Serum Aminotransferase Concentrations Research Articles

Liver dysfunction in children with hematologic malignancy or solid tumor

Background Deficiencies in liver synthetic function can only bedetected if the damage is severe, which are more often due to nonhepatic factors such as malignancies, both hematologic and solidtumor.Objective To assess liver function in children with either hemato-logic malignancy or solid tumor and to find out which one of themmostly affects liver function.Methods A retrospective study was conducted on 125 childrenwith malignancies in the Sub division of Hemato-Oncology De-partment of Child Health, Adam Malik Hospital, Medan, from Janu-ary 1999 until May 2000. The inclusion criteria included all pa-tients who were younger than 15 years and had not received anytreatment yet. The differences between prevalent liver dysfunctionin both groups were assessed by using chi-square test; Fisher’sexact test was used to know the type of liver cell damage.Results Liver dysfunction occurred in both types of malignancies. Adecrease of albumin level was not significant in both groups. Therewas a statistically significant difference between the prolongedprothrombine time (PT) in hematologic malignancy (26.4%) and thatin solid tumor (10.4%) with p=0.03. There was no significant differ-ence in the elevation of serum transaminase concentration, totalbilirubin, and alkaline phosphatase. Based on aspartate aminotrans-ferase (AST) and alanine aminotransferase (ALT) ratio, we foundthat the type of liver cell damages was infiltrative disorders, occurred13 out of 20 cases with elevated AST and ALT.Conclusion Liver dysfunction occurred in both types of malig-nancy; it occurred more frequently in hematologic malignancy thanin solid tumors

Serum aminotransferases in nonalcoholic fatty liver disease are a signature of liver metabolic perturbations at the amino acid and Krebs cycle level

Background: Extensive epidemiologic studies have shown that cardiovascular disease and the metabolic syndrome (MetS) are associated with serum concentrations of liver enzymes; however, fundamental characteristics of this relation are currently unknown.Objective: We aimed to explore the role of liver aminotransferases in nonalcoholic fatty liver disease (NAFLD) and MetS.Design: Liver gene- and protein-expression changes of aminotransferases, including their corresponding isoforms, were evaluated in a case-control study of patients with NAFLD (n = 42), which was proven through a biopsy (control subjects: n = 10). We also carried out a serum targeted metabolite profiling to the glycolysis, gluconeogenesis, and Krebs cycle (n = 48) and an exploration by the next-generation sequencing of aminotransferase genes (n = 96). An in vitro study to provide a biological explanation of changes in the transcriptional level and enzymatic activity of aminotransferases was included.Results: Fatty liver was associated with a deregulated liver expression of aminotransferases, which was unrelated to the disease severity. Metabolite profiling showed that serum aminotransferase concentrations are a signature of liver metabolic perturbations, particularly at the amino acid metabolism and Krebs cycle level. A significant and positive association between systolic hypertension and liver expression levels of glutamic-oxaloacetic transaminase 2 (GOT2) messenger RNA (Spearman R = 0.42, P = 0.03) was observed. The rs6993 located in the 3′ untranslated region of the GOT2 locus was significantly associated with features of the MetS, including arterial hypertension [P = 0.028; OR: 2.285 (95% CI: 1.024, 5.09); adjusted by NAFLD severity] and plasma lipid concentrations.Conclusions: In the context of an abnormal hepatic triglyceride accumulation, circulating aminotransferases rise as a consequence of the need for increased reactions of transamination to cope with the liver metabolic derangement that is associated with greater gluconeogenesis and insulin resistance. Hence, to maintain homeostasis, the liver upregulates these enzymes, leading to changes in the amounts of amino acids released into the circulation.

Role of inflammation in intrahepatic cholestasis of pregnancy.

