Serum Aminotransferase Concentrations Research Articles

Hepatic centrilobular zonal necrosis with positive antinuclear antibody: a unique subtype or early disease of autoimmune hepatitis?

Centrilobular zonal necrosis (CZN) is not a pattern typically associated with autoimmune hepatitis (AIH). However, it has occasionally been reported that CZN occurs without the classic histologic features of AIH in patients with autoimmune abnormalities. In this study, we examined the clinicopathological features of 5 cases of CZN with autoimmune features not associated with classic AIH. The patients were 1 man and 4 women (24-82 years). Three patients had subjective symptoms (general malaise, arthralgia, and fever). All had antinuclear antibodies (1:40 to 1:1280). Liver biopsy showed CZN without any histologic features of classic AIH. Liver injury was sustained without medication in 4 cases, whereas it was spontaneously improved in 1 case. However, 2 months later, this patient was found to have recurrent liver dysfunction. Liver biopsy at the time of recurrence again showed CZN without the features of classic AIH. All patients were effectively treated with prednisone. Based on a review of a total of 17 cases of CZN with autoimmune features, including previously reported cases, the patients could be classified into 3 groups: cases without recurrence, cases with recurrent CZN, and cases with progression to classic AIH. Patients of the 2 former groups did not develop classic AIH during follow-up. Factors predictive of recurrence were younger age, being male, and high serum bilirubin or transaminase concentrations at first presentation (P < .05). This study suggested that CZN with autoimmune features corresponds to the early stage of classic AIH in some cases and might be a distinct type of autoimmune liver disease in others.

Hepatitis C virus infection among HIV‐1 infected individuals from northern Mexico

The prevalence of hepatitis C virus (HCV) infection, risk factors and HCV genotypes in 140 HIV-1 infected individuals from northern Mexico was determined. Hepatitis C infection was confirmed by the detection of anti-HCV antibodies and HCV-RNA in sera, and genotyping was performed by the InnoLiPA-HCV genotype assay. Seventeen (12.1%) out of 140 HIV-infected individuals were found to be HCV-positive. Coinfected individuals were more likely to be male (87%). The most frequent genotype was 1a (41%), followed by 1b (29.4%), 2a/c (17.6%), 2b (5.9%) and 3 (5.9%). Serum transaminase concentrations (AST and ALT) were higher in coinfected patients. Among the risk factors for coinfection: sexual transmission was the most frequently observed (men who have sex with men (MSM); 64.7% and bisexual behavior; 64.7%) followed by intravenous drug users (IVDU) (53%). There was no association of the HCV genotypes with the age and risk factors for HIV-1 and HCV infection observed in the studied patients. The results suggest that the prevalence of HIV-1/HCV coinfection in Mexico is lower than in other American countries.

Identifying patients, on the first day of life, at high-risk of developing parenteral nutrition-associated liver disease

Prolonged use of parenteral nutrition (PN) in neonates can lead to parenteral nutrition-associated liver disease (PNALD), manifested by elevated direct bilirubin concentrations, and in some cases progressing to hepatic failure. When new potential means of preventing PNALD in the neonatal intensive care unit (NICU), such as Omegaven usage, are tested in clinical trials, the studies should enroll neonates at a very high risk of developing PNALD. However, it is not always clear, in the first days of life, which neonates are most likely to develop PNALD. Therefore, preparatory to devising studies of prophylaxis against PNALD, we conducted an evaluation of all NICU patients who received PN for >or=14 day, assessing their likelihood of developing PNALD. We performed an historic cohort analysis of all neonates in the Intermountain Healthcare system, receiving PN for 14 days or more during their stay, with dates of birth between 1 January, 2002 and 30 June, 2006. During the 4(1/2)-year period, 9861 neonates were cared for in the Intermountain Healthcare NICUs. Of these, 9547 (96.8%) survived for at least 28 days, and of these 6543 (68.5%) received PN. Twenty-one percent (1366 patients) of those receiving PN, received it for >or=14 days. PNALD was ascertained in this group by a direct bilirubin >or=2.0 mg/dl. Neonates receiving PN for 14-28 days had a 14% incidence of PNALD, those receiving PN for 29-56 days had a 43% incidence, those receiving PN for 57-100 days had a 72% incidence and those receiving PN for >100 days had a 85% incidence. Groups of patients identifiable on the first day of life as having the highest risk of developing PNALD were birth weight <500 g (odds ratio (OR), 30.7), birth weight 500-749 g (OR, 13.1), gastrochisis (OR, 20.3) and jejunal atresia (OR, 24.0). Among 357 patients who developed PNALD, the highest direct bilirubin concentrations correlated with the highest serum alkaline phosphatase and transaminase concentrations. Deaths after 28 days were much more common in those with the highest direct bilirubin and transaminase concentrations (P<0.0001). In the first days of life, certain NICU patients can be identified as being at very high risk for developing PNALD. These are patients <750 g birth weight, those with gastrochisis and those with jejunal atresia. We speculate that these groups would be reasonable subjects for including in a PNALD prophylaxis trial, testing new preventative strategies such as Omegaven usage.

