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Hepatitis C virus genotypes: epidemiological and clinical associations. Benelux Study Group on Treatment of Chronic Hepatitis C. 丙型肝炎病毒基因型:流行病学和临床相关性慢性丙型肝炎治疗比荷卢研究小组。
Liver Pub Date : 1998-02-01
B Kleter, J T Brouwer, F Nevens, L J van Doorn, A Elewaut, J Versieck, P P Michielsen, M L Hautekeete, R A Chamuleau, R Brénard, N Bourgeois, M Adler, W G Quint, C M Bronkhorst, R A Heijtink, W J Hop, J Fevery, S W Schalm
{"title":"Hepatitis C virus genotypes: epidemiological and clinical associations. Benelux Study Group on Treatment of Chronic Hepatitis C.","authors":"B Kleter,&nbsp;J T Brouwer,&nbsp;F Nevens,&nbsp;L J van Doorn,&nbsp;A Elewaut,&nbsp;J Versieck,&nbsp;P P Michielsen,&nbsp;M L Hautekeete,&nbsp;R A Chamuleau,&nbsp;R Brénard,&nbsp;N Bourgeois,&nbsp;M Adler,&nbsp;W G Quint,&nbsp;C M Bronkhorst,&nbsp;R A Heijtink,&nbsp;W J Hop,&nbsp;J Fevery,&nbsp;S W Schalm","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>In a cohort of 292 chronic hepatitis C patients living in the Benelux countries the relationship between viral genotype and geographical origin, route of transmission, clinical characteristics and severity of liver disease was analyzed. HCV-RNA isolates could be classified by the Line Probe Assay (LiPA) as 1a, 1b, 2, 3, 4 or 5 in 286 (98%) cases. Patients of European origin were predominantly infected with HCV subtype 1b (164/254, 65%, CI 58-70%), as were patients of Asian origin (7/13, 54%). Patients originating from Surinam (South America) had predominantly type 2 (9/10, 90%), whereas Africans were mainly infected with type 4 (7/9, 77%). Blood transfusion was the mode of transmission in 142 (50%) patients, intravenous drug abuse (IVDA) in 40 (14%), occupational needle accident or tattoo in 11 (4%); no obvious source of infection was found in 93 (33%). In patients infected by blood transfusion, subtype 1b was predominant (70%, CI 61-77%), whereas subtypes la and 3 were predominant in those infected by IVDA (25% and 45%, respectively, p<0.001). Cirrhosis was observed in 68 (24%) patients; in multivariate analysis, factors independently related to cirrhosis were: the duration of infection, age and prior hepatitis B. No significant relationship was found between the severity of fibrosis or liver inflammation and the HCV (sub)types. In summary, in this large cohort of patients in the Benelux countries the hepatitis C virus (sub)type present was clearly related to the country of origin and the route of transmission, but not to the severity of liver disease.</p>","PeriodicalId":18183,"journal":{"name":"Liver","volume":"18 1","pages":"32-8"},"PeriodicalIF":0.0,"publicationDate":"1998-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20471034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Gene expression in liver after toxic injury: analysis of heat shock response and oxidative stress-inducible genes. 中毒性损伤后肝脏的基因表达:热休克反应和氧化应激诱导基因的分析。
Liver Pub Date : 1997-08-01 DOI: 10.1111/j.1600-0676.1997.tb00804.x
L Schiaffonati, L Tiberio
{"title":"Gene expression in liver after toxic injury: analysis of heat shock response and oxidative stress-inducible genes.","authors":"L Schiaffonati,&nbsp;L Tiberio","doi":"10.1111/j.1600-0676.1997.tb00804.x","DOIUrl":"https://doi.org/10.1111/j.1600-0676.1997.tb00804.x","url":null,"abstract":"<p><p>In the liver, CCl4 induces cell necrosis followed by regeneration. Cell injury is caused by free radical damage and may be due, at least in part, to oxidative stress and the subsequent formation of reactive oxygen intermediates (ROIs). In a rat model of acute CCl4-induced hepatic injury, we examined the expression of genes involved in cellular response to different kinds of stress, including oxidative stress (hsp 70 family, heme oxygenase), in free radical detoxification (Mn superoxide dismutase and Cu/ Zn superoxide dismutase), in iron homeostasis (H and L ferritin subunits) and in the cell cycle (c-fos, c-jun, histone H3). As an experimental approach, we first analysed the pattern of protein synthesised by liver slices in vitro. Then we studied the mechanisms regulating the expression of different genes, by analysing both mRNA steady state levels and transcription rates. Activation of the specific heat shock transcription factor (HSF) by CCl4 was also investigated. We observed that different members of the hsp70 family (hsp70, hsc73, grp78) are activated by different kinetics and are regulated mainly at the transcriptional level. Induction