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Original Article Open Access
Advanced Liver Fibrosis Predicts Liver Outcomes in Biopsy-proven Metabolic Dysfunction-associated Steatotic Liver Disease: A U.S.-based Single-center Retrospective Cohort Study
Robert Lam, Dhanpat Jain, Yanhong Deng, Eesha Acharya, Joseph K. Lim
Published online October 17, 2024
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00189
Abstract
Data regarding risk factors and long-term outcomes of U.S. patients with biopsy-proven metabolic dysfunction-associated steatotic liver disease (MASLD) are limited. This study aimed [...] Read more.

Data regarding risk factors and long-term outcomes of U.S. patients with biopsy-proven metabolic dysfunction-associated steatotic liver disease (MASLD) are limited. This study aimed to investigate the role of clinical and histologic risk factors on long-term outcomes in patients with MASLD.

A retrospective cohort study of 451 adults with biopsy-proven MASLD was conducted at a U.S. academic hospital from 2012 to 2020. An experienced pathologist evaluated the index liver biopsy. Patients with a prior liver transplant or alternative etiologies of chronic liver disease were excluded. The duration of the risk exposure was determined from the date of the index liver biopsy to an outcome event or the last follow-up examination. Outcome events of interest included incident liver-related events, liver decompensation, and all-cause mortality.

In the final cohort of 406 patients followed for a median of 3.7 years (interquartile range: 4.8 years), 35 patients died, 41 developed hepatic decompensation, and 70 experienced a liver-related event. Among histologic risk factors, stage 3 (adjusted Hazard ratio (aHR) 2.68, 95% confidence interval (CI) 1.18–6.11) and stage 4 (aHR 6.96, 95% CI 3.55–13.64) fibrosis were associated with incident liver-related events compared to stage 0–1 fibrosis. Stage 4 (aHR 8.46, 95% CI 3.26–21.99) fibrosis alone was associated with incident liver decompensation events compared to stage 0–1 fibrosis. Among clinical risk factors, hypertension (aHR 2.58, 95% CI 1.05–6.34) was associated with incident liver decompensation.

In a U.S. single-center cohort of patients with biopsy-proven MASLD, advanced fibrosis was the primary risk factor for incident liver decompensation and liver-related events.

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Hot Topic Commentary Open Access
Ketamine Hepatotoxicity: An Underappreciated Cause of Liver Damage - Analysis by RUCAM
Bianca Thakkar, George Y. Wu
Published online April 11, 2025
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00478
Original Article Open Access
Impact of Intermediate-term Oral Contraceptive Use on Oxidative Stress, Lipid Profile, and Liver Function in Iraqi Women: A Comprehensive Biochemical Assessment
Hayder Hatem Sultan, Amir Teimourpour, Ziba Majidi, Fariba Nabatchian
Published online January 25, 2025
Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2024.00035
Abstract
Oral contraceptive pills (OCPs) are commonly used for contraception, but their long-term effects on oxidative stress, lipid profiles, and liver function remain unclear. This study [...] Read more.

Oral contraceptive pills (OCPs) are commonly used for contraception, but their long-term effects on oxidative stress, lipid profiles, and liver function remain unclear. This study aimed to evaluate the impact of intermediate-term OCP use (Yasmin) on oxidative stress, lipid profile, and liver function, with particular emphasis on antioxidant markers, lipid metabolism, and hepatic enzyme activity, to better understand the potential metabolic and hepatic effects.

A case-control study was conducted in Maysan Governorate, Iraq, involving 150 women (100 OCP users and 50 non-users). Blood samples were collected from Al-Sadr Teaching Hospital and a specialized clinic between February and April 2023. Serum levels of antioxidants, lipids, and liver enzymes were measured using biochemical assays.

OCP users had significantly lower levels of glutathione peroxidase vitamin E and uric acid (p < 0.001) compared to non-users. Lipid profiles showed that OCP users had higher levels of triglyceride and low-density lipoprotein (p < 0.05), whereas total cholesterol was significantly higher in non-users (p < 0.05). Liver enzyme activity, including alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and total serum bilirubin, did not show statistically significant differences (p > 0.05). Longer duration of OCP use was significantly negatively correlated with vitamin E levels (r = −0.67), glutathione peroxidase activity (r = −0.56), uric acid levels (r = −0.45) and high-density lipoprotein (r = −0.54). Positive correlations were found between the duration of OCP use and total cholesterol (r = 0.62), triglyceride (r = 0.58), low-density lipoprotein (r = 0.60), and liver enzymes alanine aminotransferase (r = 0.66) and aspartate aminotransferase (r = 0.64).