Protective effect of curcumin against liver warm ischemia/reperfusion injury in rat model is associated with regulation of heat shock protein and antioxidant enzymes

To investigate the hypothesis that the protective effects of curcumin in hepatic warm ischemia/reperfusion (I/R) injury are associated with increasing heat shock protein 70 (Hsp70) expression and antioxidant enzyme activity. Sixty Sprague-Dawley male rats were randomly divided into sham, I/R, C + I/R groups. The model of reduced-size liver warm ischemia and reperfusion was used. Curcumin (50 mg/kg) was administered by injection through a branch of superior mesenteric vein at 30 min before ischemia in C + I/R group. Five rats were used to investigate the survival during 1 wk after operation in each group. Blood samples and liver tissues were obtained in the remaining animals after 3, 12, and 24 h of reperfusion to assess serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), liver tissue NO(2)(-) + NO(3)(-), malondialdehyde (MDA) content, superoxide dismutase (SOD), catalase (CAT), nitricoxide synthase (NOS) and myeloperoxidase (MPO) activity, Hsp70 expression and apoptosis ratio. Compared with I/R group, curcumin pretreatment group showed less ischemia/reperfusion-induced injury. CAT and SOD activity and Hsp70 expression increased significantly. A higher rate of apoptosis was observed in I/R group than in C + I/R group, and a significant increase of MDA, NO(2)(-) + NO(3)(-) and MPO level in liver tissues and serum transaminase concentration was also observed in I/R group compared to C + I/R group. Curcumin also decreased the activity of inducible NO synthase (iNOS) in liver after reperfusion, but had no effect on the level of endothelial NO synthase (eNOS) after reperfusion in liver. The 7 d survival rate was significantly higher in C + I/R group than in I/R group. Curcumin has protective effects against hepatic I/R injury. Its mechanism might be related to the overexpression of Hsp70 and antioxidant enzymes.

Development of a tomato-based food for special medical purposes as therapy adjuvant for patients with HCV infection

The present study aimed to develop a food for special medical purposes (FSMP) and to assess its efficacy as adjuvant therapy in patients with chronic hepatitis C virus (HCV). Open randomized clinical trials with a tomato-based FSMP used as adjuvant treatment to the pharmacological therapy with pegilated interferon and ribavirin. Eight healthy volunteers and 39 HCV patients. For the bioavailability study, healthy subjects consumed 100 g/die FSMP for a week and their serum carotenoid profile at baseline, after the week of administration and 7 days later was determined. The same quantity of FSMP for 6 months by 20 of the 39 HCV patients was consumed in the clinical trial. Serum transaminase, haemoglobin (Hb) and hydroperoxide concentrations during the therapy were monitored in all patients. FSMP consumption caused a fourfold increase of lycopene serum concentration in healthy subjects. A significant increase of carotenoids after 1 month of consumption also in patients with HCV was recorded. Transaminase and Hb serum levels, as well as therapeutic response, were not influenced by FSMP. The decrease in serum hydroperoxides was independent from FSMP consumption in long-term responder patients, whereas nonresponder (NR) patients of FSMP group showed higher reductions than NR patients of Control group. The FSMP was effective in improving carotenoid status in healthy subjects. In HCV patients, it did not influence the therapeutic response, but it prevented carotenoid serum depletion and it was effective in improving the oxidative status during antiviral therapy in NR patients.

