The natural history of cirrhosis varies and therefore prognostic prediction is critical given the sizable patient population. A variety of clinical prognostic indicators have been developed and enable patient risk str...The natural history of cirrhosis varies and therefore prognostic prediction is critical given the sizable patient population. A variety of clinical prognostic indicators have been developed and enable patient risk stratification although their performance is somewhat limited especially within relatively earlier stage of disease. Molecular prognostic indicators are expected to refine the prediction,and potentially link a subset of patients with molecular targeted interventions that counteract poor prognosis. Here we overview clinical and molecular prognostic indicators in the literature,and discuss critical issues to successfully define,evaluate,and deploy prognostic indicators as clinical scores or tests. The use of liver biopsy has been diminishing due to sampling variability on fibrosis assessment and emergence of imaging- or lab testbased fibrosis assessment methods. However,recent rapid developments of genomics technologies and selective molecular targeted agents has highlighted the need for biopsy tissue specimen to explore and establish molecular information-guided personalized/stratified clinical care,and eventually achieve "precision medicine".展开更多
Hepatocellular carcinoma(HCC)is the sixth most common cancer worldwide and leading cause of death among patients with cirrhosis.Treatment guidelines are based according to the Barcelona Clinic Liver Cancer staging sys...Hepatocellular carcinoma(HCC)is the sixth most common cancer worldwide and leading cause of death among patients with cirrhosis.Treatment guidelines are based according to the Barcelona Clinic Liver Cancer staging system.The choice among therapeutic options that include liver resection,liver transplantation,locoregional,and systemic treatments must be individualized for each patient.The aim of this paper is to review the outcomes that can be achieved in the treatment of HCC with the heterogeneous therapeutic options currently available in clinical practice.展开更多
Early detection of hepatocellular carcinoma(HCC)while in its early stages is critical for reducing HCC mortality in high-risk patients.However,highly sensitive and specific surveillance biomarkers for early-stage HCC ...Early detection of hepatocellular carcinoma(HCC)while in its early stages is critical for reducing HCC mortality in high-risk patients.However,highly sensitive and specific surveillance biomarkers for early-stage HCC detection are still lacking.In recent years,great efforts have been made to research tumor-derived molecular features that are detectable in circulation,such as circulating tumor deoxyribonucleic acid and circulating tumor ribonucleic acid,in order to explore their potential as noninvasive biomarker candidates in many tumor types.In this review,we summarize current studies on these new approaches and their application in early HCC detection.展开更多
Viral hepatitis,alcohol-associated liver disease(ALD)and non-alcoholic fatty liver disease(NAFLD)are the three major causes of chronic liver diseases,which account for approximately 2 million deaths per year worldwide...Viral hepatitis,alcohol-associated liver disease(ALD)and non-alcoholic fatty liver disease(NAFLD)are the three major causes of chronic liver diseases,which account for approximately 2 million deaths per year worldwide.The current direct-acting antiviral drugs and vaccinations have effectively reduced and ameliorated viral hepatitis infection,but there are still no effective drug treatments for ALD,NAFLD and liver cancer due to the poor understanding of their pathogenesis.To better understand the pathogenesis,the fifth Chinese American Liver Society/Society of Chinese Bioscientists in America Hepatology Division Annual Symposium,which was held virtually on 21–22 October 2022,focused on the topics related to ALD,NAFLD and liver cancer.Here,we briefly highlight the presentations that focus on the current progress in basic and translational research in ALD,NAFLD and liver cancer.The roles of non-coding RNA,autophagy,extrahepatic signalling,macrophages,etc in liver diseases are deliberated,and the application of single-cell RNA sequencing in the study of liver disease is also discussed.展开更多
Immune-based therapies such as immune checkpoint inhibitors have revolutionized the systemic treatment of various cancer types.The therapeutic application of monoclonal antibodies targeting inhibitory pathways such as...Immune-based therapies such as immune checkpoint inhibitors have revolutionized the systemic treatment of various cancer types.The therapeutic application of monoclonal antibodies targeting inhibitory pathways such as programmed cell death-1(PD-1)/programmed cell death ligand 1(PD-L1)and CTLA-4 to cells of the adaptive immune system has recently been shown to generate meaningful improvement in the clinical outcome of hepatocellular carcinoma(HCC).Nevertheless,current immunotherapeutic approaches induce durable responses in only a subset of HCC patients.Since immunologic mechanisms such as chronic inflammation due to chronic viral hepatitis or alcoholic and nonalcoholic fatty liver disease play a crucial role in the initiation,development,and progression of HCC,it is important to understand the underlying mechanisms shaping the unique tumor microenvironment of liver cancer.The liver is an immunologic organ with large populations of innate and innate-like immune cells and is exposed to bacterial,viral,and fungal antigens through the gut-liver axis.Here,we summarize and highlight the role of these cells in liver cancer and propose strategies to therapeutically target them.We also discuss current immunotherapeutic strategies in HCC and outline recent advances in our understanding of how the therapeutic potential of these agents might be enhanced.展开更多