of the hsp70 gene occurs rapidly and transiently and is preceded by the activation of HSF DNA-binding activity. We demonstrated an increase in the steady-state levels of mRNAs for heme oxygenase, Mn and Cu/Zn superoxide dismutases and H and L ferritin subunits. However, different kinetics and regulatory mechanisms occurred with different genes. We showed that induction of c-fos and c-jun protooncogenes is the earliest event after CCl4 administration, whereas histone H3 expression peaked at 24-48 h. The results of this study are interpreted as evidence that activation of specific stress response genes is primarily related to the defence against the rapidly occurring cell damage, but may also be related to subsequent processes of tissue inflammation and cell proliferation.</p>","PeriodicalId":18183,"journal":{"name":"Liver","volume":"17 4","pages":"183-91"},"PeriodicalIF":0.0,"publicationDate":"1997-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1600-0676.1997.tb00804.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20239316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 87
In vivo and in vitro hepatic 31P magnetic resonance spectroscopy and electron microscopy of the cirrhotic liver. 肝31P磁共振波谱及肝硬化电镜观察。
Liver Pub Date : 1997-08-01 DOI: 10.1111/j.1600-0676.1997.tb00806.x
S D Taylor-Robinson, J Sargentoni, J D Bell, N Saeed, K K Changani, B R Davidson, K Rolles, A K Burroughs, H J Hodgson, C S Foster, I J Cox
{"title":"In vivo and in vitro hepatic 31P magnetic resonance spectroscopy and electron microscopy of the cirrhotic liver.","authors":"S D Taylor-Robinson,&nbsp;J Sargentoni,&nbsp;J D Bell,&nbsp;N Saeed,&nbsp;K K Changani,&nbsp;B R Davidson,&nbsp;K Rolles,&nbsp;A K Burroughs,&nbsp;H J Hodgson,&nbsp;C S Foster,&nbsp;I J Cox","doi":"10.1111/j.1600-0676.1997.tb00806.x","DOIUrl":"https://doi.org/10.1111/j.1600-0676.1997.tb00806.x","url":null,"abstract":"<p><p>In vivo 31P magnetic resonance spectroscopy (MRS) provides direct biochemical information on hepatic metabolic processes. To assess in vivo changes in hepatic 31P MRS in liver transplant candidates, we studied 31 patients with cirrhosis of varying aetiology; 14 with compensated cirrhosis (Pugh's score < or = 7) and 17 with decompensated cirrhosis (Pugh's score > or = 8). Underlying cellular abnormalities were characterised using in vitro 31P MRS and electron microscopy. In vitro spectra were obtained from liver extracts, freeze-clamped at recipient hepatectomy, from all subjects. Electron microscopy of liver tissue was also performed in 17 cases. Relative to nucleotide triphosphates, elevations in phosphomonoesters and reductions in phosphodiesters were observed in vivo with worsening liver function. In vitro spectra showed elevated phosphoethanolamine and phosphocholine, and reduced glycerophosphorylethanolamine and glycerophosphorylcholine, mirroring the in vivo changes, but no distinction was noted between compensated and decompensated cirrhosis. With electron microscopy, functional decompensation was associated with reduced endoplasmic reticulum in parenchymal liver disease, but elevated levels in biliary cirrhosis. We conclude that in vivo spectral abnormalities in cirrhosis are consistent with alterations in phospholipid metabolism and quantity of endoplasmic reticulum. However, in individual patients the biopsy results do not always mirror in vivo findings.</p>","PeriodicalId":18183,"journal":{"name":"Liver","volume":"17 4","pages":"198-209"},"PeriodicalIF":0.0,"publicationDate":"1997-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1600-0676.1997.tb00806.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20239193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 64
Deleted form of hepatocyte growth factor (dHGF) increases the number of platelets in rats with liver cirrhosis. 肝细胞生长因子(dHGF)的缺失形式增加了肝硬化大鼠的血小板数量。
Liver Pub Date : 1997-08-01 DOI: 10.1111/j.1600-0676.1997.tb00805.x
H Masunaga, N Fujise, Y Yamashita, A Shiota, H Yasuda, K Higashio
