Kamya Sankar, Ashley N Pearson, Tejaswi Worlikar, Matthew D Perricone, Erin A Holcomb, Mishal Mendiratta-Lala, Zhen Xu, Neil Bhowmick, Michael D Green
The liver is a functionally unique organ with an immunosuppressive microenvironment. The liver is the sixth most common site of primary cancer in humans and is a frequent site of metastasis from other solid tumors. The development of effective therapies for primary and metastatic liver cancer has been challenging due to the complex metabolic and immune microenvironment of the liver. The liver tumor microenvironment (TME) in primary and secondary (metastatic) liver cancers is heterogenous and consists of unique immune and stromal cell populations. Crosstalk between these cell populations and tumor cells creates an immunosuppressive microenvironment within the liver which potentiates cancer progression. Immune checkpoint inhibitors (ICIs) are now clinically approved for the management of primary and secondary liver cancer and can partially overcome liver immune tolerance, but their efficacy is limited. In this review, we describe the liver microenvironment and the use of immunotherapy in primary and secondary liver cancer. We discuss emerging combination strategies utilizing locoregional and systemic therapy approaches which may enhance efficacy of immunotherapy in primary and secondary liver cancer. A deeper understanding of the immunosuppressive microenvironment of the liver will inform novel therapies and therapeutic combinations in order to improve outcomes of patients with primary and secondary liver cancer.
{"title":"Impact of immune tolerance mechanisms on the efficacy of immunotherapy in primary and secondary liver cancers.","authors":"Kamya Sankar, Ashley N Pearson, Tejaswi Worlikar, Matthew D Perricone, Erin A Holcomb, Mishal Mendiratta-Lala, Zhen Xu, Neil Bhowmick, Michael D Green","doi":"10.21037/tgh-23-11","DOIUrl":"https://doi.org/10.21037/tgh-23-11","url":null,"abstract":"<p><p>The liver is a functionally unique organ with an immunosuppressive microenvironment. The liver is the sixth most common site of primary cancer in humans and is a frequent site of metastasis from other solid tumors. The development of effective therapies for primary and metastatic liver cancer has been challenging due to the complex metabolic and immune microenvironment of the liver. The liver tumor microenvironment (TME) in primary and secondary (metastatic) liver cancers is heterogenous and consists of unique immune and stromal cell populations. Crosstalk between these cell populations and tumor cells creates an immunosuppressive microenvironment within the liver which potentiates cancer progression. Immune checkpoint inhibitors (ICIs) are now clinically approved for the management of primary and secondary liver cancer and can partially overcome liver immune tolerance, but their efficacy is limited. In this review, we describe the liver microenvironment and the use of immunotherapy in primary and secondary liver cancer. We discuss emerging combination strategies utilizing locoregional and systemic therapy approaches which may enhance efficacy of immunotherapy in primary and secondary liver cancer. A deeper understanding of the immunosuppressive microenvironment of the liver will inform novel therapies and therapeutic combinations in order to improve outcomes of patients with primary and secondary liver cancer.</p>","PeriodicalId":23267,"journal":{"name":"Translational gastroenterology and hepatology","volume":"8 ","pages":"29"},"PeriodicalIF":3.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/5c/58/tgh-08-23-11.PMC10432235.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10305937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rizwan Ishtiaq, Laraib Zulfiqar, Manesh Kumar Gangwani, Muhammad Aziz
is known as the ‘One and done’ approach. In operators who are focused on using ADR as a quality indicator, it is very well possible that they may perform a quality examination until they find one adenoma and then unintentionally decrease the quality of the rest of the examination of the colonoscopy, which will indirectly affect the quality of the procedure without affecting ADR (7). Additionally, operator-based variability is also exhibited by differences in proximal and distal adenoma detection rate, and ADR metric by its calculable metric standard cannot account for these differences (8)
{"title":"Adenoma detection rate <i>vs</i>. adenoma per colonoscopy as quality indicators for colon cancer screening.","authors":"Rizwan Ishtiaq, Laraib Zulfiqar, Manesh Kumar Gangwani, Muhammad Aziz","doi":"10.21037/tgh-22-92","DOIUrl":"https://doi.org/10.21037/tgh-22-92","url":null,"abstract":"is known as the ‘One and done’ approach. In operators who are focused on using ADR as a quality indicator, it is very well possible that they may perform a quality examination until they find one adenoma and then unintentionally decrease the quality of the rest of the examination of the colonoscopy, which will indirectly affect the quality of the procedure without affecting ADR (7). Additionally, operator-based variability is also exhibited by differences in proximal and distal adenoma detection rate, and ADR metric by its calculable metric standard cannot account for these differences (8)","PeriodicalId":23267,"journal":{"name":"Translational gastroenterology and hepatology","volume":"8 ","pages":"24"},"PeriodicalIF":3.