{"title":"Revamping hepatitis C global eradication efforts: towards simplified and enhanced screening, prevention, and treatment.","authors":"Calvin Q Pan, James S Park","doi":"10.21037/tgh-23-104","DOIUrl":"10.21037/tgh-23-104","url":null,"abstract":"","PeriodicalId":94362,"journal":{"name":"Translational gastroenterology and hepatology","volume":"9 ","pages":"30"},"PeriodicalIF":0.0,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11074485/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140878362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jasleen Singh, Brittney Ibrahim, Nicholas J Jackson, Haydar Khalil, Julia Valenzuela, Beshoy Yanny, Sammy Saab
{"title":"Lower FIB-4 threshold in patients with diabetes improves diagnostic accuracy of the test in a Hispanic population.","authors":"Jasleen Singh, Brittney Ibrahim, Nicholas J Jackson, Haydar Khalil, Julia Valenzuela, Beshoy Yanny, Sammy Saab","doi":"10.21037/tgh-23-62","DOIUrl":"10.21037/tgh-23-62","url":null,"abstract":"<p><strong>Background: </strong>Non-invasive tests (NITs) can be used to estimate the severity of fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) but their diagnostic accuracy is variable. Hispanic patients are at increased risk of NAFLD and diabetes. We evaluate the diagnostic performance of the fibrosis index based on 4 factors (FIB-4) in a population of Hispanic patients who underwent vibration-controlled transient elastography (VCTE).</p><p><strong>Methods: </strong>A total of 1,524 patients underwent VCTE at University of California, Los Angeles from July 18, 2019 to June 7, 2022. Ultimately 110 patients were identified as Hispanic, with confirmed NAFLD. Sensitivity, specificity, positive predictive value and negative predictive value of FIB-4 threshold ≥1.3 were calculated. Logistic regression models were used to determine updated thresholds for patients with and without diabetes based on Youden's index.</p><p><strong>Results: </strong>Of the 110 patients, the majority (65%) were female. Prevalence of diabetes was higher in the group with clinically significant fibrosis (76% <i>vs.</i> 36%, P<0.001). Using a FIB-4 threshold ≥1.3 to predict clinically significant fibrosis (F2-F4 on VCTE), area under the receiver operating characteristic (AUROC) was 0.74. By incorporating diabetes status, AUROC was 0.81 when employing a FIB-4 threshold of ≥1.0 in patients with diabetes and ≥1.5 in patients without diabetes.</p><p><strong>Conclusions: </strong>Using a FIB-4 threshold of ≥1.0 in patients with diabetes and ≥1.5 in patients without diabetes improves the diagnostic performance of the test. The new FIB-4 including diabetes status will lead to improved screening in patients who are at risk of clinically significant fibrosis.</p>","PeriodicalId":94362,"journal":{"name":"Translational gastroenterology and hepatology","volume":"9 ","pages":"16"},"PeriodicalIF":0.0,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11074489/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140878327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhi-Hui Chen, Ying-Ying Tang, Si-Yuan Sheng, Chuan-Gang Lu, Kai-Wu Xu, Guan-Jun Chen, Yan-Feng Wang, Yong Gu, Xin-Ming Song, Hai Hong
{"title":"Crohn's disease treatment and memory T-cell subset changes: insights from a case series.","authors":"Zhi-Hui Chen, Ying-Ying Tang, Si-Yuan Sheng, Chuan-Gang Lu, Kai-Wu Xu, Guan-Jun Chen, Yan-Feng Wang, Yong Gu, Xin-Ming Song, Hai Hong","doi":"10.21037/tgh-23-21","DOIUrl":"10.21037/tgh-23-21","url":null,"abstract":"<p><strong>Background: </strong>Crohn's disease (CD) is a chronic inflammatory bowel disease with significant morbidity, affecting millions worldwide. The intricacies of immune responses in CD, especially post-treatment, remain a vital area of exploration. While memory T (Tm)-cell subsets play a pivotal role in adaptive immunity, their specific function in patients with CD after treatment is not well-understood. This study aims to investigate the effect and function of Tm-cell subsets in these patients, addressing a crucial knowledge gap in the context of CD therapeutics.