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1

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

2

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

3

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

4

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

PubMed

Ursolic acid (UA), a natural pentacyclic triterpenoid, has been reported to have many benefits and medicinal properties. However, its protective effects against carbon tetrachloride (CCl(4)) induced hepatotoxicity have not been clarified. The aim of the present study was to investigate the effects of UA on oxidative stress and inflammation in liver of CCl(4) treated mice. Male ICR mice were injected with CCl(4) with or without UA co-administration (25 and 50 mg/kg intragastrically once daily) for one week. Our data showed that UA significantly prevented CCl(4)-induced hepatotoxicity in a dose-dependent manner, indicated by both diagnostic indicators of liver damage (serum aminotransferase activities) and histopathological analysis. Moreover, CCl(4)-induced profound elevation of reactive oxygen species (ROS) production and oxidative stress, as evidenced by increasing of lipid peroxidation level and depleting of the total antioxidant capacity (TAC) level in liver, were suppressed by treatment with UA. Furthermore, western blot analysis showed that UA significantly decreased CYP2E1 expression levels and production of pro-inflammatory markers including TNF-?, IL-1? and COX-2 in CCl(4)-treated mouse liver. In exploring the underlying mechanisms of UA action, we found that UA decreased the activation of mitogen-activated protein kinases (JNK, p38 MAPK, ERK), which in turn inactivated the immunoregulatory transcription factor nuclear factor kappa B (NF-?B) in liver of CCl(4) treated mice. In conclusion, these results suggested that the inhibition of CCl(4)-induced inflammation by UA is due at least in part to its anti-oxidant activity and its ability to modulate the MAPK and NF-?B signaling pathway. PMID:24727148

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

2014-05-01

5

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

6

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

PubMed

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

7

Differential protective effects of polyphenol extracts from apple peels and fleshes against acute CCl4-induced liver damage in mice.  

PubMed

The present study reports the phenolic profiles and antioxidant and hepatoprotective properties of Red Fuji apple peel polyphenolic extract (APP) and its flesh polyphenolic extract (AFP) against CCl4-induced acute hepatic damage in mice. It was found that the polyphenol and flavonoid contents of APP were significantly higher than those of AFP. APP was shown to exhibit stronger in vitro antioxidant activities than AFP in a dose-dependent manner. Administration of APP at 250 and 500 mg per kg bw to mice ahead of CCl4 injection was further shown to exhibit stronger in vivo protective effects than those of AFP and could observably antagonize the CCl4-induced increase in serum alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase activities and hepatic malondialdehyde levels, and prevent the CCl4-caused decrease in antioxidant superoxide dismutase and glutathione peroxidase activities, compared to CCl4-treated mice (p < 0.05). This finding demonstrates that the polyphenolic extract from apple, particularly its peel, can be explored as a chemopreventive or chemotherapeutic agent against oxidative-stress-related liver disorders. PMID:25492718

Nie, Yan; Ren, Daoyuan; Lu, Xinshan; Sun, Yanfei; Yang, Xingbin

2015-02-11

8

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

PubMed

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

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

2008-07-01

9

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

PubMed Central

Background Carbon tetra chloride (CCl4), an industrial solvent, is a hepatotoxic agent and it is the well established animal model for free radical-induced liver injury. The present investigation was carried out to establish the protective effect of natansnin, a novel dibenzoyl glycoside from Salvinia natans against CCl4 induced oxidative stress and cellular degeneration in rat liver. Results CCl4 significantly increased the levels of lipid peroxides, oxidized glutathione and decreased the levels of reduced glutathione, SOD and CAT. CCl4 induce marked histopathological changes and increase in the levels of apoptotic proteins. CCl4 treatment significantly increased the levels of apoptotic proteins such as caspases-3, PARP, Bax, Bid and cytochrome C and also increased the levels of inflammatory mediators iNos and Cox-2. Natansnin treatment significantly decreased the levels of CCl4 induced apoptotic proteins and inflammatory mediators. Further natansinin treatment significantly inhibited the CCl4 induced apoptosis which was evident form the reduced TUNEL positive cells. Conclusions In conclusion, our study demonstrated the protective effect of natansnin against CCl4 induced oxidative stress and cellular degeneration in rat liver tissue. This protective effect of natansnin can be correlated to its direct antioxidant effect. PMID:20939865

2010-01-01

10

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

PubMed Central

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

2013-01-01

11

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

12

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

13

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

14

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

15

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

16

Hepatoprotective and in vitro antioxidant effect of Carthamus tinctorious L, var Annigeri-2-, an oil-yielding crop, against CCl4 -induced liver injury in rats  

PubMed Central

Background: The present investigation evaluates the hepatoprotective and in vitro antioxidant effect of methanolic extract and its isolated constituent, dehydroabietylamine, in Carthamus tinctorious L, var Annigeri-2-, an oil yielding crop. Materials and Methods: The hepatoprotective effects were estimated for the parameters viz, total bilirubin, total protein, serum alanine amino transaminase (ALT) and serum aspartate aminotransferase (AST) and alkaline phosphatase (ALP) and along with the pathological findings of hepatotoxicity. The in vitro antioxidant activity was evaluated by using free radical scavenging assays: DPPH, nitric oxide radical scavenging, hydroxyl radical, reducing power, ferrous ion chelating ability and total antioxidant capacity. Results: Both the methanolic extract (at 150 and 300 mg/kg bw) and dehydroabietylamine (at 50 mg/kg bw) showed significant liver protection against CCl4 -induced liver damage that was comparable with the standard drug, silymarin (100 mg/kg bw), in reducing the elevated serum enzyme markers. The liver sections of the animals treated with dehydroabietylamine elicit a significant liver protection compared with the methanolic extract against CCl4 -induced liver damage. Further, both the methanolic extract and dehydroabietylamine exhibited a considerable and dose-dependent scavenging activity of DPPH, nitric oxide and hydroxyl radical. Similarly, in the reducing power assay, the results were very persuasive. In addition, the Fe2+ chelating activity and the total antioxidant assay established the antioxidant property of the methanolic extract and its isolated constituent. Among the two experimental samples, dehydroabietylamine proved to be more effective for the said parameters. Conclusion: The potent antioxidant and its correlative hepatoprotective activity of the methanolic extract and isolated constituent dehydroabietylamine is therefore attributed to its antioxidant and free radical scavenging activities. PMID:22262931

Paramesha, Mahadevappa; Ramesh, Chapeyil K.; Krishna, Venkatarangaiah; Ravi Kumar, Yelegara S.; Parvathi, Karur M. M.

2011-01-01

17

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

PubMed Central

Activation of spermine/spermidine-N1-acetyltransferase (SSAT) leads to DNA damage and growth arrest in mammalian cells, and its ablation reduces the severity of ischemic and endotoxic injuries. Here we have examined the role of SSAT in the pathogenesis of toxic liver injury caused by carbon tetrachloride (CCl4). The expression and activity of SSAT increase in the liver subsequent to CCl4 administration. Furthermore, the early liver injury after CCl4 treatment was significantly attenuated in hepatocyte-specific SSAT knockout mice (Hep-SSAT-Cko) compared with wild-type (WT) mice as determined by the reduced serum alanine aminotransferase levels, decreased hepatic lipid peroxidation, and less severe liver damage. Cytochrome P450 2e1 levels remained comparable in both genotypes, suggesting that SSAT deficiency does not affect the metabolism of CCl4. Hepatocyte-specific deficiency of SSAT also modulated the induction of cytokines involved in inflammation and repair as well as leukocyte infiltration. In addition, Noxa and activated caspase 3 levels were elevated in the livers of WT compared with Hep-SSAT-Cko mice. Interestingly, the onset of cell proliferation was significantly more robust in the WT compared with Hep-SSAT Cko mice. The inhibition of polyamine oxidases protected the animals against CCl4-induced liver injury. Our studies suggest that while the abrogation of polyamine back conversion or inhibition of polyamine oxidation attenuate the early injury, they may delay the onset of hepatic regeneration. PMID:22723264

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

2012-01-01

18

Tonsil-derived Mesenchymal Stem Cells Ameliorate CCl4-induced Liver Fibrosis in Mice via Autophagy Activation.  

PubMed

Liver transplantation is the treatment of choice for chronic liver failure, although it is complicated by donor shortage, surgery-related complications, and immunological rejection. Cell transplantation is an alternative, minimally invasive treatment option with potentially fewer complications. We used human palatine tonsil as a novel source of mesenchymal stem cells (T-MSCs) and examined their ability to differentiate into hepatocyte-like cells in vivo and in vitro. Carbon tetrachloride (CCl4) mouse model was used to investigate the ability of T-MSCs to home to the site of liver injury. T-MSCs were only detected in the damaged liver, suggesting that they are disease-responsive. Differentiation of T-MSCs into hepatocyte-like cells was confirmed in vitro as determined by expression of hepatocyte markers. Next, we showed resolution of liver fibrosis by T-MSCs via reduction of TGF-? expression and collagen deposition in the liver. We hypothesized that autophagy activation was a possible mechanism for T-MSC-mediated liver recovery. In this report, we demonstrate for the first time that T-MSCs can differentiate into hepatocyte-like cells and ameliorate liver fibrosis via autophagy activation and down-regulation of TGF-?. These findings suggest that T-MSCs could be used as a novel source for stem cell therapy targeting liver diseases. PMID:25722117

Park, Minhwa; Kim, Yu-Hee; Woo, So-Youn; Lee, Hye Jin; Yu, Yeonsil; Kim, Han Su; Park, Yoon Shin; Jo, Inho; Park, Joo-Won; Jung, Sung-Chul; Lee, Hyukjin; Jeong, Byeongmoon; Ryu, Kyung-Ha

2015-01-01

19

Effect of pumpkin seed (Cucurbita pepo) protein isolate on the activity levels of certain plasma enzymes in CCl4-induced liver injury in low-protein fed rats.  

PubMed

The effects of pumpkin seed (Cucurbita pepo) protein isolate on the activity levels of lactate dehydrogenase (LD), alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP) against carbon tetrachloride (CCl4)-induced acute liver injury in low-protein fed rats were investigated. A group of male Sprague-Dawley rats maintained on a low-protein diet for 5 days were divided into three subgroups. Two subgroups were injected with carbon tetrachloride and the other group with an equivalent amount of olive oil. Two hours after CCl4 intoxication one of the two subgroups was administered with pumpkin seed protein isolate. All three subgroups of rats were maintained on the low-protein diet for the duration of the investigation. Groups of rats from the different subgroups were killed at 24, 48 and 72 h after their respective treatments. After 5 days on the low-protein diet the activity levels of all four enzymes were significantly higher than their counterparts on a normal balanced diet. CCl4 intoxication resulted in significant increases in the activity levels of all four enzymes investigated. The administration of pumpkin seed protein isolate after CCl4 intoxication resulted in significantly reduced activity levels of all four enzymes. It is concluded that pumpkin seed protein isolate administration was effective in alleviating the detrimental effects associated with protein malnutrition. PMID:16041732

Nkosi, C Z; Opoku, A R; Terblanche, S E

2005-04-01

20

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 2000 mg/kg bw, didn't show any toxicity and mortality in acute toxicity studies. During "in-vivo" study, hepatic injury was established by intraperitoneal administration of CCl4 3 ml/kg bw (30% CCl4 in olive oil; v/v) twice a week for 4 weeks in Sprague-Dawley rats. Further, hepatoprotective activity of MIL assessed using two different doses (100 and 200mg/kg bw) showed that intra-gastric administration of MIL (200mg/kg bw) 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

21

Protective Effect of L-Carnitine and Coenzyme Q10 on CCl4-Induced Liver Injury in Rats  

PubMed Central

This study provides an information about the mechanisms of liver injury induced by CCl4, and determines the influence of administration of L-carnitine or/and CoQ10 as prophylactic agents against CCl4 deteriorative effect. The study was carried out on 80 adult male albino rats divided into eight groups, 10 animals each, as follows: four normal groups (control, treated with L-carnitine, treated with CoQ10, and treated with a combination of Lcarnitine and CoQ10) and four liver injury groups treated with CCl4 (control, treated with L-carnitine, treated with CoQ10, and treated with a combination of L-carnitine and CoQ10). Liver injury was induced by s.c. injection of a single dose of CCl4 (1 ml/kg). L-carnitine (50 mg/kg/day) was given i.p. for four successive days 24 hours before CCl4 injection, and CoQ10 (200 mg/kg) was given as a single i.p. dose 24 hours before CCl4 injection. Animals were sacrificed 24 hours after CCl4 injection, blood samples were withdrawn and liver tissue samples were homogenized. The levels of the following parameters were determined: hepatic reduced glutathione, serum ALT and AST, hepatic lipid peroxides, hepatic vitamin C, hepatic and serum total protein, serum albumin, serum sialic acid, serum nitrite, and serum and hepatic total LDH activities and LDH isoenzymes. The obtained data revealed that CCl4 injection produced a significant decrease in reduced glutathione content, vitamin C, total protein and albumin levels. However, there was a significant increase in serum ALT and AST activities, lipid peroxides, sialic acid, nitric oxide, serum and hepatic total LDH activities. On the other hand, groups treated with L-carnitine or/and CoQ10 prior to CCl4 injection showed an improvement in most parameters when compared with cirrhotic control group. It has been concluded that L-carnitine and coenzyme Q10 have a pronounced prophylactic effect against liver damage induced by halogenated alkanes such as carbon tetrachloride. PMID:21179323

Ali, Sanaa Ahmed; Faddah, Lilla; Abdel-Baky, Ateff; Bayoumi, Asmaa

2010-01-01

22

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

23

Antioxidative effects of pumpkin seed (Cucurbita pepo) protein isolate in CCl4-induced liver injury in low-protein fed rats.  

PubMed

The effects of pumpkin seed (Cucurbita pepo) protein isolate on the plasma activity levels of catalase (CA), superoxide dismutase (SOD), glutathione peroxidase (GSHpx) and total antioxidant capacity (TAC) as well as glucose-6-phosphatase (G6Pase) in liver homogenates and lipid peroxidation (LPO-malondialdehyde-MDA) levels in liver homogenates and liver microsomal fractions against carbon tetrachloride (CCl(4))-induced acute liver injury in low-protein fed Sprague-Dawley rats (Rattus norvegicus) were investigated. A group of male Sprague-Dawley rats maintained on a low-protein diet for 5 days were divided into three subgroups. Two subgroups were injected with carbon tetrachloride and the other group with an equivalent amount of olive oil. Two hours after CCl(4) intoxication one of the two subgroups was administered with pumpkin seed protein isolate and thereafter switched onto a 20% pumpkin seed protein isolate diet. The other two groups of rats were maintained on the low-protein diet for the duration of the investigation. Groups of rats from the different subgroups were killed at 24, 48 and 72 h after their respective treatments. After 5 days on the low-protein diet the activity levels of all the enzymes as well as antioxidant levels were significantly lower than their counterparts on a normal balanced diet. However, a low-protein diet resulted in significantly increased levels of lipid peroxidation. The CCl(4) intoxicated rats responded in a similar way, regarding all the variables investigated, to their counterparts on a low-protein diet. The administration of pumpkin seed protein isolate after CCl(4) intoxication resulted in significantly increased levels of all the variables investigated, with the exception of the lipid peroxidation levels which were significantly decreased. From the results of the present study it is concluded that pumpkin seed protein isolate administration was effective in alleviating the detrimental effects associated with protein malnutrition and CCl(4) intoxication. It is therefore apparent that pumpkin seed protein isolate has components that have antiperoxidative properties. PMID:16909447

Nkosi, C Z; Opoku, A R; Terblanche, S E

2006-11-01

24

Pathogenesis of liver cirrhosis  

PubMed Central

Liver cirrhosis is the final pathological result of various chronic liver diseases, and fibrosis is the precursor of cirrhosis. Many types of cells, cytokines and miRNAs are involved in the initiation and progression of liver fibrosis and cirrhosis. Activation of hepatic stellate cells (HSCs) is a pivotal event in fibrosis. Defenestration and capillarization of liver sinusoidal endothelial cells are major contributing factors to hepatic dysfunction in liver cirrhosis. Activated Kupffer cells destroy hepatocytes and stimulate the activation of HSCs. Repeated cycles of apoptosis and regeneration of hepatocytes contribute to pathogenesis of cirrhosis. At the molecular level, many cytokines are involved in mediation of signaling pathways that regulate activation of HSCs and fibrogenesis. Recently, miRNAs as a post-transcriptional regulator have been found to play a key role in fibrosis and cirrhosis. Robust animal models of liver fibrosis and cirrhosis, as well as the recently identified critical cellular and molecular factors involved in the development of liver fibrosis and cirrhosis will facilitate the development of more effective therapeutic approaches for these conditions. PMID:24966602

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

2014-01-01

25

The sympathetic nervous system promotes carbon tetrachloride-induced liver cirrhosis in rats by suppressing apoptosis and enhancing the growth kinetics of regenerating hepatocytes  

Microsoft Academic Search

:   Norepinephrine is considered to possess potent anti-apoptotic action in regenerating hepatocytes. To clarify the role of\\u000a the sympathetic nervous system in apoptosis that occurs in chronic liver damage and following the promotion of liver cirrhosis,\\u000a we studied a carbon tetrachloride (CCl4)-induced liver injury model, using spontaneously hypertensive rats (SHR), Wistar-Kyoto rats (WKY), and chemically sympathectomized\\u000a WKY. At 24 h

Koumei Hamasaki; Masahiro Nakashima; Shinji Naito; Yuri Akiyama; Akira Ohtsuru; Yoichi Hamanaka; Chao-Tien Hsu; Masahiro Ito; Ichiro Sekine

2001-01-01

26

Chicory (Cichorium intybus L.) Root Extract Regulates the Oxidative Status and Antioxidant Gene Transcripts in CCl4-Induced Hepatotoxicity.  

PubMed

The ability of Cichorium intybus root extract (chicory extract) to protect against carbon tetrachloride (CCl4)-induced oxidative stress and hepatotoxicity was evaluated in male rats. The rats were divided into four groups according to treatment: saline (control); chicory extract (100 mg/kg body weight daily, given orally for 2 weeks); CCl4 (1 ml/kg body weight by intraperitoneal injection for 2 consecutive days only); or chicory extract (100 mg/kg body weight daily for 2 weeks) + CCl4 injection on days 16 and 17. The levels of hepatic lipid peroxidation, antioxidants, and molecular biomarkers were estimated twenty-four hours after the last CCl4 injection. Pretreatment with chicory extract significantly reduced CCl4-induced elevation of malondialdehyde levels and nearly normalized levels of glutathione and activity of glutathione S-transferase, glutathione peroxidase (GPx), glutathione reductase, catalase (CAT), paraoxonase-1 (PON1), and arylesterase in the liver. Chicory extract also attenuated CCl4-induced downregulation of hepatic mRNA expression levels of GPx1, CAT and PON1 genes. Results of DNA fragmentation support the ability of chicory extract to ameliorate CCl4-induced liver toxicity. Taken together, our results demonstrate that chicory extract is rich in natural antioxidants and able to attenuate CCl4-induced hepatocellular injury, likely by scavenging reactive free radicals, boosting the endogenous antioxidant defense system, and overexpressing genes encoding antioxidant enzymes. PMID:25807561

El-Sayed, Yasser S; Lebda, Mohamed A; Hassinin, Mohammed; Neoman, Saad A

2015-01-01

27

Chicory (Cichorium intybus L.) Root Extract Regulates the Oxidative Status and Antioxidant Gene Transcripts in CCl4-Induced Hepatotoxicity  

PubMed Central

The ability of Cichorium intybus root extract (chicory extract) to protect against carbon tetrachloride (CCl4)-induced oxidative stress and hepatotoxicity was evaluated in male rats. The rats were divided into four groups according to treatment: saline (control); chicory extract (100 mg/kg body weight daily, given orally for 2 weeks); CCl4 (1 ml/kg body weight by intraperitoneal injection for 2 consecutive days only); or chicory extract (100 mg/kg body weight daily for 2 weeks) + CCl4 injection on days 16 and 17. The levels of hepatic lipid peroxidation, antioxidants, and molecular biomarkers were estimated twenty-four hours after the last CCl4 injection. Pretreatment with chicory extract significantly reduced CCl4-induced elevation of malondialdehyde levels and nearly normalized levels of glutathione and activity of glutathione S-transferase, glutathione peroxidase (GPx), glutathione reductase, catalase (CAT), paraoxonase-1 (PON1), and arylesterase in the liver. Chicory extract also attenuated CCl4-induced downregulation of hepatic mRNA expression levels of GPx1, CAT and PON1 genes. Results of DNA fragmentation support the ability of chicory extract to ameliorate CCl4-induced liver toxicity. Taken together, our results demonstrate that chicory extract is rich in natural antioxidants and able to attenuate CCl4-induced hepatocellular injury, likely by scavenging reactive free radicals, boosting the endogenous antioxidant defense system, and overexpressing genes encoding antioxidant enzymes. PMID:25807561

El-Sayed, Yasser S.; Lebda, Mohamed A.; Hassinin, Mohammed; Neoman, Saad A.

2015-01-01

28

Effect of dried fruits of Solanum nigrum LINN against CCl4-induced hepatic damage in rats.  

PubMed

Ethanol extract of Solanum nigrum LINN was investigated for its hepatoprotective activity against CCl4-induced hepatic damage in rats. The ethanol extract showed remarkable hepatoprotective activity. The activity was evaluated using biochemical parameters such as serum aspartate amino transferase (AST), alanine amino transferase (ALT), alkaline phosphatase (ALP) and total bilirubin. The histopathological changes of liver sample in treated animals were compared with respect to control. PMID:14600413

Raju, Kuppuswamy; Anbuganapathi, Govindaraju; Gokulakrishnan, Velusamy; Rajkapoor, Balasubramanian; Jayakar, Balasundarm; Manian, Sellamuthu

2003-11-01

29

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. Søgaard

1987-01-01

30

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

31

Gastrointestinal dysfunction in liver cirrhosis  

PubMed Central

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

2014-01-01

32

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

33

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

34

Reversing effects of lignans on CCl4-induced hepatic CYP450 down regulation by attenuating oxidative stress.  

PubMed

Oxidative stress has been proved to be a critical reason of regulating CYP450s under hepatic injury status. The study was aimed to investigate the effect of pretreatment of schisandra lignan extracts (SLE) and dimethyl diphenyl bicarboxylate (DDB) on expressions and activities of the main liver P450 isoenzymes in CCl4 induced liver injury rats and their anti-oxidative effects on both CCl4 induced liver injury rats and a CCl4 induced HepG2 cell injury model. Acute experimental liver injury induced by CCl4 caused drastically decreasing activities of the main liver P450 isoenzymes such as CYP1A2, CYP2C6, CYP2E1 and CYP3A2, as well as their protein expressions. Pretreatment of SLE (500 mg/kg) and DDB (200 mg/kg) twice a day for three days significantly decreased the losses of activities of CYP1A2, CYP2C6, CYP2E1 and CYP3A2. Similar results were observed in protein expressions. In addition, in the CCl4 induced HepG2 cells injury model and the CYP3A activity level correlated well with ROS level in several ingredients of SLE treated groups, especially in ?-schisandrin group. These results indicated that the reversion of P450 after SLE/DDB treatment were, on one hand, due to hepatoprotective effects of these lignans on livers; on the other hand, due to their regulation of P450 through anti-oxidative effect and ?-schisandrin might be the most powerful ingredient of SLE. Also, there might be potential interactions between SLE or DDB and co-administered medicines and it is necessary to adjust the dosage of co-administrated medicines in clinical medication of liver disease. PMID:24910408

Xie, Yuan; Hao, Haiping; Wang, Hong; Guo, Cen; Kang, An; Wang, Guangji

2014-08-01

35

Embryonic liver fodrin involved in hepatic stellate cell activation and formation of regenerative nodule in liver cirrhosis  

PubMed Central

Abstract Transforming growth factor (TGF) ?1 plays a critical role in liver fibrosis. Previous studies demonstrated embryonic liver fodrin (ELF), a ?-spectrin was involved in TGF-?/Smad signalling pathway as Smad3/4 adaptor. Here we investigate the role of ELF in pathogenesis of liver cirrhosis. In carbon tetrachloride (CCl4)-induced mice model of liver cirrhosis, ELF is up-regulated in activated hepatic stellate cells (HSCs), and down-regulated in regenerative hepatocytes of cirrhotic nodules. In activated HSCs in vitro, reduction of ELF expression mediated by siRNA leads to the inhibition of HSC activation and procollagen I expression. BrdU assay demonstrates that down-regulation of ELF expression does not inhibit proliferation of activated HSCs in vitro. Immunostaining of cytokeratin 19 and Ki67 indicates that regenerative hepatocytes in cirrhotic liver are derived from hepatic progenitor cells (HPC). Further study reveals that HPC expansion occurs as an initial phase, before the reduction of ELF expression in regenerative hepatocytes. Regenerative hepatocytes in cirrhotic liver show the change in proliferative activity and expression pattern of proteins involved in G1/S transition, which suggests the deregulation of cell cycle in regenerative hepatocytes. Finally, we find that ELF participates in TGF-?/Smad signal in activated HSCs and hepatocytes through regulating the localization of Smad3/4. These data reveal that ELF is involved in HSC activation and the formation of regenerative nodules derived from HPC in cirrhotic liver. PMID:21388516

Wang, Zhijun; Liu, Fang; Tu, Wei; Chang, Ying; Yao, Jinjian; Wu, Wei; Jiang, Xiang; He, Xingxing; Lin, Jusheng; Song, Yuhu

2012-01-01

36

Arrhythmia risk in liver cirrhosis  

PubMed Central

Interactions between the functioning of the heart and the liver have been described, with heart diseases affecting the liver, liver diseases affecting the heart, and conditions that simultaneously affect both. The heart is one of the most adversely affected organs in patients with liver cirrhosis. For example, arrhythmias and electrocardiographic changes are observed in patients with liver cirrhosis. The risk for arrhythmia is influenced by factors such as cirrhotic cardiomyopathy, cardiac ion channel remodeling, electrolyte imbalances, impaired autonomic function, hepatorenal syndrome, metabolic abnormalities, advanced age, inflammatory syndrome, stressful events, impaired drug metabolism and comorbidities. Close monitoring of cirrhotic patients is needed for arrhythmias, particularly when QT interval-prolonging drugs are given, or if electrolyte imbalances or hepatorenal syndrome appear. Arrhythmia risk may persist after liver transplantation due to possible QT interval prolongation, persistence of the parasympathetic impairment, post-transplant reperfusion and chronic immunosuppression, as well as consideration of the fact that the transplant itself is a stressful event for the cardiovascular system. The aims of the present article were to provide a review of the most important data regarding the epidemiology, pathophysiology, and biomarkers of arrhythmia risk in patients with liver cirrhosis, to elucidate the association with long-term outcome, and to propose future research directions. PMID:25866603

Mozos, Ioana

2015-01-01

37

Metabonomic analysis reveals the CCl4-induced systems alterations for multiple rat organs.  

