Pub Date : 2023-12-01DOI: 10.1016/j.livres.2023.11.001
Mingna Li , Kuerbannisa Wulayin , Shutao Lin , Chao Wu , Lubiao Chen
Although direct-acting antivirals (DAAs) have notably increased the sustained virological response (SVR) rates in hepatitis C virus (HCV)-infected adolescent patients, the efficacy and safety for young children under 3 years old remain unclear. Currently, no guidelines recommend DAA therapy for this situation worldwide. Furthermore, the China National Medical Products Administration has not approved any DAA for treating children below 12 years old. Here, we described the characteristics of two children approximately 2 years old, who were infected by HCV genotype 1b and had significant clinical symptoms. Both received 12 weeks of ledipasvir/sofosbuvir (Case 1: 45.00 mg/200 mg per day, weight 17 kg; Case 2: 33.75 mg/150 mg per day, weight 12 kg). They achieved SVR at 12 weeks after treatment completion without obvious treatment-related adverse effects. Therefore, the safety and benefits of ledipasvir/sofosbuvir treatment in children under 3 years old seem to be confirmed. Our findings require further evaluation.
{"title":"Should they wait? Two children under 3 years old infected by HCV 1b successfully treated by ledipasvir/sofosbuvir: A report of two cases","authors":"Mingna Li , Kuerbannisa Wulayin , Shutao Lin , Chao Wu , Lubiao Chen","doi":"10.1016/j.livres.2023.11.001","DOIUrl":"10.1016/j.livres.2023.11.001","url":null,"abstract":"<div><div>Although direct-acting antivirals (DAAs) have notably increased the sustained virological response (SVR) rates in hepatitis C virus (HCV)-infected adolescent patients, the efficacy and safety for young children under 3 years old remain unclear. Currently, no guidelines recommend DAA therapy for this situation worldwide. Furthermore, the China National Medical Products Administration has not approved any DAA for treating children below 12 years old. Here, we described the characteristics of two children approximately 2 years old, who were infected by HCV genotype 1b and had significant clinical symptoms. Both received 12 weeks of ledipasvir/sofosbuvir (Case 1: 45.00 mg/200 mg per day, weight 17 kg; Case 2: 33.75 mg/150 mg per day, weight 12 kg). They achieved SVR at 12 weeks after treatment completion without obvious treatment-related adverse effects. Therefore, the safety and benefits of ledipasvir/sofosbuvir treatment in children under 3 years old seem to be confirmed. Our findings require further evaluation.</div></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"7 4","pages":"Pages 361-364"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135668997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-01DOI: 10.1016/j.livres.2023.11.004
Walaa Abdelhamed , Mohamed El-Kassas
Hepatocellular carcinoma (HCC), the sixth most common cancer globally, is associated with high mortality rates and more than 830,000 annual deaths. Despite advances in the available management options including surgical resection and local ablative therapies, recurrence rates after the initial treatment exceed 50%, even among patients who have undergone curative-intent therapy. Moreover, postsurgical HCC recurrence occurs in about 70% of cases five years postoperatively. The management of recurrent HCC remains undefined. This review discusses different predictors for HCC recurrence after each treatment modality and different approaches available to stratify these patients. More specific guidelines for managing HCC recurrence and strict surveillance protocols for such recurrence after initial HCC management are needed.
