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1

Estrogen reduces CCL4- induced liver fibrosis in rats  

Microsoft Academic Search

AIM: Chronic liver diseases, such as fibrosis or cirrhosis, are more common in men than in women. This gender difference may be related to the effects of sex hormones on the liver. The aim of the present work was to investigate the effects of estrogen on CCL4-induced fibrosis of the liver in rats. METHODS: Liver fibrosis was induced in male,

Jun-Wang Xu; Jun Gong; Xin-Ming Chang; Jin-Yan Luo; Lei Dong; Zhi-Ming Hao; Ai Jia; Gui-Ping Xu

2002-01-01

2

Dysregulation of renal aquaporins and NaCl cotransporter in CCl4-induced cirrhosis  

Microsoft Academic Search

Dysregulation of renal aquaporins and Na-Cl cotransporter in CCl4-induced cirrhosis.BackgroundSevere hepatic cirrhosis is associated with abnormal renal water retention.MethodsSemiquantitative immunoblotting was employed to investigate the abundance of the major renal aquaporins (water channels) and sodium-dependent cotransporters in kidneys from control rats and rats with cirrhosis secondary to chronic CCl4 inhalation.ResultsThe cirrhotic rats had ascites and manifested a water excretion defect

Patricia Fernández-Llama; Wladimiro Jimenez; Marta Bosch-Marcé; Vicente Arroyo; Sřren Nielsen; Mark A. Knepper

2000-01-01

3

Ginkgo biloba extract reverses CCl4 -induced liver fibrosis in rats  

Microsoft Academic Search

AIM: To study the reversing effect of Ginkgo biloba extract (GbE) on established liver fibrosis in rats. METHODS: Following confirmation of CCl4-induced liver fibrosis, GbE or saline was administrated to the rats for 4 weeks. The remaining rats received neither CCl4 nor GbE as normal control. The four groups were compared in terms of serum enzymes, tissue damage, expression of

Yan-Jun Luo; Jie-Ping Yu; Zhao-Hong Shi; Li Wang

2004-01-01

4

The Protective Effect of Stauntonia Chinensis Polysaccharide on CCl4-induced Acute Liver Injuries in Mice  

PubMed Central

Objective: To investigate the protective effect of Stauntonia chinensis polysaccharides (SCP) on carbon tetrachloride (CCl4) induced acute liver injuries in mice. Methods: Kunming mice were randomly divided into three groups: the control group, the pathological model group, and the SCP group. The SCP group was further divided into three subgroups based on SCP treatment: Low dosage (50 mg/kg), medium dosage (100 mg/kg) and high dosage (200 mg/kg). After being fed for 7 days, mixed-edible-oil solution was intraperitoneally injected into the control group, while the other two groups were injected with 0.15% CCl4 mixed with mixed-edible-oil. Sera were collected from mice 24 h later to determine the activity of serum alanine transaminase (ALT). Mice were then sacrificed to prepare liver homogenate. Levels of liver malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and nitric oxide (NO) were determined. Pathological changes in livers were also analyzed. Results: SCP significantly reduced the ALT activity in the serum and inhibited the decrease of serum GSH, GSH-PX and SOD and rose the levels of MDA and NO (P<0.05-0.01). This lessened the pathological damage to the liver tissues. Conclusion: SCP protects against CCl4-induced acute liver injuries in mice. PMID:24711744

Yang, Jiaojiao; Xiong, Qingming; Zhang, Jing; Yan, Shirong; Zhu, Lihua; Zhu, Bo

2014-01-01

5

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. PMID:24707405

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

2014-01-01

6

The prevention of CCl4-induced liver necrosis in mice by naturally occurring methylenedioxybenzenes.  

PubMed

Methylenedioxybenzenes (MDBs) and structurally related alkenylbenzenes were compared for their effectiveness in preventing carbon tetrachloride (CCl4)-induced liver necrosis in mice. Pretreatment with isosafrole, safrole, dihydrosafrole, and benzodioxole at dosages as low as 10 mg/kg significantly prevented the increase in plasma transaminase levels and histochemical changes associated with CCl4-induced liver necrosis, whereas piperonyl butoxide (PBO), eugenol, isoeugenol, sesamol, and curcumin did not prevent CCl4 hepatotoxicity even at 200 mg/kg. However, isosafrole was only partly hepatoprotective if administered 10 min after the toxicant. Liver microsomes isolated 1 hr after isosafrole but not after PBO administration had a markedly decreased CYP2E1 activity. Isosafrole, safrole, dihydrosafrole, and benzodioxole in vitro also inhibited CYP2E1-dependent metabolism more effectively than eugenol and isoeugenol, whereas PBO did not inhibit CYP2E1 activity. The protective effects of isosafrole, safrole, and benzodioxole were therefore predominantly attributed to their ability to inactivate CYP2E1, the major isozyme involved in CCl4 bioactivation. The marked potentiation of CCl4 hepatotoxicity in CYP2E1-induced mice was also completely prevented by isosafrole but not PBO pretreatment, supporting the hypothesis that CYP2E1 inhibition by isosafrole contributes to its hepatoprotective effect against CCl4. Isosafrole and safrole also prevented bromotrichloromethane (BrCCl3)-induced hepatocyte cytotoxicity, whereas PBO was ineffective. PMID:8887459

Zhao, Z S; O'Brien, P J

1996-10-01

7

Antioxidant and protective effect of inulin and catechin grafted inulin against CCl4-induced liver injury.  

PubMed

In this study, the antioxidant activity and hepatoprotective effect of inulin and catechin grafted inulin (catechin-g-inulin) against carbon tetrachloride (CCl4)-induced acute liver injury were investigated. Results showed that both inulin and catechin-g-inulin had moderate scavenging activity on superoxide radical, hydroxyl radical and H2O2, as well as lipid peroxidation inhibition effect. The antioxidant activity decreased in the order of Vc > catechin >catechin-g-inulin > inulin. Administration of inulin and catechin-g-inulin could significantly reduce the elevated levels of serum aspartate transaminase, alanine transaminase and alkaline phosphatase as compared to CCl4 treatment group. Moreover, inulin and catechin-g-inulin significantly increased the levels of hepatic superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione and total antioxidant capacity, whereas markedly decreased the malondialdehyde level when compared with CCl4 treatment group. Notably, catechin-g-inulin showed higher hepatoprotective effect than inulin. In addition, the hepatoprotective effect of catechin-g-inulin was comparable to positive standard of silymarin. Our results suggested that catechin-g-inulin had potent antioxidant activity and potential protective effect against CCl4-induced acute liver injury. PMID:25316429

Liu, Jun; Lu, Jian-feng; Wen, Xiao-yuan; Kan, Juan; Jin, Chang-hai

2015-01-01

8

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. PMID:22792126

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

9

Adiponectin Agonist ADP355 Attenuates CCl4-Induced Liver Fibrosis in Mice  

PubMed Central

Liver fibrosis is a growing global health problem characterized by excess deposition of fibrillar collagen, and activation of hepatic stellate cells (HSCs). Adiponectin is known to possess anti-fibrotic properties; however a high physiological concentration and multiple forms circulating in blood prohibit clinical use. Recently, an adiponectin-like small synthetic peptide agonist (ADP355: H-DAsn-Ile-Pro-Nva-Leu-Tyr-DSer-Phe-Ala-DSer-NH2) was synthesized for the treatment of murine breast cancer. The present study was designed to evaluate the efficacy of ADP355 as an anti-fibrotic agent in the in vivo carbon tetrachloride (CCl4)-induced liver fibrosis model. Liver fibrosis was induced in eight-week old male C57BL/6J mice by CCl4-gavage every other day for four weeks before injection of a nanoparticle-conjugated with ADP355 (nano-ADP355). Control gold nanoparticles and nano-ADP355 were administered by intraperitoneal injection for two weeks along with CCl4-gavage. All mice were sacrificed after 6 weeks, and serum and liver tissue were collected for biochemical, histopathologic and molecular analyses. Biochemical studies suggested ADP355 treatment attenuates liver fibrosis, determined by reduction of serum aspartate aminotransferase (AST), alanine aminotransferase ALT) and hydroxyproline. Histopathology revealed chronic CCl4-treatment results in significant fibrosis, while ADP355 treatment induced significantly reversed fibrosis. Key markers for fibrogenesis–?-smooth muscle actin (?-SMA), transforming growth factor-beta1 (TGF-?1), connective tissue growth factor (CTGF), and the tissue inhibitor of metalloproteinase I (TIMP1) were also markedly attenuated. Conversely, liver lysates from ADP355 treated mice increased phosphorylation of both endothelial nitric oxide synthase (eNOS) and AMPK while AKT phosphorylation was diminished. These findings suggest ADP355 is a potent anti-fibrotic agent that can be an effective intervention against liver fibrosis. PMID:25310107

Kumar, Pradeep; Smith, Tekla; Rahman, Khalidur; Thorn, Natalie E.; Anania, Frank A.

2014-01-01

10

H3 Propranolol serum levels following lidocaine administration in rats with CCL4 induced liver damage.  

PubMed

Liver disease alters the pharmacokinetic and pharmacodynamic properties of hepatically eliminated drugs. The main factors influenced are plasma albumin levels, enzyme balance (induction & inhibition) and drug binding to tissue proteins. The influence of lidocaine on serum, heart and liver propranolol levels in Wistar rats after liver injury induced by carbon tetrachloride CCl4 0.4 ml/kg x 2/wkl, was investigated. 40 male Wistar rats were divided into four groups (I, II, III, IV; n=10), Group I animals received only propranolol (labelled + cold substance) 40 mg/kg/12 h p.o., group II propranolol plus lidocaine in a single dose of 4mg/kg s.c., group III was treated with CCl4 for 6 weeks and received propranolol x2 at the same dosage as group I, while group VI was treated with CCl4 and the same drug dosage as group II. The simultaneous administration of H3-propranolol and lidocaine increased propranolol levels in the serum and tissues. The liver in damaged animals showed an increase of propranolol level under lidocaine co-administration, probably due to CCl4 induced liver enzyme activity, resulting in a rapid propranolol metabolism or to competition between both drug protein binding sites. The increased propranolol levels in the heart after lidocaine administration were probably due to attributed to its high affinity for heart tissue. Consequently, as regards the therapeutic approach for patients with liver disease receiving propranolol their propranolol dosage should be reduced when lidocaine is co-administered. PMID:16898077

Kotsiou, A; Tsamouri, M; Anagnostopoulou, S; Tzivras, M; Vairactaris, E; Tesseromatis, C

2006-01-01

11

Diethylcarbamazine Reduces Chronic Inflammation and Fibrosis in Carbon Tetrachloride- (CCl4-) Induced Liver Injury in Mice  

PubMed Central

This study investigated the anti-inflammatory effects of DEC on the CCl4-induced hepatotoxicity in C57BL/6 mice. Chronic inflammation was induced by i.p. administration of CCl4 0.5??L/g of body weight through two injections a week for 6 weeks. DEC (50?mg/kg) was administered by gavage for 12 days before finishing the CCl4 induction. Histological analyses of the DEC-treated group exhibited reduced inflammatory process and prevented liver necrosis and fibrosis. Immunohistochemical and immunofluorescence analyses of the DEC-treated group showed reduced COX-2, IL1?, MDA, TGF-?, and ?SMA immunopositivity, besides exhibiting decreased IL1?, COX-2, NF?B, IFN?, and TGF? expressions in the western blot analysis. The DEC group enhanced significantly the IL-10 expression. The reduction of hepatic injury in the DEC-treated group was confirmed by the COX-2 and iNOS mRNA expression levels. Based on the results of the present study, DEC can be used as a potential anti-inflammatory drug for chronic hepatic inflammation. PMID:25374445

Rocha, Sura Wanessa Santos; de França, Maria Eduarda Rocha; Rodrigues, Gabriel Barros; Barbosa, Karla Patrícia Sousa; Nunes, Ana Karolina Santana; Pastor, André Filipe; Oliveira, Anne Gabrielle Vasconcelos; Oliveira, Wilma Helena; Luna, Rayana Leal Almeida; Peixoto, Christina Alves

2014-01-01

12

Protective Mechanisms of Moringa oleifera against CCl4Induced Oxidative Stress in Precision-Cut Liver Slices  

Microsoft Academic Search

SummaryObjective: The present study was designed to evaluate the efficacy of Moringa oleifera leaves against carbon tetrachloride (CCl4)-treated liver slices in vitro. Material and Methods: The study evaluated the antioxidant properties of Moringa oleifera leaves against CCl4-induced oxidative damage in liver slices. Results: CCl4 treatment significantly decreased the activities of antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase, glutathione

S. Sreelatha; P. R. Padma

2010-01-01

13

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. PMID:25003132

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

2014-01-01

14

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. PMID:25182950

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

2014-01-01

15

Red Sea Suberea mollis Sponge Extract Protects against CCl4-Induced Acute Liver Injury in Rats via an Antioxidant Mechanism  

PubMed Central

Recent studies have demonstrated that marine sponges and their active constituents exhibited several potential medical applications. This study aimed to evaluate the possible hepatoprotective role as well as the antioxidant effect of the Red Sea Suberea mollis sponge extract (SMSE) on carbon tetrachloride- (CCl4-) induced acute liver injury in rats. In vitro antioxidant activity of SMSE was evaluated by 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) assay. Rats were orally administered three different concentrations (100, 200, and 400?mg/kg) of SMSE and silymarin (100?mg/kg) along with CCl4 (1?mL/kg, i.p., every 72?hr) for 14 days. Plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and total bilirubin were measured. Hepatic malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide (NO), superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) were also measured. Liver specimens were histopathologically examined. SMSE showed strong scavenging activity against free radicals in DPPH assay. SMSE significantly reduced liver enzyme activities. Moreover, SMSE significantly reduced hepatic MDA formation. In addition, SMSE restored GSH, NO, SOD, GPx, and CAT. The histopathological results confirmed these findings. The results of this study suggested a potent protective effect of the SMSE against CCl4-induced hepatic injury. This may be due to its antioxidant and radical scavenging activity. PMID:25214875

Abbas, Aymn T.; El-Shitany, Nagla A.; Shaala, Lamiaa A.; Ali, Soad S.; Azhar, Esam I.; Abdel-dayem, Umama A.; Youssef, Diaa T. A.

2014-01-01

16

Hepatoprotective and antioxidative properties of Salacia reticulata: preventive effects of phenolic constituents on CCl4-induced liver injury in mice.  

PubMed

The hepatoprotective effects of the hot water (SRHW) and methanolic (SRM) extracts from the roots and stems of Salacia reticulata were examined using an oxidative stress-induced liver injury model. Both SRHW and SRM extracts (400 mg/kg, p.o.) significantly suppressed the increase in glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) activities in carbon tetrachloride (CCl4)-treated mice. These extracts also inhibited CCl4-induced thiobarbituric acid-reactive substance (TBA-RS) formation, which indicates increased lipid peroxidation in the liver. A good correlation (r=0.945, p<0.01) was observed between the amount of phenolic compounds in the extracts and their inhibitions of TBA-RS formation. The IC50 values of the extracts on 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging were less than 10 microg/ml and the antioxidative activities of six phenolic compounds from the roots of S. reticulata were examined. Mangiferin, (-)-4'-O-methylepigallocatechin, and (-)-epicatechin-(4beta-->8)-(-)-4'-O-methylepigallocatechin, which a principal phenolic compounds, showed potent scavenging activity on DPPH radicals and their concentrations required for 50% reduction of 40 microM DPPH radicals were 5.9, 10, and 3.2 microM, respectively. On the other hand, against the CCl4-induced serum GOT and GPT elevations and TBA-RS formation in mice, mangiferin and (-)-4'-O-methylepigallocatechin showed potent activity at a dose of 100 mg/kg, but (-)-epicatechin-(4beta-->8)-(-)-4'-O-methylepigallocatechin did not. These results suggest that the antioxidative activity of the principal phenolic compounds is involved in the hepatoprotective activity of S. reticulata. PMID:11824561

Yoshikawa, Masayuki; Ninomiya, Kiyofumi; Shimoda, Hiroshi; Nishida, Norihisa; Matsuda, Hisashi

2002-01-01

17

Protective effects of polyphenols-enriched extract from Huangshan Maofeng green tea against CCl4-induced liver injury in mice.  

PubMed

The study was to characterize the polyphenolic composition, antioxidant properties, and hepatoprotective effects of a polyphenols-enriched extract (HMTP) from Huangshan Maofeng green tea. HPLC analysis showed that three predominantly polyphenolic compounds present in HMTP were epigallocatechin (271.2 ?g/mg extract), rutin (239.3 ?g/mg) and epicatechin (89.3 ?g/mg). HMTP was shown to exhibit strong scavenging activities against DPPH, O2(-), and OH, and ferric-reducing antioxidant power in vitro. Administration of HMTP at 200, 400 and 800 mg/kg bw in mice prior to CCl4 injury significantly decreased the CCl4-induced elevation of serum ALT, AST and ALP activities, and prevented an increase in hepatic MDA levels (p<0.05). Mice with HMTP pretreatment displayed a better profile of hepatosomatic index and the improved GSH-Px and SOD activities in the liver, relative to CCl4-intoxicated mice. Liver pathological observation also confirmed the protection on CCl4-caused histological alteration, suggesting that HMTP has potential to be explored as valuable hepatoprotective function food. PMID:24973642

Cui, Yanmang; Yang, Xingbin; Lu, Xinshan; Chen, Jinwen; Zhao, Yan

2014-09-01

18

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

Microsoft Academic Search

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

Polimetla Srilaxmi; Gangadhara Reddy Sareddy; Polavarapu Bilhan Kavi kishor; Oruganti Hussainaiah Setty; Phanithi Prakash Babu

2010-01-01

19

The protective effects of Hibiscus sabdariffa extract on CCl 4-induced liver fibrosis in rats  

Microsoft Academic Search

Dried flower Hibiscus sabdariffa L. (HSE) extracts, a local soft drink material and medicinal herb, were studied for their protective effects against liver fibrosis induced using carbon tetrachloride (CCl4) in rats. Male Wistar rats were administered CCl4 by intraperitoneal injection for 7weeks and received a normal diet or normal diet with various HSE doses (1–5%) for 9weeks. HSE significantly reduced

Jer-Yuh Liu; Chang-Che Chen; Wen-Hong Wang; Jeng-Dong Hsu; Mon-Yuan Yang; Chau-Jong Wang

2006-01-01

20

Effects of curcumin on antioxidative activities and cytokine production in Jian carp (Cyprinus carpio var. Jian) with CCl4-induced liver damage.  

PubMed

We investigated the protective effects of curcumin on liver-damaged Cyprinus carpio var. Jian (Jian carp). The carp were fed 0.1%, 0.5%, or 1.0% curcumin for 60 days, then injected intraperitoneally with 30% carbon tetrachloride solution. Liver and blood samples were collected to measure the liver index, serum- and liver-associated enzymes, liver histology, nuclear factor-?B (NF-?B)/c-Rel, interleukin-1? (IL-1?), tumor necrosis factor-? (TNF-?), and IL-12 mRNA expression, and the level of NF-?B/c-Rel protein in the liver, and for a comet assay. We found that 0.5% and 1.0% curcumin significantly reduced the CCl4-induced increase in the liver index. The comet assay showed that the tail moment, olive tail moment, tail length, and tail DNA% improved in fish pretreated with 0.5 or 1.0% curcumin. CCl4-induced histological changes, including extensive hepatocyte degeneration, indistinct cell borders, nuclear condensation, and karyolysis were clearly reduced after treatment with 0.5% and 1.0% curcumin. Moreover, 0.5% and 1.0% curcumin significantly inhibited the CCl4-induced increase in serum glutamic oxaloacetic transaminase and promoted the restoration of superoxide dismutase in the liver; 1.0% curcumin significantly reduced serum glutamic pyruvic transaminase and lactate dehydrogenase and hepatic malondialdehyde, but significantly increased the total antioxidant capacity and glutathione levels in the liver. The CCl4-induced upregulation of NF-?B/c-Rel, IL-1?, and TNF-? mRNAs and NF-?B/c-Rel protein levels was inhibited by 0.5% and 1.0% curcumin, and IL-12 mRNA was reduced by all three doses of curcumin. The effects of curcumin on the liver index, enzymes, histological changes, and cytokines were dose-dependent. Our results indicate that curcumin reduces CCl4-induced liver damage in Jian carp by upregulating antioxidative activities and inhibiting NF-?B, IL-1?, TNF-?, and IL-12 expression. PMID:25549934

Cao, Liping; Ding, Weidong; Du, Jingliang; Jia, Rui; Liu, Yingjuan; Zhao, Caiyuan; Shen, Yujin; Yin, Guojun

2015-03-01

21

Evaluation of the Effectiveness of Piper cubeba Extract in the Amelioration of CCl4-Induced Liver Injuries and Oxidative Damage in the Rodent Model.  

PubMed

Background. Liver diseases still represent a major health burden worldwide. Moreover, medicinal plants have gained popularity in the treatment of several diseases including liver. Thus, the present study was to evaluate the effectiveness of Piper cubeba fruits in the amelioration of CCl4-induced liver injuries and oxidative damage in the rodent model. Methods. Hepatoprotective activity was assessed using various biochemical parameters like SGOT, SGPT, ?-GGT, ALP, total bilirubin, LDH, and total protein. Meanwhile, in vivo antioxidant activities as LPO, NP-SH, and CAT were measured in rat liver as well as mRNA expression of cytokines such as TNF?, IL-6, and IL-10 and stress related genes iNOS and HO-1 were determined by RT-PCR. The extent of liver damage was also analyzed through histopathological observations. Results. Treatment with PCEE significantly and dose dependently prevented drug induced increase in serum levels of hepatic enzymes. Furthermore, PCEE significantly reduced the lipid peroxidation in the liver tissue and restored activities of defense antioxidant enzymes NP-SH and CAT towards normal levels. The administration of PCEE significantly downregulated the CCl4-induced proinflammatory cytokines TNF? and IL-6 mRNA expression in dose dependent manner, while it upregulated the IL-10 and induced hepatoprotective effect by downregulating mRNA expression of iNOS and HO-1 gene. PMID:25654097

AlSaid, Mansour; Mothana, Ramzi; Raish, Mohammad; Al-Sohaibani, Mohammed; Al-Yahya, Mohammed; Ahmad, Ajaz; Al-Dosari, Mohammed; Rafatullah, Syed

2015-01-01

22

Evaluation of the Effectiveness of Piper cubeba Extract in the Amelioration of CCl4-Induced Liver Injuries and Oxidative Damage in the Rodent Model  

PubMed Central

Background. Liver diseases still represent a major health burden worldwide. Moreover, medicinal plants have gained popularity in the treatment of several diseases including liver. Thus, the present study was to evaluate the effectiveness of Piper cubeba fruits in the amelioration of CCl4-induced liver injuries and oxidative damage in the rodent model. Methods. Hepatoprotective activity was assessed using various biochemical parameters like SGOT, SGPT, ?-GGT, ALP, total bilirubin, LDH, and total protein. Meanwhile, in vivo antioxidant activities as LPO, NP-SH, and CAT were measured in rat liver as well as mRNA expression of cytokines such as TNF?, IL-6, and IL-10 and stress related genes iNOS and HO-1 were determined by RT-PCR. The extent of liver damage was also analyzed through histopathological observations. Results. Treatment with PCEE significantly and dose dependently prevented drug induced increase in serum levels of hepatic enzymes. Furthermore, PCEE significantly reduced the lipid peroxidation in the liver tissue and restored activities of defense antioxidant enzymes NP-SH and CAT towards normal levels. The administration of PCEE significantly downregulated the CCl4-induced proinflammatory cytokines TNF? and IL-6 mRNA expression in dose dependent manner, while it upregulated the IL-10 and induced hepatoprotective effect by downregulating mRNA expression of iNOS and HO-1 gene. PMID:25654097

AlSaid, Mansour; Mothana, Ramzi; Raish, Mohammad; Al-Sohaibani, Mohammed; Al-Yahya, Mohammed; Ahmad, Ajaz; Al-Dosari, Mohammed; Rafatullah, Syed

2015-01-01

23

In vivo antioxidant effect of aqueous root bark, stem bark and leaves extracts of Vitex doniana in CCl4 induced liver damage rats  

PubMed Central

Objective The antioxidant effects of aqueous root bark, stem bark and leaves of Vitex doniana (V. doniana) were evaluated 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 (148 mg·ml?1·kg?1 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 V. doniana and vitamin E as standard drug (100 mg/kg body weighy 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 three weeks. Results The liver of CCl4 induced not treated group showed that the induction with CCl4, significantly (P<0.05) increased thiobarbituric acid reactive substance (TBARS) and significantly (P<0.05) decreased superoxide dismutase (SOD) and catalase (CAT). However there was no significant (P>0.05) difference between TBARS, SOD and CAT in the liver of the induced treated groups and normal control group. In the kidney, TBARS showed no significant (P>0.05) difference between the normal and the induced groups, SOD was significantly (P<0.05) reduced in the CCl4 group compared to standard drug and normal control groups, CAT was significantly (P<0.05) increased in root and vitamin E groups when compared to induced not treated group. The studies also showed that when the extracts were administered to normal animals, there was no significant (P>0.05) change in the liver and kidney level of TBARS, SOD and CAT compared with the normal control except in the kidney of animals treated with stem extract where TBARS was significantly (P<0.05) lowered compared to control group. Conclusion The result of the present study suggests that application of V. doniana plant would play an important role in increasing the antioxidant effect and reducing the oxidative damage that formed both in liver and in kidney tissues. However stem bark has potential to improve renal function in normal rats. PMID:23646304

Adetoro, Kadejo Olubukola; Bolanle, James Dorcas; Abdullahi, Sallau Balarebe; Ahmed, Ozigi Abdulrahaman

2013-01-01

24

Mechanism of the Inhibitory Effects of Eucommia ulmoides Oliv. Cortex Extracts (EUCE) in the CCl4-Induced Acute Liver Lipid Accumulation in Rats  

PubMed Central

Eucommia ulmoides Oliv. (EU) has been used for treatment of liver diseases. The protective effects of Eucommia Ulmoides Oliv. cortex extracts (EUCE) on the carbon tetrachloride- (CCl4-) induced hepatic lipid accumulation were examined in this study. Rats were orally treated with EUCE in different doses prior to an intraperitoneal injection of 1?mg/kg CCl4. Acute injection of CCl4 decreased plasma triglyceride but increased hepatic triglyceride and cholesterol as compared to control rats. On the other hand, the pretreatment with EUCE diminished these effects at a dose-dependent manner. CCl4 treatment decreased glutathione (GSH) and increased malondialdehyde (MDA) accompanied by activated P450 2E1. The pretreatment with EUCE significantly improved these deleterious effects of CCl4. CCl4 treatment increased P450 2E1 activation and ApoB accumulation. Pretreatment with EUCE reversed these effects. ER stress response was significantly increased by CCl4, which was inhibited by EUCE. One of the possible ER stress regulatory mechanisms, lysosomal activity, was examined. CCl4 reduced lysosomal enzymes that were reversed with the EUCE. The results indicate that oral pretreatment with EUCE may protect liver against CCl4-induced hepatic lipid accumulation. ER stress and its related ROS regulation are suggested as a possible mechanism in the antidyslipidemic effect of EUCE. PMID:24027582

Jin, Chang-Feng; Li, Bo; Lin, Shun-Mei; Yadav, Raj-Kumar; Kim, Hyung-Ryong; Chae, Han-Jung

2013-01-01

25

Antioxidant properties of proanthocyanidins attenuate carbon tetrachloride (CCl4)-induced steatosis and liver injury in rats via CYP2E1 regulation.  

PubMed

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

26

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

27

NF-?B activation and proinflammatory cytokines mediated protective effect of Indigofera caerulea Roxb. on CCl4 induced liver damage in rats.  

PubMed

Indigofera caerulea Roxb. is a well known shrub among native medical practitioners in folk medicine used for the treatment of jaundice, epilepsy, night blindness and snake bites. It is also reported to have antioxidant and antimicrobial properties. However its actual efficacy and hepatoprotective mechanism in particular is uncertain. Thus the present study investigates the hepatoprotective effect of the methanolic extract of I. caerulea Roxb. leaves (MIL) and elucidation of its mode of action against carbon tetrachloride (CCl4) induced liver injury in rats. HPLC analysis of MIL when carried out showed peaks close to standard ferulic acid and quercetin. Intragastric administration of MIL up to 2000mg/kgbw, didn't show any toxicity and mortality in acute toxicity studies. During "in-vivo" study, hepatic injury was established by intraperitoneal administration of CCl4 3ml/kgbw (30% CCl4 in olive oil; v/v) twice a week for 4weeks in Sprague-Dawley rats. Further, hepatoprotective activity of MIL assessed using two different doses (100 and 200mg/kgbw) showed that intra-gastric administration of MIL (200mg/kgbw) significantly attenuates liver injury. Investigation of the underlying mechanism revealed that MIL treatment was capable of reducing inflammation by an antioxidant defense mechanism that blocks the activation of NF-?B as well as inhibits the release of proinflammatory cytokine TNF-? and IL-1?. The results suggest that MIL has a significant hepatoprotective activity which might be due to the presence of phytochemicals namely analogues of ferulic acid and other phytochemicals which together may suppress the inflammatory signaling pathways and promote hepatoprotective activity against CCl4 intoxicated liver damage. PMID:25445959

Ponmari, Guruvaiah; Annamalai, Arunachalam; Gopalakrishnan, Velliyur Kanniappan; Lakshmi, P T V; Guruvayoorappan, C

2014-12-01

28

Mutant MMP-9 and HGF Gene Transfer Enhance Resolution of CCl4-Induced Liver Fibrosis in Rats: Role of ASH1 and EZH2 Methyltransferases Repression  

PubMed Central

Hepatocyte growth factor (HGF) gene transfer inhibits liver fibrosis by regulating aberrant cellular functions, while mutant matrix metalloproteinase-9 (mMMP-9) enhances matrix degradation by neutralizing the elevated tissue inhibitor of metalloproteinase-1 (TIMP-1). It was shown that ASH1 and EZH2 methyltransferases are involved in development of liver fibrosis; however, their role in the resolution phase of liver fibrosis has not been investigated. This study evaluated the role of ASH1 and EZH2 in two mechanistically different therapeutic modalities, HGF and mMMP-9 gene transfer in CCl4 induced rat liver fibrosis. Liver fibrosis was induced in rats with twice a week intraperitoneal injection of CCl4 for 8 weeks. Adenovirus vectors encoding mMMP-9 or HGF genes were injected through tail vein at weeks six and seven and were sacrificed one week after the second injection. A healthy animal group was likewise injected with saline to serve as a negative control. Rats treated with mMMP-9 showed significantly lower fibrosis score, less Sirius red stained collagen area, reduced hydroxyproline and ALT concentration, decreased transforming growth factor beta 1 (TGF-?1) mRNA and lower labeling indices of ? smooth muscle actin (?-SMA) and proliferating cell nuclear antigen (PCNA) stained cells compared with HGF- or saline-treated rats. Furthermore, TIMP-1 protein expression in mMMP-9 group was markedly reduced compared with all fibrotic groups. ASH1 and EZH2 protein expression was significantly elevated in fibrotic liver and significantly decreased in mMMP-9- and HGF-treated compared to saline-treated fibrotic livers with further reduction in the mMMP-9 group. Conclusion: Gene transfer of mMMP-9 and HGF reduced liver fibrosis in rats. ASH1 and EZH2 methyltransferases are significantly reduced in mMMP-9 and HGF treated rats which underlines the central role of these enzymes during fibrogenesis. Future studies should evaluate the role of selective pharmacologic inhibitors of ASH1 and EZH2 in resolution of liver fibrosis. PMID:25380300

Atta, Hussein; El-Rehany, Mahmoud; Hammam, Olfat; Abdel-Ghany, Hend; Ramzy, Maggie; Roderfeld, Martin; Roeb, Elke; Al-Hendy, Ayman; Raheim, Salama Abdel; Allam, Hatem; Marey, Heba

2014-01-01

29

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. PMID:23203085

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

2012-01-01

30

Protein extracts of Crassostrea gigas alleviate CCl4-induced hepatic fibrosis in rats by reducing the expression of CTGF, TGF-?1 and NF-?B in liver tissues.  

PubMed

Hepatic fibrosis may contribute to liver carcinoma and the mortality of patients with hepatic fibrosis is gradually increasing. However, no definitive treatment has been established for hepatic fibrosis. The hepatic fibrotic process is reversible and can be controlled; therefore, the creation of novel and effective therapeutic methods to prevent or reverse the disease is required. The aim of the present study was to identify whether protein extracts from Pacific oysters (PEPO) could alleviate the hepatic fibrosis induced by CCl4 and to examine the mechanisms involved. A total of sixty rats were randomly divided into the following experimental groups: The normal control group; the hepatic fibrosis model group; the high?dose; medium?dose; and low?dose PEPO groups; and the colchicine group. The results indicated that compared with those of the model group, PEPO treatment significantly decreased the serum levels of alanine aminotransferase, aspartate aminotransferase, ??glutamyltransferase, alkaline phosphatase, hyaluronic acid, laminin, collagen type IV and procollagen III in rats with hepatic fibrosis. The hematoxylin and eosin staining demonstrated that PEPO markedly alleviated hepatic fibrosis. The experiments using immunohistochemistry, western blotting and quantitative PCR indicated that protein and mRNA expression levels of connective tissue growth factor (CTGF), transforming growth factor ?1 (TGF??1) and nuclear factor ?B (NF??B) in the liver tissues were significantly reduced by PEPO treatment. Therefore, it was concluded that PEPO successfully alleviated hepatic fibrosis induced by CCl4 and reversed the effects of hepatotoxicity by regulating the serum levels of enzymes and decreasing the expression levels of CTGF, TGF??1 and NF??B in liver tissues. These findings may provide a novel treatment option for patients with hepatic fibrosis in the future. PMID:25434425

Zhou, Jue; Liang, Yi; Pan, Jie-Xue; Wang, Fang-Fang; Lin, Xian-Ming; Ma, Rui-Jie; Qu, Fan; Fang, Jian-Qiao

2015-04-01

31

Inhibitory effects of phenolic compounds on CCl 4 -induced microsomal lipid peroxidation  

Microsoft Academic Search

Summary The antiperoxidative effects of 35 phenolic compounds, most of them belonging to the flavonoid class, were investigated using CCl4-induced peroxidation of rat liver microsomes. This system was rather insensitive to gallic acid, methyl gallate and ellagic acid. Nevertheless it was inhibited by flavonoids and structure\\/activity relationships were established. The most potent compounds were gardenin D, luteolin, apigenin (flavones), datiscetin,

M. R. Cholbi; M. Paya; M. J. Alcaraz

1991-01-01

32

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

33

Methotrexate-Induced Liver Cirrhosis  

Microsoft Academic Search

Studies on serial liver biopsies from 25 patients with methotrexate-induced liver cirrhosis, taken from 1 to 13 years after cirrhosis was established, confirm that this type is not of aggressive nature. When evaluated blind no progression was found in most of the later biopsies. Alcohol and previous use of hepatotoxic drugs such as the combination of arsenics and vitamin A

H. Zachariae; H. Sřgaard

1987-01-01

34

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. 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

35

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

36

Protective effect of chitosan from Sepia kobiensis (Hoyle 1885) cuttlebone against CCl4 induced hepatic injury.  

PubMed

Carbon tetrachloride (CCl4) is a potent hepatotoxic agent causing hepatic necrosis and it is widely used in animal models for induction of acute and chronic liver damage. The antioxidative and hepatoprotective effects of chitosan from Sepia kobiensis against CCl4 induced liver toxicity in Wistar rats was studied by measuring the activity of lipid peroxidation (TBARS, lipid hydroperoxides), non enzymatic antioxidant (GSH), antioxidant enzyme activities (SOD, CAT and GPx), liver marker enzymes (ALT and AST), lipid profile (FFA, TG, cholesterol and HDL cholesterol) and histopathological changes. Rats treated with chitosan against CCl4 toxicity showed significantly decreased levels of ALT and AST activities, total cholesterol, triglyceride and free fatty acid in plasma and tissue. Whereas the treatment with chitosan along with CCl4 showed markedly increased level of hepatic and circulatory in SOD, CAT, GPx and reduced glutathione and decreased the malondialdehyde level. Histopathological observations proved the marked hepatoprotective effect of chitosan. The CCl4 induced alterations in circulatory and hepatic antioxidant defense system were normalized by chitosan and it could be concluded that the hepatoprotective effect of chitosan may be due to its antioxidant and antilipidemic properties. PMID:24530330

Ramasamy, Pasiyappazham; Subhapradha, Namasivayam; Shanmugam, Vairamani; Shanmugam, Annaian

2014-04-01

37

Gastrointestinal dysfunction in liver cirrhosis.  

PubMed

Patients with liver cirrhosis exhibit several features of gut dysfunction which may contribute to the development of cirrhosis complications as well as have an impact on nutritional status and health-related quality of life. Gastrointestinal symptoms are common in cirrhosis and their pathophysiology probably involves factors related to liver disease severity, psychological distress, and gut dysfunction (e.g., increased gastric sensitivity to distension and delayed gut transit). They may lead to reduced food intake and, thus, may contribute to the nutritional status deterioration in cirrhotic patients. Although tense ascites appears to have a negative impact on meal-induced accommodation of the stomach, published data on gastric accommodation in cirrhotics without significant ascites are not unanimous. Gastric emptying and small bowel transit have generally been shown to be prolonged. This may be related to disturbances in postprandial glucose, insulin, and ghrelin levels, which, in turn, appear to be associated to insulin resistance, a common finding in cirrhosis. Furthermore, small bowel manometry disturbances and delayed gut transit may be associated with the development of small bowel bacterial overgrowth. Finally, several studies have reported intestinal barrier dysfunction in patients with cirrhosis (especially those with portal hypertension), which is related to bacterial translocation and permeation of intestinal bacterial products, e.g., endotoxin and bacterial DNA, thus potentially being involved in the pathogenesis of complications of liver cirrhosis. PMID:25356031

Kalaitzakis, Evangelos

2014-10-28

38

Mutation in collagen-I that confers resistance to the action of collagenase results in failure of recovery from CCl4-induced liver fibrosis, persistence of activated hepatic stellate cells, and diminished hepatocyte regeneration  

Microsoft Academic Search

Collagen-I, which predominates in the neomatrix of fibrotic liver, regulates hepatocyte and hepatic stellate cell (HSC) phenotypes. Recovery from liver fibrosis is accompanied by hepatocyte regeneration, matrix degradation, and HSC apoptosis. Using mice bearing a mutated collagen-I gene (r\\/r mice), which confers resistance to collagenase degradation, we have investigated the hypothesis that collagen-I degradation is critical to HSC apoptosis and

Razao Issa; Xiaoying Zhou; Nathan Trim; Harry Millward-Sadler; Stephen Krane; Christopher Benyon; John Iredale

2002-01-01

39

Antioxidant properties of colchicine in acute carbon tetrachloride induced rat liver injury and its role in the resolution of established cirrhosis.  

PubMed

Antioxidant and antifibrotic properties of colchicine were investigated in the carbon tetrachloride (CCl(4)) rat model. (1) The protective effect of colchicine pretreatment on CCl(4) induced oxidant stress was examined in rats subsequently receiving a single lethal dose of CCl(4). Urinary 8-isoprostane, kidney and liver malondialdehyde and kidney glutathione levels increased following CCl(4) treatment, but only the rise in kidney malondialdehyde was significantly inhibited by colchicine pretreatment. Serum total antioxidant levels were significantly higher in the colchicine pretreatment group. (2) The long term effects of colchicine treatment on CCl(4) induced liver damage were investigated using liver histology and biochemical markers (hydroxyproline and type III procollagen peptide). Co-administration of colchicine with sub-lethal doses of CCl(4) over 10 weeks did not prevent progression to cirrhosis. However, rats made cirrhotic with repeated CCl(4) challenge and subsequently treated with colchicine for 12 months, all showed histological regression of cirrhosis. (3) The antioxidant effect of colchicine in vitro was evident only at very high concentrations compared to other plasma antioxidants. In summary, colchicine has only weak antioxidant properties, but does afford some protection against oxidative stress; more importantly, long term treatment with this drug may be of value in producing regression of established cirrhosis. PMID:11068178

Das, D; Pemberton, P W; Burrows, P C; Gordon, C; Smith, A; McMahon, R F; Warnes, T W

2000-11-15

40

Hepatoprotective effects of Portulaca oleracea extract against CCl4-induced damage in rats.  

PubMed

Abstract Context: Purslane (Portulaca oleracea L., Portulacaceae) has been traditionally used in folk medicine to afford protection against liver injury, although its actual efficacy remains uncertain. Objective: To evaluate purslane as a hepatoprotective agent, we investigated the protective effect of its ethanol extract against carbon tetrachloride (CCl4)-induced hepatic toxicity in rats. Materials and methods: A total of 108 male Wistar rats were randomly divided into 12 groups. The first group was maintained as normal control, whereas CCl4 (0.5?ml/kg bw, 50% CCl4 in olive oil, i.p.), purslane extract (0.005, 0.01, 0.05, 0.1, and 0.15?g/kg bw, intragastrically), and purslane extract (five doses as above) along with CCl4 were administered to the Groups II, III-VII, and VIII-XII, respectively. The rats were sacrificed on the 30th day, and blood was withdrawn by cardiac puncture. Liver damage was assessed by measuring hepatic marker enzymes (ALT, AST, ALP, GGT, and SOD) and histopathological observation. Results: Treatment with CCl4 resulted in increased serum activities of marker enzymes with a concomitant decrease in SOD. Histological alterations were also observed in the liver tissue upon CCl4 treatment. Administration of purslane extract (0.01, 0.05, 0.1, and 0.15?g/kg b.w.) significantly showed a marked tendency towards normalization of all measured biochemical parameters in CCl4-treated rats. Histopathological changes also paralleled the detected alteration in markers of liver function. Discussion and conclusion: These results demonstrate that purslane exerts protective effects against CCl4-induced damage in rat liver and supports a potential therapeutic use of purslane as an alternative for patients with liver diseases. PMID:25472695

Eidi, Akram; Mortazavi, Pejman; Moghadam, Jalal Zarringhalam; Mardani, Parisa Mousavi

2014-12-01

41

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. PMID:25182286

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

2014-01-01

42

Hepatoprotective effect of ethanol extract from Berchemia lineate against CCl4-induced acute hepatotoxicity in mice.  

PubMed

Abstract Context: The roots of Berchemia lineate (L.) DC. (Rhamnaceae) have been long used as a remedy for the treatment of some diseases in Guangxi Province, China. Objective: The present study investigates the hepatoprotective effect of Berchemia lineate ethanol extract (BELE) on CCl4-induced acute liver damage in mice. Materials and methods: Effect of BELE administrated for 7 consecutive days was evaluated in mice by the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TBIL), albulin (ALB), globulin (GLB), and total protein (TP) levels, as well as liver superoxide dismutase (SOD) activity and malondialdehyde (MDA) level. Moreover, histopathological examinations were also taken. Results: Compared with the model group, administration of 400?mg/kg BELE for 7?d in mice significantly decreased the serum ALT (56.25?U/L), AST (297.67?U/L), ALP (188.20?U/L), and TBIL (17.90?mol/L), along with the elevation of TP (64.67?g/L). In addition, BELE (100, 200, and 400?mg/kg, i.g.) treated mice recorded a dose-dependent increment of SOD (291.17, 310.32, and 325.67?U/mg prot) and reduction of MDA (7.27, 6.77, and 5.33?nmol/mg prot) levels. Histopathological examinations also confirmed that BELE can ameliorate CCl4-induced liver injuries, characterized by extensive hepatocellular degeneration/necrosis, inflammatory cell infiltration, congestion, and sinusoidal dilatation. Discussion and conclusion: The results indicated that BELE possessed remarkable protective effect against acute hepatotoxicity and oxidative injuries induced by CCl4, and that the hepatoprotective effects of BELE may be due to both the inhibition of lipid peroxidation and the increase of antioxidant activity. PMID:25431325

Li, Cong; Yi, Li-Tao; Geng, Di; Han, Yuan-Yuan; Weng, Lian-Jin

2014-11-28

43

Infectious complications in patients with liver cirrhosis.  

PubMed

Liver cirrhosis is the end stage of any chronic liver disease. Complications occurring in patients with liver cirrhosis may be specific to this pathology and to gastroenterology (upper gastrointestinal bleeding, hepatic encephalopathy) or may interfere with other specialties (hepatorenal syndrome, spontaneous bacterial peritonitis, and other localized infectious complications). Over the past few decades, major efforts have been made to increase survival in patients with cirrhosis, but unfortunately, few therapeutic methods have been proven effective. Bacterial infections are frequent and serious complications of liver cirrhosis, resulting in high morbidity and mortality, especially in hospitalized patients, despite significant progress in health care for those with advanced liver disease. PMID:25341269

Preda, Sînziana; Trifan, Anca; Gîrleanu, Irina; Stanciu, C; Cojocariu, Camelia

2014-01-01

44

Cirrhosis  

MedlinePLUS

Liver cirrhosis; Cryptogenic chronic liver disease ... Cirrhosis is the end result of chronic liver damage caused by chronic liver disease. Common causes of chronic liver disease in the United States are: Hepatitis B or C infection Alcohol ...

45

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. 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

46

Hepatoprotective and Antioxidant Effects of Licorice Extract against CCl4-Induced Oxidative Damage in Rats  

PubMed Central

Licorice has been used in Chinese folk medicine for the treatment of various disorders. Licorice has the biological capabilities of detoxication, antioxidation, and antiinfection. In this study, we evaluated the antihepatotoxic effect of licorice aqueous extract (LE) on the carbon tetrachloride (CCl4)-induced liver injury in a rat model. Hepatic damage, as reveled by histology and the increased activities of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) activities, and decreased levels of serum total protein (TP), albumin (Alb) and globulin (G) were induced in rats by an administration of CCl4 at 3 mL/kg b.w. (1:1 in groundnut oil). Licorice extract significantly inhibited the elevated AST, ALP and ALT activities and the decreased TP, Alb and G levels caused by CCl4 intoxication. It also enhanced liver super oxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GR), Glutathione S-transferase (GST) activities and glutathione (GSH) level, reduced malondialdehyde (MDA) level. Licorice extract still markedly reverses the increased liver hydroxyproline and serum TNF-? levels induced by CCl4 intoxication. The data of this study support a chemopreventive potential of licorice extract against liver oxidative injury. PMID:22072903

Huo, Hai Zhong; Wang, Bing; Liang, Yong Kang; Bao, Yong Yang; Gu, Yan

2011-01-01

47

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. PMID:24829584

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

2014-01-01

48

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

49

Nrf2 pathway activation contributes to anti-fibrosis effects of ginsenoside Rg1 in a rat model of alcohol- and CCl4-induced hepatic fibrosis  

PubMed Central

Aim: To investigate the anti-fibrosis effects of ginsenoside Rg1 on alcohol- and CCl4-induced hepatic fibrosis in rats and to explore the mechanisms of the effects. Methods: Rats were given 6% alcohol in water and injected with CCl4 (2 mL/kg, sc) twice a week for 8 weeks. Rg1 (10, 20 and 40 mg/kg per day, po) was administered in the last 2 weeks. Hepatic fibrosis was determined by measuring serum biochemical parameters, HE staining, Masson's trichromic staining, and hydroxyproline and ?-SMA immunohistochemical staining of liver tissues. The activities of antioxidant enzymes, lipid peroxidation, and Nrf2 signaling pathway-related proteins (Nrf2, Ho-1 and Nqo1) in liver tissues were analyzed. Cultured hepatic stellate cells (HSCs) of rats were prepared for in vitro studies. Results: In the alcohol- and CCl4-treated rats, Rg1 administration dose-dependently suppressed the marked increases of serum ALT, AST, LDH and ALP levels, inhibited liver inflammation and HSC activation and reduced liver fibrosis scores. Rg1 significantly increased the activities of antioxidant enzymes (SOD, GSH-Px and CAT) and reduced MDA levels in liver tissues. Furthermore, Rg1 significantly increased the expression and nuclear translocation of Nrf2 that regulated the expression of many antioxidant enzymes. Treatment of the cultured HSCs with Rg1 (1 ?mol/L) induced Nrf2 translocation, and suppressed CCl4-induced cell proliferation, reversed CCl4- induced changes in MDA, GPX, PCIII and HA contents in the supernatant fluid and ?-SMA expression in the cells. Knockdown of Nrf2 gene diminished these actions of Rg1 in CCl4-treated HSCs in vitro. Conclusion: Rg1 exerts protective effects in a rat model of alcohol- and CCl4-induced hepatic fibrosis via promoting the nuclear translocation of Nrf2 and expression of antioxidant enzymes. PMID:24976156

Li, Jian-ping; Gao, Yan; Chu, Shi-feng; Zhang, Zhao; Xia, Cong-yuan; Mou, Zheng; Song, Xiu-yun; He, Wen-bin; Guo, Xiao-feng; Chen, Nai-hong

2014-01-01

50

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

51

Alternative complement pathway component Factor D contributes to efficient clearance of tissue debris following acute CCl4-induced injury.  

PubMed

Complement, part of the innate immune system, is involved with immune protection against invading pathogens as well as cell survival and tissue regeneration. It is known that complement activation is required for timely hepatocyte recovery following an acute toxic injury, but which pathway of complement activation is involved in response to hepatocyte injury has not been identified. In these studies we utilize mice deficient in C1qa, C4 and Factor D, lacking the classical, classical/MBL, and alternative pathways of complement activation, respectively, to identify an essential role for Factor D in the ability of the liver to recover from acute toxic injury. Here we demonstrate that following an acute CCl4-induced injury, the involvement of the alternative complement pathway is essential for efficient liver recovery. PMID:25467802

Cresci, Gail A; Allende, Daniela; McMullen, Megan R; Nagy, Laura E

2015-03-01

52

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. PMID:22888266

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

53

Cardiac abnormalities in liver cirrhosis.  

PubMed Central

Cirrhosis is associated with several circulatory abnormalities. A hyperkinetic circulation characterized by increased cardiac output and decreased arterial pressure and peripheral resistance is typical. Despite this hyperkinetic circulation, some patients with alcoholic cirrhosis have subclinical cardiomyopathy with evidence of abnormal ventricular function unmasked by physiologic or pharmacologic stress. Florid congestive alcoholic cardiomyopathy develops in a small percentage, but the concurrent presence of cirrhosis seems to retard the occurrence of overt heart failure. Even nonalcoholic cirrhosis may be associated with latent cardiomyopathy, although overt heart failure is not observed. Tense ascites is associated with some cardiac compromise, and removing or mobilizing ascitic fluid by paracentesis or peritoneovenous shunting results in short-term increases in cardiac output. Cirrhosis also appears to be associated with a decreased risk of major coronary atherosclerosis and an increased risk of bacterial endocarditis. Small hemodynamically insignificant pericardial effusions may be seen in ascitic patients. The release of atrial natriuretic peptide appears to be unimpaired in cirrhosis, although the kidney may be hyporesponsive to its natriuretic effects. PMID:2690463

Lee, S S

1989-01-01

54

Daily Drinking May Raise Risk of Liver Cirrhosis  

MedlinePLUS

... enable JavaScript. Daily Drinking May Raise Risk of Liver Cirrhosis, Study Warns Everyday habits appear to matter ... Daily drinking increases the risk of alcohol-related liver cirrhosis, a new study found. It's generally believed ...

