Marked Elevation Of Transaminases Research Articles

P450 ADVANCED ATRIOVENTRICULAR BLOCK AT LOOP RECORDER MONITORING IN A YOUNG PATIENT WITH BRUGADA SYNDROME AND CONDUCTION ABNORMALITIES: CAUSE OF SYNCOPE OR INCIDENTAL FINDING?

Abstract A 32–year–old man healthy man presented to the emergency department because of remittent fever. His past medical history, physical examination and chest X–ray were unremarkable except for a body temperature of 39 Celsius degrees. Laboratory exams showed a marked elevation of transaminases, cholestasis markers and C–reactive protein, while an abdomen ultrasound revealed hepatomegaly and diffuse hyperechogenicity of the liver. He was diagnosed with acute hepatitis and admitted to the Gastroenterology Unit. Due to the persistent hyperpyrexia despite antipyretics and antibiotics, he was successfully treated with intravenous diclofenac, resulting in temporary remission of fever. First electrocardiogram during apyrexia showed sinus rhythm, first–degree atrioventricular block (PR interval 240 milliseconds), and non–specific intraventricular conduction delay. In the following days, liver and cholestasis markers improved, but he underwent two syncopal episodes without prodromes, the former while he was walking and the latter during meal. A new electrocardiogram revealed a type 1 Brugada pattern. At the time of its recording, however, his body temperature was 38.6 Celsius degrees. He was then admitted to the Cardiology Unit for monitoring and further investigations. 2D–echocardiogram and cardiac magnetic resonance imaging were unremarkable. Telemetry monitoring showed nocturnal episodes of marked sinus bradycardia (up to 35 beats per minute), but no ventricular arrhythmias were documented. He also underwent an invasive electrophysiological study with programmed ventricular stimulation, but again no ventricular arrhythmias were induced. Recording of His bundle electrogram, however, revealed the prolongation of both AH and HV interval (190 and 76 milliseconds respectively). Given the syncopal episodes, an implantable cardioverter defibrillator implantation was proposed, but the patient refused, so he underwent an implantable loop recorder implantation. After three months, at remote monitoring, a nocturnal episode of complete atrioventricular block with a pause of 15 seconds was recorded, thus he was again admitted to the Cardiology Unit. This time he was apyretic, but his electrocardiogram showed a spontaneous type 1 Brugada pattern with “high arrhythmic risk” features as first–degree atrioventricular block and a prominent S wave in lead I. He then underwent a successful implantable cardioverter defibrillator implantation with still an uneventful follow up.

Severe Toxicity in Nonhuman Primates and Piglets Following High-Dose Intravenous Administration of an Adeno-Associated Virus Vector Expressing Human SMN.

Neurotropic adeno-associated virus (AAV) serotypes such as AAV9 have been demonstrated to transduce spinal alpha motor neurons when administered intravenously (i.v.) at high doses. This observation led to the recent successful application of i.v. AAV9 delivery to treat infants with spinal muscular atrophy, an inherited deficiency of the survival of motor neuron (SMN) protein characterized by selective death of lower motor neurons. To evaluate the efficiency of motor neuron transduction with an AAV9 variant (AAVhu68) using this approach, three juvenile nonhuman primates (NHPs; aged 14 months) and three piglets (aged 7-30 days) were treated with an i.v. injection of an AAVhu68 vector carrying a human SMN transgene at a dose similar to that employed in the spinal muscular atrophy clinical trial. Administration of 2 × 1014 genome copies per kilogram of body weight resulted in widespread transduction of spinal motor neurons in both species. However, severe toxicity occurred in both NHPs and piglets. All three NHPs exhibited marked transaminase elevations. In two NHPs, the transaminase elevations resolved without clinical sequelae, while one NHP developed acute liver failure and shock and was euthanized 4 days after vector injection. Degeneration of dorsal root ganglia sensory neurons was also observed, although NHPs exhibited no clinically apparent sensory deficits. There was no correlation between clinical findings and T-cell responses to the vector capsid or transgene product in NHPs. Piglets demonstrated no evidence of hepatic toxicity, but within 14 days of vector injection, all three animals exhibited proprioceptive deficits and ataxia, which profoundly impaired ambulation and necessitated euthanasia. These clinical findings correlated with more severe dorsal root ganglia sensory neuron lesions than those observed in NHPs. The liver and sensory neuron findings appear to be a direct consequence of AAV transduction independent of an immune response to the capsid or transgene product. The present results and those of another recent study utilizing a different AAV9 variant and transgene indicate that systemic and sensory neuron toxicity may be general properties of i.v. delivery of AAV vectors at high doses, irrespective of the capsid serotype or transgene. Preclinical and clinical studies involving high systemic doses of AAV vectors should include careful monitoring for similar toxicities.