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/2f/21/tgh-08-22-92.PMC10432231.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10406182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pancreatic fluid collections (PFCs) are frequent complications in severe acute pancreatitis that are the result of damage to the pancreas to include but not limited to trauma, surgery, autoimmune diseases, alcohol abuse, infections, medications, gallstones, metabolic disorders, and premalignant or malignant conditions. The majority of these collections resolve spontaneously; however, if the collection is infected or causes symptoms to include abdominal pain, nausea, vomiting, diarrhea, fevers, and tachycardia, drainage is indicated. Drainage of PFCs can be accomplished surgically, percutaneously, or endoscopically and should be approached in a multidisciplinary fashion for best overall patient care and outcomes. Before the introduction of endoscopic procedures, surgical and percutaneous drainage was the preferred modality. Today a minimally-invasive "step-up" approach is generally accepted depending upon the specific characteristics of the PFC and clinical presentation. Endoscopic ultrasound-guided PFC drainage is favored due to high success rates, shorter hospital stays, and lower cost. Direct debridement of walled-off pancreatitis can now be performed endoscopically with higher success rates with larger caliber fully covered metal stents. At large, the field of endoscopic techniques has evolved, and more specifically, the management of PFCs continues to evolve with increasing experience and with the advent of new stents and accessories, leading to increased efficacy with less adverse events.
{"title":"Management of severe acute pancreatitis in 2019.","authors":"Eddie Copelin, Jessica Widmer","doi":"10.21037/tgh-2020-08","DOIUrl":"https://doi.org/10.21037/tgh-2020-08","url":null,"abstract":"<p><p>Pancreatic fluid collections (PFCs) are frequent complications in severe acute pancreatitis that are the result of damage to the pancreas to include but not limited to trauma, surgery, autoimmune diseases, alcohol abuse, infections, medications, gallstones, metabolic disorders, and premalignant or malignant conditions. The majority of these collections resolve spontaneously; however, if the collection is infected or causes symptoms to include abdominal pain, nausea, vomiting, diarrhea, fevers, and tachycardia, drainage is indicated. Drainage of PFCs can be accomplished surgically, percutaneously, or endoscopically and should be approached in a multidisciplinary fashion for best overall patient care and outcomes. Before the introduction of endoscopic procedures, surgical and percutaneous drainage was the preferred modality. Today a minimally-invasive \"step-up\" approach is generally accepted depending upon the specific characteristics of the PFC and clinical presentation. Endoscopic ultrasound-guided PFC drainage is favored due to high success rates, shorter hospital stays, and lower cost. Direct debridement of walled-off pancreatitis can now be performed endoscopically with higher success rates with larger caliber fully covered metal stents. At large, the field of endoscopic techniques has evolved, and more specifically, the management of PFCs continues to evolve with increasing experience and with the advent of new stents and accessories, leading to increased efficacy with less adverse events.</p>","PeriodicalId":23267,"journal":{"name":"Translational gastroenterology and hepatology","volume":"7 ","pages":"16"},"PeriodicalIF":3.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9081916/pdf/tgh-07-2020-08.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10248972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-04-05DOI: 10.21037/TGH-2019-RLD-12
Melissa A Gilbert, K. Loomes
The observation of bile duct paucity is an important diagnostic finding in children, occurring in roughly 11% of pediatric liver biopsies. Alagille syndrome (ALGS) is a well-defined syndromic form of intrahepatic bile duct paucity that is accompanied by a number of other key features, including cardiac, facial, ocular, and vertebral abnormalities. In the absence of these additional clinical characteristics, intrahepatic bile duct paucity results in a broad differential diagnosis that requires supplementary testing and characterization. Nearly 30 years after ALGS was first described, genetic studies identified a causative gene, JAGGED1, which spearheaded over two decades of research aimed to meticulously delineate the molecular underpinnings of ALGS. These advancements have characterized ALGS as a genetic disease and led to testing strategies that offer the ability to detect a pathogenic genetic variant in almost 97% of individuals with ALGS. Having a molecular understanding of ALGS has allowed for the development of numerous in vitro and in vivo disease models, which have provided hope and promise for the future generation of gene-based and protein-based therapies. Generation of these disease models has offered scientists a mechanism to study the dynamics of bile duct development and regeneration, and in doing so, produced tools that are applicable to the understanding of other congenital and acquired liver diseases.
