Acute liver failure(ALF),a fatal clinical disease featured with overwhelming hepatocyte necrosis,is a grand challenge in global health.However,a satisfactory therapeutic option for curing ALF is still absent,other tha...Acute liver failure(ALF),a fatal clinical disease featured with overwhelming hepatocyte necrosis,is a grand challenge in global health.However,a satisfactory therapeutic option for curing ALF is still absent,other than liver transplantation.Nanobiomaterials are currently being developed for the diagnosis and treatment of ALF.The liver can sequester most of nanoparticles from blood circulation,which becomes an intrinsic superiority for nanobiomaterials targeting hepatic diseases.Nanobiomaterials can enhance the bioavailability of free drugs,thereby significantly improving the therapeutic effects in ALF.Nanobiomaterials can also increase the liver accumulation of therapeutic agents and enable more effective targeting of the liver or specific liver cells.In addition,stimuli-responsive,optical,or magnetic nanomaterials exhibit great potential in the therapeutical,diagnostic,and imaging applications in ALF.Therefore,therapeutic agents in combination with nanobiomaterials increase the specificity of ALF therapy,diminish adverse systemic effects,and offer a multifunctional theranostic platform.Nanobiomaterial holds excellent significance and prospects in ALF theranostics.In this review,we summarize the therapeutic mechanisms and targeting strategies of various nanobiomaterials in ALF.We highlight recent developments of diverse nanomedicines for ALF therapy,diagnosis,and imaging.Furthermore,the challenges and future perspectives in the theranostics of ALF are also discussed.展开更多
BACKGROUND:Acute liver failure(ALF) caused by viral and non-viral hepatitis is often accompanied with severe metabolic disorders,the accumulation of toxic substances and continuous release and accumulation of a large ...BACKGROUND:Acute liver failure(ALF) caused by viral and non-viral hepatitis is often accompanied with severe metabolic disorders,the accumulation of toxic substances and continuous release and accumulation of a large number of endogenous toxins and inflammatory mediators. The present study aimed to investigate the effects of various combined non-biological artif icial liver treatments for patients with acute liver failure(ALF) complicated by multiple organ dysfunction syndrome(MODS).METHODS:Thirty-one patients with mid- or late-stage liver failure complicated by MODS(score 4) were randomly divided into three treatment groups:plasmapheresis(PE) combined with hemoperfusion(HP) and continuous venovenous hemodiafiltration(CVVHDF),PE+CVVHDF,and HP+CVVHDF,respectively. Heart rate(HR) before and after treatment,mean arterial pressure(MAP),respiratory index(PaO2/FiO2),hepatic function,platelet count,and blood coagulation were determined.RESULTS:Signifi cant improvement was observed in HR,MAP,PaO2/FiO2,total bilirubin(TBIL) and alanine aminotransferase(ALT) levels after treatment(P<0.05). TBIL and ALT decreased more signifi cantly after treatment in the PE+CVVHDF and PE+HP+CVVHDF groups(P<0.01). Prothrombin time(PT) and albumin were signifi cantly improved only in the PE+CVVHDF and PE+HP+CVVHDF groups(P<0.05). TBIL decreased more significantly in the PE+HP+CVVHDF group than in the HP+CVVHDF and PE+CVVHDF groups(P<0.05). The survival rate of the patients was 58.1%(18/31),viral survival rate 36.4%(4/11),and non-viral survival rate 70%(14/20).CONCLUSION:Liver function was relatively improved after treatment,but PE+HP+CVVHDF was more efficient for the removal of toxic metabolites,especially bilirubin. The survival rate was signifi cantly higher in the patients with non-viral liver failure than in those with viral liver failure.展开更多
High-dependency units(HDUs)provide high-level care to patients who suffer from single organ failure,with the exception of respiratory failure requiring mechanical ventilation;HDUs serve as an intermediary between gene...High-dependency units(HDUs)provide high-level care to patients who suffer from single organ failure,with the exception of respiratory failure requiring mechanical ventilation;HDUs serve as an intermediary between general wards and Intensive Care Units.Due to military and civilian needs,our hospital has established a unique HDU for patients with liver disease in China.A Chinese military officer in the United Nations Peacekeeping Forces in South Sudan was transferred to our HDU for liver failure treatment in 2018.The patient’s disease status,nutrition,sleep habits,and psychological behaviour were monitored on different scales.The patient was provided with vascular monitoring,telemetry,pulse oximetry,drug treatment,nutritional support,sleep intervention,psychological intervention,and humanistic care by a multidisciplinary treatment team.After treatment,the patient recovered and avoided liver transplantation.Based on the experience with this HDU,this new model may create an efficient treatment process for military and civilian patients with severe liver disease at home or abroad.展开更多