Low-dose ATRA supplementation abolishes PRM formation in rat liver and ameliorates ethanol-induced liver injury

The effects of all-trans-retinoic acid (ATRA) in low doses supplementation on concentrations of polar retinoid metabolites (PRM) and retinoids in the ethanol-fed rat liver, and on hepatocyte injury were investigated. The rat model of alcoholic liver disease (ALD) was induced by intragastric infusion of ethanol, and then the rats were administrated with ATRA in two different doses (150 microg/kg body weight and 1.5 mg/kg body weight) for 4 weeks. Concentrations of retinoids in rat liver and plasma were determined by using HPLC. Liver tissues pathologic changes were observed under the light microscopy and electron microscopy. The serum transaminases concentrations were measured. The results showed that the HPLC analysis of retinoids revealed that retinoids (vitamin A, RA, retinyl palmitate) concentrations in ethanol-fed rat liver and RA concentration in ethanol-fed rat plasma were markedly diminished (P<0.01) after ethanol feeding for 12 weeks. Furthermore, obvious peaks of PRM were formed in livers of ethanol-fed rats. ATRA 150 microg/kg supplementation in ethanol-fed rats for 4 weeks raised RA concentration in both liver and plasma, and also raised vitamin A concentration in liver to control levels, partially restored retinyl palmitate concentration (P<0.05) in liver. ATRA 1.5 mg/kg supplementation raised not only RA concentrations in liver and plasma but also retinyl palmitate concentrations in liver. However, the vitamin A concentration in liver of ATRA-supplemented rats (1.5 mg/kg) was higher than that of controls (P<0.05). The histologic observation of liver tissues indicated that ATRA treatment notably alleviated hepatocellular swelling, steatosis, the swelling of mitochondria and proliferation of smooth endoplasmic reticulum (SER). ATRA treatment greatly decreased levels of serum transaminases as compared with the only ethanol-fed group (P<0.05). It was concluded that low-dose ATRA treatment could restore retinoids concentrations and abolish the PRM formation in liver of ALD rats, and then ameliorate the injury of liver cells.

Dalteparin, a low molecular weight heparin, attenuates inflammatory responses and reduces ischemia-reperfusion–induced liver injury in rats*

To examine whether dalteparin, a low molecular weight heparin, prevents hepatic damage by inhibiting leukocyte activation, we analyzed its effect on ischemia/reperfusion (I/R) injury of rat liver in which activated leukocytes play a critical role. Prospective, randomized, controlled study. Research laboratory at a university medical center. Male Wistar rats weighing 220-280 g. Hepatic damage was evaluated by changes in serum transaminase concentrations after I/R. Coagulation abnormalities were evaluated by changes in serum concentrations of fragment E of fibrin and fibrinogen degradation products after I/R. Hepatic tissue blood flow was measured by laser-Doppler flow meter. Hepatic edema was evaluated by determination of the change in the wet/dry tissue weight ratio. Rats were intravenously injected with dalteparin or unfractionated heparin (300 units/kg) and subcutaneously injected with DX9056a, a selective inhibitor of activated factor X (3 mg/kg). To determine whether dalteparin inhibits leukocyte activation, we examined the effect of dalteparin on hepatic concentrations of interleukin-12, tumor necrosis factor-alpha, and hepatic myeloperoxidase activity after I/R in vivo. In addition, we examined increases in tumor necrosis factor-alpha production in rat monocytes and in intracellular calcium concentrations in neutrophils in vitro. We also examined the effect of dalteparin on endothelial production of prostacyclin using isolated rat hepatic sinusoidal cells in vitro. Intravenous administration of dalteparin inhibited increases in serum levels of both transaminases and serum concentrations of fragment E of fibrin and fibrinogen degradation products in animals subjected to hepatic I/R. Hepatic tissue blood flow after reperfusion was increased by dalteparin. Dalteparin inhibited hepatic edema, increases in hepatic tissue levels of interleukin-12 and tumor necrosis factor-alpha, and accumulation of neutrophils in animals subjected to hepatic I/R. Neither DX9065a nor unfractionated heparin showed any therapeutic effects, despite potent inhibition of increases in serum levels of fragment E of fibrin and fibrinogen degradation products. Neither monocytic tumor necrosis factor-alpha production nor neutrophil activation was inhibited by dalteparin in vitro. Dalteparin enhanced the hepatic I/R-induced increases in hepatic tissue levels of 6-keto-prostaglandin (PG) F1alpha, a stable metabolite of prostacyclin, which is capable of inhibiting monocytic tumor necrosis factor-alpha production. Pretreatment with indomethacin completely reversed both of the therapeutic effects of dalteparin, whereas pretreatment with NS-398, a selective inhibitor of cyclooxygenase-2, did not. Dalteparin did not directly increase the endothelial production of prostacyclin in vitro. Dalteparin might reduce I/R-induced liver injury in rats by attenuating inflammatory responses. These therapeutic effects might be independent of its anticoagulant activity but dependent on its capacity to enhance endothelial production of prostacyclin via cyclooxygenase-1 activation. Furthermore, the mechanism or mechanisms by which dalteparin promotes the endothelial production of prostacyclin in vivo might involve unknown factors other than endothelial cells.

