Note: This page contains sample records for the topic ccl4-induced liver cirrhosis from Science.gov.
While these samples are representative of the content of Science.gov,
they are not comprehensive nor are they the most current set.
We encourage you to perform a real-time search of Science.gov
to obtain the most current and comprehensive results.
Last update: August 15, 2014.
1

Mononuclear phagocyte system responsiveness in CCl4-induced liver cirrhosis.  

PubMed Central

In rats with CCl4-induced liver cirrhosis, a twofold decrease of blood clearance rate and a fourfold reduction in number of Kupffer cells taking up colloidal carbon particles has been demonstrated. Zymosan stimulation does not lead to granuloma-like structures in the liver of CCl4-cirrhotic rats. In cirrhotic rats, unlike controls, the cathepsin D activity of liver tissue is very little increased by zymosan treatment and there is virtually no increase in collagenolytic activity. The increase in PGE content in cirrhotic rat liver after prodigiosan stimulation was 2.5 times less than in stimulated control animals. In cirrhotic rats, the IL-1 producing capacity of blood monocytes in vitro in response to lipopolysaccharide drops almost fivefold. The total count of bone marrow-derived myeloid colonies in cirrhotic zymosan-stimulated animals was reduced by 1.5-fold whereas in control animals zymosan induced a 1.8-fold increase in the number of myeloid colonies. The number, uptake and nitroblue tetrazolium-reducing capacities of lung, spleen, peritoneal and bone marrow macrophages in animals with liver cirrhosis were only slightly increased in response to zymosan as compared to control animals. The low response of extrahepatic macrophages to stimuli in cirrhotic animals is thought to be due to their premobilization during the development of cirrhosis. Images Figure 2

Mayanski, D. N.; Schwartz, Y. S.; Kutina, S. N.; Zubakhin, A. A.; Mayanskaya, N. N.; Tsyrendorjiev, D. D.

1993-01-01

2

Mononuclear phagocyte system responsiveness in CCl4-induced liver cirrhosis.  

PubMed

In rats with CCl4-induced liver cirrhosis, a twofold decrease of blood clearance rate and a fourfold reduction in number of Kupffer cells taking up colloidal carbon particles has been demonstrated. Zymosan stimulation does not lead to granuloma-like structures in the liver of CCl4-cirrhotic rats. In cirrhotic rats, unlike controls, the cathepsin D activity of liver tissue is very little increased by zymosan treatment and there is virtually no increase in collagenolytic activity. The increase in PGE content in cirrhotic rat liver after prodigiosan stimulation was 2.5 times less than in stimulated control animals. In cirrhotic rats, the IL-1 producing capacity of blood monocytes in vitro in response to lipopolysaccharide drops almost fivefold. The total count of bone marrow-derived myeloid colonies in cirrhotic zymosan-stimulated animals was reduced by 1.5-fold whereas in control animals zymosan induced a 1.8-fold increase in the number of myeloid colonies. The number, uptake and nitroblue tetrazolium-reducing capacities of lung, spleen, peritoneal and bone marrow macrophages in animals with liver cirrhosis were only slightly increased in response to zymosan as compared to control animals. The low response of extrahepatic macrophages to stimuli in cirrhotic animals is thought to be due to their premobilization during the development of cirrhosis. PMID:8334074

Mayanski, D N; Schwartz, Y S; Kutina, S N; Zubakhin, A A; Mayanskaya, N N; Tsyrendorjiev, D D

1993-06-01

3

Prevention of CCL4-induced liver cirrhosis by silymarin.  

PubMed

The efficacy of silymarin treatment in preventing biochemical and histological alterations in CCL4-induced liver cirrhosis in rats was studied. Four groups of rats were treated with: (1) CCL4; (2) mineral oil; (3) CCL4 + silymarin; and (4) silymarin. All animals were sacrificed 72 h after the end of treatments. The activities of alkaline phosphatase (alk. phosp.), gamma-glutamyl transpeptidase (GGTP), glutamic pyruvic transaminase (GPT) and glucose-6-phosphatase (G6Pase), and bilirubin content were determined in serum. Na+, K+-ATPase and Ca++-ATPase activities were measured in isolated plasma membranes. Lipoperoxidation, triglycerides (TG), and glycogen contents were also measured in liver homogenates. Liver cirrhosis was evidenced by significant increases in liver collagen, lipoperoxidation, serum activities of alk. phosp., GGTP, GPT, G6Pase, bilirubin content, and liver TG. Activities of ATPases determined in plasma membranes were significantly reduced, as was liver glycogen content. Silymarin cotreatment (50 mg/kg b.wt) completely prevented all the changes observed in CCL4-cirrhotic rats, except for liver collagen content which was reduced only 30% as compared to CCL4-cirrhotic rats. Silymarin protection can be attributed to the agent's antioxidant and membrane-stabilizing actions. PMID:2548940

Mourelle, M; Muriel, P; Favari, L; Franco, T

1989-01-01

4

Cimetidine prevents and partially reverses CCl4-induced liver cirrhosis.  

PubMed

Liver injury produced by CCl4 depends on its metabolism by the liver cytochrome P450 enzyme system to a highly reactive intermediate (CCl3.). Cimetidine impairs cytochrome P450 and stimulates regenerative processes acting on DNA synthesis. This work was performed to investigate whether cimetidine may prevent CCl4-induced liver cirrhosis. Male Wistar rats were used: animals in group 1 received CCl4 (0.04 g per 100 g, i.p.) three times a week for 8 weeks; group 2 was treated with CCl4 plus cimetidine (120 mg kg-1, p.o.) three times a week for 8 weeks; group 3 received CCl4 for 8 weeks and then cimetidine for 4 weeks. Alkaline phosphatase, gamma-glutamyl transpeptidase (gamma-GTP) and alanine aminotransferase (ALT) activities, as well as protein and bilirubin, were measured in serum; collagen and lipoperoxidation were quantified in liver. Intoxication with CCl4 increased (P < 0.05) serum activities of alkaline phosphatase, gamma-GTP and ALT, and bilirubin concentration; liver collagen and lipoperoxidation were also increased. Cimetidine treatment prevented or reverted the increases in the three enzyme activities and in bilirubin content and the fall in proteins. It is worth noting that cimetidine co-treatment completely prevented both the increase in collagen content and the lipid peroxidation. The protective effect of cimetidine can be attributed to a reduction in cytochrome P450. However, it could also stimulate regenerative processes. PMID:7913103

Mera, E; Muriel, P; Castillo, C; Mourelle, M

1994-01-01

5

Thymus quantitative morphological changes during CCl4-induced liver cirrhosis.  

PubMed

The dynamics of the thymus cell densities was studied during CCl4-induced cirrhogenic hepatopathy. The results show that all thymus compartments take part in immune phenomena occurring in the whole lymphatic system. The maximal intensity of thymus participation is attained in precirrhosis and evolutive cirrhosis. Within the cortical zone, the cell density pyroninophilia and blast-transformed cells increase during the first two months. After two months, there is a decrease of the pyroninophilic elements within the cortical zone, concomitantly with their increase at the medullary level, thus suggesting a migration process of the cells, which change the cortical-medullary ratio. PMID:151224

Chirculescu, A R; Laky, D

1978-01-01

6

Herbal Supplement Ameliorates Cardiac Hypertrophy in Rats with CCl4-Induced Liver Cirrhosis  

PubMed Central

We used the carbon tetrachloride (CCl4) induced liver cirrhosis model to test the molecular mechanism of action involved in cirrhosis-associated cardiac hypertrophy and the effectiveness of Ocimum gratissimum extract (OGE) and silymarin against cardiac hypertrophy. We treated male wistar rats with CCl4 and either OGE (0.02?g/kg B.W. or 0.04?g/kg B.W.) or silymarin (0.2?g/kg B.W.). Cardiac eccentric hypertrophy was induced by CCl4 along with cirrhosis and increased expression of cardiac hypertrophy related genes NFAT, TAGA4, and NBP, and the interleukin-6 (IL-6) signaling pathway related genes MEK5, ERK5, JAK, and STAT3. OGE or silymarin co-treatment attenuated CCl4-induced cardiac abnormalities, and lowered expression of genes which were elevated by this hepatotoxin. Our results suggest that the IL-6 signaling pathway may be related to CCl4-induced cardiac hypertrophy. OGE and silymarin were able to lower liver fibrosis, which reduces the chance of cardiac hypertrophy perhaps by lowering the expressions of IL-6 signaling pathway related genes. We conclude that treatment of cirrhosis using herbal supplements is a viable option for protecting cardiac tissues against cirrhosis-related cardiac hypertrophy.

Li, Ping-Chun; Chiu, Yung-Wei; Lin, Yueh-Min; Day, Cecilia Hsuan; Hwang, Guang-Yuh; Pai, Peiying; Tsai, Fuu-Jen; Tsai, Chang-Hai; Kuo, Yu-Chun; Chang, Hsiao-Chuan; Liu, Jer-Yuh; Huang, Chih-Yang

2012-01-01

7

Low-level laser therapy ameliorates CCl4-induced liver cirrhosis in rats.  

PubMed

This study investigated the effects of low-level laser therapy (LLLT) in the liver function, structure and inflammation in a experimental model of carbon tetrachloride (CCl(4))-induced liver cirrhosis. Wistar rats were divided into Control, LLLT, CCl(4) and CCl(4) +LLLT groups. CCl(4) groups received CCl(4) (0.4 g kg(-1); i.p.), three times a week, for 12 weeks. A 830 nm LLLT was performed with a continuous wave, 35 mW, 2.5 J cm(-2) per point, applied to four points of the liver (right and left upper and lower extremities, in the four lobes of the liver) for 2 weeks. Liver structure and inflammation (cirrhotic areas, collagen deposition, inflammation, density of Kupffer and hepatic stellate cells) and function (aspartate aminotransferase, alkaline phosphatase, gamma glutamyltransferase, lactate dehydrogenase, total proteins and globulins) were evaluated. LLLT significantly reduced CCl(4)-increased aspartate aminotransferase (P < 0.001), alkaline phosphatase (P < 0.001), gamma-glutamyl transferase (P < 0.001) and lactate dehydrogenase (P < 0.01) activity, as well as total proteins (P < 0.05) and globulins (P < 0.01). LLLT also reduced the number of cirrhotic areas, the collagen accumulation and the hepatic inflammatory infiltrate. Of note, LLLT reduced CCl(4)-increased number of Kupffer cells (P < 0.05) and hepatic stellate cells (P < 0.05). We conclude that LLLT presents beneficial effects on liver function and structure in an experimental model of CCl(4)-induced cirrhosis. PMID:22827550

Oliveira-Junior, Manoel Carneiro; Monteiro, Aldaíza Salomão; Leal-Junior, Ernesto César Pinto; Munin, Egberto; Osório, Rodrigo Aléxis Lazo; Ribeiro, Wellington; Vieira, Rodolfo Paula

2013-01-01

8

Acute phase reactants enhance CCl4 induced liver cirrhosis in the rat.  

PubMed

High levels of acute phase proteins (acute phase reactants, APR) suppress acute inflammatory reactions in the rat. As many APR have antiprotease properties, including an anticollagenase activity, the effect of APR on the development of CCl4-induced liver fibrosis was investigated in rats. APR were provoked by repeated injections of epinephrine, inducing a broad spectrum of APR. This reaction can be monitored measuring alpha 2-macroglobulin levels in the rat (alpha 2-macrofetoprotein, alpha M FP). This protein was found to inhibit both acute galactosamine hepatitis and acute CCl4-induced liver toxicity. The animals with high levels of APR at the start of CCl4 treatment developed a more severe degree of fibrosis and cirrhosis than the control group in which no acute phase reaction was induced. Epinephrine alone had no such effects. Additionally, the APR positive group showed an initially lower degree of hepatocellular damage when compared to control animals. This uncoupling of liver cell damage and subsequent fibrosis may demonstrate that higher levels of APR might be important as to the development of cirrhosis, possibly based on the anticollagenase activity of these proteins. PMID:3699134

van Gool, J; van Vugt, H; de Nie, I

1986-04-01

9

Depressed function of Kupffer cells in rats with CCl4-induced liver cirrhosis.  

PubMed

In the present study, the Kupffer cell function of rats with CCl4-induced liver cirrhosis was tested by analyzing the changes in the host defense system. In rats without liver cirrhosis injected with CCl4 for 3 weeks concomitant with the high opsonic activity the endocytic index was significantly increased. Rats treated for 9 and 13 weeks developed cirrhosis, and their endocytic indices were not increased despite the rise in their opsonic activity. Particularly, the endocytic index of 13-week-treated rats with advanced liver cirrhosis was significantly lower than that of the other groups. The organic distribution of 51Cr-endotoxin injected intravenously exhibited characteristic changes in 9-week- and 13-week-treated rats: decreased hepatic uptake and increased splenic uptake. In contrast, pulmonary uptake was increased in all CCl4-treated rats. The superoxide production by Kupffer cells from 13-week-treated rats was greatly reduced, accompanied by the decreased superoxide dismutase activity of liver homogenate. Thus, results of this study suggest that Kupffer cell dysfunction is one of the main factors affecting host defenses in liver cirrhosis. PMID:2164243

Arii, S; Monden, K; Itai, S; Sasaoki, T; Adachi, Y; Funaki, N; Higashitsuji, H; Tobe, T

1990-01-01

10

Oxidative stress modulation by Rosmarinus officinalis in CCl4-induced liver cirrhosis.  

PubMed

Rosmarinus officinalis (Lamiaceae) possesses antioxidant activity and hepatoprotective effects, and so may provide a possible therapeutic alternative for chronic liver disease. The effect produced by a methanolic extract of Rosmarinus officinalis on CCl(4)-induced liver cirrhosis in rats was investigated using both prevention and reversion models. Over the course of the development of cirrhosis, the increased enzymatic activities of gamma-glutamyl transpeptidase and alanine aminotransferase, and the rise in bilirubin levels caused by CCl(4) administration, were prevented by Rosmarinus officinalis co-administration. When the cirrhosis by oxidative stress was evaluated as an increase on liver lipoperoxidation, total lipid peroxides, nitric oxide in serum, and loss of erythrocyte plasma membrane stability, R. officinalis was shown to prevent such alterations. On cirrhotic animals treated with CCl(4), histological studies showed massive necrosis, periportal inflammation and fibrosis which were modified by R. officinalis. These benefits on experimental cirrhosis suggest a potential therapeutic use for R. officinalis as an alternative for liver cirrhosis. PMID:19827016

Gutiérrez, Rosalinda; Alvarado, José L; Presno, Manuel; Pérez-Veyna, Oscar; Serrano, Carmen J; Yahuaca, Patricia

2010-04-01

11

Erythrocyte defects precede the onset of CCl4-induced liver cirrhosis. Protection by silymarin.  

PubMed

The time-course of some alterations produced in erythrocytes during the onset of CCl4-induced liver cirrhosis was studied in rats. Erythrocyte membranes were isolated to measure Na+, K+ and Ca+2-ATPase activities. Membrane lipid composition was determined to calculate the cholesterol/phospholipid ratio and serum samples were used to measure lipoperoxidation. The results demonstrated that as CCl4 treatment progressed, serum lipoperoxidation and membrane cholesterol/phospholipid ratio increased while ATPase activities decreased. ATPase activities in red blood cells of cirrhotic rats were 50% below normal values but those determined in cells of animals treated simultaneously with CCl4 + silymarin were significantly improved. Silymarin co-treatment also preserved the normal cholesterol/phospholipid ratio in the membranes. Our results suggest that the measure of ATPase activities in erythrocytes membranes could be a simple, safe and useful early marker of liver damage and also valuable to test the effectiveness of a given drug therapy. PMID:1847733

Mourelle, M; Franco, M T

1991-01-01

12

Chemical mediator release and surface marker expression of hepatic macrophages in rats with CCl4-induced liver cirrhosis.  

PubMed

The present study was performed to analyze possible functional alterations of hepatic macrophages (HM phi) in rats with carbon tetrachloride (CCl4)-induced liver cirrhosis. HM phi from rats injected with CCl4 for 13 weeks and cultured for 24 hours released less than normal amounts of prostaglandin E2 (PGE2) and tumor necrosis factor (TNF) and very large amounts of interleukin-1 (IL-1). In rats injected with CCl4 for 9 weeks, only PGE2 production was reduced. Interleukin-2 receptor (IL-2R), Ia antigen and asialo GM1 antigen expressions on HM phi from both the 9- and 13-week groups were significantly decreased. IL-2R and Ia antigen expressions showed larger decreases in the 13-week group. Thus, it is concluded that HM phi derived from CCl4-induced cirrhotic livers show a functional alteration in the release of cytokines (except for IL-1) and a decrease in surface marker expression, as cirrhosis advances. These results should provide a basis for further investigation into the host-compromised status in the presence of liver cirrhosis. PMID:8208064

Funaki, N; Arii, S; Monden, K; Sasaoki, T; Adachi, Y; Higashitsuji, H; Tanaka, J; Imamura, M

1994-01-01

13

Malotilate completely inhibits CCl4-induced liver cirrhosis in rats: biochemical and morphological analysis.  

PubMed

Malotilate, diisopropyl 1,3-dithiol-2-ylidenemalonate, is a relatively recently synthesized hepatotrophic chemical substance. Its inhibitory effect on rat liver cirrhosis induced by carbon tetrachloride (CCl4) was biochemically and morphologically investigated for 10 weeks, since this chemical had been reported to suppress liver damage caused by CCl4 or in vitro collagenogenesis of human fibroblasts. Concomitant administration of malotilate with CCl4 completely suppressed liver cell necrosis and markedly inhibited fatty change of hepatocytes in the first three weeks of the experiment. During the six to ten weeks of the experimental period, liver cirrhosis was perfectly inhibited by malotilate. Previously established liver cirrhosis, however, could not be normalized by malotilate treatment. Precise mechanism of the inhibitory effect of malotilate on liver cirrhosis is not elucidated, but this substance is clearly effective for preventing liver cell damage and/or liver cirrhosis caused by CCl4. PMID:1292970

Suzuki, T

1992-06-01

14

Defect of sinusoidal Fc receptors and immune complex uptake in CCl4-induced liver cirrhosis in rats.  

PubMed

The purpose of this paper is to provide a histopathologic basis for abnormalities in immune-complex clearance in liver disease. Fc receptors in CCl4-induced liver cirrhosis in rats were studied by applying peroxidase-antiperoxidase immunoglobulin G complex as a ligand to the frozen sections. Intravenous injection of bovine serum albumin-antibovine serum albumin complexes or colloidal carbon was combined with histological staining for endogenous peroxidase, fibronectin, laminin, or a lectin, Bandeiraea simplicifolia agglutinin I. In the cirrhotic process, sinusoidal Fc receptors showed a weakened reactivity to the ligand with focal absence, and the length of the Fc receptor-positive portion of the sinusoids in unit area decreased to about 50% of the normal value in the advanced cirrhosis. Fibronectin and the lectin showed the presence of sinusoids where Fc receptors were absent. The endothelium in Fc receptor-negative areas did not take up either immune complexes or carbon, and Kupffer cells were absent in these areas. A disturbed immune-complex metabolism was thus suggested to occur in association with the defect of sinusoidal Fc receptors in liver cirrhosis. These abnormalities appeared to not be directly related to perisinusoidal laminin deposition, i.e., capillarization of the sinusoid. PMID:2344926

Muro, H; Shirasawa, H; Kosugi, I; Ito, I

1990-07-01

15

CCL4-induced liver cirrhosis and hepatocellular carcinoma in rats: relationship to plasma zinc, copper and estradiol levels.  

PubMed

A number of biochemical events accompany the development of chronic liver disease and its evolution into hepatic cancer. Low plasma zinc and high plasma copper levels have been observed in individuals with advanced hepatocellular liver disease. Moreover, many investigators have demonstrated an increase in serum estradiol levels in individuals with chronic liver disease and hepatocellular carcinoma (HCC). In the present study, the relationship between these biochemical events and HCC was investigated in an animal model. Specifically, carbon tetrachloride (CCL4) was administered intragastrically to 20 female Sprague Dawley rats for 30 weeks. All 20 animals developed cirrhosis. Six (30%) developed HCC. Significantly higher serum estradiol, zinc and copper levels were observed in the rats developing HCC as compared with those with cirrhosis alone (P < or = 0.05, 0.01 and 0.001, respectively). A trend toward increased serum levels of progesterone, ALT and total bilirubin (0.1 > or = P < or = 0.05) was found in the animals developing HCC. No differences in serum testosterone and alkaline phosphatase levels were noted between animals with and without HCC. These studies demonstrate that in animals with experimental CCL4-induced cirrhosis and HCC serum levels of estradiol, zinc and copper are increased, as is the case in man. PMID:7959573

Frezza, E E; Gerunda, G E; Farinati, F; DeMaria, N; Galligioni, A; Plebani, F; Giacomin, A; Van Thiel, D H

1994-08-01

16

The gene expression of adrenomedullin, calcitonin-receptor-like receptor and receptor activity modifying proteins (RAMPs) in CCl4-induced rat liver cirrhosis.  

PubMed

This study was undertaken to determine AM expression in carbon tetrachloride (CCl4)-induced liver cirrhosis developed with peritoneal ascites. Sprague-Dawley rats received subcutaneous injections of CCl4 twice weekly in olive oil (1:1, 0.3 ml per kg body weight) for 6 or 12 weeks until ascites developed, or saline in olive oil as control. At 6 weeks, fibrosis developed and at 12 weeks cirrhosis developed with ascites formation. At both 6 and 12 weeks, increases in plasma renin and AM were evident, as was the gene expression of AM. At 12 weeks after CCl4 injection, the gene expression of calcitonin-like-receptor (CRLR) and receptor activity modifying proteins (RAMP1, RAMP2 and RAMP3) were all elevated when compared to the control. The results suggest that liver cirrhosis increases mRNA expressions of AM, CRLR and RAMP1, RAMP2 and RAMP3 and that the increase in AM gene expression precedes the development of cirrhosis. The increase in AM synthesis as reflected by an increase in AM gene expression, together with a lack of increase in AM peptide at both 6 and 12 weeks may suggest an elevation of AM release. Given the potent vasodilatory action of AM, the increase in the synthesis and release of AM in the cirrhotic liver may also contribute to peripheral vasodilatation in liver cirrhosis. PMID:16713642

Hwang, Isabel Shui Shan; Tang, Fai; Leung, Pauline P; Li, Yuk Yin; Fan, Sheung Tat; Luk, John Moon Ching

2006-07-15

17

The bradykinin B2 receptor antagonist Icatibant (HOE 140) corrects avid Na+ retention in rats with CCl4-induced liver cirrhosis: possible role of enhanced microvascular leakage.  

PubMed

Avid Na+ retention is a hallmark of liver cirrhosis. The aim of this study was to investigate whether and how bradykinin is involved in Na+ retention in rats with CCl4-induced liver cirrhosis. To this end the bradykinin B2 receptor antagonist Icatibant (HOE 140) was used. On one hand, bradykinin has a renal natriuretic action. On the other hand, bradykinin is a potent mediator of both vasodilation and microvascular leakage. Both vascular mechanisms, which are reported for cirrhosis, could cause vascular underfilling and Na+ retention by activating the renin-angiotensin-aldosterone system. Icatibant normalised Na+ retention and reduced the hyperactivity of the renin-angiotensin-aldosterone system, suggesting a bradykinin-induced vascular disturbance. Icatibant had no significant effect on the mild hypotension which developed with CCl4 treatment. However, there was indirect evidence for enhanced microvascular leakage that was strongly inhibited by Icatibant. Our experimental results demonstrate that bradykinin is a key mediator of Na+ retention in liver cirrhosis and suggest that a bradykinin-induced increase in microvascular leakage is mainly responsible. PMID:9389380

Wirth, K J; Bickel, M; Hropot, M; Günzler, V; Heitsch, H; Ruppert, D; Schölkens, B A

1997-10-15

18

Glutathione in plasma, liver, and kidney in the development of CCL 4 -induced cirrhosis of the rat  

Microsoft Academic Search

Plasma glutathione is markedly decreased in human cirrhosis of the liver. This decrease is said to be caused by reduced concentrations\\u000a of liver glutathione. However, several studies on hepatic glutathione have revealed its concentrations to be unchanged, decreased,\\u000a or even elevated. To test these inconsistencies we investigated the glutathione status of plasma, liver, and kidney in rats\\u000a chronically exposed to

E. Purucker; W. Wernze; G. Krandik

1995-01-01

19

Effect of increased hepatic platelet activating factor and its receptor portal hypertension in CCl4-induced liver cirrhosis  

PubMed Central

AIM: To evaluate the changes in hepatic platelet activating factor (PAF) and its receptors and their effect on portal pressure of cirrhotic rats induced by CCl4. METHODS: A model of liver cirrhosis was replicated in rats by intra-peritoneal injection of CCl4 for 8 wk. We determined the effect of hepatic PAF and its receptor level on portal and arterial pressure by EIA, saturation binding and RT-PCR technique. RESULTS: Compared to control rats, cirrhotic rats had higher hepatic PAF levels and output as well as higher plasma PAF levels (P?cirrhosis, and the increased release of PAF into the circulation has impacts on the systemic hemodynamics.

Yang, Yong-Ping; Ma, Xue-Mei; Wang, Chun-Ping; Han, Jun; Lu, Yin-Ying; Xiang, Yi; Su, Shu-Hui; Feng, Yong-Yi

2006-01-01

20

[A quantitative study on alpha-1 adrenergic receptor in the liver of Wistar rats during the process of CCl4-induced hepatic cirrhosis].  

PubMed

In this study, radioligand binding analysis was used to quantitatively measure the concentration and affinity of alpha-1 adrenergic receptor in the liver of Wistar rats during the process of CCl4-induced liver cirrhosis. It was found that compared with normal controls, the maximal binding capacity (Bmax) of alpha-1 adrenergic receptor in the liver of 13 pre-cirrhotic rats decreased from 132.8 +/- 25.0fmol/mg to 96.9 +/-20.8fmol/mg of protein (P < 0.01) with increased dissociation constant (Kd, from 0.1633 +/- 0.0322nM to 0.3079 +/- 0.0786nM, P < 0.01). The Bmax in 20 cirrhotic rats decreased significantly from 132.8 +/- 25.0fmol/mg to 71.9 +/- 17.7fmol/mg of protein (P < 0.01), while Kd values increased from 0.1633 +/- 0.0322nM to 0.4012 +/- 0.0965nM (P < 0.01). These findings indicate that the decrease of binding capacity and affinity of alpha adrenergic receptor may play a role in the disturbances of metabolism of catecholamine often seen in some cirrhotic patients and have implications in the pathogenesis of portal hypertension. PMID:8731902

Zhang, Y; Leng, X; Wei, Y

1995-10-01

21

Prevention of CCl4-induced liver cirrhosis by ribbon antisense to transforming growth factor-beta1.  

PubMed

Transforming growth factor-beta1 (TGF-beta1) is an important mediator of tissue fibrosis, including liver cirrhosis. Ribbon-type antisense oligonucleotide to TGF-beta1 (TGF-beta1 RiAS) was designed and combined with cationic peptide derived from the nuclear localization signal of human immunodeficiency virus-1 Tat protein for enhanced cellular uptake. When Hepa1c1c7 cells were transfected with TGF-beta1 RiAS, the level of TGF-beta1 mRNA was reduced by >70%. TGF-beta1 RiAS, mismatched RiAS, and normal saline were each injected into mice via the tail vein, beginning the week after intraperitoneal CCl4 injection and continuing for 7 weeks, in order to determine whether TGF-beta1 RiAS prevents the fibrotic changes induced by the CCl4 injection. After 8 weeks of the experiment, all of the mice treated with TGF-beta1 RiAS survived, compared to 50% of the control group and 65% of the mismatched RiAS-treated group. Upon examining the biochemical effects on the liver, TGF-beta1 mRNA levels were reduced significantly only in the TGF-beta1 RiAS-treated group. Immunohistochemical studies showed a reduced accumulation of collagen and alpha-smooth muscle actin. Our experimental results suggest that ribbon antisense to TGF-beta1, with efficient uptake, effectively blocks the expression of TGF-beta1 and prevents fibrosis of the liver. PMID:18097613

Doh, Kyung-Oh; Jung, Hyun-Kyung; Moon, Ik-Jae; Kang, Hyun-Gu; Park, Jeong-Hoh; Park, Jong-Gu

2008-01-01

22

NO as an indicator of portal hemodynamics and the role of iNOS in increased NO production in CCl4-induced liver cirrhosis.  

PubMed

It is well known that nitric oxide, a vasodilator, is overproduced in liver cirrhosis. This study was designed to elucidate the role of nitric oxide (NO) in portal hemodynamics and to determine the mechanism underlying the increased serum NO levels in rats with liver cirrhosis induced by the oral intake of CCl4. Using rats, liver cirrhosis was induced by oral administration of CCl4. The serum levels of NO2-/NO3-(NOx) were measured, and portal hemodynamic parameters were evaluated with and without the administration of the NO synthase inhibitor N omega-nitro-L-arginine (NNA). Furthermore, Northern blot analysis was used to detect iNOS and cNOS mRNA, and immunohistochemical methods were used to detect iNOS-like immunoreactivity. In cirrhotic rats, the portal flow had increased significantly and the portal resistance had decreased significantly when compared with normal control rats. Hepatic capillary flow in the cirrhotic rats was similar to the control rats. NNA decreased portal flow and increased portal resistance in both groups, but the change was greater in the cirrhotic rats than in controls. The serum levels of NOx were significantly higher in cirrhotic rats than in normal control rats and were positively correlated with portal flow and negatively correlated with portal resistance. The expression of iNOS mRNA, which was barely detectable in control rats, had increased in all organs of the cirrhotic rats, whereas no significant increase in cNOS mRNA was found in any of the organs from cirrhotic rats. The immunohistochemical analysis was generally consistent with the results of the Northern blot analysis. In the control rats, only the bronchial epithelial cells were stained with the anti-iNOS antibody, but in cirrhotic rats, the bronchial cells in the lungs as well as the histiocytic mesenchymal cells in all organs, and the alveolar epithelial cells of the lungs, were stained. This study demonstrated that NO plays a significant role in portal hypertensive hemodynamics in CCl4-induced liver cirrhosis, and that NO is a useful indicator for the evaluation of portal hypertension. Furthermore, the increased serum levels of NO were found to be derived at least in part from the increased expression of iNOS mRNA in the liver, spleen, and lung. PMID:9245560

Mizumoto, M; Arii, S; Furutani, M; Nakamura, T; Ishigami, S; Monden, K; Ishiguro, S; Fujita, S; Imamura, M

1997-07-01

23

Sulfasalazine prevents the increase in TGF-?, COX-2, nuclear NF?B translocation and fibrosis in CCl4-induced liver cirrhosis in the rat.  

PubMed

It has been demonstrated that this sulfasalazine (SF) inhibits the nuclear factor ?B (NF?B) pathway, which regulates important genes during inflammation and immune answer. The aim of this work was to evaluate the effects of SF on carbon tetrachloride (CCl(4))-induced liver fibrosis. We formed the following experimental groups of rats: controls, damage induced by chronic CCl(4) (0.4 g/kg, intraperitoneally, three times a week for 8 weeks) administration and CCl(4) + SF (100 mg/kg/day, postoperatively for 8 weeks) administration. We determined the activities of alanine aminotransferase (ALT), ?-glutamyl transpeptidase (?-GTP), cyclooxygenase (COX)-1 and COX-2, lipid peroxidation, glutathione levels, collagen content, expression of transforming growth factor-? (TGF-?) and nuclear translocation of NF?B. SF was capable to inhibit the ALT and ?-GTP elevated levels induced with the CCl(4) administration. SF had antioxidant properties, prevented the lipid peroxidation and the imbalance of reduced and oxidized glutathione produced by CCl(4). Importantly, SF blocked the accumulation of collagen in the liver, the expression of TGF-?, the nuclear translocation of NF?B and the activity of COX-2, all induced with the administration of CCl(4) in the rat. These results show that SF has strong antifibrotic properties because of its antioxidant properties and its ability to prevent nuclear translocation of NF?B and consequently the expression of TGF-? and the activity of COX-2. PMID:22381741

Chávez, E; Castro-Sánchez, L; Shibayama, M; Tsutsumi, V; Moreno, M G; Muriel, P

2012-09-01

24

Beta-hexosaminidase activity in alcoholic fatty liver and in CCl4-induced liver fibrosis of the rat.  

PubMed

beta-Hexosaminidase (Hex) activity was previously found to be increased in the sera of patients with liver cirrhosis, cholestasis and acute alcohol intoxication, as well as in rats with CCl4-induced liver cirrhosis. We studied this enzymatic activity in the sera and liver tissue of rats with alcoholic fatty liver due to prolonged alcohol intake and CCl4-induced liver fibrosis in association with moderate alterations in liver function tests. Serum and liver Hex activity did not show any significant change in both experimental models. These data suggest that Hex is not an alcohol-induced enzyme, and that severe, but not moderate, liver damage can determine the increase in this lysosomal enzymatic activity. PMID:2574105

Antoniello, S; Auletta, M; Vatiero, V; Nigro, C; Cacciatore, L

1989-01-01

25

FXR regulates liver repair after CCl4-induced toxic injury.  

PubMed

Liver repair is key to resuming homeostasis and preventing fibrogenesis as well as other liver diseases. Farnesoid X receptor (FXR, NR1H4) is an emerging liver metabolic regulator and cell protector. Here we show that FXR is essential to promote liver repair after carbon tetrachloride (CCl(4))-induced injury. Expression of hepatic FXR in wild-type mice was strongly suppressed by CCl(4) treatment, and bile acid homeostasis was disrupted. Liver injury was induced in both wild-type and FXR(-/-) mice by CCl(4), but FXR(-/-) mice had more severe defects in liver repair than wild-type mice. FXR(-/-) livers had a decreased peak of regenerative DNA synthesis and reduced induction of genes involved in liver regeneration. Moreover, FXR(-/-) mice displayed increased mortality and enhanced hepatocyte deaths. During the early stages of liver repair after CCl(4) treatment, we observed overproduction of TNFalpha and a strong decrease of phosphorylation and DNA-binding activity of signal transducer and activator of transcription 3 in livers from FXR(-/-) mice. Exogenous expression of a constitutively active signal transducer and activator of transcription 3 protein in FXR(-/-) liver effectively reduced hepatocyte death and liver injury after CCl(4) treatment. These results suggest that FXR is required to regulate normal liver repair by promoting regeneration and preventing cell death. PMID:20211986

Meng, Zhipeng; Wang, Yandong; Wang, Lin; Jin, Wen; Liu, Nian; Pan, Hao; Liu, Lucy; Wagman, Lawrence; Forman, Barry M; Huang, Wendong

2010-05-01

26

High-mobility group box 1 exacerbates CCl4-induced acute liver injury in mice.  

PubMed

High-mobility group box 1 (HMGB1) is a nuclear factor that can also serve as an imflammatory mediator once released into extracellular milieu. Therefore, HMGB1 has been recognized to play a pivotal role in inflammatory diseases such as sepsis, acute lung injury, ischemia reperfusion injury and type 1 diabetes. Nevertheless, its impact on carbon tetrachloride (CCl4)-induced hepatic injury is yet to be elucidated. In the present report, we demonstrated evidence indicating that high levels of HMGB1 were not only present in the necrotic area of liver but also in the serum after CCl4 challenge. In line with these observations, administration of exogenous recombinant HMGB1 exacerbated CCl4-induced hepatic injury, while HMGB1 blocking antibody provided protection for mice against CCl4-induced acute liver injury as evidenced by the decrease of serum transaminase and reduction of hepatic tissues necrosis. Mechanistic studies revealed that blockade of HMGB1 attenuated CCl4-induced MDA accumulation along with improved SOD and GSH activity. Treatment of mice with HMGB1 neutralizing antibody also significantly inhibited the production of proinflammatory mediators TNF-? and IL-6 along with attenuated HMGB1 expression and its extracellular release. Together, our data suggest an essential role for HMGB1 in CCl4-induced acute liver injury, while HMGB1 neutralizing antibody could be served as an effective regimen for preventing CCl4-induced acute liver injury. PMID:24726765

Chen, Maojian; Huang, Wenjian; Wang, Chao; Nie, Hao; Li, Gang; Sun, Ting; Yang, Fei; Zhang, Yanxiang; Shu, Kegang; Wang, Congyi; Gong, Quan

2014-07-01

27

Antioxidant activity of the oyster mushroom, Pleurotus ostreatus, on CCl 4-induced liver injury in rats  

Microsoft Academic Search

This study was undertaken to investigate the putative antioxidant activity of the oyster mushroom Pleurotus ostreatus on CCl4-induced liver damage in male Wistar rats. Intraperitoneal administration of CCl4 (2ml\\/kg) to rats for 4 days resulted in significantly elevated (p<0.05) serum levels of glutamic oxaloacetic transaminase (SGOT), glutamic pyruvate transaminase (SGPT) and alkaline phosphatase (SALP) compared to controls. In the liver,

T. Jayakumar; E. Ramesh; P. Geraldine

2006-01-01

28

Prevention of CCl4-induced liver necrosis by the calcium chelator arsenazo III.  

PubMed

Arsenazo III (AIII) (100 mg/kg ip in saline) administration to Sprague-Dawley male rats 30 min before or 6 or 10 hr after CCl4 [1 ml/kg ip as a 20% (v/v) solution in olive oil] significantly prevented liver necrosis but not fatty liver caused by the hepatotoxin at 24 hr as demonstrated either by histology or by determination of isocitric acid dehydrogenase in plasma. AIII did not modify the CCl4 concentrations reaching the liver, the intensity of the covalent binding of CCl4-reactive metabolites to hepatic microsomal lipids, or the CCl4-promoted lipid peroxidation process at either 1 or 3 hr of poisoning. AIII administration enhanced glutathione (GSH) levels in liver and significantly prevented the CCl4-induced minor decreases in GSH content and the CCl4-induced increases in calcium content at 24 hr of intoxication. AIII treatment further enhanced the CCl4-induced decreases in body temperature of the poisoned rats. Results suggest that AIII's preventive effects might be related to its very well-known calcium-chelating properties, but that additional factors related to AIII's ability to increase GSH content in liver or to decrease body temperature of CCl4-intoxicated animals may also play a role. PMID:8519346

de Ferreyra, E C; Bernacchi, A S; Villarruel, M C; de Fenos, O M; Castro, J A

1993-06-01

29

The Protective Effect of ENA Actimineral Resource A on CCl 4 Induced Liver Injury in Rats  

Microsoft Academic Search

ENA Actimineral Resource A (ENA-A) is alkaline water that is composed of refined edible cuttlefish bone and two different\\u000a species of seaweed, Phymatolithon calcareum and Lithothamnion corallioides. In the present study, ENA-A was investigated as an antioxidant to protect against CCl4-induced oxidative stress and hepatotoxicity in rats. Liver injury was induced by either subacute or chronic CCl4 administration, and the

Il-Hwa Hong; Hoon Ji; Sung-Yong Hwa; Won-Il Jeong; Da-Hee Jeong; Sun-Hee Do; Ji-Min Kim; Mi-Ran Ki; Jin-Kyu Park; Moon-Jung Goo; Ok-Kyung Hwang; Kyung-Sook Hong; Jung-Youn Han; Hae-Young Chung; Kyu-Shik Jeong

2011-01-01

30

Protective effects of Ziyang tea polysaccharides on CCl4-induced oxidative liver damage in mice.  

PubMed

This study was designed to investigate the hepatoprotective effects of the tea polysaccharides (ZTPs) extracted from a selenium-enriched Ziyang green tea (Camellia sinensis). ZTPs were identified as the heteropolysaccharides with glucose (31.4%), arabinose (23.5%) and galactose (21.8%) being the main constitutive monosaccharides. ZTPs displayed noteworthy scavenging effects against DPPH, OH and O2(-), and high antioxidant effects in vitro, and the effects were further verified by suppressing CCl4-induced oxidative liver damage in mice at 100, 200 and 400mg/kg BW. Administration of ZTPs in mice prior to CCl4 significantly prevented the CCl4-induced increases in serum alanine aminotransferase, aspartate aminotransferase and lactic dehydrogenase, as well as hepatic malondialdehyde level. Mice treated with ZTPs showed normal glutathione peroxidase and superoxide dismutase activities, relative to CCl4-treated group. ZTPs also prevented the CCl4-caused liver histological alteration, as indicated by histopathological evaluation. These findings demonstrate that ZTPs have protective effects against acute CCl4-induced oxidative liver damage. PMID:24054254

Wang, Dongying; Zhao, Yan; Sun, Yanfei; Yang, Xingbin

2014-01-15

31

Betanin attenuates carbon tetrachloride (CCl4)-induced liver injury in common carp (Cyprinus carpio L.).  

PubMed

This study investigates the protective effect of betanin against liver injury induced by carbon tetrachloride (CCl4) in common carp (Cyprinus carpio L.). The fish were treated with 1, 2, and 4 % betanin in fodder throughout the experiment. After 20 days of treatment, the fish were intraperitoneally injected with 20 % (v/v in peanut oil) CCl4 at a volume of 0.5 mL/kg body weight. The fish were killed 3 days after CCl4 intoxication, and then, histological and biochemical assays were performed. Results showed that CCl4-induced liver CYP2E1 activity, oxidative stress, and injury, as indicated by the depleted glycogen storage, increased serum aspartate aminotransferase (AST)/alanine aminotransferase (ALT) activities and liver histological damage. Compared with the CCl4 control group, the betanin-treated groups exhibited reduced CYP2E1 activity, decreased malondialdehyde level, increased liver antioxidative capacity (increased glutathione level and superoxide dismutase and catalase activities), increased liver glycogen storage, and reduced serum AST/ALT activities, with significant differences in the 2 and 4 % groups (p < 0.05). Histological assay further confirmed the protective effect of betanin. In conclusion, betanin attenuates CCl4-induced liver damage in common carp. Moreover, the inhibition of CYP2E1 activity and oxidative stress may have significant roles in the protective effect of betanin. PMID:24271879

Han, Junyan; Gao, Cheng; Yang, Shaobin; Wang, Jun; Tan, Dehong

2014-06-01

32

Effect of Platelet-Rich Plasma on CCl4-Induced Chronic Liver Injury in Male Rats  

PubMed Central

Platelet-rich plasma (PRP) has been of great concern to the scientists and doctors who are involved in wound healing and regenerative medicine which focuses on repairing and replacing damaged cells and tissues. Growth factors of platelet-rich plasma are cost-effective, available, and is more stable than recombinant human growth factors. Given these valuable properties, we decided to assess the effect of PRP on CCl4-induced hepatotoxicity on rats. The rats received CCl4 (1?mL/kg, i.p. 1?:?1 in olive oil) twice per week for 8 weeks. Five weeks after CCl4 injection, the rats also received PRP (0.5?mL/kg, s.c.) two days a week for three weeks. Twenty-four hours after last CCl4 injection, the animals bled and their livers dissected for biochemical and histopathological studies. Blood analysis was performed to evaluate enzyme activity. The results showed that PRP itself was not toxic for liver and could protect the liver from CCl4-induced histological damages and attenuated oxidative stress by increase in glutathione content and decrease in lipid peroxidative marker of liver tissue. The results of the present study lend support to our beliefs in hepatoprotective effects of PRP.

Hesami, Zahra; Jamshidzadeh, Akram; Ayatollahi, Maryam; Farshad, Omid; Vahdati, Akbar

2014-01-01

33

The protective effect of ENA Actimineral resource A on CCl4-induced liver injury in rats.  

PubMed

ENA Actimineral Resource A (ENA-A) is alkaline water that is composed of refined edible cuttlefish bone and two different species of seaweed, Phymatolithon calcareum and Lithothamnion corallioides. In the present study, ENA-A was investigated as an antioxidant to protect against CCl(4)-induced oxidative stress and hepatotoxicity in rats. Liver injury was induced by either subacute or chronic CCl(4) administration, and the rats had free access to tap water mixed with 0% (control group) or 10% (v/v) ENA-A for 5 or 8 weeks. The results of histological examination and measurement of antioxidant activity showed that the reactive oxygen species production, lipid peroxidation, induction of CYP2E1 were decreased and the antioxidant activity, including glutathione and catalase production, was increased in the ENA-A groups as compared with the control group. On 2-DE gel analysis of the proteomes, 13 differentially expressed proteins were obtained in the ENA-A groups as compared with the control group. Antioxidant proteins, including glutathione S-transferase, kelch-like ECH-associated protein 1, and peroxiredoxin 1, were increased with hepatocyte nuclear factor 3-beta and serum albumin precursor, and kininogen precursor decreased more in the ENA-A groups than compared to the control group. In conclusion, our results suggest that ENA-A does indeed have some protective capabilities against CCl(4)-induced liver injury through its antioxidant function. PMID:20922552

Hong, Il-Hwa; Ji, Hoon; Hwa, Sung-Yong; Jeong, Won-Il; Jeong, Da-Hee; Do, Sun-Hee; Kim, Ji-Min; Ki, Mi-Ran; Park, Jin-Kyu; Goo, Moon-Jung; Hwang, Ok-Kyung; Hong, Kyung-Sook; Han, Jung-Youn; Chung, Hae-Young; Jeong, Kyu-Shik

2011-06-01

34

Beneficial Effects of Ocimum gratissimum Aqueous Extract on Rats with CCl4-Induced Acute Liver Injury  

PubMed Central

Ocimum gratissimum (OG) is known as a food spice and traditional herb, which has been recommended for the treatment of various diseases. To investigate the hepatoprotective effect of OG aqueous extract (OGAE), male Wistar rats challenged by carbon tetrachloride (CCl4) were used as the animal model of chronic hepatic injury. Significantly increased serum catalase and DPPH levels were detected in CCl4-administrated rats that were treated with OGAE or silymarin as compared to those rats that were treated with saline or CCl4. In contrast, significantly decreased stress proteins including HSP70 and iNOS were observed in livers of CCl4-administrated rats that were treated with OGAE or sylimarin as compared to those rats that were treated with saline or CCl4. Moreover, significant decreases of MMP-9/MMP-2 ratio, uPA, phosphorylated ERK (p-ERK) and NF-?B (p-P65) were detected in livers of CCl4-administrated rats that were treated with OGAE or sylimarin as compared to those rats that were treated with saline or CCl4. These findings imply that OGAE can efficiently inhibit CCl4-induced liver injuries in rats and may therefore be a potential food or herb for preventing liver injuries.

Chiu, Chun-Ching; Huang, Chih-Yang; Chen, Tzy-Yen; Kao, Shao-Hsuan; Liu, Jer-Yuh; Wang, Yi-Wen; Tzang, Bor-Show; Hsu, Tsai-Ching

2012-01-01

35

Hepatic Protection by Noni Fruit Juice Against CCl 4 Induced Chronic Liver Damage in Female SD Rats  

Microsoft Academic Search

Morinda citrifolia L. (noni) has been used throughout the Pacific, Southeast Asia, Central America, and the Caribbean for a variety of health\\u000a conditions, including heart and liver ailments. In this study, we examined the hepatoprotective effects of TAHITIAN NONI®\\u000a Juice (TNJ) against CCl4-induced chronic liver damage in female Sprague Dawley (SD) rats. Twelve female SD rats were divided into control,

Mian-Ying Wang; Gary Anderson; Diane Nowicki; Jarakae Jensen

2008-01-01

36

Ursolic acid protects mouse liver against CCl4-induced oxidative stress and inflammation by the MAPK/NF-?B pathway.  

PubMed

Ursolic acid (UA), a natural pentacyclic triterpenoid, has been reported to have many benefits and medicinal properties. However, its protective effects against carbon tetrachloride (CCl4) induced hepatotoxicity have not been clarified. The aim of the present study was to investigate the effects of UA on oxidative stress and inflammation in liver of CCl4 treated mice. Male ICR mice were injected with CCl4 with or without UA co-administration (25 and 50mg/kg intragastrically once daily) for one week. Our data showed that UA significantly prevented CCl4-induced hepatotoxicity in a dose-dependent manner, indicated by both diagnostic indicators of liver damage (serum aminotransferase activities) and histopathological analysis. Moreover, CCl4-induced profound elevation of reactive oxygen species (ROS) production and oxidative stress, as evidenced by increasing of lipid peroxidation level and depleting of the total antioxidant capacity (TAC) level in liver, were suppressed by treatment with UA. Furthermore, western blot analysis showed that UA significantly decreased CYP2E1 expression levels and production of pro-inflammatory markers including TNF-?, IL-1? and COX-2 in CCl4-treated mouse liver. In exploring the underlying mechanisms of UA action, we found that UA decreased the activation of mitogen-activated protein kinases (JNK, p38 MAPK, ERK), which in turn inactivated the immunoregulatory transcription factor nuclear factor kappa B (NF-?B) in liver of CCl4 treated mice. In conclusion, these results suggested that the inhibition of CCl4-induced inflammation by UA is due at least in part to its anti-oxidant activity and its ability to modulate the MAPK and NF-?B signaling pathway. PMID:24727148

Ma, Jie-Qiong; Ding, Jie; Zhang, Li; Liu, Chan-Min

2014-05-01

37

Hepatoprotective Effect of Superfine Particles of Herbal Medicine against CCl4-Induced Acute Liver Damage in Rats  

PubMed Central

This study aimed to examine the hepatoprotective effects of the superfine particles of Radix Tetrastigma (SPRT) against CCl4-induced acute liver damage in rats. Animals were treated with SPRT (0.3, 0.6, and 1.2?g/kg) and showed remarkable hepatoprotection against CCl4-induced hepatotoxicity. CCl4 altered various biochemical parameters in rat liver, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), malondialdehyde (MDA), superoxide dismutase (SOD), histopathological changes, and Bax and caspase-3 expressions. SPRT significantly prevented increases in ALT and AST levels, reduced MDA level, decreased Bax and caspase-3 protein expression, enhanced SOD activity, and provided significant amelioration in the histopathological lesions. These findings suggested that SPRT has significant protective effect against acute hepatotoxicity induced by CCl4 in rats.

Cao, Gang; Li, Qinglin; Chen, Xiaocheng; Cai, Hao; Tu, Sicong

2014-01-01

38

Hepatocurative potential of Vitex doniana root bark, stem bark and leaves extracts against CCl4-induced liver damage in rats  

PubMed Central

Objective To evaluate the hepatocurative effects of aqueous root bark, stem bark and leaves of Vitex doniana in carbon tetrachloride (CCl4) induced liver damage and non induced liver damage albino rats. Methods A total of 60 albino rats (36 induced liver damage and 24 non induced liver damage) were assigned into liver damage and non liver damage groups of 6 rats in a group. The animals in the CCl4 induced liver damage groups, were induced by intraperitoneal injection with a single dose of CCl4 (1 mL/kg body weight) as a 1:1(v/v) solution in olive oil and were fasted for 36 h before the subsequent treatment with aqueous root bark, stem bark and leaves extracts of Vitex doniana and vitamin E as standard drug (100 mg/kg body weight per day) for 21 d, while the animals in the non induced groups were only treated with the daily oral administration of these extracts at the same dose. The administration of CCl4 was done once a week for a period of 3 weeks. Results There was significant (P<0.05) increase in concentration of all liver marker enzymes, alanine aminotransferase, aspartate aminotransferase and alkaline aminotransferase (ALT, AST and ALP) and significant (P<0.05) decrease in albumin in the CCl4 induced liver damage control when compared to the normal control. The extracts caused a significant (P<0.05) reduction in the serum activities of liver marker enzymes (ALT, AST and ALP) and a significant (P<0.05) increase in albumin of all the induced treated groups. Only stem bark extract and vitamin E significantly (P<0.05) increased total protein. All the extracts significantly (P<0.05) lowered serum creatinine whereas only root bark extract significantly (P<0.05) lowered serum level of urea in the rats with CCl4 induced liver damage. Conclusion Hepatocurative study shows that all the plant parts (root bark, stem bark and leaves) possess significant hepatocurative properties among other therapeutic values justifying their use in folklore medicine.

Bolanle, James Dorcas; Adetoro, Kadejo Olubukola; Balarabe, Sallau Abdullahi; Adeyemi, Owolabi Olumuyiwa

2014-01-01

39

Effect of Phyllanthus niruri Linn. treatment on liver, kidney and testes in CCl4 induced hepatotoxic rats.  

PubMed

Phyllanthus niruri extract is extensively used in treating liver ailments. Effects of aqueous extract of P. niruri on liver, kidney and testes of CCl4 induced hepatotoxic rats were studied. High levels of malondialdehyde (MDA) were observed in the CCl4 test group with significant reduction of MDA levels in all groups on P. niruri extract administration. Highest levels of glutathione (GSH) were found in P. niruri group. Activities of alanine transaminase, aspartate transaminase and alkaline phosphatase enzymes were significantly reduced in the curative group (P. niruri treatment after CCl4 injection). Histopathology of liver showed lesser degree of inflammation in all P. niruri treated groups while the renal and seminiferous tubules showed eosinophilic protein casts with signs of tubular damage and degeneration. Testes also showed decreased amount of mature spermatozoa. The results suggest that P. niruri has anti-oxidant and hepato-protective activity with associated deleterious effects on kidney and testes. PMID:18807755

Manjrekar, A P; Jisha, V; Bag, P P; Adhikary, B; Pai, M M; Hegde, A; Nandini, M

2008-07-01

40

The protective effect of silymarin on the carbon tetrachloride (CCl4)-induced liver injury in common carp (Cyprinus carpio).  

PubMed

Silymarin, a mixture of bioactive flavonolignans from the milk thistle (Silybum marianum), is traditionally used in herbal medicine to defend against various hepatotoxic agents. The aim of the present study was to evaluate the protective effect of silymarin against carbon tetrachloride (CCl4)-induced liver injury in fish. Common carp, with an average initial weight of 17.0?±?1.1 g, were fed diet containing four doses of silymarin (0, 0.1, 0.5, and 1 g/kg diet) for 60 d. Fish were then given an intraperitoneal injection of CCl4 (30% in arachis oil) at a dose of 0.5 ml/kg body weight. At 72 h after CCl4 injection, blood and liver samples were collected for the analyses of serum biochemical parameters, liver index, peroxidation product, glutathione, and antioxidant enzyme activities. The results showed that administration of silymarin at 0.5 and 1 g/kg diet for 60 d prior to CCl4 intoxication significantly reduced the elevated activities of glutamate pyruvate transaminase, glutamate oxalate transaminase, lactate dehydrogenase (LDH), and increased the reduced levels of total protein and albumin in the serum. The reduced levels of liver index, superoxide dismutase, glutathione peroxidase, catalase, glutathione, and total antioxidant capacity were markedly increased, and malondialdehyde formation was significantly restrained in the liver. However, these parameters, except LDH, were not significantly changed in fish fed with silymarin at 0.1 g/kg diet. Based on the results, it can be concluded that silymarin has protective effect against CCl4-induced hepatotoxicity in fish. It is suggested that silymarin may be used as a hepatoprotective agent to prevent liver diseases in fish. PMID:23435858

Jia, Rui; Cao, Liping; Du, Jinliang; Xu, Pao; Jeney, Galina; Yin, Guojun

2013-03-01

41

Protective efficacy of natansnin, a dibenzoyl glycoside from Salvinia natans against CCl4 induced oxidative stress and cellular degeneration in rat liver  

PubMed Central

Background Carbon tetra chloride (CCl4), an industrial solvent, is a hepatotoxic agent and it is the well established animal model for free radical-induced liver injury. The present investigation was carried out to establish the protective effect of natansnin, a novel dibenzoyl glycoside from Salvinia natans against CCl4 induced oxidative stress and cellular degeneration in rat liver. Results CCl4 significantly increased the levels of lipid peroxides, oxidized glutathione and decreased the levels of reduced glutathione, SOD and CAT. CCl4 induce marked histopathological changes and increase in the levels of apoptotic proteins. CCl4 treatment significantly increased the levels of apoptotic proteins such as caspases-3, PARP, Bax, Bid and cytochrome C and also increased the levels of inflammatory mediators iNos and Cox-2. Natansnin treatment significantly decreased the levels of CCl4 induced apoptotic proteins and inflammatory mediators. Further natansinin treatment significantly inhibited the CCl4 induced apoptosis which was evident form the reduced TUNEL positive cells. Conclusions In conclusion, our study demonstrated the protective effect of natansnin against CCl4 induced oxidative stress and cellular degeneration in rat liver tissue. This protective effect of natansnin can be correlated to its direct antioxidant effect.

2010-01-01

42

Mest Attenuates CCl4-Induced Liver Fibrosis in Rats by Inhibiting the Wnt/?-Catenin Signaling Pathway  

PubMed Central

Background/Aims The Wnt/?-catenin signaling pathway has been reported to play an important role in liver fibrosis. This study was designed to investigate whether mesoderm-specific transcript homologue (Mest), a strong negative regulator of Wnt/?-catenin signaling, could inhibit liver fibrosis. Methods pcDNA-Mest was transfected into hepatic stellate cells (HSCs) and rats. Rats were randomly divided into four groups: normal group (normal saline), treatment group (pcDNA-Mest+CCl4), control group (pcDNA-neo+CCl4), and model group (normal saline+CCl4). Changes in liver pathology were evaluated by hematoxylin and eosin and Masson's trichrome staining. The levels of alanine transaminase, aspartate transaminase, lactic dehygrogenase, hyaluronic acid, and laminin in the serum and hydroxyproline in the liver were detected by biochemical examination and radioimmunoassay, respectively. The expression and distribution of ?-catenin, ?-smooth muscle actin (?-SMA), Smad3, and tissue inhibitor of metalloproteinase type I were determined, and the viability of the HSCs was tested. Results Our data demonstrate that Mest alleviated CCl4-induced collagen deposition in liver tissue and improved the condition of the liver in rats. Mest also significantly reduced the expression and distribution of ?-catenin, ?-SMA and Smad3 both in vivo and in vitro, in addition to the viability of HSCs in vitro. Conclusions We found that Mest attenuates liver fibrosis by repressing ?-catenin expression, which provides a new therapeutic approach for treating liver fibrosis.

Li, Wenting; Zhu, Chuanlong; Li, Yi

2014-01-01

43

Hepatic protection by noni fruit juice against CCl(4)-induced chronic liver damage in female SD rats.  

PubMed

Morinda citrifolia L. (noni) has been used throughout the Pacific, Southeast Asia, Central America, and the Caribbean for a variety of health conditions, including heart and liver ailments. In this study, we examined the hepatoprotective effects of TAHITIAN NONI Juice (TNJ) against CCl(4)-induced chronic liver damage in female Sprague Dawley (SD) rats. Twelve female SD rats were divided into control, placebo and TNJ (6 mL/rat/day) groups. On day 15, animals in the placebo and TNJ groups received 0.25 mL/kg CCl(4) in corn oil once a week for 12 successive weeks. All animals were sacrificed at week 16. Blood and liver were collected for liver function, lipid panel tests, and histological observation. Histopathological examination revealed that liver sections from the TNJ + CCl(4) appeared similar to controls, whereas typical hepatic steatosis was observed in the placebo + CCl(4) group. Serum alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine transaminase (ALT), total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL) levels were increased in the placebo group compared with the TNJ group. In contrast, high-density lipoprotein (HDL) was increased in the TNJ group and decreased in the placebo group. Thus, TNJ juice appears to protect the liver from chronic exogenous CCl(4) exposures. Such protective mechanisms are supportive evidence for the utility of noni in traditional medicine for liver ailments. PMID:18654853

Wang, Mian-Ying; Anderson, Gary; Nowicki, Diane; Jensen, Jarakae

2008-09-01

44

Antioxidant and hepatoprotective effects of Schisandra chinensis pollen extract on CCl4-induced acute liver damage in mice.  

PubMed

The aim of the present study was to investigate the antioxidant and hepatotective effects of Schisandra chinensis pollen extract (SCPE) on CCl4-induced acute liver damage in mice. Total phenolic content, total flavonoid content, individual phenolic compounds and antioxidant activities (1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, chelating activity, and reducing power assay) were determined. In vivo study, SCPE (10, 20 and 40g/kg) administered daily orally for 42days prior to CCl4-intoxicated. Our results showed that SCPE had high total phenolic content (53.74±1.21mg GAE/g), total flavonoid content (38.29±0.91mg Rutin/g), quercetin and hesperetin may be the major contributor to strong antioxidant activities. Moreover, SCPE significantly prevented the increase in serum ALT and AST level in acute liver damage induced by CCl4, decreased the extent of malondialdehyde (MDA) formation in liver and elevated the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in liver. The results indicated that SCPE has strong antioxidant activities and significant protective effect against acute hepatotoxicity induced by CCl4, and have been supported by the evaluation of liver histopathology in mice. The hepatoprotective effect may be related to its free radical scavenging effect, increasing antioxidant activity and inhibiting lipid peroxidation. PMID:23201450

Cheng, Ni; Ren, Naiyan; Gao, Hui; Lei, Xingsheng; Zheng, Jianbin; Cao, Wei

2013-05-01

45

Toxicological evaluation of Terminalia paniculata bark extract and its protective effect against CCl4-induced liver injury in rodents.  