Lesión hepática severa inducida por carbamazepina asociado a necrolisis epidérmica tóxica. Reporte de un caso.

La necrolisis epidérmica toxica y el síndrome de Stevens- johnson son trastornos raros y mortales, caracterizado por una lesión severa de la piel y mucosa. Estos trastornos son una misma condición, se diferencia por el grado de afección de la superficie corporal total. La reacción de hipersensibilidad de los fármacos es la etiología más frecuente de estas dos entidades; por otro lado, el hígado es también una diana de las lesiones causadas por medicamentos, pudiendo conducir hasta una hepatitis severa y hasta en peor de los casos falla hepática aguda, llevando a ictericia, encefalopatía y coagulopatia. El presente caso es un paciente que sufre un trauma craneoencefálico con presencia de hematoma subdural, días después inicia el consumo de carbamazepina como profilaxis anticonvulsivante y acetaminofén para el dolor, generando lesión en piel que comprometían más de un 30% de la superficie corporal, lesión hepática severa con elevación marcada de transaminasas y encefalopatía, que bien podría corresponder al hematoma subdural o a la lesión hepática; esto genero gran interés.

A New Paradigm in Gallstones Diseases and Marked Elevation of Transaminases: An Observational Study

Background. In clinical practice, it is assumed that a severe rise in transaminases is caused by ischemic, viral or toxic hepatitis. Nevertheless, cases of biliary obstruction have increasingly been associated with significant hypertransaminemia. With this study, we sought to determine the true etiology of marked rise in transaminases levels, in the context of an emergency department.Material and methods. We retrospectively identified all patients admitted to the emergency unit at Centro Hospitalar e Universitário de Coimbra between 1st January 2010 and 31st December 2010, displaying an increase of at least one of the transaminases by more than 15 times. All patient records were analyzed in order to determine the cause of hypertransaminemia.Results. We analyzed 273 patients – 146 males, mean age 65.1 ± 19.4 years. The most frequently etiology found for marked hypertransaminemia was pancreaticobiliary acute disease (n = 142;39.4%), mostly lithiasic (n = 113;79.6%), followed by malignancy (n = 74;20.6%), ischemic hepatitis (n = 61;17.0%), acute primary hepatocellular disease (n = 50;13.9%) and muscle damage (n = 23;6.4%). We were not able to determine a diagnosis for 10 cases. There were 27 cases of recurrence in the lithiasic pancreaticobiliary pathology group. Recurrence was more frequent in the group of patients who had not been submitted to early cholecystectomy after the first episode of biliary obstruction (p = 0.014). The etiology of hypertransaminemia varied according to age, cholestasis and glutamic-pyruvic transaminase values.Conclusion. Pancreaticobiliary lithiasis is the main cause of marked hypertransaminemia. Hence, it must be considered when dealing with such situations. Not performing cholecystectomy early on, after the first episode of biliary obstruction, may lead to recurrence.

1117 Marked Elevation of Transaminases and Bilirubin in Choledocholithiasis

1117 Marked Elevation of Transaminases and Bilirubin in Choledocholithiasis

Acute hepatotoxicity associated with therapeutic doses of intravenous acetaminophen