{"title":"Alagille syndrome and non-syndromic paucity of the intrahepatic bile ducts.","authors":"Melissa A Gilbert, K. Loomes","doi":"10.21037/TGH-2019-RLD-12","DOIUrl":"https://doi.org/10.21037/TGH-2019-RLD-12","url":null,"abstract":"The observation of bile duct paucity is an important diagnostic finding in children, occurring in roughly 11% of pediatric liver biopsies. Alagille syndrome (ALGS) is a well-defined syndromic form of intrahepatic bile duct paucity that is accompanied by a number of other key features, including cardiac, facial, ocular, and vertebral abnormalities. In the absence of these additional clinical characteristics, intrahepatic bile duct paucity results in a broad differential diagnosis that requires supplementary testing and characterization. Nearly 30 years after ALGS was first described, genetic studies identified a causative gene, JAGGED1, which spearheaded over two decades of research aimed to meticulously delineate the molecular underpinnings of ALGS. These advancements have characterized ALGS as a genetic disease and led to testing strategies that offer the ability to detect a pathogenic genetic variant in almost 97% of individuals with ALGS. Having a molecular understanding of ALGS has allowed for the development of numerous in vitro and in vivo disease models, which have provided hope and promise for the future generation of gene-based and protein-based therapies. Generation of these disease models has offered scientists a mechanism to study the dynamics of bile duct development and regeneration, and in doing so, produced tools that are applicable to the understanding of other congenital and acquired liver diseases.","PeriodicalId":23267,"journal":{"name":"Translational gastroenterology and hepatology","volume":"19 1","pages":"22"},"PeriodicalIF":3.0,"publicationDate":"2021-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90804033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-04-05DOI: 10.21037/TGH-2019-RLD-10
M. Moini, Uyen To, M. Schilsky
Wilson disease (WD) is rare genetic disorder that presents with varied phenotype that can at times make the diagnosis challenging. Medical treatments are available, but there are still unmet needs for patients. Since life-long therapy is necessary, adherence to medical therapy and best practices for monitoring and individualizing therapy continue to evolve. Studies are ongoing that address some of these issues. In the current review we focused our attention to recent advances in the diagnosis of WD, current medical treatments, future potential therapies and treatment monitoring. We include discussion of new methodology for detection and quantitation of ophthalmologic signs of WD, new brain imaging modalities for early detection of neurologic involvement in patients and potential new diagnostic methodology using blood samples that may be applicable to newborn screening and adult disease diagnosis. In addition, there are new strategies aimed at improving adherence and outcomes with currently available therapies, including once daily chelation dosing and discussion of the efficacy of different zinc salt compounds. With respect to new therapies with different mechanisms of action, we discuss studies on Bis-choline tetrathiomolybdate (TTM) in patients, pre-clinical studies of a novel chelator methanobactin and other animal studies exploring cures for WD with gene therapy using adeno-associated vectors (AAVs) that introduce ATP7B into liver cells. There are also promising advances in the more accurate measurement of non-ceruloplasmin bound copper and exchangeable copper in the circulation which would potentially help with monitoring and individualization of treatment and possibly play a role in future disease diagnosis.