PubMed

BACKGROUND: Based on the reported antioxidant and anti-inflammatory potential of Terminalia paniculata, the bark aqueous extract (TPW) was investigated against liver damage. METHODS: Intrinsic cytotoxicity was tested on normal human liver (Chang) cell lines, followed by acute and sub-chronic toxicity studies in mice. TPW was then evaluated against CCl4-induced liver toxicity in rats. Liver enzymes (AST, ALT, and ALP) and antioxidant markers were assessed. The effect of TPW on isolated hepatic cells, post-CCl4 administration, was assessed by isolated mitochondrial membrane staining. The actions of TPW on apoptotic pathway in CCl4-treated Chang cells were also elucidated. RESULTS: TPW was found to be safe at all doses tested in both in vitro and in vivo toxicity studies. TPW (400 mg/kg, p.o.) significantly (*p <0.05) improved liver enzyme activity as compared to CCl4. Also, it improved antioxidant status (GSH, GST, MDA and total thiol) and preserved hepatic cell architecture. TPW pre-treatment significantly attenuated the levels of phospho-p53, p53, cleaved caspase-3, phospho-Bad, Bad and cleaved PARP in CCl4-treated Chang cells, improving the viability considerably. CONCLUSION: The findings support a protective role for Terminalia paniculata in pathologies involving oxidative stress. PMID:23742226

Talwar, Sahil; Jagani, Hitesh V; Nayak, Pawan G; Kumar, Nitesh; Kishore, Anoop; Bansal, Punit; Shenoy, Rekha R; Nandakumar, Krishnadas

2013-06-01

46

Toxicological evaluation of Terminalia paniculata bark extract and its protective effect against CCl4-induced liver injury in rodents  

PubMed Central

Background Based on the reported antioxidant and anti-inflammatory potential of Terminalia paniculata, the bark aqueous extract (TPW) was investigated against liver damage. Methods Intrinsic cytotoxicity was tested on normal human liver (Chang) cell lines, followed by acute and sub-chronic toxicity studies in mice. TPW was then evaluated against CCl4-induced liver toxicity in rats. Liver enzymes (AST, ALT, and ALP) and antioxidant markers were assessed. The effect of TPW on isolated hepatic cells, post-CCl4 administration, was assessed by isolated mitochondrial membrane staining. The actions of TPW on apoptotic pathway in CCl4-treated Chang cells were also elucidated. Results TPW was found to be safe at all doses tested in both in vitro and in vivo toxicity studies. TPW (400 mg/kg, p.o.) significantly (*p <0.05) improved liver enzyme activity as compared to CCl4. Also, it improved antioxidant status (GSH, GST, MDA and total thiol) and preserved hepatic cell architecture. TPW pre-treatment significantly attenuated the levels of phospho-p53, p53, cleaved caspase-3, phospho-Bad, Bad and cleaved PARP in CCl4-treated Chang cells, improving the viability considerably. Conclusion The findings support a protective role for Terminalia paniculata in pathologies involving oxidative stress.

2013-01-01

47

Hepatoprotective potential of ether insoluble phenolic components of n-butanol fraction (EPC-BF) of flaxseed against CCl4 -induced liver damage in rats  

PubMed Central

Objective: to investigate the hepatoprotective potential of ether insoluble phenolic components of n-butanol fraction (EPC-BF) of flaxseed against CCl4 -induced liver damage in rats. Materials and Methods: Hepatotoxicity was induced to Wistar rats by administration of 0.2% CCl4 in olive oil (8 mL/kg, i.p.) on the seventh day of treatment. Hepatoprotective potential of EPC-BF at doses, 250 and 500 mg/kg, p.o. was assessed through biochemical and histological parameters. Results: EPC-BF and silymarin pretreated animal groups showed significantly decreased activities of Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and level of total bilirubin, elevated by CCl4 intoxication. Hepatic lipid peroxidation elevated by CCl4 intoxication were also found to be alleviated at almost normal level in the EPC-BF and silymarin pretreated groups. Histological studies supported the biochemical findings and treatment of EPC-BF at doses 250 and 500 mg/kg, p.o. was found to be effective in restoring CCl4 -induced hepatic damage. However, EPC-BF did not show dose-dependent hepatoprotective potential. EPC-BF depicted maximum protection against CCl4 -induced hepatic damage at lower dose 250 mg/kg than higher dose (500 mg/ kg). Conclusion: EPC-BF possesses the significant hepatoprotective activity against CCl4 induced liver damage, which could be mediated through increase in antioxidant defenses.

Kasote, D. M.; Badhe, Y. S.; Zanwar, A. A.; Hegde, M. V.; Deshmukh, K. K.

2012-01-01

48

Hepatoprotective Effect of Lonchocarpus sericeus Leaves in CCl4- Induced Liver Damage  

Microsoft Academic Search

Lonchocarpus sericeus (Poir.) Kunth ex DC (Fabaceae) is used in traditional medicine for the treatment of pathological conditions such as gastrointestinal and hepatic disorders. To investigate the hepatoprotective effect of L. sericeus ethanolic extract on liver damage induced by carbon tetrachloride (CCl4), test animals were administered orally 200 and 400 mg kg of L. sericeus extract four times after CCl4

Amegnona Agbonon; Messanvi Gbeassor

2009-01-01

49

Agaricus blazei Murill extract abrogates CCl4-induced liver injury in rats.  

PubMed

Agaricus blazei Murill (ABM) is enriched with polysaccharides, lipids, vitamins, fibers and minerals. Many studies have shown that ABM possesses immune-enhancing and anti-tumor effects. However, little is known about its protective effects on liver function. We employed carbon tetrachloride (CCl(4)) to induce hepatic fibrosis in a rat model to examine the protective effects of ABM on the liver in this study. The experiments included non-treatment control, CCl(4)-only control, and treatment with 200 mg and 2,000 mg of ABM extracts (per kilogram rat weight). All groups other than the non-treatment control were treated with intraperitoneal injections of CCl(4) twice a week. Experimental and control rats were tube-fed with experimental ABM extracts or double-distilled water, respectively, on the remaining four days each week. The whole experimental protocol lasted 8 weeks; blood and liver samples were collected for biochemical and tissue histochemical analysis. Plasma alanine aminotransferase and aspartate aminotransferase, and the activities of the anti-oxidative enzymes glutathione peroxidase, superoxide dismutase and catalase in the liver were measured. We found that high-dose ABM treatment reduced hepatic necrosis and fibrosis caused by CCl(4) in comparison with the CCl(4) control group. ALT and AST activities in the sera collected from ABM-treated rats were lower than those in the CCl(4) control rats. These results suggested that ABM extract was capable of either enhancing liver recovering from CCl(4) damage or attenuating CCl(4) toxicity. Results of anti-oxidative enzyme activity analysis showed no apparent differences among ABM-treated groups and CCl(4) control groups, indicating that removal of free radicals does not explain the protective/recovery effects observed in this study. PMID:21282732

Wu, Ming-Fang; Hsu, Yu-Ming; Tang, Ming-Chu; Chen, Hsueh-Chin; Chung, Jing-Gung; Lu, Hsu-Feng; Lin, Jing-Pin; Tang, Nou-Ying; Yeh, Chun; Yeh, Ming-Yang

2011-01-01

50

Effects of TGF-?1 Ribbon Antisense on CCl4-induced Liver Fibrosis  

PubMed Central

Ribbon-type antisense oligonucleotide to TGF-?1 (TGF-?1 RiAS) was designed and tested to prevent or resolve the fibrotic changes induced by CCl4 injection. When Hepa1c1c7 cells were transfected with TGF-?1 RiAS, the level of TGF-?1 mRNA was effectively reduced. TGF-?1 RiAS, mismatched RiAS, and normal saline were each injected to mice via tail veins. When examined for the biochemical effects on the liver, TGF-?1 mRNA levels were significantly reduced only in the TGF-?1 RiAS-treated group. The results of immunohistochemical studies showed that TGF-?1 RiAS prevented the accumulation of collagen and ?-smooth muscle actin, but could not resolve established fibrosis. These results indicate that ribbon antisense to TGF-?1 with efficient uptake can effectively prevent fibrosis of the liver.

2008-01-01

51

Antioxidant and hepatoprotective effects of Solanum xanthocarpum leaf extracts against CCl4-induced liver injury in rats.  

PubMed

Abstract Context: Solanum xanthocarpum Schard. and Wendl. (Solanaceae) has been used in traditional Indian medicines for its antioxidant, anti-inflammatory, and antiasthmatic properties. Objective: The present study demonstrates the antioxidant and hepatoprotective effects of S. xanthocarpum. On the basis of in vitro antioxidant properties, the active fraction from column chromatography of the methanol extract of S. xanthocarpum leaves (SXAF) was chosen as the potent fraction and used for hepatoprotective studies in rats. Materials and methods: The antioxidant activity was evaluated by 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and reducing power assays. Rats were pre-treated with 100 and 200?mg/kg b.w. of SXAF for 14?d with a single dose of CCl4 in the last day. Hepatoprotective properties were determined by serum biochemical enzymes, aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), antioxidant enzymes (SOD, CAT, GSH, and GST), and histopathology studies. Results: SXAF exhibited significant antioxidant activity in scavenging free radicals with IC50 values of 11.72?µg (DPPH) and 17.99?µg (ABTS). Rats pre-treated with SXAF demonstrated significantly reduced levels of serum LDH (1.7-fold), ALP (1.6-fold), and AST (1.8-fold). Similarly, multiple dose SXAF administration at 200?mg/kg b.w. demonstrated significantly enhanced levels of SOD (1.78?±?0.13), CAT (34.63?±?1.98), GST (231.64?±?14.28), and GSH (8.23?±?0.48) in liver homogenates. Histopathological examination showed lowered liver damage in SXAF-treated groups. Discussion and conclusion: These results demonstrate that SXAF possesses potent antioxidant properties as well as hepatoprotective effects against CCl4-induced hepatotoxicity. PMID:24646306

Jalali Ghassam, Behrouz; Ghaffari, Hadi; Prakash, H S; Kini, Kukkundoor Ramachandra

2014-08-01

52

Insulin-degrading activity in experimental liver cirrhosis of the rat.  

PubMed

Liver cirrhosis in man is often associated with hyperinsulinemia but its pathogenesis is still unexplained. To investigate whether insulin degradation is impaired in cirrhotic liver, the specific insulin-degrading enzyme activity (EC 3.4.22.11) was assayed in liver cytosol of rats with CCl4-induced liver cirrhosis. No difference was found between liver cytosol of cirrhotic and control rats. The results show that experimental CCl4-induced liver cirrhosis does not damage the specific insulin-degrading activity and support the hypothesis that impaired hepatic insulin handling is not an important cause of hyperinsulinemia in liver cirrhosis. PMID:8821707

Auletta, M; Antoniello, S; Abrescia, N

53

Liver regeneration in a retrorsine\\/CCl 4induced acute liver failure model: do bone marrow-derived cells contribute?  

Microsoft Academic Search

Background\\/Aims: Adult bone marrow contains progenitors capable of generating hepatocytes. Here a new liver failure model is introduced to assess whether bone marrow-derived progeny contribute to liver regeneration after acute hepatotoxic liver failure.Methods: Retrorsine was used to inhibit endogenous hepatocyte proliferation, before inducing acute liver failure by carbon tetrachloride. Bone marrow chimeras were generated before inducing liver failure to trace

Marc H Dahlke; Felix C Popp; Ferdinand H Bahlmann; Heiko Aselmann; Mark D Jäger; Michael Neipp; Pompiliu Piso; Jürgen Klempnauer; Hans J Schlitt

2003-01-01

54

Toll like receptor 2 knock-out attenuates carbon tetrachloride (CCl4)-induced liver fibrosis by downregulating MAPK and NF-?B signaling pathways.  

PubMed

Innate immune signaling associated with Toll-like receptors (TLRs) is a key pathway involved in the progression of liver fibrosis. In this study, we reported that TLR2 is required for hepatic fibrogenesis induced by carbon tetrachloride (CCl4). After CCl4 treatment, TLR2(-/-) mice had reduced liver enzyme levels, diminished collagen deposition, decreased inflammatory infiltration and impaired activation of hepatic stellate cells (HSCs) than wild type (WT) mice. Furthermore, after CCl4 treatment, TLR2(-/-) mice demonstrated downregulated expression of profibrotic and proinflammatory genes and impaired mitogen-activated protein kinases (MAPK) and nuclear factor kappa B (NF-?B) activation than WT mice. Collectively, our data indicate that TLR2 deficiency protects against CCl4-induced liver fibrosis. PMID:24815695

Ji, Lingling; Xue, Ruyi; Tang, Wenqing; Wu, Weibin; Hu, Tingting; Liu, Xijun; Peng, Xiaomin; Gu, Jianxin; Chen, She; Zhang, Si

2014-06-01

55

Hepatocyte-specific ablation of spermine/spermidine-N1-acetyltransferase gene reduces the severity of CCl4-induced acute liver injury  

PubMed Central

Activation of spermine/spermidine-N1-acetyltransferase (SSAT) leads to DNA damage and growth arrest in mammalian cells, and its ablation reduces the severity of ischemic and endotoxic injuries. Here we have examined the role of SSAT in the pathogenesis of toxic liver injury caused by carbon tetrachloride (CCl4). The expression and activity of SSAT increase in the liver subsequent to CCl4 administration. Furthermore, the early liver injury after CCl4 treatment was significantly attenuated in hepatocyte-specific SSAT knockout mice (Hep-SSAT-Cko) compared with wild-type (WT) mice as determined by the reduced serum alanine aminotransferase levels, decreased hepatic lipid peroxidation, and less severe liver damage. Cytochrome P450 2e1 levels remained comparable in both genotypes, suggesting that SSAT deficiency does not affect the metabolism of CCl4. Hepatocyte-specific deficiency of SSAT also modulated the induction of cytokines involved in inflammation and repair as well as leukocyte infiltration. In addition, Noxa and activated caspase 3 levels were elevated in the livers of WT compared with Hep-SSAT-Cko mice. Interestingly, the onset of cell proliferation was significantly more robust in the WT compared with Hep-SSAT Cko mice. The inhibition of polyamine oxidases protected the animals against CCl4-induced liver injury. Our studies suggest that while the abrogation of polyamine back conversion or inhibition of polyamine oxidation attenuate the early injury, they may delay the onset of hepatic regeneration.

Barone, Sharon L.; Xu, Jie; Steinbergs, Nora; Schuster, Rebecca; Lentsch, Alex B.; Amlal, Hassane; Wang, Jiang; Casero, Robert A.; Soleimani, Manoocher

2012-01-01

56

Liver cirrhosis.  

PubMed

Cirrhosis is an increasing cause of morbidity and mortality in more developed countries, being the 14th most common cause of death worldwide but fourth in central Europe. Increasingly, cirrhosis has been seen to be not a single disease entity, but one that can be subclassified into distinct clinical prognostic stages, with 1-year mortality ranging from 1% to 57% depending on the stage. We review the current understanding of cirrhosis as a dynamic process and outline current therapeutic options for prevention and treatment of complications of cirrhosis, on the basis of the subclassification in clinical stages. The new concept in management of patients with cirrhosis should be prevention and early intervention to stabilise disease progression and to avoid or delay clinical decompensation and the need for liver transplantation. The challenge in the 21st century is to prevent the need for liver transplantation in as many patients with cirrhosis as possible. PMID:24480518

Tsochatzis, Emmanuel A; Bosch, Jaime; Burroughs, Andrew K

2014-05-17

57

Antioxidant Properties of Proanthocyanidins Attenuate Carbon Tetrachloride (CCl4)-Induced Steatosis and Liver Injury in Rats via CYP2E1 Regulation.  

PubMed

Abstract Liver steatosis is characterized by lipid dysregulation and fat accumulation in the liver and can lead to oxidative stress in liver. Since proanthocyanidins are present in plant-based foods and have powerful antioxidant properties, we investigated whether proanthocyanidins can prevent oxidative stress and subsequent liver injury. Carbon tetrachloride (CCl4) treatment can cause steatosis in rats that models both alcoholic and non-alcoholic fatty liver disease in humans. We pre-treated rats by oral administration of proanthocyanidins extracted from grape seeds 7 days prior to intragastrically administering CCl4. Proanthocyanidin treatment continued for an additional 2 weeks, after which time liver and serum were harvested, and mediators of liver injury, oxidative stress, and histological features were evaluated. CCl4-treated rats exhibited significant increases in the following parameters as compared to non-treated rats: fat droplets in the liver, liver injury (ALT, AST), and DNA damage (8-OHdG). Additionally, CCl4 treatment decreased antioxidant enzymes SOD, GSH, GPX, and CAT in the liver due to their rapid depletion after battling against oxidative stress. Compared to CCl4-treated rats, treatment with proanthocyanidins effectively suppressed lipid accumulation, liver injury, DNA damage, as well as restored antioxidant enzyme levels. Further investigation revealed that proanthocyanidins treatment also inhibited expression of CYP2E1 in liver, which prevented the initial step of generating free radicals from CCl4. The data presented here show that treatment with orally administered proanthocyanidins prevented liver injury in the CCl4-induced steatosis model, likely through exerting antioxidant actions to suppress oxidative stress and inhibiting the free radical-generating CYP2E1 enzyme. PMID:24712752

Dai, Ning; Zou, Yuan; Zhu, Lei; Wang, Hui-Fang; Dai, Mu-Gen

2014-06-01

58

Induction of Gas6 protein in CCl4-induced rat liver injury and anti-apoptotic effect on hepatic stellate cells.  

PubMed

The protein product of the growth arrest-specific gene 6 (Gas6) is a secreted ligand for tyrosine kinase receptors, among which Axl is the most widely distributed and displays the highest affinity for Gas6. The Gas6/Axl signaling pathway has been increasingly implicated in growth and survival processes occurring during development and tissue repair. In liver, after an acute or chronic injury, repair involves macrophages and hepatic stellate cells (HSC) activated into myofibroblastic cells (HSC/MFB), which produce cytokines and matrix proteins. We investigated the expression and the role of Gas6 and its receptor Axl in liver repair. Three days after CCl4-induced liver injury in the rat, we detected the expression of Gas6 in ED1-positive macrophages as well as in desmin-positive HSC, which accumulated in injured areas. Axl, the high-affinity receptor for Gas6, was detected in macrophages, HSC, and HSC/MFB. In vitro, expression of gamma-carboxylated Gas6 was strongly induced in HSC along with their transformation into myofibroblasts, and it exerted an anti-apoptotic effect on both HSC and HSC/MFB mediated by the Axl/PI3-kinase/Akt pathway. In conclusion, Gas6 is a survival factor for these cells and we suggest that Gas6, secreted by macrophages and HSC/MFB in vivo after liver injury, promotes HSC and HSC/MFB survival and might support transient HSC/MFB accumulation during liver healing. PMID:16799993

Lafdil, Fouad; Chobert, Marie Noële; Couchie, Dominique; Brouillet, Arthur; Zafrani, Elie Serge; Mavier, Philippe; Laperche, Yannick

2006-07-01

59

Changes in expression of the albumin, fibronectin and type I procollagen genes in CCl4-induced liver fibrosis: effect of pyridoxol L,2-pyrrolidon-5 carboxylate.  

PubMed

The protective activity of pyridoxol L,2-pyrrolidon-5 carboxylate (metadoxine) was investigated in a rat model of carbon tetrachloride (CCL4)-induced hepatic fibrosis. After 6 weeks of CCl4 treatment, the animals developed fibrosis and inflammation of the liver while those treated with CCl4 + metadoxine had less severe lesions (P < 0.05). Since in liver fibroplasia there are quantitative changes of the extracellular matrix components and almost invariably a decrease in albumin synthesis, we have also investigated by Northern blot analysis the expression of the cellular fibronectin, pro-alpha 2(I)collagen and albumin genes. There were striking increases in fibronectin and pro-alpha 2(I)collagen mRNA contents in the livers of CCL4-treated animals and these enhancements were less evident in the metadoxine-treated rats. In contrast, albumin mRNA levels, almost identical in control and metadoxine-treated rats, were lower in the CCl4-treated animals. These data suggest that metadoxine might slow the development of CCl4-mediated liver fibrosis. PMID:7512265

Arosio, B; Santambrogio, D; Gagliano, N; Annoni, G

1993-12-01

60

Potential antioxidant properties and hepatoprotective effects of an aqueous extract formula derived from three Chinese medicinal herbs against CCl(4)-induced liver injury in rats.  

PubMed

The hepatoprotective effects of an aqueous extract formula (AEF) derived from Artemisia capillaris, Lonicera japonica and Silybum marianum (ratio 1:1:1) were evaluated by its antioxidant properties and its attenuation of carbon tetrachloride (CCl(4))-induced liver damage in rats. The antioxidant analyses revealed that the AEF showed higher 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and superoxide anion radical scavenging activities as well as ferric reducing antioxidant potential (FRAP) and Trolox equivalent antioxidant capacity (TEAC) compared with the individual herbs, suggesting a synergism in antioxidation between the three herbs. The animal experiments showed that the CCl(4) treatment increased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, but decreased triglyceride (TG) and glutathione (GSH) levels as well as glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) activities. However, AEF administration can successfully lower serum ALT and AST activities, restore the GSH level, ameliorate or restore GPx and CAT activities as well as improve SOD action depending on AEF dosage. Histological examination of liver showed that CCl(4) increased the extent of bile duct proliferation, necrosis, fibrosis and fatty vacuolation throughout the liver, but AEF can improve bile duct proliferation, vacuolation and fibrosis, and restore necrosis. The present study demonstrated the hepatoprotective potential of AEF as an alternative to the traditional silymarin. PMID:23142091

Yang, Chi-Ching; Fang, Jong-Yi; Hong, Tuan-Liang; Wang, Tzu-Ching; Zhou, Ya-En; Lin, Ta-Chen

2013-01-01

61

Kupffer cells are a major source of increased platelet activating factor in the CCl 4-induced cirrhotic rat liver  

Microsoft Academic Search

Background\\/Aims: Endothelin-1 (ET-1) stimulates the synthesis of platelet-activating factor (PAF) by Kupffer cells in vitro. Hepatic concentrations of both ET-1 (a potent vasoconstrictor) and PAF (a mediator of hepatic vasoconstriction and the cirrhotic hyperdynamic state) increase in cirrhosis. The aim of this study was to determine if the responsiveness of Kupffer cells to produce PAF upon ET-1 challenge is modified

Yongping Yang; Stephen A. K Harvey; Chandrashekhar R Gandhi

2003-01-01

62

Agaricus blazei Murill as an efficient hepatoprotective and antioxidant agent against CCl4-induced liver injury in rats.  

PubMed

Agaricus blazei Murill is one of the very popular edible medicinal mushrooms. The present study investigated the protective effect of this biologically active mushroom on the tissue peroxidative damage and abnormal antioxidant levels in carbon tetrachloride induced hepatotoxicity in male albino rats. Male albino rats of Sprague-Dawley strain weighting (120-150 g) were categorized into five groups. The first group served as the normal control, the second and the third groups were treated with Agaricus blazei Mushroom extract and carbon tetrachloride dose, respectively. Fourth group (protective group) was first treated with Agaricus blazei Mushroom extract followed by carbon tetrachloride treatment and fifth (therapeutic group) with carbon tetrachloride first followed by Agaricus blazei Mushroom treatment. The wet fruiting bodies of mushroom Agaricus blazei Murill, crushed and suspended in distilled water was administered orally to the treated groups of male albino rats. The activities of various enzymes (aspartate and alanine transaminase, lactate dehydrogenase, glutathione reductase), levels of non-enzymatic antioxidants (glutathione, vitamin C, vitamin E) and level of lipid peroxidation (malondialdehyde) were determined in the serum of all the experimental animals. Decrease in all the enzymes and non-enzymatic antioxidant, along with an increase in the lipid peroxidative index (malondialdehyde) was found in all the carbon tetrachloride treated rats as compared with normal controls. Also increase level of non-enzymatic antioxidant along with the decrease level in malondialdehyde was found in all experimental animals which were treated with Agaricus blazei Mushroom extract as compared with normal controls. The findings indicate that the extract of Agaricus blazei Murill can protect the liver against carbon tetrachloride induced oxidative damage in rats and is an efficient hepatoprotective and antioxidant agent against carbon tetrachloride induced liver injury. PMID:23961190

Al-Dbass, Abeer M; Al-Daihan, Sooad K; Bhat, Ramesa Shafi

2012-07-01

63

Agaricus blazei Murill as an efficient hepatoprotective and antioxidant agent against CCl4-induced liver injury in rats  

PubMed Central

Agaricus blazei Murill is one of the very popular edible medicinal mushrooms. The present study investigated the protective effect of this biologically active mushroom on the tissue peroxidative damage and abnormal antioxidant levels in carbon tetrachloride induced hepatotoxicity in male albino rats. Male albino rats of Sprague–Dawley strain weighting (120–150 g) were categorized into five groups. The first group served as the normal control, the second and the third groups were treated with Agaricus blazei Mushroom extract and carbon tetrachloride dose, respectively. Fourth group (protective group) was first treated with Agaricus blazei Mushroom extract followed by carbon tetrachloride treatment and fifth (therapeutic group) with carbon tetrachloride first followed by Agaricus blazei Mushroom treatment. The wet fruiting bodies of mushroom Agaricus blazei Murill, crushed and suspended in distilled water was administered orally to the treated groups of male albino rats. The activities of various enzymes (aspartate and alanine transaminase, lactate dehydrogenase, glutathione reductase), levels of non-enzymatic antioxidants (glutathione, vitamin C, vitamin E) and level of lipid peroxidation (malondialdehyde) were determined in the serum of all the experimental animals. Decrease in all the enzymes and non-enzymatic antioxidant, along with an increase in the lipid peroxidative index (malondialdehyde) was found in all the carbon tetrachloride treated rats as compared with normal controls. Also increase level of non-enzymatic antioxidant along with the decrease level in malondialdehyde was found in all experimental animals which were treated with Agaricus blazei Mushroom extract as compared with normal controls. The findings indicate that the extract of Agaricus blazei Murill can protect the liver against carbon tetrachloride induced oxidative damage in rats and is an efficient hepatoprotective and antioxidant agent against carbon tetrachloride induced liver injury.

Al-Dbass, Abeer M.; Al- Daihan, Sooad K.; Bhat, Ramesa Shafi

2012-01-01

64

Hydrogen Sulfide Attenuates Carbon Tetrachloride-Induced Hepatotoxicity, Liver Cirrhosis and Portal Hypertension in Rats  

PubMed Central

Background Hydrogen sulfide (H2S) displays vasodilative, anti-oxidative, anti-inflammatory and cytoprotective activities. Impaired production of H2S contributes to the increased intrahepatic resistance in cirrhotic livers. The study aimed to investigate the roles of H2S in carbon tetrachloride (CCl4)-induced hepatotoxicity, cirrhosis and portal hypertension. Methods and Findings Sodium hydrosulfide (NaHS), a donor of H2S, and DL-propargylglycine (PAG), an irreversible inhibitor of cystathionine ?-lyase (CSE), were applied to the rats to investigate the effects of H2S on CCl4-induced acute hepatotoxicity, cirrhosis and portal hypertension by measuring serum levels of H2S, hepatic H2S producing activity and CSE expression, liver function, activity of cytochrome P450 (CYP) 2E1, oxidative and inflammatory parameters, liver fibrosis and portal pressure. CCl4 significantly reduced serum levels of H2S, hepatic H2S production and CSE expression. NaHS attenuated CCl4-induced acute hepatotoxicity by supplementing exogenous H2S, which displayed anti-oxidative activities and inhibited the CYP2E1 activity. NaHS protected liver function, attenuated liver fibrosis, inhibited inflammation, and reduced the portal pressure, evidenced by the alterations of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), hyaluronic acid (HA), albumin, tumor necrosis factor (TNF)-?, interleukin (IL)-1?, IL-6 and soluble intercellular adhesion molecule (ICAM)-1, liver histology, hepatic hydroxyproline content and ?-smooth muscle actin (SMA) expression. PAG showed opposing effects to NaHS on most of the above parameters. Conclusions Exogenous H2S attenuates CCl4-induced hepatotoxicity, liver cirrhosis and portal hypertension by its multiple functions including anti-oxidation, anti-inflammation, cytoprotection and anti-fibrosis, indicating that targeting H2S may present a promising approach, particularly for its prophylactic effects, against liver cirrhosis and portal hypertension.

Tan, Gang; Pan, Shangha; Li, Jie; Dong, Xuesong; Kang, Kai; Zhao, Mingyan; Jiang, Xian; Kanwar, Jagat R.; Qiao, Haiquan; Jiang, Hongchi; Sun, Xueying

2011-01-01

65

Radix Paeoniae Rubra and Radix Paeoniae Alba Attenuate CCl4-Induced Acute Liver Injury: An Ultra-Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS) Based Metabolomic Approach for the Pharmacodynamic Study of Traditional Chinese Medicines (TCMs)  

PubMed Central

Metabolomics has been frequently used in pharmacodynamic studies, especially those on traditional Chinese medicine (TCM). Radix Paeoniae Alba and Radix Paeoniae Rubra are popularly used in TCM, and both have hepatoprotective effects. In this study, a CCl4-induced acute liver injury rat model was established and confirmed by the observed serum aminotransferase activities. The metabolomics approach was applied to study the influence of Radix Paeoniae Alba and Radix Paeoniae Rubra on the metabolic changes in rats with acute liver injury. The partial least-squares-discriminant analysis (PLS-DA) of rat serum and their ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) fingerprints allowed discrimination of controlled, acute liver injury-model rats after administration of the two types of TCMs. The time-dependent PLS-DA plots showed that the changes in the metabolic patterns of the rats, which were administered with the TCMs, had stabilized within 2 h after they received the intraperitoneal CCl4 injection. The results indicated the protective effect of TCMs against liver injury. Several potential biomarkers were detected and identified, which included creatine, deoxycholic acid, choline, 5-methylenetetrahydrofolate, folic acid, and glycocholic acid. The physiological significance of these metabolic changes was discussed.

Wang, Rui; Xiong, Ai-Zhen; Teng, Zhong-Qiu; Yang, Qi-Wei; Shi, Yan-Hong; Yang, Li

2012-01-01

66

Radix Paeoniae Rubra and Radix Paeoniae Alba Attenuate CCl4-Induced Acute Liver Injury: An Ultra-Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS) Based Metabolomic Approach for the Pharmacodynamic Study of Traditional Chinese Medicines (TCMs).  

PubMed

Metabolomics has been frequently used in pharmacodynamic studies, especially those on traditional Chinese medicine (TCM). Radix Paeoniae Alba and Radix Paeoniae Rubra are popularly used in TCM, and both have hepatoprotective effects. In this study, a CCl(4)-induced acute liver injury rat model was established and confirmed by the observed serum aminotransferase activities. The metabolomics approach was applied to study the influence of Radix Paeoniae Alba and Radix Paeoniae Rubra on the metabolic changes in rats with acute liver injury. The partial least-squares-discriminant analysis (PLS-DA) of rat serum and their ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) fingerprints allowed discrimination of controlled, acute liver injury-model rats after administration of the two types of TCMs. The time-dependent PLS-DA plots showed that the changes in the metabolic patterns of the rats, which were administered with the TCMs, had stabilized within 2 h after they received the intraperitoneal CCl(4) injection. The results indicated the protective effect of TCMs against liver injury. Several potential biomarkers were detected and identified, which included creatine, deoxycholic acid, choline, 5-methylenetetrahydrofolate, folic acid, and glycocholic acid. The physiological significance of these metabolic changes was discussed. PMID:23203085

Wang, Rui; Xiong, Ai-Zhen; Teng, Zhong-Qiu; Yang, Qi-Wei; Shi, Yan-Hong; Yang, Li

2012-01-01

67

Insulin transport by thoracic duct of male rabbits with CCI4-induced liver cirrhosis.  

PubMed

Insulin concentration in the peripheral blood and the thoracic duct lymph from male rabbits with CCl4-induced liver cirrhosis was measured using a radioimmunoassay technique. Although insulin concentration in the lymph was lower in the cirrhotic animals than in the control ones, the hourly transport of the hormone by the lymphatic vessel of the cirrhotic animals markedly increased in company with the higher flow rate of the lymph. PMID:1231997

Imanishi, Y; Seiki, K

1975-12-01

68

Human umbilical cord blood-derived mesenchymal stem cells improve glucose homeostasis in rats with liver cirrhosis.  

PubMed

Disturbance of glucose metabolism is a common feature in liver cirrhosis which is associated with insulin resistance and is an established risk factor for disease progression and survival in patients with chronic liver diseases. We investigated whether umbilical cord blood-derived mesenchymal stem cells (HMSCs) have an effect on the expression of molecules responsible for glucose utilization and hepatic gluconeogenesis, focusing on the insulin signaling pathway in rats with liver cirrhosis. Rats received a dose of CCl4 (100 µl/100 g 4:1 in corn oil) thrice-weekly. HMSCs were infused at 4 weeks after induction of liver cirrhosis by CCl4. Infusion of HMSCs improved insulin resistance which was associated with increased glucose levels and decreased insulin sensitivity in CCl4-induced cirrhotic rats. HMSCs increased activities in the proximal part of the insulin signaling cascade, as evidenced by increased expression of key enzymes such as phosphatidylinositol-3-kinase (PI 3-kinase), protein kinase B (PKB), protein kinase C-? (PKC-?), and the decrease of glycogen synthase kinase 3 (GSK-3) compared to CCl4-induced liver cirrhotic rats. We also observed that glucose-6-phosphatase (G-6-P) and phosphoenolpyruvate kinase (PEPCK), two hepatic enzymes involved in gluconeogenesis were strongly decreased over 40-50% after infusion of HMSCs. Taken together, our results showed that HMSCs could improve insulin resistance in CCl4-induced liver cirrhosis, thereby contributing to glucose homeostasis. PMID:21537835

Jung, Kyung Hee; Uhm, Yun-Kyung; Lim, Yun Jeong; Yim, Sung-Vin

2011-07-01

69

Pathogenesis of liver cirrhosis  

PubMed Central

Liver cirrhosis is the final pathological result of various chronic liver diseases, and fibrosis is the precursor of cirrhosis. Many types of cells, cytokines and miRNAs are involved in the initiation and progression of liver fibrosis and cirrhosis. Activation of hepatic stellate cells (HSCs) is a pivotal event in fibrosis. Defenestration and capillarization of liver sinusoidal endothelial cells are major contributing factors to hepatic dysfunction in liver cirrhosis. Activated Kupffer cells destroy hepatocytes and stimulate the activation of HSCs. Repeated cycles of apoptosis and regeneration of hepatocytes contribute to pathogenesis of cirrhosis. At the molecular level, many cytokines are involved in mediation of signaling pathways that regulate activation of HSCs and fibrogenesis. Recently, miRNAs as a post-transcriptional regulator have been found to play a key role in fibrosis and cirrhosis. Robust animal models of liver fibrosis and cirrhosis, as well as the recently identified critical cellular and molecular factors involved in the development of liver fibrosis and cirrhosis will facilitate the development of more effective therapeutic approaches for these conditions.

Zhou, Wen-Ce; Zhang, Quan-Bao; Qiao, Liang

2014-01-01

70

Lymphatic role in the pathogenesis of fat malabsorption in liver cirrhosis in rats.  

PubMed

Intestinal fat absorption was examined in rats with CCl4-induced liver cirrhosis. Marked lymphangiectasia of the small intestine was observed in rats after CCl4 was given subcutaneously biweekly for 10--12 weeks. Intestinal epithelial uptake of linoleic acid administered in the loop was not impaired, but accumulation of lipid droplets in the intestinal epithelial cells and disturbed lymphatic transport of absorbed fat were observed in these rats. These data suggest that lymphostasis of the intestine may play an important role in fat malabsorption in liver cirrhosis. PMID:7140488

Miura, S; Asakura, H; Munakata, Y; Kobayashi, K; Yoshioka, M; Morishita, T; Tsuchiya, M

1982-11-01

71

Decreased activity of hepatic alkaline protease in rats with carbon tetrachloride-induced liver cirrhosis.  

PubMed

To investigate the cause of accumulation of oxidised proteins in the livers of rats with carbon tetrachloride (CCl4) induced liver cirrhosis, the activity of alkaline protease (a high molecular weight, multisubunit cysteine proteinase) was determined in the cirrhotic livers. A significant decrease (P < 0.05) in the activity of hepatic alkaline protease was observed in the cirrhotic rats. Decreased activity of alkaline protease in the liver of cirrhotic rats may contribute to the accumulation of the oxidised proteins in the liver. PMID:10865892

Abraham, P; Wilfred, G; Ramakrishna, B

1999-12-01

72

Antioxidant and hepatoprotective activities of Ocimum basilicum Linn. and Trigonella foenum-graecum Linn. against H2O2 and CCL4 induced hepatotoxicity in goat liver.  

PubMed

Significant hepatoprotective effects were obtained by ethanolic extract of leaves of O. basilicum and T. foenum-graecum against liver damage induced by H2O2 and CCl4 as evidenced by decreased levels of antioxidant enzymes (enzymatic and non enzymatic). The extract also showed significant anti lipid peroxidation effects in vitro, besides exhibiting significant activity in superoxide radical and nitric oxide radical scavenging, indicating their potent antioxidant effects. PMID:19761043

Meera, R; Devi, P; Kameswari, B; Madhumitha, B; Merlin, N J

2009-07-01

73

Protein deficiency and muscle damage in carbon tetrachloride induced liver cirrhosis.  

PubMed

Protein undernutrition, alterations of hormones such as IGF-1, testosterone and cortisol, and increased lipid peroxidation-which may be related with deranged metabolism of some elements such as iron (Fe), zinc (Zn), manganese (Mn), selenium (Se) or copper (Cu)-may contribute to muscle damage in non alcoholic cirrhosis. Here, we analyse the effect of protein deficiency on muscle Cu, Fe, Zn, Mn and Se in carbon-tetrachloride (CCl(4)) induced liver cirrhosis. We also study the association between protein undernutrition and these trace elements with the activity of glutathione peroxidase (GPX), superoxide dismutase (SOD) and lipid peroxidation products, and how all these are related with muscle morphological changes in 40 male adult Sprague-Dawley rats. Liver cirrhosis was induced by intraperitoneal injection of CCl(4) to 10 rats fed a 2% protein diet, and to another 10 fed a 18% protein control diet. Two further groups included rats without cirrhosis fed the 2% protein and the 18% protein diets. After sacrifice (6 weeks later), we found type IIa fibre atrophy in the cirrhotic animals, especially in the low-protein fed ones and this was due to protein deficiency. Muscle Fe increased in low protein fed cirrhotic rats. No relationship was found between muscle changes and any of the hormones, enzymes and trace elements analysed, or with liver fibrosis. These results suggest that muscle atrophy observed in CCl(4)-induced cirrhosis is related with protein deficiency, but not with cirrhosis itself. PMID:14563404

López-Lirola, A; González-Reimers, E; Martín Olivera, R; Santolaria-Fernández, F; Galindo-Martín, L; Abreu-González, P; González-Hernández, T; Valladares-Parrilla, F

2003-12-01

74

[Functional restructurings of the mononuclear phagocyte system in experimental liver cirrhosis].  

PubMed

In rats with CCl4-induced liver cirrhosis the clearance rate of colloid carbon particles was more than 2 times lower than in control animals. Simultaneously the uptake capacity of liver Kupffer calls falls. The number of phagocytizing liver macrophages decreased. Along with the diminished functional activity of liver macrophages in cirrhotic liver, the total number of lung and spleen macrophages increased 1.5-fold, with their uptake capacity increasing 10- and 3-fold, respectively. The nitroblue tetrazolium dye reduction and methacrylate particles uptake by alveolar macrophages in vitro rises. The liver, lung, spleen and peritoneal macrophages during liver fibrosis become less sensitive to zymosan stimulation. The incidence of zymosan-induced liver infiltrates decreases 50-fold, while in the lungs they do not develop at all. Such a decreased macrophage reactivity may be closely linked with progressing, poorly reversible liver fibrosis. PMID:3349155

Maianski?, D N; Shvarts, Ia Sh; Tsyrendorzhiev, D D; Kutina, S N

1988-02-01

75

Hepatoprotective properties of sesamin against CCl4 induced oxidative stress-mediated apoptosis in mice via JNK pathway.  

PubMed

Sesamin (Ses), one of the major lignan derived from sesame seeds, has been reported to have many benefits and medicinal properties. However, its protective effects against carbon tetrachloride (CCl4) induced injury in liver have not been clarified. The aim of the present study was to investigate the hepatoprotective effects of sesamin on oxidative stress and apoptosis in mice exposed to CCl4. Our data showed that sesamin significantly prevented CCl4-induced hepatotoxicity in a dose-dependent manner, indicated by both diagnostic indicators of liver damage (serum aminotransferase activities) and histopathological analysis. Moreover, CCl4-induced profound elevation of reactive oxygen species (ROS) production and oxidative stress, as evidenced by increasing of lipid peroxidation level and depleting of the total antioxidant capacity (TAC) in liver, were suppressed by treatment with sesamin. Furthermore, TUNEL assay showed that CCl4-induced apoptosis in mouse liver was significantly inhibited by sesamin. In exploring the underlying mechanisms of sesamin action, we found that activities of caspase-3 were markedly inhibited by the treatment of sesamin in the liver of CCl4 treated mice. Sesamin increased expression levels of phosphorylated Jun N-terminal kinases (JNK) in liver, which in turn inactivated pro-apoptotic signaling events restoring the balance between mitochondrial pro- and anti-apoptotic Bcl-2 proteins and decreasing the release of mitochondrial cytochrome c in liver of CCl4 treated mice. JNK was also involved in the mitochondrial extrinsic apoptotic pathways of sesamin effects against CCl4 induced liver injury by regulating the expression levels of phosphorylated c-Jun proteins, necrosis factor-alpha (TNF-?) and Bak. In conclusion, these results suggested that the inhibition of CCl4-induced apoptosis by sesamin is due at least in part to its anti-oxidant activity and its ability to modulate the JNK signaling pathway. PMID:24287204

Ma, Jie-Qiong; Ding, Jie; Zhang, Li; Liu, Chan-Min

2014-02-01

76

Brain serotonin metabolism and behavior in rats with carbon tetrachloride-induced liver cirrhosis.  

PubMed

Increased brain serotonin metabolism has been suggested as an etiologic factor in the development of portal-systemic encephalopathy (PSE) in connection with liver disease. We therefore investigated brain serotonin metabolism and open-field behavior (spontaneous activity and exploration) in rats with carbon tetrachloride (CCl4)-induced liver cirrhosis. Brain serotonin metabolism was evaluated in rats pretreated with an amino acid decarboxylase inhibitor. The 5-hydroxyindoles were analyzed by high-performance liquid chromatography (HPLC) with electrochemical detection. The results revealed an increased serotonin synthesis rate in all investigated brain regions in rats with histologically verified diffuse micronodular cirrhosis of the liver. Slightly impaired open-field behavior (i.e., decreased spontaneous activity) in the cirrhotic rats could not be excluded. However, the elevated brain serotonin synthesis rate could not be correlated to any abnormalities in open-field behavior. PMID:3441684

Bengtsson, F; Bugge, M; Vagianos, C; Jeppsson, B; Nobin, A

1987-01-01

77

Protective effect of rutin on paracetamol- and CCl 4-induced hepatotoxicity in rodents  

Microsoft Academic Search

Rutin, a well-known flavonoid was investigated for its possible protective effect against paracetamol- and CCl4-induced hepatic damage. Paracetamol produced 100% mortality at the dose of 1 g\\/kg in mice while pre-treatment of animals with rutin (20 mg\\/kg) reduced the death rate to 40%. Oral administration of a sub-lethal dose of paracetamol (640 mg\\/kg) produced liver damage in rats as manifested

Khalid H. Janbaz; Sheikh A. Saeed; Anwar H. Gilani

2002-01-01

78

Intestinal permeability in rats with CCl4-induced portal hypertension  

PubMed Central

AIM: To investigate the intestinal barrier changes in rats with CCl4-induced portal hypertension. METHODS: The permeability of intestinal barrier detected by Lanthanum as a tracer was evaluated in rats. Bacterial translocation and plasma endotoxin were also determined. RESULTS: The incidence of bacterial translocation was 85% in rats with CCl4-induced portal hypertension, which was significantly higher than that in control rats (20%, P<0.01). Plasma endotoxin level was significantly higher in experimental group than in control group. Permeability of the epithelial mucosa and pathological alteration were increased in the ileum and the microvilli became shorter and thinner in rats with portal hypertension. CONCLUSION: Bacterial translocation occurs in rats with CCl4-induced portal hypertension and increased permeability between epithelial cells contributes to the translocation.

Yao, Guo-Xiang; Shen, Zhong-Yi; Xue, Xin-Bo; Yang, Zhen

2006-01-01

79

SHSST Cyclodextrin Complex Prevents the Fibrosis Effect on CCl4-Induced Cirrhotic Cardiomyopathy in Rats through TGF-? Pathway Inhibition Effects  

PubMed Central

Patients with liver cirrhosis also have subtle cardiac structure or function abnormalities. This cardiac dysfunction commonly occurs in 56% of waiting orthotopic liver transplantation (OLT) patients and is defined as cirrhotic cardiomyopathy (CCM). Up to now, there is no standard treatment because CCM does not have a solidly established diagnosis and is based on high clinical suspicion. The liver function of CCM is particularly limited, making patients vulnerable to more drug treatments. Here, we use silymarin (100 mg/kg/day), baicalein (30 mg/kg/day), San Huang Shel Shin Tang (SHSST, 30 mg/kg/day) and ?-cyclodextrin modified SHSST (SHSSTc, 30 and 300 mg/kg/day) treatments for a CCl4-induced CCM rat model. The results show that silymarin, baicalein and SHSST treatments can only slightly reduce the collagen accumulation in CCM rat hearts. However, SHSSTc treatment protects the heart in CCM and significantly inhibits collagen acumination and the fibrosis regulating transforming growth factor-? (TGF-?) pathway expression. SHSSTc treatments further reduced the heart weight and the ratio between left ventricular weight (LVW) and tibia length (TL). This experimental data show that water solubility improved ?-cyclodextrin modified Chinese herbal medicine formula (SHSSTc) can provide an excellent heart protection effect through TGF-? pathway inhibition.

Yang, Cheng-Hsun; Ting, Wei-Jen; Day, Cecilia Hsuan; Ju, Da-Tong; Yeh, Yu-Lan; Chung, Li-Chin; Tsai, Fu-Jenn; Tsai, Chang-Hai; Tsai, Yuhsin; Huang, Chih-Yang

2014-01-01

80

SHSST Cyclodextrin Complex Prevents the Fibrosis Effect on CCl4-Induced Cirrhotic Cardiomyopathy in Rats through TGF-? Pathway Inhibition Effects.  

PubMed

Patients with liver cirrhosis also have subtle cardiac structure or function abnormalities. This cardiac dysfunction commonly occurs in 56% of waiting orthotopic liver transplantation (OLT) patients and is defined as cirrhotic cardiomyopathy (CCM). Up to now, there is no standard treatment because CCM does not have a solidly established diagnosis and is based on high clinical suspicion. The liver function of CCM is particularly limited, making patients vulnerable to more drug treatments. Here, we use silymarin (100 mg/kg/day), baicalein (30 mg/kg/day), San Huang Shel Shin Tang (SHSST, 30 mg/kg/day) and ?-cyclodextrin modified SHSST (SHSSTc, 30 and 300 mg/kg/day) treatments for a CCl4-induced CCM rat model. The results show that silymarin, baicalein and SHSST treatments can only slightly reduce the collagen accumulation in CCM rat hearts. However, SHSSTc treatment protects the heart in CCM and significantly inhibits collagen acumination and the fibrosis regulating transforming growth factor-? (TGF-?) pathway expression. SHSSTc treatments further reduced the heart weight and the ratio between left ventricular weight (LVW) and tibia length (TL). This experimental data show that water solubility improved ?-cyclodextrin modified Chinese herbal medicine formula (SHSSTc) can provide an excellent heart protection effect through TGF-? pathway inhibition. PMID:24815066

Yang, Cheng-Hsun; Ting, Wei-Jen; Day, Cecilia Hsuan; Ju, Da-Tong; Yeh, Yu-Lan; Chung, Li-Chin; Tsai, Fu-Jenn; Tsai, Chang-Hai; Tsai, Yuhsin; Huang, Chih-Yang

2014-01-01

81

Effects of protein deficiency on liver trace elements and antioxidant activity in carbon tetrachloride-induced liver cirrhosis.  

PubMed

In liver cirrhosis, liver tissue becomes progressively substituted by fibrosis, ultimately leading to architectural distortion, liver circulatory changes, and liver failure. Some data support the hypothesis that protein undernutrition may play a role in the development and progression of nonalcoholic liver cirrhosis and that this progression is at least partially mediated by changes in glutathione peroxidase (GPX), superoxide dismutase (SOD), and other antioxidative systems, leading to an increase in lipid peroxidation. We analyzed the effects of protein deficiency on liver Cu, Fe, Zn, Mn, and Se in carbon tetrachloride (CCl4)-induced liver cirrhosis, the relation of protein undernutrition and these trace elements with the activity of some hepatic antioxidative enzymatic mechanisms, and the relation of all of them with morphological and biochemical changes in 40 male adult Sprague-Dawley rats divided in four groups. Liver cirrhosis was induced by intraperitoneal injection of CCl4 to 10 rats fed a 2% protein diet and another 10 fed a 18% protein control diet; two further groups included rats without cirrhosis fed the 2% protein and the 18% protein diets. The study period lasted 6 wk. GPX, SOD, and lipid peroxidation products as well as Zn, Cu, Mn, Se, and Fe were determined in liver samples. We found that liver GPX and Se were reduced in the cirrhotic animals, especially in the low-protein-fed ones, protein deficiency, but not cirrhosis, exerting the main effects. A close correlation was found between liver GPX and serum albumin and weight loss and an inverse one among GPX and hepatocyte ballooning, liver fibrosis, and fat, histomorphometrically determined. These results suggest a pathogenetic role of decreased GPX in the progression of liver disease, which may become enhanced by concomitant protein undernutrition. In addition to iron, the levels of which were increased in the malnourished rats, no differences were found regarding the other trace elements, SOD activity, and lipid peroxidation products. PMID:12835497

González-Reimers, E; López-Lirola, A; Olivera, R Martín; Santolaria-Fernández, F; Galindo-Martín, L; Abreu-González, P; Sánchez-Sanchez, J J; Martínez-Riera, A

2003-01-01

82

Hepatoprotective effects of methanol extract of Carissa opaca leaves on CCl 4 -induced damage in rat  

Microsoft Academic Search

Background  \\u000a Carissa opaca (Apocynaceae) leaves possess antioxidant activity and hepatoprotective effects, and so may provide a possible therapeutic\\u000a alternative in hepatic disorders. The effect produced by methanolic extract of Carissa opaca leaves (MCL) was investigated on CCl4-induced liver damages in rat.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  30 rats were divided into five groups of six animals of each, having free access to food and water

Sumaira Sahreen; Muhammad R Khan; Rahmat A Khan

2011-01-01

83

Liver cirrhosis in rats: regeneration and assessment of the role of phenobarbital.  

PubMed

A common model for producing experimental liver cirrhosis is the administration of CCl4 to phenobarbital (PhB)-stimulated rats. However, concern may arise due to the complex actions of PhB upon liver metabolism. This study examined the role of PhB in the production of CCl4-induced liver cirrhosis in the rat. In addition, regenerative capacity of the liver after partial hepatectomy (PH) or portal branch ligation (PBL) was studied in cirrhotic rats, rats treated with CCl4 alone, and in PhB-treated controls. In rats given PhB throughout the CCl4-induction period, ascitic form of micronodular cirrhosis was found in 93% with only 3% mortality. In contrast, rats pretreated with PhB for only 2 weeks followed by CCl4 alone for 18 weeks did not develop liver cirrhosis. In most of the cirrhotic rats, PH induced hepatic regeneration associated with improved liver histology. PBL was less effective. Treatment with PhB alone for 10 weeks resulted in liver atrophy and reduced hepatic regenerative capacity. Impaired regeneration response was also found in rats treated with CCl4 alone. In conclusion, treatment with PhB throughout the CCl4-induction period seems necessary for the production of liver cirrhosis in rats. However, prolonged treatment with PhB alone results in liver atrophy and an impaired regenerative response. Therefore, though necessary for the cirrhotic model, PhB by itself has negative hepatotrophic influences which questions the thoroughness of the PhB/CCl4 experimental model. PMID:1921373

Rozga, J; Foss, A; Alumets, J; Ahren, B; Jeppsson, B; Bengmark, S

1991-10-01

84

Hepatoprotective effects of the polysaccharide isolated from Tarphochlamys affinis (Acanthaceae) against CCl4-induced hepatic injury.  

PubMed

This study was designed to investigate the protective effects of the polysaccharide isolated from Tarphochlamys affinis (PTA) against CCl4-induced hepatotoxicity in rats. Liver injury was induced in rats by the administration of CCl4 twice a week for 2 weeks. During the experiment, the model group received CCl4 only; the treatment groups received various drugs plus CCl4, whereas the normal control group received an equal volume of saline. Compared with the CCl4 group, PTA significantly decreased the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) in the serum and increased the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) in the liver. Moreover, the content of hepatic malondialdehyde (MDA) was reduced. Histological findings also confirmed the anti-hepatotoxic characterisation. In addition, PTA significantly inhibited the proinflammatory mediators, such as prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), tumour necrosis factor-? (TNF-?) and myeloperoxidase (MPO). Further investigation showed that the inhibitory effect of PTA on the pro-inflammatory cytokines was associated with the down-regulation of nuclear factor-kappa B (NF-?B). In brief, our results show that the protective effect of PTA against CCl4-induced hepatic injury may rely on its ability to reduce oxidative stress and suppress inflammatory responses. PMID:22975511

Lin, Xing; Liu, Xi; Huang, Quanfang; Zhang, Shijun; Zheng, Li; Wei, Ling; He, Min; Jiao, Yang; Huang, Jianchun; Fu, Shujie; Chen, Zhaoni; Li, Yongwen; Zhuo, Lang; Huang, Renbin

2012-01-01

85

Hepatoprotective and antioxidant effects of Commiphora berryi (Arn) Engl bark extract against CCl(4)-induced oxidative damage in rats.  

PubMed

Oxidative damage is involved in the pathogenesis of various hepatic injuries. In the present study the capacity of Commiphora berryi (Arn) Engl bark as an antioxidant to protect against CCl(4)-induced oxidative stress and hepatotoxicity in Albino Wistar rats was investigated. Intraperitoneal injection of CCl(4), administered twice a week, produced a marked elevation in the serum levels of aspartate transaminase, alanine transaminase, alkaline phosphatase and bilirubin. Histopathological analysis of the liver of CCl(4)-induced rats revealed marked liver cell necrosis with inflammatory collections that were conformed to increase in the levels of SOD, GPx and CAT. Daily oral administration of methanolic extract of C. berryi (Arn) Engl bark at 100 and 200mg/kg doses for 15 days produced a dose-dependent reduction in the serum levels of liver enzymes. Treatment with C. berryi normalized various biochemical parameters of oxidative stress and was compared with standard Silymarin. Therefore, the results of this study show that C. berryi (Arn) Engl bark can be proposed to protect the liver against CCl(4)-induced oxidative damage in rats, and the hepatoprotective effect might be correlated with its antioxidant and free radical scavenger effects. PMID:18691629

Gowri Shankar, N L; Manavalan, R; Venkappayya, D; David Raj, C

2008-09-01

86

Ameliorative effect of alkaloid extract of Cyclea peltata (Poir.) Hook. f. & Thoms. roots (ACP) on APAP/CCl4 induced liver toxicity in Wistar rats and in vitro free radical scavenging property  

PubMed Central

Objective To evaluate the hepatoprotective and antioxidant properties of alkaloid extract of Cyclea peltata (C. peltata) against paracetamol/carbon tetra chloride induced liver damage in Wistar rats. Methods In vivo paracetamol/carbon tetrachloride induced liver damage in Wistar rats, in vitro free radical scavenging studies, HPTLC estimation of tetrandrine and direct analysis in real time- mass spectrometry of alkaloid extract of C. peltata were used for the validation. Results The results showed that pretreatment with alkaloid extract of C. peltata caused significant reduction of serum glutamate pyruvate transaminase, serum glutamate oxaloacetate transaminase, serum alkaline phosphatase, serum cholesterol, liver malondialdehyde levels. The reduced glutathione, catalase, superoxide dismutase levels in liver were increased with alkaloid extract of C. peltata treatment. These results were almost comparable to silymarin and normal control. Histopathological studies also substantiated the biochemical findings. The in vitro hydroxyl, superoxide and DPPH scavenging study of alkaloid extract of C. peltata showed significant free radical scavenging property. Conclusions The hepatoprotective property of alkaloid extract of C. peltata against paracetamol/carbon tetrachloride may be due the synergistic action of alkaloids especially tetrandrine, fangchinoline through free radical scavenging and thus preventing oxidative stress.

Shine, Varghese Jancy; Latha, Panikamparambil Gopalakrishnan; Suja, Somasekharan Nair Rajam; Anuja, Gangadharan Indira; Raj, Gopan; Rajasekharan, Sreedharan Nair

2014-01-01

87

Attenuation of CCl(4)-induced hepatic oxidative stress in rat by Launaea procumbens.  

PubMed

Antioxidant effects of Launaea procumbens methanol extract (LPME) were evaluated against CCl(4)-induced oxidative stress in liver of rat. 48 male rats were equally divided in to 8 groups (06 rats each). Group I (control) remained untreated, while Group II was given vehicles (olive oil and DMSO). Animals of Groups III, IV, V, VI and VII were injected intraperitoneally with CCl(4) (3 ml/kg b.w.; i.p., 20% CCl(4)/olive oil) twice a week for four weeks. Group III received only CCl(4) while Group IV was given rutin (50 mg/kg b.w.). Group V, VI and VII were administered LPME at a dose of 100, 150 and 200 mg/kg b.w., respectively. Animals of Group VIII received LPME (200 mg/kg b.w.) alone. Oxidative stress induced with CCl(4) in liver was evident by a significant increase in triglycerides, total cholesterol, LDL-cholesterol, and enzymatic activities of AST, ALT, ALP, LDH, ?-GT activities in serum. Level of lipid peroxidation, nitrite, and hydrogen peroxide concentration, DNA injuries in liver samples was also increased with CCl(4). GSH concentration in liver was significantly decreased, as were the activities of antioxidant enzymes; CAT, POD, SOD, GSH-Px, GST, GSR, QR. Co-treatment of rats with LPME and rutin prevented all the changes observed with CCl(4). Hepatic lesions and telomerase activity induced with CCl(4) was also suppressed with LPME and rutin. It is suggested that LPME effectively prevented the CCl(4)-induced oxidative injuries in liver, possibly through antioxidant and/or free radical scavenging effects of flavonoids and phenolic compounds in the extract. PMID:22134123

Khan, Rahmat Ali; Khan, Muhammad Rashid; Sahreen, Sumaira

2013-03-01

88

Hepatoprotective activity of leaves of Zanthoxylum armatum DC in CCl4 induced hepatotoxicity in rats.  

PubMed

Zanthoxylum armatum DC (Rutaceae) is extensively used in indigenous system of medicine as a tonic, carminative, stomachic and anthelmintic. In the present study, the hepatoprotective activity of the leaves ethanolic extract of Z. armatum (EEZA) was evaluated in CCl4-induced hepatotoxicity in rats. The extract at a dose of 500 mg/kg registered a significant decrease in the levels of serum glutamyl oxalacetic acid transaminase (SGOT), serum glutamyl pyruvate transaminase (SGPT), alkaline phosphatase (ALKP), and serum bilurubin (SBLN) and liver inflammation, which was supported by histopathological studies on liver, thus exhibited a significant hepatoprotective activity. The phytochemical screening of defatted ethanolic extract showed the presence of sterols, alkaloids, flavonoids, and reducing sugars. PMID:20521628

Verma, Nitin; Khosa, R L

2010-04-01

89

Paracrine renal endothelin system in rats with liver cirrhosis.  

PubMed

1. Liver cirrhosis was induced in rats by CCl4 administration. We analysed the expression of endothelin receptor subtypes in the renal cortex and medulla using Scatchard analysis and receptor autoradiography, and measured plasma as well as renal-tissue endothelin-1 concentrations using a specific radioimmunoassay. Furthermore, we analysed the effects of the non-selective (A/B) endothelin receptor antagonist, bosentan (6 and 100 mg kg-1 day-1) on mean arterial blood pressure, water and sodium excretion and glomerular filtration rate. 2. Our study revealed an overexpression of the endothelin B receptor (ETB) in the renal medulla of rats with liver cirrhosis (Cir: 2775 +/- 299 fmol mg-1; Con: 1695 +/- 255 fmol mg-1; n = 8; means +/- s.d., P < 0.01), whereas the density of ETB in the cortex and the endothelin A receptor (ETA) in the cortex and medulla were similar in both cirrhotic and control rats. Receptor autoradiography showed that the upregulation of medullary ETB in cirrhotic rats was due to an upregulation of ETB in the inner medullary collecting duct cells. 3. The tissue endothelin-1 concentrations were increased in the renal medulla of cirrhotic rats (Cir: 271 +/- 68 pg g-1wet wt.; Con: 153 +/- 36 pg g-1 wet wt., n = 8; means +/- s.d., P < 0.01). 4. The glomerular filtration rate was slightly decreased in cirrhotic rats but not altered after bosentan treatment in either cirrhotic or control rats. Bosentan decreased sodium excretion to a similar extent in both cirrhotic and control rats, whereas water excretion was significantly reduced by both dosages of bosentan in cirrhotic rats only (Cir + vehicle: 12.5 +/- 0.62 m day-1, Cir + 6 mg kg-1 day-1 bosentan: 8.6 +/- 1.0 ml day-1; Cir + 100 mg kg-1 day-1 bosentan: 7.4 +/- 0.6 ml day-1; n = 10; means +/- s.e.mean). 5. We therefore suggest that the upregulation of the medullary ETB in cirrhotic rats is involved in the regulation of water excretion in rats with CCl4-induced liver cirrhosis. PMID:8735618

Hocher, B; Zart, R; Diekmann, F; Rohmeiss, P; Distler, A; Neumayer, H H; Bauer, C; Gross, P

1996-05-01

90

Paracrine renal endothelin system in rats with liver cirrhosis.  