PubMed

CCl(4)-induced metabonomic changes have been extensively studied for mammalian liver, and such changes have not been reported for other organs. To investigate the CCl(4) effects on other organs, we analyzed the CCl(4)-induced metabonomic changes in rat kidney, lung, and spleen using (1)H NMR-based metabonomics approaches with complementary information on serum clinical chemistry and histopathology. We found that acute CCl(4) exposure caused significant level elevation for creatine and decline for glucose, taurine, trimethylamine, uridine, and adenosine in rat kidney. CCl(4)-treatment also induced elevation of amino acids (isoleucine, leucine, valine, threonine, alanine, lysine, ornithine, methionine, tyrosine, phenylalanine, and histidine), creatine, and betaine in rat lung together with depletion of glycogen, glucose, taurine, glycine, and hypoxanthine. Furthermore, CCl(4) caused elevation of lactate, alanine, betaine, and uracil in rat spleen accompanied with decline for glucose, choline, and hypoxanthine. These observations indicated that CCl(4) caused oxidative stresses to multiple rat organs and alterations of their functions including renal osmotic regulations, accelerated glycolysis, and protein and nucleotide catabolism. These findings provide essential information on CCl(4) toxicity to multiple rat organs and suggest that systems toxicological views are required for metabonomic studies of toxins by taking many other organs into consideration apart from so-called targeted ones. PMID:22612988

Jiang, Limiao; Huang, Jing; Wang, Yulan; Tang, Huiru

2012-07-01

38

Drinking patterns and liver cirrhosis mortality.  

PubMed

Using the 1986 National Mortality Followback Survey, alcohol consumption patterns were compared for decedents with and without mention of cirrhosis of the liver as a cause of death. Approximately 55% of cirrhosis decedents had 3 drinks or more daily (80% of decedents with alcoholic cirrhosis, and 40% of decedents with unspecified or other specified cirrhosis). In contrast, only 10% of decedents without cirrhosis had at least 3 drinks daily. Forty percent of decedents with alcoholic cirrhosis had 7 drinks or more daily, compared with 17% for unspecified cirrhosis, and 21% for other specified cirrhosis. The comparable figure was 3% for decedents without cirrhosis. An average of 3 drinks per day was associated with increased cirrhosis proportional mortality, and cirrhosis proportional mortality increased with higher numbers of daily drinks. PMID:1845557

Parrish, K M; Dufour, M C

1991-01-01

39

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

40

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 ...

41

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

42

Dendrobium candidum Wall. ex Lindl. attenuates CCl4-induced hepatic damage in imprinting control region mice  

PubMed Central

The aim of the present study was to determine the preventive effect of the traditional Chinese medicine, Dendrobium candidum Wall ex Lindl. (D. candidum), on CCl4-induced hepatic damage in mice. The CCl4-induced hepatic damage mice were treated with D. candidum, and the serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), triglyceride (TG) and total cholesterol (TC) were determined. In addition, serum cytokine levels of interleukin (IL)-6, IL-12, tumor necrosis factor (TNF)-? and interferon (IFN)-? were analyzed with kits, while liver tissues were analyzed using hematoxylin and eosin staining and reverse transcription polymerase chain reaction (RT-PCR). Furthermore, the contents of D. candidum were determined by nuclear magnetic resonance (NMR). D. candidum was demonstrated to successfully prevent hepatic damage in mice. The serum levels of AST, ALT and LDH were significantly decreased when the mice were treated with 200 and 400 mg/kg D. candidum, as compared with the control mice (P<0.05). The lowest enzymatic activities were exhibited in the 400 mg/kg D. candidum group, which produced similar results to the positive control drug, silymarin. In addition, in the 400 mg/kg D. candidum group, the highest levels of TG and TC were observed among the treated groups. D. candidum-treated groups also demonstrated reduced levels of the serum proinflammatory cytokines, IL-6, IL-12, TNF-? and IFN-?. The sections of liver tissue examined during histopathology in the high concentration 400 mg/kg D. candidum group recovered well from CCl4 damage; however, the sections in the 200 mg/kg D. candidum group revealed necrosis to a more serious degree. RT-PCR analysis was conducted on inflammation-associated genes, including nuclear factor (NF)-?B, I?B-?, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, in the livers of the mice. The 400 mg/kg D. candidum group demonstrated significantly decreased mRNA expression levels of NF-?B, iNOS and COX-2, but an increased expression level of I?B-? when compared with the CCl4-treated control group. Furthermore, using NMR, 11 compounds were identified in the D. candidum leaf, whose functional contents may aid the preventive effect observed in the current study. Therefore, D. candidum may potentially contribute to the prevention of CCl4-induced hepatic damage in vivo. PMID:25120640

LI, GUI-JIE; SUN, PENG; WANG, QIANG; QIAN, YU; ZHU, KAI; ZHAO, XIN

2014-01-01

43

HCV-associated liver cancer without cirrhosis  

Microsoft Academic Search

Chronic infection with hepatitis C virus (HCV) is regarded as a risk factor for hepatocellular cancer, mostly in patients with liver cirrhosis. We looked for HCV genomes in the livers of patients with hepatocellular cancer who did not have cirrhosis to see whether HCV was directly oncogenic. Cancerous and non-cancerous liver tissue, and serum samples from 19 patients negative for

M. S. De Mitri; E. Pisi; K. Poussin; P. Paterlini; C. Bréchot; P. Baccarini; A. D'Errico; W. Grigiani; A. Alberti; P. Pontisso; N. Simon; M. Beaugrand

1995-01-01

44

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

PubMed

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

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

2013-01-01

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

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

PubMed Central

Bamboo salt, a Korean folk medicine, is prepared with solar salt (sea salt) and baked several times at high temperatures in a bamboo case. In this study, we compared the preventive effects of bamboo salt and purified and solar salts on hepatic damage induced by carbon tetrachloride in Sprague-Dawley rats. Compared with purified and solar salts, bamboo salts prevented hepatic damage in rats, as evidenced by significantly reduced serum levels of aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase (P < 0.05). Bamboo salt (baked 9×) triggered the greatest reduction in these enzyme levels. In addition, it also reduced the levels of the proinflammatory cytokines interleukin (IL)-6, interferon (IFN)-?, and tumor necrosis factor (TNF)-?. Histopathological sections of liver tissue demonstrated the protective effect of bamboo salt, whereas sections from animals treated with the other salt groups showed a greater degree of necrosis. We also performed reverse transcription-polymerase chain reaction and western blot analyses of the inflammation-related genes iNOS, COX-2, TNF-?, and IL-1? in rat liver tissues. Bamboo salt induced a significant decrease (~80%) in mRNA and protein expression levels of COX-2, iNOS, TNF-?, and IL-1?, compared with the other salts. Thus, we found that baked bamboo salt preparations could prevent CCl4-induced hepatic damage in vivo. PMID:23964314

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

2013-01-01

50

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

51

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 ...

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

Hepatoprotective Activity of Bi-Herbal Ethanolic Extract on CCl4 Induced Hepatic Damage in Rats  

Microsoft Academic Search

The combined hepatoprotective effect of Bi- herbal ethanolic extract (BHEE) was evaluated against carbon tetra chloride (CCl4) induced hepatic damage in rats. Ethanolic extract from the leaves of Eclipta alba and seeds of Piper longum at a dose level of 50 mg\\/kg body weight was administered orally daily once for 14 days. The substantially elevated serum marker enzymes such as

P. Samudram; Rajeshwari Hari; R. Vasuki; A. Geetha; P. Sathiya Moorthi

2008-01-01

54

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

55

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

56

Preventive and curative effects of Artemisia absinthium on acetaminophen and CCl 4-induced hepatotoxicity  

Microsoft Academic Search

1.1. Effect of aqueous-methanolic extract of Artemisia absinthium (Compositae) was investigated against acetaminophen- and CCl4-induced hepatic damage.2.2. Acetaminophen produced 100% mortality at the dose of 1 g\\/kg in mice while pretreatment of animals with plant extract (500 mg\\/kg) reduced the death rate to 20%.3.3. Pretreatment of rats with plant extract (500 mg\\/kg, orally twice daily for two days) prevented (P

Anwar-Ul Hassan Gilani; Khalid Hussain Janbaz

1995-01-01

57

Prevention of CCl 4-induced nephrotoxicity with Sonchus asper in rat  

Microsoft Academic Search

Sonchus asper (SA) is locally used in renal aliments. The present work investigated the antioxidant effects of S. asper methanolic extract (SAME) against CCl4-induced nephrotoxicity in Sprague–Dawley male rats. CCl4 (3ml\\/kg b.w., i.p.; 30% in olive oil) biweekly for 4weeks induced lipid peroxidation, as reflected by significant increase of TBARS; diminished the renal antioxidant defenses, as revealed by a decrease

Rahmat Ali Khan; Muhammad Rashid Khan; Sumaira Sahreen; Jasia Bokhari

2010-01-01

58

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

59

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

60

Ultrasonographic prediction of esophageal varices in patients with liver cirrhosis  

Microsoft Academic Search

AIM: To study the value of ultrasonographic prediction of the esophageal varices in patients with liver cirrhosis. METHODS: All 207 cases were examined by ultrasonography and endoscopy, and classified according to the Child-Pugh score. The valuable ultrasonographic variables were selected to form regression formulae to predict the esophageal varices degrees in patients with liver cirrhosis. RESULTS: The esophageal varices degree

Xiao-Hong Zhang; Yu-Feng Zhang; Fang-Qin Ning; Shao-Ji Yang

61

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

62

Puerarin mediates hepatoprotection against CCl4-induced hepatic fibrosis rats through attenuation of inflammation response and amelioration of metabolic function.  

PubMed

This study was designed to evaluate the potential effects of puerarin (PR), an effective isoflavonoid compound purified from Pueraria lobata, in treating hepatic fibrosis (HF) rats induced by carbon tetrachloride (CCl(4), 2 mL kg(-1) d(-1)). Compared to model control, PR treatment effectively lowered the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (Alb), total protein (TP) in HF rats. Masson stained analysis showed that the condition of HF rats was mitigated. Meanwhile, the tumor necrosis factor alpha (TNF-?), nuclear factor-kappa B (NF-?B) expressions were significantly down-regulated at protein level by PR intervention. Additionally, the activity of superoxide dismutase (SOD) was elevated, while the content of malondialdehyde (MDA) was lessened in liver tissue. As revealed by immunohistochemistry assay, PR therapy resulted in reduced production of transforming growth factor-?l (TGF-?l). Moreover, it also was attributed to decreased mRNA level of inducible nitric oxide synthase (iNOS) using RT-PCR analysis. These findings demonstrate that puerarin successfully reverses hepatotoxicity in CCl(4)-induced HF rats via the underlying mechanisms of regulating serum enzymes and attenuating TNF-?/NF-?B pathway for anti-inflammation response, as well as improving metabolic function in liver tissue. PMID:23146695

Li, Rong; Xu, Lingyuan; Liang, Tao; Li, Yongwen; Zhang, Shijun; Duan, Xiaoqun

2013-02-01

63

Attenuation of CCl(4)-induced hepatic fibrosis by GdCl(3) treatment or dietary glycine.  

PubMed

The role of Kupffer cells in CCl(4)-induced fibrosis was investigated in vivo. Male Wistar rats were treated with phenobarbital and CCl(4) for 9 wk, and a group of rats were injected with the Kupffer cell toxicant gadolinium chloride (GdCl(3)) or were fed glycine, which inactivates Kupffer cells. After CCl(4) alone, the fibrosis score was 3.0 +/- 0.1 and collagen protein and mRNA expression were elevated, but GdCl(3) or glycine blunted these parameters. Glycine did not alter cytochrome P-450 2E1, making it unlikely that glycine affects CCl(4) metabolism. Treatment with GdCl(3) or glycine prevented CCl(4)-induced increases in transforming growth factor (TGF)-beta 1 protein levels and expression. CCl(4) treatment increased alpha-smooth muscle actin staining (score 3.0 +/- 0.2), whereas treatment with GdCl(3) and glycine during CCl(4) exposure blocked this effect (1.2 +/- 0.5); there was no staining with glycine treatment. These results support previous in vitro data and demonstrate that treatment of rats with the selective Kupffer cell toxicant GdCl(3) prevents stellate cell activation and the development of fibrosis. PMID:11408273

Rivera, C A; Bradford, B U; Hunt, K J; Adachi, Y; Schrum, L W; Koop, D R; Burchardt, E R; Rippe, R A; Thurman, R G

2001-07-01

64

Traditional extract of Pithecellobium dulce fruits protects mice against CCl(4) induced renal oxidative impairments and necrotic cell death.  

PubMed

The present study has been carried out to investigate the role of the aqueous extract of the fruits of Pithecellobium dulce (AEPD) against carbon tetrachloride (CCl(4)) induced renal oxidative injury in mice. HPLC analysis shows that AEPD contains phenolics, flavonoids and saponins as the major active components. Creatinine and blood urea nitrogen (BUN) levels were assayed to determine renal protective action of AEPD in CCl(4)-induced renal pathophysiology. Its antioxidant activity was determined by measuring radical scavenging activity, antioxidant enzymes activities, GSH content, protein carbonylation and lipid peroxidation. In addition, FACS analysis, DNA fragmentation and histological studies were carried out to determine its effect in CCl(4) induced renal oxidative injury and cell death. CCl(4) exposure increased the intracellular reactive oxygen species production, decreased intracellular antioxidant defence, reduced mitochondrial membrane potential, attenuated the intracellular ATP content and caused renal cell death mainly via the necrotic pathway as revealed by DNA fragmentation analysis. Treatment with AEPD both prior and post to the toxin exposure protected the organ from CCl(4) induced oxidative insult. Histological studies also support our results. Combining, results suggest that the protective role of AEPD against CCl(4) induced renal oxidative impairments is probably due to the antioxidative properties present in its active constituents. PMID:22424982

Pal, Pabitra Bikash; Pal, Sankhadeep; Manna, Prasenjit; Sil, Parames C

2012-04-01

65

Histological changes in the thyroid in cirrhosis of the liver  

PubMed Central

The thyroid has been examined histologically in 77 cases of cirrhosis of the liver and in an equal number of control cases. Contrary to expectation, no difference was found between the incidence or the severity of lymphocytic infiltration of the thyroid in the two groups. A conspicuous fibrosis or `cirrhosis' of the thyroid, not related to lymphocytic infiltration, was associated with cirrhosis of the liver, especially in elderly women. The significance of this lesion is not clear but its origin is probably to be sought in liver dysfunction rather than in auto-immunization. Images PMID:14479499

Nicol, A.; Sclare, G.

1962-01-01

66

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

67

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

68

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

PubMed Central

Background Launaea procumbens (L.) is traditionally used in the treatment of various human ailments including pulmonary damages. The present study was arranged to evaluate the role of Launaea procumbens methanol extract (LME) against carbon tetrachloride (CCl4) induced oxidative pulmonary damages in rat. Methods 36 Sprague–Dawley male rats (170-180?g) were randomly divided into 06 groups. After a week of acclamization, group I was remained untreated while group II was given olive oil intraperitoneally (i.p.) and dimethyl sulfoxide (DMSO) orally, groups III, IV, V and VI were administered CCl4, 3?ml/kg body weight (30% in olive oil i.p.). Groups IV, V were treated with 100?mg/kg, 200?mg/kg of LME whereas group VI was administered with 50?mg/kg body weight of rutin (RT) after 48?h of CCl4 treatment for four weeks. Antioxidant profile in lungs were evaluated by estimating the activities of antioxidant enzymes; catalase (CAT), peroxidase (POD), superoxide dismutase (SOD), glutathione-S-transferase (GST), glutathione reductase (GSR), glutathione peroxidase (GSH-Px), quinone reductase (QR) and reduced glutathione (GSH). CCl4-induced lipid peroxidation was determined by measuring the level of thiobarbituric acid reactive substances (TBARS) with conjugation of deoxyribonucleic acid (DNA) damages, argyrophilic nucleolar organizer regions (AgNORs) counts and histopathology. Results Administration of CCl4 for 6?weeks significantly (p?CCl4-induced oxidative stress possibly by improving the antioxidant defence system. PMID:22909101

2012-01-01

69

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

70

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

PubMed Central

Hawk tea (Litsea coreana Levl. var. lanuginose) is a traditional Chinese drink similar to green tea. In the present study, the preventive effects of Hawk tea on hepatic damage induced by carbon tetrachloride (CCl4) were studied in Sprague-Dawley rats. Silymarin was used as a positive control. Hawk tea was successfully shown to prevent hepatic damage in the rats. Serum levels of AST, ALT and LDH were significantly decreased when the rats were treated with varying concentrations of Hawk tea compared with silymarin (P<0.05). The lowest enzyme activities were exhibited in the 400 mg/kg Hawk tea group. This group showed reduced levels of the serum proinflammatory cytokines IL-6, IFN-? and TNF-?. In particular, the IFN-? level decreased markedly compared with the other concentration groups. The histopathology sections of liver tissue in the 400 mg/kg Hawk tea group recovered well from the CCl4 damage, but the sections of the other concentration groups showed necrosis to a more serious degree. Reverse transcription-polymerase chain reaction (RT-PCR) and western blot analyses of the inflammation-related genes iNOS, COX-2, TNF-? and IL-1? in the rat livers were tested. The 400 mg/kg Hawk tea group showed significantly decreased mRNA and protein expression levels of iNOS, COX-2, TNF-? and IL-1? compared with the control group. Accordingly, 400 mg/kg Hawk tea potentially contributes to the prevention of CCl4-induced hepatic damage in vivo. A 200 or 100 mg/kg dose of Hawk tea also demonstrated preventive effects against hepatic damage. PMID:23403509

ZHAO, XIN

2013-01-01

71

[Pain management in patients with liver cirrhosis].  

PubMed

Pain management in patients with liver cirrhosis is a real challenge and is often inadequate due to a lack of therapeutic efficacy or the high incidence of adverse effects. The focus of treatment differs depending on whether the pain is acute or chronic and involves understanding the causative pathophysiological mechanism. Analgesics should be started with the minimum effective dose and should be titrated slowly with avoidance of polypharmacy. Adverse effects must be monitored, especially sedation and constipation, which predispose the patient to the development of hepatic encephalopathy. The first-line drug is paracetamol, which is safe at doses of 2-3g/day. Non-steroidal anti-inflammatory agents are contraindicated because they can cause acute renal failure and/or gastrointestinal bleeding. Tramadol is a safe option for moderate-severe pain. The opioids with the best safety profile are fentanyl and hydromorphone, with methadone as an alternative. Topical treatment can reduce oral drug consumption. In neuropathic pain the first-line therapeutic option is gabapentin. The use of antidepressants such as amitriptyline can be considered in some patients. Interventional techniques are a valuable tool in moderate to severe pain, since they allow a reduction in drug therapy and consequently its adverse effects. Psychological treatment, physical therapy and rehabilitation should be considered as part of multimodality therapy in the management of chronic pain. PMID:24309482

Ojeda, Antonio; Moreno, Luis A

2014-01-01

72

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

73

Treatment of ascites in patients with cirrhosis of the liver  

Microsoft Academic Search

The clinical course of patients with cirrhosis of the liver is frequently complicated by the accumulation of fluid within the peritoneal cavity. The development of this complication is a consequence of a profound impairment of liver and renal function and of splanchnic and systemic hemodynamics and, not surprisingly, it is associated with a poor prognosis. The 20 month survival rate

V. Arroyo; P. Ginés; J. Rodés

1987-01-01

74

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

75

Antifibrotic effects of ZK14, a novel nitric oxide-donating biphenyldicarboxylate derivative, on rat HSC-T6 cells and CCl4-induced hepatic fibrosis  

PubMed Central

Aim: To study the pharmacologic effect of ZK14, a novel nitric oxide-donating biphenyldicarboxylate (DDB) derivative, on HSC-T6 cells and on CCl4-induced hepatic fibrosis. Methods: Inhibition of HSC-T6 cell growth by ZK14 was evaluated by MTT assay. The effect of ZK14 on the percentage of HSC-T6 cells undergoing apoptosis was measured using Annexin-V/PI double-staining and TUNEL assay. Mitochondrial membrane potential (MMP) and caspase activities were tested. Hepatic fibrosis was induced in Sprague-Dawley rats by intraperitoneal injection with 14% CCl4. Rats with hepatic fibrosis were randomly divided into four groups: model control, ZK14 (20 mg/kg), ZK14 (10 mg/kg) and DDB (5 mg/kg). Levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), hyaluronic acid (HA), type III collagen (PCIII), and nitric oxide (NO) were assessed, and liver samples were stained with hematoxylin-eosin. The NO level in cells treated with ZK14 in vitro was also measured. Results: The effect of ZK14 on HSC-T6 cell apoptosis was concentration- and time-dependent, with up to 50% of cells becoming apoptotic when exposed to 100 ?mol/L ZK14 for 18 h. ZK14 treatment resulted in mitochondrial membrane depolarization and activation of caspases 3 and 9. At a dose of 20 mg/kg, ZK14 significantly decreased serum transaminase (AST, ALT) activities and fibrotic index (HA, PCIII) levels and significantly inhibited fibrogenesis. Conclusion: These data indicate that ZK14, a novel NO-donating DDB derivative, promotes HSC-T6 apoptosis in vitro through a signaling mechanism involving mitochondria and caspase activation and it inhibits CCl4-induced hepatic fibrosis in vivo. The results suggest that ZK14 has potential therapeutic value in the treatment of hepatic fibrosis. PMID:19966836

Dai, Li; Ji, Hui; Kong, Xiang-wen; Zhang, Yi-hua

2010-01-01

76

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

PubMed Central

Background Carissa opaca are used traditionally in Pakistan for the treatment of various human ailments. Therefore, the study is arranged out to assess the cardio protective potential of different fractions of Carissa opaca leaves on CCl4-induced oxidative trauma in kidney. Methods The parameters studied in this respect were the cardiac function test (CK (U/l), CKMB (U/l), genotoxicity (% DNA fragmentation), characteristic morphological findings and antioxidant enzymatic level of cardiac tissue homogenate. Result The protective effects of various fractions of Carissa opaca (C. opaca) leaves extract against CCl4 administration was reviewed by rat cardiac functions alterations. Chronic toxicity caused by eight week treatment of CCl4 to the rats significantly changed the cardiac function test, decreased the activities of antioxidant enzymes and glutathione contents whereas significant increase was found in lipid peroxidation comparative to control group. Administration of various fractions of C. opaca leaves extract with CCl4 showed protective ability against CCl4 intoxication by restoring the cardiac functions alterations, activities of antioxidant enzymes and lipid peroxidation in rat. CCl4 induction in rats also caused DNA fragmentation and histopathalogical abnormalities which were restored by co-admistration of various fraction of C. opaca leaves extract. Conclusion Results revealed that various fraction of C. opaca are helpful in cardiac dysfunctions. PMID:24716654

2014-01-01

77

Prevention of CCl4-induced nephrotoxicity with Sonchus asper in rat.  