{"title":"Recent advances in Wilson disease.","authors":"M. Moini, Uyen To, M. Schilsky","doi":"10.21037/TGH-2019-RLD-10","DOIUrl":"https://doi.org/10.21037/TGH-2019-RLD-10","url":null,"abstract":"Wilson disease (WD) is rare genetic disorder that presents with varied phenotype that can at times make the diagnosis challenging. Medical treatments are available, but there are still unmet needs for patients. Since life-long therapy is necessary, adherence to medical therapy and best practices for monitoring and individualizing therapy continue to evolve. Studies are ongoing that address some of these issues. In the current review we focused our attention to recent advances in the diagnosis of WD, current medical treatments, future potential therapies and treatment monitoring. We include discussion of new methodology for detection and quantitation of ophthalmologic signs of WD, new brain imaging modalities for early detection of neurologic involvement in patients and potential new diagnostic methodology using blood samples that may be applicable to newborn screening and adult disease diagnosis. In addition, there are new strategies aimed at improving adherence and outcomes with currently available therapies, including once daily chelation dosing and discussion of the efficacy of different zinc salt compounds. With respect to new therapies with different mechanisms of action, we discuss studies on Bis-choline tetrathiomolybdate (TTM) in patients, pre-clinical studies of a novel chelator methanobactin and other animal studies exploring cures for WD with gene therapy using adeno-associated vectors (AAVs) that introduce ATP7B into liver cells. There are also promising advances in the more accurate measurement of non-ceruloplasmin bound copper and exchangeable copper in the circulation which would potentially help with monitoring and individualization of treatment and possibly play a role in future disease diagnosis.","PeriodicalId":23267,"journal":{"name":"Translational gastroenterology and hepatology","volume":"36 1","pages":"21"},"PeriodicalIF":3.0,"publicationDate":"2021-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91286809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-04-05DOI: 10.21037/TGH-2019-RLD-05
Bruce Wang
The acute hepatic porphyrias (AHP) are a group of four inherited diseases of heme biosynthesis. They present with similar severe, episodic, acute neurovisceral symptoms due to abnormally elevated levels of porphyrin precursors delta-aminolevulinic acid (ALA). Recently genetic screening indicates that the prevalence of mutation carrier state is more common than previously thought, occurring in 1 in 1,500, though the clinical penetrance of symptomatic AHP is low at ~1%. Symptomatic attacks occur primarily in females during their reproductive years. In an acute porphyria attack, the primary symptom is abdominal pain, due to intestinal dysmotility from autonomic nerve injury. Other manifestations include seizures, weakness and mood changes, point to injury involving peripheral and central nervous system. Due to the non-specific nature of the symptoms and signs in AHP, the diagnosis is often delayed by many years. The diagnosis of AHP depends on biochemical evidence of elevated ALA and PBG levels in urine during symptomatic attacks. Genetic testing is used for confirmation of the gene involved and the exact mutation. Treatment involves administration of heme, which downregulates production of ALA. Long-term management centers on educating genetic carriers on avoiding triggers that increase the risk of acute attacks and screening family members.