{"title":"Hepatocellular carcinoma recurrence: Predictors and management","authors":"Walaa Abdelhamed , Mohamed El-Kassas","doi":"10.1016/j.livres.2023.11.004","DOIUrl":"10.1016/j.livres.2023.11.004","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC), the sixth most common cancer globally, is associated with high mortality rates and more than 830,000 annual deaths. Despite advances in the available management options including surgical resection and local ablative therapies, recurrence rates after the initial treatment exceed 50%, even among patients who have undergone curative-intent therapy. Moreover, postsurgical HCC recurrence occurs in about 70% of cases five years postoperatively. The management of recurrent HCC remains undefined. This review discusses different predictors for HCC recurrence after each treatment modality and different approaches available to stratify these patients. More specific guidelines for managing HCC recurrence and strict surveillance protocols for such recurrence after initial HCC management are needed.</div></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"7 4","pages":"Pages 321-332"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139304518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-01DOI: 10.1016/j.livres.2022.11.005
Miranda Claire Gilbert, Tahereh Setayesh, Yu-Jui Yvonne Wan
Over 20% of mortality during acute liver failure is associated with the development of hepatic encephalopathy (HE). Thus, HE is a complication of acute liver failure with a broad spectrum of neuropsychiatric abnormalities ranging from subclinical alterations to coma. HE is caused by the diversion of portal blood into systemic circulation through portosystemic collateral vessels. Thus, the brain is exposed to intestinal-derived toxic substances. Moreover, the strategies to prevent advancement and improve the prognosis of such a liver-brain disease rely on intestinal microbial modulation. This is supported by the findings that antibiotics such as rifaximin and laxative lactulose can alleviate hepatic cirrhosis and/or prevent HE. Together, the significance of the gut-liver-brain axis in human health warrants attention. This review paper focuses on the roles of bacteria metabolites, mainly ammonia and bile acids (BAs) as well as BA receptors in HE. The literature search conducted for this review included searches for phrases such as BA receptors, BAs, ammonia, farnesoid X receptor (FXR), G protein-coupled bile acid receptor 1 (GPBAR1 or TGR5), sphingosine-1-phosphate receptor 2 (S1PR2), and cirrhosis in conjunction with the phrase hepatic encephalopathy and portosystemic encephalopathy. PubMed, as well as Google Scholar, was the search engines used to find relevant publications.
急性肝衰竭期间超过 20% 的死亡率与肝性脑病（HE）的发生有关。因此，肝性脑病是急性肝衰竭的一种并发症，可引起从亚临床改变到昏迷等多种神经精神异常。HE 是由于门静脉血液通过门静脉侧支血管转入全身循环所致。因此，大脑会接触到肠源性有毒物质。此外，防止这种肝脑疾病恶化和改善预后的策略依赖于肠道微生物调节。利福昔明等抗生素和通便剂乳果糖能缓解肝硬化和/或预防肝脑病的研究结果也支持这一观点。总之，肠道-肝脏-大脑轴在人类健康中的重要性值得关注。本综述论文重点研究细菌代谢产物（主要是氨、胆汁酸和胆汁酸受体）在肝硬化中的作用。本综述的文献检索包括对 BA 受体、BAs、氨、类雌激素 X 受体 (FXR)、G 蛋白偶联胆汁酸受体 1 (GPBAR1 或 TGR5)、鞘氨醇-1-磷酸受体 2 (S1PR2)、肝硬化等词组以及肝性脑病和门静脉脑病等词组的检索。PubMed 和 Google Scholar 是用于查找相关出版物的搜索引擎。
{"title":"The contributions of bacteria metabolites to the development of hepatic encephalopathy","authors":"Miranda Claire Gilbert, Tahereh Setayesh, Yu-Jui Yvonne Wan","doi":"10.1016/j.livres.2022.11.005","DOIUrl":"10.1016/j.livres.2022.11.005","url":null,"abstract":"<div><div>Over 20% of mortality during acute liver failure is associated with the development of hepatic encephalopathy (HE). Thus, HE is a complication of acute liver failure with a broad spectrum of neuropsychiatric abnormalities ranging from subclinical alterations to coma. HE is caused by the diversion of portal blood into systemic circulation through portosystemic collateral vessels. Thus, the brain is exposed to intestinal-derived toxic substances. Moreover, the strategies to prevent advancement and improve the prognosis of such a liver-brain disease rely on intestinal microbial modulation. This is supported by the findings that antibiotics such as rifaximin and laxative lactulose can alleviate hepatic cirrhosis and/or prevent HE. Together, the significance of the gut-liver-brain axis in human health warrants attention. This review paper focuses on the roles of bacteria metabolites, mainly ammonia and bile acids (BAs) as well as BA receptors in HE. The literature search conducted for this review included searches for phrases such as BA receptors, BAs, ammonia, farnesoid X receptor (FXR), G protein-coupled bile acid receptor 1 (GPBAR1 or TGR5), sphingosine-1-phosphate receptor 2 (S1PR2), and cirrhosis in conjunction with the phrase hepatic encephalopathy and portosystemic encephalopathy. PubMed, as well as Google Scholar, was the search engines used to find relevant publications.