Parenteral Nutrition‐Associated Liver Disease in Adult and Pediatric Patients

There are essentially 3 types of hepatobiliary disorders associated with parenteral nutrition (PN) therapy: steatosis, cholestasis, and gallbladder sludge/stones. Reported prevalence rates of PN-associated liver disease (PNALD) vary greatly, and there are distinct differences between adult and pediatric patients. Various etiologic factors have been evaluated for significance in contributing to PNALD, including enteral feeding history, septic events, bacterial overgrowth, length of intestinal resection, and prematurity/low birth weight. Etiologic factors specifically related to the PN formulation or nutrient intake have also been evaluated, including excessive calorie intake, dextrose-to-lipid ratio, amino acid dose, taurine deficiency, IV fat emulsion (IVFE) dose, carnitine deficiency, choline deficiency, and continuous vs cyclic infusion. Minor increases in serum aminotransferase concentrations are relatively common in patients receiving PN therapy and generally require no intervention. The primary indicator of cholestasis is a serum conjugated bilirubin >2 mg/dL. When a patient receiving PN develops liver complications, it is necessary to rule out all treatable causes and minimize other risk factors. All potential hepatotoxic medications and herbal supplements should be eliminated. Modifications to the PN regimen that may be helpful include reduction of calories, reduction of IVFE dose to <1 g/kg/d, supplementation of taurine in the infant, and use of cyclic infusion. Initiation of even small amounts of enteral nutrition and use of ursodiol may be beneficial in stimulating bile flow. In the long-term PN patient with severe and progressive liver disease, intestinal or liver transplantation may be the only remaining treatment option.

Chronic Hepatitis B: A Critical Appraisal of Current Approaches to Therapy

Treatment of chronic hepatitis B (CHB) involves a number of complex and controversial issues. Expert opinions may differ from those of practicing hepatologists and gastroenterologists. We aimed to explore this issue further after a critical review of the literature. A panel of 14 international experts graded the strength of evidence for 16 statements addressing 3 content areas: patient selection, therapeutic end points, and treatment options. Available data relating to the statements were reviewed critically in 3 small work groups. After discussion of each statement with the entire panel, the experts voted anonymously to accept or reject statements based on the strength of evidence and their experience. A total of 241 members of the American Association for the Study of Liver Diseases (AASLD) responded to the same statements and their responses were compared with those of the experts. A discordant response was defined as a difference of more than 20% in any of the 5 graded levels of response (accept or reject) between the 2 groups. With the exception of 2 statements, the experts' responses were relatively uniform. However, the responses of the AASLD members were discordant from the experts in 12 statements, spanning all 3 content areas. Several areas of disagreement on the management of CHB exist between experts and AASLD members. Our results indicate a potential knowledge gap among practicing hepatologists. Better educational efforts are needed to meet the challenge of managing this complex disorder in which even expert opinion occasionally may disagree.

