Page 2

Effects of supplementation with unsaturated fatty acids on plasma and membrane lipid composition and platelet function in patients with cirrhosis and defective aggregation.
Marra F; Riccardi D; Melani L; Spadoni S; Galli C; Fabrizio P; Tosti-Guerra C; Carloni V; Gentilini P; Laffi G
Istituto di Medicina Interna, Universita di Firenze, Florence, Italy.
J Hepatol (Denmark) Apr 1998, 28 (4) p654-61

BACKGROUND/AIMS: Defective platelet aggregation and reduced platelet production of thromboxane A2, a metabolite of arachidonic acid, are common findings in patients with cirrhosis . We evaluated the effects of dietary supplementation with two combinations of unsaturated fatty acids on platelet function and plasma and membrane fatty acids in patients with liver cirrhosis .

METHODS: In a double-blind study, 15 patients with cirrhosis and defective aggregation were randomized to receive a 6-week supplementation with gamma-linolenic and linoleic acid (1 g/day of each fatty acid) or with oleic acid and linoleic acid (groups GLA and OA, respectively).

RESULTS: Under baseline conditions, patients showed elevated concentrations of monounsaturated fatty acids and a reduction in polyunsaturated fatty acids. The product/precursor ratios for delta6 and delta5 desaturases, two key enzymes in the pathway leading to arachidonic acid, were significantly reduced in the group of patients. In the GLA group, a significant increase in the levels of dihomo-gamma-linolenic acid (20:3omega6) was observed in plasma and membranes, together with a parallel decrease in the 20:4/20:3omega6 ratio after supplementation. No significant changes were observed in the OA group. The levels of arachidonic acid did not change significantly in either group of patients. Platelet aggregation to collagen was unchanged in the GLA group, but significantly improved in the OA group.

CONCLUSIONS: These results show that supplementation with precursors of arachidonic acid is ineffective in elevating plasma or membrane arachidonate levels and does not improve platelet aggregation, suggesting that synthesis of arachidonic acid through the delta5 desaturase cannot be correspondingly activated or that incorporation/retention of the produced fatty acid into lipids is impaired. The increased platelet aggregation in the OA group is likely to be explained by the effect of oleic acid contained in the diet, the effects of which may have been counteracted by the elevation in 20:3omega6, a source of anti-aggregatory prostanoids, in the GLA group.

Effects of L-arginine on the systemic, mesenteric, and hepatic circulation in patients with cirrhosis.
Kakumitsu S; Shijo H; Yokoyama M; Kim T; Akiyoshi N; Ota K; Kubara K; Okumura M; Inoue K
First Department of Internal Medicine, School of Medicine, Fukuoka University, Japan.
Hepatology (United States) Feb 1998, 27 (2) p377-82

Nitric oxide (NO) is known to play an important role in modulating both the hepatic and mesenteric circulation under physiological and pathological conditions. We investigated how L-arginine, a precursor of NO, modifies the hepatic and mesenteric circulation in patients with cirrhosis . The study design was a single-blind controlled study. We measured the systemic and portal hemodynamics before and following intravenous L-arginine and saline infusion using pulsed Doppler ultrasonography in 20 patients with cirrhosis, and then the effects were compared with those found in 20 healthy subjects. In these patients, the effects of L-arginine on hepatic circulation were investigated using hepatic catheterization. L-Arginine infusion induced systemic vasodilation in both the healthy controls and the cirrhotic patients in a similar hemodynamic manner. In these patients, the L-arginine-induced increase in the portal flow was significantly higher than that of cardiac output (CO); however, the relation was the inverse in healthy subjects. Moreover, the L-arginine-induced increase in the portal flow was greater in the cirrhotic patients than that seen in healthy subjects. As a result, L-arginine infusion was thus found to selectively augment the hepatopetal portal blood flow in the cirrhotic liver. In patients, L-arginine infusion induced marked hepatic vasodilation as demonstrated by the reduced hepatic sinusoidal resistance (HSR) and increased estimated hepatic blood flow (EHBF) associated with the ameliorated intrinsic clearance of indocyanine green. Despite the fall in HSR, the hepatic venous pressure gradient (HVPG) increased following L-arginine infusion. The mesenteric and hepatic vascular areas of cirrhosis exhibited an increased susceptibility to the dilator action of L-arginine. These findings suggest that the enhanced NO production in the splanchnic vascular area has an important role in the hepatic circulation in patients with cirrhosis .

Consequences of cholestasis from the hepatologist's viewpoint
Krahenbuhl S
Departement Innere Medizin, Universitatsspital Zurich.
Schweiz Med Wochenschr (Switzerland) May 10 1997, 127 (19) p821-8,

Chronic cholestasis is associated with a variety of symptoms and dysfunction of most organs. Among them, jaundice and pruritus are the first to be recognized, usually prompting the patients to see a physician. Besides the skin, however, cholestasis also affects, inter alia, the metabolism of plasma lipids and fat-soluble vitamins, as well as bone and liver. In the following article the pathogenesis and therapy of metabolic disturbances and organ dysfunctions occurring frequently in patients with chronic cholestasis are discussed. (56 Refs.)