</div></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"7 4","pages":"Pages 296-303"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10786625/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47665658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alcoholic liver disease (ALD) has a multifaceted development, progressing from alcoholic steatosis to alcoholic hepatitis and ultimately to alcoholic cirrhosis, irreversible liver damage that can even result in hepatocellular carcinoma. The prevalence of ALD is increasing globally, particularly among middle-aged adults. Gender-based studies have revealed that ALD affects more men; however, disease progression differs between men and women. Despite this, the molecular understanding of alcohol-induced liver injury among genders and its association with changes in sex hormone metabolism, particularly with estrogen and estrogen receptors (ERs) in ALD, remains poor. This review focuses on experimental and human studies describing alcohol and its association with estrogen metabolism and signaling via ERs. Chronic alcohol consumption affects the immune response, and whether estrogen has any contributory effect remains inadequately studied. This review also discusses various therapeutic approaches currently in use and future approaches that can affect the response or progression via estrogen signaling. The role of gender on alcohol consumption and its association with steroid hormones must be elucidated for a better understanding of the pathogenesis of ALD, the development of effective therapeutic approaches, and better disease management in both men and women, as ALD remains a major public health concern.
{"title":"Unveiling the effect of estrogen receptors in alcoholic liver disease: A novel outlook","authors":"Sukriti Baweja , Ashmit Mittal , Swati Thangariyal , P. Debishree Subudhi , Shivani Gautam , Rashmi Kaul","doi":"10.1016/j.livres.2023.10.002","DOIUrl":"10.1016/j.livres.2023.10.002","url":null,"abstract":"<div><div>Alcoholic liver disease (ALD) has a multifaceted development, progressing from alcoholic steatosis to alcoholic hepatitis and ultimately to alcoholic cirrhosis, irreversible liver damage that can even result in hepatocellular carcinoma. The prevalence of ALD is increasing globally, particularly among middle-aged adults. Gender-based studies have revealed that ALD affects more men; however, disease progression differs between men and women. Despite this, the molecular understanding of alcohol-induced liver injury among genders and its association with changes in sex hormone metabolism, particularly with estrogen and estrogen receptors (ERs) in ALD, remains poor. This review focuses on experimental and human studies describing alcohol and its association with estrogen metabolism and signaling via ERs. Chronic alcohol consumption affects the immune response, and whether estrogen has any contributory effect remains inadequately studied. This review also discusses various therapeutic approaches currently in use and future approaches that can affect the response or progression via estrogen signaling. The role of gender on alcohol consumption and its association with steroid hormones must be elucidated for a better understanding of the pathogenesis of ALD, the development of effective therapeutic approaches, and better disease management in both men and women, as ALD remains a major public health concern.</div></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"7 4","pages":"Pages 333-341"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136127684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-01DOI: 10.1016/j.livres.2023.11.006
Peng Zou, Lin Wang
The liver is the leading site for lipid metabolism, involving not only fatty acid beta-oxidation but also de novo synthesis of endogenous triglycerides and ketogenesis. The liver maintains systemic lipid homeostasis by regulating lipid synthesis, catabolism, and transportation. Dysregulation of hepatic lipid metabolism precipitates disorders, such as non-alcoholic fatty liver disease (NAFLD), affecting the whole body. Thus, comprehending and studying hepatic lipid metabolism is crucial for preventing and treating metabolic liver diseases. Traditionally, researchers have investigated the impact of a single nutrient on hepatic lipid metabolism. However, real-life dietary patterns encompass diverse nutrients rather than single components. In recent years, there have been increased studies and notable progress regarding the effects of distinct dietary patterns on hepatic lipid metabolism. This review summarizes the influence of diverse dietary patterns on hepatic lipid metabolism, elucidating underlying molecular mechanisms and appraising the therapeutic potential of dietary patterns in managing hepatic steatosis.