Exaggerated Liver Injury Induced by Ischemia–Reperfusion in Spontaneously Hypertensive Rats

The functions of polymorphonuclear leukocytes (PMNs), which play a critical role in organ damage, are primed in patients with essential hypertension and spontaneously hypertensive rats (SHR). Hepatic ischemia-reperfusion (I/R) injury is shown to be caused and aggravated by the PMNs. We examined whether the hepatic I/R injury was exaggerated in SHR. The portal vein and artery were partially occluded for 60 min. Blood samples were obtained to determine the degree of liver damage during 48 h after reperfusion. The increase in serum transaminase concentration and hepatic myeloperoxidase content, which reflects the number of PMNs in liver tissue, in SHR were significantly greater than those of their control rats, Wistar-Kyoto rat (WKY). However, the elevations in hepatic transaminases induced by I/R did not differ between other hypertensive animal models (N-nitro-L-arginine methyl ester [L-NAME]-treated and deoxycorticosterone acetate [DOCA]/salt-treated rats) and their controls. These results suggest that the elevated PMNs, but not high blood pressure per se, contributes to the exaggerated hepatic I/R injury in SHR.

Ambrisentan Therapy for Pulmonary Arterial Hypertension

The purpose of this study was to examine the efficacy and safety of four doses of ambrisentan, an oral endothelin type A receptor-selective antagonist, in patients with pulmonary arterial hypertension (PAH). Pulmonary arterial hypertension is a life-threatening and progressive disease with limited treatment options. Endothelin is a vasoconstrictor and smooth muscle cell mitogen that plays a critical role in the pathogenesis and progression of PAH. In this double-blind, dose-ranging study, 64 patients with idiopathic PAH or PAH associated with collagen vascular disease, anorexigen use, or human immunodeficiency virus infection were randomized to receive 1, 2.5, 5, or 10 mg of ambrisentan once daily for 12 weeks followed by 12 weeks of open-label ambrisentan. The primary end point was an improvement from baseline in 6-min walk distance (6MWD); secondary end points included Borg dyspnea index, World Health Organization (WHO) functional class, a subject global assessment, and cardiopulmonary hemodynamics. At 12 weeks, ambrisentan increased 6MWD (+36.1 m, p < 0.0001) with similar and statistically significant increases for each dose group (range, +33.9 to +38.1 m). Improvements were also observed in Borg dyspnea index, WHO functional class, subject global assessment, mean pulmonary arterial pressure (-5.2 mm Hg, p < 0.0001), and cardiac index (+0.33 l/min/m2, p < 0.0008). Adverse events were mild and unrelated to dose, including the incidence of elevated serum aminotransferase concentrations >3 times the upper limit of normal (3.1%). Ambrisentan appears to improve exercise capacity, symptoms, and hemodynamics in patients with PAH. The incidence and severity of liver enzyme abnormalities appear to be low.

P38 mitogen-activated protein kinase inhibition attenuates burn-induced liver injury in rats

This study was made to evaluate the effect of SB203580, a specific p38 MAP kinase inhibitor, on burn-induced hepatic injury as well as the activation of nuclear factor (NF)-κB in severely burned rats. Sprague–Dawley rats were divided into three groups: (1) sham group, rats underwent sham burn; (2) burn group, rats given third-degree burns over 30% total body surface area (TBSA) and treated with vehicle plus lactated Ringer solution for resuscitation 4 ml/(kg % TBSA); and (3) burn plus SB203580 group, rats given burn injury and fluid resuscitation plus SB203580 (10 mg/kg i.v., 15 min and 12 h after burn). Hepatocellular injury (measured by serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT)) and hepatocellular function (determined by the indocyanine green dye retention rate (ICG R15)) were assessed at 24 h post-burn. Liver histologic changes were also analyzed. Burn trauma resulted in increased serum aminotransferases concentrations, decreased ICG R15, elevated serum tumor necrosis factor (TNF)-α and interleukin (IL)-1β levels and hepatic TNF-α and IL-1β mRNA expressions, and worsen histologic condition. The level of Nuclear Factor (κ) inhibitor (IκBα) in liver was decreased and DNA-binding activity of Nuclear Factor-κB (NF-κB) was increased after thermal injury. p38 MAP kinase was more significantly activated in liver harvested from burn rats than from shams. SB203580 inhibited the activation of p38 MAP kinase, reduced the levels of TNF-α and IL-1β, and prevented burn-mediated liver injury. Both the IκBα level and NF-κB activity in the liver following burns was not affected by administration with SB203580. These findings suggest that (1) p38 MAP kinase activation is one important aspect of the signaling event that may mediate the release of TNF-α and IL-1β and contributes to burn-induced liver injury and (2) p38 MAP kinase does not influence the activation of NF-κB directly in the liver of severely burned rats.