Ursodeoxycholic acid in the treatment of liver diseases.
Saksena S; Tandon RK
Department of Gastroenterology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India.
Postgrad Med J (England) Feb 1997, 73 (856) p75-80

Ursodeoxycholic acid is a dihydroxy bile acid with a rapidly expanding spectrum of usage in acute and chronic liver diseases. The various mechanisms of action of this hydrophilic bile acid include direct cytoprotection, detergent action on dysfunctional microtubules, immunomodulation and induction of hypercholeresis. Its efficacy in primary biliary cirrhosis and primary sclerosing cholangitis as an adjunct to medical therapy has been well established. Newer indications include its use in the management of chronic hepatitis, cirrhosis, post liver transplant rejection, graft-versus-host disease and acute viral hepatitis, where it not only relieves symptoms of cholestasis but also arrests ongoing hepatocyte necrosis. (78 Refs.)

Lamivudine treatment of chronic hepatitis B
Dusheiko G.
Prof. G. Dusheiko, Department of Medicine, Pond Street, Hampstead, London NW3 2QG United Kingdom
Reviews in Medical Virology (United Kingdom), 1998, 8/3 (153-159)

Several new nucleoside analogues have been developed which can inhibit hepatitis B replication by at least two logs. Lamivudine is the most widely studied of these new agents. Extensive phase II and III studies in patients with chronic hepatitis B have been completed. The sustained HBeAg seroconversion rate in patients who have received 100 mg lamivudine increases from 17% after a year of treatment to 27% after 2 years of treatment. Histological improvement has been noted in 38%-52% of lamivudine-treated patients, exceeding the improvement seen in placebo recipients. Similar histological improvement has been noted in anti-HBe-positive, DNA-positive patients. Lamivudine can prevent recurrence of hepatitis B after liver transplantation. It is likely that in the absence of immune clearance to accelerate elimination of infected hepatocytes, inhibitors of virus replication such as lamivudine will need to be administered for a long period to reduce the burden of infected hepatocytes in the liver, and to prevent relapse. The drug is generally well tolerated with few direct adverse events. Genotypic mutations have been observed in 23% (range 13-32%). In a study in Asian patients treated for two years the incidence of these mutants increased to 38% (as detected by PCR). Loss of susceptibility to lamivudine has been found to be due to reverse transcriptase amino acid substitutions. Lamivudine is likely to be reserved for patients with replicative hepatitis B infection with active chronic hepatitis, and/or active cirrhosis.

Ursodeoxycholic acid, new approach to the treatment of gravidic cholestasis? Three case reports
Calmelet P.; Coumaros D.; Viville B.; Raiga J.; Favreau J.-J.; Treisser A.
P. Calmelet, Svc. de Gynecologie et Obstetrique, Hopital Civil, 67091 Strasbourg Cedex France
Journal de Gynecologie Obstetrique et Biologie de la Reproduction (France), 1998, 27/6 (617-621)

Ursodeoxycholic acid, employed in treatment of intrahepatic cholestasis as seen in primary biliary cirrhosis, primary sclerosing cholangitis, and chronic hepatitis; does not have marketing approval for prescription during pregnancy because of lack of data. In 3 cases of gravidic cholestasis, we administred oral ursodeoxycholic acid 1 g a day from the 34(th) week of amenorrhea to delivery. In each case, it tooks 3 days of treatment for the pruritus to regress incompletely and for plasma levels of biliary acid and transaminases to decrease. The infants, born between the 36(th) and 38(th) week of amenorrhea, presented with no problem. Forty-eight cases of gravidic cholestasies treated by ursodeoxycholic acid (0,4 to 1 g a day) have been reported in the literature; 18 cases belonging to 2 randomized studies. In 46 cases pruritus disappeared generally 3 days after treatment onset, and plasma level of biliary acid and transaminase decreased in one week. Only two patients experienced persisting pruritus despite biological improvement . No foetal adverse effect is reported. Ursodeoxycholic acid seems to be an efficient treatment of gravidic cholestasis. Long term observation of fetuses exposed in utero to this treatment is required to assess safety.

Spontaneous pulsatility and pharmacokinetics of growth hormone in liver cirrhotic patients
Baruch Y.; Assy N.; Amit T.; Krivoy N.; Strickovsky D.; Orr Z.S.; Hochberg Z.
Y. Baruch, Liver Unit, Department of Medicine B, Rambam Medical Center, P.O.B. 9602, 31096 Haifa Israel
Journal of Hepatology (Denmark), 1998, 29/4 (559-564)

Background/Aims: Liver cirrhosis is characterized by high serum growth hormone levels and low serum insulin-like growth factor I and growth hormone- binding protein levels. The present study was designed to characterize the serum profile of growth hormone and growth hormone pharmacokinetics in postnecrotic liver cirrhosis, correlating it with liver function and nutritional states.

