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Transaminase Elevation (transaminase + elevation)
Selected AbstractsLiver damage underlying unexplained transaminase elevation in human immunodeficiency virus-1 mono-infected patients on antiretroviral therapy,HEPATOLOGY, Issue 2 2009Patrick Ingiliz Liver damage associated with chronic unexplained high serum transaminases in human immunodeficiency virus (HIV)-infected patients under combined antiretroviral therapy is unknown. Liver histology was prospectively investigated in patients presenting serum transaminase elevation for more than 6 months, after exclusion of alcohol abuse, hepatitis C virus (HCV) or hepatitis B virus (HBV) infection, autoimmune, and genetic liver diseases. In a subgroup of patients, liver mitochondrial activities were measured by spectrophotometry and mitochondrial DNA (mtDNA) by real-time polymerase chain reaction (PCR). Thirty patients were included with median values of alanine aminotransferase (ALT) levels: 80 U/L, age: 46 years, body mass index: 23 kg/m2, HIV RNA: 200 copies/mL, CD4 count: 365/mm3, duration of HIV infection: 13 years, and duration of treatment exposure: 118, 41, and 53 months for nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, and protease inhibitors, respectively. Histological anomalies were found in 22 of 30 patients. Steatosis was present in 18 patients, severe in nine patients, and associated with inflammation in 16 patients with a diagnosis of non-alcoholic steatohepatitis (NASH). Fibrosis was found in 18 patients, severe in six patients and associated with steatosis in 13 patients. Significant liver respiratory complex I defect, contrasting with high complex IV activity and normal mitochondrial DNA content, was observed in the group of patients compared with controls. The presence of NASH was correlated with high fasting glycemia and insulin levels, not with liver mitochondrial function or mitochondrial DNA content. Conclusions: HIV-infected patients on combined antiretroviral therapy with chronic transaminase elevation of unknown origin have a high rate of liver lesions, mostly consistent with NASH related to insulin resistance. (HEPATOLOGY 2008.) [source] Apoptosis in hepatitis CJOURNAL OF VIRAL HEPATITIS, Issue 5 2003J. Kountouras Summary. The apoptotic process appears to be a host defence mechanism against viral infections and tumourigenesis. However, many viral genomes encode proteins, which repress apoptosis so as to escape from immune attack by the host. Therefore, virus,host interactions may determine viral persistence, extent and severity of liver inflammation and possibly viral hepatocarcinogenesis. Apoptosis of liver cells may play a significant role in the pathogenesis of hepatitis C. Pathomorphologic features of increased apoptosis include shrinkage and fragmentation of nuclei/cytoplasm in piecemeal necrosis areas, acidophilic bodies, and focal cell dropout in the liver lobule. The hepatitis C virus (HCV) core protein exhibits both proapoptotic or antiapoptotic actions. Modulation of apoptosis may involve binding of HCV core protein to the intracellular signal transducing portion of death receptors and displacement of signalling molecules. Apoptosis may occur in the absence of significant transaminase elevation, thereby explaining the lack of correlation between biochemical activity and liver cell histological injury. Monitoring caspase activation might provide a reliable tool to estimate the efficacy of HCV therapy, and might open challenging therapeutic strategies in HCV infection. The antiviral effect of interferon may be mediated through induction of apoptosis. Lastly, administration of the antiapoptotic ursodeoxycholic acid in HCV infection is compatible with the notion that apoptosis may represent a mechanism for viral shedding rather than for viral elimination, thereby raising the concept that inhibition of apoptosis could ameliorate hepatitis C. [source] Changing aetiology of liver dysfunction in the new generation of a hepatitis B and C-endemic area: cross-sectional studies on adolescents born in the first 10 years after universal hepatitis B vaccinationLIVER INTERNATIONAL, Issue 9 2008Jung-Ta Kao Abstract Background/Aim: Geographical variation in viral hepatitis infection complicates various levels of liver diseases. This study elucidates the changing aetiology of alanine transaminase elevation (ALT levels >40 IU/L) in a previously hepatitis-endemic township. Design/Methods: Five cross-sectional screenings were performed on teenagers born