Sabrina Sidali, Claudia Campani, Jihyun An, Ju Hyun Shim, Jean-Charles Nault
Hepatocellular carcinoma (HCC) is the most common primary liver cancer and remains a major cause of cancer-related mortality worldwide. Systemic therapies, including targeted therapies and immune checkpoint inhibitors (ICIs), have revolutionized the management of advanced HCC. Although the prognosis of patients with advanced HCC remains poor, significant progress has been made with recent advances in drug development, particularly with the introduction of effective treatments such as atezolizumab plus bevacizumab or durvalumab plus tremelimumab. Indeed, treatment response varies significantly among patients, highlighting the need for robust biomarkers. In addition, the development of molecular driver-targeted therapies remains an active research focus as most genetic alterations observed in HCC are currently undruggable. Meeting these goals will require additional efforts to obtain histological material in clinical trials, in order to enable robust translational research. This review explores the current landscape of biomarkers of response to systemic treatments in HCC, including molecular, immune-based markers as well as circulating tumor DNA and highlights potential paths of improvement.
{"title":"Tumor-based biomarkers and circulating tumor DNA for precision medicine in advanced hepatocellular carcinoma.","authors":"Sabrina Sidali, Claudia Campani, Jihyun An, Ju Hyun Shim, Jean-Charles Nault","doi":"10.3350/cmh.2025.0746","DOIUrl":"10.3350/cmh.2025.0746","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is the most common primary liver cancer and remains a major cause of cancer-related mortality worldwide. Systemic therapies, including targeted therapies and immune checkpoint inhibitors (ICIs), have revolutionized the management of advanced HCC. Although the prognosis of patients with advanced HCC remains poor, significant progress has been made with recent advances in drug development, particularly with the introduction of effective treatments such as atezolizumab plus bevacizumab or durvalumab plus tremelimumab. Indeed, treatment response varies significantly among patients, highlighting the need for robust biomarkers. In addition, the development of molecular driver-targeted therapies remains an active research focus as most genetic alterations observed in HCC are currently undruggable. Meeting these goals will require additional efforts to obtain histological material in clinical trials, in order to enable robust translational research. This review explores the current landscape of biomarkers of response to systemic treatments in HCC, including molecular, immune-based markers as well as circulating tumor DNA and highlights potential paths of improvement.</p>","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":16.9,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144882252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"\"Surrogates Without Substance?\" Questioning the Evidence for Histologic Improvement With HTD1801.","authors":"Zhihao Lei","doi":"10.3350/cmh.2025.0868","DOIUrl":"10.3350/cmh.2025.0868","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":16.9,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Letter to the editor on \"HTD1801 demonstrates promising potential for histologic improvements in metabolic dysfunction-associated steatohepatitis in both a preclinical and phase 2 study. \".","authors":"Xi-Lin Gao","doi":"10.3350/cmh.2025.0804","DOIUrl":"10.3350/cmh.2025.0804","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":16.9,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lu Jiang, Lan-Duoduo Du, Jing Zeng, Hui-Kuan Chu, Zhong Peng, Jian-Gao Fan
Metabolic dysfunction-associated steatotic liver disease (MASLD), formally known as non-alcoholic fatty liver disease, has become the most common form of chronic liver disease in children. The spectrum of pediatric MASLD ranges from simple steatosis to steatohepatitis, fibrosis, cirrhosis, and in rare cases, hepatocellular carcinoma. Its pathogenesis involves a complex interplay among genetic, epigenetic, and environmental factors, along with alterations in the gut microbiota and its associated metabolites. Given the staggering prevalence and the distinct etiopathogenesis of pediatric MASLD, characterization of the gut microbiota and microbial products could facilitate the development of diagnostic tools and inform targeted therapeutic strategies. Current research on the gut microbiome in the context of pediatric MASLD is limited by small sample size, inadequate use of liver biopsy, methodological inconsistencies in sequencing, and confounding effects from metabolic comorbidities. In this review, we summarize clinical studies on alterations in the gut microbiota and microbial products (short-chain fatty acids, bile acids, and ethanol) that impact the pathogenesis of pediatric MASLD. We discuss the therapeutic potential of dietary modification, pharmacological treatments, and probiotics in improving disease progression by summarizing current clinical studies. Enhancing our understanding of the gut-liver axis may aid in the development of effective therapeutic strategies for pediatric MASLD.
{"title":"Pediatric metabolic dysfunction-associated steatotic liver disease and the gut microbiome: from research landscape to targeted modulation.","authors":"Lu Jiang, Lan-Duoduo Du, Jing Zeng, Hui-Kuan Chu, Zhong Peng, Jian-Gao Fan","doi":"10.3350/cmh.2025.0718","DOIUrl":"10.3350/cmh.2025.0718","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease (MASLD), formally known as non-alcoholic fatty liver disease, has become the most common form of chronic liver disease in children. The spectrum of pediatric MASLD ranges from simple steatosis to steatohepatitis, fibrosis, cirrhosis, and in rare cases, hepatocellular carcinoma. Its pathogenesis involves a complex interplay among genetic, epigenetic, and environmental factors, along with alterations in the gut microbiota and its associated metabolites. Given the staggering prevalence and the distinct etiopathogenesis of pediatric MASLD, characterization of the gut microbiota and microbial products could facilitate the development of diagnostic tools and inform targeted therapeutic strategies. Current research on the gut microbiome in the context of pediatric MASLD is limited by small sample size, inadequate use of liver biopsy, methodological inconsistencies in sequencing, and confounding effects from metabolic comorbidities. In this review, we summarize clinical studies on alterations in the gut microbiota and microbial products (short-chain fatty acids, bile acids, and ethanol) that impact the pathogenesis of pediatric MASLD. We discuss the therapeutic potential of dietary modification, pharmacological treatments, and probiotics in improving disease progression by summarizing current clinical studies. Enhancing our understanding of the gut-liver axis may aid in the development of effective therapeutic strategies for pediatric MASLD.</p>","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":16.9,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Reply to correspondence on \"Factors associated with hepatitis B mother-to-child transmission in a national prevention program\".","authors":"Eunho Choi, Ji Hoon Kim, Young-Sun Lee","doi":"10.3350/cmh.2025.0871","DOIUrl":"10.3350/cmh.2025.0871","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":16.9,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Reply to correspondence on: Methodological Concerns Regarding GLP-1RA Effects on MASLD Outcomes.","authors":"Xingyu Yao","doi":"10.3350/cmh.2025.0892","DOIUrl":"10.3350/cmh.2025.0892","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":16.9,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Letter \"GLP-1 RA and Reduced Liver and Non-Liver Complications in Adults with T2D and MASLD: A Target Trial Emulation Study\".","authors":"Chunyan Wang, Xu Han, Yinyan Li","doi":"10.3350/cmh.2025.0676","DOIUrl":"10.3350/cmh.2025.0676","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":16.9,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Beyond Diagnostic Accuracy: Economic and Clinical Considerations for NC-MRI in Late HCC Recurrence Surveillance.","authors":"Qi-Feng Chen, Sui-Xing Zhong, Ming Zhao","doi":"10.3350/cmh.2025.0769","DOIUrl":"10.3350/cmh.2025.0769","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":16.9,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号