Methods: Fifteen patients were grouped by the ChildPugh score (group 1, score of 5 to 8; group 2, score of 9 to 12). Five healthy subjects served as controls. Nutritional status was assessed by the creatinine-height index. Baseline growth hormone, insulin-like growth factor, and growth hormone binding protein were measured, and growth hormone pharmacokinetics was followed for 48 h after administration of subcutaneous recombinant human growth hormone (0.06 mg/kg).

Results: Trough serum growth hormone (microg/I) was higher in both patient groups (5.3plus or minus3.6) than in controls (1.0plus or minus0.3; p<0.01). More pulses were recorded in cirrhotic patients, and mean pulse amplitude (microg/I) was higher in cirrhotic patients than in controls (p<0.01). After subcutaneous recombinant human growth hormone injection, maximal growth hormone was higher in cirrhotic patients and the area under the curve over 24 h was greater (626plus or minus120) than in controls (330plus or minus54; p<0.01). Single regression analysis showed a weak correlation of both the Child-Pugh score and the creatinine-height index with the pharmacokinetic parameters.

Conclusions: Due to decreased growth hormone clearance, patients with liver cirrhosis have increased trough and peak serum growth hormone levels, as well as lower serum growth hormone binding protein and insulin- like growth factor. Recombinant human growth hormone pharmacokinetics are typical of a high hepatic extraction substance administered to patients with liver disease and portal hypertension, and this may be relevant to the further use of growth hormone therapy .

A pregnancy complicated with intrahepatic cholestasis managed by ursodeoxycholic acid
Corakci A.; Karabacak O.; Himmetoglu O.; Bilgihan A.; Erdem A.; Eskenndari R.
O. Karabacak, Kocaeli Universitesi Tip Fakultesi, PK 226, 41100 Kocaeli Turkey
Jinekoloji ve Obstetri Bulteni (Turkey), 1998, 7/3 (120-123)

A 27-year-old women with a history of four previous pregnancies, all complicated with intrahepatic cholestasis of pregnancy, is presented. She was admitted because of icterus at the 29th week of pregnancy. Serum liver enzymes were in normal limits while total and direct bilirubine levels, alkaline phosphatase, gama glutamyl transferase, prothrombine time, and activated partial thromboplastine time were elevated. Acute hepatitis, autoimmune chronic liver disease and obstructive biliary liver disease were ruled out. She was put on ursodeoxycholic acid (UDA) 250 mg qid. At the 33rd week of pregnancy, amniocentesis was performed because of progressive intrauterin growth retardation and preterm labor. Amniotic fluid had thick meconium and was in Liley Zone 3. She was delivered a 1800 gr male fetus. Postpartum liver biopsy revealed fibroblastic proliferation and cholestasis, consistant with cirrhosis . Although intrahepatic cholestasis of pregnancy is a benign disease, recurrence. may lead to chronic liver disease. Ursodeoxycholic acid does not change biochemical parameters, but may be beneficial for fetal survival.

Pharmacological management of chronic viral hepatitis
Lam N.P.
N.P. Lam, University of Illinois at Chicago, Department of Pharmacy Practice, College of Pharmacy, 833 South Wood Street, Chicago, IL 60612 United States
Journal of Pharmaceutical Care in Pain and Symptom Control (United States), 1998, 6/3 (41-62)

Chronic viral hepatitis is a worldwide health problem. Complications associated with chronic viral hepatitis include liver failure, cirrhosis and hepatocellular carcinoma. The disease often is asymptomatic, but malaise, weakness and fatigue can occur. Alfa-interferon (alpha-IFN) is the only treatment with proven benefit in chronic viral hepatitis. Common adverse physical and psychiatric effects of therapy are described. The efficacy, however, varies widely. In chronic hepatitis B, alpha-IFN improves liver aminotransferases and histology, and leads to loss of viral replication in 25-40% of patients. Nucleoside analogues are being evaluated as an alternative treatment. In chronic hepatitis C, alpha-IFN leads to improvement in liver aminotransferases and histology, and clearance of HCV RNA in 10-25% of patients. The new treatment under investigation is a combination of alpha-IFN and ribavirin. In chronic hepatitis D, prolonged treatment using similar dosing regimens of alpha-IFN in chronic hepatitis B result in clearance of HDV RNA in 50% of patients. Relapses are common after treatment discontinuation. Future treatment approaches for chronic viral hepatitis will most likely utilize combination therapies .