55

FastStats: Chronic Liver Disease and Cirrhosis  

MedlinePLUS

... Submit What's this? Submit Button NCHS Home Chronic Liver Disease and Cirrhosis Share Compartir Data are for ... Hospital inpatient care Number of discharges with chronic liver disease and cirrhosis as the first-listed diagnosis: ...

56

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. PMID:22862950

2012-01-01

57

Cirrhosis  

MedlinePLUS

Cirrhosis is scarring of the liver. Scar tissue forms because of injury or long-term disease. Scar ... the blood, help digest food and store energy. Cirrhosis can lead to Easy bruising or bleeding, or ...

58

[Nutritional support in patients with liver cirrhosis].  

PubMed

Given the liver's multiple synthetic, regulatory and detoxifying functions, one of the characteristics accompanying severe hepatocellular dysfunction is the presence of malnutrition. This disorder is highly frequent in liver cirrhosis, even in the relatively early stages of the disease. Independently of the cause of the cirrhosis, poor nutritional status is associated with a worse prognosis and therefore early intervention to correct nutrient deficiency can prolong life expectancy, improve quality of life, reduce complications and increase the probability of successful transplantation. The present article reviews current knowledge of the diagnosis and management of malnutrition in patients with cirrhosis. Special attention is paid to the concept of the late evening snack and its characteristics, composition and probable benefits in the course of the disease. PMID:22657567

Rivera Irigoin, Robin; Abilés, Jimena

2012-10-01

59

Undaria pinnatifida fucoidan extract protects against CCl 4 -induced oxidative stress  

Microsoft Academic Search

This study was performed to elucidate the effects of Undaria pinnatifida fucoidan extract (UPFE) in preventing CCl4-induced oxidative stress. UPFE (100 mg\\/kg) was intraperitoneally administered to rats for 14 days. On day 15, CCl4 dissolved in olive oil (50% CCl4) was injected 12 h before they were anesthetized and dissected. To measure UPFE-mediated antioxidation, we examined the levels\\u000a of glutamate

Kum Suk Kang; In Deok Kim; Ryun Hee Kwon; Bae Jin Ha

2008-01-01

60

Hepatoprotection of tea seed oil ( Camellia oleifera Abel.) against CCl 4-induced oxidative damage in rats  

Microsoft Academic Search

The oil of tea seed (Camellia oleifera Abel.) is used extensively in China for cooking. This study was designed to evaluate the effects of tea seed oil on CCl4-induced acute hepatotoxicity in rats. Male SD rats (200±10g) were pre-treated with tea seed oil (50, 100, and 150g\\/kg diet) for six weeks before treatment with a single dose of CCl4 (50%

Chia-Pu Lee; Ping-Hsiao Shih; Chin-Lin Hsu; Gow-Chin Yen

2007-01-01

61

Cardiovascular dysfunction in patients with liver cirrhosis  

PubMed Central

Hyperdynamic syndrome is a well-known clinical condition found in patients with cirrhosis and portal hypertension, characterized by increased heart rate and cardiac output, and reduced systemic vascular resistance and arterial blood pressure. The leading cause of hyperdynamic circulation in cirrhotic patients is peripheral and splanchnic vasodilatation, due to an increased production/activity of vasodilator factors and decreased vascular reactivity to vasoconstrictors. The term “cirrhotic cardiomyopathy” describes impaired contractile responsiveness to stress, diastolic dysfunction and electrophysiological abnormalities in patients with cirrhosis without known cardiac disease. Underlying circulatory and cardiac dysfunctions are the main determinant in the development of hepatorenal syndrome in advanced cirrhosis. Moreover, the clinical consequences of cirrhosis-related cardiovascular dysfunction are evident during and after liver transplantation, and after transjugular intrahepatic portosystemic shunt insertion. Cardiovascular complications following these procedures are common, with pulmonary edema being the most common complication. Other complications include overt heart failure, arrhythmia, pulmonary hypertension, pericardial effusion, and cardiac thrombus formation. This review discusses the circulatory and cardiovascular dysfunctions in cirrhosis, examining the pathophysiologic and clinical implications in light of the most recent published literature. PMID:25608575

Fede, Giuseppe; Privitera, Graziella; Tomaselli, Tania; Spadaro, Luisa; Purrello, Francesco

2015-01-01

62

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. PMID:24667392

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

2014-01-01

63

Telomere shortening as genetic risk factor of liver cirrhosis.  

PubMed

Cirrhosis is the main complication of chronic liver disease, leads to progressive liver function impairment and is the main risk factor for the development of liver cancer. Liver failure at endstage cirrhosis is associated with increased mortality with liver transplantation as the only possible treatment at this stage. The pathogenesis of liver cirrhosis is not completely elucidated. Although the common factors leading to liver injury, such as viral hepatitis, alcohol consume or fatty liver disease can be identified in the majority of patients a small percentage of patients have no apparent risk factors. Moreover given the same risk factors, some patients progress to cirrhosis whereas others have a benign course, the reason remains unclear. In order to develop new diagnostic and therapeutic tools, it is s essential to understand the pathogenesis of cirrhosis. The identification of genetic risk factors associated with cirrhosis is one of the possible approach to achieve these goal. In the past years several studies have supported the role of telomere shortening and cirrhosis. In the recent year several studies on the relation between several single nucleotide polymorphism (SNPs) and cirrhosis have been published; it has been proposed also a cirrhosis risk score based on seven SNPs. Also epidemiological studies on identical twins and in different ethnic groups have been supporting the importance of the role of genetic risk factors. Finally in the very recent years it has been suggested that telomere shortening may represent a genetic risk factor for the development of cirrhosis. PMID:25593453

Carulli, Lucia

2015-01-14

64

Telomere shortening as genetic risk factor of liver cirrhosis  

PubMed Central

Cirrhosis is the main complication of chronic liver disease, leads to progressive liver function impairment and is the main risk factor for the development of liver cancer. Liver failure at endstage cirrhosis is associated with increased mortality with liver transplantation as the only possible treatment at this stage. The pathogenesis of liver cirrhosis is not completely elucidated. Although the common factors leading to liver injury, such as viral hepatitis, alcohol consume or fatty liver disease can be identified in the majority of patients a small percentage of patients have no apparent risk factors. Moreover given the same risk factors, some patients progress to cirrhosis whereas others have a benign course, the reason remains unclear. In order to develop new diagnostic and therapeutic tools, it is s essential to understand the pathogenesis of cirrhosis. The identification of genetic risk factors associated with cirrhosis is one of the possible approach to achieve these goal. In the past years several studies have supported the role of telomere shortening and cirrhosis. In the recent year several studies on the relation between several single nucleotide polymorphism (SNPs) and cirrhosis have been published; it has been proposed also a cirrhosis risk score based on seven SNPs. Also epidemiological studies on identical twins and in different ethnic groups have been supporting the importance of the role of genetic risk factors. Finally in the very recent years it has been suggested that telomere shortening may represent a genetic risk factor for the development of cirrhosis. PMID:25593453

Carulli, Lucia

2015-01-01

65

Coffee, Caffeine, and the Risk of Liver Cirrhosis  

Microsoft Academic Search

PURPOSE: To evaluate the effect of the consumption of caffeine-containing beverages on the risk of symptomatic liver cirrhosis (LC).METHODS: From 1994 to 1998, all the consecutive cirrhotic inpatients admitted in 19 collaborative hospitals for signs of liver decompensation in whom the diagnosis of liver cirrhosis was made for the first time (274 cases) and one or two gender, age, and

Giovanni Corrao; Antonella Zambon; Vincenzo Bagnardi; Amleto D'Amicis; Arthur Klatsky

2001-01-01

66

Motor dysfunction in patients with liver cirrhosis: impairment of handwriting  

Microsoft Academic Search

Motor dysfunction is an important clinical finding in patients with liver cirrhosis and mild forms of hepatic encephalopathy.\\u000a The mechanisms and clinical appearance of motor impairment in patients with liver cirrhosis are not completely understood.\\u000a We studied fine motor control in forty four patients with advanced liver cirrhosis (excluding those with hepatic encephalopathy\\u000a grade II) and 48 healthy controls using

Sergei Mechtcheriakov; Ivo W. Graziadei; André Kugener; Ingrid Schuster; Joerg Mueller; Hartmann Hinterhuber; W. Vogel; J. Marksteiner

2006-01-01

67

Hypoxaemia and cirrhosis of the liver.  

PubMed Central

In order to determine the frequency of hypoxaemia and to evaluate the role of increased closing capacity in producing hypoxaemia in patients with cirrhosis of the liver, 13 patients with well-established cirrhosis were studied. Arterial blood gases, spirometry, lung volume, and closing capacity measurements were made with the patients in the seated and recumbent positions after exclusion of cardiopulmonary dysfunction. Four of 13 and six of 12 patients exhibited significant hypoxaemia in the seated and recumbent positions respectively. Five of 13 patients showed a closing capacity greater than predicted. This frequency of increased closing capacity was not higher than in a group of smokers of the same age. Unlike Ruff et al. (1971), we did not find a consistent relationship between hypoxaemia and closing capacity. PMID:941116

Funahashi, A; Kutty, A V; Prater, S L

1976-01-01

68

Therapeutic efficacy of Nigella sativa Linn. seed extract against CCl4 induced hepatic injury in Wistar rats.  

PubMed

Carbon tetrachloride (CCl4) intake damages liver. We evaluated therapeutic potential of aqueous extract of Nigella sativa seeds against CCl4 induced liver damage in rats. The hepatic damage induced by CCl4 @ 1.5 mL/kg, ip was evidenced by a significant increase in the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin, protein and urea lipid peroxidation (LPO) as well as reduction in hepatic antioxidant system e.g. reduced glutathione. Hepatic total protein and glucose-6-phosphatase activity were found decreased. Histological studies substantiated the above biochemical findings. However, after 48 h of administration of aqueous extract of N. sativa seeds (250, 500 and 750 mg/kg, po) it not only detoxified the toxicity but also reversed LPO, GSH, AST, ALT and serum protein changes at all the three doses. Both higher doses of extract were found effective in monitoring urea, albumin, total protein and G-6-Pase activity. However, on the basis of percent protection highest dose i.e., 750 mg/kg proved better. The result suggests that the aqueous extract of N. sativa seeds can be used as a hepatoprotective agent. PMID:25675711

Jaswal, Amita; Shukla, Sangeeta

2015-01-01

69

Protective effect of red-stemmed type of Ipomoea aquatica Forsk against CCl4-induced oxidative damage in mice.  

PubMed

Water spinach (Ipomoea aquatica Forsk; I. aquatica) of the green-stemmed type (green type) is widely consumed, but there also exists a red-stemmed variety (red type). In the present study, the antioxidant capacity of the red type was compared to that of the green type in carbon tetrachloride (CCl(4))-treated mice. CCl(4)-induced thiobarbituric acid reactive substrate (TBARS) formation in the liver was significantly suppressed in mice fed 5% red-type I. aquatica, while the green type showed no effect. Hydrophobic oxygen radical absorbance capacity (H-ORAC(FL)) in the red type showed a lower level than that in the green type; however, lipophilic ORAC (L-ORAC(FL)) and total-ORAC(FL) levels were significantly higher in the red type than in the green type. ?-Tocopherol, anthocyanidin/proanthocyanidin, and ?-carotene contents were all significantly higher in the red type than in the green type. These results suggest that the wild red-type I. aquatica contains certain lipophilic components that exert antioxidant capacities not only in vitro but also in vivo. Such effective components in the red type would be beneficial phytochemicals for suppressing several diseases related to oxidative stress. PMID:22041914

Hirai, Shizuka; Ishibuchi, Toyohito; Watabe, Shinpei; Makita, Miki; Kishida, Chiaki; Takagaki, Michiko; Kurauchi, Nobuyuki; Egashira, Yukari

2011-01-01

70

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

71

[Minimally invasive splenectomy for thrombocytopenia associated with liver cirrhosis].  

PubMed

Thrombocytopenia is a common complication in patients with chronic liver disease and corelates with the severity of cirrhosis. Severe trombocytopenia can sinificantly increase the risk of spontaneous bleeding, but even if it is not symptomatic it can complicate the medical management of the cirrhotic patient by postponing diagnistic or therapeutic procedures (liver biopsy, interferon therapy, hepatocellular carcinoma resection). In consequence, numerous procedures were imagined to reverse thrombocytopenia associated with liver cirrhosis, among wich splenectomy. Due to the extreme invasiveness of the clasic approach in patients with hipersplenism (risk of bleeding, postoperative pain) especially in those with advanced cirrhosis, minimally invasive splenectomy appears to offer a safe and effective method for reversing thrombocytopenia in a highly selected group of patients with liver cirrhosis (Child A cirrhosis without other significant medical comorbid conditions). In these cases the surgical procedure is associated with low morbidity, blood loss and short hospital stay. PMID:20405675

Popa, M; Vasilescu, C

2010-01-01

72

Biosynthesis of silver nanoparticles from Premna serratifolia L. leaf and its anticancer activity in CCl4-induced hepato-cancerous Swiss albino mice  

NASA Astrophysics Data System (ADS)

In this study, we report the biosynthesis of silver nanoparticles using the ethanolic leaf powder extract of Premna serratifolia L. and its anticancer activity in carbon tetra chloride (CCl4)-induced liver cancer in Swiss albino mice (Balb/c). The synthesized silver nanoparticles were characterized by SEM, FTIR and XRD analyses. The Debye-Scherrer equation was used to calculate particle size and the average size of silver nanoparticles synthesized from P. serratifolia leaf extract was 22.97 nm. The typical pattern revealed that the sample contained cubic structure of silver nanoparticles. FTIR analysis confirmed that the bioreduction of silver ions to silver nanoparticles is due to reduction by capping material of the plant extract. The silver nanoparticles of P. serratifolia leaf extract were effective in treating liver cancer in Swiss albino mice when compared with P. serratifolia leaf extract with isoleucine.

Arockia John Paul, J.; Karunai Selvi, B.; Karmegam, N.

2015-01-01

73

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. PMID:24763616

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

74

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. PMID:24914367

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

2014-01-01

75

Nutritional assessment in various stages of liver cirrhosis  

Microsoft Academic Search

OBJECTIVES: The aims of this study were to determine the prevalence of protein-calorie malnutrition, characteristics, and clinical importance of nutrition disorders in patients with liver cirrhosis according to severity of disease.METHODS: Nutrition assessments such as subjective global assessment, anthropometric and biochemical measurements, immunocompentency, thiamin and riboflavin status in 60 patients with cirrhosis (33 male and 27 female) were recorded between

Chulaporn Roongpisuthipong; Aphasnee Sobhonslidsuk; Kanokrat Nantiruj; Sriwatana Songchitsomboon

2001-01-01

76

Unilateral pleural effusion without ascites in liver cirrhosis  

SciTech Connect

The source of massive pleural effusion was not apparent in a 58-year-old man who had cirrhosis but no demonstrable ascites. Intraperitoneal injection of technetium Tc 99m sulfur colloid established the presence of peritoneopleural communication. This diagnostic technique can be helpful in evaluating patients with cirrhosis of the liver and pleural effusion with or without ascites.

Faiyaz, U.; Goyal, P.C.

1983-09-01

77

Preventive supplementation with fresh and preserved peach attenuates CCl4-induced oxidative stress, inflammation and tissue damage.  

PubMed

The present study was elaborated to comparatively evaluate the preventive effect of different peach-derived products obtained from preserved fruits (Syrup and Preserve Pulp Peach [PPP]) and from fresh peels and pulps (Peel and Fresh Pulp Peach [FPP]) in a model of liver/renal toxicity and inflammation induced by carbon tetrachloride (CCl4) in rats. Tissue damage (carbonyl, thiobarbituric acid reactive species and sulfhydril), antioxidant enzymes activity (catalase and superoxide dismutase) and inflammatory parameters [tumor necrosis factor (TNF)-? and interleukin (IL)-1? levels, and receptor for advanced glycation end-products (RAGE) and nuclear factor (NF)?B-p65 immunocontent] were investigated. Our findings demonstrated that Peel, PPP and FPP (200 or 400 mg/kg) daily administration by oral gavage for 30 days conferred a significant protection against CCl4-induced antioxidant enzymes activation and, most importantly, oxidative damage to lipids and proteins as well as blocked induction of inflammatory mediators such as TNF-?, IL-1?, RAGE and NF?B. This antioxidant/anti-inflammatory effect seems to be associated with the abundance of carotenoids and polyphenols present in peach-derived products, which are enriched in fresh-fruit-derived preparations (Peel and FPP) but are also present in PPP. The Syrup - which was the least enriched in antioxidants - displayed no protective effect in our experiments. These effects cumulated in decreased levels of transaminases and lactate dehydrogenase leakage into serum and maintenance of organ architecture. Therefore, the herein presented results show evidence that supplementation with peach products may be protective against organ damage caused by oxidative stress, being interesting candidates for production of antioxidant-enriched functional foods. PMID:25287815

Gasparotto, Juciano; Somensi, Nauana; Bortolin, Rafael Calixto; Girardi, Carolina Saibro; Kunzler, Alice; Rabelo, Thallita Kelly; Schnorr, Carlos Eduardo; Moresco, Karla Suzana; Bassani, Valquiria Linck; Yatsu, Francini Kiyono Jorge; Vizzotto, Márcia; Raseira, Maria do Carmo Bassols; Zanotto-Filho, Alfeu; Moreira, José Claudio Fonseca; Gelain, Daniel Pens

2014-12-01

78

Serum levels of cytokines in alcoholic liver cirrhosis and pancreatitis.  

PubMed

Although altered cytokine homeostasis has been implicated in the pathogenesis of both alcoholic liver and pancreas diseases, the serum cytokine pattern characteristic of concomitant alcoholic liver cirrhosis and pancreatitis has not been examined. In this paper we examine the serum levels of proinflammatory cytokines, such as IL-6, IL-8, TNF-alpha, and also antiinflammatory ones, such as IL-10 and TGF-beta, in 22 patients with alcoholic liver cirrhosis and 28 patients with chronic pancreatitis and compare them with those detected in the sera of 14 patients with concomitant alcoholic cirrhosis and pancreatitis. All patients were heavy alcohol drinkers, consuming more than 70 g of pure alcohol per day for at least 5 years. The control group consisted of 33 age- and sex-matched healthy subjects receiving an annual health examination. They were not addicted to alcohol and confirmed to be free of major cardiopulmonary, gastrointestinal and hepatobiliary-pancreatic diseases. The results indicated that the cytokine pattern in the sera of patients with concomitant liver cirrhosis and pancreatitis was characterized by increased levels of two proinflammatory cytokines: TNF-alpha, the concentration of which seemed to be influenced by both liver and pancreas injury, and IL-6, which seemed to be rather connected with pancreas injury. Increased levels of IL-8, which were detected in the sera of patients with cirrhosis, pancreatitis and concomitant cirrhosis and pancreatitis, were rather connected with exacerbation of the disease processes which occurred only in some of the patients. No significant changes in the levels of IL-10 or TGF-beta were detected in the sera of patients with chronic pancreatitis and concomitant cirrhosis and pancreatitis, while in patients with cirrhosis significantly decreased levels of IL-10 were found. A significant imbalance between proinflammatory/antiinflammatory signals was especially characteristic of alcoholic cirrhosis and concomitant cirrhosis with pancreatitis. PMID:11059648

Szuster-Ciesielska, A; Daniluk, J; Kandefer-Zersze?, M

2000-01-01

79

Liver transplantation in cirrhosis due to hepatitis D virus infection.  

PubMed

In a series of 49 patients transplanted for cirrhosis due to hepatitis D virus (HDV) infection and receiving anti-HBs immunoglobulins, the 2-year actuarial rate of hepatitis B virus (HBV) reinfection was only 13%, a prevalence much lower than the 29% rate in patients transplanted for HBV-DNA-negative cirrhosis and the 96% rate in patients transplanted for HBV-DNA-positive cirrhosis. HBV reinfection after transplantation in patients with cirrhosis due to HDV infection was invariably associated with HDV reinfection. In a few patients, in the absence of HBV reinfection, transient replication of HDV took place and was not associated with liver lesions of hepatitis. In conclusion, patients with cirrhosis due to HDV infection are good candidates for liver transplantation. PMID:8509633

Samuel, D; Bismuth, H; Benhamou, J P

1993-01-01

80

[Regional difference in the etiology of liver cirrhosis in Iwate].  

PubMed

To assess regional differences in the etiology of liver cirrhosis in Iwate, we analyzed 324 patients with liver cirrhosis treated at various hospitals. The etiology was HCV 44.8%, HBV 11.1%, HBV + HCV 4.6%, alcohol 27.5% (including heavy drinkers 17.9%), PBC 1.5% and non-B non-C 10.5% in Iwate. The incidence of alcoholic cirrhosis was higher than that in other prefectures, while that of HCV was lower. Especially in the northern area of Iwate, the rate of alcoholic cirrhosis was very high (39.1%--including heavy drinkers 21.8%) while viral cirrhosis was relatively low. Although the alcohol consumption volume in Iwate was not very high, marked alcohol consumption, especially shochu, was observed in the northern area of Iwate. The volume and kind of alcohol consumed in each area differed, and the etiology of liver cirrhosis differed regionally in Iwate. Thus, we should consider these districts and levels of alcohol consumption when treating patients with liver cirrhosis. PMID:9436390

Yoshida, T; Katsurashima, T; Abe, K; Kato, A; Suzuki, K; Sasaki, S; Ikuta, T; Narita, T; Isogai, K; Moriai, O; Murakami, A; Ono, M; Watanabe, T; Abe, H; Ueda, S; Saito, Y; Takahashi, T; Kooka, F; Chiba, T; Katsura, Y; Ono, Y; Kosaka, Y; Yasumi, S; Kawata, T; Sato, S

1997-12-01

81

Pistacia chinensis: A Potent Ameliorator of CCl4 Induced Lung and Thyroid Toxicity in Rat Model  

PubMed Central

In the current study protective effect of ethanol extract of Pistacia chinensis bark (PCEB) was investigated in rats against CCl4 induced lung and thyroid injuries. PCEB dose dependently inhibited the rise of thiobarbituric acid-reactive substances, hydrogen peroxide, nitrite, and protein content and restored the levels of antioxidant enzymes, that is, catalase, peroxidase, superoxide dismutase, glutathione-S-transferase, glutathione reductase, glutathione peroxidase, ?-glutamyl transpeptidase, and quinone reductase in both lung and thyroid tissues of CCl4 treated rats. Decrease in number of leukocytes, neutrophils, and hemoglobin and T3 and T4 content as well as increase in monocytes, eosinophils, and lymphocytes count with CCl4 were restored to normal level with PCEB treatment. Histological study of CCl4 treated rats showed various lung injuries like rupture of alveolar walls and bronchioles, aggregation of fibroblasts, and disorganized Clara cells. Similarly, histology of CCl4 treated thyroid tissues displayed damaged thyroid follicles, hypertrophy, and colloidal depletion. However, PCEB exhibited protective behaviour for lungs and thyroid, with improved histological structure in a dose dependant manner. Presence of three known phenolic compounds, that is, rutin, tannin, and gallic acid, and three unknown compounds was verified in thin layer chromatographic assessment of PCEB. In conclusion, P. chinensis exhibited antioxidant activity by the presence of free radical quenching constituents. PMID:25180176

Naz, Kiran; Khan, Muhammad Rashid; Shah, Naseer Ali; Sattar, Saadia; Noureen, Farah; Awan, Madeeha Latif

2014-01-01

82

Upper gastrointestinal bleeding in patients with liver cirrhosis.  

PubMed Central

Patients with liver cirrhosis may develop upper gastrointestinal hemorrhage from a variety of lesions, which include those that arise by virtue of portal hypertension, namely gastroesophageal varices and portal hypertensive gastropathy and other lesions seen in the general population. Do patients with liver cirrhosis, hemorrhage from varices and other lesions equally, or are they more likely to bleed from varices? The aim of this study is to determine predominant causes of bleeding in patients with liver cirrhosis and upper gastrointestinal bleeding. PATIENTS AND METHODS: A retrospective review of 40 patients with liver cirrhosis based on the clinical and biochemical parameters of the Child-Pugh score, and upper gastrointestinal bleeding was carried out at an inner city hospital. Endoscopy diagnoses were documented. RESULTS: Of 40 patients, 38 patients had cirrhosis associated with alcohol consumption. Twelve of the above 38 patients who consumed alcohol also had hepatitis C virus (HCV) infection. Eleven patients had only varices on endoscopic examination, 17 had varices plus coexisting lesions. From these 17 patients, nine were found to have bled from varices, and eight were found to have bled from coexisting lesions. Twelve patients who had no varices bled from other lesions. Of 40 patients, 28 had varices, and 20 actually bled from varices. In this study there was no correlation between severity of liver cirrhosis as determined by the Child-Pugh score and the absence or presence of varices. CONCLUSION: Patients with liver cirrhosis and upper gastrointestinal bleeding hemorrhage from a variety of lesions. In this study of 40 patients, (70%) had gastroesophageal varices diagnosed at upper endoscopy, while 50% actually bled from varices. PMID:12152928

Odelowo, Olajide O.; Smoot, Duane T.; Kim, Kyungsook

2002-01-01

83

Readthrough Acetylcholinesterase Is Increased in Human Liver Cirrhosis  

PubMed Central

Background & Aims There have been many studies on plasma butyrylcholinesterase in liver dysfunction. However, no data is available about acetylcholinesterase in human cirrhosis, although profound changes have been described in cirrhotic rat models. Methods Human serum and liver acetylcholinesterase and its molecular forms were determined enzymatically, after butyrylcholinesterase immunodepletion. The distinct species of acetylcholinesterase, with a distinct C-terminus, were determined by western blotting, and the level of liver transcripts by real-time PCR. Liver acetylcholinesterase was also evaluated by immunocytochemistry. Results In patients with liver cirrhosis, the activity of plasma acetylcholinesterase (rich in light species), appeared to be apparently unaffected. However, the levels of the soluble readthrough (R) acetylcholinesterase form, an acetylcholinesterase species usually associated with stress and pathology, was increased compared to controls. Human liver acetylcholinesterase activity levels were also unchanged, but protein levels of the acetylcholinesterase-R and other acetylcholinesterase subunit species were increased in the cirrhotic liver. This increase in acetylcholinesterase protein expression in the cirrhotic liver was confirmed by PCR analysis. Immunohistological examination confirmed that acetylcholinesterase immunoreactivity is increased in parenchymal cells of the cirrhotic liver. Conclusions We demonstrate significant changes in acetylcholinesterase at the protein and mRNA levels in liver cirrhosis, with no difference in enzymatic activity. The altered expression of acetylcholinesterase protein may reflect changes in its pathophysiological role. PMID:23028565

García-Ayllón, María-Salud; Millán, Cristina; Serra-Basante, Carol; Bataller, Ramón; Sáez-Valero, Javier

2012-01-01

84

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

85

Nodular regenerative hyperplasia mimicking cirrhosis of the liver.  

PubMed Central

Nodular regenerative hyperplasia of the liver usually presents with signs of portal hypertension with little evidence of obvious liver disease. We report a 47 year old man who presented with clinical signs of decompensated cirrhosis, recurrent encephalopathy, and tense ascites but at liver transplant was found to have nodular regenerative hyperplasia associated with a portal vein thrombosis. Images Figure 1 Figure 2 Figure 3 PMID:2379880

McDonald, J A; Painter, D M; Gallagher, N D; McCaughan, G W

1990-01-01

86

Suspected azathioprine induced liver cirrhosis: an unusual side effect  

PubMed Central

In recent years, the hepatotoxic potential of thiopurines, in particular 6-thioguanine (6-TG) has been discussed in literature. However, cirrhosis was exceptionally reported. We report the case of a 56-year-old woman with ileocaecal Crohn's disease treated with azathioprine. After taking azathioprine (2 mg/kg daily) for four years, she underwent surgical treatment for acute intestinal obstruction. In peroperative, we noticed a cirrhotic liver. A surgical biopsy was performed and the diagnosis of cirrhosis was confirmed. Autoimmune and viral liver diseases were ruled out by laboratory parameters. Therefore, Azathioprine is believed to be the causative actor for inducing liver cirrhosis. Thus, treating inflammatory bowel disease effectively while trying to limit iatrogenic disease is a continuous struggle. PMID:25392720

Trabelsi, Aida Ben Slama; Hamami, Eya; Souguir, Ahlem; Ksiaa, Mehdi; Ajmi, Salem; Jmaa, Ali

2014-01-01

87

Management of thrombocytopenia due to liver cirrhosis: A review  

PubMed Central

Thrombocytopenia is a common complication in liver disease and can adversely affect the treatment of liver cirrhosis, limiting the ability to administer therapy and delaying planned surgical/diagnostic procedures because of an increased risk of bleeding. Multiple factors, including splenic sequestration, reduced activity of the hematopoietic growth factor thrombopoietin, bone marrow suppression by chronic hepatitis C virus infection and anti-cancer agents, and antiviral treatment with interferon-based therapy, can contribute to the development of thrombocytopenia in cirrhotic patients. Of these factors, the major mechanisms for thrombocytopenia in liver cirrhosis are (1) platelet sequestration in the spleen; and (2) decreased production of thrombopoietin in the liver. Several treatment options, including platelet transfusion, interventional partial splenic embolization, and surgical splenectomy, are now available for severe thrombocytopenia in cirrhotic patients. Although thrombopoietin agonists and targeted agents are alternative tools for noninvasively treating thrombocytopenia due to liver cirrhosis, their ability to improve thrombocytopenia in cirrhotic patients is under investigation in clinical trials. In this review, we propose a treatment approach to thrombocytopenia according to our novel concept of splenic volume, and we describe the current management of thrombocytopenia due to liver cirrhosis. PMID:24627595

Hayashi, Hiromitsu; Beppu, Toru; Shirabe, Ken; Maehara, Yoshihiko; Baba, Hideo

2014-01-01

88

Alterations of the human gut microbiome in liver cirrhosis.  

PubMed

Liver cirrhosis occurs as a consequence of many chronic liver diseases that are prevalent worldwide. Here we characterize the gut microbiome in liver cirrhosis by comparing 98 patients and 83 healthy control individuals. We build a reference gene set for the cohort containing 2.69 million genes, 36.1% of which are novel. Quantitative metagenomics reveals 75,245 genes that differ in abundance between the patients and healthy individuals (false discovery rate < 0.0001) and can be grouped into 66 clusters representing cognate bacterial species; 28 are enriched in patients and 38 in control individuals. Most (54%) of the patient-enriched, taxonomically assigned species are of buccal origin, suggesting an invasion of the gut from the mouth in liver cirrhosis. Biomarkers specific to liver cirrhosis at gene and function levels are revealed by a comparison with those for type 2 diabetes and inflammatory bowel disease. On the basis of only 15 biomarkers, a highly accurate patient discrimination index is created and validated on an independent cohort. Thus microbiota-targeted biomarkers may be a powerful tool for diagnosis of different diseases. PMID:25079328

Qin, Nan; Yang, Fengling; Li, Ang; Prifti, Edi; Chen, Yanfei; Shao, Li; Guo, Jing; Le Chatelier, Emmanuelle; Yao, Jian; Wu, Lingjiao; Zhou, Jiawei; Ni, Shujun; Liu, Lin; Pons, Nicolas; Batto, Jean Michel; Kennedy, Sean P; Leonard, Pierre; Yuan, Chunhui; Ding, Wenchao; Chen, Yuanting; Hu, Xinjun; Zheng, Beiwen; Qian, Guirong; Xu, Wei; Ehrlich, S Dusko; Zheng, Shusen; Li, Lanjuan

2014-09-01

89

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. PMID:23382623

Trifan, Anca; Chiriac, Stefan; Stanciu, Carol

2013-01-01

90

Serum cytokine levels in alcohol-related liver cirrhosis.  

PubMed

Chronic alcoholism complicated by alcoholic liver disease is characterized by activation of the inflammatory response system. To evaluate the role of cytokines in the progress of alcoholic cirrhosis, we assessed serum level of the proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, and IL-8 and the antiinflammatory cytokines IL-2, IL-10, and transforming growth factor (TGF)-beta in patients with compensated and decompensated alcoholic liver cirrhosis. Compensated alcoholic cirrhosis was characterized by increased IL-6 (6.3+/-2.9 vs. HP 2.2+/-1.4 pg/ml in controls) and decreased IL-10 (HP 4.1+/-3.5 vs. 6.4+/-5.4 pg/ml in controls). TNF-alpha, IL-8, and TGF-beta1 levels were comparable to those found in controls. In sera of patients with decompensated alcoholic liver cirrhosis, besides increased IL-6 (11.2+/-7.7 pg/ml), increased concentrations of TNF-alpha (25.1+/-4.5 vs. 9.1+/-7.0 pg/ml in controls) and IL-8 (171.7+/-294.0 vs. 2.7+/-2.9 pg/ml in controls) were also detected. TGF-beta1 and IL-10 levels were similar to those found in controls. These results strongly indicate that a significant derangement of the balance between proinflammatory and antiinflammatory signals is characteristic of compensated and especially of decompensated alcoholic cirrhosis. PMID:11282449

Daniluk, J; Szuster-Ciesielska, A; Drabko, J; Kandefer-Szersze?, M

2001-01-01

91

Hepatoprotective effect of the aqueous extract of Simarouba amara Aublet (Simaroubaceae) stem bark against carbon tetrachloride (CCl4)-induced hepatic damage in rats.  

PubMed

Simarouba amara stem bark decoction has been traditionally used in Brazil to treat malaria, inflammation, fever, abdominal pain, diarrhea, wounds and as a tonic. In this study, we investigate the hepatoprotective effects of the aqueous extract of S. amara stem bark (SAAE) on CCl4-induced hepatic damage in rats. SAAE was evaluated by high performance liquid chromatography. The animals were divided into six groups (n = 6/group). Groups I (vehicle-corn oil), II (control-CCl4), III, IV, V and VI were pretreated during 10 consecutive days, once a day p.o, with Legalon® 50 mg/kg b.w, SAAE at doses 100, 250 and 500 mg/kg b.w, respectively. The hepatotoxicity was induced on 11th day with 2 mL/kg of 20% CCl4 solution. 24 h after injury, the blood samples were collected and their livers were removed to biochemical and immunohistochemical analyzes. The SAAE decreased the levels of liver markers and lipid peroxidation in all doses and increased the catalase levels at doses 250 and 500 mg/kg. Immunohistochemical results suggested hepatocyte proliferation in all doses. These results may be related to catechins present in SAAE. Thus, SAAE prevented the oxidative damage at the same time that increased regenerative and reparative capacities of the liver. PMID:25365298

Maranhăo, Hélida M L; Vasconcelos, Carlos F B; Rolim, Larissa A; Neto, Pedro J Rolim; Neto, Jacinto da C Silva; Filho, Reginaldo C da Silva; Fernandes, Mariana P; Costa-Silva, Joăo H; Araújo, Alice V; Wanderley, Almir G

2014-01-01

92

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

93

Serum cytokine levels in alcohol-related liver cirrhosis  

Microsoft Academic Search

Chronic alcoholism complicated by alcoholic liver disease is characterized by activation of the inflammatory response system. To evaluate the role of cytokines in the progress of alcoholic cirrhosis, we assessed serum level of the proinflammatory cytokines tumor necrosis factor-? (TNF-?), interleukin (IL)-6, and IL-8 and the antiinflammatory cytokines IL-2, IL-10, and transforming growth factor (TGF)-? in patients with compensated and

Jadwiga Daniluk; Agnieszka Szuster-Ciesielska; Jaros Drabko; Martyna Kandefer-Szersze?

2001-01-01

94

Hemosiderosis in cirrhosis: A study of 447 native livers  

Microsoft Academic Search

BACKGROUND & AIMS: Hemosiderosis may have a detrimental effect on some chronic liver diseases. The aim of this study was to determine the prevalence and diagnostic implications of hemosiderosis in cirrhosis.METHODS: Tissue iron in 447 cirrhotic livers was studied histologically and chemically.RESULTS: Positive iron staining was found in 145 cases (32.4%), and increased chemical hepatic iron concentration was found in

J Ludwig; E Hashimoto; MK Porayko; TP Moyer; WP Baldus

1997-01-01

95

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. PMID:24966592

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

2014-01-01

96

Non invasive tools for the diagnosis of liver cirrhosis  

PubMed Central

Liver cirrhosis (LC), the end stage of many forms of chronic hepatitis of different etiologies is a diffuse process characterized by fibrosis and the conversion of normal liver architecture into structurally abnormal nodules surrounded by annular fibrosis. This chronic progressive clinical condition, leads to liver cell failure and portal hypertension, which can favour the onset of hepatocellular carcinoma. Defining the phase of the natural history is crucial for therapeutic choice and prognosis. Liver biopsy is currently considered the best available standard of reference but it has some limits, so alternative tools have been developed to substitute liver biopsy when assessing liver fibrosis. Serum markers offer a cost-effective alternative to liver biopsy being less invasive and theoretically without complications. They can be classified into direct and indirect markers which may be used alone or in combination to produce composite scores. Diagnostic imaging includes a number of instruments and techniques to estimate liver fibrosis and cirrhosis like ultrasound (US), US Doppler, contrast enhanced US and Elastography. US could be used for the diagnosis of advanced LC while is not able to evaluate progression of fibrosis, in this case Elastography is more reliable. This review aims to revise the most recent data from the literature about non invasive methods useful in defining liver fibrosis. PMID:25561782

Soresi, Maurizio; Giannitrapani, Lydia; Cervello, Melchiorre; Licata, Anna; Montalto, Giuseppe

2014-01-01

97

Glycerol metabolism in patients with alcohol-induced liver cirrhosis.  

PubMed

The clearance rate of glycerol has been found to be impaired in alcoholic liver disease. However it remains unclear, if this can be ascribed to a defect of hepatic gluconeogenesis. Thus, the purpose of this work was to investigate glycerol clearance and hepatic glucose production in patients with liver cirrhosis. 13 patients with alcohol-induced Child B cirrhosis and 8 healthy volunteers were studied. Rates of appearance (R(a)) of glycerol, glucose and alanine were determined using stable isotope techniques. In addition indocyanine green clearance (ICGC) and plasma substrate concentrations were measured. Clearance rates were calculated as R(a) divided by the corresponding substrate concentration. R(a) of glycerol in patients was not different from controls, but glycerol clearance was significantly reduced (29 +/- 3 vs. 41 +/- 4 ml/kg/min). No differences in R(a) of glucose and alanine and corresponding plasma concentrations were observed. ICGC in patients was about 35% lower than reference values. Diminished glycerol clearance in patients with liver cirrhosis was not due to impaired hepatic gluconeogenesis. Since glycerol is almost completely extracted by the liver decreased glycerol clearance possibly simply reflected compromised liver perfusion as seen by reduced ICGC. PMID:16843937

Schricker, T; Albuszies, G; Weidenbach, H; Beckh, K H; Ensinger, H; Adler, G; Wachter, U; Georgieff, M

1995-08-01

98

Opisthorchis viverrini infection causes liver and biliary cirrhosis in gerbils.  

PubMed

Opisthorchis viverrini infection causes many hepatobiliary diseases, including cholangiocarcinoma. Hence, the study of O. viverrini infection in humans is subject to ethical limitations, so an animal model, the Syrian hamster, is often used. O. viverrini can develop into the adult stage not only in Syrian hamsters but also in other animals, including gerbils, but until now, there has been no report on pathology and susceptibility in gerbils. The present study revealed the pathology of O. viverrini infection in gerbils through gross appearance, histopathology, and worm recovery at various time points. Gerbils were infected with 50 O. viverrini metacercariae and then sacrificed at the time of observation. The gross appearance of the liver showed micronodules at the liver surface, suggesting liver and biliary cirrhosis. Light microscopic observation was correlated to the gross appearance with cholecystitis, fatty liver changes, fibrous septa, and generalized cirrhosis. The range of worm burden fluctuated from 1 to 25 worms with large body size, which was correlated with pathology. These novel findings indicate that O. viverrini infection can cause liver and biliary cirrhosis in gerbils, depending on the worm burden, worm size, and habitat. PMID:21340565

Wonkchalee, Orasa; Boonmars, Thidarut; Kaewkes, Sasithron; Chamgramol, Yaovaluk; Pairojkul, Chawalit; Wu, Zhiliang; Juasook, Amornrat; Sudsarn, Pakkayanee; Boonjaraspinyo, Sirintip

2011-09-01

99

Primary biliary cirrhosis in the era of liver transplantation.  

PubMed

Primary biliary cirrhosis (PBC) is an autoimmune disease of the liver, characterized by the presence of antimitochondrial antibodies (AMA) and progressive immune-mediated destruction of biliary ductules, which lead to cirrhosis. Theories of the PBC etiopathogenesis assume that the disease develops secondarily as an improper immunological reaction to undefined environmental and/or infectious factors in genetically predisposed individuals. Ursodeoxycholic acid (UDCA) is the only drug recommended to treat PBC; it delays the progression of liver disease, but remains only a symptomatic treatment. In the advanced stage of PBC, the treatment of choice is liver transplantation (LTx). Nowadays, PBC is the third indication for LTx, after viral-related and alcoholic liver cirrhosis. Unfortunately, PBC recurs in 21-37% of patients at 10 years after LTx, and in 43% at 15 years after LTx, with the median time to recurrence of 3-5.5 years. Diagnosis of recurrent PBC (rPBC) is based on the liver histopathology. Although various risk factors of rPBC have been investigated, the cause of the recurrence is not clear. There is no specific treatment of rPBC. Together with immunosuppression after LTx, UDCA remains the treatment of choice. New diagnostic technologies (e.g., genomics, proteomics, cell-based therapy, and clinical study of the rPBC patients) may be helpful in understanding the pathogenesis of PBC and the development of new treatment modalities. PMID:25262831

Raczy?ska, Joanna; Habior, Andrzej; P?czek, Leszek; Foroncewicz, Bartosz; Pawe?as, Andrzej; Mucha, Krzysztof

2014-01-01

100

Noninvasive tests for liver disease, fibrosis, and cirrhosis: Is liver biopsy obsolete?  

PubMed

Liver biopsy has been used to diagnose chronic liver disease and to assess the degree of hepatic inflammation and fibrosis. However, it is an invasive test with many possible complications and the potential for sampling error. Noninvasive tests are increasingly precise in identifying the cause of many cases of liver disease and even the amount of liver injury (fibrosis). This review discusses the role of noninvasive tests to diagnose liver disease and to assess hepatic fibrosis and cirrhosis. PMID:20682514

Carey, Emily; Carey, William D

2010-08-01

101

Beta-blockers in liver cirrhosis  

PubMed Central

Since the original description of the effectiveness of ?-blockers in lowering the portal pressure and therefore the risk of variceal bleeding, more than 500 articles in the English literature on the use of non selective ?-blockers (NSBB) in cirrhosis have been published. The use of NSBB in pre-primary prophylaxis of variceal bleeding is currently not indicated. In primary prophylaxis, patients with high risk small varices or large/medium varices should receive primary prophylaxis either with NSBB or with endoscopic band ligation if there are contraindications to NSBB. For secondary prophylaxis the current recommendation is to receive a combination of NSBB and endoscopic variceal ligation. In addition to lowering portal pressure, NSBB can also reduce bacterial translocation, potentially exerting multiple beneficial effects which go beyond the reduction of bleeding risk. Carvedilol is a NSBB with intrinsic anti-?(1)-adrenergic activity, possibly more effective than propranolol in lowering portal hypertension. A potential harmful effect of propranolol in patients with cirrhosis with refractory ascites deserves further confirmation. NSBB remain the cornerstone of therapy in cirrhotic patients with portal hypertension. PMID:24714633

Giannelli, Valerio; Lattanzi, Barbara; Thalheimer, Ulrich; Merli, Manuela

2014-01-01

102

Beta-blockers in liver cirrhosis.  

PubMed

Since the original description of the effectiveness of ?-blockers in lowering the portal pressure and therefore the risk of variceal bleeding, more than 500 articles in the English literature on the use of non selective ?-blockers (NSBB) in cirrhosis have been published. The use of NSBB in pre-primary prophylaxis of variceal bleeding is currently not indicated. In primary prophylaxis, patients with high risk small varices or large/medium varices should receive primary prophylaxis either with NSBB or with endoscopic band ligation if there are contraindications to NSBB. For secondary prophylaxis the current recommendation is to receive a combination of NSBB and endoscopic variceal ligation. In addition to lowering portal pressure, NSBB can also reduce bacterial translocation, potentially exerting multiple beneficial effects which go beyond the reduction of bleeding risk. Carvedilol is a NSBB with intrinsic anti-?(1)-adrenergic activity, possibly more effective than propranolol in lowering portal hypertension. A potential harmful effect of propranolol in patients with cirrhosis with refractory ascites deserves further confirmation. NSBB remain the cornerstone of therapy in cirrhotic patients with portal hypertension. PMID:24714633

Giannelli, Valerio; Lattanzi, Barbara; Thalheimer, Ulrich; Merli, Manuela

2014-01-01

103

Cryptogenic cirrhosis: clinicopathologic findings at and after liver transplantation.  

PubMed

The incidence of cryptogenic cirrhosis (CC) has decreased since the discovery of hepatitis C virus (HCV), still the etiology in 5% of cases with cirrhosis remains unresolved. Our aims were to define the clinicopathologic features of CC at liver transplantation (LT), evaluate the post-LT course with outcome and define the possible pathogenetic mechanisms. 27/534 LT recipients (5%) over a period of 16.5 years were entered in the LT database as cases of CC. A detailed analysis of pre- and post-LT clinical and all liver pathology specimens was performed. Based on clinicopathologic findings, a more definite diagnosis was possible in 23 of 27 (85%): Nonalcoholic steatohepatitis (NASH) in 9 (33%), autoimmune liver disease (AILD) in 6 (22%), alcoholic liver disease in 4, secondary biliary cirrhosis in 2 and 1 each of hepatitis C and portal venopathy. 4/27 cases remained unresolved. In the NASH group, native livers had focal steatosis, Mallory's hyalin, glycogenated hepatocytic nuclei, high-grade inflammation, and 3+ bile duct proliferation. Large cell dysplasia was more common in this group compared to other patients. Two patients had recurrence of NASH after LT. In AILD group native livers had little or no bile duct proliferation. Two patients had recurrence in AILD group. Of 27 patients 19 are alive (70%) with a follow-up of 407-3647 days. Based on the study results, the following conclusions were reached: (1) CC results from varying etiologies, which can be defined by a careful clinicopathologic analysis in a majority (85%) of cases; (2) Nonalcoholic steatohepatitis (33%) and AILD (22%) are the common underlying causes of CC; and (3) Post-LT outcome for CC is disease dependent with, recurrent disease seen in both nonalcoholic steatohepatitis (22%) and autoimmune liver disease (33%). PMID:12454814

Ayata, Gamze; Gordon, Fredric D; Lewis, W David; Pomfret, Elizabeth; Pomposelli, James J; Jenkins, Roger L; Khettry, Urmila

2002-11-01

104

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

Microsoft Academic Search

In liver cirrhosis, liver tissue becomes progressively substituted by fibrosis, ultimately leading to architectural distortion,\\u000a liver circulatory changes, and liver failure. Some data support the hypothesis that protein undernutrition may play a role\\u000a in the development and progression of nonalcoholic liver cirrhosis and that this progression is at least partially mediated\\u000a by changes in glutathione peroxidase (GPX), superoxide dismutase (SOD),

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

2003-01-01

105

Ex vivo assessment of carbon tetrachloride (CCl(4))-induced chronic injury using polarized light spectroscopy.  

PubMed

The liver performs various functions, such as the production and detoxification of chemicals; therefore, it is susceptible to hepatotoxins such as carbon tetrachloride (CCl4), which causes chronic injury. Thus, assessment of injury and its status of severity are of prime importance. Current work reports an ex vivo study for probing the severance of hepatic injury induced by CCl4 with polarized light over the spectral range 400-800 nm. Different concentrations of CCl4 were used to induce varying severity of hepatic injury in a rat model. Linear retardance, depolarization rates, and diagonal Mueller matrix elements (m22, m33, and m44), were successfully used as the distinguishing criterion for normal and different liver injuries. Our results show that linear retardance for injured liver samples with lower doses of CCl4 tends to increase when compared with normal liver samples, while samples injured at higher doses of CCl4 offer almost no retardance. Total, linear, and circular depolarizations follow decreasing trends with increased liver injury severity over the entire investigated wavelength range. Linear polarization states were observed to be better maintained as compared to circular polarization states for all samples. Furthermore, numerical values of diagonal elements of the experimentally measured Mueller matrix also increase with increasing doses of CCl4. Liver fibroses, change in transport albedo, and the relative refractive index of the extracellular matrix caused by CCl4 are responsible for the observed differences. These results will provide a pathway to gauge the severity of injury caused by toxic chemicals. PMID:24359651

Ahmad, Manzoor; Ali, Safdar; Mehmood, Malik Sajjad; Ali, Hamid; Khurshid, Ahmat; Firdous, Shamaraz; Muhammad, Saleh; Ikram, Masroor

2013-12-01

106

Verapamil pharmacokinetics and liver function in patients with cirrhosis.  

PubMed

In seven patients with liver cirrhosis, verapamil plasma levels were measured in blood drawn simultaneously from the hepatic vein and from an artery during the post-distributive phase after an intravenous bolus infusion of 5 mg of verapamil. In addition the hepatic plasma flow was measured using the indocyanine-green constant infusion technique. From these data the verapamil hepatic clearance and verapamil intrinsic clearance were calculated. The verapamil hepatic clearance was 423 +/- 92 ml/m, the hepatic plasma flow was 819 +/- 318 ml/m, and the verapamil intrinsic clearance was 1431 +/- 961 ml/m. As compared to values reported in the literature, a decrease of the verapamil hepatic clearance by 50% approximately was found, while the hepatic plasma flow was in the normal range and the verapamil intrinsic clearance was reduced by 75%. These data show that in patients with cirrhosis the decrease in verapamil clearance is due to an impairment in the capacity of the liver to remove the drug, and not to a decrease in liver perfusion. PMID:3378854

Finucci, G F; Padrini, R; Piovan, D; Melica, E; Merkel, C; Gatta, A; Zuin, R

1988-01-01

107

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...

108

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

109

Ultrasound predictors of compensated liver cirrhosis in hemodialysis patients with hepatitis C.  

PubMed

Ultrasound examination was performed in 80 hemodialysis (HD) patients with chronic hepatitis C in order to determine the ultrasound predictors of compensated liver cirrhosis. The ultrasound score (US) was calculated from the morphological parameters (liver size, morphology, surface, echogenicity and spleen volume) and the hemodynamic parameters (portal vein diameter and portal vein mean flow velocity). The US ranged from 0 to 200, with a cut-off value of 66, for discrimination between absence and presence of liver cirrhosis. A logistic regression model with stepwise variable selection was used to determine predictors of the progression of liver disease. According to the calculated US, patients were divided into two groups. The first group consisted of 37 (46.3%) patients with US greater than 66, indicating the presence of compensated liver cirrhosis. The second group included 43 (53.7%) patients without liver cirrhosis, with US equal to or less than 66. The value of liver morphology was significantly higher, but the portal vein flow velocity was significantly lower in patients with compensated liver cirrhosis compared with those without cirrhosis. Furthermore, rounded liver surfaces and increased liver echogenicity were significantly more frequent in patients with compensated liver cirrhosis compared with the non-compensated group. Logistic regression model with stepwise discriminant analysis identified liver morphology, liver echogenicity and portal vein mean flow velocity as independent ultrasound predictors of compensated liver cirrhosis in HD patients with chronic hepatitis C. Ultrasound examination could be used for non-invasive diagnosis of compensated liver cirrhosis, with accurate estimation of the disease severity in HD patients with chronic hepatitis C. PMID:23354188

Dzekova-Vidimliski, P; Dzikova, S; Selim, Gj; Gelev, S; Trajceska, L; Pushevski, V; Sikole, A

2013-01-01

110

Effect of the carotenoid-producing alga, Dunaliella bardawil, on CCl4-induced toxicity in rats.  