Intrahepatic cholestasis of pregnancy (ICP), the most common liver disease in pregnancy, is characterized by elevated serum total bile acid and/or transaminase concentration, and pruritus. Interleukin-6 (IL-6) is a key regulator of the immune response, hematopoiesis and inflammation. We examined both IL-6 and the frequently used inflammatory marker high-sensitivity C-reactive protein (hs-CRP) at baseline in the same study population as for the primary endpoint, in order to provide a new perspective on the pathogenesis of ICP. In this controlled cross-sectional study 65 consecutive pregnant women with ICP (34 with mild and 31 with severe disease) and 40 healthy women with uncomplicated pregnancies (control group) were examined. IL-6 and hs-CRP were compared between the groups. While serum IL-6 was significantly higher in the mild ICP (P = 0.01) and severe ICP (P = 0.001) groups than in the control group, hs-CRP was similar between the groups. Interleukin-6 may have an essential role, apart from CRP, in the pathogenesis of ICP and, also, is a more sensitive marker of inflammation.

Increasing serum transaminase is not associated with the serum isoniazid and rifampicin levels in tuberculosis patients treated with fixed-dose combination antituberculosis in Yogyakarta

ABSTRACT Tuberculosis is still a major health problem in Indonesia. Isoniazid and rifampicin are major antituberculosis drugs. These two drugs have been known to cause hepatotoxicity which is characterized by an increase of serum transaminase concentration. Previous study proved the increase of hepatotoxicity due to isoniazid and rifampicin but did not explain about the correlation with the drugs concentration. The aim of this study is to know the relation between increasing serum transaminase and the serum concentration of isoniazid and rifampicin of tuberculosis patients which given antituberculosis fixed dose combination in Yogyakarta. We carried out a cross sectional study involving 31 TB patients who received antituberculosis fixed dose combination containing isoniazid and rifampicin. Serum transaminase was measured with an automatic chemical analyzer. Isoniazid and rifampicin concentration was measured by using HPLC. We used t- test, Mann Whitney, Fisher and Spearman to analyze the data. There is no correlation between mean isoniazid concentration with high (7,07±6,24mg/ml) and normal ALT (2,42±0,26mg/ml) (p>0,05). There is no correlation between mean isoniazid concentration with high (5,03 + 4,14 mg/ml) and normal AST (p>0,05). There is no correlation between mean rifampicin concentration with high (10,67 + 3,76 mg/ml) and normal ALT (3,66 + 0,30 mg/ml) (p>0,05). There is no correlation between mean rifampicin concentration with high (8,52 + 3,06 mg/ml) and normal AST (3,64 + 0,32 mg/ml) (p>0,05). Mean of rifampicin concentration in this study are low (4, 12 + 0,46 mg/ml). So the conclusion that there are no correlation between isoniazid serum concentration with an increase of serum transaminase and no correlation between rifampicin serum concentration with an increase of serum transaminase.

Coffee consumption is associated with lower serum aminotransferases in the general Korean population and in those at high risk for hepatic disease.

The favourable effects of coffee on liver enzymes have been reported worldwide. This study investigated the association between coffee consumption and serum aminotransferase concentration in Korean adults. Data were obtained from the fourth and fifth Korea National Health and Nutrition Examination Surveys. Elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) concentration were defined as >30 IU/L for men and >19 IU/L for women. The risk of elevated ALT and AST according to general characteristics and frequency of coffee consumption were tested by chi-square tests and multiple logistic regression analyses. The prevalence of elevated ALT was 27.4%, 27.8%, and 26.9% in subjects who drank <1, 1, and >=2 times/day, respectively. The proportions of individuals with elevated AST were 32.5%, 33.1%, and 26.7% in subjects who drank <1, 1, and >=2 times/day, respectively. The aORs for elevated ALT and AST were significantly lower in subjects who drank >=2 times of coffee/day than in those who drank <1 time/day (ALT: aOR=0.86, 95% CI=0.79-0.94; AST: aOR=0.83, 95% CI=0.76-0.91). In subgroup analysis, consumption of >=2 times/day was associated with lower ORs for elevated ALT in the high-risk group overall and in the viral hepatitis and obesity subgroups, respectively. In sensitivity analysis, reduced frequency of coffee consumption was associated with an increased risk for elevated liver enzymes, although an association between coffee consumption and elevated ALT was not observed in women or current smokers. Higher coffee consumption was associated with lower risk of elevated aminotransferase concentration in Korean adults.

