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PubMed2002

Pirfenidone effectively reverses experimental liver fibrosis.

BACKGROUND/AIMS: Our group has been involved in searching for different strategies to ameliorate hepatic cirrhosis. The aim of this study was to evaluate the effect of Pirfenidone in the reversion or prevention of cirrhosis experimentally induced in rats by chronic administration of CCl(4) and bile-duct ligation (BDL). METHODS: Male cirrhotic Wistar rats (8 weeks of intoxication and then hepatotoxin was discontinued) received either oral saline or Pirfenidone at 500 mg/kg per day. RESULTS: High levels of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase decreased significantly (P<0.001) in animals treated with Pirfenidone (n=11) with regard to saline-administrated animals (n=9). Prothrombin activity and bilirubins were also reduced. Computerized fibrosis index demonstrated a 70% decrease (P<0.001) along with less hydroxyproline content, reduction in activated HSC and higher active cell regeneration. A rearrangement of the parenchyma was also noted and gene expression of collagens I, III and IV, transforming growth factor beta-1, Smad-7, TIMP-1 and PAI-1 decreased considerably in treated animals. Cirrhotic rats in which CCl(4) was not discontinued displayed 40% liver fibrosis reduction. In a different cirrhosis model, 4-week BDL rats treated with the drug showed a significant 50% reduction in hepatic fibrosis (P<0.01). CONCLUSIONS: This new drug might be useful in healing human disease.

Alanine Transaminase↗
PubMed2003

Retrospective study of hepatic enzyme elevations in children treated with olanzapine, divalproex, and their combination.

OBJECTIVE: To evaluate hepatic enzyme elevations during treatment with olanzapine, divalproex, and their combination. METHOD: Fifty-two children, aged 4 to 18 years, with hepatic enzyme levels measured during treatment with olanzapine (n = 17), divalproex (n = 23), or their combination (n = 12), were identified in the computerized records at a pediatric medical center. Clinical characteristics as well as serial alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase levels were collected. RESULTS: Mean and peak hepatic enzyme levels were significantly higher for the combined treatment group compared to the olanzapine or divalproex groups. All 12 patients who received combined treatment had at least one peak enzyme elevation during the treatment. For 42% of these patients, at least one enzyme level remained elevated during the time for which values were available (mean 8 +/- 6 months). For those treated with divalproex either alone or in combination, the findings were not explained by variations in divalproex plasma levels. Two patients receiving combined treatment had the combination treatment discontinued because of medical complications (pancreatitis in one and steatohepatitis in the other). CONCLUSIONS: Combined treatment with olanzapine and divalproex was associated with more elevations of hepatic enzymes than treatment with either agent alone. The long-term significance of this is unknown but warrants study.

Adolescent↗
PubMedDate not supplied

Parenteral nutrition-associated cholestasis in preterm neonates: evaluation of ursodeoxycholic acid treatment.

BACKGROUND/OBJECTIVE: Parenteral nutrition is an integral part of the care of premature infants. Cholestatic liver disease is a frequent complication of prolonged parenteral nutrition, especially in premature infants. It has been suggested that ursodeoxycholic acid may alter the course of parenteral nutrition-associated cholestasis in children and adults. We attempted to determine the efficacy of ursodeoxycholic acid in premature infants with parenteral nutrition-associated cholestasis. METHODS: Retrospective chart review of all infants receiving ursodeoxycholic acid for parenteral nutrition-associated cholestasis in a 40 bed neonatal intensive care unit. Efficacy of ursodeoxycholic acid was evaluated by response of bilirubin, alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase over a treatment period of at least 1 month. RESULTS: Six infants with parenteral nutrition-associated cholestasis who had received ursodeoxycholic acid for one month were identified. Doses of ursodeoxycholic acid ranged from 15-30 mg/kg/day. Cholestasis appeared at a mean age of 47 +/- 17 (mean +/- SD) days after a mean of 42 +/- 15 days of parenteral nutrition. Transaminase levels decreased in three, and either increased or did not change in the other three infants. Bilirubin levels decreased in all infants. Alkaline phosphatase showed a non significant trend to decreased levels. Consistent improvement in all infants was noted only after 10 days of full enteral nutrition. No toxicity was found during ursodeoxycholic acid treatment. CONCLUSIONS: Ursodeoxycholic acid treatment in premature infants appears to be safe, and leads to an early sustained decrease in bilirubin levels by two weeks of therapy. The response of transaminase levels was not sustained in our small cohort.

