BACKGROUND Acoustic radiation force impulse(ARFI)is used to measure liver fibrosis and predict outcomes.The performance of elastography in assessment of fibrosis is poorer in hepatitis B virus(HBV)than in other etiolo...BACKGROUND Acoustic radiation force impulse(ARFI)is used to measure liver fibrosis and predict outcomes.The performance of elastography in assessment of fibrosis is poorer in hepatitis B virus(HBV)than in other etiologies of chronic liver disease.AIM To evaluate the performance of ARFI in long-term outcome prediction among different etiologies of chronic liver disease.METHODS Consecutive patients who received an ARFI study between 2011 and 2018 were enrolled.After excluding dual infection,alcoholism,autoimmune hepatitis,and others with incomplete data,this retrospective cohort were divided into hepatitis B(HBV,n=1064),hepatitis C(HCV,n=507),and non-HBV,non-HCV(NBNC,n=391)groups.The indexed cases were linked to cancer registration(1987-2020)and national mortality databases.The differences in morbidity and mortality among the groups were analyzed.RESULTS At the enrollment,the HBV group showed more males(77.5%),a higher prevalence of prediagnosed hepatocellular carcinoma(HCC),and a lower prevalence of comorbidities than the other groups(P<0.001).The HCV group was older and had a lower platelet count and higher ARFI score than the other groups(P<0.001).The NBNC group showed a higher body mass index and platelet count,a higher prevalence of pre-diagnosed non-HCC cancers(P<0.001),especially breast cancer,and a lower prevalence of cirrhosis.Male gender,ARFI score,and HBV were independent predictors of HCC.The 5-year risk of HCC was 5.9%and 9.8%for those ARFI-graded with severe fibrosis and cirrhosis.ARFI alone had an area under the receiver operating characteristic curve(AUROC)of 0.742 for prediction of HCC in 5 years.AUROC increased to 0.828 after adding etiology,gender,age,and platelet score.No difference was found in mortality rate among the groups.CONCLUSION The HBV group showed a higher prevalence of HCC but lower comorbidity that made mortality similar among the groups.Those patients with ARFI-graded severe fibrosis or cirrhosis should receive regular surveillance.展开更多
AIM: To build up the research models of hepatic fibrosis in mice.METHODS: Inbred wild-type FVB/N mice were either treated with alpha-naphthyl-isothiocyanate (ANIT), allyl alcohol (AA),carbon tetrachloride (CCl4), 3,5-...AIM: To build up the research models of hepatic fibrosis in mice.METHODS: Inbred wild-type FVB/N mice were either treated with alpha-naphthyl-isothiocyanate (ANIT), allyl alcohol (AA),carbon tetrachloride (CCl4), 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC), and silica, or subjected to common bile duct ligation (CBDL) to induce hepatic injury. Liver biopsies were performed every 4 wk to evaluate hepatic fibrosis over a period of 6 mo. Cumulative cirrhosis and survival curves were constructed by life table method and compared with Wilcoxon test.RESULTS: Under the dosages used, there was neither mortality nor cirrhosis in AA and silica-treated groups. DDC and ANIT caused cirrhosis within 4-12 and 12-24 wk, respectively.Both showed significantly faster cirrhosis induction at high dosages without significant alteration of survival. The duration for cirrhosis induction by CCl4 ranged from 4 to 20 wk, mainly dependent upon the dosage. However, the increase in CCl4dosage significantly worsened survival. Intraperitoneal CCl4administration resulted in better survival in comparison with gavage administration at high dosage, but not at medium and low dosages. After CBDL, all the mice developed liver cirrhosis within 4-8 wk and then died by the end of 16 wk.CONCLUSION: CBDL and administrations of ANIT, CCl4, and DDC ensured liver cirrhosis. CBDL required the least amount of time in cirrhosis induction, but caused shortened lives of mice. It was followed by DDC and ANIT administration with favorable survival. As for CCl4, the speed of cirrhosis induction and the mouse survival depended upon the dosages and the administration route.展开更多