PubMed Central

1. Liver cirrhosis was induced in rats by CCl4 administration. We analysed the expression of endothelin receptor subtypes in the renal cortex and medulla using Scatchard analysis and receptor autoradiography, and measured plasma as well as renal-tissue endothelin-1 concentrations using a specific radioimmunoassay. Furthermore, we analysed the effects of the non-selective (A/B) endothelin receptor antagonist, bosentan (6 and 100 mg kg-1 day-1) on mean arterial blood pressure, water and sodium excretion and glomerular filtration rate. 2. Our study revealed an overexpression of the endothelin B receptor (ETB) in the renal medulla of rats with liver cirrhosis (Cir: 2775 +/- 299 fmol mg-1; Con: 1695 +/- 255 fmol mg-1; n = 8; means +/- s.d., P < 0.01), whereas the density of ETB in the cortex and the endothelin A receptor (ETA) in the cortex and medulla were similar in both cirrhotic and control rats. Receptor autoradiography showed that the upregulation of medullary ETB in cirrhotic rats was due to an upregulation of ETB in the inner medullary collecting duct cells. 3. The tissue endothelin-1 concentrations were increased in the renal medulla of cirrhotic rats (Cir: 271 +/- 68 pg g-1wet wt.; Con: 153 +/- 36 pg g-1 wet wt., n = 8; means +/- s.d., P < 0.01). 4. The glomerular filtration rate was slightly decreased in cirrhotic rats but not altered after bosentan treatment in either cirrhotic or control rats. Bosentan decreased sodium excretion to a similar extent in both cirrhotic and control rats, whereas water excretion was significantly reduced by both dosages of bosentan in cirrhotic rats only (Cir + vehicle: 12.5 +/- 0.62 m day-1, Cir + 6 mg kg-1 day-1 bosentan: 8.6 +/- 1.0 ml day-1; Cir + 100 mg kg-1 day-1 bosentan: 7.4 +/- 0.6 ml day-1; n = 10; means +/- s.e.mean). 5. We therefore suggest that the upregulation of the medullary ETB in cirrhotic rats is involved in the regulation of water excretion in rats with CCl4-induced liver cirrhosis. Images Figure 1 Figure 5

Hocher, B.; Zart, R.; Diekmann, F.; Rohmeiss, P.; Distler, A.; Neumayer, H. H.; Bauer, C.; Gross, P.

1996-01-01

91

Protective effect of chrysin on carbon tetrachloride (CCl4)-induced tissue injury in male Wistar rats.  

PubMed

Chrysin, a natural flavonoid has been reported to possess potent anti-inflammatory, anti-cancer and antioxidation properties. In the present study, we aimed to evaluate the putative protective effect of chrysin, an isoflavone, on carbon tetrachloride (CCl(4))-induced toxicity in male Wistar rats. Intraperitoneal administration of CCl(4) (2 ml/kg) to rats for 4 days resulted in significantly elevated (p < 0.05) serum levels of glutamic oxaloacetic transaminase (SGOT), glutamic pyruvate transaminase (SGPT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH), when compared to normal rats. In addition, the tissues (liver, kidney and brain) and haemolysate samples showed considerable increase in levels (p < 0.05) of malondialdehyde (MDA) and lowered levels (p < 0.05) of reduced glutathione (GSH), vitamin C and E when compared to values in normal rats. Quantitative analysis of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (Gpx) exhibited lower activities of these antioxidant enzymes in the tissues and haemolysate of CCl(4)-administered rats. The protective action of chrysin on CCl(4)-induced rat was demonstrated with SGPT, SGOT, ALP and LDH resuming to near normal levels, while the mean levels of GSH and of vitamin C and E were elevated, the mean activities of CAT, SOD and Gpx were enhanced and the mean level of MDA was lowered in the tissue and haemolysate samples when compared to the CCl(4)-exposed untreated rats. The expression of the iNOS gene appeared to be up-regulated in the liver and kidney samples of CCl(4)-exposed untreated rats, whereas in CCl(4)-exposed chrysin-treated rats, the mRNA transcript levels of iNOS approximated normal levels. These results strongly suggest that chrysin is able to prevent the oxidative damage induced by CCl(4) in the liver, brain, kidney and haemolysate of male Wistar rats. PMID:21511893

Anand, Kalaiselvi Velayutham; Anandhi, Ramalingam; Pakkiyaraj, Murugesan; Geraldine, Pitchairaj

2011-11-01

92

Protective effects of amburoside A, a phenol glucoside from Amburana cearensis, against CCl4-induced hepatotoxicity in rats.  

PubMed

The aim of this study was to investigate the possible beneficial effects of amburoside A, AMB [4-(O-beta- D-glycopyranosyl)benzyl protocatechoate], against carbon tetrachloride (CCl (4)) toxicity in rats. AMB is a phenol glucoside from the Brazilian medicinal plant Amburana cearensis, popularly used for the treatment of respiratory tract affections. Acute AMB (25 and 50 mg/kg, I. P. or P. O.) treatments of CCl (4)-intoxicated rats significantly inhibited the increase in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, as compared to the group treated with CCl (4) only. Histological studies showed less centrolobular necrosis and inflammatory cell infiltrates in the liver of animals treated with AMB plus CCl (4), when compared to the group treated with CCl (4) alone. In hepatic tissues, AMB at both doses inhibited CCl (4)-induced thiobarbituric acid-reactive substances (TBARS) formation, indicating a blockade of CCl (4)-induced lipid peroxidation. AMB also reversed the decrement in glutathione contents of hepatic tissues in CCl (4)-intoxicated rats. Furthermore, it restored catalase activity to normal values, which was significantly increased after CCl (4) treatment. Our results indicate that CCl (4)-induced oxidative damage in hepatic tissues is reversed by AMB treatment. The protective effect of AMB is probably due to the phenolic nature of this glucoside. PMID:18404596

Leal, Luzia K; Fonseca, Francisco Noé; Pereira, Fábio Azevedo; Canuto, Kirley M; Felipe, Cícero F; Fontenele, Juvênia Bezerra; Pitombeira, Márcia V; Silveira, Edilberto R; Viana, Glauce S

2008-04-01

93

Hepatoprotective and antioxidant activities of flowers of Calotropis procera (Ait) R. Br. in CCl4 induced hepatic damage.  

PubMed

Hepatoprotective activity of 70% ethanolic extract of flowers of C. procera was studied against CCl4 induced hepatic injury in albino rats and mice. In addition, antioxidant activity was studied by in vitro models. Pre-treatment with 70% ethanolic extract (CPA) reduced the biochemical markers of hepatic injury like serum glutamate pyruvate transaminase, serum glutamate oxaloacetate transaminase, alkaline phosphatase, bilirubin, cholesterol, HDL and tissue glutathione (GSH) levels. Similarly pretreatment with CPA reduced the CCl4 induced elevation in the pentobarbitone sleeping time. Histopathological observations also revealed that pretreatment with CPA protected the animals from CCl4 induced liver damage. CPA demonstrated dose dependant reduction in the in vitro and in vivo lipid peroxidation induced by CCl4. In addition it showed dose dependant free radical scavenging activity. The results indicate that flowers of C. procera possess hepatoprotective property possibly because of its anti-oxidant activity. This property may be attributed to the quercetin related flavonoids present in the flowers of Calotropis procera. PMID:17373378

Qureshi, Absar Ahmed; Prakash, T; Patil, Tushar; Viswanath Swamy, A H M; Gouda, A Veeran; Prabhu, K; Setty, S Ramachandra

2007-03-01

94

Protective effect of alcoholic extract of Entada pursaetha DC. against CCl4-induced hepatotoxicity in rats.  

PubMed

The alcoholic extract of stem of E. pursaetha (PSE, 30, 100, 300 mg/kg body weight, po for 7 days) showed hepatoprotective activity against CCl4 (2 mL/kg body weight, ip)-induced hepatotoxicity. The extract exhibited a significant dose-dependent hepatoprotective effect comparable to standard drug silymarin, by preventing increase in serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total protein, and total bilirubin, lactate dehydrogenase; by lowering hepatic levels of malonaldehyde, nitrate-nitrite, myeloperoxidase activity; enhancing activities of antioxidant enzymes, superoxide dismutase, catalase and increasing reduced glutathione levels in liver, which suggests the antioxidant property of PSE. Histopathological studies also supported the above biochemical parameters. The results suggested that alcoholic extract of E. pursaetha possesses significant hepatoprotective activity in CCl4-induced acute hepatotoxicity in rats and this is likely to be mediated through its antioxidant activities. PMID:24669663

Gupta, Gaurav; More, Amar Sunil; Kumari, Rashmi Rekha; Lingaraju, Madhu Cholenahalli; Kumar, Dhirendra; Kumar, Dinesh; Mishra, Santosh Kumar; Tandan, Surender Kumar

2014-03-01

95

Portal vein thrombosis in liver cirrhosis  

PubMed Central

Portal vein thrombosis (PVT) is considered to be a frequent complication of liver cirrhosis. However, unlike PVT in patients without cirrhosis, very few data are available on the natural history and management of PVT in cirrhosis, despite its association with potentially life-threatening conditions, such as gastroesophageal bleeding and acute intestinal ischemia. Moreover, no consensus regarding PVT in cirrhosis exists. Suggested causes of PVT in cirrhosis include reduced portal blood flow velocity, multiple congenital or acquired thrombophilic factors, inherited or acquired conditions, and derangement of liver architecture. However, the understanding of PVT in cirrhosis is incomplete. In addition, information on the management of PVT in cirrhosis is inadequate. The aims of this review are to: (1) assemble data on the physiopathological mechanism, clinical findings, diagnosis and management of PVT in cirrhosis; (2) describe the principal factors most frequently involved in PVT development; and (3) summarize the recent knowledge concerning diagnostic and therapeutic procedures.

Kinjo, Nao; Kawanaka, Hirofumi; Akahoshi, Tomohiko; Matsumoto, Yoshihiro; Kamori, Masahiro; Nagao, Yoshihiro; Hashimoto, Naotaka; Uehara, Hideo; Tomikawa, Morimasa; Shirabe, Ken; Maehara, Yoshihiko

2014-01-01

96

Isoflavones-Enriched Soy Protein Prevents CCL4-Induced Hepatotoxicity in Rats  

PubMed Central

The burden of liver disease in Egypt is exceptionally high due to the highest prevalence of hepatitis C virus (HCV) resulting in rising rates of hepatocellular carcinoma (HCC). The aim of the current study was to determine the isoflavones in soy and to evaluate the protective role of soy against CCl4-induced liver damage in rats. Four experimental groups were treated for 8 weeks and included the control group, soy-supplemented diet (20%?w/w) group, the group treated orally with CCl4 (100?mg/kg bw) twice a week, and the group fed soy-supplemented diet and treated with CCl4. Blood and liver tissue samples were collected for biochemical analyses and histological examination. The results indicated that protein content was 45.8% and the total isoflavones recorded 167.3?mg/100?g soy. Treatment with CCl4 resulted in a significant biochemical changes in serum liver tissue accompanied with severe oxidative stress and histological changes. Supplementation with soy succeeded to restore the elevation of liver enzymes activities and improved serum biochemical parameters. Moreover, soy supplementation improved the antioxidant enzymes, decreased lipid peroxidation, and improved the histological picture of the liver tissue. It could be concluded that soy-protein-enriched isoflavones may be a promising agent against liver diseases.

Sarhan, Nesma A. Z.; El-Denshary, Ezzeldein S.; Hassan, Nabila S.; Abu-Salem, Ferial M.; Abdel-Wahhab, Mosaad A.

2012-01-01

97

Acute myopathy associated with liver cirrhosis  

Microsoft Academic Search

AIM: Many cirrhotic patients have muscular symptoms and rhabdomyolysis. However, myopathy associated with liver cirrhosis has not been established as a disease entity. We evaluated the clinical significance of acute myopathy associated with liver cirrhosis. METHODS: We retrospectively reviewed the medical records of 5 440 cirrhotic patients who had been admit- ted to Gyeongsang National University Hospital from Au- gust

Ok-Jae Lee; Jee-Hyang Yoon; Eun-Jeong Lee; Hyun-Jin Kim; Tae-Hyo Kim

98

Attenuation of CCl4-Induced Oxidative Stress and Hepatonephrotoxicity by Saudi Sidr Honey in Rats.  

PubMed

The present study was undertaken to investigate the possible protective effect of Saudi Sidr honey (SSH) on carbon tetrachloride (CCl4) induced oxidative stress and liver and kidney damage in rat. Moreover, the antioxidant activity and the phenolic and flavonoidal contents were determined. The hepatorenal protective activity of the SSH was determined by assessing biochemical, hematological, and histological parameters. Serum transaminases, ALP, GGT, creatinine, bilirubin urea, uric acid, and MDA level in liver and kidney tissues were significantly elevated, and the antioxidant status of nonprotein sulfhydryls, albumin, and total protein levels in liver and kidney were declined significantly in CCl4 alone treated animals. Pretreatment with SSH and silymarin prior to the administration of CCl4 significantly prevented the increase of the serum levels of enzyme markers and reduced oxidative stress. SSH also exhibited a significant lipid-lowering effect and caused an HDL-C enhanced level in serum. The histopathological evaluation of the liver and kidney also revealed that honey protected incidence of both liver and kidney lesions. Moreover, SSH showed a strong antioxidant activity in DPPH and ? -carotene-linoleic acid assays. SSH was found to contain phenolic compounds. Additionally, the SSH supplementation restored the hepatocytes viability against 2',7'-dichlorofluorescein (DCF) toxicity in ex vivo test. PMID:23533498

Al-Yahya, Mohammed; Mothana, Ramzi; Al-Said, Mansour; Al-Dosari, Mohammed; Al-Musayeib, Nawal; Al-Sohaibani, Mohammed; Parvez, Mohammad Khalid; Rafatullah, Syed

2013-01-01

99

Attenuation of CCl4-Induced Oxidative Stress and Hepatonephrotoxicity by Saudi Sidr Honey in Rats  

PubMed Central

The present study was undertaken to investigate the possible protective effect of Saudi Sidr honey (SSH) on carbon tetrachloride (CCl4) induced oxidative stress and liver and kidney damage in rat. Moreover, the antioxidant activity and the phenolic and flavonoidal contents were determined. The hepatorenal protective activity of the SSH was determined by assessing biochemical, hematological, and histological parameters. Serum transaminases, ALP, GGT, creatinine, bilirubin urea, uric acid, and MDA level in liver and kidney tissues were significantly elevated, and the antioxidant status of nonprotein sulfhydryls, albumin, and total protein levels in liver and kidney were declined significantly in CCl4 alone treated animals. Pretreatment with SSH and silymarin prior to the administration of CCl4 significantly prevented the increase of the serum levels of enzyme markers and reduced oxidative stress. SSH also exhibited a significant lipid-lowering effect and caused an HDL-C enhanced level in serum. The histopathological evaluation of the liver and kidney also revealed that honey protected incidence of both liver and kidney lesions. Moreover, SSH showed a strong antioxidant activity in DPPH and ?-carotene-linoleic acid assays. SSH was found to contain phenolic compounds. Additionally, the SSH supplementation restored the hepatocytes viability against 2?,7?-dichlorofluorescein (DCF) toxicity in ex vivo test.

Al-Yahya, Mohammed; Mothana, Ramzi; Al-Said, Mansour; Al-Dosari, Mohammed; Al-Musayeib, Nawal; Al-Sohaibani, Mohammed; Parvez, Mohammad Khalid; Rafatullah, Syed

2013-01-01

100

Hepatoprotective effects of methanol extract of Carissa opaca leaves on CCl4-induced damage in rat  

PubMed Central

Background Carissa opaca (Apocynaceae) leaves possess antioxidant activity and hepatoprotective effects, and so may provide a possible therapeutic alternative in hepatic disorders. The effect produced by methanolic extract of Carissa opaca leaves (MCL) was investigated on CCl4-induced liver damages in rat. Methods 30 rats were divided into five groups of six animals of each, having free access to food and water ad libitum. Group I (control) was given olive oil and DMSO, while group II, III and IV were injected intraperitoneally with CCl4 (0.5 ml/kg) as a 20% (v/v) solution in olive oil twice a week for 8 weeks. Animals of group II received only CCl4. Rats of group III were given MCL intragastrically at a dose of 200 mg/kg bw while that of group IV received silymarin at a dose of 50 mg/kg bw twice a week for 8 weeks. However, animals of group V received MCL only at a dose of 200 mg/kg bw twice a week for 8 weeks. The activities of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and ?-glutamyltransferase (?-GT) were determined in serum. Catalase (CAT), peroxidase (POD), superoxide dismutase (SOD), glutathione-S-transferase (GST), glutathione peroxidase (GSH-Px), glutathione reductase (GSR) and quinone reductase (QR) activity was measured in liver homogenates. Lipid peroxidation (thiobarbituric acid reactive substances; TBARS), glutathione (GSH) and hydrogen peroxide (H2O2) concentration was also assessed in liver homogenates. Phytochemicals in MCL were determined through qualitative and high performance liquid chromatography (HPLC) analysis. Results Hepatotoxicity induced with CCl4 was evidenced by significant increase in lipid peroxidation (TBARS) and H2O2 level, serum activities of AST, ALT, ALP, LDH and ?-GT. Level of GSH determined in liver was significantly reduced, as were the activities of antioxidant enzymes; CAT, POD, SOD, GSH-Px, GSR, GST and QR. On cirrhotic animals treated with CCl4, histological studies showed centrilobular necrosis and infiltration of lymphocytes. MCL (200 mg/kg bw) and silymarin (50 mg/kg bw) co-treatment prevented all the changes observed with CCl4-treated rats. The phytochemical analysis of MCL indicated the presence of flavonoids, tannins, alkaloids, phlobatannins, terpenoids, coumarins, anthraquinones, and cardiac glycosides. Isoquercetin, hyperoside, vitexin, myricetin and kaempherol was determined in MCL. Conclusion These results indicate that MCL has a significant protective effect against CCl4 induced hepatotoxicity in rat, which may be due to its antioxidant and membrane stabilizing properties.

2011-01-01

101

Protective Effect of Cornus mas Fruits Extract on Serum Biomarkers in CCl4-Induced Hepatotoxicity in Male Rats  

PubMed Central

Background: Nowadays attention to use herbs such as cornelian cherry (Cornus mas) is increasing, which contains high levels of antioxidants and anthocyanins. Cornus mas fruits have been used for gastrointestinal and excretory disorders for many years in traditional medicine, also may improve liver and kidney functions, and have protective effects such as anti-allergic, antidiabetic, antibacterial, antimicrobial, antihistamine and antimalarial properties. Objectives: The aim of this study was to investigate protective effects of Cornus mas fruits extract on serum biomarkers in CCl4-induced hepatotoxicity in male rats. Materials and Methods: Hepatotoxicity was induced by administration of carbon tetrachloride (1 mL/kg i.p.) in 1:1 dilution with olive oil. To evaluate the effect of Cornus mas fruits extract on disease progression, serum marker enzymes, serum total protein and albumin and liver lipid peroxidation were determined in CCl4-induced hepatotoxicity. Results: Oral administration of Cornus mas fruits extract to rats for 14 days provided a significant (P < 0.05) hepatoprotection by decreasing elevated serum level of enzymes, total serum protein, albumin and liver lipid peroxidation content. Conclusions: Cornus mas fruit extract effect may be due to including some antioxidant components, which caused membrane stabilizing and normalization of fluctuated biochemical profiles induced by CCl4 exposure. Our results validated the traditional use of Cornus mas in the treatment of liver disorders.

Alavian, Seyed Moayed; Banihabib, Nafiseh; Es. Haghi, Masoud; Panahi, Farid

2014-01-01

102

Effect of leaf extracts of Taraxacum officinale on CCl4 induced Hepatotoxicity in rats, in vivo study.  

PubMed

Taraxacum officinale L is a medicinal plant, which has enormous medicinal values against various types of liver disorders and it has traditionally been used for the treatment of liver problems by people from the South East Asia. Previously we have screened the crude methanolic extract of T. officinale against cytotoxicity induced by CCl4. Present study was designed to compare the protective effect of ethanolic and n-hexane extract of leaves in carbon tetrachloride (CCl4) induced liver toxicity in rats. The extract (200 mg/kg and 400mg/kg body weight) along with silymarin (100 mg/kg) a standard drug was administered to experimental animals. It was observed that ethanolic plant extract has significantly reduced the negative effect of CCl4 as compared to n-hexane extract and effect of extract was increased with increasing dose level. Although both leaf extracts decreased the concentration of TBARS, H2O2 and nitrite contents which enhance due to CCl4 toxicity but effect was higher in ethanolic extract. The results clearly indicated that Taraxacum officinale ethanolic leaves extract has better protective effect against CCl4 induced liver tissues toxicity. This claim was also supported by histopathological results obtained during this study and this might be due to presence of various polar phytochemicals that might be more prevent in this extract. PMID:25015447

Gulfraz, Muhammad; Ahamd, Dawood; Ahmad, Muhammad Sheeraz; Qureshi, Rehmatullah; Mahmood, Raja Tahir; Jabeen, Nyla; Abbasi, Kashif Sarfraz

2014-07-01

103

Hepatoprotective effect of acetonic and methanolic extracts of Heterotheca inuloides against CCl(4)-induced toxicity in rats.  

PubMed

A model of hepatotoxicity by carbon tetrachloride (CCl(4)) in rats was used in order to evaluate the protective potential of the acetonic and methanolic extracts of Heterotheca inuloides. Pretreatment with the two H. inuloides extracts attenuated the increase in the activity of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) observed in CCl(4)-induced liver injury. The protective effect was confirmed by the analysis of tissue slides stained with hematoxylin-eosin and periodic acid/Schiff's reagent. Additionally, the two extracts are scavengers to the superoxide radical as was observed by electron paramagnetic resonance. Due to the fact that the methanolic extract resulted in a better protective effect in the previous experiments, it was used to investigate in more detail the mechanism of hepatoprotection. Quercetin, one of the main components of the extract, with known hepatoprotective and antioxidant activity was used as a positive control. Pretreatment of animals with the methanolic extract or quercetin, was associated with the prevention of 4-hydroxynonenal and 3-nitrotyrosine increase in the liver, two markers of oxidative stress. Furthermore, the decrease in the activity of several antioxidant enzymes including superoxide dismutase, catalase and glutathione peroxidase in CCl(4)-induced liver injury was alleviated by the pretreatment with H. inuloides methanolic extract or quercetin. These results suggest that the hepatoprotective capacity of H. inuloides methanolic extract is associated with its antioxidant properties, which would also explain the biomedical properties attributed to this plant. PMID:20227265

Coballase-Urrutia, Elvia; Pedraza-Chaverri, José; Cárdenas-Rodríguez, Noemí; Huerta-Gertrudis, Bernardino; García-Cruz, Mercedes Edna; Ramírez-Morales, Aline; Sánchez-González, Dolores Javier; Martínez-Martínez, Claudia María; Camacho-Carranza, Rafael; Espinosa-Aguirre, Jesús Javier

2011-05-01

104

Bamboo salt attenuates CCl4-induced hepatic damage in Sprague-Dawley rats  

PubMed Central

Bamboo salt, a Korean folk medicine, is prepared with solar salt (sea salt) and baked several times at high temperatures in a bamboo case. In this study, we compared the preventive effects of bamboo salt and purified and solar salts on hepatic damage induced by carbon tetrachloride in Sprague-Dawley rats. Compared with purified and solar salts, bamboo salts prevented hepatic damage in rats, as evidenced by significantly reduced serum levels of aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase (P < 0.05). Bamboo salt (baked 9×) triggered the greatest reduction in these enzyme levels. In addition, it also reduced the levels of the proinflammatory cytokines interleukin (IL)-6, interferon (IFN)-?, and tumor necrosis factor (TNF)-?. Histopathological sections of liver tissue demonstrated the protective effect of bamboo salt, whereas sections from animals treated with the other salt groups showed a greater degree of necrosis. We also performed reverse transcription-polymerase chain reaction and western blot analyses of the inflammation-related genes iNOS, COX-2, TNF-?, and IL-1? in rat liver tissues. Bamboo salt induced a significant decrease (~80%) in mRNA and protein expression levels of COX-2, iNOS, TNF-?, and IL-1?, compared with the other salts. Thus, we found that baked bamboo salt preparations could prevent CCl4-induced hepatic damage in vivo.

Zhao, Xin; Song, Jia-Le; Kil, Jeung-Ha

2013-01-01

105

Naringenin attenuates CCl4 -induced hepatic inflammation by the activation of an Nrf2-mediated pathway in rats.  

PubMed

The possible protective effects of naringenin, a naturally occurring citrus flavonone, on carbon tetrachloride (CCl4 )-induced liver injury in rats and the mechanism underlying its effects were investigated. Forty rats were divided into five groups. Rats in Groups I and II served as the normal and injured liver groups, respectively; Group III rats were treated with the standard drug silymarin as a positive control; and rats in Groups IV and V (naringenin-treated groups) were administrated 50 mg/kg, p.o., naringenin for 7 days. Liver samples were collected to evaluate mRNA and protein expression, histological changes and oxidative stress. Naringenin inhibited lipid peroxidation and reduced serum levels of hepatic enzymes induced by CCl4 . In addition, naringenin increased the liver content of reduced glutathione and the activity of anti-oxidant enzymes in rats treated with CCl4 . Naringenin attenuated liver inflammation by downregulating CCl4 -induced activation of tumour necrosis factor (TNF)-?, inducible nitric oxide synthase (iNOS) and cyclo-oxygenase (COX-2) at both the protein and mRNA levels. Naringenin treatment significantly increased NF-E2-related factor 2 (Nrf2) and heme oxygenase (HO-1) expression in injured livers. In rats treated with CCl4 alone, decreases were seen in nuclear Nrf2 expression and in the mRNA levels of its target genes (e.g. HO-1, NQO1 and glutathione S-transferase alpha 3 (GST-a3)). Together, the results suggest that naringenin can protect the liver against oxidative stress, presumably by activating the nuclear translocation of Nrf2 as well as attenuating the TNF-? pathway to elicit an anti-inflammatory response in liver tissue. PMID:24684352

Esmaeili, Mohammad Ali; Alilou, Mostafa

2014-06-01

106

Management of Alcoholic Cirrhosis of the Liver  

Microsoft Academic Search

Patients with liver disease require skilled, complex management of the inevitable complications associated with hepatic dysfunction. Portal hypertension, a major consequence of cirrhosis of the liver, causes ascites and esophageal variceal hemorrhages. Many clinical and surgical treatment options are available to manage these complications; however, they often produce only temporary symptom control and may beget further morbidity. This article focuses

Donna R. McEwen

1996-01-01

107

Decision of Cirrhosis Using Liver's Ultrasonic Images  

Microsoft Academic Search

Feature extraction techniques in the ultrasonic images of a liver were studied firstly. As an initial result, total 25 parameters relating to cirrhosis were extracted. They were obtained from the motion curve of the liver in an M-mode image, and from the texture using a B-mode image. Then the efficiency of every parameter was analyzed, and with the use of

Guohui Zhou; Yuanyuan Wang; Weiqi Wang; Ying Sun; Yue Chen

2005-01-01

108

Depressed sensitivity of the hepatoportal NaCl receptors in rats with carbon tetrachloride-induced liver cirrhosis.  

PubMed

In normal rats, the activity of the hepatoportal NaCl-sensitive afferent nerves is increased by portal injection of hypertonic NaCl. In the present article, we have found this effect to be markedly reduced in rats with CCl4-induced liver cirrhosis (CT rats). Liver tissue norepinephrine content, a marker of tissue innervation, was also decreased in the treated rats. Over the 12 wk CCl4-treatment period, no significant difference in Na balance was found between control and CT rats when both groups were given normal NaCl (0.45%) food. However, when both were given high NaCl (8%) food, the Na balance of CT rats was positive and greater than that of controls. These results indicate that the sensitivity of the hepatoportal NaCl receptors is decreased even when the degree of liver cirrhosis is slight. This mechanism plays an important role in maintaining Na balance during intake of high NaCl food. PMID:8594941

Tanaka, K; Matsuda, T; Morita, H; Hosomi, H

1995-12-01

109

The roles of ER stress and P450 2E1 in CCl(4)-induced steatosis.  

PubMed

The role of ER stress on hepatic steatosis was investigated in a rat model. We injected CCl(4) into rats and found that CCl(4) could induce hepatic lipid accumulation, confirmed by Oil Red O staining and by measurement of triglyceride and cholesterol. The expression of ApoB, an apolipoprotein, was decreased in plasma and increased in the liver of CCl(4)-treated animals. The ER stress response was also significantly increased by CCl(4). P450 2E1 expression and activity were increased through interactions of P450 2E1 with NADPH-dependent P450 reductase (NPR) under CCl(4)-treated conditions. In HepG2 cells, intracellular lipid accumulation and its signaling were comparable to in vivo results. In order to elucidate the effect of the ER stress response itself, tunicamycin, an N-acetyl-glycosylation inhibitor, was injected into rats, followed by Oil Red O staining, lipid/triglyceride/cholesterol accumulation analysis, and examination of ApoB expression. Additionally, the ER stress response and upregulation of P450 2E1 were also confirmed in the tunicamycin-treated rats. All of the responses were similar to those seen with CCl(4). The P450 2E1 inhibitor diallyl sulphide (DAS), N-acetylcysteine (NAC), and reduced glutathione (GSH) antioxidants also regulated processes, including ApoB expression and lipid accumulation in CCl(4)-treated animals. In the presence of tunicamycin, DAS or NAC/GSH regulated all of the pathological phenomena with the exception of the ER stress response. In summary, CCl(4) induces liver steatosis, a process involving ER stress-induced P450 2E1 activation and ROS production. PMID:21722752

Lee, Geum-Hwa; Bhandary, Bidur; Lee, Eun-Mi; Park, Jin-Kyu; Jeong, Kyu-Shik; Kim, In-Ki; Kim, Hyung-Ryong; Chae, Han-Jung

2011-10-01

110

Evaluation of protective effect of Sapindus mukorossi saponin fraction on CCl4-induced acute hepatotoxicity in rats  

PubMed Central

Aim This investigation aimed to assess the hepatoprotective effect of saponin fraction isolated from the fruit pericarp of Sapindus mukorossi on carbon tetrachloride (CCl4)-induced hepatotoxicity. Methods Fruit of S. mukorossi was collected and authenticated, and dried pericarp powder subjected to extraction with cold ethanol (70%) by maceration followed by isolation of total saponin fraction. Hepatoprotective activity was demonstrated in the CCl4-damaged primary monolayer culture. In in vivo studies, pretreatment with total saponin fraction (50,100 and 150 mg/kg per os once a day for 4 days before CCl4 introduction and continued afterward for 3 days) attenuated the CCl4-induced acute increase in serum glutamic pyruvic transaminase, serum glutamic oxaloacetic transaminase, and alkaline phosphatase activities and considerably reduced histopathological alterations. Further, saponin fraction reduced thiopentone-induced (4 mg/kg, intraperitoneal) sleeping time in rats. Results Saponin fraction pretreatment improves bromsulphalein clearance and also increases cellular viability. Saponin administration replenished depleted hepatic glutathione and superoxide dismutase by improving the antioxidant status of the liver and liver function enzymes. These effects substantiate protection of cellular phospholipids from peroxidative damage induced by highly reactive toxic intermediate radicals formed during biotransformation of CCl4. Conclusion The above findings lead to the conclusion that the saponin fraction of S. mukorossi has a protective capability both in vitro on primary hepatocyte cultures and in vivo in a rat model of CCl4-mediated liver injury. Hence, we suggest that the inclusion of this S. mukorossi fruit pericarp in the management of liver disorders is justified.

Rao, M Srinivasa; Asad, B Syed; Fazil, MA; Sudharshan, RD; Rasheed, SA; Pradeep, HA; Aboobacker, S; Thayyil, AH; Riyaz, AK; Mansoor, M; Aleem, MA; Zeeyauddin, K; Narasu, M Lakshmi; Anjum, A; Ibrahim, M

2012-01-01

111

FastStats: Chronic Liver Disease/Cirrhosis  

MedlinePLUS

... Related Links Accessibility NCHS Home FastStats Home Chronic Liver Disease and Cirrhosis (Data are for the U.S.) ... Hospital Inpatient Care Number of discharges with chronic liver disease and cirrhosis as the first-listed diagnosis: ...

112

Liver cirrhosis and arterial hypertension  

PubMed Central

Characteristic findings in patients with cirrhosis are vasodilatation with low overall systemic vascular resistance, high arterial compliance, increased cardiac output, secondary activation of counter-regulatory systems (renin-angiotensin-aldosterone system, sympathetic nervous system, release of vasopressin), and resistance to vasopressors. The vasodilatory state is mediated through adrenomedullin, calcitonin gene-related peptide, nitric oxide, and other vasodilators, and is most pronounced in the splanchnic area. This constitutes an effective (although relative) counterbalance to increased arterial blood pressure. This review considers the alterations in systemic hemodynamics in patients with cirrhosis in relation to essential hypertension and arterial hypertension of the renal origin. Subjects with arterial hypertension (essential, secondary) may become normotensive during the development of cirrhosis, and arterial hypertension is rarely manifested in patients with cirrhosis, even in cases with renovascular disease and high circulating renin activity. There is much dispute as to the understanding of homoeostatic regulation in cirrhotic patients with manifest arterial hypertension. This most likely includes the combination of vasodilatation and vasoconstriction in parallel.

Henriksen, Jens H; Moller, Soren

2006-01-01

113

Plexogenic pulmonary arteriopathy and liver cirrhosis.  

PubMed Central

Primary pulmonary hypertension with plexiform vascular changes in the lungs and liver cirrhosis is a rare combination of unclear pathogenesis. Until now, the real prevalence has not been known. The diagnosis of this association is usually made retrospectively. The criteria are morphological--that is, right ventricular hypertrophy and the characteristic pulmonary arterial lesions, as well as clinical--based on ECG and chest radiography. Between 1970 and 1977, two such cases have been found among a total of 11988 necropsies performed on adults. In the same necropsy series, 765 cases of liver cirrhosis were found. The prevalence of this combination is 0.26% of the cirrhosis and 0.016% of all necropsies of adults. This low prevalence raises serious doubts as to whether the association is more than coincidental. Images

Ruttner, J R; Bartschi, J P; Niedermann, R; Schneider, J

1980-01-01

114

Liver cirrhosis in glycogen storage disease Ib.  

PubMed

Glycogen storage disease Ib is an inborn error of carbohydrate metabolism leading to impaired glycogenolysis and gluconeogenesis. Cardinal symptoms include fasting hypoglycemia, lactic acidosis and hepatomegaly as well as neutropenia. We report for the first time on the development of liver cirrhosis in a nine-year-old boy in the course of glycogen storage disease Ib and discuss possible underlying pathomechanisms. PMID:23357201

Baertling, Fabian; Mayatepek, Ertan; Gerner, Patrick; Baba, Hideo A; Franzel, Julia; Schlune, Andrea; Meissner, Thomas

2013-03-01

115

Hepatoprotection with a chloroform extract of Launaea procumbens against CCl4-induced injuries in rats  

PubMed Central

Background Launaea procumbens (Asteraceae) is used as a folk medicine to treat hepatic disorders in Pakistan. The effect of a chloroform extract of Launaea procumbens (LPCE) was evaluated against carbon-tetrachloride (CCl4)-induced liver damage in rats. Methods To evaluate the hepatoprotective effects of LPCE, 36 male Sprague–Dawley rats were equally divided into six groups. Animals of group 1 (control) had free access to food and water. Group II received 3 ml/kg of CCl4 (30% in olive oil v/v) via the intraperitoneal route twice a week for 4 weeks. Group III received 1 ml of silymarin via gavage (100 mg/kg b.w.) after 48 h of CCl4 treatment whereas groups IV and V were given 1 ml of LPCE (100 and 200 mg/kg b.w., respectively) after 48 h of CCl4 treatment. Group VI received 1 ml of LPCE (200 mg/kg b.w.) twice a week for 4 weeks. The activities of the antioxidant enzymes catalase, peroxidase (POD), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione S-transferase (GST), glutathione reductase (GSR), glutathione (GSH) and lipid peroxidation (thiobarbituric acid reactive substances (TBARS)) were measured in liver homogenates. DNA damage, argyrophilic nucleolar organizer regions (AgNORs) counts and histopathology were studied in liver samples. Serum was analyzed for various biochemical parameters. Phytochemical composition in LPCE was determined through high-performance liquid chromatography (HPLC). Results LPCE inhibited lipid peroxidation, and reduced the activities of aspartate transaminase, alanine transaminase, alkaline phosphatase, and lactate dehydrogenase in serum induced by CCl4. GSH contents were increased as were the activities of antioxidant enzymes (catalase, SOD, GST, GSR, GSH-Px) when altered due to CCl4 hepatotoxicity. Similarly, absolute liver weight, relative liver weight and the number of hepatic lesions were reduced with co-administration of LPCE. Phyochemical analyses of LPCE indicated that it contained catechin, kaempferol, rutin, hyperoside and myricetin. Conclusion These results indicated that Launaea procumbens efficiently protected against the hepatotoxicity induced by CCl4 in rats, possibly through the antioxidant effects of flavonoids present in LPCE.

2012-01-01

116

Correlation of caffeine elimination and child's classification in liver cirrhosis  

Microsoft Academic Search

Summary Apparent pharmacokinetic parameters of caffeine elimination from the circulation were determined in 27 patients with histologically confirmed liver cirrhosis, 8 patients with miscellaneous liver disease, and 8 patients with other than liver disease. The usefullness of this quantitative test to assess the severity of liver cirrhosis was compared to the Child-Turcotte or Child-Pugh classification score as well as to

A. Holstege; M. Staiger; K. Haag; W. Gerok

1989-01-01

117

[Hepatic osteodystrophy in patients with liver cirrhosis].  

PubMed

The article presents research data of BMD in 106 patients with liver cirrhosis. The core group of examined patients presented with LC patients the etiology of alcohol--37.7% and primary biliary cirrhosis--35.8%. In 68.9% of patients with established deficits of bone mineral density, by 24.6%--at the level of osteoporosis. Was detected influence of the etiology of the disease on the frequency of osteopenia and osteoporosis containment. Was made analysis of dependence of the frequency of osteopenia, and/or osteoporosis of population risk factors, duration of disease, grade of liver failure on the Child-Pugh. A comparative assessment of the effectiveness treatment of disorders of BMD active metabolite of vitamin D3--alpha caltsidol and drugs from the group of bisphosphonates. PMID:20731172

Topcheeva, O N

2010-01-01

118

Portal hypertensive colopathy in patients with liver cirrhosis  

Microsoft Academic Search

Abstract Abstract Abstract Abstract AIM: In patients with liver cirrhosis and portal hypertension, portal hypertensive colopathy is thought to be an important cause of lower gastrointestinal hemorrhage. In this study, we evaluated the prevalence of colonic mucosal changes in patients with liver cirrhosis and its clinical significance. METHODS: We evaluated the colonoscopic findings and liver function of 47 patients with

Keiichi Ito; Katsuya Shiraki; Takahisa Sakai; Hitoshi Yoshimura; Takeshi Nakano

119

Cryptogenic cirrhosis and posttransplantation nonalcoholic fatty liver disease  

Microsoft Academic Search

Some patients diagnosed with cryptogenic cirrhosis may have “burned-out” nonalcoholic fatty liver disease (NAFL). To test this hypothesis, we used our liver transplant database (November 1984 to November 1998) to assess the incidence of NAFL in patients with cryptogenic cirrhosis after orthotopic liver transplantation (OLT). We also examined the clinicodemographic features associated with post-OLT NAFL, obtained by chart review and

Janus Ong; Zobair M. Younossi; Vishnu Reddy; Lori Lyn Price; Terry Gramlich; James Mayes; Navdeep Boparai

2001-01-01

120

Impaired splanchnic and peripheral glucose uptake in liver cirrhosis  

Microsoft Academic Search

Background\\/Aim: Patients with liver cirrhosis are insulin-resistant and frequently glucose-intolerant. Although peripheral glucose uptake has been shown to be impaired in liver cirrhosis, little is known about the significance of splanchnic (hepatic) glucose uptake after oral glucose load.Methods\\/Results: We performed an oral glucose tolerance test and euglycemic hyperinsulinemic clamp with oral glucose load for eight patients with liver cirrhosis and

Eiichi Imano; Tsutomu Kanda; Yoshihisa Nakatani; Masaaki Motomura; Katsumi Arai; Munehide Matsuhisa; Yoshimitsu Yamasaki; Masatsugu Hori

1999-01-01

121

Involvement of the TNF and FasL Produced by CD11b Kupffer Cells/Macrophages in CCl4-Induced Acute Hepatic Injury  

PubMed Central

We previously reported that F4/80+ Kupffer cells are subclassified into CD68+ Kupffer cells with phagocytic and ROS producing capacity, and CD11b+ Kupffer cells with cytokine-producing capacity. Carbon tetrachloride (CCl4)-induced hepatic injury is a well-known chemical-induced hepatocyte injury. In the present study, we investigated the immunological role of Kupffer cells/macrophages in CCl4-induced hepatitis in mice. The immunohistochemical analysis of the liver and the flow cytometry of the liver mononuclear cells showed that clodronate liposome (c-lipo) treatment greatly decreased the spindle-shaped F4/80+ or CD68+ cells, while the oval-shaped F4/80+ CD11b+ cells increased. Notably, severe hepatic injury induced by CCl4 was further aggravated by c-lipo-pretreatment. The population of CD11b+ Kupffer cells/macrophages dramatically increased 24 hour (h) after CCl4 administration, especially in c-lipo-pretreated mice. The CD11b+ Kupffer cells expressed intracellular TNF and surface Fas-ligand (FasL). Furthermore, anti-TNF Ab pretreatment (which decreased the FasL expression of CD11b+ Kupffer cells), anti-FasL Ab pretreatment or gld/gld mice attenuated the liver injury induced by CCl4. CD1d?/? mouse and cell depletion experiments showed that NKT cells and NK cells were not involved in the hepatic injury. The adoptive transfer and cytotoxic assay against primary cultured hepatocytes confirmed the role of CD11b+ Kupffer cells in CCl4-induced hepatitis. Interestingly, the serum MCP-1 level rapidly increased and peaked at six h after c-lipo pretreatment, suggesting that the MCP-1 produced by c-lipo-phagocytized CD68+ Kupffer cells may recruit CD11b+ macrophages from the periphery and bone marrow. The CD11b+ Kupffer cells producing TNF and FasL thus play a pivotal role in CCl4-induced acute hepatic injury.

Sato, Atsushi; Nakashima, Hiroyuki; Nakashima, Masahiro; Ikarashi, Masami; Nishiyama, Kiyoshi; Kinoshita, Manabu; Seki, Shuhji

2014-01-01

122

Effect of pretreatment of Cassia fistula Linn. leaf extract against subacute CCl4 induced hepatotoxicity in rats.  

PubMed

CCl4 alone treatment (0.lml of liquid paraffin/100g body weight, ip) for 7 days followed by 0.l ml of CCl4 (in liquid parafiin/100g body weight, ip) from day 8 till day 14, caused a 16 fold increase in lipid peroxidation and a 50% reduction in catalase and glutathione reductase in liver tissue of rats accompanied by an increase in the activities of transaminases. alkaline phosphatase, lactate dehydrogenase and gamma - glutamyl transpeptidase in serum as compared to liquid paraffin treated control. Pretreatment of ethanolic leaf extract of C. fistula (500mg/kg body weight/day for 7 days) followed by CCl4 treatment (0.1 ml/100g body weight from day 8 till day 14) completely reversed back lipid peroxidation and the activities of catalase and glutathione reductase in the liver tissue towards normalcy. This treatment also reversed the elevated levels of the enzymes in the serum. Ethanolic leaf extract alone treatment did not produce any change in all the parameters studied. The results suggest antioxidant and hepatoprotective properties of C. fistula during its pretreatment against CCl4 induced hepatotoxicity. PMID:15991578

Pradeep, K; Mohan, C Victor Raj; Anand, K Gobi; Karthikeyan, S

2005-06-01

123

What I Need to Know about Cirrhosis of the Liver  

MedlinePLUS

... Information Clearinghouse Publications Tools and Resources E-News Alternate Version Print PDF Version (1,536 KB) * Spanish ... form of sugar that your body uses for energy Cirrhosis is scarring of the liver. A liver ...

124

Inhibitory effects of saikosaponin-d on CCl4-induced hepatic fibrogenesis in rats  

PubMed Central

AIM: To investigate the suppressive effect of saikosaponin-d (SSd) on hepatic fibrosis in rats induced by CCl4 injections in combination with alcohol and high fat, low protein feeding and its relationship with the expression of nuclear factor-?B (NF-?B), tumor necrosis factor-alpha (TNF-?) and interleukins-6 (IL-6). METHODS: Hepatic fibrosis models were induced by subcutaneous injection of CCl4 at a dosage of 3 mL/kg in rats. At the same time, rats in treatment groups were injected intraperitoneally with SSd at different doses (1.0, 1.5 and 2.0 mg/kg) once daily for 6 wk in combination with CCl4, while the control group received olive oil instead of CCl4. At the end of the experiment, rats were anesthetized and killed (except for 8 rats which died during the experiment; 2 from the model group, 3 in high-dose group, 1 in medium-dose group and 2 in low-dose group). Hematoxylin and eosin (HE) staining and Van Gieson staining were used to examine the changes in liver pathology. The levels of alanine aminotransferase (ALT), triglyeride (TG), albumin (ALB), globulin (GLB), hyaluronic acid (HA) and laminin (LN) in serum and the content of hydroxyproline (HYP) in liver were measured by biochemical examinations and radioimmuneoassay, respectively. In addition, the expression of TNF-? and IL-6 in liver homogenate was evaluated by enzyme-linked immunosorbent assay (ELISA) and the levels of NF-?Bp65 and I-?B? in liver tissue were analyzed by Western blotting. RESULTS: Both histological examination and Van Gieson staining demonstrated that SSd could attenuate the area and extent of necrosis and reduce the scores of liver fibrosis. Similarly, the levels of ALT, TG, GLB, HA, and LN in serum, and the contents of HYP, TNF-? and IL-6 in liver were all significantly increased in model group in comparison with those in control group. Whereas, the treatment with SSd markedly reduced all the above parameters compared with the model group, especially in the medium group (ALT: 412 ± 94.5 IU/L vs 113.76 ± 14.91 IU/L, TG: 0.95 ± 0.16 mmol/L vs 0.51 ± 0.06 mmol/L, GLB: 35.62 ± 3.28 g/L vs 24.82 ± 2.73 g/L, HA: 42.15 ± 8.25 ng/mL vs 19.83 ± 3.12 ng/mL, LN: 27.56 ± 4.21 ng/mL vs 13.78 ± 2.57 ng/mL, HYP: 27.32 ± 4.32 ?g/mg vs 16.20 ± 3.12 ?g/mg, TNF-?: 4.38 ± 0.76 ng/L vs 1.94 ± 0.27 ng/L, IL-6: 28.24 ± 6.37 pg/g vs 12.72 ± 5.26 pg/g, respectively, P < 0.01). SSd also decreased ALB in serum (28.49 ± 4.93 g/L vs 37.51 ± 3.17 g/L, P < 0.05). Moreover, the expression of NF-?B p65 in the liver of treated groups was lower than that in model groups while the expression of I-?B? was higher in treated group than in model group (P < 0.01). The expression of NF-?Bp65 and TNF-? had a positive correlation with the level of HA in serum of rats after treatment with CCl4 (r = 0.862, P < 0.01; r = 0.928, P < 0.01, respectively). CONCLUSION: SSd attenuates CCl4-induced hepatic fibrosis in rats, which may be related to its effects of hepato-protective and anti-inflammation properties, the down-regulation of liver TNF-?, IL-6 and NF-?Bp65 expression and the increased I-?B? activity in liver.

Dang, Shuang-Suo; Wang, Bao-Feng; Cheng, Yan-An; Song, Ping; Liu, Zhen-Guo; Li, Zong-Fang

2007-01-01

125

Antioxidant and hepatoprotective effects of silymarin phytosomes compared to milk thistle extract in CCl4 induced hepatotoxicity in rats.  

PubMed

Milk thistle extract is a well-known hepatoprotectant with low bioavailability (20-50%). The objective of the present study is to prepare and characterize silymarin phytosomes and to test the hepatoprotective effect of the phytosomes in CCl4 induced liver injury in rats compared to milk thistle extract. Phytosomes were prepared using lecithin from soybeans and from egg yolk. The prepared phytosomes were examined using scanning electron microscopy, transmission electron microscopy, differential scanning calorimetry, Fourier transform infrared spectroscopy and proton nuclear magnetic resonance spectroscopy (H(1)NMR). The loading efficiency was >85% in all phytosomal formulations. Formula P2 (with the molar ratio of soybean lecithin to silybin 1:1) and P4 (with the molar ratio of egg-yolk lecithin to silybin 0.25:1) exhibited significantly (p?

El-Gazayerly, O N; Makhlouf, A I A; Soelm, A M A; Mohmoud, M A

2014-01-01

126

Herbal supplement attenuation of cardiac fibrosis in rats with CCl?-induced liver cirrhosis.  

PubMed

Previously we found carbon tetrachloride (CCl?) induced cirrhosis associated cardiac hypertrophy and apoptosis. The purpose of this study is to determine whether further CCl? treatment would induce cardiac cell fibrosis. The cardiac tissues were analyzed by H&E. histological staining, Trichrome Masson staining and Western blotting. The results showed that the CCl?-treated-only group exhibits more trichrome staining, meaning that more fibrosis is present. Moreover, CCl? could further induce cardiac-fibrosis via TGF-?-p-Smad2/3-CTGF pathway. However, our data showed that the CCl?- indcued cardiac abnormalities were attenuated by Ocimum gratissimum extract (OGE) and silymarin co- treatments. In conclusion, our results indicated that the OGE and silymarin may be a potential traditional herb for the protection of cardiac tissues from the CCl4 induced cirrhosis associated cardiac fibrosis through modulating the TGF-? signaling pathway. PMID:24621337

Chang, Hsiao-Chuan; Chiu, Yung-Wei; Lin, Yueh-Min; Chen, Ray-Jade; Lin, James A; Tsai, Fuu-Jen; Tsai, Chang-Hai; Kuo, Yu-Chun; Liu, Jer-Yuh; Huang, Chih-Yang

2014-02-28

127

Inhibitory effect on proliferation of vascular smooth muscle cells and protective effect on CCl(4)-induced hepatic damage of HEAI extract.  

PubMed

The effects of methanol extract from Hericium erinaceus cultivated with Artemisia iwayomogi (HEAI) on proliferation of vascular smooth muscle cells and CCl(4)-induced hepatic damage were evaluated. HEAI was shown to have a potent inhibitory effect on the proliferation of vascular smooth muscle cells (VSMCs). Interestingly, a methanol extract of Hericium erinaceus showed no inhibitory effect on the proliferation of VSMCs, while a methanol extract of Artemisia iwayomogi possessed strong inhibitory effects on the proliferation of VSMCs. Therefore, the inhibitory effects of HEAI may be caused by the changes of chemical components in the culture broth after the addition of Artemisia iwayomogi in the HEAI growth media. HEAI also had a strong protective effect on CCl(4)-induced hepatic damage in rats. The activity was evaluated using biochemical parameters such as glutamic oxalacetic transaminase (GOT), glutamic pyruvic transaminase (GPT) and alkaline phosphatase (ALP). HEAI treatment caused a significant reduction in the activity of GOT but not of GPT and ALP in comparison with CCl(4) treatment alone. Histopathological studies showed that liver samples treated with HEAI were significantly different when compared to non-treated animals after CCl(4) exposure. PMID:15941638

Choi, Won-Sik; Kim, Chang-Jin; Park, Byeoung-Soo; Lee, Sung-Eun; Takeoka, Gary R; Kim, Dong-Goo; Lanpiao, Xiang; Kim, Jeong-Han

2005-08-22

128

Protective effect of Launaea procumbens (L.) on lungs against CCl4-induced pulmonary damages in rat  

PubMed Central

Background Launaea procumbens (L.) is traditionally used in the treatment of various human ailments including pulmonary damages. The present study was arranged to evaluate the role of Launaea procumbens methanol extract (LME) against carbon tetrachloride (CCl4) induced oxidative pulmonary damages in rat. Methods 36 Sprague–Dawley male rats (170-180?g) were randomly divided into 06 groups. After a week of acclamization, group I was remained untreated while group II was given olive oil intraperitoneally (i.p.) and dimethyl sulfoxide (DMSO) orally, groups III, IV, V and VI were administered CCl4, 3?ml/kg body weight (30% in olive oil i.p.). Groups IV, V were treated with 100?mg/kg, 200?mg/kg of LME whereas group VI was administered with 50?mg/kg body weight of rutin (RT) after 48?h of CCl4 treatment for four weeks. Antioxidant profile in lungs were evaluated by estimating the activities of antioxidant enzymes; catalase (CAT), peroxidase (POD), superoxide dismutase (SOD), glutathione-S-transferase (GST), glutathione reductase (GSR), glutathione peroxidase (GSH-Px), quinone reductase (QR) and reduced glutathione (GSH). CCl4-induced lipid peroxidation was determined by measuring the level of thiobarbituric acid reactive substances (TBARS) with conjugation of deoxyribonucleic acid (DNA) damages, argyrophilic nucleolar organizer regions (AgNORs) counts and histopathology. Results Administration of CCl4 for 6?weeks significantly (p?CCl4-induced oxidative stress possibly by improving the antioxidant defence system.

2012-01-01

129

Can Quantitative Tests of Liver Function Discriminate Between Different Etiologies of Liver Cirrhosis?  

Microsoft Academic Search

Studies comparing quantitative testing of liver function (QTLF) in large numbers of patients with defined etiology of cirrhosis are lacking. In all 316 patients with proven cirrhosis underwent QTLF, including aminopyrine breath test (ABT), galactose elimination capacity (GEC), sorbitol (SCI), and indocyanine green clearance (ICG). Values were correlated with the Child-Pugh classification (CP) and the etiology of liver cirrhosis. Fifty-five

Christoph Herold; Sabine Regn; Marion Ganslmayer; Matthias Ocker; Eckhart G. Hahn; Detlef Schuppan

2002-01-01

130

Melatonin prevents experimental liver cirrhosis induced by thioacetamide in rats.  

PubMed

Liver cirrhosis is a critical stage of chronic liver diseases that can produce liver failure, portal hypertension and hepatocarcinoma. Sustained oxidative stress plays a key role in cell damage and fibrosis induced during liver cirrhosis. We evaluated the effect of oxidative stress regulation by melatonin on the development of parenchymal destruction and stellate cell activation in experimental liver cirrhosis. Melatonin was administered to rats with liver cirrhosis induced by thioacetamide (TAA) for 1 or 3 months. Liver injury was assessed by serological analysis, as well as hematoxylin-eosin staining and the in situ apoptosis detection assay in liver sections. Oxidative stress was evaluated by lipoperoxide and reduced glutathione levels, and by the measurement of catalase and superoxide dismutase activities in liver and serum respectively. The activation of stellate cells was evaluated by alpha-smooth muscle actin expression in liver sections. Our results showed that TAA induced oxidative stress with extensive tissue damage and enhanced alpha-smooth muscle actin expression in liver. Melatonin prevented the oxidative stress-related changes associated with TAA toxicity. In conclusion, the study showed that melatonin prevents the tissue damage and fibrosis associated with TAA-induced liver cirrhosis in rats. PMID:16098091

Cruz, Adolfo; Padillo, Francisco J; Torres, Eva; Navarrete, Carmen M; Muñoz-Castañeda, Juan R; Caballero, Francisco J; Briceño, Javier; Marchal, Trinidad; Túnez, Isaac; Montilla, Pedro; Pera, Carlos; Muntané, Jordi

2005-09-01

131

Thioacetamide and Carbon Tetrachloride-Induced Liver Cirrhosis  

Microsoft Academic Search

Two methods of inducing liver cirrhosis in the rat were studied. Intragastric administration of CCl4 for 16 weeks according to Proctor and Chatamra was compared to the administration of thioacetamide in the drinking water (0.3 g\\/l) for the same period. CCl4 administration induced micronodular cirrhosis in 6\\/8 animals with a 27% mortality. Thioacetamide induced cirrhosis in 6\\/8 animals without mortality.

H. Dashti; B. Jeppsson; I. Hägerstrand; B. Hultberg; U. Srinivas; M. Abdulla; S. Bengmark

1989-01-01

132

Virus-related liver cirrhosis: Molecular basis and therapeutic options  

PubMed Central

Chronic infections with hepatitis B virus (HBV) and/or hepatitis C virus (HCV) are the major causes of cirrhosis globally. It takes 10-20 years to progress from viral hepatitis to cirrhosis. Intermediately active hepatic inflammation caused by the infections contributes to the inflammation-necrosis-regeneration process, ultimately cirrhosis. CD8+ T cells and NK cells cause liver damage via targeting the infected hepatocytes directly and releasing pro-inflammatory cytokine/chemokines. Hepatic stellate cells play an active role in fibrogenesis via secreting fibrosis-related factors. Under the inflammatory microenvironment, the viruses experience mutation-selection-adaptation to evade immune clearance. However, immune selection of some HBV mutations in the evolution towards cirrhosis seems different from that towards hepatocellular carcinoma. As viral replication is an important driving force of cirrhosis pathogenesis, antiviral treatment with nucleos(t)ide analogs is generally effective in halting the progression of cirrhosis, improving liver function and reducing the morbidity of decompensated cirrhosis caused by chronic HBV infection. Interferon-? plus ribavirin and/or the direct acting antivirals such as Vaniprevir are effective for compensated cirrhosis caused by chronic HCV infection. The standard of care for the treatment of HCV-related cirrhosis with interferon-? plus ribavirin should consider the genotypes of IL-28B. Understanding the mechanism of fibrogenesis and hepatocyte regeneration will facilitate the development of novel therapies for decompensated cirrhosis.

Lin, Ji; Wu, Jian-Feng; Zhang, Qi; Zhang, Hong-Wei; Cao, Guang-Wen

2014-01-01

133

Pathological Changes in Pulmonary Circulation in Carbon Tetrachloride (ccl4)-Induced Cirrhotic Mice  

PubMed Central

Rationale Lack of an experimental model of portopulmonary hypertension (POPH) has been a major obstacle in understanding of pathophysiological mechanisms underlying the disease. Objective We investigated the effects of CCl4-mediated cirrhosis on the pulmonary vasculature, as an initial step towards an improved understanding of POPH. Methods And Results Male C57BL/6 mice received intraperitoneal injection of either sterile olive oil or CCl4 3 times/week for 12 weeks. Cirrhosis and portal hypertension were confirmed by evidence of bridging fibrosis and nodule formation in CCl4-treated liver determined by trichrome/picrosirius red staining and an increase in spleen weight/body weight ratio, respectively. Staining for the oxidative stress marker, 4-hydroxynonenal (4-HNE), was strong in the liver but was absent in the lung, suggesting that CCl4 did not directly induce oxidative injury in the lung. Pulmonary acceleration time (PAT) and the ratio of PAT/pulmonary ejection time (PET) measured by echocardiography were significantly decreased in cirrhotic mice. Increase in right ventricle (RV) weight/body weight as well as in the weight ratio of RV/(left ventricle + septum) further demonstrated the presence of pathological changes in the pulmonary circulation in these mice. Histological examination revealed that lungs of cirrhotic mice have excessive accumulation of perivascular collagen and thickening of the media of the pulmonary artery. Conclusion Collectively, our data demonstrate that chronic CCl4 treatment induces pathological changes in pulmonary circulation in cirrhotic mice. We propose that this murine cirrhotic model provides an exceptional tool for future studies of the molecular mechanisms mediating pulmonary vascular diseases associated with cirrhosis and for evaluation of novel therapeutic interventions.

Das, Mita; Boerma, Marjan; Goree, Jessica R.; Lavoie, Elise G.; Fausther, Michel; Gubrij, Igor B.; Pangle, Amanda K.; Johnson, Larry G.; Dranoff, Jonathan A.

2014-01-01

134

Hawk tea (Litsea coreana Levl. var. lanuginose) attenuates CCl4-induced hepatic damage in Sprague-Dawley rats  

PubMed Central

Hawk tea (Litsea coreana Levl. var. lanuginose) is a traditional Chinese drink similar to green tea. In the present study, the preventive effects of Hawk tea on hepatic damage induced by carbon tetrachloride (CCl4) were studied in Sprague-Dawley rats. Silymarin was used as a positive control. Hawk tea was successfully shown to prevent hepatic damage in the rats. Serum levels of AST, ALT and LDH were significantly decreased when the rats were treated with varying concentrations of Hawk tea compared with silymarin (P<0.05). The lowest enzyme activities were exhibited in the 400 mg/kg Hawk tea group. This group showed reduced levels of the serum proinflammatory cytokines IL-6, IFN-? and TNF-?. In particular, the IFN-? level decreased markedly compared with the other concentration groups. The histopathology sections of liver tissue in the 400 mg/kg Hawk tea group recovered well from the CCl4 damage, but the sections of the other concentration groups showed necrosis to a more serious degree. Reverse transcription-polymerase chain reaction (RT-PCR) and western blot analyses of the inflammation-related genes iNOS, COX-2, TNF-? and IL-1? in the rat livers were tested. The 400 mg/kg Hawk tea group showed significantly decreased mRNA and protein expression levels of iNOS, COX-2, TNF-? and IL-1? compared with the control group. Accordingly, 400 mg/kg Hawk tea potentially contributes to the prevention of CCl4-induced hepatic damage in vivo. A 200 or 100 mg/kg dose of Hawk tea also demonstrated preventive effects against hepatic damage.

ZHAO, XIN

2013-01-01

135

Biomechanics and functionality of hepatocytes in liver cirrhosis.  

PubMed

Cirrhosis is a life-threatening condition that is generally attributed to overproduction of collagen fibers in the extracellular matrix that mechanically stiffens the liver. Chronic liver injury due to causes including viral hepatitis, inherited and metabolic liver diseases and external factors such as alcohol abuse can result in the development of cirrhosis. Progression of cirrhosis leads to hepatocellular dysfunction. While extensive studies to understand the complexity underlying liver fibrosis have led to potential application of anti-fibrotic drugs, no such FDA-approved drugs are currently available. Additional studies of hepatic fibrogenesis and cirrhosis primarily have focused on the extracellular matrix, while hepatocyte biomechanics has received limited attention. The role of hepatocyte biomechanics in liver cirrhosis remains elusive, and how the cell stiffness is correlated with biological functions of hepatocytes is also unknown. In this study, we demonstrate that the biomechanical properties of hepatocytes are correlated with their functions (e.g., glucose metabolism), and that hepatic dysfunction can be restored through modulation of the cellular biomechanics. Furthermore, our results indicate the hepatocyte functionality appears to be regulated through a crosstalk between the Rho and Akt signaling. These novel findings may lead to biomechanical intervention of hepatocytes and the development of innovative tissue engineering for clinical treatment to target liver cells rather than exclusively focusing on the extracellular matrix alone in liver cirrhosis. PMID:24262849

Sun, Shan; Song, Zhenyuan; Cotler, Scott J; Cho, Michael

2014-06-27

136

Could Coffee Lower Death Risk from Liver Cirrhosis?  