{"title":"The acute hepatic porphyrias.","authors":"Bruce Wang","doi":"10.21037/TGH-2019-RLD-05","DOIUrl":"https://doi.org/10.21037/TGH-2019-RLD-05","url":null,"abstract":"The acute hepatic porphyrias (AHP) are a group of four inherited diseases of heme biosynthesis. They present with similar severe, episodic, acute neurovisceral symptoms due to abnormally elevated levels of porphyrin precursors delta-aminolevulinic acid (ALA). Recently genetic screening indicates that the prevalence of mutation carrier state is more common than previously thought, occurring in 1 in 1,500, though the clinical penetrance of symptomatic AHP is low at ~1%. Symptomatic attacks occur primarily in females during their reproductive years. In an acute porphyria attack, the primary symptom is abdominal pain, due to intestinal dysmotility from autonomic nerve injury. Other manifestations include seizures, weakness and mood changes, point to injury involving peripheral and central nervous system. Due to the non-specific nature of the symptoms and signs in AHP, the diagnosis is often delayed by many years. The diagnosis of AHP depends on biochemical evidence of elevated ALA and PBG levels in urine during symptomatic attacks. Genetic testing is used for confirmation of the gene involved and the exact mutation. Treatment involves administration of heme, which downregulates production of ALA. Long-term management centers on educating genetic carriers on avoiding triggers that increase the risk of acute attacks and screening family members.","PeriodicalId":23267,"journal":{"name":"Translational gastroenterology and hepatology","volume":"5 1","pages":"24"},"PeriodicalIF":3.0,"publicationDate":"2021-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88298405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-04-05DOI: 10.21037/TGH-2019-RLD-14
L. Fabris, M. Strazzabosco
According to the statement of the European Commission of Public Health, rare diseases (RDs) are a group of ‘life-threatening or chronically debilitating diseases which are of such low prevalence that special combined efforts are needed to address them’ (1). Epidemiological criteria are essential for their definition. In Europe, a disease whose prevalence is lower than one in 2,000 people is considered a RD, while in the USA prevalence of a RD is less than one in 1,500 people, derived from the definition of a disease affecting fewer than 200,000 Americans. The difference in the prevalence thresholds between Europe and the USA reflects the wide variability among individual jurisdictions dependent on the current estimates of the population size in the different countries (2). At present, about 7,000 different diseases are recognized as ‘rare’, and altogether, affect about 400 million people worldwide (3). In a considerable percentage of patients (nearly 30%), the diseases prolong into the adult age or manifest in the adult age. Thus, this is a field of medicine that concerns both pediatrician and adult physicians and spans across all medical and surgical specialties. Most RDs (about 80%) are caused by monogenic defects. However, a perturbed homeostatic response of the cell may activate other disease mechanisms, including autoimmunity and autoinflammation, susceptibility to infectious agents and cancer. In addition, the correlation between genotype and phenotype is often quite variable. In fact, in a number of RDs, affected genes control fundamental development processes resulting in a multifaceted clinical phenotype and multiorgan involvement. According to the Orphanet database, about 25% of rare patients die before 5 years, whereas an additional 37% have a reduced life expectancy, variably dependent on the severity of the RD (4). Too often, the diagnosis represents a big challenge. Because of the limited awareness of these conditions and the scarcity of centers with adequate clinical experience and laboratory skills, the diagnosis is difficult to achieve and is thus often delayed. Notably, the average time for a patient with a rare disease to receive an accurate diagnosis is nearly 5 years (3). Unfortunately, despite repeated costand time-consuming efforts, several (6%) remain undiagnosed (5). Even when a diagnosis is reached, often the treatment options are limited. In spite of the recent progresses, it is estimated that 95% of RDs still lack an FDA approved treatment. It may take 10–12 years for a new drug to be approved for the cure of rare disease patients (6). This long avenue is also partly dependent on the difficulties in conducting clinical trials in rare diseases (small cohorts of widely dispersed patients in both pediatric and adult age, lack of validated biomarkers and qualified endpoints). Therefore, RDs are also often referred to as ‘orphan’ to highlight the concept that effective treatments are lacking as not enough research and drug