PubMed

Sonchus asper (SA) is locally used in renal aliments. The present work investigated the antioxidant effects of S. asper methanolic extract (SAME) against CCl(4)-induced nephrotoxicity in Sprague-Dawley male rats. CCl(4) (3 ml/kg b.w., i.p.; 30% in olive oil) biweekly for 4 weeks induced lipid peroxidation, as reflected by significant increase of TBARS; diminished the renal antioxidant defenses, as revealed by a decrease of the level of GSH, CAT, SOD, GST, GSR, GSH-Px and QR while elevated the level of gamma-GT, H(2)O(2) and nitrite contents. CCl(4) caused histopathological injuries and significantly increased the renal AgNORs count and DNA damage. Telomerase activity in kidney was determined positive with CCl(4) treatment. Creatinine, urobilinogen and urea concentration was increased whereas creatinine clearance was decreased in serum and urine. Level of protein and albumin was increased in urine while reduced in serum. Serum level of nitrite was increased with CCl(4) treatment. Treatment of rats with SAME (100, 200mg/kg b.w.) effectively ameliorated the alterations induced with CCl(4) in lipid peroxidation, antioxidant defenses, biochemical markers, genotoxicity and renal lesions. The present data suggests that SAME protect the kidneys possibly by alleviating the oxidative stress induced with CCl(4) in rat. PMID:20550952

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

2010-01-01

78

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

79

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

80

Pharmacokinetics of oltipraz in diabetic rats with liver cirrhosis  

PubMed Central

Background and purpose: The incidence of diabetes mellitus is increased in patients with liver cirrhosis. Oltipraz is currently in trials to treat patients with liver fibrosis and cirrhosis induced by chronic hepatitis types B and C and is primarily metabolized via hepatic cytochrome P450 isozymes CYP1A1/2, 2B1/2, 2C11, 2D1 and 3A1/2 in rats. We have studied the influence of diabetes mellitus on pharmacokinetics of oltipraz and on expression of hepatic, CYP1A, 2B1/2, 2C11, 2D and 3A in rats with experimental liver cirrhosis. Experimental approach: Oltipraz was given intravenously (10 mg·kg?1) or orally (30 mg·kg?1) to rats with liver cirrhosis induced by N-dimethylnitrosamine (LC rats) or with diabetes, induced by streptozotocin (DM rats) or to rats with both liver cirrhosis and diabetes (LCD rats) and to control rats, and pharmacokinetic variables measured. Protein expression of hepatic CYP1A, 2B1/2, 2C11, 2D and 3A was measured using Western blot analysis. Key results: After i.v. or p.o. administration of oltipraz to LC and DM rats, the AUC was significantly greater and smaller, respectively, than that in control rats. In LCD rats, the AUC was that of LC and DM rats (partially restored towards control rats). Compared with control rats, the protein expression of hepatic CYP1A increased, that of CYP2C11 and 3A decreased, but that of CYP2B1/2 and 2D was not altered in LCD rats. Conclusions and implications: In rats with diabetes and liver cirrhosis, the AUC of oltipraz was partially restored towards that of control rats. PMID:19226288

Ahn, CY; Bae, SK; Bae, SH; Kim, T; Jung, YS; Kim, YC; Lee, MG; Shin, WG

2009-01-01

81

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

82

Profiling of Human Serum Glycans Associated with Liver Cancer and Cirrhosis by IMS-MS  

E-print Network

Profiling of Human Serum Glycans Associated with Liver Cancer and Cirrhosis by IMS-MS D. Isailovic healthy control patients and 39 individuals with known diseases (20 with cirrhosis of the liver and 19 to distinguish patients with liver cancer or cirrhosis. Measurements of glycan conformational and isomeric

Clemmer, David E.

83

Protective effect of Cucurbita pepo fruit peel against CCl4 induced neurotoxicity in rat.  

PubMed

Cucurbita pepo is a common vegetable used all over the world. In folk medicine it is used in gastroenteritis, hepatorenal and in brain anomalies. In the present study, protective effect of Cucurbita pepo fruit peel against CCl4-induced neurotoxicity in rats was investigated. In this study, 36 Sprague-Dawley female rats (190±15 g) were randomly divided into 6 groups of 6 rats each. Group I was given 1 ml/kg bw (body weight) of corn oil intraperotoneally (i.p); Group II, III and IV were treated with 20% CCl4 in corn oil (1ml/kg bw i.p.). However, animals of Group III and IV were also treated with CPME (methanol extract of C. pepo fruit peel) at 200 and 400mg/kg bw respectively. Animals of Group V and VI were administered only with CPME at 200 and 400mg/kg bw respectively. These treatments were administered 3 days a week for two weeks. Administration of CCl4 cause acute neurotoxicity as depicted by significant depletion (p<0.05) in the activities of antioxidant enzymes; catalase, superoxide dismutase, peroxidase, glutathione reductase, glutathione-S-transferase, glutathione peroxidase, quinone reductase, while enhanced the ?-glutamyl transferase level in brain samples. CCl4 intoxication decreased the reduced glutathione (GSH) level whereas markedly (p<0.05) enhanced lipid peroxidation in brain samples. Co-treatment of CPME significantly (p<0.05) protected the brain tissues against CCl4 constituted injuries by restoring activities of antioxidant enzymes and ameliorated lipid peroxidation in a dose dependent fashion. These neuroprotective effects might be due to the presence of antioxidant constituents. PMID:25362619

Zaib, Sania; Khan, Muhammad Rashid

2014-11-01

84

Prevention of CCl(4)-induced oxidative damage in adrenal gland by Digera muricata extract in rat.  

PubMed

Digera muricata (L.) Mart. is a weed and commonly found in waste places, road sides and in maize fields during the summer season. It possesses antioxidant capacity and is locally used for various disorders such as inflammation, urination, as refrigerant, aperient and in sexual anomalies. In this study antioxidant potential of Digera muricata methanol extract (DMME) and n-hexane extract (DMHE) was evaluated against CCl(4)-induced oxidative stress in adrenal gland of Sprague-Dawley male rats. 42 rats were equally divided into 7 groups of 6 rats in each. Group I remained untreated, while Group II treated with vehicles. Group III received only CCl(4) (1 ml/kg b.w., 10% in olive oil) once a week for 16 weeks. Group IV and VI received DMME and DMHE at a dose of 200 mg/kg b.w. along with CCl(4). Animals of Group V and VII administered with DMME and DMHE alone at a dose of 200 mg/kg b.w. once a week for 16 weeks. Lipid peroxidation significantly increased while activities of antioxidant enzymes (CAT, SOD, GST, GSR and GSH-Px) were reduced in adrenal gland samples by the administration of CCl(4). Glutathione (GSH) concentration was significantly decreased whereas DNA fragmentation% and AgNORs count was increased in adrenal gland by CCl(4) administration. Treatment of rat by both the extracts (DMME, DMHE) and CCl(4) increased the glutathione level and activities of antioxidant enzymes while reduced the lipid peroxidation, DNA fragmentation percent and AgNORs count in adrenal gland. These results indicate that Digera muricata extract is able to ameliorate oxidative stress in adrenal gland induced by CCl(4) in rat. PMID:21959806

Khan, Muhammad Rashid; Younus, Tahira

2011-10-01

85

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

86

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

87

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

88

Diagnosis of fibrosis and cirrhosis using liver stiffness measurement in nonalcoholic fatty liver disease  

Microsoft Academic Search

edinghen 3,4 Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases in affluent countries. Accurate noninvasive tests for liver injury are urgently needed. The aim of this study was to evaluate the accuracy of transient elastography for the diagnosis of fibrosis and cirrhosis in patients with NAFLD and to study factors associated with discordance between transient

Vincent Wai-Sun Wong; Julien Vergniol; Grace Lai-Hung Wong; Juliette Foucher; Henry Lik-Yuen Chan; Brigitte Le Bail; Paul Cheung-Lung Choi; Mathurin Kowo; Anthony Wing-Hung Chan; Wassil Merrouche; Joseph Jao-Yiu Sung; Victor de Lédinghen

2009-01-01

89

Progression from idiopathic portal hypertension to incomplete septal cirrhosis with liver failure requiring liver transplantation  

Microsoft Academic Search

We report the case of a 30-year-old male patient suffering from what was initially thought to be end-stage cryptogenic cirrhosis with portal hypertension and liver failure, who underwent liver transplantation. Histological examination of the surgical specimen showed incomplete septal cirrhosis. At the age of 17 this patient had presented pancytopenia and splenomegaly, which were treated by splenetomy. The surgeon discovered

Pierre-Henri Bernard; Brigitte Le Bail; Martine Cransac; Maria Garcia Barcina; Jacques Carles; Charles Balabaud; Paulette Bioulas-Sage

1995-01-01

90

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

91

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

92

Liver surgery in the presence of cirrhosis or steatosis: Is morbidity increased?  

Microsoft Academic Search

BACKGROUND DATA: The prevalence of steatosis and hepatitis-related liver cirrhosis is dramatically increasing together worldwide. Cirrhosis and, more recently, steatosis are recognized as a clinically important feature that influences patient morbidity and mortality after hepatic resection when compared with patients with healthy liver. OBJECTIVE: To review present knowledge regarding how the presence of cirrhosis or steatosis can influence postoperative outcome

Lucas McCormack; Pablo Capitanich; Emilio Quiñonez

2008-01-01

93

Signal changes in liver and spleen after Endorem administration in patients with and without liver cirrhosis.  

PubMed

The goal of this study was compare the effect of Endorem on the signal intensity of the spleen in patients with normal liver tissue and in patients with liver cirrhosis. Thirty patients with normal liver tissue and 47 with liver cirrhosis were examined before and after i.v. Endorem administration. The patients were examined with a 1.5-T magnet system (Magnetom Vision) using a semiflexible cp-array coil. Three different pulse sequences were used: a T1-weighted gradient-echo sequence, a T2-weighted fast spin-echo sequence with spectral fat suppression, and a T2*-weighted gradient-echo sequence. The signal-to-noise ratios (SNRs) of two areas of the liver and spleen were determined. The mean SNRs of the liver and spleen in patients with and without liver cirrhosis were compared. For assessment of statistical significance, the t-test at a level of P < 0.05 was applied. After i.v. administration of Endorem, no differences were seen with the T1-weighted gradient-echo sequence for the liver and spleen and, with the T2-weighted fast spin-echo sequence, no differences were found for the spleen. Significant differences between both groups were seen for the liver with the T2-weighted fast spin-echo sequence. The SNR in the noncirrhotic liver group was 57.4% lower than the SNR in the cirrhotic liver group. With the T2*-weighted gradient-echo sequence, the SNRs of the liver and spleen in the noncirrhotic liver group, compared with the cirrhotic liver group, were 126.8% and 45.6% less, respectively. The effect of Endorem on the liver in patients with Child C-stage liver cirrhosis was 32.1% less than in patients with Child B-stage liver cirrhosis. Likewise, the Endorem effect on the spleen was 27.1% less in patients with Child C-stage compared with Child B-stage liver cirrhosis. Hepatic and splenic uptake of Endorem is significantly decreased in patients with liver cirrhosis. PMID:10756987

Hundt, W; Petsch, R; Helmberger, T; Reiser, M

2000-01-01

94

[Anemic syndrome in chronic hepatitis and liver cirrhosis].  

PubMed

Regularities in the development of anemia in patients with chronic hepatitis or hepato-cirrhosis were studied with regard to the pattern and stage of the affection of the liver. The impact of inefficient erythropoiesis on anemia development in patients with chronic diffuse diseases of the liver was demonstrated. Reasons of the red cells imperfection that caused their rapid hemolysis were indicated. In the bone marrow of chronically ill patients there were lower levels of early precursors of erythropoiesis with their proliferative activity reduced. On the basis of the data obtained the authors gave practical recommendations for anemia treatment. PMID:8301986

Korolko, Iu R; Sarycheva, T G; Kotel?ikov, V M; Kozinets, G I; Zherebtsov, L A

1993-01-01

95

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

PubMed

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

Raj, Sreena; Gothandam, K M

2014-05-01

96

Hepatoprotective effects of Lycium chinense Miller fruit and its constituent betaine in CCl4-induced hepatic damage in rats.  

PubMed

The hepatoprotective activities of Lycium chinense Miller (LC) fruit extract and its component betaine were investigated under carbon tetrachloride (CCl4)-induced hepatotoxicity in rats. The treatment of LC fruit extract significantly suppressed the increase of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the sera of CCl4 injured rats, and restored the decreased levels of anti-oxidant enzymes such as total antioxidant capacity (TAC), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) and suppressed the expression of inflammatory mediators including inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-1 and -2. To visualize the potential activity of betaine, a component of LC fruit, betaine was substituted for LC extract in CCl4 injured rats. The biochemical profile in CCl4 injured rats co-treated with betaine matched those of LC fruit treated CCl4 injured rats. The ameliorative effects of LC extract, as well as betaine, were also confirmed by histopathological examination. Collectively, the present findings imply that LC fruit, via its component betaine, mitigate CCl4-induced hepatic injury by increasing antioxidative activity and decreasing inflammatory mediators including iNOS and COX-1/COX-2. PMID:24998029

Ahn, Meejung; Park, Jong Sang; Chae, Sungwook; Kim, Seungjoon; Moon, Changjong; Hyun, Jin Won; Shin, Taekyun

2014-07-01

97

Quantitative Analysis of Aldolase A mRNA in Liver Discriminates between Hepatocellular Carcinoma and Cirrhosis  

Microsoft Academic Search

Background: Chronic liver diseases can progress to cirrhosis and to hepatocellular carcinoma. Timely and unequivocal recognition of the neoplastic evolution of cirrhosis is critical. To this aim, we used a noncompet- itive reverse transcription-PCR procedure to analyze aldolase A mRNA in liver tissue from patients with chronic liver diseases at different stages. Methods: We studied 12 patients with hepatocellular carcinoma,

Giuseppe Castaldo; Giuseppe Calcagno; Raffaella Sibillo; Rosario Cuomo; Gerardo Nardone; Luigi Castellano; Camillo Del Vecchio Blanco; Gabriele Budillon; Francesco Salvatore

2000-01-01

98

Liver transplantation in patients with liver cirrhosis and active pneumonia: an observational study.  

PubMed

Patients with chronic liver disease are at high risk for severe infection because of increased bacterial translocation and immune suppression associated with liver dysfunction. Patients presenting with severe pneumonia and acute decompensation of cirrhosis are generally not considered for liver transplantation because it is unknown if these patients can recover from infection while under immunosuppression. We performed an observational study where patients with cirrhosis of the liver remained on the waiting list, although suffering from active pneumonia. Nine patients were included, but only six patients improved under goal-directed therapy and subsequently underwent liver transplantation. All six patients recovered quickly from infection; five patients recovered without sequelae and one patient died because of late complications. We propose that in patients with chronic liver disease and active pneumonia transplantation is a treatment option that should not hastily be abandoned. PMID:21883503

Goralczyk, Armin D; Abu-Ajaj, Wijdan; Tsui, Tung Yu; Bauer, Martin; Lorf, Thomas; Ramadori, Giuliano; Obed, Aiman

2011-11-01

99

Gut Microbiota Dysbiosis Is Associated with Inflammation and Bacterial Translocation in Mice with CCl4-Induced Fibrosis  

PubMed Central

Background Gut is the major source of endogenous bacteria causing infections in advanced cirrhosis. Intestinal barrier dysfunction has been described in cirrhosis and account for an increased bacterial translocation rate. Hypothesis and Aims We hypothesize that microbiota composition may be affected and change along with the induction of experimental cirrhosis, affecting the inflammatory response. Animals and Methods Progressive liver damage was induced in Balb/c mice by weight-controlled oral administration of carbon tetrachloride. Laparotomies were performed at weeks 6, 10, 13 and 16 in a subgroup of treated mice (n?=?6/week) and control animals (n?=?4/week). Liver tissue specimens, mesenteric lymph nodes, intestinal content and blood were collected at laparotomies. Fibrosis grade, pro-fibrogenic genes expression, gut bacterial composition, bacterial translocation, host's specific butyrate-receptor GPR-43 and serum cytokine levels were measured. Results Expression of pro-fibrogenic markers was significantly increased compared with control animals and correlated with the accumulated dose of carbon tetrachloride. Bacterial translocation episodes were less frequent in control mice than in treated animals. Gram-positive anaerobic Clostridia spp count was decreased in treated mice compared with control animals and with other gut common bacterial species, altering the aerobic/anaerobic ratio. This fact was associated with a decreased gene expression of GPR43 in neutrophils of treated mice and inversely correlated with TNF-alpha and IL-6 up-regulation in serum of treated mice along the study protocol. This pro-inflammatory scenario favoured blood bacterial translocation in treated animals, showing the highest bacterial translocation rate and aerobic/anaerobic ratio at the same weeks. Conclusions Gut microbiota alterations are associated with the development of an inflammatory environment, fibrosis progression and bacterial translocation in carbon tetrachloride-treated mice. PMID:21829583

Gómez-Hurtado, Isabel; Santacruz, Arlette; Peiró, Gloria; Zapater, Pedro; Gutiérrez, Ana; Pérez-Mateo, Miguel; Sanz, Yolanda; Francés, Rubén

2011-01-01

100

Late evening snack and the change of blood glucose level in patients with liver cirrhosis  

Microsoft Academic Search

It has been reported that patients with liver cirrhosis suffer from energy malnutrition and late evening snacks (LES) can be effective for this malnutrition. On the other hand, it is also known that some patients with liver cirrhosis have glucose intolerance as a complication. We have shown that 1 week LES treatment using as an oral supplement with branched chain

Isao Sakaida; Masako Tsuchiya; Mariko Okamoto; Kiwamu Okita

2004-01-01

101

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

102

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

103

Natural History of Clinically Compensated Hepatitis C Virus–Related Graft Cirrhosis After Liver Transplantation  

Microsoft Academic Search

The natural history of clinically compensated hepatitis C virus (HCV) cirrhosis after liver transplantation is unknown. This information is relevant to transplant centers to improve the management of these patients and decide the optimal timing for retransplantation. The aims of the study were (1) to describe the natural history of patients with HCV-cirrhosis transplants in a center with annual liver

Marina Berenguer; Mart??n Prieto; José M Rayón; Julio Mora; Miguel Pastor; Vicente Ortiz; Domingo Carrasco; Manuel-de-Juan Burgueño; José Mir; Joaqu??n Berenguer

2000-01-01

104

Diagnostic Value of Plasma Cystatin Ca s a Glomerular Filtration Marker in Decompensated Liver Cirrhosis  

Microsoft Academic Search

Background: Plasma creatinine concentration and cal- culated creatinine clearance are of limited value as glomerular filtration rate (GFR) markers in patients with decompensated liver cirrhosis. We assessed plasma cystatin C as an indicator of GFR in such patients. Methods: We studied 36 patients with decompensated liver cirrhosis and 56 noncirrhotic controls, both groups including individuals with normal and impaired renal

Rocco Orlando; Michele Mussap; Mario Plebani; Pierpaolo Piccoli; Sara De Martin; Maura Floreani; Roberto Padrini; Pietro Palatini

2002-01-01

105

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

106

Gut-liver axis in liver cirrhosis: How to manage leaky gut and endotoxemia  

PubMed Central

A “leaky gut” may be the cutting edge for the passage of toxins, antigens or bacteria into the body, and may play a pathogenic role in advanced liver cirrhosis and its complications. Plasma endotoxin levels have been admitted as a surrogate marker of bacterial translocation and close relations of endotoxemia to hyperdynamic circulation, portal hypertension, renal, cardiac, pulmonary and coagulation disturbances have been reported. Bacterial overgrowth, increased intestinal permeability, failure to inactivate endotoxin, activated innate immunity are all likely to play a role in the pathological states of bacterial translocation. Therapeutic approach by management of the gut-liver axis by antibiotics, probiotics, synbiotics, prebiotics and their combinations may improve the clinical course of cirrhotic patients. Special concern should be paid on anti-endotoxin treatment. Adequate management of the gut-liver axis may be effective for prevention of liver cirrhosis itself by inhibiting the progression of fibrosis. PMID:25848468

Fukui, Hiroshi

2015-01-01

107

Gut-liver axis in liver cirrhosis: How to manage leaky gut and endotoxemia.  

PubMed

A "leaky gut" may be the cutting edge for the passage of toxins, antigens or bacteria into the body, and may play a pathogenic role in advanced liver cirrhosis and its complications. Plasma endotoxin levels have been admitted as a surrogate marker of bacterial translocation and close relations of endotoxemia to hyperdynamic circulation, portal hypertension, renal, cardiac, pulmonary and coagulation disturbances have been reported. Bacterial overgrowth, increased intestinal permeability, failure to inactivate endotoxin, activated innate immunity are all likely to play a role in the pathological states of bacterial translocation. Therapeutic approach by management of the gut-liver axis by antibiotics, probiotics, synbiotics, prebiotics and their combinations may improve the clinical course of cirrhotic patients. Special concern should be paid on anti-endotoxin treatment. Adequate management of the gut-liver axis may be effective for prevention of liver cirrhosis itself by inhibiting the progression of fibrosis. PMID:25848468

Fukui, Hiroshi

2015-03-27

108

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

Microsoft Academic Search

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

Mohammad R. Taheri; Thomas R. Riley III

109

Liver collagen in cirrhosis correlates with portal hypertension and liver dysfunction.  

PubMed

Liver collagen proportionate area (CPA) assessed by computer-assisted digital image analysis has been proposed as an accurate and objective histological variable for subclassifying cirrhosis. The study aimed to examine the relationship between CPA and relevant clinical parameters in cirrhotic patients and to evaluate the sampling variability for CPA. The study included 48 consecutive liver transplantation patients with established cirrhosis. Hepatic venous pressure gradient (HVPG) and serum markers of liver failure were determined prior to transplantation. CPA was assessed in the explanted livers. In 20 of the livers, CPA was measured in more than one tissue sample. CPA showed significant correlations with HVPG and with various surrogate markers of hepatic dysfunction including albumin, bilirubin, INR, MELD score and Child-Pugh score. CPA reliably discriminated HVPG ?10 mmHg, termed 'clinically significant portal hypertension' (area under receiver operator curve: 0.923, p < 0.001; odds ratio: 1.209, p = 0.003). CPA measured on tissue blocks showed no significant sampling variability (p > 0.5). In conclusion, the study correlated portal hypertension and hepatic dysfunction with the amount of collagen in cirrhotic livers. The findings support the presumption of CPA as a useful histological marker for subclassifying cirrhosis and as a helpful supplement to the qualitative description of hepatic architectural changes in routine pathology. PMID:25053449

Nielsen, Kåre; Clemmesen, Jens Otto; Vassiliadis, Efstathios; Vainer, Ben

2014-12-01

110

68 FR 42602 - Presumption of Service Connection for Cirrhosis of the Liver in Former Prisoners of War  

Federal Register 2010, 2011, 2012, 2013, 2014

...Service Connection for Cirrhosis of the Liver in Former Prisoners of War AGENCY: Department...certain diseases by adding cirrhosis of the liver to the list of diseases for which entitlement...adjudication regulations to add cirrhosis of the liver to the list of diseases for which...

2003-07-18

111

Predictors of liver failure in primary biliary cirrhosis.  

PubMed

Abstract Background. The disease progression of patients with primary biliary cirrhosis (PBC) varies significantly, and the prognostic markers that identify those patients who will develop liver failure have been scarcely studied from a Chinese cohort. Aims. We aimed to determine the predictive factors of liver failure in patients with PBC. Methods. Patients who were first diagnosed as PBC with hepatic compensation between January 2007 and December 2009 were enrolled in this cohort study. Results. Altogether 398 patients were finally included. Of these patients, 80% were women, 98% had positive antimitochondrial antibodies, and 45% had positive antinuclear antibodies (ANA). To December 2012, a total of 38 patients developed liver failure. According to the outcome, patients who developed liver failure had had higher serum concentration of baseline total bilirubin (TBil) (p = 0.013) and total bile acid (TBA) (p < 0.001), and lower concentrations of baseline total cholesterol (Tch) (p = 0.008), than patients who did not develop liver failure. Additionally, the proportion of ANA positivity was statistically different between the two groups (p = 0.009). In the established model for predicting liver failure in PBC, three variables were finally selected out, including Tch (odds ratio (OR) 0.552, 95% confidence interval (CI) 0.394-0.774, p < 0.001), TBA (OR 1.006, 95% CI 1.002-1.010, p = 0.002), and ANA (+ versus -, OR 5.518, 95% CI 1.155-26.376, p = 0.032). Conclusions. ANA, Tch, and TBA are predictors of liver failure in PBC. PMID:25430562

Zhao, Pan; Liu, Wei-Wei; Li, Jin-Feng; Wang, Chun-Ya; Wang, Hao; Xu, Jun; Wang, Rui-Fang; Yang, Hao-Zhen; Jin, Cheng; Wei, Zhen-Man

2015-03-01

112

Hepatoprotective activity of leaves of Rhododendron arboreum in CCl4 induced hepatotoxicity in rats  

Microsoft Academic Search

The study was designed to evaluate the hepatoprotective activity of pre-treatment with ethanolic extract of leaves of Rhododendron arboreum against carbon tetrachloride-induced hepatotoxicity in Wistar rat model. Liver damage was induced in experimental animals by administering CCl4. The ethanolic extract of R. arboreum (40, 60 and 100 mg\\/kg, po) was given for five days. Silymarin (100 mg\\/kg, po) was given

T. Prakash; Snehal Dayalal Fadadu; Uday Raj Sharma; V. Surendra; Divakar Goli; Perfect Stamin; D. Kotresha

113

Amiodarone-Induced Cirrhosis of Liver: What Predicts Mortality?  