MedlinePLUS

... features on this page, please enable JavaScript. Could Coffee Lower Death Risk From Liver Cirrhosis? Large study ... Nutrition THURSDAY, April 3, 2014 (HealthDay News) -- Drinking coffee may reduce the risk of death from certain ...

137

Laboratory parameters in the natural history of liver cirrhosis  

Microsoft Academic Search

Summary  The aim of the present study was to evaluate the changes of common laboratory parameters in the natural evolution of liver\\u000a cirrhosis, as well as their relationships with the occurrence of ascites onset and death. Routine laboratory findings of 458\\u000a patients suffering from liver cirrhosis admitted to a 9-year follow-up period were retrospectively investigated, but only\\u000a data of the 138

Alessandro Milani; Laura Marra; Massimo Siciliano; Lodovico Rossi

1989-01-01

138

Regenerative pattern of liver cells in primary biliary cirrhosis, alcoholic cirrhosis, posthepatitic cirrhosis (HBV-related) and hepatocellular carcinoma: comparative analysis by computerized morphometry.  

PubMed

Computerized morphometrical measurements were made of liver cells and their nuclei taken from biopsy specimens of primary biliary cirrhosis (PBC), alcoholic cirrhosis, posthepatitic cirrhosis (HBV-related), and hepatocellular carcinoma (HCC). The specimens were stained with hematoxylin-eosin (HE), Mallory's stain for collagen fibers, orcein method, periodic acid Schiff (PAS) reaction, and silver impregnation. Light microscopic views were then selected and original liver cells were magnified x 1000. The size of liver cell nuclei, distance between corresponding liver cell nuclei and distribution pattern of hepatocytes were calculated by computer. Variation in regenerative activity among the four disease groups was noted. Regenerative features of liver cells were mild in degree in PBC. In alcoholic cirrhosis, regenerative features of liver cells were less prominent than in posthepatitic cirrhosis. In posthepatitic cirrhosis, regenerative liver cells were well developed, showing remarkable pleomorphism of liver cell nuclei and expansive arrangement of liver cell cords. This tendency towards regenerative activity suggests that the possibility of HCC occurring is greater in posthepatitic cirrhosis than in PBC or alcoholic cirrhosis. It was concluded that morphologically, there is a greater possibility of occurrence of HCC in posthepatitic cirrhosis than in any other type of cirrhosis, because of its high regenerative hepatocytic activity. Also etiological factors of liver diseases are more important in the development of liver cell regeneration. Furthermore, regenerative activity can be measured by computerized morphometry as an established methodology. PMID:8726850

Rahman, S M; Itakura, H; Motoda, A

1996-04-01

139

Hepatoprotective and antioxidant effects of Commiphora berryi (Arn) Engl bark extract against CCl 4-induced oxidative damage in rats  

Microsoft Academic Search

Oxidative damage is involved in the pathogenesis of various hepatic injuries. In the present study the capacity of Commiphora berryi (Arn) Engl bark as an antioxidant to protect against CCl4-induced oxidative stress and hepatotoxicity in Albino Wistar rats was investigated. Intraperitoneal injection of CCl4, administered twice a week, produced a marked elevation in the serum levels of aspartate transaminase, alanine

N. L. Gowri Shankar; R. Manavalan; D. Venkappayya; C. David Raj

2008-01-01

140

The protective effects of aqueous extracts of wild-growing and fermented Royal Sun mushroom, Agaricus brasiliensis S. Wasser et al. (higher basidiomycetes), in CCl4-induced oxidative damage in rats.  

PubMed

Culinary-medicinal Royal Sun mushroom, Agaricus brasiliensis (AbS), has traditionally been used for the prevention of a range of diseases, including cancer, hepatitis, atherosclerosis, hypercholesterolemia, diabetes, and dermatitis. The hepatoprotective effect of the fermented mushroom of A. brasiliensis (FMAE) and wild-growing A. brasiliensis (WMAE) were studied in this paper. An in vivo study of carbon tetrachloride (CCl4)-induced antioxidant activity in 2-month-old rats was conducted by examining the levels of activities of alanine aminotransaminase (ALT) and aspartate aminotransaminase (AST) and the antioxidant enzymes, including glutathione peroxidase (GSHPx) and catalase (CAT). Rats were divided into four groups, each containing six rats. The first group served as a control group. The second group was the CCl4 group. Group I and group II were treated orally with distilled water for 14 days respectively. Group III and Group IV were treated orally by WMAE and FMAE at oral doses of 50 mg/kg-day, respectively. Both WMAE and FMAE could reduce CCl4-induced toxicity, particularly hepatotoxicity, by suppressing ALT and AST activities, and increasing antioxidant enzyme activity. The studies demonstrate that both the fermented and wild-growing A. brasiliensis could protect the liver against CCl4-induced oxidative damage in rats. PMID:23510249

Zhang, Chunjing; Han, Chunchao; Zhao, Baosheng; Yu, Haitao

2012-01-01

141

CCl4-induced hepatotoxicity: protective effect of rutin on p53, CYP2E1 and the antioxidative status in rat  

PubMed Central

Background Rutin is a polyphenolic natural flavonoid which possesses antioxidant and anticancer activity. In the present study the hepatoprotective effect of rutin was evaluated against carbon tetrachloride (CCl4)-induced liver injuries in rats. Methods and materials 24 Sprague–Dawley male rats were equally divided into 4 groups for the assessment of hepatoprotective potential of rutin. Rats of group I (control) received only vehicles; 1 ml/kg bw of saline (0.85%) and olive oil (3 ml/kg) and had free access to food and water. Rats of group II, III and IV were treated with CCl4 (30% in olive oil, 3 ml/kg bw) via the intraperitoneal route twice a week for four weeks. The rutin at the doses of 50 and 70 mg/kg were administered intragastrically after 48 h of CCl4 treatment to group III and IV, respectively. Protective effect of rutin on serum enzyme level, lipid profile, activities of antioxidant enzymes and molecular markers were calculated in CCl4-induced hepatotoxicity in rat. Results Rutin showed significant protection with the depletion of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transpeptidase (?-GT) in serum as was raised by the induction of CCl4. Concentration of serum triglycerides, total cholesterol and low density lipoproteins was increased while high-density lipoprotein was decreased with rutin in a dose dependent manner. Activity level of endogenous liver antioxidant enzymes; catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSHpx), glutathione-S-transferase (GST) and glutathione reductase (GSR) and glutathione (GSH) contents were increased while lipid peroxidation (TBARS) was decreased dose dependently with rutin. Moreover, increase in DNA fragmentation and oxo8dG damages while decrease in p53 and CYP 2E1 expression induced with CCl4 was restored with the treatment of rutin. Conclusion From these results, it is suggested that rutin possesses hepatoprotective properties.

2012-01-01

142

Cardioprotective role of leaves extracts of Carissa opaca against CCl4 induced toxicity in rats  

PubMed Central

Background Carissa opaca are used traditionally in Pakistan for the treatment of various human ailments. Therefore, the study is arranged out to assess the cardio protective potential of different fractions of Carissa opaca leaves on CCl4-induced oxidative trauma in kidney. Methods The parameters studied in this respect were the cardiac function test (CK (U/l), CKMB (U/l), genotoxicity (% DNA fragmentation), characteristic morphological findings and antioxidant enzymatic level of cardiac tissue homogenate. Result The protective effects of various fractions of Carissa opaca (C. opaca) leaves extract against CCl4 administration was reviewed by rat cardiac functions alterations. Chronic toxicity caused by eight week treatment of CCl4 to the rats significantly changed the cardiac function test, decreased the activities of antioxidant enzymes and glutathione contents whereas significant increase was found in lipid peroxidation comparative to control group. Administration of various fractions of C. opaca leaves extract with CCl4 showed protective ability against CCl4 intoxication by restoring the cardiac functions alterations, activities of antioxidant enzymes and lipid peroxidation in rat. CCl4 induction in rats also caused DNA fragmentation and histopathalogical abnormalities which were restored by co-admistration of various fraction of C. opaca leaves extract. Conclusion Results revealed that various fraction of C. opaca are helpful in cardiac dysfunctions.

2014-01-01

143

Poly (ADP-ribose) polymerase-1 is a key mediator of liver inflammation and fibrosis.  

PubMed

Poly (ADP-ribose) polymerase 1 (PARP-1) is a constitutive enzyme, the major isoform of the PARP family, which is involved in the regulation of DNA repair, cell death, metabolism, and inflammatory responses. Pharmacological inhibitors of PARP provide significant therapeutic benefits in various preclinical disease models associated with tissue injury and inflammation. However, our understanding the role of PARP activation in the pathophysiology of liver inflammation and fibrosis is limited. In this study we investigated the role of PARP-1 in liver inflammation and fibrosis using acute and chronic models of carbon tetrachloride (CCl4 )-induced liver injury and fibrosis, a model of bile duct ligation (BDL)-induced hepatic fibrosis in vivo, and isolated liver-derived cells ex vivo. Pharmacological inhibition of PARP with structurally distinct inhibitors or genetic deletion of PARP-1 markedly attenuated CCl4 -induced hepatocyte death, inflammation, and fibrosis. Interestingly, the chronic CCl4 -induced liver injury was also characterized by mitochondrial dysfunction and dysregulation of numerous genes involved in metabolism. Most of these pathological changes were attenuated by PARP inhibitors. PARP inhibition not only prevented CCl4 -induced chronic liver inflammation and fibrosis, but was also able to reverse these pathological processes. PARP inhibitors also attenuated the development of BDL-induced hepatic fibrosis in mice. In liver biopsies of subjects with alcoholic or hepatitis B-induced cirrhosis, increased nitrative stress and PARP activation was noted. Conclusion: The reactive oxygen/nitrogen species-PARP pathway plays a pathogenetic role in the development of liver inflammation, metabolism, and fibrosis. PARP inhibitors are currently in clinical trials for oncological indications, and the current results indicate that liver inflammation and liver fibrosis may be additional clinical indications where PARP inhibition may be of translational potential. (Hepatology 2014;59:1998-2009). PMID:24089324

Mukhopadhyay, Partha; Rajesh, Mohanraj; Cao, Zongxian; Horváth, Béla; Park, Ogyi; Wang, Hua; Erdelyi, Katalin; Holovac, Eileen; Wang, Yuping; Liaudet, Lucas; Hamdaoui, Nabila; Lafdil, Fouad; Haskó, György; Szabo, Csaba; Boulares, A Hamid; Gao, Bin; Pacher, Pal

2014-05-01

144

New diagnostic method for liver fibrosis and cirrhosis.  

PubMed

Liver fibrosis, i.e. excessive accumulation of extracellular matrix proteins, occurs in most types of chronic liver diseases. The prognosis and management of chronic liver diseases depend on the degree of liver fibrosis. Therefore, the assessment of liver fibrosis provides useful information not only for diagnosis but also for treatment planning. Although liver biopsy is still the gold standard for assessing hepatic fibrosis, it has some technical limitations and risks. Furthermore, the dynamic process of liver fibrosis resulting from progression and regression cannot be quantified by liver biopsy. Therefore, alternative, simple, reliable and noninvasive tests are needed to assess the stage of fibrosis. Several noninvasive direct and indirect serum markers able to predict the presence of significant fibrosis or cirrhosis in patients with chronic liver disease with considerable accuracy have been reported. However, since most of these markers require complicated calculations, clinical application is difficult. Transient elastography (FibroScan) is a new method for the evaluation of liver stiffness. The technique is based on changes in tissue elasticity induced by hepatic fibrosis. Liver stiffness measured by transient elastography is a noninvasive, reproducible and reliable method to assess hepatic fibrosis as well as to diagnose liver cirrhosis. Based on accumulating clinical data, clinical applications of elastography will increase in the near future. PMID:18544943

Han, Kwang-Hyub; Yoon, Ki Tae

2008-01-01

145

Update on adrenal insufficiency in patients with liver cirrhosis  

PubMed Central

Liver cirrhosis is a major cause of mortality worldwide, often with severe sepsis as the terminal event. Over the last two decades, several studies have reported that in septic patients the adrenal glands respond inappropriately to stimulation, and that the treatment with corticosteroids decreases mortality in such patients. Both cirrhosis and septic shock share many hemodynamic abnormalities such as hyperdynamic circulatory failure, decreased peripheral vascular resistance, increased cardiac output, hypo-responsiveness to vasopressors, increased levels of proinflammatory cytokines [interleukine(IL)-1, IL-6, tumor necrosis factor-alpha] and it has, consequently, been reported that adrenal insufficiency (AI) is common in critically ill cirrhotic patients. AI may also be present in patients with stable cirrhosis without sepsis and in those undergoing liver transplantation. The term hepato-adrenal syndrome defines AI in patients with advanced liver disease with sepsis and/or other complications, and it suggests that it could be a feature of liver disease per se, with a different pathogenesis from that of septic shock. Relative AI is the term given to inadequate cortisol response to stress. More recently, another term is used, namely “critical illness related corticosteroid insufficiency” to define “an inadequate cellular corticosteroid activity for the severity of the patient’s illness”. The mechanisms of AI in liver cirrhosis are not completely understood, although decreased levels of high-density lipoprotein cholesterol and high levels of proinflammatory cytokines and circulatory endotoxin have been suggested. The prevalence of AI in cirrhotic patients varies widely according to the stage of the liver disease (compensated or decompensated, with or without sepsis), the diagnostic criteria defining AI and the methodology used. The effects of corticosteroid therapy on cirrhotic patients with septic shock and AI are controversial. This review aims to summarize the existing published information regarding AI in patients with liver cirrhosis.

Trifan, Anca; Chiriac, Stefan; Stanciu, Carol

2013-01-01

146

Update on adrenal insufficiency in patients with liver cirrhosis.  

PubMed

Liver cirrhosis is a major cause of mortality worldwide, often with severe sepsis as the terminal event. Over the last two decades, several studies have reported that in septic patients the adrenal glands respond inappropriately to stimulation, and that the treatment with corticosteroids decreases mortality in such patients. Both cirrhosis and septic shock share many hemodynamic abnormalities such as hyperdynamic circulatory failure, decreased peripheral vascular resistance, increased cardiac output, hypo-responsiveness to vasopressors, increased levels of proinflammatory cytokines [interleukine(IL)-1, IL-6, tumor necrosis factor-alpha] and it has, consequently, been reported that adrenal insufficiency (AI) is common in critically ill cirrhotic patients. AI may also be present in patients with stable cirrhosis without sepsis and in those undergoing liver transplantation. The term hepato-adrenal syndrome defines AI in patients with advanced liver disease with sepsis and/or other complications, and it suggests that it could be a feature of liver disease per se, with a different pathogenesis from that of septic shock. Relative AI is the term given to inadequate cortisol response to stress. More recently, another term is used, namely "critical illness related corticosteroid insufficiency" to define "an inadequate cellular corticosteroid activity for the severity of the patient's illness". The mechanisms of AI in liver cirrhosis are not completely understood, although decreased levels of high-density lipoprotein cholesterol and high levels of proinflammatory cytokines and circulatory endotoxin have been suggested. The prevalence of AI in cirrhotic patients varies widely according to the stage of the liver disease (compensated or decompensated, with or without sepsis), the diagnostic criteria defining AI and the methodology used. The effects of corticosteroid therapy on cirrhotic patients with septic shock and AI are controversial. This review aims to summarize the existing published information regarding AI in patients with liver cirrhosis. PMID:23382623

Trifan, Anca; Chiriac, Stefan; Stanciu, Carol

2013-01-28

147

Anti-fibrotic effects of puerarin on CCl4-induced hepatic fibrosis in rats possibly through the regulation of PPAR-? expression and inhibition of PI3K/Akt pathway.  

PubMed

Hepatic fibrosis (HF) is a chronic disease, which primarily leads to liver unregulated metabolism. In this study, we aimed to investigate the therapeutic effects of puerarin (PR), an active ingredient from kudzu root, on CCl4-induced HF rats. PR effectively ameliorated the liver metabolic function, resulting in reduced serum enzymatic activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total-bilirubin (T-bilirubin), extracellular matrix (ECM) contents and increased levels of albumin, total-protein (T-protein) in HF rats. Similarly, pathological examination showed that the CCl4-lesioned liver was mitigated by PR treatments. Meanwhile, we also detected significantly reduced levels of hydroxyproline (Hyp), type III precollagen (PCIII) and collagen I (Col I) in the liver tissue of HF rats, whereas the peroxisome proliferator-activated receptor-gamma (PPAR-?) expression was effectively increased. Moreover, the expression of tissue inhibitor of metal protease-1 (TIMP-1) was decreased, while the expression of matrix metalloproteinase-2 (MMP-2) was increased. In addition, the expression of p-PI3K and p-Akt was significantly down-regulated by PR treatments. Taken together, PR could attenuate the CCl4-induced toxicity in the hepatocytes of HF rats. It played a protective role in the liver tissue probably through regulating the PPAR-? expression and blocking the PI3K/Akt pathway to inhibit the excessive deposition of collagen. PMID:23500774

Guo, Chao; Xu, Lingyuan; He, Qiaoling; Liang, Tao; Duan, Xiaoqun; Li, Rong

2013-06-01

148

Liver Transplantation for Solitary Hepatocellular Carcinoma Less than 3 cm in Diameter in Child A Cirrhosis  

Microsoft Academic Search

Liver transplantation for hepatocellular carcinoma (HCC) is the treatment of choice for patients with unresectable tumors within the Milan criteria associated with Child B or C cirrhosis. Liver transplantation provides the best cure for both the HCC and the underlying cirrhosis. In recent years, some authors have advocated liver transplantation even for resectable early HCC associated with Child A cirrhosis,

Ronnie T. P. Poon

2007-01-01

149

Motor dysfunction in patients with liver cirrhosis: impairment of handwriting.  

PubMed

Motor dysfunction is an important clinical finding in patients with liver cirrhosis and mild forms of hepatic encephalopathy. The mechanisms and clinical appearance of motor impairment in patients with liver cirrhosis are not completely understood. We studied fine motor control in forty four patients with advanced liver cirrhosis (excluding those with hepatic encephalopathy grade II) and 48 healthy controls using a kinematic analysis of standardized handwriting tests. We analysed parameters of velocity, the ability to coordinate and the level of automatisation of handwriting movements. Furthermore, we studied the association between impairment of handwriting and clinical neuro-psychiatric symptoms. As compared with control subjects, patients showed a statistically significant reduction of movement peak velocity in all handwriting tasks as well as a substantial increase of number of velocity inversions per stroke. Using a z-score based assessment we found impairment of handwriting in fourteen out of forty four patients (31.8 %). The deterioration of handwriting was associated with clinical symptoms of motor dysfunction, such as bradykinesia, adiadochokinesia, dysmetria of upper extremities and gait ataxia. This is the first study that quantitatively investigates impairment of handwriting in patients with liver cirrhosis. Our findings suggest the application of kinematic analysis of handwriting for diagnostics of motor dysfunction in patients with mild forms of hepatic encephalopathy. PMID:16244813

Mechtcheriakov, Sergei; Graziadei, Ivo W; Kugener, André; Schuster, Ingrid; Mueller, Joerg; Hinterhuber, Hartmann; Vogel, Wolfgang; Marksteiner, Josef

2006-03-01

150

Influence of unrecorded alcohol consumption on liver cirrhosis mortality  

PubMed Central

Unrecorded alcohol includes illegally distributed alcohol as well as homemade or surrogate alcohol which is unintended for consumption by humans (e.g., cosmetics containing alcohol). The highest unrecorded alcohol consumption occurs in Eastern Europe and some of these countries have an over proportional liver cirrhosis mortality. Compounds besides ethanol have been hypothesized as being responsible for this observation. On the other hand, chemical investigations were unable to prove that unrecorded alcohol regularly contains contaminants above toxicological thresholds. However, illegally produced spirits regularly contain higher percentages of alcohol (above 45% by volume), but for considerably less costs compared with licit beverages, potentially causing more problematic patterns of drinking. In this review, it is investigated whether patterns of drinking rather than product composition can explain the liver cirrhosis mortality rates. Statistical examination of World Health Organization country data shows that the originally detected correlation of the percentage of unrecorded alcohol consumption and liver cirrhosis mortality rates disappears when the data is adjusted for the prevalence of heavy episodic drinking. It may be concluded that there is currently a lack of data to demonstrate causality between the composition of illicit spirits (e.g., higher levels of certain contaminants in home-produced products) and liver toxicity on a population scale. Exceptions may be cases of poisoning with antiseptic liquids containing compounds such as polyhexamethyleneguanidine, which were reported to be consumed as surrogate alcohol in Russia, leading to an outbreak of acute cholestatic liver injury, histologically different from conventional alcoholic liver disease.

Lachenmeier, Dirk W; Monakhova, Yulia B; Rehm, Jurgen

2014-01-01

151

Alteration of micronutrient status in compensated and decompensated liver cirrhosis.  

PubMed

Decompensation followed by death is the most serious outcome in patients suffering from cirrhosis of the liver. Alteration of trace elements may play a vital role in the process of decompensation. To examine the change in status of trace elements during the decompensation process, we analysed the zinc, copper, iron, magnesium, bilirubin and albumin levels in the serum of compensated (n = 34) and decompensated (n = 31) liver cirrhosis patients and compared them with healthy control group (n = 36) by post hoc ANOVA. We observed significant alteration in the selected micronutrients in the diseased group relative to healthy controls (P < 0.05). Moreover, mean serum zinc and iron levels were significantly lower with a higher level of serum copper in decompensated cirrhosis group than in compensated group (P < 0.05). However, no significant decrease of serum magnesium was found between the two diseased groups. Our findings imply that the trace elements like zinc, copper and iron might exert important contributory roles in decompensation process in liver cirrhosis and hence, may be utilized as important biomarkers for these patients. Furthermore, we propose that replacements of those micronutrients at an early stage can delay or prevent the severe outcomes like hepatic encephalopathy, gastrointestinal bleeding, severe jaundice or ascites in these patients. PMID:24757308

Kar, Kaushik; Dasgupta, Anindya; Vijaya Bhaskar, M; Sudhakar, K

2014-04-01

152

Liver-Spleen Scintigrams, Epigastric Sonograms and Liver Function Scintigram for Comparative Studies of Various Cases of Liver Cirrhosis.  

National Technical Information Service (NTIS)

23 patients where liver cirrhosis was established were subjected to an epigastric sonogram, a liver-spleen scintigram, a liver-function scintigram, and to various relevant laboratory tests. The liver-spleen scintigram was evaluated for size of the liver, ...

R. Geiger

1983-01-01

153

Increased risk and case fatality rate of pyogenic liver abscess in patients with liver cirrhosis: a nationwide study in Denmark  

PubMed Central

BACKGROUND—Patients with liver cirrhosis are at increased risk of serious bacterial infections carrying a high case fatality rate. Case reports have suggested an association between liver cirrhosis and pyogenic liver abscess.?AIMS—To estimate the risk and case fatality rate of pyogenic liver abscess in Danish patients with liver cirrhosis compared with the background population.?METHODS—Identification of all patients with liver cirrhosis and pyogenic liver abscess over a 17 year period in the National Registry of Patients. Information on death was obtained from the Danish Central Person Registry.?RESULTS—We identified 22 764 patients with liver cirrhosis and 665 patients with pyogenic liver abscess, of whom 21 were cirrhotics and 644 were non-cirrhotics. The crude incidence rate of liver abscess in cirrhotics was 23.3 (95% CI 14.4-35.6) per 100 000 person years. The age adjusted risk of liver abscess was increased 15-fold in patients with cirrhosis compared with the background population. The 30 day case fatality rates in patients with liver abscess and cirrhosis were 38.5% (13.9-68.4) in alcoholic cirrhosis and 62.5% (24.5-91.5) in non-alcoholic cirrhosis compared with 26.9% (23.5-30.5) in liver abscess patients from the background population. After adjustment for sex, age, and comorbidity, the relative risk of death was increased more than fourfold in alcoholic cirrhosis and non-alcoholic cirrhosis compared with the background population.?CONCLUSIONS—Liver cirrhosis is a strong risk factor for pyogenic liver abscess associated with a poor prognosis.???Keywords: bacterial infections; complications; epidemiology; liver abscess; liver cirrhosis; mortality

Molle, I; Thulstrup, A; Vilstrup, H; Sorensen, H

2001-01-01

154

Hypogonadism is not related to the etiology of liver cirrhosis.  

PubMed

We investigated the clinical and laboratory findings of hypogonadism and feminization in male patients with viral or alcoholic cirrhosis to determine whether chronic liver disease plays a primary role in the development of sexual dysfunction and hormonal changes. Two groups of male patients with liver cirrhosis (23 alcoholic, 33 viral) age- and Child's grade-matched, and 20 age-matched healthy men, as a control group, were included in this study. Clinical signs of hypogonadism and feminization were examined in the cirrhotic patients. Follicle-stimulating hormone, luteinizing hormone, prolactin, testosterone, free testosterone, estradiol, androstenedione, dehydroepiandrosterone sulfate, and sex hormone-binding globulin were estimated in all groups. Seminal fluid was also analyzed in 7 alcoholic and 15 viral cirrhotics. Serum levels of estradiol, androstenedione, and sex hormone-binding globulin were significantly higher, and free testosterone and dehydroepiandrosterone sulfate levels were significantly lower in both groups of cirrhotics compared with the control group. Child's C patients in both groups of cirrhotics were found to have higher estradiol and lower free testosterone levels than child's A and B patients. Alcoholic and viral cirrhotics had markedly reduced sperm motility and density. The differences between alcoholic and viral cirrhotic patients in the clinical signs of hypogonadism, serum levels of sex steroids, and the results of seminal fluid analysis were not statistically significant. These findings suggest that liver cirrhosis per se, independent of etiology, causes hypogonadism and feminization, and that the degree of hypogonadism and feminization correlates well with the severity of liver failure. PMID:8963392

Kaymako?lu, S; Okten, A; Cakalo?lu, Y; Bozta?, G; Be?i?ik, F; Ta?çio?lu, C; Yalçin, S

1995-12-01

155

An endothelin receptor antagonist TAK-044 ameliorates carbon tetrachloride-induced acute liver injury and portal hypertension in rats.  

PubMed

Hepatic levels of a powerful vasoconstrictor endothelin-1 (ET-1) and its receptors increase in human and carbon tetrachloride (CCl4)-induced liver cirrhosis. The aim of this study was to determine whether antagonism of hepatic ET-1 receptors ameliorates CCl4-induced hepatic injury and portal hypertension in rats. Acute liver injury was induced by a single intraperitoneal injection of CCl4 (0.3 ml/kg), whereas cirrhosis and portal hypertension were induced by CCl4 treatment (0.15 ml/kg twice a week) for 8 weeks. Hepatic morphology, ET-1 and its receptors, and portal venous pressures were determined. Increases in ET-1 and its receptors occurred within 24 h of CCl4 administration, and progressively thereafter during the development of cirrhosis. The acute CCl4-induced hepatic injury was characterized by significant increases in portal pressure (from 8.7+/-1.8 to 17.6+/-3.3 mmHg; p<0.01) and serum levels of liver enzymes, as well as massive hepatocellular necrosis (62+/-8%). Intravenous administration of an ET-1 receptor antagonist TAK-044 reduced portal pressure to 13.6+/-2.8 mmHg (p<0.05), and ameliorated hepatocellular necrosis by about 35% (p<0.001). TAK-044 treatment also produced significant reduction in serum levels of liver enzymes. In cirrhotic rats, portal venous infusion of TAK-044 reduced portal hypertension by about 40% (p<0.05). In conclusion, these results indicate involvement of ET-1 in acute liver injury as well as portal hypertension associated with hepatic cirrhosis, and a potential for ET-1 receptor antagonists in the treatment of these pathologic conditions. PMID:9548266

Gandhi, C R; Nemoto, E M; Watkins, S C; Subbotin, V M

1998-02-01

156

Cyclosporine rescue therapy in autoimmune liver cirrhosis: a case report.  

PubMed

Autoimmune hepatitis is an inflammatory condition of the liver that can lead to significant morbidity and mortality. Corticosteroids with or without azathioprine have been shown to improve outcome and are the current standard of care in autoimmune hepatitis patients. However, long-term use of corticosteroids and use of azathioprine could be associated with significant adverse effects that prevent their continued use at optimal dosages or may even require complete cessation. We present a patient with autoimmune liver cirrhosis who was intolerant of corticosteroid and azathioprine, who was successfully treated with cyclosporine. To our knowledge, cyclosporine use has not been reported previously in autoimmune cirrhosis, although it has been used in autoimmune hepatitis patients with reported success and good tolerability. We conclude that cyclosporine seems to be an effective alternative to azathioprine as a steroid-sparing agent in both non-cirrhotic and cirrhotic autoimmune hepatitis. PMID:23161309

Wah-Kheong, Chan; Jaganathan, Vijayasangkar; Sanjiv, Mahadeva

2012-01-01

157

Littoral cell angioma (LCA) associated with liver cirrhosis.  

PubMed

A littoral cell angioma (LCA) is a rare benign vascular tumor of the spleen. A 60-year-old man, with multiple nodules in imaging study and liver cirrhosis graded as Child-Pugh classification class A, was transferred for splenomegaly. A thrombocytopenia was found on hematological evaluation. Because there was no evidence of hematological and visceral malignancy, a splenectomy was performed for a definitive diagnosis. The histological and immunohistochemical features of the splenic specimens were consistent with a LCA. After the splenectomy, the thrombocytopenia recovered to the normal platelet count. There has been no previous report of a LCA combined with liver cirrhosis. Herein, the first case of a LCA in Korea, diagnosed and treated by a splenectomy, is reported. PMID:15744827

Kim, Hi-Gu; Park, In-Suh; Lee, Jung-Il; Jeong, Seok; Lee, Jin-Woo; Kwon, Kye-Suk; Lee, Don-Haeng; Kim, Pum-Soo; Kim, Hyung-Gil; Shin, Yong-Woon; Kim, Young-Soo; Ahn, In-Sun; Lee, Keon-Young

2005-02-28

158

Littoral Cell Angioma (LCA) Associated with Liver Cirrhosis  

PubMed Central

A littoral cell angioma (LCA) is a rare benign vascular tumor of the spleen. A 60-year-old man, with multiple nodules in imaging study and liver cirrhosis graded as Child-Pugh classification class A, was transferred for splenomegaly. A thrombocytopenia was found on hematological evaluation. Because there was no evidence of hematological and visceral malignancy, a splenectomy was performed for a definitive diagnosis. The histological and immunohistochemical features of the splenic specimens were consistent with a LCA. After the splenectomy, the thrombocytopenia recovered to the normal platelet count. There has been no previous report of a LCA combined with liver cirrhosis. Herein, the first case of a LCA in Korea, diagnosed and treated by a splenectomy, is reported.

Kim, Hi-Gu; Park, In-Suh; Lee, Jung-Il; Jeong, Seok; Lee, Jin-Woo; Kwon, Kye-Suk; Lee, Don-Haeng; Kim, Pum-Soo; Kim, Hyung-Gil; Kim, Young-Soo; Ahn, In-Sun; Lee, Keon-Young

2005-01-01

159

Distribution of constitutive (COX-1) and inducible (COX-2) cyclooxygenase in postviral human liver cirrhosis: a possible role for COX-2 in the pathogenesis of liver cirrhosis  

PubMed Central

Aims: Prostaglandins produced by the action of cyclooxygenases (COX) are important mediators of systemic vasodilatation and inflammation in liver cirrhosis. The aim of this study was to investigate the distribution of COX-1 and COX–2 in postviral cirrhosis. Methods: The immunohistochemical expression of the constitutive (COX-1) and the inducible (COX-2) isoenzymes was investigated in 15 patients with cirrhosis after hepatitis B and C infection; three normal control livers were also analysed. Results: COX-2 was absent from normal liver but was highly expressed in cirrhosis, mainly in the inflammatory, sinusoidal, vascular endothelial, and biliary epithelial cells. Low amounts of COX-1 were expressed in both normal and cirrhotic livers, exclusively in sinusoidal and vascular endothelial cells, with no differences seen between normal and cirrhotic livers. Conclusions: COX-2 is overexpressed in liver cirrhosis, and possibly contributes to prostaglandin overproduction, which may be a major component of the inflammation and hyperdynamic circulation associated with cirrhosis. Because COX-2 is thought to contribute to tumour development, high COX-2 production could be a contributor to hepatocellular carcinoma development in cirrhosis. The finding of COX-2 and not COX-1 upregulation in cirrhosis could provide a possible new role for selective COX-2 inhibitors in reducing inflammation and minimising the occurrence of hepatocellular carcinoma in patients with cirrhosis.

Mohammed, N A; El-Aleem, S A; El-Hafiz, H A; McMahon, R F T

2004-01-01

160

Tolvaptan for the treatment of liver cirrhosis oedema.  

PubMed

No alternative therapeutic option exists if liver cirrhosis patients have insufficient response to conventional diuretics and/or experience conventional diuretic-related adverse events. In 2013, tolvaptan (7.5 mg/day), an arginine vasopressin V2 receptor antagonist, was approved in Japan for the treatment of liver cirrhosis with oedema. Short-term use of tolvaptan produced decreases in body weight, reduction in ascites volume and increases in urine volume when compared to placebo, despite the use of conventional diuretics. Additionally, approximately 60% of patients with oedema-related symptoms improved. Low-dose tolvaptan, 3.75 mg, was also efficacious. Even in patients with low serum albumin (<2.5 g/dL), decrease in body weight was greater with tolvaptan than with placebo. For future research, the efficacy and safety of lower tolvaptan doses for the treatment of liver cirrhosis patients with oedema should be confirmed in Japan. The results of this research could be used as an indicator or a guideline for physicians around the world. PMID:24678622

Sakaida, Isao

2014-07-01

161

Experimental liver cirrhosis induced by alcohol and iron.  

PubMed Central

To determine if alcoholic liver fibrogenesis is exacerbated by dietary iron supplementation, carbonyl iron (0.25% wt/vol) was intragastrically infused with or without ethanol to rats for 16 wk. Carbonyl iron had no effect on blood alcohol concentration, hepatic biochemical measurements, or liver histology in control animals. In both ethanol-fed and control rats, the supplementation produced a two- to threefold increase in the mean hepatic non-heme iron concentration but it remained within or near the range found in normal human subjects. As previously shown, the concentrations of liver malondialdehyde (MDA), liver 4-hydroxynonenal (4HNE), and serum aminotransferases (ALT, AST) were significantly elevated by ethanol infusion alone. The addition of iron supplementation to ethanol resulted in a further twofold increment in mean MDA, 4HNE, ALT, and AST. On histological examination, focal fibrosis was found < 30% of the rats fed ethanol alone. In animals given both ethanol and iron, fibrosis was present in all, with a diffuse central-central bridging pattern in 60%, and two animals (17%) developed micronodular cirrhosis. The iron-potentiated alcoholic liver fibrogenesis was closely associated with intense and diffuse immunostaining for MDA and 4HNE adduct epitopes in the livers. Furthermore, in these animals, accentuated increases in procollagen alpha 1(I) and TGF beta 1 mRNA levels were found in both liver tissues and freshly isolated hepatic stellate cells, perisinusoidal cells believed to be a major source of extracellular matrices in liver fibrosis. The dietary iron supplementation to intragastric ethanol infusion exacerbates hepatocyte damage, promotes liver fibrogenesis, and produces evident cirrhosis in some animals. These results provide evidence for a critical role of iron and iron-catalyzed oxidant stress in progression of alcoholic liver disease. Images

Tsukamoto, H; Horne, W; Kamimura, S; Niemela, O; Parkkila, S; Yla-Herttuala, S; Brittenham, G M

1995-01-01

162

Hepatoprotective effect of polyphenols rich methanolic extract of Amorphophallus commutatus var. wayanadensis against CCl4 induced hepatic injury in swiss albino mice.  

PubMed

The present study is to evaluate the hepatoprotective and antioxidant activity of methanolic extract of Amorphophallus commutatus var. wayanadensis against carbon tetrachloride induced hepatotoxicity in mice models. Hepatic injury was induced by injecting 0.2% CCl4 in olive oil intra peritoneally on 15th day of drug administration. Hepatoprotective activity was evaluated by estimating the levels of serum markers like alanine aminotransferase (ALT) and aspartate aminotransferase (AST), alkaline phosphatase (ALP), bilirubin and histopathological studies. Antioxidant potential of the extract was estimated by measuring the levels of antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), glutathione-s-transferase (GST), glutathione peroxidase (GPx) and total reduced glutathione in the liver samples. Histopathological and biochemical results elicited the methanolic extract of A. commutatus has significant hepatoprotective activity comparable to the standard silymarin. The extract also showed dose dependent increase of antioxidant enzymes in CCl4 induced hepatotoxicity models. The methanolic extract of A. commutatus showed significant hepatoprotective and antioxidant activity which might be attributed due to the polyphenolic compounds present in the extract. PMID:24569068

Raj, Sreena; Gothandam, K M

2014-05-01

163

Atlas of Histopathology of Liver: Hepatitis and Cirrhosis.  

National Technical Information Service (NTIS)

The Atlas focuses attention on acute and chronic hepatitis and cirrhosis. Representative lesions have been illustrated accompanied by brief textual descriptions. Uncommon forms of cirrhosis, such as pigment cirrhosis and also cirrhosis due to extrahepatic...

S. iramachari T. V. Madhavan

1974-01-01

164

Nitric Oxide Metabolites in Decompensated Liver Cirrhosis  

Microsoft Academic Search

High levels of nitric oxide are thought to bethe cause of some of the complications associated withdecompensated end-stage liver disease. To assess nitricoxide metabolism in cirrhotic patients, we measured the levels of nitric oxide metabolites(nitrosohemoglobin, methemoglobin, nitrate, and nitrite)in normal subjects, in patients with decompensatedcirrhosis, in patients with renal failure (model forimpaired NO metabolites excretion), and in patients withmononitrates-treated anginal

N. Barak; R. Zemel; Z. Ben-Ari; M. Braun; R. Tur-Kaspa

1999-01-01

165

Small Intestinal Motility Disturbances and Bacterial Overgrowth in Patients With Liver Cirrhosis and Portal Hypertension  

Microsoft Academic Search

OBJECTIVES:Altered small bowel motility and a high prevalence of small intestinal bacterial overgrowth (SIBO) has been observed in patients with liver cirrhosis. Our aim was to explore the relationship between motility abnormalities, portal hypertension, and SIBO.METHODS:Twenty-four patients with liver cirrhosis were included. Twelve had portal hypertension (PH) and 12 had liver cirrhosis (LC) alone. Child-Pugh score was the same in

Steingerdur Anna Gunnarsdottir; Riadh Sadik; Steven Shev; Magnus Simrén; Henrik Sjövall; Per-Ove Stotzer; Hasse Abrahamsson; Rolf Olsson; Einar S. Bjornsson; Anna Gunnarsdottir

2003-01-01

166

Carbon tetrachloride-induced experimental cirrhosis in the rat: a reappraisal of the model.  

PubMed

The goal of this study was to evaluate the presence of extrahepatic damage and the uniformity and reversibility of the histological findings in CCl4-induced liver cirrhosis in the rat. To verify these findings rats were sacrificed 2 and 10 weeks after a treatment consisting of ten intragastric doses of CCl4, administered weekly. All treated rats developed an irreversible micronodular cirrhosis with no damage to the brain, kidney and pancreas. Moreover, rats sacrificed 2 weeks after the last CCl4 dose showed a number of functional alterations usually observed in man. In particular, low branched chain/aromatic amino acids (BCAA/AAA) plasma ratio, high ammonia, low zinc and high insulin with normal blood glucose were obtained. PMID:2627982

Ariosto, F; Riggio, O; Cantafora, A; Colucci, S; Gaudio, E; Mechelli, C; Merli, M; Seri, S; Capocaccia, L

1989-01-01

167

Portal hypertension and varices in patients with liver cirrhosis.  

PubMed

Portal hypertension is a complication seen in patients with liver cirrhosis and is characterised by high pressure in the portal vein. As portal hypertension worsens, varices can form, leading to increased morbidity and mortality if these rupture. Bleeding can be prevented with pharmacological agents and endoscopic therapy; however, some patients will experience variceal haemorrhage. Medical and nursing management of acute variceal haemorrhage is key to a successful outcome, and after initial resuscitation, endoscopic therapy should be undertaken. Long-term management to prevent re-bleeding may involve surgery to implant shunts, which aim to reduce portal venous pressure. However, patients often require referral to specialist centres for transplant assessment. PMID:22916658

Fullwood, Danielle

168

[Relation of hepatic pathologic changes and portal venous pressure in the course of cirrhosis in rats].  

PubMed

In order to pinpoint the site causing increased intrahepatic vascular resistance, we observed the relationship between hepatic pathologic changes and free portal pressure (FPP) during the development of CCl4-induced liver cirrhosis of rat. The results suggested that the degeneration necrosis and regeneration of liver cells, and consequent stenosis, or obliteration of sinusoidal spaces caused by the swelling and disarrangement of the liver cell plates led to the occurrence of portal hypertension. The possibility of pre- or post-sinusoidal obstruction was excluded by the manifestation of the pathologic lesions. It is the authors' belief that the exact site of the increased intrahepatic vascular resistance was most likely at the level of hepatic sinusoids. Furthermore, there was certain positive correlation between plasma glucagon concentration and FPP, indicating that glucagon was also involved in the pathogenesis of portal hypertension. PMID:2379424

Wu, Z Y

1990-03-01

169

DETECTION OF CCL4-INDUCED OXIDATION OF HEPATIC TISSUE IN VIVO BY OXYGEN-18 TRACING  

EPA Science Inventory

Oxygen can become a damaging influence in tissues and cells exposed to environmental pollutants. The paper describes the first application of a new technique for tracing oxygen in tissues exposed to pollutants. Carbon tetrachloride (CCl4) was found to cause oxidation of liver tis...

170

Metronidazole-induced encephalopathy in a patient with liver cirrhosis  

PubMed Central

Encephalopathy is a disorder characterized by altered brain function, which can be attributed to various causes. Encephalopathy associated with metronidazole administration occurs rarely and depends on the cumulative metronidazole dose, and most patients with this condition recover rapidly after discontinuation of therapy. Because metronidazole is metabolized in the liver and can be transported by the cerebrospinal fluid and cross the blood-brain barrier, it may induce encephalopathy even at a low cumulative dose in patients with hepatic dysfunction. We experienced a patient who showed ataxic gait and dysarthric speech after receiving metronidazole for the treatment of hepatic encephalopathy that was not controlled by the administration of lactulose. The patient was diagnosed as metronidazole-induced encephalopathy, and stopping drug administration resulted in a complete recovery from encephalopathy. This case shows that caution should be exercised when administering metronidazole because even a low dose can induce encephalopathy in patients with liver cirrhosis.

Cheong, Hyeong Cheol; Jeong, Taek Geun; Cho, Young Bum; Yang, Bong Joon; Kim, Tae Hyeon; Kim, Haak Cheoul

2011-01-01

171

Efficacy of Lamivudine Therapy on Decompensated Liver Cirrhosis Due to Chronic Hepatitis B  

Microsoft Academic Search

Background and Aims: The aim of this study was to determine the effect of lamivudine on liver function and clinical status of the patients with decompensated cirrhosis arising from hepatitis B virus (HBV). Methods: In a clinical trial on the basis of liver consideration in 55 patients with cirrhosis that had positive HBsAg and HBV DNA, Child-Pugh score more than

Mahmood Yousefi-M Mashhour; Fariborz Mansour-G Ghanaei; Hosein Foroutan; Hadi Ghofrani; Zahra Purrasuli; Farahnaz Joukar

172

Specific psychiatric morbidity in liver cirrhosis in a Nigerian general hospital setting  

Microsoft Academic Search

The purpose of this investigation was to explore the psychiatric complications of liver cirrhosis in a Nigerian general hospital setting. The mental state of 31 consecutive patients with liver cirrhosis seen in a gastroenterology unit, from July 1996 to August 1998, was assessed using the 30-item General Health Questionnaire (GHQ-30) and Present State Examination (PSE) and compared with those of

Henry S Aghanwa; Dennis Ndububa

2002-01-01

173

Antioxidant activity of Aulosira fertilisima on CCl4 induced hepatotoxicity in rats.  

PubMed

Free radicals cause cell injury, when they are generated in excess or when the antioxidant defense is impaired. Carbon tetrachloride (CCl4) is used as a model for liver injury. In this study antioxidant activity of ethanol extract of A. fertilisima (EEA) was investigated using CCl4 intoxicated rat liver as the experimental model. Oral administration of EEA at a dose of 100 mg/kg body weight, for 14 consecutive days, the rate of the production of antioxidant enzymes like super oxide dismutase, catalase, glutathione peroxidase and glutathione transferase in rats compared to the CCl4 treated group without any supporting treatment. Liver damage is detected by the measurement of the activities of serum enzymes like aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transpeptidase and alkaline phosphatase which were released in to the blood from damaged cells. The normalization of these enzymes levels was observed in rats treated with EEA (100 mg/kg body weight) by reducing the leakage of the above enzymes in to the blood. The findings provide a rationale for further studies on isolation of active principles and its pharmacological evaluation. Protection offered by silymarin (standard reference drug) seemed relatively greater. PMID:18697572

Kuriakose, Gini C; Kurup, G Muraleedhara

2008-01-01

174

Inhibitory effect on proliferation of vascular smooth muscle cells and protective effect on CCl 4-induced hepatic damage of HEAI extract  

Microsoft Academic Search

The effects of methanol extract from Hericium erinaceus cultivated with Artemisia iwayomogi (HEAI) on proliferation of vascular smooth muscle cells and CCl4-induced hepatic damage were evaluated. HEAI was shown to have a potent inhibitory effect on the proliferation of vascular smooth muscle cells (VSMCs). Interestingly, a methanol extract of Hericium erinaceus showed no inhibitory effect on the proliferation of VSMCs,

Won-Sik Choi; Chang-Jin Kim; Byeoung-Soo Park; Sung-Eun Lee; Gary R. Takeoka; Dong-Goo Kim; Xiang LanPiao; Jeong-Han Kim

2005-01-01

175

Peptic ulcer surgery in patients with liver cirrhosis.  

PubMed Central

OBJECTIVE: This study identified risk factors of surgical treatment for gastroduodenal ulcer disease in patients with liver cirrhosis. SUMMARY BACKGROUND DATA: Liver cirrhosis is frequently associated with complicated peptic ulcer disease. Surgery in liver cirrhotics has a high mortality and morbidity especially when abdominal operations are performed. METHODS: Sixty-nine patients undergoing surgery for gastroduodenal ulcer disease between 1972 and 1991 were studied, retrospectively. RESULTS: Ninety percent of patients required emergency surgery for bleeding ulcer (n = 45) or perforation (n = 17). Mortality was 29% for elective patients (n = 7), 35% for patients with perforation and 64% for patients with bleeding. Overall mortality of 69 patients was 54%. Only 15 of 69 patients (22%) had an uncomplicated postoperative course. Postoperative bleeding, septic complications, and renal failure were the most frequent postoperative complications. Bleeding and multiple organ failure were the leading causes of death in 70% of patients. A univariate analysis determined preoperative hemoglobin < 12 g/L (p < 0.05), systolic blood pressure < 100 mm Hg (p < 0.025), prothrombin time < 60% (p < 0.05) and the presence of portal hypertension (p < 0.01) as prognostic factors. No significant correlation with survival could be established for excretory liver function (serum bilirubin) and partial thromboplastin time. CONCLUSIONS: To improve treatment results it is recommended (1) to substitute blood products (particularly coagulation factors) early and in sufficient quantities, (2) to diligently search for and to treat septic foci and administer antibiotics in a nonrestrictive manner, and (3) to restrict the operative procedure to the treatment required for control of the ulcer complication.

Lehnert, T; Herfarth, C

1993-01-01

176

Hepatic vein waveforms in liver cirrhosis re-evaluated  

PubMed Central

Objective There are many studies on changes in Doppler waveforms of hepatic veins in cirrhotic liver. It is postulated that dampening of phasic oscillations appears with worsening of liver function. Our aim was to reevaluate the significance of Doppler waveforms of hepatic vein in cirrhotic patients and to correlate with hepatic blood flow. Patients and method One hundred and thirty-five consecutive patients of liver cirrhosis and 60 age and sex matched non-cirrhotic controls were enrolled in this study. Doppler waveforms were obtained from right hepatic vein during normal respiration. Other parameters measured were flow volume of portal trunk, right portal vein and proper hepatic artery. Result Waveforms of the hepatic vein were classified into triphasic, biphasic and flat patterns. Flat waveform was rare and appeared in only 3% cases. There was no correlation between liver dysfunction and patterns of waveforms. Inflow, particularly to the right lobe, was significantly elevated in cases associated with the non-triphasic waveforms. Conclusion This study shows that the flat waveforms have no diagnostic value. Role of hepatic blood flow seems to be important suggesting hemodynamic changes rather than liver dysfunction as a plausible cause of change in waveforms.

Sharma, Dilip; Chataut, Saroj Prasad

2010-01-01

177

Liver cirrhosis induces renal and liver phospholipase A2 activity in rats.  

PubMed Central

Maintenance of renal function in liver cirrhosis requires increased synthesis of arachidonic acid derived prostaglandin metabolites. Arachidonate metabolites have been reported to be involved in modulation of liver damage. The purpose of the present study was to establish whether the first enzyme of the prostaglandin cascade synthesis, the phospholipase A2(PLA2) is altered in liver cirrhosis induced by bile duct excision. The mRNA of PLA2(group I and II) and annexin-I a presumptive inhibitor of PLA2 enzyme was measured by PCR using glyceraldehyde 3-phosphate dehydrogenase (GAPDH) as an internal standard. The mean mRNA ratio of group II PLA2/GAPDH was increased in liver tissue by 126% (P < 0.001) and in kidney tissue by 263% (P < 0.006) following induction of liver cirrhosis. The increase in group II PLA2 mRNA in cirrhotic animals was reflected by an increase in PLA2 protein and enzyme activity in both liver and kidney tissues. Since the mRNA of group I PLA2 was not detectable and Group IV PLA2 activity measured in liver and kidney tissue samples was very low and not changed following induction of cirrhosis, it is likely that the major PLA2 activity measured in liver and kidney corresponds to group II PLA2 enzyme. The mean mRNA ratio of annexin-I/GAPDH was increased in liver tissue by 115% (P < 0.05) but unchanged in kidney tissue following induction of cirrhosis. The protein content of annexin-I and -V were not affected by bile duct excision in liver and kidney tissue indicating that upregulation of group II PLA2 activity was not due to downregulation of annexin-I or -V. Group II PLA2 activity of glomerular mesangial cells stimulated by interleukin-1 beta was enhanced by bile juice and various bile salts. In conclusion, activity of group II PLA2 is upregulated partly due to enhanced transcription and translation in cirrhosis and is furthermore augmented by elevated levels of bile salts.

Vishwanath, B S; Frey, F J; Escher, G; Reichen, J; Frey, B M

1996-01-01

178

Preventive Approaches in Chronic Liver Diseases Part III: Decompensated Liver Cirrhosis  

Microsoft Academic Search

Medical complications are frequent in patients with decompensated liver cirrhosis (LC). This article addresses preventive measures in the setting of decompensated LC. A 2 gram sodium and 1-1.5 grams of protein per kilogram of body weight per day diet is recommended. The use of prophylactic antibiotic in spontaneous bacte- rial peritonitis (SBP) is considered only in selected cases, and never

Mohammad R. Taheri; Thomas R. Riley III

179

Prevalence of spontaneous bacterial peritonitis in liver cirrhosis with ascites  

PubMed Central

Introduction Spontaneous bacterial peritonitis (SBP) is a common bacterial infection in patients with cirrhosis and ascites requiring prompt recognition and treatment. The aim of this study was to determine the prevalence, and characteristics of SBP among in-patients with cirrhosis and ascites seen at our facility. Methods Thirty one patients with liver cirrhosis and ascites who were admitted into the Medical ward of the Ekiti State University Teaching Hospital (EKSUTH), Ado-Ekiti, Nigeria from August 2009 to July 2010 were retrospectively studied. All the patients had abdominal paracentesis done within 48 hours of admission under aseptic condition and the data obtained were analyzed. Results The mean age of the studied population was 62±9 years (age range 43-78 years). Of the 21 that developed SPB, culture positive SBP was present in 66.7% (14/21) while CNNA was found in 33.3% (7/21). The prevalence of MNB was 26% (8/31) in this study. Of those with SBP, 93% had monomicrobial infection with aerobic Gram negative bacilli being responsible in 66.7% of the cases with E.coli (70%) being the predominant organism followed by Klebsiella species. Gram positive organisms accounted for 33.3% with Streptococcal species (60%) being the predominant organism followed by Staphylococcus aureus (40%). Patients with SBP had significantly lower platelet count when compared with those without SBP, p < 0.05. Also, international normalization ratio (INR) was significantly higher in those patients with SBP compared with those without SBP, p < 0.05. The poor prognostic indicators found in this study were; low ascitic protein, hepatic encephalopathy, coagulopathy, renal dysfunction (creatinine >2mg/dl) and leukocytosis (p < 0.05). Conclusion It is therefore imperative to do diagnostic abdominal paracentesis for cell count and culture in any patient with onset of ascites or cirrhotic patients with ascites and suggestive symptoms compatible or suggestive of SBP.

Oladimeji, Ajayi Akande; Temi, Adegun Patrick; Adekunle, Ajayi Ebenezer; Taiwo, Raimi Hassan; Ayokunle, Dada Samuel

2013-01-01

180

Laparoscopic Cholecystectomy for Cholelithiasis in Patients With Liver Cirrhosis  

PubMed Central

We performed laparoscopic cholecystectomy for symptomatic cholelithiasis on four patients with cirrhosis of the liver, two of whom had clinical portal hypertension and splenomegaly. Preoperative examination disclosed hypersplenism in one patient, while mild thrombocytopenia and decreased prothrombin concentration were noted in three patients. However, no remarkable bleeding tendency was recognized clinically in any of the patients. Preoperatively, by Child-Pugh's criteria, three patients had class B disease and one class A disease. Intraoperatively, remarkable inflammatory change or fibrotic change of the gallbladder wall and Calot's triangle was observed in two cases, and collateral veins and lymphangial congestion were observed in all four cases. In the first case, extreme bleeding and lymphorrhea from dissected sites were observed, and a 1.5 unit of transfusion of whole blood was required during operation. Postoperatively, increase in ascites which was controlled with diuretics was recognized in one case. However, the postoperative course was uneventful in all cases, and no serious complications were recognized. That laparoscopic cholecystectomy can be safely performed in patients with cirrhosis if careful and appropriate management of bleeding and lymphorrhea from sites of dissection is ensured, is encouraging.

Sowa, Michio; Nagayama, Masayoshi; Nishiguchi, Yukio

1995-01-01

181

Potent hepatoprotective effect in CCl4-induced hepatic injury in mice of phloroacetophenone from Myrcia multiflora  

PubMed Central

Background This study investigated the hepatoprotective effect and antioxidant properties of phloroacetophenone (2?,4?,6?-trihydroxyacetophenone – THA), an acetophenone derived from the plant Myrcia multiflora. Material & Method The free radical scavenging activity in vitro and induction of oxidative hepatic damage by carbon tetrachloride (CCl4) (0.5 ml/kg, i.p.) were tested in male Swiss mice (25±5 g). Results This compound exhibited in vitro antioxidant effects on FeCl2–ascorbate-induced lipid peroxidation (LPO) in mouse liver homogenate, scavenging hydroxyl and superoxide radicals, and 2,2-diphenyl-1-picrylhydrazyl. The in vivo assays showed that THA significantly (p<0.01) prevented the increases of hepatic LPO as measured by the levels of thiobarbituric acid-reactive substances, mitochondrial swelling. It also protected hepatocytes against protein carbonylation and oxidative DNA damage. Consistent with these observations, THA pre-treatment normalized the activities of antioxidant enzymes, such as catalase, glutathione peroxidase, and superoxide dismutase, and increased the levels of reduced glutathione (GSH) in CCl4-treated mice. In addition, THA treatment significantly prevented the elevation of serum enzymatic activities of alanine amino transferase, aspartate amino transferase, and lactate dehydrogenase, as well as histological alterations induced by CCl4. Silymarin (SIL) (24 mg/kg), a known hepatoprotective drug used for comparison, led to a significant decrease (p<0.01) in activities of theses enzymes in way very similar to that observed in pre-treatment with THA. Conclusion These results suggest that the protective effects are due to reduction of oxidative damage induced by CCl4 resulting from the antioxidant properties of THA.

Ferreira, Eduardo Antonio; Gris, Eliana Fortes; Felipe, Karina Bettega; Correia, Joao Francisco Gomes; Cargnin-Ferreira, Eduardo; Wilhelm Filho, Danilo; Pedrosa, Rozangela Curi

2010-01-01

182

Protective effects of Sonchus asper (L.) Hill, (Asteraceae) against CCl4-induced oxidative stress in the thyroid tissue of rats  

PubMed Central

Background Sonchus asper (L.) Hill, (Asteraceae) is used in Pakistan as a traditional (“folk”) medicine for the treatment of hormonal disorders and oxidative stress. The present study was aimed to evaluate the efficacy of Sonchus asper (L.) Hill, (Asteraceae) methanolic extract (SAME) on hormonal dysfunction in thyroid tissue after carbon tetrachloride (CCl4)-induced oxidative stress. Methods To examine the effects of SAME against the oxidative stress of CCl4 in thyroid tissue, 30 male albino rats were used. Protective effects of SAME were observed on thyroid hormonal levels, activities of antioxidant enzymes, lipid peroxidation (TBARS) and DNA damage. Results Treatment with CCl4 significantly (P<0.01) reduced the levels of T3 and T4 and increased TSH levels. CCl4 exposure in rats reduced the activities of antioxidant enzymes but increased lipid peroxidation and DNA damage. Co-administration of SAME significantly (P<0.01) improved these alterations with respect to hormonal levels, activities of antioxidant enzymes and lipid peroxidation close to those seen in control rats. Conclusion These results suggest that SAME can protect thyroid tissue against oxidative damage, possibly through the antioxidant effects of its bioactive compounds.

2012-01-01

183

CCl4 induces tissue-type plasminogen activator in rat brain; protective effects of oregano, rosemary or vitamin E.  

PubMed

The high metabolic rate and relatively low antioxidant defenses of the lipid-rich brain tissue render it highly susceptible to reactive oxygen species (ROS) and oxidative stress, whereas the implication of ROS in the pathogenesis of several diseases in the central nervous system is well-established. The plasminogen activator (PA) system is a key modulator of extracellular proteolysis, extracellular matrix remodeling and neuronal cell signaling and has been implicated in the pathogenesis of these diseases. This study evaluates the role of tissue-type PA (t-PA) in oxidative stress and the protective role of dietary antioxidants in the rat brain. We used the CCl4 experimental model of ROS-induced lipid peroxidation and evaluated the antioxidant effect of oregano, rosemary or vitamin E. CCl4-treated Wistar rats exhibited elevated brain t-PA activity, which was decreased upon long-term administration of oregano, rosemary or vitamin E. PA inhibitor-1 (PAI-1) activity was also slightly elevated by CCl4, but this increase was not affected by the antioxidants. We hypothesize that the CCl4-induced t-PA activity indicates extracellular proteolytic activity that may be linked to neuronal cell death and brain damage. Vitamin E or antioxidants present in oregano or rosemary are effective in inhibiting t-PA elevation and can be considered as a potential protection against neuronal damage. PMID:23831191

Lavrentiadou, Sophia N; Tsantarliotou, Maria P; Zervos, Ioannis A; Nikolaidis, Efstathios; Georgiadis, Marios P; Taitzoglou, Ioannis A

2013-11-01

184

Intestinal bacterial translocation in rats with cirrhosis is related to compromised Paneth cell antimicrobial host defense.  

PubMed

Liver cirrhosis is associated with bacterial translocation (BT) and endotoxemia. Most translocating bacteria belong to the common intestinal microbiota, suggesting a breakdown of intestinal barrier function. We hypothesized that diminished mucosal antimicrobial host defense could predispose to BT. Two rodent models of portal hypertension with increased BT were used, CCl(4)-induced ascitic cirrhosis and 2-day portal vein-ligated (PVL) animals. BT was assessed by standard microbiological techniques on mesenteric lymph nodes. Total RNA was isolated systematically throughout the intestinal tract, and expression of Paneth cell ?-cryptdins and ?-defensins was determined by real-time quantitative polymerase chain reaction (qPCR). To determine functional consequences, mucosal antimicrobial activity was assessed with a fluorescence-activated cell sorting assay. BT was detectable in 40% of rats with cirrhosis. Compared with the group without BT, these animals exhibited diminished intestinal Paneth cell ?-cryptdin 5 and 7 expression. In contrast, PVL was associated with BT in all animals but did not affect antimicrobial peptides. The decrease in Paneth cell antimicrobials was most pronounced in the ileum and the coecum. Other antimicrobials showed no changes or even an induction in the case of BT at different sites. Antimicrobial activity toward different commensal strains was reduced, especially in the distal ileum and the cecum in experimental cirrhosis with BT (excluding PVL). Conclusion: Compromised Paneth cell antimicrobial host defense seems to predispose to BT in experimental cirrhosis. Understanding this liver-gut axis including the underlying mechanisms could help us to find new treatment avenues. PMID:22095436

Teltschik, Zora; Wiest, Reiner; Beisner, Julia; Nuding, Sabine; Hofmann, Claudia; Schoelmerich, Juergen; Bevins, Charles L; Stange, Eduard F; Wehkamp, Jan

2012-04-01

185

Chronic pancreatitis associated with chylous ascites simulating liver cirrhosis.  

