Background:Excessive alcohol intake with hepatitis B virus(HBV)infection accelerates chronic liver disease progression and patients with HBV infection are more susceptible to alcohol-induced liver disease.Hepatitis B ...Background:Excessive alcohol intake with hepatitis B virus(HBV)infection accelerates chronic liver disease progression and patients with HBV infection are more susceptible to alcohol-induced liver disease.Hepatitis B virus X protein(HBx)plays a crucial role in disease pathogenesis,while its specific role in alcoholic liver disease(ALD)progression has not yet been elucidated.Here,we studied the role of HBx on the development of ALD.Methods:HBx-transgenic(HBx-Tg)mice and their wild-type littermates were exposed to chronic plus binge alcohol feeding.Primary hepatocytes,cell lines,and human samples were used to investigate the interaction between HBx and acetaldehyde dehydrogenase 2(ALDH2).Lipid profiles in mouse livers and cells were assessed by using liquid chromatography–mass spectrometry.Results:We identified that HBx significantly aggravated alcohol-induced steatohepatitis,oxidative stress,and lipid peroxidation in mice.In addition,HBx induced worse lipid profiles with high lysophospholipids generation in alcoholic steatohepatitis,as shown by using lipidomic analysis.Importantly,serum and liver acetaldehyde were markedly higher in alcoholfed HBx-Tg mice.Acetaldehyde induced lysophospholipids generation through oxidative stress in hepatocytes.Mechanistically,HBx directly bound to mitochondrial ALDH2 to induce its ubiquitin–proteasome degradation,resulting in acetaldehyde accumulation.More importantly,we also identified that patients with HBV infection reduced ALDH2 protein levels in the liver.Conclusions:Our study demonstrated that HBx-induced ubiquitin-dependent degradation of mitochondrial ALDH2 aggravates alcoholic steatohepatitis.展开更多
Clonorchiasis,also known as the liver fluke disease,is caused by eating raw freshwater fish or shrimps that contain Clonorchis sinensis cyst larvae,which mainly involves the hepatobiliary system.Chronic abdominal pain...Clonorchiasis,also known as the liver fluke disease,is caused by eating raw freshwater fish or shrimps that contain Clonorchis sinensis cyst larvae,which mainly involves the hepatobiliary system.Chronic abdominal pain and distention,loss of appetite,and hepatomegaly are the most common clinical manifestation.Persistent infection with Clonorchis sinensis would result in chronic inflammation,epithelial hyperplasia,and periductal fibrosis and even progress to cholangiocarcinoma.Nevertheless,the majority of the infected people are asymptomatic or mildly symptomatic,contributing to its high misdiagnosis rate.Alpha-fetoprotein(AFP)is a well-known biomarker for hepatocellular carcinoma(HCC).A high level of AFP can also be caused by several benign diseases,causing confusion and influ-encing treatment decisions.So far,clonorchiasis with a markedly elevated level of AFP has been rarely reported.We present a case of clonorchiasis with a high level of AFP in a 52-year-old man.We hope to raise clinical awareness of this food-borne disease.Clonorchiasis should be considered in patients with extremely high levels of AFP,excluding HCC and germ cell tumors,especially if the patient has a history of ingesting raw freshwater fish or shrimps.展开更多
基金supported by grants from the National Natural Science Foundation of China[82170604,82070574,82122009]the Natural Science Foundation Team Project of Guangdong Province[2018B03031200].
文摘Background:Excessive alcohol intake with hepatitis B virus(HBV)infection accelerates chronic liver disease progression and patients with HBV infection are more susceptible to alcohol-induced liver disease.Hepatitis B virus X protein(HBx)plays a crucial role in disease pathogenesis,while its specific role in alcoholic liver disease(ALD)progression has not yet been elucidated.Here,we studied the role of HBx on the development of ALD.Methods:HBx-transgenic(HBx-Tg)mice and their wild-type littermates were exposed to chronic plus binge alcohol feeding.Primary hepatocytes,cell lines,and human samples were used to investigate the interaction between HBx and acetaldehyde dehydrogenase 2(ALDH2).Lipid profiles in mouse livers and cells were assessed by using liquid chromatography–mass spectrometry.Results:We identified that HBx significantly aggravated alcohol-induced steatohepatitis,oxidative stress,and lipid peroxidation in mice.In addition,HBx induced worse lipid profiles with high lysophospholipids generation in alcoholic steatohepatitis,as shown by using lipidomic analysis.Importantly,serum and liver acetaldehyde were markedly higher in alcoholfed HBx-Tg mice.Acetaldehyde induced lysophospholipids generation through oxidative stress in hepatocytes.Mechanistically,HBx directly bound to mitochondrial ALDH2 to induce its ubiquitin–proteasome degradation,resulting in acetaldehyde accumulation.More importantly,we also identified that patients with HBV infection reduced ALDH2 protein levels in the liver.Conclusions:Our study demonstrated that HBx-induced ubiquitin-dependent degradation of mitochondrial ALDH2 aggravates alcoholic steatohepatitis.
基金This work was supported by the Science and Technology Foundation of Guangzhou of China(201903010099)to X.Wei.
文摘Clonorchiasis,also known as the liver fluke disease,is caused by eating raw freshwater fish or shrimps that contain Clonorchis sinensis cyst larvae,which mainly involves the hepatobiliary system.Chronic abdominal pain and distention,loss of appetite,and hepatomegaly are the most common clinical manifestation.Persistent infection with Clonorchis sinensis would result in chronic inflammation,epithelial hyperplasia,and periductal fibrosis and even progress to cholangiocarcinoma.Nevertheless,the majority of the infected people are asymptomatic or mildly symptomatic,contributing to its high misdiagnosis rate.Alpha-fetoprotein(AFP)is a well-known biomarker for hepatocellular carcinoma(HCC).A high level of AFP can also be caused by several benign diseases,causing confusion and influ-encing treatment decisions.So far,clonorchiasis with a markedly elevated level of AFP has been rarely reported.We present a case of clonorchiasis with a high level of AFP in a 52-year-old man.We hope to raise clinical awareness of this food-borne disease.Clonorchiasis should be considered in patients with extremely high levels of AFP,excluding HCC and germ cell tumors,especially if the patient has a history of ingesting raw freshwater fish or shrimps.
