Markers Of Hepatic Dysfunction Research Articles

Significance of End-Diastolic Forward Flow in Patients With Repaired Tetralogy of Fallot - Its Interaction With the Left Ventricular Property and End Organ Damage.

Although right ventricular (RV) enlargement may affect RV diastolic dysfunction assessed by end-diastolic forward flow (EDFF) in patients with repaired tetralogy of Fallot (TOF), EDFF may also be modified by left ventricular (LV) hemodynamics. We hypothesized that EDFF is affected by LV hemodynamics, not limited to RV diastolic stiffening.Methods and Results: Among 145 consecutive patients with repaired TOF who underwent catheterization, hemodynamic properties in 47 with consistent EDFF and 75 without EDFF were analyzed. Compared with patients without EDFF, those with EDFF had a large RV volume with a high regurgitant fraction. Although cardiac index and central venous pressure (CVP) were similar, contrast injection augmented CVP and LV end-diastolic pressure (EDP) in patients with vs. those without EDFF, suggesting compromised diastolic reserve. In patients with EDFF, the velocity-time integral (VTI) of EDFF was positively correlated with LVEDP and systemic vascular resistance, in addition to RV EDP. EDFF-VTI was correlated with hepatic venous wedge pressure and markers of hepatic dysfunction. Subanalysis of the older (≥6 years) half of the study cohort revealed that EDFF was associated with bi-atrial enlargement independent of RV volume, highlighting the pronounced role of EDFF on the diastolic property in the aged cohort. EDFF-VTI in patients with repaired TOF reflects RV diastolic dysfunction, affected by the left heart system. EDFF-VTI indicates blood stagnation, which may be attributed to end-organ damage.

Cross-sectional assessment of haemostatic profile and hepatic dysfunction in Fontan patients

BackgroundFontan-associated liver disease is accompanied by a hypercoagulable state. While hepatic dysfunction in Fontan patients is common, its relationship with haemostatic changes and clinical outcomes in this patient population remains...

Coenzyme Q10 deficiency in patients with hereditary hemochromatosis

AimHereditary hemochromatosis (HH) is a group of inherited disorders that causes a slow and progressive iron deposition in diverse organs, particularly in the liver. Iron overload induces oxidative stress and tissue damage. Coenzyme Q10 (CoQ10) is a cofactor in the electron-transport chain of the mitochondria, but it is also a potent endogenous antioxidant. CoQ10 interest has recently grown since various studies show that CoQ10 supplementation may provide protective and safe benefits in mitochondrial diseases and oxidative stress disorders. In the present study we sought to determine CoQ10 plasma level in patients recently diagnosed with HH and to correlate it with biochemical, genetic, and histological features of the disease. Methods: Plasma levels of CoQ10, iron, ferritin, transferrin and vitamins (A, C and E), liver tests (transaminases, alkaline phosphatase and bilirubin), and histology, as well as three HFE gene mutations (H63D, S654C and C282Y), were assessed in thirty-eight patients (32 males, 6 females) newly diagnosed with HH without treatment and in twenty-five age-matched normolipidemic healthy subjects with no HFE gene mutations (22 males, 3 females) and without clinical or biochemical signs of iron overload or liver diseases. ResultsPatients with HH showed a significant decrease in CoQ10 levels respect to control subjects (0.31 ± 0.03 µM vs 0.70 ± 0.06 µM, p < 0.001, respectively) independently of the genetic mutation, cirrhosis, transferrin saturation, ferritin level or markers of hepatic dysfunction. Although a decreasing trend in CoQ10 levels was observed in patients with elevated iron levels, no correlation was found between both parameters in patients with HH. Vitamins C and A levels showed no changes in HH patients. Vitamin E was significantly decreased in HH patients (21.1 ± 1.3 µM vs 29.9 ± 2.5 µM, p < 0.001, respectively), but no correlation was observed with CoQ10 levels. Conclusion: The decrease in CoQ10 levels found in HH patients suggests that CoQ10 supplementation could be a safe intervention strategy complementary to the traditional therapy to ameliorate oxidative stress and further tissue damage induced by iron overload.