Intrahepatic cholangiocarcinoma(iCCA)is an aggressive and heterogeneous biliary cancer with a poor prognosis and limited treatment options.The molecular pathogenesis of iCCA involves a highly complex process entailing...Intrahepatic cholangiocarcinoma(iCCA)is an aggressive and heterogeneous biliary cancer with a poor prognosis and limited treatment options.The molecular pathogenesis of iCCA involves a highly complex process entailing multiple genetic alterations and dysregulation of signaling pathways.Recent advancements in our understanding of the genetic landscape of iCCA have opened new opportunities for therapeutic interventions.Technologies such as next-generation sequencing(NGS)have contributed to elucidating the genetic heterogeneity of iCCA,leading to the identification of numerous potentially actionable genetic alterations.Despite these advances,the prognosis of iCCA patients remains dismal.In this review,we provide an extensive summary of the current knowledge on genetic alterations in iCCA,their biological impact on patients,potential therapeutic targets,approved targeted therapies,and ongoing clinical trials with targeted agents.Furthermore,we discuss the main technologies available for studying genetic alterations and their advantages and limitations.Finally,we highlight future directions in studying genetic alterations and the development of new targeted therapies and personalized medicine approaches.展开更多
Hepatocellular carcinoma(HCC)is an increasingly prevalent and deadly disease that is initiated by different etiological factors,such as alcohol-associated liver disease(ALD),metabolic dysfunction-associated steatohepa...Hepatocellular carcinoma(HCC)is an increasingly prevalent and deadly disease that is initiated by different etiological factors,such as alcohol-associated liver disease(ALD),metabolic dysfunction-associated steatohepatitis(MASH),viral hepatitis,and other hepatotoxic and hepatocarcinogenic agents.The tumor microenvironment(TME)of HCC is characterized by several different fibroblastic and immune cell types,all of which affect the initiation,progression and metastasis of this malignant cancer.This complex immune TME can be divided into an innate component that includes macrophages,neutrophils,dendritic cells,myeloid-derived suppressor cells,mucosal-associated invariant T cells,natural killer cells,natural killer T cells,and innate lymphoid cells,as well as an adaptive component that includes CD4+T cells,CD8+T cells,regulatory T cells,and B cells.In this review,we discuss the latest findings shedding light on the direct or indirect roles of these immune cells(and fibroblastic-like cells such as hepatic stellate cells)in the pathogenesis of HCC.Henceforth,further characterization of this heterogeneous TME is highly important for studying the progression of HCC and developing novel immunotherapeutic treatment options.In line with this,we also review novel groundbreaking experimental techniques and animal models aimed at specifically elucidating this complex TME and discuss emerging immune-based therapeutic strategies intended to treat HCC and predict the efficacy of these immunotherapies.展开更多
基金Supported by FLAGS FoundationNuovo-Soldati Cancer Research Foundation+1 种基金advanced training grant from Geneva University Hospital to NG,NIH/NIDDK R01 DK099558the Irma T Hirschl Trust to YH
文摘The natural history of cirrhosis varies and therefore prognostic prediction is critical given the sizable patient population. A variety of clinical prognostic indicators have been developed and enable patient risk stratification although their performance is somewhat limited especially within relatively earlier stage of disease. Molecular prognostic indicators are expected to refine the prediction,and potentially link a subset of patients with molecular targeted interventions that counteract poor prognosis. Here we overview clinical and molecular prognostic indicators in the literature,and discuss critical issues to successfully define,evaluate,and deploy prognostic indicators as clinical scores or tests. The use of liver biopsy has been diminishing due to sampling variability on fibrosis assessment and emergence of imaging- or lab testbased fibrosis assessment methods. However,recent rapid developments of genomics technologies and selective molecular targeted agents has highlighted the need for biopsy tissue specimen to explore and establish molecular information-guided personalized/stratified clinical care,and eventually achieve "precision medicine".
文摘Hepatocellular carcinoma(HCC)is the sixth most common cancer worldwide and leading cause of death among patients with cirrhosis.Treatment guidelines are based according to the Barcelona Clinic Liver Cancer staging system.The choice among therapeutic options that include liver resection,liver transplantation,locoregional,and systemic treatments must be individualized for each patient.The aim of this paper is to review the outcomes that can be achieved in the treatment of HCC with the heterogeneous therapeutic options currently available in clinical practice.
文摘Early detection of hepatocellular carcinoma(HCC)while in its early stages is critical for reducing HCC mortality in high-risk patients.However,highly sensitive and specific surveillance biomarkers for early-stage HCC detection are still lacking.In recent years,great efforts have been made to research tumor-derived molecular features that are detectable in circulation,such as circulating tumor deoxyribonucleic acid and circulating tumor ribonucleic acid,in order to explore their potential as noninvasive biomarker candidates in many tumor types.In this review,we summarize current studies on these new approaches and their application in early HCC detection.