Hepatitis B and C: Current treatment
Bruch H.-R.; Hohner U.; Muller R.
Dr. R. Muller, Medizinische Klinik, Gastroenterologie-Hepatologie, Krankenhaus Siegburg, Ringstr. 49, D-53721 Siegburg Germany
Schweizerische Rundschau fur Medizin/Praxis (Switzerland), 1998, 87/42 (1408-1412)

Treatment of acute viral hepatitis B is symptomatic, fulminant cases may require liver transplantation. In chronic hepatitis B interferon (IFN)-alpha will induce sustained response rates of 30-40%. Nucleoside analogues such as famciclovir or lamivudine appear to be promising for treatment in non- responders or cirrhotic and immunosuppressed patients. IFN-alpha may reduce the rate of chronic courses in acute hepatitis C infections. Chronic hepatitis C patients with elevated ALT activities, positive serum HCV RNA and portal or bridging fibrosis on biopsy are recommended for treatment with IFN-alpha. Sustained responses are observed in less than 20% of treated patients. Re- treatment with IFN-alpha may be indicated in non-responders or in case of relapse. Combination therapy of IFN-alpha plus ribavirin may emerge as treatment of choice for patients with a relapse in the near future.

Zinc deficiency in liver cirrhosis: Curiosity or problem?
Marchetti P.; Amodio P.; Caregaro L.; Gatta A.
Dr. P. Amodio, Dipto. Medicina Clinica/Sperimentale, Reparto di Clinica Medica V, Universita degli Studi, Via Giustiniani 2, 35126 Padova Italy
Annali Italiani di Medicina Interna (Italy), 1998, 13/3 (157-162)

This article reviews the literature on the role of zinc in liver cirrhosis and dietary zinc supplementation for cirrhotic patients with hepatic encephalopathy. Zinc is a trace metal found in many proteins and enzymes having catalytical, cocatalytical and structural functions. Zinc deficiency has been demonstrated in cirrhotic patients, and dietary supplementation of this metal could benefit the urea cycle, glucose and protein metabolism, and central nervous system neurotransmission in these subjects. After some brief considerations on normal zinc metabolism, the role zinc plays in the central nervous system, and its conduct in patients with hepatic encephalopathy, possible links between zinc deficiency and the pathophysiology of central nervous system dysfunction in cirrhotic patients are discussed. The article concludes with a critical review of favorable and unfavorable evidence for zinc supplementation in patients with hepatic encephalopathy.

Effects of ribavirin on hepatitis C-associated nephrotic syndrome in four liver transplant recipients
Pham H.-P.; Feray C.; Samuel D.; Gigou M.; Azoulay D.; Paradis V.; Ducret F.; Charpentier B.; Debuire B.; Lemoine A.
A. Lemoine, Service de Biochimie, Hopital Paul Brousse, 14 Avenue Paul Vaillant Couturier, 94804 Villejuif Cedex France
Kidney International (United States), 1998, 54/4 (1311-1319)

Background. Hepatitis C virus infection (HCV) is associated with a variety of extrahepatic disorders such as membranoproliferatire glomerulonephritis (MPGN), which is generally due to cryoglobulinemia. After liver transplantation for HCV cirrhosis, alpha-interferon treatment against the recurrence of HCV in the liver graft is poorly effective and may induce intractable graft rejection. Methods. We describe the cases of four liver transplant recipients treated with ribavirin for HCV-related glomerulopathy and nephrotic syndrome. Results. The nephrotic syndrome was attenuated or disappeared during ribavirin therapy, and patients showed a marked decrease in proteinuria and an increase in albuminemia. The syndrome relapsed in two patients when ribavirin therapy was stopped, and a favorable response was again obtained in both cases when the treatment was resumed. The main adverse effect of ribavirin was anemia in two patients with renal impairment. No graft rejection occurred. Conclusions. These findings suggest that continuous therapy with low doses of oral ribavirin may improve the proteinuria of hepatitis C-related glomerulonephritis, at least in liver transplant recipients.

Ursodeoxycholic acid therapy for primary biliary cirrhosis. A 10-year British single-centre population-based audit of efficacy and survival
Bateson M.C.; Gedling P.
M.C. Bateson, Bishop Auckland General Hospital, Bishop Auckland DL14 6AD United Kingdom
Postgraduate Medical Journal (United Kingdom), 1998, 74/874 (482-485)

The effect of ursodeoxycholic acid treatment on survival in primary biliary cirrhosis was studied in 40 patients with symptomatic disease. Two patients developed early exacerbation of symptoms and stopped therapy in days; they are both alive 4 and 4one-quarter years later. The other 38 patients have continued on treatment for up to 10 years. Results were compared with 12 other similar cases previously seen but not given specific therapy . Kaplan-Meier analysis showed that ursodeoxycholic acid treatment was associated with better survival (p < 0.05) after the first two years of therapy . Predictors of favourable outcome included histological stage I disease. In 26 patients with primary biliary cirrhosis stage II, III or IV, therapy showed a trend to improved survival, but this was still significantly worse than the general population. Prognosis was not different between these different advanced stages. Symptoms improved in 28 out of 40 patients on ursodeoxycholic acid, but 50% had a recurrence by two years.