Alanine Transaminase↗
PubMed2005

Ischemic preconditioning in deceased donor liver transplantation: a prospective randomized clinical trial of safety and efficacy.

Ischemic preconditioning (IPC) has the potential to decrease graft injury and morbidity after liver transplantation. We prospectively investigated the safety and efficacy of 5 minutes of IPC induced by hilar clamping in local deceased donor livers randomized 1:1 to standard (STD) recovery (N = 28) or IPC (N = 34). Safety was assessed by measurement of heart rate, blood pressure, and visual inspection of abdominal organs during recovery, and efficacy by recipient aminotransferases (aspartate aminotransferase [AST] and alanine aminotransferase [ALT], both measured in U/L), total bilirubin, and international normalized ratio of prothrombin time (INR) after transplantation. IPC performed soon after laparotomy did not cause hemodynamic instability or visceral congestion. Recipient median AST, median ALT, and mean INR, in STD vs. IPC were as follows: day 1 AST 696 vs. 841 U/L; day 3 AST 183 vs. 183 U/L; day 1 ALT 444 vs. 764 U/L; day 3 ALT 421 vs. 463 U/L; day 1 INR 1.7 +/- .4 vs. 2.0 +/- .8; and day 3 INR 1.3 +/- .2 vs. 1.4 +/- .3; all P > .05. No instances of nonfunction occurred. The 6-month graft and patient survival STD vs. IPC were 82 vs. 91% and median hospital stay was 10 vs. 8 days; both P > .05. In conclusion, deceased donor livers tolerated 5 minutes of hilar clamping well, but IPC did not decrease graft injury. Further trials with longer periods of preconditioning such as 10 minutes are needed.

Alanine Transaminase↗
PubMed2006

Evaluation of surrogate markers for passive transfer of immunity in kittens.

OBJECTIVE: To identify surrogate markers of passive transfer of immunity in kittens. DESIGN: Prospective clinical trial. ANIMALS: 55 kittens from 12 specific-pathogen-free queens. PROCEDURE: Kittens were allocated at birth into colostrum-fed (n = 27) and colostrum-deprived (28) groups. Blood was collected at birth and on days 1, 2, 4, 7, 14, 28, and 56. Serum samples were analyzed for activities of alkaline phosphatase (ALP), alanine aminotransferase, aspartate aminotransferase, creatine kinase, lactate dehydrogenase, gamma-glutamyltransferase, amylase, and lipase and for concentrations of albumin, total protein, bilirubin, urea nitrogen, creatinine, cholesterol, glucose, calcium, phosphorus, and triglycerides by use of an automated analyzer. Total serum solids concentrations were estimated by use of refractometry. Serum IgG concentrations were quantified by use of radial immunodiffusion. RESULTS: All kittens were agammaglobulinemic at birth. Colostrum-fed kittens had significantly higher IgG concentrations than did colostrum-deprived kittens from 1 though 28 days of age. Transient significant differences in serum biochemical variables between the colostrum-deprived and colostrum-fed groups were substantially resolved by day 4. Passive transfer of immunity could be reliably determined at 1 day of age and to a lesser extent at 2 days of age only by measurement of serum activity of ALP. CONCLUSIONS AND CLINICAL RELEVANCE: Adequacy of passive transfer in kittens initially correlated with serum activity of ALP, but quantification of serum IgG concentration was necessary after 2 days of age.

Aging↗
PubMed1994

Cholelithiasis during pregnancy and lactation. Prospective study.