Predictive value of elevated alanine aminotransferase for in-hospital mortality in patients with acute myocardial infarction

Background and aimsLiver enzymes, including alanine aminotransferase (ALT) and aspartate aminotransferase (AST), are markers of hepatic dysfunction and fatty liver disease. Although ALT and AST have been suggested as risk factors for cardiovascular disease, their role as predictors of mortality after acute myocardial infarction (AMI) has not been established. The objective of this study was to investigate the predictive value of ALT and AST for mortality in patients with AMI.MethodsWe analyzed records of 712 patients with AMI and no known liver disease treated at the Department of Cardiovascular Center in the First Hospital of Jilin University. The primary outcome was all-cause in-hospital mortality. Relationships between primary outcome and various risk factors, including serum transaminase levels, were assessed using multivariate logistic regression analysis.ResultsAge (P < 0.001), hypertension (P = 0.034), prior myocardial infarction (P < 0.001), AST (P < 0.001), ALT (P < 0.001), creatinine (P = 0.007), blood urea nitrogen (P = 0.006), and troponin I (P < 0.001) differed significantly between ST-segment elevation myocardial infarction (STEMI) and non-STEMI. The following factors were associated with an increased risk of in-hospital all-cause mortality in patients with AMI: ALT ≥ 2ULN (adjusted odds ratio [AOR] 2.240 [95% confidence interval (CI), 1.331–3.771]; P = 0.002); age ≥ 65 year (AOR 4.320 [95% CI 2.687–6.947]; P < 0.001); increased fasting plasma glucose (FPG) (AOR 2.319 [95% CI 1.564–3.438]; P < 0.001); elevated D-dimer (AOR 2.117 [95% CI 1.407–3.184]; P < 0.001); elevated fibrinogen (AOR 1.601 [95% CI 1.077–2.380]; P = 0.20); and reduced estimated glomerular filtration rate (eGFR) (AOR 2.279 [95% CI 1.519–3.419]; P < 0.001).ConclusionsOur findings demonstrated that elevated ALT was independently associated with increased in-hospital all-cause mortality in patients with AMI. Other risk factors were increased age, FPG, D-dimer, and fibrinogen and decreased eGFR.

Secretion of heat shock ‐60, ‐70 kD protein, IL‐1β and TNFα levels in serum of a term normal pregnancy and patients with pre‐eclampsia development

The extracellular heat shock proteins (eHsp) family act as molecular chaperones regulating folding, transporting protein and are associated with immune modulation in different physiological and pathological processes. They have been localized in different gestational tissues and their concentration in amniotic fluid and serum has been determined. In the present study, we proposed to determine the concentration of eHsp‐60, ‐70, IL‐1β and TNFα in the serum of pregnant patients with 34 weeks of gestation with and without clinical evidences of preeclampsia (PE). Our results indicate significant increase of these markers in patients with PE with respect to healthy pregnant patients without active labor. Finally, the concentration of eHsp‐60 and ‐70 correlated positively with the hepatic dysfunction markers uric acid, lactate dehydrogenase (LDH), glutamic oxaloacetic transaminase (GOT) glutamic pyruvic transaminase (GPT), and inflammatory IL‐1β and TNFα response. In conclusion, our results demonstrate a strong associated between Hsp and marker of hepatic dysfunction.

Bilirubin in the early course of venovenous extracorporeal membrane oxygenation support for refractory ARDS.

Bilirubin is known as a marker of hepatic dysfunction and is incorporated in scoring algorithms to assess prognosis in critically ill patients. No data are so far available on the prognostic role of hepatic dysfunction in patients with severe ARDS on venovenous extracorporeal membrane oxygenation (VV-ECMO) support. In 112 consecutive patients with severe ARDS treated with VV-ECMO, we aimed at assessing whether increased bilirubin during the first 72h could affect early death. Increased serum bilirubin (≥1.2mg/dl) was detectable in 29 patients (25.9%) who were older (p=0.031), exhibited a higher SOFA score (p=0.006), were more frequently given pre-ECMO muscular blockers (p=0.001) and supported with ECMO for a longer period (p=0.024), when compared to patients with normal bilirubin. No difference in in-ICU mortality rate was observed between the two subgroups. In survivors, bilirubin showed a progressive and significant decrease (p=0.032) during the first 72h of ECMO support, while it increased in dead patients (p=0.007).The mortality rate was higher in patients with increased bilirubin at 24, 48 and 72h after ECMO start in respect to that of patients with normal values. Pre-ECMO increased bilirubin values (≥1.2mg/dl), being detectable in about one-fourth of the entire population, is not associated with increased in-ICU mortality, while the persistence of increased bilirubin values after 24h of ECMO start and within the first 3days identified a subgroup of patients at higher risk of death.