Specific type IV phosphodiesterase inhibitor ameliorates thioacetamide‐induced liver injury in rats

Rolipram is a specific type IV phosphodiesterase inhibitor that suppresses the activity of immune cells and the production of pro-inflammatory cytokines. In this study, we assessed the effect of rolipram on acute liver injury using thioacetamide (TAA)-induced liver injury in rats as a model. Rats were treated with rolipram (0.5-5 mg/kg, intraperitoneally) or vehicle and injected 30 min later with TAA (100 mg/kg, subcutaneously). Serum transaminase concentrations and tumor necrosis factor-alpha (TNF-alpha), interleukin 1beta (IL-1beta) and growth related oncogene/cytokine-induced neutrophil chemoattractant-1 (GRO/CINC-1) levels were measured and livers were examined for microscopic changes. Dose-dependent protection against TAA liver injury was based on transaminase levels and inflammatory cytokine production, and was measured 9 h after TAA when the peak release of cytokines occurred. Rolipram suppressed liver injury based on serum aspartate transaminase (AST), alanine transaminase (ALT) and histology and reduced TNF-alpha, IL-1beta and GRO/CINC-1 levels. Rolipram, at doses of 0.5-5 mg/kg, suppressed serum transaminase and TNF-alpha production in a dose-dependent manner, and these effects were significant at doses of 2.5 and 5 mg/kg. In our rodent model of acute liver injury, rolipram clearly reduced liver damage and inhibited pro-inflammatory cytokine production. These results suggest that specific type IV phosphodiesterase inhibitors, such as rolipram, have potent hepatoprotective effects that are associated with suppressing inflammatory cytokine production.

The G20210A Prothrombin Gene Mutation and the Plasminogen Activator Inhibitor (PAI) 844GG Genotype Increase the Risk of Premature Onset of Severe Preeclampsia.

Obstetrical complications such as severe preeclampsia and HELLP syndrome are associated with abnormal placental vasculature and inadequate placental maternal-fetal circulation. Hereditary risk determinants of venous thrombosis have been reported to be associated with these obstetrical complications.The magnitude of the association between thrombophilia and the obstetrical complications varies in the published studies, according to type of obstetrical complication and type of thrombophilia. No data exist so far whether these risk determinants are related to premature onset of severe preeclampsia.We used a case-control design in 99 women with severe preeclampsia (blood pressure higher than 160/100 mm Hg; urinary protein excretion greater than 5 g per day, platelet count of less than 100.000/μl; combination of hemolysis, high serum aminotransferase concentration, and platelet count below 100.000/μl; or eclampsia) in previous pregnancies and 277 normal women to assess hereditary risk factors of venous thrombosis as risk determinants for severe preeclampsia. Moreover, a case-only design was used to assess these risk factors as risk determinants for premature severe preeclampsia. We determined the genetic risk markers factor V Leiden G1691A (FVL), the G20210A prothrombin gene mutation, the methylenetetrahydrofolate reductase polymorphism (MTHFR C677T), and the PAI A844G polymorphism. None of the women had a combined or homozygous defect of the FVL or the G20210A prothrombin gene mutation. Women with antiphospholipid syndrome were excluded. None of the women had a deficiency of antithrombin, protein C, or protein S.Using the case-control design, there was no significant risk association of the hereditary risk factors with severe preeclampsia (FVL p=0.680, prothrombin mutation p=0.479, MTHFR 677TT genotype p=0.565, PAI 844GG genotype p=0.641). In the case-only design, the onset of severe preeclampsia was significantly earlier in women with the G20210A prothrombin gene mutation (24.5 weeks vs. 30.5 weeks, p=0.04) and in women with the PAI 844GG genotype (27.2 weeks vs. 30.7, p=0.025). No such significant difference was observed in carriers of the FVL or the MTHFR 677TT genotype. Hereditary risk factors for venous thrombosis are not risk determinants for severe preeclampsia. However, women who are carriers of the G20210A prothrombin gene mutation and the PAI 844GG genotype are at risk for premature onset of severe preeclampsia. Based on our results it appears that these risk factors do not induce the pathomechanism but modulate the course of preeclampsia.

