Agrimonia eupatoria L. (Agrimony) Extract Alters Liver Health in Subjects with Elevated Alanine Transaminase Levels: A Controlled, Randomized, and Double-Blind Trial.

Agrimonia eupatoria L. has been shown to protect against liver injury due to its lipid lowering and antioxidant activities. The aim of this research was to evaluate the effect of A. eupatoria L. aqueous extract (AEE) on 80 subjects with elevated alanine transaminase (ALT) levels in a randomized, double-blind, placebo-controlled, 8-week study. This trial was conducted between January 2013 and July 2013 at the Oriental Medical Hospital (Jecheon) of Semyung University. The trial included subjects aged 20 years or older who were diagnosed with mildly to moderately elevated ALT levels (between 45 and 135 IU/L). Subjects received two capsules of placebo or AEE twice a day for 8 weeks. Adverse events were recorded. Eighty subjects were randomized to placebo or AEE groups who had similar baseline characteristics. During the 8 weeks of treatment, 11 subjects were excluded from the analysis for protocol violation or consent withdrawal; efficacy of treatment was, therefore, evaluated in 69 subjects (placebo = 35, AEE = 34). The AEE group showed a significant reduction in ALT and serum triglyceride (TG) at 8 weeks compared with the placebo group (ALT P = .044, TG P = .020). Significant group and time interactions were found in ALT (P = .038), aspartate aminotransferase (P = .040), and TG (P = .010). Alkaline phosphatase, total bilirubin, and gamma-glutamyl transferase levels were not different between the two groups. There were no reported severe adverse events during this study, and total protein, albumin, blood urea nitrogen, creatine, and total cholesterol levels were normal in both groups. AEE consumption was safe and generally well tolerated without severe adverse events.

Parenteral fish oil and liver function tests in hospitalized adult patients receiving parenteral nutrition: A propensity score-matched analysis.

BACKGROUND & AIMS: Intravenous fat emulsions are associated with liver disease and there is some evidence that the administration of intravenous fish oil (FO) may be useful in reversing it. The aim of our study was to assess whether there are differences in the changes of liver function tests (LFTs) in hospitalized adult patients with parenteral nutrition (PN) with FO and vegetal lipids vs patients without FO. The secondary aim was to study the relationship between impaired LFT and FO. METHODS: This was a 4-year, propensity score-matched analysis including patients aged ≥18 years treated with PN for ≥10 days. The exclusion criteria were previous liver disease, biliary disorders or pancreatic cancer, and altered initial LFT values. Patients were classified into 2 groups: FO cohort (patients who received FO - in addition to vegetal oil - after the first week of PN) and the vegetal oil cohort (patients who received only vegetal oil). A propensity score matched cohort design was developed. Univariate analyses were used to study the changes in LFTs. To evaluate whether LFT alterations vary with FO administration, four stepwise multiple linear regression models were conducted. RESULTS: 52 patients were included, 52% men, median 66 (55-75) years and 69 kg (61.7-78.8), with 18.5 (14-31.8) days of PN treatment. Maximum FO supplementation was 23%. During the first week with PN (none of the groups receiving FO), gammaglutamyl transferase (GGT), alkaline phosphatase (AP) and total bilirubin (BIL) increased significantly. Comparing LFT values at seven days of PN with at the end of PN treatment, the univariate analysis showed a better response for the FO group. The group without FO showed a significant increase for GGT and AP. In multivariate models, the percentage of FO administered was associated with a decrease in GGT, B = -0.33 [CI 95% = -0.54/-0.12], in AP, B = -0.12 [CI 95% = -0.20/-0.03] and ALT, B = -0.12 [CI 95% = -0.21/-0.024]. CONCLUSIONS: Lipid composition plays a significant role in LFT alteration associated with PN, and FO intravenous lipid emulsions (ILEs) minimize disturbance of LFTs in hospitalized adult patients.

Primary coenzyme Q10 deficiency presenting as fatal neonatal multiorgan failure.

Coenzyme Q10 deficiency is a clinically and genetically heterogeneous disorder, with manifestations that may range from fatal neonatal multisystem failure, to adult-onset encephalopathy. We report a patient who presented at birth with severe lactic acidosis, proteinuria, dicarboxylic aciduria, and hepatic insufficiency. She also had dilation of left ventricle on echocardiography. Her neurological condition rapidly worsened and despite aggressive care she died at 23 h of life. Muscle histology displayed lipid accumulation. Electron microscopy showed markedly swollen mitochondria with fragmented cristae. Respiratory-chain enzymatic assays showed a reduction of combined activities of complex I+III and II+III with normal activities of isolated complexes. The defect was confirmed in fibroblasts, where it could be rescued by supplementing the culture medium with 10 µM coenzyme Q10. Coenzyme Q10 levels were reduced (28% of controls) in these cells. We performed exome sequencing and focused the analysis on genes involved in coenzyme Q10 biosynthesis. The patient harbored a homozygous c.545T>G, p.(Met182Arg) alteration in COQ2, which was validated by functional complementation in yeast. In this case the biochemical and morphological features were essential to direct the genetic diagnosis. The parents had another pregnancy after the biochemical diagnosis was established, but before the identification of the genetic defect. Because of the potentially high recurrence risk, and given the importance of early CoQ10 supplementation, we decided to treat with CoQ10 the newborn child pending the results of the biochemical assays. Clinicians should consider a similar management in siblings of patients with CoQ10 deficiency without a genetic diagnosis.