Antifibrotic effect of heparin on liver fibrosis model in rats

To evaluate the effect of chronic thrombin inhibition by heparin on experimentally induced chronic liver injury (liver fibrosis) in rats. Chronic liver injury (liver fibrosis) was induced in Wistar rats by oral administration of carbon tetrachloride (CCl4) for 7 wk, an animal model with persistent severe hepatic fibrosis. Intravenous administration of the thrombin antagonist (heparin) started 1 wk after the start of CCl4 intoxication for 6 wk. After completion of treatment (7 wk), markers of hepatic dysfunction were measured and changes evaluated histopathologically. Higher serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), alkaline phosphatase (ALP), total, direct and indirect bilirubin levels, as well as lower fibrinogen levels, were found in CCl4 intoxicated rats. Heparin, silymarin and combination of drug (heparin and silymarin) treatment for 6 wk prevented a rise in SGOT, SGPT, ALP, total, direct and indirect bilirubin levels and improved fibrinogen levels. Deterioration in hepatic function determined by the fibrosis area was retarded, as evident from hepatic histopathology. Total protein levels were not changed in all groups. Heparin, a thrombin antagonist, preserved hepatic function and reduced severity of hepatic dysfunction/fibrogenesis. Combination of heparin and silymarin produced additional benefits on liver fibrosis.

Association between &amp;gamma;-Glutamyltransferase, Adiponectin and Arterial Stiffness

Serum γ-glutamyltransferase (GGT) is used as a marker of hepatic dysfunction. Recently, several studies reported that GGT is significantly associated with cardiovascular mortality and atherosclerosis. Adiponectin is known to play an important role in the development of atherosclerosis, but its physiologic role has yet to be fully determined. In this study, we investigated the relationships among serum GGT, adiponectin and arterial stiffness. Of 4236 subjects recruited from 17 different medical centers in Seoul, Korea, 2846 subjects were enrolled in our study. The parameters of metabolic syndrome (MetS) were assessed in these subjects, and their plasma adiponectin levels and pulse wave velocity (PWV) were measured along with anthropometric and biochemical profiles, including GGT. The subjects were stratified into 3 groups according to GGT values. PWV values gradually increased and the adiponectin level decreased with GGT tertiles. Aortic PWV showed a significant correlation with age, SBP, FPG, but there was no correlation among aortic PWV, GGT and adiponectin. Peripheral PWV demonstrated a significant correlation with age, SBP, DBP, BMI, WC, FPG and GGT, but there was no correlation between peripheral PWV and adiponectin. In multiple logistic regression analysis after adjusting for risk factors, GGT was a significant contributor to increased peripheral PWV. These findings indicate that serum GGT is independently associated with increased arterial stiffness, but there was no correlation between adiponectin and arterial stiffness in both males and females.

Placental Growth Factor Is Elevated in Patients with Sickle Cell Disease and Associated with Pulmonary Hypertension, Hemolysis, Inflammation, Iron Overload, and Hepatic Dysfunction.

Abstract 1531Poster Board I-554Placental Growth Factor (PlGF) is a functional cytokine in the vascular endothelial growth factor (VEGF) family that generally promotes angiogenesis, depending on the specific context, and can also promote atherogenesis. Produced in erythroid cells, its level in patients with sickle cell disease (SCD) has been previously related to the rate of erythropoiesis. We evaluated PlGF plasma levels in SCD patients by ELISA, and related it to biomarkers of pulmonary hypertension (PH), an emerging and serious complication of SCD linked to early mortality. We find that PlGF levels are significantly higher in SCD (n=95) than healthy African American control subjects (n=19) (median 16.6 vs. 2.1 pg/mL, p<0.001). PlGF levels were higher in SCD patients with elevated pulmonary pressure (normal pulmonary pressure vs. mildly elevated vs. highly elevated: medians 13.7 vs. 16.7 vs. 19.8 pg/mL, p<0.0001). Supporting a linkage to rate of hemolysis, PlGF correlated with LDH (p=0.001) and inversely with hemoglobin level (p<0.0001). Suggesting a link to inflammation, PlGF correlated significantly with C-reactive protein (p=0.001) and erythrocyte sedimentation rate (p<0.001). PlGF correlated with markers of iron overload, including ferritin, transferrin saturation and inversely with transferrin (all p<0.001). Finally, PlGF correlated with markers of hepatic dysfunction, including low albumin and high direct bilirubin (p<0.001).We found significantly higher PlGF levels in SCD patients taking hydroxyurea compared to those not taking it (median 17.4 vs. 14.0 pg/ml, p<0.01). Confirming that hydroxyurea increases PlGF levels, in a separate cohort of seven patients, PlGF levels rose significantly from their baseline values after initiating hydroxyurea (median approx 22 vs. 27, p<0.05). Our data suggest that elevated PlGF level is associated with PH in patients with SCD, and PlGF is correlated with severity of hemolysis, inflammation, iron overload and hepatic dysfunction. Considering the variable evidence in the literature for either stimulating or inhibiting angiogenesis, it is not clear whether pathologic elevation of PlGF may be mediating pulmonary hypertension, or perhaps conversely providing an adaptive response to vascular damage. It has been suggested by Perelman et al. that PlGF may mediate leukocyte activation that might promote disease severity in SCD. However, hydroxyurea, which tends to ameliorate SCD complications, stimulates PlGF level in an unexpected manner, possibly related to the ability of hydroxyurea to stimulate erythropoietin production, which might in turn induce PlGF. Further research is needed to reconcile the role of PlGF in PH in SCD. DisclosuresTailor:Mesoscale: Employment.