PubMed

Dunaliella bardawil is a carotenoid-producing alga that is being considered for use in nutraceuticals. To evaluate potential protective effects of consumption of this alga, rats were treated with two different doses of D. bardawil (2.5 and 5.0 g kg(-1) body weight [bw]) as a biomass suspension daily for 14 days. Animals were tested against Carbon tetrachloride (CCl4; 2 ml kg(-1))-induced liver toxicity as measured by various biochemical marker enzymes in liver and blood. All measurements were taken 6 h following the single dose of CCl4. The results of this study show that there was a slight, but statistically significant mean serum enzyme values, with D. bardawil treatment, compared to higher mean values in animals receiving CCl4 alone. Lipid peroxidation is measured by thiobarbituric acid-reactive substance (TBARS) activity was likewise slightly less elevated with algae treatment. The results also demonstrated protection against DNA strand breaks in hepatocytes, as measured by single cell gel electrophoresis. Liver histopathology was less severe with D. bardawil treatment, supporting the apparent protective action of 14-day treatment on hepatic oxidative injury. PMID:17454256

Vanitha, A; Murthy, K N Chidambara; Kumar, Vinod; Sakthivelu, G; Veigas, Jyothi M; Saibaba, P; Ravishankar, Gokare A

2007-01-01

111

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. PMID:8755646

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

1996-01-01

112

Vascular invasion and histopathologic grading determine outcome after liver transplantation for hepatocellular carcinoma in cirrhosis  

Microsoft Academic Search

Selection of patients suffering from hepatocellular carcinoma (HCC) in cirrhosis for liver transplantation follows limits of number and diameter of tumor nodules. It has not been investigated whether there is a correlation of these parameters with vascular invasion. From 1989 to 2000, 1,188 liver transplantations were performed in 1,087 patients, including 120 patients (11%) with an HCC in cirrhosis. Selection

Sven Jonas; Wolf O. Bechstein; Thomas Steinmüller; Martin Herrmann; Cornelia Radke; Thomas Berg; Utz Settmacher; Peter Neuhaus

2001-01-01

113

Observer error and sampling variability tested in evaluation of hepatitis and cirrhosis by liver biopsy  

Microsoft Academic Search

In 50 patients with chronic active liver disease, observer and sampling error in histologically evaluating hepatitis and cirrhosis after blind-needle biopsy of the liver was assessed from coded tissue. This was done by repeated readings of the same specimens by the same pathologist, by sequential biopsies from the same patients with cirrhosis, and by multiple simultaneous biopsies from adjacent areas

Roger D. Soloway; Archie H. Baggenstoss; Leslie J. Schoenfield; W. H. J. Summerskill

1971-01-01

114

Low dose splenic irradiation for the treatment of hypersplensim in compensated and decompensated liver cirrhosis  

Microsoft Academic Search

Hypersplenism is a complication of splenomegaly in portal hypertension due to liver cirrhosis. Surgical splenectomy is an effective procedure in most patients, but it carries significant perioperative morbidity and mortality rates and may be contraindicated in advanced cases. To evalu- ate the effect of external low dose splenic irradiation (SI) for controlling hypersplenic cytopenias in compensated and decompensated liver cirrhosis.

Zaki Sheir; Gamal Badr; Eman Rewisha; Mohamed Mostafa; Tarek Hashem; Hany El-Deeb

115

Hepatic perfusion changes in patients with liver metastases: comparison with those patients with cirrhosis  

Microsoft Academic Search

Previous studies using dynamic scintigraphy have shown that the measurement of changes in hepatic perfusion may be exploited to detect liver metastases. Similar hepatic haemodynamic changes also occur in cirrhosis, however, thereby reducing the diagnostic power of the technique. The ability of duplex colour Doppler sonography (DCDS) to differentiate between the changes in liver perfusion in patients with cirrhosis and

E Leen; J A Goldberg; J R Anderson; J Robertson; B Moule; T G Cooke; C S McArdle

1993-01-01

116

Liver cirrhosis in Fontan patients does not affect 1-year post-heart transplant mortality or markers of liver function  

PubMed Central

Background Liver cirrhosis is recognized with long-term follow-up of patients after the Fontan procedure. The effect of liver cirrhosis on the use of heart transplant (HT) and on post-HT outcomes is unknown. Methods We reviewed Fontan patients evaluated for HT from 2004 to 2012 with hepatic computed tomography (CT) imaging, classified as normal, non-cirrhotic changes, or cirrhosis. The primary outcome was 1-year all-cause mortality, and the secondary outcome was differences in serial post-HT liver evaluation. Results CT imaging in 32 Fontan patients evaluated for HT revealed 20 (63%) with evidence of liver disease, including 13 (41%) with cirrhosis. Twenty underwent HT, including 5 non-cirrhotic and 7 cirrhosis patients. Characteristics at listing between normal or non-cirrhotic (n = 13) and cirrhosis (n = 7) groups were similar, except cirrhosis patients were older (median 17.6 vs 9.6 years, p = 0.002) and further from Fontan (median 180 vs 50 months, p < 0.05). Serial liver evaluation was similar, including aspartate aminotransferase, alanine aminotransferase, bilirubin, albumin, and tacrolimus dose at 1, 3, 6, 9, and 12 months. Overall patient survival was 80% at 1 year, with no difference between cirrhosis and non-cirrhosis patients (86% vs 77%, p = 0.681). Liver biopsies were performed in 7 patients before HT, and all specimens showed architectural changes with bridging fibrosis. Conclusions Most patients evaluated for HT had abnormal liver findings by CT, with cirrhosis in 41%. One-year mortality and serial liver evaluation were similar between groups after HT. Liver cirrhosis identified by CT imaging may not be an absolute contraindication to HT alone in this population. PMID:24365764

Simpson, Kathleen E.; Esmaeeli, Amir; Khanna, Geetika; White, Francis; Turnmelle, Yumirle; Eghtesady, Pirooz; Boston, Umar; Canter, Charles E.

2014-01-01

117

The pharmacokinetics of perindopril in patients with liver cirrhosis.  

PubMed Central

Perindopril is a non-sulphydryl angiotensin converting enzyme (ACE) inhibitor which requires hydrolysis to its active metabolite, perindoprilat, to produce its effects. Ten cirrhotic patients with mild to severe disease were studied after oral administration of a single 8 mg dose of perindopril as its tert-butylamine salt. Compared with a historical control group of young healthy volunteers receiving the same single oral dose of perindopril, mean AUC values of the prodrug perindopril were double in patients with liver cirrhosis (602 +/- 294 s.d. ng ml-1 h vs 266 +/- 70 s.d. ng ml-1 h) whereas the mean AUC of perindoprilat was found to be similar (134 +/- 139 ng ml-1 h vs 120 +/- 29 ng ml-1 h). The partial metabolic clearance of perindopril to perindoprilat was much lower in the cirrhotics (26 +/- 12 ml min-1 vs 58 +/- 22 ml min-1). The maximum inhibition of plasma ACE activity measured in the cirrhotic patients (87.5 +/- 5.1%) was comparable with that previously reported with perindopril in patients with mild hepatic impairment as well as in patients with essential hypertension. We suggest that liver cirrhosis may be associated with imparied deesterification of perindopril to its active metabolite perindoprilat but that no dosage adjustment of perindopril is required in cirrhotic patients. PMID:1576057

Thiollet, M; Funck-Brentano, C; Grangé, J D; Midavaine, M; Resplandy, G; Jaillon, P

1992-01-01

118

A Mixture of Experts Model for the Diagnosis of Liver Cirrhosis by Measuring the Liver Stiffness  

PubMed Central

Objectives The mixture-of-experts (ME) network uses a modular type of neural network architecture optimized for supervised learning. This model has been applied to a variety of areas related to pattern classification and regression. In this research, we applied a ME model to classify hidden subgroups and test its significance by measuring the stiffness of the liver as associated with the development of liver cirrhosis. Methods The data used in this study was based on transient elastography (Fibroscan) by Kim et al. We enrolled 228 HBsAg-positive patients whose liver stiffness was measured by the Fibroscan system during six months. Statistical analysis was performed by R-2.13.0. Results A classical logistic regression model together with an expert model was used to describe and classify hidden subgroups. The performance of the proposed model was evaluated in terms of the classification accuracy, and the results confirmed that the proposed ME model has some potential in detecting liver cirrhosis. Conclusions This method can be used as an important diagnostic decision support mechanism to assist physicians in the diagnosis of liver cirrhosis in patients. PMID:22509471

Chang, Ji Hong; Song, Kijun

2012-01-01

119

Study of liver transplant rejection in alcoholism-induced cirrhosis.  

PubMed

Rejection is the most usual cause of primary dysfunction of hepatic allograft transplants. Acute rejection (AR) often occurs in the early post-transplantation weeks, with an incidence of 12%-19%. Chronic rejection (CR) is less usual (2.5%-17%) and irreversible. Our aim was to determine the incidence of AR and CR in patients who underwent transplantaton due to alcoholism-induced cirrhosis and the survival of these groups. We undertook a retrospective study of the 93 patients who received a liver transplant due to hepatic cirrhosis between 2005 and 2012. AR occurred in 23.7% of cases, and CR in 11.8%. The median time from implantation to the appearance of AR was 34.5 days, and for CR it was 334 days. The survival of the patients with AR and CR showed no significant differences as compared with the control group (P = .77). From our clinical appraisal, symptoms of previous AR may lead to CR, although the relationship was not significant. PMID:24314985

González, J Tinoco; Bellido, C Bernal; Riera, G Jimenez; Marente, V Camacho; Gómez, L M Marín; Artacho, G Suárez; Martínez, J M Álamo; Díez-Canedo, J Serrano; Ruíz, R J Padillo; Bravo, M A Gómez

2013-01-01

120

Serum concentration of zinc, copper, manganese and magnesium in patients with liver cirrhosis.  

PubMed

The role of trace elements in the pathogenesis of liver cirrhosis and its complications is still not clearly understood. Serum concentrations of zinc, copper, manganese and magnesium were determined in 105 patients with alcoholic liver cirrhosis and 50 healthy subjects by means of plasma sequential spectrophotometer. Serum concentrations of zinc were significantly lower (median 0.82 vs. 11.22 micromol/L, p < 0.001) in patients with liver cirrhosis in comparison to controls. Serum concentrations of copper were significantly higher in patients with liver cirrhosis (median 21.56 vs. 13.09 micromol/L, p < 0.001) as well as manganese (2.50 vs. 0.02 micromol/L, p < 0.001). The concentration of magnesium was not significantly different between patients with liver cirrhosis and controls (0.94 vs. 0.88 mmol/L, p = 0.132). There were no differences in the concentrations of zinc, copper, manganese and magnesium between male and female patients with liver cirrhosis. Only manganese concentration was significantly different between Child-Pugh groups (p = 0.036). Zinc concentration was significantly lower in patients with hepatic encephalopathy in comparison to cirrhotic patients without encephalopathy (0.54 vs. 0.96 micromol/L, p = 0.002). The correction of trace elements concentrations might have a beneficial effect on complications and maybe progression of liver cirrhosis. It would be recommendable to provide analysis of trace elements as a routine. PMID:17058518

Raheli?, Dario; Kujundzi?, Milan; Romi?, Zeljko; Brki?, Kristina; Petrovecki, Mladen

2006-09-01

121

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

122

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. PMID:25061487

Raszeja-Wyszomirska, Joanna

2014-01-01

123

The Frequency of Complications and the Etiology of Disease in Patients with Liver Cirrhosis in Erzurum  

PubMed Central

Objective: This study included 100 patients diagnosed with liver cirrhosis who presented at Atatürk University Faculty of Medicine Gastroenterology clinic and polyclinic. Materials and Methods: The etiology of liver cirrhosis and the incidence of its complications have been investigated. Results: The etiological classification of liver cirrhosis in our patients was as follows: 47 hepatitis B virus hepatitis, 11 hepatitis C virus hepatitis, 5 HBV+HDV hepatitis, 4 Budd Chiari syndrome, 2 chronic alcohol abuse, 2 ischemic heart disease, 1 autoimmune hepatitis, 1 sclerosing cholangitis, 1 hydatid cyst. In 26 patients we could not find any etiological condition. These patients were called cryptogenic cirrhosis patients.When we examined the complications of liver cirrhosis, it appeared that there were ascites in 83 patient. In 56 patients, esophageal variceal bleeding occurred. There was spontaneous bacterial peritonitis in 42 patients. Hepatorenal syndrome occurred in 26 patients. Finally, in 3 patients we detected hepatorenal syndrome. Conclusion: The most common causes in the etiology of liver cirrhosis are viral, especially HBV. Many of the patients were in decompensated phase when diagnosed. We found that there was a close relation between the frequency of complications and mortality in liver cirrhosis. PMID:25610308

Topdagi, Omer; Okcu, Nihat; Bilen, Nurhan

2014-01-01

124

Insulin resistance in liver cirrhosis. Positron-emission tomography scan analysis of skeletal muscle glucose metabolism.  

PubMed Central

BACKGROUND. Insulin resistance and glucose intolerance are a major feature of patients with liver cirrhosis. However, site and mechanism of insulin resistance in cirrhosis are unknown. We investigated insulin-induced glucose metabolism of skeletal muscle by positron-emission tomography to identify possible defects of muscle glucose metabolism in these patients. METHODS. Whole body glucose disposal and oxidation were determined by the combined use of the euglycemic-hyperinsulinemic clamp technique (insulin infusion rate: 1 mU/kg body wt per min) and indirect calorimetry in seven patients with biopsy-proven liver cirrhosis (Child: 1A, 5B, and 1C) and five healthy volunteers. Muscle glucose uptake of the thighs was measured simultaneously by dynamic [18F]fluorodeoxyglucose positron-emission tomography scan. RESULTS. Both whole body and nonoxidative glucose disposal were significantly reduced in patients with liver cirrhosis (by 48%, P < 0.001, and 79%, P < 0.0001, respectively), whereas glucose oxidation and the increase in plasma lactate were normal. Concomitantly, skeletal muscle glucose uptake was reduced by 69% in liver cirrhosis (P < 0.003) and explained 55 or 92% of whole body glucose disposal in cirrhotics and controls, respectively. Analysis of kinetic constants using a three-compartment model further indicated reduced glucose transport (P < 0.05) but unchanged phosphorylation of glucose in patients with liver cirrhosis. CONCLUSIONS. Patients with liver cirrhosis show significant insulin resistance that is characterized by both decreased glucose transport and decreased nonoxidative glucose metabolism in skeletal muscle. Images PMID:8486761

Selberg, O; Burchert, W; vd Hoff, J; Meyer, G J; Hundeshagen, H; Radoch, E; Balks, H J; Müller, M J

1993-01-01

125

Alpha interferon treatment may prevent hepatocellular carcinoma in HCV-related liver cirrhosis  

Microsoft Academic Search

Background\\/Aims: The aims of ?-interferon treatment for chronic viral liver infections are clearance of the virus and healing of the disease. Hepatocellular carcinoma is a complication of viral cirrhosis; but it is not yet known whether treatment of viral cirrhosis with ?-interferon prevents this complication.Methods: The incidence and the risk (Cox regression analysis) of developing hepatocellular carcinoma were calculated in

Giuseppe Mazzella; Esterita Accogli; Sandra Sottili; Davide Festi; Monica Orsini; Antonio Salzetta; Vieri Novelli; Antonio Cipolla; Carlo Fabbri; Alessandro Pezzoli; Enrico Roda

1996-01-01

126

Hypertrophic osteoarthropathy related to end stage cholestatic cirrhosis: reversal after liver transplantation.  

PubMed Central

A case is reported of hypertrophic osteoarthropathy with recovery after a liver graft in a young man with end stage cholestatic cirrhosis related to non-Wilsonian copper overload. To our knowledge this is the first case in the literature illustrating the curative role of liver grafting on hypertrophic osteoarthropathy associated with chronic cholestatic liver disease. Images PMID:3296968

Huaux, J P; Geubel, A; Maldague, B; Michielsen, P; de Hemptinne, B; Otte, J B; de Deuxchaisnes, C N

1987-01-01

127

Hepatic-Associated Immunoglobulin-A Nephropathy in a Child with Liver Cirrhosis and Portal Hypertension  

PubMed Central

Hepatic-associated immunoglobulin A (IgA) nephropathy is a relatively common condition that occurs in adults with liver cirrhosis and portal hypertension. However, it is rare in children. This condition is characterized by the deposition of IgA in the renal glomeruli. The present report describes a 14-year-old boy with cryptogenic liver cirrhosis and portal hypertension who presented with hematuria and proteinuria associated with histological changes of IgA nephropathy. PMID:22626802

Alghamdi, Sharifa A.; Saadah, Omar I.; Almatury, Nesreen; Al-Maghrabi, Jaudah

2012-01-01

128

Deep vein thrombosis in patients with advanced liver cirrhosis: a rare condition?  

PubMed Central

Purpose Patients with liver cirrhosis are generally considered to be “auto-anticoagulated” because of coagulopathy and thrombocytopenia. However, deep vein thrombosis (DVT) has been reported in patients with liver cirrhosis. The objectives of this study were to know the prevalence of DVT among cirrhotic patients and to compare clinical pictures between cirrhotic patients with and without DVT. Methods A case–control study was performed on the basis of medical record data of patients with liver cirrhosis admitted between August 2004 and July 2007 in Medistra hospital in Jakarta. Diagnosis of DVT was established by duplex Doppler ultrasonography of the lower extremities. Patients with splanchnic thrombosis were excluded from this study. Diagnosis of liver cirrhosis was based on history and clinical manifestation, consistent with liver cirrhosis and confirmed by ultrasonography or computed tomography. Results A total of 256 patients with liver cirrhosis were included in this study; 164 (64.1%) among them were men. Patients’ mean age was 60.5 ± 12.5 years, ranging from 16 to 88 years. Viral hepatitis accounted for 74.6% of patients with liver cirrhosis. DVT was found in 12 (4.7%) patients. There was no significant laboratory difference between cirrhotic patients with and without DVT (serum albumin, platelet count, aminotransferases, ?-glutamyl transpeptidase, alkaline phosphatase, total bilirubin levels, and prothrombin time). Diabetes mellitus was significantly higher in the DVT group than that in the control group (66.6 vs. 34.0%, P = 0.025). Multivariate analysis confirmed diabetes mellitus as an independent risk factor for the occurrence of DVT (odds ratio = 4.26; 95% confidence interval = 1.206–15.034; P = 0.024). Conclusions The prevalence of DVT in patients with liver cirrhosis was 4.7%, and Deep vein thrombosis is not a rare condition in cirrhotic patients with coagulopathy and warrants further studies on the mechanisms and prevention. PMID:20305762

Inggriani, Sri; Cahyadinata, Lidwina; Lesmana, Laurentius A.

2010-01-01

129

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. PMID:25062038

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

2014-01-01

130

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. PMID:24966599

Toshikuni, Nobuyuki; Arisawa, Tomiyasu; Tsutsumi, Mikihiro

2014-01-01

131

Hagen-Poiseuille's law: The link between cirrhosis, liver stiffness, portal hypertension and hepatic decompensation.  

PubMed

The onset of hepatic decompensation in cirrhosis heralds an accelerated downhill course with poor outcome. The sole predictor of this decompensation in cirrhosis is increased hepatic vein to portal vein gradient hepatic venous pressure gradient (HVPG). Surrogate markers of liver function or hepatic reserve appear to be less relevant. The hepatic sinusoids become less elastic and more rigid as liver fibrosis and cirrhosis progress. We propose that the Hagen-Poiseuille's law, which applies to rigid, but not elastic vessels, determines the pressure-flow characteristics in the sinusoids. In the rigid cirrhotic liver, HVPG rises dramatically with any change in net surface area or radius, r(4) of the vasculature that follows surgical resection. This review relates liver stiffness to the risk of decompensation in patients with cirrhosis. The liver has a unique dual blood supply comprising a low pressure portal vein and high pressure hepatic artery. We compare the complexity of autoregulation in the normal elastic liver with that in the rigid cirrhotic liver. Therapeutic modalities to reduce portal pressure may reduce the risk of hepatic decompensation and improve outcomes in cirrhosis. PMID:25624993

Lake-Bakaar, Gerond; Ahmed, Muneeb; Evenson, Amy; Bonder, Alan; Faintuch, Salomao; Sundaram, Vinay

2015-01-27

132

Hagen-Poiseuille’s law: The link between cirrhosis, liver stiffness, portal hypertension and hepatic decompensation  

PubMed Central

The onset of hepatic decompensation in cirrhosis heralds an accelerated downhill course with poor outcome. The sole predictor of this decompensation in cirrhosis is increased hepatic vein to portal vein gradient hepatic venous pressure gradient (HVPG). Surrogate markers of liver function or hepatic reserve appear to be less relevant. The hepatic sinusoids become less elastic and more rigid as liver fibrosis and cirrhosis progress. We propose that the Hagen-Poiseuille’s law, which applies to rigid, but not elastic vessels, determines the pressure-flow characteristics in the sinusoids. In the rigid cirrhotic liver, HVPG rises dramatically with any change in net surface area or radius, r4 of the vasculature that follows surgical resection. This review relates liver stiffness to the risk of decompensation in patients with cirrhosis. The liver has a unique dual blood supply comprising a low pressure portal vein and high pressure hepatic artery. We compare the complexity of autoregulation in the normal elastic liver with that in the rigid cirrhotic liver. Therapeutic modalities to reduce portal pressure may reduce the risk of hepatic decompensation and improve outcomes in cirrhosis. PMID:25624993

Lake-Bakaar, Gerond; Ahmed, Muneeb; Evenson, Amy; Bonder, Alan; Faintuch, Salomao; Sundaram, Vinay

2015-01-01

133

New concepts in liver cirrhosis: clinical significance of sarcopenia in cirrhotic patients.  

PubMed

The natural history of cirrhotic patients is highly variable due to several factors including hepatic synthetic function, presence and degree of portal hypertension, the cause of cirrhosis, the possibility of resolution of the underlying damaging process, and the occurrence of liver cancer. Currently, D'Amico stage classification and Child-Pugh and Model for End-Stage Liver Disease (MELD) scores constitute the best tools to predict mortality in patients with cirrhosis; however, one of their main limitations is the lack of evaluation of the nutritional and functional status. Most widely recognized complications in cirrhotic patients include ascites, hepatic encephalopathy, variceal bleeding, kidney dysfunction, and hepatocellular carcinoma; however, sarcopenia or severe muscle wasting is one of the most common and frequently hidden complications which negatively impact survival, quality of life, and response to stressor, such as infection and surgery. In this review, we discuss the current accepted and new methods to evaluate prognosis in cirrhosis, and also analyze the current knowledge regarding incidence and clinical impact of malnutrition and sarcopenia in cirrhosis and their impact after liver transplantation. We also discuss existing and potential novel therapeutic strategies for malnutrition in cirrhosis, emphasizing the recognition of sarcopenia in cirrhosis in an effort to improve survival and reduced morbidity related to cirrhosis. Finally, we propose that future studies including sarcopenia with the MELD score may allow better prediction of mortality among cirrhotic patients waiting for liver transplantation; however, due to the worldwide shortage of organs for transplants, one of the vital clinical questions is the feasibility to treat sarcopenia in cirrhosis without the need of liver transplant. PMID:23831908

Montano-Loza, A J

2013-06-01

134

Inhibition of Experimental Liver Cirrhosis in Mice by Telomerase Gene Delivery  

NASA Astrophysics Data System (ADS)

Accelerated telomere loss has been proposed to be a factor leading to end-stage organ failure in chronic diseases of high cellular turnover such as liver cirrhosis. To test this hypothesis directly, telomerase-deficient mice, null for the essential telomerase RNA (mTR) gene, were subjected to genetic, surgical, and chemical ablation of the liver. Telomere dysfunction was associated with defects in liver regeneration and accelerated the development of liver cirrhosis in response to chronic liver injury. Adenoviral delivery of mTR into the livers of mTR-/- mice with short dysfunctional telomeres restored telomerase activity and telomere function, alleviated cirrhotic pathology, and improved liver function. These studies indicate that telomere dysfunction contributes to chronic diseases of continual cellular loss-replacement and encourage the evaluation of ``telomerase therapy'' for such diseases.

Rudolph, Karl Lenhard; Chang, Sandy; Millard, Melissa; Schreiber-Agus, Nicole; DePinho, Ronald A.

2000-02-01

135

Transient elastography improves detection of liver cirrhosis compared to routine screening tests  

PubMed Central

AIM: To investigate the diagnostic significance of transient elastography (TE) in a daily routine clinical setting in comparison to clinical signs, laboratory parameters and ultrasound. METHODS: TE, ultrasound, laboratory parameters and cutaneous liver signs were assessed in 291 consecutive patients with chronic liver disease of various aetiologies who underwent liver biopsy in daily routine. RESULTS: Sensitivity of TE for the detection of liver cirrhosis was 90.4%, compared to 80.1% for ultrasound, 58.0% for platelet count and 45.1% for cutaneous liver signs (P < 0.0001 for comparisons with histology). AUROC for TE was 0.760 (95%CI: 0.694-0.825). Combination of TE with ultrasound increased sensitivity to 96.1% and AUROC to 0.825 (95%CI: 0.768-0.882). TE correlated with laboratory parameters of cirrhosis progression like albumin (r = -0.43), prothrombin time (r = -0.44), and bilirubin (r = 0.34; P < 0.001 for each). Particularly, in patients with Child Pugh score A or normal platelet count TE improved sensitivity for the detection of liver cirrhosis compared to ultrasound by 14.1% (P < 0.04) and 16.3% (P < 0.02), respectively. CONCLUSION: Transient elastography is superior to routine diagnostic tests allowing detection of liver cirrhosis in additional 10%-16% of patients with chronic liver disease that would have been missed by clinical examinations.

Göbel, Thomas; Schadewaldt-Tümmers, Janine; Greiner, Lucas; Poremba, Christopher; Häussinger, Dieter; Erhardt, Andreas

2015-01-01

136

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

137

The outcome of patients with cirrhosis and Type-1 hepatorenal sydrome treated with liver transplantation.  

PubMed

Hepatorenal syndrome type 1 (HRS-1) is acute renal failure in advanced cirrhosis, resulting from hemodynamic derangements, which should be fully reversible after liver transplantation. However, the rate of HRS reversal, and factors predicting renal outcome post-transplant have not been fully elucidated. Aim: To assess outcome of HRS-1 patients post-liver transplant and factors predicting HRS reversal. PMID:25422261

Wong, Florence; Leung, Wesley; Al Beshir, Mohammed; Marquez, Max; Renner, Eberhard L

2014-11-25

138

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. PMID:23520531

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

2013-01-01

139

Large intestine permeability is increased in patients with compensated liver cirrhosis.  

PubMed

Intestinal barrier dysfunction, facilitating translocation of bacteria and bacterial products, plays an important role in the pathophysiology of liver cirrhosis and its complications. Increased intestinal permeability has been found in patients with liver cirrhosis, but data on small and large intestine permeability and tight junctions (TJs) in patients with compensated cirrhosis are scarce. We aimed to investigate both small and large intestine permeability in patients with stable compensated cirrhosis compared with healthy controls and evaluated the expression of TJ proteins in mucosal biopsies at duodenal and sigmoid level. Intestinal permeability was assessed in 26 patients with compensated cirrhosis and 27 matched controls using a multisugar test. Duodenal and sigmoid biopsies were available from a subgroup for analyses of gene transcription and expression of key TJ proteins by qRT-PCR and ELISA, respectively. Median 0-5-h urinary sucrose excretion and lactulose/rhamnose ratio were comparable between patients with compensated cirrhosis and controls, whereas 5-24-h urinary sucralose/erythritol ratio was increased in these patients. Downregulation of gene transcription was found for claudin-3 in duodenal biopsies and claudin-4 in sigmoid biopsies, and at the protein level occludin expression was significantly increased in both duodenal and sigmoid biopsies. This study shows that gastroduodenal and small intestine permeability are not altered, whereas large intestine permeability is increased in patients with stable compensated cirrhosis. Only limited alterations were found regarding the expression of TJ proteins in both the small and large intestine. PMID:24264047

Pijls, Kirsten E; Koek, Ger H; Elamin, Elhaseen E; de Vries, Hanne; Masclee, Ad A M; Jonkers, Daisy M A E

2014-01-01

140

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

141

What I Need to Know about Cirrhosis of the Liver  

MedlinePLUS

... passed from parent to child—can cause cirrhosis: hemochromatosis, a disease that causes iron to collect in ... eh-DEE-muh) esophagus (uh-SOF-uh-guhss) hemochromatosis (HEE-moh-KROH-muh-TOH-siss) hepatitis (HEP- ...

142

Assessment of liver function in primary biliary cirrhosis using Gd-EOB-DTPA-enhanced liver MRI  

PubMed Central

Objectives Gd-EOB-DTPA (gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid) is a gadolinium-based hepatocyte-specific contrast agent for magnetic resonance imaging (MRI). The aim of this study was to determine whether the hepatic uptake and excretion of Gd-EOB-DTPA differ between patients with primary biliary cirrhosis (PBC) and healthy controls, and whether differences could be quantified. Methods Gd-EOB-DTPA-enhanced liver MRI was performed in 20 healthy volunteers and 12 patients with PBC. The uptake of Gd-EOB-DTPA was assessed using traditional semi-quantitative parameters (Cmax, Tmax and T1/2), as well as model-free parameters derived after deconvolutional analysis (hepatic extraction fraction [HEF], input-relative blood flow [irBF] and mean transit time [MTT]). In each individual, all parameters were calculated for each liver segment and the median of the segmental values was used to define a global liver median (GLM). Results Although the PBC patients had relatively mild disease according to their Model for End-stage Liver Disease (MELD), Child–Pugh and Mayo risk scores, they had significantly lower HEF and shorter MTT values compared with the healthy controls. These differences significantly increased with increasing MELD and Child–Pugh scores. Conclusions Dynamic hepatocyte-specific contrast-enhanced MRI (DHCE-MRI) has a potential role as an imaging-based liver function test. The high spatial resolution of MRI enables hepatic function to be assessed on segmental and sub-segmental levels. PMID:20887325

Nilsson, Henrik; Blomqvist, Lennart; Douglas, Lena; Nordell, Anders; Jonas, Eduard

2010-01-01

143

TOP1 and 2, polysaccharides from Taraxacum officinale, attenuate CCl(4)-induced hepatic damage through the modulation of NF-kappaB and its regulatory mediators.  

PubMed

In this work, we estimate the inhibitory effect of two polysaccharides from Taraxacum officinale (TOP) on CCl(4)-induced oxidative stress and inflammation in Sprague-Dawley rats. TOP1 and 2 (304, 92 mg/kg bw) were administered for 7 days via a stomach sonde, and hepatitis was induced by a single dose of CCl(4) (50% CCl(4)/olive oil; 0.5 mL/kg bw) administration. CCl(4) significantly elevated serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities. Histopathological observation further revealed that CCl(4)-induced moderate levels of inflammatory cell infiltration, centrilobular fatty change, apoptosis, and necrosis. However, TOPs pretreatment markedly decreased AST and ALT activities as well as hepatic lesions. TOPs also increased free radical scavenging activity, as exhibited by a lowered TBARS concentration. TOPs pretreatment also reversed other hepatitis-associated symptoms, including GSH depletion, inhibited anti-oxidative enzyme activities, up-regulation of NF-kappaB and increased expression of its regulatory inflammatory mediators, such as inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-1beta. These results suggest that TOPs have a hepatoprotective effect by modulating inflammatory responses and ameliorating oxidative stress. PMID:20170702

Park, Chung Mu; Youn, Hyun Joo; Chang, Hee Kyung; Song, Young Sun

2010-05-01

144

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. PMID:25009590

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

2014-01-01

145

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. PMID:23496995

2013-01-01

146

Trace element analysis by PIXE in liver samples from dogs with chronic active hepatitis and liver cirrhosis  

NASA Astrophysics Data System (ADS)

Trace element levels of liver samples obtained from necropsied dogs suffering from hepatitis and/or liver cirrhosis were determined by PIXE. Two different techniques for preparation of the samples were compared: the pellet press method and wet digestion. Both methods gave similar results, but the pellet press method was chosen for the subsequent routine analyses because of its simplicity due to few preparation steps and little risk of contamination. Preliminary results indicate elevated levels of Cu in chronic hepatitis and cirrhosis. In hereditary copper-induced hepatitis (Bedlington hepatitis) Fe and Br levels were increased as well.

Andersson, Marianne; Ekholm, Ann-Kristin; Sevelius, Ewa

1990-04-01

147

Bacillus cereus septicemia and necrotizing fasciitis in a patient with liver cirrhosis: a case report.  

PubMed

A 54-year-old woman with hematemesis was referred to our hospital. She had a history of liver cirrhosis and diabetes mellitus. After inserting a Sengstaken-Blakemore tube, we performed endoscopic variceal ligation for ruptured esophageal varices. On the third day of admission, she developed septicemia and necrotizing fasciitis caused by Bacillus cereus. She was successfully treated with early debridement of both lower extremities and intravenous treatment with vancomycin, ciprofloxacin, and clindamycin. Although B. cereus is an attenuate bacterium, it can occasionally cause fatal infection in immuno-compromised individuals, such as those with liver cirrhosis. PMID:25283231

Matsuda, Shogo; Kirishima, Toshihiko; Okamoto, Naoki; Hisano, Yasuko; Takai, Koji; Motoyoshi, Takayuki; Nishikata, Makoto; Yamashita, Yasuhide; Yoshinami, Naomi; Shintani, Hiroyuki

2014-10-01

148

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. PMID:22988470

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

2012-01-01

149

MNGIE Syndrome: Liver Cirrhosis Should Be Ruled Out Prior to Bone Marrow Transplantation.  

PubMed

Mitochondrial neurogastrointestinal encephalopathy (MNGIE) is an autosomal recessive mitochondriopathy caused by loss-of-function mutations in the thymidine phosphorylase gene. The disease leads to premature death and is characterized by gastrointestinal dysmotility and cachexia, external ophthalmoplegia, a sensorimotor neuropathy, and leukoencephalopathy. Bone marrow transplantation (BMT) is the only potentially curative treatment that can achieve a sustained biochemical correction of the metabolic imbalances.We report a 23-year-old male homozygous for the c.866A > C, p.Glu289Ala mutation of the TYMP gene, who presented with fatty liver and cachexia. Laboratory examinations were unremarkable except for increased transaminase activities. Grade II fibrosis and steatosis was found in an initial and a follow-up liver biopsy 4 years later. Myeloablative conditioning and BMT was performed 10 years after initial presentation due to the progressive weight loss and polyneuropathy. Pre-transplant liver staging was normal except for an elevated transient elastography of 31.6 kPa. Severe ascites developed after transplantation and liver function deteriorated progressively to liver failure. Despite engraftment on day +15, the patient died on day +18 from liver failure. Autopsy revealed micronodular liver cirrhosis, and postmortem diagnosis of acute-on-chronic liver failure was done.This case illustrates the difficulties and importance of diagnosing liver cirrhosis in MNGIE. Before BMT, patients must be carefully evaluated by transient elastography, liver biopsy, or assessment of hepatic venous pressure gradient. In patients with liver cirrhosis, further studies should evaluate if liver transplantation may be an alternative to BMT. Considerable amounts of thymidine phosphorylase are expressed in liver tissue which may prevent accumulation of toxic metabolites. PMID:23430799

Finkenstedt, Armin; Schranz, Melanie; Bösch, Sylvia; Karall, Daniela; Bürgi, Sabine Scholl; Ensinger, Christian; Drach, Mathias; Mayr, Johannes A; Janecke, Andreas R; Vogel, Wolfgang; Nachbaur, David; Zoller, Heinz

2013-01-01

150

Safety and Efficacy of Hepatitis B Vaccination in Cirrhosis of Liver  

PubMed Central

Introduction. Patients with chronic liver disease (CLD) are more likely to have severe morbidity and fatality rate due to superimposed acute or chronic hepatitis B (HBV) infection. The literature has shown that hepatitis B vaccines are safe and effective in patients with CLD, but the data in cirrhosis liver is lacking. We assessed the safety and immunogenicity of HBV vaccine in patients with cirrhosis liver. Methods. CTP classes A and B CLD patients negative for hepatitis B surface antigen and antibody to hepatitis B core antigen were included. All patients received three doses of hepatitis B vaccine 20?mcg intramuscularly at 0, 30, and 60 days. Anti-HBs antibody was measured after 120 days. Results. 52 patients with mean age 47.48 ± 9.37 years were studied. Response rates in CTP classes A and B were 88% and 33.3%. We observed that the alcoholic chronic liver disease had less antibody response (44%) than other causes of chronic liver disease such as cryptogenic 69% and HCV 75%. Conclusions. Patients with cirrhosis liver will have low antibody hepatitis B titers compared to general population. As the age and liver disease progress, the response rate for hepatitis B vaccination will still remain to be weaker. PMID:23840211

Roni, D. Ajith; Pathapati, Rama Mohan; Kumar, A. Sathish; Nihal, Lalit; Sridhar, K.; Tumkur Rajashekar, Sujith

2013-01-01

151

Hepatocellular Carcinoma and Liver Cirrhosis: Assessment of the Liver Function after Yttrium90 Radioembolization with Resin Microspheres or after CT-Guided High-Dose-Rate Brachytherapy  

Microsoft Academic Search

Purpose: To identify changes of liver function after single-fraction irradiation or yttrium-90 radioembolization (90Y-RE) of hepatocellular carcinoma associated with liver cirrhosis on the basis of laboratory data. Methods and Materials: 24 patients with primary liver carcinoma and liver cirrhosis classified Child-Pugh A or B were treated either by image-guided high-dose-rate brachytherapy (HDR-BT) (12 patients) or by 90Y-RE (12 patients). The

Ricarda Rühl; Max Seidensticker; Nils Peters; Konrad Mohnike; Jan Bornschein; Kerstin Schütte; Holger Amthauer; Peter Malfertheiner; Maciej Pech; Jens Ricke

2009-01-01

152

Microbiota and the gut-liver axis: Bacterial translocation, inflammation and infection in cirrhosis.  

PubMed

Liver disease is associated with qualitative and quantitative changes in the intestinal microbiota. In cirrhotic patients the alteration in gut microbiota is characterized by an overgrowth of potentially pathogenic bacteria (i.e., gram negative species) and a decrease in autochthonous familiae. Here we summarize the available literature on the risk of gut dysbiosis in liver cirrhosis and its clinical consequences. We therefore described the features of the complex interaction between gut microbiota and cirrhotic host, the so called "gut-liver axis", with a particular attention to the acquired risk of bacterial translocation, systemic inflammation and the relationship with systemic infections in the cirrhotic patient. Such knowledge might help to develop novel and innovative strategies for the prevention and therapy of gut dysbiosis and its complication in liver cirrhosis. PMID:25492994

Giannelli, Valerio; Di Gregorio, Vincenza; Iebba, Valerio; Giusto, Michela; Schippa, Serena; Merli, Manuela; Thalheimer, Ulrich

2014-12-01

153

Microbiota and the gut-liver axis: Bacterial translocation, inflammation and infection in cirrhosis  

PubMed Central

Liver disease is associated with qualitative and quantitative changes in the intestinal microbiota. In cirrhotic patients the alteration in gut microbiota is characterized by an overgrowth of potentially pathogenic bacteria (i.e., gram negative species) and a decrease in autochthonous familiae. Here we summarize the available literature on the risk of gut dysbiosis in liver cirrhosis and its clinical consequences. We therefore described the features of the complex interaction between gut microbiota and cirrhotic host, the so called “gut-liver axis”, with a particular attention to the acquired risk of bacterial translocation, systemic inflammation and the relationship with systemic infections in the cirrhotic patient. Such knowledge might help to develop novel and innovative strategies for the prevention and therapy of gut dysbiosis and its complication in liver cirrhosis. PMID:25492994

Giannelli, Valerio; Di Gregorio, Vincenza; Iebba, Valerio; Giusto, Michela; Schippa, Serena; Merli, Manuela; Thalheimer, Ulrich

2014-01-01

154

Antiviral therapy of patients with decompensated cirrhosis to prevent recurrence of hepatitis C after liver transplantation  

Microsoft Academic Search

Background\\/Aims: After liver transplantation (LT) infection of the graft with the hepatitis C virus (HCV) is almost universal and chronic hepatitis and cirrhosis develop in a significant proportion of patients. One of the possible strategies to prevent HCV infection recurrence is to eradicate HCV before LT.Methods: We evaluated the efficacy and safety of antiviral therapy to prevent HCV recurrence in

Xavier Forns; Montserrat Garc??a-Retortillo; Trinidad Serrano; Anna Feliu; Francisco Suarez; Manuel de la Mata; Juan Carlos Garc??a-Valdecasas; Miquel Navasa; Antoni Rimola; Juan Rodés

2003-01-01

155

Systemic lupus erythematosus complicated with liver cirrhosis in a patient with Papillon-Lefčvre syndrome.  

PubMed

We report the first case of a girl who presented with Papillon-Lefčvre syndrome (PLS) and subsequently developed systemic lupus erythematosus and liver cirrhosis. This indicates that autoimmune diseases can be a complication in patients with PLS. Cathepsin C gene mutations were not found in our patient or her mother. Thus, other genetic factors may have been involved in this patient. PMID:25124675

Yasudo, H; Ando, T; Takeuchi, M; Nakano, H; Itonaga, T; Takehara, H; Isojima, T; Miura, K; Harita, Y; Takita, J; Oka, A

2014-12-01

156

Application of an Electronic Nose to Diagnose Liver Cirrhosis from the Skin Surface  

Microsoft Academic Search

The human body odor contains of different volatile organic compounds. In patients with liver cirrhosis and patients who are\\u000a addicted to alcohol the compound of sweat and volatile gases are changed because of the liver dysfunction and remaining alcoholics\\u000a and alcoholic decomposition products within the blood. This leads to changes of the metabolic balance. Therefore, the purpose\\u000a of this study

K. Witt; T. Jochum; W. Poitz; K. J. Bär; A. Voss

157

Enhancement by estradiol 3-benzoate in thioacetamide-induced liver cirrhosis of rats.  

PubMed

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 = 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 without TAA. For the exposure period, EB pellets were implanted subcutaneously to give doses of 0 (groups 1 and 5), 1 (group 2), 10 (group 3), and 100 mug (groups 4 and 6) simultaneously. All animals were sacrificed at week 12. Significant increase of liver cirrhosis, liver weight, collagen content, and lipid peroxidation in the livers was evident in groups 3 and 4 (p < 0.05) compared with group 1. Formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) was significantly elevated in group 4 (p < 0.01), along with expression of alpha-smooth muscle actin (alpha-SMA) and stellate cell activation-associated protein (STAP), as determined by RT-PCR analysis (p < 0.01). However, there were no differences in liver weight, collagen content, lipid peroxidation, 8-OHdG formation, and alpha-SMA and STAP mRNA expression between groups 5 and 6. We conclude that EB treatment enhances TAA-induced cirrhosis, associated with increase of oxidative stress and activation of hepatic stellate cells. PMID:15716488

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

2005-05-01

158

Aflatoxin Exposure and Viral Hepatitis in the Etiology of Liver Cirrhosis in The Gambia, West Africa  

PubMed Central

Background Cirrhosis of the liver is thought to be a major cause of morbidity and mortality in sub-Saharan Africa, but few controlled studies on the etiology of cirrhosis have been conducted in this region. Objectives We aimed to elucidate the association between environmental and infectious exposures and cirrhosis in The Gambia. Methods Ninety-seven individuals were diagnosed with cirrhosis using a validated ultrasound scoring system and were compared with 397 controls. Participants reported demographic and food frequency information. Blood samples were tested for hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), hepatitis C virus (HCV) antibody, HCV RNA, and the aflatoxin-associated 249ser TP53 mutation. Results HBsAg seropositivity was associated with a significant increase in risk of cirrhosis [odds ratio (OR) = 8.0; 95% confidence interval (CI), 4.4–14.7] as was the presence of HBeAg (OR = 10.3; 95% CI, 2.0–53.9) and HCV infection (OR = 3.3; 95% CI, 1.2–9.5). We present novel data that exposure to aflatoxin, as assessed both by high lifetime groundnut (peanut) intake and by the presence of the 249ser TP53 mutation in plasma, is associated with a significant increase in the risk for cirrhosis (OR = 2.8; 95% CI, 1.1–7.7 and OR = 3.8; 95% CI, 1.5–9.6, respectively). Additionally, aflatoxin and hepatitis B virus exposure appeared to interact synergistically to substantially increase the risk of cirrhosis, although this was not statistically significant. Conclusions Our results suggest that the spectrum of morbidity associated with aflatoxin exposure could include cirrhosis. PMID:19057710

Kuniholm, Mark H.; Lesi, Olufunmilayo A.; Mendy, Maimuna; Akano, Aliu O.; Sam, Omar; Hall, Andrew J.; Whittle, Hilton; Bah, Ebrima; Goedert, James J.; Hainaut, Pierre; Kirk, Gregory D.

2008-01-01

159

Effects of Thalidomide on the Expression of Adhesion Molecules in Rat Liver Cirrhosis  

PubMed Central

This study was to evaluate the effects of thalidomide on expression of adhesion molecules in liver cirrhosis. The cirrhosis was induced in Wistar rats by intraperitoneal injection of CCl4, and thalidomide (10 mg/kg/day or 100 mg/kg/day) was given by intragastric administration for 8 weeks. Liver histopathology and immunohistochemistry were significantly improved and the expressions of ICAM-1, VCAM-1, E-selectin, and TNF-? mRNA and protein were decreased significantly in rats treated with a high dose of thalidomide. Close positive correlation was observed in the expression of the TNF-? mRNA and that of ICAM-1, VCAM-1, and E-selectin mRNA, respectively. These results indicate that thalidomide exerts its effect on the downregulation of adhesion molecules via TNF-? signaling pathway to inhibit liver fibrosis. PMID:17047296

Lv, Peng; Paul, Shelley Chireyath; Xiao, Yanjv; Liu, Shiquan; Luo, Hesheng

2006-01-01

160

Liver Cirrhosis Induced by Porphyria Cutanea Tarda: A Case Report and Review  

PubMed Central

Porphyria cutanea tarda (PCT) is a metabolic disorder that results in a decrease in uroporphyrinogen decarboxylase activity. It is characterized by photosensitivity, bullae formation, and skin pigmentation. There are four types of PCT: acquired, familial, toxic, and hepatoerythropoietic. Uroporphyrin levels are elevated in the urine of PCT patients. PCT can be differentiated from other porphyrias by its clinical characteristics and the porphyrin levels in the serum, erythrocytes, urine, and feces. This metabolic disorder can lead to liver dysfunction as well as histological changes such as fatty infiltration or hepatic fibrosis. PCT rarely manifests as liver cirrhosis. We report herein a case of PCT-induced liver cirrhosis that progressed to hepatic failure. PMID:21253308

Lee, Kwang Gyun; Hyun, Jong Jin; Seo, Yeon Seok; Keum, Bora; Yim, Hyung Joon; Jeen, Yoon Tae; Lee, Hong Sik; Chun, Hoon Jai; Kim, Chang Duck; Ryu, Ho Sang

2010-01-01

161

Atorvastatin and rosuvastatin do not prevent thioacetamide induced liver cirrhosis in rats  

PubMed Central

AIM: To examine whether the administration of atorvastatin and rosuvastatin would prevent experimentally-induced hepatic cirrhosis in rats. METHODS: Liver cirrhosis was induced by injections of thioacetamide (TAA). Rats were treated concurrently with TAA alone or TAA and either atorvastatin (1,10 and 20 mg/kg) or rosuvastatin (1, 2.5, 5, 10 and 20 mg/kg) given daily by nasogastric gavage. RESULTS: Liver fibrosis and hepatic hydroxyproline content, in the TAA-treated group was significantly higher than those of the controls [11.5 ± 3.2 vs 2.6 ± 0.6 mg/g protein (P = 0.02)]. There were no differences in serum aminotransferase levels in the TAA controls compared to all the groups treated concomitantly by statins. Both statins used in our study did not prevent liver fibrosis or reduce portal hypertension, and had no effect on hepatic oxidative stress. Accordingly, the hepatic level of malondialdehyde was not lower in those groups treated by TAA + statins compared to TAA only. In vitro studies, using the BrdU method have shown that atorvastatin had no effect of hepatic stellate cells proliferation. Nevertheless, statin treatment was not associated with worsening of liver damage, portal hypertension or survival rate. CONCLUSION: Atorvastatin or rosuvastatin did not inhibit TAA-induced liver cirrhosis or oxidative stress in rats. Whether statins may have therapeutic applications in hepatic fibrosis due to other etiologies deserve further investigation. PMID:23345947

Shirin, Haim; Sharvit, Efrat; Aeed, Hussein; Gavish, Dov; Bruck, Rafael

2013-01-01

162

Genetic diseases that predispose to early liver cirrhosis.  

PubMed

Inherited liver diseases are a group of metabolic and genetic defects that typically cause early chronic liver involvement. Most are due to a defect of an enzyme/transport protein that alters a metabolic pathway and exerts a pathogenic role mainly in the liver. The prevalence is variable, but most are rare pathologies. We review the pathophysiology of such diseases and the diagnostic contribution of laboratory tests, focusing on the role of molecular genetics. In fact, thanks to recent advances in genetics, molecular analysis permits early and specific diagnosis for most disorders and helps to reduce the invasive approach of liver biopsy. PMID:25132997

Scorza, Manuela; Elce, Ausilia; Zarrilli, Federica; Liguori, Renato; Amato, Felice; Castaldo, Giuseppe

2014-01-01

163

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

164

Hepatic venography in noncirrhotic idiopathic portal hypertension: comparison with cirrhosis of the liver  

SciTech Connect

Free and wedged hepatic venography were carried out in 37 patients with idiopathic portal hypertension (IPH) and the findings compared with those in 88 patients with cirrhosis of the liver. Characteristic changes in IPH included frequent vein-to-vein anastomoses, narrower angles between large veins and their tributaries, smooth and wavy middle-sized to large branches (giving a general ''weeping willow'' appearance), homogeneous sinusoidal filling, and minimal to absent filling of the portal venous system on wedged retrograde portography. In cirrhosis, by contrast, changes included rare vein-to-vein anastomoses, wide angles between veins and tributaries, irregular stenoses of large veins and branches at various levels, spotty sinusoidal filling, and frequent retrograde flow in the portal venous system. Hepatic venography is helpful in differentiating IPH from cirrhosis.

Futagawa, S.; Fukazawa, M.; Musha, H.

1981-11-01

165

Small RNA- and DNA-based gene therapy for the treatment of liver cirrhosis, where we are?  