In addition to causing cirrhosis and hepatocellular carcinoma, hepatitis C virus(HCV) is thought to cause hypolipidemia, hepatic steatosis, insulin resistance, metabolic syndrome, and diabetes. The viral life cycle of...In addition to causing cirrhosis and hepatocellular carcinoma, hepatitis C virus(HCV) is thought to cause hypolipidemia, hepatic steatosis, insulin resistance, metabolic syndrome, and diabetes. The viral life cycle of HCV depends on cholesterol metabolism in host cells. HCV core protein and nonstructural protein 5A perturb crucial lipid and glucose pathways, such as the sterol regulatory element-binding protein pathway and t he prot e in kinase B /mammal ian t arget of rapamycin/S6 kinase 1 pathway. Although several lines of transgenic mice expressing core or full HCV proteins exhibit hepatic steatosis and/or dyslipidemia, whether they completely reflect the metabolic alterations in humans with HCV infection remains unknown. Many cross-sectional studies have demonstrated increased prevalences of metabolic alterations and cardiovascular events in patients with chronic hepatitis C(CHC); however, conflicting results exist, primarily due to unavoidable individual variations. Utilizing anti-HCV therapy, most longitudinal cohort studies of CHC patients have demonstrated the favorable effects of viral clearance in attenuating metabolic alterations and cardiovascular risks. To determine the risks of HCV-associated metabolic alterations and associated complications in patients with CHC, it is necessary to adjust for crucial confounders, such as HCV genotype and host baseline glucose metabolism, for a long follow-up period after anti-HCV treatment. Adipose tissue is an important endocrine organ due to its release of adipocytokines, which regulate lipid and glucose metabolism. However, most data on HCV infection and adipocytokine alteration are inconclusive. A comprehensive overview of HCV-associated metabolic and adipocytokine alterations, from bench to bedside, is presented in this topic highlight.展开更多
AIM: To investigate a specific association between hepatic steatosis and hepatitis C virus (HCV) core. METHODS: HeLa cells and primary mouse hepatocytes were transfected with HCV core plasmid, and conditional transgen...AIM: To investigate a specific association between hepatic steatosis and hepatitis C virus (HCV) core. METHODS: HeLa cells and primary mouse hepatocytes were transfected with HCV core plasmid, and conditional transgenics in which hepatic over-expression of HCV core is regulated by the tetracycline-off system, were developed. The expression of the HCV core was assessed over one to six months after withdrawal of doxycycline (dox) by immunohistochemistry (IHC) and Western blotting and by sequential liver biopsy. Hepatic steatosis was evaluated using oil red stain. 8-hydroxydeoxyguanosine (8-OHdG) stains and caspase levels were conducted to clarify hepatic oxidative stress and apoptosis rate. Serum aminotransferase was checked. RESULTS: The transfected hepatocytes had globular cores under the lipid vesicles. In transgenic mice on control diet, core expression was robust, localized to the cytoplasmic vesicle membrane and strongly associatedwith microvesicular steatosis, which was gradually replaced by macrovesicular steatosis. However, both steatosis and core positive hepatocytes diminished with time. Increases in aminotransferase, caspase and 8-OHdG were associated with peak core expression. CONCLUSION: The core protein was readily detected and morphologically associated with steatosis in individual hepatocytes both in vitro and in vivo. In vivo, oxidative stress caused by the core potentially reduced the number of core positive hepatocytes and in parallel the level of steatosis. To our knowledge, this is the f irst animal model that directly shows topological relationship between HCV core and hepatic lipid vesicles.展开更多
