Maria Pia Gargante

Bifidobacterium longum with Fructo-Oligosaccharide (FOS) Treatment in Minimal Hepatic Encephalopathy: A Randomized, Double-Blind, Placebo-Controlled Study

Minimal hepatic encephalopathy (MHE) describes patients with chronic liver disease or cirrhosis who have no clinical symptoms of brain dysfunction but perform worse on psychometric tests compared with healthy subjects. The pathogenesis of hepatic encephalopathy is controversial although ammonia has been found to induce cerebral dysfunction. Increased intestinal ammonia production is due to bacterial urease activity and the production of other toxin methabolities, such as mercaptans, thioles. This study assesses the clinical efficacy of Bifidobacterium longum plus fructo-oligosaccharides (FOS) in the treatment of MHE. A total of 60 cirrhotic patients were randomly and equally divided into two groups receiving Bifidobacterium+FOS (17 males, 13 females; mean age, 46±11 years) or placebo (16 males, 14 females; mean age, 45±12 years), respectively. All patients underwent clinical and laboratory assessment psychometric tests and automated EEG analysis: neurophysiological assessment, liver function assessment, amd neuropsychological assessment. After 90 days of treatment, fasting NH4 serum levels were significantly decreased (P=0.003), performance on Trail Making Test-A was significantly decreased (P=0.000), performance on Trail Making Test-B was significantly decreased (P=0.000), performance on the symbol digit modalities test was significantly improved (P<0.05), performance on block design was significantly improved (P=0.000), and performance on the MMSE test was significantly improved (P=0.000). We conclude that the improvement in biochemical and neuropsychological tests of the group treated with Bifidobacterium longum+FOS are interesting and merit further, close examination.

L -Carnitine Supplementation to Diet: A New Tool in Treatment of Nonalcoholic Steatohepatitis — A Randomized and Controlled Clinical Trial

OBJECTIVES:Nonalcoholic steatohepatitis (NASH) is a known metabolic disorder of the liver. No treatment has been conclusively shown to improve NASH or prevent disease progression. The function of L-carnitine to modulate lipid profile, glucose metabolism, oxidative stress, and inflammatory responses has been shown. The aim of this study was to evaluate the effects of L-carnitines supplementation on regression of NASH.METHODS:In patients with NASH and control subjects, we randomly dispensed one 1-g L-carnitine tablet after breakfast plus diet and one 1 g tablet after dinner plus diet for 24 weeks or diet alone at the same dosage and regimen. We evaluated liver enzymes, lipid profile, fasting plasma glucose, C-reactive protein (CRP), tumor necrosis factor (TNF)-α, homeostasis model assessment (HOMA)-IR, body mass index, and histological scores.RESULTS:At the end of the study, L-carnitine-treated patients showed significant improvements in the following parameters: aspartate aminotransferase (P=0.000), alanine aminotransferase (ALT) (P=0.000), γ-glutamyl-transpeptidase (γ-GT) (P=0.000), total cholesterol (P=0.000), low-density lipoprotein (LDL) (P=0.000), high-density lipoprotein (HDL) (P=0.000), triglycerides (P=0.000), glucose (P=0.000), HOMA-IR (P=0.000), CRP (P=0.000), TNF-α (P=0.000), and histological scores (P=0.000).CONCLUSIONS:L-carnitine supplementation to diet is useful for reducing TNF-α and CRP, and for improving liver function, glucose plasma level, lipid profile, HOMA-IR, and histological manifestations of NASH.

Bifidobacterium combined with fructo-oligosaccharide versus lactulose in the treatment of patients with hepatic encephalopathy