Flomoxef in neonates and young infants; clinical efficacy, pharmacokinetic evaluation and effect on the intestinal bacterial flora

Forty-three newborn and young infants including 13 low-birth-weight (LBW) infants were treated with flomoxef (FMOX) and the clinical efficacy and side effect were evaluated. The ages of the patients ranged from 0 to 99 days, and their body weights from 797 to 9,000 g. Dose levels were 10.5 to 48.5 mg/kg every 6 to 8 hours for 3 to 12 days. Those patients who responded to the FMOX treatment included 8 infants with sepsis, 14 with suspected sepsis, 6 with intrauterine infection, 2 with meningitis, 7 with pneumonia, 1 with staphylococcal scalded skin syndrome, 1 with epididymitis and 4 with urinary tract infections. The results were excellent in 17 and good in 22 patients. The drug was well tolerated, although diarrhea occurred in 2, slightly elevated serum concentrations of transaminases in 2, and eosinophilia and thrombocytosis in 1 patient each. Pharmacokinetic studies on FMOX with 20 mg/kg dose were done in 19 patients including 8 LBW infants. Serum concentrations at 15 minutes after intravenous bolus injection in five 1- to 6-day-old LBW, five 1- to 6-day-old and four 8- to 19-day-old mature infants were 52.6, 52.7 and 58.0 micrograms/ml, respectively, and those at 4 hours were 22.1, 13.3 and 5.2 micrograms/ml, respectively. Serum half-lives of the drug were 3.93, 2.29 and 1.62 hours, respectively, and excretion rates of this drug into urine in the first 6 hours after administration were 30.4, 45.1 and 58.7%, respectively. Mean serum concentrations just after intravenous 1-hour drip infusion in three 8- to 54-day-old LBW and two 8- and 10-day-old mature infants, were 31.5 and 18.9 micrograms/ml, respectively, and those at 4 hours were 15.3 and 4.3 micrograms/ml, respectively. Serum half-lives of the drug were 2.88 and 1.75 hours, respectively, and excretion rates of the drug into urine in the first 6 hours were 22.6 and 47.5%, respectively. The cerebrospinal fluid level at 3 hours after a dose was 7.09 micrograms/ml on the second day of treatment in a patient with Staphylococcus aureus meningitis receiving 50 mg/kg of the drug every 6 hours per day. Its level at 1 hour after a dose was 3.52 micrograms/ml on the 8th day of treatment in the same patient. The influence of FMOX on the fecal flora was studied in 7 patients. The characteristic pattern observed during the drug administration was the disappearance of Bifidobacterium, the decrease or disappearance of Enterobacteriaceae and the preservation of Streptococcus.(ABSTRACT TRUNCATED AT 250 WORDS)

Ceftriaxone in neonates and young infants; clinical efficacy, pharmacokinetic evaluation and effect on intestinal bacterial flora

Twenty-two newborn and young infants, including 13 premature infants, were treated with ceftriaxone (CTRX) and the clinical efficacy and side effects were evaluated. Ages of the patients ranged from 0 to 106 days, and their body weights from 1.19 to 3.92 kg. Dose levels were 15 to 23 mg/kg every 12 to 24 hours for 2 to 13.5 days. Eighteen infants with sepsis and 1 infant with purulent coxitis were considered to have responded to the CTRX treatment. The results were excellent in 13 and good in 6 patients. The drug was well tolerated, although diarrhea occurred in 2 patients, eosinophilia in 6 patients, slightly elevated serum concentrations of transaminases in 2 patients and thrombocytosis in 1 among the 22 patients. The pharmacokinetic studies on CTRX were done in 8 patients including 3 premature infants. The ages ranged from 3 to 50 days, and body weight from 2.20 to 3.94 kg. Plasma concentrations 30 minutes after single 10 mg/kg intravenous bolus injection in two 4- to 5-day-old premature neonates were 48.4 and 50.0 micrograms/ml and those at 6 hours were 22.7 and 23.4 micrograms/ml, respectively. In 2 mature neonates, plasma levels were 42.2 and 39.1 micrograms/ml at 30 minutes and 23.4 and 26.6 micrograms/ml at 6 hours after single 20 mg/kg doses. In four 12- to 50-day-old patients, plasma concentrations ranged from 35.9 to 175.0 micrograms/ml at 30 minutes and from 21.9 to 32.8 micrograms/ml at 6 hours after multiple doses of 20 mg/kg intravenous bolus injection. The plasma half-lives of the drug ranged from 6.6 to 16.8 hours in these 8 patients. Excretion rates of this drug into urine within 12 hours were 21.4 to 63.4% in 7 patients. Urine concentrations of the drug in 34 samples collected at various times from the 7 patients ranged from 28.3 to 469.0 micrograms/ml. The cerebrospinal fluid level at 2 hours after a dose was 3.33 micrograms/ml on the 5th day of treatment in 1 patient with sepsis receiving 18 mg/kg of the drug every 12 hours. Its level at 3 hours after a dose was 6.07 micrograms/ml on the 6th day of treatment in another patient with aseptic meningitis receiving 20 mg/kg every 12 hours. The influence of CTRX on the fecal flora was studied in 3 patients receiving 20 mg/kg X 2/day. The characteristic pattern observed during the drug administration was the disappearance of Bifidobacterium and Enterobacteriaceae, the preservation of Streptococcus and Staphylococcus, and the increase in Candida.(ABSTRACT TRUNCATED AT 400 WORDS)