{"title":"Rare and undiagnosed liver diseases: challenges and opportunities.","authors":"L. Fabris, M. Strazzabosco","doi":"10.21037/TGH-2019-RLD-14","DOIUrl":"https://doi.org/10.21037/TGH-2019-RLD-14","url":null,"abstract":"According to the statement of the European Commission of Public Health, rare diseases (RDs) are a group of ‘life-threatening or chronically debilitating diseases which are of such low prevalence that special combined efforts are needed to address them’ (1). Epidemiological criteria are essential for their definition. In Europe, a disease whose prevalence is lower than one in 2,000 people is considered a RD, while in the USA prevalence of a RD is less than one in 1,500 people, derived from the definition of a disease affecting fewer than 200,000 Americans. The difference in the prevalence thresholds between Europe and the USA reflects the wide variability among individual jurisdictions dependent on the current estimates of the population size in the different countries (2). At present, about 7,000 different diseases are recognized as ‘rare’, and altogether, affect about 400 million people worldwide (3). In a considerable percentage of patients (nearly 30%), the diseases prolong into the adult age or manifest in the adult age. Thus, this is a field of medicine that concerns both pediatrician and adult physicians and spans across all medical and surgical specialties. Most RDs (about 80%) are caused by monogenic defects. However, a perturbed homeostatic response of the cell may activate other disease mechanisms, including autoimmunity and autoinflammation, susceptibility to infectious agents and cancer. In addition, the correlation between genotype and phenotype is often quite variable. In fact, in a number of RDs, affected genes control fundamental development processes resulting in a multifaceted clinical phenotype and multiorgan involvement. According to the Orphanet database, about 25% of rare patients die before 5 years, whereas an additional 37% have a reduced life expectancy, variably dependent on the severity of the RD (4). Too often, the diagnosis represents a big challenge. Because of the limited awareness of these conditions and the scarcity of centers with adequate clinical experience and laboratory skills, the diagnosis is difficult to achieve and is thus often delayed. Notably, the average time for a patient with a rare disease to receive an accurate diagnosis is nearly 5 years (3). Unfortunately, despite repeated costand time-consuming efforts, several (6%) remain undiagnosed (5). Even when a diagnosis is reached, often the treatment options are limited. In spite of the recent progresses, it is estimated that 95% of RDs still lack an FDA approved treatment. It may take 10–12 years for a new drug to be approved for the cure of rare disease patients (6). This long avenue is also partly dependent on the difficulties in conducting clinical trials in rare diseases (small cohorts of widely dispersed patients in both pediatric and adult age, lack of validated biomarkers and qualified endpoints). Therefore, RDs are also often referred to as ‘orphan’ to highlight the concept that effective treatments are lacking as not enough research and drug ","PeriodicalId":23267,"journal":{"name":"Translational gastroenterology and hepatology","volume":"1 1","pages":"18"},"PeriodicalIF":3.0,"publicationDate":"2021-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82289392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dhanpat Jain, Richard Torres, Romulo Celli, Jeremy Koelmel, Georgia Charkoftaki, Vasilis Vasiliou
Liver biopsies are commonly used to evaluate a wide variety of medical disorders, including neoplasms and post-transplant complications. However, its use is being impacted by improved clinical diagnosis of disorders, and non-invasive methods for evaluating liver tissue and as a result the indications of a liver biopsy have undergone major changes in the last decade. The evolution of highly effective treatments for some of the common indications for liver biopsy in the last decade (e.g., viral hepatitis B and C) has led to a decline in the number of liver biopsies in recent years. At the same time, the emergence of better technologies for histologic evaluation, tissue content analysis and genomics are among the many new and exciting developments in the field that hold great promise for the future and are going to shape the indications for a liver biopsy in the future. Recent advances in slide scanners now allow creation of "digital/virtual" slides that have image of the entire tissue section present in a slide [whole slide imaging (WSI)]. WSI can now be done very rapidly and at very high resolution, allowing its use in routine clinical practice. In addition, a variety of technologies have been developed in recent years that use different light sources and/or microscopes allowing visualization of tissues in a completely different way. One such technique that is applicable to liver specimens combines multiphoton microscopy (MPM) with advanced clearing and fluorescent stains known as Clearing Histology with MultiPhoton Microscopy (CHiMP). Although it has not yet been extensively validated, the technique has the potential to decrease inefficiency, reduce artifacts, and increase data while being readily integrable into clinical workflows. Another technology that can provide rapid and in-depth characterization of thousands of molecules in a tissue sample, including liver tissues, is matrix assisted laser desorption/ionization (MALDI) mass spectrometry. MALDI has already been applied in a clinical research setting with promising diagnostic and prognostic capabilities, as well as being able to elucidate mechanisms of liver diseases that may be targeted for the development of new therapies. The logical next step in huge data sets obtained from such advanced analysis of liver tissues is the application of machine learning (ML) algorithms and application of artificial intelligence (AI), for automated generation of diagnoses and prognoses. This review discusses the evolving role of liver biopsies in clinical practice over the decades, and describes newer technologies that are likely to have a significant impact on how they will be used in the future.
