{"title":"Challenges and Innovations in PSC Clinical Trials: Evaluating HK-660S and the Path Forward.","authors":"Nilanga Nishad","doi":"10.3350/cmh.2024.0942","DOIUrl":"https://doi.org/10.3350/cmh.2024.0942","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":14.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567586","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}
Edilmar Alvarado-Tapias, Elisa Pose, Jordi Gratacós, Ana Clemente-Sánchez, Hugo Hugo López-Pelayo, Ramón Bataller
Alcohol consumption is a leading cause of preventable morbidity and mortality worldwide and the primary cause of advanced liver disease. Alcohol use disorder (AUD) is a chronic, frequently relapsing condition characterized by persistent alcohol consumption despite its negative consequences. Alcohol-associated liver disease (ALD) encompasses a series of stages, from fatty liver (steatosis) to inflammation (steatohepatitis), fibrosis, and, ultimately, liver cirrhosis and its complications. The development of ALD is complex, involving both genetic and environmental factors, yet the exact mechanisms at play remain unclear. Alcohol-associated hepatitis (AH), a severe form of ALD, presents with sudden jaundice and liver failure. Currently, there are no approved targeted therapies able to interfere in the pathogenesis of ALD to stop the progression of the disease, making alcohol abstinence the most effective way to improve prognosis across all stages of ALD. For patients with advanced ALD who do not respond to medical therapy, liver transplantation is the only option that can improve prognosis. Recently, AH has become an early indication for liver transplantation in non-responders to medical treatment, showing promising results in carefully selected patients. This review provides an update on the epidemiology, natural history, pathogenesis, and current treatments for ALD. A deeper insight into novel targeted therapies investigated for AH focusing on new pathophysiologically-based agents is also discussed, including anti-inflammatory and antioxidative stress drugs, gut-liver axis modulators, and hepatocyte regenerative molecules.
{"title":"ALCOHOL-ASSOCIATED LIVER DISEASE: NATURAL HISTORY, MANAGEMENT AND NOVEL TARGETED THERAPIES.","authors":"Edilmar Alvarado-Tapias, Elisa Pose, Jordi Gratacós, Ana Clemente-Sánchez, Hugo Hugo López-Pelayo, Ramón Bataller","doi":"10.3350/cmh.2024.0709","DOIUrl":"https://doi.org/10.3350/cmh.2024.0709","url":null,"abstract":"<p><p>Alcohol consumption is a leading cause of preventable morbidity and mortality worldwide and the primary cause of advanced liver disease. Alcohol use disorder (AUD) is a chronic, frequently relapsing condition characterized by persistent alcohol consumption despite its negative consequences. Alcohol-associated liver disease (ALD) encompasses a series of stages, from fatty liver (steatosis) to inflammation (steatohepatitis), fibrosis, and, ultimately, liver cirrhosis and its complications. The development of ALD is complex, involving both genetic and environmental factors, yet the exact mechanisms at play remain unclear. Alcohol-associated hepatitis (AH), a severe form of ALD, presents with sudden jaundice and liver failure. Currently, there are no approved targeted therapies able to interfere in the pathogenesis of ALD to stop the progression of the disease, making alcohol abstinence the most effective way to improve prognosis across all stages of ALD. For patients with advanced ALD who do not respond to medical therapy, liver transplantation is the only option that can improve prognosis. Recently, AH has become an early indication for liver transplantation in non-responders to medical treatment, showing promising results in carefully selected patients. This review provides an update on the epidemiology, natural history, pathogenesis, and current treatments for ALD. A deeper insight into novel targeted therapies investigated for AH focusing on new pathophysiologically-based agents is also discussed, including anti-inflammatory and antioxidative stress drugs, gut-liver axis modulators, and hepatocyte regenerative molecules.</p>","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":14.0,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557300","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}
Kwanjoo Lee, Jaeyu Park, Jinseok Lee, Hayeon Lee, Yeonjung Ha, Dong Keon Yon