PubMed Central

Chronic liver diseases with different aetiologies rely on the chronic activation of liver injuries which result in a fibrogenesis progression to the end stage of cirrhosis and liver failure. Based on the underlying cellular and molecular mechanisms of a liver fibrosis, there has been proposed several kinds of approaches for the treatment of liver fibrosis. Recently, liver gene therapy has been developed as an alternative way to liver transplantation, which is the only effective therapy for chronic liver diseases. The activation of hepatic stellate cells, a subsequent release of inflammatory cytokines and an accumulation of extracellular matrix during the liver fibrogenesis are the major obstacles to the treatment of liver fibrosis. Several targeted strategies have been developed, such as antisense oligodeoxynucleotides, RNA interference and decoy oligodeoxynucleotides to overcome this barriers. With this report an overview will be provided of targeted strategies for the treatment of liver cirrhosis, and particularly, of the targeted gene therapy using short RNA and DNA segments. PMID:25356032

Kim, Kyung-Hyun; Park, Kwan-Kyu

2014-01-01

166

Acoustic structure quantification ultrasound software proves imprecise in assessing liver fibrosis or cirrhosis in parenchymal liver diseases.  

PubMed

The present study was conducted to assess the diagnostic accuracy of Acoustic Structure Quantification (ASQ) ultrasound software in liver biopsy of patients with liver fibrosis and cirrhosis. Eighty patients (47 ± 14 y, 41 men) with chronic liver diseases underwent ultrasound examination of the liver and liver biopsy. In addition to the standard-care ultrasound examination, three valid gray-scale images were obtained for each patient. With the ASQ software, the average and peak values (Cm(2)) of each ultrasound gray-scale image were calculated and then compared with histologic fibrosis staging (F0-F4). No correlation was found between ASQ values and histologic fibrosis stage (p > 0.05). Areas under the curve for the diagnosis of no or mild fibrosis (F0 and F1), moderate/severe fibrosis (F2 and F3) and cirrhosis (F4) using average/peak Cm(2) values of small regions of interest were 0.46/0.43, 0.62/0.68 and 0.38/0.33. Determination of liver fibrosis with ASQ in its present form as an alternative approach to liver biopsy is too imprecise. PMID:25308947

Krämer, Christiane; Jaspers, Natalie; Nierhoff, Dirk; Kuhr, Kathrin; Bowe, Andrea; Goeser, Tobias; Michels, Guido

2014-12-01

167

Dynamic study of rectally absorbed ammonia in liver cirrhosis using (13N)ammonia and a positron camera  

SciTech Connect

(13N)Ammonia produced by the cyclotron was instilled intrarectally in patients with cirrhosis and other liver diseases to study the turnover of rectally absorbed (12N)ammonia. In the control, (13N)ammonia was absorbed quickly and visualized the liver, whereas in patients with cirrhosis, the lungs and heart were first visualized, and 13N activity over the head was also higher. It was suggested that a large proportion of absorbed (13N)ammonia bypassed hepatocytes and reached peripheral tissues in cirrhosis. The heart/liver ratio of 13N and 13N over the head were correlated with various indices of portal hypertension. The relative proportion of nonammonia 13N metabolites in blood was lower at 5 and 15 min after administration in cirrhosis, suggesting a reduced capacity of the liver to remove and metabolize ammonia.

Koen, H.; Okuda, K.; Musha, H.; Tateno, Y.; Fukuda, N.; Matsumoto, T.; Shisido, F.; Rikitake, T,; Iinuma, T.; Kurisu, A.; Arimizu, N.

1980-11-01

168

Evaluation of the effect of partial splenic embolization on platelet values for liver cirrhosis patients with thrombocytopenia  

Microsoft Academic Search

AIM: To investigate the effect of partial splenic embolization (PSE) on platelet values in liver cirrhosis patients with thrombocytopenia and to determine the effective embolization area for platelet values improvement.

Chi-Ming Lee; Ting-Kai Leung; Hung-Jung Wang; Wei-Hsing Lee; Li-Kuo Shen; Jean-Dean Liu; Chun-Chao Chang; Ya-Yen Chen; Lee CM; Leung TK; Wang HJ; Lee WH; Shen LK; Liu JD

2007-01-01

169

Impact of antithrombin III on hepatic and intestinal microcirculation in experimental liver cirrhosis and bowel inflammation: An in vivo analysis  

PubMed Central

AIM: To analyze the hepatic and intestinal microcirculation in an animal model of liver cirrhosis and inflammatory bowel disease (IBD) and to characterize the anti-inflammatory action of antithrombin III (ATIII) on leukocyte kinetics and liver damage. METHODS: Hepatic and intestinal microcirculation was investigated by intravital videomicroscopy. Standardized models of experimental chronic liver cirrhosis and bowel inflammation were employed. Animals were divided into four groups (n = 6/group): controls, animals with cirrhosis, animals with cirrhosis and IBD, animals with cirrhosis and IBD treated with ATIII. RESULTS: Cirrhosis facilitated leukocyte rolling and sticking in hepatic sinusoids (1.91±0.28 sticker/µm vs 0.5±0.5 sticker/µm in controls, P<0.05). The effect enhanced in animals with cirrhosis and IBD (5.4±1.65 sticker/µm), but reversed after ATIII application (3.97±1.04 sticker/µm, P<0.05). Mucosal blood flow showed no differences in cirrhotic animals and controls (5.3±0.31 nL/min vs 5.4±0.25 nL/min) and was attenuated in animals with cirrhosis and IBD significantly (3.49±0.6 nL/min). This effect was normalized in the treatment group (5.13±0.4 nL/min, P<0.05). Enzyme values rose during development of cirrhosis and bowel inflammation, and reduced after ATIII application (P<0.05). CONCLUSION: Liver cirrhosis in the presence of IBD leads to a significant reduction in mucosal blood flow and an increase in hepatic leukocyte adherence with consecutive liver injury, which can be prevented by administration of ATIII. PMID:16124052

Maksan, Sasa-Marcel; Ülger, Zilfi; Gebhard, Martha Maria; Schmidt, Jan

2005-01-01

170

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. PMID:24829669

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

2013-01-01

171

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

172

Chronic active hepatitis and liver cirrhosis in association with combined tamoxifen/tegafur adjuvant therapy.  

PubMed

Two female breast cancer patients who received combined tamoxifen and tegafur as postsurgical adjuvant therapy developed severe hepatotoxicity after being treated for three and eight months, respectively. Shortly after the cessation of the treatment, routine liver tests showed gradual recovery, but liver biopsies revealed chronic active hepatitis in one patient and liver cirrhosis in the other. Four and five years, respectively, after the cessation of the treatment, the results of liver tests were normal and distinct histological improvement was observed in both patients. Because these patients had no viral and immunoserological markers nor any history of alcohol abuse, this study suggested that the tamoxifen and tegafur regimen induced reversible chronic active liver disease. PMID:8536519

Maruyama, S; Hirayama, C; Abe, J; Tanaka, J; Matsui, K

1995-12-01

173

Mössbauer studies of hemoglobin of the patients with liver cancer and cirrhosis  

NASA Astrophysics Data System (ADS)

Red blood cells (RBC) of the patients with primary liver cancer and with cirrhosis were investigated by using Mössbauer spectroscopy. Control measurements were carried out on RBC from normal adults. The Mössbauer spectra of normal RBC are composed of two doublets corresponding to deoxy-Hb and Oxy-Hb. Besides disappearance or a decrease of the doublets corresponding to deoxy-Hb, no additional peak was detected in the samples from the patients.

Ni, Xinlei; Hsia, Yuanfu; Liu, Rongchuan; Lu, Qingyou; Huang, Runsheng; Sun, Yunhan; Wang, Quanxing; Long, Jianxui

1992-04-01

174

The development of hepatocellular carcinoma from liver cirrhosis during a follow-up study  

Microsoft Academic Search

Summary  A prospective study was carried out in 126 cases with liver cirrhosis attending the outpatient clinic of Hepatology of the\\u000a Department of Internal Medicine, Dr. Cipto Mangunkusmo Hospital Jakarta, between August 1,1982 and Dec. 31, 1985. The patients\\u000a consisted of 82 men and 44 women and there were 45 HBsAg positive cases (36.7%). HBeAg was posotive in 35.6% (16\\/45) and

H. Ali Sulaiman

1989-01-01

175

Intestinal absorption of cholecalciferol in alcoholic liver disease and primary biliary cirrhosis  

Microsoft Academic Search

The intestinal absorption of (3H)cholecalciferol was studied in five patients with alcoholic liver disease, six patients with primary biliary cirrhosis, and 15 healthy subjects. The rate of appearance in plasma of (3H)cholecalciferol after oral ingestion and the subsequent appearance of (3H) polar metabolites in the alcoholic subjects were similar to those in the healthy subjects. In subjects with primary biliary

J M Barragry; R G Long; M W France; M R Wills; B J Boucher; S Sherlock

1979-01-01

176

Enhanced expression of monocyte tissue factor in patients with liver cirrhosis  

Microsoft Academic Search

Background—Previous studies have shown that cirrhotic patients produce increased amounts of thrombin but the underlying mechanism is still unknown.Aims—To analyse the relation between the rate of thrombin generation and monocyte expression of tissue factor (TF) in cirrhosis.Patients—Thirty three cirrhotic patients classified as having low (n=7), moderate (n=17), or severe (n=9) liver failure according to Child-Pugh criteria.Methods—Prothrombin fragment F1+2, monocyte TF

M Saliola; R Lorenzet; D Ferro; S Basili; C Caroselli; A Di Santo; M Sallese; F Violi

1998-01-01

177

Comparative Study of TCM Syndrome Scale for Liver Disease and Chronic Liver Disease Questionnaire Based on Assessment of Posthepatitic Cirrhosis  

PubMed Central

Objective. To compare and analyze the relevance and applied value of chronic liver disease questionnaire (CLDQ) and Traditional Chinese Medicine liver disease questionnaire (TCMLDQ) in patients with posthepatitic cirrhosis. Methods. The data of 146 patients' scales of CLDQ and TCMLDQ which based on the characteristics of chinese medical symptoms were collected. We made comparative analysis of the relationship between these two scales by the linear regression model and canonical correlation method and evaluated the advantages and disadvantages of two scales about its items setting and dimension definition. Result. There is a negative correlation in total scores between the two scales and the linear regression equation: CLDQ = 239.38 ? 1.232TCMLDQ. The further canonical correlation analysis was used to analyze the two extracted canonical correlative variables with significances (P < 0.05), and the results showed that the overall negative correlation between the two scales mainly came from contributions of both the four dimensions of TCMLDQ (CS, GSYX, GYPX, and OS) and the five dimensions of CLDQ (AS, FA, SS, AC, and EF). Conclusion. These two scales have good consistency in the evaluation of severity and life quality of liver cirrhosis patients, so we suggested that TCMLDQ can be used to evaluate the severity and life quality of patients with posthepatitic cirrhosis. PMID:22690246

Zhang, Hua; Lv, Hua; Huang, Pin-Xian; Lin, Yan; Hu, Xin-Cai; Liu, Ping

2012-01-01

178

A case of variceal bleeding from the jejunum in liver cirrhosis  

PubMed Central

While esophagogastric varices are common manifestations of portal hypertension, variceal bleeding from the jejunum is a rare complication of liver cirrhosis. In addition, ectopic variceal bleeding occurs in the duodenum and at sites of previous bowel surgery in most cases, including of stomas. We report a case of obscure overt gastrointestinal bleeding from jejunal varices in a 55-year-old woman who had not previously undergone abdominal surgery, who had liver cirrhosis induced by the hepatitis C virus. Emergency endoscopy revealed the presence of esophageal varices without stigmata of recent bleeding, and no bleeding focus was found at colonoscopy. She continued to produce recurrent melena with hematochezia and received up to 21 units of packed red blood cells. CT angiography revealed the presence of jejunal varices, but no active bleeding was found. Capsule endoscopy revealed fresh blood in the jejunum. The patient submitted to embolization of the jejunal varices via the portal vein, after which she had a stable hemoglobin level and no recurrence of the melena. This is a case of variceal bleeding from the jejunum in a liver cirrhosis patient without a prior history of abdominal surgery. PMID:23593613

Park, Chan Woong; Yang, Hyeon Woong; Lee, Yun Jung; Jung, Sung Hee; Song, Ho Sup; Lee, Sang Ok; Kim, Anna; Cha, Sang Woo

2013-01-01

179

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

180

Eosinophilic Ascites and Duodenal Obstruction in a Patient with Liver Cirrhosis  

PubMed Central

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

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

2014-01-01

181

Impact of liver cirrhosis on nutritional and immunological status.  

PubMed

The aims of the study were to determine the prevalence of protein calorie malnutrition (PCM) in Thai cirrhotic patients and to evaluate nutritional and immunological status in various stages of cirrhosis. Subjective Global Assessment (SGA) and anthropometric measurement were used as nutritional assessment in sixty cirrhotic patients. Delayed-type hypersensitivity skin test, lymphocyte count, immunoglobulin and complement were assessed for immune status. Blood samples were sent for routine tests, prealbumin, thiamine and riboflavin level. There were 7/60 (11.7%) patients with percentage of ideal body weight (%IBW) less than 90 per cent. SGA, hemoglobin, protein indices and cholesterol level showed the deterioration of nutritional status in the late stage of the disease. Five (8.3%) patients with thiamine deficiency, and thirteen (21.7%) patients with riboflavine deficiency were detected. Lowest levels of complement and highest levels of immunoglobulin also occurred in the late stage of the disease. In conclusion, defining %IBW <90 per cent as malnutrition, the prevalence of malnutrition in Thai cirrhotic patients was 11.7 per cent. Nutritional and immunological status deteriorated according to the advanced stage of disease. If nutritional support is given in the early stage, it may improve nutritional status and reduce morbidity and mortality in cirrhotic patients. PMID:11759979

Sobhonslidsuk, A; Roongpisuthipong, C; Nantiruj, K; Kulapongse, S; Songchitsomboon, S; Sumalnop, K; Bussagorn, N

2001-07-01

182

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

183

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

2014-01-01

184

A rare cause of hypoxia in a patient with liver cirrhosis  

PubMed Central

Pulmonary syndromes in the setting of hepatic disease with portal hypertension include portopulmonary hypertension (POPH), hepatopulmonary syndrome (HPS) and hepatic hydrothorax. POPH is defined as pulmonary arterial hypertension with portal hypertension in the absence of other causes of pulmonary arterial hypertension. HPS is a defect in arterial oxygenation as a result of pulmonary micro vascular dilatation in the setting of liver disease. We discuss a case of 63-year-old female with liver cirrhosis, exertional dyspnea and hypoxia associated with coexistence of POPH and HPS. The coexistence of POPH and HPS is rare entity which can generate a renewal of interest in further understanding the intricate pathologies behind these diseases.

Singh, Amita; Girdhar, Ankur; Usman, Faisal; Cury, James; Bajwa, Abubakr

2012-01-01

185

Future therapy of portal hypertension in liver cirrhosis – a guess  

PubMed Central

In patients with chronic liver disease, portal hypertension is driven by progressive fibrosis and intrahepatic vasoconstriction. Interruption of the initiating and perpetuating etiology—mostly leading to necroinflammation—is possible for several underlying causes, such as autoimmune hepatitis, hepatitis B virus (HBV) infection, and most recently hepatitis C virus (HCV) infection. Thus, in the long run, lifestyle-related liver damage due to chronic alcoholism or morbid obesity will remain the main factor leading to portal hypertension. Both causes are probably more easily countered by socioeconomic measures than by individual approaches. If chronic liver injury supporting fibrogenesis and portal hypertension cannot be interrupted, a wide variety of tools are available to modulate and reduce intrahepatic resistance and therewith portal hypertension. Many of these have been evaluated in animal models. Also, some well-established drugs, which are used in humans for other indications (for example, statins), are promising if applied early and concomitantly to standard therapy. In the future, more individually tailored strategies must also be considered in line with the spectrum of portal hypertensive complications and risk factors defined by high-throughput analysis of the patient’s genome, transcriptome, metabolome, or microbiome. PMID:25374673

Trebicka, Jonel

2014-01-01

186

Development of autoimmune hepatitis following liver transplantation for primary biliary cirrhosis.  

PubMed

Two patients undergoing liver transplantation for classical end-stage primary biliary cirrhosis (PBC) are described, who went on to develop de novo autoimmune hepatitis (AIH) in the transplanted liver. The presentation, in both instances, was with malaise and lethargy. Markedly elevated serum transaminases were found, together with a raised serum IgG and/or globulin fraction and histological features on liver biopsy typical of AIH. Both cases had had changes in their immunosuppressive therapy before the onset of AIH episodes, and both rapidly responded to reinstitution of steroid therapy. The finding, in each case, of a coincidental multiple HLA class I allele match between the recipient and their liver donor suggests that HLA class I-restricted mechanisms may play an important role in the pathogenesis of AIH. PMID:10385638

Jones, D E; James, O F; Portmann, B; Burt, A D; Williams, R; Hudson, M

1999-07-01

187

Could post-liver transplantation course be helpful for the diagnosis of so called cryptogenic cirrhosis?  

PubMed

Cryptogenic cirrhosis (CC) is diagnosed in 5-30% of cirrhotic patients overall and 7% of patients who undergo liver transplantation for cirrhosis. In our series of patients transplanted for CC, pre-transplant clinical and histological data and the post-transplant course were reexamined in an attempt to identify the aetiology. Among the 881 patients transplanted in our centre between 1987 and 2000, 28 patients with a median age of 46 yr (range: 18-69) at transplantation were initially classified as having CC. Two patients were excluded because of intense ischaemic lesions caused by chemoembolization prevented histological analysis of the native liver (n = 1) and because of cryptic HBV infection (n = 1). Among the remaining 26 patients, four groups were individualized: (i) patients with chronic inflammatory liver disease with autoimmune features (n = 14, 54%); (ii) patients with features suggestive of non-alcoholic fatty liver disease (n = 3, 11.5%); (iii); patients with incomplete septal cirrhosis (ISC) and vascular liver disease (n = 3), and (iv) patients with unresolved CC (n = 6, 23%). In the autoimmune liver disease group, the median International Autoimmune Hepatitis score was 12.5 (range: 11-19) after reevaluation and review of the post-transplantation course was helpful to confirm the diagnosis with the occurrence of active graft hepatitis in nine patients, with autoantibodies in five patients. The vascular group was characterized by lesions of obliterative portal venopathy and ISC in all native livers. Diagnosis of NAFLD was based on the clinical background of obesity and/or type 2 diabetes and the presence of steatosis or steatohepatitis in native livers and graft biopsies. A definite aetiological diagnosis can be achieved in the majority of patients initially diagnosed with CC. Autoimmune liver disease emerged as the main aetiology (14 of 26 patients, 54%) and frequently recurred on the grafted liver (nine cases). In all cases a precise diagnosis is obviously of practical interest for better management of post-transplant survey and treatment. PMID:16146549

Duclos-Vallée, Jean-Charles; Yilmaz, Funda; Johanet, Catherine; Roque-Afonso, Anne-Marie; Gigou, Michelle; Trichet, Catherine; Féray, Cyrille; Ballot, Eric; Dussaix, Elisabeth; Castaing, Denis; Bismuth, Henri; Samuel, Didier; Guettier, Catherine

2005-10-01

188

Hepatoprotective Activity of the Total Saponins from Actinidia valvata Dunn Root against Carbon Tetrachloride-Induced Liver Damage in Mice  

PubMed Central

The protective activity of the total saponins from Actinidia valvata Dunn root (TSAV) was studied against carbon-tetrachloride- (CCl4-) induced acute liver injury in mice. Mice were orally administered TSAV (50, 100, and 200?mg/kg) for five days and then given CCl4. TSAV pretreatment significantly prevented the CCl4-induced hepatic damage as indicated by the serum marker enzymes (AST, ALT, and ALP). Parallel to these changes, TSAV also prevented CCl4-induced oxidative stress by inhibiting lipid peroxidation (MDA) and restoring the levels of antioxidant enzymes (SOD, CAT, GR, and GPX), GSH and GSSG. In addition, TSAV attenuated the serum TNF-? and IL-6 levels and inhibited the serum iNOS and NO levels. Liver histopathology indicated that TSAV alleviated CCl4-induced inflammatory infiltration and focal necrosis. TSAV (200?mg/kg) also significantly decreased Bak, Bax mRNA and Fas, FasL, p53, and NF-?B p65 protein expressions and increased Bcl-2 mRNA and protein expressions. Meanwhile, TSAV significantly downregulated caspase-3 and caspase-8 activities and prevented CCl4-induced hepatic cell apoptosis. In addition, TSAV exhibited antioxidant activity through scavenging hydroxyl and DPPH free radicals in vitro. These results indicated that TSAV could protect mice against CCl4-induced acute liver damage possibly through antioxidant, anti-inflammatory activities and regulating apoptotic-related genes. PMID:23243434

Qu, Liping; Xin, Hailiang; Zheng, Guoyin; Su, Yonghua; Ling, Changquan

2012-01-01

189

Taurine has a protective effect against thioacetamide-induced liver cirrhosis by decreasing oxidative stress.  

PubMed

Thioacetamide (TAA) administration (0.3 g/l of tap water for a period of 3 months) to rats resulted in hepatic cirrhosis as assessed by biochemical and histopathological findings. This treatment caused an increase in the levels of malondialdehyde (MDA) and diene conjugates (DCs) and a decrease in the levels of glutathione (GSH), vitamin E, vitamin C and the activities of glutathione peroxidase (GSH-Px) in the liver of rats. Superoxide dismutase (SOD) activities were unchanged. Taurine (2% w/w, added to the chow diet) was administered together with TAA (0.3 g/l of drinking water) for 3 months. Taurine was found to decrease TAA-induced hepatic lipid peroxidation and to increase TAA-depleted vitamin E levels and GSH-Px activities. Histopathological findings also suggested that taurine has an inhibitive effect on TAA-induced hepatic cirrhosis. These results indicate that taurine treatment has a protective effect against TAA-induced liver cirrhosis by decreasing oxidative stress. PMID:11476157

Balkan, J; Do?ru-Abbaso?lu, S; Kanba?li, O; Cevikba?, U; Aykaç-Toker, G; Uysal, M

2001-05-01

190

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. PMID:24719131

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

2014-01-01

191

Demonstrating alcoholic cirrhosis of the liver by Tc-99m BIDA scintigram  

SciTech Connect

Six patients with decompensated cirrhosis of the liver underwent Tc-99m BIDA studies. All demonstrated 1) persistently high blood pool activity in the heart, lung, and soft tissue, 2) slow hepatic tracer uptake, 3) prolonged liver-to-bowel transit time, and 4) visualization of an enlarged spleen. Four of the six patients demonstrated evidence of ascites and in one patient there were visible collateral veins of the abdomen. These findings are due primarily to hepatic dysfunction and retaining Tc-99m BIDA in blood pool because of Tc-99m BIDA exclusively hepatic excretion and little or no alternative renal excretion. All six Tc-99m sulfur colloid studies were performed concomitantly. Except for bone marrow uptake and reversal of the normal liver-spleen ratio of radioactivity, the imaging abnormalities observed with Tc-99m BIDA were similar to those seen by Tc-99m SC. It is concluded that with Tc-99m BIDA studies, three of six abnormal findings, as described, suggest a decompensated stage of cirrhosis of the liver.

Shih, W.J.; DeLand, F.H.; Domstad, P.A.

1984-08-01

192

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. PMID:24944496

García-Compeán, Diego; Jáquez-Quintana, Joel Omar; Lavalle-González, Fernando Javier; González-González, José Alberto; Muńoz-Espinosa, Linda Elsa; Villarreal-Pérez, Jesús Zacarías; Maldonado-Garza, Héctor J

2014-01-01

193

Perioperative levels of glutathione reductase in liver transplant recipients with hepatitis C virus cirrhosis.  

PubMed

Surgical intervention causes oxidative stress leading to an adaptive responses by the body. To evaluate changes in the defense capacity of antioxidant enzymes, we determined the activity of glutathione reductase (GR) levels among liver transplant recipients with due to hepatitis C virus cirrhosis. The study was performed in 22 patients (16 males and 6 females) of average ages 52.63 ± 5.49 years for males and 59.67 ± 5.65 years for females. Blood samples for glutathione reductase activity were drawn on admission before as well as at 1, 6, and 12 h and 1, 2, 3, 5 and 7 days after the liver transplantation. Perioperative glutathione reductase levels were significant (P = .014) over the period using Bonferroni tests. GR activity reached a maximum (15.6112 ± 6.56035 nmol/mg protein) at 3 days after liver transplantation (T3d) (P = .001). The increased GR activity values detected perioperatively indicated scavenging of reactive oxygen species generated after liver transplantation of hepatitis C virus cirrhosis patients. PMID:22841208

Villegas, T; Olmedo, C; Muffak-Granero, K; Comino, A; Garrote, D; Bueno, P; Ferrón, J-A

2012-01-01

194

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. PMID:24966598

Acalovschi, Monica

2014-01-01

195

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

PubMed

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. PMID:24966598

Acalovschi, Monica

2014-06-21

196

A case of Gaucher's disease progressing to liver cirrhosis.  

PubMed

We are going to present a 17 year old female with Gaucher's disease. The patient presented with fever, cough, respiratory distress & abdominal heaviness. There was mild pallor, redness of palm of hands & raised temperature. Liver was hugely enlarged along with splenomegaly. X-ray chest showed non specific bronchiectatic change in both lungs. Ultrasonography of abdomen revealed marked hepatosplenomegaly with no ascites. Bone marrow examination showed cellular marrow with plenty of megakaryocytes. Most of the cells were smear cells & there was histiocytes proliferation & infiltration of bone marrow by small atypical cells. Histologically, lipid was found in hepatocytes in moderate amount. The portal areas showed high lipid contents in macrophages. Different clinical findings & incidental diagnosis of lipid storage disease submerged us in diagnostic dilemma. We give conservative treatment with antibiotic cefuroxime, syrup lactulose & vitamins and this patient was improved. PMID:23715368

Debnath, C R; Debnath, M R; Nabi, N; Khan, N A; Chakraborty, S

2013-04-01

197

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

198

The Association Between the Serum Sodium Level and the Severity of Complications in Liver Cirrhosis  

PubMed Central

Background/Aims Dilutional hyponatremia associated with liver cirrhosis is caused by impaired free water clearance. Several studies have shown that serum sodium levels correlate with survival in cirrhotic patients. Little is known, however, regarding the relationship between the degree of dilutional hyponatremia and development of cirrhotic complications. The aim of this study was to evaluate the association between the serum sodium level and the severity of complications in liver cirrhosis. Methods Data of inpatients with cirrhotic complications were collected retrospectively. The serum sodium levels and severity of complications of 188 inpatients were analyzed. Results The prevalence of dilutional hyponatremia, classified as serum sodium concentrations of ?135 mmol/L, ?130 mmol/L, and ?125 mmol/L, were 20.8%, 14.9%, and 12.2%, respectively. The serum sodium level was strongly associated with the severity of liver function impairment as assessed by Child-Pugh and MELD scores (p<0.0001). Even a mild hyponatremia with a serum sodium concentration of 131-135 mmol/L was associated with severe complications. Sodium levels less than 130 mmol/L indicated the existence of massive ascites (OR, 2.685; CI, 1.316-5.477; p=0.007), grade III or higher hepatic encephalopathy (OR, 5.891; CI, 1.490-23.300; p=0.011), spontaneous bacterial peritonitis (OR, 2.562; CI, 1.162-5.653; p=0.020), and hepatic hydrothorax (OR, 5.723; CI, 1.889-17.336; p=0.002). Conclusions Hyponatremia, especially serum levels ?130 mmol/L, may indicate the existence of severe complications associated with liver cirrhosis. PMID:19543488

Kim, Jong Hoon; Lee, Seuk Hyun; Bae, Won Ki; Kim, Nam-Hoon; Kim, Kyung-Ah; Moon, Young-Soo

2009-01-01

199

Studies on the incidence of hepatocellular carcinoma in heavy drinkers with liver cirrhosis.  

PubMed

The incidence of hepatocellular carcinoma (HCC) in heavy drinkers who drank more than 130 g per day for more than 10 years, and non-drinkers with cirrhosis who were positive or negative hepatitis C virus (HCV) markers, was analyzed in order to evaluate the effect of a large amount of alcohol on the development of HCC. A parallel study was also conducted in some patients from the aspect of HCV genotypes. Among 57 heavy drinkers with liver cirrhosis, HCV marker was positive in 36 patients (C+Al group) and negative in 21 patients (Al-alone group). Eighty-one patients with liver cirrhosis of non-drinkers were positive for HCV markers (C-alone group). HCV infection was involved in 63% of heavy drinkers with cirrhosis and 44% of patients with HCC. The majority of HCC patients in the C+Al group was infected with HCV through routes other than blood transfusion. HCC developed at a younger age in patients of the C+Al group than in patients of the C-alone group without relation to history of blood transfusion. In more than a third of patients who had tattoos or used stimulants in the C+Al group, HCC developed without a history of blood transfusion. These results suggest that heavy drinking enhances the development of HCC. The HCV genotypes in patients with HCC were all type II, except for one case of type III and one unclassified. The mixed type of HCV was often found in patients who had a blood transfusion or tattoo, suggesting that there may be some correlation between the routes of HCV infection and the diversity of genotypes. PMID:8003123

Suzuki, M; Suzuki, H; Mizuno, H; Tominaga, T; Kono, M; Kato, Y; Sato, A; Okabe, K

1993-01-01

200

Primary follicular lymphoma of the spleen incidentally found in a patient with alcohol- and hepatitis C-related liver cirrhosis  

PubMed Central

Primary splenic lymphoma is rare as non-Hodgkin lymphomas. Splenic infiltration of lymphoma cells may cause splenomegaly in many cases. However, splenomegaly is caused not only by tumor involvement but also by non-tumorous disorders. One of the most prevalent non-neoplastic causes is portal hypertension mostly due to liver cirrhosis. On the other hand, liver cirrhosis may underlie various extrahepatic manifestations including development of B-cell non-Hodgkin lymphomas. Here, we report a case of primary follicular lymphoma of the spleen in a patient with liver cirrhosis related to hepatitis C and alcohol. The lymphoma was incidentally found in an enlarged spleen resected palliatively to alleviate symptomatic pancytopenia of the patient. The main characteristic of our case is an incidental finding of a rare situation brought by careful pathological examination. Our case illustrates the importance to recognize a possibility of co-occurrence of chronic liver disease and extrahepatic lymphoma. PMID:25120838

Matsuda, Ikuo; Okada, Masaya; Inoue, Takayuki; Tokugawa, Tazuko; Ogawa, Hiroyasu; Hirota, Seiichi

2014-01-01

201

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

202

Bone marrow-derived mesenchymal stem cell therapy for decompensated liver cirrhosis: A meta-analysis  

PubMed Central

AIM: To assess the efficacy and safety of bone marrow-derived mesenchymal stem cell (BM-MSC) in the treatment of decompensated liver cirrhosis. METHODS: The search terms “bone marrow stem cell” “chronic liver disease” “transfusion” and “injection” were used in the Cochrane Library, Med-Line (Pub-Med) and Embase without any limitations with respect to publication date or language. Journals were also hand-searched and experts in the field were contacted. The studies which used BM-MSC in the treatment of any chronic liver disease were included. Comprehensive Review Manager and Meta-Analyst software were used for statistical analysis. Publication bias was evaluated using Begg’s test. RESULTS: Out of 78 studies identified, five studies were included in the final analysis. The studies were conducted in China, Iran, Egypt and Brazil. Analysis of pooled data of two controlled studies by Review Manager showed that the mean decline in scores for the model for end-stage liver disease (MELD) was -1.23 [95%CI: -2.45-(-0.01)], -1.87 [95%CI: -3.16-(-0.58)], -2.01 [95%CI: -3.35-(-0.68)] at 2, 4 and 24 wk, respectively after transfusion. Meta-analysis of the 5 studies showed that the mean improvement in albumin levels was -0.28, 2.60, 5.28, 4.39 g/L at the end of 8, 16, 24, and 48 wk, respectively, after transfusion. MELD scores, alanine aminotransferase, total bilirubin levels and prothrombin times improved to some extent. BM-MSC injections resulted in no serious adverse events or complications. CONCLUSION: BM-MSC infusion in the treatment of decompensated liver cirrhosis improved liver function. At the end of year 1, there were no serious side effects or complications. PMID:25320545

Pan, Xing-Nan; Zheng, Lian-Qiu; Lai, Xiao-Huan

2014-01-01

203

Role of vaptans in the management of hydroelectrolytic imbalance in liver cirrhosis  

PubMed Central

Ascites and hyponatremia are the most common complications in patients with liver cirrhosis and develop as a consequence of a severe impairment of liver function and portal hypertension. Increasing evidences support the central role of renal function alterations in the pathogenesis of hydroelectrolytic imbalances in cirrhotic patients, thus implying a dense cross-talk between liver and kidney in the systemic and splanchnic vascular homeostasis in such subjects. Since Arginin Vasopressin (AVP) hyperincretion occurs at late stage of cirrhosis and plays an important role in the development of refractory ascites, dilutional hyponatremia and finally hepato-renal syndrome, selective antagonists of AVP receptors V2 (vaptans) have been recently introduced in the therapeutic algorithm of advanced cirrhotic patients. Despite the promising results of earlier phase-two studies, randomized controlled trials failed to find significant results in terms of efficacy of such drugs both in refractory ascites and hyponatremia. Moreover, concerns on their safety profile arise, due to the number of potentially severe side effects of vaptans in the clinical setting, such as hypernatremia, dehydration, renal impairment, and osmotic demyelination syndrome. More robust data from randomized controlled trials are needed in order to confirm the potential role of vaptans in the management of advanced cirrhotic patients. PMID:25429317

Facciorusso, Antonio; Amoruso, Annabianca; Neve, Viviana; Antonino, Matteo; Prete, Valentina Del; Barone, Michele

2014-01-01

204

Fecal metabolome profiling of liver cirrhosis and hepatocellular carcinoma patients by ultra performance liquid chromatography-mass spectrometry.  

PubMed

Fecal metabolome of healthy humans and patients suffering from liver cirrhosis and hepatocellular carcinoma (HCC) were studied using ultra performance liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry (UPLC/Q-TOF MS). Metabolic features detected by the method were then statistically treated using partial least squares to latent structure-discriminant analysis (PLS-DA) models to discriminate between healthy and diseased states. PLS-DA was also used to discriminate between cirrhosis and HCC stressed fecal metabolomes and to identify potential biomarkers for cirrhosis and HCC that are expressed at significantly different amounts in fecal metabolomes. Score plots of pattern recognition analysis distinguished liver cirrhosis and HCC patients from healthy humans. Based on the variable of importance in the project (VIP) values and S-plots, six metabolites were considered as potential biomarkers with a strong increase in lysophosphatidylcholines and a dramatic decrease in bile acids and bile pigments in patients with liver cirrhosis and HCC in comparison with healthy humans. Results demonstrate the potential of UPLC-MS as an efficient and convenient method that can be applied to screen fecal samples and aid in the early diagnosis of cirrhosis and hepatocellular carcinoma. PMID:21458633

Cao, Hongcui; Huang, Haijun; Xu, Wei; Chen, Deying; Yu, Jiong; Li, Jun; Li, Lanjuan

2011-04-01

205

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; Mřrch, Kristine; Wejstĺl, Rune; Norkrans, Gunnar; Lindh, Magnus; Färkkilä, Martti; Westin, Johan

2014-01-01

206

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. PMID:24699777

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

2014-01-01

207

Diabetic myonecrosis in a patient with hepatitis B-induced liver cirrhosis.  

PubMed

Diabetic myonecrosis-a rare complication of long-standing, poorly controlled diabetes mellitus-typically presents with acute-onset muscle pain, is self-limiting, and responds well to conservative management. We report a case of diabetic myonecrosis in a 33-year-old man with hepatitis B-induced liver cirrhosis and type 2 diabetes who presented with abdominal distension and pain in the left thigh. Diabetic myonecrosis was diagnosed based on clinical presentation, radiological findings, magnetic resonance imaging and histopathological investigations; he was successfully treated conservatively with insulin and analgesics. Diabetic myonecrosis should be considered in the differential diagnosis of muscle pain in patients with diabetes. PMID:25305801

Park, Su Min; Kim, You Jeong; Kim, Seung Man; Han, Na; Lee, Eun Ju; Kim, Tae Kyoon; Kim, Tae Nyun; Kwon, Min Jeong; Kim, Mi Kyung; Lee, Soon Hee; Park, Jeong Hyun; Rhee, Byung Doo; Kim, Bo Mi; Lee, Sun Joo

2015-02-01

208

Protective effect of L-theanine on carbon tetrachloride-induced acute liver injury in mice.  

PubMed

We studied effects of L-theanine, a unique amino acid in tea, on carbon tetrachloride (CCl(4))-induced liver injury in mice. The mice were pre-treated orally with L-theanine (50, 100 or 200 mg/kg) once daily for seven days before CCl(4) (10 ml/kg of 0.2% CCl(4) solution in olive oil) injection. L-theanine dose-dependently suppressed the increase of serum activity of ALT and AST and bilirubin level as well as liver histopathological changes induced by CCl(4) in mice. L-theanine significantly prevented CCl(4)-induced production of lipid peroxidation and decrease of hepatic GSH content and antioxidant enzymes activities. Our further studies demonstrated that L-theanine inhibited metabolic activation of CCl(4) through down-regulating cytochrome P450 2E1 (CYP2E1). As a consequence, L-theanine inhibited oxidative stress-mediated inflammatory response which included the increase of TNF-? and IL-1? in sera, and expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in livers. CCl(4)-induced activation of apoptotic related proteins including caspase-3 and PARP in mouse livers was also prevented by L-theanine treatment. In summary, L-theanine protects mice against CCl(4)-induced acute liver injury through inhibiting metabolic activation of CCl(4) and preventing CCl(4)-induced reduction of anti-oxidant capacity in mouse livers to relieve inflammatory response and hepatocyte apoptosis. PMID:22583898

Jiang, Wei; Gao, Min; Sun, Shuai; Bi, Aijing; Xin, Yinqiang; Han, Xiaodong; Wang, Liangbin; Yin, Zhimin; Luo, Lan

2012-06-01

209

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. PMID:24659879

Toshikuni, Nobuyuki; Arisawa, Tomiyasu; Tsutsumi, Mikihiro

2014-01-01

210

A proteomic analysis of thioacetamide-induced hepatotoxicity and cirrhosis in rat livers.  

PubMed

Thioacetamide (TAA) administration is an established technique for generating rat models of liver fibrosis and cirrhosis. Oxidative stress is believed to be involved as TAA-induced liver fibrosis is initiated by thioacetamide S-oxide, which is derived from the biotransformation of TAA by the microsomal flavine-adenine dinucleotide (FAD)-containing monooxygense (FMO) and cytochrome P450 systems. A two-dimensional gel electrophoresis-mass spectrometry approach was applied to analyze the protein profiles of livers of rats administered with sublethal doses of TAA for 3, 6 and 10 weeks respectively. With this approach, 59 protein spots whose expression levels changed significantly upon TAA administration were identified, including three novel proteins. These proteins were then sorted according to their common biochemical properties and functions, so that pathways involved in the pathogenesis of rat liver fibrosis due to TAA-induced toxicity could be elucidated. As a result, it was found that TAA-administration down-regulated the enzymes of the primary metabolic pathways such as fatty acid beta-oxidation, branched chain amino acids and methionine breakdown. This phenomenon is suggestive of the depletion of succinyl-CoA which affects heme and iron metabolism. Up-regulated proteins, on the other hand, are related to oxidative stress and lipid peroxidation. Finally, these proteomics data and the data obtained from the scientific literature were integrated into an "overview model" for TAA-induced liver cirrhosis. This model could now serve as a useful resource for researchers working in the same area. PMID:15526343

Low, Teck Yew; Leow, Chon Kar; Salto-Tellez, Manuel; Chung, Maxey C M

2004-12-01

211

Transaldolase Deficiency: Liver Cirrhosis Associated with a New Inborn Error in the Pentose Phosphate Pathway  

PubMed Central

This article describes the first patient with a deficiency of transaldolase (TALDO1 [E.C.2.2.1.2]). Clinically, the patient presented with liver cirrhosis and hepatosplenomegaly during early infancy. In urine and plasma, elevated concentrations of ribitol, d-arabitol, and erythritol were found. By incubating the patient's lymphoblasts and erythrocytes with ribose-5-phosphate and subsequently analyzing phosphate sugar metabolites, we discovered a deficiency of transaldolase. Sequence analysis of the transaldolase gene from this patient showed a homozygous deletion of 3 bp. This deletion results in absence of serine at position 171 of the transaldolase protein. This amino acid is invariable between species and is located in a conserved region, indicating its importance for enzyme activity. The detection of this new inborn error of pentose metabolism has implications for the diagnostic workup of liver problems of unknown etiology. PMID:11283793

Verhoeven, Nanda M.; Huck, Jojanneke H. J.; Roos, Birthe; Struys, Eduard A.; Salomons, Gajja S.; Douwes, Adriaan C.; van der Knaap, Marjo S.; Jakobs, Cornelis

2001-01-01

212

Effect of carnosine against thioacetamide-induced liver cirrhosis in rat.  

PubMed

Carnosine (beta-alanyl-L-histidine) is a dipeptide with antioxidant properties. Oxidative stress has been proposed to be involved in thioacetamide (TAA)-induced liver cirrhosis in rats, that is similar to human disease. In this study we aimed to investigate the role of carnosine on the development of TAA-induced cirrhosis. 200mg TAA/kg body weight has been given i.p. twice a week for three months to female wistar rats. Another group received same dose of TAA in the same pattern plus 2g carnosine/L of drinking water for three months. TAA administration resulted in hepatic fibrosis, significant increases in plasma transaminase activities as well as hepatic hydroxyproline and lipid peroxide levels, while liver glutathione (GSH) and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) protein expressions and activities decreased. Carnosine was found to behave as an antioxidant reducing malondialdehyde (MDA) and diene conjugate (DC) levels although it was not effective on increased transaminase activities and decreased antioxidants. It also did not affect the histopathological changes observed in TAA group. Thus our findings indicate that carnosine appears to attenuate peroxidation as an antioxidant itself but does not seem to prevent the development of TAA-induced cirrhotic process. PMID:19958806

Aydin, A Fatih; Küskü-Kiraz, Zeynep; Do?ru-Abbaso?lu, Semra; Güllüo?lu, Mine; Uysal, Müjdat; Koçak-Toker, Necla

2010-01-01

213

Hepatocellular Carcinoma in Liver Cirrhosis: Surgical Resection versus Transarterial Chemoembolization—A Meta-Analysis  

PubMed Central

We compare the value of TACE to liver resection for patients with BCLC stage A and B HCC. For patients with HCC in cirrhosis LT is the treatment of choice. TACE represents the current standard for unresectable BCLC stage B patients not eligible for LT. Recently liver resection for HCC and significant cirrhosis has become increasingly popular. A systematic search of the literature and meta-analysis was conducted to identify studies, reporting short- and long-term results of hepatic resection versus TACE for HCC treatment. The data were analyzed regarding the odds for 30-day mortality and hazard ratio for overall-survival. 12 studies comparing short- and long-term outcome of HR versus TACE for HCC were identified. Peri-interventional mortality and overall survival were investigated. Peri-interventional mortality was higher for surgical resection (n.s.), and overall-survival was significantly better for surgically treated patients at one year (P = 0.002) and 3 years (P ? 0.00001). The hazard ratio of overall-survival for all twelve studies was 0.70 (P = 0.0001) and significantly in favor of surgical treatment. Although large RCTs are missing and the available data are limited and not homogeneous a reappraisal of the current treatment guidelines should be considered based on the superior long-term outcome for surgically treated patients. PMID:25642245

Kapitanov, Teodor; Neumann, Ulf P.; Schmeding, Maximilian

2015-01-01

214

Renal Effects of the Novel Selective Adenosine A1 Receptor Blocker SLV329 in Experimental Liver Cirrhosis in Rats  

PubMed Central

Liver cirrhosis is often complicated by an impaired renal excretion of water and sodium. Diuretics tend to further deteriorate renal function. It is unknown whether chronic selective adenosine A1 receptor blockade, via inhibition of the hepatorenal reflex and the tubuloglomerular feedback, might exert diuretic and natriuretic effects without a reduction of the glomerular filtration rate. In healthy animals intravenous treatment with the novel A1 receptor antagonist SLV329 resulted in a strong dose-dependent diuretic (up to 3.4-fold) and natriuretic (up to 13.5-fold) effect without affecting creatinine clearance. Male Wistar rats with thioacetamide-induced liver cirrhosis received SLV329, vehicle or furosemide for 12 weeks. The creatinine clearance of cirrhotic animals decreased significantly (?36.5%, p<0.05), especially in those receiving furosemide (?41.9%, p<0.01). SLV329 was able to prevent this decline of creatinine clearance. Mortality was significantly lower in cirrhotic animals treated with SLV329 in comparison to animals treated with furosemide (17% vs. 54%, p<0.05). SLV329 did not relevantly influence the degree of liver fibrosis, kidney histology or expression of hepatic or renal adenosine receptors. In conclusion, chronic treatment with SLV329 prevented the decrease of creatinine clearance in a rat model of liver cirrhosis. Further studies will have to establish whether adenosine A1 receptor antagonists are clinically beneficial at different stages of liver cirrhosis. PMID:21423778

von Websky, Karoline; Arafat, Ayman M.; Rahnenführer, Jan; Alter, Markus; Kalk, Philipp; Ziegler, Dieter; Fischer, Yvan; Pfab, Thiemo

2011-01-01

215

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

216

Eugenol-rich Fraction of Syzygium aromaticum (Clove) Reverses Biochemical and Histopathological Changes in Liver Cirrhosis and Inhibits Hepatic Cell Proliferation  

PubMed Central

Background: Dried flower bud of Syzygium aromaticum (clove) is rich in eugenol, an antioxidant and antiinflammatory compound that can protect liver against injury. Clove, besides eugenol, also contains other pharmacologically active phytochemicals such as ?-sitosterol and ascorbic acid. This study reports the effect of eugenol-rich fraction (ERF) of clove on liver cirrhosis induced by thioacetamide. Methods: Cirrhosis of the liver, which predisposes to hepatocellular carcinoma, was induced by administering thioacetamide (0.03%) in drinking water for 16 weeks. Cirrhotic animals were divided into two groups; the treated group was administered ERF for 9 weeks, one week after discontinuation of thioacetamide, while the other group received normal saline for a similar duration of time. Results: The treatment with ERF, as determined by histopathology and through a battery of biochemical markers of hepatic injury, oxidative stress and drug metabolizing enzymes, significantly ameliorated the signs of liver cirrhosis. It lowered the elevated levels of alkaline phosphatase, ?-glutamyl transferase and other biochemical changes in liver cirrhosis. Histopathology of the liver corroborated the effect of ERF with biochemical findings. ERF treatment further inhibited cell proliferation, as demonstrated by reduced [3H]-thymidine uptake. Conclusions: Data provide evidence supporting the protective action of ERF on liver cirrhosis. The study assumes significance because cirrhosis predisposes the liver to cancer, which is characterized by abnormal cell proliferation. ERF in this study is reported to inhibit hepatic cell proliferation and at the same time decrease oxidative stress, which might be the mechanism of protection against liver cirrhosis. PMID:25574464

Ali, Shakir; Prasad, Ram; Mahmood, Amena; Routray, Indusmita; Shinkafi, Tijjani Salihu; Sahin, Kazim; Kucuk, Omer

2014-01-01

217

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. PMID:25024623

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

218

Liver Resection as a Bridge to Transplantation for Hepatocellular Carcinoma on Cirrhosis  

PubMed Central

Objective: To assess the viability of a strategy of primary resection with secondary liver transplantation (LT) for hepatocellular carcinoma (HCC) on cirrhosis Summary Background Data: LT is the optimal treatment of HCC with cirrhosis. Owing to organ shortage, liver resection is considered as a reasonable first-line treatment of patients with small HCC and good liver function, with secondary LT as a perspective in case of recurrence. The viability of such strategy, positively explored in theoretical models, is not documented in clinical practice. Methods: Among 358 consecutive patients with HCC on cirrhosis treated by liver resection (n = 163; 98 of whom were transplantable) or transplantation (n = 195), the feasibility and outcome of secondary transplantation was evaluated in a 2-step fashion. First, secondary LT for tumor recurrence after resection (n = 17) was compared with primary LT (n = 195), to assess the risk and the outcome of secondary LT in patients who effectively succeeded to be treated by this approach. Second, primary resection in transplantable patients (n = 98) was compared with that of primary LT (n = 195) on an intention-to-treat basis, to assess the outcome of each treatment strategy and to determine the proportion of resected patients likely to be switched for secondary LT. Transplantability of resected patients was retrospectively determined according to selection criteria of LT for HCC. Results: Operative mortality (?2 months) of secondary LT was significantly higher than that of primary LT (28.6% versus 2.1%; P = 0.0008) as was intraoperative bleeding (mean transfused blood units, 20.7 versus 10.5; P = 0.0001). Tumor recurrence occurred more frequently after secondary than after primary LT (54% versus 18%; P = 0.001). Posttransplant 5-year overall survival was 41% versus 61% (P = 0.03), and disease-free survival was 29% versus 58% (P = 0.003) for secondary and primary LT, respectively. Of 98 patients treated by resection while initially eligible for transplantation, only 20 (20%) were secondarily transplanted, 17 of whom (17%) for tumor recurrence and 3 (3%) for hepatic decompensation. Transplantability of tumoral recurrence was 25% (17 of 69 recurrences). Compared with primarily transplanted patients, transplantable resected patients had a decreased 5-year overall survival (50% versus 61%; P = 0.05) and disease-free survival (18% versus 58%; P < 0.0001), despite the use of secondary LT. On a multivariate analysis including 271 patients eligible for transplantation and treated by either liver resection or primary LT, liver resection alone (P < 0.0001; risk ratio [RR] = 3.27) or liver resection with secondary LT (P < 0.05; RR= 1.87) emerged as negative independent factors of disease-free survival as compared with primary LT. A number of nodules > 3 (P = 0.002; RR= 2.02) and a maximum tumor size exceeding 30 mm (P < 0.0001; RR=1.93) were also predictive of lower disease-free survival. Conclusions: LT after liver resection is associated with a higher operative mortality, an increased risk of recurrence, and a poorer outcome than primary LT. In addition, liver resection as a bridge to LT impairs the patient transplantability and the chance of long-term survival of cirrhotic patients with HCC. Primary LT should therefore remain the ideal choice of treatment of a cirrhotic patient with HCC, even when the tumor is resectable. PMID:14530722

Adam, René; Azoulay, Daniel; Castaing, Denis; Eshkenazy, Rony; Pascal, Gérard; Hashizume, Kentaro; Samuel, Didier; Bismuth, Henri

2003-01-01

219

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. PMID:24431897

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

2013-01-01

220

[Indications and results of liver transplantation in the treatment of hepatocellular carcinoma in cirrhosis].  