A 27-year-old male patient with rheumatoid arthritis was diagnosed with acute liver failure when he was taking leflunomide, a new immunosuppressant. This case illustrates the risk that leflunomide may lead to severe h...A 27-year-old male patient with rheumatoid arthritis was diagnosed with acute liver failure when he was taking leflunomide, a new immunosuppressant. This case illustrates the risk that leflunomide may lead to severe hepatotoxicity.展开更多
Objective： Hepatic progenitor cell transplantation has shed light on the treatment of liver failure. The present study was designed to evaluate whether xenogeneic liver epithelial progenitor cells （LEPCs） transplan...Objective： Hepatic progenitor cell transplantation has shed light on the treatment of liver failure. The present study was designed to evaluate whether xenogeneic liver epithelial progenitor cells （LEPCs） transplantation could promote liver recovery in a rat model of acute liver failure. The engraftment and hepatocytic differentiation of transplanted hepatic progenitor cells in the rat spleen was also investigated. Methods： LEPCs were propagated in vitro for long and transduced with lentiviral vector carrying mCherry gene. Intraperitoneal injection of CC14 followed by 2/3 partial hepatectomy three days later were used to establish rat models of acute liver failure. Rats were intrasplenically injected with mCherry modified LEPCs （n=20, 1× 107 cells/0.5 mL） or the same volume of medium （n=20）. Serum liver enzymes （ALT, AST） and liver histology were evaluated for 21 days after transplantation. The engraftment of transplanted LEPCs in the spleens was tested by polymerase chain reaction （PCR） amplification targeting mCherry gene. The differentiation into hepatocytic lineage of transplanted LEPCs was investigated usingimmunohistochemistry staining against Alb. Results： LEPCs were effectively transduced with lentiviral vector showing a transduction efficiency of 90%. Compared with control, cell-injected group displayed significantly lower levels of ALT and AST （P〈0.05） and better histological features including less swelling change and hepatocyte death. PCR amplification of mCherry sequences confirmed the engraftment of LEPCs in the spleens. Alb-positive cells first appeared 5 days after cell transplantation and the number of Alb-positive cells increased substantially （P〈0.05）, which revealed the hepatocytic differentiation process Conclusion： Xenogeneic hepatic progenitor cells can engraft and differentiate into hepatocytes in the splenic parenchyma. Intrasplenic delivery of hepatic progenitor cells ameliorates CCh/partial hepatectomy-induced liver injury in rats展开更多
基金supported by the National Key Research and Development Program of China(2019YFA0111300)the National Natural Science Foundation of China(21907113,51903256,32001012)the Guangdong Province Science and Technology Innovation Special Fund(International Scientific Cooperation,2018A050506035).
文摘Acute liver failure(ALF),a fatal clinical disease featured with overwhelming hepatocyte necrosis,is a grand challenge in global health.However,a satisfactory therapeutic option for curing ALF is still absent,other than liver transplantation.Nanobiomaterials are currently being developed for the diagnosis and treatment of ALF.The liver can sequester most of nanoparticles from blood circulation,which becomes an intrinsic superiority for nanobiomaterials targeting hepatic diseases.Nanobiomaterials can enhance the bioavailability of free drugs,thereby significantly improving the therapeutic effects in ALF.Nanobiomaterials can also increase the liver accumulation of therapeutic agents and enable more effective targeting of the liver or specific liver cells.In addition,stimuli-responsive,optical,or magnetic nanomaterials exhibit great potential in the therapeutical,diagnostic,and imaging applications in ALF.Therefore,therapeutic agents in combination with nanobiomaterials increase the specificity of ALF therapy,diminish adverse systemic effects,and offer a multifunctional theranostic platform.Nanobiomaterial holds excellent significance and prospects in ALF theranostics.In this review,we summarize the therapeutic mechanisms and targeting strategies of various nanobiomaterials in ALF.We highlight recent developments of diverse nanomedicines for ALF therapy,diagnosis,and imaging.Furthermore,the challenges and future perspectives in the theranostics of ALF are also discussed.