</p><p><strong>Methods: </strong>A total of eight patients diagnosed with CD were selected based on predefined inclusion criteria. All patients were treated with either anti-inflammatory agents, immunosuppressive drugs, or a combination of both. For comparison, healthy donors were enrolled based on exclusion of autoimmune or inflammatory diseases. Peripheral blood mononuclear cells (PBMCs) and lymphocytes were isolated from blood and lymph node tissue respectively. The phenotype and cytokine production of T lymphocytes from both CD patients and healthy donors were analyzed using flow cytometry. Statistical comparisons of the outcomes between CD patients and healthy donors were made using Mann-Whitney test (two-tailed) and Student <i>t</i>-test.</p><p><strong>Results: </strong>Post-treatment CD patients exhibited an altered T cell distribution with a notable increase in CD8<sup>+</sup> T cells in PBMCs (P=0.0005), and altered frequencies of CD4<sup>+</sup> and CD8<sup>+</sup> T cells in mesenteric lymph nodes (MLNs). Tm cells showed decreased interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) production, with significant alterations in the frequency of IFN-γ-producing CD8<sup>+</sup> stem cell-like Tm (Tscm) cells in lesions of the MLNs from patients with CD (CD-M-Lys) compared to healthy MLNs from patients with CD (N-M-Lys) (P=0.0152). Differences in tissue-resident Tm (Trm)-cell subset frequencies were observed between the MLNs and small intestinal mucosa in CD patients.</p><p><strong>Conclusions: </strong>The treatments with anti-inflammatory agents and/or immunosuppressive drugs have a significant effect on the frequency and function of Tm-cell subsets. Clinically, these findings suggest a potential therapeutic avenue in modulating Tm-cell responses, which might be particularly beneficial for conditions where immune response modulation is crucial. Further clinical studies are warranted to explore the full therapeutic implications of these findings.</p>","PeriodicalId":94362,"journal":{"name":"Translational gastroenterology and hepatology","volume":"9 ","pages":"18"},"PeriodicalIF":0.0,"publicationDate":"2024-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11074482/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140878323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Isosteviol plays a protective role on hepatic ischemia and reperfusion injury in mice through MAPK/NF-κB signaling pathway.","authors":"Yuwei Chen, Ronghua Li, Hongjiao Xu, Long Guo","doi":"10.21037/tgh-23-66","DOIUrl":"10.21037/tgh-23-66","url":null,"abstract":"<p><strong>Background: </strong>Hepatic ischemia and reperfusion (I/R) injury is of common occurrence during liver surgery and transplantation, isosteviol (ISV) is an acid hydrolysate of stevioside, the major component of Stevia rebaudiana. Stevioside and its metabolites have been shown to have varieties of pharmacological activities, However, the effect of ISV on hepatic I/R injury has not determined. The purpose of this paper is to study the effect of ISV on mice with hepatic I/R injury and further investigate its underlying mechanism.</p><p><strong>Methods: </strong>The blood vessels supplying the left/middle lobe of the liver in mice were clamped to cause liver ischemia for 1h, and then removed the clamp to conduct reperfusion for 6 h. ISV or saline was injected intraperitoneally after reperfusion. The expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and IL-10 in serum and tissues were evaluated by enzyme linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qRT-PCR). The infiltration of neutrophils and macrophages into the liver tissue was determined by flow cytometry and myeloperoxidase. Liver hematoxylin-eosin (HE) staining, terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling (TUNEL) and Annexin V probe were used to determine liver injury and hepatocyte apoptosis. western blots (WB) was used to investigate the activation of nuclear factor kappa-B (NF-κB) and c-JunNH2 terminal kinase (JNK), p38 and extracellular regulated protein kinase (ERK), while the expression of apoptosis-related proteins B-cell lymphoma-2 (BCL-2), BCL2-associated X protein (BAX), caspase-3 was detected.</p><p><strong>Results: </strong>ISV reduced aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels to alleviate liver injury. ISV significantly reduced the release of inflammatory cytokines and the accumulation of liver neutrophils and macrophages. Meanwhile, ISV can promote the expression of anti-apoptosis-related protein BCL-2 and inhibit the expression of pro-apoptotic protein BAX and the activation of the protease caspase-3, and reduce the occurrence of hepatocyte apoptosis. Finally, ISV can reduce the phosphorylation level and activation of NF-κB, JNK, p38 and ERK.