PubMed

Purpose. Ascites, esophageal varicose veins, and acute digestive bleeding are unusual in the clinical presentation of chronic pancreatitis; however, these symptoms are frequently observed in patients with liver cirrhosis. Moreover, it is unlikely to observe chylous ascites in both presentations. Method. We report a patient who presented with chronic pancreatitis with splenic vein thrombosis, necrosis of the pancreatic neck and tail, esophageal varicose veins with previous bleeding, and chylous ascites. After partial pancreatectomy, his treatment was based on low-fat oral diet with medium-chain triglycerides with remarkable resolution of the chylous ascites. After 3 years, he presented with decompensated chronic pancreatitis and underwent plexus alcoholization and biliary-enteric deviation with an unremarkable postoperative course. Conclusion. Ascites is rarely associated with chronic pancreatitis, and chylous ascites is even rarer. The treatment of atraumatic chylous ascites is based on resolution of the obstructive causes and should include drainage and a low-fat diet with medium-chain triglycerides. PMID:24363949

Andraus, Wellington; Nacif, Lucas Souto; Araujo, Raphael L C; Buscariolli, Yuri Dos Santos; Salvato, Mayara; D'Albuquerque, Luiz Augusto Carneiro

2013-01-01

186

Chronic Pancreatitis Associated with Chylous Ascites Simulating Liver Cirrhosis  

PubMed Central

Purpose. Ascites, esophageal varicose veins, and acute digestive bleeding are unusual in the clinical presentation of chronic pancreatitis; however, these symptoms are frequently observed in patients with liver cirrhosis. Moreover, it is unlikely to observe chylous ascites in both presentations. Method. We report a patient who presented with chronic pancreatitis with splenic vein thrombosis, necrosis of the pancreatic neck and tail, esophageal varicose veins with previous bleeding, and chylous ascites. After partial pancreatectomy, his treatment was based on low-fat oral diet with medium-chain triglycerides with remarkable resolution of the chylous ascites. After 3 years, he presented with decompensated chronic pancreatitis and underwent plexus alcoholization and biliary-enteric deviation with an unremarkable postoperative course. Conclusion. Ascites is rarely associated with chronic pancreatitis, and chylous ascites is even rarer. The treatment of atraumatic chylous ascites is based on resolution of the obstructive causes and should include drainage and a low-fat diet with medium-chain triglycerides.

Nacif, Lucas Souto; Araujo, Raphael L. C.; Buscariolli, Yuri dos Santos; Salvato, Mayara; D'Albuquerque, Luiz Augusto Carneiro

2013-01-01

187

Osteoporosis in primary biliary cirrhosis of the liver  

PubMed Central

Osteoporosis is a metabolic bone disease associated with a reduction in bone mass and deterioration of bone architecture, leading to increased fragility and subsequent low-trauma fractures in the vertebral column, hip, forearm and other bones. In literature, metabolic bone diseases such as osteoporosis and osteomalacia have been recognised as a complication of chronic liver disease, although the mechanisms of this association remain unclear. An increasing body of research data indicates a strong relationship between osteoporosis and primary biliary cirrhosis (PBC), which mainly results from early diagnosis of the disease, usually when it is still asymptomatic. The incidence of osteoporosis in PBC ranges from 20% to 44% and increases with the progression of the disease. Similarly, the incidence of bone fractures is high in this group of patients (10–20%). In this article, current knowledge on risk factors, pathogenesis, diagnosis and treatment of osteoporosis in PBC is reviewed.

Raszeja-Wyszomirska, Joanna

2014-01-01

188

Terahertz spectroscopy of liver cirrhosis: investigating the origin of contrast  

NASA Astrophysics Data System (ADS)

We have previously demonstrated that terahertz pulsed imaging is able to distinguish between rat tissues from different healthy organs. In this paper we report our measurements of healthy and cirrhotic liver tissues using terahertz reflection spectroscopy. The water content of the fresh tissue samples was also measured in order to investigate the correlations between the terahertz properties, water content, structural changes and cirrhosis. Finally, the samples were fixed in formalin to determine whether water was the sole source of image contrast in this study. We found that the cirrhotic tissue had a higher water content and absorption coefficient than the normal tissue and that even after formalin fixing there were significant differences between the normal and cirrhotic tissues' terahertz properties. Our results show that terahertz pulsed imaging can distinguish between healthy and diseased tissue due to differences in absorption originating from both water content and tissue structure.

Sy, Stanley; Huang, Shengyang; Wang, Yi-Xiang J.; Yu, Jun; Ahuja, Anil T.; Zhang, Yuan-ting; Pickwell-MacPherson, Emma

2010-12-01

189

Glutathione status in liver and plasma during development of biliary cirrhosis after bile duct ligation  

Microsoft Academic Search

We do not know much about the changes that occur in reduced (GSH) and oxidized (GSSG) glutathione in the development of liver cirrhosis. Therefore, we investigated the glutathione redox system during development of liver cirrhosis after bile-duct ligation in rats. We compared the GSH and GSSG content of liver and plasma between bile-duct-ligated rats and sham-operated controls 6 and 24

Edmund Purucker; Ron Winograd; Elke Roeb; Siegfried Matern

1998-01-01

190

Oral health and liver function in children and adolescents with cirrhosis of the liver  

PubMed Central

Introduction People with cirrhosis of the liver are predisposed to developing oral lesions. The occurrence and type of lesion depend on the degree of liver function impairment and its type, and on the severity and duration of systemic diseases. In children, the age at which the early symptoms of liver disease are experienced is also of great importance. Aim To assess the prevalence of oral pathological lesions in children and adolescents with cirrhosis of the liver, and their correlation with the degree of liver function impairment. Material and methods Clinical and laboratory results of liver function tests (Model of End-Stage Liver Disease/Score of Paediatric End-Stage Liver Disease, Child-Pugh score) were assessed in 35 patients with cirrhosis of the liver. The average age of the patients was 10.7 ±4.74 years. All patients also had their oral cavities examined (mucosa, gingiva – GI, hygiene – PLI, teeth – dmft/dmfs and DMFt/DMFs, DDE Index and Candida spp. presence) and this was then correlated to the degree of liver function impairment. Results According to the Child-Pugh scale, 16 patients were class A and 19 were class B/C. Jaundice during the first 3 years of life occurred in 9 patients. Mucosal lesions were found in 26 out of 35 patients (74%), including 10 out of 16 (63%) in Child-Pugh group A, and 16 out of 19 (84%) in group B/C (NS – non significant). Oral candidiasis occurred more often in class B/C than in class A (47.4% vs. 12.5%; p < 0.05). The GI index (Gingival Index) and PLI index (Dental Plaque Index) did not differ between the groups (A vs. B/C) but correlated in the whole group (R = 0.58) as well as in subgroups A (R = 0.65) and B/C (R = 0.59). Dmft/dmfs and DMFt/DMFs indexes did not differ between groups A and B/C, and neither did the DMFt/DMFs in patients with/without enamel defects. Conclusions Oral mucosal lesions are commonly found in children with cirrhosis of the liver. Advanced liver disease promotes oral candidiasis. Severity of gingivitis correlates with the presence of dental plaque.

Kowalczyk, Wojciech; Krasuska-Slawinska, Ewa; Dadalski, Maciej; Kostewicz, Krzysztof; Pawlowska, Joanna

2014-01-01

191

Polysomnographic sleep aspects in liver cirrhosis: A case control study  

PubMed Central

AIM: To study sleep aspects and parameters in cirrhotic patients and assess the role of liver dysfunction severity in polysomnographic results. METHODS: This was a case-control study. Patients with a diagnosis of liver cirrhosis were consecutively enrolled in the study. Clinical examinations and laboratory liver tests were performed in all patients, and disease severity was assessed using the Child-Pugh score. The control group consisted of age- and gender-matched healthy volunteers. All individuals answered a questionnaire about habits, behaviors, and complaints related to sleep and were submitted to polysomnography. Sleep parameters were compared between the two groups, and separate analyses were performed among classes of Child-Pugh classification in the cirrhotic group. RESULTS: Forty-two cirrhotic patients and forty-two controls were enrolled. Compared to the control group, the cirrhotic group exhibited lower sleep efficiency (mean ± SD: 73.89% ± 14.99% vs 84.43% ± 8.55%, P < 0.01), increased latency (151.27 ± 93.24 min vs 90.62 ± 54.74 min, P < 0.01) and a lower percentage of rapid eye movement (REM) sleep (14.04% ± 5.64% vs 20.71% ± 6.77%, P < 0.05) as well as a higher frequency of periodic limb movements (10.56 ± 2.85/h vs 2.79 ± 0.61/h, P < 0.01). The comparison of sleep parameters among Child A, B and C cirrhotic patients revealed a significant reduction of REM sleep stage occurrence in individuals with severe liver disease (Child C patients) compared to Child A/B patients (polysomnography percentage of REM sleep stage of patients Child A: 16.1% ± 1.2%; Child B: 14.9% ± 1.2%; Child C: 8.6% ± 1.6%, P < 0.05). CONCLUSION: Cirrhosis was associated with shorter sleep time, reduced sleep efficiency, increased sleep latency, increased REM latency and reduced REM sleep. Additionally, disease severity influences sleep parameters.

Teodoro, Vinicius Vasconcelos; Junior, Mauricio Augusto Bragagnolo; Lucchesi, Ligia Mendonca; Cavignolli, Daniel; de Mello, Marco Tulio; Kondo, Mario; Tufik, Sergio

2013-01-01

192

Alcohol Cirrhosis Alters Nuclear Receptor and Drug Transporter Expression in Human Liver  

PubMed Central

Unsafe use of alcohol results in approximately 2.5 million deaths worldwide, with cirrhosis contributing to 16.6% of reported deaths. Serum insulin levels are often elevated in alcoholism and may result in diabetes, which is why alcoholic liver disease and diabetes often are present together. Because there is a sizable population with these diseases alone or in combination, the purpose of this study was to determine whether transporter expression in human liver is affected by alcoholic cirrhosis, diabetes, and alcoholic cirrhosis coexisting with diabetes. Transporters aid in hepatobiliary excretion of many drugs and toxic chemicals and can be determinants of drug-induced liver injury. Drug transporter expression and transcription factor–relative mRNA and protein expression in normal, diabetic, cirrhotic, and cirrhosis with diabetes human livers were quantified. Cirrhosis significantly increased ABCC4, 5, ABCG2, and solute carrier organic anion (SLCO) 2B1 mRNA expression and decreased SLCO1B3 mRNA expression in the liver. ABCC1, 3–5, and ABCG2 protein expression was also upregulated by alcoholic cirrhosis. ABCC3-5 and ABCG2 protein expression was also upregulated in diabetic cirrhosis. Cirrhosis increased nuclear factor E2–related factor 2 mRNA expression, whereas it decreased pregnane-X-receptor and farnesoid-X-receptor mRNA expression in comparison with normal livers. Hierarchical cluster analysis indicated that expressions of ABCC2, 3, and 6; SLCO1B1 and 1B3; and ABCC4 and 5 were more closely related in the livers from this cohort. Overall, alcoholic cirrhosis altered transporter expression in human liver.

More, Vijay R.; Cheng, Qiuqiong; Donepudi, Ajay C.; Buckley, David B.; Lu, Zhenqiang James; Cherrington, Nathan J.

2013-01-01

193

Renal Hemodynamics in Patients with Cirrhosis: Relationship with Ascites and Liver Failure  

Microsoft Academic Search

In patients with cirrhosis and ascites decreased renal blood flow might be related to the severity of liver disease but the relationship beween the severity of cirrhosis and renal perfusion has not yet been established. Thus we measured renal, systemic and splanchnic hemodynamics in 63 patients with ascites and in 28 without ascites. When compared to patients without ascites, patients

R. Moreau; C. Gaudin; A. Hadengue; A. Braillon; D. Roulot; Y. Bacq; D. Lebrec

1993-01-01

194

Liver Cirrhosis Mortality in The United States, 1970-99. Surveillance Report 60.  

National Technical Information Service (NTIS)

The surveillance report published by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) presents trends in liver cirrhosis mortality in the United States. Data on the underlying cause of death were compiled from public-use data tapes published...

Y. H. Yoon H. Y. Yi B. F. Grant F. S. Stinson M. C. Dufour

2002-01-01

195

Small intestinal motility disturbances and bacterial overgrowth in patients with liver cirrhosis and portal hypertension  

Microsoft Academic Search

ObjectivesAltered small bowel motility and a high prevalence of small intestinal bacterial overgrowth (SIBO) has been observed in patients with liver cirrhosis. Our aim was to explore the relationship between motility abnormalities, portal hypertension, and SIBO.

Steingerdur Anna Gunnarsdottir; Riadh Sadik; Steven Shev; Magnus Simrén; Henrik Sjövall; Per-Ove Stotzer; Hasse Abrahamsson; Rolf Olsson; Einar S Björnsson

2003-01-01

196

Prevalence of tuberculosis in patients with cirrhosis of liver in western India.  

PubMed

Tuberculosis is a common disease in India. Its prevalence is higher in patients with cirrhosis of the liver. This study was conducted to determine the prevalence of tuberculosis in patients with liver cirrhosis in Western India. The prevalence was fifteen times higher than in the general population. It was significantly higher in alcoholics. The response to treatment and outcome were found to be favourable. PMID:20478985

Baijal, R; Praveenkumar, H R; Amarapurkar, D N; Nagaraj, K; Jain, M

2010-07-01

197

Development of a New Animal Model of Liver Cirrhosis in Swine  

Microsoft Academic Search

This study aimed to develop a new experimental model of liver cirrhosis in swine by using carbon tetrachloride (CCl4) and ethanol. Liver cirrhosis was induced by intraperitoneal injection of CCl4 twice a week for 9 weeks. Maize flour was the only food provided and the animals drunk a 5% alcohol-water mixture. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin, bilirubin and

J.-J. Zhang; X.-K. Meng; C. Dong; J.-L. Qiao; R.-F. Zhang; G.-Q. Yue; H.-Y. Zhong

2009-01-01

198

Cohort effect of HCV infection in liver cirrhosis assessed by a 25 year study  

Microsoft Academic Search

Background: The role of HCV infection in the development of chronic liver disease is still unclear. Objectives: Assess the presence of HCV infection in patients with liver cirrhosis. Study design: 123 cases of cirrhotic liver randomly selected over a 25 years period (1969–1994) from the autopsy archives of the Pathology Department of the University of Trieste, Italy, were analyzed for

Giorgio Stanta; Lory S Crocè; Serena Bonin; Sergio G Tisminetzky; Francisco E Baralle; Claudio Tiribelli

2000-01-01

199

Liver cirrhosis as a consequence of iron overload caused by hereditary nonspherocytic hemolytic anemia  

Microsoft Academic Search

Abstract Abstract Abstract Abstract Nonspherocytic hereditary anemias are occasionally accompanied by significant iron overload but the significance for the development of chronic liver disease is not clear. We described two cases of patients with chronic liver disease and severe iron overload due to chronic hereditary hemolysis. Both patients have had signs of liver cirrhosis and severe hemolysis since childhood. A

Philip Hilgard; Guido Gerken

200

Physiologic and laboratory correlates of depression, anxiety, and poor sleep in liver cirrhosis  

PubMed Central

Background Studies have shown psychological distress in patients with cirrhosis, yet no studies have evaluated the laboratory and physiologic correlates of psychological symptoms in cirrhosis. This study therefore measured both biochemistry data and heart rate variability (HRV) analyses, and aimed to identify the physiologic correlates of depression, anxiety, and poor sleep in cirrhosis. Methods A total of 125 patients with cirrhosis and 55 healthy subjects were recruited. Each subject was assessed through routine biochemistry, 5-minutes ECG monitoring, and psychological ratings of depression, anxiety, and sleep. HRV analysis were used to evaluate autonomic functions. The relationship between depression, sleep, and physiologic correlates was assessed using a multiple regression analysis and stepwise method, controlling for age, duration of illness, and severity of cirrhosis. Results Reduced vagal-related HRV was found in patients with severe liver cirrhosis. Severity of cirrhosis measured by the Child-Pugh score was not correlated with depression or anxiety, and only had a weak correlation with poor sleep. The psychological distress in cirrhosis such as depression, anxiety, and insomnia were correlated specifically to increased levels of aspartate aminotransferase (AST), increased ratios of low frequency to high frequency power, or reduced nonlinear properties of HRV (?1 exponent of detrended fluctuation analysis). Conclusions Increased serum AST and abnormal autonomic nervous activities by HRV analysis were associated with psychological distress in cirrhosis. Because AST is an important mediator of inflammatory process, further research is needed to delineate the role of inflammation in the cirrhosis comorbid with depression.

2013-01-01

201

Serum Autotaxin Is a Parameter for the Severity of Liver Cirrhosis and Overall Survival in Patients with Liver Cirrhosis - A Prospective Cohort Study  

PubMed Central

Background Autotaxin (ATX) and its product lysophosphatidic acid (LPA) are considered to be involved in the development of liver fibrosis and elevated levels of serum ATX have been found in patients with hepatitis C virus associated liver fibrosis. However, the clinical role of systemic ATX in the stages of liver cirrhosis was unknown. Here we investigated the relation of ATX serum levels and severity of cirrhosis as well as prognosis of cirrhotic patients. Methods Patients with liver cirrhosis were prospectively enrolled and followed until death, liver transplantation or last contact. Blood samples drawn at the day of inclusion in the study were assessed for ATX content by an enzyme-linked immunosorbent assay. ATX levels were correlated with the stage as well as complications of cirrhosis. The prognostic value of ATX was investigated by uni- and multivariate Cox regression analyses. LPA concentration was determined by liquid chromatography-tandem mass spectrometry. Results 270 patients were enrolled. Subjects with liver cirrhosis showed elevated serum levels of ATX as compared to healthy subjects (0.814±0.42 mg/l vs. 0.258±0.40 mg/l, P<0.001). Serum ATX levels correlated with the Child-Pugh stage and the MELD (model of end stage liver disease) score and LPA levels (r?=?0.493, P?=?0.027). Patients with hepatic encephalopathy (P?=?0.006), esophageal varices (P?=?0.002) and portal hypertensive gastropathy (P?=?0.008) had higher ATX levels than patients without these complications. Low ATX levels were a parameter independently associated with longer overall survival (hazard ratio 0.575, 95% confidence interval 0.365–0.905, P?=?0.017). Conclusion Serum ATX is an indicator for the severity of liver disease and the prognosis of cirrhotic patients.

Pleli, Thomas; Martin, Daniel; Kronenberger, Bernd; Brunner, Friederike; Koberle, Verena; Grammatikos, Georgios; Farnik, Harald; Martinez, Yolanda; Finkelmeier, Fabian; Labocha, Sandra; Ferreiros, Nerea; Zeuzem, Stefan

2014-01-01

202

Cytochrome P450 4F2 polymorphism in patients with liver cirrhosis.  

PubMed

1297C/T polymorphism of CYP4F2 gene was studied in 108 patients with chronic liver diseases. No significant correlation with predisposition to rapid liver cirrhosis was revealed without consideration for cirrhosis etiology (OR=0.93, 95% CI=0.28-2.99, p=0.885). In patients with viral cirrhosis, a tendency to association of 1297T allele genotypes with rapid cirrhosis development was found (OR=6.0, 95% CI=0.28-382.64, p=0.222). At the same time, CYP4F2 1297T allele was associated with mild (Child-Pugh class A-B) cirrhosis (OR=2.9, p=0.044). PMID:24319743

Vavilin, V A; Nepomnyashchikh, D L; Shchepotina, E G; Karavaeva, Yu Yu; Makarova, S I; Vinogradova, E V; Kudryashov, A V; Nokhrina, Zh V; Lyakhovich, V V

2013-12-01

203

Life-threatening coagulopathy and hypofibrinogenaemia induced by tigecycline in a patient with advanced liver cirrhosis.  

PubMed

Bacterial infections because of multidrug-resistant (MDR) bacteria are spreading worldwide. In patients with advanced liver cirrhosis, healthcare-acquired and hospital-acquired infections are common and are frequently sustained by MDR bacteria. In these settings, tigecycline, a new antibiotic, has been shown to be useful in the treatment of MDR bacteria, and it has been proposed for the treatment of hospital-acquired infections in patients with cirrhosis. Nevertheless, poor data exist on the safety profile of tigecycline in patients with cirrhosis. Here, an experience is reported in a female patient with advanced liver cirrhosis, who developed sepsis by an MDR Stenotrophomonas maltophilia and was treated with tigecycline. She experienced life-threatening side effects consisting of severe coagulopathy with hypofibrinogenaemia and subsequent gastrointestinal haemorrhage. The side effect disappeared after the withdrawal of tigecycline. Therefore, a strict monitoring of coagulation parameters in patients with cirrhosis treated with tigecycline is recommended. PMID:24667348

Rossitto, Giacomo; Piano, Salvatore; Rosi, Silvia; Simioni, Paolo; Angeli, Paolo

2014-06-01

204

Gd-EOB-DTPA-enhanced MRI for the assessment of liver function and volume in liver cirrhosis  

PubMed Central

Objective: The aims of this study were to use dynamic hepatocyte-specific contrast-enhanced MRI to evaluate liver volume and function in liver cirrhosis, correlate the results with standard scoring models and explore the inhomogeneous distribution of liver function in cirrhotic livers. Methods: 10 patients with liver cirrhosis and 20 healthy volunteers, serving as controls, were included. Hepatic extraction fraction (HEF), input relative blood flow and mean transit time were calculated on a voxel-by-voxel basis using deconvolutional analysis. Segmental and total liver volumes as well as segmental and total hepatic extraction capacity, expressed in HEFml, were calculated. An incongruence score (IS) was constructed to reflect the uneven distribution of liver function. The Mann–Whitney U-test was used for group comparison of the quantitative liver function parameters, liver volumes and ISs. Correlations between liver function parameters and clinical scores were assessed using Spearman rank correlation. Results: Patients had larger parenchymal liver volume, lower hepatocyte function and more inhomogeneous distribution of function compared with healthy controls. Conclusion: The study demonstrates the non-homogeneous nature of liver cirrhosis and underlines the necessity of a liver function test able to compensate for the heterogeneous distribution of liver function in patients with diseased liver parenchyma. Advances in knowledge: The study describes a new way to quantitatively assess the hepatic uptake of gadoxetate or gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid in the liver as a whole as well as on a segmental level.

Blomqvist, L; Douglas, L; Nordell, A; Janczewska, I; Naslund, E; Jonas, E

2013-01-01

205

Nutrition and exercise in the management of liver cirrhosis  

PubMed Central

Liver cirrhosis (LC) patients often have protein-energy malnutrition (PEM) and decreased physical activity. These conditions often lead to sarcopenia, which is the loss of skeletal muscle volume and increased muscle weakness. Recent studies have demonstrated that PEM and sarcopenia are predictors for poor survival in LC patients. Nutrition and exercise management can improve PEM and sarcopenia in those patients. Nutrition management includes sufficient dietary intake and improved nutrient metabolism. With the current high prevalence of obesity, the number of obese LC patients has increased, and restriction of excessive caloric intake without the exacerbation of impaired nutrient metabolism is required for such patients. Branched chain amino acids are good candidates for supplemental nutrients for both obese and non-obese LC patients. Exercise management can increase skeletal muscle volume and strength and improve insulin resistance; however, nutritional status and LC complications should be assessed before an exercise management regimen is implemented in LC patients. The establishment of optimal exercise regimens for LC patients is currently required. In this review, we describe nutritional status and its clinical impact on the outcomes of LC patients and discuss general nutrition and exercise management in LC patients.

Toshikuni, Nobuyuki; Arisawa, Tomiyasu; Tsutsumi, Mikihiro

2014-01-01

206

Liver biopsy in primary biliary cirrhosis: clinicopathological data and stage.  

PubMed

The purpose of the present study was to characterize histopathological lesions in primary biliary cirrhosis (PBC) and to assess the relationship between histopathological lesions and biochemistry. Liver biopsies of 252 patients with PBC were investigated. A laboratory database was established. Histopathological characterization was performed. Relationships between detailed histopathological features and biochemistry were calculated statistically. Combining the data, a PBC group, consisting of an anti-mitochondrial antibody (AMA)-positive and -negative subgroup, and an overlap group were defined, with a female preponderance of >90% and higher activity of aspartate aminotransferase (AST) in the overlap group. Histopathological changes were characteristic in >80%. Periductal concentric fibrosis, lobular granuloma formation and steatosis were frequently remarkable. Correlations were found between alanine aminotransferase activity and modified hepatitis activity index in the overlap group and the AMA-positive group. A positive significant relationship was demonstrated between mean AST activity and portal fibrosis for the AMA-positive group. A highly significant positive link was seen between mean concentration of bilirubin and stage of fibrosis. Biochemistry reflects only in part the degree of severity of histopathological lesions in PBC. Histopathology indicates comorbidity in a high percentage of patients. PMID:19627538

Drebber, Uta; Mueller, Juliane J M; Klein, Ellen; Kasper, Hans U; Schulze, Falko; Schardt, Katharina; Quasdorff, Maria; Schulte, Sigrid; Odenthal, Margarete; Dienes, Hans P

2009-08-01

207

[The experimental study of the canine auxiliary partial liver transplantation for the liver failure].  

PubMed

A model of hepatic failure was established by injection of galactosamine in CCL4-induced liver cirrhosis. Auxiliary partial liver transplantation (APLT) was carried out to treat those dogs. The survival rate, biochemical change patterns, and histologic changes were investigated in both APLT group and control group. The survival rate in APLT and control group was 59.1% and 7.1% respectively, (P < 0.01). Fair supporting graft function was demonstrated by uptake and excretion of 99mTC-HIDA and 99mTC-DIASA at cholescintigraphy, ammonia aetoxification, synthesis of clotting factors and glucohomeostasis. The results indicate that auxiliary transplantation of a partial liver proviae metabolic support and improve survival in animals with hepatic failure. The character of the model, the advantages and the disadvantages of the APLT, were also discussed. PMID:7842965

Huang, J F; He, X S; Xuan, W H

1994-06-01

208

Soluble interleukin-2 receptor and soluble CD8 in liver cirrhosis and obstructive jaundice.  

PubMed Central

Activated lymphocytes secrete soluble interleukin-2 receptor (sIL-2R); CD8-positive lymphocytes secrete soluble CD8 (sCD8). Liver dysfunction in cirrhosis and obstructive jaundice is known to result in depressed cellular immunity. To evaluate whether this is due to real inactivation of the immune system, we measured sIL-2R and sCD8 in the serum of 46 patients with liver cirrhosis, 25 patients with obstructive jaundice, 32 patients with alcoholic liver disease without evidence of cirrhosis, 23 healthy persons and 43 patients with unrelated disease. sIL-2R in patients with cirrhosis (mean +/- s.e.m. 1499 +/- 140 U/ml) and obstructive jaundice (1517 +/- 204) was significantly increased compared with healthy subjects (363 +/- 29) and patients with unrelated diseases (685 +/- 92); sCD8 was significantly increased in patients with cirrhosis (737 +/- 63) but not in patients with obstructive jaundice (419 +/- 32) compared with healthy subjects (322 +/- 23) and patients with unrelated diseases (375 +/- 22). No difference was found between patients with cirrhosis due to alcohol abuse (n = 15) and chronic hepatitis B (n = 6). The Child-Pugh score had no significant influence on the sIL-2R or sCD8 value. In obstructive jaundice, sIL-2R correlated with alkaline phosphatase as marker of cholestasis (r = 0.43). These data show that in spite of the apparent depressed cellular immune defense both in liver cirrhosis and obstructive jaundice there is a general activation of the immune system but the CD8+ cell compartment is only activated in liver cirrhosis. The great changes of sIL-2R and sCD8 in liver dysfunction are important for the interpretation of studies using these serum proteins as markers for immune activation.

Wagner, F; Assemi, C; Lersch, C; Hart, R; Classen, M

1990-01-01

209

The relationship between aminopyrine breath test and severity of liver disease in cirrhosis  

Microsoft Academic Search

Twenty-two patients with cirrhosis were evaluated by the 2 hr.-(C14)-aminopyrine breath test, the conventional liver tests and two systems for grading the severity of liver disease. Twenty-three patients with noncirrhotic liver disease and 15 controls were also studied. Reduced 14CO2 values were found in 21 of the 22 cirrhotic patients and seven of those had noncirrhotic liver disease associated with

A. Morelli; F. Narducci; M. A. Pelli; F. Farroni; A. Vedovelli

1981-01-01

210

Synthesis of platelet-activating factor and its receptor expression in Kupffer cells in rat carbon tetrachloride-induced cirrhosis  

PubMed Central

AIM: To determine the platelet-activating factor (PAF) synthesis and its receptor expression in Kupffer cells in rat carbon tetrachloride-induced cirrhosis. METHODS: Kupffer cells, isolated from the livers of control and CCl4-induced cirrhotic rats, were placed in serum-free medium overnight. PAF saturation binding, ET-1 saturation and competition binding were assayed. ET-1 induced PAF synthesis, mRNA expression of PAF, preproendothelin-1, endothelin A (ETA) and endothelin B (ETB) receptors were also determined. RESULTS: A two-fold increase of PAF synthesis (1.42 ± 0.14 vs 0.66 ± 0.04 pg/?g DNA) and a 1.48-fold increase of membrane-bound PAF (1.02 ± 0.06 vs 0.69 ± 0.07 pg/?g DNA) were observed in activated Kupffer cells of cirrhotic rats. The application of ET-1 to Kupffer cells induced PAF synthesis in a concentration-dependent manner in both cirrhotic and normal rats via ETB receptor, but PAF synthesis in the activated Kupffer cells was more effective than that in the normal Kupffer cells. In activated Kupffer cells, PAF receptor expression and PAF binding capacity were markedly enhanced. Activated Kupffer cells raised the [125I]-ET-1 binding capacity, but changed neither the affinity of the receptors, nor the expression of ETA receptor. CONCLUSION: Kupffer cells in the course of CCl4-induced cirrhosis are the main source of increased PAF. ET-1 is involved endogenously in stimulating the PAF synthesis in activated Kupffer cells via ETB receptor by paracrine. ETA receptor did not appear in activated Kupffer cells, which may exacerbate the hepatic and extrahepatic complications of cirrhosis.

Lu, Yin-Ying; Wang, Chun-Ping; Zhou, Lin; Chen, Yan; Su, Shu-Hui; Feng, Yong-Yi; Yang, Yong-Ping

2008-01-01

211

Open-Heart Surgery in Patients with Liver Cirrhosis: Indications, Risk Factors, and Clinical Outcomes  

Microsoft Academic Search

Background: Because of recent advances in cardiopulmonary bypass (CPB) surgery, there are broadened indications to approach patients with a high operative risk. Meanwhile, there is an increasing number of patients with severe liver dysfunction subjected to open-heart surgery. This retrospective study was designed to evaluate the operative indications and clinical outcomes in patients with liver cirrhosis (LC) undergoing open-heart surgery.

Y. An; Y. B. Xiao; Q. J. Zhong

2007-01-01

212

Liver Iron, HFE Gene Mutations, and Hepatocellular Carcinoma Occurrence in Patients With Cirrhosis  

Microsoft Academic Search

Background & Aims: The influence of HFE gene mu- tations and liver iron overload on hepatocellular car- cinoma (HCC) occurrence in patients with cirrhosis is subjected to controversial results. The aim of this work was to clarify this influence in a large cohort of prospectively followed-up cirrhotic patients classified according to the cause of their liver disease. Methods: Three hundred

PIERRE NAHON; ANGELA SUTTON; PIERRE RUFAT; MARIANNE ZIOL; GABRIEL THABUT; PIERRE-OLIVIER SCHISCHMANOFF; DOMINIQUE VIDAUD; NATHALIE CHARNAUX; PHILIPPE COUVERT; NATHALIE GANNE-CARRIE; JEAN-CLAUDE TRINCHET; LILIANE GATTEGNO; MICHEL BEAUGRAND; UPRES EA; Service de Biochimie

2008-01-01

213

Diagnosing and monitoring cirrhosis: Liver biopsy, hepatic venous pressure gradient and elastography.  

PubMed

In this review we summarize the role of liver biopsy, transient elastography and hepatic venous pressure gradient (HVPG) in the diagnosis and monitoring of patients with liver cirrhosis. Transient elastography is useful for the non-invasive diagnosis of cirrhosis, but relevant information is lost if it is used as a dichotomous test. The development of clinically significant portal hypertension (defined as a hepatic venous pressure gradient ? 10 mmHg) is associated with the development of varices and decompensation and it is something that it is worth testing for. Transient elastography has some value for the prediction of clinically significant portal hypertension, but a large proportion of patients have non-diagnostic values. It has also some value for the diagnosis of varices, but non-invasive markers cannot substitute endoscopic screening in cirrhosis. Better dynamic, easily repeatable non-invasive tools are needed to monitor compensated cirrhosis. PMID:22560536

Abraldes, Juan G; Araujo, Isis K; Turón, Fanny; Berzigotti, Annalisa

2012-01-01

214

Impact of liver disease severity and etiology on the occurrence of diabetes mellitus in patients with liver cirrhosis.  

PubMed

The association between liver cirrhosis (LC) and diabetes mellitus (DM) is well known. However, the impact of the severity or etiology of LC on the occurrence of DM is relatively unknown. We aimed to determine the prevalence and clinical correlates of DM in a large cohort of patients with cirrhosis. A total of 1,068 patients with LC were included in this cross sectional study (CIRCE study). The diagnosis of cirrhosis irrespective of its etiology was based on histological confirmation by liver biopsy or, in the absence of biopsy, on typical clinical, morphological and biological data. Data related to the cirrhosis etiology: alcohol, viral markers of hepatitis B, C, iron load parameters and autoimmune markers were collected for each patient. Venous blood samples were taken in the morning after 12-h overnight fasting. There were 383 patients with cirrhosis associated with hepatocellular carcinoma (HCC). DM was found in 412 (39.7 %) patients. Patients with DM were older and more likely to be overweight and male, with a family history of DM and a diagnosis of HCC. DM was not associated with a history of stroke or myocardial infarction. Cirrhosis secondary to hepatitis infection was less strongly associated with DM than with NASH or alcoholic cirrhosis. The severity of LC was not associated with DM. In multivariate analysis, the factors associated with DM were age, BMI, a family history of DM, and statin use. There was a significant interaction between HCC and cirrhosis etiology for the risk of DM. Cirrhosis secondary to hepatitis was associated with a lesser presence of DM only in patients with HCC (interaction p = 0.0015). LC was strongly associated with DM, with around 40 % of diabetic patients. In the group of patients with LC without HCC, diabetes was not associated with the etiology of cirrhosis. PMID:24352343

Petit, Jean Michel; Hamza, Samia; Rollot, Fabien; Sigonney, Vanessa; Crevisy, Elodie; Duvillard, Laurence; Raab, Jean Jacques; Bronowicki, Jean Pierre; Bernard-Chabert, Brigitte; Di Martino, Vincent; Doffoel, Michel; Barraud, Helene; Richou, Carine; Jouve, Jean Louis; Hillon, Patrick

2014-06-01

215

Chronic pancreatitis prevalence in liver cirrhosis. Morphological and functional study.  

PubMed

Ductal pancreatic changes and functional exocrine assessment have been studied, in a group of 60 cirrhotic patients. In these patients the aetiology of cirrhosis was alcoholism in 35, hepatitis B virus-hepatitis C virus infection in 19, primary biliary cirrhosis in 2 and not determinable in 4. Eighteen patients (30%) showed an endoscopic retrograde pancreatography picture consistent with chronic pancreatitis (14 mild, 2 moderate and 2 severe). Mild pancreatographic changes were present in 7 alcoholic (20%) and in 7 non-alcoholic cirrhosis patients (28%). Moderate and severe abnormalities were present only in alcoholic cirrhosis (4 patients, 11.4%). No correlation was found between presence or pancreatopathy degree and Child-Pugh score or cirrhosis duration. Functional exocrine tests were abnormal only in severe endoscopic retrograde pancreatography picture. Mild type ductal lesions can mimic either age-dependent changes or chronic pancreatitis. The absence of impaired functional tests makes it impossible to discriminate between these two possibilities. These findings emphasize that in our cirrhotic group the prevalence of chronic pancreatitis (with a moderate or severe endoscopic retrograde pancreatography picture) is low (6.6%) and alcoholism is always present. Possibly, cirrhosis with secretion of high-volume low protein concentration juice confers a protective effect on the pancreas. PMID:8782001

Caradonna, P; Costamagna, G; Benedetti, G; Gentiloni, N; Gasbarrini, G B

1996-01-01

216

Effect of Meal Ingestion on Liver Stiffness in Patients with Cirrhosis and Portal Hypertension  

PubMed Central

Background and Aims Liver stiffness is increasingly used in the non-invasive evaluation of chronic liver diseases. Liver stiffness correlates with hepatic venous pressure gradient (HVPG) in patients with cirrhosis and holds prognostic value in this population. Hence, accuracy in its measurement is needed. Several factors independent of fibrosis influence liver stiffness, but there is insufficient information on whether meal ingestion modifies liver stiffness in cirrhosis. We investigated the changes in liver stiffness occurring after the ingestion of a liquid standard test meal in this population. Methods In 19 patients with cirrhosis and esophageal varices (9 alcoholic, 9 HCV-related, 1 NASH; Child score 6.9±1.8), liver stiffness (transient elastography), portal blood flow (PBF) and hepatic artery blood flow (HABF) (Doppler-Ultrasound) were measured before and 30 minutes after receiving a standard mixed liquid meal. In 10 the HVPG changes were also measured. Results Post-prandial hyperemia was accompanied by a marked increase in liver stiffness (+27±33%; p<0.0001). Changes in liver stiffness did not correlate with PBF changes, but directly correlated with HABF changes (r?=?0.658; p?=?0.002). After the meal, those patients showing a decrease in HABF (n?=?13) had a less marked increase of liver stiffness as compared to patients in whom HABF increased (n?=?6; +12±21% vs. +62±29%,p<0.0001). As expected, post-prandial hyperemia was associated with an increase in HVPG (n?=?10; +26±13%, p?=?0.003), but changes in liver stiffness did not correlate with HVPG changes. Conclusions Liver stiffness increases markedly after a liquid test meal in patients with cirrhosis, suggesting that its measurement should be performed in standardized fasting conditions. The hepatic artery buffer response appears an important factor modulating postprandial changes of liver stiffness. The post-prandial increase in HVPG cannot be predicted by changes in liver stiffness.

Berzigotti, Annalisa; De Gottardi, Andrea; Vukotic, Ranka; Siramolpiwat, Sith; Abraldes, Juan G.; Garcia-Pagan, Juan Carlos; Bosch, Jaime

2013-01-01

217

Invasive Mucormycosis in a Patient With Liver Cirrhosis: Case Report and Review of the Literature  

PubMed Central

Introduction Cutaneous Mucormycosis is a rare opportunistic infection caused by Zygomycetes class of fungi that is often fatal, requiring aggressive local control as well as systemic therapy. Few cases of mucormycosis were described in patients with liver cirrhosis, mostly rhino-orbital. To our knowledge, only two cases of upper extremity involvement was reported in cirrhosis while a few cases were reported in the post-transplant setting. We report herein the third case of upper extremity mucor infection in the setting of liver cirrhosis. Case Presentation We described a rare case of forearm infection originating in a traumatic intravenous access portal in a 25 year-old woman with liver cirrhosis secondary to autoimmune hepatitis. Discussion She developed acute on chronic liver failure during the last trimester of pregnancy, which was terminated. Painful, erythematous lesion was noted on her right forearm in the area of intravenous access, which later became necrotic. Extensive debridement was done and histopathological examination confirmed the diagnosis of mucormycosis. The patient started on Amphotericin B. Her condition continued to deteriorate and ended up with above elbow amputation followed by right shoulder disarticulation. She died two days later due to multi-organ failure. In conclusion, forearm mucromycosis in liver cirrhosis can be fatal.

Elsiesy, Hussien; Saad, Mohamed; Shorman, Mahmoud; Amr, Samir; Abaalkhail, Faisal; Hashim, Almoutaz; Al Hamoudi, Waleed; Al Sebayel, Mohamed; Selim, Khalid

2013-01-01

218

Profiles of perfluoroalkyl substances in the liver and serum of patients with liver cancer and cirrhosis in Australia.  

PubMed

The present cross-sectional study investigated 12 perfluoroalkyl substances (PFASs) in serum (n=79) and liver (n=66) samples from patients who had undergone liver transplantation for a range of conditions, such as hepatocellular carcinoma (HCC), cirrhosis due to chronic hepatitis C viral infection (HCV), both HCC and HCV, amyloidosis or acute liver failure. PFAS data from patients were compared to those in control serum (n=25) samples from liver donors with no known liver disease and to those in control liver (n=9) tissues collected during liver resection surgery. All samples showed detectable PFOS (serum: 0.621-126ng/mL; liver: 0.375-42.5ng/g wet wt) and PFOA (serum: 0.437-45.5ng/mL; liver: 0.101-2.25ng/g wet wt) concentrations. In general, in paired serum and liver samples, serum had higher PFOS, PFHxS, PFDA, PFNA, and PFOA concentrations than those in explanted livers from patients. These findings also suggest that pathological changes in diseased livers alter the distribution of PFASs between liver and serum. The results from control serum (2007-2008) suggested that PFOS, PFHxS, PFOA, and PFNA concentrations were lower than those previously reported from Australia for 2002-2003, and 2006-2007. The present study demonstrates, for the first time, the detection and comparison of a range of PFASs in the liver of patients with liver cancer and/or liver cirrhosis. PMID:23849467

Yeung, Leo W Y; Guruge, Keerthi S; Taniyasu, Sachi; Yamashita, Nobuyoshi; Angus, Peter W; Herath, Chandana B

2013-10-01

219

New Diagnostic Method for Liver Fibrosis and Cirrhosis  

Microsoft Academic Search

Liver fibrosis, i.e. excessive accumulation of extracellular matrix proteins, occurs in most types of chronic liver diseases. The prognosis and management of chronic liver diseases depend on the degree of liver fibrosis. Therefore, the assessment of liver fibrosis provides useful information not only for diagnosis but also for treatment planning. Although liver biopsy is still the gold standard for assessing

Kwang-Hyub Han; Ki Tae Yoon

2008-01-01

220

Dysregulation of ENaC in Animal Models of Nephrotic Syndrome and Liver Cirrhosis  

PubMed Central

Nephrotic syndrome and liver cirrhosis are common clinical manifestations, and are associated with avid sodium retention leading to the development of edema and ascites. However, the mechanism for the sodium retention is still incompletely understood and the molecular basis remains undefined. We examined the changes of sodium (co)transporters and epithelial sodium channels (ENaCs) in the kidneys of experimental nephrotic syndrome and liver cirrhosis. The results demonstrated that puromycin- or HgCl2-induced nephrotic syndrome was associated with 1) sodium retention, decreased urinary sodium excretion, development of ascites, and increased plasma aldosterone level; 2) increased apical targeting of ENaC subunits in connecting tubule and collecting duct segments; and 3) decreased protein abundance of type 2 11?-hydroxysteroid dehydrogenase (11?HSD2). Experimental liver cirrhosis was induced in rats by CCl4 treatment or common bile duct ligation. An increased apical targeting of alpha-, beta-, and gamma-ENaC subunits in connecting tubule, and cortical and medullary collecting duct segments in sodium retaining phase of liver cirhosis but not in escape phase of sodium retention. Immunolabeling intensity of 11?HSD2 in the connecting tubule and cortical collecting duct was significantly reduced in sodium retaining phase of liver cirrhosis, and this was confirmed by immunoblotting. These observations therefore strongly support the view that the renal sodium retention associated with nephrotic syndrome and liver cirrhosis is caused by increased sodium reabsorption in the aldosterone sensitive distal nephron including the connecting tubule and collecting duct, and increased apical targeting of ENaC subunits plays a role in the development of sodium retention in nephrotic syndrome and liver cirrhosis.

Kim, Soo Wan

2006-01-01

221

Successful treatment of invasive gastric mucormycosis in a patient with alcoholic liver cirrhosis: A case report  

PubMed Central

Gastrointestinal (GI) mucormycosis is a rare and life-threatening invasive fungal infection. GI mucormycosis occur in all parts of the alimentary tract, with the stomach being the most common site. Diabetes mellitus and other types of conditions associated with immunodeficiency, including hematologic malignancies, solid organ transplantation and glucocorticoid therapy, are risk factors for GI mucormycosis. There are few studies reporting cases of gastric mucormycosis in patients with liver cirrhosis, and even fewer reporting the successful treatment of invasive gastric mucormycosis in a patient with liver cirrhosis. This study presents a case of invasive gastric mucormycosis in a patient with liver cirrhosis, which was treated successfully by prompt diagnosis, metabolic support, surgical debridement of involved tissues and antifungal therapy.

LEE, SEUNG HYOUNG; SON, YOUNG GIL; SOHN, SOO SANG; RYU, SEUNG WAN

2014-01-01

222

[Decompensated liver cirrhosis caused by galactosemia in a 52-year-old man].  

PubMed

A 52-year-old oligophrenic man hospitalized for esophageal hemorrhage had histologically proven liver cirrhosis and died from massive rehemorrhage. As a neonate he had survived severe jaundice, had had delayed psychomotor development and remained severely retarded. At age 15 years, bilateral cataracts had been excised and from 18 to 25 years he had had occasional grand mal seizures. The triad oligophrenia, liver cirrhosis and cataracts, prompted suspicion of galactosemia. Deficiency of galactose-1-phosphate uridyltransferase was demonstrated in blood and post mortem tissue. At autopsy, liver cirrhosis and esophageal varices were confirmed and unilateral chronic pyelonephritis, bilateral nephrolithiasis and testicular atrophy were found. There was not brain pathology. The patient appeared to be the oldest nondiagnosed galactosemic and the first male patient in whom hypogonadism was documented. PMID:7455652

Vogt, M; Gitzelmann, R; Allemann, J

1980-11-22

223

[A case of liver cirrhosis due to non-alcoholic steatohepatitis complicated by myotonic dystrophy].  

PubMed

A female in her 50s with a four-year history of myotonic dystrophy was admitted to our hospital with hematochezia. She was diagnosed with synchronous colonic cancer of the transverse and sigmoid colon, for which she underwent partial transverse and sigmoid colectomy, respectively. Postoperative respiratory failure resulted in prolonged stay in the intensive care unit. Her liver and renal function gradually deteriorated, and she eventually died from these sequelae on postoperative day 26. Intraoperative liver biopsy revealed cirrhosis arising from non-alcoholic steatohepatitis (NASH). Although myotonic dystrophy is believed to be a multisystem disease, its association with cirrhosis has not been reported in Japan. We therefore report this rare case of liver cirrhosis arising from NASH in a patient with myotonic dystrophy. PMID:24005104

Ariake, Kyohei; Miura, Masahito; Takahashi, Michinaga; Ueno, Tatsuya; Sato, Shun; Akada, Masanori; Maeda, Shimpei; Fujisaka, Yasuyuki; Ohto, Takashi; Naito, Hiroo

2013-09-01

224

Activation of Platelet-Derived Growth Factor Receptor Alpha Contributes to Liver Fibrosis  

PubMed Central

Chronic liver injury leads to fibrosis, cirrhosis, and loss of liver function. Liver cirrhosis is the 12th leading cause of death in the United States, and it is the primary risk factor for developing liver cancer. Fibrosis and cirrhosis result from activation of hepatic stellate cells (HSCs), which are the primary collagen producing cell type in the liver. Here, we show that platelet-derived growth factor receptor ? (PDGFR?) is expressed by human HSCs, and PDGFR? expression is elevated in human liver disease. Using a green fluorescent protein (GFP) reporter mouse strain, we evaluated the role of PDGFR? in liver disease in mice and found that mouse HSCs express PDGFR? and expression is upregulated during carbon tetrachloride (CCl4) induced liver injury and fibrosis injection. This fibrotic response is reduced in Pdgfr? heterozygous mice, consistent with the hypothesis that liver fibrosis requires upregulation and activation of PDGFR?. These results indicate that Pdgfr? expression is important in the fibrotic response to liver injury in humans and mice, and suggest that blocking PDGFR?–specific signaling pathways in HSCs may provide therapeutic benefit for patients with chronic liver disease.

Hayes, Brian J.; Riehle, Kimberly J.; Shimizu-Albergine, Masami; Bauer, Renay L.; Hudkins, Kelly L.; Johansson, Fredrik; Yeh, Matthew M.; Mahoney, William M.; Yeung, Raymond S.; Campbell, Jean S.

2014-01-01

225

Structural Characteristics of Oversulfated Chondroitin\\/Dermatan Sulfates in the Fibrous Lesions of the Liver with Cirrhosis  

Microsoft Academic Search

The structural characteristics of oversulfated chondroitin\\/dermatan sulfates (C\\/DSs) in the fibrous lesions of the rat liver with cirrhosis were examined. Long–Evans Cinnamon rats were subjected to the present study as the model animals with cirrhosis. The serial polyester wax sections of liver with cirrhosis were processed into the fibrous lesions and the nonfibrous lesions. The oversulfated C\\/DSs in the tissue

Ichiro Koshiishi; Michinari Takenouchi; Toshio Imanari

1999-01-01

226

Liver cirrhosis and diabetes: Risk factors, pathophysiology, clinical implications and management  

PubMed Central

About 30% of patients with cirrhosis have diabetes mellitus (DM). Nowadays, it is a matter for debate whether type 2 DM in the absence of obesity and hypertriglyceridemia may be a risk factor for chronic liver disease. DM, which develops as a complication of cirrhosis, is known as “hepatogenous diabetes”. Insulin resistance in muscular and adipose tissues and hyperinsulinemia seem to be the pathophysiologic bases of diabetes in liver disease. An impaired response of the islet ?-cells of the pancreas and hepatic insulin resistance are also contributory factors. Non-alcoholic fatty liver disease, alcoholic cirrhosis, chronic hepatitis C (CHC) and hemochromatosis are more frequently associated with DM. Insulin resistance increases the failure of the response to treatment in patients with CHC and enhances progression of fibrosis. DM in cirrhotic patients may be subclinical. Hepatogenous diabetes is clinically different from that of type 2 DM, since it is less frequently associated with microangiopathy and patients more frequently suffer complications of cirrhosis. DM increases the mortality of cirrhotic patients. Treatment of the diabetes is complex due to liver damage and hepatotoxicity of oral hypoglycemic drugs. This manuscript will review evidence that exists in relation to: type 2 DM alone or as part of the metabolic syndrome in the development of liver disease; factors involved in the genesis of hepatogenous diabetes; the impact of DM on the clinical outcome of liver disease; the management of DM in cirrhotic patients and the role of DM as a risk factor for the occurrence and exacerbation of hepatocellular carcinoma.

Garcia-Compean, Diego; Jaquez-Quintana, Joel Omar; Gonzalez-Gonzalez, Jose Alberto; Maldonado-Garza, Hector

2009-01-01

227

Hepatoprotective effect of ethanolic extract of Curcuma longa on thioacetamide induced liver cirrhosis in rats  

PubMed Central

Background Hepatology research has focused on developing traditional therapies as pharmacological medicines to treat liver cirrhosis. Thus, this study evaluated mechanisms of the hepatoprotective activity of Curcuma longa rhizome ethanolic extract (CLRE) on thioacetamide-induced liver cirrhosis in rats. Methods The hepatoprotective effect of CLRE was measured in a rat model of thioacetamide-induced liver cirrhosis over 8 weeks. Hepatic cytochrome P450 2E1 and serum levels of TGF-?1 and TNF-? were evaluated. Oxidative stress was measured by malondialdehyde, urinary 8-hydroxyguanosine and nitrotyrosine levels. The protective activity of CLRE free-radical scavenging mechanisms were evaluated through antioxidant enzymes. Protein expression of pro-apoptotic Bax and anti-apoptotic Bcl-2 proteins in animal blood sera was studied and confirmed by immunohistochemistry of Bax, Bcl2 proteins and proliferating cell nuclear antigen. Results Histopathology, immunohistochemistry and liver biochemistry were significantly lower in the Curcuma longa-treated groups compared with controls. CLRE induced apoptosis, inhibited hepatocytes proliferation but had no effect on hepatic CYP2E1 levels. Conclusion The progression of liver cirrhosis could be inhibited by the antioxidant and anti-inflammatory activities of CLRE and the normal status of the liver could be preserved.

2013-01-01

228

Clinical findings in 19 cases of invasive pulmonary aspergillosis with liver cirrhosis  

PubMed Central

Background Aspergillus infection was mostly reported with high mortality rates and a bad prognosis in immunocompromised patients, but data were lacking on the clinical characteristics of aspergillus infection in liver cirrhosis. The aim of this study was to retrospectively assess the morbidity and mortality rate, clinical manifestation, risk factors, and medication of invasive pulmonary aspergillosis (IPA) in liver cirrhosis in The First Affiliated Hospital, College of Medicine, Zhejiang University. Methods Patients with liver cirrhosis who had been diagnosed with proven or probable IPA by clinical and laboratory parameters from 1st December 2008 to 1st May2012 were retrospectively evaluated for predisposing factors for IPA and clinical outcome. The follow up ended on 30th July2012. IPA was defined according to European Organization for Research and Treatment of Cancer/Mysoses Study group criteria. Results In total, 6,600 patients with liver cirrhosis were enrolled, and 19 out of these developed IPA. Seventeen out of 19 patients died. Imaging findings such as the halo sign and lower respiratory tract infection symptoms contributed to the early diagnosis of IPA. Possible risk factors for IPA included a high Child-Turcotte-Pugh (CTP) score, broad antibiotic usage and steroid exposure. The use of antifungal compounds may prolong a patient’s life. Conclusions The mortality of liver cirrhosis with IPA is high. Liver cirrhosis should be considered a risk factor of IPA. Once patients with high CTP scores and steroid and broad spectrum antibiotics exposure present cough and fever, IPA should be taken into consideration and antifungal agents should be used as soon as possible.

2014-01-01

229

Status and prospects of liver cirrhosis treatment by using bone marrow-derived cells and mesenchymal cells.  

PubMed

In 2003, we started autologous bone marrow cell infusion (ABMi) therapy for treating liver cirrhosis. ABMi therapy uses 400 mL of autologous bone marrow obtained under general anesthesia and infused mononuclear cells from the peripheral vein. The clinical study expanded and we treated liver cirrhosis induced by HCV and HBV infection and alcohol consumption. We found that the ABMi therapy was effective for cirrhosis patients and now we are treating patients with combined HIV and HCV infection and with metabolic syndrome-induced liver cirrhosis. Currently, to substantiate our findings that liver cirrhosis can be successfully treated by the ABMi therapy, we are conducting randomized multicenter clinical studies designated "Advanced medical technology B" for HCV-related liver cirrhosis in Japan. On the basis of our clinical study, we developed a proof-of-concept showing that infusion of bone marrow cells (BMCs) improved liver fibrosis and sequentially activated proliferation of hepatic progenitor cells and hepatocytes, further promoting restoration of liver functions. To treat patients with severe forms of liver cirrhosis, we continued translational research to develop less invasive therapies by using mesenchymal stem cells derived from bone marrow. We obtained a small quantity of BMCs under local anesthesia and expanded them into mesenchymal stem cells that will then be used for treating cirrhosis. In this review, we present our strategy to apply the results of our laboratory research to clinical studies. PMID:24450831

Terai, Shuji; Takami, Taro; Yamamoto, Naoki; Fujisawa, Koichi; Ishikawa, Tsuyoshi; Urata, Yohei; Tanimoto, Haruko; Iwamoto, Takuya; Mizunaga, Yuko; Matsuda, Takashi; Oono, Takashi; Marumoto, Miho; Burganova, Guzel; Fernando Quintanilha, Luiz; Hidaka, Isao; Marumoto, Yoshio; Saeki, Issei; Uchida, Koichi; Yamasaki, Takahiro; Tani, Kenji; Taura, Yasuho; Fujii, Yasuhiko; Nishina, Hiroshi; Okita, Kiwamu; Sakaida, Isao

2014-06-01

230

Pharmacokinetics of ornidazole in patients with severe liver cirrhosis.  

PubMed

Pharmacokinetics of ornidazole, a nitroimidazole derivative, was studied after intravenous injection in 10 patients with severe alcoholic cirrhosis and 10 healthy volunteers. Plasma concentrations of ornidazole and its two major hydroxylated metabolites, M1 (alpha-(chloromethyl)-2-hydroxymethyl-5-nitroimidazole-1-ethanol) and M4 (3-(2-methyl-5-nitroimidazole 1-yl) 1,2 propane diol), were measured by HPLC. The t1/2 of ornidazole was 14.1 +/- 0.5 hours for normal subjects and 21.9 +/- 2.9 hours for patients with cirrhosis. Mean plasma clearance was 50.6 +/- 2.1 ml/min in control subjects and 34.9 +/- 4.9 ml/min in patients, whereas apparent V SS was not modified in hepatic insufficiency. In healthy volunteers, M1 and M4 levels are well below levels of the parent drug; in cirrhosis both metabolites accumulate in plasma as a result of decreased elimination. Hepatic cirrhosis prolongs ornidazole elimination, and to avoid cumulation the interval between repeated doses could be doubled. PMID:3742940

Taburet, A M; Delion, F; Attali, P; Thebault, J J; Singlas, E

1986-09-01

231

Bile salt secretion in cirrhosis of the liver  

Microsoft Academic Search

Secretion of bile salts into the duodenum was studied in eight normal subjects, in 10 patients with cirrhosis, and in two cholecystectomized subjects. Duodenal juice was aspirated continuously through a double-lumen tube during an unstimulated period, after an intravenous injection of pancreozymin\\/cholecystokinin, and during a continuous intravenous infusion of secretin given at a rate of 3 units per kilogram body

Leslie A. Turnberg; Gordon Grahame

1970-01-01

232

Prevalence of Helicobacter pylori and occurrence of gastroduodenal lesions in patients with liver cirrhosis  

PubMed Central

Background/Aims: The role of H. pylori in the pathogenesis of ulcer disease in cirrhotic patients is poorly defined. Therefore, we sought to investigate the prevalence of H. pylori infection and the occurrence of gastroduode-nal lesions in patients with liver cirrhosis. Methods and Patients: Seroprevalence of H. pylori was tested in 110 patients with liver cirrhosis and 44 asymptomatic patients with chronic hepatitis without cirrhosis using an anti-H. pylori-IgG-ELISA. Cirrhotic patients underwent upper intestinal endoscopy for macroscopic and histological evaluation of gastric mucosa, and for the detection of mucosal colonisation of H. pylori using Giemsa staining and urease test. Results: There was no significant difference between the H. pylori seroprevalence in patients with liver cirrhosis (76/110; 69%) and patients with chronic viral hepatitis (27/44, 63%, p=0.465). Gastric mucosal colonization with H. pylori in cirrhotic patients was significantly lower than the serologically determined H. pylori prevalence (45% vs. 69%, p=0.001). Etiology of liver cirrhosis did not influence the prevalence of H. pylori infection. 8 of 110 cirrhotic patients had gastric ulcers and 10 had duodenal ulcers. 61% of cirrhotic patients with peptic ulcers were asymptomatic. H. pylori was histologically identified in 61% of gastroduodenal ulcers, and 47% of gastroduodenal erosions. Conclusions: Patients with liver cirrhosis have a high prevalence of gastroduodenal ulcers. The lack of a firm association between H. pylori prevalence and ulcer frequency in cirrhotic patients argues against a pivotal role of H. pylori in the etiology of ulcers in cirrhotic patients.

Kirchner, Gabriele I; Beil, Winfried; Bleck, Joerg S; Manns, Micheal P; Wagner, Siegfried

2011-01-01

233

[Peritoneal dialysis in patients with liver cirrhosis and/or ascites].  

PubMed

In older textbooks the use of peritoneal dialysis (PD) in patients with liver cirrhosis and/or ascites was contraindicated. Only a small number of papers have focused on this problem and they mainly consist of case reports and retrospective studies of small numbers of patients. In addition, most nephrologists' experience of performing PD in patients with liver diseases is rather limited. Nevertheless, for these patients PD offers a wide range of advantages, such as a simplified ascites management, since repeated abdominal punctures become unnecessary. Furthermore, because of continuous peritoneal ultrafiltration, hemodynamic tolerance during PD is significantly better than in hemodialysis and results in a markedly lower frequency of hypotensive episodes. The risk of nosocomial infection with hepatitis B or C viruses can also be reduced by treating these patients with home PD. Although some authors suggest that PD patients with liver cirrhosis have an especially increased risk of Gram-negative peritonitis, currently available data show controversial results. There is also little information in the literature on the impact of increased peritoneal protein loss on malnutrition and outcome of these patients. Nevertheless, recent studies have shown that protein loss into the peritoneal cavity in PD patients with liver cirrhosis is high only initially, stabilizing at a lower level in the further course of treatment. In conclusion, in patients with end-stage renal disease suffering from liver cirrhosis and/or ascites, PD can be considered as a good or adequate treatment option. PMID:16437334

Paul, Gernot

2005-01-01

234

Efficacy of Boesenbergia rotunda Treatment against Thioacetamide-Induced Liver Cirrhosis in a Rat Model  

PubMed Central

Background. Experimental research in hepatology has focused on developing traditional medicines into potential pharmacological solutions aimed at protecting liver from cirrhosis. Along the same line, this study investigated the effects of ethanol-based extract from a traditional medicine plant Boesenbergia rotunda (BR) on liver cirrhosis. Methodology/Results. The BR extract was tested for toxicity on 3 groups of rats subjected to vehicle (10% Tween 20, 5?mL/kg) and 2g/kg and 5g/kg doses of the extract, respectively. Next, experiments were conducted on a rat model of cirrhosis induced by thioacetamide injection. The rats were divided into five groups and, respectively, administered orally with 10% Tween-20 (5?mL/kg) (normal control group), 10% Tween-20 (5?mL/kg) (cirrhosis control group), 50 mg/kg of silymarin (reference control group), and 250?mg/kg and 500?mg/kg of BR extract (experimental groups) daily for 8 weeks. The rats in normal group were intraperitoneally injected with sterile distilled water (1?mL/kg) 3 times/week, and those in the remaining groups were injected intraperitoneally with thioacetamide (200 mg/kg) thrice weekly. At the end of the 8 weeks, the animals were sacrificed and samples were collected for comprehensive histopathological, coagulation profile and biochemical evaluations. Also, the antioxidant activity of the BR extract was determined and compared with that of silymarin. Data from the acute toxicity tests showed that the extract was safe to use. Histological analysis of the livers of the rats in cirrhosis control group revealed uniform coarse granules on their surfaces, hepatocytic necrosis, and lymphocytes infiltration. But, the surfaces morphologically looked much smoother and the cell damage was much lesser in those livers from the normal control, silymarin and BR-treated groups. In the high-dose BR treatment group, the livers of the rats exhibited nearly normal looking lobular architecture, minimal inflammation, and minimal hepatocyte damage, the levels of the serum biomarkers and liver enzymes read nearly normal, and these results were all comparable to those observed or quantified from the normal and silymarin-treated groups. The BR extract had the antioxidant activity about half of what was recorded for silymarin. Conclusion. The progression of the liver cirrhosis can be intervened using the ethanol-based BR extract, and the liver's status quo of property, structure, and function can be preserved. This capability of the extract warrants further studies exploring the significance of its pharmacologic potential in successfully treating the liver cirrhosis in humans.