基金supported by a grant from Xuzhou Municipal,China
文摘BACKGROUND:Acute liver failure(ALF) caused by viral and non-viral hepatitis is often accompanied with severe metabolic disorders,the accumulation of toxic substances and continuous release and accumulation of a large number of endogenous toxins and inflammatory mediators. The present study aimed to investigate the effects of various combined non-biological artif icial liver treatments for patients with acute liver failure(ALF) complicated by multiple organ dysfunction syndrome(MODS).METHODS:Thirty-one patients with mid- or late-stage liver failure complicated by MODS(score 4) were randomly divided into three treatment groups:plasmapheresis(PE) combined with hemoperfusion(HP) and continuous venovenous hemodiafiltration(CVVHDF),PE+CVVHDF,and HP+CVVHDF,respectively. Heart rate(HR) before and after treatment,mean arterial pressure(MAP),respiratory index(PaO2/FiO2),hepatic function,platelet count,and blood coagulation were determined.RESULTS:Signifi cant improvement was observed in HR,MAP,PaO2/FiO2,total bilirubin(TBIL) and alanine aminotransferase(ALT) levels after treatment(P<0.05). TBIL and ALT decreased more signifi cantly after treatment in the PE+CVVHDF and PE+HP+CVVHDF groups(P<0.01). Prothrombin time(PT) and albumin were signifi cantly improved only in the PE+CVVHDF and PE+HP+CVVHDF groups(P<0.05). TBIL decreased more significantly in the PE+HP+CVVHDF group than in the HP+CVVHDF and PE+CVVHDF groups(P<0.05). The survival rate of the patients was 58.1%(18/31),viral survival rate 36.4%(4/11),and non-viral survival rate 70%(14/20).CONCLUSION:Liver function was relatively improved after treatment,but PE+HP+CVVHDF was more efficient for the removal of toxic metabolites,especially bilirubin. The survival rate was signifi cantly higher in the patients with non-viral liver failure than in those with viral liver failure.
文摘High-dependency units(HDUs)provide high-level care to patients who suffer from single organ failure,with the exception of respiratory failure requiring mechanical ventilation;HDUs serve as an intermediary between general wards and Intensive Care Units.Due to military and civilian needs,our hospital has established a unique HDU for patients with liver disease in China.A Chinese military officer in the United Nations Peacekeeping Forces in South Sudan was transferred to our HDU for liver failure treatment in 2018.The patient’s disease status,nutrition,sleep habits,and psychological behaviour were monitored on different scales.The patient was provided with vascular monitoring,telemetry,pulse oximetry,drug treatment,nutritional support,sleep intervention,psychological intervention,and humanistic care by a multidisciplinary treatment team.After treatment,the patient recovered and avoided liver transplantation.Based on the experience with this HDU,this new model may create an efficient treatment process for military and civilian patients with severe liver disease at home or abroad.
文摘A 27-year-old male patient with rheumatoid arthritis was diagnosed with acute liver failure when he was taking leflunomide, a new immunosuppressant. This case illustrates the risk that leflunomide may lead to severe hepatotoxicity.
基金Supported by the National Natural Science Foundation of China(30600575,30830099)
文摘Objective： Hepatic progenitor cell transplantation has shed light on the treatment of liver failure. The present study was designed to evaluate whether xenogeneic liver epithelial progenitor cells （LEPCs） transplantation could promote liver recovery in a rat model of acute liver failure. The engraftment and hepatocytic differentiation of transplanted hepatic progenitor cells in the rat spleen was also investigated. Methods： LEPCs were propagated in vitro for long and transduced with lentiviral vector carrying mCherry gene. Intraperitoneal injection of CC14 followed by 2/3 partial hepatectomy three days later were used to establish rat models of acute liver failure. Rats were intrasplenically injected with mCherry modified LEPCs （n=20, 1× 107 cells/0.5 mL） or the same volume of medium （n=20）. Serum liver enzymes （ALT, AST） and liver histology were evaluated for 21 days after transplantation. The engraftment of transplanted LEPCs in the spleens was tested by polymerase chain reaction （PCR） amplification targeting mCherry gene. The differentiation into hepatocytic lineage of transplanted LEPCs was investigated usingimmunohistochemistry staining against Alb. Results： LEPCs were effectively transduced with lentiviral vector showing a transduction efficiency of 90%. Compared with control, cell-injected group displayed significantly lower levels of ALT and AST （P〈0.05） and better histological features including less swelling change and hepatocyte death. PCR amplification of mCherry sequences confirmed the engraftment of LEPCs in the spleens. Alb-positive cells first appeared 5 days after cell transplantation and the number of Alb-positive cells increased substantially （P〈0.05）, which revealed the hepatocytic differentiation process Conclusion： Xenogeneic hepatic progenitor cells can engraft and differentiate into hepatocytes in the splenic parenchyma. Intrasplenic delivery of hepatic progenitor cells ameliorates CCh/partial hepatectomy-induced liver injury in rats