{"title":"Correspondence on editorial regarding \"Understanding the impact on digestive disease in the post-COVID-19 condition\".","authors":"Kwanjoo Lee, Jaeyu Park, Jinseok Lee, Hayeon Lee, Yeonjung Ha, Dong Keon Yon","doi":"10.3350/cmh.2024.0935","DOIUrl":"https://doi.org/10.3350/cmh.2024.0935","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":14.0,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521159","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}
Lin Guan, Xinhe Zhang, Shanghao Liu, Xiaolong Qi, Yiling Li
{"title":"Prevalence of steatotic liver disease and associated fibrosis in the general population: an epidemiological survey.","authors":"Lin Guan, Xinhe Zhang, Shanghao Liu, Xiaolong Qi, Yiling Li","doi":"10.3350/cmh.2024.0921","DOIUrl":"https://doi.org/10.3350/cmh.2024.0921","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":14.0,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521161","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":"Momentum Towards Simplifying and Expanding Treatment for Chronic Hepatitis B: The Body of Evidence Continues to Grow.","authors":"Robert J Wong","doi":"10.3350/cmh.2024.0929","DOIUrl":"https://doi.org/10.3350/cmh.2024.0929","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":14.0,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521160","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}
One-third of adults across the globe exhibit metabolic dysfunction-associated steatotic liver disease (MASLD) - formerly known as nonalcoholic fatty liver disease (NAFLD). To date, MASLD is the fastest-growing etiology of chronic liver disease and hepatocellular carcinoma (HCC). Besides the population with obesity, MASLD can also be found in lean populations, accounting for 13% of the global population, especially Asians. Notably, individuals with lean MASLD face equal or higher overall mortality rates compared to their non-lean counterparts. Risk modifiers encompass advanced age, hepatic fibrosis, and type 2 diabetes mellitus (T2DM). Moreover, the population with lean MASLD is associated with an increased risk of HCC, while their non-lean counterparts are more prone to cardiovascular outcomes and T2DM. Existing evidence indicates a similar risk of liver-related events and extrahepatic cancer between the two groups. However, MASLD-related genetic variants, such as PNPLA3 and TM6SF2, did not significantly affect mortality between the two populations. Still, underreporting alcohol consumption and regional representation limits the study's comprehensiveness. Longitudinal studies and mechanistic explorations are needed to understand differences in lean versus non-lean MASLD populations. This review highlights the need for awareness and tailored interventions in managing MASLD, considering lean individuals' unique risks.
{"title":"Long-term Outcomes and Risk Modifiers of MASLD Between Lean and Non-Lean Populations.","authors":"Pojsakorn Danpanichkul, Kanokphong Suparan, Vitchapong Prasitsumrit, Aijaz Ahmed, Karn Wijarnpreecha, Donghee Kim","doi":"10.3350/cmh.2024.0631","DOIUrl":"https://doi.org/10.3350/cmh.2024.0631","url":null,"abstract":"<p><p>One-third of adults across the globe exhibit metabolic dysfunction-associated steatotic liver disease (MASLD) - formerly known as nonalcoholic fatty liver disease (NAFLD). To date, MASLD is the fastest-growing etiology of chronic liver disease and hepatocellular carcinoma (HCC). Besides the population with obesity, MASLD can also be found in lean populations, accounting for 13% of the global population, especially Asians. Notably, individuals with lean MASLD face equal or higher overall mortality rates compared to their non-lean counterparts. Risk modifiers encompass advanced age, hepatic fibrosis, and type 2 diabetes mellitus (T2DM). Moreover, the population with lean MASLD is associated with an increased risk of HCC, while their non-lean counterparts are more prone to cardiovascular outcomes and T2DM. Existing evidence indicates a similar risk of liver-related events and extrahepatic cancer between the two groups. However, MASLD-related genetic variants, such as PNPLA3 and TM6SF2, did not significantly affect mortality between the two populations. Still, underreporting alcohol consumption and regional representation limits the study's comprehensiveness. Longitudinal studies and mechanistic explorations are needed to understand differences in lean versus non-lean MASLD populations. This review highlights the need for awareness and tailored interventions in managing MASLD, considering lean individuals' unique risks.</p>","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":14.0,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496187","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}
