, which was complicated by a peri-pancreatic abscess that required drainage. This case highlights the importance of distinguishing MCNs from other pancreatic cystic lesions, as misdiagnosis or delayed intervention can lead to adverse outcomes. It underscores the need for vigilant diagnostic imaging and individualized treatment strategies, particularly in young patients, to avoid unnecessary morbidity and ensure optimal outcomes. The report contributes to the growing understanding of MCNs, emphasizing early diagnosis, tailored surgical management, and the significance of postoperative care.

Full article
Original Article Open Access
Floating Nanoballoons for Improved Bioavailability and Sustained Release Anti-inflammatory Effect of Ibuprofen
Anil K. Philip, Betty Annie Samuel, Bassim A Mohammed, Hayder A Al-Aubaidy
Published online December 25, 2024
Journal of Exploratory Research in Pharmacology. doi:10.14218/JERP.2024.00027
Abstract
Poor bioavailability and a short half-life limit the therapeutic efficacy of ibuprofen. This study developed floating nanoballoons to enhance ibuprofen’s bioavailability and sustain [...] Read more.

Poor bioavailability and a short half-life limit the therapeutic efficacy of ibuprofen. This study developed floating nanoballoons to enhance ibuprofen’s bioavailability and sustain its anti-inflammatory effects through improved gastric retention.

Ibuprofen-loaded nanoballoons were synthesized using solvent evaporation with ethyl cellulose as the polymer matrix. The formulation was characterized for morphology, buoyancy, drug loading, and release kinetics. In vivo studies assessed the anti-inflammatory efficacy in acute and chronic inflammation models using male Sprague-Dawley rats.

The nanoballoons exhibited optimal characteristics, including 96% buoyancy and a drug loading efficiency of 96.54 ± 1.32%. Scanning Electron Microscopy revealed a spherical morphology with a porous structure. Drug release followed a biphasic pattern: an initial release of 35.23 ± 2.13% over 2 h, followed by sustained release reaching 97.54 ± 1.30% at 12 h. In acute inflammation studies, the nanoballoon formulation showed superior edema inhibition (68.12%) compared to pure ibuprofen (51.67%). Chronic inflammation studies demonstrated significant improvements in inflammatory markers: reduced TNF-α (19.12 ± 0.48 vs. 31.11 ± 1.23 pg/mL), hs-CRP (201.7 ± 11.02 vs. 232.12 ± 11.33 ng/mL), and IL-6 (100.01 ± 18.40 vs. 135 ± 11.22 pg/mL), with increased anti-inflammatory IL-10 (507.18 ± 10.11 vs. 276.11 ± 19.16 pg/mL).

The developed floating nanoballoon system significantly enhanced ibuprofen’s bioavailability and anti-inflammatory efficacy, presenting a promising gastro-retentive delivery platform for poorly water-soluble drugs.

Full article
Original Article Open Access
Global Trends and Cross-country Inequalities of Acute Hepatitis E in the Elderly, 1990–2021: A Comprehensive Analysis
Deliang Huang, Jinyan Jiang, Jinghan Peng, Zhibin Zhu, Yuanyuan Chen, Siyu Zhang, Huiyi Lai, Hong Yu, Qi Zhao, Yanna Wu, Yanping Chen, Jun Chen
Published online May 30, 2025
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00101
Abstract
Acute hepatitis E (AHE) in the elderly can lead to severe complications including liver failure and mortality, yet the epidemiological landscape remains poorly characterized. This [...] Read more.

Acute hepatitis E (AHE) in the elderly can lead to severe complications including liver failure and mortality, yet the epidemiological landscape remains poorly characterized. This study aimed to assess the burden, trends, and health inequalities of AHE among the elderly over the past three decades, and to further predict its changes by 2030.

Data on AHE in the elderly were obtained from the Global Burden of Disease 2021. The burden of AHE was analyzed by trends, decomposition, cross-country inequalities, and predictive analysis.

In 2021, the global incidence and Disability-Adjusted Life Years (DALYs) for AHE among the elderly were recorded as 1,130,013.35 and 20,084.77, respectively. Although there were significant differences in the incidence and DALYs across countries, the number of incident cases increased from 1990 to 2021, with a slight rise in age-standardized rates, while the number and age-standardized rate of DALYs showed a declining trend. Decomposition analysis revealed that population growth and aging are the drivers of changes in incidence, while epidemiological changes somewhat offset the increases in DALYs driven by population growth. Low socio-demographic index countries bear a disproportionate burden of elderly AHE, although inequality gaps have narrowed over time. Notably, up to 2030, the number of incident cases and DALYs will continue increasing. The burden in elderly women was more pronounced than in men.