PubMed Central

Introduction. Amiodarone has been used for more than 5 decades for the treatment of various tachyarrhythmias and previously for the treatment of refractory angina. There are multiple well-established side effects of amiodarone. However, amiodarone-induced cirrhosis (AIC) of liver is an underrecognized complication. Methods. A systematic search of Medline from January 1970 to November 2012 by using the following terms, amiodarone and cirrhosis, identified 37 reported cases of which 30 were used in this analysis. Patients were divided into 2 subsets, survivors versus nonsurvivors, at 5 months. Results. Aspartate aminotransferase was significantly lower (P = 0.03) in patients who survived at 5-months (mean 103.33?IU/L) compared to nonsurvivors (mean 216.88?IU/L). There was no statistical difference in the levels of prothrombin time, total bilirubin, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, cumulative dose, and latency period between the two groups. The prevalence of DM, HTN, HLD, CAD, and CHF was similar in the two groups. None of the above-mentioned variables could be identified as a predictor of survival at 5 months. Conclusion. AIC carries a mortality risk of 60% at 5 months once the diagnosis is established. Further prospective studies are needed to identify predictors of AIC and of mortality or survival in cases of AIC. PMID:23577267

Hussain, Nasir

2013-01-01

114

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

PubMed Central

Introduction People with cirrhosis of the liver are predisposed to developing oral lesions. The occurrence and type of lesion depend on the degree of liver function impairment and its type, and on the severity and duration of systemic diseases. In children, the age at which the early symptoms of liver disease are experienced is also of great importance. Aim To assess the prevalence of oral pathological lesions in children and adolescents with cirrhosis of the liver, and their correlation with the degree of liver function impairment. Material and methods Clinical and laboratory results of liver function tests (Model of End-Stage Liver Disease/Score of Paediatric End-Stage Liver Disease, Child-Pugh score) were assessed in 35 patients with cirrhosis of the liver. The average age of the patients was 10.7 ±4.74 years. All patients also had their oral cavities examined (mucosa, gingiva – GI, hygiene – PLI, teeth – dmft/dmfs and DMFt/DMFs, DDE Index and Candida spp. presence) and this was then correlated to the degree of liver function impairment. Results According to the Child-Pugh scale, 16 patients were class A and 19 were class B/C. Jaundice during the first 3 years of life occurred in 9 patients. Mucosal lesions were found in 26 out of 35 patients (74%), including 10 out of 16 (63%) in Child-Pugh group A, and 16 out of 19 (84%) in group B/C (NS – non significant). Oral candidiasis occurred more often in class B/C than in class A (47.4% vs. 12.5%; p < 0.05). The GI index (Gingival Index) and PLI index (Dental Plaque Index) did not differ between the groups (A vs. B/C) but correlated in the whole group (R = 0.58) as well as in subgroups A (R = 0.65) and B/C (R = 0.59). Dmft/dmfs and DMFt/DMFs indexes did not differ between groups A and B/C, and neither did the DMFt/DMFs in patients with/without enamel defects. Conclusions Oral mucosal lesions are commonly found in children with cirrhosis of the liver. Advanced liver disease promotes oral candidiasis. Severity of gingivitis correlates with the presence of dental plaque. PMID:24868295

Kowalczyk, Wojciech; Krasuska-S?awi?ska, Ewa; D?dalski, Maciej; Kostewicz, Krzysztof; Paw?owska, Joanna

2014-01-01

115

Immune complex type glomerulonephritis in cirrhosis of the liver.  

PubMed Central

Glomerular lesions were detected in 9 of 10 patients with liver cirrhosis: these lesions consisted of a) thickening of basement-membrane-like material, b) electron-dense deposits in mesangial areas and in capillary walls, c) round areas of rarefaction in the membrane-like material and in some deposits, and d) presence of IgA, with IgG and/or IgM and/or C3, in the deposits. The association of these four abnormalities seems to be characteristic of "cirrhotic glomerulonephritis." The deposits could be the result of precipitation in the glomeruli of either aggregated immunoglobulins or circulating immune complexes. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:126021

Callard, P.; Feldmann, G.; Prandi, D.; Belair, M. F.; Mandet, C.; Weiss, Y.; Druet, P.; Benhamou, J. P.; Bariety, J.

1975-01-01

116

Hyperkalemia due to hyporeninemic hypoaldosteronism with liver cirrhosis and hypertension.  

PubMed

A 49-year-old man with liver cirrhosis and hypertension was found to have hyperkalemia out of a degree of renal insufficiency and metabolic acidosis with low to normal anion gap, aggravated by volume contraction with diarrhea and medications (captopril, spironolactone and atenolol) interfering with potassium homeostasis. Plasma renin activity and serum aldosterone levels of this patient on a regular diet after discontinuation of medications were very low compared to those of five other cirrhotic patients with normokalemia as controls. Also, the renin-aldosterone stimulation testing on this patient performed by sodium restricted diet and furosemide, upright position and by angiotensin converting enzyme inhibition (captopril, 50 mg) showed the blunted renin and aldosterone responses to each of these stimuli, almost no changes from baseline renin and aldosterone levels, it was concluded that the underlying defect responsible for hyperkalemia in this case was hyporeninemic hypoaldosteronism and this was aggravated by other factors or drugs affecting potassium homeostasis. PMID:8179835

Kee, C S; Choi, J W; Chang, D K; Ahn, Y H; Kim, H J

1993-12-01

117

Hyperkalemia due to hyporeninemic hypoaldosteronism with liver cirrhosis and hypertension.  

PubMed Central

A 49-year-old man with liver cirrhosis and hypertension was found to have hyperkalemia out of a degree of renal insufficiency and metabolic acidosis with low to normal anion gap, aggravated by volume contraction with diarrhea and medications (captopril, spironolactone and atenolol) interfering with potassium homeostasis. Plasma renin activity and serum aldosterone levels of this patient on a regular diet after discontinuation of medications were very low compared to those of five other cirrhotic patients with normokalemia as controls. Also, the renin-aldosterone stimulation testing on this patient performed by sodium restricted diet and furosemide, upright position and by angiotensin converting enzyme inhibition (captopril, 50 mg) showed the blunted renin and aldosterone responses to each of these stimuli, almost no changes from baseline renin and aldosterone levels, it was concluded that the underlying defect responsible for hyperkalemia in this case was hyporeninemic hypoaldosteronism and this was aggravated by other factors or drugs affecting potassium homeostasis. PMID:8179835

Kee, C. S.; Choi, J. W.; Chang, D. K.; Ahn, Y. H.; Kim, H. J.

1993-01-01

118

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

119

Tissue antibodies in primary biliary cirrhosis, active chronic (lupoid) hepatitis, cryptogenic cirrhosis and other liver diseases and their clinical implications  

PubMed Central

The sera of virtually all patients with primary biliary cirrhosis contained non-organ specific antibodies, probably directed against mitochondria, which give rise to cytoplasmic `M' immunofluorescence in unfixed sections from various organs in high titres. They were also found in 31% of patients with cryptogenic cirrhosis particularly those with obstructive features, and 28% of cases of active chronic (lupoid) hepatitis. In contrast only two patients out of twenty-eight with extrahepatic biliary obstruction and one patient out of twenty-five with infective hepatitis gave positive reactions and then in very low titre. Uniformly negative results for `M' immunofluorescence were obtained in alcoholic cirrhosis, cholestatic drug jaundice and cholestasis associated with ulcerative colitis. These findings suggest that `M' antibodies do not arise merely in response to liver damage and confirm the value of the test for the differential diagnosis between primary biliary cirrhosis and extrahepatic biliary obstruction although care must be taken in interpretation of the results in cases with associated connective tissue disorders where a significant incidence of positive reactions was observed. Seventy-seven per cent of juvenile cirrhosis, 46% of primary biliary cirrhosis and 38% of the cryptogenic cirrhosis patients had anti-nuclear factors. The incidence of ANF in the other liver groups was no higher than in mixed hospital controls. A high incidence of antibodies staining smooth muscle was observed in the juvenile and primary biliary cirrhosis groups. No liver specific antibodies could be detected by precipitation or tanned red cell agglutination although non-organ-specific antibodies were demonstrated in some instances with the latter technique. Thyroid specific autoantibodies were increased four-fold in females with active chronic hepatitis but the incidence of thyroid and gastric autoantibodies was not significantly different from the controls in all other liver conditions studied. Autoimmune reactions are prominent in primary biliary cirrhosis and in active chronic hepatitis but their role in the pathogenesis of these diseases is still undefined. ImagesFig. 1 and 2Fig. 4Fig. 5Fig. 6 PMID:5330183

Doniach, Deborah; Roitt, I. M.; Walker, J. G.; Sherlock, Sheila

1966-01-01

120

Cirrhosis, Liver Transplantation and HIV Infection Are Risk Factors Associated with Hepatitis E Virus Infection  

PubMed Central

Background Acute and chronic hepatitis E have been associated with high mortality and development of cirrhosis, particularly in solid-organ recipients and patients infected by human immunodeficiency virus. However, data regarding the epidemiology of hepatitis E in special populations is still limited. Aims Investigate seroprevalence and possible factors associated with HEV infection in a large cohort of immunosuppressed patients. Methods Cross-sectional study testing IgG anti-HEV in serum samples from 1373 consecutive individuals: 332 liver-transplant, 296 kidney-transplant, 6 dual organ recipients, 301 non-transplanted patients with chronic liver disease, 238 HIV-infected patients and 200 healthy controls. Results IgG anti-HEV was detected in 3.5% controls, 3.7% kidney recipients, 7.4% liver transplant without cirrhosis and 32.1% patients who developed post-transplant cirrhosis (p<0.01). In patients with chronic liver disease, IgG anti-HEV was also statistically higher in those with liver cirrhosis (2% vs 17.5%, p<0.01). HIV-infected patients showed an IgG anti-HEV rate of 9.2%, higher than those patients without HIV infection (p<0.03). Multivariate analysis showed that the factors independently associated with anti-HEV detection were liver cirrhosis, liver transplantation and HIV infection (OR: 7.6, 3.1 and 2.4). HCV infection was a protective factor for HEV infection (OR: 0.4). Conclusions HEV seroprevalence was high in liver transplant recipients, particularly those with liver cirrhosis. The difference in anti-HEV prevalence between Liver and Kidney transplanted cases suggests an association with advanced liver disease. Further research is needed to ascertain whether cirrhosis is a predisposing factor for HEV infection or whether HEV infection may play a role in the pathogeneses of cirrhosis. PMID:25068388

Riveiro-Barciela, Mar; Buti, María; Homs, María; Campos-Varela, Isabel; Cantarell, Carmen; Crespo, Manuel; Castells, Lluís; Tabernero, David; Quer, Josep; Esteban, Rafael; Rodriguez-Frías, Francisco

2014-01-01

121

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

PubMed Central

Background Sonchus asper (L.) Hill, (Asteraceae) is used in Pakistan as a traditional (“folk”) medicine for the treatment of hormonal disorders and oxidative stress. The present study was aimed to evaluate the efficacy of Sonchus asper (L.) Hill, (Asteraceae) methanolic extract (SAME) on hormonal dysfunction in thyroid tissue after carbon tetrachloride (CCl4)-induced oxidative stress. Methods To examine the effects of SAME against the oxidative stress of CCl4 in thyroid tissue, 30 male albino rats were used. Protective effects of SAME were observed on thyroid hormonal levels, activities of antioxidant enzymes, lipid peroxidation (TBARS) and DNA damage. Results Treatment with CCl4 significantly (P<0.01) reduced the levels of T3 and T4 and increased TSH levels. CCl4 exposure in rats reduced the activities of antioxidant enzymes but increased lipid peroxidation and DNA damage. Co-administration of SAME significantly (P<0.01) improved these alterations with respect to hormonal levels, activities of antioxidant enzymes and lipid peroxidation close to those seen in control rats. Conclusion These results suggest that SAME can protect thyroid tissue against oxidative damage, possibly through the antioxidant effects of its bioactive compounds. PMID:23043630

2012-01-01

122

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

PubMed

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

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

2013-11-01

123

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

124

Albumin dialysis in cirrhosis with superimposed acute liver injury: A prospective, controlled study  

Microsoft Academic Search

Patients with liver cirrhosis and a superimposed acute injury with progressive hyperbilirubinemia have a high mortality. A prospective, controlled study was performed to test whether hyperbilirubinemia, 30-day survival, and encephalopathy would be improved by extracorporeal albumin dialysis (ECAD). Twenty-four patients were studied; 23 patients had cirrhosis; 1 had a prolonged cholestatic drug reaction and was excluded from per protocol (PP)

Uwe Heemann; Ulrich Treichel; Jan Loock; Thomas Philipp; Guido Gerken; Massimo Malago; Sebastian Klammt; Matthias Loehr; Stephan Liebe; Steffen Mitzner; Reinhardt Schmidt; Jan Stange

2002-01-01

125

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

PubMed Central

Background This study investigated the hepatoprotective effect and antioxidant properties of phloroacetophenone (2?,4?,6?-trihydroxyacetophenone – THA), an acetophenone derived from the plant Myrcia multiflora. Material & Method The free radical scavenging activity in vitro and induction of oxidative hepatic damage by carbon tetrachloride (CCl4) (0.5 ml/kg, i.p.) were tested in male Swiss mice (25±5 g). Results This compound exhibited in vitro antioxidant effects on FeCl2–ascorbate-induced lipid peroxidation (LPO) in mouse liver homogenate, scavenging hydroxyl and superoxide radicals, and 2,2-diphenyl-1-picrylhydrazyl. The in vivo assays showed that THA significantly (p<0.01) prevented the increases of hepatic LPO as measured by the levels of thiobarbituric acid-reactive substances, mitochondrial swelling. It also protected hepatocytes against protein carbonylation and oxidative DNA damage. Consistent with these observations, THA pre-treatment normalized the activities of antioxidant enzymes, such as catalase, glutathione peroxidase, and superoxide dismutase, and increased the levels of reduced glutathione (GSH) in CCl4-treated mice. In addition, THA treatment significantly prevented the elevation of serum enzymatic activities of alanine amino transferase, aspartate amino transferase, and lactate dehydrogenase, as well as histological alterations induced by CCl4. Silymarin (SIL) (24 mg/kg), a known hepatoprotective drug used for comparison, led to a significant decrease (p<0.01) in activities of theses enzymes in way very similar to that observed in pre-treatment with THA. Conclusion These results suggest that the protective effects are due to reduction of oxidative damage induced by CCl4 resulting from the antioxidant properties of THA. PMID:21483585

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

2010-01-01

126

68 FR 6679 - Presumption of Service Connection for Cirrhosis of the Liver in Former Prisoners of War  

Federal Register 2010, 2011, 2012, 2013, 2014

...Service Connection for Cirrhosis of the Liver in Former Prisoners of War AGENCY: Department...proposed amendment would add cirrhosis of the liver to the list of diseases for which entitlement...higher mortality rate from diseases of the liver, including chronic liver disease and...

2003-02-10

127

Study of trace elements in liver cirrhosis patients and their role in prognosis of disease.  

PubMed

The objectives of this study are to evaluate trace elements in patients with liver cirrhosis and to assess their association with severity of the disease. One hundred fifty cirrhotic subjects of either sex ranging in age from 20-70 years were included in the study, and the results were compared with 50 age- and sex-matched healthy control subjects. All cirrhotic subjects were assessed for severity of disease as mild (Child A), moderate (Child B), and severe (Child C) as per Child-Pugh classification. Routine investigations were done and trace elements (Cu, Zn, Se, and Mg) were analyzed on atomic absorption spectrophotometer. Serum level of copper was found significantly increased in patients with liver cirrhosis as compared to control group. Whereas serum zinc, selenium, and magnesium levels were significantly decreased in cirrhotic subjects as compared to controls. Trace elements were compared with severity of liver cirrhosis. Serum copper concentration was slightly increased in patients with more severe clinical state of liver cirrhosis; however, mean level difference of copper among the Child-Pugh groups were statistically not significant. Moreover, there was no significant correlation between copper and Child-Pugh Score. However, copper showed a significant negative correlation with zinc. Serum zinc, magnesium, and selenium levels were significantly decreased with advancement of liver disease as compared to early stage of liver cirrhosis and showed a significant negative correlation with Child-Pugh Score. Trace element abnormalities may reflect the condition of liver dysfunction. These results suggest that liver dysfunction may alter the metabolism of trace elements. Our study shows that micronutrients status in liver cirrhosis correlates well with severity of liver cirrhosis. Micronutrients supplementation in liver cirrhotic patients may prevent progression of disease and development of complications; however, further research needs to be done. PMID:25613584

Nangliya, Vijaylaxmi; Sharma, Anjali; Yadav, Dharamveer; Sunder, Shyam; Nijhawan, Sandeep; Mishra, Sandhya

2015-05-01

128

Valeriana jatamansi partially reverses liver cirrhosis and tissue hyperproliferative response in rat.  

PubMed

Valeriana jatamansi (family, Valerianaceae) is a traditional medicinal herb in the Indian subcontinent. This study provides experimental evidence indicating the therapeutic effect of the extract prepared from the dried rhizome of the herb in an animal model of liver cirrhosis and on cell proliferation. Liver cirrhosis was induced in rats by thioacetamide (0.03% in drinking water for 16 weeks). After inducing liver cirrhosis, rats were administered the extract orally for 9 weeks. Treatment was found to partially reverse the elevated levels of alkaline phosphatase, ?-glutamyl transferase and selected biochemical markers of hepatic injury including drug-metabolizing enzymes. Histopathology of the hepatic tissue confirmed the therapeutic effect of the extract which corroborated with the biochemical changes. The extract is also reported to ameliorate hepatic cell proliferation in rats injected with thioacetamide. The study has implications in finding a treatment for liver cirrhosis in humans. PMID:21225006

Prasad, R; Naime, M; Routray, I; Mahmood, A; Khan, F; Ali, S

2010-12-01

129

Oral Glucose Tolerance Test Predicts Prognosis of Patients with Liver Cirrhosis  

Microsoft Academic Search

OBJECTIVE:The aim of this study was to evaluate whether oral glucose tolerance test (OGTT) was useful in evaluating the prognosis of patients with liver cirrhosis.METHODS:Fifty-six patients with liver cirrhosis were enrolled in a prospective cohort study. In all cases, glucose tolerance was diagnosed by a 75-g OGTT according to World Health Organization (WHO) criteria. The relationship of clinical variables to

Tsutomu Nishida; Shingo Tsuji; Masahiko Tsujii; Shoko Arimitsu; Yoshimichi Haruna; Eiichi Imano; Masaaki Suzuki; Tsutomu Kanda; Sunao Kawano; Naoki Hiramatsu; Norio Hayashi; Masatsugu Hori

2006-01-01

130

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

131

Adeno-associated virus-mediated heme oxygenase-1 gene transfer suppresses the progression of micronodular cirrhosis in rats  

PubMed Central

AIM: To test the hypothesis that enhancement of the activity of heme oxygenase can interfere with processes of fibrogenesis associated with recurrent liver injury, we investigated the therapeutic potential of over-expression of heme oxygense-1 in a CCl4-induced micronodular cirrhosis model. METHODS: Recombinant adeno-associated viruses carrying rat HO-1 or GFP gene were generated. 1×1012 vg of adeno-associated viruses were administered through portal injection at the time of the induction of liver fibrosis. RESULTS: Conditioning the rat liver with over-expression of HO-1 by rAAV/HO-1 significantly increased the HO enzymatic activities in a stable manner. The development of micronodular cirrhosis was significantly inhibited in rAAV/HO-1-transduced animals as compared to controls. Portal hypertension was markedly diminished in rAAV/HO-1-transduced animals as compared to controls, whereas there are no significant changes in systolic blood pressure. This finding was accompanied with improved liver biochemistry, less infiltrating macrophages and less activated hepatic stellate cells (HSCs) in rAAV/HO-1-transduced livers. CONCLUSIONS: Enhancement of HO activity in the livers suppresses the development of cirrhosis. PMID:16610050

Tsui, Tung-Yu; Lau, Chi-Keung; Ma, Jian; Glockzin, Gabriel; Obed, Aiman; Schlitt, Hans J; Fan, Sheung-Tat

2006-01-01

132

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

PubMed Central

Background Studies have shown psychological distress in patients with cirrhosis, yet no studies have evaluated the laboratory and physiologic correlates of psychological symptoms in cirrhosis. This study therefore measured both biochemistry data and heart rate variability (HRV) analyses, and aimed to identify the physiologic correlates of depression, anxiety, and poor sleep in cirrhosis. Methods A total of 125 patients with cirrhosis and 55 healthy subjects were recruited. Each subject was assessed through routine biochemistry, 5-minutes ECG monitoring, and psychological ratings of depression, anxiety, and sleep. HRV analysis were used to evaluate autonomic functions. The relationship between depression, sleep, and physiologic correlates was assessed using a multiple regression analysis and stepwise method, controlling for age, duration of illness, and severity of cirrhosis. Results Reduced vagal-related HRV was found in patients with severe liver cirrhosis. Severity of cirrhosis measured by the Child-Pugh score was not correlated with depression or anxiety, and only had a weak correlation with poor sleep. The psychological distress in cirrhosis such as depression, anxiety, and insomnia were correlated specifically to increased levels of aspartate aminotransferase (AST), increased ratios of low frequency to high frequency power, or reduced nonlinear properties of HRV (?1 exponent of detrended fluctuation analysis). Conclusions Increased serum AST and abnormal autonomic nervous activities by HRV analysis were associated with psychological distress in cirrhosis. Because AST is an important mediator of inflammatory process, further research is needed to delineate the role of inflammation in the cirrhosis comorbid with depression. PMID:23339829

2013-01-01

133

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

134

Hepatocyte Turnover in Chronic HCV-Induced Liver Injury and Cirrhosis  

PubMed Central

Chronic hepatitis C virus (HCV) infection may eventually lead to progressive liver fibrosis and cirrhosis through a complex, multistep process involving hepatocyte death and regeneration. Despite common pathogenetic pathways present in all forms of liver cirrhosis irrespective of etiology, hepatocyte turnover and related molecular events in HCV-induced cirrhosis are increasingly being distinguished from even “similar” causes, such as hepatitis B virus- (HBV-) related cirrhosis. New insights in HCV-induced hepatocellular injury, differential gene expression, and regenerative pathways have recently revealed a different pattern of progression to irreversible parenchymal liver damage. A shift to the significant role of the host immune response rather than the direct effect of HCV on hepatocytes and the imbalance between antiapoptotic and proapoptotic signals have been investigated in several studies but need to be further elucidated. The present review aims to comprehensively summarize the current evidence on HCV-induced hepatocellular turnover with a view to outline the significant trends of ongoing research.

Karidis, Nikolaos P.; Delladetsima, Ioanna; Theocharis, Stamatios

2015-01-01

135

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

136

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

137

Sudden Onset Abdominal Wall Swellings in Patient of Liver Cirrhosis  

PubMed Central

Spontaneous hematomas in cirrhotic patients are uncommon. Severe coagulopathy in advanced hepatic disease is characterized by both coagulation factor deficiencies and accelerated fibrinolysis. Hyperfibrinolysis in cirrhosis is a result of excess fibrin breakdown leading to defective hemostasis. We present a case of spontaneous hematomas with an acute drop in hemoglobin level, in a patient with cirrhosis which was due to primary hyperfibrinolysis.

Patil, Mallikarjun; Sheth, Keyur A.; Prasanna, Kullembella S.; Adarsh, Channagiri K.; Girisha, Balaraju

2012-01-01

138

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

139

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. PMID:25624730

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

2015-01-01

140

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

141

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

142

CD14 promoter polymorphism in Chinese alcoholic patients with cirrhosis of liver and acute pancreatitis  

Microsoft Academic Search

Abstract Abstract Abstract Abstract AIM: To investigate the relationship between genetic polymorphism of the CD14 promoter and the occurrence of alcoholic cirrhosis and alcoholic pancreatitis, and to challenge the conclusion made earlier that the patients with acute alcoholic pancreatitis and patients with alcoholic cirrhosis of liver are two different subpopulations. METHODS: Using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)

You-Chen Chao; Heng-Cheng Chu; Wei-Kuo Chang; Hsin-Hung Huang; Tsai-Yuan Hsieh

2005-01-01

143

Activity of MMP1 and MMP13 and Amino Acid Metabolism in Patients with Alcoholic Liver Cirrhosis.  

PubMed

Background Alcoholic liver disease remains one of the most common causes of chronic liver disease worldwide. The aim of this study was to assess the usefulness of metalloproteinases (MMP1 and MMP13) as diagnostic markers of alcoholic liver disease and to determine the changes in free amino acid profile in the patients with alcoholic liver cirrhosis. Material and Methods Sixty patients with alcoholic liver cirrhosis treated in various hospitals of the Lublin region were randomly enrolled. The control group consisted of 10 healthy individuals without liver disease, who did not drink alcohol. Additionally, a group of alcoholics (22 persons) without liver cirrhosis was included in the study. The activity of MMP-1 and MMP-13 in blood plasma of patients and controls was measured using the sandwich enzyme immunoassay technique with commercially available quantitative ELISA test kits. Amino acids were determined by automated ion-exchange chromatography. Results No significant differences were observed in the activity of MMP-1 in alcoholics with or without liver cirrhosis or in controls. Increased serum MMP-13 was found in patients with liver cirrhosis (stage A, B, C) compared to the control group. Patients with alcoholic liver cirrhosis (stage A, B, C) demonstrated reduced concentrations of glutamic acid and glutamine compared to the control group. Plasma levels of valine, isoleucine, leucine, and tryptophan were significantly lower in patients with alcoholic liver cirrhosis (stage C) than in controls. Conclusions MMP-13 can be useful to confirm the diagnosis of alcoholic liver cirrhosis, but levels of MMP-1 are not significantly increased in patients with liver cirrhosis compared to controls. The serum branched-chain amino acid (BCAA) is markedly reduced in patients with stage C alcoholic liver cirrhosis. PMID:25863779

Prystupa, Andrzej; Szpetnar, Maria; Boguszewska-Czubara, Anna; Grzybowski, Andrzej; Sak, Jaros?aw; Za?uska, Wojciech

2015-01-01

144

Aberrant Expression of Fetal RNA-Binding Protein p62 in Liver Cancer and Liver Cirrhosis  

PubMed Central

p62 is a RNA-binding protein that was isolated by immunoscreening a cDNA expression library with autoantibodies from patients with hepatocellular carcinoma (HCC). This autoantigen binds to mRNA encoding insulin-like growth factor II, which has been found to be overexpressed in HCC and is tumorigenic in transgenic animals. Immunohistochemical analysis of HCC liver showed that 33% (9 of 27) exhibited readily detectable staining of p62 protein in the cytoplasm of all malignant cells in cancer nodules, whereas it was undetectable in adjacent nonmalignant liver cells. In addition one of two patients with cholangiocarcinoma expressed p62 in malignant bile duct epithelial cells. p62 expression was also detected in scattered cells in cirrhotic nodules in contrast to uniform expression in all cells in HCC nodules. In HCC nodules, p62 mRNA was also detected by reverse transcriptase-polymerase chain reaction analysis. Nine normal adult livers did not contain detectable p62 mRNA or p62 protein whereas five fetal livers were all positive for mRNA and protein. The observations show that p62 is developmentally regulated, expressed in fetal, but not in adult liver, and aberrantly expressed in HCC and could be playing a role in abnormal cell proliferation in HCC and cirrhosis by modulating expression of growth factors such as insulin-like growth factor II. PMID:11549587

Lu, Maolong; Nakamura, Robert M.; Dent, E. DuBose; Zhang, Jian-Ying; Nielsen, Finn C.; Christiansen, Jan; Chan, Edward K. L.; Tan, Eng M.

