A. Federico

Trace Elements and Chronic Liver Diseases

The relationships between chronic liver diseases and trace element (TE) contents are debated. Particularly, no defined data are available about the TE levels in viral liver disease patients with or without malnutrition. In this study we evaluated blood and plasma levels of various trace elements in patients with HCV-related chronic liver disease, at different stages of liver damage (8 patients with chronic hepatitis and 32 with liver cirrhosis) with or without malnutrition. We also studied 10 healthy volunteers as control group. We found that cirrhotic subjects had a significant decrease of blood levels of Zn and Se, independently on the nutritional status, whereas plasma levels of Fe were significantly reduced only in malnourished cirrhotic patients. Our data indicate that liver impairment is the main cause of the blood decrease of Se and Zn levels in patients with non alcoholic liver disease, whereas the malnutrition affects Fe levels only.

Effects of selenium and zinc supplementation on nutritional status in patients with cancer of digestive tract.

Objective: To evaluate the effect of oral administration of selenium and zinc tablets in patients with cancer of the digestive tract during chemotherapy.Design: A case–control, randomized study.Setting: Medical Oncology, II University of Naples, Naples, Italy.Subjects: A total of 60 patients (median age 55 y, range 46–61 y) with diagnosis of gut cancer were randomized in 1999. Patients were treated for 60 days with chemotherapy.Interventions: Trace elements were measured by atomic absorption spectroscopy. The nutritional status of the patients was assessed by biochemical and bio-impedance analysis (BIA) parameters in basal condition and after 60 days of treatment. Oral administration of selenium and zinc in oral tablet form for 50 days was Se 200 μg/day (50 μg/tablet) and Zn 21 mg/day (7 mg/tablet).Results: Both in the basal condition and at 60 days all patients were malnourished. Selenium and zinc concentrations were significantly lower (P<0.01) whereas copper concentration was significantly higher (P<0.01) in cancer patients than in control subjects. However, 21/30 (70%) of those treated with Se and Zn did not showed a further worsening of nutritional status and experienced a significant decrease of asthenia with an increase of appetite. On the other hand, 24/30 (80%) untreated patients had a significant decline of all parameters studied after 60 days (prealbumin, cholesterol, transferrin, P<0.05 vs 0 time; total proteins, albumin/globulin ratio, P<0.01 vs 0 time; fat-free mass, fat mass, Na+/K+ ratio, body mass index P<0.05 vs 0 time; fat free mass/fat mass, total body water, extra cellular/intra cellular water, basal metabolic rate: P<0.01 vs 0 time).Conclusions: Data indicate that Se and Zn supplementation may improve the clinical course of general conditions in patients with gut cancer. These effects of Se and Zn require confirmation in an independent trial of appropriate design before new public health recommendations regarding Se and Zn supplementation can be made.European Journal of Clinical Nutrition (2001) 55, 293–297

A new silybin-vitamin E-phospholipid complex improves insulin resistance and liver damage in patients with non-alcoholic fatty liver disease: preliminary observations

Non-alcoholic fatty liver disease (NAFLD) may occur as an expression of a metabolic syndrome or in association with hepatitis C virus (HCV) chronic infection. The contemporaneous presence of NAFLD in this later group of patients may negatively affect the progression of fibrosis and the response to antiviral treatment.1,2 It has been suggested that in the future a therapeutic approach to chronic liver disease would consist of a number of complementary approaches considering the multitude of pathogenic mechanisms.3 Silybin is a natural flavonoid that has been conjugated to vitamin E and phospholipids to improve its bioavailability, and antioxidant and antifibrotic activity.4 After approval of the ethics committee and informed consent, 85 outpatients were consecutively enrolled in the study: 59 were affected by primitive NAFLD (group A) …

Relationship of Blood Trace Elements to Liver Damage, Nutritional Status, and Oxidative Stress in Chronic Nonalcoholic Liver Disease