OBJECTIVE: To assess the incidence of formation of gallstones during pregnancy and lactation, the time when gallstones first appear, and any changes in predisposing factors. DESIGN: Prospective study. SETTING: District hospital, Greece. SUBJECTS: 669 pregnant women seen between 1988 and 1991. MAIN OUTCOME MEASURES: Body mass index (kg/m2); real time ultrasonography; and measurements of serum concentrations of bilirubin, total cholesterol, low density lipoprotein cholesterol, and triglycerides, and of activities of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and amylase. All measurements were made at the beginning of pregnancy; at the third, sixth and ninth months; and 7 days and 6 months after delivery. RESULTS: 6 women (1%) mean age 26 years, had pre-existent gallstones and 14 further women (2%) mean age 27 years, developed gallstones; 13 were discovered during pregnancy (8 during the second trimester, and 5 during the third) and one during lactation. Women who had 3 or more pregnancies (6/110, 5%) were significantly more likely to develop gallstones than those who had not been pregnant before (3/304, 1%, p = 0.01). Gallbladder volume more than doubled during pregnancy from a mean (SD) of 12 (4) to 26 (4) ml. Total cholesterol, low density lipoprotein cholesterol and triglyceride concentrations, and alkaline phosphatase activity increased gradually, and reverted to the value found at the beginning of pregnancy immediately after delivery. CONCLUSIONS: The risk of developing gallstones increased with the number of pregnancies, and most of the stones developed during the second or third trimester.

Adult↗
PubMed1993

Circadian rhythms of serum concentrations of 12 enzymes of clinical interest.

A total of 25 apparently healthy adults (13 men and 12 women), 29.5 years (SD = 3.6 years) of age, served as subjects in a 24-h study conducted in Barcelona, Spain, in the spring of 1990. The group had a homogeneous pattern of meals, activity, and behavior. Six blood samples were collected at 4-h intervals over a single 24-h period beginning at 10:00 h. The oral temperature was measured at 2-h intervals to facilitate an independent biological time reference for the local population being studied. The serum concentration of 12 enzymes of clinical interest were measured in each sample: creatine kinase, creatine kinase 2, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase, alkaline phosphatase, cholinesterase, lactate dehydrogenase, lactate dehydrogenase 1, 5'-nucleotidase, pancreatic alpha-amylase, and triacylglycerol lipase. We supposed that all experimental data obtained for a quantity came from a single "hypothetical subject" that represented the central tendency of the population and then these data were analyzed for circadian rhythm by single cosinor. A statistically significant circadian rhythm was detected in all quantities studied (p < or = 0.05) except for serum concentrations of pancreatic alpha-amylase and triacylglycerol lipase. The maximum daily rhythmic variation was approximately 10% (interval, 6-14%) for all quantities studied except pancreatic alpha-amylase (2.6%). This rhythmic variation is greater than the analytical variation except for 5'-nucleotidase and pancreatic alpha-amylase. The acrophases for the quantities studied (except that of triacylglycerol lipase) coincide with times near those of the oral temperature acrophase (18:01 local time). The results of this study will doubtless contribute to further documentation of the structure of the human circadian timing system and to establishment of time-qualified reference intervals for a defined group of subjects.

5'-Nucleotidase↗
PubMed1998

Impact of distal aortic and visceral perfusion on liver function during thoracoabdominal and descending thoracic aortic repair.

PURPOSE: We examined the impact of distal aortic and visceral perfusion on liver function during thoracoabdominal and descending thoracic aortic repair. METHODS: Between January 1991 and July 1996, 367 patients underwent thoracoabdominal and descending thoracic aortic repair. Baseline and postoperative total bilirubin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, fibrinogen, prothrombin time (PT), and partial thromboplastin time (PTT) were measured for 286 patients. We examined the impact of distal aortic and direct visceral perfusion on liver function-related clinical laboratory values. Univariate and multivariate statistical methods for categorical and continuous variables were used. RESULTS: In categorical analysis, type II thoracoabdominal aortic aneurysm, history of hepatitis, and emergency presentation had a statistically significant multivariate association with abnormal laboratory values. In continuous-distributed multivariate data analysis, type II thoracoabdominal aortic aneurysm and visceral perfusion were statistically significant predictors of postoperative alkaline phosphatase, PT, and PTT. Type II aneurysms increased postoperative liver function-related laboratory values significantly above other aneurysm types (alkaline phosphatase, +114 IU, p < 0.0001; PT, +1.99 seconds, p < 0.02; PTT, +6.7 seconds, p < 0.03). Visceral perfusion was associated with a concomitant decrease (alkaline phosphatase, -101.2 IU, p < 0.0001; PT, -1.8 seconds, p < 0.07; PTT, -5.6 seconds, p < 0.02). CONCLUSIONS: Visceral perfusion negates the rise in postoperative liver function-related clinical laboratory values associated with type II thoracoabdominal aortic aneurysm repair.

