Pub Date : 2022-08-01Epub Date: 2022-09-01DOI: 10.1055/s-0042-1755328
Frederik Nevens, Schalk van der Merwe
Promising preclinical data suggested that bone marrow-derived mesenchymal stem cells (BM-MSC) can reduce hepatic fibrosis and stimulate liver regeneration. Preclinical studies moreover suggested that the immunomodulatory and anti-inflammatory functions of MSCs may reduce hepatic inflammation, improve liver function, and decrease infection incidences which are deemed especially important in the case of acute-on-chronic liver failure (ACLF). Studies in patients with decompensated cirrhosis demonstrated that injection of BM-MSC resulted in an improvement of biochemical tests and led to a survival benefit in ACLF. Most of these studies were performed in hepatitis B virus infected patients. However, two adequately powered studies performed in Europe could not confirm these data. A possible alternative to mobilize BM-MSC into the liver is the use of granulocyte colony-stimulating factor (G-CSF) which has proregenerative and immunomodulatory effects. In Indian studies, the use of G-CSF was associated with improvement of survival, although this finding could not be confirmed in European studies. Human allogeneic liver-derived progenitor cell therapy represents a potential treatment for ACLF, of which the main action is paracrine. These human liver-derived MSC can perform various functions, including the downregulation of proinflammatory responses. The clinical beneficial effect of these cells is further explored in patients with alcoholic cirrhosis and ACLF in Europe.
{"title":"Mesenchymal Stem Cell Transplantation in Liver Diseases.","authors":"Frederik Nevens, Schalk van der Merwe","doi":"10.1055/s-0042-1755328","DOIUrl":"https://doi.org/10.1055/s-0042-1755328","url":null,"abstract":"<p><p>Promising preclinical data suggested that bone marrow-derived mesenchymal stem cells (BM-MSC) can reduce hepatic fibrosis and stimulate liver regeneration. Preclinical studies moreover suggested that the immunomodulatory and anti-inflammatory functions of MSCs may reduce hepatic inflammation, improve liver function, and decrease infection incidences which are deemed especially important in the case of acute-on-chronic liver failure (ACLF). Studies in patients with decompensated cirrhosis demonstrated that injection of BM-MSC resulted in an improvement of biochemical tests and led to a survival benefit in ACLF. Most of these studies were performed in hepatitis B virus infected patients. However, two adequately powered studies performed in Europe could not confirm these data. A possible alternative to mobilize BM-MSC into the liver is the use of granulocyte colony-stimulating factor (G-CSF) which has proregenerative and immunomodulatory effects. In Indian studies, the use of G-CSF was associated with improvement of survival, although this finding could not be confirmed in European studies. Human allogeneic liver-derived progenitor cell therapy represents a potential treatment for ACLF, of which the main action is paracrine. These human liver-derived MSC can perform various functions, including the downregulation of proinflammatory responses. The clinical beneficial effect of these cells is further explored in patients with alcoholic cirrhosis and ACLF in Europe.</p>","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40337213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
N. Chew, C. Ng, Emily Truong, M. Noureddin, K. Kowdley
Non-alcoholic steatohepatitis (NASH) is a burgeoning global health crisis that mirrors the obesity pandemic. This global health crisis has stimulated active research to develop novel NASH pharmacotherapies targeting dysregulated inflammatory, cellular stress and fibrogenetic processes that include: 1) metabolic pathways to improve insulin sensitivity, de-novo lipogenesis, and mitochondrial utilization of fatty acids, 2) cellular injury or inflammatory targets that reduce inflammatory cell recruitment and signalling, 3) liver-gut axis targets that influence bile acid enterohepatic circulation and signalling, and 4) anti-fibrotic targets. In this review, we summarize several of the therapeutic agents that have been studied in phase 2 and 3 randomized trials. In addition to reviewing novel therapeutic drugs targeting nuclear receptor pathways, liver chemokine receptors, liver lipid metabolism, lipotoxicity or cell death, and glucagon-like peptide-1 receptors, we also discuss the rationale behind the use of combination therapy and the lessons learned from unsuccessful or negative clinical trials.