AIM: To examine the differences of clinical behaviors between hepatocellular carcinomas (HCC) and hepatoblastomas (HB) in children.METHODS: From 1979 to 1997, we collected 73 HCC and 54 HB from two major medical cente...AIM: To examine the differences of clinical behaviors between hepatocellular carcinomas (HCC) and hepatoblastomas (HB) in children.METHODS: From 1979 to 1997, we collected 73 HCC and 54 HB from two major medical centers in Taiwan. Demographic, laboratory and radiological data, and survival curves were statistically compared.RESULTS: HCC clinically differed from HB in mean age (10.6 vs2.5 years; P＜0.001), status of hepatitis B infection (56/56 vs4/35, P＜0.001) and accompanying liver cirrhosis (26/40 vs 0/30, P＜0.001), portal vein thrombi (22/56 vs 5/38, P = 0.006) and para-aortic lymphadenopathy (10/56vs 1/38, P = 0.026). Due to a higher recurrence rate (7/12vs 2/13, P = 0.041), stage I HCC compared poorly in survivals with stage I HB (P= 0.0183). Chemotherapy could only benefit HB as evidenced by 66.7% of resectability conversion and improve survivals for advanced HB, even with unsuccessful conversion. The survival difference between stage I HB and advanced HB with delayed complete resection was of borderline insignificance (P = 0.0507).CONCLUSION: HCC and HB were preliminarily distinguishable by some dinical clues. Delayed resection after chemotherapy was only possible for HB. However, further studies are needed to strengthen our observation that appropriate reliance upon chemotherapy to subsequently resect advanced HB could achieve the comparable survival to that of stage I HB.展开更多
AIM: To evaluate the hepatic dysfunction in leptospirosis is usually mild and resolved eventually. However,sequential follow-up of liver biochemical data remained lacking..METHODS: The biochemistry data and clinical s...AIM: To evaluate the hepatic dysfunction in leptospirosis is usually mild and resolved eventually. However,sequential follow-up of liver biochemical data remained lacking..METHODS: The biochemistry data and clinical symptoms of 11 sporadic patients were collected and analyzed, focusing on the impacts of leptospirosis upon liver biochemistry tests.RESULTS: The results disclosed that of the 11 cases, 5 or 45% died. The liver biochemistry data in the beginning of the disease course were only mildly elevated.Nevertheless, late exaggerated aspartate transaminase (AST)elevations were noted in three cases who finally died when compared with the typical course. Besides, significant higher AST/alanine transaminase (ALT) ratios (AARs) of the peak levels for transaminase were also noted in the cases who eventually succumbed. The mean±SD of AARs for the survival group and dead group were 5.65±2.27 (n = 5)and 1.86±0.64 (n = 6) respectively (P= 0.006). The ratios of the cases who finally died were all more than 3.0.Conversely, the survival group's ratios were less than 3.0.CONCLUSION: Serial follow-up of transaminase might provide evidence to predict some rare evolutions in leptospirosis. If AST elevated progressively without a concomitant change of ALT, it might indicate an acute disease course with ensuing death. Additionally, AAR is another prognostic parameter for leptospirosis. Once the value was higher than 3.0, a grave prognosis is inevitable.展开更多
A seven-month-old infant was admitted to our hospital with a 1-wk history of shortness of breath, dysphagia, and fever. Diagnosis of esophageal perforation follow- ing fish vertebra ingestion was made by history revie...A seven-month-old infant was admitted to our hospital with a 1-wk history of shortness of breath, dysphagia, and fever. Diagnosis of esophageal perforation follow- ing fish vertebra ingestion was made by history review, pneumomediastinum and an irregular hyperdense lesion noted in initial chest radiogram. Neck computed tomo- graphy (CT) confirmed that the foreign body located at the cricopharyngeal level and a small esophageal tra- cheal fistula was shown by esophagogram. The initial re- sponse to treatment of fish bone removal guided by pan- endoscopy and antibiotics administration was poor since pneumothorax plus empyema developed. Fortunately, the patient’s condition finally improved after decortica- tion, mediastinotomy and perforated esophagus repair. To our knowledge, this is the first case report of esopha- geal perforation due to fish bone ingestion in infancy. In addition to particular caution that has to be taken when feeding the innocent, young victim, it may indicate the importance of surgical intervention for complicated esophageal perforation in infancy.展开更多
基金Supported by the Chang Gung Memorial Hospital and PAII Inc.(a United States subsidiary company of Ping An Insurance Group),No.SMRPG3I0011.
