Studies performed in experimental small animalswith hepatic-based metabolic disorders but nostructural liver disease,including Gunn andanalbuminaemic rats and rabbits with inherited low-density lipoprotein receptor de...Studies performed in experimental small animalswith hepatic-based metabolic disorders but nostructural liver disease,including Gunn andanalbuminaemic rats and rabbits with inherited low-density lipoprotein receptor deficiency,have shownthat up to 95% of hepatocytes transplanted into thespleen or liver remain in these sites,withimprovement in metabolic function展开更多
AIM: To establish if a distinct urinary metabolic profile could be identified in Bangladeshi hepatitis-B hepatocellular carcinoma(HCC) patients compared to cirrhosis patients and controls. METHODS: Urine samples from ...AIM: To establish if a distinct urinary metabolic profile could be identified in Bangladeshi hepatitis-B hepatocellular carcinoma(HCC) patients compared to cirrhosis patients and controls. METHODS: Urine samples from 42 Bangladeshi patients with HCC(39 patients with hepatitis-B HCC), 47 with cirrhosis on a background of hepatitis B, 46 with chronic hepatitis B, and seven ethnically-matched healthy controls were analyzed using nuclear magnetic resonance(NMR) spectroscopy. A full dietary and medication history was recorded for each subject. The urinary NMR data were analyzed using principal component analysis(PCA) and orthogonal partial leastsquared discriminant analysis(OPLS-DA) techniques. Differences in relative signal levels of the most discriminatory metabolites identified by PCA and OPLSDA were compared between subject groups using an independent samples Kruskal-Wallis one-way analysis of variance(ANOVA) test with all pairwise multiple comparisons. Within the patient subgroups, the MannWhitney U test was used to compare metabolite levels depending on hepatitis B e-antigen(HBe Ag) status and treatment with anti-viral therapy. A BenjaminiHochberg adjustment was applied to acquire the level of significance for multiple testing, with a declared level of statistical significance of P < 0.05.RESULTS: There were significant differences in age(P < 0.001), weight(P < 0.001), and body mass index(P < 0.001) across the four clinical subgroups. Serum alanine aminotransferase(ALT) was significantly higher in the HCC group compared to controls(P < 0.001); serum α-fetoprotein was generally markedly elevated in HCC compared to controls; and serum creatinine levels were significantly reduced in the HCC group compared to the cirrhosis group(P = 0.004). A threefactor PCA scores plot showed clustering of the urinary NMR spectra from the four subgroups. Metabolites that contributed to the discrimination between the subgroups included acetate, creatine, creatinine, dimethyamine(DMA), formate, glycine, hippurate, and trimethylamine-N-oxide(TMAO). A comparison of relative metabolite levels confirmed that carnitine was significantly increased in HCC; and creatinine, hippurate, and TMAO were significantly reduced in HCC compared to the other subgroups. HBe Ag negative patients showed a significant increase in creatinine(P = 0.001) compared to HBe Ag positive patients in the chronic hepatitis B subgroup, whilst HBe Ag negative patients showed a significant decrease in DMA(P = 0.004) in the cirrhosis subgroup compared to HBe Ag positive patients. There were no differences in metabolite levels in HCC patients who did or did not receive antiviral treatment. CONCLUSION: Urinary NMR changes in Bangladeshi HCC were identified, corroborating previous findings from Egypt and West Africa. These findings could form the basis for the development of a cost-effective HCC dipstick screening test.展开更多
Introduction In my presentation to the 4th International Symposium on Hepatic Failure and Artificial Liver Support in Chongqing on which this paper is based, I was specifically asked to address the question of whether...Introduction In my presentation to the 4th International Symposium on Hepatic Failure and Artificial Liver Support in Chongqing on which this paper is based, I was specifically asked to address the question of whether albumin dialysis, as in the Molecular Adsorbents Recirculating System (MARS) did correct known abnormalities of the disturbed pathophysiology in liver failure. Before doing this展开更多
Over the past five years, we have gained much new knowledge of the cirrhotic patient with liver failure, sick enough to require admission to hospital. In Europe, this has come from the outstanding work of the Chronic ...Over the past five years, we have gained much new knowledge of the cirrhotic patient with liver failure, sick enough to require admission to hospital. In Europe, this has come from the outstanding work of the Chronic Liver Failure (CLIF) Consortium set up by Rajiv Jalan, Vicente Arroyo, and other leading hepatologists to which I will be mainly referring to.[1] Shiv Sarin and colleagues in Asia Pacific despite using somewhat different definitions have reported similar findings and for their latest views on acute-on-chronic liver failure (ACLF). I would refer you to the excellent review of Sarin and Choudhury[2] in Nature Reviews Gastroenterology & Hepatology, published in 2016. The characterisation of a syndrome of ACLF with defined subgroups has led to an improved prognostic assessment and provides a new basis for determining selection criteria for liver transplantation (LT) and of measures to enhance recovery from ACLF.展开更多