PubMed

Liver transplantation is a treatment for hepatocellular carcinoma in cirrhosis which is both recognized, because potentially radical, and controversial because associated with a high risk of recurrence. This study reports the results of a consecutive series of 125 patients transplanted for hepatocellular carcinoma in cirrhosis over an 11-year period. Liver transplantation was indicated because of the tumour in 92 cases (74%) and the tumour was an incidental finding in 13 cases (10%) or was discovered on histological examination of the hepatectomy specimen in 20 cases (16%). The operative mortality at two months was 4% with a 20% morbidity, due to vascular (6%) or biliary (14%) complications. Tumour recurrence was observed in 26 patients (21%) Recurrence was exceptional in the incidental or histological forms of hepatocellular carcinoma (5%) and more frequent when the tumour constituted the indication for transplantation (27%). The risk of recurrence and the survival were significantly influenced by the maximal tumour diameter (greater than 30 mm), the number of tumour nodules (greater than 3) and the presence of portal invasion. Inclusion of these factors in patient selection during the second phase of the study allowed a reduction of the risk of recurrence from 33 to 11% and improvement of the 3-year post-transplantation survival from 53 to 76%. Tumours less than or equal to 30 mm in diameter, with no more than 3 nodules, and without portal invasion are ideal indications for transplantation. Tumours with more than 3 nodules and larger than 30 mm appear to constitute a contraindication to transplantation, unless tumour reduction can be achieved by chemoembolization. Intermediate forms of hepatocellular carcinoma between these two extreme forms are possible indications for transplantation, depending on the availability of liver transplants. PMID:9752505

Adam, R; Castaing, D; Azoulay, D; Majno, P; Samuel, D; Bismuth, H

1998-01-01

221

The role of gut-liver axis in the pathogenesis of liver cirrhosis and portal hypertension.  

PubMed

Because of the anatomical position and its unique vascular system, the liver is susceptible to the exposure to the microbial products from the gut. Although large amount of microbes colonize in the gut, translocation of the microbes or microbial products into the liver and systemic circulation is prevented by gut epithelial barrier function and cleansing and detoxifying functions of the liver in healthy subjects. However, when the intestinal barrier function is disrupted, large amount of bacterial products can enter into the liver and systemic circulation and induce inflammation through their receptors. Nowadays, there have been various reports suggesting the role of gut flora and bacterial translocation in the pathogenesis of chronic liver disease and portal hypertension. This review summarizes the current knowledge about bacterial translocation and its contribution to the pathogenesis of chronic liver diseases and portal hypertension. PMID:23323248

Seo, Yeon Seok; Shah, Vijay H

2012-12-01

222

Regression of fibrosis and reversal of cirrhosis in rats by galectin inhibitors in thioacetamide-induced liver disease.  

PubMed

Galectin-3 protein is critical to the development of liver fibrosis because galectin-3 null mice have attenuated fibrosis after liver injury. Therefore, we examined the ability of novel complex carbohydrate galectin inhibitors to treat toxin-induced fibrosis and cirrhosis. Fibrosis was induced in rats by intraperitoneal injections with thioacetamide (TAA) and groups were treated with vehicle, GR-MD-02 (galactoarabino-rhamnogalaturonan) or GM-CT-01 (galactomannan). In initial experiments, 4 weeks of treatment with GR-MD-02 following completion of 8 weeks of TAA significantly reduced collagen content by almost 50% based on Sirius red staining. Rats were then exposed to more intense and longer TAA treatment, which included either GR-MD-02 or GM-CT-01 during weeks 8 through 11. TAA rats treated with vehicle developed extensive fibrosis and pathological stage 6 Ishak fibrosis, or cirrhosis. Treatment with either GR-MD-02 (90 mg/kg ip) or GM-CT-01 (180 mg/kg ip) given once weekly during weeks 8-11 led to marked reduction in fibrosis with reduction in portal and septal galectin-3 positive macrophages and reduction in portal pressure. Vehicle-treated animals had cirrhosis whereas in the treated animals the fibrosis stage was significantly reduced, with evidence of resolved or resolving cirrhosis and reduced portal inflammation and ballooning. In this model of toxin-induced liver fibrosis, treatment with two galectin protein inhibitors with different chemical compositions significantly reduced fibrosis, reversed cirrhosis, reduced galectin-3 expressing portal and septal macrophages, and reduced portal pressure. These findings suggest a potential role of these drugs in human liver fibrosis and cirrhosis. PMID:24130706

Traber, Peter G; Chou, Hsin; Zomer, Eliezer; Hong, Feng; Klyosov, Anatole; Fiel, Maria-Isabel; Friedman, Scott L

2013-01-01

223

Regression of Fibrosis and Reversal of Cirrhosis in Rats by Galectin Inhibitors in Thioacetamide-Induced Liver Disease  

PubMed Central

Galectin-3 protein is critical to the development of liver fibrosis because galectin-3 null mice have attenuated fibrosis after liver injury. Therefore, we examined the ability of novel complex carbohydrate galectin inhibitors to treat toxin-induced fibrosis and cirrhosis. Fibrosis was induced in rats by intraperitoneal injections with thioacetamide (TAA) and groups were treated with vehicle, GR-MD-02 (galactoarabino-rhamnogalaturonan) or GM-CT-01 (galactomannan). In initial experiments, 4 weeks of treatment with GR-MD-02 following completion of 8 weeks of TAA significantly reduced collagen content by almost 50% based on Sirius red staining. Rats were then exposed to more intense and longer TAA treatment, which included either GR-MD-02 or GM-CT-01 during weeks 8 through 11. TAA rats treated with vehicle developed extensive fibrosis and pathological stage 6 Ishak fibrosis, or cirrhosis. Treatment with either GR-MD-02 (90 mg/kg ip) or GM-CT-01 (180 mg/kg ip) given once weekly during weeks 8–11 led to marked reduction in fibrosis with reduction in portal and septal galectin-3 positive macrophages and reduction in portal pressure. Vehicle-treated animals had cirrhosis whereas in the treated animals the fibrosis stage was significantly reduced, with evidence of resolved or resolving cirrhosis and reduced portal inflammation and ballooning. In this model of toxin-induced liver fibrosis, treatment with two galectin protein inhibitors with different chemical compositions significantly reduced fibrosis, reversed cirrhosis, reduced galectin-3 expressing portal and septal macrophages, and reduced portal pressure. These findings suggest a potential role of these drugs in human liver fibrosis and cirrhosis. PMID:24130706

Traber, Peter G.; Chou, Hsin; Zomer, Eliezer; Hong, Feng; Klyosov, Anatole; Fiel, Maria-Isabel; Friedman, Scott L.

2013-01-01

224

A diagnostic model for cirrhosis in patients with non-alcoholic fatty liver disease: an artificial neural network approach  

PubMed Central

Background: Timely diagnosis of liver cirrhosis is vital for preventing further liver damage and giving the patient the chance of transplantation. Although biopsy of the liver is the gold standard for cirrhosis assessment, it has some risks and limitations and this has led to the development of new noninvasive methods to determine the stage and prognosis of the patients. We aimed to design an artificial neural network (ANN) model to diagnose cirrhosis patients with non-alcoholic fatty liver disease (NAFLD) using routine laboratory data. Methods: Data were collected from 392 patients with NAFLD by the Middle East Research Center in Tehran. Demographic variables, history of diabetes, INR, complete blood count, albumin, ALT, AST and other routine laboratory tests, examinations and medical history were gathered. Relevant variables were selected by means of feature extraction algorithm (Knime software) and were accredited by the experts. A neural network was developed using the MATLAB software. Results: The best obtained model was developed with two layers, eight neurons and TANSIG and PURLIN functions for layer one and output layer, respectively. The sensitivity and specificity of the model were 86.6% and 92.7%, respectively. Conclusion: The results of this study revealed that the neural network modeling may be able to provide a simple, noninvasive and accurate method for diagnosing cirrhosis only based on routine laboratory data.

Pournik, Omid; Dorri, Sara; Zabolinezhad, Hedieh; Alavian, Seyyed Moayed; Eslami, Saeid

2014-01-01

225

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. PMID:24106408

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

226

Chobert MN et al LIVER PRECURSOR CELLS INCREASE HEPATIC FIBROSIS INDUCED BY CHRONIC  

E-print Network

Chobert MN et al LIVER PRECURSOR CELLS INCREASE HEPATIC FIBROSIS INDUCED BY CHRONIC CARBON liver CCl4-induced fibrosis Pages of text: 27 Tables: 1 Black and white or grayscale figures: 1 Color complication of virtually all types of chronic liver damage, usually begins in portal areas, and its severity

Boyer, Edmond

227

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

228

Andrographis paniculata leaf extract prevents thioacetamide-induced liver cirrhosis in rats.  

PubMed

This study investigated the hepatoprotective effects of ethanolic Andrographis paniculata leaf extract (ELAP) on thioacetamide-induced hepatotoxicity in rats. An acute toxicity study proved that ELAP is not toxic in rats. To examine the effects of ELAP in vivo, male Sprague Dawley rats were given intraperitoneal injections of vehicle 10% Tween-20, 5 mL/kg (normal control) or 200 mg/kg TAA thioacetamide (to induce liver cirrhosis) three times per week. Three additional groups were treated with thioacetamide plus daily oral silymarin (50 mg/kg) or ELAP (250 or 500 mg/kg). Liver injury was assessed using biochemical tests, macroscopic and microscopic tissue analysis, histopathology, and immunohistochemistry. In addition, HepG2 and WRL-68 cells were treated in vitro with ELAP fractions to test cytotoxicity. Rats treated with ELAP exhibited significantly lower liver/body weight ratios and smoother, more normal liver surfaces compared with the cirrhosis group. Histopathology using Hematoxylin and Eosin along with Masson's Trichrome stain showed minimal disruption of hepatic cellular structure, minor fibrotic septa, a low degree of lymphocyte infiltration, and minimal collagen deposition after ELAP treatment. Immunohistochemistry indicated that ELAP induced down regulation of proliferating cell nuclear antigen. Also, hepatic antioxidant enzymes and oxidative stress parameters in ELAP-treated rats were comparable to silymarin-treated rats. ELAP administration reduced levels of altered serum liver biomarkers. ELAP fractions were non-cytotoxic to WRL-68 cells, but possessed anti-proliferative activity on HepG2 cells, which was confirmed by a significant elevation of lactate dehydrogenase, reactive oxygen species, cell membrane permeability, cytochrome c, and caspase-8,-9, and, -3/7 activity in HepG2 cells. A reduction of mitochondrial membrane potential was also detected in ELAP-treated HepG2 cells. The hepatoprotective effect of 500 mg/kg of ELAP is proposed to result from the reduction of thioacetamide-induced toxicity, normalizing reactive oxygen species levels, inhibiting cellular proliferation, and inducing apoptosis in HepG2 cells. PMID:25280007

Abdulaziz Bardi, Daleya; Halabi, Mohammed Farouq; Hassandarvish, Pouya; Rouhollahi, Elham; Paydar, Mohammadjavad; Moghadamtousi, Soheil Zorofchian; Al-Wajeeh, Nahla Saeed; Ablat, Abdulwali; Abdullah, Nor Azizan; Abdulla, Mahmood Ameen

2014-01-01

229

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. PMID:24708568

2014-01-01

230

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. PMID:23467463

Lutz, Philipp; Strunk, Holger; Schild, Hans Heinz; Sauerbruch, Tilman

2013-01-01

231

[Severe megaloblastic anaemia by triamterene in a patient with alcoholic liver cirrhosis (author's transl)].  

PubMed

Mucosal ulceration and severe bone-marrow insufficiency with marked megaloblastic transformation occurred during treatment with triamterene in a patient with decompensated alcoholic liver cirrhosis and malnutrition. When the triamterene-containing preparation was stopped and folinic acid administered the haematological picture improved, but the patient died, with signs of hepatocellular insufficiency, of gastro-intestinal bleeding. The serum folic-acid level was markedly reduced due to the chronic malnutrition, while the vitamin B12 level was within normal limits. This observation indicates that when the pool of folic-acid coenzymes is reduced, triamterene can cause megaloblastic anaemia due to its folic-acid antagonism. Triamterene should, therefore, be given to patients with borderline folic-acid reservoirs, chronic alcoholism or during pregnancy, only under careful serial control of the blood picture. PMID:313333

Wilms, K; Wiedmann, K H; Castrillón-Oberndorfer, W L

1979-06-01

232

Gastric ischemia after epinephrine injection in a patient with liver cirrhosis  

PubMed Central

Endoscopic epinephrine injection is relatively easy, quick and inexpensive. Furthermore, it has a low rate of complications, and it is widely used for the management of nonvariceal upper gastrointestinal bleeding. There have been several case reports of gastric ischemia after endoscopic injection therapy. Inadvertent intra-arterial injection may result in either spasm or thrombosis, leading to subsequent tissue ischemia or necrosis, although the stomach has a rich vascular supply and the vascular reserve of the intramural anastomosis. In addition to endoscopic injection therapy, smoking, hypertension and atherosclerosis are risk factors of gastric ischemia. We report a case of gastric ischemia after submucosal epinephrine injection in a 51-year-old woman with hypertension and liver cirrhosis. PMID:23372366

Kim, Su Young; Han, Seung-Hee; Kim, Kyung Han; Kim, Sang Ock; Han, Sang-Young; Lee, Sung-Wook; Baek, Yang Hyun

2013-01-01

233

Inositol-requiring enzyme 1-mediated endoplasmic reticulum stress triggers apoptosis and fibrosis formation in liver cirrhosis rat models.  

PubMed

Long?term and advanced cirrhosis is usually irreversible and often coincides with variceal hemorrhage or development of hepatocellular carcinoma; therefore, liver cirrhosis is a major cause of morbidity and mortality globally. The aim of the present study was to investigate the specific mechanism behind the formation of fibrosis or cirrhosis using rat models of hepatic fibrosis. The cirrhosis model was established by intraperitoneally administering dimethylnitrosamine to the rats. Hematoxylin and eosin staining was performed on the hepatic tissues of the rats to observe the fibrosis or cirrhosis, and western blot analysis was employed to detect ??smooth muscle actin and desmin protein expression. Flow cytometric analysis was used to examine early and late apoptosis, and the protein and mRNA expression of endoplasmic reticulum (ER) stress-associated unfolded protein response (UPR) pathway proteins and apoptotic proteins [C/EBP homologous protein (CHOP) and caspase?12] was detected by western blotting and the reverse-transcription polymerase chain reaction, respectively. The results indicated that the cirrhosis model was established successfully and that fibrosis was significantly increased in the cirrhosis model group compared with that in the normal control group. Flow cytometric analysis showed that early and late apoptosis in the cirrhosis model was significantly higher compared with that in the control group. The expression of the UPR pathway protein inositol-requiring enzyme (IRE) 1, as well as the expression of CHOP, was increased significantly in the cirrhotic rat tissues compared with that in the control group tissues (P<0.05). In conclusion, apoptosis was clearly observed in the hepatic tissue of cirrhotic rats, and the apoptosis was caused by activation of the ER stress-mediated IRE1 and CHOP. PMID:25434505

Jiang, Tianpeng; Wang, Lizhou; Li, Xing; Song, Jie; Wu, Xiaoping; Zhou, Shi

2015-04-01

234

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

235

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. PMID:20886039

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

236

Effects of Increased Von Willebrand Factor Levels on Primary Hemostasis in Thrombocytopenic Patients with Liver Cirrhosis  

PubMed Central

In patients with liver cirrhosis procoagulant and anticoagulant changes occur simultaneously. During primary hemostasis, platelets adhere to subendothelial structures, via von Willebrand factor (vWF). We aimed to investigate the influence of vWF on primary hemostasis in patients with liver cirrhosis. Therefore we assessed in-vitro bleeding time as marker of primary hemostasis in cirrhotic patients, measuring the Platelet Function Analyzer (PFA-100) closure times with collagen and epinephrine (Col-Epi, upper limit of normal ?165 s) or collagen and ADP (Col-ADP, upper limit of normal ?118 s). If Col-Epi and Col-ADP were prolonged, the PFA-100 was considered to be pathological. Effects of vWF on primary hemostasis in thrombocytopenic patients were analyzed and plasma vWF levels were modified by adding recombinant vWF or anti-vWF antibody. Of the 72 included cirrhotic patients, 32 (44.4%) showed a pathological result for the PFA-100. They had mean closure times (± SD) of 180±62 s with Col-Epi and 160±70 s with Col-ADP. Multivariate analysis revealed that hematocrit (P?=?0.027) and vWF-antigen levels (P?=?0.010) are the predictors of a pathological PFA-100 test in cirrhotic patients. In 21.4% of cirrhotic patients with platelet count ?150/nL and hematocrit ?27.0%, pathological PFA-100 results were found. In thrombocytopenic (<150/nL) patients with cirrhosis, normal PFA-100 results were associated with higher vWF-antigen levels (462.3±235.9% vs. 338.7±151.6%, P?=?0.021). These results were confirmed by multivariate analysis in these patients as well as by adding recombinant vWF or polyclonal anti-vWF antibody that significantly shortened or prolonged closure times, respectively. In conclusion, primary hemostasis is impaired in cirrhotic patients. The effect of reduced platelet count in cirrhotic patients can at least be partly compensated by increased vWF levels. Recombinant vWF could be an alternative to platelet transfusions in the future. PMID:25397410

Wannhoff, Andreas; Müller, Oliver J.; Friedrich, Kilian; Rupp, Christian; Klöters-Plachky, Petra; Leopold, Yvonne; Brune, Maik; Senner, Mirja; Weiss, Karl-Heinz; Stremmel, Wolfgang; Schemmer, Peter; Katus, Hugo A.; Gotthardt, Daniel N.

2014-01-01

237

Survival, liver failure, and hepatocellular carcinoma in obesity-related cryptogenic cirrhosis  

Microsoft Academic Search

Despite the rising incidence of obesity and diabetes, there is little emphasis on morbidity and mortality from obesity-related cirrhosis, usually considered a rare and asymptomatic condition. Our aim was to assess survival and the occurrence of hepatocellular carcinoma and complications of hepatic insufficiency in obesity-related cryptogenic cirrhosis compared with cirrhosis of other origins. We analyzed retrospectively 27 overweight patients with

Vlad Ratziu; Luminita Bonyhay; Vincent Di Martino; Frederic Charlotte; Lucas Cavallaro; Marie-Hélčne Sayegh-Tainturier; Philippe Giral; André Grimaldi; Pierre Opolon; Thierry Poynard

2002-01-01

238

E3 Ubiquitin Ligase Synoviolin Is Involved in Liver Fibrogenesis  

PubMed Central

Background and Aim Chronic hepatic damage leads to liver fibrosis, which is characterized by the accumulation of collagen-rich extracellular matrix. However, the mechanism by which E3 ubiquitin ligase is involved in collagen synthesis in liver fibrosis is incompletely understood. This study aimed to explore the involvement of the E3 ubiquitin ligase synoviolin (Syno) in liver fibrosis. Methods The expression and localization of synoviolin in the liver were analyzed in CCl4-induced hepatic injury models and human cirrhosis tissues. The degree of liver fibrosis and the number of activated hepatic stellate cells (HSCs) was compared between wild type (wt) and Syno+/? mice in the chronic hepatic injury model. We compared the ratio of apoptosis in activated HSCs between wt and Syno+/? mice. We also analyzed the effect of synoviolin on collagen synthesis in the cell line from HSCs (LX-2) using siRNA-synoviolin and a mutant synoviolin in which E3 ligase activity was abolished. Furthermore, we compared collagen synthesis between wt and Syno?/? mice embryonic fibroblasts (MEF) using quantitative RT-PCR, western blotting, and collagen assay; then, we immunohistochemically analyzed the localization of collagen in Syno?/? MEF cells. Results In the hepatic injury model as well as in cirrhosis, synoviolin was upregulated in the activated HSCs, while Syno+/? mice developed significantly less liver fibrosis than in wt mice. The number of activated HSCs was decreased in Syno+/? mice, and some of these cells showed apoptosis. Furthermore, collagen expression in LX-2 cells was upregulated by synoviolin overexpression, while synoviolin knockdown led to reduced collagen expression. Moreover, in Syno?/? MEF cells, the amounts of intracellular and secreted mature collagen were significantly decreased, and procollagen was abnormally accumulated in the endoplasmic reticulum. Conclusion Our findings demonstrate the importance of the E3 ubiquitin ligase synoviolin in liver fibrosis. PMID:21049091

Hasegawa, Daisuke; Fujii, Ryoji; Yagishita, Naoko; Matsumoto, Nobuyuki; Aratani, Satoko; Izumi, Toshihiko; Azakami, Kazuko; Nakazawa, Minako; Fujita, Hidetoshi; Sato, Tomoo; Araya, Natsumi; Koike, Junki; Tadokoro, Mamoru; Suzuki, Noboru; Nagata, Kazuhiro; Senoo, Haruki; Friedman, Scott L.; Nishioka, Kusuki; Yamano, Yoshihisa; Itoh, Fumio; Nakajima, Toshihiro

2010-01-01

239

The transhepatic endotoxin gradient is present despite liver cirrhosis and is attenuated after transjugular portosystemic shunt (TIPS).  

PubMed Central

Background Translocation of gut-derived bacterial products such as endotoxin is a major problem in liver cirrhosis. Methods To assess the hepatic clearance of bacterial products in individuals with cirrhosis, we tested concentrations of Gram-negative bacterial lipopolysaccharide (LPS), LPS-binding protein (LBP), and the precursor of nitric oxide (NO), L-arginine, in a cohort of 8 stable patients with liver cirrhosis before and after elective transjugular portosystemic shunt (TIPS) implantation, including central venous, hepatic venous, and portal venous measurements. Results Using an adapted LPS assay, we detected high portal venous LPS concentrations (mean 1743 ± 819 pg/mL). High concentrations of LPS were detectable in the central venous blood (931 ± 551 pg/mL), as expected in persons with cirrhosis. The transhepatic LPS gradient was found to be 438 ± 287 pg/mL, and 25 ± 12% of portal LPS was cleared by the cirrhotic liver. After TIPS, central venous LPS concentrations increased in the hepatic and central veins, indicating shunting of LPS with the portal blood through the stent. This paralleled a systemic increase of L-arginine, whereas the NO synthase inhibitor asymmetric dimethylarginine (ADMA) remained unchanged, suggesting that bacterial translocation may contribute to the pathogenesis of circulatory dysfunction post-TIPS. Conclusions This study provides quantitative estimates of the role of the liver in the pathophysiology of bacterial translocation. The data indicate that the cirrhotic liver retains the capacity for clearance of bacterial endotoxin from the portal venous blood and that TIPS implantation attenuates this clearance. Thus, increased endotoxin concentrations in the systemic circulation provide a possible link to the increased encephalopathy in TIPS patients. PMID:21978390

2011-01-01

240

Abnormalities in the serum phospholipids fatty acid profile in patients with alcoholic liver cirrhosis - a pilot study.  

PubMed

The fatty acid composition of serum phospholipids were analyzed in 20 patients with alcoholic liver cirrhosis (11 with malnutrition and 9 with acceptable nutritional status); 25 healthy age and sex-matched adults were used as controls. Cirrhotic patients showed higher levels of palmitic acid and total saturated fatty acids than healthy subjects. Total n-6 and n-3 polyunsaturated fatty acids (PUFA), and levels of linoleic, dihomo-gama linolenic, arachidonic, and docosahexaenoic acid were significantly lower (p<0.001) in patients with alcoholic cirrhosis compared to healthy controls. Significant changes were also found between patients stratified according to nutritional status. In particular, the sum of n-3 PUFA was significantly lower (p<0.001) and ratio of n-6/n-3 fatty acids was higher (p<0.01) in malnourished patients when compared to the patients with acceptable nutritional status. Furthermore, important changes in the levels of saturated fatty acids, palmitoleic and oleic acid and long-chain PUFA were found in well-nourished patients with alcoholic cirrhosis as well. Our present data confirmed evidence that malnutrition is one of the factors that led to lower levels of polyunsaturated fatty acids in patients with alcoholic liver cirrhosis. PUFA supplementation in the latter needs further investigation. PMID:23874070

Risti?-Medi?, Danijela; Taki?, Marija; Vu?i?, Vesna; Kandi?, Dragoslav; Kosti?, Nada; Glibeti?, Marija

2013-07-01

241

Abnormalities in the serum phospholipids fatty acid profile in patients with alcoholic liver cirrhosis - a pilot study  

PubMed Central

The fatty acid composition of serum phospholipids were analyzed in 20 patients with alcoholic liver cirrhosis (11 with malnutrition and 9 with acceptable nutritional status); 25 healthy age and sex-matched adults were used as controls. Cirrhotic patients showed higher levels of palmitic acid and total saturated fatty acids than healthy subjects. Total n-6 and n-3 polyunsaturated fatty acids (PUFA), and levels of linoleic, dihomo-gama linolenic, arachidonic, and docosahexaenoic acid were significantly lower (p<0.001) in patients with alcoholic cirrhosis compared to healthy controls. Significant changes were also found between patients stratified according to nutritional status. In particular, the sum of n-3 PUFA was significantly lower (p<0.001) and ratio of n-6/n-3 fatty acids was higher (p<0.01) in malnourished patients when compared to the patients with acceptable nutritional status. Furthermore, important changes in the levels of saturated fatty acids, palmitoleic and oleic acid and long-chain PUFA were found in well-nourished patients with alcoholic cirrhosis as well. Our present data confirmed evidence that malnutrition is one of the factors that led to lower levels of polyunsaturated fatty acids in patients with alcoholic liver cirrhosis. PUFA supplementation in the latter needs further investigation. PMID:23874070

Risti?-Medi?, Danijela; Taki?, Marija; Vu?i?, Vesna; Kandi?, Dragoslav; Kosti?, Nada; Glibeti?, Marija

2013-01-01

242

Factors associated with 25-hydroxyvitamin D levels in patients with liver cirrhosis.  

PubMed

Introduction. Lower 25-hydroxyvitamin D [25(OH)D] levels have been observed in cirrhotic patients and have been related to disease severity. However, most previous studies included patients with very advanced disease, lacking an adequate control for other variables that could interfere with vitamin D levels. We sought to investigate the prevalence of hypovitaminosis D and the factors related to its occurrence. Material and methods. This cross-sectional study included 133 cirrhotic patients and 30 healthy controls. Bivariate and multivariate analyses were performed to determine factors associated with 25(OH)D levels below the lower tertile. Thirty patients who had been recently hospitalized were compared in two time points. Results. Mean 25(OH)D levels were 32.34 ± 11.38 in controls and 27.03 ± 6.22 ng/mL in patients (P = 0.018). 25(OH)D levels were < 30 ng/mL in 69.9% and < 20 ng/mL in 14.3% of the sample. Levels of 25(OH)D below the lower tertile (< 24 ng/mL) were independently associated with higher triceps skinfold and non-Caucasian race. Parathyroid hormone above the reference value (65 pg/mL) was found in 24.6% of patients without association with 25(OH)D or severity of liver disease. Significantly lower levels of 25(OH)D were found at the time of acute decompensation of cirrhosis. Conclusions. In conclusion, hypovitaminosis D was prevalent in cirrhotics and it was associated with adiposity and non-Caucasian race in stable patients with relatively well preserved liver function. However, significantly lower levels were observed during admission for acute decompensation suggesting an impact of systemic inflammation or liver dysfunction on 25(OH)D levels. PMID:25536647

Costa Silva, Mariana; Erotides Silva, Telma; Alentar, Maria Luiza Aires de; Honório Coelho, Mara Sérgia Pacheco; Wildner, Letícia Muraro; Bazzo, Maria Luiza; González-Chica, David Alejandro; Dantas-Corręa, Esther Buzaglo; Narciso-Schiavon, Janaína Luz; Schiavon, Leonardo de Lucca

2015-01-01

243

Vitamin D inhibits development of liver fibrosis in an animal model but cannot ameliorate established cirrhosis.  

PubMed

1,25(OH)2D3, the active form of vitamin D, has an antiproliferative and antifibrotic effect on hepatic stellate cells. Our aim was to investigate the potential of 1,25(OH)2D3 to inhibit the development of liver fibrosis and to ameliorate established fibrosis in vivo. The antifibrotic effect of 1,25(OH)2D3 was investigated in a thioacetamide (TAA) model (as a preventive treatment and as a remedial treatment) and in a bile duct ligation model. In the preventive model, rats received simultaneously intraperitoneum injection of TAA and/or 1,25(OH)2D3 for 10 wk. In the remedial model, rats were treated with TAA for 10 wk and then received 1,25(OH)2D3 or saline for 8 wk. Fibrotic score was determined by Masson staining. Collagen I, ?-smooth muscle actin (?-SMA), tissue inhibitor of metalloproteinase-1 (TIMP1), platelet-derived growth factor (PDGF), and transforming growth factor-? (TGF-?) expression were measured by Western blot analysis and real-time PCR. Hypercalemia was detected by chemistry measurements. Preventive treatment of 1,25(OH)2D3 significantly suppressed liver fibrosis both macroscopically and microscopically and significantly lowered the fibrotic score of the TAA + 1,25(OH)2D3 group compared with the TAA group. 1,25(OH)2D3 significantly inhibited expression of PDGF and TGF-? by ?50% and suppressed the expression of collagen I?1, TIMP1, and ?-SMA by approximately three-, two-, and threefold, respectively. In contrast, 1,25(OH)2D3 was inefficient in amelioration of established liver fibrosis. Administration of 1,25(OH)2D3 to bile duct ligation rats led to a high mortality rate probably caused by hypercalcemia. We conclude that 1,25(OH)2D3 may be considered as a potential preventive treatment in an in vivo model but failed to ameliorate established cirrhosis. PMID:25214398

Abramovitch, Shirley; Sharvit, Efrat; Weisman, Yosef; Bentov, Amir; Brazowski, Eli; Cohen, Gili; Volovelsky, Oded; Reif, Shimon

2015-01-15

244

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. PMID:23300494

Hammam, Olfat; Mahmoud, Ola; Zahran, Manal; Aly, Sohair; Hosny, Karim; Helmy, Amira; Anas, Amgad

2012-01-01

245

Albumin and magnetic resonance imaging-liver volume to identify hepatitis B-related cirrhosis and esophageal varices  

PubMed Central

AIM: To investigate whether liver lobe volume and albumin (ALB) could predict the presence and severity of liver cirrhosis, and esophageal varices. METHODS: Seventy-one cirrhotic patients with hepatitis B and 21 healthy individuals were enrolled in this study. All the participants underwent abdominal enhanced magnetic resonance imaging to measure each liver lobe volume, and biochemical workup for testing ALB and Child-Pugh class. All cirrhotic patients underwent upper gastrointestinal endoscopy to show the presence of cirrhotic esophageal varices. Right liver lobe volume (RV), left medial liver lobe volume (LMV), left lateral liver lobe volume (LLV), and caudate lobe volume (CV) were measured using enhanced magnetic resonance imaging. The ratios of RV to ALB (RV/ALB), LMV to ALB (LMV/ALB), LLV to ALB (LLV/ALB) and CV to ALB (CV/ALB) were calculated. Statistical analyses were performed to determine whether and how the combination of liver lobe volume measured using magnetic resonance imaging and albumin could predict the presence and severity of liver cirrhosis, and the presence of esophageal varices. RESULTS: RV, LMV, LLV and CV decreased (r = -0.51-0.373; all P < 0.05), while RV/ALB increased (r = 0.424; P < 0.05), with the progress of Child-Pugh class of liver cirrhosis. RV, LMV, CV, LLV/ALB and CV/ALB could identify presence of liver cirrhosis; LLV and LMV could distinguish Child-Pugh class A from B; RV, LMV, LLV, CV, RV/ALB and LLV/ALB could distinguish class A from C; RV and LLV/ALB could differentiate B from C; and RV, RV/ALB and CV/ALB could identify presence of esophageal varices (all P < 0.05). Among these parameters, CV/ALB could best identify the presence of liver cirrhosis, with an area under receiver operating characteristic curve (AUC) of 0.860, a sensitivity of 82.0% and a specificity of 83.0%. LLV could best distinguish class A from B, with an AUC of 0.761, a sensitivity of 74.4% and a specificity of 73.1%. RV could best distinguish class A from C, with an AUC of 0.900, a sensitivity of 90.3% and a specificity of 84.5%. LLV/ALB could best distinguish class B from C, with an AUC of 0.900, a sensitivity of 93.8% and a specificity of 81.5%. RV/ALB could best identify esophageal varices, with an AUC of 0.890, a sensitivity of 80.0% and a specificity of 83.5%. CONCLUSION: The combination of liver lobe volume and ALB has potential to identify presence and severity of cirrhosis, and presence of esophageal varices.

Li, Hang; Chen, Tian-Wu; Li, Zhen-Lin; Zhang, Xiao-Ming; Li, Cheng-Jun; Chen, Xiao-Li; Chen, Guang-Wen; Hu, Jia-Ni; Ye, Yong-Quan

2015-01-01

246

Leptin receptor blockade reduces intrahepatic vascular resistance and portal pressure in an experimental model of rat liver cirrhosis.  

PubMed

Increased hepatic vascular resistance mainly due to elevated vascular tone and to fibrosis is the primary factor in the development of portal hypertension in cirrhosis. Leptin, a hormone associated with reduction in nitric oxide bioavailability, vascular dysfunction, and liver fibrosis, is increased in patients with cirrhosis. We aimed at evaluating whether leptin influences the increased hepatic resistance in portal hypertension. CCl4-cirrhotic rats received the leptin receptor-blocker ObR antibody, or its vehicle, every other day for 1 wk. Hepatic and systemic hemodynamics were measured in both groups. Hepatic nitric oxide production and bioavailability, together with oxidative stress, nitrotyrosinated proteins, and liver fibrosis, were evaluated. In cirrhotic rats, leptin-receptor blockade significantly reduced portal pressure without modifying portal blood flow, suggesting a reduction in the intrahepatic resistance. Portal pressure reduction was associated with increased nitric oxide bioavailability and with decreased O2(-) levels and nitrotyrosinated proteins. No changes in systemic hemodynamics and liver fibrosis were observed. In conclusion, the present study shows that blockade of the leptin signaling pathway in cirrhosis significantly reduces portal pressure. This effect is probably due to a nitric oxide-mediated reduction in the hepatic vascular tone. PMID:23886859

Delgado, María Gabriela; Gracia-Sancho, Jordi; Marrone, Giusi; Rodríguez-Vilarrupla, Aina; Deulofeu, Ramon; Abraldes, Juan G; Bosch, Jaume; García-Pagán, Juan Carlos

2013-10-01

247

Linkage Specific Fucosylation of Alpha-1-Antitrypsin in Liver Cirrhosis and Cancer Patients: Implications for a Biomarker of Hepatocellular Carcinoma  

PubMed Central

Background We previously reported increased levels of protein-linked fucosylation with the development of liver cancer and identified many of the proteins containing the altered glycan structures. One such protein is alpha-1-antitrypsin (A1AT). To advance these studies, we performed N-linked glycan analysis on the five major isoforms of A1AT and completed a comprehensive study of the glycosylation of A1AT found in healthy controls, patients with hepatitis C- (HCV) induced liver cirrhosis, and in patients infected with HCV with a diagnosis of hepatocellular carcinoma (HCC). Methodology/Principal Findings Patients with liver cirrhosis and liver cancer had increased levels of triantennary glycan-containing outer arm (?-1,3) fucosylation. Increases in core (?-1,6) fucosylation were observed only on A1AT from patients with cancer. We performed a lectin fluorophore-linked immunosorbent assay using Aleuria Aurantia lectin (AAL), specific for core and outer arm fucosylation in over 400 patients with liver disease. AAL-reactive A1AT was able to detect HCC with a sensitivity of 70% and a specificity of 86%, which was greater than that observed with the current marker of HCC, alpha-fetoprotein. Glycosylation analysis of the false positives was performed; results indicated that these patients had increases in outer arm fucosylation but not in core fucosylation, suggesting that core fucosylation is cancer specific. Conclusions/Significance This report details the stepwise change in the glycosylation of A1AT with the progression from liver cirrhosis to cancer and identifies core fucosylation on A1AT as an HCC specific modification. PMID:20811639

Comunale, Mary Ann; Rodemich-Betesh, Lucy; Hafner, Julie; Wang, Mengjun; Norton, Pamela; Di Bisceglie, Adrian M.; Block, Timothy; Mehta, Anand

2010-01-01

248

Truncated Active Human Matrix Metalloproteinase-8 Delivered by a Chimeric Adenovirus-Hepatitis B Virus Vector Ameliorates Rat Liver Cirrhosis  

PubMed Central

Background Liver cirrhosis is a potentially life-threatening disease caused by progressive displacement of functional hepatocytes by fibrous tissue. The underlying fibrosis is often driven by chronic infection with hepatitis B virus (HBV). Matrix metalloproteinases including MMP-8 are crucial for excess collagen degradation. In a rat model of liver cirrhosis, MMP-8 delivery by an adenovirus (Ad) vector achieved significant amelioration of fibrosis but application of Ad vectors in humans is subject to various issues, including a lack of intrinsic liver specificity. Methods HBV is highly liver-specific and its principal suitability as liver-specific gene transfer vector is established. HBV vectors have a limited insertion capacity and are replication-defective. Conversely, in an HBV infected cell vector replication may be rescued in trans by the resident virus, allowing conditional vector amplification and spreading. Capitalizing on a resident pathogen to help in its elimination and/or in treating its pathogenic consequences would provide a novel strategy. However, resident HBV may also reduce susceptibility to HBV vector superinfection. Thus a size-compatible truncated MMP-8 (tMMP8) gene was cloned into an HBV vector which was then used to generate a chimeric Ad-HBV shuttle vector that is not subject to superinfection exclusion. Rats with thioacetamide-induced liver cirrhosis were injected with the chimera to evaluate therapeutic efficacy. Results Our data demonstrate that infectious HBV vector particles can be obtained via trans-complementation by wild-type virus, and that the tMMP8 HBV vector can efficiently be shuttled by an Ad vector into cirrhotic rat livers. There it exerted a comparable beneficial effect on fibrosis and hepatocyte proliferation markers as a conventional full-length MMP-8Ad vector. Conclusions Though the rat cirrhosis model does not allow assessing in vivo HBV vector amplification these results advocate the further development of Ad-HBV vectors for liver-specific gene therapy, including and perhaps particularly for HBV-related disease. PMID:23301066

Wang, Zihua; Li, Dong; Kang, Fubiao; Li, Haijun; Li, Baosheng; Cao, Zhichen; Nassal, Michael; Sun, Dianxing

2013-01-01

249

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

250

Antioxidant effects of insulin-like growth factor-I (IGF-I) in rats with advanced liver cirrhosis  

PubMed Central

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 copper play an important role in oxidative mechanisms, producing the deleterious hydroxyl radical (*OH) that peroxides lipid membranes and damages DNA. Myeloperoxidase (MPO) and nitric oxide (NO) are known sources of free radicals and induce reduction of ferritin-Fe3+ into free Fe2+, contributing to oxidative damage. Methods Liver cirrhosis was induced by CCl4 inhalation in Wistar male rats for 30 weeks. Healthy controls were studied in parallel (n = 10). Fe and Cu were assessed by atomic absoption spectrometry and iron content was also evaluated by Perls' staining. MPO was measured by ELISA and transferrin and ferritin by immunoturbidimetry. iNOS expression was studied by immuno-histochemistry. Results Liver cirrhosis was histologically proven and ascites was observed in all cirrhotic rats. Compared to controls untreated cirrhotic rats showed increased hepatic levels of iron, ferritin, transferrin (p < 0.01), copper, MPO and iNOS expression (p < 0.01). However, IGF-treatment induced a significant reduction of all these parameters (p < 0.05). Conclusion the hepatoprotective and antifibrogenic effects of IGF-I in cirrhosis are associated with a diminution of the hepatic contents of several factors all of them involved in oxidative damage. PMID:15745444

García-Fernández, María; Castilla-Cortázar, Inma; Díaz-Sanchez, Matías; Navarro, Ińigo; Puche, Juan Enrique; Castilla, Alberto; Casares, Amelia Díaz; Clavijo, Encarna; González-Barón, Salvador

2005-01-01

251

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

252

Liver Stiffness Measurement, Better than APRI, Fibroindex, Fib-4, and NBI Gastroscopy, Predicts Portal Hypertension in Patients with Cirrhosis.  

PubMed

Liver stiffness measurement (LSM) is frequently used as non-invasive alternative for liver fibrosis including cirrhosis, which can lead to portal hypertension. This study was conducted to evaluate the predictive value of LSM in cirrhosis-induced portal hypertension patients. Between July 2011 and December 2013, 153 participants were enrolled into a single-center, prospective, cross-sectional study. Each subject received both gastroscopy and LSM. Baseline biochemical, APRI, Fibroindex, and Fib-4 were also performed. LSM of cirrhosis patients with portal hypertension was significantly higher compared to those without portal hypertension (P < 0.05). A LSM ? 13.6 kPa had a sensitivity of 83.87 % and a specificity of 72.53 % with an accuracy of 77.1 for the prediction of portal hypertension, which are higher than those of APRI, Fib-4, and Fibroscan separately. A combination of Fibroscan combined with Fib-4 achieved a maximum AUC of 0.833 and accuracy of 77.8. Discriminant and internal validation analysis showed that Fibroscan plus APRI obtained a lower false negative rate compared to Fibroscan plus Fib-4 and Fibroscan plus Fibroindex (9.68, 17.74, and 11.29 %, respectively). A good relationship was found between LSM and NBI mean optical density both by linear and polynomial correlation analysis (r = 0.5533 and r = 0.7349, both P < 0.001). There was a trend toward a better performance of LSM for assessing portal hypertension compared with NBI gastroscopy mean optical density (P = 0.028 and P = 0.05, respectively). Better than APRI, Fibroindex, Fib-4, and NBI gastroscopy, LSM can predict portal hypertension in cirrhosis patients. A LSM of 13.6 kPa can be considered to be the predictive value for portal hypertension. PMID:25417057

Zhang, Wei; Wang, Liqiong; Wang, Lei; Li, Gang; Huang, Aoshuang; Yin, Ping; Yang, Zhenhua; Ling, Changquan; Wang, Lingtai

2014-11-23

253

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. PMID:24714519

Sathar, Shanid Abdul; Kunnathuparambil, Sojan George; Sreesh, Srijaya; Narayanan, Premaletha; Vinayakumar, Kattoor Ramakrishnan

2014-01-01

254

Primary Biliary Cirrhosis  

MedlinePLUS

... the test or may develop bacterial cholangitis or pancreatitis—inflammation of the pancreas. Liver biopsy. A liver ... are unknown. Most research suggests it is an autoimmune disease. Primary biliary cirrhosis is more common in ...

255

Effects of zedoary turmeric oil on P450 activities in rats with liver cirrhosis induced by thioacetamide.  

PubMed

The aim of this study was to elucidate the effects of zedoary turmeric oil (ZTO) on P450 activities (CYP1A2, CYP2C9, CYP2C19, CYP2B6, CYP2D6 and CYP3A4) in rats with liver cirrhosis induced by thioacetamide (TAA). For the induction of liver cirrhosis, rats were given TAA in their drinking water at a concentration of 0.03% for consecutive 5 weeks and then 0.04% for the next consecutive 5 weeks throughout the establishment of cirrhosis. Then the cirrhotic rats were ip given saline, ZTO 100, 200 and 400 mg/kg, respectively, once daily for 2 weeks. When cirrhosis model was established at week 10, all rats of five groups were administered intragastrically with 15 mg/kg phenacetin, 0.6 mg/kg tolbutamide, 15 mg/kg omeprazole, 15 mg/kg bupropion, 15 mg/kg metoprolol, and 10 mg/kg midazolam. Blood samples were collected at a series of time-points and the concentrations of probe drugs in plasma were determined by HPLC-MS/MS. The degree of liver cirrhosis was assessed by HE staining. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) from the model group increased by approximately 4-fold, and a decreased level of albumin (Alb) was also observed, as compared to the control group (P < 0.05). However, ZTO was found to reverse those changes of serum levels observed in the model group, and the 200 mg/kg ZTO treatment group showed the most obvious reverse tendency with significantly decreased ALT, AST and increased Alb levels (P < 0.05). The results indicated that ZTO with the dose of 100 mg/kg could inhibit the activities of CYP450 isoforms CYP2C9 and CYP2D6 in vivo in cirrhotic rats induced by TAA, while ZTO with the dose of 400 mg/kg could induce the activity of CYP2C19 in vivo in cirrhotic rats induced by TAA. However, ZTO showed no influence on cirrhotic rat hepatic CYP1A2, CYP2B6 and CYP3A4 activity in vivo. This has certain guiding significance to clinical treatment. PMID:25550825

Cheng, Jing-Jing; Yang, Nai-Bin; Wu, Liang; Lin, Jia-Le; Dai, Ge-Xin; Zhu, Jia-Yin

2014-01-01

256

Effects of zedoary turmeric oil on P450 activities in rats with liver cirrhosis induced by thioacetamide  

PubMed Central

The aim of this study was to elucidate the effects of zedoary turmeric oil (ZTO) on P450 activities (CYP1A2, CYP2C9, CYP2C19, CYP2B6, CYP2D6 and CYP3A4) in rats with liver cirrhosis induced by thioacetamide (TAA). For the induction of liver cirrhosis, rats were given TAA in their drinking water at a concentration of 0.03% for consecutive 5 weeks and then 0.04% for the next consecutive 5 weeks throughout the establishment of cirrhosis. Then the cirrhotic rats were ip given saline, ZTO 100, 200 and 400 mg/kg, respectively, once daily for 2 weeks. When cirrhosis model was established at week 10, all rats of five groups were administered intragastrically with 15 mg/kg phenacetin, 0.6 mg/kg tolbutamide, 15 mg/kg omeprazole, 15 mg/kg bupropion, 15 mg/kg metoprolol, and 10 mg/kg midazolam. Blood samples were collected at a series of time-points and the concentrations of probe drugs in plasma were determined by HPLC-MS/MS. The degree of liver cirrhosis was assessed by HE staining. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) from the model group increased by approximately 4-fold, and a decreased level of albumin (Alb) was also observed, as compared to the control group (P < 0.05). However, ZTO was found to reverse those changes of serum levels observed in the model group, and the 200 mg/kg ZTO treatment group showed the most obvious reverse tendency with significantly decreased ALT, AST and increased Alb levels (P < 0.05). The results indicated that ZTO with the dose of 100 mg/kg could inhibit the activities of CYP450 isoforms CYP2C9 and CYP2D6 in vivo in cirrhotic rats induced by TAA, while ZTO with the dose of 400 mg/kg could induce the activity of CYP2C19 in vivo in cirrhotic rats induced by TAA. However, ZTO showed no influence on cirrhotic rat hepatic CYP1A2, CYP2B6 and CYP3A4 activity in vivo. This has certain guiding significance to clinical treatment.

Cheng, Jing-Jing; Yang, Nai-Bin; Wu, Liang; Lin, Jia-Le; Dai, Ge-Xin; Zhu, Jia-Yin

2014-01-01

257

[Spontaneous and interferon-induced activity of natural killer cells in patients with liver cirrhosis and chronic active hepatitis].  

PubMed

We investigated spontaneous and gamma-interferon stimulated natural killer (NK) cell activity and antibody-dependent cellular cytotoxicity (ADCC) in patients with chronic liver disease: A significantly reduced NK activity was found in alcoholic liver cirrhosis (LZ) and in chronic active hepatitis (CAH), as compared to healthy control individuals (p less than 0.001 and p less than 0.005, respectively). Patients with primary biliary cirrhosis (PBC) or with alcoholic non-cirrhotic liver disease had normal NK activities. Furthermore, ADCC was found to be significantly reduced in patients with CAH (p less than 0.05). The addition of gamma-interferon to peripheral blood mononuclear cells in vitro induced a similar increase in NK cell activity in all studied groups of patients. The reduced NK cell activity found in patients with LZ and CAH could constitute an important mechanism in the pathogenesis and contribute to the high incidence of virus-associated hepatic malignancies in these disorders. PMID:3125713

Müller, C; Zielinski, C C

1987-01-01

258

Metabolomic approach by 1H NMR spectroscopy of serum for the assessment of chronic liver failure in patients with cirrhosis.  

PubMed

Assessment of chronic liver failure (CLF) in cirrhotic patients is needed to make therapeutic decisions. A biological score is usually performed, using the Model for End-Stage Liver Disease (MELD), to evaluate CLF. Nevertheless, MELD does not take into account metabolic perturbations produced by liver-function impairment. In contrast, metabolomics can investigate many metabolic perturbations within biological systems. The purpose of this study was to assess whether metabolomic profiles of serum, obtained by proton NMR spectroscopy from cirrhotic patients, are affected by the severity of CLF. An orthogonal projection to latent-structure analysis was performed to compare MELD scores and NMR spectra of 124 patients with cirrhosis. The statistical model obtained showed a good explained variance (R(2)X = 0.87 and R(2)Y = 0.86) and a good predictability (Q(2)Y = 0.64). Metabolomic profiles showed significant differences regarding various metabolites depending of severity of CLF: levels of high-density lipoprotein and phosphocholine resonances were significantly higher in patients with mild CLF compared to severe CLF. Other metabolites such as lactate, pyruvate, glucose, amino acids, and creatinine were significantly higher in patients with severe CLF than mild CLF. Our conclusion is that metabolomic NMR analysis provides new insights into metabolic processes related to the severity of hepatic function impairment in cirrhosis. PMID:21568267

Amathieu, Roland; Nahon, Pierre; Triba, Mohamed; Bouchemal, Nadia; Trinchet, Jean-Claude; Beaugrand, Michel; Dhonneur, Gilles; Le Moyec, Laurence

2011-07-01

259

Hepatoprotective effect of ghrelin on carbon tetrachloride-induced acute liver injury in rats  

Microsoft Academic Search

Background & AimsRecent studies have revealed that ghrelin may be an antioxidant and antiinflammatory agent. Oxidative stress are considered to play a prominent causative role in the development of various hepatic disorders. We investigated whether ghrelin plays a protective role against carbon tetrachloride (CCl4)-induced acute liver injury in rats.

Ebru Çetin; Murat Kanbur; Nazmi Çetin; Gökhan Eraslan; Ayhan Atasever

2011-01-01

260

Clinical outcome and predictors of survival after TIPS insertion in patients with liver cirrhosis  

PubMed Central

AIM: To determine the clinical outcome and predictors of survival after transjugular intrahepatic portosystemic stent shunt (TIPS) implantation in cirrhotic patients. METHODS: Eighty-one patients with liver cirrhosis and consequential portal hypertension had TIPS implantation (bare metal) for either refractory ascites (RA) (n = 27) or variceal bleeding (VB) (n = 54). Endpoints for the study were: technical success, stent occlusion and stent stenosis, rebleeding, RA and mortality. Clinical records of patients were collected and analysed. Baseline characteristics [e.g., age, sex, CHILD score and the model for end-stage liver disease score (MELD score), underlying disease] were retrieved. The Kaplan-Meier method was employed to calculate survival from the time of TIPS implantation and comparisons were made by log rank test. A multivariate analysis of factors influencing survival was carried out using the Cox proportional hazards regression model. Results were expressed as medians and ranges. Comparisons between groups were performed by using the Mann-Whitney U-test and the ?2 test as appropriate. RESULTS: No difference could be seen in terms of age, sex, underlying disease or degree of portal pressure gradient (PPG) reduction between the ascites and the bleeding group. The PPG significantly decreased from 23.4 ± 5.3 mmHg (VB) vs 22.1 ± 5.5 mmHg (RA) before TIPS to 11.8 ± 4.0 vs 11.7 ± 4.2 after TIPS implantation (P = 0.001 within each group). There was a tendency towards more patients with stage CHILD A in the bleeding group compared to the ascites group (24 vs 6, P = 0.052). The median survival for the ascites group was 29 mo compared to > 60 mo for the bleeding group (P = 0.009). The number of radiological controls for stent patency was 6.3 for bleeders and 3.8 for ascites patients (P = 0.029). Kaplan-Meier calculation indicated that stent occlusion at first control (P = 0.027), ascites prior to TIPS implantation (P = 0.009), CHILD stage (P = 0.013), MELD score (P = 0.001) and those patients not having undergone liver transplantation (P = 0.024) were significant predictors of survival. In the Cox regression model, stent occlusion (P = 0.022), RA (P = 0.043), CHILD stage (P = 0.015) and MELD score (P = 0.004) turned out to be independent prognostic factors of survival. The anticoagulation management (P = 0.097), the porto-systemic pressure gradient (P = 0.460) and rebleeding episodes (P = 0.765) had no significant effect on the overall survival. CONCLUSION: RA, stent occlusion, initial CHILD stage and MELD score are independent predictors of survival in patients with TIPS, speaking for a close follow-up in these circumstances. PMID:23066315

Heinzow, Hauke S; Lenz, Philipp; Köhler, Michael; Reinecke, Frank; Ullerich, Hansjörg; Domschke, Wolfram; Domagk, Dirk; Meister, Tobias

2012-01-01

261

Plasma levels and urinary excretion of lormetazepam in patients with liver cirrhosis and in healthy volunteers.  