Lei Cai, Chao Li, Li-Yang Sun, Yong-Kang Diao, Ming-Da Wang, Tian Yang
{"title":"Urgent Need for Education on Hepatocellular Carcinoma Surveillance Among High-Risk Population in China.","authors":"Lei Cai, Chao Li, Li-Yang Sun, Yong-Kang Diao, Ming-Da Wang, Tian Yang","doi":"10.3350/cmh.2024.0813","DOIUrl":"https://doi.org/10.3350/cmh.2024.0813","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":14.0,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496188","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}
Wen-Ying Chen, Jia-Hui Zhang, Li-Li Chen, Christopher D Byrne, Giovanni Targher, Liang Luo, Yan Ni, Ming-Hua Zheng, Dan-Qin Sun
Metabolites produced as intermediaries or end-products of microbial metabolism provide crucial signals for health and diseases, such as metabolic dysfunction-associated steatotic liver disease (MASLD). These metabolites include products of the bacterial metabolism of dietary substrates, modification of host molecules [such as bile acids (BAs), trimethylamine-N-oxide, and short-chain fatty acids], or products directly derived from bacteria. Recent studies have provided new insights into the association between MASLD and the risk of developing chronic kidney disease (CKD). Furthermore, alterations in microbiota composition and metabolite profiles, notably altered BAs, have been described in studies investigating the association between MASLD and the risk of CKD. This narrative review discusses alterations of specific classes of metabolites, BAs, fructose, vitamin D, and microbiota composition that may be implicated in the link between MASLD and CKD.
作为微生物代谢的中间产物或最终产物产生的代谢物为健康和疾病(如代谢功能障碍相关性脂肪性肝病(MASLD))提供了重要信号。这些代谢物包括细菌代谢食物底物的产物、宿主分子的修饰物[如胆汁酸(BA)、三甲胺-N-氧化物和短链脂肪酸],或直接来自细菌的产物。最近的研究对 MASLD 与慢性肾病(CKD)发病风险之间的关系提供了新的见解。此外,在调查 MASLD 与患慢性肾脏病风险之间关系的研究中,也描述了微生物群组成和代谢物谱的改变,尤其是 BAs 的改变。这篇叙述性综述讨论了可能与 MASLD 和 CKD 之间的联系有关的特定代谢物、BAs、果糖、维生素 D 和微生物群组成的改变。
{"title":"Bioactive metabolites: a clue to the link between MASLD and CKD?","authors":"Wen-Ying Chen, Jia-Hui Zhang, Li-Li Chen, Christopher D Byrne, Giovanni Targher, Liang Luo, Yan Ni, Ming-Hua Zheng, Dan-Qin Sun","doi":"10.3350/cmh.2024.0782","DOIUrl":"https://doi.org/10.3350/cmh.2024.0782","url":null,"abstract":"<p><p>Metabolites produced as intermediaries or end-products of microbial metabolism provide crucial signals for health and diseases, such as metabolic dysfunction-associated steatotic liver disease (MASLD). These metabolites include products of the bacterial metabolism of dietary substrates, modification of host molecules [such as bile acids (BAs), trimethylamine-N-oxide, and short-chain fatty acids], or products directly derived from bacteria. Recent studies have provided new insights into the association between MASLD and the risk of developing chronic kidney disease (CKD). Furthermore, alterations in microbiota composition and metabolite profiles, notably altered BAs, have been described in studies investigating the association between MASLD and the risk of CKD. This narrative review discusses alterations of specific classes of metabolites, BAs, fructose, vitamin D, and microbiota composition that may be implicated in the link between MASLD and CKD.</p>","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":14.0,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459434","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}
Shunda Du, Karin Wisskirchen, Ke Zhang, Ulrike Protzer
{"title":"Correspondence on Editorial regarding \"Genetically modified, redirected T cells target hepatitis B surface antigen-positive hepatocytes and hepatocellular carcinoma lesions in a clinical setting\".","authors":"Shunda Du, Karin Wisskirchen, Ke Zhang, Ulrike Protzer","doi":"10.3350/cmh.2024.0781","DOIUrl":"https://doi.org/10.3350/cmh.2024.0781","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":14.0,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459437","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}