The burden of elderly AHE, as a major public health issue, remains substantial. While cross-country inequities have been alleviated over time, the pressure on lower socio-demographic index countries to control the disease remains high. AHE in elderly women requires further attention. This emphasizes the significant challenges faced in controlling and managing elderly AHE.

Full article
Case Report Open Access
Diagnostic Challenges in Philadelphia Chromosome-positive B-Lymphoblastic Leukemia/Lymphoma with Persistent BCR::ABL1 Fusion after Treatment: A Pediatric Case Report
Qihan Guo, Wei Xie, Andrea Fuentes, Wen Shuai
Published online May 9, 2025
Journal of Clinical and Translational Pathology. doi:10.14218/JCTP.2025.00012
Abstract
Philadelphia chromosome-positive (Ph+) B-lymphoblastic leukemia/lymphoma (B-ALL/LBL) is an aggressive hematologic malignancy driven by the BCR::ABL1 fusion. While many cases respond [...] Read more.

Philadelphia chromosome-positive (Ph+) B-lymphoblastic leukemia/lymphoma (B-ALL/LBL) is an aggressive hematologic malignancy driven by the BCR::ABL1 fusion. While many cases respond well to treatment, some patients exhibit persistent BCR::ABL1 expression after therapy, presenting significant diagnostic challenges.

We present the case of a seven-year-old girl diagnosed with Ph+ B-ALL. Despite low percentages or negative results for blasts post-treatment, molecular and cytogenetic studies persistently detected high levels of BCR::ABL1, suggesting a high disease burden at the genetic level. This discordance supported multilineage involvement and the potential for retrospective revision of the initial diagnosis to lymphoblast crisis of chronic myeloid leukemia (LBC-CML).

Classifying such cases as de novo Ph+ B-ALL with multilineage involvement or LBC-CML is challenging, as there is currently no consensus among experts. Further studies are necessary to clarify the distinction, given the different management strategies and treatment responses between these two conditions.

Full article
Original Article Open Access
Chemical Analysis of Polyphenolic Content and Antioxidant Screening of 17 African Propolis Samples Using RP-HPLC and Spectroscopy
Shankar Katekhaye, Bhagyashree Kamble, Ghaida Mustafa, James Fearnley, Anant Paradkar
Published online May 13, 2025
Future Integrative Medicine. doi:10.14218/FIM.2025.00004
Abstract
Propolis is a resinous material produced by honeybees. Its chemical composition is highly complex and varies significantly depending on geographic region and season. This intrinsic [...] Read more.

Propolis is a resinous material produced by honeybees. Its chemical composition is highly complex and varies significantly depending on geographic region and season. This intrinsic variability presents challenges to the standardization and quality control of propolis. This study aimed to evaluate the chemical composition, total phenolic content, and antioxidant potential of propolis collected from seventeen geographical regions across Africa.

A reverse-phase high-performance liquid chromatography (RP-HPLC) method coupled with a photodiode array detector (PDA) was used for analysis of propolis samples. The flavonoid and phenolic contents of the samples were determined using colorimetric and Folin-Ciocalteu methods. Antioxidant capacity was assessed using the 2,2-diphenyl-1-picrylhydrazyl assay.

Five flavonoids (naringenin, pinocembrin, galangin, chrysin, and quercetin), one flavonoid glycoside (rutin), six phenolic acids (caffeic acid, p-coumaric acid, cinnamic acid, chlorogenic acid, ferulic acid, and gallic acid), and an aromatic ester - caffeic acid phenethyl ester were simultaneously detected and quantified using RP-HPLC with an ACE-5 C18 column (250 mm × 4.6 mm i.d., 5 µm) and PDA detector. The reference standards showed good linearity with regression coefficients (R2) ranging from 0.96 to 0.99. For precision, repeatability, and stability studies, the relative standard deviation for all reference standards was below 2.5%. The 2,2-diphenyl-1-picrylhydrazyl assay yielded EC50 values ranging from 17.6 ± 0.39 to 0.16 ± 0.001 mg/mL.

RP-HPLC method for the simultaneous quantification of thirteen reference standards will serve as a reliable tool for the standardization and quality evaluation of propolis. The flavonoid and phenolic contents are key contributors to the antioxidant activity of propolis and reflect local plant biodiversity and bee–plant interactions within the ecosystem.

Full article
Mini Review Open Access
The Mechanisms behind Thrombocytopenia in Patients with Portal Hypertension and Chronic Liver Disease
Valeria M. Fernández-Garibay, Mariana M. Ramírez-Mejia, Guadalupe Ponciano-Rodriguez, Ran Wang, Xingshun Qi, Nahum Méndez-Sánchez
Published online September 3, 2025
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00279
Abstract
Persistent liver injury halts the regenerative capacity of hepatocytes and activates mechanisms that result in the replacement of normal hepatic parenchyma with extracellular matrix [...] Read more.