PubMed

Plasma levels and urinary excretion of lormetazepam (Noctamid-ampoules; 2 mg/10 ml) were studied after i.v. (0.015 mg/kg b.w.) and after p.o (0.03 mg/kg b.w.) administration of the drug to five patients with cirrhosis of the liver (C) and to five young male volunteers (N). The cirrhotic patients exhibited higher drug plasma levels (Cmax p.o.: 11-43 ng/ml [C] vs. 11-16 ng/ml [N]) and higher AUC0-24 values of the unchanged drug (i.v.: 66-102 ng.h/ml [C] vs. 54-72 ng.h/ml [N]; p.o.: 83-188 ng.h/ml [C] vs. 74-113 ng.h/ml [N]). The absolute bioavailability was increased in the C-group with 57-134% vs. 52-84% [N]. The total plasma clearance of lormetazepam was 3 ml/min/kg in the C-group and 4 ml/min/kg in the N-group and thus within the range known for elderly and young male subjects. Conversely to the parent compound, the AUC-figures of its 3-OH-glucuronide were higher in the N-group (346-434 ng.h/ml) than in the C-group (149-371 ng.h/ml). In 24 h pooled urine samples of both groups, the glucuronide of lorazepam, the N-demethylated metabolite, accounted for approximately 5-14% of the dose fraction excreted as lormetazepam glucuronide. Apart from increased levels of the unchanged drug due to porto-systemic shunt and/or disease-dependent lower glucuronidation rate, the pharmacokinetics of lormetazepam were not altered in cirrhotic patients. It can therefore be concluded that for this group of patients the drug can be administered according to the same dose regimen as that used for normal subjects. PMID:1974495

Hildebrand, M; Hellstern, A; Hümpel, M; Hellenbrecht, D; Saller, R

1990-01-01

262

Cirrhosis and liver failure: expanding phenotype of Acid sphingomyelinase-deficient niemann-pick disease in adulthood.  

PubMed

Acid sphingomyelinase-deficient Niemann-Pick disease (ASMD) includes the severe neuronopathic type A, the non-neuronopathic type B, and rare intermediate cases. Here we report on such an atypical type B patient who died at 31 years of age from liver failure. This male subject was first seen in a paediatric department at the age of 3 years because of significant hepatosplenomegaly. Foam cells in bone marrow, interstitial pneumonitis, a slight facial dysmorphy and normal psychomotor development were additional findings. Acid sphingomyelinase studies in lymphocytes (and later SMPD1 gene studies [c.151_154delGACT; c.1341-21_1341-18delAATG]) established the diagnosis of ASMD. Between the ages 6-27, he developed growth retardation, peripheral neuropathy, kyphoscoliosis, alopecia, and aortic valve insufficiency requiring valve replacement. Surgery for bilateral inguinal hernias was performed twice, when the patient was 10 and 21 years of age, respectively. At the age of 28, he was noted to have hepatosplenomegaly and follow-up investigations revealed ascites and gastric varices. Liver biopsy showed cirrhosis without areas of necrosis (A6 in Child-Pugh classification). He developed haematemesis and worsening encephalopathy leading to his death at age 31. In conclusion, cirrhosis should be considered as a possible complication of ASMD in adult patients, even if hepatic tests are normal. PMID:24718843

Lidove, Olivier; Sedel, Frédéric; Charlotte, Frédéric; Froissart, Roseline; Vanier, Marie T

2015-01-01

263

Hypoxia and hydrothoraces in a case of liver cirrhosis: correlation of physiological, radiographic, scintigraphic, and pathological findings  

PubMed Central

Stanley, N. N., Williams, A. J., Dewar, C. A., Blendis, L. M., and Reid, Lynne (1977).Thorax, 32, 457-471. Hypoxia and hydrothoraces in a case of liver cirrhosis: correlation of physiological, radiographic, scintigraphic, and pathological findings. A case is reported of liver cirrhosis complicated by cyanosis and recurrent right hydrothorax. A diagnostic pneumoperitoneum demonstrated that direct movement of ascites through a diaphragmatic defect was responsible for the hydrothoraces. Pulmonary function tests between episodes of hydrothorax showed severe arterial hypoxaemia, a 23% right-to-left shunt, and a reduction in the carbon monoxide transfer factor to less than half of the predicted value. Evidence of abnormal intrapulmonary arteriovenous communications was obtained by perfusion scanning. At necropsy the central tendon of the diaphragm showed numerous areas of thinning which were easily ruptured. Injection of the pulmonary arterial tree demonstrated precapillary arteriovenous anastomoses and pleural spider naevi. A morphometric analysis provided quantitative evidence of pulmonary vasodilatation limited to the intra-acinar arteries, consistent with the effect of a circulating vasodilator. The scintigraphic and pathological findings suggested that shunting had been greater in the right than the left lung. Examination of thin lung sections by light microscopy showed that the walls of small veins were thickened, and electron microscopy showed that this was due to a layer of collagen. The walls of capillaries were similarly thickened, which caused an approximately two-fold increase in the minimum blood-gas distance and contributed to the reduction in transfer factor. Images PMID:929488

Stanley, N. N.; Williams, A. J.; Dewar, C. A.; Blendis, L. M.; Reid, Lynne

1977-01-01

264

Concurrent Liver Hodgkin Lymphoma and Nodular Regenerative Hyperplasia on an Explanted Liver with Clinical Diagnosis of Alcoholic Cirrhosis at University Hospital Fundación Santa Fe de Bogotá  

PubMed Central

Liver involvement by Hodgkin lymphoma (HL) is well documented. However, secondary liver failure to this neoplastic process is rare and usually presents late in the course of the disease. We present a case of a HL associated with nodular regenerative hyperplasia (NRH) diagnosed on an explanted liver from a 53-year-old patient with clinical diagnosis of alcoholic cirrhosis. Hematoxylin and eosin stain (H&E) showed abnormal liver architecture with hepatocytes nodules highlighted by reticulin stain with absent fibrosis on the trichrome stain. The portal spaces had diffuse infiltration by Reed-Sternberg cells positive for CD15, CD30, and latent membrane protein (LMP) on immunohistochemical studies. The patient also had a concurrent hilar lymph node biopsy that also showed HL involvement. Liver failure as the initial presentation of Hodgkin' lymphoma is rare. We believe that more research about the utility of performing liver biopsies in patients candidates for transplantation with noncirrhotic hepatic failure is needed in order to establish the etiology and the optimal treatment. PMID:24511402

López, R.; Barrera, L.; Vera, A.; Andrade, R.

2014-01-01

265

Role of transforming growth factor-?1 in serum and ? 509 C>T promoter gene polymorphism in development of liver cirrhosis in Egyptian patients  

PubMed Central

Objectives Liver cirrhosis is a condition in which the liver slowly deteriorates and malfunctions due to chronic injury. HCV is one of the major causes of liver fibrosis and ultimate progression to cirrhosis. Transforming growth factor-beta1 (TGF-?1), one of the three isoforms of TGF-?, is a pleiotrophic cytokine that regulates the proliferation and differentiation of cells, embryonic development, wound healing and angiogenesis. This study aimed to evaluate the role of serum TGF-?1 and ? 509 C>T promoter gene polymorphism in the development of liver cirrhosis. Design and methods Besides routine liver profiles, serum TGF-?1 was measured in 40 liver cirrhosis patients and 40 controls using ELISA technique. TGF-?1 ? 509 C>T promoter gene polymorphism was detected using PCR-RFLP technique. Results TGF-?1 ? 509 CT and TT genotype frequencies were significantly higher in the cirrhotic group (52.5%, 25%; respectively) than control group (10%, 7.5%; respectively); OR = 16.238 (95% CI 5.391–48.914, p < 0.05). The ? 509 T allele carriers are more prone to develop liver cirrhosis than ? 509 C allele carriers; OR = 7.359 (95% CI 3.325–16.288, p < 0.05). Serum TGF-?1 was significantly higher in cirrhotic group (11.79 ± 1.45 ng/ml) than control group (8.67 ± 1.23 ng/ml); p < 0.05. Also serum TGF-?1 was significantly higher in TT genotype than CT and CC genotypes (p < 0.05). A significant positive correlation was observed between serum TGF-?1 and alkaline phosphatase (r = 0.559, p < 0.05); AST (r = 0.573, p < 0.05). A significant negative correlation was observed between serum TGF-?1 and albumin (r = ? 0.331, p < 0.05). Conclusion There is an association between serum TGF-?1, ? 509 CT and TT genotypes of TGF-?1 gene and the higher risk for liver cirrhosis development of liver cirrhosis. PMID:25606446

Mohy, Abeer; Fouad, Ahmed

2014-01-01

266

Serum 1H-NMR Metabolomic Fingerprints of Acute-On-Chronic Liver Failure in Intensive Care Unit Patients with Alcoholic Cirrhosis  

PubMed Central

Introduction Acute-on-chronic liver failure is characterized by acute deterioration of liver function in patients with compensated or decompensated, but stable, cirrhosis. However, there is no accurate definition of acute-on-chronic liver failure and physicians often use this term to describe different clinical entities. Metabolomics investigates metabolic changes in biological systems and identifies the biomarkers or metabolic profiles. Our study assessed the metabolomic profile of serum using proton nuclear magnetic resonance (1H-NMR) spectroscopy to identify metabolic changes related to acute-on-chronic liver failure. Patients Ninety-three patients with compensated or decompensated cirrhosis (CLF group) but stable liver function and 30 patients with cirrhosis and hospitalized for the management of an acute event who may be responsible of acute-on-chronic liver failure (ACLF group), were fully analyzed. Blood samples were drawn at admission, and sera were separated and stored at –80°C until 1H-NMR spectral analysis. Using orthogonal projection to latent-structure discriminant analyses, various metabolites contribute to the complete separation between these both groups. Results The predictability of the model was 0.73 (Q2Y) and the explained variance was 0.63 (R2Y). The main metabolites that had increased signals related to acute-on-chronic liver failure were lactate, pyruvate, ketone bodies, glutamine, phenylalanine, tyrosine, and creatinine. High-density lipids were lower in the ALCF group than in CLF group. Conclusion A serum metabolite fingerprint for acute-on-chronic liver failure, obtained with 1H-NMR, was identified. Metabolomic profiling may aid clinical evaluation of patients with cirrhosis admitted into intensive care units with acute-on-chronic liver failure, and provide new insights into the metabolic processes involved in acute impairment of hepatic function. PMID:24586615

Nahon, Pierre; Bouchemal, Nadia; Kamoun, Walid; Haouache, Hakim; Trinchet, Jean-Claude; Savarin, Philippe; Le Moyec, Laurence; Dhonneur, Gilles

2014-01-01

267

Investigating the biochemical progression of liver disease through fibrosis, cirrhosis, dysplasia, and hepatocellular carcinoma using Fourier transform infrared spectroscopic imaging  

NASA Astrophysics Data System (ADS)

Hepatocellular carcinoma (HCC) is the most common form of primary hepatic carcinoma. HCC ranks the fourth most prevalent malignant tumor and the third leading cause of cancer related death in the world. Hepatocellular carcinoma develops in the context of chronic liver disease and its evolution is characterized by progression through intermediate stages to advanced disease and possibly even death. The primary sequence of hepatocarcinogenesis includes the development of cirrhosis, followed by dysplasia, and hepatocellular carcinoma.1 We addressed the utility of Fourier Transform Infrared (FT-IR) spectroscopic imaging, both as a diagnostic tool of the different stages of the disease and to gain insight into the biochemical process associated with disease progression. Tissue microarrays were obtained from the University of Illinois at Chicago tissue bank consisting of liver explants from 12 transplant patients. Tissue core biopsies were obtained from each explant targeting regions of normal, liver cell dysplasia including large cell change and small cell change, and hepatocellular carcinoma. We obtained FT-IR images of these tissues using a modified FT-IR system with high definition capabilities. Firstly, a supervised spectral classifier was built to discriminate between normal and cancerous hepatocytes. Secondly, an expanded classifier was built to discriminate small cell and large cell changes in liver disease. With the emerging advances in FT-IR instrumentation and computation there is a strong drive to develop this technology as a powerful adjunct to current histopathology approaches to improve disease diagnosis and prognosis.

Sreedhar, Hari; Pant, Mamta; Ronquillo, Nemencio R.; Davidson, Bennett; Nguyen, Peter; Chennuri, Rohini; Choi, Jacqueline; Herrera, Joaquin A.; Hinojosa, Ana C.; Jin, Ming; Kajdacsy-Balla, Andre; Guzman, Grace; Walsh, Michael J.

2014-03-01

268

Lacosamide as add-on treatment of focal symptomatic epilepsy in a patient with alcoholic liver cirrhosis  

PubMed Central

The occurrence of epileptic seizures in the presence of hepatic disease is not uncommon in clinical practice. Selecting an appropriate AED for patients affected by liver failure who have new-onset epileptic seizures can be challenging. We describe a 64-year-old man affected by liver cirrhosis. The patient developed partial epilepsy with secondary generalization because of an intracerebral hemorrhage in the left parieto-occipital regions. After the neurosurgery procedure, seizures reappeared and were initially managed with levetiracetam. After one month, the patient experienced clusters of seizures while on stable treatment with levetiracetam. Pregabalin as add-on was not tolerated; therefore, he received a low dose of phenobarbital as add-on treatment. The patient developed hepatic encephalopathy. Phenobarbital was immediately stopped, and oral lacosamide was added. A rapid recovery of encephalopathy with a 6-month seizure freedom was obtained. The patient died 6 months later because of progressive impairment of liver function. Lacosamide may represent an alternative to other AEDs in patients with liver failure; however, further prospective evaluation of its efficacy and safety in this clinical setting is needed.

Romigi, A.; Placidi, F.; Liguori, C.; Izzi, F.; Marchi, A.; Tarquini, E.; Albanese, M.; Mercuri, N.B.

2014-01-01

269

Apoptosis of blood mononuclear cells in alcoholic liver cirrhosis. The influence of in vitro ethanol treatment and zinc supplementation.  

PubMed

Ethanol consumption induces apoptosis in a variety of tissues, among others in liver and lymphoid tissue. Zinc has been shown to influence apoptosis of blood mononuclear cells by inhibiting the mitochondrial pathway of cell death. The aim of this study was to examine the influence of zinc on spontaneous and in vitro alcohol-induced apoptosis of peripheral blood mononuclear cells (PBMCs) of patients with alcoholic cirrhosis. PBMCs were isolated from the blood of 26 patients with cirrhosis and 20 healthy controls. PBMCs and among them CD4+ T helper cells of cirrhotic patients exhibited accelerated spontaneous (without treatment) apoptosis in vitro. When apoptosis was induced in vitro by treating cells with 80 mM ethanol, CD8+ T lymphocytes of a healthy control were more sensitive to ethanol treatment than those of cirrhotic patients. Thirty micromolar zinc supplementation inhibited both spontaneous and ethanol-induced apoptosis of immune cells derived from the blood of the healthy control and cirrhotic patients. In sera of patients with cirrhosis, an elevated level of IL-12, but also sFas (CD95) and sFas ligand (sFasL) was detected. Moreover, in vitro, PBMCs of cirrhotic patients spontaneously released more sFas and sFasL than control PBMCs. Ethanol treatment significantly increased sFas, but decreased sFasL release from PBMCs of cirrhotic patients, while it only slightly affected control cells. As zinc supplementation did not significantly influence sFas or sFasL release, it seems likely that it is rather the mitochondrial pathway of ethanol-related immune cell death that may be inhibited by zinc supplementation. PMID:15964121

Szuster-Ciesielska, Agnieszka; Daniluk, Jadwiga; Bojarska-Junak, Agnieszka

2005-09-01

270

Disappearance of Oral Lichen Planus After Liver Transplantation for Primary Biliary Cirrhosis and Immunosuppressive Therapy in a 63-year-Old Japanese Woman  

PubMed Central

Introduction: There are few reports concerning association between primary biliary cirrhosis (PBC) and lichen planus. In addition, there is only one report about lichen planus after liver transplantation. Case Presentation: We describe a case of oral lichen planus (OLP) accompanied with PBC that resolved following liver transplantation 14 years later. This patient received immunosuppressive drugs after liver transplantation. Discussion: The disappearance of OLP might be due to immunosuppressive therapy following liver transplantation. Further observations and studies are necessary to clarify the relationship between OLP and PBC. PMID:24734093

Nagao, Yumiko; Sata, Michio

2014-01-01

271

Measurement and correlation of wedged hepatic, intrahepatic, intrasplenic and intravariceal pressures in patients with cirrhosis of liver and non-cirrhotic portal fibrosis  

Microsoft Academic Search

In order to examine the relationship of various haemodynamic parameters in two different liver diseases, 10 patients with cirrhosis of liver and 14 patients with non-cirrhotic portal fibrosis were studied. In cirrhotics, mean (+\\/- SD) wedged hepatic (25.8 +\\/- 6.4 mmHg), intrahepatic (24.5 +\\/- 6.2 mmHg) and intrasplenic (25.0 +\\/- 5.6 mmHg) pressures correlated significantly (p less than 0.001) with

S K Sarin; K K Sethi; R Nanda

1987-01-01

272

Functional Analysis of Complex Hepatitis B Virus Variants Associated With Development of Liver Cirrhosis  

Microsoft Academic Search

Background & Aims: Development of cirrhosis in renal transplant recipients with chronic hepatitis B is associated with the accumulation of complex hepatitis B virus (HBV) variants carrying deletions in the C gene and\\/or preS region and deletions\\/insertions in the core promoter. Here, we char- acterized for the first time the phenotype of these complex HBV variants. Methods: Representative full-length ge-

STEFANIE MÄRSCHENZ; ANNE-SOPHIE ENDRES; ANJA BRINCKMANN; TILMAN HEISE; GLEN KRISTIANSEN; PETER NÜRNBERG; DETLEV H. KRÜGER; STEPHAN GÜNTHER; HELGA MEISEL

2006-01-01

273

5-lipoxygenase inhibition reduces intrahepatic vascular resistance of cirrhotic rat livers: A possible role of cysteinyl-leukotrienes  

Microsoft Academic Search

Background & Aims:Cysteinyl-leukotrienes (Cys-LTs) increase intrahepatic vascular resistance in normal rat livers. CCI4 cirrhotic rat livers have increased Cys-LT production and 5-Lipoxygenase messenger RNA (mRNA) expression. The aim of this study was to investigate the role of 5-lipoxygenase-derived eicosanoids regulating intrahepatic vascular tone in control and CCl4-induced cirrhotic rat livers.Methods:In different groups of portally perfused control and cirrhotic rat livers,

Mariona Graupera; Juan-Carlos García-Pagán; Esther Titos; Joan Claria; Anna Massaguer; Jaime Bosch; Juan Rodes

2002-01-01

274

The changes in renal function after a single dose of intravenous furosemide in patients with compensated liver cirrhosis  

PubMed Central

Background Patients with compensated Child-A cirrhosis have sub clinical hypovolemia and diuretic treatment could result in renal impairment. Aim To evaluate the changes in renal functional mass as reflected by DMSA uptake after single injection of intravenous furosemide in patients with compensated liver cirrhosis. Methods Eighteen cirrhotic patients were divided in two groups; eight patients (group 1, age 56 ± 9.6 yrs, Gender 5M/3F, 3 alcoholic and 5 non alcoholic) were given low intravenous 40 mg furosemide and ten other patients (group 2, age 54 ± 9.9, Gender 6M/4F, 4 alcoholic and 6 non alcoholic) were given high 120 mg furosemide respectively. Renoscintigraphy with 100MBq Of Tc 99 DMSA was given intravenously before and 90 minutes after furosemide administration and SPECT imaging was determined 3 hours later. All patients were kept under low sodium diet (80mEq/d) and all diuretics were withdrawn for 3 days. 8-hours UNa exertion, Calculated and measured Creatinine clearance (CCT) were performed for all patients. Results Intravenous furosemide increased the mean renal DMSA uptake in 55% of patients with compensated cirrhosis and these changes persist up to three hours after injection. This increase was at the same extent in either low or high doses of furosemide. (From 12.8% ± 3.8 to 15.2% ± 2.2, p < 0.001 in Gr I as compared to 10.6% ± 4.6 to 13.5% ± 3.6 in Gr 2, p < 0.001). In 8 patients (45%, 3 pts from Gr 1 and 5 pts from Gr 2) DMSA uptake remain unchanged. The mean 8 hrs UNa excretion after intravenous furosemide was above 80 meq/l and was higher in Gr 2 as compared to Gr 1 respectively (136 ± 37 meq/l) VS 100 ± 36.6 meq/l, P = 0.05). Finally, basal global renal DMSA uptake was decreased in 80% of patients; 22.5 ± 7.5% (NL > 40%), as compared to normal calculated creatinine clearance (CCT 101 ± 26), and measured CCT of 87 ± 30 cc/min (P < 0.001). Conclusion A single furosemide injection increases renal functional mass as reflected by DMSA in 55% of patients with compensated cirrhosis and identify 45% of patients with reduced uptake and who could develop renal impairment under diuretics. Whether or not albumin infusion exerts beneficial effect in those patients with reduced DMSA uptake remains to be determined. PMID:17134488

Assy, Nimer; kayal, Mohib; Mejirisky, Yoram; Gorenberg, Miguel; Hussein, Osamah; Schlesinger, Sorina

2006-01-01

275

Isoprinosine and levamisole as stimulators of interferon production in blood leukocytes of patients with alcoholic liver cirrhosis.  

PubMed

Blood leukocytes of 16 patients with alcoholic liver cirrhosis and 18 healthy controls were induced for interferon (IFN) production by phytohemagglutinin (PHA) and concanavalin A (ConA) in the presence or absence of isoprinosine and levamisole at concentrations of 10 micrograms/ml and 1 ng/ml. This interferon was neutralized in 87-95% by anti-HuIFN-gamma monoclonal antibodies. In the presence of the drugs the IFN-gamma production was enhanced, however, IFN-gamma titers yielded from leukocytes of cirrhotic patients were still below the titers observed in stimulated and unstimulated blood leukocytes of healthy controls. For example, IFN titers induced by PHA in the presence of levamisole (1 ng/ml) in cirrhotic patients were 2.5 times lower (20.2 +/- 11.1 U/ml) in comparison to healthy subjects (50.6 +/- 27.3 U/ml). PMID:9597085

Daniluk, J; Kandefer-Szersze?, M

1997-01-01

276

Abnormal fecal microbiota community and functions in patients with hepatitis B liver cirrhosis as revealed by a metagenomic approach  

PubMed Central

Background Assessment and characterization of human colon microbiota is now a major research area in human diseases, including in patients with hepatitis B liver cirrhosis (HBLC). Methods We recruited 120 patients with HBLC and 120 healthy controls. The fecal microbial community and functions in the two groups were analyzed using high-throughput Solexa sequencing of the complete metagenomic DNA and bioinformatics methods. Results Community and metabolism-wide changes of the fecal microbiota in 20 HBLC patients and 20 healthy controls were observed and compared. A negative correlation was observed between the Child-Turcotte-Pugh scores and Bacteroidetes (P?liver cirrhosis microbiota samples from normal ones. The functional diversity was significantly reduced in the fecal microbiota of cirrhotic patients compared with in the controls. At the module or pathway levels, the fecal microbiota of the HBLC patients showed enrichment in the metabolism of glutathione, gluconeogenesis, branched-chain amino acid, nitrogen, and lipid (P?

2013-01-01

277

Optimized contrast-enhanced ultrasonography for characterization of focal liver lesions in cirrhosis: A single-center retrospective study  

PubMed Central

Background Hepatocellular carcinoma (HCC) is the leading cause of death amongst cirrhotic patients. Its diagnosis and discrimination from non-HCC malignant lesions in cirrhosis includes contrast enhanced computed tomography (CECT), contrast enhanced magnetic resonance imaging (CEMRI), or, in selected cases, liver biopsy. The role of contrast-enhanced ultrasonography (CEUS) is still controversial. Aims To evaluate whether, by selecting an appropriate ‘time to wash-out’ cut-off value, CEUS capability of discriminating between HCC and non-HCC malignancies in cirrhotic patients may be enhanced. Methods We enrolled 282 cirrhotic patients who underwent CEUS at our institute, from January 2008 to January 2012, for focal liver lesions (FLLs) detected at ultrasound (US). We used liver biopsy and subsequent histological evaluation as the gold standard for correct classification of FLLs. We calculated the area under receiver operator characteristic curves for CEUS to distinguish patients with HCC from those with non-HCC malignancies. The best ‘time to wash-out’ cut-off values were selected. Results Histological diagnosis of FLLs was as follows: 34 benign lesions (i.e. 25 regenerative nodules and 9 dysplastic nodules) and 248 malignant lesions (223 well-to-moderately differentiated HCCs; 7 poorly-differentiated HCCs; 5 intrahepatic colangiocellular carcinomas (ICCs); 5 primary non-Hodgkin B-cell lymphomas (NHBLs); and 8 metastatic liver tumors). A time to wash-out?>?55?s identified patients with HCC with the highest level of accuracy (92.7%). Similarly, a time to wash-out???55?s correctly identified the vast majority of the non-HCC malignancies (100% sensitivity, 98.2% specificity and diagnostic accuracy of 98.3%). Conclusions CEUS is an accurate and safe procedure for discriminating FLLs in cirrhotic patients, especially when a cut-off time to wash-out of 55?s is chosen as a reference value. PMID:25083285

de Sio, Ilario; Vitale, Luigi M; Niosi, Marco; Del Prete, Anna; de Sio, Chiara; Romano, Lorenzo; Funaro, Annalisa; Meucci, Rosaria; Federico, Alessandro; Loguercio, Carmelina; Romano, Marco

2014-01-01

278

Regulation of dipeptidyl peptidase 8 and 9 expression in activated lymphocytes and injured liver  

PubMed Central

AIM: To investigate the expression of dipeptidyl peptidase (DPP) 8 and DPP9 in lymphocytes and various models of liver fibrosis. METHODS: DPP8 and DPP9 expression were measured in mouse splenic CD4+ T-cells, CD8+ T-cells and B-cells (B220+), human lymphoma cell lines and mouse splenocytes stimulated with pokeweed mitogen (PWM) or lipopolysaccharide (LPS), and in dithiothreitol (DTT) and mitomycin-C treated Raji cells. DPP8 and DPP9 expression were measured in epidermal growth factor (EGF) treated Huh7 hepatoma cells, in fibrotic liver samples from mice treated with carbon tetrachloride (CCl4) and from multidrug resistance gene 2 (Mdr2/Abcb4) gene knockout (gko) mice with biliary fibrosis, and in human end stage primary biliary cirrhosis (PBC). RESULTS: All three lymphocyte subsets expressed DPP8 and DPP9 mRNA. DPP8 and DPP9 expression were upregulated in both PWM and LPS stimulated mouse splenocytes and in both Jurkat T- and Raji B-cell lines. DPP8 and DPP9 were downregulated in DTT treated and upregulated in mitomycin-C treated Raji cells. DPP9-transfected Raji cells exhibited more annexin V+ cells and associated apoptosis. DPP8 and DPP9 mRNA were upregulated in CCl4 induced fibrotic livers but not in the lymphocytes isolated from such livers, while DPP9 was upregulated in EGF stimulated Huh7 cells. In contrast, intrahepatic DPP8 and DPP9 mRNA expression levels were low in the Mdr2 gko mouse and in human PBC compared to non-diseased livers. CONCLUSION: These expression patterns point to biological roles for DPP8 and DPP9 in lymphocyte activation and apoptosis and in hepatocytes during liver disease pathogenesis. PMID:23704821

Chowdhury, Sumaiya; Chen, Yiqian; Yao, Tsun-Wen; Ajami, Katerina; Wang, Xin M; Popov, Yury; Schuppan, Detlef; Bertolino, Patrick; McCaughan, Geoffrey W; Yu, Denise MT; Gorrell, Mark D

2013-01-01

279

Cirrhosis-related changes in left ventricular function and correlation with the model for end-stage liver disease score  

PubMed Central

Objective: The purpose of our study is to investigate cirrhosis-related left ventricular remodeling and functional changes, further to analyze the correlations with model for end-stage liver disease (MELD) score. Methods: A total of 89 cirrhotic patients were enrolled for study and subgrouped according to MELD score: ? 9, 10-19, and ? 20. Thirty healthy individuals were enrolled as controls. All study participants underwent cardiac assessment of the left ventricle with Doppler echocardiography; the parameters assessed included left ventricular-end systolic diameter (LVESD), left ventricular end-diastolic diameter (LVEDD), interventricular septal thickness (IVST), left ventricular posterior wall thickness (LVPWT), left atrial diameter (LAD), left ventricular ejection fraction (LVEF), cardiac output (CO), mitral flow velocity (VE/VA ratio), and E-wave deceleration time (DT). Results: The cirrhotic patients had significantly higher LVESD, LVEDD, IVST, LAD, CO and DT than the control group, but significantly lower VE/VA ratio (all P < 0.05). Subgroup analysis showed that the higher the MELD score, the greater the increase in LVESD, LVEDD, IVST, LAD and DT (all P < 0.05). Nearly one-half of the cirrhotic patients showed left atrial enlargement and a VE/VA ratio ? 1, and these features were more common in patients with MELD score ? 20. LAD, LVEDD and DT were positively correlated with MELD score (r = 0.208, 0.319 and 0.197, respectively; all P < 0.05). Conclusions: Patients with cirrhosis had impaired cardiac function, mainly present as left ventricular diastolic dysfunction, and the extent of dysfunction was correlated with the MELD score. Left atrial enlargement and VE/VA ratio ? 1 may serve as useful diagnostic indexes for cirrhotic cardiomyopathy. PMID:25664102

Li, Xiaopeng; Yu, Shanshan; Li, Lu; Han, Donggang; Dai, Shejiao; Gao, Ya

2014-01-01

280

Liver transplant - series (image)  

MedlinePLUS

The liver is in the right upper abdomen. The liver serves many functions, including the detoxification of substances delivered ... A liver transplant may be recommended for: liver damage due to alcoholism (Alcoholic cirrhosis) primary biliary cirrhosis long-term ( ...

281

The Increased Level of Serum p53 in Hepatitis B-Associated Liver Cirrhosis  

PubMed Central

Background: The ability of tumour suppressor protein p53 (P53) to regulate cell cycle processes can be modulated by hepatitis B virus (HBV). While preliminary evidences indicates the involvement of protein-x of HBV (HBx) in altering p53 DNA binding, no further data have been accumulated for the significance of serum p53 in chronic hepatitis B virus infected patients. Methods: 72 non-cirrhotic and 19 cirrhotic patients infected by HBV were enrolled for the analysis in this study. Enzyme linked immunosorbent assay (ELISA) was performed to study the concentrations of serum p53 protein. The tertiary structures of HBx and P53 were docked by Z-dock and Hex servers for in-silico protein-protein interaction analysis. Results: There was a significant association between the serum p53 and cirrhosis (OR=1.81 95% CI: 1.017-3.2, P=0.044). Cirrhotic patients had higher level of serum p53 compare with chronic infection of HBV (1.98±1.22 vs. 1.29±0.72 U/ml, P=0.05). No evidence of correlation was seen between the different variables such as age, gender, log viral load, serum alkaline phosphatase (ALP) and alanine aminotransferase (ALT) with serum p53. Tertiary model shows that the amino acid residues from Arg110 to Lys132 of the N-terminal of P53 which is critical for ubiquitination, are bonded to a region in N- terminal of HBx amino acid residues from Arg19 to Ser33. Conclusion: There is an increase in serum p53 in HBV-related cirrhosis patients. In this case, HBx might be responsible for such higher concentration of p53 through HBx-p53 protein-protein interaction, as is shown by molecular modeling approach. PMID:25242843

Shahnazari, Parisa; Sayehmiri, Kourosh; Minuchehr, Zarrin; Parhizkar, Ardavan; Poustchi, Hossein; Montazeri, Ghodratollah; Mohamadkhani, Ashraf

2014-01-01

282

Evaluation of genome-wide loci of iron metabolism in hereditary hemochromatosis identifies PCSK7 as a host risk factor of liver cirrhosis.  

PubMed

Genome-wide association studies (GWAS) have revealed genetic determinants of iron metabolism, but correlation of these with clinical phenotypes is pending. Homozygosity for HFE C282Y is the predominant genetic risk factor for hereditary hemochromatosis (HH) and may cause liver cirrhosis. However, this genotype has a low penetrance. Thus, detection of yet unknown genetic markers that identify patients at risk of developing severe liver disease is necessary for better prevention. Genetic loci associated with iron metabolism (TF, TMPRSS6, PCSK7, TFR2 and Chr2p14) in recent GWAS and liver fibrosis (PNPLA3) in recent meta-analysis were analyzed for association with either liver cirrhosis or advanced fibrosis in 148 German HFE C282Y homozygotes. Replication of associations was sought in additional 499 Austrian/Swiss and 112 HFE C282Y homozygotes from Sweden. Only variant rs236918 in the PCSK7 gene (proprotein convertase subtilisin/kexin type 7) was associated with cirrhosis or advanced fibrosis (P = 1.02 × 10(-5)) in the German cohort with genotypic odds ratios of 3.56 (95% CI 1.29-9.77) for CG heterozygotes and 5.38 (95% CI 2.39-12.10) for C allele carriers. Association between rs236918 and cirrhosis was confirmed in Austrian/Swiss HFE C282Y homozygotes (P = 0.014; ORallelic = 1.82 (95% CI 1.12-2.95) but not in Swedish patients. Post hoc combined analyses of German/Swiss/Austrian patients with available liver histology (N = 244, P = 0.00014, ORallelic = 2.84) and of males only (N = 431, P = 2.17 × 10(-5), ORallelic = 2.54) were consistent with the premier finding. Association between rs236918 and cirrhosis was not confirmed in alcoholic cirrhotics, suggesting specificity of this genetic risk factor for HH. PCSK7 variant rs236918 is a risk factor for cirrhosis in HH patients homozygous for the HFE C282Y mutation. PMID:24556216

Stickel, Felix; Buch, Stephan; Zoller, Heinz; Hultcrantz, Rolf; Gallati, Sabina; Österreicher, Christoph; Finkenstedt, Armin; Stadlmayr, Andreas; Aigner, Elmar; Sahinbegovic, Enijad; Sarrazin, Christoph; Schafmayer, Clemens; Braun, Felix; Erhart, Wiebke; Nothnagel, Michael; Lerch, Markus M; Mayerle, Julia; Völzke, Henry; Schaller, André; Kratzer, Wolfgang; Boehm, Bernhard O; Sipos, Bence; D'Amato, Mauro; Torkvist, Leif; Stal, Per; Arlt, Alexander; Franke, Andre; Becker, Thomas; Krawczak, Michael; Zwerina, Jochen; Berg, Thomas; Hinrichsen, Holger; Krones, Elisabeth; Dejaco, Christian; Strasser, Michael; Datz, Christian; Hampe, Jochen

2014-07-15

283

Accessory splenectomy with gastroesophageal devascularization for recurrent hypersplenism and refractory bleeding varices in a patient with liver cirrhosis: report of a case.  

PubMed

We report a case of recurrent thrombocytopenia associated with symptomatic enlargement of an accessory spleen, 2 years after splenectomy, in a 36-year-old man with posthepatitic liver cirrhosis. The patient suffered three episodes of variceal bleeding, but the esophageal varices were not eradicated by two sessions of endoscopic injection sclerotherapy and endoscopic band ligation. Abdominal ultrasonography and computed tomography showed a giant accessory spleen (6 x 6 x 5 cm), gallbladder stones, and complete postsplenectomy splenomesoportal thrombosis. Subsequent 99mTc scintigraphy confirmed the presence of a functioning residual splenic nodule. Thus, we performed gastroesophageal devascularization (Hassab-Paquet procedure) with accessory splenectomy and cholecystectomy, after which the platelet count normalized and no further variceal bleeding occurred during 17 months of follow-up. To our knowledge, this is the first report in the English medical literature of accessory splenectomy for recurrent thrombocytopenia in a patient with liver cirrhosis. PMID:15580390

Mishin, Igor; Ghidirim, Gheorghe

2004-01-01

284

Ammonia and amino acid profiles in liver cirrhosis: Effects of variables leading to hepatic encephalopathy.  

PubMed

Hyperammonemia and severe amino acid imbalances play central role in hepatic encephalopathy (HE). In the article is demonstrated that the main source of ammonia in cirrhotic subjects is activated breakdown of glutamine (GLN) in enterocytes and the kidneys and the main source of GLN is ammonia detoxification to GLN in the brain and skeletal muscle. Branched-chain amino acids (BCAA; valine, leucine, and isoleucine) decrease due to activated GLN synthesis in muscle. Aromatic amino acids (AAA; phenylalanine, tyrosine, and tryptophan) and methionine increase due to portosystemic shunts and reduced ability of diseased liver. The effects on aminoacidemia of the following variables that may affect the course of liver disease are discussed: nutritional status, starvation, protein intake, inflammation, acute hepatocellular damage, bleeding from varices, portosystemic shunts, hepatic cancer, and renal failure. It is concluded that (1) neither ammonia nor amino acid concentrations correlate closely with the severity of liver disease; (2) BCAA/AAA ratio could be used as a good index of liver impairment and for early detection of derangements in amino acid metabolism; (3) variables potentially leading to overt encephalopathy exert substantial but uneven effects; and (4) careful monitoring of ammonia and aminoacidemia may discover important break points in the course of liver disease and indicate appropriate therapeutic approach. Of special importance might be isoleucine deficiency in bleeding from varices, arginine deficiency in sepsis, and a marked rise of GLN and ammonia levels that may appear in all events leading to HE. PMID:25220875

Holecek, Milan

2015-01-01

285

Hepatoprotective Effects of Orthosiphon stamineus Extract on Thioacetamide-Induced Liver Cirrhosis in Rats  

PubMed Central

Orthosiphon stamineus as medicinal plant is commonly used in Malaysia for treatment of hepatitis and jaundice; in this study, the ethanol extracts were applied to evaluate the hepatoprotective effects in a thioacetamide-induced hepatotoxic model in Sprague Dawley rats. Five groups of adult rats were arranged as follows: Group 1 (normal control group), Group 2 Thioacetamide (TAA) as positive control (hepatotoxic group), Group 3 Silymarin as a well-known standard drug (hepatoprotective group), and Groups 4 and 5 as high and low dose (treatment groups). After 60-day treatment, all rats were sacrificed. The hepatotoxic group showed a coarse granulation on the liver surface when compared to the smooth aspect observed on the liver surface of the other groups. Histopathological study confirmed the result; moreover, there was a significant increase in serum liver biochemical parameters (ALT, AST, ALP, and Bilirubin) and the level of liver Malondialdehyde (MDA), accompanied by a significant decrease in the level of total protein and Albumin in the TAA control group when compared with that of the normal group. The high-dose treatment group (200?mg/kg) significantly restored the elevated liver function enzymes near to normal. This study revealed that 200?mg/kg extracts of O. stamineus exerted a hepatoprotective effect. PMID:21647311

Alshawsh, Mohammed A.; Abdulla, Mahmood Ameen; Ismail, Salmah; Amin, Zahra A.

2011-01-01

286

Ultrasonographic Prevalence and Factors Predicting Left Ventricular Diastolic Dysfunction in Patients with Liver Cirrhosis: Is There a Correlation between the Grade of Diastolic Dysfunction and the Grade of Liver Disease?  

PubMed Central

Presence of cardiac dysfunction has been associated with an unfavorable prognosis in patients with liver cirrhosis. In the present study, 92 consecutive, newly-diagnosed patients with liver cirrhosis were prospectively evaluated. Liver disease was graded according to the modified Child-Turcotte-Pugh (CTP) score whereas left ventricular diastolic function was assessed by Doppler-echocardiography and graded (Stage 0 to 4) according to current guidelines. Overall, DD was diagnosed in 55/92 (59.8%) patients [DD-stage-1: 36/92 (39.1%), DD-stage-2: 19/92 (20.6%)]. Prevalence of DD-stage-1 among the different stages of liver cirrhosis was: CTP-class A: 11/29 (37.9%), B: 15/39 (38.5%), C: 10/24 (41.6%), (P > 0.05 in all comparisons), whereas for DD-stage-2 the corresponding proportions were CTP-class A: 3/29 (10.3%), B: 5/39 (12.8%), C: 11/24 (45.8%), (P = 0.0009 between CTP-class C versus A and B). Age > 53 years (Odd's Ratio [OR]: 4.2; 95% confidence interval [CI]: 1.5–12.1) and CTP-class C (OR: 4.6; 95% CI: 1.1–20) could independently predict DD. No relation between presence of DD and the etiology of the liver disease was found. We conclude that DD is a common feature in liver cirrhosis. DD-stage-1 is fairly prevalent among all CTP-classes whereas DD-stage-2 seems to be characteristic of the advanced liver disease (CTP-class C). A high level of awareness for the presence of the syndrome is required, especially if cirrhotic patients are CTP-class C and/or of older age. PMID:22888308

Papastergiou, Vasilios; Skorda, Lamprini; Lisgos, Phillipos; Papakonstantinou, Nikolaos; Giakoumakis, Tsampikos; Ntousikos, Konstantinos; Karatapanis, Stylianos

2012-01-01

287

Resolution of liver cirrhosis using vitamin A–coupled liposomes to deliver siRNA against a collagen-specific chaperone  

Microsoft Academic Search

There are currently no approved antifibrotic therapies for liver cirrhosis. We used vitamin A–coupled liposomes to deliver small interfering RNA (siRNA) against gp46, the rat homolog of human heat shock protein 47, to hepatic stellate cells. Our approach exploits the key roles of these cells in both fibrogenesis as well as uptake and storage of vitamin A. Five treatments with

Yasushi Sato; Kazuyuki Murase; Junji Kato; Masayoshi Kobune; Tsutomu Sato; Yutaka Kawano; Rishu Takimoto; Kouichi Takada; Koji Miyanishi; Takuya Matsunaga; Tetsuji Takayama; Yoshiro Niitsu

2008-01-01

288

The challenges of providing renal replacement therapy in decompensated liver cirrhosis.  

PubMed

Development of renal failure requiring renal replacement therapy (RRT) in the cirrhotic patient is a devastating complication. Survival without RRT is less than 10% on average at 6 months. However, it is now appreciated that all renal failure in this group of patients is not due solely to hepatorenal syndrome, and the cause of the renal failure affects the prognosis. This paper reviews the prognosis depending on cause and points out the difficulty in making the correct diagnosis. Provision of RRT is difficult in this group of patients due to hypotension and coagulopathy which is highly prevalent. Survival with RRT is still poor with only 30-60% of patients surviving to liver transplant. Provision of RRT should be offered as a bridge to patients awaiting liver transplant or those undergoing liver transplant evaluation. Provision of long-term RRT is usually not indicated in other cirrhotic patients who develop a need for RRT except as a trial to see if renal function will return. The decision between intermittent hemodialysis or continuous renal replacement therapy (CRRT) is usually based on the clinical characteristics of the patient. Neither has been demonstrated to be superior to the other, although CRRT may be better tolerated in the unstable patient. CRRT is clearly indicated in cases of fulminant hepatic failure as it does not raise intracranial pressure. Provision of intraoperative CRRT during liver transplant may be indicated to help control volume and electrolytes in those patients presenting for liver transplant with renal failure. Newer extracorporeal support systems, such as extracorporeal albumin dialysis (MARS) and fractional plasma separation and adsorption with hemodialysis (Prometheus), have recently been developed to provide both renal and liver support in this group of patients. These are still considered experimental, although the MARS system has been utilized to treat patients with hepatorenal syndrome, and is available outside the United States. PMID:22269395

Gonwa, Thomas A; Wadei, Hani M

2012-01-01

289

Noninvasive assessment of portal hypertension in cirrhosis: Liver stiffness and beyond  

PubMed Central

Liver stiffness measurement (LSM) is a good, but still limited tool to noninvasively assess complications and prognosis in patients with advanced liver disease. This review aims to consider the role of LSM for the diagnosis of portal hypertension-related complications and for assessment of prognosis in cirrhotic patients, and to highlight the drawbacks as well as some alternatives for improving the performance. Hence, this field is far from being closed, and deserves more attention. There is still a place for more carefully designed studies to find new, innovative and reliable approaches. PMID:25492995

Stefanescu, Horia; Procopet, Bogdan

2014-01-01

290

The Risk Factors for Bleeding of Fundal Varices in Patients with Liver Cirrhosis  

PubMed Central

Background/Aims The relationship between portal hemodynamics and fundal varices has not been well documented. The purpose of this study was to understand the pathophysiology of fundal varices and to investigate bleeding risk factors related to the presence of spontaneous portosystemic shunts, and to examine the hepatic venous pressure gradient (HVPG) between fundal varices and other varices. Methods In total, 85 patients with cirrhosis who underwent HVPG and gastroscopic examination between July 2009 and March 2011 were included in this study. The interrelationship between HVPG and the types of varices or the presence of spontaneous portosystemic shunts was studied. Results There was no significant difference in the HVPG between fundal varices (n=12) and esophageal varices and gastroesophageal varices type 1 (GOV1) groups (n=73) (17.1±7.7 mm Hg vs 19.7±5.3 mm Hg). Additionally, there was no significant difference in the HVPG between varices with spontaneous portosystemic shunts (n=28) and varices without these shunts (n=57) (18.3±5.8 mm Hg vs 17.0±8.1 mm Hg). Spontaneous portosystemic shunts increased in fundal varices compared with esophageal varices and GOV1 (8/12 patients [66.7%] vs 20/73 patients [27.4%]; p=0.016). Conclusions Fundal varices had a high prevalence of spontaneous portosystemic shunts compared with other varices. However, the portal pressure in fundal varices was not different from the pressure in esophageal varices and GOV1. PMID:24312712

Park, Eui Ju; Lee, Ji Eun; Jeong, Soung Won; Lee, Sae Hwan; Kim, Sang Gyune; Cha, Sang-Woo; Kim, Young Seok; Cho, Young Deok; Cho, Joo Young; Kim, Hong Soo; Kim, Boo Sung; Kim, Yong Jae

2013-01-01

291

Chronic Hepatitis C Therapy in Liver Cirrhosis Complicated by Telaprevir-Induced DRESS  

PubMed Central

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare yet severe adverse drug-induced reaction with up to 10% mortality rate. Recent clinical trials reported an association between DRESS and telaprevir (TVR), an NS3/4A protease inhibitor of chronic hepatitis C (CHC) virus genotype 1. Its diagnosis is challenging given the variable pattern of cutaneous eruption and the myriad internal organ involvement. We present two patients who are middle-aged, obese, and white with CHC cirrhosis. They both developed a progressive diffuse, painful pruritic maculopapular rash at weeks 8 and 10 of CHC therapy with TVR, Peg-Interferon alfa-2a, and Ribavirin. They had no exposures to other medications that can cause this syndrome. Physical exam and labs and skin biopsy supported a “Definite” clinical diagnosis of DRESS, per RegiSCAR criteria. Thus Telaprevir-based triple therapy was discontinued and both patients experienced rapid resolution of the systemic symptoms with gradual improvement of eosinophilia and the skin eruption. These two cases illustrate the paramount importance of having a high index of suspicion for TVR-induced DRESS, critical for early diagnosis. Immediate discontinuation of TVR is essential in prevention of a potentially life-threatening complication. Risk factors for development of DRESS in patients receiving TVR remain to be elucidated. PMID:25214847

Mousa, Omar Y. S.; Khalaf, Rossa; Shannon, Rhonda L.; Egwim, Chukwuma I.; Zela, Scott A.; Ankoma-Sey, Victor

2014-01-01

292

VITAMIN B COMPLEX STUDIES IN DOGS: PRODUCTION OF CIRRHOSIS OF LIVER  

Microsoft Academic Search

Fonts, Helmer and Lepkovsky ( '40) found that adult dogs fed a synthetic casein (4:1%) diet supplemented with thiamine chloride, riboflavin, nicotinic acid and pyridoxine developed a deficiency state characterized by loss of appetite, marked loss of weight, intermittent diarrhea, moderate anemia and death. The livers of these animals appeared fatty, and in some there were ulcers in the gastrointestinal

PAUL J. FOUTS

293

[Clinical efficacy of autologous mesenclyme multipotential stem cells transplantation in the liver cirrhosis and portal hypertension treatment].  

PubMed

In 14 patients with cirrhosis and portal hypertention autologous mesenclyme multipotential stem cells (AMMSC) transplanation was performed in portal vein (I group, n=7) and common trunk of the hepatic artery (II group, n=6). Duration of pathological processes since diagnosis is 1-8 years (3,7±2,4 years). The initial severity was evaluated by a set of child-Pugh score: Class A - 6 (42,9%), Class B - 8 (57,1%). Cell cultures indentication and characteristics consistent with International Society of cell technology guidanes (ISCT) since 2006.   The treatment results and patients survival were determined in period 2 month - 5 years according Kaplan-Meir survival curve analysis. Morphology of liver bioptats also was performed.   It was shown that AMMSC transplantation generally positivly affects on the morpho-functional dynamics and basic hepatic syndromes. Aterial perivascular zone is the most optimal for transplantation in terms of migration, engraftment and differentiation of cells in comparison with portal field, as evidenced by the transition of some patients from class B to class A by child-Pugh score. PMID:25341236

2014-09-01

294

Reversibility of intrapulmonary arteriovenous shunts in liver cirrhosis documented by serial radionuclide perfusion lung scans  

SciTech Connect

Using serial perfusion lung scans, the opening up and closure of right-to-left intrapulmonary arteriovenous shunts has been documented over a period of several weeks in a patient with chronic alcoholic liver disease. The presence of the shunts correlates well with the severity of hypoxemia and the presence of nodular mottling on chest radiographs. The time course of these changes with clinical status suggests lability and the functional nature of these shunts.

Chen, N.S.; Barnett, C.A.; Farrer, P.A.