{"title":"Deleted form of hepatocyte growth factor (dHGF) increases the number of platelets in rats with liver cirrhosis.","authors":"H Masunaga,&nbsp;N Fujise,&nbsp;Y Yamashita,&nbsp;A Shiota,&nbsp;H Yasuda,&nbsp;K Higashio","doi":"10.1111/j.1600-0676.1997.tb00805.x","DOIUrl":"https://doi.org/10.1111/j.1600-0676.1997.tb00805.x","url":null,"abstract":"<p><p>The effect of the deleted form of hepatocyte growth factor (dHGF) on thrombopoiesis was studied in rats. When normal rats were injected with dHGF (0.5 mg/kg i.v. twice a day), the number of platelets increased to about 1.5-fold the initial level. In addition, the treatment with dHGF (0.5 mg/kg i.v. twice daily) significantly increased the number of platelets in rats with liver cirrhosis induced by carbon tetrachloride and phenobarbital. When dHGF was given to rats at a dose of 0.05 or 0.5 mg/kg from the beginning of the induction of dimethylnitrosamine liver cirrhosis to day 28, dHGF dose-dependently ameliorated thrombocytopenia and completely prevented it at a dose of 0.5 mg/kg. These results indicate that dHGF may be applicable to the treatment of thrombocytopenia associated with liver cirrhosis.</p>","PeriodicalId":18183,"journal":{"name":"Liver","volume":"17 4","pages":"192-7"},"PeriodicalIF":0.0,"publicationDate":"1997-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1600-0676.1997.tb00805.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20239192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 4
Expression of transforming growth factor alpha and epidermal growth factor receptor in human hepatocellular carcinoma. 转化生长因子α和表皮生长因子受体在人肝细胞癌中的表达。
Liver Pub Date : 1997-08-01 DOI: 10.1111/j.1600-0676.1997.tb00803.x
S Kira, T Nakanishi, S Suemori, M Kitamoto, Y Watanabe, G Kajiyama
{"title":"Expression of transforming growth factor alpha and epidermal growth factor receptor in human hepatocellular carcinoma.","authors":"S Kira,&nbsp;T Nakanishi,&nbsp;S Suemori,&nbsp;M Kitamoto,&nbsp;Y Watanabe,&nbsp;G Kajiyama","doi":"10.1111/j.1600-0676.1997.tb00803.x","DOIUrl":"https://doi.org/10.1111/j.1600-0676.1997.tb00803.x","url":null,"abstract":"<p><p>Transforming growth factor alpha (TGF-alpha) is thought to be involved in liver regeneration, cellular proliferation, and hepatocarcinogenesis. We have looked at the relationship between TGF-alpha and it's receptor, and have attempted to relate the expression of TGF-alpha and it's receptor to the differentiation of hepatocellular carcinoma (HCC) on serial sections of HCC. We examined immunohistochemically the expression of the TGF-alpha and of epidermal growth factor receptor (EGFR) proteins in the same area of 53 nodules (< 5 cm in diameter) of HCC obtained from patients. Immunoreactive proteins were visualized by using a biotin-streptoavidin system (LSAB Kil, Dako). TGF-alpha was strongly expressed in 29 of 53 (54.7%) nodules. Specimens strongly positive for TGF-alpha were found mainly in well-differentiated HCC, while specimens positive for EGFR were found mainly in poorly differentiated HCC (p < 0.05). In the tissues that stained weakly positive for TGF-alpha, the expression of EGFR differed significantly, according to the degree of HCC histologic differentiation (p < 0.05). These results led us to speculate that the expression of TGF-alpha and EGFR might be related to the pattern of histologic differentiation of HCC.</p>","PeriodicalId":18183,"journal":{"name":"Liver","volume":"17 4","pages":"177-82"},"PeriodicalIF":0.0,"publicationDate":"1997-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1600-0676.1997.tb00803.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20239315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 99
Unusual spontaneous hepatic vein to paraumbilical vein shunt in a patient with Budd-Chiari syndrome and cirrhosis: a case report. 布-恰里综合征合并肝硬化患者不寻常的自发肝静脉至脐旁静脉分流一例报告。
Liver Pub Date : 1997-08-01 DOI: 10.1111/j.1600-0676.1997.tb00807.x
A I Bloom, S E Cohen, P D Lebensart, O Pappo, A Eid
{"title":"Unusual spontaneous hepatic vein to paraumbilical vein shunt in a patient with Budd-Chiari syndrome and cirrhosis: a case report.","authors":"A I Bloom,&nbsp;S E Cohen,&nbsp;P D Lebensart,&nbsp;O Pappo,&nbsp;A Eid","doi":"10.1111/j.1600-0676.1997.tb00807.x","DOIUrl":"https://doi.org/10.1111/j.1600-0676.1997.tb00807.x","url":null,"abstract":"<p><p>A very unusual portosystemic shunt was identified using color flow Doppler sonography in an adult male with Budd-Chiari syndrome and cirrhosis secondary to a hypercoagulability state. Hepatofugal blood flow was demonstrated between the middle hepatic vein and a recanalized paraumbilical vein, resulting clinically in prominent periumbilical veins. The clinical and radiological features are described.</p>","PeriodicalId":18183,"journal":{"name":"Liver","volume":"17 4","pages":"210-3"},"PeriodicalIF":0.0,"publicationDate":"1997-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1600-0676.1997.tb00807.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20239195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 2