文摘Studies performed in experimental small animalswith hepatic-based metabolic disorders but nostructural liver disease,including Gunn andanalbuminaemic rats and rabbits with inherited low-density lipoprotein receptor deficiency,have shownthat up to 95% of hepatocytes transplanted into thespleen or liver remain in these sites,withimprovement in metabolic function
文摘AIM: To establish if a distinct urinary metabolic profile could be identified in Bangladeshi hepatitis-B hepatocellular carcinoma(HCC) patients compared to cirrhosis patients and controls. METHODS: Urine samples from 42 Bangladeshi patients with HCC(39 patients with hepatitis-B HCC), 47 with cirrhosis on a background of hepatitis B, 46 with chronic hepatitis B, and seven ethnically-matched healthy controls were analyzed using nuclear magnetic resonance(NMR) spectroscopy. A full dietary and medication history was recorded for each subject. The urinary NMR data were analyzed using principal component analysis(PCA) and orthogonal partial leastsquared discriminant analysis(OPLS-DA) techniques. Differences in relative signal levels of the most discriminatory metabolites identified by PCA and OPLSDA were compared between subject groups using an independent samples Kruskal-Wallis one-way analysis of variance(ANOVA) test with all pairwise multiple comparisons. Within the patient subgroups, the MannWhitney U test was used to compare metabolite levels depending on hepatitis B e-antigen(HBe Ag) status and treatment with anti-viral therapy. A BenjaminiHochberg adjustment was applied to acquire the level of significance for multiple testing, with a declared level of statistical significance of P < 0.05.RESULTS: There were significant differences in age(P < 0.001), weight(P < 0.001), and body mass index(P < 0.001) across the four clinical subgroups. Serum alanine aminotransferase(ALT) was significantly higher in the HCC group compared to controls(P < 0.001); serum α-fetoprotein was generally markedly elevated in HCC compared to controls; and serum creatinine levels were significantly reduced in the HCC group compared to the cirrhosis group(P = 0.004). A threefactor PCA scores plot showed clustering of the urinary NMR spectra from the four subgroups. Metabolites that contributed to the discrimination between the subgroups included acetate, creatine, creatinine, dimethyamine(DMA), formate, glycine, hippurate, and trimethylamine-N-oxide(TMAO). A comparison of relative metabolite levels confirmed that carnitine was significantly increased in HCC; and creatinine, hippurate, and TMAO were significantly reduced in HCC compared to the other subgroups. HBe Ag negative patients showed a significant increase in creatinine(P = 0.001) compared to HBe Ag positive patients in the chronic hepatitis B subgroup, whilst HBe Ag negative patients showed a significant decrease in DMA(P = 0.004) in the cirrhosis subgroup compared to HBe Ag positive patients. There were no differences in metabolite levels in HCC patients who did or did not receive antiviral treatment. CONCLUSION: Urinary NMR changes in Bangladeshi HCC were identified, corroborating previous findings from Egypt and West Africa. These findings could form the basis for the development of a cost-effective HCC dipstick screening test.
文摘Introduction In my presentation to the 4th International Symposium on Hepatic Failure and Artificial Liver Support in Chongqing on which this paper is based, I was specifically asked to address the question of whether albumin dialysis, as in the Molecular Adsorbents Recirculating System (MARS) did correct known abnormalities of the disturbed pathophysiology in liver failure. Before doing this
文摘Over the past five years, we have gained much new knowledge of the cirrhotic patient with liver failure, sick enough to require admission to hospital. In Europe, this has come from the outstanding work of the Chronic Liver Failure (CLIF) Consortium set up by Rajiv Jalan, Vicente Arroyo, and other leading hepatologists to which I will be mainly referring to.[1] Shiv Sarin and colleagues in Asia Pacific despite using somewhat different definitions have reported similar findings and for their latest views on acute-on-chronic liver failure (ACLF). I would refer you to the excellent review of Sarin and Choudhury[2] in Nature Reviews Gastroenterology & Hepatology, published in 2016. The characterisation of a syndrome of ACLF with defined subgroups has led to an improved prognostic assessment and provides a new basis for determining selection criteria for liver transplantation (LT) and of measures to enhance recovery from ACLF.