2001-01-01

145

Endotoxin and liver diseases. High titres of enterobacterial common antigen antibodies in patients with alcoholic cirrhosis.  

PubMed Central

We have measured antibodies to the enterobacterial common antigen (ECA) in sera of 86 patients with various liver diseases. ECA is a component of the cell wall of all enteric bacteria, and ECA antibodies are a specific indication of the presence of enterobacterial components. Patients with alcoholic cirrhosis with or without signs of alcoholic hepatitis had significantly raised anti-ECA titres compared with healthy control subjects. Other groups of patients (alcoholic hepatitis and/or fatty liver, primary biliary cirrhosis, chronic active hepatitis, or liver metastases) did not differ significantly from controls in the height of their anti-ECA titres. The results support the concept that Gram-negative bacterial components may have some role in the pathophysiology of alcoholic cirrhosis. PMID:7297916

Turunen, U; Malkamäki, M; Valtonen, V V; Larinka?i, U; Pikkarainen, P; Salaspuro, M P; Mäkelä, P H

1981-01-01

146

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

PubMed

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

2014-08-01

147

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

148

Mortality after cardiac surgery in patients with liver cirrhosis classified by the Child-Pugh score.  

PubMed

Liver cirrhosis is a known risk factor for postoperative mortality in patients undergoing cardiac surgery. Clinical assessment of liver cirrhosis using the widely accepted Child-Pugh (CP) score is thus vital for evaluation of surgical options and perioperative care. However, detailed mortality rates as a consequence of liver cirrhosis are unclear. This review aimed to stratify the risk of short-term (<30 days) and overall (up to 10 years) mortality after cardiac surgery in patients with liver cirrhosis, classified by the CP score. Thus, PubMed, Embase, CINAHL and the Cochrane Library were systematically reviewed by two independent investigators for studies published up to February 2014, in which mortality in cirrhotic patients, classified by the CP classification, undergoing cardiac surgery was evaluated postoperatively. A total of 993 articles were identified. After critical appraisal of 21 articles, 19 were selected for final analysis. Weighted short-term mortality of cirrhotic patients undergoing cardiac surgery was 19.3% [95% confidence interval (CI): 16.4-22.5%]. Across the different CP groups, short-term mortality appeared to be 9.0% (95% CI: 6.6-12.2%), 37.7% (95% CI: 30.8-44.3%) and 52.0% (95% CI: 33.5-70.0%) in Groups A, B and C, respectively. Weighted overall mortality within 1 year was 42.0% (95% CI: 36.0-48.3%) in all cirrhotic patients. Subdivided in groups, overall mortality within that 1 year was 27.2% (95% CI: 20.9-34.7%), 66.2% (95% CI: 54.3-76.3%) and 78.9% (95% CI: 56.1-92.1%) in Groups A, B and C, respectively. In conclusion, short-term mortality is considerably increased in patients with liver cirrhosis CP class B and C. Overall mortality is significantly high in all classes of liver cirrhosis. PMID:25612743

Jacob, Kirolos A; Hjortnaes, Jesper; Kranenburg, Guido; de Heer, Frederiek; Kluin, Jolanda

2015-04-01

149

Effect of a late evening snack on the blood glucose level and energy metabolism in patients with liver cirrhosis  

Microsoft Academic Search

Background\\/aim: Patients with liver cirrhosis suffer from energy malnutrition. Late evening snacks (LESs) have been recently reported to be effective for this. However, it is known that a significant proportion of patients with liver cirrhosis have glucose intolerance as a complication. For this reason, the influence of LES on the blood glucose level should be examined. Subjects\\/method: We administered an

Mariko Okamoto; Isao Sakaida; Masako Tsuchiya; Chieko Suzuki; Kiwamu Okita

2003-01-01

150

Cirrhosis  

MedlinePLUS

... in metabolism—the way cells change food into energy after food is digested and absorbed into the blood. The liver has many functions, including taking up, storing, and processing nutrients from food— ...

151

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

152

[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

153

[Spontaneous splenic vein rupture complicating liver cirrhosis: an autopsy case report].  

PubMed

A 70-year-old woman, who had hepatitis-C related liver cirrhosis died suddenly. Autopsy showed a massive retroperitoneal hematoma and ruptured splenic vein, as well as densely bloody ascites. This suggested that chronic and unnoticed retroperitoneal leak from the ruptured vein preceded the acute and fatal outcome of the intra-abdominal bleeding. Spontaneous rupture of the splenic vein is rarely reported in liver cirrhosis despite the presence of portal hypertension. This rare association is discussed with a literature review. PMID:23459537

Okubo, Satoshi; Kiriyama, Kazuo; Usui, Takeo; Takemura, Tadaharu; Ikeda, Kouichiro; Kanayama, Yoshio

2013-03-01

154

[A case of spontaneous bleeding of multiple lumbar arteries in a patient with liver cirrhosis].  

PubMed

Esophageal and gastric varix, portal hypertensive gastropathy, Mallory-Weiss tear and gastric ulcer are common causes of bleeding in patients with liver cirrhosis. However, spontaneous arterial bleeding without a history of trauma is a rare cause of bleeding which can be fatal. We report a case of a 55-year-old woman with alcoholic liver cirrhosis who developed spontaneous bleeding of multiple right lumbar arteries and died in spite of repetitive transfusion and embolization. (Korean J Gastroenterol 2015;65:186-189). PMID:25797384

Hong, Jong Sam; Jeong, Woo Jin; Han, Yang Hee; Shin, Sa Young; Jun, Jae Hyuck; Woo, Yeong Min; Yun, Jung Ho; Cheon, Gab Jin

2015-03-25

155

Incidence and prognosis of tuberculosis in patients with cirrhosis of the liver. A Danish nationwide population based study.  

PubMed Central

We examined the incidence rate and prognosis of tuberculosis in a cohort of patients with liver cirrhosis in Denmark. In a study cohort of 22675 patients with liver cirrhosis, we identified 151 cases of tuberculosis from 1977 to 1993. The incidence rate was 168.6 per 100000 person-years of risk, and the highest incidence rate was among men above 65 years of age, with an incidence rate of 246.0 per 100000 person-years of risk. The 30-day case-fatality rate was 27.3% and the 1-year case fatality rate was 47.7%. The results demonstrate that patients with liver cirrhosis are at increased risk of tuberculosis. Additionally, it is suggested that liver cirrhosis is an independent risk factor for tuberculosis, and that patients with liver cirrhosis who acquire tuberculosis have a poor prognosis. PMID:10813146

Thulstrup, A. M.; Mølle, I.; Svendsen, N.; Sørensen, H. T.

2000-01-01

156

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

157

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

158

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

159

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

160

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

Microsoft Academic Search

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

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

2007-01-01

161

Development of Hodgkin's disease in the course of liver cirrhosis and impaired monocyte function.  

PubMed Central

The monocyte function, as measured by phagocytosis and killing of Candida albicans and Candida pseudotropicalis by peripheral blood monocytes, was found impaired in a patient with cirrhosis of the liver on two separate determinations before the occurrence of bleeding from oesophageal varices. Unexpectedly, Hodgkin's disease was diagnosed in enlarged abdominal lymph nodes found on the occasion of an emergency portocaval shunt operation. PMID:6463000

Dan, M.; Hassner, A.; Jedwab, M.; Shibolet, S.

1984-01-01

162

Laparoscopic Liver Resection for Hepatocellular Carcinoma in Cirrhosis: Long-Term Outcomes  

Microsoft Academic Search

Background:Few data regarding survival or pattern of recurrence after laparoscopic liver resection (LLR) for hepatocellular carcinoma (HCC) on cirrhosis have been reported so far. Methods: A retrospective analysis of a prospectively maintained database of 109 laparoscopic interventional procedures performed for HCC in cirrhotic liver between 2000 and 2008 was conducted. Results: Sixty-five patients underwent an LLR. Morbidity rates were 20%

Giulio Belli; Corrado Fantini; Andrea Belli; Paolo Limongelli

2011-01-01

163

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

164

What I Need to Know about Cirrhosis of the Liver  

MedlinePLUS

... drugs, medicines, and harmful chemicals infections chronic hepatitis B, C, or D—viral infections that attack the liver autoimmune hepatitis, which causes the body’s immune system to destroy liver cells nonalcoholic fatty liver disease, which is often caused by obesity diseases that ...

165

Occult Hepatitis B Infection in Patients With Cryptogenic Liver Cirrhosis in Southwest of Iran  

PubMed Central

Background: Chronic hepatitis B virus (HBV) infection has a broad spectrum of manifestation, ranging from silent carrier state to advanced cirrhosis and hepatocellular carcinoma. The persistence of HBV DNA in serum and hepatocytes of the cirrhotic patient could be detected by molecular techniques in spite of negative HBV serologic markers. Objectives: This case-control study was designed to evaluate the prevalence of occult HBV infection (OBI) in patients with cryptogenic liver cirrhosis in comparison with healthy subjects. Patients and Methods: Of 165 patients with liver cirrhosis, 50 consecutive patients with cryptogenic cirrhosis and 80 healthy individual without any risk factors as a control group were enrolled in this study. Their sera were tested for HBV DNA using nested PCR method. Results: Of 50 patients with cryptogenic cirrhotic, 36 (72%) were male. The mean age of patients was 53.34 ± 14.73 years; 80 healthy subjects were selected as control group with mean age of 32.65 ± 8.51 years; 7 (14%) of the patients with cryptogenic cirrhosis showed positive HBV DNA by PCR, while HBV DNA was negative for the control group (P = 0.0001); 4 (57%) cases with positive HBV shown by PCR were negative for anti-HBc and anti-HBs tests. The mean level of transaminases was significantly higher in patients with cirrhosis. There were no significant differences in demographic parameters, transaminases level and degree of hepatic failure among cirrhotic patients with and without OBI. Conclusions: The prevalence of OBI was relatively high in patients with cryptogenic cirrhosis. OBI was found among the patients above 40 years old. Prospective cohort studies are needed to evaluate the clinical significance of OBI.

Hashemi, Seyed Jalal; Hajiani, Eskandar; Masjedizadeh, Abdolrahim; Makvandi, Manoochehr; Shayesteh, Ali Akbar; Alavinejad, Seyed Pejman; Kadkhodaei, Ahmad; Shahbazian, Heshmatollah; Jasemi, Farzad; Karimi, Mohamad

2015-01-01

166

The Expression of Embryonic Liver Development Genes in Hepatitis C Induced Cirrhosis and Hepatocellular Carcinoma  

PubMed Central

Hepatocellular carcinoma (HCC) remains a difficult disease to study even after a decade of genomic analysis. Patient and disease heterogeneity, differences in statistical methods and multiple testing issues have resulted in a fragmented understanding of the molecular basis of tumor biology. Some researchers have suggested that HCC appears to share pathways with embryonic development. Therefore we generated targeted hypotheses regarding changes in developmental genes specific to the liver in HCV-cirrhosis and HCV-HCC. We obtained microarray studies from 30 patients with HCV-cirrhosis and 49 patients with HCV-HCC and compared to 12 normal livers. Genes specific to non-liver development have known associations with other cancer types but none were expressed in either adult liver or tumor tissue, while 98 of 179 (55%) genes specific to liver development had differential expression between normal and cirrhotic or HCC samples. We found genes from each developmental stage dysregulated in tumors compared to normal and cirrhotic samples. Although there was no single tumor marker, we identified a set of genes (Bone Morphogenetic Protein inhibitors GPC3, GREM1, FSTL3, and FST) in which at least one gene was over-expressed in 100% of the tumor samples. Only five genes were differentially expressed exclusively in late-stage tumors, indicating that while developmental genes appear to play a profound role in cirrhosis and malignant transformation, they play a limited role in late-stage HCC. PMID:23667740

Behnke, Martha; Reimers, Mark; Fisher, Robert

2012-01-01

167

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

168

Genetic Diseases That Predispose to Early Liver Cirrhosis  

PubMed Central

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

Liguori, Renato

2014-01-01

169

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

PubMed Central

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

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

2012-01-01

170

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

171

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

172

Nodular regenerative hyperplasia of the liver, CREST syndrome and primary biliary cirrhosis: an overlap syndrome?  

PubMed Central

Nodular regenerative hyperplasia of the liver (NRHL) has been found in association with collagen vascular diseases, after drug therapy, with autoimmune disease, and with a variety of haematological disorders. The association of NRHL with the syndrome of Calcinosis cutis, Raynaud's phenomenon, oesophageal dysfunction, sclerodactyly and telangiectasia (CREST syndrome) has only been reported on two previous occasions. The liver disease usually associated with CREST syndrome is primary biliary cirrhosis (PBC) and recently nodular hyperplasia of the liver has been reported in patients with early stage PBC. We present a case of NRHL with CREST syndrome and serological and biochemical features of PBC, a newly recognised overlap syndrome. Images Figure PMID:2583572

McMahon, R F; Babbs, C; Warnes, T W

1989-01-01

173

Nodular regenerative hyperplasia of the liver, CREST syndrome and primary biliary cirrhosis: an overlap syndrome?  

PubMed

Nodular regenerative hyperplasia of the liver (NRHL) has been found in association with collagen vascular diseases, after drug therapy, with autoimmune disease, and with a variety of haematological disorders. The association of NRHL with the syndrome of Calcinosis cutis, Raynaud's phenomenon, oesophageal dysfunction, sclerodactyly and telangiectasia (CREST syndrome) has only been reported on two previous occasions. The liver disease usually associated with CREST syndrome is primary biliary cirrhosis (PBC) and recently nodular hyperplasia of the liver has been reported in patients with early stage PBC. We present a case of NRHL with CREST syndrome and serological and biochemical features of PBC, a newly recognised overlap syndrome. PMID:2583572

McMahon, R F; Babbs, C; Warnes, T W

1989-10-01

174

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

175

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

PubMed Central

Liver cirrhosis (LC) can lead to a clinical state of liver failure, which can exacerbate through the course of the disease. New therapies aimed to control the diverse etiologies are now more effective, although the disease may result in advanced stages of liver failure, where liver transplantation (LT) remains the most effective treatment. The extended lifespan of these patients and the extended possibilities of liver support devices make their admission to an intensive care unit (ICU) more probable. In this paper the LC is approached from the point of view of the pathophysiological alterations present in LC patients previous to ICU admission, particularly cardiovascular, but also renal, coagulopathic, and encephalopathic. Infections and available liver detoxifications devices also deserve mentioning. We intend to contribute towards ICU physician readiness to the care for this particular type of patients, possibly in dedicated ICUs. PMID:22666568

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

2012-01-01

176

Autoimmune hepatitis-primary biliary cirrhosis concurrent with biliary stricture after liver transplantation.  

PubMed

Although the development of de novo autoimmune liver disease after liver transplantation (LT) has been described in both children and adults, autoimmune hepatitis (AIH)-primary biliary cirrhosis (PBC) overlap syndrome has rarely been seen in liver transplant recipients. Here, we report a 50-year-old man who underwent LT for decompensated liver disease secondary to alcoholic steatohepatitis. His liver function tests became markedly abnormal 8 years after LT. Standard autoimmune serological tests were positive for anti-nuclear and anti-mitochondrial antibodies, and a marked biochemical response was observed to a regimen consisting of prednisone and ursodeoxycholic acid added to maintain immunosuppressant tacrolimus. Liver biopsy showed moderate bile duct lesions and periportal lymphocytes infiltrating along with light fibrosis, which confirmed the diagnosis of AIH-PBC overlap syndrome. We believe that this may be a case of post-LT de novo AIH-PBC overlap syndrome; a novel type of autoimmune overlap syndrome. PMID:25717264

Kang, Yong-Zhen; Sun, Xiao-Ye; Liu, Yi-He; Shen, Zhong-Yang

2015-02-21

177

Effect of hepatocyte growth factor encapsulated in targeted liposomes on liver cirrhosis.  

PubMed

Hepatocyte growth factor (HGF) was encapsulated into sterically stabilized liposomes (SSL) in order to protect it from in vivo degradation. Cyclic Arg-Gly-Asp (RGD) peptides were combined with maleimide-[poly (ethylene glycol)]-1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (MAL-PEG-DOPE) incorporated into SSL. The average percentage of HGF encapsulated into liposomes was 32.38%, the size of liposomes was 91.56 nm and the polydispersity index was 0.164. In vivo, histological observation of the rat livers revealed that injection of RGD-SSL-HGF induced more significant remission of liver cirrhosis than injection of SSL-HGF, HGF alone, HGF plus RGD-SSL and saline. When the histological score, the collagen surface density, the hydroxyproline content and the expression of procollagen alpha1 (I) and alpha1 (III) mRNA in the liver were evaluated, all values were smallest in the RGD-SSL-HGF group. In contrast, an increase in apoptotic alpha-SMA-positive cells was noted in the RGD-SSL-HGF group. Together, this data suggests that targeted liposomes encapsulating HGF is a promising therapeutic modality in terms of promoting the remission of liver cirrhosis by promoting collagen fiber digestion, inhibiting collagen production, and promoting apoptosis of alpha-SMA-positive cells in rats with cirrhosis. PMID:18692530

Li, Feng; Sun, Jian-Yong; Wang, Ji-Yao; Du, Shi-Lin; Lu, Wei-Yue; Liu, Min; Xie, Chao; Shi, Jian-Ying

2008-10-01

178

Daily Drinking May Raise Risk of Liver Cirrhosis  

MedlinePLUS

... National Institute of Public Health, University of Southern Denmark. "Since the details of alcohol-induced liver injury ... 56,000 people, aged 50 to 64, in Denmark. Participants filled out food frequency questionnaires and answered ...

179

Anti-apoptotic effect of San Huang Shel Shin Tang cyclodextrin complex (SHSSTc) on CCl4 -induced hepatotoxicity in rats.  

PubMed

The metabolic loading is heavier in liver especially when injured or inflammation. San Huang Shel Shin Tang (SHSST) was an old traditional herbal decoction, which composed with Rheum officinale Baill, Scutellaria baicalnsis Geprgi and Coptis chinensis Franch (1:1:2 in weight), can provide a liver protection effects. We used a beta-cyclodextrin (?-CD) drug modification method in reduce of the necessary dose of the SHSST. As the results, the FAS-FADD expressions leaded apoptosis in CCl4 intraperitoneal (IP) injection induced acute liver injury in rats. Silymarin, baicalein, SHSST, and SHSST ?-CD complex (SHSSTc) pretreatments protected liver through the decreasing of the expressions of FAS-FADD and downstream caspase-3 and caspase-8. Particularly, SHSSTc (30 mg/kg day) treatment enhanced cell survival pathway activation through the PI3K, Akt and Bad phosphorylation. Compared with SHSST as well as silymarin and baicalein, SHSSTc provided a magnificent liver protection effect, especially in survival pathway activation/TUNEL-apoptotic cell reduction/serum cholesterol level suppression. All these data suggested that ?-CD complex modified the SHSST and promoted the bioavailability and liver protection effects. © 2014 Wiley Periodicals, Inc. Environ Toxicol, 2014. PMID:25447754

Yang, Cheng-Hsun; Ting, Wei-Jen; Shen, Chia-Yao; Hsu, Hsi-Hsien; Lin, Yueh-Min; Kuo, Chia-Hua; Tsai, Fuu-Jen; Tsai, Chang-Hai; Tsai, Yuhsin; Huang, Chih-Yang

2014-11-28

180

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

181

Role of Tc99m sulfur colloid scintigraphy in differentiating non-cirrhotic portal fibrosis from cirrhosis liver  

PubMed Central

Background: Two most important causes of portal hypertension are cirrhosis of liver and non-cirrhotic portal fibrosis (NCPF). The purpose of this study was to assess the scintigraphic appearances of Tc99m sulfur colloid liver scan in differentiating liver cirrhosis from NCPF. Materials and Methods: Retrospective analysis records of 146 patients (91 male and 55 female) with diffuse hepatocellular disease was done for liver size, liver uptake, spleen size, spleen uptake, colloid shift to bone marrow and lungs. Methods: Retrospective analysis records of 146 patients (91 male and 55 female) with diffuse hepatocellular disease was done for liver size, liver uptake, spleen size, spleen uptake, colloid shift to bone marrow and lungs. Results: Cirrhotic livers showed patchy and lower uptake than NCPF (59% vs. 20%, P-value 0.041). Spleen size was significantly increased in NCPF compared to cirrhosis (100% vs. 67%, P-value 0.0137). Significant colloid shift to bone marrow was noted in cirrhosis (84% vs. 7%, P-value<0.0001). Conclusion: Tc99m sulfur colloid liver scan is a non-invasive procedure having a useful adjunctive role in clinical differentiation of cirrhosis from NCPF. PMID:21713221

Chakraborty, Dhritiman; Sunil, Hejjaji Venkataramarao; Mittal, Bhagwant Rai; Bhattacharya, Anish; Singh, Baljinder; Chawla, Yogesh

2010-01-01

182

Association between dietary nutrient composition and the incidence of cirrhosis or liver cancer in the united states population  

Microsoft Academic Search

Little is known about the impact of dietary factors on the progression of liver disease. Our aim was to determine whether dietary intake was associated with the risk of cirrhosis-related or liver cancer-related death or hospitalization in the U.S. population. Participants included 9221 persons aged 25-74 years without evidence of cirrhosis at entry into the study or during the first

George N. Ioannou; Olivia B. Morrow; Marah L. Connole; Sum P. Lee

2009-01-01

183

The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide q  

Microsoft Academic Search

Background\\/Aims: End-stage liver disease accounts for one in forty deaths worldwide. Chronic infections with hepatitis B virus (HBV) and hepatitis C virus (HCV) are well-recognized risk factors for cirrhosis and liver cancer, but estimates of their contributions to worldwide disease burden have been lacking. Methods: The prevalence of serologic markers of HBV and HCV infections among patients diagnosed with cirrhosis

Joseph F. Perz; Gregory L. Armstrong; Leigh A. Farrington; Yvan J. F. Hutin; Beth P. Bell

2006-01-01

184

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

185

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

186

Mechanism of thrombocytopenia in liver cirrhosis: kinetics of indium-111 tropolone labelled platelets  

Microsoft Academic Search

Using indium-111 tropolone-labelled platelets, a study of platelet kinetics was performed on the basis of the relationship between platelet count, platelet survival time, platelet dynamics, platelet-associated immunoglobulin G (PA-IgG) and splenic volume in 31 patients with liver cirrhosis and a platelet count of less than 100 × 109\\/l. The mean platelet count was 46.6±25.3 × 109\\/l, and the mean platelet

Yoshinori Aoki; Kenji Hirai; Kyuichi Tanikawa

1993-01-01

187

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

188

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

189

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

190

Correlation between hepatic blood flow and liver function in alcoholic liver cirrhosis  

PubMed Central

AIM: To elucidate the correlation between hepatic blood flow and liver function in alcoholic liver cirrhosis (AL-LC). METHODS: The subjects included 35 patients with AL-LC (34 men, 1 woman; mean age, 58.9 ± 10.7 years; median age, 61 years; range: 37-76 years). All patients were enrolled in this study after obtaining written informed consent. Liver function was measured with tests measuring albumin (Alb), prothrombin time (PT), brain natriuretic peptide (BNP), branched amino acid and tyrosine ratio (BTR), branched chain amino acid (BCAA), tyrosine, ammonia (NH3), cholinesterase (ChE), immunoreactive insulin (IRI), total bile acid (TBA), and the retention rate of indocyanine green 15 min after administration (ICG R15). Hepatic blood flow, hepatic arterial tissue blood flow (HATBF), portal venous tissue blood flow (PVTBF), and total hepatic tissue blood flow (THTBF) were simultaneously calculated using xenon computed tomography. RESULTS: PVTBF, HATBF and THTBF were 30.2 ± 10.4, 20.0 ± 10.7, and 50.3 ± 14.9 mL/100 mL/min, respectively. Alb, PT, BNP, BTR, BCAA, tyrosine, NH3, ChE, IRI, TBA, and ICG R15 were 3.50 ± 0.50 g/dL, 72.0% ± 11.5%, 63.2 ± 56.7 pg/mL, 4.06 ± 1.24, 437.5 ± 89.4 ?mol/L, 117.7 ± 32.8 ?mol/L, 59.4 ± 22.7 ?g/dL, 161.0 ± 70.8 IU/L, 12.8 ± 5.0 ?g/dL, 68.0 ± 51.8 ?mol/L, and 28.6% ± 13.5%, respectively. PVTBF showed a significant negative correlation with ICG R15 (r = -0.468, P <0.01). No significant correlation was seen between ICG 15R, HATBF and THTBF. There was a significant correlation between PVTBF and Alb (r = 0.2499, P < 0.05), and NH3 tended to have an inverse correlation with PVTBF (r = -0.2428, P = 0.0894). There were also many significant correlations between ICG R15 and liver function parameters, including Alb, NH3, PT, BNP, TBA, BCAA, and tyrosine (r = -0.2156, P < 0.05; r = 0.4318, P < 0.01; r = 0.4140, P < 0.01; r = 0.3610, P < 0.05; r = 0.5085, P < 0.001; r = 0.4496, P < 0.01; and r = 0.4740, P < 0.05, respectively). CONCLUSION: Our investigation showed that there is a close correlation between liver function and hepatic blood flow. PMID:25493018

Takahashi, Hideaki; Shigefuku, Ryuta; Yoshida, Yoshihito; Ikeda, Hiroki; Matsunaga, Kotaro; Matsumoto, Nobuyuki; Okuse, Chiaki; Sase, Shigeru; Itoh, Fumio; Suzuki, Michihiro

2014-01-01

191

Magnitude of peripheral neuropathy in cirrhosis of liver patients from central rural India  

PubMed Central

Context: Cirrhosis of liver is an important cause of morbidity and mortality and if associated with peripheral neuropathy (PN) it also poses a huge financial, psychological burden for the patients and their families. Aim: The aim of the present study was to study the magnitude of PN among subjects with cirrhosis of liver presenting to tertiary care teaching hospital in central rural India. Settings and Design: A cross-sectional study was performed in a tertiary care teaching hospital. Materials and Methods: In all patients of cirrhosis of liver irrespective of etiology, aged 15 and above, undergone clinical assessment for peripheral nervous systems damage and confirmed by nerve conduction studies. Statistical Analysis Used: We used chi square test to study associations. P value ?0.05 was considered as significant. Crude odds ratios were computed to assess the strength of association between independent variables and dependent variables along with their 95% confidence intervals. Results: We included 207 of cirrhosis of liver patients admitted in medicine department from November 2010 through November 2013. Nearly 83% patients were male and 63.2% patients were under the age of 45 years. Common features in these patients were ascites (71%) splenomegaly (63.3%) pedal edema (61.4%) icterus (46.4%) tingling (44.9%) gastrointestinal bleeding(39.1%), ataxia (26.6%), numbness(26.6%), distal motor weakness (21.7%) and paresthesia(20.8%). Among the manifestation of peripheral nerve involvement, loss of ankle reflex was the most common feature in 51.7%, followed by loss of temperature sense 29.5%, loss of vibration sense 20.8%, loss of touch 16.4%, loss of position sense 14.5% and loss of pain in 6.3% of the patients. Peripheral neuropathy was found in 53.6% [95% CI: 46.58- 60.56] study subjects on electrophysiological study. Conclusions: Analysis of electrophysiological study shows that the PN is very common in study subjects with cirrhosis of liver, especially in male subjects, during the middle age group. PMID:25506162

Jain, Jyoti; Singh, Ramji; Banait, Shashank; Verma, Nitin; Waghmare, Satish

2014-01-01

192

[Baclofen and liver cirrhosis: literature review and safety precautions implemented within the system CAMTEA].  