Colchicine: 1998 update
Ben-Chetrit E.; Levy M.
Dr. E. Ben-Chetrit, Rheumatology Unit, Department of Medicine, Hadassah University Hospital, PO Box 12000, Jerusalem Israel
Seminars in Arthritis and Rheumatism (United States), 1998, 28/1 (48-59)

Objective: To present an update of the use of colchicine in patients with familial Mediterranean fever (FMF) and other rheumatic and nonrheumatic diseases.

Data Sources: Published studies on colchicine retrieved from MEDLINE searches from 1987 to 1997 and reports presented at national and international meetings.

Studies Selection and Extraction: All studies were reviewed by the authors. Reports addressing the topics of colchicine pharmacokinetics, biological effects, indications for use, and side effects were selected.

Data Synthesis: Colchicine is an alkaloid that may interfere with microtubule formation, thereby affecting mitosis and other microtubule- dependent functions. It has a bioavailability of 25% to 50% when administered orally. Colchicine and its metabolites are excreted through the urinary and biliary tracts. It may be used while breast feeding; however, amniocentesis should be performed when used in pregnancy. The drug may be given to children with FMF. The efficacy of colchicine has been proved in FMF, gout, Behcet's disease, and cirrhosis . Its place in the treatment of scleroderma, sarcoidosis, and skin disorders remains to be determined. Gastrointestinal side effects occur early and are most common manifestations of colchicine toxicity. Severe colchicine toxicity results in multiple organ failure, convulsions, coma, and death. Potentially, effective treatment with Fab anti- colchicine antibodies unfortunately is unavailable; therefore, treatment is supportive.

Conclusions: Colchicine is a relatively safe and effective medication for several disorders when used in appropriate dosage in patients with normal kidney and liver function.

Heavy and moderate drinking: Risks and benefits
Lieber C.S.
Dr. C.S. Lieber, Bronx Veterans Affairs Medical Ctr., 130 West Kingsbridge Road, Bronx, NY 10468 United States
Journal of the Irish Colleges of Physicians and Surgeons (Ireland), 1998, 27/3 (161-176)

The goals of this article are to assess the evidence for medical risks of moderate alcohol consumption versus benefits by firstly reviewing the metabolism of alcohol, including effects of moderate amounts, on hepatic metabolism and toxicity; and secondly, evaluating the relationship of consumption of moderate amounts of alcohol and the risks versus benefits in terms of nutrients (including carotenoids and folate), liver disease and other medical complications of alcoholism, such as cardiovascular diseases and cancer.

Antioxidants: A therapy of the future?
Vicedo T.B.; Correas F.J.H.
T.B. Vicedo, Servicio de Farmacia, Hospital Severo Ochoa, Leganes, Madrid Spain
Nutricion Hospitalaria (Spain), 1997, 12/3 (108-120)

In the present review piece, we analyze the formation of free radicals as a consequence of the cellular metabolism in aerobe organisme, and the beneficious and harmful actions thereof on cellular structures. The balance existing between free radicals and the so-called antioxidant defenses, is a key factor for preventing the development of noxious processes at the cellular and tissue level. In accordance with the present scientific knowledge, the excessive production of free radicals in the organism, and the imbalance between the concentrations of these and the antioxidant defenses, may be related to processes such as aging and several diseases, among which we find cancer, ischemic processes, senile dementia, diabetes, pulmonary and pancreatic diseases, lupus erythematosus, cirrhosis, intestinal inflammatory disease, multiple sclerosis, arthritis, arteriosclerosis, cardiovascular disease, diseases of the central nervous system and the brain. According to the results of numerous research works conducted with the administration of several molecules with an antioxidant activity, one is beginning to see what their role will be in the pharmacological therapeutics for the treatment of a large number of patients such as those with burns, traumas, septics, shock, surgery, transplantation, radiation or chemotherapy, respiratory distress syndrome, AIDS, etc. We may possibly be facing a therapeutic tool which is of great interest in the clinical area, which shall be developed in the near future, as clinical trials which permit confirmation of their efficacy are conducted.

Zinc therapy in gastroenterology
Grungreiff K.
Dr. K. Grungreiff, Heydeckstrasse 9, D-39104 Magdeburg Germany
Medizinische Welt (Germany), 1998, 49/2 (78-83)

Zinc is an essential trace element required for several metabolic and immunologic functions in the organism. Nutritional zinc deficits produce multiform symptoms and zinc defiencies have been implicated in disorders such as liver cirrhosis, inflammatory bowel disease, chronic pancreatic and chronic renal disease. Determination of zinc in serum or plasma is used for diagnostic purposes. In all patients zinc substitution is indicated and effective when deficiency and corresponding symptoms are found. A longterm zinc supplementation should not exceed a daily dose of 45 mg elemental zinc.