Hypophosphataemia after major hepatectomy and the risk of post-operative hepatic insufficiency and mortality: an analysis of 719 patients.

BACKGROUND: Hypophosphataemia after a hepatectomy suggests hepatic regeneration. It was hypothesized that the absence of hypophosphataemia is associated with post-operative hepatic insufficiency (PHI) and complications. METHODS: Patients who underwent a major hepatectomy from 2000-2012 at a single institution were identified. Post-operative serum phosphorus levels were assessed. Primary outcomes were PHI (peak bilirubin >7 mg/dl), major complications, and 30- and 90-day mortality. RESULTS: Seven hundred and nineteen out of 749 patients had post-operative phosphorus levels available. PHI and major complications occurred in 63 (8.8%) and 169 (23.5%) patients, respectively. Thirty- and 90-day mortality were 4.0% and 5.4%, respectively. The median phosphorus level on post-operative-day (POD) 2 was 2.2 mg/dl; 231 patients (32.1%) had phosphorus >2.4 on POD2. Patients with POD2 phosphorus >2.4 had a significantly higher incidence of PHI, major complications and mortality. On multivariate analysis, POD2 phosphorus >2.4 remained a significant risk factor for PHI [(hazard ratio HR):1.78; 95% confidence interval (CI):1.02-3.17; P = 0.048], major complications (HR:1.57; 95%CI:1.02-2.47; P = 0.049), 30-day mortality (HR:2.70; 95%CI:1.08-6.76; P = 0.034) and 90-day mortality (HR:2.51; 95%CI:1.03-6.15; P = 0.044). Similarly, patients whose phosphorus level reached nadir after POD3 had higher PHI, major complications and mortality. CONCLUSION: Elevated POD2 phosphorus levels >2.4 mg/dl and a delayed nadir in phosphorus beyond POD3 are associated with increased post-operative hepatic insufficiency, major complications and early mortality. Failure to develop hypophosphataemia within 72 h after a major hepatectomy may reflect insufficient liver remnant regeneration.

Effect of decreased parenteral soybean lipid emulsion on hepatic function in infants at risk for parenteral nutrition-associated liver disease: a pilot study.

PURPOSE: We performed a pilot trial to compare reduced dose versus standard soybean lipid emulsion in neonates at risk for parenteral nutrition-associated liver disease. METHODS: A prospective randomized controlled trial was performed (2009-2011) enrolling surgical patients ≥ 26 weeks' gestation anticipated to require >50% of daily caloric intake from parenteral nutrition (PN) for at least 4 weeks. Randomization occurred into either reduced (1.0 g/kg/day) or standard (3g/kg/day) groups. Co-primary outcomes for interpretation of the results were conjugated bilirubin and total bile acids. Additional outcomes included ALT, AST, GGT, alkaline phosphatase, growth, and essential fatty acid levels. Outcomes were compared between treatment groups using Wilcoxon rank sums tests. RESULTS: Twenty-eight patients (47% enrollment rate) were included in the study with an average treatment duration of 5.4 weeks. Groups had similar PN calories and protein intake throughout the study. Total increase from baseline was smaller in the reduced vs. standard group for conjugated bilirubin (p=0.04) and total bile acids (p=0.02). Weight z-score increased more in the standard group, and no patient experienced essential fatty acid deficiency. CONCLUSION: Markers of cholestasis rose at a slower rate using reduced lipid doses. This pilot study demonstrates feasibility and need for a larger study evaluating the effects of reduced lipids in patients at risk for developing parenteral nutrition-associated liver disease.

Evaluation of biological and biochemical quality of whey protein.

Nutritional and biochemical properties of noncommercial whey protein have been described since 1950. However, comparisons between commercial whey protein for human consumption and casein are rarely found. The aim of this study was to compare biological quality of a commercial whey protein with casein and its effect on biochemical parameters of rats. Thirty-two weanling Fisher rats were divided into three groups and given the following diets: casein group, standard diet (AOAC); whey protein group, modified AOAC diet with whey protein instead of casein; and casein:whey group, modified AOAC diet with 70%:30% casein:whey. A protein-free group was used for determination of endogenous nitrogen losses. Net protein ratio, protein efficiency ratio, and true digestibility were determined, and blood was collected for biochemical analysis. When compared with casein, whey protein showed significant differences for all biological parameters evaluated, as well as for albumin, total protein, total cholesterol, and glucose concentrations. Replacing 30% of casein with whey protein did not affect these parameters. A positive relation among whey protein, high-density lipoprotein-cholesterol, and paraoxonase activity was found. Hepatic or renal dysfunctions were not observed. In conclusion, in comparison with casein, commercial whey protein had higher values of biological parameters, and biochemical evaluation revealed it improved glycemic homeostasis, lipid status, and paraoxonase activity in rats.