Salama, Suzy M.; Bilgen, Mehmet; Al Rashdi, Ahmed S.; Abdulla, Mahmood A.

2012-01-01

235

Hepatoprotective effect of electrolyzed reduced water against carbon tetrachloride-induced liver damage in mice.  

PubMed

The study investigated the protective effect of electrolyzed reduced water (ERW) against carbon tetrachloride (CCl(4))-induced liver damage. Male ICR mice were randomly divided into control, CCl(4), CCl(4)+silymarin, and CCl(4)+ERW groups. CCl(4)-induced liver lesions include leukocytes infiltration, hepatocyte necrosis, ballooning degeneration, mitosis, calcification, fibrosis and an increase of serum alanine aminotransferase (ALT), and aminotransferase (AST) activity. In addition, CCl(4) also significantly decreased the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). By contrast, ERW or silymarin supplement significantly ameliorated the CCl(4)-induced liver lesions, lowered the serum levels of hepatic enzyme markers (ALT and AST) and increased the activities of SOD, catalase, and GSH-Px in liver. Therefore, the results of this study show that ERW can be proposed to protect the liver against CCl(4)-induced oxidative damage in mice, and the hepatoprotective effect might be correlated with its antioxidant and free radical scavenging effect. PMID:19477216

Tsai, Chia-Fang; Hsu, Yu-Wen; Chen, Wen-Kang; Chang, Wen-Huei; Yen, Cheng-Chieh; Ho, Yung-Chyuan; Lu, Fung-Jou

2009-08-01

236

Does an association exist between chronic pancreatitis and liver cirrhosis in alcoholic subjects?  

Microsoft Academic Search

AIM: To study the possible association between chronic pancreatitis (CP) and liver cirrhosis (LC) of alcoholic etiology, after excluding any other causes. METHODS: One hundred and forty consecutive alcoholic patients were subdivided into three groups: CP (n = 53), LC (n = 57), and asymptomatic alcoholic (n = 30). Clinical, biochemical and morphological characteristics, Child-Pugh index, indocyanine green test, and

Luis Aparisi; Luis Sabater; Juan Del-Olmo; Juan Sastre; Miguel-Angel Serra; Ricardo Campello; Daniel Bautista; Abdalla Wassel

2008-01-01

237

Monitoring oxidative damage in patients with liver cirrhosis and different daily alcohol intake  

Microsoft Academic Search

This study looked at the possible association between alcohol abuse and free radical mediated oxidative injury by examining the presence of oxidative damage, as monitored by erythrocyte malonildialdehyde and plasma lipid hydroperoxides, in patients with liver cirrhosis and different lifetime daily alcohol intake. All patients with an alcohol intake above 100 g\\/day (ALC) showed concentrations of malonildialdehyde and lipid hydroperoxide

P Clot; M Tabone; S Aricò; E Albano

1994-01-01

238

Antimitochondrial antibodies in acute liver failure: Implications for primary biliary cirrhosis  

Microsoft Academic Search

In our previous work, including analysis of more than 10,000 sera from control patients and patients with a variety of liver diseases, we have demonstrated that with the use of recombi- nant autoantigens, antimitochondrial autoantibodies (AMAs) are only found in primary biliary cirrhosis (PBC) and that a positive AMA is virtually pathognomonic of either PBC or future development of PBC.

Patrick S. C. Leung; Lorenzo Rossaro; Paul A. Davis; Atsushi Tanaka; Kentaro Kikuchi; Hiroshi Miyakawa; Gary L. Norman; William Lee; M. Eric Gershwin

2007-01-01

239

Nifedipine: Kinetics and hemodynamic effects in patients with liver cirrhosis after intravenous and oral administration  

Microsoft Academic Search

The pharmacokinetics and hemodynamic effects of nifedipine were studied in patients with liver cirrhosis and in age-matched healthy control subjects. In a randomized order each subject received nifedipine by intravenous infusion (4.5 mg in 45 minutes) and as a tablet (20 mg). After intravenous nifedipine patients had a longer elimination t½ (420 ± 254 vs. 111 ± 22 minutes; P

C H Kleinbloesem; J van Harten; J P H Wilson; M Danhof; P van Brummelen; D D Breimer

1986-01-01

240

Increased intestinal macromolecular permeability and urine nitrite excretion associated with liver cirrhosis with ascites  

Microsoft Academic Search

AIM: To determine intestinal permeability, the serum tumor necrosis factor (TNF)-? level and urine nitric oxide (NO) metabolites are altered in liver cirrhosis (LC) with or without ascites. METHODS: Fifty-three patients with LC and 26 healthy control subjects were enrolled in the study. The intestinal permeability value is expressed as the percentage of polyethylene glycol (PEG) 400 and 3350 retrieval

Soong Lee; Seung-Cheol Son; Moon-Jong Han; Woo-Jin Kim; Soo-Hyun Kim; Hye-Ran Kim; Woo-Kyu Jeon; Ki-Hong Park; Myung-Geun Shin

2008-01-01

241

Elevated soluble CD30 characterizes patients with hepatitis C virus-induced liver allograft cirrhosis.  

PubMed

Hepatitis C virus (HCV) recurrence after orthotopic liver transplantation (OLT) significantly accelerates progression to allograft cirrhosis. Current biochemical parameters to monitor progression of chronic HCV after OLT have yielded low specificity and sensitivity. Here we investigated the HCV-specific immunity and serum levels of soluble CD30 (sCD30), a novel marker of Th2 immunity, in patients with and without allograft cirrhosis. Patients with hepatic inflammation but no cirrhosis (HIN, n=20) revealed elevated serum interferon (IFN)-gamma and high frequency of IFN-gamma producing CD4 T(h1) cells compared to those with hepatic cirrhosis (HFC, n=20) that had high interleukin (IL)-5 and IL-5 producing CD4 T(h2) cells. Patients with HFC, but not HIN, were found to have significantly higher levels of sCD30. Therefore, we conclude that lack of optimal Th1-type CD4 T cells is associated with HCV-induced allograft cirrhosis. Further, sCD30 may represent a novel marker for surveillance of hepatic cirrhosis in transplant recipients with chronic HCV infection. PMID:18165785

Bharat, Ankit; Narayanan, Kishore; Golocheikine, Anjali; Steward, Nancy; Crippin, Jeffrey; Lisker-Melman, Mauricio; Shenoy, Surendra; Lowell, Jeffrey; Chapman, William C; Mohanakumar, Thalachallour

2007-12-27

242

Enhancement by Estradiol 3Benzoate in Thioacetamide-Induced Liver Cirrhosis of Rats  

Microsoft Academic Search

As part of an investigation on the role of estrogen in liver disease, we tested the effects of estradiol-3-benzoate (EB) in the thioacetamide (TAA)-induced rat liver cirrhosis model. Male F344 rats (n ¼ 100) were divided into six groups. Animals of groups 1-4 received TAA (0.03% in drinking water) for 12 weeks, and groups 5 and 6 served as controls

Jin Seok Kang; Hideki Wanibuchi; Keiichirou Morimura; Rawiwan Puatanachokchai; Elsayed I. Salim; Atsushi Hagihara; Shuichi Seki; Shoji Fukushima

2005-01-01

243

Ultrasound imaging in an experimental model of fatty liver disease and cirrhosis in rats  

PubMed Central

Background Domestic dogs and cats are very well known to develop chronic hepatic diseases, including hepatic lipidosis and cirrhosis. Ultrasonographic examination is extensively used to detect them. However, there are still few reports on the use of the ultrasound B-mode scan in correlation with histological findings to evaluate diffuse hepatic changes in rodents, which represent the most important animal group used in experimental models of liver diseases. The purpose of this study was to determine the reliability of ultrasound findings in the assessment of fatty liver disease and cirrhosis when compared to histological results in Wistar rats by following up a murine model of chronic hepatic disease. Results Forty Wistar rats (30 treated, 10 controls) were included. Liver injury was induced by dual exposure to CCl4 and ethanol for 4, 8 and 15 weeks. Liver echogenicity, its correlation to the right renal cortex echogenicity, measurement of portal vein diameter (PVD) and the presence of ascites were evaluated and compared to histological findings of hepatic steatosis and cirrhosis. Liver echogenicity correlated to hepatic steatosis when it was greater or equal to the right renal cortex echogenicity, with a sensitivity of 90%, specificity of 100%, positive and negative predictive values of 100% and 76.9% respectively, and accuracy of 92.5%. Findings of heterogeneous liver echogenicity and irregular surface correlated to liver cirrhosis with a sensitivity of 70.6%, specificity of 100%, positive and negative predictive values of 100% and 82.1% respectively, and accuracy of 87.5%. PVD was significantly increased in both steatotic and cirrhotic rats; however, the later had greater diameters. PVD cut-off point separating steatosis from cirrhosis was 2.1 mm (sensitivity of 100% and specificity of 90.5%). One third of cirrhotic rats presented with ascites. Conclusion The use of ultrasound imaging in the follow-up of murine diffuse liver disease models is feasible and efficient, especially when the studied parameters are used in combination. The potential implication of this study is to provide a non-invasive method that allows follow-up studies of fatty liver disease and cirrhosis of individual rats for pre-clinical drug or cell based therapies.

2010-01-01

244

Bone marrow cell transplant does not prevent or reverse murine liver cirrhosis.  

PubMed

We tested the effect of bone marrow cell (BMC) transplantation in either preventing or reversing cirrhosis on an experimental model of chronic liver disease. Female Wistar rats were fed a liquid alcohol diet and received intraperitoneal injections of carbon tetrachloride (CCl4) over 15 weeks. Ten animals (cell-treated group) received five injections of BMCs during the cirrhosis induction protocol (on the 4th, 6th, 8th, 10th, and 12th weeks) and four animals received the cells after liver injury was established through tail vein. Nine animals (nontreated group) were submitted to the previously described protocols; however, they received vehicle injections. Analyses were performed to verify whether the infusion of cells was effective in preventing the development of cirrhosis in our model of induction, and if the cells could reverse cirrhosis once it was established. Hepatic architecture and fibrotic septa were analyzed in liver slices stained with hematoxilin & eosin and Sirius red, respectively. Fibrosis quantification was measured by Sirius red histomorphometry. Indirect immunofluorescence was performed to detect the amount of tissue transglutaminase 2. Blood analyses were performed to assess liver injury and function by the assessment of alanine aminotransferase and albumin. Ultrasound was performed to analyze the portal vein caliber and presence of ascitis. Cirrhosis features (regenerative nodules and fibrous septa) were observed in histopathology after 15 weeks of continuous hepatic injury in nontreated and cell-treated groups. Collagen content, immunofluorescence analysis, and biochemical and ultrasound parameters were similar in nontreated and cell-treated groups; however, both groups showed significant differences compared to a normal control group. Cell infusions with bone marrow-derived cells seem to be ineffective in improving morphofunctional parameters of the liver when applied to chronic cases either during or after establishment of the hepatic lesion. PMID:19069636

Quintanilha, L F; Mannheimer, E G; Carvalho, A B; Paredes, B D; Dias, J V; Almeida, A S; Gutfilen, B; Barbosa da Fonseca, L M; Resende, C M C; Rezende, G F M; Campos de Carvalho, A C; Goldenberg, R C S

2008-01-01

245

Nitric oxide synthase and heme oxygenase expressions in human liver cirrhosis  

PubMed Central

AIM: Portal hypertension is a common complication of liver cirrhosis. Intrahepatic pressure can be elevated in several ways. Abnormal architecture affecting the vasculature, an increase in vasoconstrictors and increased circulation from the splanchnic viscera into the portal system may all contribute. It follows that endogenous vasodilators may be able to alleviate the hypertension. We therefore aimed to investigate the levels of endogenous vasodilators, nitric oxide (NO) and carbon monoxide (CO) through the expression of nitric oxide synthase (NOS) and heme oxygenase (HO). METHOD: Cirrhotic (n?=?20) and non-cirrhotic (n?=?20) livers were obtained from patients who had undergone surgery. The mRNA and protein expressions of the various isoforms of NOS and HO were examined using competitive PCR, Western Blot and immunohistochemistry. RESULTS: There was no significant change in either inducible NOS (iNOS) or neuronal NOS (nNOS) expressions while endothelial NOS (eNOS) was up-regulated in cirrhotic livers. Concomitantly, caveolin-1, an established down-regulator of eNOS, was up-regulated. Inducible HO-1 and constitutive HO-2 were found to show increased expression in cirrhotic livers albeit in different localizations. CONCLUSION: The differences of NOS expression might be due to their differing roles in maintaining liver homeostasis and/or involvement in the pathology of cirrhosis. Sheer stress within the hypertensive liver may induce increased expression of eNOS. In turn, caveolin-1 is also increased. Whether this serves as a defense mechanism against further cirrhosis or is a consequence of cirrhosis, is yet unknown. The elevated expression of HO-1 and HO-2 suggest that CO may compensate in its role as a vasodilator albeit weakly. It is possible that CO and NO have parallel or coordinated functions within the liver and may work antagonistically in the pathophysiology of portal hypertension.

Goh, Beatrice J; Tan, Bee Tee; Hon, Wei Min; Lee, Kang Hoe; Khoo, Hoon Eng

2006-01-01

246

Dual therapeutic effects of interferon-alpha gene therapy in a rat hepatocellular carcinoma model with liver cirrhosis.  

PubMed

Human hepatocellular carcinoma (HCC) often arises from a background of liver cirrhosis. Therefore, in order to develop therapeutic strategies for HCC, an animal model bearing multifocal liver tumors accompanied by liver cirrhosis is a preferred experimental setting. In this study, we developed a rapid and reproducible method for generating such a model in rats by weekly administration of diethylnitrosamine (DEN) at doses based on body weight (BW). By adjusting the duration of administration of DEN, the animals could be induced to develop HCC alone, or HCC and liver cirrhosis simultaneously. The latter model was used for evaluating the therapeutic effects of adenoviral delivery of interferon-alpha (IFN-alpha). Our results demonstrated that targeting of IFN-alpha expression to the liver significantly reduced liver tumor volume and ameliorated liver cirrhosis. Mechanistic studies revealed that IFN-alpha gene therapy induced immunomodulatory, antiproliferative, and proapoptotic activities that were effective in the control of tumor growth, and reduced the expressions of transforming growth factor-beta (TGF-beta) and tissue inhibitor of metalloproteinase-1 (TIMP-1), leading to amelioration of liver cirrhosis. These results suggest that IFN-alpha gene therapy is a promising strategy to treat HCC patients who have concomitant liver cirrhosis. PMID:18665156

Huang, Kai-Wen; Huang, Yung-Chi; Tai, Kuo-Feng; Chen, Bo-Hua; Lee, Po-Huang; Hwang, Lih-Hwa

2008-10-01

247

Interleukin-22 predicts severity and death in advanced liver cirrhosis: a prospective cohort study  

PubMed Central

Background Interleukin-22 (IL-22), recently identified as a crucial parameter of pathology in experimental liver damage, may determine survival in clinical end-stage liver disease. Systematic analysis of serum IL-22 in relation to morbidity and mortality of patients with advanced liver cirrhosis has not been performed so far. Methods This is a prospective cohort study including 120 liver cirrhosis patients and 40 healthy donors to analyze systemic levels of IL-22 in relation to survival and hepatic complications. Results A total of 71% of patients displayed liver cirrhosis-related complications at study inclusion. A total of 23% of the patients died during a mean follow-up of 196 ± 165 days. Systemic IL-22 was detectable in 74% of patients but only in 10% of healthy donors (P < 0.001). Elevated levels of IL-22 were associated with ascites (P = 0.006), hepatorenal syndrome (P < 0.0001), and spontaneous bacterial peritonitis (P = 0.001). Patients with elevated IL-22 (>18 pg/ml, n = 57) showed significantly reduced survival compared to patients with regular (?18 pg/ml) levels of IL-22 (321 days versus 526 days, P = 0.003). Other factors associated with reduced overall survival were high CRP (?2.9 mg/dl, P = 0.005, hazard ratio (HR) 0.314, confidence interval (CI) (0.141 to 0.702)), elevated serum creatinine (P = 0.05, HR 0.453, CI (0.203 to 1.012)), presence of liver-related complications (P = 0.028, HR 0.258, CI (0.077 to 0.862)), model of end stage liver disease (MELD) score ?20 (P = 0.017, HR 0.364, CI (0.159 to 0.835)) and age (P = 0.011, HR 0.955, CI (0.922 to 0.989)). Adjusted multivariate Cox proportional-hazards analysis identified elevated systemic IL-22 levels as independent predictors of reduced survival (P = 0.007, HR 0.218, CI (0.072 to 0.662)). Conclusions In patients with liver cirrhosis, elevated systemic IL-22 levels are predictive for reduced survival independently from age, liver-related complications, CRP, creatinine and the MELD score. Thus, processes that lead to a rise in systemic interleukin-22 may be relevant for prognosis of advanced liver cirrhosis.

2012-01-01

248

Ultrasonographic scoring system score versus liver stiffness measurement in prediction of cirrhosis  

PubMed Central

Background/Aims We compared the cirrhosis-prediction accuracy of an ultrasonographic scoring system (USSS) combining six representative sonographic indices with that of liver stiffness measurement (LSM) by transient elastography, and prospectively investigated the correlation between the USSS score and LSM in predicting cirrhosis. Methods Two hundred and thirty patients with chronic liver diseases (187 men, 43 women; age, 50.4±9.5 y, mean±SD) were enrolled in this prospective study. The USSS produces a combined score for nodularity of the liver surface and edge, parenchyma echogenicity, presence of right-lobe atrophy, spleen size, splenic vein diameter, and abnormality of the hepatic vein waveform. The correlations of the USSS score and LSM with that of a pathological liver biopsy (METAVIR scoring system: F0-F4) were evaluated. Results The mean USSS score and LSM were 7.2 and 38.0 kPa, respectively, in patients with histologically overt cirrhosis (F4, P=0.017) and 4.3 and 22.1 kPa in patients with fibrotic change without overt cirrhosis (F0-F3) (P=0.025). The areas under the receiver operating characteristic (ROC) curves of the USSS score and LSM for F4 patients were 0.849 and 0.729, respectively. On the basis of ROC curves, criteria of USSS ?6: LSM ?17.4 had a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 89.2%:77.6%, 69.4%:61.4%, 86.5%:83.7%, 74.6%:51.9% and 0.83:0.73, respectively, in predicting F4. Conclusions The results indicate that this USSS has comparable efficacy to LSM in the diagnosis of cirrhosis.

Moon, Kyoung Min; Kim, Gaeun; Choi, Eunhee; Kim, Moon Young; Kim, Hyoun A; Cho, Mee Yon; Shin, Seung Yong; Kim, Jung Min; Park, Hong Jun; Kwon, Sang Ok; Eom, Young Woo

2013-01-01

249

Protective effects of gomisin A isolated from Schisandra chinensis against CCl(4)-induced hepatic and renal injury.  

PubMed

The aim of the present study was to investigate the protective effects of gomisin A, a lignan compound isolated from Schisandra chinensis, against liver and kidney damage induced by CCl(4) exposure. We assessed alterations in organ weights, levels of serum biochemical indicators, and activation of the caspase-3 and MAPK signaling pathways and carried out histological analysis of liver and kidney tissue in rats pretreated with gomisin A for four days. In the gomisin A/CCl(4)-treated group, only the liver experienced a significant increase in weight, whereas the other organs did not undergo any changes. Five biochemical indicators in serum indicated that liver and kidney toxicity dramatically decreased upon gomisin A pretreatment, although the decrease in ratios varied. Upon histological analysis, the gomisin A/CCl(4)-treated group showed less hepatocellular necrosis, a poorly dilated central vein in the liver section, decreased diameter of the glomerulus, a lower number of capillaries, and a convoluted tubule in the kidney section. Furthermore, the formation of active caspase-3 was inhibited by gomisin A pretreatment in the gomisin A/CCl(4)-treated group, whereas the expression level of Bax protein was slightly increased. Western blot analysis revealed that there were differences between the liver and kidney in terms of activation of the MAPK signaling pathway. In the liver, gomisin A pretreatment increased phosphorylation of three members of the MAPK pathway when compared to that in the vehicle pretreatment group. However, in the kidney, only the phosphorylation level of p38 was elevated upon gomisin A pretreatment, whereas levels of the other two members were decreased. These results suggest that gomisin A induces marked protective effects against hepatic and renal injury induced by CCl(4) exposure through differential regulation of the MAPK signal transduction pathway. PMID:23381504

Hwang, In Sik; Kim, Jee Eun; Lee, Yong Ju; Kwak, Moon Hwa; Choi, Young Hwan; Kang, Byeong Cheol; Hong, Jin Tae; Hwang, Dae Youn

2013-04-01

250

MDCT Imaging Findings of Liver Cirrhosis: Spectrum of Hepatic and Extrahepatic Abdominal Complications  

PubMed Central

Hepatic cirrhosis is the clinical and pathologic result of a multifactorial chronic liver injury. It is well known that cirrhosis is the origin of multiple extrahepatic abdominal complications and a markedly increased risk of hepatocellular carcinoma (HCC). This tumor is the sixth most common malignancy worldwide and the third most common cause of cancer related death. With the rising incidence of HCC worldwide, awareness of the evolution of cirrhotic nodules into malignancy is critical for an early detection and treatment. Adequate imaging protocol selection with dynamic multiphase Multidetector Computed Tomography (MDCT) and reformatted images is crucial to differentiate and categorize the hepatic nodular dysplasia. Knowledge of the typical and less common extrahepatic abdominal manifestations is essential for accurately assessing patients with known or suspected hepatic disease. The objective of this paper is to illustrate the imaging spectrum of intra- and extrahepatic abdominal manifestations of hepatic cirrhosis seen on MDCT.

Sangster, Guillermo P.; Previgliano, Carlos H.; Nader, Mathieu; Chwoschtschinsky, Elisa; Heldmann, Maureen G.

2013-01-01

251

Protective Role of Phyllanthus niruri Extract against Thioacetamide-Induced Liver Cirrhosis in Rat Model.  

PubMed

A preclinical study was performed to determine if the extract from Phyllanthus niruri (PN) plays a protective role against liver cirrhosis induced by thioacetamide (TAA) in rats. Initially, acute toxicity was tested and the results showed that the extract was benign when applied to healthy rats. Next, the therapeutic effect of the extract was investigated using five groups of rats: control, TAA, silymarin, and PN high dose and low dose groups. Significant differences were observed between the TAA group and the other groups regarding body and liver weights, liver biochemical parameters, total antioxidant capacity, lipid peroxidation, and oxidative stress enzyme levels. Gross visualization indicated coarse granules on the surface of the hepatotoxic rats' livers, in contrast to the smoother surface in the livers of the silymarin and PN-treated rats. Histopathological analysis revealed necrosis, lymphocytes infiltration in the centrilobular region, and fibrous connective tissue proliferation in the livers of the hepatotoxic rats. But, the livers of the treated rats had comparatively minimal inflammation and normal lobular architecture. Silymarin and PN treatments effectively restored these measurements closer to their normal levels. Progression of liver cirrhosis induced by TAA in rats can be intervened using the PN extract and these effects are comparable to those of silymarin. PMID:22649471

Amin, Zahra A; Bilgen, Mehmet; Alshawsh, Mohammed A; Ali, Hapipah M; Hadi, A Hamid A; Abdulla, Mahmood A

2012-01-01

252

Protective Role of Phyllanthus niruri Extract against Thioacetamide-Induced Liver Cirrhosis in Rat Model  

PubMed Central

A preclinical study was performed to determine if the extract from Phyllanthus niruri (PN) plays a protective role against liver cirrhosis induced by thioacetamide (TAA) in rats. Initially, acute toxicity was tested and the results showed that the extract was benign when applied to healthy rats. Next, the therapeutic effect of the extract was investigated using five groups of rats: control, TAA, silymarin, and PN high dose and low dose groups. Significant differences were observed between the TAA group and the other groups regarding body and liver weights, liver biochemical parameters, total antioxidant capacity, lipid peroxidation, and oxidative stress enzyme levels. Gross visualization indicated coarse granules on the surface of the hepatotoxic rats' livers, in contrast to the smoother surface in the livers of the silymarin and PN-treated rats. Histopathological analysis revealed necrosis, lymphocytes infiltration in the centrilobular region, and fibrous connective tissue proliferation in the livers of the hepatotoxic rats. But, the livers of the treated rats had comparatively minimal inflammation and normal lobular architecture. Silymarin and PN treatments effectively restored these measurements closer to their normal levels. Progression of liver cirrhosis induced by TAA in rats can be intervened using the PN extract and these effects are comparable to those of silymarin.

Amin, Zahra A.; Bilgen, Mehmet; Alshawsh, Mohammed A.; Ali, Hapipah M.; Hadi, A. Hamid A.; Abdulla, Mahmood A.

2012-01-01

253

Diagnosis of fibrosis and cirrhosis. Liver biopsy is not always necessary.  

PubMed

Needle biopsy of the liver is considered the "gold-standard" for diagnosis of hepatic fibrosis and cirrhosis. However, it is not risk-free, lacks accuracy, and is poorly accepted by some patients. This review examines available literature on the use and diagnostic performance of non-invasive methods for assessment of hepatic fibrosis and cirrhosis in adults, based on the standard Prescrire methodology. Transient elastography (FibroScan) measures liver stiffness in kilopascals. The results are less reliable in patients with a thick chest wall, hepatic congestion of cardiac origin, and acute exacerbations of hepatitis. Transient elastography has been evaluated in more than 8000 patients, most of whom had chronic hepatitis C. With a cutoff value of about 7-8 kPa, elastography identified about 70% of patients with histological signs of moderate to severe fibrosis. With a cutoff of 14-15 kPa, it identified about 85% of patients with histological signs of cirrhosis. Transient elastography is reliable in detecting moderate to severe fibrosis and cirrhosis and in ruling out cirrhosis, but is less reliable in ruling out moderate fibrosis. Composite scores based on blood assay values and complex calculations are unreliable when at least one of the score components is influenced by intercurrent conditions. FibroTest, FibroMeter and Hepascore have been tested in several thousand patients with chronic hepatitis C. With the manufacturers' recommended cutoff values, FibroTest identifies about 70% of patients with histological signs of moderate to severe fibrosis and about 90% of patients with histological signs of cirrhosis. It can reliably diagnose or rule out moderate fibrosis, and diagnose cirrhosis. It is also very reliable in ruling out cirrhosis. Hepascore has similar diagnostic performance. FibroMeter has been less extensively evaluated but also seems to have diagnostic performance similar to that of FibroTest. Some studies suggest that FibroTest has similar accuracy in forms of liver fibrosis other than chronic hepatitis C. In practice, the main issue involved in making therapeutic decisions in patients with chronic hepatitis C is the risk-benefit balance of available treatments rather than precise diagnosis of fibrosis. PMID:20455345

2010-02-01

254

The Triad of Lichen Planus, Thymoma and Liver Cirrhosis-Hepatoma. First Reported Case  

PubMed Central

We describe a patient with liver cirrhosis who presented with erosive oral and cutaneous lichen planus (LP) and incidentally was found simultaneously to have thymoma and hepatoma. We support the notion forwarded earlier that LP and chronic liver disease is more than a mere coincidence and that there is a non-coincidental association between LP and thymoma. We believe this is also the first reported case in the English Literature of coexistence of the three condition LP, thymoma and hepatoma complicating liver disease.

Hassan, J. A.; Saadiah, S; Roslina, A M; Atan, M; Masir, Noraidah; Hussein, S; Ganesapillai, T

2000-01-01

255

PAI-1 plays a protective role in CCl4-induced hepatic fibrosis in mice: role of hepatocyte division  

PubMed Central

Plasminogen activator inhibitor-1 (PAI-1) is an acute phase protein that has been shown to play a role in experimental fibrosis caused by bile duct ligation (BDL) in mice. However, its role in more severe models of hepatic fibrosis (e.g., carbon tetrachloride; CCl4) has not been determined and is important for extrapolation to human disease. Wild-type or PAI-1 knockout mice were administered CCl4 (1 ml/kg body wt ip) 2×/wk for 4 wk. Plasma (e.g., transaminase activity) and histological (e.g., Sirius red staining) indexes of liver damage and fibrosis were evaluated. Proliferation and apoptosis were assessed by PCNA and TdT-mediated dUTP nick-end labeling (TUNEL) staining, respectively, as well as by indexes of cell cycle (e.g., p53, cyclin D1). In contrast to previous studies with BDL, hepatic fibrosis was enhanced in PAI-1?/? mice after chronic CCl4 administration. Indeed, all indexes of liver damage were elevated in PAI-1?/? mice compared with wild-type mice. This enhanced liver damage correlated with impaired hepatocyte proliferation. A similar effect on proliferation was observed after one bolus dose of CCl4, without concomitant increases in liver damage. Under these conditions, a decrease in phospho-p38, coupled with elevated p53 protein, was observed; these results suggest impaired proliferation and a potential G1/S cell cycle arrest in PAI-1?/? mice. These data suggest that PAI-1 may play multiple roles in chronic liver diseases, both protective and damaging, the latter mediated by its influence on inflammation and fibrosis and the former via helping maintain hepatocyte division after an injury.

von Montfort, Claudia; Beier, Juliane I.; Kaiser, J. Phillip; Guo, Luping; Joshi-Barve, Swati; Pritchard, Michele T.; States, J. Christopher

2010-01-01

256

The End-Organ Impairment in Liver Cirrhosis: Appointments for Critical Care  

PubMed Central

Liver cirrhosis (LC) can lead to a clinical state of liver failure, which can exacerbate through the course of the disease. New therapies aimed to control the diverse etiologies are now more effective, although the disease may result in advanced stages of liver failure, where liver transplantation (LT) remains the most effective treatment. The extended lifespan of these patients and the extended possibilities of liver support devices make their admission to an intensive care unit (ICU) more probable. In this paper the LC is approached from the point of view of the pathophysiological alterations present in LC patients previous to ICU admission, particularly cardiovascular, but also renal, coagulopathic, and encephalopathic. Infections and available liver detoxifications devices also deserve mentioning. We intend to contribute towards ICU physician readiness to the care for this particular type of patients, possibly in dedicated ICUs.

Figueiredo, Antonio; Romero-Bermejo, Francisco; Perdigoto, Rui; Marcelino, Paulo

2012-01-01

257

[Enzymes participating in the formation of ammonia in various experimental liver diseases].  

PubMed

The activity of adenosine desaminase AMP-desaminase and glutaminase was studied in blood serum and the liver tissue at the normal state and with acute, subacute experimental affection of the liver as well as with the CCl4-induced liver cirrhosis and obturation jaundice in different periods. It is shown that the degree and trend of changes in the enzyme activity in the affected liver depend on the character and duration of the affecting agents action. The acute and subacute affection of the liver and one-day obturation jaundice are accompanied by a decrease in the activity of all the studied enzymes in the liver tissue. With cirrhosis induced by a multiple administration of CCl4 for three months or with a month obturation jaundice the activity of glutaminase in the liver tissue lowers and that of adenosine desaminase and AMP-desaminase increased sharply. In blood serum the activity of adenosine desaminase and AMP-desaminase increases more considerably with acute affection and cirrhosis, especially with billar one. PMID:943874

Hromashevs'ka, L L; Magarlamov, A H; Shkirova, O S

1976-01-01

258

[Studies on diagnostic and prognostic validity of aminophenazone breath test in liver cirrhosis].  

PubMed

In 59 patients with liver cirrhosis (23 female, 36 male; aged between 30 and 73 years) the aminophenazone breath-test according to the Haustein-Schenker modification was performed. The results were related to morphological, clinical and haemodynamic criteria. In contrast to a control group, consisting of 8 women and 8 men aged between 23 and 27 years with healthy livers, the aminophenazone elimination proved to be heavily delayed (p less than 0.001). In consideration of the Havanna-classification the 14CO2-elimination was most heavily retarded in patients with portal cirrhosis, but compared with non-portal cirrhosis, the difference was below significance level. A significant dependence on the clinical degree of severity was found. The aminophenazone-elimination was frequently low in portal hypertension and considerably decreased after portocaval shunt with values below 200 DPM/mmol CO2/70 kg body weight. In some cases it could be demonstrated, that the test is not only of diagnostic relevance, but reflects the progression of cirrhosis. PMID:1811653

Sensing, H; Treutler, J; Haustein, K O; Hüller, G

1991-01-01

259

Effects of S-adenosylmethionine on lipid peroxidation and liver fibrogenesis in carbon tetrachloride-induced cirrhosis  

Microsoft Academic Search

Background\\/Aim: The aim of this study was to investigate the effects of S-adenosyhnethionine on liver peroxidation and liver fibrogenesis in carbon tetrachloride-induced cirrhosis. Methods: Cirrhosis was induced in three groups of six rats by repeated iqjections of carbon tetrachlo- ride over 9 weeks. One group of animals was treat- ed only with carbon tetrachloride, and the other two received carbon

Marta Gas; Mireia Rubio; Gregorio Varela; Maria Cabre; Joan Caballerfa; Elena Alonso; Ramon Deulofem; Jordi Camps; America Gimenez; Marfa Pajares; Albert Pares; Jose M. Mato; Joan Rod

1996-01-01

260

Etiology and Complications of Liver Cirrhosis in Children:Report of a Single Center from Southern Iran  

PubMed Central

BACKGROUND Liver cirrhosis is one of the major causes of hospitalization and mortality in children. A wide spectrum of disorders including developmental abnormalities, infections, metabolic and genetic disorders can lead to liver cirrhosis in pediatric patients. Determination of its etiology is important for treatment, prevention of progressive liver damage, family counseling and prioritizing liver transplantation. The aim of this study is to evaluate causes of liver cirrhosis in children in Southern Iran. METHODS We included all cirrhotic children aged less than 18 years who referred to an outpatient pediatric gastroenterology clinic affiliated with Shiraz University of Medical Sciences between March 2009 and September 2010 in this cross-sectional study. The etiology of cirrhosis was determined according to clinical findings, laboratory tests, imaging studies such as ultrasonography or computed tomography scan, hepatobiliary scintigraphy and histopathologic examination of the liver biopsy. Cirrhosis with unknown etiology was considered as cryptogenic. RESULTS A total of 106 cirrhotic children aged between 5 months to 18 years with a mean age of 8.24 ± 6.12 years that included 60 boys (56.6%) and 46 girls (43.4%) were enrolled in the study. The most common causes of liver cirrhosis were Wilson disease (n=22; 20.7%), biliary atresia (n=19; 17.9%), and cryptogenic cirrhosis (n=14; 13.2%). Other causes were autoimmune hepatitis (n=12; 11.3%), idiopathic neonatal hepatitis (n=10; 9.4%), hepatorenal tyrosinemia (n=9; 8.5%), glycogen storage disease (n=6; 5.7%), and progressive familial intrahepatic cholestasis (n=4; 3.8%). CONCLUSION Considering the most common etiology of liver cirrhosis in children in this part of Iran we suggest testing for Wilson disease in all cirrhotic children.

Dehghani, Seyed Mohsen; Imanieh, Mohammad Hadi; Haghighat, Mahmood; Malekpour, Abdorrasoul; Falizkar, Zeinab

2013-01-01

261

Infusion of human umbilical cord?derived mesenchymal stem cells effectively relieves liver cirrhosis in DEN?induced rats.  

PubMed

Cirrhosis is the long?term outcome of chronic hepatic injury and no effective therapy is currently available for this disease. Mesenchymal stromal cells (MSCs) are multipotent cells that are easily acquired and amplified, and may be potential candidates for cell therapy against cirrhosis. This study aimed to determine the therapeutic effects of human umbilical cord?derived MSCs (hUCMSCs) for the treatment of liver cirrhosis and identify an effective method for engrafting MSCs. The model of liver cirrhosis was established by induction of diethylnitrosamine (DEN) in rats. The isolated hUCMSCs were identified by morphology, flow cytometry and multilineage differentiation; they were injected into the vein of DEN?induced rats at varied cell doses and infusion times. Biochemical analyses of the serum and histopathological analysis of the liver tissues were performed to evaluate the therapeutic effects of hUCMSCs in all treatment groups. The results indicated that isolated hUCMSCs were capable of self?replication and differentiated into multiple lineages, including osteoblast?, adipocyte? and hepatocyte?like cells. Compared with the control group, administration of hUCMSCs at different cell doses and infusion times relieved DEN?induced cirrhosis to varying degrees. The therapeutic effects of hUCMSCs on liver cirrhosis gradually improved with increased cell dose and infusion times. The improvement of cirrhosis was due to the capacity of hUCMSCs to breakdown collagen fibers in the liver. It was demonstrated that infusion of hUCMSCs effectively relieved liver cirrhosis by facilitating the breakdown of collagen fibers in a dose?dependent manner and multiple infusions caused a relatively greater improvement in cirrhosis compared with a single infusion of hUCMSCs. PMID:24481983

Hong, Jingxin; Jin, Huajun; Han, Junling; Hu, Huanzhang; Liu, Jian; Li, Linfang; Huang, Yao; Wang, Dandan; Wu, Mengchao; Qiu, Lugui; Qian, Qijun

2014-04-01

262

What are the implications of the spontaneous spleno-renal shunts in liver cirrhosis?  

Microsoft Academic Search

BACKGROUND: Although significant advances are expected to be made in the assessment of the portal hypertension-related complications, the prognostic role of spleno-renal shunts has not been fully explored so far. Clarifying this aspect could help tackle the life-treating events occurring in patients suffering from liver cirrhosis. The aim of the study was to analyze the relationships between the spleno-renal shunts

Giovanni Tarantino; Vincenzo Citro; Paolo Conca; Antonio Riccio; Marianna Tarantino; Domenico Capone; Michele Cirillo; Roberto Lobello; Vittorio Iaccarino

2009-01-01

263

Simultaneous determination of pulmonary and intestinal permeability in patients with alcoholic liver cirrhosis  

Microsoft Academic Search

The aim of this prospective study was to assess pulmonary and intestinal permeability (PP and IP, respectively) in patients with alcoholic liver cirrhosis (ALC). Thirty-five non-smoking patients with biopsy-proven ALC were included (mean grade B in Child's classification). None had a previous history of pulmonary disease and all had a normal chest radiograph and computed tomography scan. Lung function tests

Damien Huglo; Stéphane De Botton; Valérie Canva-Delcambre; Jean-Fréderic Colombel; Benoit Wallaert; Marc Steinling; Xavier Marchandise

2001-01-01

264

Clinical implications of alpha-fetoprotein in liver cirrhosis: five-year follow-up study.  

PubMed

The level of alpha-fetoprotein (AFP) was estimated by radioimmunoassay or passive hemagglutination method in a series of 159 patients with liver cirrhosis, and the incidence of serum hepatitis B antigen, histopathologic features of the liver, incidence of development of hepatocellular carcinoma (HCC) and mortality in AFP-positive cases were studied. Approximately 40 per cent of the patients had an AFP level higher than 20 ng/per ml, and all the elevations of AFP over 100 ng per ml were transient. In contrast, patients who developed HCC during the course of the disease always exhibited an increasing value of AFP. The seropositivity for AFP was significantly related to the presence of serum hepatitis B surface antigen and also to liver cell dysplasia as well as to thickening of the liver cell plates. As compared with a group of AFP-negative cases, the AFP-positive group showed a higher incidence of development of HCC and poorer prognosis over a five-year follow-up period. The data obtained suggested that increased AFP-production in patients with liver cirrhosis might reflect, largely an abnormal or altered liver cell regeneration, probably associated with hepatitis B virus, and that patients with transiently elevated AFP values might be at greater risk for the development of HCC. PMID:6161869

Harada, T; Shigeta, K; Noda, K; Fukumoto, Y; Nishimura, H; Mizuta, M; Takemoto, T

1980-06-01

265

The relationship between aminopyrine breath test and severity of liver disease in cirrhosis  

SciTech Connect

Twenty-two patients with cirrhosis were evaluated by the 2 hr.-(C14)-aminopyrine breath test, the conventional liver tests and two systems for grading the severity of liver disease. Twenty-three patients with noncirrhotic liver disease and 15 controls were also studied. Reduced 14CO2 values were found in 21 of the 22 cirrhotic patients and seven of those had noncirrhotic liver disease associated with severe functional reserve impairment. The values in patients with minor liver diseases or cholestasis were normal. In the cirrhotic patients 2 hr.-(C14)-aminopyrine breath test scores correlated with prothrombin time, retention of bromosulfalein, fasting serum bile acid, albumin, bilirubin, serum aspartate aminotransferase and, above all, with the scores of the two clinical rating systems. The 2 hr.-(C14)-aminopyrine breath test was superior to conventional tests in quantifying the degree of hepatic functional reserve and forecasting the prognosis.

Morelli, A.; Narducci, F.; Pelli, M.A.; Farroni, F.; Vedovelli, A.

1981-08-01

266

Health-State Utilities in Liver Cirrhosis: A Cross-sectional Study  

PubMed Central

Objectives: Liver cirrhosis can change many aspects of life of the patients and their family and effects society. We aimed to study the utility of cirrhosis from the point of view of the patients, their family, and their care takers to find appropriate interventions, and training and counselling programmes to support patients. Methods: In this cross-sectional study with a goal-based sampling method, 66 individuals constructed of 30 decompensated patients with cirrhosis, 21 of the patients family members, and 15 care takers were included. The data were collected through face to face interview and completing of questionnaire consisted of demographic information (age, gender, marital status, and income), the duration of illness, and assessment of utility of cirrhosis using techniques of time trade, standard gamble, rating scale, and the willingness to pay. Results: 52% of participants were men and 48% women which consisted of 58 married, 4 single, and 4 divorced or widowed with the mean duration of having cirrhosis of 3.7 ± 1.4 years. The mean scores of utility of the three groups in all preference-based measures had significant differences (P < 0.05). Different techniques of patient utility in this research from the highest to the lowest were standard gamble (0.55), willingness to pay (0.54), rating scale (0.25), and rating scale (0.05), respectively. Conclusions: The results of the currents study suggested that the cirrhosis status has had the most negative effect on patients, and that patients had a lower utility rate than their family members and caretakers.

Adibi, Peyman; Akbari, Leila; Kahangi, Leila Sadat; Abdi, Fatemeh

2012-01-01

267

Laparoscopic splenectomy for hypersplenism secondary to liver cirrhosis and portal hypertension  

PubMed Central

Since the first laparoscopic splenectomy (LS) was reported in 1991, LS has become the gold standard for the removal of normal to moderately enlarged spleens in benign conditions. Compared with open splenectomy, fewer postsurgical complications and better postoperative recovery have been observed, but LS is contraindicated for hypersplenism secondary to liver cirrhosis in many institutions owing to technical difficulties associated with splenomegaly, well-developed collateral circulation, and increased risk of bleeding. With the improvements of laparoscopic technique, the concept is changing. This article aims to give an overview of the latest development in laparoscopic splenectomy for hypersplenism secondary to liver cirrhosis and portal hypertension. Despite a lack of randomized controlled trial, the publications obtained have shown that with meticulous surgical techniques and advanced instruments, LS is a technically feasible, safe, and effective procedure for hypersplenism secondary to cirrhosis and portal hypertension and contributes to decreased blood loss, shorter hospital stay, and less impairment of liver function. It is recommended that the dilated short gastric vessels and other enlarged collateral circulation surrounding the spleen be divided with the LigaSure vessel sealing equipment, and the splenic artery and vein be transected en bloc with the application of the endovascular stapler. To support the clinical evidence, further randomized controlled trials about this topic are necessary.

Zhan, Xiao-Li; Ji, Yun; Wang, Yue-Dong

2014-01-01

268

Eosinophilic ascites and duodenal obstruction in a patient with liver cirrhosis.  

PubMed

Eosinophilic gastroenteritis (EG) is a rare disease characterized by eosinophilic infiltration of portions of the gastrointestinal tract. Eosinophilic ascites is probably the most unusual and rare presentation of EG and is generally associated with the serosal form of EG. Hereby, we report a case of eosinophilic ascites with duodenal obstruction in a patient with liver cirrhosis. A 50-year-old woman was admitted to our hospital because of abdominal pain, nausea, bloating, and constipation. She had a history of laparotomy because of duodenal obstruction 2 years ago. Based on clinical, radiological, endoscopic, and pathological findings, and given the excluding the other causes of peripheral eosinophilia, the diagnosis of eosinophilic gastroenteritis along with liver cirrhosis and spontaneous bacterial peritonitis was established. Based on the findings of the present case, it is highly recommended that, in the patients presented with liver cirrhosis associated with peripheral blood or ascitic fluid eosinophilia, performing gastrointestinal endoscopy and biopsy can probably reveal this rare disorder of EG. PMID:24772356

Maleki, Nasrollah; Kalantar Hormozi, Mohammadreza; Bahtouee, Mehrzad; Tavosi, Zahra; Mosallai Pour, Hamidreza; Taghiyan Jamaleddin Kolaii, Seiiedeh Samaneh

2014-01-01

269

Comparison of measured and predicted energy expenditure in patients with liver cirrhosis.  

PubMed

Obesity is a risk factor for the onset of liver cancer in patients with cirrhosis. To prevent overfeeding and obesity, estimation of energy requirement is important, but energy expenditure in patients with liver cirrhosis has not been fully elucidated. This study aimed to investigate resting energy expenditure (REE) and energy intake in patients with cirrhosis and determine adequate energy intake criteria. In this cross-sectional study, indirect calorimetry measurement was conducted in 488 Japanese inpatients with cirrhosis. We compared REE measured by indirect calorimetry (M-REE) with basal energy expenditure (BEE) predicted by the Harris-Benedict equation (H-BEE) and Dietary Reference Intakes (DRI) for Japanese (D-BEE). Mean M-REE (1256 kcal) was significantly lower than H-BEE (1279 kcal); however, it was not significantly different from D-BEE (1254 kcal). Mean M-REE expressed in relation to body weight (BW; REE/kg BW) was 21.7 kcal/kg BW. H-BEE was significantly higher than M-REE in patients in the first and second quartiles of BMI, and D-BEE was significantly different from MREE in patients in the highest and lowest quartiles of BMI. Average energy intake was 30.5 kcal/kg BW, which was 1.4 times greater than REE/kg BW. Although DRI is a useful tool for the estimation of REE in patients in the second and third quartiles of BMI, M-REE is recommended to ensure the provision of adequate nutritional care to patients with cirrhosis, including those in the highest and lowest quartiles of BMI. PMID:24901087

Teramoto, Arisa; Yamanaka-Okumura, Hisami; Urano, Eri; Nakamura-Kutsuzawa, Taki; Sugihara, Kohei; Katayama, Takafumi; Miyake, Hidenori; Imura, Satoru; Utsunomiya, Tohru; Shimada, Mitsuo; Takeda, Eiji

2014-06-01

270

Impaired hepatic handling and processing of lysophosphatidylcholine in rats with liver cirrhosis  

SciTech Connect

Lysophosphatidylcholine is a major metabolic product in the plasma and cellular turnover of phospholipids, with well-known membrane-toxic and proinflammatory properties. Because the liver plays a key role in plasma lysophosphatidylcholine removal and biotransformation and because virtually nothing is known of these processes in a diseased organ, the hepatobiliary metabolism of lysophosphatidylcholine was investigated in rats with carbon tetrachloride-induced liver cirrhosis. Twelve adult male Wistar rats with histologically confirmed cirrhosis and 8 control animals were fitted with jugular and biliary catheters and allowed to recover. The animals were kept under constant IV infusion of taurocholate (1 mumol/min). Two microcuries of sn-1{sup 14}Cpalmitoyl-lysophosphatidylcholine was administered as a single bolus. The fate of the injected radioactivity, including removal from plasma, uptake, and subcellular location in the liver and molecular and aggregative forms, was studied by combined chromatographic and radiochemical methods. Major findings were (a) that lysophosphatidylcholine has a prolonged permanence in plasma of cirrhotic rats, due both to decreased hepatic clearance and to depressed conversion into phosphatidylcholine; (b) that the rate of lysophosphatidylcholine acylation is much slower in the cirrhotic than in the normal liver, both at the microsomal and at the cytosolic level; (c) that cytosolic lysophosphatidylcholine in the cirrhotic liver, but not in the normal liver, is predominantly non-protein bound; (d) that the strict molecular selectivity of lysophosphatidylcholine acylation observed in controls is partially lost in cirrhosis; and (e) that a consistent fraction of lysophosphatidylcholine is converted into triacylglycerols in cirrhotics but not in controls.

Angelico, M.; Alvaro, D.; Cantafora, A.; Masella, R.; Gaudio, E.; Gandin, C.; Ginanni Corradini, S.; Ariosto, F.; Riggio, O.; Capocaccia, L. (II Division of Gastroenterology, University of Rome La Sapienza (Italy))

1991-07-01

271

Hepatocellular nodules in liver cirrhosis: contrast-enhanced ultrasound  

Microsoft Academic Search

Contrast-enhanced ultrasound (CEUS) using microbubble contrast agents has expanded the role of US in the diagnosis of liver\\u000a nodules in high risk patients for hepatocellular carcinoma (HCC). HCC is typically characterized by arterial hypervascularity\\u000a and later washout (negative enhancement). Washout in the portal phase is often not obvious until late (>90 s). Benign nodules\\u000a such as regenerative nodules or dysplastic nodules

Tae Kyoung Kim; Kyoung Ho Lee; Korosh Khalili; Hyun-Jung Jang

2011-01-01

272

Soluble membrane attack complex in ascites in patients with liver cirrhosis without infections  

PubMed Central

AIM: To study complement activation in 46 patients with alcoholic cirrhosis and ascites but no spontaneous bacterial peritonitis (SBP) and 10 healthy controls. METHODS: Complement activation was determined by the measurement of soluble membrane attack complex (sMAC) concentrations in ascites and plasma. In patients, metabolic liver function was determined by the galactose elimination capacity and the clinical status assessed by the Model of End-Stage Liver Disease and Child-Pugh scores. RESULTS: Ascites sMAC levels were markedly higher than in the corresponding plasma sample (median (range): 596 (170 - 1519) vs 160 (77 - 848) ?g/L; P < 0.01). Ascites sMAC levels correlated positively with liver status. There was no relationship between ascites sMAC and leukocyte count. No relationship between ascites sMAC and blood C-reactive protein, albumin or neutrophile count was found. Plasma sMAC concentrations were slightly higher in patients than in controls [130 ?g/L (70 - 204); P = 0.04]. Neither sMAC in ascites nor plasma was related to mortality. CONCLUSION: The increased sMAC concentration in ascites and plasma indicate an activation of the complement system in cirrhosis even in the absence of SBP. This was particularly evident in the peritoneal fluid and most marked in patients with preserved liver status. The high ascites sMAC levels may reflect transudation of membrane attack complexes from the liver. Whether this complement activation has any clinical implications remains to be clarified.

Bjerre, Mette; Holland-Fischer, Peter; Gr?nbaek, Henning; Frystyk, Jan; Hansen, Troels K; Vilstrup, Hendrik; Flyvbjerg, Allan

2010-01-01

273

Hepatoprotective and antioxidant effects of Glycyrrhiza glabra extract against carbon tetrachloride (CCl(4))-induced hepatocyte damage in common carp (Cyprinus carpio).  

PubMed

The present study is aiming at evaluating the hepatoprotective and antioxidant effects of Glycyrrhiza glabra extract (2.5, 5 and 10 ?g/ml) on the carbon tetrachloride (CCl(4))-induced carp hepatocyte damage in vitro. Glycyrrhiza glabra extract was added to the carp primary hepatocytes before (pre-treatment), after (post-treatment) and both before and after (pre- and post-treatment) the incubation of the hepatocytes with CCl(4). CCl(4) at 8 mM in the culture medium produced significantly elevated levels of lactate dehydrogenase (LDH), glutamate oxalate transaminase (GOT), glutamate pyruvate transaminase (GPT) and malondialdehyde (MDA) and significantly reduced levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Pre-treatment (5 ?g/ml) and pre- and post-treatment (5 and 10 ?g/ml) of the hepatocytes with Glycyrrhiza glabra extract significantly reduced the elevated levels of LDH, GOT, GPT and MDA and increased the reduced levels of SOD and GSH-Px by CCl(4); post-treatment of the hepatocytes with Glycyrrhiza glabra extract at 5 ?g/ml reduced the GPT and GOT levels and increased the GSH-Px level, but had no effect on the other parameters at all the studied concentrations. The results support the use of Glycyrrhiza glabra extract as a hepatoprotective and antioxidant agent in fish. PMID:20865324

Yin, Guojun; Cao, Liping; Xu, Pao; Jeney, Galina; Nakao, Miki; Lu, Chengping

2011-03-01

274

Increased hepatic platelet activating factor (PAF) and PAF receptors in carbon tetrachloride induced liver cirrhosis  

PubMed Central

Background and aims: The liver is a major site for the synthesis and actions of platelet activating factor (PAF), a potent hepatic vasoconstrictor and systemic vasodilator. As PAF is implicated in portal hypertension and hyperdynamic circulation associated with liver cirrhosis, we characterised changes in the hepatic PAF system in experimental cirrhosis. Methods: In rats made cirrhotic by carbon tetrachloride (CCl4) administration for eight weeks, we determined hepatic levels of PAF and its cognate receptor, and the effects of PAF and PAF antagonist (BN52021) on portal and arterial pressure. Results: Compared with control rats, cirrhotic rats had higher hepatic PAF levels, higher apparent hepatic efflux of PAF, and higher PAF levels in arterial blood (p<0.01, p<0.01, p<0.05, respectively). Relative to controls, cirrhotic livers had elevated hepatic PAF receptors (by mRNA and protein levels and [3H]PAF binding), higher (p<0.01) baseline hepatic portal pressure, and an augmented (p?=?0.03) portal pressure response to PAF infusion (1 ?g/kg). Portal infusion of BN52021 (5 mg/kg) showed that elevated endogenous PAF was responsible for 23% of the cirrhotic portal pressure increase but made no contribution to systemic hypotension. Finally, increased PAF receptor density was observed in the contractile perisinusoidal stellate cells isolated from cirrhotic livers relative to those from control livers. Conclusions: In cirrhosis, increased hepatic release of PAF elevates systemic PAF; in combination with upregulated hepatic PAF receptors in stellate cells, this contributes to portal hypertension.

Yang, Y; Nemoto, E M; Harvey, S A K; Subbotin, V M; Gandhi, C R

2004-01-01

275

Primary biliary cirrhosis  

MedlinePLUS

Primary biliary cirrhosis is irritation and swelling (inflammation) of the bile ducts of the liver, which blocks ... ducts in the liver is not known. However, primary biliary cirrhosis is an autoimmune disorder. That means ...

276

Long-term effectiveness of high-dosed ornithine-aspartate on urea synthesis rate and portal hypertension in human liver cirrhosis  

Microsoft Academic Search

The effectiveness of ammonia reducing amino acids on hyperammonemia and hepatic encephalopathy is well known in patients suffering from liver cirrhosis. Data concerning long-term therapy on hepatic function and urea synthesis rate (UNSR) are still lacking. According to Vilstrup\\/Poulsen it is a good standard for functioning liver mass. Therefore, 25 patients with histologically proven liver cirrhosis and distinct portal hypertension

D. Miiting; J.-F. Kalk; C.-P. Klein

1992-01-01

277

Androgen receptor roles in hepatocellular carcinoma, fatty liver, cirrhosis and hepatitis.  

PubMed

Androgen/androgen receptor (AR) signaling plays important roles in normal liver function and in progression of liver diseases. In studies of noncancerous liver diseases, AR knockout mouse models of liver disease have revealed that androgen/AR signaling suppresses the development of steatosis, virus-related hepatitis, and cirrhosis. In addition, studies have shown that targeting AR in bone marrow-derived mesenchymal stem cells (BM-MSCs) improves their self-renewal and migration potentials, thereby increasing the efficacy of BM-MSC transplantation as a way to control the progression of cirrhosis. Androgen/AR signaling is known to be involved in the initiation of carcinogen- or hepatitis B virus-related hepatocellular carcinoma (HCC). However, studies have demonstrated that AR, rather than androgen, plays the dominant role in cancer initiation. Therefore, targeting AR might be an appropriate therapy for patients with early-stage HCC. In contrast, androgen/AR signaling has been shown to suppress metastasis of HCC in patients with late-stage disease. In addition, there is evidence that therapy comprising Sorafenib and agents that enhance the functional expression of AR may suppress the progression of late-stage HCC. PMID:24424503

Ma, Wen-Lung; Lai, Hsueh-Chou; Yeh, Shuyuan; Cai, Xiujun; Chang, Chawnshang

2014-01-01

278

Subclinical abnormal glucose tolerance is a predictor of death in liver cirrhosis  

PubMed Central

AIM: To determine if subclinical abnormal glucose tolerance (SAGT) has influence on survival of non-diabetic patients with liver cirrhosis. METHODS: In total, 100 patients with compensated liver cirrhosis and normal fasting plasma glucose were included. Fasting plasma insulin (FPI) levels were measured, and oral glucose tolerance test (OGTT) was performed. According to OGTT results two groups of patients were formed: those with normal glucose tolerance (NGT) and those with SAGT. Patients were followed every three months. The mean follow-up was 932 d (range of 180-1925). Survival was analyzed by the Kaplan-Meyer method, and predictive factors of death were analyzed using the Cox proportional hazard regression model. RESULTS: Of the included patients, 30 showed NGT and 70 SAGT. Groups were significantly different only in age, INR, FPI and HOMA2-IR. Patients with SAGT showed lower 5-year cumulated survival than NGT patients (31.7% vs 71.6%, P = 0.02). Differences in survival were significant only after 3 years of follow-up. SAGT, Child-Pugh B, and high Child-Pugh and Model for End-Stage Liver Disease (MELD) scores were independent predictors of death. The causes of death in 90.3% of cases were due to complications related to liver disease. CONCLUSION: SAGT was associated with lower survival. SAGT, Child-Pugh B, and high Child-Pugh and MELD scores were independent negative predictors of survival.

Garcia-Compean, Diego; Jaquez-Quintana, Joel Omar; Lavalle-Gonzalez, Fernando Javier; Gonzalez-Gonzalez, Jose Alberto; Munoz-Espinosa, Linda Elsa; Villarreal-Perez, Jesus Zacarias; Maldonado-Garza, Hector J

2014-01-01

279

The endocannabinoid system in advanced liver cirrhosis: pathophysiological implication and future perspectives.  

PubMed

Endogenous cannabinoids (EC) are ubiquitous lipid signalling molecules providing different central and peripheral effects that are mediated mostly by the specific receptors CB1 and CB2. The EC system is highly upregulated during chronic liver disease and consistent experimental and clinical findings indicate that it plays a role in the pathogenesis of liver fibrosis and fatty liver disease associated with obesity, alcohol abuse and hepatitis C. Furthermore, a considerable number of studies have shown that EC and their receptors contribute to the pathogenesis of the cardio-circulatory disturbances occurring in advanced cirrhosis, such as portal hypertension, hyperdynamic circulatory syndrome and cirrhotic cardiomyopathy. More recently, the EC system has been implicated in the development of ascites, hepatic encephalopathy and the inflammatory response related to bacterial infection. Rimonabant, a selective CB1 antagonist, was the first drug acting on the EC system approved for the treatment of obesity. Unfortunately, it has been withdrawn from the market because of its neuropsychiatric side effects. Compounds able to target selectively the peripheral CB1 receptors are under evaluation. In addition, molecules stimulating CB2 receptor or modulating the activity of enzymes implicated in EC metabolism are promising areas of pharmacological research. Liver cirrhosis and the related complications represent an important target for the clinical application of these compounds. PMID:23890208

Baldassarre, Maurizio; Giannone, Ferdinando A; Napoli, Lucia; Tovoli, Alessandra; Ricci, Carmen S; Tufoni, Manuel; Caraceni, Paolo

2013-10-01

280

Histogram Analysis of Hepatobiliary Phase MR Imaging as a Quantitative Value for Liver Cirrhosis: Preliminary Observations  

PubMed Central

Purpose To investigate whether histogram analysis of the hepatobiliary phase on gadoxetate enhanced-MRI could be used as a quantitative index for determination of liver cirrhosis. Materials and Methods A total of 63 patients [26 in a normal liver function (NLF) group and 37 in a cirrhotic group] underwent gadoxetate-enhanced MRI, and hepatobiliary phase images were obtained at 20 minutes after contrast injection. The signal intensity of the hepatic parenchyma was measured at four different regions of interest (ROI) of the liver, avoiding vessels and bile ducts. Standard deviation (SD), coefficient of variation (CV), and corrected CV were calculated on the histograms at the ROIs. The distributions of CVs calculated from the ROI histogram were examined and statistical analysis was carried out. Results The CV value was 0.041±0.009 (mean CV±SD) in the NLF group, while that of cirrhotic group was 0.071±0.020. There were statistically significant differences in the CVs and corrected CV values between the NLF and cirrhotic groups (p<0.001). The most accurate cut-off value among CVs for distinguishing normal from cirrhotic group was 0.052 (sensitivity 83.8% and specificity 88.5%). There was no statistically significant differences in SD between NLF and cirrhotic groups (p=0.307). Conclusion The CV of histograms of the hepatobiliary phase on gadoxetate-enhanced MRI may be useful as a quantitative value for determining the presence of liver cirrhosis.

Kim, Honsoul; Sun, Mark; Sirlin, Claude B.