文摘BACKGROUND Acoustic radiation force impulse(ARFI)is used to measure liver fibrosis and predict outcomes.The performance of elastography in assessment of fibrosis is poorer in hepatitis B virus(HBV)than in other etiologies of chronic liver disease.AIM To evaluate the performance of ARFI in long-term outcome prediction among different etiologies of chronic liver disease.METHODS Consecutive patients who received an ARFI study between 2011 and 2018 were enrolled.After excluding dual infection,alcoholism,autoimmune hepatitis,and others with incomplete data,this retrospective cohort were divided into hepatitis B(HBV,n=1064),hepatitis C(HCV,n=507),and non-HBV,non-HCV(NBNC,n=391)groups.The indexed cases were linked to cancer registration(1987-2020)and national mortality databases.The differences in morbidity and mortality among the groups were analyzed.RESULTS At the enrollment,the HBV group showed more males(77.5%),a higher prevalence of prediagnosed hepatocellular carcinoma(HCC),and a lower prevalence of comorbidities than the other groups(P<0.001).The HCV group was older and had a lower platelet count and higher ARFI score than the other groups(P<0.001).The NBNC group showed a higher body mass index and platelet count,a higher prevalence of pre-diagnosed non-HCC cancers(P<0.001),especially breast cancer,and a lower prevalence of cirrhosis.Male gender,ARFI score,and HBV were independent predictors of HCC.The 5-year risk of HCC was 5.9%and 9.8%for those ARFI-graded with severe fibrosis and cirrhosis.ARFI alone had an area under the receiver operating characteristic curve(AUROC)of 0.742 for prediction of HCC in 5 years.AUROC increased to 0.828 after adding etiology,gender,age,and platelet score.No difference was found in mortality rate among the groups.CONCLUSION The HBV group showed a higher prevalence of HCC but lower comorbidity that made mortality similar among the groups.Those patients with ARFI-graded severe fibrosis or cirrhosis should receive regular surveillance.
基金Supported by the Chang Gung Memorial Hospital, Taoyuan, Taiwan, China, CMRPG 33014, CMRPG 33063 and CMRP 800
文摘AIM: To build up the research models of hepatic fibrosis in mice.METHODS: Inbred wild-type FVB/N mice were either treated with alpha-naphthyl-isothiocyanate (ANIT), allyl alcohol (AA),carbon tetrachloride (CCl4), 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC), and silica, or subjected to common bile duct ligation (CBDL) to induce hepatic injury. Liver biopsies were performed every 4 wk to evaluate hepatic fibrosis over a period of 6 mo. Cumulative cirrhosis and survival curves were constructed by life table method and compared with Wilcoxon test.RESULTS: Under the dosages used, there was neither mortality nor cirrhosis in AA and silica-treated groups. DDC and ANIT caused cirrhosis within 4-12 and 12-24 wk, respectively.Both showed significantly faster cirrhosis induction at high dosages without significant alteration of survival. The duration for cirrhosis induction by CCl4 ranged from 4 to 20 wk, mainly dependent upon the dosage. However, the increase in CCl4dosage significantly worsened survival. Intraperitoneal CCl4administration resulted in better survival in comparison with gavage administration at high dosage, but not at medium and low dosages. After CBDL, all the mice developed liver cirrhosis within 4-8 wk and then died by the end of 16 wk.CONCLUSION: CBDL and administrations of ANIT, CCl4, and DDC ensured liver cirrhosis. CBDL required the least amount of time in cirrhosis induction, but caused shortened lives of mice. It was followed by DDC and ANIT administration with favorable survival. As for CCl4, the speed of cirrhosis induction and the mouse survival depended upon the dosages and the administration route.