Perioperative indocyanine green clearance is predictive for prolonged intensive care unit stay after coronary artery bypass grafting - an observational study

IntroductionDuring cardiac surgery with cardiopulmonary bypass (CPB) haemodilution occurs. Hepatic dysfunction after CPB is a rare, but serious, complication. Clinical data have validated the plasma-disappearance rate of indocyanine green (PDR ICG) as a marker of hepatic function and perfusion. Primary objective of this analysis was to investigate the impact of haemodilutional anaemia on hepatic function and perfusion by the time course of PDR ICG and liver enzymes in elective CABG surgery. Secondary objective was to define predictors of prolonged ICU treatment like decreased PDR ICG after surgery.Methods60 Patients were subjected to normothermic CPB with predefined levels of haemodilution anaemia (haemotacrit (Hct) of 25% versus 20% during CPB). Hepatic function and perfusion was assessed by PDR ICG, plasma levels of aspartate aminotransferase (ASAT) and α-GST. Prolonged ICU treatment was defined as treatment ≥ 48 hours.ResultsLogistic regression analysis showed that all postoperative measurements of PDR ICG (P < 0.01), and the late postoperative ASAT (P < 0.01) measurement were independent risk factors for prolonged ICU treatment. The predictive capacity for prolonged ICU treatment was best of the PDR ICG one hour after admission to the ICU. Furthermore, the time course of PDR ICG as well as ASAT and α-GST did not differ between groups of haemodilutional anaemia.ConclusionsOur study provides evidence that impaired PDR ICG as a marker of hepatic dysfunction and hypoperfusion may be a valid marker of prolonged ICU treatment. Additionally this study provides evidence that haemodilutional anaemia to a Hct of 20% does not impair hepatic function and perfusion.Trial registration[ISRCTN35655335]

Hepatotoxicity of fast food?

In the dictionary, fast food is defined as any food which may be cooked easily, and is sold by restaurants to be eaten quickly or taken away. Changes in the...

Serum biotinidase is a sensitive and specific biochemical marker of hepatic dysfunction: A preliminary report

Biotinidase is an enzyme synthesized predominantly by the liver. Serum activity of this enzyme has been shown to be low in chronic liver disease. In this study, we endeavored to assess the diagnostic value of serum biotinidase as a marker of hepatic biosynthetic function in acute and chronic liver dysfunction. Twenty-three patients with acute liver disease and 46 with chronic liver disease, as diagnosed by clinical examination, laboratory tests, histopathology and tests for viral markers, were inducted into the study. Forty-six healthy volunteers were selected as controls. Serum biotinidase activity was estimated in all the subjects. Biotinidase activity was found to be significantly lower in the serum of patients with acute (4.59 +/- 1.26 IU/L vs 7.56 +/- 0.82 IU/L in controls; P</= 0.001) and chronic (2.98 +/- 1.18 IU/L vs 7.56 +/- 0.82 IU/L in controls; P</= 0.001) liver disease. Using receiver-operator characteristic curves, serum biotinidase was found to have high values of sensitivity and specificity when applied as a diagnostic test in both acute and chronic liver disease. These results suggest that serum biotinidase may be a sensitive and specific diagnostic marker of hepatic biosynthetic function in both acute and chronic liver disease.