2014-01-01

281

Gallstones in patients with liver cirrhosis: Incidence, etiology, clinical and therapeutical aspects  

PubMed Central

Gallstones occur in about one third of the patients having liver cirrhosis. Pigment gallstones are the most frequent type, while cholesterol stones represent about 15% of all stones in cirrhotics. Increased secretion of unconjugated bilirubin, increased hydrolysis of conjugated bilirubin in the bile, reduced secretion of bile acids and phospholipds in bile favor pigment lithogenesis in cirrhotics. Gallbladder hypomotility also contributes to lithogenesis. The most recent data regarding risk factors for gallstones are presented. Gallstone prevalence increases with age, with a ratio male/female higher than in the general population. Chronic alcoholism, viral C cirrhosis, and non-alcoholic fatty liver disease are the underlying liver diseases most often associated with gallstones. Gallstones are often asymptomatic, and discovered incidentally. If asymptomatic, expectant management is recommended, as for asymptomatic gallstones in the general population. However, a closer follow-up of these patients is necessary in order to earlier treat symptoms or complications. For symptomatic stones, laparoscopic cholecystectomy has become the therapy of choice. Child-Pugh class and MELD score are the best predictors of outcome after cholecystectomy. Patients with severe liver disease are at highest surgical risk, therefore gallstone complications should be treated using noninvasive or minimally invasive procedures, until stabilization of the patient condition.

Acalovschi, Monica

2014-01-01

282

Gene network profiling before and after transplantation in alcoholic cirrhosis liver transplant recipients.  

PubMed

The main objective of this study was to define a gene network profile network in liver transplant recipients with alcoholic cirrhosis before and after liver transplantation. Genes were selected from data obtained in a previous study of liver transplant recipients with alcoholic cirrhosis. Selected up-regulated genes were further validated by quantitative real-time polymerase chain reaction in different groups of liver transplant recipients with alcoholic cirrhosis (n=5). Selected genes up-regulated before transplantation were: TNFRSF9 (tumor necrosis factor [TNF] receptor superfamily, member 9); IL2RB (interleukin-2 receptor beta); BCL2L2 (BCL2-like 2); NOX5 (NADPH) oxidase, EF-hand calcium binding domain 5); PEX5 (peroxisomal biogenesis factor 5); PPARG (peroxisome proliferator-activated receptor gamma); NIBP (IKK2 binding protein); NKIRAS2 (NFKappaBeta inhibitor interacting Ras-like 2); IL4 (interleukin-4); IL-4R (interleukin 4 receptor); ADH1A (alcohol dehydrogenase 1A, class 1); ALDH1L1 (aldehyde dehydrogenase 1 family, member L1); MPO (myeloperoxidase); NPPA (natriuretic peptide precursor A); BCL2A1 (BCL2-related protein A1); GADD45A (growth arrest and DNA-damage-inducible alpha); TEGT (Bax inhibitor 1); PIK3CA (phosphoinositide-3-kinase, catalytic, alpha polypeptide); IFNGR2 (interferon gamma receptor 2); JAK2 (Janus Kinase 2); FAS (Fas, TNF receptor superfamily, member 6); TANK (TRAF family member-associated NFKB activator); TTRAP (TRAF and TNF receptor-associated protein); and ANXA5 (annexin A5). PMID:22841193

Muffak-Granero, K; Olmedo, C; Garcia-Alcalde, F; Comino, A; Villegas, T; Villar, J M; Garrote, D; Blanco, A; Bueno, P; Ferron, J-A

2012-01-01

283

Utilization of Metabolomics to Identify Serum Biomarkers for Hepatocellular Carcinoma in Patients with Liver Cirrhosis  

PubMed Central

Characterizing the metabolic changes pertaining to hepatocellular carcinoma (HCC) in patients with liver cirrhosis is believed to contribute towards early detection, treatment, and understanding of the molecular mechanisms of HCC. In this study, we compare metabolite levels in sera of 78 HCC cases with 184 cirrhotic controls by using ultra performance liquid chromatography coupled with a hybrid quadrupole time-of-flight mass spectrometry (UPLC-QTOF MS). Following data preprocessing, the most relevant ions in distinguishing HCC cases from patients with cirrhosis are selected by parametric and non-parametric statistical methods. Putative metabolite identifications for these ions are obtained through mass-based database search. Verification of the identities of selected metabolites is conducted by comparing their MS/MS fragmentation patterns and retention time with those from authentic compounds. Quantitation of these metabolites is performed in a subset of the serum samples (10 HCC and 10 cirrhosis) using isotope dilution by selected reaction monitoring (SRM) on triple quadrupole linear ion trap (QqQLIT) and triple quadrupole (QqQ) mass spectrometers. The results of this analysis confirm that metabolites involved in sphingolipid metabolism and phospholipid catabolism such as sphingosine-1-phosphate (S-1-P) and lysophosphatidylcholine (lysoPC 17:0) are up-regulated in sera of HCC vs. those with liver cirrhosis. Down-regulated metabolites include those involved in bile acid biosynthesis (specifically cholesterol metabolism) such as glycochenodeoxycholic acid 3-sulfate (3-sulfo-GCDCA), glycocholic acid (GCA), glycodeoxycholic acid (GDCA), taurocholic acid (TCA), and taurochenodeoxycholate (TCDCA). These results provide useful insights into HCC biomarker discovery utilizing metabolomics as an efficient and cost-effective platform. Our work shows that metabolomic profiling is a promising tool to identify candidate metabolic biomarkers for early detection of HCC cases in high risk population of cirrhotic patients.

Ressom, Habtom W.; Xiao, Jun Feng; Tuli, Leepika; Varghese, Rency S.; Zhou, Bin; Tsai, Tsung-Heng; Nezami Ranjbar, Mohammad R.; Zhao, Yi; Wang, Jinlian; Di Poto, Cristina; Cheema, Amrita K.; Tadesse, Mahlet G.; Goldman, Radoslav; Shetty, Kirti

2012-01-01

284

Liver cirrhosis treated by living donor liver transplantation in a patient with AGL mutation c.2607-2610delATTC and c.1672dupA.  

PubMed

Glycogen storage disease type III (GSD III) is an inherited disorder characterized by the accumulation of abnormal glycogen in the liver. Hepatic manifestations were considered as improving with age; however, patients live longer and liver cirrhosis is being recognized. We report a patient of GSD IIIa with liver cirrhosis, which was treated successfully by living donor liver transplantation. The patient proved to be a compound heterozygote for a novel small deletion c.2607-2610delATTC and a known duplication c.1672dupA in AGL, a gene coding glycogen debranching enzyme responsible for GSD III. Molecular diagnosis helped clinical decision-making. PMID:23688858

Kondo, Yuichi; Usui, Hiromi; Ishige-Wada, Mika; Murase, Toshio; Owada, Misao; Okubo, Minoru

2013-09-23

285

Effect of Experimentally Induced Liver Cirrhosis on Wound Healing of the Post-Extraction Tooth Socket in Rats  

Microsoft Academic Search

Background: Wound healing in liver cirrhosis is known to be impaired possibly due to liver insufficiency and subsequent malnutrition status; however, there is no study to examine healing effectiveness of the tooth socket following an extraction in such patients. Materials and Methods: Irreversible cirrhosiswas induced in 30 Wistar rats by repetitive weekly doses of CCl4 and continuous administration of phenobarbital

M. Karalis; T. E. Pavlidis; K. Psarras; K. Ballas; T. Zaraboukas; S. Rafailidis; N. Symeonidis; G. N. Marakis; A. K. Sakantamis

2008-01-01

286

Clinical significance of therapy using branched-chain amino acid granules in patients with liver cirrhosis and hepatocellular carcinoma.  

PubMed

The liver is the major organ for the metabolism of protein, fat and carbohydrate. A nutritional approach is required in the treatment of cirrhosis, which is frequently complicated with protein-energy malnutrition. Several advanced treatment approaches for hepatocellular carcinoma (HCC) have been established in the past decade. HCC is often complicated by cirrhosis, so treatment of the underlying liver diseases is also necessary to improve the prognosis. Branched-chain amino acid (BCAA) granules were developed originally for the treatment of hypoalbuminemia associated with decompensated cirrhosis. However, subsequent studies found various other pharmacological actions of this agent. We review the clinical significance of therapy using BCAA granules in patients receiving different treatment approaches for cirrhosis and HCC based on the published work as well as our own data. PMID:23819582

Nishikawa, Hiroki; Osaki, Yukio

2014-02-01

287

Assessment of Hemodynamics in a Rat Model of Liver Cirrhosis with Precancerous Lesions Using Multislice Spiral CT Perfusion Imaging  

PubMed Central

Rationale and Objectives. To develop an optimal scanning protocol for multislice spiral CT perfusion (CTP) imaging to evaluate hemodynamic changes in liver cirrhosis with diethylnitrosamine- (DEN-) induced precancerous lesions. Materials and Methods. Male Wistar rats were randomly divided into the control group (n = 80) and the precancerous liver cirrhosis group (n = 40). The control group received saline injection and the liver cirrhosis group received 50?mg/kg DEN i.p. twice a week for 12 weeks. All animals underwent plain CT scanning, CTP, and contrast-enhanced CT scanning. Scanning parameters were optimized by adjusting the diatrizoate concentration, the flow rate, and the delivery time. The hemodynamics of both groups was further compared using optimized multislice spiral CTP imaging. Results. High-quality CTP images were obtained with following parameters: 150?kV; 150?mAs; 5?mm thickness, 5?mm interval; pitch, 1; matrix, 512 × 512; and FOV, 9.6?cm. Compared to the control group, the liver cirrhosis group had a significantly increased value of the hepatic arterial fraction and the hepatic artery perfusion (P < 0.05) but significantly decreased hepatic portal perfusion and mean transit time (P < 0.05). Conclusion. Multislice spiral CTP imaging can be used to evaluate the hemodynamic changes in the rat model of liver cirrhosis with precancerous lesions.

Ma, Guolin; Bai, Rongjie; Jiang, Huijie; Ling, Zaisheng

2013-01-01

288

Automatic seed selection for segmentation of liver cirrhosis in laparoscopic sequences  

NASA Astrophysics Data System (ADS)

For computer aided diagnosis based on laparoscopic sequences, image segmentation is one of the basic steps which define the success of all further processing. However, many image segmentation algorithms require prior knowledge which is given by interaction with the clinician. We propose an automatic seed selection algorithm for segmentation of liver cirrhosis in laparoscopic sequences which assigns each pixel a probability of being cirrhotic liver tissue or background tissue. Our approach is based on a trained classifier using SIFT and RGB features with PCA. Due to the unique illumination conditions in laparoscopic sequences of the liver, a very low dimensional feature space can be used for classification via logistic regression. The methodology is evaluated on 718 cirrhotic liver and background patches that are taken from laparoscopic sequences of 7 patients. Using a linear classifier we achieve a precision of 91% in a leave-one-patient-out cross-validation. Furthermore, we demonstrate that with logistic probability estimates, seeds with high certainty of being cirrhotic liver tissue can be obtained. For example, our precision of liver seeds increases to 98.5% if only seeds with more than 95% probability of being liver are used. Finally, these automatically selected seeds can be used as priors in Graph Cuts which is demonstrated in this paper.

Sinha, Rahul; Marcinczak, Jan Marek; Grigat, Rolf-Rainer

2014-03-01

289

Nifedipine: kinetics and hemodynamic effects in patients with liver cirrhosis after intravenous and oral administration.  

PubMed

The pharmacokinetics and hemodynamic effects of nifedipine were studied in patients with liver cirrhosis and in age-matched healthy control subjects. In a randomized order each subject received nifedipine by intravenous infusion (4.5 mg in 45 minutes) and as a tablet (20 mg). After intravenous nifedipine patients had a longer elimination t1/2 (420 +/- 254 vs. 111 +/- 22 minutes; P less than 0.01), a greater volume of distribution (1.29 +/- 0.60 vs. 0.97 +/- 0.42 L/kg), and a lower systemic clearance (233 +/- 109 vs. 588 +/- 140 ml/min; P less than 0.001). Plasma protein binding of nifedipine was lower in the patients (P less than 0.001). After oral nifedipine systemic availability was much higher in patients (90.5% +/- 26.2% vs. 51.1% +/- 17.1%; P less than 0.01) and maximal in patients with a portacaval shunt. Blood pressure decreased and heart rate increased after intravenous nifedipine and these effects could be fitted to plasma concentrations by a sigmoidal model. Maximal effects on heart rate and diastolic blood pressure were not different in liver cirrhosis. When free drug levels were considered, the concentrations corresponding to half the maximal effect were also not different. Blood pressure changes with oral nifedipine were comparable with those after intravenous infusion. We conclude that in patients with liver cirrhosis the pharmacokinetics of nifedipine are considerably altered; dose reduction is recommended when such patients need oral nifedipine. PMID:3720176

Kleinbloesem, C H; van Harten, J; Wilson, J P; Danhof, M; van Brummelen, P; Breimer, D D

1986-07-01

290

[The blood level of gamma-aminobutyric acid in patients with liver cirrhosis and portacaval anastomosis].  

PubMed

Venous blood was collected from 21 patients with liver cirrhosis and portocaval anastomosis for routine laboratory tests and determination of GABA levels by radioreceptor assay. The patients additionally underwent psychometric tests for determining the degree of hepatic encephalopathy. No differences were seen in psychometric tests and laboratory parameters between patients and normals. However, GABA serum levels showed a 10-fold increase and the difference was highly significant. The fact that these patients did not show any signs of hepatic encephalopathy is probably due to an intact blood-brain barrier that prevents the uncontrolled influx of GABA. Therefore, not even high GABA serum levels are associated with symptoms of encephalopathy. PMID:1888423

Kretz, F J; Löscher, W; Dillinger, U

1991-01-01

291

Small intestinal transit in patients with liver cirrhosis and portal hypertension: a descriptive study  

PubMed Central

Background Gastrointestinal dysmotility may be involved in the development of bacterial translocation and infection in patients with liver cirrhosis. The aim of the present study was to describe gastric, small intestinal and colorectal motility and transit in patients with liver cirrhosis and portal hypertension using a magnet-based Motility Tracking System (MTS-1) and standard radiopaque markers. Methods We included 15 patients with liver cirrhosis (8 Child-Pugh A, 6 Child-Pugh B, and 1 Child-Pugh C) and portal hypertension (11 males, median age 54?years (range 38–73), median hepatic venous pressure gradient 18?mmHg (range 12–37)), and 18 healthy controls (8 males, median age 58?years (range 34–64)). The gastric emptying time and small intestinal motility were evaluated by MTS-1, and the total gastrointestinal transit time was assessed by radiopaque markers and abdominal radiographs. Results The velocity through the proximal small intestine was significantly higher in cirrhotic patients (median 1.27 metres (m)/hour, range 0.82–2.68) than in the healthy controls (median 1.00?m/hour, range 0.46–1.88) (p?=?0.03). Likewise, the magnet travelled significantly longer in both fast (p?=?0.04) and slow movements (p?=?0.05) in the patient group. There was no significant difference in either gastric emptying time—23?minutes (range 5–131) in patients and 29?minutes (range 10.5–182) in healthy controls (p?=?0.43)—or total gastrointestinal transit time—1.6?days (range 0.5–2.9) in patients and 2.0?days (range 1.0–3.9) in healthy controls (p?=?0.33). No correlation was observed between the hepatic venous pressure gradient and the velocity of the magnet through the small intestine. Conclusion Patients with liver cirrhosis and portal hypertension demonstrated faster-than-normal transit through the proximal small intestine. This may be due to an overactive bowel, as suggested by previous studies.

2012-01-01

292

Urinary Biomarkers of Acute Kidney Injury in Patients with Liver Cirrhosis  

PubMed Central

Acute kidney injury (AKI) is a common complication in cirrhotic patients. Serum creatinine is a poor biomarker for detection of renal impairment in cirrhotic patients. This study aimed to evaluate urinary neutrophil gelatinase-associated lipocalin (NGAL) and urinary interleukin-18 (IL-18) as early biomarkers of acute kidney injury in cirrhotic patients. 160 patients with cirrhosis admitted to the Liver Units at Zagazig University Hospitals were classified into three groups: (I) nonascitic patients, (II) ascitic patients without renal impairment, and (III) ascitic patients with renal impairment. Patients with renal impairment were further divided into four subgroups: [A] prerenal azotemia, [B] chronic kidney disease (CKD), [C] hepatorenal syndrome (HRS), and [D] acute tubular necrosis (ATN). Significant elevation of both urinary NGAL and urinary IL-18 in cirrhotic patients with renal impairment especially in patients with ATN was observed. Urinary NGAL and urinary IL-18 have the ability to differentiate between AKI types in patients with cirrhosis. This could improve risk stratification for patients admitted to the hospital with cirrhosis, perhaps leading to early ICU admission, transplant evaluation, and prompt initiation of HRS therapy and early management of AKI.

Qasem, Anass Ahmed; Farag, Salama Elsayed; Hamed, Emad; Emara, Mohamed; Bihery, Ahmed; Pasha, Heba

2014-01-01

293

A novel fibrosis index comprising a non-cholesterol sterol accurately predicts HCV-related liver cirrhosis.  

PubMed

Diagnosis of liver cirrhosis is essential in the management of chronic hepatitis C virus (HCV) infection. Liver biopsy is invasive and thus entails a risk of complications as well as a potential risk of sampling error. Therefore, non-invasive diagnostic tools are preferential. The aim of the present study was to create a model for accurate prediction of liver cirrhosis based on patient characteristics and biomarkers of liver fibrosis, including a panel of non-cholesterol sterols reflecting cholesterol synthesis and absorption and secretion. We evaluated variables with potential predictive significance for liver fibrosis in 278 patients originally included in a multicenter phase III treatment trial for chronic HCV infection. A stepwise multivariate logistic model selection was performed with liver cirrhosis, defined as Ishak fibrosis stage 5-6, as the outcome variable. A new index, referred to as Nordic Liver Index (NoLI) in the paper, was based on the model: Log-odds (predicting cirrhosis)?=?-12.17+ (age × 0.11) + (BMI (kg/m(2)) × 0.23) + (D7-lathosterol (?g/100 mg cholesterol)×(-0.013)) + (Platelet count (x10(9)/L) × (-0.018)) + (Prothrombin-INR × 3.69). The area under the ROC curve (AUROC) for prediction of cirrhosis was 0.91 (95% CI 0.86-0.96). The index was validated in a separate cohort of 83 patients and the AUROC for this cohort was similar (0.90; 95% CI: 0.82-0.98). In conclusion, the new index may complement other methods in diagnosing cirrhosis in patients with chronic HCV infection. PMID:24699777

Ydreborg, Magdalena; Lisovskaja, Vera; Lagging, Martin; Brehm Christensen, Peer; Langeland, Nina; Buhl, Mads Rauning; Pedersen, Court; Mørch, Kristine; Wejstål, Rune; Norkrans, Gunnar; Lindh, Magnus; Färkkilä, Martti; Westin, Johan

2014-01-01

294

A Novel Fibrosis Index Comprising a Non-Cholesterol Sterol Accurately Predicts HCV-Related Liver Cirrhosis  

PubMed Central

Diagnosis of liver cirrhosis is essential in the management of chronic hepatitis C virus (HCV) infection. Liver biopsy is invasive and thus entails a risk of complications as well as a potential risk of sampling error. Therefore, non-invasive diagnostic tools are preferential. The aim of the present study was to create a model for accurate prediction of liver cirrhosis based on patient characteristics and biomarkers of liver fibrosis, including a panel of non-cholesterol sterols reflecting cholesterol synthesis and absorption and secretion. We evaluated variables with potential predictive significance for liver fibrosis in 278 patients originally included in a multicenter phase III treatment trial for chronic HCV infection. A stepwise multivariate logistic model selection was performed with liver cirrhosis, defined as Ishak fibrosis stage 5–6, as the outcome variable. A new index, referred to as Nordic Liver Index (NoLI) in the paper, was based on the model: Log-odds (predicting cirrhosis)?=??12.17+ (age×0.11) + (BMI (kg/m2)×0.23) + (D7-lathosterol (?g/100 mg cholesterol)×(?0.013)) + (Platelet count (x109/L)×(?0.018)) + (Prothrombin-INR×3.69). The area under the ROC curve (AUROC) for prediction of cirrhosis was 0.91 (95% CI 0.86–0.96). The index was validated in a separate cohort of 83 patients and the AUROC for this cohort was similar (0.90; 95% CI: 0.82–0.98). In conclusion, the new index may complement other methods in diagnosing cirrhosis in patients with chronic HCV infection.

Ydreborg, Magdalena; Lisovskaja, Vera; Lagging, Martin; Brehm Christensen, Peer; Langeland, Nina; Buhl, Mads Rauning; Pedersen, Court; M?rch, Kristine; Wejstal, Rune; Norkrans, Gunnar; Lindh, Magnus

2014-01-01

295

Occult Hepatitis C Virus Infection in Candidates for Liver Transplant With Cryptogenic Cirrhosis  

PubMed Central

Background Occult hepatitis C virus (HCV) infection is a new entity described by the presence of HCV-RNA in liver biopsy and/or peripheral blood mononuclear cell (PBMC) specimens, and undetectable levels or absence of HCV-RNA and in the absence or presence of anti HCV antibodies in plasma by current laboratory methods. Objectives To evaluate the detection of HCV-RNA in PBMC specimens of the liver transplant candidates with cryptogenic cirrhosis by reverse transcriptase-nested polymerase chain reaction (RT-nested PCR). Patients and Methods From November 2007 to March 2013, 45 patients from Liver Transplant Center of Imam Khomeini Hospital, Tehran, were enrolled in this cross sectional study. PBMC specimens were separated from the peripheral blood sample. After extraction of RNA from plasma and PBMC specimens, HCV-RNA status was tested by RT-nested PCR. The 5?-untranslated region (5?-UTR) genotyping of HCV-RNA amplified from PBMC specimens was performed by a standard methodology with the INNO-LiPATM HCV II kit. The PCR products of 5?-UTR were sequenced after cloning into the pJET1.2 / blunt cloning vector. Results Of 45 patients, 4 (8.9% [95% CI: 4.4-15.6]) had detectable genomic HCV-RNA in their PBMC specimens. HCV genotypes were determined in the PBMCs of these subjects showed that 2 (50.0%) subjects with occult HCV infection had HCV subtype 3a, and 2 (50.0%) had HCV subtype 1b. Conclusions This study found that 8.9 % of the Iranian candidates for liver transplant with cryptogenic cirrhosis had occult HCV infection. Therefore, designing prospective studies focusing on the diagnosis of occult HCV infection in these subjects prior to liver transplantation could be valuable.

Keyvani, Hossein; Bokharaei-Salim, Farah; Monavari, Seyed Hamidreza; Esghaei, Maryam; Nassiri Toosi, Mohssen; Fakhim, Shahin; Sadigh, Zohreh Azita; Alavian, Seyed Moayed

2013-01-01

296

Hepatitis C-related liver cirrhosis - strategies for the prevention of hepatic decompensation, hepatocarcinogenesis, and mortality  

PubMed Central

Liver cirrhosis (LC) is a critical stage of chronic liver disease, including that caused by hepatitis C virus (HCV). In the absence of antiviral therapy, 67%-91% of patients with HCV-related LC patients die of liver-related causes, including hepatocellular carcinoma (HCC) and liver failure. Among the therapeutic strategies used to prevent liver-related complications in these patients is standard therapy with pegylated interferon and ribavirin, which induces a sustained virological response (SVR) in 25% of HCV genotype 1-infected patients and in 69% of patients infected with genotypes 2 and 3. SVR in patients with HCV-related LC has been associated with reduced rates of hepatic decompensation, HCC, and mortality. More recently developed direct-acting antiviral agents have shown excellent antiviral efficacy, with preliminary data demonstrating that an interferon-free regimen that includes these direct-acting antiviral agents achieved SVR in more than 50% of patients with HCV genotype 1 LC. Branched-chain amino acid supplementation, improvement of insulin resistance, and the use of ?-blockers for portal hypertension may also reduce liver-related complications. Here, we review advances in antiviral and adjunctive therapies for improved outcomes in patients with HCV-associated LC.

Toshikuni, Nobuyuki; Arisawa, Tomiyasu; Tsutsumi, Mikihiro

2014-01-01

297

Hepatitis C-related liver cirrhosis - strategies for the prevention of hepatic decompensation, hepatocarcinogenesis, and mortality.  

PubMed

Liver cirrhosis (LC) is a critical stage of chronic liver disease, including that caused by hepatitis C virus (HCV). In the absence of antiviral therapy, 67%-91% of patients with HCV-related LC patients die of liver-related causes, including hepatocellular carcinoma (HCC) and liver failure. Among the therapeutic strategies used to prevent liver-related complications in these patients is standard therapy with pegylated interferon and ribavirin, which induces a sustained virological response (SVR) in 25% of HCV genotype 1-infected patients and in 69% of patients infected with genotypes 2 and 3. SVR in patients with HCV-related LC has been associated with reduced rates of hepatic decompensation, HCC, and mortality. More recently developed direct-acting antiviral agents have shown excellent antiviral efficacy, with preliminary data demonstrating that an interferon-free regimen that includes these direct-acting antiviral agents achieved SVR in more than 50% of patients with HCV genotype 1 LC. Branched-chain amino acid supplementation, improvement of insulin resistance, and the use of ?-blockers for portal hypertension may also reduce liver-related complications. Here, we review advances in antiviral and adjunctive therapies for improved outcomes in patients with HCV-associated LC. PMID:24659879

Toshikuni, Nobuyuki; Arisawa, Tomiyasu; Tsutsumi, Mikihiro

2014-03-21

298

[Value of three-dimensional measurement of the caudate lobe in the diagnosis of liver cirrhosis by ultrasound].  

PubMed

To assess the changes of the caudate lobe in the sonographic diagnosis of liver cirrhosis, 96 patients were studied at the Hospital Vargas de Caracas. 27 with histologically proved cirrhosis. 43 with other disease (30 no related with liver and 13 with hepatic disease without cirrhosis, and 26 patients without clinical evidence of liver disease. The longitudinal (CL), transverse (CT), and anteroposterior (CAP) diameters of the caudate lobe and the transverse diameter of the right lobe (RL) were measured and one, two and three dimensional caudate lobe, indexes and ratios were calculated. The analysis of these criteria revealed that the ratio of the three dimensional caudate index (C13) to the right lobe diameter (C13)/RL = iCL x CT x CAP/RL was superior to all other calculated criteria. PMID:1843948

Urdaneta, C; Rodríguez, M; Veitía, G; Pernalete, B; Malaver, M; Khassale, M; Nardulli, G; Poleo, J R

1991-01-01

299

A Simple Noninvasive Score Based on Routine Parameters can Predict Liver Cirrhosis in Patients With Chronic Hepatitis C  

PubMed Central

Background Liver biopsy has remained the gold standard for the diagnosis of chronic hepatitis C; even though, it has a low but non-negligible rate of both false negative and complications. Several authors have proposed noninvasive tools to diagnose cirrhosis. But none of them showed complete concordance with liver biopsy. Objectives To devise a score based on noninvasive routine parameters that discriminate between patients with a high risk, and those with a low risk of cirrhosis among patients with chronic hepatitis C without performing liver biopsy, and to compare this score with other ones using routine parameters devoted to this aim. Patients and Methods We reviewed the charts of patients with chronic hepatitis C who performed a liver biopsy between 2000 and 2004. Multivariate analysis was used to identify independent predictors of cirrhosis. An independent group of patients with chronic hepatitis C admitted for a liver biopsy between 2007 and 2012 constituted the validation set. Results We enrolled 249 patients who had complete laboratoristic data, and sufficient liver tissue for fibrosis staging. Age, AST, prothrombin activity, and platelets were identified as independent predictors of histological cirrhosis. We categorized these variables, and devised a novel score called CISCUN (Cirrhosis Score University of Naples), giving one point to each of the following predictors: age > 40 years; AST > 2 upper normal values; platelet count < 160.000/mmc; prothrombin activity < 100%. Cirrhosis rate was 2.9% for the 103 patients with a CISCUN = 0 or 1, 23.4% for the 124 patients with a CISCUN of 2 or 3, and 86.4% for the 22 patients with a CISCUN = 4. These results were confirmed in the independent validation group of 285 patients with similar characteristics. Conclusions Patients with chronic hepatitis C and with a CISCUN ? 1 had a very low rate of cirrhosis while those with a CISCUN = 4 had a high risk of cirrhosis. Patients with CISCUN = 2 or 3 had an intermediate rate of cirrhosis, and therefore needed to perform a liver biopsy to receive a reliable diagnosis.

Gentile, Ivan; Coppola, Nicola; Pasquale, Giuseppe; Liuzzi, Raffaele; D'Armiento, Maria; Di Lorenzo, Maria Emma; Capoluongo, Nicolina; Buonomo, Antonio Riccardo; Sagnelli, Evangelista; Morisco, Filomena; Caporaso, Nicola; Borgia, Guglielmo

2013-01-01

300

Role of cystatin C and renal resistive index in assessment of renal function in patients with liver cirrhosis  

PubMed Central

AIM: To evaluate the clinical significance of cystatin C and renal resistive index for the determination of renal function in patients with liver cirrhosis. METHODS: We conducted a study of 63 patients with liver cirrhosis. A control group comprised of 30 age and gender-matched healthy persons. Serum cystatin C was determined in all study subjects and renal Doppler ultrasonography was made. Estimated glomerular filtration rate from serum creatinine (GFRCr) and cystatin C (GFRCys) was calculated. RESULTS: We confirmed significant differences in values of cystatin C between patients with different stages of liver cirrhosis according to Child-Pugh (P = 0.01), and a significant correlation with model of end stage liver disease (MELD) score (rs = 0.527, P < 0.001). More patients with decreased glomerular filtration rate were identified based on GFRCys than on GFRCr (P < 0.001). Significantly higher renal resistive index was noted in Child-Pugh C than in A (P < 0.001) and B stage (P = 0.001). Also, a significant correlation between renal resistive index and MELD score was observed (rs = 0.607, P < 0.001). Renal resistive index correlated significantly with cystatin C (rs = 0.283, P = 0.028) and showed a negative correlation with GFRCys (rs = -0.31, P = 0.016). CONCLUSION: Cystatin C may be a more reliable marker for assessment of liver insufficiency. Additionally, cystatin C and renal resistive index represent sensitive indicators of renal dysfunction in patients with liver cirrhosis.

Culafic, ?or?e; Stulic, Milos; Obrenovic, Radmila; Miletic, Danijela; Mijac, Dragana; Stojkovic, Milica; Jovanovic, Marija; Culafic, Milica

2014-01-01

301

Blood ammonia levels in liver cirrhosis: a clue for the presence of portosystemic collateral veins  

PubMed Central

Background Portal hypertension leads to the formation of portosystemic collateral veins in liver cirrhosis. The resulting shunting is responsible for the development of portosystemic encephalopathy. Although ammonia plays a certain role in determining portosystemic encephalopathy, the venous ammonia level has not been found to correlate with the presence or severity of this entity. So, it has become partially obsolete. Realizing the need for non-invasive markers mirroring the presence of esophageal varices in order to reduce the number of endoscopy screening, we came back to determine whether there was a correlation between blood ammonia concentrations and the detection of portosystemic collateral veins, also evaluating splenomegaly, hypersplenism (thrombocytopenia) and the severity of liver cirrhosis. Methods One hundred and fifty three consecutive patients with hepatic cirrhosis of various etiologies were recruited to participate in endoscopic and ultrasonography screening for the presence of portosystemic collaterals mostly esophageal varices, but also portal hypertensive gastropathy and large spontaneous shunts. Results Based on Child-Pugh classification, the median level of blood ammonia was 45 mcM/L in 64 patients belonging to class A, 66 mcM/L in 66 patients of class B and 108 mcM/L in 23 patients of class C respectively (p < 0.001). The grade of esophageal varices was concordant with venous ammonia levels (rho 0.43, p < 0.001). The best area under the curve was given by ammonia concentrations, i, e., 0.78, when comparing areas of ammonia levels, platelet count and spleen longitudinal diameter at ultrasonography. Ammonia levels predicted hepatic decompensation and ascites presence (Odds Ratio 1.018, p < 0.001). Conclusion Identifying cirrhotic patients with high blood ammonia concentrations could be clinically useful, as high levels would lead to suspicion of being in presence of collaterals, in clinical practice of esophageal varices, and pinpoint those patients requiring closer follow-up and endoscopic screening.

2009-01-01

302

Modulation of thioacetamide-induced liver fibrosis/cirrhosis by sildenafil treatment.  

PubMed

Sildenafil citrate is a phosphodiesterase-5 inhibitor, approved for the treatment of erectile dysfunction. It enhances nitric-oxide-induced vasodilatation and it promotes angiogenesis. A relationship between angiogenesis and hepatic fibrosis has long been speculated, where the 2 are believed to progress together. In this study, the ability of sildenafil (10 mg·(kg body mass)(-1), orally, once daily) to prevent and also reverse liver fibrosis/cirrhosis experimentally induced by thioacetamide injection (200 mg·kg(-1), intraperitoneal (i.p.), 3 times·week(-1)) in male Sprague-Dawley rats has been investigated. Sildenafil administration, either to prevent or to reverse liver fibrosis/cirrhosis significantly improved the estimated hepatic functions, reduced hepatic hydroxyproline and, in turn, hepatic collagen content, as well as reducing serum levels of the pro-fibrogenic mediator transforming growth factor ?1. In co-ordination with such improvement, fibrosis grades declined and fibrosis retracted. Herein, the observed results provide evidence for the potential therapeutic efficacy of sildenafil as an antifibrotic agent. PMID:24289076

Said, Eman; Said, Shehta A; Gameil, Nariman M; Ammar, Elsayed M

2013-12-01

303

Over-expression of c-raf-1 proto-oncogene in liver cirrhosis and hepatocellular carcinoma.  

PubMed

Liver cirrhosis accompanies at least 70% of hepatocellular carcinomas world-wide. To evaluate the dysregulation of apoptosis and the MAPK pathway in hepatocarcinogenesis, we investigated the expression profiles of the genes involved in apoptosis and MAPK pathway in cirrhosis and hepatocellular carcinoma. A total of 94 tissue specimens (61 cirrhosis and 33 hepatocellular carcinoma) obtained from 67 patients were analyzed by microarray, quantitative PCR and Western blot experiments. Of 71 apoptosis-associated genes, c-raf-1 and S6 were up-regulated in 42.9% and 32.1% of 28 cirrhosis tissues, respectively, and both genes were well correlated in a five-cluster K-means analysis. For c-raf-1 and down stream genes in the MAPK pathway, c-raf-1, MEK, and MAPK were up-regulated in 40%, 80%, and 86.7% of 45 cirrhosis specimens, respectively, and in 50%, 63.6%, and 59.1% of 22 hepatocellular carcinoma specimens, respectively. Western blot analysis showed that activated Raf-1 was over-expressed in 91.2% (52/57) of cirrhosis and in 100% (30/30) of hepatocellular carcinoma. The expression level of Raf-1 in 14 of 26 paired samples (53.8%) was significantly higher in hepatocellular carcinoma than in cirrhosis ( [Formula: see text] -fold, [Formula: see text] ). These results suggest that the activation of Raf-1 plays an important role in the development of hepatocellular carcinoma. PMID:15163433

Hwang, Yeo Hyeon; Choi, Jong Young; Kim, Soyoun; Chung, Eun Sun; Kim, Taeuk; Koh, Sang Seok; Lee, Bogman; Bae, Si Hyun; Kim, Jin; Park, Young Min

2004-06-01

304

Outcomes of autologous bone marrow mononuclear cell transplantation in decompensated liver cirrhosis  

PubMed Central

AIM: To determine the long-term efficacy of autologous bone marrow mononuclear cells (BM-MNCs) transplantation in terms of improving liver function and reducing complications in patients with decompensated cirrhosis. METHODS: A total of 47 inpatients with decompensated liver cirrhosis were enrolled in this trial, including 32 patients undergoing a single BM-MNCs transplantation plus routine medical treatment, and 15 patients receiving medical treatment only as controls. Forty-three of 47 patients were infected with hepatitis B virus. Bone marrow of 80-100 mL was obtained from each patient and the BM-MNCs suspension was transfused into the liver via the hepatic artery. The efficacy of BM-MNCs transplantation was monitored during a 24-mo follow-up period. RESULTS: Liver function parameters in the two groups were observed at 1 mo after BM-MNCs transfusion. Prealbumin level was 118.3 ± 25.3 mg/L vs 101.4 ± 28.7 mg/L (P = 0.047); albumin level was 33.5 ± 3.6 g/L vs 30.3 ± 2.2 g/L (P = 0.002); total bilirubin 36.9 ± 9.7 mmol/L vs 45.6 ± 19.9 mmol/L (P = 0.048); prothrombin time 14.4 ± 2.3 s vs 15.9 ± 2.8 s (P = 0.046); prothrombin activity 84.3% ± 14.3% vs 74.4% ± 17.8% (P = 0.046); fibrinogen 2.28 ± 0.53 g/L vs 1.89 ± 0.44 g/L (P = 0.017); and platelet count 74.5 ± 15.7 × 109/L vs 63.3 ± 15.7 × 109/L (P = 0.027) in the treatment group and control group, respectively. Differences were statistically significant. The efficacy of BM-MNCs transplantation lasted 3-12 mo as compared with the control group. Serious complications such as hepatic encephalopathy and spontaneous bacterial peritonitis were also significantly reduced in BM-MNCs transfused patients compared with the controls. However, these improvements disappeared 24 mo after transplantation. CONCLUSION: BM-MNCs transplantation is safe and effective in patients with decompensated cirrhosis. It also decreases the incidence of serious complications.

Bai, Yang-Qiu; Yang, Yu-Xiu; Yang, Ya-Ge; Ding, Song-Ze; Jin, Fang-Li; Cao, Ming-Bo; Zhang, Yan-Rui; Zhang, Bing-Yong

2014-01-01

305

Interleukin 10 promoter haplotype is associated with alcoholic liver cirrhosis in Taiwanese patients.  

PubMed

Alcoholic liver cirrhosis is a severe form of alcohol-related liver damage. More than 95% of heavy drinkers develop a fatty liver, but only 35% of them develop cirrhosis. We postulate that genetic factors may play a role in this difference. Genetic polymorphisms of the cytokine genes may influence Kupffer cells cytokine genes expression. In this study, we evaluated the promoter polymorphisms of interleukin (IL) 1?, IL 6, IL 10, and tumor necrosis factor alpha (TNF?) and aimed to clarify the association between the polymorphisms and the disease. Forty alcoholic patients with liver cirrhosis and 64 healthy volunteers were included in our investigation. Genotyping on IL 1? -511 T>C, IL 6 -572 G>C, IL 10 -819 C>T, IL 10 -1082 G>A, and TNF? -308 G>A was done. Another 36 patients with recurrent alcoholic pancreatitis were included as an additional control group. Genotyping on IL 10 -819 C>T and IL 10 -1082 G>A was done. The polymorphisms on IL 1 and IL 6 showed no significant association. The p value for TNF? -308 G>A was 0.028 in comparison with healthy volunteers. Although the p value was less than 0.05, it did not reach significance after Bonferroni correction. The p values for IL 10 -819 C>T and IL 10 -1082 G>A were respectively 0.031 and 0.026 in healthy volunteers and 0.028 and 0.023 in the alcoholic pancreatitis group. The results also did not reach significance after Bonferroni correction. Among the participants with the GCC haplotype, healthy volunteers had p = 0.027 (p < 0.05) and an odds ratio (OR) of 0.124 [confidence interval (95%) CI, 0.015-0.997], whereas the alcoholic pancreatitis group had p = 0.023 (p < 0.05) and an OR of 0.106 (95% CI, 0.012-0.912). The odds ratio of people having one ATA haplotype was 6.233 (95% CI, 0.739-52.547) in healthy volunteers and 6.588 (95% CI, 0.727-59.679) in the alcoholic pancreatitis group; the corresponding rate was 10.521 (95% CI, 1.252-88.440) and 12.833 (95% CI 1.408-117.008) for people with two ATA haplotypes. The p values in these groups were 0.031 (p < 0.05) and 0.028 (p < 0.05), respectively. The presence of a GCC haplotype could have protective effect against alcoholic liver disease, whereas the presence of an ATA haplotype could predispose carriers to the disease. The IL 10 promoter haplotype is associated with alcoholic liver cirrhosis in Taiwanese patients. PMID:24835349

Yang, An-Ming; Wen, Li-Li; Yang, Chang-Shyue; Wang, Sun-Chong; Chen, Chien-Sheng; Bair, Ming-Jong

2014-06-01

306

Primary liver carcinoma and liver cirrhosis in atomic bomb survivors, Hiroshima and Nagasaki, 1961-75, with special reference to hepatitis B surface antigen  

SciTech Connect

During 1961-75, 128 cases of primary liver carcinoma (PLC) in the Radiation Effects Research Foundation life-span study extended sample and 301 cases of liver cirrhosis in the pathology study sample were observed. The presence of hepatitis B surface antigen (HBsAg) was assessed in all of the cases with the use of orcein and aldehyde fuchsin stains and was confirmed by the immunofluorescence technique. The incidence of PLC was two times higher in Nagasaki than in Hiroshima, which was statistically significant, but little difference was noted in the prevalence of cirrhosis in the two cities. Findings that might possibly explain the higher PLC incidence in Nagasaki were 1) the 2.3 times higher presence in Nagasaki than in Hiroshima of HBsAg in the livers of subjects without liver disease and 2) the two times higher prevalence in Nagasaki than in Hiroshima of cirrhosis with PLC. We believe that the higher incidence of PLC in Nagasaki is attributable to hepatitis B virus infection, although other factors (e.g., immunologic competence affected by radiation) cannot be excluded. In both cities, a suggestive relationship of radiation dose to cirrhosis prevalence, but not to PCL prevalence, was noted. To clarify possible radiation effects on cirrhosis prevalence, further follow-up of the populations of these two cities is necessary.

Asano, M.; Kato, H.; Yoshimoto, K.; Seyama, S.; Itakura, H.; Hamada, T.; Iijima, S.

1982-12-01

307

Gene expression profiling of HCV genotype 3a initial liver fibrosis and cirrhosis patients using microarray  

PubMed Central

Background Hepatitis C virus (HCV) causes liver fibrosis that may lead to liver cirrhosis or hepatocellular carcinoma (HCC), and may partially depend on infecting viral genotype. HCV genotype 3a is being more common in Asian population, especially Pakistan; the detail mechanism of infection still needs to be explored. In this study, we investigated and compared the gene expression profile between initial fibrosis stage and cirrhotic 3a genotype patients. Methods Gene expression profiling of human liver tissues was performed containing more than 22000 known genes. Using Oparray protocol, preparation and hybridization of slides was carried out and followed by scanning with GeneTAC integrator 4.0 software. Normalization of the data was obtained using MIDAS software and Significant Microarray Analysis (SAM) was performed to obtain differentially expressed candidate genes. Results Out of 22000 genes studied, 219 differentially regulated genes found with P ? 0.05 between both groups; 107 among those were up-regulated and 112 were down-regulated. These genes were classified into 31 categories according to their biological functions. The main categories included: apoptosis, immune response, cell signaling, kinase activity, lipid metabolism, protein metabolism, protein modulation, metabolism, vision, cell structure, cytoskeleton, nervous system, protein metabolism, protein modulation, signal transduction, transcriptional regulation and transport activity. Conclusion This is the first study on gene expression profiling in patients associated with genotype 3a using microarray analysis. These findings represent a broad portrait of genomic changes in early HCV associated fibrosis and cirrhosis. We hope that identified genes in this study will help in future to act as prognostic and diagnostic markers to differentiate fibrotic patients from cirrhotic ones.

2012-01-01

308

Recurrent Primary Biliary Cirrhosis: Peritransplant Factors and Ursodeoxycholic Acid Treatment Post-Liver Transplant  

PubMed Central

Primary biliary cirrhosis (PBC) recurs after orthotopic liver transplantation (OLT) in up to one-third of patients. These patients are typically asymptomatic, can be identified by abnormal liver biochemistries, and have evidence of histologic recurrence on liver biopsy. The effect of treatment on recurrence has not been determined. This pilot study evaluates the factors associated with recurrent PBC and describes our experience using ursodeoxycholic acid treatment in this patient population. Forty-eight patients with PBC were followed for at least 1 yr post-OLT, and 27 patients (56%) developed abnormal serum alkaline phosphatase. Seventeen patients (35%) had evidence of recurrent PBC by liver biopsy. Patients with recurrent PBC had a trend toward longer warm ischemia times and more episodes of acute cellular rejection in the first year posttransplant, but this was not significant in multivariate analysis. Donor or recipient age, donor and recipient cytomegalovirus status, and dose of immunosuppression did not correlate with recurrence of PBC. Those patients diagnosed with recurrent PBC were placed on ursodeoxycholic acid, 15 mg/kg daily, with improvement in serum alkaline phosphatase in the majority. In conclusion, recurrent PBC is not infrequent post-OLT, and ursodeoxycholic acid can be used with some benefit post-OLT. Treatment effects on long-term survival are not known.

Guy, Jennifer E.; Qian, Peiqing; Lowell, Jeffrey A.; Peters, Marion G.

2014-01-01

309

A patient with Simpson-Golabi-Behmel syndrome, biliary cirrhosis and successful liver transplantation.  

PubMed

Simpson-Golabi-Behmel syndrome type 1 (SGBS1) -OMIM 312870- is a rare X-linked inherited overgrowth syndrome caused by a loss of function mutation in the GPC3 gene. Affected patients present a variable phenotype with pre- and post-natal macrosomia, distinctive facial dysmorphism, organomegaly, and multiple congenital anomalies. Intellectual disability is not constant. About 10% of patients have an increased risk of developing embryonic tumors in early childhood. Only one case of biliary disease has been described so far. GPC3 is localized on Xq26. It encodes for glypican 3, a heparan sulfate proteoglycan, which among its different known roles, negatively regulates liver regeneration and hepatocyte proliferation. This report concerns a male with a SGBS1, carrier of a GPC3 pathogenic mutation, and neonatal liver disease, who developed an early biliary cirrhosis. Together with the associated risk of cancer and developmental delay, liver transplantation was discussed and then successfully performed at the age of 19 months. A hypothesis on the role of GPC3 in the patient's liver disease is also proposed. PMID:24357529

Jedraszak, Guillaume; Girard, Muriel; Mellos, Antonio; Djeddi, Djamal-Dine; Chardot, Christophe; Vanrenterghem, Audrey; Moizard, Marie-Pierre; Gondry, Jean; Sevestre, Henri; Mathieu-Dramard, Michele; Lacaille, Florence; Demeer, Benedicte

2014-03-01

310

Amelioration of carbon tetrachloride-induced cirrhosis and portal hypertension in rat using adenoviral gene transfer of Akt  

PubMed Central

AIM: To investigate whether a virus constitutively expressing active Akt is useful to prevent cirrhosis induced by carbon tetrachloride (CCl4). METHODS: Using cre-loxp technique, we created an Ad-myr-HA-Akt virus, in which Akt is labeled by a HA tag and its expression is driven by myr promoter. Further, through measuring enzyme levels and histological structure, we determined the efficacy of this Ad-myr-HA-Akt virus in inhibiting the development of cirrhosis induced by CCl4 in rats. Lastly, using western blotting, we examined the expression levels and/or phosphorylation status of Akt, apoptotic mediators, endothelial nitric oxide synthase (eNOS), and markers for hepatic stellate cells activation to understand the underlying mechanisms of protective role of this virus. RESULTS: The Ad-myr-HA-Akt virus was confirmed using polymerase chain reaction amplification of inserted Akt gene and sequencing for full length of inserted fragment, which was consistent with the sequence reported in the GenBank. The concentrations of Ad-myr-HA-Akt and adenoviral enhanced green fluorescent protein (Ad-EGFP) virus used in the current study were 5.5 × 1011 vp/mL. The portal vein diameter, peak velocity of blood flow, portal blood flow and congestion index were significantly increased in untreated, saline and Ad-EGFP cirrhosis groups when compared to normal control after the virus was introduced to animal through tail veil injection. In contrast, these parameters in the Akt cirrhosis group were comparable to normal control group. Compared to the normal control, the liver function (Alanine aminotransferase, Aspartate aminotransferase and Albumin) was significantly impaired in the untreated, saline and Ad-EGFP cirrhosis groups. The Akt cirrhosis group showed significant improvement of liver function when compared to the untreated, saline and Ad-EGFP cirrhosis groups. The Hyp level and portal vein pressure in Akt cirrhosis groups were also significantly lower than other cirrhosis groups. The results of HE and Van Gieson staining indicated that Akt group has better preservation of histological structure and less fibrosis than other cirrhosis groups. The percentage of apoptotic cell was greatly less in Akt cirrhosis group than in other cirrhosis groups. Akt group showed positive HA tag and an increased level of phosphorylated Akt as well as decreased levels of Fas. In contrast, Caspase-3 and Caspase-9 levels in Akt group were significantly lower than other cirrhosis groups. Noticeable decrease of DR5 and ?-SMA and increase of phosphorylated eNOS were observed in the Akt group when compared to other cirrhosis groups. The NO level in liver was significantly higher in Akt group than other cirrhosis groups, which was consistent with the level of phosphorylated eNOS in these groups. CONCLUSION: This study suggest that Ad-myr-HA-Akt virus is a useful tool to prevent CCl4-induced cirrhosis in rat model and Akt pathway may be a therapeutic target for human cirrhosis.

Deng, Gang; Huang, Xiang-Jun; Luo, Hong-Wu; Huang, Fei-Zhou; Liu, Xun-Yang; Wang, Yong-Heng

2013-01-01

311

Polymorphisms in the DNA repair gene XRCC1 and susceptibility to alcoholic liver cirrhosis in older Southeastern Brazilians  

Microsoft Academic Search

The population of Southeastern Brazil has a very high mortality rate from liver cirrhosis, a disease that is considered an irreversible pre-malignant condition. This is largely due to the high prevalence of alcohol abuse in the region. Chronic alcohol consumption is associated with the production of free radical intermediates that can cause several DNA lesions. Reduced repair of these DNA

Andréa Regina B. Rossit; Isabel Rosa Cabral; Christine Hackel; Rita de Cássia M. A. da Silva; N??vea D. T. Conforti Froes; Sherif Z. Abdel-Rahman

2002-01-01

312

S-Adenosylmethionine in alcoholic liver cirrhosis: a randomized, placebo-controlled, double-blind, multicenter clinical trial  

Microsoft Academic Search

Background\\/Aim: The efficacy of S-adenosylmethionine (AdoMet) in the treatment of liver cell injury has been demonstrated in several experimental models. The aim of this study was to investigate the effects of AdoMet treatment in human alcoholic liver cirrhosis.Methods: A randomized, double-blind trial was performed in 123 patients treated with AdoMet (1200 mg\\/day, orally) or placebo for 2 years. All patients

Jose M Mato; Javier Cámara; Javier Fernández de Paz; Llorenç Caballería; Susana Coll; Antonio Caballero; Luisa García-Buey; Joaquín Beltrán; Vicente Benita; Joan Caballería; Ricard Solà; Ricardo Moreno-Otero; Félix Barrao; Antonio Martín-Duce; Jose A Correa; Albert Parés; Elena Barrao; Inmaculada García-Magaz; Jose Luis Puerta; Jorge Moreno; Gabrielle Boissard; Pablo Ortiz; Joan Rodés

1999-01-01

313

Prevalence of pre-transplant electrocardiographic abnormalities and post-transplant cardiac events in patients with liver cirrhosis  

PubMed Central

Background Although cardiovascular disease is thouht to be common in cirrhosis, there are no systematic investigations on the prevalence of electrocardiographic (ECG) abnormalities in these patients and data on the occurrence of post-transplant cardiac events in comparison with the general population are lacking. We aimed to study the prevalence and predictors of ECG abnormalities in patients with cirrhosis undergoing liver transplantation and to define the risk of cardiac events post-transplant compared to the general population. Methods Cirrhotic patients undergoing first-time liver transplantation between 1999–2007 were retrospectively enrolled. ECGs at pre-transplant evaluation were reviewed using the Minnesota classification and compared to healthy controls. Standardized incidence ratios for post-transplant cardiac events were calculated. Results 234 patients with cirrhosis were included, 186 with an available ECG (36% with alcoholic and 24% with viral cirrhosis; mean follow-up 4 years). Cirrhotics had a prolonged QTc interval, a Q wave, abnormal QRS axis deviation, ST segment depression and a pathologic T wave more frequently compared to controls (p?cirrhosis severity and etiology were related to ECG abnormalities. Compared to the general Swedish population, patients were 14 times more likely to suffer a cardiac event post-transplant (p?cirrhosis and are associated with cardiovascular risk factors and cirrhosis severity and etiology. Post-transplant cardiac events are more common than in the general population.

2014-01-01

314

Transjugular intrahepatic portosystemic shunt in refractory chylothorax due to liver cirrhosis  

PubMed Central

A pleural effusion containing chylomicrons is termed chylothorax and results from leakage of lymph fluid into the pleural cavity. We report on the case of a 59-year-old woman with severe dyspnea due to a large chylothorax. She was known to have liver cirrhosis but no ascites. There was no history of trauma, cardiac function was normal and thorough diagnostic work-up did not reveal any signs of malignancy. In summary, no other etiology of the chylothorax than portal hypertension could be found. Therapy with diuretics as well as parenteral feeding failed to relieve symptoms. After a transjugular intrahepatic portosystemic shunt (TIPS) had successfully been placed, pleural effusion decreased considerably. Eight months later, TIPS revision had to be performed because of stenosis, resulting in remission from chylothorax. This case shows that even in the absence of ascites, chylothorax might be caused by portal hypertension and that TIPS can be an effective treatment option.

Lutz, Philipp; Strunk, Holger; Schild, Hans Heinz; Sauerbruch, Tilman

2013-01-01

315

Management of ascites in patients with liver cirrhosis: recent evidence and controversies.  

PubMed

Ascites formation in patients with cirrhosis, portal hypertension, or both usually results from hyperdynamic circulatory dysfunction, where the retention of sodium and water is associated with the activation of the sympathetic and renin-angiotensin-aldosterone systems. The presence of ascites indicates the development of liver decompensation. Furthermore, complications seen in conjunction with ascites such as spontaneous bacterial peritonitis, hepatorenal syndrome, and hepatic hydrothorax may result in increased morbidity and mortality. Although nonpharmacological, pharmacological, and surgical approaches have been introduced and clinically practiced, their therapeutic effects are still suboptimal or limited by their potential side effects, such as large-volume paracentesis-induced postparacentesis circulatory dysfunction. Herein, we discuss strategies to prevent and properly manage ascites-related complications, including a review of the literature and controlled studies that assess these strategies. PMID:23497963

Hsu, Shao-Jung; Huang, Hui-Chun

2013-03-01

316

Relation of different grades of esophageal varices with Child-Pugh classes in cirrhosis of liver.  

PubMed

This cross-sectional observational study was conducted in the Department of Medicine, Mymensingh Medical College Hospital, Mymensingh, Bangladesh over a period of 6 months from October 2011 to April 2012 and was carried out to evaluate the relation of different grades of esophageal varices with Child-Pugh classes of cirrhosis of liver patients. A total 37 patients were included. Child-Pugh score and esophageal varices of each patient were noted. Relation was carried out using the Chi-square test through determining the association of different variables. P value <0.05 was considered significant. Among 37 patients, 27(73%) were male and 10(27%) were female and their frequency of age were found, 7(18.9%) from 18-38 years, 18(48.7%) from 39-59 years and 12(32.4%) from 60 years of age and above. The etiology of liver cirrhosis revealed 18(48.7%) hepatitis B virus, 3(8.1%) hepatitis C virus and 16(43.2%) others causes. Child-Pugh classes were observed 3(8.2%) Class A, 17(45.9%) Class B and 17(45.9%) Class C and grades of esophageal varies were 13(35.1%) F1, 20(54.1%) F2 and 4(10.8%) F3 patients among total. A statistically significant positive relation was found that higher grade of esophageal varices was seen in the more advanced class of Child-Pugh classes with a p value 0.001. PMID:23416806

Sumon, S M; Sutradhar, S R; Chowdhury, M; Khan, N A; Uddin, M Z; Hasan, M I; Rozana, F K; Haque, M F; Barman, T K; Ferdous, J

2013-01-01

317

Site-specific Glycoforms of Haptoglobin in Liver Cirrhosis and Hepatocellular Carcinoma*  

PubMed Central

Haptoglobin is a liver-secreted glycoprotein with four N-glycosylation sites. Its glycosylation was reported to change in several cancer diseases, which prompted us to examine site-specific glycoforms of haptoglobin in liver cirrhosis and hepatocellular carcinoma. To this end, we have used two-dimensional separation composed of hydrophilic interaction and nano-reverse phase chromatography coupled to QTOF mass spectrometry of the enriched glycopeptides. Our results show increased fucosylation of haptoglobin in liver disease with up to six fucoses associated with specific glycoforms of one glycopeptide. Structural analysis using exoglycosidase treatment and MALDI-MS/MS of detached permethylated glycans led to the identification of Lewis Y-type structures observed particularly in the pooled hepatocellular carcinoma sample. To confirm the increase of the Lewis Y structures observed by LC-MS, we have used immunoaffinity detection with Lewis Y-specific antibodies. The presence of multiply fucosylated Lewis Y glycoforms of haptoglobin in the disease context could have important functional implications.

Pompach, Petr; Brnakova, Zuzana; Sanda, Miloslav; Wu, Jing; Edwards, Nathan; Goldman, Radoslav

2013-01-01

318

Imatinib-induced liver cirrhosis in a patient with advanced gastrointestinal stroma tumor (GIST)  

PubMed Central

Background The use of imatinib mesylate is associated with a progression free survival of 41?months in first line treatment of metastatic or locally advanced gastrointestinal stromal tumors (GIST) and other studies approved that adjuvant imatinib treatment improves the recurrence-free survival in patients with GIST. Current recommendations include 1?year adjuvant treatment in GIST patients at risk but active studies explore different durations of treatment with an interval of up to 5?years. While the most frequent adverse events (AEs) are blood count alterations, abdominal discomfort and edema, the occurrence of grade 3 or 4 increase of AST or ALT is specified with 2.1% and 2.7% respectively. Case presentation We report a 49-year old male with a gastrointestinal stromal tumor (GIST) of the small bowel who developed liver cirrhosis under adjuvant imatinib treatment. Conclusions Our report supports the notion that imatinib-induced hepatotoxicity may lead to acute liver damage with subsequent cirrhotic remodelling. Patients developing grade 3 or 4 hepatotoxicity during imatinib treatment should therefore be carefully evaluated for chronic liver disease.

2012-01-01

319

[Exocrine function of the pancreas in patients with chronic hepatitis and liver cirrhosis of various etiologies].  

PubMed

Exocrinous performance of the pancreatic gland under secretin-pancreozymin stimulation was studied in 76 patients with chronic diffuse diseases of the liver who were distinguished into 6 groups: those who suffered from chronic persistent hepatitis of viral and alcohol origin, chronic active hepatitis of viral origin, cirrhosis of the liver of viral and alcohol origin, primary biliary hepatocirrhosis. The results obtained were correlated with those from 11 normal persons (controls). Out of 76 examinees the disorders of exocrinous performance of the pancreatic gland were revealed in 75 persons. The most characteristic features were: a decrease in the basal and an increase in the stimulated volume of the pancreatic juice; a reduction of both basal and stimulated production of bicarbonates; a decrease in the trypsin and amylase fasting levels and their increment in the stimulated juice of the pancreatic gland. Disorder in the production of bicarbonates was stated as a most characteristic feature in the patients both with viral and alcohol origin of the disease but it was mostly manifest in the patients with hepatocirrhosis. Pronounced elevation of the activity of amylase and trypsin in the pancreatic juice was observed in patients with very high activity of disease development and in the patients who continuously used large amounts of alcohol. The authors suspected that alcohol abuse and the effect of hepatitis virus had an equal pathogenic impact on the liver and pancreatic gland. PMID:8145501

Kataev, S S; Vasil'eva, N S; Avdeev, V G; Gil'var, L L; Starodvortseva, V G; Za?rat'iants, O V

1993-01-01

320

Mechanisms of fibrogenesis in liver cirrhosis: The molecular aspects of epithelial-mesenchymal transition  

PubMed Central

Liver injuries are repaired by fibrosis and regeneration. The cause of fibrosis and diminished regeneration, especially in liver cirrhosis, is still unknown. Epithelial-mesenchymal transition (EMT) has been found to be associated with liver fibrosis. The possibility that EMT could contribute to hepatic fibrogenesis reinforced the concept that activated hepatic stellate cells are not the only key players in the hepatic fibrogenic process and that other cell types, either hepatic or bone marrow-derived cells could contribute to this process. Following an initial enthusiasm for the discovery of this novel pathway in fibrogenesis, more recent research has started to cast serious doubts upon the real relevance of this phenomenon in human fibrogenetic disorders. The debate on the authenticity of EMT or on its contribution to the fibrogenic process has become very animated. The overall result is a general confusion on the meaning and on the definition of several key aspects. The aim of this article is to describe how EMT participates to hepatic fibrosis and discuss the evidence of supporting this possibility in order to reach reasonable and useful conclusions.

Lee, Sun-Jae; Kim, Kyung-Hyun; Park, Kwan-Kyu

2014-01-01

321

Mechanisms of fibrogenesis in liver cirrhosis: The molecular aspects of epithelial-mesenchymal transition.  

PubMed

Liver injuries are repaired by fibrosis and regeneration. The cause of fibrosis and diminished regeneration, especially in liver cirrhosis, is still unknown. Epithelial-mesenchymal transition (EMT) has been found to be associated with liver fibrosis. The possibility that EMT could contribute to hepatic fibrogenesis reinforced the concept that activated hepatic stellate cells are not the only key players in the hepatic fibrogenic process and that other cell types, either hepatic or bone marrow-derived cells could contribute to this process. Following an initial enthusiasm for the discovery of this novel pathway in fibrogenesis, more recent research has started to cast serious doubts upon the real relevance of this phenomenon in human fibrogenetic disorders. The debate on the authenticity of EMT or on its contribution to the fibrogenic process has become very animated. The overall result is a general confusion on the meaning and on the definition of several key aspects. The aim of this article is to describe how EMT participates to hepatic fibrosis and discuss the evidence of supporting this possibility in order to reach reasonable and useful conclusions. PMID:24799989

Lee, Sun-Jae; Kim, Kyung-Hyun; Park, Kwan-Kyu

2014-04-27

322

Presence of Anti-Microbial Antibodies in Liver Cirrhosis - A Tell-Tale Sign of Compromised Immunity?  