基金Supported by Grants from the Chang Gung Medical Research ProgramNo.CMRPG380353+7 种基金No.CMRPG3B1251No.CMRPG3B0401No.CMRPG3B1741No.CMRPG3B1742 and No.XMRPG3A0521the National Science CouncilTaiwanNo.100-2314-B-182-069-No.101-2314-B-182-083-and No.102-2628-B-182-021-MY3
文摘In addition to causing cirrhosis and hepatocellular carcinoma, hepatitis C virus(HCV) is thought to cause hypolipidemia, hepatic steatosis, insulin resistance, metabolic syndrome, and diabetes. The viral life cycle of HCV depends on cholesterol metabolism in host cells. HCV core protein and nonstructural protein 5A perturb crucial lipid and glucose pathways, such as the sterol regulatory element-binding protein pathway and t he prot e in kinase B /mammal ian t arget of rapamycin/S6 kinase 1 pathway. Although several lines of transgenic mice expressing core or full HCV proteins exhibit hepatic steatosis and/or dyslipidemia, whether they completely reflect the metabolic alterations in humans with HCV infection remains unknown. Many cross-sectional studies have demonstrated increased prevalences of metabolic alterations and cardiovascular events in patients with chronic hepatitis C(CHC); however, conflicting results exist, primarily due to unavoidable individual variations. Utilizing anti-HCV therapy, most longitudinal cohort studies of CHC patients have demonstrated the favorable effects of viral clearance in attenuating metabolic alterations and cardiovascular risks. To determine the risks of HCV-associated metabolic alterations and associated complications in patients with CHC, it is necessary to adjust for crucial confounders, such as HCV genotype and host baseline glucose metabolism, for a long follow-up period after anti-HCV treatment. Adipose tissue is an important endocrine organ due to its release of adipocytokines, which regulate lipid and glucose metabolism. However, most data on HCV infection and adipocytokine alteration are inconclusive. A comprehensive overview of HCV-associated metabolic and adipocytokine alterations, from bench to bedside, is presented in this topic highlight.
基金grants from National Science Council, Taiwan, China. No. NSC 93-2314-B-182A-148, 94-2314-B-182A-185 and 95-3112-B-182A-002 Chang Gung Memorial Hospital, Taoyuan, Taiwan, China. No. CMRPG 33014, CMRPG 340341 and SMRPG350081
文摘AIM: To investigate a specific association between hepatic steatosis and hepatitis C virus (HCV) core. METHODS: HeLa cells and primary mouse hepatocytes were transfected with HCV core plasmid, and conditional transgenics in which hepatic over-expression of HCV core is regulated by the tetracycline-off system, were developed. The expression of the HCV core was assessed over one to six months after withdrawal of doxycycline (dox) by immunohistochemistry (IHC) and Western blotting and by sequential liver biopsy. Hepatic steatosis was evaluated using oil red stain. 8-hydroxydeoxyguanosine (8-OHdG) stains and caspase levels were conducted to clarify hepatic oxidative stress and apoptosis rate. Serum aminotransferase was checked. RESULTS: The transfected hepatocytes had globular cores under the lipid vesicles. In transgenic mice on control diet, core expression was robust, localized to the cytoplasmic vesicle membrane and strongly associatedwith microvesicular steatosis, which was gradually replaced by macrovesicular steatosis. However, both steatosis and core positive hepatocytes diminished with time. Increases in aminotransferase, caspase and 8-OHdG were associated with peak core expression. CONCLUSION: The core protein was readily detected and morphologically associated with steatosis in individual hepatocytes both in vitro and in vivo. In vivo, oxidative stress caused by the core potentially reduced the number of core positive hepatocytes and in parallel the level of steatosis. To our knowledge, this is the f irst animal model that directly shows topological relationship between HCV core and hepatic lipid vesicles.