PubMed

The off-label prescribing of high dose baclofen (HDB) has been recently spreading in France. The impact of HDB on subjects with liver cirrhosis remains poorly known. The main pharmacodynamic and pharmacokinetic data on baclofen result from studies on healthy subjects or using low doses of treatment. The specific biodisponibility and elimination of HDB have not been studied yet in cirrhosis. National pharmacovigilance reports suggest that a careful use of baclofen or even HDB could be possible in compensated cirrhosis. However, theoretical risks of baclofen overdose exist in cases of hepatorenal syndrome or portosystemic shunt. Baclofen could also induce a specific pharmacological potentiation of hepatic encephalopathy and gastropathy. Within CAMTEA, a regional team-based multidisciplinary system for delivering and monitoring off-label medications in alcohol use disorders, a set of predefined precautions for using baclofen in cirrhosis have been implemented, until further information becomes available. These precautions notably consist of a protocolized process for declaring adverse events, and a hepatologic follow-up associated with the usual multidisciplinary care system set up within CAMTEA. PMID:24926632

Rolland, Benjamin; Deheul, Sylvie; Louvet, Alexandre; Gautier, Sophie; Cottencin, Olivier; Bordet, Régis

2014-01-01

193

Taste alterations in liver cirrhosis: are they related to zinc deficiency?  

PubMed

Patients with chronic liver disease may have taste impairment and altered zinc metabolism. We evaluated Taste Detection Thresholds (TDTs) in 60 patients with liver cirrhosis and correlated the findings with disease severity and alcoholic etiology. Plasma zinc levels and urinary output were also measured. A placebo-controlled treatment trial with zinc sulphate was made in 15 patients with compensated cirrhosis in order to ascertain whether zinc deficiency caused taste alterations. Taste detection of salty, sweet and acid tastants was significantly impaired in all cirrhotic patients in comparison with normal subjects. TDTs were not influenced either by the etiology or the severity of the disease. All groups of patients had low plasma zinc levels and decompensated cirrhosis had a significantly increased urinary output of zinc. No correlation was found between taste acuity and plasma zinc levels when only cirrhotic patients were considered. The effect of zinc supplementation on TDTs did not appear to be inferior to that of the placebo. Our results indicate that taste impairment in cirrhotics is due to the disease process per se and not to zinc deficiency. PMID:1638179

Sturniolo, G C; D'Incà, R; Parisi, G; Giacomazzi, F; Montino, M C; D'Odorico, A; Soranzo, P; Naccarato, R

1992-03-01

194

Safety and efficacy of Mangafodipir trisodium in patients with liver lesions and cirrhosis.  

PubMed

Mangafodipir trisodium (Mn-DPDP, Teslascan) is a well-tolerated liver contrast agent. Although the enhancement characteristics of the cirrhotic liver after Mangafodipir trisodium administration have been studied, at present there is no published data on the impact that cirrhosis might have on the safety and efficacy profiles of this agent. Our objective is to evaluate by means of a retrospective comparison the safety and efficacy of Mangafodipir trisodium in patients with underlying cirrhosis who were examined for suspicion of focal liver lesions. A total of 923 patients received Mangafodipir trisodium (5 micromol/kg) in 11 prospective randomized European clinical trials. Adverse events and discomfort were recorded and graded in all patients. The efficacy analyses were performed on the subsets consisting of 617 patients with independent lesion counts (detection), and on the subset with 399 patients with independent and onsite final lesion diagnosis (characterization). Of the 399 patients, 149 had histologic confirmation. One hundred eighty of 923 patients (19.5%) had cirrhosis. There were no main differences between cirrhotic and non-cirrhotic patients. Adverse events were observed in 64 patients (6.9%), 6.7% in the cirrhotic group and 7.0% in the non-cirrhotic group, a non-significant difference. Adverse events in most patients were mild or moderate. The presence and intensity of the events did not differ between groups. Discomfort was recorded in 79 patients (8.6%), equally distributed in cirrhotic (6.1%) and non-cirrhotic (9.2%) patients. Regarding lesion count, significantly more lesions were found in the post- than in the precontrast images in both the cirrhotic and non-cirrhotic groups ( p<0.0001). This increase was not influenced by the presence of liver cirrhosis ( p=0.94). Lesion characterization was significantly improved in cirrhotic patients after administration of Mangafodipir trisodium ( p=0.002) but not in non-cirrhotic patients ( p=0.13). Mangafodipir trisodium is a safe and well-tolerated useful contrast agent in patients with cirrhosis. PMID:12835986

Martí-Bonmatí, Luis; Fog, Amura F; de Beeck, Bart Op; Kane, Pauline; Fagertun, Hans

2003-07-01

195

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

196

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

197

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

198

Liver cirrhosis in patients newly diagnosed with neurological phenotype of Wilson’s disease  

PubMed Central

Summary Wilson’s disease (WD) can manifest itself in different clinical forms, the neurological and hepatic ones being the most common. It is suggested that neurological signs and psychiatric symptoms develop secondary to liver involvement. The aim of this study was to characterize the liver disease in patients newly diagnosed with the neurological form of WD. Treatment-naive patients diagnosed with WD were classified into three phenotypic groups: hepatic, neurological and pre-symptomatic. Liver involvement was ascertained through surrogate markers: abdominal ultrasound and laboratory parameters. In addition, study participants were screened for esophageal varices. Of 53 consecutively diagnosed WD patients, 23 individuals (43.4%) had a predominantly neurological presentation. In this group, cirrhosis was diagnosed in 11 (47.8%) subjects. Esophageal varices were present in all of them. In every patient with neurological WD, there was at least one sign of hepatic disease on ultrasound examination, indicating universal presence of liver involvement. The prevalence of surrogate signs of cirrhosis was similar in patients with the neurological and in those with the hepatic phenotype. PMID:25014046

Przyby?kowski, Adam; Gromadzka, Gra?yna; Chabik, Grzegorz; Wierzchowska, Agata; Litwin, Tomasz; Cz?onkowska, Anna

2014-01-01

199

Role of Human Albumin in the Management of Complications of Liver Cirrhosis  

PubMed Central

Albumin is a negatively charged, relatively small protein synthesized by liver cells. Is the most abundant protein in extracellular fluid and accounts for about 70% of the plasma colloid osmotic pressure. Therefore it plays a crucial role in regulating fluid distribution in the body. In addition, albumin possesses functional domains with important non-oncotic properties, such as potent anti-oxydant and scavenging activities, binding of highly toxic reactive metal species and a great amount of endogenous and exogenous substances. We have recently learned that albumin in cirrhosis undergoes a number of post-transcriptional changes that greatly impair its non-oncotic properties. The overall assessment of these changes clearly shows that the relative abundance of the native form of albumin is significantly reduced in hospitalized patients with cirrhosis and that these abnormalities worsen in parallel with the increasing severity of the disease. Thus, it is time to abandon the concept of serum albumin concentration and refer to the effective albumin concentration, that is the native intact albumin. Given the pathophysiological context in which we use human albumin in patients with cirrhosis, who are characterized by peripheral vasodilation and a low-grade but sustained inflammatory state, the use of albumin in patients with cirrhosis should aim at enhancing effective hypovolemia and exploiting its antioxidant and scavenging activities. The indications for the use of albumin in cirrhosis that clearly emerge from evidence-based medicine are represented by conditions characterized by an acute aggravation of effective hypovolemia and inflammation, such as such post-paracentesis circulatory dysfunction, spontaneous bacterial peritonitis, and hepatorenal syndrome. Other indications to the use of albumin that still require further studies are represented by bacterial infections other than spontaneous bacterial peritonitis, hepatic encephalopathy and long-term treatment of ascites, which has been debated for the last half-century. PMID:25755577

Bernardi, Mauro; Ricci, Carmen S.; Zaccherini, Giacomo

2014-01-01

200

Role of human albumin in the management of complications of liver cirrhosis.  

PubMed

Albumin is a negatively charged, relatively small protein synthesized by liver cells. Is the most abundant protein in extracellular fluid and accounts for about 70% of the plasma colloid osmotic pressure. Therefore it plays a crucial role in regulating fluid distribution in the body. In addition, albumin possesses functional domains with important non-oncotic properties, such as potent anti-oxydant and scavenging activities, binding of highly toxic reactive metal species and a great amount of endogenous and exogenous substances. We have recently learned that albumin in cirrhosis undergoes a number of post-transcriptional changes that greatly impair its non-oncotic properties. The overall assessment of these changes clearly shows that the relative abundance of the native form of albumin is significantly reduced in hospitalized patients with cirrhosis and that these abnormalities worsen in parallel with the increasing severity of the disease. Thus, it is time to abandon the concept of serum albumin concentration and refer to the effective albumin concentration, that is the native intact albumin. Given the pathophysiological context in which we use human albumin in patients with cirrhosis, who are characterized by peripheral vasodilation and a low-grade but sustained inflammatory state, the use of albumin in patients with cirrhosis should aim at enhancing effective hypovolemia and exploiting its antioxidant and scavenging activities. The indications for the use of albumin in cirrhosis that clearly emerge from evidence-based medicine are represented by conditions characterized by an acute aggravation of effective hypovolemia and inflammation, such as such post-paracentesis circulatory dysfunction, spontaneous bacterial peritonitis, and hepatorenal syndrome. Other indications to the use of albumin that still require further studies are represented by bacterial infections other than spontaneous bacterial peritonitis, hepatic encephalopathy and long-term treatment of ascites, which has been debated for the last half-century. PMID:25755577

Bernardi, Mauro; Ricci, Carmen S; Zaccherini, Giacomo

2014-12-01

201

Inhibitory Control Test for the Detection of Minimal Hepatic Encephalopathy in Patients with Cirrhosis of Liver  

PubMed Central

Background & aims Minimal hepatic encephalopathy (MHE) has significant impact on future clinical outcomes, such as occurrence of overt HE (OHE) and survival in patients of cirrhosis. In the absence of a ‘gold standard’, psychometric hepatic encephalopathy score (PHES) is widely used for the diagnosis of MHE. This cross-sectional and prospective study was carried out to determine the usefulness of inhibitory control test (ICT) for the diagnosis of MHE. Methods One hundred and two patients with cirrhosis and without a history of OHE were enrolled in to the study and were subjected to PHES and ICT. MHE was diagnosed when the PHES was ? ?5. ICT was considered abnormal when the numbers of ICT lures were more than 14. Results Forty-one (40.2%) patients had MHE. There were 40 patients with normal PHES and ICT, 32 with abnormal PHES and ICT, 9 with abnormal PHES and normal ICT, and 21 with abnormal ICT and normal PHES score. ICT had 78% sensitivity and 65.6% specificity and an area-under-the-curve value of 0.735 (95% CI = 0.632–0.830) for the diagnosis of MHE. In patients with cirrhosis, ICT did not correlate with severity of liver disease as measured by CTP score (r = 0.044, P = 0.658) and MELD score (r = 0.176, P = 0.077). ICT did not predict survival as well as PHES; while 6 (11.3%) patients died among those who had altered ICT compared to 4 (8.2%) patients who did not have altered ICT (P = 0.74), 8 (19.5%) patients died among those who had altered PHES compared to 2 (3.3%) patients who did not have altered PHES (P = 0.013). Conclusion ICT is not as useful as PHES in diagnosing MHE in patients with cirrhosis of the liver. It does not correlate with disease severity and predict survival as well as PHES.

Taneja, Sunil; Dhiman, Radha K.; Khatri, Amit; Goyal, Sandeep; Thumbru, Kiran K.; Agarwal, Ritesh; Duseja, Ajay; Chawla, Yogesh

2012-01-01

202

Progression of liver cirrhosis to HCC: an application of hidden Markov model  

PubMed Central

Background Health service databases of administrative type can be a useful tool for the study of progression of a disease, but the data reported in such sources could be affected by misclassifications of some patients' real disease states at the time. Aim of this work was to estimate the transition probabilities through the different degenerative phases of liver cirrhosis using health service databases. Methods We employed a hidden Markov model to determine the transition probabilities between two states, and of misclassification. The covariates inserted in the model were sex, age, the presence of comorbidities correlated with alcohol abuse, the presence of diagnosis codes indicating hepatitis C virus infection, and the Charlson Index. The analysis was conducted in patients presumed to have suffered the onset of cirrhosis in 2000, observing the disease evolution and, if applicable, death up to the end of the year 2006. Results The incidence of hepatocellular carcinoma (HCC) in cirrhotic patients was 1.5% per year. The probability of developing HCC is higher in males (OR = 2.217) and patients over 65 (OR = 1.547); over 65-year-olds have a greater probability of death both while still suffering from cirrhosis (OR = 2.379) and if they have developed HCC (OR = 1.410). A more severe casemix affects the transition from HCC to death (OR = 1.714). The probability of misclassifying subjects with HCC as exclusively affected by liver cirrhosis is 14.08%. Conclusions The hidden Markov model allowing for misclassification is well suited to analyses of health service databases, since it is able to capture bias due to the fact that the quality and accuracy of the available information are not always optimal. The probability of evolution of a cirrhotic subject to HCC depends on sex and age class, while hepatitis C virus infection and comorbidities correlated with alcohol abuse do not seem to have an influence. PMID:21457586

2011-01-01

203

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

PubMed Central

Characterizing the metabolic changes pertaining to hepatocellular carcinoma (HCC) in patients with liver cirrhosis is believed to contribute towards early detection, treatment, and understanding of the molecular mechanisms of HCC. In this study, we compare metabolite levels in sera of 78 HCC cases with 184 cirrhotic controls by using ultra performance liquid chromatography coupled with a hybrid quadrupole time-of-flight mass spectrometry (UPLC-QTOF MS). Following data preprocessing, the most relevant ions in distinguishing HCC cases from patients with cirrhosis are selected by parametric and non-parametric statistical methods. Putative metabolite identifications for these ions are obtained through mass-based database search. Verification of the identities of selected metabolites is conducted by comparing their MS/MS fragmentation patterns and retention time with those from authentic compounds. Quantitation of these metabolites is performed in a subset of the serum samples (10 HCC and 10 cirrhosis) using isotope dilution by selected reaction monitoring (SRM) on triple quadrupole linear ion trap (QqQLIT) and triple quadrupole (QqQ) mass spectrometers. The results of this analysis confirm that metabolites involved in sphingolipid metabolism and phospholipid catabolism such as sphingosine-1-phosphate (S-1-P) and lysophosphatidylcholine (lysoPC 17:0) are up-regulated in sera of HCC vs. those with liver cirrhosis. Down-regulated metabolites include those involved in bile acid biosynthesis (specifically cholesterol metabolism) such as glycochenodeoxycholic acid 3-sulfate (3-sulfo-GCDCA), glycocholic acid (GCA), glycodeoxycholic acid (GDCA), taurocholic acid (TCA), and taurochenodeoxycholate (TCDCA). These results provide useful insights into HCC biomarker discovery utilizing metabolomics as an efficient and cost-effective platform. Our work shows that metabolomic profiling is a promising tool to identify candidate metabolic biomarkers for early detection of HCC cases in high risk population of cirrhotic patients. PMID:22882828

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

2012-01-01

204

The antifibrotic effect of TGF-beta1 siRNAs in murine model of liver cirrhosis.  

PubMed

Liver fibrosis results from chronic damage to the liver by chronic hepatitis, alcohol, and toxic agents. A characteristic of liver fibrosis is an accumulation of extracellular matrix (ECM) protein, which distorts the hepatic architecture by forming a fibrous scar, and the subsequent development of regenerating nodules defines cirrhosis. Transforming growth factor (TGF)-beta1, one of the most powerful profibrogenic mediators, plays a major role in the development of liver cirrhosis and regulates ECM gene expression and matrix degradation. This study elucidates the changes of TGF-beta1-mediated signals during liver fibrogenesis by using RNA interference. In this experiment, the TGF-beta1 siRNAs reduced the expression of TGF-beta1 in the livers of CCl(4) injection compared with those of control group, and the expression of type I collagen and alpha-smooth muscle actin was decreased. In conclusion, this study demonstrates that TGF-beta1 siRNAs inhibit TGF-beta1 expression in the murine model of liver cirrhosis and might be a good therapeutic strategy to prevent liver cirrhosis in human. PMID:16579972

Kim, Kyung-Hyun; Kim, Hyun-Chul; Hwang, Mee-Yul; Oh, Hoon-Kyu; Lee, Tae-Sung; Chang, Young-Chae; Song, Ho-Jung; Won, Nam-Hee; Park, Kwan-Kyu

2006-05-19

205

Two-dimensional Shear-Wave Elastography and Conventional US: The Optimal Evaluation of Liver Fibrosis and Cirrhosis.  

PubMed

Purpose To evaluate the individual and combined performances of two-dimensional (2D) shear-wave elastography (SWE) and conventional ultrasonography (US) in assessing liver fibrosis and cirrhosis to determine when 2D SWE should be added to routine US. Materials and Methods This prospective study was approved by the institutional ethics committee, and the patients provided written informed consent. Between April 2012 and March 2013, conventional US and 2D SWE examinations were performed in 198 patients (mean age, 37.7 years; age range, 18-67 years) with chronic liver disease. Liver biopsy was used as a reference standard for 167 patients; the other 31 patients had decompensated liver cirrhosis. Receiver operating characteristic (ROC) curves were obtained to assess the diagnostic performance. Differences between the areas under the ROC curves (AUCs) were compared by using a Delong test. Results Two-dimensional SWE was significantly superior to US in diagnosis of significant fibrosis (score of F2 or greater) (AUC, 0.862 vs 0.725; P = .001) and early cirrhosis (score of F4) (AUC, 0.926 vs 0.789; P = .007). Combining 2D SWE with US did not increase the performance of depicting either significant fibrosis or liver cirrhosis (P = .713 and 0.410, respectively) relative to 2D SWE alone. There was no significant difference between 2D SWE and US in diagnosis of decompensated cirrhosis (AUC, 0.878 vs 0.925; P = .323). In addition, combining 2D SWE with US did not increase the performance relative to that of US alone (P = .372). Conclusion Conventional US is sufficient to detect decompensated cirrhosis. Two-dimensional SWE is significantly superior to US in detecting liver fibrosis. Combining 2D SWE and US did not improve the diagnostic performance for either fibrosis or cirrhosis. (©) RSNA, 2015. PMID:25575116

Zheng, Jian; Guo, Huanyi; Zeng, Jie; Huang, Zeping; Zheng, Bowen; Ren, Jie; Xu, Erjiao; Li, Kai; Zheng, Rongqin

2015-04-01

206

A multilevel modeling framework to study hepatic perfusion characteristics in case of liver cirrhosis.  

