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Hepatocellular Dysfunction (hepatocellular + dysfunction)
Selected AbstractsImmunopathogenesis of hepatitis C virus infection and hepatic fibrosis: New insights into antifibrotic therapy in chronic hepatitis CHEPATOLOGY RESEARCH, Issue 8 2007Rosāngela Teixeira Fibrosis and cirrhosis represent the consequences of a sustained wound-healing response to chronic liver injury of any cause. Chronic hepatitis C virus (HCV) has emerged as a leading cause of cirrhosis in the USA and throughout the world. HCV may induce fibrogenesis directly by hepatic stellate cell activation or indirectly by promoting oxidative stress and apoptosis of infected cells. The ultimate result of chronic HCV injury is the accumulation of extracellular matrix with high density type I collagen within the subendothelial space of Disse, culminating in cirrhosis with hepatocellular dysfunction. The treatment of hepatitis C with the combination of pegylated interferon and ribavirin is still both problematic and costly, has suboptimal efficacy, serious side effects and a high level of intolerance, and is contraindicated in many patients. Hence, new approaches have assumed greater importance, for which there is an urgent need. The sustained progress in understanding the pathophysiology of hepatic fibrosis in the past two decades has increased the possibility of developing drugs specifically targeting the fibrogenic process. Future efforts should identify genetic markers associated with fibrosis risk in order to tailor the treatment of HCV infection based on genetically regulated pathways of injury and/or fibrosis. Such advances will expand the arsenal to overcome liver fibrosis, particularly in patients with hepatic diseases who have limited treatment options, such as those patients with chronic hepatitis C who have a high risk of fibrosis progression and recurrent HCV disease after liver transplantation. [source] Patients with stable uncomplicated cirrhosis have normal neutrophil functionJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 11 2000Richard Kirsch Abstract Background: Neutrophil function has been reported to be abnormal in patients with cirrhosis. In order to evaluate the relative contribution of hepatocellular dysfunction and portalsystemic shunting of blood to these abnormalities, neutrophil function was studied in 18 patients with cirrhosis and portal hypertension. Nine patients, with extrahepatic portal hypertension (EPH) caused by portal vein thrombosis, who had no clinical, biochemical or histologic evidence of liver disease were also studied. Methods: Superoxide generation, phagocytosis, degranulation, leukotriene B4 release, candidacidal activity and quantitative and qualitative expression of the cell surface adhesive marker CD11b/CD18 were measured in these patients as well as in age- and gender-matched controls. Results: Patients with cirrhosis were found to have a small but statistically significant decrease in the expression of the CD18 component of MAC1 in N -formyl-methionyl-leucyl-phenylalanine-stimulated neutrophils (P = 0.04). No significant differences were found between either of the two patient groups and the control group for any of the other parameters of neutrophil function tested. Conclusions: These were unexpected findings in the light of data published elsewhere, which indicate impaired neutrophil function in patients with cirrhosis. The study suggests that patients with stable, uncomplicated cirrhosis and patients with EPH have normal neutrophil function. [source] Prolongation of the prothrombin time and activated partial thromboplastin time in children with sickle cell diseasePEDIATRIC BLOOD & CANCER, Issue 5 2006Leslie J. Raffini MD Abstract Background Patients with sickle cell disease (SCD) have high rates of perioperative complications, including bleeding 1,2. Procedures We conducted a retrospective review of pre-operative coagulation studies in pediatric patients with SCD followed by a prospective study of 100 well children with SCD to determine the prevalence of abnormal coagulation screening tests, and to evaluate potential etiologies. Results In the retrospective study, 32/84 (38.1%) had a prolonged prothrombin time (PT), compared to 8/100 in the prospective study. Prolongations of the activated partial thromboplastin time (aPTT) were less common. Children in the prospective study with prolonged PTs had significantly lower levels of Factor V and VII compared to those with normal PTs. Factor VII levels were <50% in 4/8 with long PTs, compared to 3/92 with normal PTs, P,=,0.001. Though retrospectively, several patients had normalization of their PT with vitamin K, there was no laboratory evidence of vitamin K deficiency in the prospective study. In the retrospective analysis, six of seven children who had pre-operative coagulation studies and significant intraoperative blood loss had prolonged PTs (P,=,0.04). Conclusions Children with SCD admitted for surgical procedures were more likely to have prolonged PTs than those tested at a well visit. There was intra-patient variability in coagulation studies that may be related to clinical status, hepatocellular dysfunction, and/or increased clotting factor consumption. Future well-designed prospective studies to determine whether abnormal coagulation studies are associated with an increased risk of perioperative bleeding in children with SCD are necessary. Pediatr Blood Cancer 2006; 47:589,593. © 2005 Wiley-Liss, Inc. [source] Blockade of Kupffer cells by gadolinium chloride or dichloromethylene diphosphonate influences hepatic microcirculation after sepsis and haemorrhagic shockBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 7 2000C. Herzog Background The liver plays a key role in the host defence response after haemorrhagic shock,resuscitation (H/R) and sepsis. Kupffer cells (KCs) have been shown to be a trigger and motor of the subsequent inflammatory response syndrome. This may lead to hepatocellular dysfunction, microcirculatory alterations and liver injury involving, for example, tumour necrosis factor ,, interleukin (IL) 1 and IL-6. In a double-blind study the effect of KC blockade with either gadolinium chloride or liposome-entrapped dichloromethylene diphosphonate (DMD) on hepatic microvascular flow after H/R and sepsis was investigated. Methods After pretreatment with intravenous gadolinium chloride 10 mg kg,1, DMD 1 mg kg,1 or saline 24 h before induction of shock, male Sprague-Dawley rats (n = 6,10 per group and time) were subjected to either haemorrhagic shock (mean arterial pressure 40 mmHg) for 60 min followed by resuscitation or lipopolysaccharide (LPS) 1 mg kg,1 intravenously. Microvascular flow was assessed by intravital microscopy of fluorescence-marked leucocytes in liver sinusoids at baseline, and 1, 6 and 12 h after shock induction. Results In saline groups, the mean(s.d.) leucocyte flow was significantly (P < 0·05) higher at 1 h (20 759(2901) ,m3 s,1) and 6 h (16 278(2916) ,m3 s,1) after H/R as well as at 6 h after LPS (17 661(3949) ,m3 s,1) compared with the baseline value (13 509(1580) ,m3 s,1). Animals pretreated with gadolinium chloride showed a significant flow increase compared with baseline (11 797(1124) ,m3 s,1) at l h following H/R (26 269(5909) ,m3 s,1). In DMD-pretreated animals leucocyte flow showed no significant change over time, following either H/R or LPS treatment. However, flow was significantly higher at baseline (18 054(998) ,m3 s,1) versus gadolinium chloride and saline groups. In addition, DMD-treated animals showed higher flow values 1 h after LPS challenge (20 665(2337) ,m3 s,1) compared with gadolinium chloride (13 110(1224) ,m3 s,1) and saline (15 311(800) ,m3 s,1) groups. Similarly, at 12 h after H/R the DMD group (21 782(1887) ,m3 s,1) had higher flow values than the gadolinium chloride (14 026(1616) ,m3 s,1) and saline (15 999(3175) ,m3 s,1) groups. Conclusion These results imply a significant influence of KCs on regulation of microvascular perfusion in liver sinusoids under normal conditions as well as after H/R and sepsis. The data indicate differential pathways and effects of blocking KCs by gadolinium chloride and DMD. © 2000 British Journal of Surgery Society Ltd [source] | ||||||||||