Decreased activities of daily living is a strong risk factor for liver injury by anti‐tuberculosis drugs

We evaluated the association between activities of daily living and drug-induced liver injury by anti-tuberculosis drugs. This retrospective cohort study included adult inpatients with newly diagnosed smear-positive lung tuberculosis treated with standard regimen in two hospitals. (n = 346; 63.6 ± 20.3 years old; 106 (30.6%) females). Activities of daily living was divided into 'independent' (Barthel Index (BI) 80-100, 60.4%) and 'decreased' (BI 0-75, 39.6%) categories. Liver injury was defined as the withdrawal or change of treatment regimen on the basis of the following criteria: serum transaminase concentrations were more than three times the upper limit of normal range with jaundice and/or hepatitis symptoms, or more than five times the upper limit of the normal range. Compared with 'independent' patients, patients with 'decreased' activities of daily living had odds ratios for liver injury of 4.2 (P < 0.001) in univariate analysis and 5.7 (P = 0.002) in logistic regression analysis after adjusting for other risk factors. Decreased activity of daily living is a strong risk factor for liver injury among adult inpatients with newly diagnosed smear-positive lung tuberculosis treated using a standard regimen.

A life-threatening dichlorophen poisoning case: clinical features and kinetics study

Background. Human dichlorophen poisoning is rare. We aim to report a case of dichlorophen poisoning resulting in complete recovery despite life-threatening multiorgan failure and huge serum dichlorophen concentrations. Methods. Description of features and management in one dichlorophen-poisoned patient. After liquid–liquid extraction, dichlorophen concentrations in the urine and the serum were measured using liquid chromatography-heated electrospray ionization–tandem mass spectrometry (LC-HESI-MS/MS). Case report. A 74-year-old female self-ingested an anti-moss dichlorophen solution (360 g/L) in a suicidal attempt. She rapidly developed caustic esophageal and gastric mucosal injuries, confusion, profuse diarrhea, and electrolyte disturbances. Initial elevation in serum aminotransferase and γ-glutamyltransferase concentrations resolved over 6 days. Serum dichlorophen concentration measured was 708.1 μg/L on admission, and its elimination was prolonged (serum apparent elimination half-life: 35.5 h), peaking in urine on day 2. Mild elevation in serum creatine phosphokinase concentration (peaking 48 h post-ingestion) and acute renal failure (requiring hemodialysis on day 8) occurred. The final outcome was favorable with supportive management. Conclusion. Dichlorophen ingestion results in life-threatening multiorgan dysfunction including rapid onset of caustic digestive lesions, diarrhea, liver enzyme disturbances, as well as acute kidney injury and rhabdomyolysis. Recovery can be complete if prompt supportive management is provided.