Alkaline Phosphatase↗
PubMed1999

Liver abnormalities in Turner syndrome.

UNLABELLED: We evaluated whether hepatic abnormalities represent a specific feature in girls with Turner syndrome (TS) or whether they are related to an increased susceptibility to hormonal therapies and/or other factors. Alanine aminotransferase, aspartate aminotransferase and gamma-glutamyl transferase were monitored in 70 patients with TS for a mean period of 7.6+/-4.2 years. An increase in serum liver enzymes was observed in 14 out of 70 girls (20%) at a mean age of 12.7 years; it was present at entry before hormonal therapy in 3 girls and developed thereafter during the follow up in the other 11. The increase in serum liver enzymes was never observed before the age of 7 years. In the majority of cases (10/14) it was drug related: in 50% the liver abnormalities were transient and self-limiting, in the remaining cases they required interruption of hormonal therapy. Hepatotoxicity was more frequently observed in girls treated with oestrogens or oxandrolone than in those treated with growth hormone. In a small number of cases, liver disease was either auto-immunity-related (2/14), or cryptogenic (1/14) with a benign and self-limiting course. Obesity was a frequent finding, but it played a likely pivotal role only in one patient. CONCLUSION: Hepatic abnormalities are relatively frequent in Turner syndrome and surveillance of liver function should be included in the management of these patients independent of initiation of hormonal treatment.

Alanine Transaminase↗
PubMed1997

Vascular occlusion in hepatic resections in cirrhotic rat livers: an experimental study in rats.

The aim of this study was to evaluate the tolerance of normothermic liver ischemia with different degrees of hepatic function in cirrhotic rats. Liver cirrhosis was induced by administering carbon tetrachloride (CCl4) in water solution to male Wistar rats. Hepatic function was graded using the plasma levels of antithrombin III, albumin, and bilirubin and the presence of ascites. Rats were distributed in four groups: noncirrhotic (control group), compensated cirrhosis (group A), decompensated cirrhosis (group B), and decompensated cirrhosis with ascites (group C). Groups A, B, and C were significantly different in all four parameters studied (P < .003). Subtotal liver ischemia was performed for periods of 0, 30, 45, 60, and 75 minutes. At the end of the procedure, the nonischemic lobes were resected. Postoperative evolution of alanine aminotransferase, aspartate aminotransferase, and bilirubin levels was also recorded. Survival rates after the same periods of ischemia were statistically different (P < .05): control group, 7 of 7 after 45 minutes (100%), 7 of 7 after 60 minutes (100%), and 4 of 9 after 75 minutes (44%); group A, 7 of 7 after 45 minutes (100%) and 1 of 7 after 60 minutes (14%); group B, 7 of 7 after 0 minutes (100%), 5 of 7 after 30 minutes (71%), and 1 of 7 after 45 minutes (14%); and group C, 0 of 5 after 0 minutes (0%) and 1 of 7 after 30 minutes (14%). No differences were found in the postoperative course of transaminases. However, bilirubin levels found 24 hours and 7 days after ischemia were significantly greater in cirrhotic rats, and this was directly related to the degree of hepatic insufficiency (P < .001). Histological examination of the livers exposed to CCl4 showed features of liver cirrhosis with ductal proliferation. The ischemia time tolerated by cirrhotic rat livers is shorter than the time tolerated by normal rats. Tolerance to hilar vascular occlusion depends on the degree of hepatic insufficiency. Rats with decompensated cirrhosis and ascites do not tolerate any surgical procedure.