{"title":"Dietary pattern and hepatic lipid metabolism","authors":"Peng Zou, Lin Wang","doi":"10.1016/j.livres.2023.11.006","DOIUrl":"10.1016/j.livres.2023.11.006","url":null,"abstract":"<div><div>The liver is the leading site for lipid metabolism, involving not only fatty acid beta-oxidation but also <em>de novo</em> synthesis of endogenous triglycerides and ketogenesis. The liver maintains systemic lipid homeostasis by regulating lipid synthesis, catabolism, and transportation. Dysregulation of hepatic lipid metabolism precipitates disorders, such as non-alcoholic fatty liver disease (NAFLD), affecting the whole body. Thus, comprehending and studying hepatic lipid metabolism is crucial for preventing and treating metabolic liver diseases. Traditionally, researchers have investigated the impact of a single nutrient on hepatic lipid metabolism. However, real-life dietary patterns encompass diverse nutrients rather than single components. In recent years, there have been increased studies and notable progress regarding the effects of distinct dietary patterns on hepatic lipid metabolism. This review summarizes the influence of diverse dietary patterns on hepatic lipid metabolism, elucidating underlying molecular mechanisms and appraising the therapeutic potential of dietary patterns in managing hepatic steatosis.</div></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"7 4","pages":"Pages 275-284"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139296110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-01DOI: 10.1016/j.livres.2023.12.001
Trinh Van Le , Nhung Hai Truong , Ai Xuan L. Holterman
Autophagy is a physiological process that is ubiquitous and essential to the disposal or recycling of damaged cellular organelles and misfolded proteins to maintain organ homeostasis and survival. Its importance in the regulation of liver function in normal and pathological conditions is increasingly recognized. This review summarizes how autophagy regulates epithelial cell- and non-epithelial cell-specific function in the liver and how it differentially participates in hepatic homeostasis, hepatic injury response to stress-induced liver damage such as cholestasis, sepsis, non-alcoholic and alcohol-associated liver disease, viral hepatitis, hepatic fibrosis, hepatocellular and cholangiocellular carcinoma, and aging. Autophagy-based interventional studies for liver diseases that are currently registered in clinicatrials.gov are summarized. Given the broad and multidirectional autophagy response in the liver, a more refined understanding of the liver cell-specific autophagy activities in a context-dependent manner is necessary.
{"title":"Autophagy modulates physiologic and adaptive response in the liver","authors":"Trinh Van Le , Nhung Hai Truong , Ai Xuan L. Holterman","doi":"10.1016/j.livres.2023.12.001","DOIUrl":"10.1016/j.livres.2023.12.001","url":null,"abstract":"<div><div>Autophagy is a physiological process that is ubiquitous and essential to the disposal or recycling of damaged cellular organelles and misfolded proteins to maintain organ homeostasis and survival. Its importance in the regulation of liver function in normal and pathological conditions is increasingly recognized. This review summarizes how autophagy regulates epithelial cell- and non-epithelial cell-specific function in the liver and how it differentially participates in hepatic homeostasis, hepatic injury response to stress-induced liver damage such as cholestasis, sepsis, non-alcoholic and alcohol-associated liver disease, viral hepatitis, hepatic fibrosis, hepatocellular and cholangiocellular carcinoma, and aging. Autophagy-based interventional studies for liver diseases that are currently registered in <span><span>clinicatrials.gov</span><svg><path></path></svg></span> are summarized. Given the broad and multidirectional autophagy response in the liver, a more refined understanding of the liver cell-specific autophagy activities in a context-dependent manner is necessary.</div></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"7 4","pages":"Pages 304-320"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138620867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-01DOI: 10.1016/j.livres.2023.11.005
Zahraa R. Elshahawy , Entsar A. Saad , Rana R. El-Sadda
Background and aims
Combination therapy is a promising new strategy that has been proposed to increase the efficacy of cancer treatment. We aimed to investigate the anti-cancer activity of rifampicin monotherapy and its combination with doxorubicin against hepatocellular carcinoma (HCC).