基金Supported by the National Institutes of Health of the USA(DK122708,DK121330 and DK122796)to CJthe intramural research program of the Center for Cancer Research,National Cancer Institute of the USA(ZIA BC 012079 and ZIA BC 012083)to LM.
文摘Viral hepatitis,alcohol-associated liver disease(ALD)and non-alcoholic fatty liver disease(NAFLD)are the three major causes of chronic liver diseases,which account for approximately 2 million deaths per year worldwide.The current direct-acting antiviral drugs and vaccinations have effectively reduced and ameliorated viral hepatitis infection,but there are still no effective drug treatments for ALD,NAFLD and liver cancer due to the poor understanding of their pathogenesis.To better understand the pathogenesis,the fifth Chinese American Liver Society/Society of Chinese Bioscientists in America Hepatology Division Annual Symposium,which was held virtually on 21–22 October 2022,focused on the topics related to ALD,NAFLD and liver cancer.Here,we briefly highlight the presentations that focus on the current progress in basic and translational research in ALD,NAFLD and liver cancer.The roles of non-coding RNA,autophagy,extrahepatic signalling,macrophages,etc in liver diseases are deliberated,and the application of single-cell RNA sequencing in the study of liver disease is also discussed.
基金supported by the Intramural Research Program of the NIH,NCI(ZIA BC 011345).
文摘Immune-based therapies such as immune checkpoint inhibitors have revolutionized the systemic treatment of various cancer types.The therapeutic application of monoclonal antibodies targeting inhibitory pathways such as programmed cell death-1(PD-1)/programmed cell death ligand 1(PD-L1)and CTLA-4 to cells of the adaptive immune system has recently been shown to generate meaningful improvement in the clinical outcome of hepatocellular carcinoma(HCC).Nevertheless,current immunotherapeutic approaches induce durable responses in only a subset of HCC patients.Since immunologic mechanisms such as chronic inflammation due to chronic viral hepatitis or alcoholic and nonalcoholic fatty liver disease play a crucial role in the initiation,development,and progression of HCC,it is important to understand the underlying mechanisms shaping the unique tumor microenvironment of liver cancer.The liver is an immunologic organ with large populations of innate and innate-like immune cells and is exposed to bacterial,viral,and fungal antigens through the gut-liver axis.Here,we summarize and highlight the role of these cells in liver cancer and propose strategies to therapeutically target them.We also discuss current immunotherapeutic strategies in HCC and outline recent advances in our understanding of how the therapeutic potential of these agents might be enhanced.
基金DS is supported by the Tisch Cancer Institute(Icahn School of Medicine at Mount Sinai),the F.Klion Award,i3 Genesis Award and the TCI Dev.Funds Award 2023.
文摘Intrahepatic cholangiocarcinoma(iCCA)is an aggressive and heterogeneous biliary cancer with a poor prognosis and limited treatment options.The molecular pathogenesis of iCCA involves a highly complex process entailing multiple genetic alterations and dysregulation of signaling pathways.Recent advancements in our understanding of the genetic landscape of iCCA have opened new opportunities for therapeutic interventions.Technologies such as next-generation sequencing(NGS)have contributed to elucidating the genetic heterogeneity of iCCA,leading to the identification of numerous potentially actionable genetic alterations.Despite these advances,the prognosis of iCCA patients remains dismal.In this review,we provide an extensive summary of the current knowledge on genetic alterations in iCCA,their biological impact on patients,potential therapeutic targets,approved targeted therapies,and ongoing clinical trials with targeted agents.Furthermore,we discuss the main technologies available for studying genetic alterations and their advantages and limitations.Finally,we highlight future directions in studying genetic alterations and the development of new targeted therapies and personalized medicine approaches.
文摘Hepatocellular carcinoma(HCC)is an increasingly prevalent and deadly disease that is initiated by different etiological factors,such as alcohol-associated liver disease(ALD),metabolic dysfunction-associated steatohepatitis(MASH),viral hepatitis,and other hepatotoxic and hepatocarcinogenic agents.The tumor microenvironment(TME)of HCC is characterized by several different fibroblastic and immune cell types,all of which affect the initiation,progression and metastasis of this malignant cancer.This complex immune TME can be divided into an innate component that includes macrophages,neutrophils,dendritic cells,myeloid-derived suppressor cells,mucosal-associated invariant T cells,natural killer cells,natural killer T cells,and innate lymphoid cells,as well as an adaptive component that includes CD4+T cells,CD8+T cells,regulatory T cells,and B cells.In this review,we discuss the latest findings shedding light on the direct or indirect roles of these immune cells(and fibroblastic-like cells such as hepatic stellate cells)in the pathogenesis of HCC.Henceforth,further characterization of this heterogeneous TME is highly important for studying the progression of HCC and developing novel immunotherapeutic treatment options.In line with this,we also review novel groundbreaking experimental techniques and animal models aimed at specifically elucidating this complex TME and discuss emerging immune-based therapeutic strategies intended to treat HCC and predict the efficacy of these immunotherapies.