PubMed Central

Background Bacterial translocation plays important role in the complications of liver cirrhosis. Antibody formation against various microbial antigens is common in Crohn's disease and considered to be caused by sustained exposure to gut microflora constituents. We hypothesized that anti-microbial antibodies are present in patients with liver cirrhosis and may be associated with the development of bacterial infections. Methodology/Principal Findings Sera of 676 patients with various chronic liver diseases (autoimmune diseases:266, viral hepatitis C:124, and liver cirrhosis of different etiology:286) and 100 controls were assayed for antibodies to Saccharomyces cerevisiae(ASCA) and to antigens derived from two intestinal bacterial isolates (one gram positive, one gram negative, neither is Escherichia coli). In patients with liver cirrhosis, we also prospectively recorded the development of severe episodes of bacterial infection. ASCA and anti-OMP Plus™ antibodies were present in 38.5% and 62.6% of patients with cirrhosis and in 16% and 20% of controls, respectively (p<0.001). Occurrence of these antibodies was more frequent in cases of advanced cirrhosis (according to Child-Pugh and MELD score; p<0.001) or in the presence of ascites (p<0.001). During the median follow-up of 425 days, 81 patients (28.3%) presented with severe bacterial infections. Anti-microbial antibody titers (p?=?0.003), as well as multiple seroreactivity (p?=?0.036), was associated with infectious events. In logistic regression analysis, the presence of ascites (OR:1.62, 95%CI:1.16–2.25), co-morbidities (OR:2.22, 95%CI:1.27–3.86), and ASCA positivity (OR:1.59, 95%CI:1.07–2.36) were independent risk factors for severe infections. A shorter time period until the first infection was associated with the presence of ASCA (p?=?0.03) and multiple seropositivity (p?=?0.037) by Kaplan-Meier analysis, and with Child-Pugh stage (p?=?0.018, OR:1.85) and co-morbidities (p<0.001, OR:2.02) by Cox-regression analysis. Conclusions/Significance The present study suggests that systemic reactivity to microbial components reflects compromised mucosal immunity in patients with liver cirrhosis, further supporting the possible role of bacterial translocation in the formation of anti-microbial antibodies.

Papp, Maria; Norman, Gary L.; Vitalis, Zsuzsanna; Tornai, Istvan; Altorjay, Istvan; Foldi, Ildiko; Udvardy, Miklos; Shums, Zakera; Dinya, Tamas; Orosz, Peter; Lombay, Bela; Par, Gabriella; Par, Alajos; Veres, Gabor; Csak, Timea; Osztovits, Janos; Szalay, Ferenc; Lakatos, Peter Laszlo

2010-01-01

323

Efficacy and safety of tauroursodeoxycholic acid in the treatment of liver cirrhosis: a double-blind randomized controlled trial.  

PubMed

No direct comparison of tauroursodeoxycholic acid (TUDCA) and ursodeoxycholic acid (UDCA) has yet been carried out in the treatment of liver cirrhosis in China. We designed a double-blind randomized trial to evaluate the potential therapeutic efficacy of TUDCA in liver cirrhosis, using UDCA as parallel control. The enrolled 23 patients with liver cirrhosis were randomly divided into TUDCA group (n=12) and UDCA group (n=11), and given TUDCA and UDCA respectively at the daily dose of 750 mg, in a randomly assigned sequence for a 6-month period. Clinical, biochemical and histological features, and liver ultrasonographic findings were evaluated before and after the study. According to the inclusion criteria, 18 patients were included in the final analysis, including 9 cases in both two groups. Serum ALT, AST and ALP levels in TUDCA group and AST levels in UDCA group were significantly reduced as compared with baseline (P<0.05). Serum albumin levels were significantly increased in both TUDCA and UDCA groups (P<0.05). Serum markers for liver fibrosis were slightly decreased with the difference being not significant in either group. Only one patient in TUDCA group had significantly histological relief. Both treatments were well tolerated and no patient complained of side effects. It is suggested that TUDCA therapy is safe and appears to be more effective than UDCA in the treatment of liver cirrhosis, particularly in the improvement of the biochemical expression. However, both drugs exert no effect on the serum markers for liver fibrosis during 6-month treatment. PMID:23592128

Pan, Xiao-li; Zhao, Li; Li, Liang; Li, Ai-hua; Ye, Jin; Yang, Ling; Xu, Ke-shu; Hou, Xiao-hua

2013-04-01

324

Long-term clinical and virological outcome after liver transplantation for cirrhosis caused by chronic delta hepatitis.  

PubMed

Liver transplantation for liver diseases related to hepatitis B virus (HBV) and hepatitis delta virus (HDV) remains problematic because of the risk of viral recurrence. We report here the long-term virological outcome of patients transplanted for HDV-related liver cirrhosis (HDV cirrhosis). From December 1984 to December 1990, 76 patients with HDV cirrhosis underwent liver transplantation. Before transplantation, all the patients were HBsAg-positive/anti-HDV positive, and all but one were HBV DNA-negative by dot blot hybridization. HDV RNA was detected by HDV RT-PCR and liver HDAg by fluorescent HDV Ab. After transplantation, all the patients except four received continuous long-term anti-HBs passive immunoprophylaxis. The actuarial 5-year survival was 88%. All patients who did not receive anti-HBs immunoprophylaxis remained HBsAg-positive and developed hepatitis. Among the 68 patients receiving antiHBs immunoprophylaxis with a minimum follow-up of 2 months, HBsAg reappeared in 7 (10.3%) after a mean of 17 months. These seven patients developed hepatitis, with simultaneous HBV and HDV replication; and four cleared later HBsAg. Patients without HBV reinfection were studied for HDV reinfection: liver HD Ag or serum HDV RNA were present in 88% of the patients during the first year, without developing hepatitis; however, they were no longer detectable after 2 years in 95% of the patients. In conclusion, liver transplantation for HDV cirrhosis gives good results, with a 5-year actuarial survival of 88%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7843702

Samuel, D; Zignego, A L; Reynes, M; Feray, C; Arulnaden, J L; David, M F; Gigou, M; Bismuth, A; Mathieu, D; Gentilini, P

1995-02-01

325

Hepatocellular carcinoma and synchronous liver metastases from colorectal cancer in cirrhosis: A case report.  

PubMed

A 68-year-old Caucasian man with hepatitis C virus-related cirrhosis was admitted to our Unit in February 2010 for a diagnostic evaluation of three centimetric hypoechoic focal liver lesions detected by regular surveillance ultrasound. The subsequent computer tomography (CT) led to a diagnosis of unifocal hepatocellular carcinoma (HCC) in VI hepatic segment, defined the other two nodules in the VI and VII segment as suspected metastases, and showed a luminal narrowing with marked segmental circumferential thickening of the hepatic flexure of the colon. Colonoscopy detected an ulcerated, bleeding and stricturing lesion at the hepatic flexure, which was subsequently defined as adenocarcinoma with a moderate degree of differentiation at histological examination. Finally, ultrasound-guided liver biopsy of the three focal liver lesions confirmed the diagnosis of HCC for the nodule in the VI segment, and characterized the other two lesions as metastases from colorectal cancer. The patient underwent laparotomic right hemicolectomy with removal of thirty-nine regional lymph nodes (three of them tested positive for metastasis at histological examination), and simultaneous laparotomic radio-frequency ablation of both nodule of HCC and metastases. The option of adjuvant chemotherapy was excluded because of the post-surgical onset of ascites. Abdomen CT and positron emission tomography/CT scans performed after 1, 6 and 12 mo highlighted a complete response to treatments without any radiotracer accumulation. After 18 mo, the patient died due to progressive liver failure. Our experience emphasizes the potential coexistence of two different neoplasms in a cirrhotic liver and the complexity in the proper diagnosis and management of the two tumours. PMID:24409337

Maida, Marcello; Macaluso, Fabio Salvatore; Galia, Massimo; Cabibbo, Giuseppe

2013-12-27

326

Translating and testing the Liver Disease Symptom Index 2.0 for administration to people with liver cirrhosis in Egypt.  

PubMed

The Liver Disease Symptom Index (LDSI) 2.0 is a simple, short and specific liver disease questionnaire in English, but an Arabic version does not exist, therefore we translated the LDSI-2.0 into Arabic and tested its psychometric properties in a pilot cross-sectional study. A convenience sample of 38 patients with liver cirrhosis from one hospital in Cairo, Egypt, were interviewed for approximately 45 min. Patients completed a background data sheet, the translated LDSI-2.0 and the Short Form (SF)-36v(2). Construct convergent validity was examined by correlating LDSI-2.0 items with the SF-36v(2) eight domains. Reliability was estimated using measures of internal consistency, test-retest reliability and internal consistency reliability. Median completion time was 10 min. The correlation between the translated LDSI-2.0 items and the SF-36 domains confirmed that there was moderate to high overlapping between the two measures, suggesting convergent validity of the LDSI-2.0. The LDSI-2.0 showed good to very good retest reliability (kappa value 0.62-0.94). Chronbach's alpha coefficient for the multi-item scales ranged from 0.73 to 0.96. The Arabic LDSI-2.0 therefore has satisfactory validity, retest reliability and internal consistency. PMID:22845641

Youssef, Naglaa F A; Shepherd, Ashley; Evans, Josie M M; Wyke, Sally

2012-08-01

327

THE NATURAL HISTORY OF NONALCOHOLIC FATTY LIVER DISEASE WITH ADVANCED FIBROSIS OR CIRRHOSIS: AN INTERNATIONAL COLLABORATIVE STUDY  

PubMed Central

Information on the long-term prognosis of nonalcoholic fatty liver disease (NAFLD) is limited. We sought to describe the long-term morbidity and mortality of patients with NAFLD with advanced fibrosis or cirrhosis. We conducted this prospective cohort study including 247 patients with NAFLD and 264 patients with HCV infection that were either naïve or non-responders to treatment. Both cohorts were Child-Pugh class A and had advanced (stage 3) fibrosis or cirrhosis (stage 4) confirmed by liver biopsy at enrolment. In the NAFLD cohort, followed-up for 85.6 months mean (range 6-297), there were 48 (19.4%) liver-related complications and 33 (13.4%) deaths or liver transplants. In the HCV cohort, followed-up for 74.9 months mean (range 6-238), there were 47 (16.7%) liver-related complications and 25 (9.4%) deaths or liver transplants. When adjusting for baseline differences in age and gender, the cumulative incidence of liver-related complications was lower in the NAFLD than the HCV cohort (p=0.03), including incident hepatocellular cancer (6 vs 18; p=0.03), but that of cardiovascular events (p=0.17) and overall mortality (p=0.6) was similar in both groups. In the NAFLD cohort, platelet count, stage 4 fibrosis, and serum levels of cholesterol and ALT were associated with liver-related complications; an AST/ALT ratio >1 and older age were associated with overall mortality; and higher serum bilirubin levels and stage 4 fibrosis were associated with liver-related mortality. Conclusions Patients with NAFLD with advanced fibrosis or cirrhosis have lower rates of liver-related complications and hepatocellular cancer than corresponding patients with HCV infection, but similar overall mortality. Some clinical and laboratory features predict outcomes in patients with NAFLD.

Bhala, Neeraj; Angulo, Paul; van der Poorten, David; Lee, Eric; Hui, Jason M.; Saracco, Giorgio; Adams, Leon A.; Charatcharoenwitthaya, Punchai; Topping, Joanne H.; Bugianesi, Elisabetta; Day, Christopher P.; George, Jacob

2011-01-01

328

Naringenin-Loaded Nanoparticles Improve the Physicochemical Properties and the Hepatoprotective Effects of Naringenin in Orally-Administered Rats with CCl 4 Induced Acute Liver Failure  

Microsoft Academic Search

Purpose  A novel naringenin-loaded nanoparticles system (NARN) was developed to resolve the restricted bioavailability of naringenin\\u000a (NAR) and to enhance its hepatoprotective effects in vivo on oral administration.\\u000a \\u000a \\u000a \\u000a Materials and methods  Physicochemical characterizations of NARN included assessment of particle size and morphology, powder X-ray diffraction, fourier\\u000a transform infrared spectroscopy, and dissolution study. In addition, to evaluate its bioactivities and its oral treatment

Feng-Lin Yen; Tzu-Hui Wu; Liang-Tzung Lin; Thau-Ming Cham; Chun-Ching Lin

2009-01-01

329

Structural characteristics of oversulfated chondroitin/dermatan sulfates in the fibrous lesions of the liver with cirrhosis.  

PubMed

The structural characteristics of oversulfated chondroitin/dermatan sulfates (C/DSs) in the fibrous lesions of the rat liver with cirrhosis were examined. Long-Evans Cinnamon rats were subjected to the present study as the model animals with cirrhosis. The serial polyester wax sections of liver with cirrhosis were processed into the fibrous lesions and the nonfibrous lesions. The oversulfated C/DSs in the tissue sections on a glass slide were degraded to unsaturated disaccharides by chondroitinase ABC and ACII digestion in the presence of bacterial collagenase. Subsequently, the resulting unsaturated disaccharides were determined by the reversed-phase ion-pair high-performance liquid chromatography with fluorometric postcolumn derivatization using 2-cyanoacetamide as a reagent. Through these in situ investigations, we found some facts as follows: (i) in the fibrous lesion, the remarkable increase of the oversulfated C/DSs content and the decrease of the oversulfation degree of the C/DSs were observed compared with those in the nonfibrous lesion, (ii) the proportion of the iduronic acid content in the C/DSs in the fibrous lesion was significantly low compared with that in the nonfibrous lesion, and (iii) in the nonfibrous lesion close to the fibrous lesion, both quantitative and qualitative alterations of C/DSs were not observed at all. These findings indicate that the oversulfated C/DSs with low iduronic acid content are possible marker for the fibrogenesis of liver with cirrhosis. PMID:10510272

Koshiishi, I; Takenouchi, M; Imanari, T

1999-10-15

330

Branched-chain amino acid supplementation reduces oxidative stress and prolongs survival in rats with advanced liver cirrhosis.  

PubMed

Long-term supplementation with branched-chain amino acids (BCAA) is associated with prolonged survival and decreased frequency of development of hepatocellular carcinoma (HCC) in patients with liver cirrhosis. However, the pharmaceutical mechanism underlying this association is still unclear. We investigated whether continuous BCAA supplementation increases survival rate of rats exposed to a fibrogenic agent and influences the iron accumulation, oxidative stress, fibrosis, and gluconeogenesis in the liver. Further, the effects of BCAA on gluconeogenesis in cultured cells were also investigated. A significant improvement in cumulative survival was observed in BCAA-supplemented rats with advanced cirrhosis compared to untreated rats with cirrhosis (P<0.05). The prolonged survival due to BCAA supplementation was associated with reduction of iron contents, reactive oxygen species production and attenuated fibrosis in the liver. In addition, BCAA ameliorated glucose metabolism by forkhead box protein O1 pathway in the liver. BCAA prolongs survival in cirrhotic rats and this was likely the consequences of reduced iron accumulation, oxidative stress and fibrosis and improved glucose metabolism in the liver. PMID:23936183

Iwasa, Motoh; Kobayashi, Yoshinao; Mifuji-Moroka, Rumi; Hara, Nagisa; Miyachi, Hirohide; Sugimoto, Ryosuke; Tanaka, Hideaki; Fujita, Naoki; Gabazza, Esteban C; Takei, Yoshiyuki

2013-01-01

331

Plasma gelsolin protein: a candidate biomarker for hepatitis B-associated liver cirrhosis identified by proteomic approach  

PubMed Central

Background. Despite the significant improvement in internal medicine and supportive therapy in recent years, liver fibrosis/cirrhosis remains a serious health issue in hepatitis B virus (HBV) infected patients. Invasive liver biopsy is presently the best means of diagnosing cirrhosis, but it carries a significant risk and has well recognised limitations such as sampling error, hence the importance in developing early diagnosis biomarkers. With this aim, we performed a pilot proteomic study to assess this as a strategy for plasma marker detection in patients suffering from HBV-associated liver cirrhosis. Methods. Plasma from eight chronic HBV-infection patients and from eight HBV-related cirrhotic patients were selected and proteome profiles were created by two-dimensional electrophoresis. The strategy included the use of ProteoMiner enrichment kit for the reduction of highly abundance proteins (e.g. albumin and IgG) prior to proteomic analyses with the goal to improve detection of novel candidate markers. Results. One reproducible spot was found to be completely repressed in plasma samples from cirrhotic patients and mass spectrometry analysis identified this a specific variant of the gelsolin actin-depolymerizing factor. Though further investigations are needed, especially in term of clinical validation, to our knowledge this is the first time that gelsolin is proposed as potential biomarker in HBV-related liver pathologies. Conclusions. Our findings confirm the potential utility of gelsolin either as a prognostic marker or a replacement therapeutic agent to alleviate liver injury.

Marrocco, Cristina; Rinalducci, Sara; Mohamadkhani, Ashraf; D'Amici, Gian Maria; Zolla, Lello

2010-01-01

332

Possible enhancing effect of the immunosuppressive agent, 6-mercaptopurine(6-MP) on focal lesion development in cirrhotic liver induced by carbon tetrachloride but not furfural in F344 rats.  

PubMed

The modifying effects of an immunosuppressive agent, 6-mercaptopurine (6-MP), on development of focal lesions in liver cirrhosis models induced by carbon tetrachloride (CCl4) or furfural were studied in male F344 rats. Feeding of 6-MP at 50 p.p.m. for 20 weeks to animals with pre-existing liver cirrhosis caused immunosuppression, and significantly enhanced the induction of gamma-glutamyltranspeptidase (GGT)-positive foci and nodules in the CCl4 but not furfural case. Glutathione S-transferase P (GST-P)-positive preneoplastic lesions were not affected. Moreover, phenobarbital (PB) also enhanced the induction of GGT-positive hepatocellular lesions only in the CCl4-induced liver cirrhosis model, no promotion influence being exerted after treatment with the non-carcinogenic furfural. This study, therefore, suggests that 6-MP can enhance the induction of one type of preneoplastic foci and nodules and that essential differences exist between focal lesions arising in cirrhotic livers caused by CCl4 as opposed to furfural. PMID:1354082

Maruyama, H; Amanuma, T; Takashima, Y; Yoshiji, H; Nakae, D; Tsutsumi, M; Tsujiuchi, T; Denda, A; Konishi, Y

1992-08-01

333

Systemic Inflammatory Response Syndrome and MELD Score in Hospital Outcome of Patients with Liver Cirrhosis  

PubMed Central

BACKGROUND The evidence saying that the rate of Systemic Inflammatory Response Syndrome (SIRS) is high in patients with advanced cirrhosis and portal hypertension, this could have negative outcome on patients prognosis. METHODS This prospective study included 109 cirrhotic patients who were admitted to Imam Khomeini Hospital, affiliated with Orumieh University of Medical Sciences, during 2011-2012. The presence of SIRS and the model for end stage liver disease (MELD) were assessed on admission and during the hospital stay. SIRS was considered positive if patients had two or more of the following: temperature of >38ºC or <36ºC; heart rate >90 beats/min; respiratory rate >20/min or PaCO2 <32 mmHg or the use of mechanical ventilation; WBC >12000/mm3 or <4000/mm3 or more than 10% immature neutrophil count. MELD was calculated as: MELD = 3.8 [Ln serum bilirubin (mg/dl)] +11.2 [Ln INR] +9.6 [Ln serum creatinine (mg/dl)] +6.4. Hospital outcome was defined as death or hospital discharge. RESULTS A total of 109 cirrhotic patients between the ages of 14 to 84 (mean: 54.6 ±18.4) years were included. There were 65 (59%) male patients. Of the 109 patients, 76 (69.8%) were SIRS-negative and 33 (30.2%) were SIRS-positive. The mean calculated MELD score for all patients was 15.5. There was a correlation noted between SIRS and high serum creatinine levels (p=0.01) and between SIRS and a high MELD score (p=0.00). During follow-up 19 (17.4%) patients died. SIRS was correlated with death (p<0.00) on multivariate analysis, SIRS was independently associated with hospital death. CONCLUSION SIRS is a relatively frequent event in cirrhotic patients admitted to referral centers. It is closely related to the severity of liver disease as shown by the MELD score. SIRS independently and adversely affects the in-hospital outcome in patients with liver cirrhosis.

Behroozian, Ramin; Bayazidchi, Mehrdad; Rasooli, Javad

2012-01-01

334

Intestinal permeability and complications in liver cirrhosis: A prospective cohort study.  

PubMed

Aim:? Increased intestinal permeability (IP) has been implicated as an important factor for bacterial translocation (BT), leading to bacteremia and endotoxemia, resulting in various septic complications, variceal bleeding (VB), hepatic encephalopathy (HE), hepatorenal syndrome (HRS) and death in patients with liver cirrhosis (LC). This study was planned to assess IP in patients with LC and follow them for the occurrence of complications. Methods:? Patients with Child B and C cirrhosis without a history of disease-related complications were followed up for 6?months. IP was measured by lactulose and mannitol excretion ratio (LMR) in patients and 50 healthy controls (HC). Serum endotoxin levels were also assessed in 48 patients and 20 HC. Results:? Eighty patients (74 male), 41 (51.3%) Child B and 56 (70%) Child C, with a mean age of 40.7?±?9.8?years were enrolled. IP was increased in 28 (35%) patients. LMR of patients was higher than HC (patients vs HC?=?0.0238 [0.0010-1.557] vs 0.0166 [0.0018-0.720]; P?=?0.007]. No significant difference was seen in the LMR of patients among various Child classes and etiologies. Serum endotoxin levels (GMU/mL) were higher in patients than HC (patients vs HC?=?1.42 [0.68-2.13] vs 0.994 [0.067-1.382]; P?=?0.001), but comparable between patients with abnormal and normal IP. At follow up, there was no significant difference in the incidence of complications like spontaneous bacterial peritonitis, HRS, VB, HE and death between patients with abnormal and normal IP. Conclusion:? IP was increased in 35% of patients with LC; however, it was not associated with a higher incidence of disease-related complications. PMID:22726344

Benjamin, Jaya; Singla, Vikas; Arora, Indu; Sood, Seema; Joshi, Yogendra Kumar

2013-02-01

335

Glycyrrhizinate reduces portal hypertension in isolated perfused rat livers with chronic hepatitis  

PubMed Central

AIM: To investigate the effects of diammonium glycyrrhizinate (Gly) on portal hypertension (PHT) in isolated portal perfused rat liver (IPPRL) with carbon tetrachloride (CCl4)-induced chronic hepatitis. METHODS: PHT model was replicated with CCl4 in rats for 84 d. Model was identified by measuring the ascetic amounts, hepatic function, portal pressure in vivo, splenic index, and pathological alterations. Inducible nitric oxide synthase (iNOS) in liver was assessed by immunohistochemistry. IPPRLs were performed at d0, d28, d56, and d84. After phenylephrine-induced constriction, Gly was geometrically used to reduce PHT. Gly action was expressed as median effective concentration (EC50) and area under the curve (AUC). Underlying mechanism was exploited by linear correlation between AUC values of Gly and existed iNOS in portal triads. RESULTS: PHT model was confirmed with ascites, splenomegaly, serum biomarkers of hepatic injury, and elevated portal pressure. Pathological findings had shown normal hepatic structure at d0, degenerations at d28, fibrosis at d56, cirrhosis at d84 in PHT rats. Pseudo lobule ratios decreased and collagen ratios increased progressively along with PHT development. Gly does dose-dependently reduce PHT in IPPRLs with CCl4-induced chronic hepatitis. Gly potencies were increased gradually along with PHT development, characterized with its EC50 at 2.80 × 10-10, 3.03 × 10-11, 3.77 × 10-11 and 4.65×10-11 mol/L at d0, d28, d56 and d84, respectively. Existed iNOS was located at hepatocyte at d0, stellate cells at d28, stellate cells and macrophages at d56, and macrophages in portal triads at d84. Macrophages infiltrated more into portal triads and expressed more iNOS along with PHT development. AUC values of Gly were positively correlated with existed iNOS levels in portal triads. CONCLUSION: Gly reduces indirectly PHT in IPPRL with CCl4-induced chronic hepatitis. The underlying mechanisms may relate to rescue NO bioavailability from macrophage-derived peroxynitrite in portal triads.

Zhao, Xin; Deng, Bo; Xu, Xue-Yan; Yang, Shi-Jun; Zhang, Tao; Song, Yi-Jun; Liu, Xiao-Ting; Wang, Yue-Qi; Cai, Da-Yong

2013-01-01

336

Detection of alcohol consumption in patients with alcoholic liver cirrhosis during the evaluation process for liver transplantation.  

PubMed

Alcoholic liver cirrhosis (ALC) is a commonly accepted indication for liver transplantation (LT). Any alcohol consumption is considered a contraindication for LT. However, the assessment of abstinence in everyday practice mostly relies on patient self-reporting, which must be considered highly unreliable. After consumption, ethanol is eliminated by alcohol dehydrogenase, with methanol accumulating in the blood. Methanol, which is known to be a sensitive and specific indicator for recent alcohol consumption, has not been used for verifying alcohol consumption in LT assessments yet. Therefore, the purpose of this study was to test the feasibility of using methanol testing to identify recent alcohol consumption in LT candidates during routine and short-notice appointments. We compared methanol and ethanol measurements with self-reported alcohol consumption for 41 patients with ALC during the evaluation process before they were accepted onto the waiting list. In 32 of the 92 blood samples drawn from these 41 patients during the study, a relapse was detected by the methanol test. Both the ethanol test results and the self-reported data were positive in only 3 cases. Thus, the methanol test identified 29 additional cases of alcohol consumption. Furthermore, the methanol test discovered recent alcohol consumption in 5 of 10 transplant patients when both self-reported data and ethanol test results were negative. As a part of blood alcohol analysis, the methanol test is more sensitive than self-reporting and ethanol testing for the detection of recent alcohol consumption. Also, short-notice appointments for blood alcohol analysis reveal more cases of alcohol relapse than routine, long-term appointments. The measurement of methanol as a sensitive screening test for recent alcohol consumption should be implemented both in law and in daily, routine practice. Liver Transpl 18:1310-1315, 2012. © 2012 AASLD. PMID:22577089

Hempel, Johann-Martin; Greif-Higer, Gertrud; Kaufmann, Thomas; Beutel, Manfred E

2012-11-01

337

Enhanced synthesis and reduced metabolism of endothelin-1 (ET1) by hepatocytes - an important mechanism of increased endogenous levels of ET1 in liver cirrhosis  

Microsoft Academic Search

Background\\/Aims: Hepatic concentration of endothelin-1 (ET-1) is increased in human and experimental liver cirrhosis. Because of its potent actions in the liver, ET-1 has been suggested to play an important role in the pathophysiology of cirrhosis. Since hepatocytes are the major cell type to metabolize ET-1, we investigated whether their reduced capacity to degrade ET-1 is a mechanism of its

Ruhul H Kuddus; Michael A Nalesnik; Vladimir M Subbotin; Abdul S Rao; Chandrashekhar R Gandhi

2000-01-01

338

Effect of chronic administration of sildenafil on sodium retention and on the hemodynamic complications associated with liver cirrhosis in the rat  

Microsoft Academic Search

Previous studies demonstrated increased phosphodiesterase-5 (PDE5) activity and expression in the kidneys of rats with liver cirrhosis. Acute intravenous administration of PDE5 inhibitors enhanced sodium excretion in these rats. The aim of the present study was to examine the effects of chronic administration of sildenafil on renal sodium handling and hemodynamics in rats with liver cirrhosis. Male Sprague–Dawley rats underwent

Rana Ghali-Ghoul; Rima Tahseldar-Roumieh; Ramzi Sabra

2007-01-01

339

The development of low-grade cerebral edema in cirrhosis is supported by the evolution of 1H-magnetic resonance abnormalities after liver transplantation  

Microsoft Academic Search

Background\\/Aims: Liver failure may cause brain edema through an increase in brain glutamine. However, usually standard neuroimaging techniques do not detect brain edema in cirrhosis. We assessed magnetization transfer ratio and 1H-magnetic resonance (MR) spectroscopy before and after liver transplantation to investigate changes in brain water content in cirrhosis.Methods: Non-alcoholic cirrhotics without overt hepatic encephalopathy (n=24) underwent 1H-MR of the

Juan Córdoba; Juli Alonso; Alex Rovira; Carlos Jacas; Francesc Sanpedro; Llu??s Castells; V??ctor Vargas; Carles Margarit; Jaime Kulisewsky; Rafael Esteban; Jaume Guardia

2001-01-01

340

Hyperreninemic hypoaldosteronism syndrome, plasma concentrations of interleukin-6 and outcome in critically ill patients with liver cirrhosis  

Microsoft Academic Search

Objective  To investigate the relation between the adrenal production of gluco- and mineralocorticoids, the inflammatory status and the\\u000a outcome in critically ill patients with liver cirrhosis.\\u000a \\u000a \\u000a \\u000a Design  Prospective descriptive study.\\u000a \\u000a \\u000a \\u000a Setting  Medical intensive care unit (ICU) in a university hospital.\\u000a \\u000a \\u000a \\u000a Patients  Fifty consecutive patients with liver cirrhosis.\\u000a \\u000a \\u000a \\u000a Interventions  A corticotropin stimulation test within 12?h following ICU admission. Plasma cortisol concentration was measured before and\\u000a after the test.

Damien du Cheyron; Bruno Bouchet; Brigitte Cauquelin; Damien Guillotin; Michel Ramakers; Cédric Daubin; Jean-Jacques Ballet; Pierre Charbonneau

2008-01-01

341

Risk factors for alcohol relapse after liver transplantation for alcoholic cirrhosis in Japan.  

PubMed

Alcoholic liver cirrhosis (ALC) is an established indication for liver transplantation (LT). Most LT procedures in Japan are living donor liver transplantation (LDLT) because of an extreme shortage of deceased donors. Social circumstances enabling LDLT could be favorable for preventing relapse. The aims of this retrospective study were to analyze the outcomes of LDLT for ALC and to evaluate risk factors for relapse in this cohort. One hundred ninety-five subjects underwent LT [LDLT (n = 187), deceased donor LT (n = 5), or domino LT (n = 3)] for ALC in Japan from November 1997 to December 2011. Risk factors for alcohol relapse and the impact of relapse on outcomes were analyzed for 140 patients after the exclusion of 26 patients who died in the hospital and 29 patients without information about alcohol relapse. The incidence of alcohol consumption after LT was 22.9%. The risk factors for patient survival were a donor age ? 50 years (P < 0.01) and a Model for End-Stage Liver Disease score ? 19 (P = 0.03). The 10-year patient survival rates were 21.9% and 73.8% for patients who had relapsed and patients who had not relapsed 18 months after LT, respectively (P = 0.01). The relapse rates were 50.0%, 34.5%, 13.3%, 19.7%, and 14.3% for patients who had received livers from parents, siblings, spouses, sons/daughters, and deceased or domino donors, respectively. A history of treatment for psychological diseases other than alcoholism before LT was a significant indicator for the risk of recidivism (P = 0.02), and noncompliance with clinic visits after LT and smoking after transplantation were promising indicators for the risk of recidivism (P = 0.06, and P = 0.05, respectively). Preoperative alcohol consumption was not a risk factor. In conclusion, rather than selecting patients on the basis of preoperative alcohol use, we should provide sociomedical support to improve adherence after LT for ALC in Japan. PMID:24470014

Egawa, Hiroto; Nishimura, Katsuji; Teramukai, Satoshi; Yamamoto, Masakazu; Umeshita, Koji; Furukawa, Hiroyuki; Uemoto, Shinji

2014-03-01

342

Hyponatremia in cirrhosis and end-stage liver disease: treatment with the vasopressin V?-receptor antagonist tolvaptan.  

PubMed

Hyponatremia is common in patients with cirrhosis and portal hypertension, and is characterized by excessive renal retention of water relative to sodium due to reduced solute-free water clearance. The primary cause is increased release of arginine vasopressin. Hyponatremia is associated with increased mortality in cirrhotic patients, those with end-stage liver disease (ESLD) on transplant waiting lists, and, in some studies, posttransplantation patients. Clinical evidence suggests that adding serum sodium to model for ESLD (MELD) scoring identifies patients in greatest need of liver transplantation by improving waiting list mortality prediction. Hyponatremia is also associated with numerous complications in liver disease patients, including severe ascites, hepatic encephalopathy, infectious complications, renal impairment, increased severity of liver disease in cirrhosis, and increased hospital stay and neurologic/infectious complications posttransplant. Vasopressin receptor antagonists, which act to increase free water excretion (aquaresis) and thereby increase serum sodium concentration, have been evaluated in patients with hypervolemic hyponatremia (including cirrhosis and heart failure) and euvolemic hyponatremia (SIADH). Tolvaptan, a selective vasopressin V(2)-receptor antagonist, is the only oral agent in this class approved for raising sodium levels in hypervolemic and euvolemic hyponatremia. The SALT trials showed that tolvaptan treatment rapidly and effectively resolved hyponatremia in these settings, including cirrhosis, and it has been shown that this agent can be safely and effectively used in long-term treatment. Fluid restriction should be avoided during the first 24 h of treatment to prevent overly rapid correction of hyponatremia, and tolvaptan should not be used in patients who cannot sense/respond to thirst, anuric patients, hypovolemic patients, and/or those requiring urgent intervention to raise serum sodium acutely. PMID:22732834

Gaglio, Paul; Marfo, Kwaku; Chiodo, Joseph

2012-11-01

343

Antioxidant effects of insulin-like growth factor-I (IGF-I) in rats with advanced liver cirrhosis  

Microsoft Academic Search

BACKGROUND: The exogenous administration of Insulin-like Growth Factor-I (IGF-I) induces hepatoprotective and antifibrogenic actions in experimental liver cirrhosis. To better understand the possible pathways behind the beneficial effect of IGF-I, the aim of this work was to investigate severe parameters involved in oxidative damage in hepatic tissue from cirrhotic animals treated with IGF-I (2 ?g. 100 g-1. day-1). Iron and

María García-Fernández; Inma Castilla-Cortázar; Matías Díaz-Sanchez; Iñigo Navarro; Juan Enrique Puche; Alberto Castilla; Amelia Díaz Casares; Encarna Clavijo; Salvador González-Barón

2005-01-01

344

The Role of Fas/Fas Ligand System in the Pathogenesis of Liver Cirrhosis and Hepatocellular Carcinoma  

PubMed Central

Background The Fas receptor/ligand system including soluble forms is the most important apoptotic initiator in the liver. Dysregulation of this pathway may contribute to abnormal cell proliferation and cell death and is regarded as one of the mechanisms preventing the immune system from rejecting the tumor cells. Objectives To analyze the role of Fas system Fas/ Fas ligand (Fas/ FasL) in the multi-step process of hepatic fibrosis/carcinogenesis, and to use of the serum markers as possible candidate biomarkers for early detection of hepatocellular carcinoma (HCC). Patients and Methods Ninety patients were enrolled: 30 cases of chronic hepatitis C (CHC) without cirrhosis, 30 cases of CHC with liver cirrhosis, and 30 cases of HCC and hepatitis V virus (HCV) infection. Ten wedge liver biopsies, taken during laparoscopic cholecystectomy, were served as normal controls. Serum soluble Fas (sFas) levels were measured using ELISA technique; Fas and FasL proteins were detected in hepatic tissue by indirect Immuno-histochemical technique (IHC); electron microscopic (EM) and immune electron microscopic examinations were performed for detection of Fas expression on lymphocytes. Results Hepatic expression of both Fas and FasL as well as expression of Fas on separated lymphocytes were significantly increased in the diseased groups (P < 0. 01) compared to the control specimens. The highest expression was noticed in CHC specimens, particularly with the necro-inflammatory activity and advancement of the fibrosis. The sFas in cirrhotic patients and HCC were significantly higher than that in normal controls and CHC without cirrhosis group (P < 0.01). Conclusions Apoptosis and the Fas system were significantly involved in the process of converting liver cirrhosis into hepatocellular carcinoma. Down-regulation of Fas expression, up regulation of FasL expression in hepatocytes, and elevation of serum sFas levels were important in tumor evasion from immune surveillance, and in hepatic carcinogenesis.

Hammam, Olfat; Mahmoud, Ola; Zahran, Manal; Aly, Sohair; Hosny, Karim; Helmy, Amira; Anas, Amgad

2012-01-01

345

von Willebrand factor as new noninvasive predictor of portal hypertension, decompensation and mortality in patients with liver cirrhosis.  

PubMed

von Willebrand factor antigen (vWF-Ag) is elevated in patients with liver cirrhosis, but the clinical significance is unclear. We hypothesized that vWF-Ag levels may correlate with portal pressure, measured by hepatic venous pressure gradient (HVPG), and predict clinically significant portal hypertension (CSPH; HVPG ? 10 mmHg), decompensation and mortality. Portal hemodynamics were assessed by HVPG measurement, whereas vWF-Ag levels were measured by enzyme-linked immunosorbent assay. During follow-up, complications of liver cirrhosis, death or transplantation were recorded. Two hundred and eighty-six patients (205 male and 81 female; mean age, 56 years) with liver cirrhosis were included. vWF-Ag correlated with HVPG (r = 0.69; P < 0.0001) and predicted CSPH independently of Child Pugh score. Higher vWF-Ag levels were associated with varices (odds ratio [OR] = 3.27; P < 0.001), ascites (OR = 3.93; P < 0.001) and mortality (hazard ratio: 4.41; P < 0.001). Using a vWF-Ag cut-off value of ? 241%, the AUC for detection of CSPH in compensated patients was 0.85, with a positive predictive value and negative predictive value of 87% and 80%, respectively. Compensated patients had 25% mortality after 53 months if the vWF-Ag was <315% compared to 15 months in patients with vWF-Ag >315% (P < 0.001). Decompensated patients had a mortality of 25% after 37 and 7 months if their vWF-Ag was <315% and >315%, respectively (P = 0.002). In compensated patients with a vWF-Ag >315% median time to decompensation or death was 32 months compared with 59 months in patients with vWF-Ag <315%. vWF-Ag equals Model for End-Stage Liver Disease (MELD) in mortality prediction (area under the curve [AUC] = 0.71 for vWF-Ag versus AUC = 0.65 for MELD; P = 0.2). Conclusion: vWF-Ag is a new, simple and noninvasive predictor of CSPH. A vWF-Ag cut-off value at 315% can clearly stratify patients with compensated and decompensated liver cirrhosis in two groups with completely different survival. vWF-Ag may become a valuable marker for the prediction of mortality in patients with liver cirrhosis in clinical practice. PMID:22532296

Ferlitsch, Monika; Reiberger, Thomas; Hoke, Matthias; Salzl, Petra; Schwengerer, Bernadette; Ulbrich, Gregor; Payer, Berit Anna; Trauner, Michael; Peck-Radosavljevic, Markus; Ferlitsch, Arnulf

2012-10-01

346

Symptoms and distress among patients with liver cirrhosis but without hepatocellular carcinoma in Taiwan.  

PubMed

A cross-sectional study design was used to assess the items and frequency of physical symptoms and psychological distress among patients with liver cirrhosis (LC) but without hepatocellular carcinoma. Inpatients with LC were recruited from a medical center in northern Taiwan. Informants were asked to describe their frequency of symptoms and distress at 2 weeks before admission. During August 2008 and July 2009, 49 patients participated. The symptoms and distress were moderate, with a mean of 3.9 and 4.2 of 7, respectively. The mean ranking of subscales from the highest to lowest was abdominal symptoms, fatigue, fluid retention, loss of appetite, systemic symptoms, decreased attention, and bleeding. Symptoms and distress were significantly correlated (r = .59). The total scores of symptoms and distress were not associated with causes of the disease (p = .7644, p = .8548, respectively), disease severity (p = .7203, p = .3354, respectively), disease duration (p = .5820, p = .8184, respectively), or previous admission (p = .3094, p = .7365, respectively), but decreased attention was significantly associated with disease severity (p = .0317) and systemic symptoms were significantly associated with disease duration (p = .0267). The study found that physical symptoms and psychological distress are multidimensional and highly correlated. Our findings can be used to develop a symptom management program to relieve discomfort and indirectly improve the quality of life for individuals with LC. PMID:24476834

Tsai, Li-Hung; Lin, Chang-Ming; Chiang, Shu-Chen; Chen, Chia-Ling; Lan, Su-Jane; See, Lai-Chu

2014-01-01

347

Pseudomonas aeruginosa bacteremia in patients with liver cirrhosis: a comparison with bacteremia caused by Enterobacteriaceae  

PubMed Central

Background This study was performed to detect risk factors for Pseudomonas aeruginosa bacteremia in patients with liver cirrhosis. Methods A retrospective case–control study was designed to identify risk factors for P. aeruginosa bacteremia in cirrhotic patients. The cases were cirrhotic patients with P. aeruginosa bacteremia and the controls were cirrhotic patients with Enterobacteriaceae bacteremia. Results Sixty-one cases and the same number of controls were enrolled. In a multivariate analysis, younger age {adjusted odds ratio (aOR) per one year: 0.96, 95% confidence interval: 0.93 - 0.99}, nosocomial acquisition (aOR 3.87, 95% confidence interval: 1.50 - 9.94), preexisting biliary disease (aOR 4.79, 95% confidence interval: 1.92 - 10.47), and recent exposure to immunosuppressive agent (aOR 3.10, 95% confidence interval: 1.23 - 7.82) were associated with P. aeruginosa bacteremia. In the case group the frequency of appropriate initial antibiotic regimens was considerably lower than in the control group: 29.5% vs. 65.6% (P <0.01). However, thirty day mortality did not differ significantly between cases and controls (19.7% vs. 24.6%). Conclusions Nosocomial acquisition, preexisting biliary disease, and recent use of immunosuppressive agents are strong predictive factors for P. aeruginosa bacteremia in cirrhotic patients.

2013-01-01

348

Altered potassium homeostasis in cirrhosis of the liver and Crohn's disease  

SciTech Connect

In the course of patients (pts) with cirrhosis of the liver (Ci) and Crohn's disease (CD) frequently noticed arrhythmias of the heart, weakness and adynamic ileus suggest alterations in the potassium (K) homeostasis. It is the purpose of the study to assess the role of Na/sup +/-K/sup +/ pump mechanism in intracellular and extracellular K homeostasis. Relative total body potassium (TBK), serum potassium (K-S), and the number of red blood cell ouabain binding sites (n-ATPase) was studied in 21 pts with Ci, 31 pts with CD and in 31 controls (C), all were not on digitalis. TBK was measured by equilibrium binding of H-3-ouabain. A significant reduction in TBK was accompanied by normal serum potassium levels, whereas the number of Na-K pumps is increased. The results support the suggestion that changes in TBK may regulate the synthesis of Na-K pump molecules. Secondary hyperaldosteronism and diarrhea e.g. may be responsible for chronic potassium depletion. The need for a nutritional support is discussed.

Schober, O.; Bossaller, C.

1984-01-01

349

GATA4 loss in the septum transversum mesenchyme promotes liver fibrosis in mice.  

PubMed

The zinc finger transcription factor GATA4 controls specification and differentiation of multiple cell types during embryonic development. In mouse embryonic liver, Gata4 is expressed in the endodermal hepatic bud and in the adjacent mesenchyme of the septum transversum. Previous studies have shown that Gata4 inactivation impairs liver formation. However, whether these defects are caused by loss of Gata4 in the hepatic endoderm or in the septum transversum mesenchyme remains to be determined. In this study, we have investigated the role of mesenchymal GATA4 activity in liver formation. We have conditionally inactivated Gata4 in the septum transversum mesenchyme and its derivatives by using Cre/loxP technology. We have generated a mouse transgenic Cre line, in which expression of Cre recombinase is controlled by a previously identified distal Gata4 enhancer. Conditional inactivation of Gata4 in hepatic mesenchymal cells led to embryonic lethality around mouse embryonic stage 13.5, likely as a consequence of fetal anemia. Gata4 knockout fetal livers exhibited reduced size, advanced fibrosis, accumulation of extracellular matrix components and hepatic stellate cell (HSC) activation. Haploinsufficiency of Gata4 accelerated CCl4 -induced liver fibrosis in adult mice. Moreover, Gata4 expression was dramatically reduced in advanced hepatic fibrosis and cirrhosis in humans. Conclusions: Our data demonstrate that mesenchymal GATA4 activity regulates HSC activation and inhibits the liver fibrogenic process. (Hepatology 2014;59:2358-2370). PMID:24415412

Delgado, Irene; Carrasco, Manuel; Cano, Elena; Carmona, Rita; García-Carbonero, Rocío; Marín-Gómez, Luis M; Soria, Bernat; Martín, Francisco; Cano, David A; Muñoz-Chápuli, Ramón; Rojas, Anabel

2014-06-01

350

Effects of late evening snack including branched-chain amino acid on the function of hepatic parenchymal cells in patients with liver cirrhosis.  

PubMed

Aim:? A late evening snack (LES) improves protein-energy malnutrition due to overnight starvation and the catabolic state in patients with liver cirrhosis. Our aim was to examine whether LES including a branched-chain amino acid (BCAA) could maintain hepatic reserve and the function of hepatic parenchymal cells in patients with liver cirrhosis, including those in the early stage of disease. Methods:? Seventeen patients with liver cirrhosis received LES with a BCAA-enriched nutrient mixture. During the study period, each patient was instructed on energy and protein intake. Indicators of liver function measured at 6?months included maximum asialoscintigraphic removal (Rmax: indicator of total liver receptors), asialoscintigraphic imaging grade, serum albumin, ammonia, tyrosine and BTR (molar ratio of branched-chain amino acids to tyrosine). Results:? Serum albumin levels, BTR and tyrosine levels of the 17 patients were significantly improved after nutrient treatment. In patients with Rmax of 0.2 or higher, serum albumin level and tyrosine level were significantly improved. Conclusion:? LES with BCAA-enriched nutrient therapy can improve protein malnutrition in patients with liver cirrhosis, and is more useful in the early stages of liver cirrhosis in improving hepatic parenchymal cell mass. PMID:21518402

Koreeda, Chizu; Seki, Toshihito; Okazaki, Kazuichi; Ha-Kawa, Sang Kil; Sawada, Satoshi

2011-05-01

351

Effects of oral branched-chain amino acids on hepatic encephalopathy and outcome in patients with liver cirrhosis.  

PubMed

Branched-chain amino acids (BCAAs) constituting of valine, leucine, and isoleucine act as both substrates of proteins and as key regulators for various nutrient metabolisms. Patients with liver cirrhosis frequently lack sufficient BCAAs and therefore suffer from various metabolic disorders. Hepatic encephalopathy (HE) is a severe metabolic disorder with neurologic manifestations such as flapping tremors and coma in patients with liver cirrhosis. In addition, a mild form of HE known as minimal HE (MHE) is an important social issue because it occurs in up to 80% of patients with chronic liver disease and affects prognosis and activities of daily living, possibly resulting in falls and motor vehicle accidents. Although HE/MHE can be caused by various pathological conditions, including in an accumulation of mercaptans, short-chain fatty acids, and alterations in the gut flora, hyperammonemia has also been implicated in an important pathogenesis of HE/MHE. Besides urea cycle of liver, ammonia can be detoxified in the skeletal muscles by the amidation process for glutamine synthesis using BCAAs. Thus, BCAA supplementation may enhance detoxification of ammonia in skeletal muscle and may be a possible therapeutic strategy for HE/MHE. In this review, we summarize the clinical impacts of BCAA supplementation on HE/MHE and discuss possible mechanisms for a BCAA-induced improvement of HE/MHE. Furthermore, we present some modifications of oral BCAA therapy for improvement of efficacy in HE treatment. We also briefly describe pleiotropic benefits of BCAAs on life-threatening events and overall prognosis in patients with liver cirrhosis. PMID:23945292

Kawaguchi, Takumi; Taniguchi, Eitaro; Sata, Michio

2013-10-01

352

Hepatic telangiectasia and cirrhosis.  

PubMed

In a woman with hereditary hemorrhagic telangiectasia (HHT) (Osler-Weber-Rendu disease) who died of fulminant hepatitis B, autopsy revealed cirrhosis of the liver and diffuse hepatic telangiectasia. Her daughter and grandson also suffered from the hepatic involvement of HHT. Sufficient laboratory investigations were available to exclude known causes of cirrhosis. We review the relationship between Osler-Weber-Rendu disease and liver cirrhosis or fibrosis. PMID:3356877

Deviere, J; Brohee, D; Hiden, M; Bourgeois, N

1988-02-01

353

Long-term treatment with cisapride and antibiotics in liver cirrhosis: effect on small intestinal motility, bacterial overgrowth, and liver function  

Microsoft Academic Search

OBJECTIVES:Altered small-bowel motility, lengthening of the orocecal transit time, and small-intestinal bacterial overgrowth have been described in patients with liver cirrhosis. These changes might be related to the progressive course and poor prognosis of the disease. We investigated the effect of a long-term treatment with cisapride and an antibiotic regimen on small-intestinal motor activity, orocecal transit time, bacterial overgrowth, and

Ana Maria Madrid; Carmen Hurtado; Mauricio Venegas; Francisco Cumsille; Carlos Defilippi

2001-01-01

354

T cell subsets in patients with acute and chronic HBV infection, primary biliary cirrhosis and alcohol induced liver disease.  

PubMed

The proportions of inducer and cytotoxic/suppressor T cells and their concentration in peripheral blood have been determined in patients with acute and chronic type B hepatitis, hepatitis B virus (HBV) carriers with normal hepatic histology, patients with alcohol-induced liver disease (ALD), primary biliary cirrhosis (PBC) and chronic extrahepatic cholestasis. During acute type B hepatitis the inducer/suppressor ratio was decreased due to an increase in suppressor cell concentrations. When this ratio returned to normal the HBs antigen was cleared and HBs antibody was detectable. Similar abnormalities were found in patients with HBs + ve chronic hepatitis. In HBs antigen-positive patients with normal histology, normal T cell subsets were found. In some patients with primary biliary cirrhosis the ratio of inducer to suppressor cells was low due to a reduction in the concentration of inducer cells and in others high due to a reduction in suppressor cells. Administration of cyclosporin A to the latter group produced an increase in the concentration of suppressor cells and there was an improvement in liver biochemistry. In alcohol-induced hepatitis and cirrhosis the ratio of inducer/suppressor cells was normal. Whether these imbalances of the regulatory cells of the immune system in patients with chronic HBV-induced hepatitis and PBC are of primary or secondary importance is uncertain. The relationship of the depressed ratio to persistence of the hepatitis B virus is worthy of further study. PMID:6457007

Thomas, H C

1981-01-01

355

Helicobacter pylori infection in patients with liver cirrhosis: prevalence and association with portal hypertensive gastropathy  

PubMed Central

Background The role of Helicobacter pylori (H. pylori) in the pathogenesis of portal hypertensive gastropathy (PHG) in cirrhotic patients is poorly defined. The aim of this study was toinvestigate the prevalence of H. pylori infection and its association with PHG in patients with liver cirrhosis. Methods Seroprevalence of H. pylori was tested in 70 cirrhotic patients with PHG (cases) and 70 cirrhotic patients without PHG (controls) using an anti-H. pylori IgG ELISA. All patients underwent upper gastrointestinal endoscopy to assess the severity of PHG and grade of varices. Results The presence of H. pylori was observed in 31 (44.3%) cirrhotic patients with PHG (cases) compared to 19 (27.1%) cirrhotic patients without PHG (controls). The risk estimate showed a significant association between H. pylori and PHG in cirrhotic patients (P=0.034, OR 2.134, 95% CI 1.052-4.327). Out of the 31 patients with PHG and H. pylori infection, 19 had severe PHG and 12 had mild PHG while 5 patients had severe PHG and 34 had mild PHG in the group of H. pylori negative patients. The difference was statistically significant (P<0.001, OR 10.767, 95% CI 3.293-35.205). Of the 70 patients with PHG, 24 had severe PHG and of these 18 (75%) were in Child C compared to 6 (25%) in Child B. Conclusion There is significant association between H. pylori infection and PHG in cirrhotic patients which is also related to severity of PHG. Thus, H. pylori needs to be eradicated in cirrhotic patients with PHG.

Sathar, Shanid Abdul; Kunnathuparambil, Sojan George; Sreesh, Srijaya; Narayanan, Premaletha; Vinayakumar, Kattoor Ramakrishnan

2014-01-01

356

Chemical pleurodesis for the management of refractory hepatic hydrothorax in patients with decompensated liver cirrhosis  

PubMed Central

Background/Aims Hepatic hydrothorax in patients with decompensated liver cirrhosis is a challenging problem. Treatment with diuretics and intermittent thoracentesis can be effective in selected patients. However, there are few effective therapeutic options in patients who are intolerant of these therapies. This study investigated the clinical usefulness of chemical pleurodesis with or without video-assisted thoracoscopic surgery (VATS) for patients with refractory hepatic hydrothorax. Methods Eleven consecutive patients with refractory hepatic hydrothorax who underwent chemical pleurodesis with or without VATS between July 2007 and February 2011 were enrolled in this study. The medical records and radiologic imagings of these patients were thoroughly reviewed. Results The median number of chemical pleurodesis sessions performed was 3 (range: 2-10). Successful pleurodesis was achieved in 8 of the 11 patients (72.7%), 5 (62.5%) of whom remained asymptomatic and hydrothorax free for a median follow-up of 16 weeks (range: 2-52 weeks). Complications were low-grade fever/leukocytosis (n=11, 100%), pneumonia (n=1, 9.1%), pneumothorax (n=4, 36.4%), azotemia/acute renal failure (n=6, 54.6%), and hepatic encephalopathy (n=4, 36.4%). Five patients were suspected as having procedure-related mortality (45.5%) due to the occurrence of acute renal failure with hepatic failure. The overall survival was significantly longer in the success group than in the non-success group. Conclusions Although chemical pleurodesis may improve the clinical symptoms and the radiologic findings in as many as 72.7% of patients with refractory hepatic hydrothorax, a significantly high prevalence of procedure-related morbidity and mortality hinders the routine application of this procedure for such patients.

Lee, Woo Jin; Park, Jung Ho; Park, Dong Il; Cho, Yong Kyun; Sohn, Chong Il; Jeon, Woo Kyu; Kim, Byung Ik

2011-01-01

357

Micro-RNA Profiling in Human Serum Reveals Compartment-Specific Roles of miR-571 and miR-652 in Liver Cirrhosis  

PubMed Central

Background and Aims Micro-RNAs (miRNAs) have recently emerged as crucial modulators of molecular processes involved in chronic liver diseases. The few miRNAs with previously proposed roles in liver cirrhosis were identified in screening approaches on liver parenchyma, mostly in rodent models. Therefore, in the present study we performed a systematic screening approach in order to identify miRNAs with altered levels in the serum of patients with chronic liver disease and liver cirrhosis. Methods We performed a systematic, array-based miRNA expression analysis on serum samples from patients with liver cirrhosis. In functional experiments we evaluated the relationship between alterations of miRNA serum levels and their role in distinct cellular compartments involved in hepatic cirrhosis. Results The array analysis and the subsequent confirmation by qPCR in a larger patient cohort identified significant alterations in serum levels of miR-513-3p, miR-571 and miR-652, three previously uncharacterized miRNAs, in patients with alcoholic or hepatitis C induced liver cirrhosis. Of these, miR-571 serum levels closely correlated with disease stages, thus revealing potential as a novel biomarker for hepatic cirrhosis. Further analysis revealed that up-regulation of miR-571 in serum reflected a concordant regulation in cirrhotic liver tissue. In isolated primary human liver cells, miR-571 was up-regulated in human hepatocytes and hepatic stellate cells in response to the pro-fibrogenic cytokine TGF-?. In contrast, alterations in serum levels of miR-652 were stage-independent, reflecting a concordant down-regulation of this miRNA in circulating monocytes of patients with liver cirrhosis, which was inducible by proinflammatory stimuli like bacterial lipopolysaccharide. Conclusion Alterations of miR571 and miR-652 serum levels in patients with chronic liver disease reflect their putative roles in the mediation of fibrogenic and inflammatory processes in distinct cellular compartments involved in the pathogenesis of liver cirrhosis.

Roderburg, Christoph; Mollnow, Tobias; Bongaerts, Brenda; Elfimova, Natalia; Vargas Cardenas, David; Berger, Katharina; Zimmermann, Henning; Koch, Alexander; Vucur, Mihael; Luedde, Mark; Hellerbrand, Claus; Odenthal, Margarete; Trautwein, Christian; Tacke, Frank; Luedde, Tom

2012-01-01

358

The progressive elevation of alpha fetoprotein for the diagnosis of hepatocellular carcinoma in patients with liver cirrhosis  

PubMed Central

Background Hepatocellular carcinoma is the most common cause of primary liver neoplasms and is one of the main causes of death in patients with liver cirrhosis. High Alpha fetoprotein serum levels have been found in 60–70% of patients with Hepatocellular carcinoma; nevertheless, there are other causes that increase this protein. Alpha fetoprotein levels ?200 and 400 ng/mL in patients with an identifiable liver mass by imaging techniques are diagnostic of hepatocellular carcinoma with high specificity. Methods We analysed the sensitivity and specificity of the progressive increase of the levels of alpha fetoprotein for the detection of hepatocellular carcinoma in patients with liver cirrhosis. Seventy-four patients with cirrhosis without hepatocellular carcinoma and 193 with hepatic lesions diagnosed by biopsy and shown by image scans were included. Sensitivity and specificity of transversal determination of alpha fetoprotein ? 200 and 400 ng/mL and monthly progressive elevation of alpha fetoprotein were analysed. Areas under the ROC curves were compared. Positive and negative predictive values adjusted to a 5 and 10% prevalence were calculated. Results For an elevation of alpha fetoprotein ? 200 and 400 ng/mL the specificity is of 100% in both cases, with a sensitivity of 36.3 and 20.2%, respectively. For an alpha fetoprotein elevation rate ?7 ng/mL/month, sensitivity was of 71.4% and specificity of 100%. The area under the ROC curve of the progressive elevation was significantly greater than that of the transversal determination of alpha fetoprotein. The positive and negative predictive values modified to a 10% prevalence are of: 98.8% and 96.92%, respectively; while for a prevalence of 5% they were of 97.4% and 98.52%, respectively. Conclusion The progressive elevation of alpha fetoprotein ?7 ng/mL/month in patients with liver cirrhosis is useful for the diagnosis of hepatocellular carcinoma in patients that do not reach ?FP levels ?200 ng/mL. Prospective studies are required to confirm this observation.

Arrieta, Oscar; Cacho, Bernardo; Morales-Espinosa, Daniela; Ruelas-Villavicencio, Ana; Flores-Estrada, Diana; Hernandez-Pedro, Norma

2007-01-01

359

Malnutrition in Liver Cirrhosis:The Influence of Protein and Sodium  

PubMed Central

Protein calorie malnutrition (PCM) is associated with an increased risk of morbidity and mortality in patients with cirrhosis and occurs in 50%-90% of these patients. Although the pathogenesis of PCM is multifactorial, alterations in protein metabolism play an important role. This article is based on a selective literature review of protein and sodium recommendations. Daily protein and sodium requirements of patients with cirrhosis have been the subject of many research studies since inadequate amounts of both can contribute to the development of malnutrition. Previous recommendations that limited protein intake should no longer be practiced as protein requirements of patients with cirrhosis are higher than those of healthy individuals. Higher intakes of branched-chain amino acids as well as vegetable proteins have shown benefits in patients with cirrhosis, but more research is needed on both topics. Sodium restrictions are necessary to prevent ascites development, but very strict limitations, which may lead to PCM should be avoided.

Eghtesad, Sareh; Poustchi, Hossein; Malekzadeh, Reza

2013-01-01

360

Mechanism of insulin resistance in human liver cirrhosis. Evidence of a combined receptor and postreceptor defect.  

PubMed Central

Insulin resistance in liver cirrhosis may depend on either reduced sensitivity (receptor defect) and/or reduced response to insulin (postreceptor defect). To clarify the mechanism of such resistance, a [3H]glucose infusion (0.2 microCi/min) was performed for 120 min before and during a euglycemic clamp at approximately 100, 1,000, and 10,000 microU/ml steady state plasma insulin concentration in 18 compensated cirrhotics with portal hypertension and impaired glucose tolerance, and 18 healthy volunteers with no family history of diabetes, matched for sex, age, and weight. Mean fasting plasma insulin (29.2 +/- 3.4 SEM vs. 14.8 +/- 1.1 microU/ml) was significantly higher (P less than 0.001) in cirrhotics, while fasting plasma glucose was much the same in the two groups. Glucose use (milligrams per kilogram per minute) was significantly lower in cirrhotics at all three steady state plasma insulin levels: 3.04 +/- 0.34 vs. 7.72 +/- 0.61 (P less than 0.001) at approximately 100; 6.05 +/- 1.07 vs. 11.45 +/- 1.24 (P less than 0.001) at approximately 1,000; and 11.69 +/- 0.69 vs. 14.13 +/- 0.74 (P less than 0.05) at approximately 10,000 microU/ml. Mean plasma C-peptide was significantly higher in cirrhotics both basally and during the steady states (P less than 0.001); it was completely suppressed at approximately 10,000 microU/ml in controls and only 57.5% of the baseline in cirrhotics. Endogenous glucose production (milligrams per kilogram per minute) was much the same in the two groups in the fasting state and almost entirely suppressed in the controls (0.10 +/- 0.05 vs. 0.48 +/- 0.11, P less than 0.001) at approximately 100 microU/ml; at approximately 1,000 microU/ml a residual glucose production, 0.07 +/- 0.05, was observed in the cirrhotics only. In addition, insulin binding and 3-ortho-methyl-glucose transport were studied in vitro in six cirrhotics and six controls. Insulin binding to circulating monocytes and isolated adipocytes was significantly lower (P less than 0.025) in cirrhotics in all insulin concentration studies. Glucose transport values on isolated adipocytes were significantly lower in cirrhotics both basally (P less than 0.001) and at maximal insulin concentration (P less than 0.05). These results suggest that insulin resistance in human cirrhosis is more dependent on depressed peripheral glucose use than on increased endogenous glucose production, and that a combined receptor and postreceptor defect in insulin action on target cells seems to be present.

Cavallo-Perin, P; Cassader, M; Bozzo, C; Bruno, A; Nuccio, P; Dall'Omo, A M; Marucci, M; Pagano, G

1985-01-01