Transplantation of bone marrow cells decreases tumor necrosis factor-α production and blood–brain barrier permeability and improves survival in a mouse model of acetaminophen-induced acute liver disease

Acute liver failure (ALF), although rare, remains a rapidly progressive and frequently fatal condition. Acetaminophen (APAP) poisoning induces a massive hepatic necrosis and often leads to death as a result of cerebral edema. Cell-based therapies are currently being investigated for liver injuries. We evaluated the therapeutic potential of transplantation of bone marrow mononuclear cells (BMC) in a mouse model of acute liver injury. ALF was induced in C57Bl/6 mice submitted to an alcoholic diet followed by fasting and injection of APAP. Mice were transplanted with 10(7) BMC obtained from enhanced green fluorescent protein (GFP) transgenic mice. BMC transplantation caused a significant reduction in APAP-induced mortality. However, no significant differences in serum aminotransferase concentrations, extension of liver necrosis, number of inflammatory cells and levels of cytokines in the liver were found when BMC- and saline-injected groups were compared. Moreover, recruitment of transplanted cells to the liver was very low and no donor-derived hepatocytes were observed. Mice submitted to BMC therapy had some protection against disruption of the blood-brain barrier, despite their hyperammonemia, and serum metalloproteinase (MMP)-9 activity similar to the saline-injected group. Tumor necrosis factor (TNF)-α concentrations were decreased in the serum of BMC-treated mice. This reduction was associated with an early increase in interleukin (IL)-10 mRNA expression in the spleen and bone marrow after BMC treatment. BMC transplantation protects mice submitted to high doses of APAP and is a potential candidate for ALF treatment, probably via an immunomodulatory effect on TNF-α production.

Measurement of pentane in expiratory gas during rabbit hepatic ischemia/reperfusion by solid-phase microextraction and gas chromatography–mass spectrometry (SPME GC/MS)

The aim of this study was to determine the changes in the pentane concentration of expiratory gas as well as the relationship between this pentane concentration and hepatic oxidative stress during rabbit hepatic ischemia/reperfusion using solid-phase microextraction (SPME) and gas chromatography–mass spectrometry (GC/MS). 45 white male rabbits with body weights between 2.5 and 3.0 kg were randomly assigned to the following three groups: the 10 min ischemia group (group S); the 20 min ischemia group (group M); or the 30 min ischemia group (group L). Expiratory gases were collected prior to ischemia (T0) and for 1, 10, 20, 30, 60 and 120 min (T1–T6) following reperfusion. Pentane concentrations were determined using SPME and GC/MS. In addition, arterial blood samples were collected, and serum aminotransferase (AST) and malondialdehyde (MDA) concentrations were measured. In the three groups, the pentane concentrations of the expiratory gases at points T1 and T2 were significantly increased (P < 0.05) compared with those at point T0, and the serum AST and MDA concentrations at points T5 and T6 were also significantly increased (P < 0.05) compared with those at point T0. Therefore, the use of SPME in combination with GC/MS represents an improved anesthesia system that can be used to continuously measure the concentration of pentane in expiratory gases, which can reflect the degree of oxidative stress during hepatic ischemia/reperfusion.

When do the aminotransferases rise after acute acetaminophen overdose?

Context. Rising aminotransferases (ATs) [either aspartate aminotransferase (AST) or alanine aminotransferase (ALT) are one of the first signs of hepatotoxicity following acetaminophen (APAP)] overdose (OD). However, the timing and speed of such rises are not well characterized, hampering early risk prediction. Objective. To describe the kinetics of AT release in acute APAP OD patients who develop hepatotoxicity despite treatment. Methods. A descriptive study of acute APAP OD patients with peak AT > 1,000 IU/L taken from the derivation subset of the Canadian Acetaminophen Overdose Study (CAOS), a large, multicenter retrospective cohort of patients hospitalized for APAP poisoning. Results. Of 2,488 hospital admissions for acute APAP OD, 94 met inclusion criteria. Treatment with acetylcysteine, mostly intravenously, was begun in all cases within 24 h of ingestion. The initial AT concentration was already elevated in most patients at presentation [median 211 (IQR 77–511) IU/L obtained at 15.3 (12.1–19.2) h postingestion], and exceeded 100 IU/L in almost all patients within 24 h of ingestion. Serum AT concentrations rose rapidly [doubling time 9.5 h (95% CI: 8.7–10.4 h)], especially in patients who developed AT > 1,000 IU/L within 48 h of ingestion. Coagulopathy was worse in these patients and in those with an AT > 250 IU/L during the first 12 h of treatment with acetylcysteine. Discussion and conclusions. An abnormal and rapidly doubling AT at presentation is more typical in severely poisoned patients, as judged by the effects on clotting. These data suggest that risk prediction instruments may be improved by incorporating both the serum AT concentration at initiation of antidotal therapy and its rate of change. Further studies using such an approach are warranted.