Alanine Transaminase↗
PubMed1987

Comparison of two solid phase chemistry systems: Reflotron and Ektachem DT 60.

Solid phase chemistry can be used for clinical analysis at the bedside, and it is even applicable to whole blood. We compared precision, accuracy, method linearity, and practicability of two solid phase chemistry analysers. Reflotron (Boehringer Mannheim, W. Germany) and Ektachem DT 60 (Eastman Kodak Co, USA). Eight analytes, glucose, cholesterol, triacylglycerols, urea, uric acid, alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyltransferase were investigated. The precision of both instruments was good. Coefficients of variation for within run and day to day precision were below 10% for all analytes. Methods were compared by analysing 88 to 105 patients sera for each investigated analyte on Reflotron, on Ektachem DT 60 and on a wet chemistry reference instrument. Linear regression analysis showed good agreement between wet chemistry and solid phase chemistry results. Coefficients of correlation (r) ranged from 0.957 to 0.999. Reflotron and Ektachem are desk top analysers. Reflotron is the smaller instrument. Currently, it offers 9 analytes and rapid single test performance. Whole blood can be used for all tests. Test strips can be stored at room temperature. Ektachem DT 60 has a modular design, and 22 analytes are available. Series of up to 100 tests per hour are possible. Whole blood can be used for the preparation of glucose and haemoglobin test slides. The slides must be deep frozen for prolonged storage. Reflotron may be suitable for the physician's office, Ektachem for small laboratories. The problem of quality control has not yet been satisfactorily solved for either instrument, as only analyser-specific control specimens can be used. Reagent costs of solid phase chemistry tests are high, especially when large test series are performed. Operation of both instruments requires well trained personnel.

Alanine Transaminase↗
PubMedDate not supplied

Hepatic subcapsular steatosis as a complication associated with intraperitoneal insulin treatment in diabetic peritoneal dialysis patients.

OBJECTIVES: The aim of this study was to evaluate hepatic subcapsular steatosis (HSS) and its association with clinical parameters in nondiabetic continuous ambulatory peritoneal dialysis (CAPD) patients and in diabetic CAPD patients receiving intraperitoneal (IP) or subcutaneous (SC) insulin. DESIGN: Cross-sectional study. SETTING: A tertiary-care university hospital. PATIENTS: 28 CAPD patients (17 males and 11 females; mean age 53.5 +/- 14 years; mean CAPD duration 22.8 +/- 9 months) were included in the study. 14 patients had type II diabetes mellitus and 14 were nondiabetics. In the diabetic group, 8 patients were receiving IP insulin and 6 were receiving SC insulin. OUTCOME MEASURES: HSS was diagnosed on computed tomography without contrast administration. Other data collected were body mass index (BMI), weekly Kt/V, peritoneal equilibration test (PET) results, daily insulin dosage, duration of diabetes mellitus, duration of insulin treatment, dialysate glucose load, and serum findings for alanine aminotransferase, aspartate aminotransferase, albumin, and lipid profiles. RESULTS: HSS was detected in 5 of the 8 diabetics who were receiving IP insulin. None of the diabetics receiving SC insulin and none of the nondiabetic patients exhibited HSS. Daily insulin dosage [108 (95 - 108.5) vs 54 (36 - 72) U/day, p = 0.02], BMI [31 (30.5 - 36) vs 26.6 (26 - 30) kg/m2, p = 0.02], serum triglyceride level [194 (184 - 505) vs 69 (61 - 82) mg/dL, p = 0.04], and PET creatinine levels [D/P2 creat: 0.67 (0.54 - 0.74) vs 0.50 (0.50 - 0.56), p = 0.05; D/P4 creat: 0.75 (0.64 - 0.86) vs 0.60 (0.59 - 0.62), p = 0.02] were higher in diabetic patients receiving IP insulin who had HSS than in those who did not have HSS. PET glucose levels [D0/D2 glu: 0.40 (0.37 - 0.45) vs 0.50 (0.48 - 0.51), p = 0.03; D0/D4 glu: 0.36 (0.26 - 0.38) vs 0.44 (0.38 - 0.48), p = 0.04] were lower in diabetic patients receiving IP insulin who had HSS than in those who did not have HSS. CONCLUSIONS: Our results suggest that IP insulin plays a more important role in the pathogenesis of HSS than glucose levels in diabetic CAPD patients. They also indicate that HSS is associated with higher daily insulin requirement, obesity, hypertriglyceridemia, and high peritoneal transport rate in diabetic CAPD patients receiving IP insulin.