Malnutrition and bacterial infections in hepatic cirrhosis
Caly W.R.; Strauss E.
W.R. Caly, Rua Aureliano Coutinho, 18-apto. 92, 01224-020 - Sao Paulo, SP Brazil
GED - Gastrenterologia Endoscopia Digestiva (Brazil), 1997, 16/6 (226-230)

Malnutrition is an important factor in the pathogenesis of hepatic diseases and, due to its relation to immunologic alterations, it may lead to the onset of infections. The aim of this study was to prospectively evaluate the nutritional status of 170 hospitalized patients who presented with alcoholic cirrhosis, whether or not associated to bacterial infections. All patients were submitted to biochemical and hepatic blood tests, bacteriological and bacterioscopic analyses, blood and ascitic fluid cultures, Child-Pugh classification, and nutritional evaluation through subjective and objective analyses using biochemical and anthropometric assessment. Results showed that in any of the parameters evaluated, malnutrition was more severe among the patients with bacterial infections. Malnutrition was also more frequent among C cirrhotic patients (according to Child-Pugh classification). Moreover, there was a higher rate of death: 30% in the infected group versus 5.55% in the group presenting no bacterial infections (p < 0.0001). The authors concluded that malnutrition is an important factor which may lead to the onset of bacterial infections, causing high death rate. Dietetic measures that may restore the nutritional status should be implemented early.

Nutritional intervention in the alimentary tract diseases
Szczygiel B.; Ciesielski L.; Dzieniszewski J.; Grzymislawski M.; Hryniewiecki L.; Ksiazyk J.; Pertkiewicz M.; Wojcik Z.
Prof. B. Szczygiel, Kat. Klin. Chir. Gastroenterol. AM, ul. Banacha 1a, 02-097 Warszawa Poland
Gastroenterologia Polska (Poland), 1997, 4/5 (501-515)

Introducing of artificial nutrition in to the daily practice of clinical medicine significantly improved the results of treatment of many diseases in which malnutrition is one of the most important signs worsening the course of disease and results of treatment. During the 7th Congress of the Polish Society of Gastroenterology which was held in Poznan in September 1996 the Round Table Conference was organized, during which Polish experts in clinical nutrition presented their experience in the nutritional treatment of: inflammatory bowel disease (IBD), chronic pancreatitis, severe acute pancreatitis, cirrhosis of the liver, cancer patients, including patients on chemo- and rtg therapy . Undernutrition is common in patients with IBD. When adequate oral nutrition cannot be taken, enteral chemically defined diets or total parenteral nutrition (TPN) allow repletion, however the duration of remission is unpredictable. According to own experience the response in the individual patient is variable. However, use of nutritional therapy represents major advance in the management of IBD. Patients with chronic pancreatitis are chronically malnourished, many have a history of alcoholism, drug addiction and associated personality disorders. To reduce the postoperative complications often seen in those patients we prepare the patient by means of parenteral, or enteral nutrition with the tip of the feeding tube below ligament of Treitz, for up to 12 days before the operation. After operation TPN is continued or started until there is a clinical evidence of normal GI function. Most patients with acute pancreatitis do not require nutritional support. Symptoms will usually subside over a period of 5 to 8 days, allowing resumption of oral intake of nutrients. If not, TPN should be introduced to improve depleted nutritional status and keep the GI tract and the exocrine pancreas in the state of rest. Although there is general agreement that TPN should be instituted in patients with severe acute pancreatitis, the administration of lipids in these patients is still controversial. Our experience indicates that provision of lipid - associated TPN to patients with severe acute pancreatitis can be done safely, is well tolerated, improves nutritional status and significantly reduces morbidity and mortality. It has long been known that patients with liver disease usually have varying degrees of malnutrition which, in turn, favors the progress of the disease. In advanced liver disease nutritional management via the parenteral or enteral route becomes essential because an adequate oral intake is not possible. Due to disturbed amino-acid metabolism solutions enriched with branched-chain amino-acids were introduced by Fischer and associates in 1976. In advanced liver disease hepatic encephalopathy often develops with extremely poor prognosis. Specific chemically defined enteral diets or parenteral solutions with hypertonic glucose are given providing 80 g/day of protein and improving mental and nutritional status. Cachexia is particularly common in patients with cancers of the esophagus and stomach. About 50% of these patients will have lost 10-15% of body weight due to a combination of anorexia and the increased metabolic demand of the growing tumor. The magnitude of the nutritional deficit makes it obvious that a few days of nutritional replenishment cannot return the patient to an anabolic state. On the other hand, TPN in the majority of responding patients brought improvement in nutritional status after 14 days of intensive therapy . Delay of surgery for two weeks (during the preparation for surgery) will not significantly increase the risk of tumor spread but will reduce the frequency of complications.