Acute liver injury after intravenous amiodarone: A case report

Acute hepatotoxicity is a rare but potentially fatal complication of amiodarone use. Although oral long-term use of the drug is frequently complicated by an asymptomatic rise in serum aminotransferase concentrations, acute hepatotoxicity during intravenous loading is much less frequent and potentially fatal. We report a case of liver injury after intravenous administration in a patient with atrial fibrillation.

Risperidone and Lithium for Personality and Behavioral Changes With Wilson's Disease

To the Editor: Wilson's disease (hepatolenticular degeneration) is an autosomal recessive defect of cellular copper export. Patients most often present with liver disease (which can range from asymptomatic elevations in the serum aminotransferase or bilirubin concentrations to fulminant hepatic failure) or with neuropsychiatric disease.1 About 20% incidence of psychiatric disturbances has been reported in Wilson's disease.2 We report a case in which psychiatric symptoms improved with combined therapy with risperidone and lithium in a patient with Wilson's disease. Case report. Mr A, a 43-year-old man, had a diagnosis of Wilson's disease for 36 years. Although he had been treated with d-penicillamine, his symptoms had become increasingly worse. He had been diagnosed with liver cirrhosis 18 years before and stomach varices 7 years before. For the last 2 years, he had been diagnosed as hepatic encephalopathy. Moreover, he had presented with personality changes (irritability and aggressiveness) and neurologic abnormalities (dysarthria, rigidity, and tremor). In July 2005, he was admitted to our hospital because of exacerbation of hepatic encephalopathy. He was treated with diuretics, lactulose, and polymyxin B. These treatments were effective for symptoms of hepatic encephalopathy. However, his mental status was not improved. He was then referred to our department of psychiatry. At psychiatric evaluation, his symptoms were irritability, aggressiveness, emotional lability, and lack of restraint. He had no previous psychiatric illness history, nor did his family. Magnetic resonance imaging of the brain revealed enlarged ventricles, cortical atrophy, and abnormal signals of basal ganglia. He was diagnosed with DSM-IV personality and behavioral changes due to Wilson's disease. He was treated with 4 mg/d of risperidone for 2 weeks. However, his symptoms were not improved. Lithium, 400 mg/d, was added to risperidone. After 1 week, his psychiatric symptoms were relieved. After his mental status had been stable for 6 weeks, he was transferred to a facility near his home. There is a lack of consensus on the pharmacotherapy of personality and behavioral changes with Wilson's disease. Atypical antipsychotics may be useful in the treatment of its psychiatric symptoms because of their fewer extrapyramidal side effects.3 There are a few case reports regarding the use of atypical antipsychotics (quetiapine,3 clozapine4) for affective or psychotic symptoms with Wilson's disease. We decided to use atypical antipsychotics. Because Mr A's blood studies showed pancytopenia and hyperglycemia, we chose risperidone from among the atypical antipsychotics. However, we could not increase his dosage of risperidone because of concerns about his severe parkinsonian-like symptoms. Therefore, lithium was added to risperidone as a mood stabilizer. In this case, combined therapy with risperidone and lithium was effective. When neurologic symptoms are severe, the addition of mood stabilizers to low-dose atypical antipsychotics seems to be effective. Lithium, alone of the mood stabilizers, is not metabolized in the liver and is excreted through the kidneys. Considering the risk of liver dysfunction with Wilson's disease, treatment with lithium seems to be more reasonable than that with other mood stabilizers such as valproic acid or carbamazepine. We think that combined therapy with low-dose risperidone and lithium may be useful for personality and behavioral changes with Wilson's disease.