</p><p><strong>Conclusions: </strong>ISV inhibits the occurrence of inflammation and hepatocyte apoptosis through mitogen-activated protein kinase (MAPK)/NF-κB signaling pathway to relieve liver injury.</p>","PeriodicalId":94362,"journal":{"name":"Translational gastroenterology and hepatology","volume":"9 ","pages":"66"},"PeriodicalIF":3.8,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11535817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142585305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Therapeutic endoscopic ultrasound.","authors":"Rodrigo Duarte-Chavez, Michel Kahaleh","doi":"10.21037/tgh-2020-12","DOIUrl":"https://doi.org/10.21037/tgh-2020-12","url":null,"abstract":"<p><p>Endoscopic ultrasound (EUS) has been continuously evolving for the past three decades and has become widely used for both diagnostic and therapeutic purposes. The efficacy of therapeutic EUS (TEUS) has proven to be superior and better tolerated than conventional percutaneous or surgical techniques. TEUS has allowed the performance of multiple procedures including gallbladder, pancreatic duct and biliary drainage as well as gastrointestinal anastomoses. TEUS procedures generally require the following critical steps: needle access, guidewire placement, fistula creation and stent deployment. The indications and contraindication for TEUS procedures vary with different procedures but common contraindications include hemodynamic instability, severe coagulopathy unable to be reversed, large volume ascites or the inability to obtain access to the target site. Proficiency and high volume in endoscopic retrograde cholangiopancreatography (ERCP) and diagnostic EUS procedures are required for training in TEUS. The complexity of the cases performed can be seen as a pyramid with drainage of pancreatic fluid collections at the base, pancreaticobiliary decompression in the middle, and creation of digestive anastomosis at the top. The mastery of each level is crucial prior to reaching the next level of complexity. TEUS has been incorporated in our arsenal and is impacting on a daily basis the way we offer minimally invasive therapy.</p>","PeriodicalId":94362,"journal":{"name":"Translational gastroenterology and hepatology","volume":"7 ","pages":"20"},"PeriodicalIF":3.8,"publicationDate":"2022-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9081917/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142074921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anand B Shah, Katelyn R Sommerer, Khaldoun Almhanna
{"title":"Immune checkpoint inhibitors in gastrointestinal malignancies: what can we learn from experience with other tumors?","authors":"Anand B Shah, Katelyn R Sommerer, Khaldoun Almhanna","doi":"10.21037/tgh.2019.09.04","DOIUrl":"10.21037/tgh.2019.09.04","url":null,"abstract":"<p><p>Gastrointestinal (GI) malignancies are some of the most common cancers worldwide with high rates of morbidity and mortality. Immune checkpoint inhibitors have afforded additional treatment options for patients, but their success has been limited. Conversely, in other tumor types such as lung cancer, melanoma and renal cell carcinoma, treatment strategies with immune checkpoint inhibitors have propelled those agents into the front lines of treatment. Strategies utilized include combining immune checkpoint inhibitors with chemotherapy, other checkpoint inhibitors, and targeted therapy. In this review, we analyze combination strategies employed in other tumor types to help identify current and future approaches toward improving outcomes with immunotherapy in GI malignancies.</p>","PeriodicalId":94362,"journal":{"name":"Translational gastroenterology and hepatology","volume":"4 ","pages":"73"},"PeriodicalIF":3.8,"publicationDate":"2019-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6851451/pdf/tgh-04-2019.09.04.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49687115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jeremy Chuang, Joseph Chao, Andrew Hendifar, Samuel J Klempner, Jun Gong