Materials and methods
The in vitro half maximal inhibitory concentration (IC50) and selectivity index (SI) of the drugs under investigation against HepG2 and human lung fibroblast (WI38) cell lines were determined. For the in vivo experiment, male Sprague-Dawley albino rats were injected with thioacetamide at 200 mg/kg twice a week for 90 days; HCC development was confirmed histopathologically. Following HCC induction, the rats were treated with intraperitoneal doxorubicin, rifampicin, or their combination for 45 or 90 days. After sacrifice, the livers were examined histopathologically. The levels of aminotransferases, albumin, bilirubin, malondialdehyde, superoxide dismutase (SOD), catalase (CAT), total antioxidant capacity (TAC), and nitric oxide were measured by spectrophotometry. Alpha-fetoprotein, cancer antigen 19-9, tumor necrosis factor-alpha, interleukin-6, Bcl-2-associated X protein, caspase 3, caspase 8, and p53 were estimated using ELISA.
Results
In vitro, the combination of doxorubicin and rifampicin showed the highest SI of 3.43. In vivo, among the measured markers, the levels of TAC, CAT, SOD, and p53 decreased (P < 0.001) and the rest of the measured marker levels increased (P < 0.001) in the HCC-bearing rats; after treatment in all groups, all these changes improved toward normal in a time-dependent manner. The combination of doxorubicin and rifampicin optimized the effects of the two individual drugs and exerted the best antioxidant effects.
Conclusions
In general, compared with rifampicin or doxorubicin alone, combination therapy has favorable outcomes. Based on our results, the combination of rifampicin and doxorubicin might be applicable for HCC chemotherapy.
{"title":"Synergistic impacts of rifampicin and doxorubicin against thioacetamide-induced hepatocellular carcinoma in rats","authors":"Zahraa R. Elshahawy , Entsar A. Saad , Rana R. El-Sadda","doi":"10.1016/j.livres.2023.11.005","DOIUrl":"10.1016/j.livres.2023.11.005","url":null,"abstract":"<div><h3>Background and aims</h3><div>Combination therapy is a promising new strategy that has been proposed to increase the efficacy of cancer treatment. We aimed to investigate the anti-cancer activity of rifampicin monotherapy and its combination with doxorubicin against hepatocellular carcinoma (HCC).</div></div><div><h3>Materials and methods</h3><div>The <em>in vitro</em> half maximal inhibitory concentration (IC<sub>50</sub>) and selectivity index (SI) of the drugs under investigation against HepG2 and human lung fibroblast (WI38) cell lines were determined. For the <em>in vivo</em> experiment, male Sprague-Dawley albino rats were injected with thioacetamide at 200 mg/kg twice a week for 90 days; HCC development was confirmed histopathologically. Following HCC induction, the rats were treated with intraperitoneal doxorubicin, rifampicin, or their combination for 45 or 90 days. After sacrifice, the livers were examined histopathologically. The levels of aminotransferases, albumin, bilirubin, malondialdehyde, superoxide dismutase (SOD), catalase (CAT), total antioxidant capacity (TAC), and nitric oxide were measured by spectrophotometry. Alpha-fetoprotein, cancer antigen 19-9, tumor necrosis factor-alpha, interleukin-6, Bcl-2-associated X protein, caspase 3, caspase 8, and p53 were estimated using ELISA.</div></div><div><h3>Results</h3><div><em>In vitro,</em> the combination of doxorubicin and rifampicin showed the highest SI of 3.43. <em>In vivo,</em> among the measured markers, the levels of TAC, CAT, SOD, and p53 decreased (<em>P</em> < 0.001) and the rest of the measured marker levels increased (<em>P</em> < 0.001) in the HCC-bearing rats; after treatment in all groups, all these changes improved toward normal in a time-dependent manner. The combination of doxorubicin and rifampicin optimized the effects of the two individual drugs and exerted the best antioxidant effects.</div></div><div><h3>Conclusions</h3><div>In general, compared with rifampicin or doxorubicin alone, combination therapy has favorable outcomes. Based on our results, the combination of rifampicin and doxorubicin might be applicable for HCC chemotherapy.</div></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"7 4","pages":"Pages 352-360"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139298104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-01DOI: 10.1016/j.livres.2023.11.002
Tingting Sha , Yujia You , Xiaoyan Miao , Huan Deng , Wei Zhang , Huolin Ye , Ping Wang , Rongqin Zheng , Jie Ren , Tinghui Yin
Background and objective
Noninvasive non-alcoholic steatohepatitis (NASH) assessment is a clinical challenge to the management of non-alcoholic fatty liver disease. We aim to develop diagnostic models based on sequential ultrasound molecular imaging (USMI) for the noninvasive identification of NASH in mouse models.