Trace elements are involved in chronic liver diseases because these elements may have a direct hepatic toxicity or may be decreased as a consequence of the impaired liver function, particularly in patients with alcoholic cirrhosis and/or malnutrition. In this study, we determined plasma and erythrocytes trace elements in 50 inpatients with nonalcoholic chronic liver disease (11 with biopsy-proven chronic hepatitis, 39 with cirrhosis [16 in stage A according to Child-Pugh criteria, 23 Child B+C]), and in a control group of 10 healthy subjects by the proton induced x-ray emission method. The relationship between trace element concentration and the extent of liver damage, the nutritional status (by anthropometric evaluations), and various blood markers of oxidative stress—reduced glutathione, total lipoperoxides and malonyldialdehyde—was investigated. We found that cirrhotics had a significant decrease of Fe, Zn, Se, and GSH levels in the plasma and of GSH and Se in the erythrocytes with respect to the control and chronic hepatitis groups. GSH levels were related to the degree of liver damage; a significant direct correlation was observed among Se, Zn, and GSH plasma values and between GSH and Se in the erythrocytes. The trace element decrease was, on the contrary, independent of the degree of liver function impairment and only partially affected by the nutritional status. Data indicate that liver cirrhosis, even if not alcohol related, induces a decrease of Se and Zn and that, in these patients, an oxidative stress is present, as documented by the significant correlation between Se and GSH. The plasma Br level was higher in cirrhotics with respect to the control and chronic hepatitis groups.

Emerging drugs for non-alcoholic fatty liver disease

Background: Non-alcoholic fatty liver disease (NAFLD) is a condition of emerging relevance that includes different forms of chronic liver damage, from a simple fatty infiltration (steatosis) of hepatocytes to steatohepatitis (NASH) with fibrosis. This last form may evolve to cirrhosis and hepatocellular carcinoma. Objective: To discuss therapeutic management of NAFLD. Theoretically, only patients with non-alcoholic steatohepatitis (NASH) need to be treated, as only NASH may evolve to cirrhosis. Differentiation between steatosis and NASH currently requires a liver biopsy. Methods: We discuss different therapeutic approaches proposed in literature for patients with NAFLD. Results: The treatment of associated conditions leads to an improvement of NAFLD and NASH. No specific drug is actually present to treat liver steatosis or NASH. Conclusions: The treatment of NAFLD depends on the individual characteristics of each patient. Diet and physical exercise may be considered a basal universal approach. Future research will discover possible specific liver drugs.

Two-week, high-dose proton pump inhibitor, moxifloxacin triple Helicobacter pylori therapy after failure of standard triple or non-bismuth quadruple treatments

BACKGROUND Aim was to evaluate the efficacy and tolerability of a moxifloxacin-containing second-line triple regimen in patients whose previous Helicobacter pylori eradication treatment failed. METHODS Prospective multicentre study including patients in whom a triple therapy or a non-bismuth-quadruple-therapy failed. Moxifloxacin (400mg qd), amoxicillin (1g bid), and esomeprazole (40 mg bid) were prescribed for 14 days. Eradication was confirmed by (13)C-urea-breath-test. Compliance was determined through questioning and recovery of empty medication envelopes. RESULTS 250 patients were consecutively included (mean age 48 ± 15 years, 11% with ulcer). Previous (failed) therapy included: standard triple (n = 179), sequential (n = 27), and concomitant (n = 44); 97% of patients took all medications, 4 were lost to follow-up. Intention-to-treat and per-protocol eradication rates were 82.4% (95% CI, 77-87%) and 85.7% (95% CI, 81-90%). Cure rates were similar independently of diagnosis (ulcer, 77%; dyspepsia, 82%) and previous treatment (standard triple, 83%; sequential, 89%; concomitant, 77%). At multivariate analysis, only age was associated with eradication (OR = 0.957; 95% CI, 0.933-0.981). Adverse events were reported in 25.2% of patients: diarrhoea (9.6%), abdominal pain (9.6%), and nausea (9.2%). CONCLUSION 14-day moxifloxacin-containing triple therapy is an effective and safe second-line strategy in patients whose previous standard triple therapy or non-bismuth quadruple (sequential or concomitant) therapy has failed, providing a simple alternative to bismuth quadruple regimen.