Intermediate-term OCP use was associated with changes in oxidative stress and lipid metabolism, potentially increasing cardiovascular and metabolic risks. Regular monitoring of these parameters is recommended for OCP users.

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Original Article Open Access
Prevalence of Hepatitis D Virus Antibody Positivity in Chinese Patients with Chronic Hepatitis B Virus Infection
Xieer Liang, Qiaoqiao Chen, Hong Tang, Yujuan Guan, Minfeng Liang, Peng Hu, Wen Xie, Huiying Rao, Junqi Niu, Liang Chen, Li Yan, Xiaowei Chen, Xiaohe Li, Yulin Zhao, Oliver Lenz, Michael Biermer, Jinlin Hou
Published online February 24, 2025
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00313
Abstract
Large-scale data on the hepatitis D virus (HDV)/hepatitis B virus (HBV) co-infection rate is needed to estimate the current epidemiology of HDV in China. This study aimed to estimate [...] Read more.

Large-scale data on the hepatitis D virus (HDV)/hepatitis B virus (HBV) co-infection rate is needed to estimate the current epidemiology of HDV in China. This study aimed to estimate the current epidemiology of HDV.

Patients with chronic HBV infection, with documented serum hepatitis B surface antigen (HBsAg) positivity for more than six months, were enrolled across China. Blood samples were collected at baseline for central evaluations of HDV antibody and HBsAg quantification. Assessments for antibodies of hepatitis A virus, hepatitis C virus, hepatitis E virus, and human immunodeficiency virus, as well as HDV RNA quantification, were performed in patients who tested positive for HDV antibodies.

Of the 5,044 enrolled patients between September 24, 2021, and December 28, 2022, 4,936 patients were included in the analysis. The mean age (±standard deviation) was 42.9 ± 9.9 years, and 69.8% of patients were male. The mean alanine aminotransferase level was 34 ± 58 U/L, and 1,509 (30.6%) patients were hepatitis B e antigen-positive. The mean (standard deviation) HBsAg level at baseline was 3,535 ± 11,292 IU/mL among 4,842 patients who were HBsAg positive. The rate of HBV infection and HDV antibody positivity was 0.24% (95% confidence interval: 0.1–0.4%), and only one patient was HDV RNA positive.

The prevalence of HDV antibody positivity was 0.24% in Chinese patients with chronic HBV infection, and only one patient with both anti-HDV antibody and HDV RNA positivity was observed in this study.

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Illuminating and Instructive Clinical Case Open Access
Significant Response to Palbociclib Plus Lenvatinib as Second-line Treatment for CDKN2A/2B Deletion Intrahepatic Cholangiocarcinoma: A Case Report
Kai Liu, Ziyue Huang, Lijin Zhao, Haitao Zhao
Published online January 2, 2025
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00404
Abstract
Cyclin-dependent kinase inhibitor 2A/2B (CDKN2A/2B) deletions are frequently identified in patients with biliary tract cancer; however, standard treatment options for this genetic [...] Read more.

Cyclin-dependent kinase inhibitor 2A/2B (CDKN2A/2B) deletions are frequently identified in patients with biliary tract cancer; however, standard treatment options for this genetic alteration are lacking. Here, we present the case of a 64-year-old woman diagnosed with intrahepatic cholangiocarcinoma and hilar lymph node metastasis who underwent radical surgery. Postoperative pathology confirmed moderately differentiated adenocarcinoma. The tumor recurred during the second cycle of adjuvant chemotherapy following surgery, and the metastatic sites included the cranial region, right lung, and right adrenal gland. Genetic analysis revealed a CDKN2A/2B deletion, indicating palbociclib sensitivity. Subsequently, the patient received palbociclib plus lenvatinib as systemic therapy, along with stereotactic radiotherapy for the intracranial lesion. Notably, the right pulmonary metastasis significantly regressed after 12 months of treatment, with the complete disappearance of the intracranial tumor. However, the disease progressed at 32.2 months, with significant enlargement of the right adrenal gland metastasis and new metastasis in the right lung. The progression-free survival and overall survival were 32.2 months and 34.4 months, respectively. In conclusion, our case demonstrates that palbociclib plus lenvatinib is a promising chemotherapy-free second-line treatment for intrahepatic cholangiocarcinoma with a CDKN2A/2B deletion.

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Original Article Open Access
Sodium Butyrate Inhibits Necroptosis by Regulating MLKL via E2F1 in Intestinal Epithelial Cells of Liver Cirrhosis
Yimeng Zhou, Yang Ding, Yanwei Li, Qiuju Sheng, Chao Han, Yaoxin Fan, Ziyi Wang, Bingchao Lu, Xiaoguang Dou, Chong Zhang
Published online November 8, 2024
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00221
Abstract
Necroptosis is critical for regulating intestinal epithelial cells (IECs). Butyric acid (BA), produced during intestinal microbial metabolism, protects the intestinal epithelial [...] Read more.