Methods
Animal experiments were approved by the Animal Ethics Committee of South China Agricultural University. Forty-nine C57BL/6 mice were divided into normal control, non-alcoholic fatty liver, NASH, and hepatitis groups. Sequential USMI was implemented using CD36-targeted microbubbles (MBs-CD36) and intercellular adhesion molecule-1 (ICAM-1)-targeted microbubbles (MBs-ICAM-1) to visualize hepatic steatosis and inflammation. The targeting signal of USMI was quantified as the normalized intensity difference (NID) with the destruction-replenishment method. Correlation analysis was conducted between the NID-MBs-CD36 and pathological steatosis score and between the NID-MBs-ICAM-1 and pathological inflammation score. Finally, diagnostic models combining NID-MBs-CD36 with NID-MBs-ICAM-1 were established for NASH diagnosis.
Results
MBs-CD36 and MBs-ICAM-1 were successfully prepared and used for sequential USMI in all mice. NID-MBs-CD36 values increased with the progression of steatosis, while NID-MBs-ICAM-1 values increased in parallel with the progression of inflammation. A strong positive correlation was identified between NID-MBs-CD36 and pathological steatosis grade (rs = 0.9078, P < 0.0001) and between NID-MBs-ICAM-1 and pathological inflammation grade (rs = 0.9071, P < 0.0001). Among various sequential USMI-based diagnostic models, the serial testing model showed high diagnostic performance in detecting NASH, with 95% sensitivity, 97% specificity, 95% positive predictive values, 97% negative predictive values, and 96% accuracy.
Conclusions
Sequential USMI using MBs-CD36 and MBs-ICAM-1 allows noninvasive grading of hepatic steatosis and inflammation. Sequential USMI-based diagnostic models hold great potential in the noninvasive identification of NASH.
{"title":"Sequential ultrasound molecular imaging for noninvasive identification and assessment of non-alcoholic steatohepatitis in mouse models","authors":"Tingting Sha , Yujia You , Xiaoyan Miao , Huan Deng , Wei Zhang , Huolin Ye , Ping Wang , Rongqin Zheng , Jie Ren , Tinghui Yin","doi":"10.1016/j.livres.2023.11.002","DOIUrl":"10.1016/j.livres.2023.11.002","url":null,"abstract":"<div><h3>Background and objective</h3><div>Noninvasive non-alcoholic steatohepatitis (NASH) assessment is a clinical challenge to the management of non-alcoholic fatty liver disease. We aim to develop diagnostic models based on sequential ultrasound molecular imaging (USMI) for the noninvasive identification of NASH in mouse models.</div></div><div><h3>Methods</h3><div>Animal experiments were approved by the Animal Ethics Committee of South China Agricultural University. Forty-nine C57BL/6 mice were divided into normal control, non-alcoholic fatty liver, NASH, and hepatitis groups. Sequential USMI was implemented using CD36-targeted microbubbles (MBs-CD36) and intercellular adhesion molecule-1 (ICAM-1)-targeted microbubbles (MBs-ICAM-1) to visualize hepatic steatosis and inflammation. The targeting signal of USMI was quantified as the normalized intensity difference (NID) with the destruction-replenishment method. Correlation analysis was conducted between the NID-MBs-CD36 and pathological steatosis score and between the NID-MBs-ICAM-1 and pathological inflammation score. Finally, diagnostic models combining NID-MBs-CD36 with NID-MBs-ICAM-1 were established for NASH diagnosis.</div></div><div><h3>Results</h3><div>MBs-CD36 and MBs-ICAM-1 were successfully prepared and used for sequential USMI in all mice. NID-MBs-CD36 values increased with the progression of steatosis, while NID-MBs-ICAM-1 values increased in parallel with the progression of inflammation. A strong positive correlation was identified between NID-MBs-CD36 and pathological steatosis grade (r<sub>s</sub> = 0.9078, <em>P</em> < 0.0001) and between NID-MBs-ICAM-1 and pathological inflammation grade (r<sub>s</sub> = 0.9071, <em>P</em> < 0.0001). Among various sequential USMI-based diagnostic models, the serial testing model showed high diagnostic performance in detecting NASH, with 95% sensitivity, 97% specificity, 95% positive predictive values, 97% negative predictive values, and 96% accuracy.</div></div><div><h3>Conclusions</h3><div>Sequential USMI using MBs-CD36 and MBs-ICAM-1 allows noninvasive grading of hepatic steatosis and inflammation. Sequential USMI-based diagnostic models hold great potential in the noninvasive identification of NASH.</div></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"7 4","pages":"Pages 342-351"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139301470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-01DOI: 10.1016/j.livres.2023.11.003