Persistent liver injury halts the regenerative capacity of hepatocytes and activates mechanisms that result in the replacement of normal hepatic parenchyma with extracellular matrix deposits. As liver fibrosis develops, the liver undergoes architectural changes and alterations in microcirculation that lead to increased intrahepatic vascular resistance and portal hypertension. Thrombocytopenia is a prevalent condition in patients with chronic liver disease and portal hypertension. Multiple mechanisms related to increased platelet destruction or decreased platelet production contribute to thrombocytopenia. Increased platelet destruction occurs due to splenic sequestration caused by hypersplenism or immune-mediated conditions. Decreased platelet production results from a decline in thrombopoietin production, bone marrow suppression by medications, or toxic insults. Therapies aimed at improving thrombocytopenia are controversial, and individual factors must be considered. Although hepatic venous pressure gradient measurement is the gold standard for diagnosing portal hypertension, non-invasive tests show adequate correlation with hepatic venous pressure gradients. Various clinical risk scores consider platelet counts as independent predictors of adverse liver outcomes, such as the development of esophageal varices and the presence of advanced fibrosis. Nonselective beta-blockers are the cornerstone of long-term management for clinically significant portal hypertension. Indications for transjugular intrahepatic portosystemic shunt placement include failure to control portal hypertension-related bleeding, early rebleeding, and refractory or recurrent ascites. Ultimately, liver transplantation is the only definitive cure for portal hypertension and its major complications, including thrombocytopenia. Understanding the mechanisms underlying thrombocytopenia in patients with portal hypertension and chronic liver disease is essential for accurate diagnosis and effective patient management. This review aimed to evidence on the pathophysiological mechanisms linking chronic liver disease, portal hypertension, and thrombocytopenia, and to discuss their diagnostic and therapeutic implications.

Full article
Review Article Open Access
Dual Challenges and Innovative Strategies in Chimeric Antigen Receptor T-cell Therapy for Glioblastoma
Liangjin Zhang, Zhiqiang Zhang, Jiale He, Zhiheng Zhang, Huaixiang Zhou, Youheng Jiang, Xin Zhong, Yanming Yang, Ningning Li, Wu Xu, Yulong He, Qunlong Jin
Published online July 30, 2025
Oncology Advances. doi:10.14218/OnA.2025.00014
Abstract
Glioblastoma (GBM) is the most prevalent and aggressive form of primary brain malignancy in adults. Despite continuous advancements in standard treatment modalities, the prognosis [...] Read more.

Glioblastoma (GBM) is the most prevalent and aggressive form of primary brain malignancy in adults. Despite continuous advancements in standard treatment modalities, the prognosis for patients remains extremely poor, with a median survival of less than two years. In recent years, chimeric antigen receptor T-cell (CAR-T) therapy has achieved revolutionary success in hematologic malignancies, marking a significant breakthrough in the field of immunotherapy. However, the successful application of CAR-T therapy to GBM still faces dual challenges: antigen heterogeneity and the immunosuppressive tumor microenvironment. This review systematically summarizes these challenges encountered in CAR-T therapy for GBM and the innovative strategies currently under development to address these challenges, providing insights for the future clinical translation of CAR-T therapy in GBM.

Full article
Original Article Open Access
Interrater Reliability of the Nancy Histologic Index in Assessing Histologic Remission in Treated Ulcerative Colitis Biopsies: A Multi-institutional Experience Among Gastrointestinal Pathologists in the United States
Krithika D. Shenoy, Jiannan Li, Daniela Allende, Samuel J. Ballentine, Kathleen Byrnes, Parakkal Deepak, Alicia G. Dessain, Ashwini K. Esnakula, Raul S. Gonzalez, Xianyong Gui, Hwajeong Lee, Jingmei Lin, Shivani Mattay, Namrata Setia, Hanlin L. Wang, Zhaohai Yang, Xuchen Zhang, Xiuli Liu, on behalf of the SPARC-IBD Investigators
Published online June 26, 2025
Journal of Clinical and Translational Pathology. doi:10.14218/JCTP.2025.00022
Abstract
Histologic remission is recommended as an adjunctive treatment target in ulcerative colitis, and scoring systems have been proposed to enhance reproducibility. The Nancy Histologic [...] Read more.

Histologic remission is recommended as an adjunctive treatment target in ulcerative colitis, and scoring systems have been proposed to enhance reproducibility. The Nancy Histologic Index (NHI) is increasingly used in clinical trials; however, its performance in real-world settings is not fully established. This study aimed to assess the interrater reliability (IRR) of the NHI among gastrointestinal pathologists in the United States.