{"title":"Evolution of the liver biopsy and its future.","authors":"Dhanpat Jain, Richard Torres, Romulo Celli, Jeremy Koelmel, Georgia Charkoftaki, Vasilis Vasiliou","doi":"10.21037/tgh.2020.04.01","DOIUrl":"https://doi.org/10.21037/tgh.2020.04.01","url":null,"abstract":"Liver biopsies are commonly used to evaluate a wide variety of medical disorders, including neoplasms and post-transplant complications. However, its use is being impacted by improved clinical diagnosis of disorders, and non-invasive methods for evaluating liver tissue and as a result the indications of a liver biopsy have undergone major changes in the last decade. The evolution of highly effective treatments for some of the common indications for liver biopsy in the last decade (e.g., viral hepatitis B and C) has led to a decline in the number of liver biopsies in recent years. At the same time, the emergence of better technologies for histologic evaluation, tissue content analysis and genomics are among the many new and exciting developments in the field that hold great promise for the future and are going to shape the indications for a liver biopsy in the future. Recent advances in slide scanners now allow creation of \"digital/virtual\" slides that have image of the entire tissue section present in a slide [whole slide imaging (WSI)]. WSI can now be done very rapidly and at very high resolution, allowing its use in routine clinical practice. In addition, a variety of technologies have been developed in recent years that use different light sources and/or microscopes allowing visualization of tissues in a completely different way. One such technique that is applicable to liver specimens combines multiphoton microscopy (MPM) with advanced clearing and fluorescent stains known as Clearing Histology with MultiPhoton Microscopy (CHiMP). Although it has not yet been extensively validated, the technique has the potential to decrease inefficiency, reduce artifacts, and increase data while being readily integrable into clinical workflows. Another technology that can provide rapid and in-depth characterization of thousands of molecules in a tissue sample, including liver tissues, is matrix assisted laser desorption/ionization (MALDI) mass spectrometry. MALDI has already been applied in a clinical research setting with promising diagnostic and prognostic capabilities, as well as being able to elucidate mechanisms of liver diseases that may be targeted for the development of new therapies. The logical next step in huge data sets obtained from such advanced analysis of liver tissues is the application of machine learning (ML) algorithms and application of artificial intelligence (AI), for automated generation of diagnoses and prognoses. This review discusses the evolving role of liver biopsies in clinical practice over the decades, and describes newer technologies that are likely to have a significant impact on how they will be used in the future.","PeriodicalId":23267,"journal":{"name":"Translational gastroenterology and hepatology","volume":"6 ","pages":"20"},"PeriodicalIF":3.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829074/pdf/tgh-06-2020.04.01.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10176298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lack of a prompt and accurate diagnosis remains on top of the list of challenges faced by patients with rare liver diseases. Although rare liver diseases affect a significant percentage of the population as a group, when taken singularly they represent unique diseases and the approaches used for diagnosis of common liver diseases are insufficient. However, the development of new methods for the acquisition of molecular and clinical data (i.e., genomic, proteomics, metabolomics) and computational tools for their analysis and integration, together with advances in modeling diseases using stem cell-based technology [i.e., induced pluripotent stem cells (iPSCs) and tissue organoids] represent a promising and powerful tool to improve the clinical management of these patients. This is the goal of precision medicine, a novel approach of modern medicine that aims at delivering a specific treatment based on disease-specific biological insights and individual profile. This review will discuss the application and advances of these technologies and how they represent a new opportunity in hepatology.