Background: IV acetaminophen at 4 g per day is considered safe, producing no hepatic failure in more than 1400 cases. Oxidation of acetaminophen forms a reactive intermediate that binds to cellular proteins resulting in acetaminophen-protein adducts (APAP-CYS). Serum concentrations of APAP-CYS have been found to correlate with acetaminophen-induced hepatotoxicity. We report a case of hepatotoxicity associated with therapeutic doses of IV acetaminophen, with elevated serum APAP-CYS. Case details: The patient was a 92-year-old, 68 kg woman without known hepatic disease or ethanol abuse. On hospital day 3 she underwent laparoscopic reduction of internal hernias under general anesthesia. Surgery was uncomplicated and postoperatively she was treated with subcutaneous heparin and IV acetaminophen, 1 g every 6 h for almost 4 days (total dose = 13 g). At the start of therapy, transaminases were normal. On hospital day 5, she was noted to have marked transaminase elevations (AST: 4698 IU/L; ALT: 3914 IU/L) with increases in INR (1.68), ammonia (60 mcg/dL), and total bilirubin (1.8 mg/dL). Serum acetaminophen concentration was 15.3 mcg/mL 26 h after her last dose. Acetaminophen was discontinued and IV acetylcysteine was given and continued at the second maintenance dose rate for a second 16-hour infusion, at which time transaminases, INR, ammonia and total bilirubin were all improving. The patient was discharged 2 days later. Serum APAP-CYS concentrations in serum samples obtained during her hospitalization were elevated (peak = 4.81 μM on hospital day 5; expected range for therapeutic dosing <1.1 μM). Case discussion: We have identified a case of acute liver injury associated with therapeutic dosing of IV acetaminophen. The serum APAP-CYS concentrations are consistent with that seen in cases of hepatotoxicity following repeated supratherapeutic acetaminophen ingestion. Several factors that likely contributed to her susceptibility included advanced age, post-operative status, a likely catabolic state and multiple acetaminophen doses over several days. These uncommon circumstances limit the generalizability of risk. We believe the findings are most consistent with acetaminophen-induced liver injury. Conclusion: This case illustrates a potential hazard of IV acetaminophen and demonstrates the potential utility of APAP-CYS adducts in evaluating causality in acute liver injury.

A patient with typhoid fever, Giardia lamblia gastroenteritis and hepatitis E

Marked elevation of transaminases is rare in typhoid enteric fever. Co-infections with hepatitis A or E, dengue, or other pathogens should be suspected and investigated. Here we report a case of a 29-year-old Bangladesh man who presented with typhoid, hepatitis E and Giardia lamblia complicated by severely deranged liver enzymes. With early institution of antibiotics and active supportive treatment, the patient clinically recovered. The underlying mechanism of co-infection is still not clear. As clinicians, comprehensive workup for potential pathogens helps expedite diagnosis, especially in patients from endemic areas or patients who deteriorate rapidly. Current diagnostic methods, treatment modalities and preventive measures still need to be improved in the future.

Dengue death with evidence of hemophagocytic syndrome and dengue virus infection in the bone marrow.

IntroductionHPS is a potentially life-threatening histiocytic disorder that has been described in various viral infections including dengue. Its involvement in severe and fatal dengue is probably more common but is presently under recognized.Case descriptionA 38-year-old female was admitted after 5 days of fever. She was deeply jaundiced, leukopenic and thrombocytopenic. Marked elevation of transaminases, hyperbilirubinemia and hypoalbuminemia were observed. She had deranged INR values and prolonged aPTT accompanied with hypofibrinogenemia. She also had splenomegaly. She was positive for dengue IgM. Five days later she became polyuric and CT brain image showed gross generalized cerebral edema. Her conditions deteriorated by day 9, became confused with GCS of 9/15. Her BMAT showed minimal histiocytes. Her serum ferritin level peaked at 13,670.00 µg/mL and her sCD163 and sCD25 values were markedly elevated at 4750.00 ng/mL and 4191.00 pg/mL, respectively. She succumbed to the disease on day 10 and examination of her tissues showed the presence of dengue virus genome in the bone marrow.Discussion and evaluationIt is described here, a case of fatal dengue with clinical features of HPS. Though BMAT results did not show the presence of macrophage hemophagocytosis, other laboratory features were consistent with HPS especially marked elevation of ferritin, sCD163 and sCD25. Detection of dengue virus in the patient’s bone marrow, fifteen days after the onset of fever was also consistent with the suggestion that the HPS is associated with dengue virus infection.ConclusionsThe findings highlight HPS as a possible complication leading to severe dengue and revealed persistent dengue virus infection of the bone marrow. Detection of HPS markers; ferritin, sCD163 and sCD25, therefore, should be considered for early recognition of HPS-associated dengue.

Marked elevation of transaminases and pancreatic enzymes in severe malnourished male with eating disorder.