{"title":"Non-Alcoholic Steatohepatitis Drug Development Pipeline: An Update.","authors":"N. Chew, C. Ng, Emily Truong, M. Noureddin, K. Kowdley","doi":"10.1055/a-1877-9656","DOIUrl":"https://doi.org/10.1055/a-1877-9656","url":null,"abstract":"Non-alcoholic steatohepatitis (NASH) is a burgeoning global health crisis that mirrors the obesity pandemic. This global health crisis has stimulated active research to develop novel NASH pharmacotherapies targeting dysregulated inflammatory, cellular stress and fibrogenetic processes that include: 1) metabolic pathways to improve insulin sensitivity, de-novo lipogenesis, and mitochondrial utilization of fatty acids, 2) cellular injury or inflammatory targets that reduce inflammatory cell recruitment and signalling, 3) liver-gut axis targets that influence bile acid enterohepatic circulation and signalling, and 4) anti-fibrotic targets. In this review, we summarize several of the therapeutic agents that have been studied in phase 2 and 3 randomized trials. In addition to reviewing novel therapeutic drugs targeting nuclear receptor pathways, liver chemokine receptors, liver lipid metabolism, lipotoxicity or cell death, and glucagon-like peptide-1 receptors, we also discuss the rationale behind the use of combination therapy and the lessons learned from unsuccessful or negative clinical trials.","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2022-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86085809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The biliary tree comprises intrahepatic bile ducts and extrahepatic bile ducts lined with epithelial cells known as biliary epithelial cells (BECs). BECs are a common target of various cholangiopathies for which there is an unmet therapeutic need in clinical hepatology. The repair and regeneration of biliary tissue may potentially restore the normal architecture and function of the biliary tree. Hence, the repair and regeneration process in detail, including the replication of existing BECs, expansion and differentiation of the hepatic progenitor cells and biliary tree stem/progenitor cells, and transdifferentiation of the hepatocytes, should be understood. In this paper, we review biliary tree homeostasis, repair, and regeneration and discuss the feasibility of regenerative therapy strategies for cholangiopathy treatment.
{"title":"Cellular Homeostasis and Repair in the Biliary Tree.","authors":"Wei Wang, Dongfeng Chen, Jun Wang, Liangzhi Wen","doi":"10.1055/a-1869-7714","DOIUrl":"https://doi.org/10.1055/a-1869-7714","url":null,"abstract":"The biliary tree comprises intrahepatic bile ducts and extrahepatic bile ducts lined with epithelial cells known as biliary epithelial cells (BECs). BECs are a common target of various cholangiopathies for which there is an unmet therapeutic need in clinical hepatology. The repair and regeneration of biliary tissue may potentially restore the normal architecture and function of the biliary tree. Hence, the repair and regeneration process in detail, including the replication of existing BECs, expansion and differentiation of the hepatic progenitor cells and biliary tree stem/progenitor cells, and transdifferentiation of the hepatocytes, should be understood. In this paper, we review biliary tree homeostasis, repair, and regeneration and discuss the feasibility of regenerative therapy strategies for cholangiopathy treatment.","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2022-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81715578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Kulkarni, M. Premkumar, J. Arab, Karan Kumar, Mithun Sharma, N. Reddy, N. Padaki, R. Reddy
Cirrhosis is a risk factor for infections. Majority of hospital admissions in patients with cirrhosis are due to infections. Sepsis is an immunological response to an infectious process that leads to end-organ dysfunction and death. Preventing infections may avoid the downstream complications and early diagnosis of infections may improve the outcomes. In this review, we discuss the pathogenesis, diagnosis, and biomarkers of infection, as well as incremental preventive strategies for infections and sepsis and consequent organ failures in cirrhosis. Strategies for primary prevention include reducing gut translocation by selective intestinal decontamination, avoiding unnecessary proton pump inhibitors' use, appropriate use of beta-blockers and vaccinations for viral diseases, including coronavirus disease-2019. Secondary prevention includes early diagnosis and timely and judicious use of antibiotics to prevent organ dysfunction. Organ failure support constitutes tertiary intervention in cirrhosis. In conclusion, infections in cirrhosis are potentially preventable with appropriate care strategies to then enable to improve outcomes.