1984-05-01

295

Protection Effect of Kallistatin on Carbon Tetrachloride-Induced Liver Fibrosis in Rats via Antioxidative Stress  

PubMed Central

Prolonged inflammation and oxidative stress are emerging as key causes of pathological wound healing and the development of liver fibrosis. We have investigated the effects of recombinant human kallistatin, produced in Pichia. pastoris, on preventing carbon tetrachloride (CCl4)-induced liver fibrosis in rats. Daily administration of kallistatin prevented development of CCl4-induced liver fibrosis, which was evidenced by histological study. In all kallistatin treated rats, activation of hepatic stellate cells (HSC) as assessed by s-smooth muscle actin staining was attenuated, TGF- ?1 expression was inhibited, class I serum biomarkers associated with the process of fibrogenesis, such as hyaluronic acid, laminin, and procollagen III, were lowered, compared with that in the model control group. Furthermore, residual hepatic functional reserve was improved by kallistatin treatment. CCl4 induced elevation of malondialdehyde level and reduced superoxide dismutase activity in the liver, while kallistatin reduced these oxidative parameters. We also investigated the effects of kallistatin on rat primary HSC and LX-2, the human HSC cell line. Kallistatin scavenged H2O2-induced ROS in the LX-2 cells, and suppressed the activation of primary HSC. These results suggest recombinant human kallistatin might be a promising drug candidate for therapeutic intervention of liver fibrosis. PMID:24558397

Huang, Xiaoping; Wang, Xiao; Lv, Yinghui; Xu, Luli; Lin, Junsheng; Diao, Yong

2014-01-01

296

Hepatic encephalopathy in patients with acute decompensation of cirrhosis and acute-on-chronic liver failure.  

PubMed

Hepatic encephalopathy in a hospitalized cirrhotic patient is associated with a high mortality rate and its presence adds further to the mortality of patients with acute-on-chronic liver failure (ACLF). The exact pathophysiological mechanisms of HE in this group of patients are unclear but hyperammonemia, systemic inflammation (including sepsis, bacterial translocation, and insulin resistance) and oxidative stress, modulated by glutaminase gene alteration, remain as key factors. Moreover, alcohol misuse, hyponatremia, renal insufficiency, and microbiota are actively explored. HE diagnosis requires exclusion of other causes of neurological, metabolic and psychiatric dysfunction. Hospitalization in the ICU should be considered in every patient with overt HE, but particularly if this is associated with ACLF. Precipitating factors should be identified and treated as required. Evidence-based specific management options are limited to bowel cleansing and non-absorbable antibiotics. Ammonia lowering drugs, such as glycerol phenylbutyrate and ornithine phenylacetate show promise but are still in clinical trials. Albumin dialysis may be useful in refractory cases. Antibiotics, prebiotics, and treatment of diabetes reduce systemic inflammation. Where possible and not contraindicated, large portal-systemic shunts may be embolized but liver transplantation is the most definitive step in the management of HE in this setting. HE in patients with ACLF appears to be clinically and pathophysiologically distinct from that of acute decompensation and requires further studies and characterization. PMID:25218789

Romero-Gómez, Manuel; Montagnese, Sara; Jalan, Rajiv

2014-09-10

297

Effect of Tinospora crispa on thioacetamide-induced liver cirrhosis in rats  

PubMed Central

Objectives: This study was conducted to determine the effect of ethanolic extract of the dried stems of Tinospora crispa in a male rat model of hepatic fibrosis caused by the hepatotoxin, thioacetamide. Materials and Methods: The extract was gavaged daily to the rats, at doses of 100 and 200 mg/kg along with thioacetamide at a dose of 200 mg/kg twice weekly. To assess the effectivity of extract, against thioacetamide, the activity of aminotransferases (alanine aminotransferase, aspartate aminotransferase), alkaline phosphatase (AP); and bilirubin were measured, together with morphological and histopathological indices in the liver of healthy and thioacetamide-treated rats. Results: A significant increase in the activity of liver enzymes, bilirubin and G-glutamyl transferase and gross and histopathological changes were determined. Although previous in vitro study established that this extract had strong antioxidant activity, this in vivo study establishes that this extract contains hepatotoxins whose identity may be quite different from those compounds with antioxidant properties. Conclusion: The study confirms that complete reliance on data obtained using in vitro methodologies may lead to erroneous conclusions pertaining to the safety of phytopharmaceuticals. PMID:21455425

Kadir, Farkaad A.; Othman, Faizah; Abdulla, Mahmood Ameen; Hussan, Farida; Hassandarvish, Pouya

2011-01-01

298

Urinary Metabolite Profiling Offers Potential for Differentiation of Liver-Kidney Yin Deficiency and Dampness-Heat Internal Smoldering Syndromes in Posthepatitis B Cirrhosis Patients  

PubMed Central

Zheng is the basic theory and essence of traditional Chinese medicine (TCM) in diagnosing diseases. However, there are no biological evidences to support TCM Zheng differentiation. In this study we elucidated the biological alteration of cirrhosis with TCM “Liver-Kidney Yin Deficiency (YX)” or “Dampness-Heat Internal Smoldering (SR)” Zheng and the potential of urine metabonomics in TCM Zheng differentiation. Differential metabolites contributing to the intergroup variation between healthy controls and liver cirrhosis patients were investigated, respectively, and mainly participated in energy metabolism, gut microbiota metabolism, oxidative stress, and bile acid metabolism. Three metabolites, aconitate, citrate, and 2-pentendioate, altered significantly in YX Zheng only, representing the abnormal energy metabolism. Contrarily, hippurate and 4-pyridinecarboxylate altered significantly in SR Zheng only, representing the abnormalities of gut microbiota metabolism. Moreover, there were significant differences between two TCM Zhengs in three metabolites, glycoursodeoxycholate, cortolone-3-glucuronide, and L-aspartyl-4-phosphate, among all differential metabolites. Metabonomic profiling, as a powerful approach, provides support to the understanding of biological mechanisms of TCM Zheng stratification. The altered urinary metabolites constitute a panel of reliable biological evidence for TCM Zheng differentiation in patients with posthepatitis B cirrhosis and may be used for the potential biomarkers of TCM Zheng stratification.

Wang, Xiaoyan; Zhou, Mingmei; Yu, Huan; Lin, Yan; Du, Guangli; Luo, Guoan

2015-01-01

299

The benefits of using Sentinel WebDashboard in medicine: IT solution for monitoring and treatment of patient with liver cirrhosis.  

PubMed

The global assessment of the evolution of a disease in a certain geographical area or a specific domain is useful in the medical research for the preparation of practice guidelines/protocols used in the hospitals. Cirrhosis is one of the most common disorders seen today, occupying a significant place in the gastrointestinal pathology. The disease is the final stage of various affections in terms of etiology and morphology. The most frequent subjects treated on this topic are those related to the etiopathology and early diagnosis. Given the current interest in this matter and considering that UGS (upper gastrointestinal bleeding) in liver cirrhosis is a common complication and potentially fatal, the medical research found some very useful conducting retrospective studies in this area. The purpose of our study was to create an IT system implemented with Sentinel WebDashboard, which could increase the medical performances in diagnosis, monitoring and treatment of a disease. We tested our solution on a medical data set containing information about the patients with liver cirrhosis. The solution facilitates the access of the physicians to the databases containing complete information about the patients, offers the possibility to monitor the evaluation of their health and also aids physicians in optimizing the medical procedures and improve the diagnostic methods. It also offers the advantages of a web application: it does not require the installation on the client side, being accessible anytime, anywhere via a web browser, laptop, Smartphone or tablet. PMID:25408726

Dumitrescu, S R; Popescu, D; Purcarea, V L; Albu, L C

2014-06-15

300

Hesperidin, a citrus bioflavonoid, decreases the oxidative stress produced by carbon tetrachloride in rat liver and kidney  

Microsoft Academic Search

BACKGROUND: CCl4 is a well-established hepatotoxin inducing liver injury by producing free radicals. Exposure to CCl4 also induces acute and chronic renal injuries. The present study was designed to establish the protective effect of hesperidin (HDN), a citrus bioflavonoid, on CCl4-induced oxidative stress and resultant dysfunction of rat liver and kidney. METHODS: Animals were pretreated with HDN (100 and 200

Naveen Tirkey; Sangeeta Pilkhwal; Anurag Kuhad; Kanwaljit Chopra

2005-01-01

301

Melatonin promotes hepatic differentiation of human dental pulp stem cells: clinical implications for the prevention of liver fibrosis.  

PubMed

Melatonin's effect on hepatic differentiation of stem cells remains unclear. The aim of this study was to investigate the action of melatonin on hepatic differentiation as well as its related signaling pathways of human dental pulp stem cells (hDPSCs) and to examine the therapeutic effects of a combination of melatonin and hDPSC transplantation on carbon tetrachloride (CCl4 )-induced liver fibrosis in mice. In vitro hepatic differentiation was assessed by periodic acid-Schiff (PAS) staining and mRNA expression for hepatocyte markers. Liver fibrosis model was established by injecting 0.5 mL/kg CCl4 followed by treatment with melatonin (5 mg/kg, twice a week) and hDPSCs. In vivo therapeutic effects were evaluated by histopathology and by means of liver function tests including measurement of alanine transaminase (ALT), aspartate transaminase (AST), and ammonia levels. Melatonin promoted hepatic differentiation based on mRNA expression of differentiation markers and PAS-stained glycogen-laden cells. In addition, melatonin increased bone morphogenic protein (BMP)-2 expression and Smad1/5/8 phosphorylation, which was blocked by the BMP antagonist noggin. Furthermore, melatonin activated p38, extracellular signal-regulated kinase (ERK), and nuclear factor-?B (NF-?B) in hDPSCs. Melatonin-induced hepatic differentiation was attenuated by inhibitors of BMP, p38, ERK, and NF-?B. Compared to treatment of CCl4 -injured mice with either melatonin or hDPSC transplantation alone, the combination of melatonin and hDPSC significantly suppressed liver fibrosis and restored ALT, AST, and ammonia levels. For the first time, this study demonstrates that melatonin promotes hepatic differentiation of hDPSCs by modulating the BMP, p38, ERK, and NF-?B pathway. Combined treatment of grafted hDPSCs and melatonin could be a viable approach for the treatment of liver cirrhosis. PMID:25431168

Cho, Young-Ah; Noh, Kwantae; Jue, Seong-Suk; Lee, So-Youn; Kim, Eun-Cheol

2015-01-01

302

New therapeutic aspect for carvedilol: Antifibrotic effects of carvedilol in chronic carbon tetrachloride-induced liver damage  

SciTech Connect

Portal hypertension is a common complication of chronic liver diseases associated with liver fibrosis and cirrhosis. At present, beta-blockers such as carvedilol remain the medical treatment of choice for protection against variceal bleeding and other complications. Since carvedilol has powerful antioxidant properties we assessed the potential antifibrotic effects of carvedilol and the underlying mechanisms that may add further benefits for its clinical usefulness using a chronic model of carbon tetrachloride (CCl4)-induced hepatotoxicity. Two weeks after CCl4 induction of chronic hepatotoxicity, rats were co-treated with carvedilol (10 mg/kg, orally) daily for 6 weeks. It was found that treatment of animals with carvedilol significantly counteracted the changes in liver function and histopathological lesions induced by CCl4. Also, carvedilol significantly counteracted lipid peroxidation, GSH depletion, and reduction in antioxidant enzyme activities; glutathione-S-transferase and catalase that was induced by CCl4. In addition, carvedilol ameliorated the inflammation induced by CCl4 as indicated by reducing the serum level of acute phase protein marker; alpha-2-macroglobulin and the liver expression of nuclear factor-kappa B (NF-?B). Finally, carvedilol significantly reduced liver fibrosis markers including hydroxyproline, collagen accumulation, and the expression of the hepatic stellate cell (HSC) activation marker; alpha smooth muscle actin. In conclusion, the present study provides evidences for the promising antifibrotic effects of carvedilol that can be explained by amelioration of oxidative stress through mainly, replenishment of GSH, restoration of antioxidant enzyme activities and reduction of lipid peroxides as well as amelioration of inflammation and fibrosis by decreasing collagen accumulation, acute phase protein level, NF-?B expression and finally HSC activation. -- Highlights: ? Carvedilol is a beta blocker with antioxidant and antifibrotic properties. ? It restores GSH and antioxidant enzyme activities and reduces lipid peroxidation. ? It ameliorates inflammation and nuclear factor kappa-B expression. ? It ameliorates fibrosis by decreasing collagen accumulation and HSC activation.

Hamdy, Nadia [Department of Biochemistry, Faculty of Pharmacy, Ain Shams University, Cairo (Egypt)] [Department of Biochemistry, Faculty of Pharmacy, Ain Shams University, Cairo (Egypt); El-Demerdash, Ebtehal, E-mail: ebtehal_dm@yahoo.com [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo (Egypt)] [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo (Egypt)

2012-06-15

303

New therapeutic aspect for carvedilol: antifibrotic effects of carvedilol in chronic carbon tetrachloride-induced liver damage.  

PubMed

Portal hypertension is a common complication of chronic liver diseases associated with liver fibrosis and cirrhosis. At present, beta-blockers such as carvedilol remain the medical treatment of choice for protection against variceal bleeding and other complications. Since carvedilol has powerful antioxidant properties we assessed the potential antifibrotic effects of carvedilol and the underlying mechanisms that may add further benefits for its clinical usefulness using a chronic model of carbon tetrachloride (CCl4)-induced hepatotoxicity. Two weeks after CCl4 induction of chronic hepatotoxicity, rats were co-treated with carvedilol (10mg/kg, orally) daily for 6weeks. It was found that treatment of animals with carvedilol significantly counteracted the changes in liver function and histopathological lesions induced by CCl4. Also, carvedilol significantly counteracted lipid peroxidation, GSH depletion, and reduction in antioxidant enzyme activities; glutathione-S-transferase and catalase that was induced by CCl4. In addition, carvedilol ameliorated the inflammation induced by CCl4 as indicated by reducing the serum level of acute phase protein marker; alpha-2-macroglobulin and the liver expression of nuclear factor-kappa B (NF-?B). Finally, carvedilol significantly reduced liver fibrosis markers including hydroxyproline, collagen accumulation, and the expression of the hepatic stellate cell (HSC) activation marker; alpha smooth muscle actin. In conclusion, the present study provides evidences for the promising antifibrotic effects of carvedilol that can be explained by amelioration of oxidative stress through mainly, replenishment of GSH, restoration of antioxidant enzyme activities and reduction of lipid peroxides as well as amelioration of inflammation and fibrosis by decreasing collagen accumulation, acute phase protein level, NF-?B expression and finally HSC activation. PMID:22543095

Hamdy, Nadia; El-Demerdash, Ebtehal

2012-06-15

304

Modulatory effects of curcumin, silybin-phytosome and alpha-R-lipoic acid against thioacetamide-induced liver cirrhosis in rats.  

PubMed

Liver cirrhosis is the final consequence of a progressive fibrotic process characterized by excessive collagen deposition and destruction of the normal liver architecture. This study aimed to investigate the protective effects of curcumin, silybin-phytosome and alpha-R-lipoic acid against thioacetamide-induced cirrhosis. Male rats were allocated into five groups of which one group received saline and served as normal control. Animals from groups 2-5 were treated with thioacetamide administered intraperitoneally at a dose of 200 mg/kg 3 times per week for 7 weeks. Group 2 was left untreated while groups from 3 to 5 were given a daily oral dose of curcumin, silybin-phytosome or alpha-R-lipoic acid simultaneously with thioacetamide. Increases in hepatic levels of malondialdehyde (MDA) and protein carbonyls (Pr Co) associated with thioacetamide administration were partially blocked in those groups receiving supplements. Glutathione (GSH) depletion, collagen deposition, matrix metalloproteinase-2 (MMP-2) activity, transforming growth factor-?1 (TGF-?1) level as well as ?-smooth muscle actin (?-SMA) and heat shock protein-47 (HSP-47) gene expressions were also decreased in response to supplements administration. Serological analysis of liver function and histopathological examination reinforced the results. In conclusion, the present study highlights the antioxidant and the antifibrotic potentials of these supplements against chronic liver diseases caused by ongoing hepatic damage. PMID:24704557

Ali, Shimaa Omar; Darwish, Hebatallah Abd El-moeti; Ismail, Nabila Abd El-fattah

2014-06-01

305

Severe Liver Cirrhosis Markedly Reduces AhR-Mediated Induction of Cytochrome P450 in Rats by Decreasing the Transcription of Target Genes  

PubMed Central

Although the induction of cytochrome P450 (CYP) has long been investigated in patients with cirrhosis, the question whether liver dysfunction impairs the response to CYP inducers still remains unresolved. Moreover, the mechanism underlying the possible effect of cirrhosis on induction has not been investigated. Since ethical constraints do not permit methodologically rigorous studies in humans, this question was addressed by investigating the effect of the prototypical inducer benzo[a]pyrene (BP) on CYP1A1 and CYP1A2 in cirrhotic rats stratified according to the severity of liver dysfunction. We simultaneously assessed mRNA level, protein expression and enzymatic activity of the CYP1A enzymes, as well as mRNA and protein expressions of the aryl hydrocarbon receptor (AhR), which mediates the BP effect. Basal mRNA and protein expressions of CYP1A1 were virtually absent in both healthy and cirrhotic rats. On the contrary, CYP1A2 mRNA, protein and enzyme activity were constitutively present in healthy rats and decreased significantly as liver function worsened. BP treatment markedly increased the concentrations of mRNA and immunodetectable protein, and the enzymatic activities of both CYP1A enzymes to similar levels in healthy and non-ascitic cirrhotic rats. Induced mRNA levels, protein expressions and enzymatic activities of both CYPs were much lower in ascitic rats and were proportionally reduced. Both constitutive and induced protein expressions of AhR were significantly lower in ascitic than in healthy rats. These results indicate that the inducibility of CYP1A enzymes is well preserved in compensated cirrhosis, whereas it is markedly reduced when liver dysfunction becomes severe. Induction appears to be impaired at the transcriptional level, due to the reduced expression of AhR, which controls the transcription of CYP1A genes. PMID:23626760

Floreani, Maura; De Martin, Sara; Gabbia, Daniela; Barbierato, Massimo; Nassi, Alberto; Mescoli, Claudia; Orlando, Rocco; Bova, Sergio; Angeli, Paolo; Gola, Elisabetta; Sticca, Antonietta; Palatini, Pietro

2013-01-01

306

Alcoholic liver disease  

MedlinePLUS

Liver disease due to alcohol; Cirrhosis or hepatitis - alcoholic; Laennec's cirrhosis ... Alcoholic liver disease occurs after years of heavy drinking. Alcohol can cause inflammation in the liver . Over time, scarring ...

307

Efficacy and safety of faldaprevir, deleobuvir, and ribavirin in treatment-naive patients with chronic hepatitis C virus infection and advanced liver fibrosis or cirrhosis.  

PubMed

Patients with advanced hepatic fibrosis or cirrhosis with chronic hepatitis C virus (HCV) infection represent an unmet need. The HCV NS3/4A inhibitor, faldaprevir, was evaluated in combination with the nonnucleoside NS5B inhibitor, deleobuvir, with or without ribavirin in treatment-naive patients with HCV genotype 1 infection in the SOUND-C2 study. Here, the efficacy and safety of this interferon-free regimen in a subset of patients with advanced liver fibrosis, including those with compensated cirrhosis, were assessed. Patients (n = 362) were randomized to once-daily faldaprevir with either twice-daily (BID) or three-times-daily (TID) deleobuvir for 16 (TID16W), 28 (TID28W and BID28W), or 40 (TID40W) weeks with or without ribavirin (TID28W-NR). Patients were classified according to fibrosis stage (F0 to F2 versus F3 to F4) and the presence of cirrhosis (yes/no). In total, 85 (24%) patients had advanced fibrosis/cirrhosis (F3 to F4) and 33 (9%) had cirrhosis. Within each treatment arm, differences in rates of sustained virologic response 12 weeks after completion of treatment (SVR12) between patients with mild to moderate fibrosis (F0 to F2) versus F3 to F4 did not show a consistent pattern and were not statistically significant (63% versus 47% for TID16W, 53% versus 76% for TID28W, 48% versus 67% for TID40W, 70% versus 67% for BID28W, and 40% versus 36% for TID28W-NR, respectively; P > 0.05 for each arm). The most frequent adverse events in patients with/without cirrhosis were gastrointestinal and skin events, which were mostly mild or moderate in intensity. The degree of liver fibrosis did not appear to affect the probability of achieving SVR12 following treatment with the interferon-free regimen of faldaprevir, deleobuvir, and ribavirin. (This study has been registered at ClinicalTrials.gov under registration no. NCT01132313.). PMID:25512403

Zeuzem, Stefan; Soriano, Vicente; Asselah, Tarik; Gane, Edward J; Bronowicki, Jean-Pierre; Angus, Peter; Lohse, Ansgar W; Stickel, Felix; Müllhaupt, Beat; Roberts, Stuart; Schuchmann, Marcus; Manns, Michael; Bourličre, Marc; Buti, Maria; Stern, Jerry O; Gallivan, John-Paul; Voss, Florian; Sabo, John P; Böcher, Wulf; Mensa, Federico J

2015-02-01

308

Levels and values of circulating endothelial progenitor cells, soluble angiogenic factors, and mononuclear cell apoptosis in liver cirrhosis patients  

PubMed Central

Background The roles of circulating endothelial progenitor cell (EPC) and mononuclear cell apoptosis (MCA) in liver cirrhosis (LC) patients are unknown. Moreover, vascular endothelial growth factor (VEGF) and stromal cell-derived factor (SDF)-1? are powerful endogenous substances enhancing EPC migration into circulation. We assessed the level and function of EPCs [CD31/CD34 (E1), KDR/CD34 (E2), CXCR4/CD34 (E3)], levels of MCA, VEGF and SDF-1? in circulation of LC patients. Methods Blood sample was prospectively collected once for assessing EPC level and function, MCA, and plasma levels of VEGF and SDF-1? using flow cytometry and enzyme-linked immunosorbent assay (ELISA), respectively, in 78 LC patients and 25 age- and gender-matched healthy controls. Results Number of EPCs (E1, E2, E3) was lower (all p?

2012-01-01

309

Impaired evoked and resting-state brain oscillations in patients with liver cirrhosis as revealed by magnetoencephalography.  

PubMed

A number of studies suggest that the clinical manifestation of neurological deficits in hepatic encephalopathy results from pathologically synchronized neuronal oscillations and altered oscillatory coupling. In the present study spontaneous and evoked oscillatory brain activities were analyzed jointly with established behavioral measures of altered visual oscillatory processing. Critical flicker and fusion frequencies (CFF, FUF) were measured in 25 patients diagnosed with liver cirrhosis and 30 healthy controls. Magnetoencephalography (MEG) data were collected at rest and during a visual task employing repetitive stimulation. Resting MEG and evoked fields were analyzed. CFF and FUF were found to be reduced in patients, providing behavioral evidence for deficits in visual oscillatory processing. These alterations were found to be related to resting brain activity in patients, namely that the lower the dominant MEG frequency at rest, the lower the CFF and FUF. An analysis of evoked fields at sensor level indicated that in comparison to normal controls, patients were not able to dynamically adapt to flickering visual stimulation. Evoked activity was also analyzed based on independent components (ICs) derived by independent component analysis. The similarity between the shape of each IC and an artificial sine function representing the stimulation frequency was tested via magnitude squared coherence. In controls, we observed a small number of components that correlated strongly with the sine function and a high number of ICs that did not correlate with the sine function. Interestingly, patient data were characterized by a high number of moderately correlating components. Taken together, these results indicate a fundamental divergence of the cerebral resonance activity in cirrhotic patients. PMID:24179838

Götz, Theresa; Huonker, Ralph; Kranczioch, Cornelia; Reuken, Philipp; Witte, Otto W; Günther, Albrecht; Debener, Stefan

2013-01-01

310

Impaired evoked and resting-state brain oscillations in patients with liver cirrhosis as revealed by magnetoencephalography???  

PubMed Central

A number of studies suggest that the clinical manifestation of neurological deficits in hepatic encephalopathy results from pathologically synchronized neuronal oscillations and altered oscillatory coupling. In the present study spontaneous and evoked oscillatory brain activities were analyzed jointly with established behavioral measures of altered visual oscillatory processing. Critical flicker and fusion frequencies (CFF, FUF) were measured in 25 patients diagnosed with liver cirrhosis and 30 healthy controls. Magnetoencephalography (MEG) data were collected at rest and during a visual task employing repetitive stimulation. Resting MEG and evoked fields were analyzed. CFF and FUF were found to be reduced in patients, providing behavioral evidence for deficits in visual oscillatory processing. These alterations were found to be related to resting brain activity in patients, namely that the lower the dominant MEG frequency at rest, the lower the CFF and FUF. An analysis of evoked fields at sensor level indicated that in comparison to normal controls, patients were not able to dynamically adapt to flickering visual stimulation. Evoked activity was also analyzed based on independent components (ICs) derived by independent component analysis. The similarity between the shape of each IC and an artificial sine function representing the stimulation frequency was tested via magnitude squared coherence. In controls, we observed a small number of components that correlated strongly with the sine function and a high number of ICs that did not correlate with the sine function. Interestingly, patient data were characterized by a high number of moderately correlating components. Taken together, these results indicate a fundamental divergence of the cerebral resonance activity in cirrhotic patients. PMID:24179838

Götz, Theresa; Huonker, Ralph; Kranczioch, Cornelia; Reuken, Philipp; Witte, Otto W.; Günther, Albrecht; Debener, Stefan

2013-01-01

311

Mechanisms of endotoxin tolerance in patients with alcoholic liver cirrhosis: role of interleukin 10, interleukin 1 receptor antagonist, and soluble tumour necrosis factor receptors as well as effector cell desensitisation  

Microsoft Academic Search

BACKGROUNDIn patients with alcoholic liver cirrhosis, endotoxaemia is a frequent finding. Unknown mechanisms, however, prevent typical clinical symptoms of endotoxaemia in many patients.METHODSWe determined plasma levels of pro- and anti-inflammatory mediators, ex vivo cytokine secretion capacity, and expression of tumour necrosis factor (TNF) receptors on phagocytic blood cells in 49 patients with alcoholic cirrhosis and 41 age matched healthy controls.RESULTSIn

V von Baehr; W-D Döcke; M Plauth; C Liebenthal; S Küpferling; H Lochs; R Baumgarten; H-D Volk

2000-01-01

312

Recent Advances in the Diagnosis and Management of Cirrhosis-Associated Cardiomyopathy in Liver Transplant Candidates: Advanced Echo Imaging, Cardiac Biomarkers, and Advanced Heart Failure Therapies  

PubMed Central

Patients with end-stage liver disease in need of liver transplantation increasingly are older with a greater burden of cardiac disease and other co-morbidities, which may increase perioperative risk and adversely affect long-term prognosis. Cirrhosis of any etiology manifests hemodynamically as a state of low systemic vascular resistance, with high peripheral, but low central blood volume, leading to a state of neurohormonal activation and high cardiac output, which may adversely affect cardiac reserve under extreme perioperative stress, aptly termed cirrhosis-associated or cirrhotic cardiomyopathy. Evidence of asymptomatic cirrhotic cardiomyopathy may be found in subtle electrocardiographic and echocardiographic changes, but may progress to severe heart failure under the demands of bleeding and transfusions, vasopressors, rebounding peripheral vascular resistance, withdrawal of cardioprotective beta-blockers and mineralocorticoid antagonists, exacerbated by sepsis or systemic inflammatory response syndrome. This review will add to the current body of literature on cirrhotic cardiomyopathy by focusing on the role of advanced echocardiographic imaging techniques, cardiac biomarkers, and advanced heart failure therapies available to manage patients with cirrhotic cardiomyopathy while waiting for liver transplant and during the perioperative period.

Farr, Maryjane; Schulze, Paul Christian

2014-01-01

313

Late preventive effects of quinacrine on carbon tetrachloride induced liver necrosis  

Microsoft Academic Search

We have previously reported that treatments stimulating phospholipid (PL) synthesis or preventing PL degradation were late preventive agents against CCl4-induced liver necrosis. Later studies by others postulated that stimulation of phospholipase A2 (PLA2) plays a role in PL degradative processes responsible for CCl4 damage. Quinacrine (QUIN) is a well known inhibitor of PLA2. In this work we report that QUIN

A. González Padrón; E. G. D. de Toranzo; J. A. Castro

1993-01-01

314

Therapeutic detoxification of quercetin against carbon tetrachloride-induced acute liver injury in mice and its mechanism*  

PubMed Central

This study observes the therapeutic detoxification of quercetin, a well-known flavonoid, against carbon tetrachloride (CCl4) induced acute liver injury in vivo and explores its mechanism. Quercetin decreased CCl4-increased serum activities of alanine and aspartate aminotransferases (ALT/AST) when orally taken 30 min after CCl4 intoxication. The results of a histological evaluation further evidenced the ability of quercetin to protect against CCl4-induced liver injury. Quercetin decreased the CCl4-increased malondialdehyde (MDA) and reduced the glutathione (GSH) amounts in the liver. It also reduced the enhanced immunohistochemical staining of the 4-hydroxynonenal (4-HNE) in the liver induced by CCl4. Peroxiredoxin (Prx) 1, 2, 3, 5, 6, thioredoxin reductase 1 and 2 (TrxR1/2), thioredoxin 1 and 2 (Trx1/2), nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) all play critical roles in maintaining cellular redox homeostasis. Real-time polymerase chain reaction (PCR) results demonstrated that quercetin reversed the decreased mRNA expression of all those genes induced by CCl4. In conclusion, our results demonstrate that quercetin ameliorates CCl4-induced acute liver injury in vivo via alleviating oxidative stress injuries when orally taken after CCl4 intoxication. This protection may be caused by the elevation of the antioxidant capacity induced by quercetin. PMID:25471833

Zhang, Jia-qi; Shi, Liang; Xu, Xi-ning; Huang, Si-chong; Lu, Bin; Ji, Li-li; Wang, Zheng-tao

2014-01-01

315

Therapeutic detoxification of quercetin against carbon tetrachloride-induced acute liver injury in mice and its mechanism.  

PubMed

This study observes the therapeutic detoxification of quercetin, a well-known flavonoid, against carbon tetrachloride (CCl4) induced acute liver injury in vivo and explores its mechanism. Quercetin decreased CCl4-increased serum activities of alanine and aspartate aminotransferases (ALT/AST) when orally taken 30 min after CCl4 intoxication. The results of a histological evaluation further evidenced the ability of quercetin to protect against CCl4-induced liver injury. Quercetin decreased the CCl4-increased malondialdehyde (MDA) and reduced the glutathione (GSH) amounts in the liver. It also reduced the enhanced immunohistochemical staining of the 4-hydroxynonenal (4-HNE) in the liver induced by CCl4. Peroxiredoxin (Prx) 1, 2, 3, 5, 6, thioredoxin reductase 1 and 2 (TrxR1/2), thioredoxin 1 and 2 (Trx1/2), nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) all play critical roles in maintaining cellular redox homeostasis. Real-time polymerase chain reaction (PCR) results demonstrated that quercetin reversed the decreased mRNA expression of all those genes induced by CCl4. In conclusion, our results demonstrate that quercetin ameliorates CCl4-induced acute liver injury in vivo via alleviating oxidative stress injuries when orally taken after CCl4 intoxication. This protection may be caused by the elevation of the antioxidant capacity induced by quercetin. PMID:25471833

Zhang, Jia-qi; Shi, Liang; Xu, Xi-ning; Huang, Si-chong; Lu, Bin; Ji, Li-li; Wang, Zheng-tao

2014-12-01

316

Predictive role of serum procollagen III peptide and Knodell’s index in survival prognosis of patients with hepatitis B virus liver cirrhosis  

Microsoft Academic Search

Summary\\u000a Objective  The objective of the study was to improve the accuracy of survival prognosis in patients with liver cirrhosis using procollagen\\u000a III peptide (PIIIP), as a marker of inflammation and fibrogenesis, and Knodell’s histologic activity index (KI) in addition\\u000a to previously used prognostic factors.\\u000a \\u000a \\u000a \\u000a Patients and methods  Five-year survival was followed in a group of 75 patients with hepatitis B virus

Žarko Babi?; Ante Bili?; Dobroslav Babi?; Vjekoslav Jagi?; Branko Nikoli?; Martina Suni?

2003-01-01

317

A single case of rosai-dorfman disease marked by pathologic fractures, kidney failure, and liver cirrhosis treated with single-agent cladribine.  

PubMed

Rosai-Dorfman disease (RDD) is a proliferative histiocytic disorder of unknown etiology, which is characterized by sinus histiocytosis with massive lymphadenopathy (1). In most cases, RDD has a benign course and treatment is not necessary. However, severe cases of RDD require treatment, and the treatment strategy is determined on the basis of the severity of the disease or the extranodal involvement of vital organs. We report a single case of RDD with atypical presentation of persistent constitutional symptoms, progressing pathologic fractures, and end-organ dysfunction, including acute kidney failure and liver cirrhosis with esophageal varices. PMID:25401088

Sasaki, Koji; Pemmaraju, Naveen; Westin, Jason R; Wang, Wei-Lien; Khoury, Joseph D; Podoloff, Donald A; Moon, Bryan; Daver, Naval; Borthakur, Gautam

2014-01-01

318

A Single Case of Rosai–Dorfman Disease Marked by Pathologic Fractures, Kidney Failure, and Liver Cirrhosis Treated with Single-Agent Cladribine  

PubMed Central

Rosai–Dorfman disease (RDD) is a proliferative histiocytic disorder of unknown etiology, which is characterized by sinus histiocytosis with massive lymphadenopathy (1). In most cases, RDD has a benign course and treatment is not necessary. However, severe cases of RDD require treatment, and the treatment strategy is determined on the basis of the severity of the disease or the extranodal involvement of vital organs. We report a single case of RDD with atypical presentation of persistent constitutional symptoms, progressing pathologic fractures, and end-organ dysfunction, including acute kidney failure and liver cirrhosis with esophageal varices. PMID:25401088

Sasaki, Koji; Pemmaraju, Naveen; Westin, Jason R.; Wang, Wei-Lien; Khoury, Joseph D.; Podoloff, Donald A.; Moon, Bryan; Daver, Naval; Borthakur, Gautam

2014-01-01

319

Human serum fetuin A\\/?2HS-glycoprotein level is associated with long-term survival in patients with alcoholic liver cirrhosis, comparison with the Child-Pugh and MELD scores  

Microsoft Academic Search

BACKGROUND: Serum concentration of fetuin A\\/?2HS-glycoprotein (AHSG) is a good indicator of liver cell function and 1-month mortality in patients with alcoholic liver cirrhosis and liver cancer. We intended to determine whether decreased serum AHSG levels are associated with long-term mortality and whether the follow-up of serum AHSG levels can add to the predictive value of the Child-Pugh (CP) and

László Kalabay; László Gráf; Krisztián Vörös; László Jakab; Zsuzsa Benk?; László Telegdy; Béla Fekete; Zoltán Prohászka; George Füst

2007-01-01

320

The benefits of using Sentinel WebDashboard in medicine: IT solution for monitoring and treatment of patient with liver cirrhosis  

PubMed Central

Abstract The global assessment of the evolution of a disease in a certain geographical area or a specific domain is useful in the medical research for the preparation of practice guidelines/protocols used in the hospitals. Cirrhosis is one of the most common disorders seen today, occupying a significant place in the gastrointestinal pathology. The disease is the final stage of various affections in terms of etiology and morphology. The most frequent subjects treated on this topic are those related to the etiopathology and early diagnosis. Given the current interest in this matter and considering that UGS (upper gastrointestinal bleeding) in liver cirrhosis is a common complication and potentially fatal, the medical research found some very useful conducting retrospective studies in this area. The purpose of our study was to create an IT system implemented with Sentinel WebDashboard, which could increase the medical performances in diagnosis, monitoring and treatment of a disease. We tested our solution on a medical data set containing information about the patients with liver cirrhosis. The solution facilitates the access of the physicians to the databases containing complete information about the patients, offers the possibility to monitor the evaluation of their health and also aids physicians in optimizing the medical procedures and improve the diagnostic methods. It also offers the advantages of a web application: it does not require the installation on the client side, being accessible anytime, anywhere via a web browser, laptop, Smartphone or tablet. Abbreviations UGS = upper gastrointestinal bleeding; UGE = upper gastrointestinal endoscopy; SOA = Service Oriented Architecture PMID:25408726

Dumitrescu, SR; Popescu, D; Purcarea, VL; Albu, LC

2014-01-01

321

Biliary lipids, faecal steroids, and liver function in patients with chronic active hepatitis and primary biliary cirrhosis: significance of hepatic orcein-stained complexes.  

PubMed Central

Biliary lipids, faecal steroids, and serum bile acids were studied in patients with chronic active hepatitis and primary biliary cirrhosis. The results were correlated with excretory and parenchymal liver function tests and with the presence or absence of orcein-positive copper-protein complexes in histological liver specimens. In general, faecal bile acids, but not neutral and total sterols, correlated negatively with the percentage of biliary cholic acid, serum cholesterol, and serum bile acids and positively with the percentage of biliary deoxycholic acid. In orcein-positive subjects-indicative of long-standing cholestasis-the bile was undersaturated with cholesterol, biliary deoxycholic acid was subnormal, cholic acid correspondingly increased, and serum cholesterol and bile acids were raised. Only patients with marked impairment of both excretory and parenchymal liver functions had a decreased output of neutral sterols, bile acids, and total steroids, and, thus, low bile acid and cholesterol synthesis. The findings indicate that mild disturbances in parenchymal liver function infrequently cause major changes in cholesterol metabolism, while abnormalities in secretory liver function-in orcein-positive subjects especially-are frequently associated with proportionate changes in parameters of cholesterol metabolism. PMID:6167493

Kesäniemi, Y A; Miettinen, T A; Salaspuro, M P

1981-01-01

322

Cirrhosis associated with multiple transfusions in thalassaemia  

Microsoft Academic Search

The study of surgical liver biopsy specimens obtained during splenectomy in 86 children with thalassaemia indicated that such patients may develop liver disease that evolves into cirrhosis. Histological characteristics suggest that it is post-necrotic cirrhosis. Onset of cirrhosis in some patients may occur as early as 7-8 years old, and at age about 15-16 years most children with thalassaemia show

G Jean; S Terzoli; R Mauri; L Borghetti; A Di Palma; A Piga; M Magliano; M Melevendi; M Cattaneo

1984-01-01

323

Performance of Two HCV RNA Assays during Protease Inhibitor-Based Triple Therapy in Patients with Advanced Liver Fibrosis and Cirrhosis  

PubMed Central

Introduction On-treatment HCV RNA measurements are crucial for the prediction of a sustained virological response (SVR) and to determine treatment futility during protease inhibitor-based triple therapies. In patients with advanced liver disease an accurate risk/benefit calculation based on reliable HCV RNA results can reduce the number of adverse events. However, the different available HCV RNA assays vary in their diagnostic performance. Aim To investigate the clinical relevance of concordant and discordant results of two HCV RNA assays during triple therapy with boceprevir and telaprevir in patients with advanced liver fibrosis/cirrhosis. Methods We collected on-treatment samples of 191 patients with advanced liver fibrosis/cirrhosis treated at four European centers for testing with the Abbott RealTime (ART) and COBAS AmpliPrep/COBAS TaqMan HCV v2.0 (CTM) assays. Results Discordant test results for HCV RNA detectability were observed in 23% at week 4, 17% at week 8/12 and 9% at week 24 on-treatment. The ART detected HCV RNA in 41% of week 4 samples tested negative by the CTM. However, the positive predictive value of an undetectable week 4 result for SVR was similar for both assays (80% and 82%). Discordance was also found for application of stopping rules. In 27% of patients who met stopping rules by CTM the ART measured levels below the respective cut-offs of 100 and 1000 IU/ml, respectively, which would have resulted in treatment continuation. In contrast, in nine patients with negative HCV RNA by CTM at week 24 treatment would have been discontinued due to detectable residual HCV RNA by the ART assay. Importantly, only 4 of these patients failed to achieve SVR. Conclusion Application of stopping rules determined in approval studies by one assay to other HCV RNA assays in clinical practice may lead to over and undertreatment in a significant number of patients undergoing protease inhibitor-based triple therapy. PMID:25389779

Calvaruso, Vincenza; Makara, Mihály; Vermehren, Johannes; Haragh, Attila; Susser, Simone; Bremer, Birgit; Cloherty, Gavin; Manns, Michael P.; Craxě, Antonio; Wedemeyer, Heiner; Sarrazin, Christoph

2014-01-01

324

Management of pleural empyema with a vacuum-assisted closure device and reconstruction of open thoracic window in a patient with liver cirrhosis.  

PubMed

The patient is a 21-year-old female, diagnosed with cryptogenic cirrhosis at the age of 9. She presented with left post-pneumonic empyema that did not remit with conventional medical management and evolved with fistulization to the skin in the 7th intercostal space in the left subscapular region. We performed an open thoracic window procedure, and on the 6th day the patient was sent home with a portable vacuum-assisted closure device, with changes of the material every 4 days until the cavity was completed obliterated (92 days). Imaging tests showed full expansion of the lung, and chest wall reconstruction was performed with titanium rods. The high mortality of empyema in patients with liver disease requires both implementing and searching for new adjuvant therapies, like the use of vacuum-assisted closure systems and reconstruction with titanium rods. Controlled studies with a wide range of cases are needed for proper evaluation. PMID:23312986

Munguía-Canales, Daniel Alejandro; Vargas-Mendoza, Gary Kosai; Alvarez-Bestoff, Gustavo; Calderón-Abbo, Moisés Cutiel

2013-10-01

325

Immune dysfunction in cirrhosis.  

PubMed

Innate and adaptive immune dysfunction, also referred to as cirrhosis-associated immune dysfunction syndrome, is a major component of cirrhosis, and plays a pivotal role in the pathogenesis of both the acute and chronic worsening of liver function. During the evolution of the disease, acute decompensation events associated with organ failure(s), so-called acute-on chronic liver failure, and chronic decompensation with progression of liver fibrosis and also development of disease specific complications, comprise distinct clinical entities with different immunopathology mechanisms. Enhanced bacterial translocation associated with systemic endotoxemia and increased occurrence of systemic bacterial infections have substantial impacts on both clinical situations. Acute and chronic exposure to bacteria and/or their products, however, can result in variable clinical consequences. The immune status of patients is not constant during the illness; consequently, alterations of the balance between pro- and anti-inflammatory processes result in very different dynamic courses. In this review we give a detailed overview of acquired immune dysfunction and its consequences for cirrhosis. We demonstrate the substantial influence of inherited innate immune dysfunction on acute and chronic inflammatory processes in cirrhosis caused by the pre-existing acquired immune dysfunction with limited compensatory mechanisms. Moreover, we highlight the current facts and future perspectives of how the assessment of immune dysfunction can assist clinicians in everyday practical decision-making when establishing treatment and care strategies for the patients with end-stage liver disease. Early and efficient recognition of inappropriate performance of the immune system is essential for overcoming complications, delaying progression and reducing mortality. PMID:24627592

Sipeki, Nora; Antal-Szalmas, Peter; Lakatos, Peter L; Papp, Maria

2014-03-14

326

Impact of the 2011 Great East Japan Earthquake on the resumption of alcohol consumption after living-donor liver transplantation for alcoholic cirrhosis: a report of two cases.  

PubMed

Alcoholic liver disease (ALD) is a leading indication for liver transplantation (LT) in Western countries. The rate of resumption of alcohol abuse is 7% to 95% after LT for ALD. A high prevalence of alcohol abuse has been observed in disaster-exposed populations; however, little is known about the association between resumption of alcohol abuse after LT and disasters. Between June 2007 and March 2011, 3 patients with alcoholic cirrhosis (2 men and 1 woman) underwent living-donor LT (LDLT) at Tohoku University Hospital, Sendai, Japan. The female patient died of graft failure 6 months after LDLT. The other patients (ages 55 and 56 years), who survived to discharge, resumed alcohol abuse after the 2011 Great East Japan Earthquake. Before transplantation, both patients had been abusing alcohol for >35 years, with a daily ethanol intake of 110 g and 140 g, respectively. The period of abstinence from alcohol consumption ranged from 4 to 6 months. After transplantation, patients showed good compliance with treatment and seemed at low risk of relapse until the earthquake. One patient was living in the nuclear evacuation zone at Fukushima, and resumed alcohol consumption after the evacuation. Another patient resumed alcohol consumption while temporarily living apart from his family during restoration work after the disaster. Extreme stress and changes in living arrangements after the Great East Japan Earthquake seemed to trigger the desire to drink. This is the first report on patients who underwent LT for ALD and who resumed alcohol consumption after a disaster. PMID:24767400

Nakanishi, C; Kawagishi, N; Sato, K; Miyagi, S; Takeda, I; Ohuchi, N

2014-04-01

327

Lab Invest . Author manuscript Liver precursor cells increase hepatic fibrosis induced by chronic carbon  

E-print Network

of multiple porto-central bridging septa leading to cirrhosis, whereas hepatocellular necrosis ; analysis ; Liver ; pathology ; Liver Cirrhosis, Experimental ; etiology ; Male ; Rats ; Rats, Sprague liver disease). In human, fibrosis that ultimately leads to cirrhosis initiates predominantly

Paris-Sud XI, Université de

328

Does antiviral therapy reduce complications of cirrhosis?  

PubMed Central

Chronic hepatitis B infection is associated with the development of cirrhosis, hepatocellular carcinoma, and finally liver-related mortality. Each year, approximately, 2%-5% of patients with hepatitis B virus (HBV)-related compensated cirrhosis develop decompensation, with additional clinical manifestations, such as ascites, jaundice, hepatic encephalopathy, and gastrointestinal bleeding. The outcome of decompensated HBV-related cirrhosis is poor, with a 5-year survival of 14%-35% compared to 84% in patients with compensated cirrhosis. Because the risk of disease progression is closely linked to a patient’s serum HBV DNA level, antiviral therapy may suppress viral replication, stabilize liver function and improve survival. This article briefly reviews the role that antiviral therapy plays in cirrhosis complications, particularly, in decompensation and acute-on-chronic liver failure. PMID:24966601

Chung, Goh Eun; Lee, Jeong-Hoon; Kim, Yoon Jun

2014-01-01

329

An unusual case of cirrhosis.  

PubMed

49-year-old white female with remote h/o sarcoidosis was referred to GI when her liver was noted to be nodular. Physical examination revealed normal vital signs and no icterus, spider nevi, clubbing, ascites, hepatosplenomegaly, or ankle edema. LFTs, hepatitis serologies, ANA, AMA, ASMA, Ferritin, Ceruloplasmin, and ? 1-AT, level were unremarkable. Liver biopsy showed cirrhosis. She developed worsening of baseline SOB and was hospitalized. She was eventually diagnosed with constrictive pericarditis. A diagnosis of cardiac cirrhosis was made. PMID:24782928

Alkaddour, Ahmad; Vega, Kenneth J; Shujaat, Adil

2014-01-01

330

An Unusual Case of Cirrhosis  

PubMed Central

49-year-old white female with remote h/o sarcoidosis was referred to GI when her liver was noted to be nodular. Physical examination revealed normal vital signs and no icterus, spider nevi, clubbing, ascites, hepatosplenomegaly, or ankle edema. LFTs, hepatitis serologies, ANA, AMA, ASMA, Ferritin, Ceruloplasmin, and ?1-AT, level were unremarkable. Liver biopsy showed cirrhosis. She developed worsening of baseline SOB and was hospitalized. She was eventually diagnosed with constrictive pericarditis. A diagnosis of cardiac cirrhosis was made. PMID:24782928

Alkaddour, Ahmad; Vega, Kenneth J.

2014-01-01

331

[Primary biliary cirrhosis: therapeutic options].  

PubMed

Primary biliary cirrhosis (PBC) is a chronic and slowly progressive cholestatic liver disease of autoimmune etiology, characterized by injury of the intra-hepatic bile ducts that may eventually lead to liver failure. Many drugs have been performed for treatment, including agents with choleretic and immunosuppressive properties. Patients, particularly those who start ursodeoxycholic acid treatment at early-stage disease and who respond with improvement of liver biochemistry, have a good prognosis. Liver transplantation is usually an option for PBC patients with severe liver failure. PMID:19886235

Abenavoli, Ludovico

2009-09-01

332

Hepatocyte Produced Matrix Metalloproteinases Are Regulated by CD147 in Liver Fibrogenesis  

PubMed Central

Background The classical paradigm of liver injury asserts that hepatic stellate cells (HSC) produce, remodel and turnover the abnormal extracellular matrix (ECM) of fibrosis via matrix metalloproteinases (MMPs). In extrahepatic tissues MMP production is regulated by a number of mechanisms including expression of the glycoprotein CD147. Previously, we have shown that CD147 is expressed on hepatocytes but not within the fibrotic septa in cirrhosis [1]. Therefore, we investigated if hepatocytes produce MMPs, regulated by CD147, which are capable of remodelling fibrotic ECM independent of the HSC. Methods Non-diseased, fibrotic and cirrhotic livers were examined for MMP activity and markers of fibrosis in humans and mice. CD147 expression and MMP activity were co-localised by in-situ zymography. The role of CD147 was studied in-vitro with siRNA to CD147 in hepatocytes and in-vivo in mice with CCl4 induced liver injury using ăCD147 antibody intervention. Results In liver fibrosis in both human and mouse tissue MMP expression and activity (MMP-2, -9, -13 and -14) increased with progressive injury and localised to hepatocytes. Additionally, as expected, MMPs were abundantly expressed by activated HSC. Further, with progressive fibrosis there was expression of CD147, which localised to hepatocytes but not to HSC. Functionally significant in-vitro regulation of hepatocyte MMP production by CD147 was demonstrated using siRNA to CD147 that decreased hepatocyte MMP-2 and -9 expression/activity. Further, in-vivo ?-CD147 antibody intervention decreased liver MMP-2, -9, -13, -14, TGF-? and ?-SMA expression in CCl4 treated mice compared to controls. Conclusion We have shown that hepatocytes produce active MMPs and that the glycoprotein CD147 regulates hepatocyte MMP expression. Targeting CD147 regulates hepatocyte MMP production both in-vitro and in-vivo, with the net result being reduced fibrotic matrix turnover in-vivo. Therefore, CD147 regulation of hepatocyte MMP is a novel pathway that could be targeted by future anti-fibrogenic agents. PMID:25076423

Morgan, Alison J.; Tu, Thomas; Wen, Victoria W.; Yee, Christine; Mridha, Auvro; Lee, Maggie; d'Avigdor, William; Locarnini, Stephen A.; McCaughan, Geoffrey W.; Warner, Fiona J.; McLennan, Susan V.; Shackel, Nicholas A.

2014-01-01

333

Indoleamine 2,3-dioxygenase expression and activity in patients with hepatitis C virus-induced liver cirrhosis  

PubMed Central

Indoleamine 2,3-dioxygenase (IDO) is an immunoregulatory enzyme. It plays a key role in various malignancies, infection and autoimmune diseases. IDO induces immunosuppression through the depletion of tryptophan and its downstream metabolites. Hepatitis C virus (HCV) has infected more than 12 million individuals in Pakistan. The aim of the present study was to assess the expression and activity of IDO in HCV-infected patients. The functional enzymatic activity of IDO was measured by colorimetric assay. Serum samples from 100 HCV-infected patients were taken to examine IDO activity and samples from 100 healthy volunteers were used as controls. Liver sections from patients with HCV (n=35) and healthy controls (n=5) were used for immunohistochemical studies. Immunohistochemical analysis revealed that IDO was overexpressed in 28 of 35 (80%) cirrhotic liver samples, whereas 5 of 35 (14.2%) cases presented moderate and 2 of 35 (5.7%) cases presented mild expression of IDO. The enzymatic activity of IDO was significantly higher in the serum samples of HCV-infected patients as compared with those in the control. These data indicate that the expression of IDO correlated with the pathogenesis of disease. In summary, it is suggested that the high expression of IDO in the progressively cirrhotic livers of HCV-infected patients might contribute to the development of hepatocellular carcinoma. IDO may characterize a novel therapeutic target against HCV.