Nonalcoholic fatty liver disease in patients with type 2 diabetes

Background & Aims: Nonalcoholic fatty liver disease (NAFLD) is reported commonly in patients with type 2 diabetes mellitus (DM), which has been suggested as a risk factor for the progressive form of NAFLD, or nonalcoholic steatohepatitis. The aim of this study was to assess the outcome of patients with NAFLD and DM. Methods: A cohort of patients with NAFLD was identified, and patients with other causes of liver disease (alcohol, medication, etc.) were excluded. Clinical, pathological, and mortality data were available for this cohort. Patients were categorized and compared according to the presence or absence of DM. Results: Of 132 patients with NAFLD, 44 patients (33%) had an established diagnosis of DM. Patients with DM were older and had greater serum glucose and triglyceride levels and a greater aspartate aminotransferase-alanine aminotransferase ratio. Liver biopsy specimens from patients with DM showed more vacuolated nuclei and acidophilic bodies. Cirrhosis (histological or clinical) occurred in 25% of patients with DM (11 of 44 patients) and NAFLD compared with only 10.2% (9 of 88 patients) of patients without DM with NAFLD ( P = 0.04). After adjusting for potential confounders (age, body mass index, and the presence of cirrhosis), both overall mortality (risk ratio [RR], 3.30; 95% confidence interval [CI], 1.76–6.18; P = 0.002) and mortality related to liver disease (RR, 22.83; 95% CI, 2.97–175.03; P = 0.003) were greater in diabetic patients with NAFLD. Markers of hepatic dysfunction (low albumin level, high total bilirubin level, and prolonged prothrombin time) were the only independent predictors of increased mortality. Conclusions: Patients with NAFLD and DM are at risk for the development of an aggressive outcome, such as cirrhosis and mortality. This study supports the potential role of insulin resistance in the development of poor clinical outcomes in patients with NAFLD.

Hyaluronan turnover in relation to infection and sepsis.

Sepsis is a major clinical problem in intensive care. The mortality in septic shock is high, and predominantly due to cardiovascular collapse and multiple organ dysfunction. In sepsis high levels of circulating hyaluronan have been found, correlating to disease severity and prognosis. The reason behind the increased levels could be both decreased hepatic uptake and increased peripheral synthesis. Thus, plasma hyaluronan may be a clinically useful marker of hepatic dysfunction and possibly also an indicator of the increased inflammatory and reparative activity in different organs in septic conditions.

A Subacute Rabbit Model for Hepatobiliary Dysfunction During Total Parenteral Nutrition

Total parenteral nutrition (TPN) in children is associated with the complicating syndromes of cholestasis and cholelithiasis. The causes of these syndromes are not completely clear. Gastrointestinal hypomotility associated with enteral fasting may be involved in the pathogenesis of both syndromes. We compared weanling rabbits maintained solely on TPN with chow pair‐fed and free‐fed controls over a 10‐day period. Gastrointestinal transit time, assessed with a solid marker technique, was significantly greater in the TPN‐treated animals. No difference in intestinal or biliary bacterial flora was demonstrated by aerobic or anaerobic cultures. Gallbladder bile contained a higher percentage of lithocholic acid, unconjugated bilirubin, and total calcium in the TPN‐treated animals. Markers of hepatic dysfunction were elevated in the serum of the TPN‐treated animals. Mild steatosis and edema were the only histologic differences in the livers of the TPN‐treated animals. We conclude that gastrointestinal hypomotility associated with enteral fasting plays a role in the pathophysiologic changes leading to TPN‐associated hepatobiliary dysfunction. This dysfunction may be mediated by an increase in the absolute and relative concentrations of lithocholic acid in the bile of TPN‐treated animals.

A Subacute Rabbit Model for Hepatobiliary Dysfunction During Total Parenteral Nutrition

Total parenteral nutrition (TPN) in children is associated with the complicating syndromes of cholestasis and cholelithiasis. The causes of these syndromes are not completely clear. Gastrointestinal hypomotility associated with enteral fasting may be involved in the pathogenesis of both syndromes. We compared weanling rabbits maintained solely on TPN with chow pair-fed and free-fed controls over a 10-day period. Gastrointestinal transit time, assessed with a solid marker technique, was significantly greater in the TPN-treated animals. No difference in intestinal or biliary bacterial flora was demonstrated by aerobic or anaerobic cultures. Gallbladder bile contained a higher percentage of lithocholic acid, unconjugated bilirubin, and total calcium in the TPN-treated animals. Markers of hepatic dysfunction were elevated in the serum of the TPN-treated animals. Mild steatosis and edema were the only histologic differences in the livers of the TPN-treated animals. We conclude that gastrointestinal hypomotility associated with enteral fasting plays a role in the pathophysiologic changes leading to TPN-associated hepatobiliary dysfunction. This dysfunction may be mediated by an increase in the absolute and relative concentrations of lithocholic acid in the bile of TPN-treated animals.