Alanine Transaminase↗
PubMed2005

Simvastatin reduces vasospasm after aneurysmal subarachnoid hemorrhage: results of a pilot randomized clinical trial.

BACKGROUND AND PURPOSE: Cerebral vasospasm remains a major source of morbidity after aneurysmal subarachnoid hemorrhage (SAH). We demonstrate that simvastatin reduces serum markers of brain injury and attenuates vasospasm after SAH. METHODS: Patients with angiographically documented aneurysmal SAH were randomized within 48 hours of symptom onset to receive either simvastatin (80 mg daily; n=19) or placebo (n=20) for 14 days. Plasma alanine aminotransferase, aspartate aminotransferase, and creatine phosphokinase were recorded weekly to evaluate laboratory evidence of hepatitis or myositis. Serum markers of brain injury were recorded daily. The primary end point of vasospasm was defined as clinical impression (delayed ischemic deficit not associated with rebleed, infection, or hydrocephalus) in the presence of > or =1 confirmatory radiographic test (angiography or transcranial Doppler demonstrating mean V(MCA) >160 m/sec). RESULTS: There were no significant differences in laboratory-defined transaminitis or myositis between groups. No patients developed clinical symptoms of myopathy or hepatitis. Plasma von Willebrand factor and S100beta were decreased 3 to 10 days after SAH (P<0.05) in patients receiving simvastatin versus placebo. Highest mean middle cerebral artery transcranial Doppler velocities were significantly lower in the simvastatin-treated group (103+/-41 versus 149+/-47; P<0.01). In addition, vasospasm was significantly reduced (P<0.05) in the simvastatin-treated group (5 of 19) compared with those who received placebo (12 of 20). CONCLUSIONS: The use of simvastatin as prophylaxis against delayed cerebral ischemia after aneurysmal SAH is a safe and well-tolerated intervention. Its use attenuates serum markers associated with brain injury and decreases the incidence of radiographic vasospasm and delayed ischemic deficit.

Adult↗
PubMed1993

Effect of training and anabolic-androgenic steroids on drug metabolism in rat liver.

The effects of anabolic-androgenic steroid administration and exercise training on various aspects of hepatic function were investigated in sedentary and trained (treadmill for 12 wk) male and female rats treated orally with fluoxymesterone or methylandrostanolone (2 mg.kg-1 body weight, 5 d.wk-1 for 8 wk). The mean values of serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total and direct bilirubin, and total- and high-density lipoprotein-cholesterol remained within normal range in all groups of male animals. The same is true for female rats, except for an increase in alkaline phosphatase activity in the steroid-treated groups. Hepatic microsomal aniline p-hydroxylase activity was reduced in male and increased in female rats by either steroid, whereas no significant effect was detected on 7-ethoxycoumarin deethylase activity. The levels of cytochrome P-450 and cytochrome b5 were markedly decreased by the anabolic-androgenic steroid treatment in male rat microsomes, but neither the steroid administration nor exercise training induced significant changes in the cytochrome levels of female rat livers. Taking into account the significant increase in microsomal protein yield elicited by fluoxymesterone or methylandrostanolone treatment both in males and females, it is noteworthy that the total monooxygenase activities and cytochrome P-450 content, expressed on a per gram liver basis, were significantly increased in female whereas they were apparently unchanged in male rats. In conclusion, the present data show that the prolonged ingestion of high doses of anabolic-androgenic steroids, either with or without concurrent exercise training, can modify in a sex-dependent manner the capacity of rat liver to metabolize drugs without affecting classical serum indicators of hepatic function.