Background Hepatic encephalopathy (HE) is a reversible neuropsychiatric syndrome in patients with liver disease. It was suggested that Bifidobacterium+fructo-oligosaccharides (FOS) may decrease blood and brain ammonia levels. Aim The study was conducted to compare the efficacy of Bifidobacterium+FOS and lactulose in patients with HE. Methods One hundred and twenty-five patients (35 hepatitis B virus infected, 70 hepatitis C virus infected and 20 cryptogenetic cirrhosis) were enrolled in the study. Patients were randomized either to a treatment for 60 days with Bifidobacterium and FOS (group A) or into-group receiving lactulose (group B) in double-blind. Results After 30 days of the study period, the Bifidobacterium+FOS-treated patients compared with lactulose-treated patients showed a significant decrease of Trail Making Test B (TMT B) (P<0.005), and a significant increase of Symbol Digit Modalities Test (P<0.001) and Block Design Test (P<0.001). After 60 days of the study period, the Bifidobacterium+FOS-treated patients compared with lactulose-treated patients showed a significant decrease of NH4 fasting HE1 (P<0.001), TMT A (P<0.05), TMT B (P<0.001), and a significant increase of Symbol Digit Modalities Test (P<0.001) and Block Design Test (P<0.001). Conclusion The treatment with Bifidobacterium+FOS is an alternative to the use of lactulose in patients with cirrhosis, for its usefulness in reducing blood ammonia levels and improvement of psychometric tests.

A single dose of rasburicase in elderly patients with hyperuricaemia reduces serum uric acid levels and improves renal function

Aim: Given the relevance of hyperuricaemia in the development of several diseases, we evaluated rasburicase, generally used in tumor lysis syndrome for uric acid treatment. Our purpose was to evaluate the reduction of serum uric acid and the improvement in renal function. Methods: This is a pilot randomized clinical trial. The study was performed as an 8-week, placebo-controlled group comparison of rasburicase and placebo. Thirty-eight patients were randomly assigned to administration of a single dose of rasburicase (4.5 mg in 100-cc physiological solution versus only physiological solution in 15 min). Results: We observed in the first week a fast decrease in uric acid value. Two months after rasburicase administration we saw a significant reduction of urate (p < 0.05) and creatinine (p < 0.001) and an increase in creatinine clearance (p < 0.001) and urate clearance (p < 0.001). Conclusion: In hyperuricaemic elderly patients, a single dose of rasburicase is very effective in lowering serum uric acid levels. Moreover, in patients treated with rasburicase we noted an improvement of renal function. We conclude that rasburicase is an alternative resource for treating those patients who are allopurinol intolerant, have renal dysfunction or have multiple polypharmacy problems in which drug–drug interaction may be of concern.

The Supplementation of Acetyl-l-Carnitine Decreases Fatigue and Increases Quality of Life in Patients with Hepatitis C Treated with Pegylated Interferon-α 2b Plus Ribavirin

The aim of this study was to evaluate whether supplementation of acetyl-L-carnitine (ALC) to pegylated-interferon-α 2b (Peg-IFN-α 2b) and ribavirin (RBV) improves the health-related quality of life during the treatment for chronic hepatitis C, thereby decreasing the risk of treatment discontinuation. Sixty patients with chronic hepatitis C underwent treatment with Peg-IFN-α 2b + RBV (group A; n = 29) or Peg-IFN-α 2b + RBV + ALC (group B; n = 31) for 12 months. At the end of the study, the comparison between group A and group B showed significant differences in aspartate aminotransferase (AST) (-80.9 versus -110.3; P < 0.001), alanine aminotransferase (-111.6 versus -134.7; P < 0.001), Viremia (-3.26 versus -3.82; P < 0.05), mental health (0 versus 11; P < 0.001), physical functioning (-1 versus 8; P < 0.001), role-physical (1 versus 13; P < 0.001), bodily pain (1 versus 12; P < 0.001), general health (3 versus 12; P < 0.001), vitality (3 versus 13; P < 0.001), social functioning (3 versus 10; P < 0.001), physical fatigue (2.1 versus -5.4; P < 0.001), mental fatigue (-0.7 versus -2.7; P < 0.001), and fatigue severity scale (-3.4 versus -12; P < 0.001). ALC supplementation reduced both mental and physical fatigue, improved health-related quality of life, and, therefore, has the potential to increase patient adherence to the combination regimen. This, in turn, may increase the percentage of patients achieving a sustained virological response.

Myopathy with Concurrent Tadalafil and Simvastatin

A 48-year-old man, using statin, was admitted to hospital with progressive myalgia after consumption of tadalafil and simvastatin. Muscle pain and penile erection disappeared seven days after interruption of therapy. This case demonstrates the interaction of tadalafil with simvastatin resulting in myopathy. Muscle damage could be attributed to the common metabolic way of these two drugs which is cytochrome P450 isoenzyme system.