ASGHAR, KASHIF; ASHIQ, M. TAIMOUR; ZULFIQAR, BILAL; MAHROO, AMNAH; NASIR, KAENAT; MURAD, SHEEBA

2015-01-01

334

Management of primary biliary cirrhosis  

Microsoft Academic Search

Primary biliary cirrhosis (PBC) is a presumed autoim- mune disease of the liver, which predominantly affects women once over the age of 20 years. Most cases are diagnosed when asymptomatic (60%). The antimitochon- drial antibody is present in serum in most, but not in all, patients with PBC. The disease generally progresses slowly but survival is less than an age-

E. Jenny Heathcote

2000-01-01

335

Non-invasive diagnosis of advanced fibrosis and cirrhosis  

PubMed Central

Liver cirrhosis is a common and growing public health problem globally. The diagnosis of cirrhosis portends an increased risk of morbidity and mortality. Liver biopsy is considered the gold standard for diagnosis of cirrhosis and staging of fibrosis. However, despite its universal use, liver biopsy is an invasive and inaccurate gold standard with numerous drawbacks. In order to overcome the limitations of liver biopsy, a number of non-invasive techniques have been investigated for the assessment of cirrhosis. This review will focus on currently available non-invasive markers of cirrhosis. The evidence behind the use of these markers will be highlighted, along with an assessment of diagnostic accuracy and performance characteristics of each test. Non-invasive markers of cirrhosis can be radiologic or serum-based. Radiologic techniques based on ultrasound, magnetic resonance imaging and elastography have been used to assess liver fibrosis. Serum-based biomarkers of cirrhosis have also been developed. These are broadly classified into indirect and direct markers. Indirect biomarkers reflect liver function, which may decline with the onset of cirrhosis. Direct biomarkers, reflect extracellular matrix turnover, and include molecules involved in hepatic fibrogenesis. On the whole, radiologic and serum markers of fibrosis correlate well with biopsy scores, especially when excluding cirrhosis or excluding fibrosis. This feature is certainly clinically useful, and avoids liver biopsy in many cases. PMID:25492996

Sharma, Suraj; Khalili, Korosh; Nguyen, Geoffrey Christopher

2014-01-01

336

Ameliorative effects of Moringa oleifera Lam seed extract on liver fibrosis in rats.  

PubMed

This study was carried out to evaluate the effect of Moringa oleifera Lam (Moringa) seed extract on liver fibrosis. Liver fibrosis was induced by the oral administration of 20% carbon tetrachloride (CCl(4)), twice weekly and for 8 weeks. Simultaneously, M.oleifera Lam seed extract (1g/kg) was orally administered daily. The biochemical and histological results showed that Moringa reduced liver damage as well as symptoms of liver fibrosis. The administration of Moringa seed extract decreased the CCl(4)-induced elevation of serum aminotransferase activities and globulin level. The elevations of hepatic hydroxyproline content and myeloperoxidase activity were also reduced by Moringa treatment. Furthermore, the immunohistochemical study showed that Moringa markedly reduced the numbers of smooth muscle alpha-actin-positive cells and the accumulation of collagens I and III in liver. Moringa seed extract showed significant inhibitory effect on 1,1-diphenyl-2-picrylhydrazyl free radical, as well as strong reducing antioxidant power. The activity of superoxide dismutase as well as the content of both malondialdehyde and protein carbonyl, which are oxidative stress markers, were reversed after treatment with Moringa. Finally, these results suggested that Moringa seed extract can act against CCl(4)-induced liver injury and fibrosis in rats by a mechanism related to its antioxidant properties, anti-inflammatory effect and its ability to attenuate the hepatic stellate cells activation. PMID:19854235

Hamza, Alaaeldin A

2010-01-01

337

Hepatocurative potential of sesquiterpene lactones of Taraxacum officinale on carbon tetrachloride induced liver toxicity in mice.  

PubMed

The hepatocurative potential of ethanolic extract (ETO) and sesquiterpene lactones enriched fraction (SL) of Taraxacum officinale roots was evaluated against carbon tetrachloride (CCl 4 ) induced hepatotoxicity in mice. The diagnostic markers such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and total bilirubin contents were significantly elevated, whereas significant reduction in the level of reduced glutathione (GSH) and enhanced hepatic lipid peroxidation, liver weight and liver protein were observed in CCl 4 induced hepatotoxicity in mice. Post-treatment with ETO and SL significantly protected the hepatotoxicity as evident from the lower levels of hepatic enzyme markers, such as serum transaminase (ALT, AST), ALP and total bilirubin. Further, significant reduction in the liver weight and liver protein in drug-treated hepatotoxic mice and also reduced oxidative stress by increasing reduced glutathione content and decreasing lipid peroxidation level has been noticed. The histopathological evaluation of the liver also revealed that ETO and SL reduced the incidence of liver lesions induced by CCl 4 . The results indicate that sesquiterpene lactones have a protective effect against acute hepatotoxicity induced by the administration of CCl 4 in mice. Furthermore, observed activity of SL may be due to the synergistic action of two sesquiterpene lactones identified from enriched ethyl acetate fraction by HPLC method. PMID:20519172

Mahesh, A; Jeyachandran, R; Cindrella, L; Thangadurai, D; Veerapur, V P; Muralidhara Rao, D

2010-06-01

338

Diagnosis of Hepatocellular Carcinoma Complicating Liver Cirrhosis: Utility of Repeat Ultrasound-Guided Biopsy after Unsuccessful First Sampling  

SciTech Connect

Purpose: To evaluate the utility of a second ultrasound-guided fine-needle biopsy of liver nodules thought to be hepatocellular carcinoma when the original biopsy has failed to provide a reliable diagnosis. Methods: Thirty-seven cirrhotic patients underwent ultrasound-guided fine-needle biopsy of liver nodules that were subsequently diagnosed as hepatocellular carcinoma. Each biopsy involved a single puncture with a 20 G cutting needle, which yielded pathologic material used both for cytologic and histologic studies. In 23 cases (mean diameter of nodules 48 mm) the biopsy furnished exclusively necrotic material (non-diagnostic subgroup); in the other 14 cases (mean diameter 26 mm) the biopsy yielded no neoplastic elements (false-negative subgroup). All 37 nodules were subjected to repeat biopsies performed in the same manner. Results: The repeat biopsies provided a diagnosis of hepatocellular carcinoma in six of the 23 patients from the non-diagnostic subgroup and in seven of the 14 in the false-negative subgroup. Overall, repeat biopsy produced a diagnostic gain of 35.1%. Conclusion: The chance of success with repeat biopsy of hepatocellular carcinoma is limited and may depend to some extent on the characteristics of the lesions (i.e., areas of necrosis in large nodules, well-differentiated cellular populations in small ones)

Caturelli, Eugenio [Unita Operativa diGastroenterologia, Ospedale 'Casa Sollievo della Sofferenza' IRCCS, viale Cappuccini, I-71013 San Giovanni Rotondo, Foggia (Italy); Biasini, Elisabetta [Dipartimento diMedicina Interna e Scienze Biomediche, Universita degli Studi, I-43100 Parma (Italy); Bartolucci, Francesca [Dipartimento di Radiologia e Diagnostica perImmagini, Universita degli Studi, I-60100 Ancona (Italy); Facciorusso, Domenico; Decembrino, Francesco [Unita Operativa diGastroenterologia, Ospedale 'Casa Sollievo della Sofferenza' IRCCS, viale Cappuccini, I-71013 San Giovanni Rotondo, Foggia (Italy); Attino, Vito; Bisceglia, Michele [Servizio di Anatomiae Istologia Patologica, Ospedale 'Casa Sollievo della Sofferenza' IRCCS, I-71013 San Giovanni Rotondo, Foggia (Italy)

2002-08-15

339

Portal vein thrombosis during eltrombopag treatment for immune thrombocytopenic purpura in a patient with liver cirrhosis due to hepatitis C viral infection.  

PubMed

Portal vein thrombosis is a rare, aggressive and life-threatening complication of liver cirrhosis (LC). Eltrombopag is effective for the treatment of chronic hepatitis with thrombocytopenia, and portal vein thrombosis at this time has rarely been reported. We describe the case of a 78-year-old woman who suffered from LC due to hepatitis C viral infection. The patient developed immune thrombocytopenic purpura (ITP) that was diagnosed on the basis of nasal bleeding, progressive severe thrombocytopenia, elevation of platelet-associated IgG (PAIgG), no response to the transfusion of platelets and no abnormal findings on bone marrow biopsy. Although we first administered prednisolone (0.5 mg/kg/day), there was no recovery of platelet function and the nasal bleeding persisted. Subsequently, we administered eltrombopag for refractory ITP at a dose of 12.5 mg/day, and the thrombocytopenia gradually improved. Fifty-four days after the start of eltrombopag therapy, she developed portal vein thrombosis. Eltrombopag was stopped immediately, and antithrombin III was administered for prophylaxis against further portal vein thrombosis. Despite these treatments, there were subsequent deep vein and pulmonary artery thromboses. We then administered heparin for recanalization of the thrombi. One month after the initiation of heparin, there was recanalization as well as improvements of the portal vein, deep vein and pulmonary artery thromboses. There was no further thrombosis progression after switching from heparin to warfarin therapy. Our case suggests that eltrombopag may increase the risk of portal vein thrombosis ; therefore, this drug must be used carefully in the treatment of ITP in patients with LC due to hepatitis C viral infection. PMID:23995112

Kawano, Noriaki; Hasuike, Satoru; Iwakiri, Hisayoshi; Nakamura, Kenichi; Ozono, Yoshinori; Kusumoto, Hisanori; Nagata, Kenji; Kikuchi, Ikuko; Yoshida, Shuro; Kuriyama, Takuro; Yamashita, Kiyoshi; Muranaka, Takahiro; Kawaguchi, Takumi; Sata, Michio; Okamura, Takashi; Ueda, Akira; Shimoda, Kazuya

2013-01-01

340

Enhanced liver injury in acatalasemic mice following exposure to carbon tetrachloride  

Microsoft Academic Search

The hypothtical involvement of hydrogen peroxide (H2O2) in carbon tetrachloride (CCl4)-induced acute liver injury and the potential preventive effect of catalase on hepatotoxicity have been studied in acatalasemic\\u000a (C3H\\/AnLCs\\u000a bC2\\u000a b) mice and compared with normal (C3H\\/AnLCs\\u000a aCs\\u000a a) mice. A single intraperitoneal injection of CCl4 (20% in olive oil\\/g body weight) caused increases in serum aspartate aminotransferase (AST) and

Da-Hong Wang; Kunihiko Ishii; Li-Xue Zhen; Kazuhisa Taketa

1996-01-01

341

Primary biliary cirrhosis  

PubMed Central

Primary biliary cirrhosis (PBC) is a chronic and slowly progressive cholestatic liver disease of autoimmune etiology characterized by injury of the intrahepatic bile ducts that may eventually lead to liver failure. Affected individuals are usually in their fifth to seventh decades of life at time of diagnosis, and 90% are women. Annual incidence is estimated between 0.7 and 49 cases per million-population and prevalence between 6.7 and 940 cases per million-population (depending on age and sex). The majority of patients are asymptomatic at diagnosis, however, some patients present with symptoms of fatigue and/or pruritus. Patients may even present with ascites, hepatic encephalopathy and/or esophageal variceal hemorrhage. PBC is associated with other autoimmune diseases such as Sjogren's syndrome, scleroderma, Raynaud's phenomenon and CREST syndrome and is regarded as an organ specific autoimmune disease. Genetic susceptibility as a predisposing factor for PBC has been suggested. Environmental factors may have potential causative role (infection, chemicals, smoking). Diagnosis is based on a combination of clinical features, abnormal liver biochemical pattern in a cholestatic picture persisting for more than six months and presence of detectable antimitochondrial antibodies (AMA) in serum. All AMA negative patients with cholestatic liver disease should be carefully evaluated with cholangiography and liver biopsy. Ursodeoxycholic acid (UDCA) is the only currently known medication that can slow the disease progression. Patients, particularly those who start UDCA treatment at early-stage disease and who respond in terms of improvement of the liver biochemistry, have a good prognosis. Liver transplantation is usually an option for patients with liver failure and the outcome is 70% survival at 7 years. Recently, animal models have been discovered that may provide a new insight into the pathogenesis of this disease and facilitate appreciation for novel treatment in PBC. PMID:18215315

Kumagi, Teru; Heathcote, E Jenny

2008-01-01

342

Cirrhosis and its complications: Evidence based treatment  

PubMed Central

Cirrhosis results from progressive fibrosis and is the final outcome of all chronic liver disease. It is among the ten leading causes of death in United States. Cirrhosis can result in portal hypertension and/or hepatic dysfunction. Both of these either alone or in combination can lead to many complications, including ascites, varices, hepatic encephalopathy, hepatocellular carcinoma, hepatopulmonary syndrome, and coagulation disorders. Cirrhosis and its complications not only impair quality of life but also decrease survival. Managing patients with cirrhosis can be a challenge and requires an organized and systematic approach. Increasing physicians’ knowledge about prevention and treatment of these potential complications is important to improve patient outcomes. A literature search of the published data was performed to provide a comprehensive review regarding the management of cirrhosis and its complications. PMID:24833875

Nusrat, Salman; Khan, Muhammad S; Fazili, Javid; Madhoun, Mohammad F

2014-01-01

343

Emerging Therapies for Liver Fibrosis  

Microsoft Academic Search

Liver fibrosis occurs as a result of a wide range of injurious processes and in its end-stage results in cirrhosis. This gross disruption of liver architecture is associated with impaired hepatic function, portal hypertension and significant resultant morbidity and mortality. Indeed, liver fibrosis and cirrhosis represent a major worldwide healthcare burden. Recent progress in liver transplantation, the management of portal

Andrew J. Fowell; John P. Iredale

2006-01-01

344

Poly(ADP-Ribose) Polymerase 1 Promotes Oxidative-Stress-Induced Liver Cell Death via Suppressing Farnesoid X Receptor ?  

PubMed Central

Farnesoid X receptor ? (FXR) is highly expressed in the liver and regulates the expression of various genes involved in liver repair. In this study, we demonstrated that activated poly(ADP-ribose) polymerase 1 (PARP1) promoted hepatic cell death by inhibiting the expression of FXR-dependent hepatoprotective genes. PARP1 could bind to and poly(ADP-ribosyl)ate FXR. Poly(ADP-ribosyl)ation dissociated FXR from the FXR response element (FXRE), present in the promoters of target genes, and suppressed FXR-mediated gene transcription. Moreover, treatment with a FXR agonist attenuated poly(ADP-ribosyl)ation of FXR and promoted FXR-dependent gene expression. We further established the CCl4-induced acute liver injury model in wild-type and FXR-knockout mice and identified an essential role of FXR poly(ADP-ribosyl)ation in CCl4-induced liver injury. Thus, our results identified poly(ADP-ribosyl)ation of FXR by PARP1 as a key step in oxidative-stress-induced hepatic cell death. The molecular association between PARP1 and FXR provides new insight into the mechanism, suggesting that inhibition of PARP1 could prevent liver injury. PMID:24043304

Wang, Cheng; Zhang, Fengxiao; Wang, Lin; Zhang, Yanqing; Li, Xiangrao; Huang, Kun; Du, Meng; Liu, Fangmei; Huang, Shizheng; Guan, Youfei

2013-01-01

345

Hepatoprotective property of Thespesia populnea against carbon tetrachloride induced liver damage in rats.  

PubMed

The present study was carried out to evaluate the possible hepatoprotective activities of the medicinal plant Thespesia populnea in carbon tetrachloride (CCl4)-induced liver injury in rats. The water suspension (500 mg/kg b.wt.) of leaf, flower and stem bark of T. populnea showed varying levels of protective action against CCl4-induced liver damage as evidenced from significant reduction in the activities of serum marker enzymes for liver damage (alanine transaminase, aspartate transaminase, and alkaline phosphatase), and bilirubin levels when compared with CCl4-intoxicated control rats. The stem bark suspension showed maximum hepatoprotection compared with leaf and flower. An ethanol extract of the stem bark was more active than n-hexane and water extracts, showing remarkable protection at a dose of 60 mg/kg b.wt. The hepatoprotective effect of this extract was almost comparable to that of silymarin (100 mg/kg), a reference herbal drug. Thus, the present study indicates that ethanol extract of T. populnea stem bark is promising for further studies leading to hepatoprotective drug development. PMID:19662719

Yuvaraj, P; Subramoniam, A

2009-01-01

346

Urine metabolic profile changes of CCl4-liver fibrosis in rats and intervention effects of Yi Guan Jian Decoction using metabonomic approach  

PubMed Central

Background Yi Guan Jian Decoction (YGJD), a famous Chinese prescription, has long been employed clinically to treat liver fibrosis. However, as of date, there is no report on the effects of YGJD from a metabonomic approach. In this study, a urine metabonomic method based on gas chromatography coupled with mass spectrometry (GC/MS) was employed to study the protective efficacy and metabolic profile changes caused by YGJD in carbon tetrachloride (CCl4)-induced liver fibrosis. Methods Urine samples from Wistar rats of three randomly divided groups (control, model, and YGJD treated) were collected at various time-points, and the metabolic profile changes were analyzed by GC/MS with principal component analysis (PCA) and partial least squares-discriminate analysis (PLS-DA). Furthermore, histopathology and biochemical examination were also carried out to ensure the success of CCl4-induced liver fibrosis model. Results Urine metabolic profile studies suggested distinct clustering of the three groups, and YGJD group was much closer to the control group by showing a tendency of recovering towards the control group. Fourteen significantly changed metabolites were found, and YGJD treatment could reverse the levels of these metabolites to normal levels or close to normal levels. Conclusions The current study indicates that the YGJD has significant anti-fibrotic effects on CCl4-induced liver fibrosis in rats, which might be by regulating the dysfunction of energy metabolism, amino acid metabolism, tryptophan metabolism, cytochrome P450 metabolism, and gut microflora metabolism. The metabonomic approach can be recommended to study the pharmacological effect and mechanism of complex Chinese medicines. PMID:23725349

2013-01-01

347

Hyponatraemia and cirrhosis  

PubMed Central

Hyponatraemia is a common complication of advanced cirrhosis related to an impairment in the renal capacity for eliminating solute-free water, causing a retention of water that is disproportionate to the retention of sodium, thus leading to a reduction in serum sodium concentration and hypo-osmolality. The main pathogenic factor responsible for hyponatraemia is a non-osmotic hypersecretion of arginine vasopressin (AVP) or antidiuretic hormone from the neurohypophysis, related to circulatory dysfunction. Hyponatraemia in cirrhosis is associated with increased morbidity and mortality. Hyponatraemia is also associated with increased morbidity and impaired short-term survival after transplantation. The current standard of care based on restricting fluids to 1–1.5 L/day is rarely effective. Other approaches, such as albumin infusion and the use of vaptans—which act by specifically antagonizing the effects of AVP on the V2 receptors located in the kidney tubules—have been evaluated for their role in the management of hyponatraemia. The short-term treatment with vaptans is associated with a marked increase in renal solute-free water excretion and improvement of hyponatraemia; however their use in patients with end-stage liver disease is limited by hepatotoxic effects of some of these drugs. Long-term administration of vaptans seems to be effective in maintaining the improvement of serum sodium concentration, but the available information is still limited. PMID:24760233

Gianotti, Robert J.; Cardenas, Andres

2014-01-01

348

Cirrhosis-associated immune dysfunction: Distinctive features and clinical relevance.  

PubMed

The term cirrhosis-associated immune dysfunction refers to the main syndromic abnormalities of immune function, immunodeficiency and systemic inflammation that are present in cirrhosis. The course of advanced cirrhosis, regardless of its aetiology, is complicated by cirrhosis-associated immune dysfunction and this constitutes the pathophysiological hallmark of an increased susceptibility to bacterial infection, distinctive of the disease. Cirrhosis impairs the homeostatic role of the liver in the systemic immune response. Damage to the reticulo-endothelial system compromises the immune surveillance function of the organ and the reduced hepatic synthesis of proteins, involved in innate immunity and pattern recognition, hinders the bactericidal ability of phagocytic cells. Systemic inflammation, in form of activated circulating immune cells and increased serum levels of pro-inflammatory cytokines, is the result of persistent episodic activation of circulating immune cells from damage-associated molecular patterns, released from necrotic liver cells and, as cirrhosis progresses, from pathogen-associated molecular patterns, released from the leaky gut. Cirrhosis-associated immune dysfunction phenotypes switch from predominantly "pro-inflammatory" to predominantly "immunodeficient" in patients with stable ascitic cirrhosis and in patients with severely decompensated cirrhosis and extra-hepatic organ failure (e.g. acute-on-chronic liver failure), respectively. These cirrhosis-associated immune dysfunction phenotypes represent the extremes of a spectrum of reversible dynamic events that take place during the course of cirrhosis. Systemic inflammation can affect the functions of tissue somatic cells and modify the clinical manifestation of cirrhosis. The best characterized example is the contribution of systemic inflammation to the haemodynamic derangement of cirrhosis, which correlates negatively with prognosis. PMID:25135860

Albillos, Agustín; Lario, Margaret; Alvarez-Mon, Melchor

2014-12-01

349

Antioxidant and protective effect of ethyl acetate extract of podophyllum hexandrum rhizome on carbon tetrachloride induced rat liver injury.  

PubMed

The antioxidant and hepatoprotective activities of ethyl acetate extract was carefully investigated by the methods of DPPH radical scavenging activity, Hydroxyl radical scavenging activity, Superoxide radical scavenging activity, Hydrogen peroxide radical scavenging activity and its Reducing power ability. All these in vitro antioxidant activities were concentration dependent which were compared with standard antioxidants such as BHT, ?-tocopherol. The hepatoprotective potential of Podophyllum hexandrum extract was also evaluated in male Wistar rats against carbon tetrachloride (CCl(4))-induced liver damage. Pre-treated rats were given ethyl acetate extract at 20, 30 and 50?mg/kg dose prior to CCl(4) administration (1?ml/kg, 1:1 in olive oil). Rats pre-treated with Podophyllum hexandrum extract remarkably prevented the elevation of serum AST, ALT, LDH and liver lipid peroxides in CCl(4)-treated rats. Hepatic glutathione levels were significantly increased by the treatment with the extract in all the experimental groups. The extract at the tested doses also restored the levels of liver homogenate enzymes (glutathione peroxidase, glutathione reductase, superoxide dismutase and glutathione-S- transferase) significantly. This study suggests that ethyl acetate extract of P. hexandrum has a liver protective effect against CCl(4)-induced hepatotoxicity and possess in vitro antioxidant activities. PMID:21394192

Ganie, Showkat Ahmad; Haq, Ehtishamul; Masood, Akbar; Hamid, Abid; Zargar, Mohmmad Afzal

2011-01-01

350

Antioxidant and Protective Effect of Ethyl Acetate Extract of Podophyllum Hexandrum Rhizome on Carbon Tetrachloride Induced Rat Liver Injury  

PubMed Central

The antioxidant and hepatoprotective activities of ethyl acetate extract was carefully investigated by the methods of DPPH radical scavenging activity, Hydroxyl radical scavenging activity, Superoxide radical scavenging activity, Hydrogen peroxide radical scavenging activity and its Reducing power ability. All these in vitro antioxidant activities were concentration dependent which were compared with standard antioxidants such as BHT, ?-tocopherol. The hepatoprotective potential of Podophyllum hexandrum extract was also evaluated in male Wistar rats against carbon tetrachloride (CCl4)-induced liver damage. Pre-treated rats were given ethyl acetate extract at 20, 30 and 50?mg/kg dose prior to CCl4 administration (1?ml/kg, 1:1 in olive oil). Rats pre-treated with Podophyllum hexandrum extract remarkably prevented the elevation of serum AST, ALT, LDH and liver lipid peroxides in CCl4-treated rats. Hepatic glutathione levels were significantly increased by the treatment with the extract in all the experimental groups. The extract at the tested doses also restored the levels of liver homogenate enzymes (glutathione peroxidase, glutathione reductase, superoxide dismutase and glutathione-S- transferase) significantly. This study suggests that ethyl acetate extract of P. hexandrum has a liver protective effect against CCl4-induced hepatotoxicity and possess in vitro antioxidant activities. PMID:21394192

Ganie, Showkat Ahmad; Haq, Ehtishamul; Masood, Akbar; Hamid, Abid; Zargar, Mohmmad Afzal

2011-01-01

351

Further exploration of MRI techniques for liver T1rho quantification.  

PubMed

With biliary duct ligation and CCl4 induced rat liver fibrosis models, recent studies showed that MR T1rho imaging is able to detect liver fibrosis, and the degree of fibrosis is correlated with the degree of elevation of the T1rho measurements, suggesting liver T1rho quantification may play an important role for liver fibrosis early detection and grading. It has also been reported it is feasible to obtain consistent liver T1rho measurement for human subjects at 3 Tesla (3 T), and preliminary clinical data suggest liver T1rho is increased in patients with cirrhosis. In these previous studies, T1rho imaging was used with the rotary-echo spin-lock pulse for T1rho preparation, and number of signal averaging (NSA) was 2. Due to the presence of inhomogeneous B0 field, artifacts may occur in the acquired T1rho-weighted images. The method described by Dixon et al. (Magn Reson Med 1996;36:90-4), which is a hard RF pulse with 135° flip angle and same RF phase as the spin-locking RF pulse is inserted right before and after the spin-locking RF pulse, has been proposed to reduce sensitivity to B0 field inhomogeneity in T1rho imaging. In this study, we compared the images scanned by rotary-echo spin-lock pulse method (sequence 1) and the pulse modified according to Dixon method (sequence 2). When the artifacts occurred in T1rho images, we repeated the same scan until satisfactory. We accepted images if artifact in liver was less than 10% of liver area by visual estimation. When NSA =2, the breath-holding duration for data acquisition of one slice scanning was 8 sec due to a delay time of 6,000 ms for magnetization restoration. If NSA =1, the duration was shortened to be 2 sec. In previous studies, manual region of interest (ROI) analysis of T1rho map was used. In this current study, histogram analysis was also applied to evaluate liver T1rho value on T1rho maps. MRI data acquisition was performed on a 3 T clinical scanner. There were 29 subjects with 61 examinations obtained. Liver T1rho values obtained by sequence 1 (NSA =2) and sequence 2 (NSA =2) showed similar values, i.e., 43.1±2.1 ms (range: 38.6-48.0 ms, n=40 scans) vs. 43.5±2.5 ms (range: 39.0-47.7 ms, ?n=12 scans, P=0.74) respectively. For the six volunteers scanned with both sequences in one session, the intraclass correlation coefficient (ICC) was 0.939. Overall, the success rate of obtaining satisfactory images per acquisition was slightly over 50% for both sequence 1 and sequence 2. Satisfactory images can usually be obtained by asking the volunteer subjects to better hold their breath. However, sequence 2 did not increase the scan success rate. For the nine subjects scanned by sequence 2 with both NSA =2 and NSA =1 during one session, the ICC was 0.274, demonstrated poor agreement. T1rho measurement by ROI method and histogram had an ICC of 0.901 (P>0.05), demonstrated very good agreement. We conclude that by including 135° flip angle before and after the spin-locking RF pulse, the rate of artifacts occurring did not decrease. On the other hand, sequence 1 and sequence 2 measured similar T1rho value in healthy liver. While reducing the breath-holding duration significantly, NSA =1 did not offer satisfactory signal-to-noise ratio. Histogram measurement can be adopted for future studies. PMID:24404445

Zhao, Feng; Yuan, Jing; Deng, Min; Lu, Pu-Xuan; Ahuja, Anil T; Wang, Yi-Xiang J

2013-12-01

352

Primary biliary cirrhosis in adults.  

PubMed

Primary biliary cirrhosis (PBC) is a chronic, autoimmune, cholestatic liver disease. It is characterized by slow destruction of small intrahepatic bile ducts, impaired biliary secretion and stasis of toxic endogenous bile acids within the liver with progression to liver fibrosis and cirrhosis. It has an increasing prevalence worldwide. It occurs more commonly in women than men at a ratio of 10:1. In most cases, diagnosis relies on a positive antimitochondrial antibody in the context of chronic cholestasis, without the need for a liver biopsy. Ursodeoxycholic acid improves survival even in patients with advanced liver disease. Certain findings such as fatigue, anti-nuclear antibodies, anti-centromere antibodies and the GP210 antinuclear antibody predict a poor outcome. Up to 40% of patients do not respond satisfactorily to ursodeoxycholic acid therapy and should be considered for adjunctive therapies. Several adjunctive and newer therapies are being tested and some appear promising. We provide a review of PBC with a focus on advances in therapies that may impact the management of PBC in the near future. PMID:24580040

Momah, Njideka; Lindor, Keith D

2014-05-01

353

[Primary biliary cirrhosis and pregnancy].  

PubMed

Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease, asymptomatic during a protracted time, characterized by changes in the small-sized bile ducts near portal spaces. The etiology of PBC is undefined, but immunologic and environmental disturbances may contribute to the disease. Infertility is often associated with PBC and cirrhosis, but pregnancy may well occur in women with PBC and without cirrhosis or in some others with compensated cirrhosis. A pluridisciplinary approach including gastroenterologists and obstetricians is recommended. The patient must be closely monitored throughout her pregnancy with maternal and routine antenatal care. Medical treatment requires ursodeoxycholic acid (UDCA). In non-cirrhotic UDCA-treated women with PBC, pregnancy often follows a normal course with vaginal delivery. In cirrhotic patients, UDCA must be continued during pregnancy, esophageal and gastric varices must be evaluated before pregnancy, and endoscopic ligature is recommended for treating large varices. Additionally, beta-blocker therapy may be associated, especially when variceal rupture occurred previously. Elective cesarean section is recommended in patients with large esophageal or gastric varices because of the potentially increased risk of variceal bleeding during maternal expulsive efforts in case of vaginal delivery. PMID:23628147

Ducarme, G; Bernuau, J; Luton, D

2014-05-01

354

Autoimmune liver disease panel  

MedlinePLUS

Liver disease test panel - autoimmune ... Autoimmune disorders are a possible cause of liver disease. The most common of these diseases are autoimmune hepatitis and primary biliary cirrhosis. This group of tests helps your health care provider ...

355

Management of adult patients with ascites caused by cirrhosis  

Microsoft Academic Search

Ascites is the most common of the major complications of cirrhosis. The development of ascites is an important landmark in the natural history of cirrhosis and has been proposed as an indication for liver transplantation. The initial evaluation of a patient with ascites should include a history, physical evaluation, and abdominal paracentesis with ascitic fluid analysis. Treatment should consist of

Bruce A. Runyon

1998-01-01

356

Comorbidity in cirrhosis  

PubMed Central

Cirrhosis patients’ comorbidities are their other diseases than cirrhosis. Comorbidities are neither causes nor consequences of cirrhosis, but they can increase mortality and are therefore clinically important. They are also an important source of confounding in epidemiologic studies. Comorbidity scoring systems have been developed as tools to measure the cirrhosis patient’s total burden of comorbidity, and they are useful in the clinic and for epidemiologic studies. The recently developed CirCom score is the only comorbidity scoring system developed specifically for cirrhosis patients, and it may be preferred over the older, generic, and more complex Charlson comorbidity index. Studies of individual comorbid diseases can provide insight into the interactions between cirrhosis and other diseases and thus into the pathophysiology of cirrhosis. This article reviews the literature on comorbidity in cirrhosis. PMID:24966593

Jepsen, Peter

2014-01-01

357

Induction of molecular chaperones in carbon tetrachloride–treated rat liver: implications in protection against liver damage  

PubMed Central

Carbon tetrachloride (CCl4) induces liver damage, apparently through the formation of free-radical metabolites. Molecular chaperones such as heat shock protein (Hsp) of 70 kDa have been found to protect cells from various stresses. We previously found that cytosolic chaperone pairs of the Hsp70 family and their DnaJ homolog cochaperones prevent nitric oxide–mediated apoptosis and heat-induced cell death. Expression of cytosolic chaperones, including Hsp70; heat shock cognate (Hsc) 70; and DnaJ homologs dj1 (DjB1/Hsp40/hdj-1), dj2 (DjA1/HSDJ/hdj-2), dj3 (DjA2), and dj4 (DjA4), in the liver of CCl4-treated rats was analyzed. Messenger ribonucleic acids for all these chaperones were markedly induced 3–12 hours after CCl4 treatment with a maximum at 6 hours. Hsp70 and dj1 proteins were markedly induced at 6–24 hours with a maximum at 12 hours, whereas dj2 and dj4 were moderately induced at around 12 hours. Hsc70 was weakly induced after treatment, and dj3 was little induced. To better understand the significance of the induction of chaperones, the effect of preinduction of chaperones on CCl4-induced liver damage was analyzed. When chaperones were preinduced in the liver by heat treatment, increase in serum alanine aminotransferase activity after CCl4 treatment was significantly attenuated. Hsp90, another major cytosolic chaperone, also was induced by heat treatment. On the other hand, Mn- and Cu/Zn-superoxide dismutase were not induced by heat treatment or by CCl4 treatment. These results suggest that cytosolic chaperones of Hsp70 and DnaJ families or Hsp90 (or both) are induced in CCl4-treated rat liver to protect the hepatocytes from the damage being inflicted. PMID:15270078

Lee, Kwang-Jong; Terada, Kazutoyo; Oyadomari, Seiichi; Inomata, Yukihiro; Mori, Masataka; Gotoh, Tomomi

2004-01-01

358

Relationships between tryptophan in serum and CSF, and 5-hydroxyindoleacetic acid in CSF of man: effect of cirrhosis of liver and probenecid administration  

Microsoft Academic Search

Tryptophan was measured in the lumbar CSF and serum of patients undergoing neurological investigation (controls) and in patients with hepatic cirrhosis. Samples were taken from the fasting patients at 8:00 a.m. Under these conditions, in the controls the mean CSF, free )mpm-albumin-bound) and total serum tryptophan were in the approximate ratio 1:4:24. In this cross-sectional study, for the controls, CSF

S Lal; T L Sourkes; F Feldmuller; A Aronoff; J B Martin

1975-01-01

359

Alcoholic cirrhosis and hepatocellular carcinoma.  

PubMed

Hepatocellular carcinoma shows a rising incidence worldwide, and the largest burden of disease in Western countries derives from patients with alcoholic liver disease (ALD) and cirrhosis, the latter being the premier premalignant factor for HCC. The present chapter addresses key issues including the epidemiology of alcohol-associated HCC, and its link to other coexisting non-alcoholic liver diseases, and additional host and environmental risk factors including the underlying genetics. Also discussed are molecular mechanisms of alcohol-associated liver cancer evolution involving the mediators of alcohol toxicity and carcinogenicity, acetaldehyde and reactive oxygen species, as well as the recently described mutagenic adducts which these mediators form with DNA. Specifically, interference of alcohol with retinoids and cofactors of transmethylation processes are outlined. Information presented in this chapter illustrates that the development of HCC in the context of ALD is multifaceted and suggests several molecular targets for prevention and markers for the screening of risk groups. PMID:25427904

Stickel, Felix

2015-01-01

360

The Protective Effect of Esculentoside A on Experimental Acute Liver Injury in Mice  

PubMed Central

Inflammatory response and oxidative stress are considered to play an important role in the development of acute liver injury induced by carbon tetrachloride (CCl4) and galactosamine (GalN)/lipopolysaccharides (LPS). Esculentoside A (EsA), isolated from the Chinese herb phytolacca esculenta, has the effect of modulating immune response, cell proliferation and apoptosis as well as anti-inflammatory effects. The present study is to evaluate the protective effect of EsA on CCl4 and GalN/LPS-induced acute liver injury. In vitro, CCK-8 assays showed that EsA had no cytotoxicity, while it significantly reduced levels of TNF-? and cell death rate challenged by CCl4. Moreover, EsA treatment up-regulated PPAR-? expression of LO2 cells and reduced levels of reactive oxygen species (ROS) challenged by CCl4. In vivo, EsA prevented mice from CCl4-induced liver histopathological damage. In addition, levels of AST and ALT were significantly decreased by EsA treatment. Furthermore, the mice treated with EsA had a lower level of TNF-?, Interleukin (IL)-1? and IL-6 in mRNA expression. EsA prevented MDA release and increased GSH-Px activity in liver tissues. Immunohistochemical staining showed that over-expression of F4/80 and CD11b were markedly inhibited by EsA. The western bolt results showed that EsA significantly inhibited CCl4-induced phosphonated IkBalpha (P-I?B) and ERK. Furthermore, EsA treatment also alleviated GalN/LPS-induced acute liver injury on liver enzyme and histopathological damage. Unfortunately, our results exhibited that EsA had no effects on CCl4-induced hepatocyte apoptosis which were showed by TUNEL staining and Bax, Caspase-3 and cleaved Caspase-3 expression. Our results proved that EsA treatment attenuated CCl4 and GalN/LPS-induced acute liver injury in mice and its protective effects might be involved in inhibiting inflammatory response and oxidative stress, but not apoptosis with its underlying mechanism associated with PPAR-?, NF-?B and ERK signal pathways. PMID:25405982

Wang, Junjie; Fang, He; Wang, Zhihong; Sun, Yu; Xia, Zhaofan

2014-01-01

361

Opioid peptides and primary biliary cirrhosis  

Microsoft Academic Search

Patients with liver disease have increased plasma concentrations of the endogenous opioid peptides methionine enkephalin and leucine enkephalin. As an initial investigation to determine whether opioid peptides contribute to any of the clinical manifestations of hepatic disease nalmefene, a specific opioid antagonist devoid of agonist activity, was given to 11 patients with cirrhosis. They all experienced a severe opioid withdrawal

J. R. Thornton; M. S. Losowsky

1988-01-01

362

[Changes in the immunological indices of patients with obstructive jaundice and liver cirrhosis during the extracorporeal connection of a pig spleen].  

PubMed

The immunologic indices were studied in 29 patients with hepatic cirrhosis and obstructive jaundice, who had the porcine spleen been connected according to the conventional technique, and in 17 patients of the control group. The blood was collected in dynamics. The positive effect of the method on the immune status of the patients, which manifested itself in activation of a T-link of immunity, normalization of the indices of B-link, decrease in the severity of intoxication due to elimination of the middle molecular mass peptides and circulating immune complexes, was noted. PMID:7637283

Arynova, R S; Bazhenov, L G; Kornienko, V I

1994-01-01

363

Primary biliary cirrhosis: new perspectives in diagnosis and treatment  

PubMed Central

Primary biliary cirrhosis (PBC) is a chronic autoimmune disease characterised by cholestatic liver function tests, antimitochondrial antibodies, and abnormal liver histology. Early descriptions of a rare rapidly progressive disease no longer reflect the more indolent progress often seen today. Many patients have significant long term morbidity through symptoms such as fatigue and itch with a minority progressing to liver failure and need for transplantation. The current data on the diagnosis, clinical progression, and treatment of PBC are reviewed.???Keywords: primary biliary cirrhosis; liver transplantation; pruritus PMID:10727561

Prince, M.; Jones, D.

2000-01-01

364

Free-radical scavenging action of medicinal herbs from Ghana: Thonningia sanguinea on experimentally-induced liver injuries.  

PubMed

The antioxidant action of medicinal herbs used in Ghana for treating various ailments was evaluated in vitro and in vivo. Five plants, Desmodium adscendens, Indigofera arrecta, Trema occidentalis, Caparis erythrocarpus, and Thonningia sanguinea were tested for their free radical scavenging action by their interaction with 1,1-diphenyl-2-picrylhydrazyl (DPPH). Of these five plants, only Thonningia sanguinea was found to scavenge the DPPH radical. Lipid peroxidation in liver microsomes induced by H2O2 was also inhibited by T. sanguinea. The hepatoprotective effect of T. sanguinea was studied on acute hepatitis induced in rats by a single dose of galactosamine (GalN, 400 mg/kg, IP) and in mice by carbon tetrachloride (CCl4, 25 microl/kg, IP). GalN induced hepatotoxicity in rats as evidenced by an increase in alanine aminotransferase (ALT) and glutathione (GSH) S-transferase activities in serum was significantly inhibited when T. sanguinea extract (5 ml/kg, IP) was given to rats 12 hr and 1 hr before GalN treatment. The activity of liver microsomal GSH S-transferase, which is known to be activated by oxidative stress, was increased by the GaIN treatment and this increase was blocked by T. sanguinea pretreatment. Similarly, T. sanguinea pretreatment also inhibited CCl4-induced hepatotoxicity in mice. These data indicate that T. sanguinea is a potent antioxidant and can offer protection against GalN- or CCl4-induced hepatotoxicity. PMID:10401991

Gyamfi, M A; Yonamine, M; Aniya, Y

1999-06-01

365

Evaluation of four prescriptions of traditional Chinese medicine: Syh-Mo-Yiin, Guizhi-Fuling-Wan, Shieh-Qing-Wan and Syh-Nih-Sann on experimental acute liver damage in rats  

Microsoft Academic Search

Syh-Mo-Yiin (SMY), Guizhi-Fuling-Wan (GFW), Shieh-Qing-Wan (SQW) and Syh-Nih-Sann (SNS) are four prescriptions of Traditional Chinese Medicine (TCM) used in the remedy of liver trouble in various types. The hepatoprotective effects of water extracts of these four recipes against d-galactosamine (d-GalN) and carbon tetrachloride (CCl4)-induced acute hepatic damage were determined in rats. The results indicated that the serum glutamate-oxalate-transaminase (sGOT) and

Chin-Chuan Tsai; Chung-Te Kao; Chao-Tien Hsu; Chun-Ching Lin; Jaung-Geng Lin

1997-01-01

366

Hepatitis C Virus Network Based Classification of Hepatocellular Cirrhosis and Carcinoma  

E-print Network

Hepatitis C virus (HCV) is a main risk factor for liver cirrhosis and hepatocellular carcinoma, particularly to those patients with chronic liver disease or injury. The similar etiology leads to a high correlation of the ...

Huang, Tao

367

Serum and liver tissue bio-element levels, and antioxidant enzyme activities in carbon tetrachloride-induced hepatotoxicity: protective effects of royal jelly.  

PubMed

The liver is a vital organ, and its function is generally impaired by chemicals. Some natural compounds have a protective role against liver diseases such as royal jelly (RJ). To our knowledge, there are no data available on the effect of RJ therapy on the levels of bio-element metabolisms and antioxidant enzyme activities in the carbon tetrachloride (CCl(4))-induced liver damage. Therefore, in the present study, we have investigated the role of RJ therapy in the trace and major elements and antioxidant enzymes in CCl(4)-induced hepatotoxicity in rats. Antioxidant enzyme activities decreased in the CCl(4)-treated group more than they did in the sham and RJ-administered groups. Many bio-element levels were also reduced in only the CCl(4)-treated group. This showed that the depletion of trace elements was related to erythrocyte antioxidant enzyme activities. RJ administration clearly increased the trace and major element levels and antioxidant enzyme activities in RJ groups. RJ may be used as functional foods because of their naturally high antioxidant potential and rich element content. PMID:22510102

Cemek, Mustafa; Y?lmaz, Fatma; Büyükokuro?lu, Mehmet Emin; Büyükben, Ahmet; Aymelek, Fatih; Ayaz, Ahmet

2012-08-01

368

Hepatoprotective Effect of Otostegia persica Boiss. Shoot Extract on Carbon Tetrachloride-Induced Acute Liver Damage in Rats  

PubMed Central

In this study, the hepatoprotective effect of the methanol extract of aerial parts (shoot) from Otostegia persica Boiss (Golder) was investigated against the carbon tetrachloride (CCl4)-induced acute hepatotoxicity in male rats. Liver damage was induced through the oral administration of 50% CCl4 in liquid paraffin (2.5 mL/Kg bw, per os) 60 min after the administration of the methanol extract of O. persica shoot (in 200, 300, 400 mg/Kg bw doses) and assessed using biochemical parameters (plasma and liver tissue malondialdehyde (MDA), transaminase enzyme levels in plasma [aspartate transaminase (AST), alanine aminotransferase (ALT)] and liver glutathione (GSH) levels). Results show that the methanol extract of O. persica shoot is active at 300 mg/Kg (per os) and it possess remarkable antioxidant and hepatoprotective activities. Additionally, histopathological studies verified the effectiveness of this dose of extract in acute liver damage prevention. PMID:24250558

Nasiri Bezenjani, Sedighe; Pouraboli, Iran; Malekpour Afshar, Reza; Mohammadi, Gholamabbas

2012-01-01

369

Hepatoprotective effect of Vitis vinifera L. leaves on carbon tetrachloride-induced acute liver damage in rats.  

PubMed

The hepatoprotective effect of ethanolic extract and its four different fractions (CHCl(3), EtOAc, n-BuOH, and remaining water fraction) of Vitis vinifera L. leaves was investigated against carbon tetrachloride (CCl(4))-induced acute hepatotoxicity in rats. The ethanolic extract was found active at 125mg/kg dose (per os). The ethanolic extract was fractionated through successive solvent-solvent extractions and the n-BuOH fraction in 83mg/kg dose possessed remarkable antioxidant and hepatoprotective activities. Liver damage was assessed by using biochemical parameters (plasma and liver tissue MDA [malondialdehyde], transaminase enzyme levels in plasma [AST-aspartate transaminase, ALT-alanine transferase] and liver GSH [glutathione] levels). Additionally, the pathological changes in liver were evaluated by histopathological studies. Legalon 70 Protect was used as standard natural originated drug. PMID:17391882

Orhan, Didem Deliorman; Orhan, Nilüfer; Ergun, Ender; Ergun, Fatma

2007-05-30

370

Astragalus and Paeoniae radix rubra extract inhibits liver fibrosis by modulating the transforming growth factor-?/Smad pathway in rats  

PubMed Central

It has been previously demonstrated that Astragalus and Paeoniae radix rubra extract (APE) had a protective effect against liver fibrosis in mice. The present study aimed to investigate the hepatoprotective effect of APE on CCl4-induced hepatic fibrosis in rats. Liver fibrosis was induced in male Sprague-Dawley rats by intraperitoneal injection of 50% CCl4 twice a week for eight weeks. Organ coefficients, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), hexadecenoic acid (HA), laminin (LN), procollagen type III (PCIII), hydroxyproline (Hyp), glutathione (GSH-Px), malondialdehyde (MDA), superoxide dismutase (SOD) and transforming growth factor ?1 (TGF-?1) levels were measured in rats with hepatic fibrosis. Histopathological changes in affected livers were studied using hematoxylin-eosin and Masson’s trichrome staining. The expression of transforming growth factor-?/Smad pathway proteins, ?-smooth muscle actin (?-SMA), collagen I and collagen III was observed in fibrotic livers using western blot analysis. The present study observed significant reductions in serum levels of AST, ALT, HA, LN, PCIII and Hyp in APE-treated (2.6 and 5.2 g/kg) rats, indicating the significant hepatoprotective effects of APE. Furthermore, the depletion of GSH-Px and SOD, in addition to the accumulation of MDA in liver tissue was suppressed by APE (2.6 and 5.2 g/kg). Pathological assessment of CCl4-induced fibrotic livers revealed a significant reduction of liver injury and development of hepatic fibrosis in rats treated with APE (2.6 and 5.2 g/kg). Moreover, APE (2.6 and 5.2 g/kg) decreased the elevation of TGF-?1, ?-SMA, collagen I and collagen III expression, inhibited Smad2/3 phosphorylation as well as elevated the expression of the TGF-?1 inhibitor Smad7. These results suggested that APE may protect against liver damage and inhibit the progression of CCl4-induced hepatic fibrosis. The mechanism of action of APE is hypothesized to proceed via scavenging free radicals, decreasing TGF-?1 levels and blocking of the TGF-?/Smad signaling pathway. PMID:25373883

HUANG, WEIJUAN; LI, LIN; TIAN, XIAOPENG; YAN, JINJIN; YANG, XINZHENG; WANG, XINLONG; LIAO, GUOZHEN; QIU, GENQUAN

2015-01-01

371

Astragalus and Paeoniae radix rubra extract inhibits liver fibrosis by modulating the transforming growth factor??/Smad pathway in rats.  

PubMed

It has been previously demonstrated that Astragalus and Paeoniae radix rubra extract (APE) had a protective effect against liver fibrosis in mice. The present study aimed to investigate the hepatoprotective effect of APE on CCl4?induced hepatic fibrosis in rats. Liver fibrosis was induced in male Sprague?Dawley rats by intraperitoneal injection of 50% CCl4 twice a week for eight weeks. Organ coefficients, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), hexadecenoic acid (HA), laminin (LN), procollagen type III (PCIII), hydroxyproline (Hyp), glutathione (GSH?Px), malondialdehyde (MDA), superoxide dismutase (SOD) and transforming growth factor ?1 (TGF??1) levels were measured in rats with hepatic fibrosis. Histopathological changes in affected livers were studied using hematoxylin?eosin and Masson's trichrome staining. The expression of transforming growth factor??/Smad pathway proteins, ??smooth muscle actin (??SMA), collagen I and collagen III was observed in fibrotic livers using western blot analysis. The present study observed significant reductions in serum levels of AST, ALT, HA, LN, PCIII and Hyp in APE?treated (2.6 and 5.2 g/kg) rats, indicating the significant hepatoprotective effects of APE. Furthermore, the depletion of GSH?Px and SOD, in addition to the accumulation of MDA in liver tissue was suppressed by APE (2.6 and 5.2 g/kg). Pathological assessment of CCl4?induced fibrotic livers revealed a significant reduction of liver injury and development of hepatic fibrosis in rats treated with APE (2.6 and 5.2 g/kg). Moreover, APE (2.6 and 5.2 g/kg) decreased the elevation of TGF??1, ??SMA, collagen I and collagen III expression, inhibited Smad2/3 phosphorylation as well as elevated the expression of the TGF??1 inhibitor Smad7. These results suggested that APE may protect against liver damage and inhibit the progression of CCl4?induced hepatic fibrosis. The mechanism of action of APE is hypothesized to proceed via scavenging free radicals, decreasing TGF??1 levels and blocking of the TGF??/Smad signaling pathway. PMID:25373883

Huang, Weijuan; Li, Lin; Tian, Xiaopeng; Yan, Jinjin; Yang, Xinzheng; Wang, Xinlong; Liao, Guozhen; Qiu, Genquan

2015-02-01

372

Cyanosis with hepatic cirrhosis  

PubMed Central

A case is reported of cirrhosis of the liver associated with cyanosis and finger clubbing in a man of 31 years. The chest radiograph showed diffuse nodular shadows in both lower zones. Pulmonary function tests gave an arterial oxygen saturation of 91% at rest, falling to 68% on exercise; the single breath diffusing capacity for carbon monoxide was reduced to 55% of the predicted value and there was an estimated right-to-left shunt of 23%. Post-mortem injection of the lungs with Micropaque-gelatin suspension showed numerous pleural spider naevi, denser over the lower lobes, arteriovenous communications in the infrahilar regions, including leashes of dilated vessels in pleural adhesions on the diaphragm and diffuse arterial vasodilatation in the lungs; although the injection mass could be traced into the pulmonary veins in only a few regions of the lung, the dilated arterioles and spiders were possible additional channels through which blood might be shunted from the alveolar surfaces. The very low arterial oxygen saturation on exercise was probably caused by a shunt greater than the 23% estimated at rest, but the low diffusing capacity may have been partly responsible. The cause of the low diffusing capacity remains uncertain. Images PMID:6076512

Karlish, A. J.; Marshall, R.; Reid, Lynne; Sherlock, Sheila

1967-01-01

373