Serum transaminases concentrations in obese children and adolescents

The aim of the study was to investigate the relationship between liver transaminase levels and metabolic syndrome (MS) features in obese children and adolescents. A total of 132 children and adolescents (73 males and 59 females) aged 8 - 16, participated in the study. All were studied at the department of Paediatrics, University Hospital of Zaragoza (Spain). Inclusion criteria were the existence of obesity as defined by body mass index (BMI) according to Cole cut-off values (when BMI was higher than the age and sex specific equivalent to 30 kg/m2). The definition of metabolic syndrome was according to the International Diabetes Federation criteria. Weight (kg), height (cm), waist circumference (cm), blood pressure and BMI were measured. Laboratory determinations after overnight fasting included: transaminases (ALT, AST, GGT), fasting glucose, insulin, triglycerides and HDL-C. The MS was found in 21.6% of the obese children and adolescents and the prevalence was higher in males (25.9%) than in females (15.9%). Serum transaminases (ALT, AST and GGT) mean concentrations were higher in males than in females, and decreased during pubertal development. The obese children and adolescents with the MS did not show higher transaminases concentrations when compared with those without the MS. Some MS manifestations (mainly waist circumference) showed a correlation with ALT, although all transaminases values were normal according to adult references. Liver transaminases, a surrogate marker of NAFLD, did not show an early and consistent manifestation of abnormalities in the obese children and adolescents studied. In order to define the presence of the disease, it would be necessary to obtain aminotransferase reference standards for children and adolescents, considering pubertal stage and gender.

Practice corner: should we screen all patients starting chemotherapy for chronic hepatitis B virus infection?

A 64-year old Indian man presented to our hospital with jaundice 8 months after finishing R-CHOP chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) for diffuse large B cell non-Hodgkin lymphoma....

Retinol and α-Tocopherol in Morbid Obesity and Nonalcoholic Fatty Liver Disease

We aimed to study serum retinol and alpha-tocopherol in a cohort of obese patients and their possible association with several obesity-related conditions, given that the former may be implicated in a diminished capacity of anti-inflammatory and antioxidant potential in obese patients. Eighty patients with morbid obesity participated in the study. Many clinical and biochemical variables were measured including serum retinol, alpha-tocopherol, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) concentrations. Fatty liver was detected by ultrasonography. Both serum retinol and alpha-tocopherol inversely correlated with body mass index (r = -0.334, P = 0.002 and r = -0.299, P = 0.007, respectively). Serum retinol inversely correlated with AST (r = -0.236, P = 0.036) and ALT (r = -0.241, P = 0.032). Multivariate regression analyses confirmed these results after correcting for the effects of other variables. Eighty-five percent of patients had fatty liver. When restricting the analysis to them, multivariate regression identified male sex (beta = 0.451, P = 0.003), age (beta = -0.275, P = 0.039), and serum retinol concentrations (beta = -0.414, P = 0.005) as predictive variables on serum AST (R (2) = 0.230, F = 3.408, P = 0.009) and male sex (beta = 0.448, P = 0.003), age (beta = -0.236, P = 0.046), insulin resistance determined by homeostasis model assessment (beta = 0.243, P = 0.050), and serum retinol concentrations (beta = -0.305, P = 0.022) as predictive variables on serum ALT (R (2) = 0.296, F = 5.817, P = 0.001). Serum retinol and alpha-tocopherol concentrations are inversely associated with body mass index in morbid obesity, and serum retinol is also inversely associated with serum concentrations of transaminases in those patients with nonalcoholic fatty liver disease.