{"title":"Checkpoint inhibition in advanced gastroesophageal cancer: clinical trial data, molecular subtyping, predictive biomarkers, and the potential of combination therapies.","authors":"Jeremy Chuang, Joseph Chao, Andrew Hendifar, Samuel J Klempner, Jun Gong","doi":"10.21037/tgh.2019.08.04","DOIUrl":"10.21037/tgh.2019.08.04","url":null,"abstract":"<p><p>The development of checkpoint inhibitors has redefined the treatment paradigm for advanced gastroesophageal cancer. While recent developments have improved clinical outcomes, the prognosis for the disease remains meager. In this review, we discuss the rationale and detail the results from recent phase I-III trials supporting the activity of PD-1 inhibitors. Specifically, we highlight the seminal clinical trials leading to the FDA approval of pembrolizumab for advanced gastroesophageal cancer. Finally, we review the current understanding and future considerations of molecular subtyping and predictive biomarkers to help guide therapy and the promise of combination therapy to further improve the efficacy of checkpoint inhibitors.</p>","PeriodicalId":94362,"journal":{"name":"Translational gastroenterology and hepatology","volume":"4 ","pages":"63"},"PeriodicalIF":3.8,"publicationDate":"2019-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6737389/pdf/tgh-04-2019.08.04.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41226883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Palliative chemotherapy in pancreatic cancer-treatment sequences.","authors":"Rami Abbassi, Hana Algül","doi":"10.21037/tgh.2019.06.09","DOIUrl":"https://doi.org/10.21037/tgh.2019.06.09","url":null,"abstract":"<p><p>Pancreatic cancer belongs to the most deadly malignancies and is expected to become the second deadliest cancer by 2040. Still, in most of the cases the tumor is detected in a nonresectable or metastatic state and, untreated, the disease will progress rapidly. Even with chemotherapeutic treatment the prognosis is poor and the 5-year overall survival rate is less than 10%. Therefore, there is a need for proper therapeutic options for the palliative treatment of the disease. Despite great efforts to find new drugs for the treatment of pancreatic cancer, for a long time the therapy was limited to the use of gemcitabine with very limited benefit. Recently new chemotherapeutic regimens have been identified that helped to improve the overall survival significantly. In addition, even second-line therapies have been established. This review will provide an overview on the current standard of care, discusses possible treatment sequences and offer a perspective on future developments.</p>","PeriodicalId":94362,"journal":{"name":"Translational gastroenterology and hepatology","volume":"4 ","pages":"56"},"PeriodicalIF":0.0,"publicationDate":"2019-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.21037/tgh.2019.06.09","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71435077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Emerging medical therapies for non-alcoholic fatty liver disease and for alcoholic hepatitis.","authors":"Vincent Wai-Sun Wong, Ashwani K Singal","doi":"10.21037/tgh.2019.06.06","DOIUrl":"https://doi.org/10.21037/tgh.2019.06.06","url":null,"abstract":"<p><p>Non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) are currently the two most common liver diseases in the world. Alcoholic hepatitis (AH), a unique clinical syndrome among ALD patients has high short-term mortality. Apart from controlling the risk factor for individual respective disease, there are no Food and Drug Administration (FDA) approved medical therapies for these diseases. Over the last 5-10 years, the field has extensively grown with many new targets being studied in randomized clinical trials for these diseases, with many of these drugs being tested in both the conditions. In this chapter, we will describe the novel therapeutic agents and current status of ongoing clinical trials with these agents for the treatment of NAFLD and/or AH.</p>","PeriodicalId":94362,"journal":{"name":"Translational gastroenterology and hepatology","volume":"4 ","pages":"53"},"PeriodicalIF":0.0,"publicationDate":"2019-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.21037/tgh.2019.06.06","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41226884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}