Disruption of the diurnal rhythm of plasma melatonin in liver cirrhosis
Steindl P.E.; Finn B.; Bendok B.; Rothke S.; Zee P.C.; Blei A.T.
Dr. P.E. Steindl, Universitatsklinik Innere Med IV, Abteilung Gastroenterologie/Hepatol., Wahringer Gurtel 18-20, A-1090 Wien Austria
Wiener Klinische Wochenschrift (Austria), 1997, 109/18 (741-746)

Objective: To assess the 24 hr plasma melatonin profile as a marker of the output rhythm from the circadian clock and to study sleep diaries as reflection of subjective sleep quality in patients with liver cirrhosis .

Design: Prospective cohort study. Patients: A total of 14 subjects, 7 non-alcoholic cirrhotics and 7 age-, sex-, and educationally-matched controls. Exclusion criteria were factors that could affect melatonin levels (intercontinental travel, shift work, therapy with betablockers or corticosteroids).

Measurements: Plasma melatonin was measured every 30 min for 24 hr by radioimmuno assay and sleep recordings by polysomnography. Neuropsychological testing included visual reaction time, Trail-making test A and B and the Digit Symbol Test. Sleep diaries were kept for the week prior to admission.

Results: Time of onset of melatonin rise was displaced from 19:50 plus or minus 26 min in the controls to 21:30 plus or minus 13 min (p=0.013) in patients with liver cirrhosis . The time of peak melatonin levels was consistently and significantly delayed from 00:36 plus or minus 33 min in controls to 5:36 plus or minus 29 min (p < 0.001) in patients. Cirrhotic subjects showed markedly elevated melatonin levels during daytime, when melatonin is normally absent. Polysomnographic tracings showed no differences in patients and controls, but sleep diaries indicated more frequent nocturnal awakenings (p = 0.05) and daytime naps.

Conclusions: A marked alteration of plasma melatonin rhythm is found in cirrhotic patients with subclinical hepatic encephalopathy. This disruption may reflect changes in the output of the circadian pacemaker located in the suprachiasmatic nucleus (SCN) of the hypothalamus. It is possible that some of the metabolic disturbances that lead to hepatic encephalopathy may also alter the function of the biological 'clock'.

Hulagu S.; Celebi A.
Dr. S. Hulagu, Gastroenteroloji Bilim Dali, Ic Hastaliklari Anabilim Dali, Tip Fakultesi, Kocaeli Universitesi, Kocaeli Turkey
Sendrom (Turkey), 1997, 9/8 (20-27)

The basic effect of antacids which have been used approximately for 2000 years is, the neutralization of hydrochloric acid which secrete to gastric lumen. Antacids can decrease the absorption of some medicines. Antacids may also contain considerable sodium which can cause sodium overload susceptible patients (cirrhosis, chronic renal failure, heart failure). Also antacids with menthol can decrease the lower esophageal sphincter pressure. Antacids can be used in situations, for symptomatic feeling reasons to patients who are complaining about dyspepsia, to patients who has peptic ulcer with H2 receptor antagonists and in terms of continuance treatment, to stop risks of long term inhibit to acid secretion, by itself.

Zinc regulates DNA synthesis and IL-2, IL-6, and IL-10 production of PWM-stimulated PBMC and normalizes the periphere cytokine concentration in chronic liver disease
Reinhold D.; Ansorge S.; Grungreiff K.
Dr. K. Grungreiff, Heydeckstr. 9, D-39104 Magdeburg Germany
Journal of Trace Elements in Experimental Medicine (USA), 1997, 10/1 (19-27)

Zinc (zinc ions and/or chelated zinc) plays an important role in the maintenance of immune function. Patients with chronic liver disease, particularly liver cirrhosis, frequently have endotoxemia, increased serum concentrations of cytokines, e.g., interleukin-6 (IL-6), and reduced serum zinc levels. The aim of the present study was to investigate the effects of zinc (ZnCl2, ZnO, ZnSO4) on DNA synthesis and cytokine production (IL-2, IL-6, IL-10) in pokeweed mitogen (PWM)-stimulated peripheral blood mononuclear cells (PBMC). In addition, we examined the effect of long-term zinc supplementation (zinc-hydrogen-aspartate; UNIZINK 50; 3 x 1 = 29.76 mg/day) on IL-6 and IL-10 serum levels in patients with chronic liver disease (n = 16), all with reduced serum zinc levels. It could be shown that zinc concentrations up to 0.1 mM stimulate DNA synthesis and cytokine production by PWM-stimulated PBMC, whereas higher concentrations (0.2-0.4 mM) have a strongly inhibitory effect. Zinc concentrations exceeding 0.5 mM were found to have a toxic effect on these immune cells. Interestingly, in most patients with chronic liver disease (n = 10), zinc supplementation decreased IL-6, and to a lesser extent, IL-10 serum levels, and normalized the serum zinc concentrations. We conclude that zinc plays a regulatory role in DNA synthesis and cytokine production by PBMC. The critical zinc concentration for immune cells lies in the range of 0.5 mM, which is equivalent to a daily dose of similar45 mg zinc salt. Furthermore, zinc supplementation in chronic liver disease with reduced serum zinc levels appears to normalize IL-6 and IL-10 production.