We report a case of a 45 year old Caucasian malnourished male with an history of eating disorder who developed severe liver and pancreatic damage and multiorgan disfunction. At admission to our department, his body mass index (BMI) was 11.1. Biochemical evaluation showed elevated serum levels of transaminases (AST= 2291 U/L, ALT= 1792 U/L), amylase (3620 U/L), lipase (4102 U/L), CPK= 1370 U/L, LDH= 2082 U/L. No other cause of acute liver and pancreatic damage was evidenced. Haematological disorders (anemia, thrombocytopenia, leukopenia) found on admission seem related to bone marrow hypoplasia and to gelatinous marrow transformation described in severe state of malnutrition. Although a moderate increase in liver and pancreatic enzymes are a common finding in malnourished patients, only a small number of reports describes severe liver injury and multiorgan dysfunction. After a few days of treatment (hydration and nutritional support) a marked decrease of serum transaminases, lipase, amylase, CPK, LDH occurred, despite a transient increase in these levels secondary to refeeding syndrome. The association of chronic malnutrition and a decrease in systemic perfusion may be responsible for multiorgan dysfunction. In our patient the high levels of transaminases and pancreatic enzymes were the most important biochemical abnormalities normalized after refeeding.

Asymptomatic EBV Infection may Uncover Ezetimibe Liver Alterations in a Hypercholesterolemic Child

The Epstein Barr viral (EBV) infection may be associated with liver side-effects from ezetimibe treatment in children. An 11-year-old child with familial hypercholesterolemia (FH) presented with a normal biochemical liver profile before ezetimibe treatment, with no significant alterations of liver enzymes. Three months after beginning treatment with ezetimibe 10 mg/day, he complained of constant weakness, and blood testing revealed marked transaminase elevations. Administration of ezetimibe was stopped. However 15 days later alanine transferase (ALT) levels showed a further increase, followed, 10 days later, by an improvement in all pathological levels. After a further 2 months, all values had returned to normal. Tests for antibodies to the EBV were positive, suggesting a recent but not acute EBV infection. It was thus decided to test ezetimibe 10 mg/day again, and after 1 month aspartate aminotransferase (AST) and ALT levels were in a normal range, together with a very satisfactory LDL-cholesterol (LDL-C) response. This is the first report of a child with significant liver side-effects from ezetimibe treatment. Ezetimibe treatment may not have been the direct cause of liver damage in this child, because a concomitant EBV infection. Association of the two should be a warning for possible liver complications. J Med Cases. 2013;4(2):66-68 doi: https://doi.org/10.4021/jmc903w

Asymptomatic EBV Infection may Uncover Ezetimibe Liver Alterations in a Hypercholesterolemic Child

The Epstein Barr viral (EBV) infection may be associated with liver side-effects from ezetimibe treatment in children. An 11-year-old child with familial hypercholesterolemia (FH) presented with a normal biochemical liver profile before ezetimibe treatment, with no significant alterations of liver enzymes. Three months after beginning treatment with ezetimibe 10 mg/day, he complained of constant weakness, and blood testing revealed marked transaminase elevations. Administration of ezetimibe was stopped. However 15 days later alanine transferase (ALT) levels showed a further increase, followed, 10 days later, by an improvement in all pathological levels. After a further 2 months, all values had returned to normal. Tests for antibodies to the EBV were positive, suggesting a recent but not acute EBV infection. It was thus decided to test ezetimibe 10 mg/day again, and after 1 month aspartate aminotransferase (AST) and ALT levels were in a normal range, together with a very satisfactory LDL-cholesterol (LDL-C) response. This is the first report of a child with significant liver side-effects from ezetimibe treatment. Ezetimibe treatment may not have been the direct cause of liver damage in this child, because a concomitant EBV infection. Association of the two should be a warning for possible liver complications. doi: http://dx.doi.org/10.4021/jmc903w

Regularities of changes in laboratory parameters in patients with A/H1N1 influenza pneumonia

The medical records of 97 patients with A/H1N1 influenza pneumonia were analyzed. The important feature of the disease is a high risk of fatal outcomes, the direct cause of which is acute respiratory distress syndrome (ARDS). The most significant abnormalities of laboratory values were noted in this category of patients. In ARDS, leukopenia or normocytosis changed to leukocytosis, which is attributed to massive bacterial infection. These patients were also recorded to have immunodeficiency-induced lymphopenia and disseminated intravascular coagulation-induced thrombocytopenia. The marked elevation of transaminases mainly due to asparagine transaminase and the increase of creatine phosphokinase suggest that the most severe category of patients has rhabdomyolysis. Characteristic of this was a reactive rise of amylase. In ARDS, diminished renal functional capacity reflected the higher blood levels of creatinine and urea.