Zhixian Zhu , Xiaoxun Zhang , Qiong Pan , Liangjun Zhang , Jin Chai
Non-alcoholic fatty liver disease (NAFLD) is characterized by the abnormal buildup of lipids in the liver tissue. Non-alcoholic fatty liver (NAFL) may progress to non-alcoholic steatohepatitis. Triglycerides in the liver can originate from various sources, including de novo lipogenesis (DNL). Research indicates that DNL significantly escalates in NAFLD, worsening steatosis. However, the precise regulatory mechanism of DNL in the development of this disease is not fully understood. Therefore, the targeted reduction of DNL could be a crucial therapeutic strategy. Currently, numerous pharmaceutical agents targeting DNL have been developed, attracting significant attention. This review examines the mechanism of DNL upregulation in NAFLD, assessing its potential as a therapeutic target for hepatic steatosis. Furthermore, we thoroughly examine hepatocellular lipotoxicity and provide an extensive review of the application and limitations of relevant therapeutic drugs, with a focus on key enzymes involved in DNL. The implementation of these pharmacological strategies is expected to significantly improve the management and overall outcomes for patients with NAFLD.
{"title":"In-depth analysis of de novo lipogenesis in non-alcoholic fatty liver disease: Mechanism and pharmacological interventions","authors":"Zhixian Zhu , Xiaoxun Zhang , Qiong Pan , Liangjun Zhang , Jin Chai","doi":"10.1016/j.livres.2023.11.003","DOIUrl":"10.1016/j.livres.2023.11.003","url":null,"abstract":"<div><div>Non-alcoholic fatty liver disease (NAFLD) is characterized by the abnormal buildup of lipids in the liver tissue. Non-alcoholic fatty liver (NAFL) may progress to non-alcoholic steatohepatitis. Triglycerides in the liver can originate from various sources, including <em>de novo</em> lipogenesis (DNL). Research indicates that DNL significantly escalates in NAFLD, worsening steatosis. However, the precise regulatory mechanism of DNL in the development of this disease is not fully understood. Therefore, the targeted reduction of DNL could be a crucial therapeutic strategy. Currently, numerous pharmaceutical agents targeting DNL have been developed, attracting significant attention. This review examines the mechanism of DNL upregulation in NAFLD, assessing its potential as a therapeutic target for hepatic steatosis. Furthermore, we thoroughly examine hepatocellular lipotoxicity and provide an extensive review of the application and limitations of relevant therapeutic drugs, with a focus on key enzymes involved in DNL. The implementation of these pharmacological strategies is expected to significantly improve the management and overall outcomes for patients with NAFLD.</div></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"7 4","pages":"Pages 285-295"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139303326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-01DOI: 10.1016/j.livres.2023.10.001
Mary Miu Yee Waye
{"title":"Mutation of autophagy-related gene ATG7 increases the risk of severe disease in patients with non-alcoholic fatty liver disease","authors":"Mary Miu Yee Waye","doi":"10.1016/j.livres.2023.10.001","DOIUrl":"10.1016/j.livres.2023.10.001","url":null,"abstract":"","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"7 4","pages":"Pages 365-366"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135922500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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