Is mortality from liver disease associated with normal serum aminotransferase concentrations?

Is mortality from liver disease associated with normal serum aminotransferase concentrations?

Acute acetaminophen intoxication in Taiwan: outcomes and risk factors.

There is a paucity of information about acetaminophen intoxication from Taiwan. This study investigated the outcome and risk factors for acetaminophen-induced hepatotoxicity and validated the Rumack- Matthew nomogram in Taiwanese patients with acute acetaminophen intoxication. A total of 75 patients with acetaminophen intoxication admitted through the emergency department were included in this retrospective analysis. Patients with a serum acetaminophen concentration above the possible risk line on the nomogram were treated with oral N-acetylcysteine. The primary outcome measure was the development of major hepatotoxicity, which was defined as a serum aminotransferase concentration greater than 1000 IU/L. Patient outcomes in the possible risk group and probable risk group were plotted on the modified Rumack-Matthew nomogram for validation. The risk factors for acetaminophen-induced hepatotoxicity were identified by multiple logistic regression analysis. No hepatotoxicity developed in patients with an initial acetaminophen concentration below the possible risk line on the nomogram. One out of 8 patients in the possible risk group developed major hepatotoxicity; 8 out of 22 patients in the probable risk group developed major hepatotoxicity, representing an incidence of 12.5% and 36.4%, respectively. Patients in the major hepatotoxicity group were older (32.5 vs 24.2 years, p = 0.019), and had a longer time to presentation (28.1 vs 6.7 hours, p < 0.01) than those in the non/minor hepatotoxicity group. Multiple logistic regression revealed that age and time to presentation were independent risk factors for hepatotoxicity (p = 0.033 and p = 0.002, respectively). The results of outcome analysis confirm that the modified Rumack-Matthew nomogram has a high sensitivity for identifying Taiwanese patients at risk for acetaminophen-induced hepatoxicity. Patient age and time to presentation were independent risk factors for acetaminophen-induced hepatotoxicity.

IS RECURRENT CHRONIC HEPATITIS C VIRUS LIVER DISEASE AFTER ORTHOTOPIC LIVER TRANSPLANTATION INEVITABLE?

Purpose: Chronic hepatitis C virus (HCV) liver disease is the commonest indication for orthotopic liver transplantation (OLT) in the USA. Important recurrent chronic liver disease is very common, but there appears to be a small number of patients who do not exhibit evidence of recurrent HCV liver disease, in some cases years after OLT. We hypothesized that certain clinico-epidemiologic factors might play a role in this phenomenon, and performed a case-control study to try and identify those factors important in the development of recurrent HCV liver disease. Methods: We identified all patients who underwent OLT for chronic HCV liver disease at our institution between 1/1991 and 5/2004, including those whose serum aminotransferase concentrations remained normal in follow-up. Control subjects transplanted during the same year for HCV liver disease were matched to cases. Specific variables were evaluated: age, gender, race, viral genotype, primary calcineurin inhibitor (PCI), anti-viral therapy, graft survival, and death. Results: 117 patients underwent OLT for chronic HCV liver disease during the study period. Seven white subjects with no evidence of recurrent HCV liver disease were identified. All were white, six were male, their median OLT age was 46 years (range 44–59), and median follow-up was 64 months. Four were infected with genotype 1, one with genotype 3, and the genotype was not known in two subjects. PCI therapy comprised CyA (5), and tacrolimus (2). One patient died nine years after OLT, of a non-liver related illness. 28 control patients were identified (matched 4:1 with cases, by year of OLT), of whom 23 were white, four were black and one was Asian; seven were women. Their median OLT age was 46 years (range 16–65). Viral genotypes were as follows: 1 (seventeen); 2 (three); 3 (two); 4 (one), and five were unknown. PCI comprised CyA (17), and tacrolimus (11). All controls demonstrated histologic evidence of recurrent chronic HCV liver disease a median of 10 months (range 1–95) post OLT. 18 received anti-viral therapy, resulting in four SVRs. Four patients died; two underwent re-OLT for recurrent HCV liver disease. Conclusions: Subjects without evidence of recurrent chronic HCV liver disease had better graft function, and overall survival than those with evidence of recurrent HCV liver disease. However, there were no clinical features that distinguished between the two patient groups. More study is required to understand why a small subgroup of patients fails to develop recurrent chronic HCV liver disease after OLT.