{"title":"Novel approaches to liver disease diagnosis and modeling.","authors":"André G Oliveira, Romina Fiorotto","doi":"10.21037/tgh-20-109","DOIUrl":"https://doi.org/10.21037/tgh-20-109","url":null,"abstract":"<p><p>Lack of a prompt and accurate diagnosis remains on top of the list of challenges faced by patients with rare liver diseases. Although rare liver diseases affect a significant percentage of the population as a group, when taken singularly they represent unique diseases and the approaches used for diagnosis of common liver diseases are insufficient. However, the development of new methods for the acquisition of molecular and clinical data (i.e., genomic, proteomics, metabolomics) and computational tools for their analysis and integration, together with advances in modeling diseases using stem cell-based technology [i.e., induced pluripotent stem cells (iPSCs) and tissue organoids] represent a promising and powerful tool to improve the clinical management of these patients. This is the goal of precision medicine, a novel approach of modern medicine that aims at delivering a specific treatment based on disease-specific biological insights and individual profile. This review will discuss the application and advances of these technologies and how they represent a new opportunity in hepatology.</p>","PeriodicalId":23267,"journal":{"name":"Translational gastroenterology and hepatology","volume":"6 ","pages":"19"},"PeriodicalIF":3.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829068/pdf/tgh-06-20-109.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9185308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-01-01DOI: 10.21037/TGH-2019-LTNA-15
Zunirah Ahmed, M. A. Khan, L. M. Vazquez-Montesino, Aijaz Ahmed
The obesity epidemic has profoundly impacted the epidemiology and trends of liver disease. In the current era, non-alcoholic fatty liver disease (NAFLD) progressing to non-alcoholic steatohepatitis (NASH) has emerged as the second leading indication for liver transplant (LT) and has been associated with the rising rates of hepatocellular carcinoma (HCC) with and without underlying cirrhosis. Obesity has been associated with poor post-transplant outcomes including lower patient and graft survival; higher risk of post-operative metabolic complications; poor wound healing; and higher infection rates. Bariatric surgery is currently the most effective management of morbid obesity and has been offered to patients both in the pre and post LT setting. The techniques attempted in LT recipients most commonly include sleeve gastrectomy (SG), gastric bypass surgery with few cases of gastric banding and biliopancreatic diversion. However, there is lack of evidence-based data on the optimal management for patients with obesity and who are liver transplant candidates and/or recipients. In the following discussion, we present the highlights from a review of the literature.
{"title":"Bariatric surgery, obesity and liver transplantation.","authors":"Zunirah Ahmed, M. A. Khan, L. M. Vazquez-Montesino, Aijaz Ahmed","doi":"10.21037/TGH-2019-LTNA-15","DOIUrl":"https://doi.org/10.21037/TGH-2019-LTNA-15","url":null,"abstract":"The obesity epidemic has profoundly impacted the epidemiology and trends of liver disease. In the current era, non-alcoholic fatty liver disease (NAFLD) progressing to non-alcoholic steatohepatitis (NASH) has emerged as the second leading indication for liver transplant (LT) and has been associated with the rising rates of hepatocellular carcinoma (HCC) with and without underlying cirrhosis. Obesity has been associated with poor post-transplant outcomes including lower patient and graft survival; higher risk of post-operative metabolic complications; poor wound healing; and higher infection rates. Bariatric surgery is currently the most effective management of morbid obesity and has been offered to patients both in the pre and post LT setting. The techniques attempted in LT recipients most commonly include sleeve gastrectomy (SG), gastric bypass surgery with few cases of gastric banding and biliopancreatic diversion. However, there is lack of evidence-based data on the optimal management for patients with obesity and who are liver transplant candidates and/or recipients. In the following discussion, we present the highlights from a review of the literature.","PeriodicalId":23267,"journal":{"name":"Translational gastroenterology and hepatology","volume":"19 1","pages":"25"},"PeriodicalIF":3.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88498566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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