Can dietary intake influence plasma levels of amino acids in liver cirrhosis

BACKGROUND Modifications in plasma amino acid patterns in cirrhotics are attributed to impaired liver function, being more evident in alcoholic than in viral cirrhosis. AIM To evaluate whether diet influences plasma amino acid concentrations in different aetiological groups of cirrhotics. PATIENTS Study population comprised 40 patients with cirrhosis (25 virus- and 15 alcohol-related], all Child A, and 30 healthy subjects (controls). METHOD A food frequency and quality questionnaire was utilized to determine dietary history and alcohol intake. Nutritional status was evaluated by anthropometric method. Amino acids were determined, on venous blood samples, using a specific analyzer while cysteine was evaluated by fluorescent high power liquid chromatography RESULTS The total daily intake of calories, proteins, lipids, and carbohydrates was similar in all individuals. Food quality distinguished the cirrhotics from the controls, but not the different aetiological groups of cirrhotics. Plasma cysteine levels were significantly lower, while aromatic amino acids and methionine were significantly higher, in all cirrhotics (p<0.001 and p<0.01, respectively, versus controls). The decrease in cysteine and the increase in other amino acids were more marked in alcoholics (p<0.01). CONCLUSIONS Ethanol intake, but not diet, further enhances the changes in plasma aromatic amino acids, methionine and cysteine induced by impaired liver function in patients with cirrhosis, suggesting a direct interference of alcohol in their metabolism.

Does Polychemotherapy With 5-Fluorouracil, Methotrexate, and L-Folinic Acid Influence the Selenium, Zinc, and Copper Serum Levels in Cancer of Digestive Tract?

This study was designed to evaluate selenium, copper, and zinc serum concentration in patients with cancer of the digestive tract before and after treatment with 5-fluorouracil, methotrexate, and L-folinic acid. Also, we evaluated whether any change was correlated with the nutritional status of the patients. Trace elements were measured by atomic absorption spectroscopy. The nutritional status of each patient was assessed through a combination of biohumoral (prealbumin, cholinesterase, cholesterol, transferrin, tot1 proteins, albumin/ globulin ratio, C-reactive protein) and bio-impedance (percent free fat mass, percent fat mass, FFM/FM, percent total body water, extra/intracellular water, Na + /K + ratio exchangeable, body mass index, basal metabolic rate, and phase angle) parameters before and after the chemotherapeutic treatment. Most patients showed significant alteration of the nutritional parameters compared with control (prealbumin, cholinesterase, percent free fat mass, percent fat mass, P < 0.01 versus controls; cholesterol, transferrin P < 0.05 versus controls; total proteins, albumin/globulin ratio P < 0.001 versus controls). However, no significant change of biochemical and bio-impedance parameters was observed at the end of the therapy. Only 4 of the 50 patients showed significant alteration of nutritional indexes after chemotherapy. Selenium and zinc concentration were significantly lower (Se 56.4 ± 8.4 mg/dL and Zn 79.5 ± 8.6 mg/dL; P < 0.01 versus controls) whereas copper concentration was significantly higher (Cu 111.9 ± 19 mg/dL; P < 0.01) in cancer patients than in control subjects. Moreover, at the end of treatment selenium and zinc serum levels showed a significant decrease compared with base line values (Se 51.4 ± 7.2 mg/dL and Zn 73.4 ± 7.4 mg/dL; P < 0.001). Copper concentration at the end of the therapy was higher compared with base line concentration (118.4 ± 11 mg/dL; P < 0.001). The change in trace element serum concentration at the end of therapy was of the same magnitude in patients who did not show significant change in their nutritional status and in those who did. In conclusion, cancer patients show an alteration in the serum concentration of trace elements. Chemo