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Significant Liver Injury (significant + liver_injury)
Selected AbstractsIncubation phase of acute hepatitis B in man: Dynamic of cellular immune mechanismsHEPATOLOGY, Issue 5 2000George J.M. Webster After hepatitis B virus (HBV) infection, liver injury and viral control have been thought to result from lysis of infected hepatocytes by virus-specific cytotoxic T cells. Patients are usually studied only after developing significant liver injury, and so the viral and immune events during the incubation phase of disease have not been defined. During a single-source outbreak of HBV infection, we identified patients before the onset of symptomatic hepatitis. The dynamics of HBV replication, liver injury, and HBV-specific CD8+ and CD4+ cell responses were investigated from incubation to recovery. Although a rise in alanine transaminase (ALT) levels was present at the time of the initial fall in HBV-DNA levels, maximal reduction in virus level occurred before significant liver injury. Direct ex vivo quantification of HBV-specific CD4+ and CD8+ cells, by using human leukocyte antigen (HLA) class I tetramers and intracellular cytokine staining, showed that adaptive immune mechanisms are present during the incubation phase, at least 4 weeks before symptoms. The results suggest that the pattern of reduction in HBV replication is not directly proportional to tissue injury during acute hepatitis B in humans. Furthermore, because virus-specific immune responses and significant reductions in viral replication are seen during the incubation phase, it is likely that the immune events central to viral control occur before symptomatic disease. [source] Clinically significant liver injury in patients treated with natalizumabALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 9 2010S. BEZABEH Aliment Pharmacol Ther,31, 1028,1035 Summary Background, Natalizumab is a recombinant monoclonal antibody approved for the treatment of patients with multiple sclerosis and patients with Crohn's disease. Because of its immunosuppressive effects, natalizumab has been associated with a number of atypical and opportunistic infections. Aim, To describe and summarize six spontaneously reported post-marketing cases of clinically significant drug induced-liver injury associated with natalizumab use. Methods, The FDA maintains a database of adverse event reports (AERS). We searched the AERS database for reports of serious liver injury associated with natalizumab use from November 2004, when the drug was approved, through 30 June 2008. Results, The search resulted in six spontaneously reported post-marketing cases of severe drug-induced liver injury. Four of six patients developed liver injury with elevations of serum transaminases and hyperbilirubinemia after only a single infusion of natalizumab. One of these patients experienced repeated increases of aminotransferases and bilirubin when natalizumab was re-administered. Conclusions, Serious hepatic injury may occur in association with natalizumab use. Health professionals should be alerted to possible serious liver injury in patients receiving natalizumab. [source] Long-term follow-up of patients with mild to moderate drug-induced liver injuryALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2007E. BJÖRNSSON Summary Aim To evaluate the long-term prognosis of patients diagnosed with drug-induced liver injury, and the nature of the liver injury. Methods Patients with a diagnosis of drug-induced liver injury between 1994 and 2005 were identified in a university hospital clinic. Patients surviving drug-induced liver injury-associated liver failure were excluded. Results Seventy-seven cases were identified and those who were alive (69) were invited to attend follow-up. Of those patients who had died, none had died of liver disease. Of those patients who had survived, 59 were reviewed in the clinic. Patients had a median follow-up of 48 months. Before the diagnosis of drug-induced liver injury, nine had a chronic liver disease, four with autoimmune hepatitis, two with non-alcoholic liver disease, one each with non-alcoholic fatty liver disease, primary biliary cirrhosis and primary sclerosing cholangitis. There was no evidence of progression of their liver disease during follow-up. Among 50 patients without a known liver disease prior to the drug-induced liver injury, 10 had abnormal liver tests. Diagnostic work-up revealed alternative cause of liver disease in all except three patients (6%), who had asymptomatic abnormal liver tests (but normal bilirubin in all). Conclusions Chronic abnormalities in liver tests, not explained by an identified liver disease, are very rare in patients previously diagnosed with drug-induced liver injury. This group of patients did not seem to have a clinically significant liver injury at long-term follow-up. [source] Review article: drug hepatotoxicityALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 10 2007C. Y. CHANG SUMMARY Background Drug toxicity is the leading cause of acute liver failure in the United States. Further understanding of hepatotoxicity is becoming increasingly important as more drugs come to market. Aims (i) To provide an update on recent advances in our understanding of hepatotoxicity of select commonly used drug classes. (ii) To assess the safety of these medications in patients with pre-existing liver disease and in the post-liver transplant setting. (iii) To review relevant advances in toxicogenomics which contribute to the current understanding of hepatotoxic drugs. Methods A Medline search was performed to identify relevant literature using search terms including ,drug toxicity, hepatotoxicity, statins, thiazolidinediones, antibiotics, antiretroviral drugs and toxicogenomics'. Results Amoxicillin-clavulanic acid is one of the most frequently implicated causes of drug-induced liver injury worldwide. Statins rarely cause clinically significant liver injury, even in patients with underlying liver disease. Newer thiazolidinediones are not associated with the degree of liver toxicity observed with troglitazone. Careful monitoring for liver toxicity is warranted in patients who are taking antiretrovirals, especially patients who are co-infected with hepatitis B and C. Genetic polymorphisms among enzymes involved in drug metabolism and HLA types may account for some of the differences in individual susceptibility to drug hepatotoxicity. Conclusions Drug-induced hepatotoxicity will remain a problem that carries both clinical and regulatory significance as long as new drugs continue to enter the market. Future results from ongoing multicentre collaborative efforts may help contribute to our current understanding of hepatotoxicity associated with drugs. [source] | ||||||||||