Acute, Clinically Evident Hepatitis C Virus Infection and Liver Injury

Purpose: Clinically evident acute (or recent) hepatitis C virus (HCV) infection and liver injury is uncommon, in contrast to chronic HCV infection and associated liver disease. However, the clinical and laboratory features of overt recent HCV infection are not dissimilar to other etiologies of acute hepatitis, i.e. fatigue, anorexia, pale stools and dark urine; serum aminotransferase concentrations are typically elevated significantly. Therefore, because clinically overt acute HCV infection is uncommon and alternative diagnoses demand consideration, e.g. autoimmune hepatitis (AIH), liver biopsy may be undertaken. A recent report drew attention to the spectrum of observed histologic abnormalities, such as those concerning for large bile duct occlusion. Methods: We describe five patients with what we believe was clinically evident acute HCV infection and liver injury, all of whom required and underwent liver biopsy on clinical grounds. Results: Five adult patients (two men; median age 41 years [range 19–47]) presented for further evaluation of acute severe liver injury, either without (two patients) or with symptoms – malaise, anorexia, nausea, abdominal pain, pale stools and dark urine. The means of recent HCV exposure was as follows: sexual (two), intranasal (two), and intravenous (one). Pertinent data are contained in the table. Alternative causes of acute severe liver injury (viral, autoimmune, drug-induced, metabolic and alcoholic) were excluded as far as possible by history-taking and laboratory testing. However, because liver injury was so marked, and in three patients alternative or additional explanations existed (Wilson's disease, AIH) liver biopsy was undertaken. Unlike classic descriptions of morphologic changes in acute viral hepatitis, namely lobular hepatocyte swelling/ballooning and acidophil necrosis, pigment-laden macrophages, and/or canalicular cholestasis (all five biopsies revealed these changes), two of the biopsy specimens demonstrated portal tract expansion by edema, with many neutrophils and evidence of bile duct injury. Chronic inflammation was minimal. This raised concern for a primary biliary process, e.g. large duct obstruction. Furthermore, one of these two specimens revealed numerous portal eosinophils concerning for drug reaction. Conclusion: All five patients had laboratory evidence of acute severe liver injury. Symptomatic patients had lower serum albumin, but higher total serum bilirubin and alanine aminotransferase (ALT) concentrations than those without symptoms. Moreover, this difference distinguished those patients with histological changes concerning for an underlying biliary process from those who did not in two of three cases. Timing between infection and liver biopsy might explain these differences.Table

Clinical Summaries

Clinical Summaries

Aminotransferases are associated with insulin resistance and atherosclerosis in rheumatoid arthritis

BackgroundSerum aminotransferase concentrations are reportedly strongly associated with insulin resistance, an established cardiovascular risk factor that is not routinely assessed in clinical practice. We therefore explored the possibility that serum aminotransferase concentrations are as closely related to large artery disease as insulin resistance in rheumatoid arthritis (RA).MethodsCarotid artery plaque (ultrasonography), insulin resistance and liver enzymes (prior to methotrexate (MTX) were determined in 77 consecutive patients with RA (43 with and 34 without MTX).ResultsSerum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were associated with insulin resistance in univariate analysis (R = 0.54, p < 0.0001 and R = 0.36, p = 0.001, respectively) and after adjustment for age, gender and waist circumference (partial R = 0.43, p = 0.0001 and partial R = 0.37, p = 0.001, respectively). ALT and AST concentrations were higher in patients with plaque as compared to in those without plaque (ALT (u/l): 27 [22-32] versus 20 [18-23], p = 0.02; AST (u/l): 25 [21-28] versus 20 [19-22], p = 0.02). The odds ratios [95% CI] for plaque were 1.92 [1.14–3.24] (p = 0.01), 1.93 [1.17–3.16] (p = 0.009) and 1.82 [1.13–2.93] (p = 0.01) for 1 SD increase in ALT (~10 u/l) and AST (~6 u/l) concentrations and in logarithmically transformed homeostasis model assessment of insulin resistance (HOMA-IR) (~0.2 uU.mmol/ml.l), respectively. After adjustment for the potentially confounding characteristics of age, sex, hypertension and hypothyroidism in logistic regression models, ALT (p = 0.049) and AST concentrations (p = 0.027) remained associated with plaque whereas the HOMA-IR did not (p = 0.08). AST concentrations (p = 0.049) were associated with plaque independent of insulin resistance whereas the HOMA-IR (p = 0.1) was not associated with plaque independent of AST concentrations.ConclusionWithin currently recommended reference ranges, serum aminotransferase concentrations may be strongly associated with insulin resistance and atherosclerosis in patients with RA. The measurement of aminotransferase concentrations could be a useful tool in cardiovascular risk stratification in patients with RA.