Alanine Transaminase↗
PubMed2001

[Role of the hemochromatosis gene in prophyria cutanea tarda. Prospective study of 56 cases].

BACKGROUND: The cause of iron overload in prophyria cutanea tada is unknown. The aim of this work was to determine the frequency of the hemochromatosis gene (HFE) in 56 patients with porphyria cutanea tarda. We analyzed the relationship between HFE mutations and biochemical abnormalities in porphyria cutanea tarda and the interaction with other triggering factors of porphyria cutanea tarda (alcohol abuse, hepatitis C, drugs). PATIENTS AND METHODS: Hepatitis C, alcohol abuse, drug intake and HFE mutations were determined in 56 patients with porphyria cutanea tarda (44 men and 12 women). Iron status was determined from transferrin saturation, serum iron, and serum ferritin. Liver metabolism was determined from liver chemistries: alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transpeptidase. RESULTS: Thirty-nine patients (69.4 p. 100) carried HFE mutations, 18 (32.1 p. 100) were H63D heterozygous, 4 (7.1 p. 100) were H63D homozygous, 9 (16 p. 100) C282Y heterozygous, 8 (14.2 p. 100) compound C282Y/H63D heterozygous and none were C282Y homozygous. Comparison between porphyria cutanea tarda with and without mutations showed that compound C282Y/H63D heterozygous status was significantly linked to iron overload: transferrin saturation=0.61 vs 0.39 (p=0.0001) and serum iron=32.9 vs 22.4 (p=0.0046). H63D homozygous status was linked to iron overload but non-significantly: transferrin sturatin=0.53 vs 0.39 (p=0.06). The class with high iron overload (transferrin saturation > 0.45) was not linked with triggering factors of porphyria cutanea tarda. Hepatatic cytolysis was linked to alcohol abuse and hepatitis C but not to HFE mutations. DISCUSSION: The frequencies of HFE mutations in Lyons France are halfway between Anglo-Saxon and Italian papers, highlighting the Celtic origin of C282Y mutation. Compound heterozygous and to a lesser degree H63D homozygous status explained the highest iron overload in our patients. This favors clinical expression of porphyria cutanea tarda. This iron overload due to HFE mutations is a new triggering factor of porphyria cutanea tarda independent of classical triggering factors: mutation of the erythrocytic uroporpyrinogen decarbocylase gene, alcohol abuse, hepatitis C, and drugs.

Adult↗
PubMed2005

Combining the audit questionnaire and biochemical markers to assess alcohol use and risk of alcohol withdrawal in medical inpatients.

AIMS: Alcohol consumption is often under-reported in patients admitted to general hospitals with acute illness. For alcohol-dependent individuals hospital admission results in an enforced period of abstinence with potential alcohol withdrawal symptoms, and possible life threatening complications. Early detection of alcohol use is therefore beneficial to patients and health services. The purpose of this study was to investigate the performance of the alcohol use disorders identification test (AUDIT) questionnaire in the acute medical setting, and the effect of combining routine biological markers-glutamyltransferase, alanine aminotransferase, aspartate aminotransferase, and mean corpuscular volume (MCV) on its performance in the early identification of in-patients with alcohol use disorders and at risk of developing symptoms of alcohol withdrawal. METHODS: Prospective study in consecutive patients admitted to an acute medical admissions ward. All patients were screened using the AUDIT questionnaire and routine blood tests. Patients were then monitored for symptoms of withdrawal using clinical institute withdrawal assessment for alcohol (CIWA-Ar). RESULTS: Of the 874 patients screened using the AUDIT, 98 (11%) screened positive of whom 17 (2% of the 874) experienced clinically significant alcohol withdrawal symptoms, when using serial CIWA-Ar. The AUDIT and serial CIWA-Ar detected all patients who went on to manifest acute withdrawal symptoms. There was no loss of sensitivity at an AUDIT cut-off of 13 or more compared with the lower cut-off of 8 or more. A positive predictive value of 17.3% for an AUDIT score of 8 or more in the detection of withdrawal, increased to 47.1% when found in combination with at least two abnormal biological markers whilst maintaining a sensitivity of 94.1% and specificity of 97.9%. CONCLUSION: These findings confirm that AUDIT is a useful alcohol screen in general medical settings and that its ability to correctly predict which patients will experience alcohol withdrawal is increased when used in combination with biological markers.