Necroptosis is critical for regulating intestinal epithelial cells (IECs). Butyric acid (BA), produced during intestinal microbial metabolism, protects the intestinal epithelial barrier. However, whether necroptosis occurs in IECs during liver cirrhosis and whether sodium butyrate (NaB) can regulate necroptosis have not yet been reported. In this study, we aimed to investigate whether IECs undergo necroptosis in cirrhosis and whether NaB can regulate necroptosis and the related regulatory mechanisms.

Serum levels of RIPK3, MLKL, and Zonulin, as well as fecal BA levels, were measured and correlated in 48 patients with liver cirrhosis and 20 healthy controls. A rat model of liver cirrhosis was established, and NaB was administered. The expressions of MLKL, p-MLKL, and tight junction proteins were measured. We conducted an in vitro investigation of the effect of NaB on necroptosis in the HT29 cell line.

Serum levels of RIPK3, MLKL, and Zonulin in the liver cirrhosis group were higher, while fecal BA levels were lower than those in the control group. Zonulin levels were positively correlated with RIPK3 and MLKL levels, while fecal BA levels were negatively correlated with serum MLKL levels, but not with RIPK3 levels. NaB reduced the mRNA and protein expression of MLKL but had no effect on RIPK1 and RIPK3 in vitro. Rescue experiments demonstrated that NaB inhibited necroptosis through E2F1-mediated regulation of MLKL.

NaB alleviates intestinal mucosal injury and reduces necroptosis in IECs in liver cirrhosis. It also inhibits the necroptosis of IECs and protects the intestinal barrier by reducing E2F1 expression and downregulating MLKL expression levels. These results can be employed to develop a novel strategy for treating complications arising from liver cirrhosis.

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Case Report Open Access
Breast Cancer Metastasizing to the Lower Gastrointestinal Tract (the Small Bowel and Colon): A Case Presentation and Comprehensive Review of the Literature
Teresa Da Cunha, Simon Abi Saleh, Murali Dharan
Published online June 25, 2024
Oncology Advances. doi:10.14218/OnA.2024.00001
Abstract
Breast cancer metastases to the lower gastrointestinal tract (small bowel and colon) are rare, but there is a growing number of case reports in the literature. The overall incidence [...] Read more.

Breast cancer metastases to the lower gastrointestinal tract (small bowel and colon) are rare, but there is a growing number of case reports in the literature. The overall incidence of this condition is not well established, and there might be underdiagnosis. The clinical presentation and endoscopic findings are often nonspecific and variable, potentially leading to misdiagnosis or underdiagnosis. Moreover, there are currently no guidelines for gastrointestinal surveillance of these patients. Given the potential diagnostic challenges, a high level of clinical suspicion is necessary. We present a clinical case to highlight subtle endoscopic findings of breast cancer metastasis to the colon, followed by a review summarizing the available literature on breast cancer metastases to the duodenum, jejunum, ileum, colon, rectum, and anus focusing on the clinical presentation, endoscopic features, imaging modalities, treatment, and outcome.

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Original Article Open Access
Molecular Profiling Using Next-generation Sequencing of Sufficient Endobronchial Ultrasound-guided Transbronchial Needle Aspiration and Liquid Biopsy Samples in Patients with Advanced Lung Cancer
Kayla Brice, Candice Arline, Luis E. Raez, Katerine Dumais, Mark Block
Published online September 25, 2024
Journal of Clinical and Translational Pathology. doi:10.14218/JCTP.2024.00021
Abstract
Tumor molecular analysis using next-generation sequencing (NGS) is the standard of care for guiding lung cancer treatment. Endobronchial ultrasound-guided transbronchial needle [...] Read more.

Tumor molecular analysis using next-generation sequencing (NGS) is the standard of care for guiding lung cancer treatment. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive technique used to sample mediastinal lymph nodes for diagnosing and staging lung cancer. This study aimed to determine if EBUS-TBNA provided adequate tissue samples for NGS.

We evaluated EBUS-TBNA samples from adult advanced non-small cell lung cancer patients who had both EBUS-TBNA and liquid biopsy samples analyzed by NGS between July 1, 2015 and June 30, 2021. Additionally, we compared the results with those from liquid biopsies performed on these patients.

Among the 44 evaluated patients, 43% were male, with a median age of 66 years at diagnosis. Seventy-five percent were smokers, 79.5% were White, 6.8% were Black, and 9.1% were Asian. EBUS-TBNA samples were sufficient for NGS in 95.5% of cases. The median turnaround time for EBUS-TBNA NGS was 38.5 days compared with eight days for NGS in liquid biopsies. Actionable genetic aberrations were detected in 71% of patients.