{"title":"EARLY DIAGNOSIS AND PREVENTION OF INFECTIONS IN CIRRHOSIS.","authors":"A. Kulkarni, M. Premkumar, J. Arab, Karan Kumar, Mithun Sharma, N. Reddy, N. Padaki, R. Reddy","doi":"10.1055/a-1869-7607","DOIUrl":"https://doi.org/10.1055/a-1869-7607","url":null,"abstract":"Cirrhosis is a risk factor for infections. Majority of hospital admissions in patients with cirrhosis are due to infections. Sepsis is an immunological response to an infectious process that leads to end-organ dysfunction and death. Preventing infections may avoid the downstream complications and early diagnosis of infections may improve the outcomes. In this review, we discuss the pathogenesis, diagnosis, and biomarkers of infection, as well as incremental preventive strategies for infections and sepsis and consequent organ failures in cirrhosis. Strategies for primary prevention include reducing gut translocation by selective intestinal decontamination, avoiding unnecessary proton pump inhibitors' use, appropriate use of beta-blockers and vaccinations for viral diseases, including coronavirus disease-2019. Secondary prevention includes early diagnosis and timely and judicious use of antibiotics to prevent organ dysfunction. Organ failure support constitutes tertiary intervention in cirrhosis. In conclusion, infections in cirrhosis are potentially preventable with appropriate care strategies to then enable to improve outcomes.","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2022-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77732300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. El‐Kassas, J. Cabezas, P. Iruzubieta, M. Zheng, J. Arab, A. Awad
The map and global disease burden of chronic liver diseases are markedly changing, with non-alcoholic fatty liver disease (NAFLD) becoming the most common cause of liver affection coinciding with the current epidemics of obesity, type 2 diabetes, and metabolic syndrome. Understanding the incidence and prevalence of NAFLD is critical because of its linkage to a significant economic burden of hospitalization and changing patterns in consequences such as liver transplantation. Moreover, the long-term average healthcare expenses of NAFLD patients have exceeded those of other liver diseases. To lessen the imminent burden of NAFLD, immediate actions to raise worldwide awareness and address metabolic risk factors are required. This review summarizes key data about the global disease burden of NAFLD, modifiable and non-modifiable risk factors, and current preventive approaches.
{"title":"Non-alcoholic Fatty Liver Disease: Current Global Burden.","authors":"M. El‐Kassas, J. Cabezas, P. Iruzubieta, M. Zheng, J. Arab, A. Awad","doi":"10.1055/a-1862-9088","DOIUrl":"https://doi.org/10.1055/a-1862-9088","url":null,"abstract":"The map and global disease burden of chronic liver diseases are markedly changing, with non-alcoholic fatty liver disease (NAFLD) becoming the most common cause of liver affection coinciding with the current epidemics of obesity, type 2 diabetes, and metabolic syndrome. Understanding the incidence and prevalence of NAFLD is critical because of its linkage to a significant economic burden of hospitalization and changing patterns in consequences such as liver transplantation. Moreover, the long-term average healthcare expenses of NAFLD patients have exceeded those of other liver diseases. To lessen the imminent burden of NAFLD, immediate actions to raise worldwide awareness and address metabolic risk factors are required. This review summarizes key data about the global disease burden of NAFLD, modifiable and non-modifiable risk factors, and current preventive approaches.","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2022-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87663175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-01Epub Date: 2022-06-23DOI: 10.1055/s-0042-1748188
Magdalena Rogalska-Taranta, Jesper B Andersen
Cholangiocarcinoma (CCA) is the second most common type of primary liver cancer. Due to its often-silent manifestation, sporadic nature, and typically late clinical presentation, it remains difficult to diagnose and lacks effective nonsurgical therapeutic options. Extensive research aiming in understanding the mechanisms underlying this disease have provided strong evidence for the significance of epigenetics contributing to its onset, progression, and dissemination. This dysregulation in a myriad of signaling pathways, leading to malignancy, spans altered deoxyribonucleic acid and histone methylation, histone acetylation, and chromatin remodeling, as well as genetic modifications in essential genes controlling these epigenetic processes. An advantage to epigenetic modifications is that they, compared with mutations, are reversible and can partially be controlled by inhibiting the responsible enzymatic machinery. This opens novel possibilities for developing new treatment modalities with benefit for CCA patients.In this article, we have reviewed the current status of epigenome modifications described in CCA, including the role of posttranslational histone modifications and chromatin remodeling, as well as novel advances in treatment options.