PubMed

Liver cirrhosis represents the end-stage of different liver disorders, progressively affecting hepatic architecture, hemodynamics, and function. Morphologically, cirrhosis is characterized by diffuse fibrosis, the conversion of normal liver architecture into structurally abnormal regenerative nodules and the formation of an abundant vascular network. To date, the vascular remodeling and altered hemodynamics due to cirrhosis are still poorly understood, even though they seem to play a pivotal role in cirrhogenesis. This study aims to determine the perfusion characteristics of the cirrhotic circulation using a multilevel modeling approach including computational fluid dynamics (CFD) simulations. Vascular corrosion casting and multilevel micro-CT imaging of a single human cirrhotic liver generated detailed datasets of the hepatic circulation, including typical pathological characteristics of cirrhosis such as shunt vessels and dilated sinusoids. Image processing resulted in anatomically correct 3D reconstructions of the microvasculature up to a diameter of about 500??m. Subsequently, two cubic samples (150?×?150?×?150??m3) were virtually dissected from vascularized zones in between regenerative nodules and applied for CFD simulations to study the altered cirrhotic microperfusion and permeability. Additionally, a conceptual 3D model of the cirrhotic macrocirculation was developed to reveal the hemodynamic impact of regenerative nodules. Our results illustrate that the cirrhotic microcirculation is characterized by an anisotropic permeability showing the highest value in the direction parallel to the central vein (kd,zz?=?1.68?×?10-13 m2 and kd,zz?=?7.79?×?10-13 m2 for sample 1 and 2, respectively) and lower values in the circumferential (kd,???=?5.78?×?10-14 m2 and kd,???=?5.65?×?10-13 m2 for sample 1 and 2, respectively) and radial (kd,rr?=?9.87?×?10-14 m2 and kd,rr?=?5.13?×?10-13 m2 for sample 1 and 2, respectively) direction. Overall, the observed permeabilities are markedly higher compared to a normal liver, implying a locally decreased intrahepatic vascular resistance (IVR) probably due to local compensation mechanisms (dilated sinusoids and shunt vessels). These counteract the IVR increase caused by the presence of regenerative nodules and dynamic contraction mechanisms (e.g., stellate cells, NO-concentration, etc.). Our conceptual 3D model of the cirrhotic macrocirculation indicates that regenerative nodules severely increase the IVR beyond about 65 vol. % of regenerative nodules. Numerical modeling allows quantifying perfusion characteristics of the cirrhotic macro- and microcirculation, i.e., the effect of regenerative nodules and compensation mechanisms such as dilated sinusoids and shunt vessels. Future research will focus on the development of models to study time-dependent degenerative adaptation of the cirrhotic macro- and microcirculation. PMID:25473885

Peeters, Geert; Debbaut, Charlotte; Cornillie, Pieter; De Schryver, Thomas; Monbaliu, Diethard; Laleman, Wim; Segers, Patrick

2015-05-01

207

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

208

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

PubMed Central

Rationale and Objectives. To develop an optimal scanning protocol for multislice spiral CT perfusion (CTP) imaging to evaluate hemodynamic changes in liver cirrhosis with diethylnitrosamine- (DEN-) induced precancerous lesions. Materials and Methods. Male Wistar rats were randomly divided into the control group (n = 80) and the precancerous liver cirrhosis group (n = 40). The control group received saline injection and the liver cirrhosis group received 50?mg/kg DEN i.p. twice a week for 12 weeks. All animals underwent plain CT scanning, CTP, and contrast-enhanced CT scanning. Scanning parameters were optimized by adjusting the diatrizoate concentration, the flow rate, and the delivery time. The hemodynamics of both groups was further compared using optimized multislice spiral CTP imaging. Results. High-quality CTP images were obtained with following parameters: 150?kV; 150?mAs; 5?mm thickness, 5?mm interval; pitch, 1; matrix, 512 × 512; and FOV, 9.6?cm. Compared to the control group, the liver cirrhosis group had a significantly increased value of the hepatic arterial fraction and the hepatic artery perfusion (P < 0.05) but significantly decreased hepatic portal perfusion and mean transit time (P < 0.05). Conclusion. Multislice spiral CTP imaging can be used to evaluate the hemodynamic changes in the rat model of liver cirrhosis with precancerous lesions. PMID:23865067

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

2013-01-01

209

Child-Pugh Score Is an Independent Risk Factor for Immediate Bleeding after Colonoscopic Polypectomy in Liver Cirrhosis  

PubMed Central

Purpose Post-polypectomy bleeding is the most common colonoscopic polypectomy complication. However, the risk of post-polypectomy bleeding in liver cirrhosis is unknown. We aimed to evaluate the risk of post-polypectomy bleeding in patients with liver cirrhosis. Materials and Methods We included 89 patients with liver cirrhosis who received colonoscopic polypectomy between January 2006 and October 2012. Three hundred forty-eight subjects without liver disease who underwent colonoscopic polypectomy comprised the control group. Risks of post-polypectomy bleeding were analyzed according to patient- and polyp-related factors. Results Among 89 patients, 75 (84.3%) were Child-Pugh class A, 10 (11.2%) were class B, and 4 (4.5%) were class C. Incidence of immediate post-polypectomy bleeding was significantly increased in cirrhosis with Child-Pugh class B or C compared to liver cirrhosis with Child-Pugh class A or control group [hazard ratio (HR) 3.5; p<0.001]. Polyp size (HR 3.6; p=0.032) and pedunculated polyps (HR 2.4; p=0.022) were also significant risk factors for immediate post-polypectomy bleeding in multivariate analysis. Conclusion Cirrhotic patients with Child-Pugh class B or C have a high risk of immediate post-polypectomy bleeding. Thus, endoscopists should be cautious about performing colonoscopic polypectomy in patients with Child-Pugh class B or C. PMID:25048486

Lee, Sangheun; Park, Soo Jung; Cheon, Jae Hee; Kim, Tae Il; Kim, Won Ho; Kang, Dae Ryong

2014-01-01

210

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

211

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

212

Influence of olive and rosemary leaves extracts on chemically induced liver cirrhosis in male rats  

PubMed Central

The current study was undertaken to evaluate the protective activity of olive and rosemary leaves extracts on experimental liver cirrhosis induced by thioacetamide (TAA) in Wistar male rats. Highly significant decline in the values of body weight gain and highly statistically increase of liver/body weight ratio were noted in rats treated with TAA. Furthermore, the levels of serum alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, alkaline phosphatase and total bilirubin were statistically increased. Additionally, light microscopic examination of liver sections from rats treated with TAA showed a marked increase in the extracellular matrix collagen content and bridging fibrosis was prominent. There were bundles of collagen surrounding the lobules that resulted in large fibrous septa and distorted tissue architecture. Interestingly, the findings of this experimental study indicated that the extracts of olive and rosemary leaves and their combination possess hepatoprotective properties against TAA-induced hepatic cirrhosis by inhibiting the physiological and histopathological alterations. Moreover, these results suggest that the hepatoprotective effects of these extracts may be attributed to their antioxidant activities. PMID:25737646

Al-Attar, Atef M.; Shawush, Nessreen A.

2014-01-01

213

An unusual cause of spontaneous bacterial peritonitis due to Campylobacter fetus with alcoholic liver cirrhosis.  

PubMed

A 40-year-old man with severe alcoholic liver cirrhosis with a 2-day history of fatigue and abdominal pain was admitted. He reported eating sushi and sliced raw chicken a few days previously. His abdomen was distended, with shifting dullness. Based on the patient's history, physical examination and the results of abdominocentesis, he was diagnosed as having spontaneous bacterial peritonitis; blood and ascitic fluid cultures were positive for Campylobacter fetus. The patient was started on treatment with cefotaxime, which was switched after 1 week to ampicillin for an additional 3 weeks. The patient was successfully treated with the 4-week course of intravenous antibiotic therapy. PMID:23417384

Hadano, Yoshiro; Iwata, Hiroyoshi

2013-01-01

214

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

215

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

PubMed Central

Background Although significant advances are expected to be made in the assessment of the portal hypertension-related complications, the prognostic role of spleno-renal shunts has not been fully explored so far. Clarifying this aspect could help tackle the life-treating events occurring in patients suffering from liver cirrhosis. The aim of the study was to analyze the relationships between the spleno-renal shunts presence at doppler ultrasound and the liver cirrhosis complications. Methods Design: eighty one patients out of 129 formed the study population (35 females). Chronic liver damage in these patients was caused by HCV (66), HBV (2), alcohol abuse (2) or unknown etiology, likely non-alcoholic steatohepatitis (11). Setting: two Liver Units of university/primary hospitals in Southern Italy. Main outcome measures: grading of esofageal varices; detection of ascites: assessment of hepatic encephalopathy; evaluation of liver cirrhosis severity; tracking hepatocellular carcinoma; doppler features of spleno-renal shunts and splenic flow velocity; spleen longitudinal diameter at sonography. Results The prevalence of spleno-renal shunts was 18.5%, without no difference concerning the etiology (HCV versus non-HCV, p = 0.870); the prevalence of hepatocellular carcinoma in patients with spleno-renal shunts was superior to that of patients without them (Pearson Chi-square, p = 0.006, power of sample size 74%), also after adjustment for liver decompensation (p = 0.024). The median score of hepatic encephalopathy in patients with and without spleno-renal shunts was similar, i.e., 0 (range, 0-2) versus 0 (0 - 3), p = 0.67. The median splenic vein flow velocity in patients with spleno-renal shunts was significantly inferior to that of patients without them, i.e., 13 cm/sec (95% confidence intervals, 6-18) versus 21 cm/sec (17-24), p < 0.0001. By far the largest percentage of large esophageal varices was in patients without spleno-renal shunts (p = 0.005). In contrast, the frequency of ascites and hepatic encephalopathy severity was overlapping in the two groups. BMI values but not Child-Pugh's classification predicted spleno-renal shunts (Ors = 1.84, 95% confidence intervals = 1.28-2.64, p = 0.001 and 1.145, 95% confidence intervals = 0.77-1.51, p = 0.66). Conclusion Taking into consideration the relatively small sample size, patients with spleno-renal shunts are burdened by an increased incidence of hepatocellular carcinoma. BMI predicted the spleno-renal shunts presence. PMID:19930687

2009-01-01

216

The role of hepatic myofibroblasts in liver cirrhosis in fallow deer (Dama dama) naturally infected with giant liver fluke (Fascioloides magna)  

PubMed Central

Background This paper describes liver cirrhosis in 35 fallow deer infected with the giant liver fluke, as well as the distribution, origin, and role of myofibroblasts in its development. Results In liver of infected deer, stripes of connective tissue are wound around groups of degenerated and regenerated liver lobuli. In the connective tissue, lymphocytes and macrophages which often contain parasite hematin are also present. The walls of the bile ducts are thickened, the epithelium multiplied with mucous metaplasia, and desquamated cells, parasite eggs and brown pigment are present in their lumen. In the livers with cirrhosis, immunopositivity to ?-SMA and desmin was observed in cells in portal and septal spaces, at the edge between fibrotic septa and the surrounding parenchyma and in perisinusoidal spaces. These cells vary in size, they are round, oval, spindle-shaped or irregular in shape, similar to vascular smooth muscle cells. The derangement of epithelial-mesenchymal interactions detected in chronic cholangiopathies is most probably the pro-fibrogenic mechanism in liver cirrhosis of fallow deer (Dama dama) infected with the giant liver fluke (Fascioloides magna). Conclusion Myofibroblasts, especially hepatic stellate cells (HSCs), play an important role in the synthesis of extracellular matrix components in the development of parasitic fibrosis and cirrhosis in the liver of fallow deer. PMID:23497565

2013-01-01

217

Overweight and obesity increase the risk for liver cancer in patients with liver cirrhosis and long-term oral supplementation with branched-chain amino acid granules inhibits liver carcinogenesis in heavier patients with liver cirrhosis.  

PubMed

We conducted a multicenter, randomized, controlled trial to investigate the effect of long-term oral supplementation with branched-chain amino acids (BCAA) on the event-free survival in 622 patients with decompensated cirrhosis. In the present study, the development of liver cancer was analyzed as an endpoint in particular. Subjects received either treatment with BCAA at 12g/day or dietary therapy containing the matched daily energy and protein intake. A Cox regression analysis was carried out to estimate the hazard ratios for different background factors stratified by treatment group. Liver cancer was noted in 89 patients. The risk for liver cancer was significantly higher for males, patients with concurrent diabetes mellitus, patients with an alpha-fetoprotein (AFP) level of 20ng/mL or higher, patients with higher body mass index (BMI), and patients with lower serum albumin levels. When the BCAA group and the diet group were compared for factors that interacted with the treatment arms, the risk for liver cancer was significantly reduced in the BCAA group with a BMI of 25 or higher and with an AFP level of 20ng/mL or higher. Oral supplemental treatment with BCAA may reduce the risk of liver cancer in cirrhotic patients with these specific factors. PMID:16737844

Muto, Yasutoshi; Sato, Shunichi; Watanabe, Akiharu; Moriwaki, Hisataka; Suzuki, Kazuyuki; Kato, Akinobu; Kato, Masahiko; Nakamura, Teiji; Higuchi, Kiyohiro; Nishiguchi, Shuhei; Kumada, Hiromitsu; Ohashi, Yasuo

2006-07-01

218

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

PubMed Central

AIM: To evaluate the clinical significance of cystatin C and renal resistive index for the determination of renal function in patients with liver cirrhosis. METHODS: We conducted a study of 63 patients with liver cirrhosis. A control group comprised of 30 age and gender-matched healthy persons. Serum cystatin C was determined in all study subjects and renal Doppler ultrasonography was made. Estimated glomerular filtration rate from serum creatinine (GFRCr) and cystatin C (GFRCys) was calculated. RESULTS: We confirmed significant differences in values of cystatin C between patients with different stages of liver cirrhosis according to Child-Pugh (P = 0.01), and a significant correlation with model of end stage liver disease (MELD) score (rs = 0.527, P < 0.001). More patients with decreased glomerular filtration rate were identified based on GFRCys than on GFRCr (P < 0.001). Significantly higher renal resistive index was noted in Child-Pugh C than in A (P < 0.001) and B stage (P = 0.001). Also, a significant correlation between renal resistive index and MELD score was observed (rs = 0.607, P < 0.001). Renal resistive index correlated significantly with cystatin C (rs = 0.283, P = 0.028) and showed a negative correlation with GFRCys (rs = -0.31, P = 0.016). CONCLUSION: Cystatin C may be a more reliable marker for assessment of liver insufficiency. Additionally, cystatin C and renal resistive index represent sensitive indicators of renal dysfunction in patients with liver cirrhosis. PMID:24914379

?ulafi?, ?or?e; Štuli?, Miloš; Obrenovi?, Radmila; Mileti?, Danijela; Mija?, Dragana; Stojkovi?, Milica; Jovanovi?, Marija; ?ulafi?, Milica

2014-01-01

219

Correlation Between Patatin-Like Phospholipase Domain-Containing Protein 3 Gene Polymorphisms and Liver Cirrhosis in a Chinese Han Population With Chronic Hepatitis B  

PubMed Central

Background: A single nucleotide polymorphism (SNP) of patatin-like phospholipase domain-containing 3 (PNPLA3) genes (rs738409) is associated with the severity of fibrosis and cirrhosis in patients with fatty liver disease. However, in a small group of Italian patients, there was no significant correlation between the rs738409 SNP and hepatitis B virus (HBV) infection-associated liver cirrhosis. Objectives: This study aimed to investigate whether PNPLA3 polymorphisms are a risk factor for liver cirrhosis in a Chinese Han population with chronic hepatitis B (CHB). Patients and Methods: The study population consisted of 344 Chinese Han patients with CHB, among which 203 presented with liver cirrhosis (LC group) and 141 had no sign of liver cirrhosis (CHB group). TaqMan genotyping assay was used to investigate the association of two PNPLA3 SNPs (rs738409 and rs2281135) with the risk of liver cirrhosis. Results: The allele and genotype distributions of PNPLA3 rs738409 and rs2281135 were not significantly different between the CHB and LC groups. After segregation on the basis of sex, no significant correlation between PNPLA3 (rs738409 and rs2281135) genotypes/alleles and liver cirrhosis was detected. Moreover, none of the haplotypes in PNPLA3 (rs738409 and rs2281135) was found to be statistically different between the two groups. Conclusions: Our results showed no association between PNPLA3 polymorphisms (rs738409 and rs2281135) and the susceptibility to HBV-related liver cirrhosis in a Chinese Han population. PMID:25337145

Tong, Jin; Guo, Jinjun; Hu, Jun; Hou, Sihui; Zhang, Yu; Li, Qingling

2014-01-01

220

Is it possible to predict HCV-related liver cirrhosis non-invasively through routine laboratory parameters?  

PubMed

It is estimated that hepatitis C virus (HCV) infects chronically about 160 million people worldwide. Between 15 and 56% of these chronic carriers will evolve towards liver cirrhosis during their lifetimes. In managing subjects with HCV chronic infection, it is crucial to perform accurate staging of the disease and specifically to ascertain whether or not they have liver cirrhosis for at least three reasons: 1) the presence of cirrhosis has prognostic relevance as it entails a relatively high risk of developing decompensation (e.g., ascites, encephalopathy, jaundice, oesophageal variceal bleeding) or evolution toward hepatocellular carcinoma (HCC); 2) the presence of liver cirrhosis is the main indication for urgent treatment and paradoxically a factor predicting a poor response to currently available therapies. The timing of therapy is particular important considering that the new era of interferon-free antivirals will be a reality in a few years; 3) finally, in the presence of liver cirrhosis current guidelines recommend periodical screening for the presence of oesophageal varices and HCC. With the exception of the most advanced stages, the diagnosis of liver cirrhosis is obtained by performing a percutaneous liver biopsy, which is an invasive technique and therefore is associated with a low but non-negligible rate of complications and even death. Finally, it has a non-null rate of false negative for the diagnosis of liver cirrhosis when compared with surgical biopsy. For these reasons several authors have devised non-invasive scores to predict cirrhosis using different means. The most useful are based on liver stiffness (fibroscan), on a panel of blood tests and a proprietary algorithm (fibrotest) or on routinely available parameters. This review focuses on the different scores based on routine parameters that differ in their ease of calculation, in their diagnostic power and in the information provided. Further studies are required to compare the diagnostic performance of different non-invasive scores with the histologic evaluation and other non-invasive methods (fibroscan or fibrotest) on independent cohorts of patients. PMID:24651085

Gentile, Ivan; Buonomo, Antonio Riccardo; Zappulo, Emanuela; Borgia, Guglielmo

2014-03-01

221

Autoantibodies, histocompatibility antigens and testosterone in males with alcoholic liver cirrhosis.  

PubMed Central

Titres and immunoglobulin classes of autoantibodies were examined in 69 male patients with alcoholic liver cirrhosis and the findings were related to particular human leucocyte antigens and serum concentration of testosterone. Both anti-nuclear antibodies (ANA) and smooth muscle antibodies (SMA) were significantly more prevalent in patients with cirrhosis than in sex- and age-matched controls. Antimitochondrial antibodies and liver cell membrane antibody were found in 4% of the patients, and in none of the controls, but this difference was not significant. Patients with HLA-B8 and/or HLA-B12 had higher titres of ANA (n.s.) and SMA (P less than 0.05) than patients without these HLA antigens. Serum concentrations of testosterone were significantly lower in ANA-positive patients than in those negative (P less than 0.05), and a similar tendency was found in SMA-positive patients. With increasing titres of ANA the concentration of testosterone fell. Serum concentration of testosterone correlated inversely (P less than 0.05) with plasma immunoglobulin G and A. It is concluded that both genetic and hormonal factors may influence the humoral immune response in these patients. PMID:6973433

Gluud, C; Tage-Jensen, U; Bahnsen, M; Dietrichson, O; Svejgaard, A

1981-01-01

222

Laparoscopic Cholecystectomy in Patients With Cirrhosis of the Liver and Symptomatic Cholelithiasis  

PubMed Central

Background: The indications and benefits of laparoscopic cholecystectomy (LC) in patients with liver cirrhosis and symptomatic cholelithiasis have not been satisfactorily documented. The aim of this study was to investigate its efficacy and safety in such patients. Methods: Medical records of 38 patients with liver cirrhosis (stages Child-Pugh A and B) who underwent LC were retrospectively reviewed. Demographic characteristics and other parameters including initial presentation, conversion rate, complication rate, mortality, and duration of hospital stay were investigated and compared with noncirrhotic patients' parameters in our database. Results: Cirrhotic patients who underwent LC were older than noncirrhotic patients (P=0.021). Both the conversion rate (15.78%) and the duration of hospital stay were increased in the cirrhotic group, but without significant differences. Major complications occurred more often in the cirrhotic group (P=0.027), increasing morbidity; however, the mortality was zero. Conclusions: LC can be safely performed in Child-Pugh A and B cirrhotic patients with symptomatic gallstone disease, with acceptable complication and conversion rates. The increased risk for a major complication, however, demands more attention than usual. PMID:19793474

Symeonidis, Nikolaos G.; Psarras, Kyriakos; Skouras, Christos; Kontoulis, Theodoros M.; Ballas, Konstantinos; Rafailidis, Savas F.; Marakis, Georgios N.; Sakantamis, Athanasios K.

2009-01-01

223

Fibroblast Growth Factor Receptor 4 Polymorphism Is Associated with Liver Cirrhosis in Hepatocarcinoma  

PubMed Central

Background Fibroblast growth factor receptor 4 (FGFR4) polymorphisms are positively correlated with tumor progression in numerous malignant tumors. However, the association between FGFR4 genetic variants and the risk of hepatocellular carcinoma (HCC) has not yet been determined. In this study, we investigated the potential associations of FGFR4 single nucleotide polymorphisms (SNPs) with HCC susceptibility and its clinicopathological characteristics. Methodology/Principal Findings Four SNPs in FGFR4 (rs1966265, rs351855, rs2011077, and rs7708357) were analyzed among 884 participants, including 595 controls and 289 patients with HCC. The samples were further analyzed to clarify the associations between these gene polymorphisms and the risk of HCC, and the impact of these SNPs on the susceptibility and clinicopathological characteristics of HCC. After adjusting for other covariants, HCC patients who carrying at least one A genotype (GA and AA) at rs351855 were observed to have a higher risk of liver cirrhosis compared with those carrying the wild-type genotype (GG) (OR: 2.113, 95% CI: 1.188–3.831). Moreover, the patients with at least one A genotype were particularly showed a high level of alpha-fetoprotein (AFP). Conclusions Our findings suggest that genetic polymorphism in FGFR4 rs351855 may be associated with the risk of HCC coupled with liver cirrhosis and may markedly increase the AFP level in Taiwanese patients with HCC. In addition, this is the first study that evaluated the risk factors associated with FGFR4 polymorphism variants in Taiwanese patients with HCC. PMID:25860955

Sheu, Ming-Jen; Hsieh, Ming-Ju; Chiang, Whei-Ling; Yang, Shun-Fa; Lee, Hsiang-Lin; Lee, Liang-Ming; Yeh, Chao-Bin

2015-01-01

224

Correlation of hepatic venous pressure gradient with variceal bleeding, size of esophageal varices, etiology, ascites and degree of liver dysfunction in cirrhosis of liver  

Microsoft Academic Search

An elevated hepatic venous pressure gradient (HVPG) has been associated with risk of variceal bleeding, and outcome and survival\\u000a after variceal bleeding. In this pilot study, we measured HVPG in 40 patients with liver cirrhosis and studied its relationship\\u000a with etiology of liver disease, esophageal variceal size, history of variceal bleeding or ascites, biochemical liver tests\\u000a and Child-Pugh class. There

Ghulam Mohamad Gulzar; Showkat Ali Zargar; Sheikh Jalal; Mohamad Sultan Alaie; Gul Javid; Pawan Kumar Suri; Nisar Ahmad Shah; Bilal-ul-Rehman; Mohamad Shafi Hakeem; Abid Shoukat; Gulzar Ahmad Dar

2009-01-01

225

Impaired Expression of Type I and Type II Interferon Receptors in HCV-Associated Chronic Liver Disease and Liver Cirrhosis  

PubMed Central

Purpose Chronic Hepatitis C Virus (HCV)-infected patients with liver cirrhosis (LC) respond poorly to interferon-alpha (IFN-?) and ribavirin (RBV) combination therapy, but the reason for this is unclear. We previously reported that HCV-infection induces endoplasmic reticulum (ER) stress and autophagy response that selectively down regulates the type I IFN-? receptor-1 (IFNAR1) and RBV transporters (CNT1 and ENT1), leading to IFN-?/RBV resistance. The goal of this study is to verify whether an increase in ER stress and autophagy response is also associated with the reduced expression of IFNAR1 and RBV transporters in chronic HCV-infected patients. Methods Primary human hepatocytes (PHH) were infected with cell culture grown HCV particles (JFH-?V3-Rluc). HCV replication was confirmed by the detection of viral RNA by RT-qPCR and HCV-core protein by Western blotting. The ER stress and autophagy response and expression of IFN receptors and RBV transporters in HCV infected PHH and liver tissues derived from patients were measured by Western blotting. Result HCV infection of PHH showed impaired expression of IFNAR1, IFN?R1 (Type II IFN receptor) and RBV transporters but not IL10R? (Type III IFN-? receptor). ER stress markers (BiP, IRE1? and peIF2?) and autophagy response (LC3II, Beclin 1 and ATG5) were induced in HCV infected chronic liver disease (CLD) and LC patients. Liver biopsies (CLD) show a 50% reduced expression of IFNAR1 and RBV transporters. Furthermore, the expression of IFNAR1 and RBV transporters was impaired in almost all LC patients. Conclusion HCV infection induces ER stress and autophagy response in infected PHH and chronically infected liver tissues. The expression of IFNAR1, IFN?R1 and RBV transporters were significantly impaired in CLD and cirrhotic livers. Our study provides a potential explanation for the reduced response rate of IFN-? and RBV combination therapy in HCV infected patients with liver cirrhosis. PMID:25265476

Chandra, Partha K.; Gunduz, Feyza; Hazari, Sidhartha; Kurt, Ramazan; Panigrahi, Rajesh; Poat, Bret; Bruce, David; Cohen, Ari J.; Behorquez, Humberto E.; Carmody, Ian; Loss, George; Balart, Luis A.; Wu, Tong; Dash, Srikanta

2014-01-01

226

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

227

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

228

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

229

The Value of MRI in the Diagnosis of Primary Biliary Cirrhosis and Assessment of Liver Fibrosis  

PubMed Central

Objectives To evaluate MRI findings in patients with primary biliary cirrhosis (PBC) and to determine the value of MRI in the diagnosis of PBC and assessment of liver fibrosis. Materials and Methods This study reviewed the prevalence of MRI abnormalities seen in 45 PBC patients in the past four years, including 33 patients who underwent liver biopsy. Correlation between the MRI findings and the pathological stage was determined. Results There were 33 patients who underwent liver biopsy. Twenty-five patients (75.8%) had non-homogeneous changes in the liver signal intensity, 25 (75.8%) had a periportal halo sign, and 29 (87.9%) had lymphadenopathy. The short axis of the enlarged lymph nodes was a mean of 1.2±0.3 cm. A strong positive correlation was observed between histological stage and the inhomogeneity of liver signal intensity (P<0.001). There were significant differences among the four histological stages based on the periportal halo sign (P=0.034), and the grading of the periportal halo sign was found to be significantly correlated with the histological stage (P<0.001). Grading of the periportal halo sign was significantly different at stage II versus III, and stage III versus IV; no significant difference was found between stages I and II. There were also no significant differences among the four histological states in the occurrence and size of enlarged lymph nodes (P=0.674 and P=0.394). Conclusion MRI is valuable in the diagnosis of PBC, and the periportal halo sign and liver signal intensity help to evaluate the degree of liver fibrosis. PMID:25781184

Meng, Ying; Liang, Yuting; Liu, Mingming

2015-01-01

230

ADAMTS13 Levels in Young Patients With ?-Thalassemia Major: Relation to Hepatitis C Virus Infection, Liver Cirrhosis, and Iron Overload.  