Our findings demonstrated that EBUS-TBNA provided sufficient tissue for identifying actionable genetic aberrations in patients with advanced non-small cell lung cancer.

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Original Article Open Access
Sociodemographic Factors Associated with Depression among People Living with Human Immunodeficiency Virus on Antiretroviral Therapy at a University Teaching Hospital in a Nigerian Cosmopolitan City
Jeremiah Onubi, Oluwagbenga Adebayo Adeola, Patricia Eseigbe, Adesegun Elisha, Grace O Sheyin, Anyuku A George Chima
Published online September 6, 2024
Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2024.00018
Abstract
Depression can lead to poor outcomes during antiretroviral therapy, and current evidence suggests high rates of depression among people living with human immunodeficiency virus [...] Read more.

Depression can lead to poor outcomes during antiretroviral therapy, and current evidence suggests high rates of depression among people living with human immunodeficiency virus (PLHIV), especially in low-and middle-income countries. This study was designed to investigate the sociodemographic factors associated with depression among PLHIV on antiretroviral therapy in a Nigerian cosmopolitan city.

A hospital-based, cross-sectional study was conducted among 592 consenting, randomly selected adult PLHIV receiving treatment at a university teaching hospital in Jos, Nigeria, in 2022, using the PHQ-9 questionnaire and an interviewer-administered sociodemographic questionnaire. Associated variables in univariate analysis were used in multivariable binary logistic regression to obtain adjusted odds ratios (AOR) with a significance level set at α = 0.05.

Depression was found to be highly prevalent among study participants, with 44.9% of them affected. Findings revealed that being male [AOR = 0.62; 95% confidence interval (CI): 0.42–0.92], being employed (AOR = 0.55; 95%CI: 0.31–0.97), and earning a monthly income of ₦50,000–100,000 ($65–130) (AOR = 0.49; 95% CI: 0.27–0.91) and >₦100,000–200,000(>$130–260) (AOR = 0.33; 95% CI: 0.13–0.77) were significantly associated with reduced odds of depression.

The significant association of being male, having formal employment, and earning a moderate monthly income with reduced odds of depression may have implications for policy and strategies for managing mental health issues among PLHIV in cosmopolitan areas like Jos, which face peculiar challenges such as cultural tensions, traffic congestion, and gentrification. PLHIV categories with a relatively higher likelihood of depression may benefit from targeted mental health support systems, in addition to other mental health management strategies generally available to PLHIV.

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Short Communication Open Access
Using Low-cost Videoscopes to Obtain Accurate Video “Oral Selfies” as Screening for HPV-associated Oropharyngeal Cancer: A New Screening Technology?
Michael W. Ross, Samir S. Khariwala, Sarah L. Bennis, I. Niles Zoschke, B.R. Simon Rosser, Alan G. Nyitray, C. Mark Nichols, Charlene Flash, J. Michael Wilkerson, Cynthia L. Stull
Published online June 25, 2024
Cancer Screening and Prevention. doi:10.14218/CSP.2024.00005
Abstract
Human papillomavirus (HPV)-related oropharyngeal cancers associated with sexual contact are increasing, with high rates in men who have sex with men. HPV-related cancers have the [...] Read more.

Human papillomavirus (HPV)-related oropharyngeal cancers associated with sexual contact are increasing, with high rates in men who have sex with men. HPV-related cancers have the advantage of being frequently detectable through oropharyngeal visual examination and having much higher survival rates than classic oropharyngeal cancers. It has been demonstrated that gay and bisexual men can take smartphone oropharyngeal “selfies” of sufficient quality for screening. However, there is an issue with the inability to move the tongue to allow a clear view of the palatine tonsils, where a majority of oropharyngeal cancer cases occur. We attempted to investigate the feasibility of using commercially available videoscopes to visualize the oropharynx. Fourteen healthy volunteers used a provided low-cost commercial endoscope to video their oropharynx. Participants used the videoscope connected to a laptop and could visualize the oropharynx on the screen. Attempts were observed, and the process was noted. A focus group of participants was carried out immediately afterwards to ascertain barriers and facilitators to using the videoscopes. All participants were able to use the videoscope and obtain videos of sufficient clarity to note major oropharyngeal landmarks. The palatine tonsils were initially difficult to visualize because the tongue could not be sufficiently controlled. Participants were given time to practice using visual cues to control the position of the tongue, which helped in obtaining good videos. Videoscopes can be used effectively with minimal instruction and provide a better view than still images, as they illuminate and magnify the site. Low-cost commercially available videoscopes may be an improvement over smartphone “selfies”.

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