Myoglobinuria After Laparoscopic Radiofrequency Ablation of Liver Tumors

BackgroundThere are scant data in the literature about myoglobinuria after radiofrequency ablation (RFA) of liver tumors. The aim of this study is to analyze the incidence and identify the risk factors involved in this complication after RFA. Patients and MethodsAn initial case of myoglobinuria and acute kidney injury (AKI) during laparoscopic liver RFA after 10 years of the liver ablation program led to the design of this study. Prospective data were collected on 41 consecutive patients undergoing laparoscopic RFA at our institution over a 9-month period. Urine myoglobin, serum creatinine kinase, and serum creatinine levels were obtained preablation and postablation. Variables were compared between patients to identify possible risk factors that might be related to this rare complication. Data are expressed as mean ± standard error of the mean. ResultsTwo patients were excluded from the study due to preoperative myoglobinuria of unknown etiology. Of the remaining 39 patients, three developed dark urine with significant myoglobinuria on postoperative day 1. Two of these patients had carcinoid liver metastases; the remaining patient had a metastatic colorectal lesion. The number of tumors ablated in these patients was 14, 11, and 3 vs. 2.4±0.4 in the rest of the patients. Cumulative tumor volume was larger in the group of patients that developed the complication vs. those who did not (127.9±59.5 vs. 48 ± 3 cm3). Two grounding pads were used in the three patients that had a complication vs. four pads in the rest of the patients. Dark urine was identified promptly intraoperatively and treated aggressively. All of these patients required intensive care unit (ICU) admission and had a prolonged hospital stay. Marked elevation of transaminases and creatinine kinase as well as a drop in hematocrit and platelet count was observed in patients with myoglobinuria. In our retrospective review of 706 patients that underwent liver RFA in the past 10 years, we detected 27 patients (3.8%) with ten or more lesions (11.9 ± 0.4). None of these patients had significant elevation of serum creatinine postoperatively. In the whole series of 706 patients, 22 (3.2%) were found to have elevated creatinine after liver RFA, with return to baseline in all but seven patients in follow-up. ConclusionMyoglobinuria after liver RFA is a rare but potentially devastating complication that may lead to AKI with significant morbidity and prolonged hospital stay. Patients with large tumor volumes requiring longer ablation times need to be monitored closely for the development of this complication. The fact that this was not observed in other patients with similar tumor characteristics suggests that individual patient-related factors might play an important role.

Fatal outcome of a patient with severe aplastic anemia after treatment with metenolone acetate

A 75-year-old man suffering from severe aplastic anemia was treated first with cyclosporin A, then with steroid pulse therapy, and subsequently with metenolone acetate. Marked elevation of transaminases was detected following initiation of treatment with metenolone acetate. This was followed by hepatic failure and death. Histopathological findings in autopsy specimens were compatible with the diagnosis of drug-induced liver impairment, for which metenolone acetate was considered the most likely causative agent. Liver impairment as a side effect of the use of this drug has been thought to be mild, reversible and rather infrequent. However, as demonstrated in the case described here, it is apparent that extreme caution should be exercised when using this drug in debilitated patients.

Ischemic hepatitis

Seven patients with cardiovascular disease had clinical episodes and marked transaminase elevations that suggested viral hepatitis, but all had morphologic evidence (from liver biopsy or autopsy specimens) that documented centrilobular necrosis (ischemic hepatitis) with no evidence of viral or drug injury. Several also had moderate or marked passive congestion of the liver so the liver biopsies of 15 additional patients were retrospectively reviewed. In this latter group congestion alone was associated with normal or minimal elevation in transaminases while all patients with notable (greater than 5 times normal) transaminase elevations had centrilobular necrosis. Congestion alone, no matter how severe or prolonged, seems to do little if any damage to the liver. Centrilobular necrosis, or ischemic hepatitis, correlates with significant hypertransaminasemia, appears to result from failure of hepatic perfusion (with or without preceding hypotension), and presents with clinical and laboratory manifestations that suggest viral hepatitis.