Transforming growth factor alpha (TGF-alpha) expression correlates with DNA replication in regenerating rat liver whatever the hepatectomy extent. 无论肝切除程度如何,转化生长因子α (tgf - α)表达与再生大鼠肝脏DNA复制相关。
Liver Pub Date : 1997-08-01 DOI: 10.1111/j.1600-0676.1997.tb00802.x
M Scotté, A Laquerrière, S Masson, M Hiron, P Ténière, J Hémet, J P Lebreton, M Daveau
{"title":"Transforming growth factor alpha (TGF-alpha) expression correlates with DNA replication in regenerating rat liver whatever the hepatectomy extent.","authors":"M Scotté,&nbsp;A Laquerrière,&nbsp;S Masson,&nbsp;M Hiron,&nbsp;P Ténière,&nbsp;J Hémet,&nbsp;J P Lebreton,&nbsp;M Daveau","doi":"10.1111/j.1600-0676.1997.tb00802.x","DOIUrl":"https://doi.org/10.1111/j.1600-0676.1997.tb00802.x","url":null,"abstract":"<p><p>Liver regeneration is a physiological mechanism that leads to restoration of the hepatic parenchyma following hepatectomy or toxic injury. As a two-third hepatectomy is the usual model to analyse this phenomenon, few studies have compared liver regeneration after minor vs major hepatectomy. We have used a quantitative RT-PCR technique to study the hepatic transcription of the TGF-alpha gene in rats submitted to 30% or 80% hepatectomy and we have correlated this transcription with the regenerative response assessed by flow cytometry and Ki-67 expression. The level of TGF-alpha expression and the regenerative response were different, according to the volume of liver removed, and were statistically correlated (r = 0.679, p = 0.002). TGF-alpha expression and phase S peaked at day 2 vs 6 in the 80% vs 30% hepatectomized rat groups, respectively. Ki-67 expression occurred at 2 h post-hepatectomy in the two groups of rats and was observed until day 14 mainly in the 80% hepatectomy group. Our results indicate that TGF-alpha expression in regenerating liver is strongly correlated with hepatocyte mitosis, that a delayed regenerative response occurs following 30% hepatectomy and that the course of regeneration differs between minor vs major hepatectomy.</p>","PeriodicalId":18183,"journal":{"name":"Liver","volume":"17 4","pages":"171-6"},"PeriodicalIF":0.0,"publicationDate":"1997-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1600-0676.1997.tb00802.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20239313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
The measure of life-time alcohol consumption in patients with cirrhosis: reproducibility and clinical relevance. 肝硬化患者终生饮酒量的测量:可重复性和临床相关性
Liver Pub Date : 1995-08-01 DOI: 10.1111/j.1600-0676.1995.tb00671.x
S Arico, G Galatola, M Tabone, G Corrao, P Torchio, M Valenti, M De la Pierre
{"title":"The measure of life-time alcohol consumption in patients with cirrhosis: reproducibility and clinical relevance.","authors":"S Arico,&nbsp;G Galatola,&nbsp;M Tabone,&nbsp;G Corrao,&nbsp;P Torchio,&nbsp;M Valenti,&nbsp;M De la Pierre","doi":"10.1111/j.1600-0676.1995.tb00671.x","DOIUrl":"https://doi.org/10.1111/j.1600-0676.1995.tb00671.x","url":null,"abstract":"<p><p>Our aims were to design a reproducible method of measuring life-time alcohol consumption in patients with cirrhosis, and to assess the risk of liver decompensation associated with alcohol intake using a case-control design and a multivariate analysis. We studied 439 patients (\"cases\") with decompensated cirrhosis, and 233 with compensated cirrhosis (\"controls\"). Mean life-time daily amount and duration of alcohol intake were measured by a standardized questionnaire, whose reproducibility, assessed by interviewing 75 relatives, was 70% for daily alcohol intake and 84% for duration of intake. Better reproducibility was found by re-interviewing patients at discharge from hospital. Daily alcohol intake was significantly higher in males, younger patients and patients with liver decompensation. After stratification according to the average life-time daily alcohol intake, we found a significant increase in the risk of liver decompensation from 125 g ethanol intake per day onwards. No association was found between duration of alcohol intake and risk of liver decompensation. We conclude that alcohol intake can be reliably and reproducibly measured: in patients with cirrhosis, increased alcohol intake is associated with increased risk of liver decompensation, with a significant dose-effect above a daily intake of 125 g ethanol.</p>","PeriodicalId":18183,"journal":{"name":"Liver","volume":"15 4","pages":"202-8"},"PeriodicalIF":0.0,"publicationDate":"1995-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1600-0676.1995.tb00671.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19524411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 21