Clinical and biochemical manifestations of syndrome X in obese children.

The aim of this study was to investigate whether the clinical and metabolic characteristics of syndrome X had their onset in childhood in otherwise healthy but obese children of Greek origin. A group of 25 obese children and 18 age- and sex matched control subjects, aged 6-14 years, underwent an oral glucose tolerance test (OGTT), assessed for determination of plasma glucose and insulin levels. Insulin sensitivity and insulin resistance were estimated by mathematical models using calculations obtained during the OGTT. Body mass index (BMI) and blood pressure were measured, as well as serum lipoprotein and aminotransferase concentrations, after an overnight fast. The obese children had significantly higher blood pressure (systolic and diastolic) (P<0.001), triglycerides, lipoprotein(a) and alanine aminotransferase levels (P<0.05) and significantly lower HDL-cholesterol and apolipoprotein A-1 values (P<0.001). Plasma glucose levels during the OGTT were similar in both obese children and control subjects, while plasma insulin levels were significantly higher in obese children (P<0.01). In mathematical models, mean values of insulin sensitivity predictors: metabolic clearance rate and insulin sensitivity index were significantly lower in obese children (P<0.001). Predictors of beta-cell function: insulin resistance index and insulin release index were significantly higher in obese children (P<0.001). Childhood adiposity was associated with all traditional components of syndrome X. The early recognition of these factors as predisposing elements of the appearance of metabolic syndrome requires the development of strategies to manage excess weight gain during childhood, with the ultimate goal being the prevention of type 2 diabetes and cardiovascular disease in adulthood.

Normal serum aminotransferase concentration and risk of mortality from liver diseases: prospective cohort study

Objective To examine the relation between the normal range of serum aminotransferase concentration and mortality from liver disease.Design Prospective cohort study.Setting Korea Medical Insurance Corporation study with eight years' follow...

Reduced urinary 6β-hydroxycortisol to cortisol ratios in patients with liver cirrhosis

While the urinary concentration ratio of 6β-hydroxycortisol (6β-HC) to cortisol (C) in 24-h urine samples is an established parameter for the induction of hepatic cytochrome P450 (CYP) 3A activity, it remains unclear whether it would be reduced in association with chronic liver damages. To clarify this issue we measured this parameter in 12 patients with chronic hepatitis, 15 patients with liver cirrhosis and 12 healthy subjects. Urinary 6β-HC and C were assayed with high-performance liquid chromatography with ultraviolet absorption. Multiple regression analysis was performed to search for which biochemical or demographic parameter(s) would be associated with the overall variability of urinary 6β-HC/C ratios. Results showed that the mean (±S.D.) 6β-HC/C ratio obtained from the patients with liver cirrhosis (4.3±2.6), but not that from patients with chronic hepatitis (7.4±7.2), was significantly ( P<0.05) lower than that obtained from the healthy controls (11.8±8.3). It was also revealed that among the clinical parameters examined (e.g. serum transaminases concentrations) only serum albumin concentrations were correlated significantly ( R=0.61, P<0.05) with the urinary 6β-HC/C ratio. In conclusion, the present study implies that that the reduced urinary 6β-HC/C ratios in patients with liver cirrhosis may be associated with attenuated hepatic CYP3A activity in these patients.