{"title":"Involvement of Epigenomic Factors in Bile Duct Cancer.","authors":"Magdalena Rogalska-Taranta, Jesper B Andersen","doi":"10.1055/s-0042-1748188","DOIUrl":"https://doi.org/10.1055/s-0042-1748188","url":null,"abstract":"<p><p>Cholangiocarcinoma (CCA) is the second most common type of primary liver cancer. Due to its often-silent manifestation, sporadic nature, and typically late clinical presentation, it remains difficult to diagnose and lacks effective nonsurgical therapeutic options. Extensive research aiming in understanding the mechanisms underlying this disease have provided strong evidence for the significance of epigenetics contributing to its onset, progression, and dissemination. This dysregulation in a myriad of signaling pathways, leading to malignancy, spans altered deoxyribonucleic acid and histone methylation, histone acetylation, and chromatin remodeling, as well as genetic modifications in essential genes controlling these epigenetic processes. An advantage to epigenetic modifications is that they, compared with mutations, are reversible and can partially be controlled by inhibiting the responsible enzymatic machinery. This opens novel possibilities for developing new treatment modalities with benefit for CCA patients.In this article, we have reviewed the current status of epigenome modifications described in CCA, including the role of posttranslational histone modifications and chromatin remodeling, as well as novel advances in treatment options.</p>","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40323313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jeffrey V Lazarus, Camila A Picchio, Christopher J Byrne, Javier Crespo, Massimo Colombo, Graham S Cooke, Gregory J Dore, Jason Grebely, John W Ward, John F Dillon
Microelimination targets specific subpopulations and/or geographic settings for hepatitis C virus (HCV) elimination. This review reports on global HCV microelimination literature published from 2013 to 2020. Data were extracted from publications to report a score based on the four key components defining microelimination. Sustained virologic response (SVR) and treatment initiation proportions were calculated for each manuscript and grouped means of these estimates were compared depending on microelimination score and care setting. A total of 83% of the studies were from high-income settings and mainly included people who use drugs or those incarcerated. Among manuscripts, 18 had "low" microelimination scores, 11 had "high" scores, and the differences in mean proportion who initiated treatment and achieved SVR between low and high score groups were statistically significant. Microelimination can be a useful complementary strategy for driving engagement in HCV treatment and cure. Our analysis suggests that adhering to more of the core microelimination components can improve outcomes. This study is registered with Prospero, registration identification: CRD42020175211.
{"title":"A Global Systematic Review of Hepatitis C Elimination Efforts through Micro-Elimination.","authors":"Jeffrey V Lazarus, Camila A Picchio, Christopher J Byrne, Javier Crespo, Massimo Colombo, Graham S Cooke, Gregory J Dore, Jason Grebely, John W Ward, John F Dillon","doi":"10.1055/a-1777-6112","DOIUrl":"https://doi.org/10.1055/a-1777-6112","url":null,"abstract":"<p><p>Microelimination targets specific subpopulations and/or geographic settings for hepatitis C virus (HCV) elimination. This review reports on global HCV microelimination literature published from 2013 to 2020. Data were extracted from publications to report a score based on the four key components defining microelimination. Sustained virologic response (SVR) and treatment initiation proportions were calculated for each manuscript and grouped means of these estimates were compared depending on microelimination score and care setting. A total of 83% of the studies were from high-income settings and mainly included people who use drugs or those incarcerated. Among manuscripts, 18 had \"low\" microelimination scores, 11 had \"high\" scores, and the differences in mean proportion who initiated treatment and achieved SVR between low and high score groups were statistically significant. Microelimination can be a useful complementary strategy for driving engagement in HCV treatment and cure. Our analysis suggests that adhering to more of the core microelimination components can improve outcomes. This study is registered with Prospero, registration identification: CRD42020175211.</p>","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10265001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-01Epub Date: 2022-06-23DOI: 10.1055/s-0042-1745871
Wen-Zheng Yuan, Tao Fu
With the spread of coronavirus disease 2019 (COVID-19) worldwide, extrapulmonary lesions, including liver dysfunction, have attracted growing attention. The mechanisms underlying liver dysfunction in COVID-19 remain unclear. The reported prevalence of liver dysfunction varies widely across studies. In addition, its impact on clinical outcomes and its recovery after discharge are still controversial. In this review, pathological and laboratory findings were analyzed to reveal the potential mechanisms of COVID-19-induced liver injury from onset to recovery. Four patterns of liver damage were summarized according to the pathological findings, including hypoxemia and shock changes, vascular thrombosis and vascular damage, bile duct damage, and other histological changes. With a strict definition, the prevalence of liver dysfunction was not as high as reported. Meanwhile, liver dysfunction improved during the process of recovery. Nevertheless, the definite liver dysfunction was significantly associated with severe clinical course, which should not be ignored.