文摘AIM: To examine the differences of clinical behaviors between hepatocellular carcinomas (HCC) and hepatoblastomas (HB) in children.METHODS: From 1979 to 1997, we collected 73 HCC and 54 HB from two major medical centers in Taiwan. Demographic, laboratory and radiological data, and survival curves were statistically compared.RESULTS: HCC clinically differed from HB in mean age (10.6 vs2.5 years; P＜0.001), status of hepatitis B infection (56/56 vs4/35, P＜0.001) and accompanying liver cirrhosis (26/40 vs 0/30, P＜0.001), portal vein thrombi (22/56 vs 5/38, P = 0.006) and para-aortic lymphadenopathy (10/56vs 1/38, P = 0.026). Due to a higher recurrence rate (7/12vs 2/13, P = 0.041), stage I HCC compared poorly in survivals with stage I HB (P= 0.0183). Chemotherapy could only benefit HB as evidenced by 66.7% of resectability conversion and improve survivals for advanced HB, even with unsuccessful conversion. The survival difference between stage I HB and advanced HB with delayed complete resection was of borderline insignificance (P = 0.0507).CONCLUSION: HCC and HB were preliminarily distinguishable by some dinical clues. Delayed resection after chemotherapy was only possible for HB. However, further studies are needed to strengthen our observation that appropriate reliance upon chemotherapy to subsequently resect advanced HB could achieve the comparable survival to that of stage I HB.
基金Supported by the Chang Gung Medical Research Project fund, No. CMRPG 33014
文摘AIM: To evaluate the hepatic dysfunction in leptospirosis is usually mild and resolved eventually. However,sequential follow-up of liver biochemical data remained lacking..METHODS: The biochemistry data and clinical symptoms of 11 sporadic patients were collected and analyzed, focusing on the impacts of leptospirosis upon liver biochemistry tests.RESULTS: The results disclosed that of the 11 cases, 5 or 45% died. The liver biochemistry data in the beginning of the disease course were only mildly elevated.Nevertheless, late exaggerated aspartate transaminase (AST)elevations were noted in three cases who finally died when compared with the typical course. Besides, significant higher AST/alanine transaminase (ALT) ratios (AARs) of the peak levels for transaminase were also noted in the cases who eventually succumbed. The mean±SD of AARs for the survival group and dead group were 5.65±2.27 (n = 5)and 1.86±0.64 (n = 6) respectively (P= 0.006). The ratios of the cases who finally died were all more than 3.0.Conversely, the survival group's ratios were less than 3.0.CONCLUSION: Serial follow-up of transaminase might provide evidence to predict some rare evolutions in leptospirosis. If AST elevated progressively without a concomitant change of ALT, it might indicate an acute disease course with ensuing death. Additionally, AAR is another prognostic parameter for leptospirosis. Once the value was higher than 3.0, a grave prognosis is inevitable.
基金Supported by grant from CGMH, Taoyuan, Taiwan, No. CMRPG 33014
文摘A seven-month-old infant was admitted to our hospital with a 1-wk history of shortness of breath, dysphagia, and fever. Diagnosis of esophageal perforation follow- ing fish vertebra ingestion was made by history review, pneumomediastinum and an irregular hyperdense lesion noted in initial chest radiogram. Neck computed tomo- graphy (CT) confirmed that the foreign body located at the cricopharyngeal level and a small esophageal tra- cheal fistula was shown by esophagogram. The initial re- sponse to treatment of fish bone removal guided by pan- endoscopy and antibiotics administration was poor since pneumothorax plus empyema developed. Fortunately, the patient’s condition finally improved after decortica- tion, mediastinotomy and perforated esophagus repair. To our knowledge, this is the first case report of esopha- geal perforation due to fish bone ingestion in infancy. In addition to particular caution that has to be taken when feeding the innocent, young victim, it may indicate the importance of surgical intervention for complicated esophageal perforation in infancy.