Adult↗
PubMed2003

Type 1 diabetic mice are protected from acetaminophen hepatotoxicity.

Streptozotocin (STZ)-induced diabetic (DB) mice challenged with single ordinarily lethal doses of acetaminophen (APAP), carbon tetrachloride (CCl4), or bromobenzene (BB) were resistant to all three hepatotoxicants. Mechanisms of protection against APAP hepatotoxicity were investigated. Plasma alanine aminotransferase, aspartate aminotransferase, and liver histopathology revealed significantly lower hepatic injury in DB mice after APAP administration. HPLC analysis of plasma and urine revealed lower plasma t1/2, increased volume of distribution (Vd), and increased plasma clearance (CLp) of APAP in the DB mice and no difference in APAP-glucuronide, a major metabolite in mice. Interestingly, covalent binding of 14C-labeled APAP to liver target proteins; arylation of APAP to 58, 56, and 44 kDa acetaminophen binding proteins (ABPs); and glutathione (GSH) depletion in the liver did not differ between nondiabetic (non-DB) and DB mice in spite of downregulated hepatic microsomal CYP2E1 and 1A2 proteins in the DB mice, known to be involved in bioactivation of APAP. Compensatory cell division measured via 3H-thymidine pulse labeling and immunohistochemical staining for proliferating cell nuclear antigen (PCNA) indicated earlier onset of S-phase in the DB mice after exposure to APAP. Antimitotic intervention of liver cell division by colchicine (CLC) after administration of APAP led to significantly higher mortality in the DB mice suggesting a pivotal role of liver cell division and tissue repair in the protection afforded by diabetes. In conclusion, the resistance of DB mice against hepatotoxic and lethal effects of APAP appears to be mediated by a combination of enhanced APAP clearance and robust compensatory tissue repair.

Acetaminophen↗
PubMed2005

Elevation of serum liver enzymes after laparoscopic cholecystectomy.

BACKGROUND: Laparoscopic cholecystectomy (LC) has been accepted as an alternative to laparotomy, and has become the standard treatment of benign gallbladder diseases. However, it has been noticed that (following LC) the serum level of certain liver enzymes raises markedly in patients who had preoperatively normal liver enzyme values. METHODS: We measured serum values of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma glutamyl transferase, bilirubin, and international normalized ratio (INR) in 72 consecutive patients who underwent laparoscopic cholecystectomy and 36 consecutive patients who underwent open cholecystectomy (OC). During laparoscopic surgery, the intra-abdominal pressure was maintained at 14 mmHg of CO2. To assess liver function, serum liver enzymes were measured before operations and at 1,3,7, and 10 days postoperation. RESULTS: Mortality was nil. Twenty-four hours after the procedure, ALT and AST increased statistically significantly in the LC group (ALTLC24: 87.1+/-24.2 U/L P<0.001; ASTLC24:82.8+/-19.1 U/L, p<0.001)--whereas in the OC group, 24 hours after the procedure, the serum value of ALT and AST was above the upper normal limits in only in one patient. A further increase in serum ALT and AST value was observed in the LC group (ALTLC72: 99.3+/-19.5 U/L, p<0.001; ASTLC72H: 103.5+/-21.6 U/L, p<0.001) 72 hours after the operation. The mean value of ALT and AST in the OC group was within normal limits 72 hours after the procedure. Slow return to normality occurred 7-10 days after the procedure in the LC group. CONCLUSION: Alterations in hepatic function occur after laparoscopic cholecystectomy and appear to be clinically insignificant. CO2 pneumoperitoneum seems to be the main reason for theses changes but other factors may also contribute. We also measured the values of ALP, GGT, INR and bilirubin. No statistically significant increase was noticed in any groups between the preoperative and postoperative values of these enzymes.

Adult↗