The arterial ketone body ratio and serum alpha-fetoprotein level in patients with acute hepatic failure. 急性肝功能衰竭患者动脉酮体比及血清甲胎蛋白水平。
Liver Pub Date : 1995-08-01 DOI: 10.1111/j.1600-0676.1995.tb00674.x
H Yamasaki, T Saibara, T Maeda, S Onishi
{"title":"The arterial ketone body ratio and serum alpha-fetoprotein level in patients with acute hepatic failure.","authors":"H Yamasaki,&nbsp;T Saibara,&nbsp;T Maeda,&nbsp;S Onishi","doi":"10.1111/j.1600-0676.1995.tb00674.x","DOIUrl":"https://doi.org/10.1111/j.1600-0676.1995.tb00674.x","url":null,"abstract":"<p><p>Hepatocyte regeneration is essential for recovery in acute hepatic failure, although it requires a large amount of energy. The ratio of acetoacetate to beta-hydroxybutyrate in arterial blood has been reported to reflect the cellular energy charge of hepatocytes, and we proposed that the recovery of the ratio in the early days of acute hepatic failure is essential for survival. However, there is no report on any marker of regeneration to confirm this hypothesis. In this study, we have assessed this ratio and the serum alpha-fetoprotein level sequentially in 26 patients with acute hepatic failure. Ten patients recovered and 16 died. The arterial blood ketone body ratio 3 days after the onset of hepatic encephalopathy of grade II or more was below 0.6 in 15 of the 16 nonsurvivors, whereas that in the 10 survivors was above 0.6. There was a positive correlation between the arterial blood ketone body ratio and the maximal concentration of alpha-fetoprotein (r = 0.465, p < 0.02 by Student's t-test). These data indicate that the arterial blood ketone body ratio is a marker for the capacity of the liver to regenerate and for the prognosis in patients with acute hepatic failure: effective hepatocyte regeneration may be impossible if these metabolic changes in acute hepatic failure impair the hepatocyte energy charge severely.</p>","PeriodicalId":18183,"journal":{"name":"Liver","volume":"15 4","pages":"219-23"},"PeriodicalIF":0.0,"publicationDate":"1995-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1600-0676.1995.tb00674.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19524925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 12
Hepatic purine and pyrimidine metabolism: implications for antiviral chemotherapy of viral hepatitis. 肝嘌呤和嘧啶代谢:对病毒性肝炎抗病毒化疗的影响。
Liver Pub Date : 1995-08-01 DOI: 10.1111/j.1600-0676.1995.tb00667.x
T Shaw, S A Locarnini
{"title":"Hepatic purine and pyrimidine metabolism: implications for antiviral chemotherapy of viral hepatitis.","authors":"T Shaw,&nbsp;S A Locarnini","doi":"10.1111/j.1600-0676.1995.tb00667.x","DOIUrl":"https://doi.org/10.1111/j.1600-0676.1995.tb00667.x","url":null,"abstract":"<p><p>The use of nucleoside analogues as antiviral agents is expanding. For most nucleoside analogues, intracellular phosphorylation is the major prerequisite for activity. Antiviral activity may be limited by poor uptake, absence of appropriate activating enzymes, catabolism, and competition from endogenous nucleotides. Appreciation of these factors, which are species-, tissue- and cell-specific is important in the understanding of the pharmacology and toxicology of nucleoside analogues. The use of nucleoside analogues against the agents of viral hepatitis is inherently problematic for many reasons including active hepatic nucleoside catabolism, probable absence of virus-specific activating enzymes, competition from endogenous nucleotides synthesised de novo or derived from RNA turnover, and factors related to mitochondrial toxicity. Despite these drawbacks, some nucleoside analogues have been found efficacious against hepatitis B virus and it is likely that as knowledge of their mechanism of action accumulates, their efficacy can be improved both by rational drug design and by use in combination with other drugs, including interferon.</p>","PeriodicalId":18183,"journal":{"name":"Liver","volume":"15 4","pages":"169-84"},"PeriodicalIF":0.0,"publicationDate":"1995-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1600-0676.1995.tb00667.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19524407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 56
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