{"title":"Liver Dysfunction in COVID-19: From Onset to Recovery.","authors":"Wen-Zheng Yuan, Tao Fu","doi":"10.1055/s-0042-1745871","DOIUrl":"https://doi.org/10.1055/s-0042-1745871","url":null,"abstract":"<p><p>With the spread of coronavirus disease 2019 (COVID-19) worldwide, extrapulmonary lesions, including liver dysfunction, have attracted growing attention. The mechanisms underlying liver dysfunction in COVID-19 remain unclear. The reported prevalence of liver dysfunction varies widely across studies. In addition, its impact on clinical outcomes and its recovery after discharge are still controversial. In this review, pathological and laboratory findings were analyzed to reveal the potential mechanisms of COVID-19-induced liver injury from onset to recovery. Four patterns of liver damage were summarized according to the pathological findings, including hypoxemia and shock changes, vascular thrombosis and vascular damage, bile duct damage, and other histological changes. With a strict definition, the prevalence of liver dysfunction was not as high as reported. Meanwhile, liver dysfunction improved during the process of recovery. Nevertheless, the definite liver dysfunction was significantly associated with severe clinical course, which should not be ignored.</p>","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40323311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-01Epub Date: 2022-06-23DOI: 10.1055/s-0042-1748924
Lauren Tal Grinspan, Augusto Villanueva
Liver cancer incidence rate continues to increase and currently ranks third in the total number of annual deaths, behind only lung and colorectal cancer. Most patients with hepatocellular carcinoma (HCC) are diagnosed at advanced stages, and they live for less than 2 years after diagnosis on average. This contrasts with those diagnosed at an early stage, who can be cured with surgery. However, even after curative resection, there remains a risk of up to 70% of postoperative HCC recurrence. There have been major changes in the management of HCC in the past 5 years, particularly for patients at advanced stages. Despite this multitude of new therapies, there is a lack of clear biomarkers to guide providers on the best approach to sequence therapies, which would maximize efficacy while minimizing toxicity. There are several areas in clinical management of HCC that are particularly challenging, and would benefit from development and implementation of new biomarkers to improve patient overall survival. Here, we review the major advances in liquid biopsy biomarkers for early detection of HCC, minimum residual disease, and predicting response to treatment.
{"title":"Biomarker Development Using Liquid Biopsy in Hepatocellular Carcinoma.","authors":"Lauren Tal Grinspan, Augusto Villanueva","doi":"10.1055/s-0042-1748924","DOIUrl":"https://doi.org/10.1055/s-0042-1748924","url":null,"abstract":"<p><p>Liver cancer incidence rate continues to increase and currently ranks third in the total number of annual deaths, behind only lung and colorectal cancer. Most patients with hepatocellular carcinoma (HCC) are diagnosed at advanced stages, and they live for less than 2 years after diagnosis on average. This contrasts with those diagnosed at an early stage, who can be cured with surgery. However, even after curative resection, there remains a risk of up to 70% of postoperative HCC recurrence. There have been major changes in the management of HCC in the past 5 years, particularly for patients at advanced stages. Despite this multitude of new therapies, there is a lack of clear biomarkers to guide providers on the best approach to sequence therapies, which would maximize efficacy while minimizing toxicity. There are several areas in clinical management of HCC that are particularly challenging, and would benefit from development and implementation of new biomarkers to improve patient overall survival. Here, we review the major advances in liquid biopsy biomarkers for early detection of HCC, minimum residual disease, and predicting response to treatment.</p>","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40323312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Circadian rhythms are approximately 24-hour cycles of variation in physiological processes, gene expression, and behavior. They result from the interplay of internal biological clocks with daily environmental rhythms, including light/dark and feeding/fasting. Note that 24-hour rhythms of liver metabolic processes have been known for almost 100 years. Modern studies reveal that, like metabolism, hepatic gene expression is highly rhythmic. Genetic or environmental changes can disrupt the circadian rhythms of the liver, leading to metabolic disorders and hepatocellular carcinoma. In this review, we summarize the current understanding of mechanisms regulating rhythmic gene expression in the liver, highlighting the roles of transcription factors that comprise the core clock molecular as well as noncanonical regulators. We emphasize the plasticity of circadian rhythms in the liver as it responds to multiple inputs from the external and internal environments as well as the potential of circadian medicine to impact liver-related diseases.
{"title":"Circadian Regulation of Gene Expression and Metabolism in the Liver.","authors":"Dongyin Guan, Mitchell A Lazar","doi":"10.1055/a-1792-4240","DOIUrl":"https://doi.org/10.1055/a-1792-4240","url":null,"abstract":"<p><p>Circadian rhythms are approximately 24-hour cycles of variation in physiological processes, gene expression, and behavior. They result from the interplay of internal biological clocks with daily environmental rhythms, including light/dark and feeding/fasting. Note that 24-hour rhythms of liver metabolic processes have been known for almost 100 years. Modern studies reveal that, like metabolism, hepatic gene expression is highly rhythmic. Genetic or environmental changes can disrupt the circadian rhythms of the liver, leading to metabolic disorders and hepatocellular carcinoma. In this review, we summarize the current understanding of mechanisms regulating rhythmic gene expression in the liver, highlighting the roles of transcription factors that comprise the core clock molecular as well as noncanonical regulators. We emphasize the plasticity of circadian rhythms in the liver as it responds to multiple inputs from the external and internal environments as well as the potential of circadian medicine to impact liver-related diseases.</p>","PeriodicalId":21724,"journal":{"name":"Seminars in liver disease","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9806798/pdf/nihms-1853541.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10454216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}