from 1984 to 1993. We examined hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (anti-HCV), ALT and body mass index, and additionally checked hepatitis B envelope antigen (HBeAg) for positive HBsAg and HCV RNA for positive anti-HCV. Teenagers with ALT elevation underwent an ultrasonography examination. Results: This study enrolled 1788 (93.7%) of 1909 students, discovering individual prevalence of HBsAg (6.3%), anti-hepatitis B core (anti-HBc) (15.5%), anti-HCV (2.2%), overweight (22.4%), obesity (12.8%) and ALT >40 IU/L (3.7%). HBsAg and anti-HBc prevalence declined with trends, while obesity increased with trends (P<0.001). Among 66 ALT-elevated teenagers, prevalence percentages of risk factors were HBsAg (22.7%), anti-HCV (1.5%), obesity (45.5%), HBsAg with obesity (7.6%) and anti-HCV with obesity (3.0%). Additionally, obesity showed predominance (85.7%) among aetiologies of teenagers with fatty livers (60.9%). The independently associated factors of ALT elevation included being male (odds ratio, 2.18; 95% confidence interval, 1.21,3.93), HBsAg (4.25; 1.06,17.13), HBeAg (7.24; 1.64,31.9), HCV RNA (29.03; 5.8,145.29) and obesity (16.5; 8.79,30.98). Conclusion: In place of viral hepatitis, obesity is becoming the major aetiology of abnormal liver function among the young generation in a previously hepatitis-endemic area. [source] Clofarabine combinations as acute myeloid leukemia salvage therapy,CANCER, Issue 8 2008Stefan Faderl MD Abstract BACKGROUND. Outcome of patients with relapsed acute myeloid leukemia (AML) remains unsatisfactory. Clofarabine is a nucleoside analog with activity in adult AML. Combinations with cytarabine in AML are feasible and effective. Idarubicin is another active AML drug, which has not yet been tested with clofarabine. METHODS. The authors therefore designed a phase I study of clofarabine ± cytarabine, plus idarubicin. Patients with primary refractory or first-relapse AML were assigned to either clofarabine plus idarubicin (CI) if previously exposed to cytarabine with a response lasting <12 months, or clofarabine and idarubicin plus cytarabine (CIA) for responses ,12 months, or if never exposed to cytarabine. A standard "3 + 3" phase 1 design was followed to define maximum tolerated dose (MTD). Forty-four patients were treated (23 CI; 21 CIA). RESULTS. Dose-limiting toxicities were hyperbilirubinemia and hepatic transaminase elevations for CI-treated patients in addition to mucositis and diarrhea for CIA-treated patients. MTD for CI was clofarabine 22.5 mg/m2 intravenously daily × 5 and idarubicin 10 mg/m2 intravenously daily × 3. MTD for CIA was clofarabine 22.5 mg/m2 intravenously × 5, idarubicin 6 mg/m2 intravenously × 3, and cytarabine 0.75 g/m2 intravenously × 5 days. CONCLUSIONS. A phase 2 randomized trial is in process to compare activity between treatment arms. Cancer 2008. © 2008 American Cancer Society. [source] The feasibility of adjuvant interferon ,-2b in children with high-risk melanomaCANCER, Issue 4 2005Fariba Navid M.D. Abstract BACKGROUND It has been shown that induction high-dose interferon ,-2b (IFN-,-2b) followed by maintenance therapy improves recurrence-free survival in adults with high-risk, resected melanoma. In this study, the feasibility and toxicity of this regimen were evaluated in newly diagnosed pediatric patients with Stage III melanoma involving regional lymph nodes. METHODS Fifteen patients age , 18 years with newly diagnosed Stage III melanoma were enrolled on an institutional protocol. Patients were treated with wide local excision, sentinel lymph node biopsy, lymph node dissection, and adjuvant biotherapy, consisting of induction therapy with 20 million IU/m2 per day IFN-,-2b intravenously 5 times per week for 4 weeks followed by maintenance therapy with IFN-,-2b 10 million IU/m2 per day subcutaneously 3 times per week for 48 weeks. Patients were monitored for toxicity and tumor recurrence. RESULTS All patients completed induction therapy, and nine patients completed maintenance therapy. Three patients currently are receiving maintenance, 2 patients developed recurrent disease on maintenance therapy, and 1 patient stopped maintenance therapy 5 weeks early. During induction therapy, Grade 3,4 toxicities included 14 episodes of neutropenia in 11 patients, 3 episodes of leukopenia in 2 patients, and 6 episodes of liver transaminase elevations in 5 patients. Dose modifications were required in four patients. During maintenance therapy, Grade 3,4 toxicities included 23 episodes of neutropenia in 10 patients