Thirty-seven whole-slide images of colorectal biopsies from 34 treated ulcerative colitis patients enrolled in a multicenter adult cohort were independently reviewed by 12 gastrointestinal pathologists. Each biopsy was reviewed twice, five months apart, and graded using the NHI. Prior to the second review, pathologists completed an online tutorial on the NHI.

The NHI showed substantial IRR in both reviews [intraclass correlation coefficient (ICC) = 0.79; 95% confidence interval (CI), 0.70–0.87 at Review 1; ICC = 0.78; 95% CI, 0.69–0.86 at Review 2]. However, considerable variability was observed in individual grade assignments, with the lowest IRR for Grade 2 (ICC = 0.24; 95% CI, 0.15–0.37; P < 0.001, and ICC = 0.23; 95% CI, 0.14–0.36; P < 0.001 for Reviews 1 and 2, respectively), followed by Grade 4 (ICC = 0.41; 95% CI, 0.29–0.55; P < 0.001, and ICC = 0.47; 95% CI, 0.35–0.61; P < 0.001). Grade 1 showed the highest IRR (ICC = 0.79; 95% CI, 0.70–0.87; P < 0.001, and ICC = 0.78; 95% CI, 0.69–0.86; P < 0.001). When Grades 2, 3, and 4 (i.e., active disease) were grouped together, the IRR remained substantial across both reviews (ICC = 0.76; 95% CI, 0.66–0.85; P < 0.001).

While the substantial IRR for active disease (Grades ≥ 2) in this study underscores the clinical utility of the NHI, refinement of criteria for Grades 2, 3, and 4 will be crucial in reducing variability among observers and enabling more accurate monitoring of treatment endpoints.

Full article
Original Article Open Access
Clinical, Microbiological, and Antibiotic Treatment Characteristics of Bacterial Infections in Patients with Liver Cirrhosis in China: A Multicenter Study
Xiuding Zhang, Haoda Weng, Qinzhi Deng, Min Deng, Xuwei Wu, Zuxiong Huang, Shourong Liu, Rui Wu, Chunlian Ma, Yao Xu, Jianfeng Zhong, Jie Yang, Yinxia Wu, Huajiang Shen, Feng Ding, Fang Wang, Xuezhen Zhai, Chunxian Peng, Haotang Ren, Jie Jin, Xiangfei Xu, Xiaofei Li, Xiaoting Ye, Guoqing Qian, Shuilin Sun, Xuebing Yao, Haifeng Miao, Qianggu Xiao, Shaoheng Ye, Qing Zhang, Xinyi Xu, Xia Yu, Yue Yu, Yan Lan, Huilan Tu, Xianbin Xu, Xinrong Zhang, Rui Huang, Xiaohan Qian, Qiao Yang, Jifang Sheng, Yu Shi
Published online July 3, 2025
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00211
Abstract
Epidemiological data on bacterial infections in cirrhosis in China remain limited. Therefore, we aimed to conduct a multicenter study to investigate the characteristics and outcomes [...] Read more.

Epidemiological data on bacterial infections in cirrhosis in China remain limited. Therefore, we aimed to conduct a multicenter study to investigate the characteristics and outcomes of patients with cirrhosis and bacterial infections in China.

We retrospectively enrolled 1,438 hospitalized adult patients with cirrhosis and bacterial or fungal infections from 24 hospitals across China between January 2018 and September 2024. Data on demographics, clinical features, microbiology, treatment, and outcomes were collected.

A total of 1,783 infection episodes were recorded, including 1,668 first infections and 115 second infections. Most infections were community-acquired (86.6%). Pneumonia was the most common infection type (26.7%), followed by spontaneous bacterial peritonitis (19.5%) and spontaneous bacteremia (14.1%). Among 754 pathogens isolated from 620 patients, Klebsiella pneumoniae (20.1%) was nearly as common as Escherichia coli (21.7%). Multidrug-resistant (MDR) organisms accounted for 41.0% of all isolates, with extended-spectrum β-lactamase-producing Escherichia coli being the most prevalent MDR strain (8.9% of patients). Adherence to empirical antibiotic treatment guidelines from the European Association for the Study of the Liver was significantly lower in this cohort compared to the global study (21.5% vs. 61.2%, P < 0.001), accompanied by a lower clinical resolution rate (63.5% vs. 79.8%, P < 0.001).

The clinical and microbiological characteristics of bacterial infections in patients with cirrhosis in China differ substantially from those reported in other regions. These findings highlight the need for region-specific management and prevention strategies, particularly in light of the changing microbiological landscape, high MDR prevalence, and suboptimal antibiotic practices.

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