Nutritional considerations and management of the child with liver disease
Novy M.A.; Schwarz K.B.
Nutrition (USA), 1997, 13/3 (177-184)

Nutritional management of the infant and child with liver disease is highly dependent upon the type of liver disease. Acute liver disease, such as that secondary to viral hepatitis, requires no specific nutritional therapy with the exception that branched-chain amino acid supplements may be indicated in the management of hepatic encephalopathy. Nutritional management of the child with chronic liver disease depends upon whether or not cholestasis is present, since in that condition, large amounts of fat- soluble vitamin supplements and medium-chain triglycerides are usually required for optimum growth. However, anicteric cirrhotic liver disease also presents nutritional challenges because of hypermetabolism, enteropathy, and increased protein oxidation. Certain inborn errors of metabolism that result in liver disease (including galactosemia, hepatorenal tyrosinemia, hereditary fructose intolerance, and Wilson's disease) have specific nutritional requirements. And, finally, the advent of pediatric liver transplantation has placed new emphasis on the importance of optimum nutritional management of the child with chronic liver disease, since improvement of nutritional status in the pretransplant period maximizes success of the transplant. This review will focus on the pathogenesis of malnutrition in childhood liver disease and will provide recommendations for nutritional assessment and monitoring as well as nutritional management of cholestatic liver disease, anicteric cirrhotic liver disease, and the inborn errors of metabolism enumerated above. Specific recommendations for nutritional management of the child awaiting liver transplantation will be provided.

Effects of extra-carbohydrate supplementation in the late evening on energy expenditure and substrate oxidation in patients with liver cirrhosis
Chang W.-K.; Chao Y.-C.; Tang H.-S.; Lang H.-F.; Hsu C.-T.
Journal of Parenteral and Enteral Nutrition (USA), 1997, 21/2 (96-99)

Background: The purpose of this study was to demonstrate the effects of extra-carbohydrate supplementation before bedtime on energy metabolism and substrate oxidation in patients with live cirrhosis .

Methods: Sixteen cirrhotic patients and eight control subjects were included in this study. To compare the effect of energy metabolism and substrate oxidation with or without a bedtime snack, indirect calorimetry was assessed at 7 to 8 AM after overnight fasting, following either dinner (6 PM) or a bedtime snack (11 PM) the evening before. The bedtime snack contained about 50 g of carbohydrate. The energy expenditure and substrate oxidation were calculated from the indirect calorimetry measurement and 24-hour urinary nitrogen excretion.

Results: In those who fasted since dinner, the respiratory quotient (RQ) was significantly lower in cirrhotic patients than in control subjects. Also, the energy utilized by cirrhotic patients was derived primarily from fat oxidation (58%), whereas the main energy source for controls was carbohydrate (55%). An extra-carbohydrate supplement before bedtime did not influence the indirect calorimetry measurement in the controls, but there were significant increases in both RQ and carbon dioxide production (VCO2) in cirrhotic patients. The extra-carbohydrate supplementation did not significantly change the absolute resting energy expenditure utilization in control subjects; however, the utilization of carbohydrate significantly increased with a decrease in fat and protein oxidation in the cirrhotic patients.

Conclusions: These preliminary data suggest that extra-carbohydrate supplementation before bedtime can shorten nocturnal fasting with a more economic fuel utilization and effectively diminish fat and protein oxidation in cirrhotic patients.

[Antioxidants in the treatment of cholelithiasis patients].
[Article in Russian]
Vagner EA, Khlebnikov VV, Terekhina NA, Palatova LF
Vestn Khir Im I I Grek 1997;156(1):36-9

Results of examination and treatment of 157 patients with cholelithiasis against the background of a liver pathology were summed up. The antioxidant system in such patients was studied. The degree of a decrease of catalase activity in the liver and blood serum as well as the ascorbic acid content were found to depend on the liver state of patients with cholelithiasis. Greatest changes were found in patients with cirrhosis of the liver and chronic active hepatitis. The method of complex treatment of cholelithiasis patients with non-enzymatic antioxidants alpha-tocopherol and ascorbic acid is proposed. Activity of organ specific liver enzymes urokaninase and histidase was used for the estimation of treatment efficiency. Complex administration of ascorbic acid and alpha-tocopherol was shown to improve the liver function in patients operated upon for cholelithiasis.

Click to go to the Life Extension Foundation Web Site

All Contents Copyright © 1995-2000 By The Life Extension Foundation