and 2 episodes of liver transaminase elevations in 2 patients. Three patients required dose modifications. All toxicities were reversible with interruption or dose modification of therapy, and no patients were taken off study due to toxicity. CONCLUSIONS High dose IFN-,-2b for 4 weeks followed by a lower dose maintenance phase for 48 weeks was feasible in children with Stage III melanoma and was associated with tolerable toxicity. Cancer 2005. © 2005 American Cancer Society. [source] Risks and benefits of continued aggressive statin therapyCLINICAL CARDIOLOGY, Issue S3 2003Antonio M. Gotto Jr. M.D., D.PHIL Abstract The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or statins, are a well-tolerated, effective class of medications for the reduction of low-density lipoprotein cholesterol (LDL-C) and total cholesterol levels. Extensive data from clinical trials demonstrate that these agents reduce fatal and nonfatal cardiovascular risk in primary and secondary prevention patients, including women and the elderly. A threshold value for LDL-C reduction below which there is no further clinical benefit has not yet been identified. In the Heart Protection Study (HPS), significant relative risk reduction occurred even among patients with LDL-C levels < 2.6 mmol/l (100 mg/dl). Statin therapy also produced reductions in cardiovascular disease in a wide range of high-risk patients regardless of baseline cholesterol levels. Rhabdomyolysis, typically defined as muscle pain or weakness associated with creatine kinase levels higher than 10 times the upper limit of normal and the presence of myoglobulinuria, is a rare but potentially serious complication of statins. Although dose-dependent transaminase elevations occur in 0.5 to 2% of cases, it has not been determined whether these elevations qualify as true drug-related hepatotoxicity. Management of myopathy and elevated transaminases is addressed in a joint publication from the American College of Cardiology (ACC), the American Heart Association (AHA), and the National Heart, Lung, and Blood Institute (NHLBI). Because statins have significant potential benefits and a low risk for serious adverse effects, aggressive therapy should be considered in patients at high risk for coronary heart disease. [source] A Multicenter, Placebo-Controlled, Double-Blind, Randomized Study of Efficacy and Safety of Ocinaplon (DOV 273,547) in Generalized Anxiety DisorderCNS: NEUROSCIENCE AND THERAPEUTICS, Issue 2 2010Pál Czobor Preclinical studies demonstrated that ocinaplon, a positive allosteric modulator of GABAA receptors, possesses anxiolytic-like actions at doses devoid of the side effects typically associated with benzodiazepines. The aim of this study was to evaluate the effects of ocinaplon in a multicenter, double-blind proof-of-concept trial of male and female outpatients who met DSM-IV criteria for GAD with no coexisting depression, and had a baseline score of ,20 on the Hamilton Scale for Anxiety (HAM-A). Patients with <20% reduction in HAM-A to placebo in a single-blind 7-day run-in period were randomly assigned to treatment with ocinaplon 90 mg t.i.d. (n = 31) or placebo for 28 days (n = 29). Ocinaplon was more effective than placebo in reducing HAM-A scores (P= 0.009). Patients assigned to ocinaplon exhibited a mean improvement of 14.2 points (SE = 2.6) on the total score of the HAM-A scale at the conclusion of the trial, while patients assigned to placebo obtained a mean improvement of 6.3 points (SE = 2.0). A significant (P= 0.023) difference in improvement between ocinaplon and placebo was observed beginning at and continuing from 1-week after the initiation of dosing. The proportion of patients with treatment-emergent adverse events (TEAE) was not statistically significant between ocinaplon and placebo. One serious adverse event (SAE) occurred in the ocinaplon group that was considered possibly related to study medication (icterus following transaminase elevations). The patient had preexisting medical conditions that may have contributed to this SAE. A full recovery was observed with no residual effects. The overall safety profile revealed no patterns of TEAEs, including those effects typically associated with other anxiolytic and/or benzodiazepine compounds, such as sedation. Ocinaplon appears to be a well-tolerated and effective treatment for GAD. It produces a rapid onset of anxiolytic action absent the side effects (e.g., dizziness, sedation) typically reported following anxiolytic doses of benzodiazepines. [source] | ||||||||||