PubMed

We measured levels of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) in 50 children and adolescents with ?-thalassemia major (25 without hepatitis C virus [HCV] infection and 25 with HCV infection) compared to 25 healthy controls and assessed their relation to iron overload, HCV infection, and liver cirrhosis. Hematological and coagulation profiles, serum ferritin, and von Willebrand factor antigen were assessed. Levels of ADAMTS13 were significantly lower in ?-thalassemia major with and without HCV infection compared to healthy controls, with a more significant reduction in levels among patients with HCV (P < .001). HCV-positive patients with thalassemia having liver cirrhosis had the lowest ADAMTS13 levels than those without cirrhosis (P = .012) or HCV-negative patients with thalassemia (P < .001). Levels of ADAMTS13 were positively correlated with platelet count while inversely correlated with partial thromboplastin time, serum ferritin, and VWF: Ag (P < .05). PMID:25430937

Hamed, Ahmad A; Darwish, Yasser W; El-Sayed, Manal Hamdy

2014-11-26

231

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

PubMed Central

Background Hepatitis C virus (HCV) causes liver fibrosis that may lead to liver cirrhosis or hepatocellular carcinoma (HCC), and may partially depend on infecting viral genotype. HCV genotype 3a is being more common in Asian population, especially Pakistan; the detail mechanism of infection still needs to be explored. In this study, we investigated and compared the gene expression profile between initial fibrosis stage and cirrhotic 3a genotype patients. Methods Gene expression profiling of human liver tissues was performed containing more than 22000 known genes. Using Oparray protocol, preparation and hybridization of slides was carried out and followed by scanning with GeneTAC integrator 4.0 software. Normalization of the data was obtained using MIDAS software and Significant Microarray Analysis (SAM) was performed to obtain differentially expressed candidate genes. Results Out of 22000 genes studied, 219 differentially regulated genes found with P ? 0.05 between both groups; 107 among those were up-regulated and 112 were down-regulated. These genes were classified into 31 categories according to their biological functions. The main categories included: apoptosis, immune response, cell signaling, kinase activity, lipid metabolism, protein metabolism, protein modulation, metabolism, vision, cell structure, cytoskeleton, nervous system, protein metabolism, protein modulation, signal transduction, transcriptional regulation and transport activity. Conclusion This is the first study on gene expression profiling in patients associated with genotype 3a using microarray analysis. These findings represent a broad portrait of genomic changes in early HCV associated fibrosis and cirrhosis. We hope that identified genes in this study will help in future to act as prognostic and diagnostic markers to differentiate fibrotic patients from cirrhotic ones. PMID:22397681

2012-01-01

232

Tissue Localization of Australia Antigen Immune Complexes in Acute and Chronic Hepatitis and Liver Cirrhosis  

PubMed Central

In a significant percentage of examined cases of fulminant hepatitis, subacute hepatitis, chronic aggressive hepatitis, liver cirrhosis and chronic persistent hepatitis, Australia (hepatitis-associated) antigen (Au HAA) was identified in the liver and in extrahepatic locations. The several immunofluorescent patterns of Au HAA localization in hepatocytes strongly suggested various stages of Au HAA accumulation and release. Deposits of a mixture of immunoglobulins G and M and occasionally ?1C-globulin were found in the cytoplasm of Au HAA containing hepatocytes, on their plasma membranes, on or in the nuclei, in the cytoplasm of Kupffer cells and, rarely, in the sinusoids. The accompanying tissue changes were hepatocellular degeneration and necrosis. These intra- and extracellular complexes of Au HAA and immunoglobulins displayed strong affinity for guinea pig complement in the immunohistochemical complement fixation reaction. When tested by immunodiffusion in agar, IgG dissociated from these complexes by potassium thiocyanate (KSCN) treatment showed anti-Au HAA specificity. In fulminant hepatitis neither Au HAA nor immunoglobulins and complement were found in the liver. In chronic aggressive hepatitis and subacute hepatitis the amount of the Au HAA immune complexes identified in the liver was approximately inversely proportional to the extent and severity of the parenchymal lesions. In liver cirrhosis and chronic persistent hepatitis there was a positive correlation between the amount of the Au HAA immune complexes found in the liver and the degree of hepatocellular damage. The deposits of Au HAA, identified in extrahepatic locations including germinal centers of lymph nodes and spleen, kidney glomeruli and blood vessel walls, were as a rule accompanied by deposits of IgG, IgM, ?1C-globulin and fibrin. All these deposits showed strong affinity for guinea pig complement in the immunohistochemical reaction of complement fixation. Germinal center activation, chronic membraneous glomerulonephritis, panarteritis and simple arteriolar hyalinosis were found at sites of localization of these deposits. ImagesFig 21Fig 22Fig 23Fig 24Fig 1Fig 2Fig 3Fig 4Fig 5Fig 6Fig 25Fig 26Fig 27Fig 28Fig 29Fig 7Fig 8Fig 9Fig 10Fig 11Fig 12Fig 13Fig 14Fig 15Fig 16Fig 17Fig 18Fig 19Fig 20 PMID:4628111

Nowos?awski, Adam; Krawczy?ski, Krzysztof; Brzosko, Witold J.; Madali?ski, Kazimierz

1972-01-01

233

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

PubMed Central

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

2012-01-01

234

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. PMID:25678995

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

2014-01-01

235

Study of liver cirrhosis over ten consecutive years in Southern China  

PubMed Central

AIM: To investigate the etiology and complications of liver cirrhosis (LC) in Southern China. METHODS: In this retrospective, cross-sectional study, we identified cases of liver cirrhosis admitted between January 2001 to December 2010 and reviewed the medical records. Patient demographics, etiologies and complications were collected, and etiological changes were illustrated by consecutive years and within two time periods (2001-2005 and 2006-2010). All results were expressed as the mean ± SD or as a percentage. The ?2 test or Student’s t-test was used to analyze the differences in age, gender, and etiological distribution, and one-way analysis of variance was applied to estimate the trends in etiological changes. We analyzed the relationship between the etiologies and complications using unconditioned logistic regression, and the risk of upper gastrointestinal bleeding (UGIB) and hepatocellular carcinoma (HCC) in the major etiological groups was evaluated as ORs. A P value less than 0.05 was considered significant. Statistical computation was performed using SPSS 17.0 software. RESULTS: In this study, we identified 6719 (83.16%) male patients and 1361 (16.84%) female patients. The average age of all of the patients was 50.5 years at the time of diagnosis. The distribution of etiological agents was as follows: viral hepatitis, 80.62% [hepatitis B virus (HBV) 77.22%, hepatitis C virus (HCV) 2.80%, (HBV + HCV) 0.58%]; alcohol, 5.68%; mixed etiology, 4.95%; cryptogenic, 2.93%; and autoimmune hepatitis, 2.03%; whereas the other included etiologies accounted for less than 4% of the total. Infantile hepatitis syndrome LC patients were the youngest (2.5 years of age), followed by the metabolic LC group (27.2 years of age). Viral hepatitis, alcohol, and mixed etiology were more prevalent in the male group, whereas autoimmune diseases, cryptogenic cirrhosis, and metabolic diseases were more prevalent in the female group. When comparing the etiological distribution in 2001-2005 with that in 2006-2010, the proportion of viral hepatitis decreased from 84.7% to 78.3% (P < 0.001), and the proportion of HBV-induced LC also decreased from 81.9% to 74.6% (P < 0.001). The incidence of mixed etiology, cryptogenic cirrhosis, and autoimmune diseases increased by 3.1% (P < 0.001), 0.5% (P = 0.158), and 1.3% (P < 0.001), respectively. Alcohol-induced LC remained relatively steady over the 10-year period. The ORs of the development of UGIB between HBV and other major etiologies were as follows: HCV, 1.07; alcohol, 1.89; autoimmune, 0.90; mixed etiology, 0.83; and cryptogenic, 1.76. The ORs of the occurrence of HCC between HBV and other major etiologies were as follows: HCV, 0.54; alcohol, 0.16; autoimmune, 0.05; mixed etiology, 0.58; and cryptogenic, 0.60. CONCLUSION: The major etiology of liver cirrhosis in Southern China is viral hepatitis. However, the proportions of viral hepatitis and HBV are gradually decreasing. Alcoholic LC patients exhibit a greater risk of experiencing UGIB, and HBV LC patients may have a greater risk of HCC. PMID:25309085

Wang, Xing; Lin, Shang-Xiong; Tao, Jin; Wei, Xiu-Qing; Liu, Yuan-Ting; Chen, Yu-Ming; Wu, Bin

2014-01-01

236

Vascular pathobiology in chronic liver disease and cirrhosis - current status and future directions.  

PubMed

Chronic liver disease is associated with remarkable alterations in the intra- and extrahepatic vasculature. Because of these changes, the fields of liver vasculature and portal hypertension have recently become closely integrated within the broader vascular biology discipline. As developments in vascular biology have evolved, a deeper understanding of vascular processes has led to a better understanding of the mechanisms of the dynamic vascular changes associated with portal hypertension and chronic liver disease. In this context, hepatic vascular cells, such as sinusoidal endothelial cells and pericyte-like hepatic stellate cells, are closely associated with one another, where they have paracrine and autocrine effects on each other and themselves. These cells play important roles in the pathogenesis of liver fibrosis/cirrhosis and portal hypertension. Further, a variety of signaling pathways have recently come to light. These include growth factor pathways involving cytokines such as transforming growth factor ?, platelet derived growth factor, and others as well as a variety of vasoactive peptides and other molecules. An early and consistent feature of liver injury is the development of an increase in intra-hepatic resistance; this is associated with changes in hepatic vascular cells and their signaling pathway that cause portal hypertension. A critical concept is that this process aggregates signals to the extrahepatic circulation, causing derangement in this system's cells and signaling pathways, which ultimately leads to the collateral vessel formation and arterial vasodilation in the splanchnic and systemic circulation, which by virtue of the hydraulic derivation of Ohm's law (pressure = resistance × flow), worsens portal hypertension. This review provides a detailed review of the current status and future direction of the basic biology of portal hypertension with a focus on the physiology, pathophysiology, and signaling of cells within the liver, as well as those in the mesenteric vascular circulation. Translational implications of recent research and the future directions that it points to are also highlighted. PMID:24911462

Iwakiri, Yasuko; Shah, Vijay; Rockey, Don C

2014-10-01

237

Andrographis paniculata Leaf Extract Prevents Thioacetamide-Induced Liver Cirrhosis in Rats  

PubMed Central

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

Bardi, Daleya Abdulaziz; 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

238

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

239

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

240

[Blood circulation in the liver after distal spleno-renal anastomosis in cirrhosis].  

PubMed

Complex hemodynamical investigations were performed in 24 patients with liver cirrhosis before and after the distal splenorenal anastomosis (DSRA) conduction according to conventional and modified methods. After the conventional DSRA formation the portal blood flow had reduced down by 39.6% and after modified method--by 14%. Linear speed of the blood flow in a portal vein after the conventional DSRA formation had reduced a twice, after the modified DSRA--did not change. The pressure in a portal vein after the conventional DSRA formation had reduced by 35%, and after the modified DSRA--by 11%. The portal perfusion lowering had promoted the compensational increase of the blood flow in hepatic artery after the conventional DSRA forming by 22% and after the modified DSRA--by 8%. PMID:10370286

Kotenko, O G

1999-01-01

241

Site-specific Glycoforms of Haptoglobin in Liver Cirrhosis and Hepatocellular Carcinoma*  

PubMed Central

Haptoglobin is a liver-secreted glycoprotein with four N-glycosylation sites. Its glycosylation was reported to change in several cancer diseases, which prompted us to examine site-specific glycoforms of haptoglobin in liver cirrhosis and hepatocellular carcinoma. To this end, we have used two-dimensional separation composed of hydrophilic interaction and nano-reverse phase chromatography coupled to QTOF mass spectrometry of the enriched glycopeptides. Our results show increased fucosylation of haptoglobin in liver disease with up to six fucoses associated with specific glycoforms of one glycopeptide. Structural analysis using exoglycosidase treatment and MALDI-MS/MS of detached permethylated glycans led to the identification of Lewis Y-type structures observed particularly in the pooled hepatocellular carcinoma sample. To confirm the increase of the Lewis Y structures observed by LC-MS, we have used immunoaffinity detection with Lewis Y-specific antibodies. The presence of multiply fucosylated Lewis Y glycoforms of haptoglobin in the disease context could have important functional implications. PMID:23389049

Pompach, Petr; Brnakova, Zuzana; Sanda, Miloslav; Wu, Jing; Edwards, Nathan; Goldman, Radoslav

2013-01-01

242

Imatinib-induced liver cirrhosis in a patient with advanced gastrointestinal stroma tumor (GIST)  

PubMed Central

Background The use of imatinib mesylate is associated with a progression free survival of 41?months in first line treatment of metastatic or locally advanced gastrointestinal stromal tumors (GIST) and other studies approved that adjuvant imatinib treatment improves the recurrence-free survival in patients with GIST. Current recommendations include 1?year adjuvant treatment in GIST patients at risk but active studies explore different durations of treatment with an interval of up to 5?years. While the most frequent adverse events (AEs) are blood count alterations, abdominal discomfort and edema, the occurrence of grade 3 or 4 increase of AST or ALT is specified with 2.1% and 2.7% respectively. Case presentation We report a 49-year old male with a gastrointestinal stromal tumor (GIST) of the small bowel who developed liver cirrhosis under adjuvant imatinib treatment. Conclusions Our report supports the notion that imatinib-induced hepatotoxicity may lead to acute liver damage with subsequent cirrhotic remodelling. Patients developing grade 3 or 4 hepatotoxicity during imatinib treatment should therefore be carefully evaluated for chronic liver disease. PMID:22612794

2012-01-01

243

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

244

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

245

Adipokines levels are associated with the severity of liver disease in patients with alcoholic cirrhosis  

PubMed Central

AIM: To investigate the adipokine levels of leptin, adiponectin, resistin, visfatin, retinol-binding protein 4 (RBP4), apelin in alcoholic liver cirrhosis (ALC). METHODS: Forty non-diabetic ALC patients [median age: 59 years, males: 35 (87.5%), Child-Pugh (CP) score: median 7 (5-12), CP A/B/C: 18/10/12, Model for End-stage Liver Disease (MELD): median 10 (6-25), follow-up: median 32.5 mo (10-43)] were prospectively included. The serum adipokine levels were estimated in duplicate by ELISA. Somatometric characteristics were assessed with tetrapolar bioelectrical impedance analysis. Pearson’s rank correlation coefficient was used to assess possible associations with adipokine levels. Univariate and multivariate Cox regression analysis was used to determine independent predictors for overall survival. RESULTS: Body mass index: median 25.9 (range: 20.1-39.3), fat: 23.4% (7.6-42.1), fat mass: 17.8 (5.49-45.4), free fat mass: 56.1 (39.6-74.4), total body water (TBW): 40.6 (29.8-58.8). Leptin and visfatin levels were positively associated with fat mass (P < 0.001/P = 0.027, respectively) and RBP4 with TBW (P = 0.025). Median adiponectin levels were significantly higher in CPC compared to CPA (CPA: 7.99 ± 14.07, CPB: 7.66 ± 3.48, CPC: 25.73 ± 26.8, P = 0.04), whereas median RBP4 and apelin levels decreased across the spectrum of disease severity (P = 0.006/P = 0.034, respectively). Following adjustment for fat mass, visfatin and adiponectin levels were significantly increased from CPA to CPC (both P < 0.001), whereas an inverse correlation was observed for both RBP4 and apelin (both P < 0.001). In the multivariate Cox regression analysis, only MELD had an independent association with overall survival (HR = 1.53, 95%CI: 1.05-2.32; P = 0.029). CONCLUSION: Adipokines are associated with deteriorating liver function in a complex manner in patients with alcoholic liver cirrhosis. PMID:25780301

Kalafateli, Maria; Triantos, Christos; Tsochatzis, Emmanuel; Michalaki, Marina; Koutroumpakis, Efstratios; Thomopoulos, Konstantinos; Kyriazopoulou, Venetsanea; Jelastopulu, Eleni; Burroughs, Andrew; Lambropoulou-Karatza, Chryssoula; Nikolopoulou, Vasiliki

2015-01-01

246

Outcomes of patients with cirrhosis and hepatorenal syndrome type 1 treated with liver transplantation.  

PubMed

Hepatorenal syndrome type 1 (HRS1) is acute renal failure in the setting of advanced cirrhosis, and it results from hemodynamic derangements, which should be fully reversible after liver transplantation. However, the rate of hepatorenal syndrome (HRS) reversal and factors predicting renal outcomes after transplantation have not been fully elucidated. The aim of this study was to assess outcomes of HRS1 patients after liver transplantation and factors predicting HRS reversal. A chart review of all liver transplant patients with HRS1 (according to International Ascites Club criteria) at Toronto General Hospital from 2001 to 2010 was conducted. Patient demographic data, pretransplant and posttransplant laboratory data, and the presence of and time to posttransplant HRS reversal (serum creatinine?Liver Disease score, 35?±?1) with HRS1 (serum creatinine, 3.37?±?0.13 mg/dL) at liver transplant were enrolled. Thirty-eight patients received midodrine, octreotide, and albumin without success and subsequently received renal dialysis. One further patient received dialysis without pharmacotherapy. After liver transplantation, HRS1 resolved in 47 of 62 patients (75.8%) at a mean time of 13?±?2 days. Patients without HRS reversal had significantly higher pretransplant serum creatinine levels (3.81?±?0.34 versus 3.23?±?0.14 mg/dL, P?=?0.06), a longer duration of HRS1 {25 days [95% confidence interval (CI), 16-42 days] versus 10 days (95% CI, 10-18 days), P?=?0.02}, a longer duration of pretransplant dialysis [27 days (95% CI, 13-41 days) versus 10 days (95% CI, 6-14 days), P?=?0.01], and increased posttransplant mortality (P?=?0.0045) in comparison with those whose renal function recovered. The only predictor of HRS1 nonreversal was the duration of pretransplant dialysis with a 6% increased risk of nonreversal with each additional day of dialysis. In conclusion, our study suggests that patients with HRS1 should receive a timely liver transplant to improve their outcome. Liver Transpl 21:300-307, 2015. © 2015 AASLD. PMID:25422261

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

2015-03-01

247

Branched-chain amino acid supplementation reduces oxidative stress and prolongs survival in rats with advanced liver cirrhosis.  

PubMed

Long-term supplementation with branched-chain amino acids (BCAA) is associated with prolonged survival and decreased frequency of development of hepatocellular carcinoma (HCC) in patients with liver cirrhosis. However, the pharmaceutical mechanism underlying this association is still unclear. We investigated whether continuous BCAA supplementation increases survival rate of rats exposed to a fibrogenic agent and influences the iron accumulation, oxidative stress, fibrosis, and gluconeogenesis in the liver. Further, the effects of BCAA on gluconeogenesis in cultured cells were also investigated. A significant improvement in cumulative survival was observed in BCAA-supplemented rats with advanced cirrhosis compared to untreated rats with cirrhosis (P<0.05). The prolonged survival due to BCAA supplementation was associated with reduction of iron contents, reactive oxygen species production and attenuated fibrosis in the liver. In addition, BCAA ameliorated glucose metabolism by forkhead box protein O1 pathway in the liver. BCAA prolongs survival in cirrhotic rats and this was likely the consequences of reduced iron accumulation, oxidative stress and fibrosis and improved glucose metabolism in the liver. PMID:23936183

Iwasa, Motoh; Kobayashi, Yoshinao; Mifuji-Moroka, Rumi; Hara, Nagisa; Miyachi, Hirohide; Sugimoto, Ryosuke; Tanaka, Hideaki; Fujita, Naoki; Gabazza, Esteban C; Takei, Yoshiyuki

2013-01-01

248

Neuropilin-1 promotes cirrhosis of the rodent and human liver by enhancing PDGF/TGF-? signaling in hepatic stellate cells  

PubMed Central

PDGF-dependent hepatic stellate cell (HSC) recruitment is an essential step in liver fibrosis and the sinusoidal vascular changes that accompany this process. However, the mechanisms that regulate PDGF signaling remain incompletely defined. Here, we found that in two rat models of liver fibrosis, the axonal guidance molecule neuropilin-1 (NRP-1) was upregulated in activated HSCs, which exhibit the highly motile myofibroblast phenotype. Additionally, NRP-1 colocalized with PDGF-receptor ? (PDGFR?) in HSCs both in the injury models and in human and rat HSC cell lines. In human HSCs, siRNA-mediated knockdown of NRP-1 attenuated PDGF-induced chemotaxis, while NRP-1 overexpression increased cell motility and TGF-?–dependent collagen production. Similarly, mouse HSCs genetically modified to lack NRP-1 displayed reduced motility in response to PDGF treatment. Immunoprecipitation and biochemical binding studies revealed that NRP-1 increased PDGF binding affinity for PDGFR?-expressing cells and promoted downstream signaling. An NRP-1 neutralizing Ab ameliorated recruitment of HSCs, blocked liver fibrosis in a rat model of liver injury, and also attenuated VEGF responses in cultured liver endothelial cells. In addition, NRP-1 overexpression was observed in human specimens of liver cirrhosis caused by both hepatitis C and steatohepatitis. These studies reveal a role for NRP-1 as a modulator of multiple growth factor targets that regulate liver fibrosis and the vascular changes that accompany it and may have broad implications for liver cirrhosis and myofibroblast biology in a variety of other organ systems and disease conditions. PMID:20577048

Cao, Sheng; Yaqoob, Usman; Das, Amitava; Shergill, Uday; Jagavelu, Kumaravelu; Huebert, Robert C.; Routray, Chittaranjan; Abdelmoneim, Soha; Vasdev, Meher; Leof, Edward; Charlton, Michael; Watts, Ryan J.; Mukhopadhyay, Debabrata; Shah, Vijay H.

2010-01-01

249

[Syndrome of overlap of autoimmune hepatitis and primary biliary cirrhosis with the outcome in cirrhosis of the liver, complicated by fatal bleeding in the small intestine].  

PubMed

The authors presents the clinical case of autoimmune overlap syndrome: autoimmune hepatitis and primary biliary cirrhosis with outcomes in the hepatic cirrhosis complicated fatal intestinal bleeding. PMID:23947168

Vinnitskaia, E V; Mareeva, D V; Vorob'eva, N N; Dorofeev, A S; Iunusova, Iu M; Kolechkina, I A; Efremov, L I; Shcherbakov, P L

2013-01-01

250

Relevance of Male-to-Female Sex Mismatch in Liver Transplantation for Primary Biliary Cirrhosis.  

PubMed

Background Because male-to-female transplantations are related to exposure to H-Y antigen, sex matching may influence the outcomes after liver transplantation for autoimmune diseases. The purpose of this retrospective study was to evaluate the relevance of male-to-female mismatch in liver transplantation for primary biliary cirrhosis (PBC). Material and Methods This retrospective study was based on the data of 82 female liver transplant recipients with PBC from a single institution. The primary outcome measure was graft survival at 10 years. The negative effects of well-known risk factors for poor outcomes were evaluated separately and compared between the female-to-female and male-to-female transplantations. Results Graft survival was similar after female-to-female and male-to-female transplantations (74.7% versus 73.1% at 10 years, respectively, p=0.676). Regarding the differential impact of other risk factors, prolonged cold ischemia and increased amount of blood transfusions adversely influenced outcomes after male-to-female transplantation (p=0.039 and p=0.039, respectively) but not after female-to-female transplantation (p=0.843 and p=0.110, respectively). Sex mismatched transplantations were associated with lower 10-year graft survival in subgroups of patients with blood transfusions >4 units (61.4% versus 100.0%, p=0.063) and >8 hours of cold ischemia (54.7% versus 75.8%, p=0.418). Conclusions Although male-to-female sex mismatch does not seem to yield a direct negative impact on outcomes following liver transplantation for PBC, it can aggravate the negative effects of prolonged cold ischemia and blood transfusions. PMID:25728977

Gr?t, Micha?; Lewandowski, Zbigniew; Patkowski, Waldemar; Wronka, Karolina Maria; Gr?t, Karolina; Krasnod?bski, Maciej; Ligocka, Joanna; Zborowska, Hanna; Krawczyk, Marek

2015-01-01

251

Effects of the deleted form of hepatocyte growth factor on serum hyaluronate levels in rats with liver cirrhosis.  

PubMed

Effects of the deleted form of hepatocyte growth factor (dHGF) on serum hyaluronate levels, an index for liver cirrhosis, were studied in rats. The levels of serum hyaluronate increased in rats with dimethylnitrosamine- or carbontetrachloride-induced cirrhotic liver with prolongation of prothrombin time, which indicates disorder of liver function. Daily intravenous injection of dHGF reduced the elevated serum hyaluronate levels with improvement of the prolonged prothrombin time. These results suggest that the amelioration of hepatic function disorder by dHGF leads to a reduction of the increased serum hyaluronate levels. PMID:9560786

Yamashita, Y; Shiota, A; Fujise, N; Ogawa, H; Masunaga, H; Yasuda, H; Higashio, K

1998-03-01

252

Oldenlandia diffusa Promotes Antiproliferative and Apoptotic Effects in a Rat Hepatocellular Carcinoma with Liver Cirrhosis.  

PubMed

Oldenlandia diffusa (OD) is commonly used with various diseases such as cancer, arthritis, and autoimmune disease. Liver cirrhosis is a predominant risk factor for hepatocellular carcinoma (HCC). Here, we show that the therapeutic effect of OD, which was investigated both in vitro and chemically, induced HCC model. OD significantly enhanced apoptosis and antiproliferative activity and reduced migration ability of HCC cells. In vivo, OD was treated twice a day for 28 days after confirmed HCC model through 2-[(18)F]-fluoro-2-deoxy-D-glucose ((18)F-FDG) imaging. The survival in OD treated groups was shown to have a greater therapeutic effect than the control group. 28 days after OD treatment, OD treated groups resulted in a significant reduction in tumor number, size, (18)F-FDG uptake, and serum levels such as alanine transaminase, aspartate transaminase, and alkaline phosphate compared to the control group. Also, proliferated cells in tumor sites by OD were reduced compared to the control group. Furthermore, several rats in OD treated group survived over 60 days and liver morphology of these rats showed the difference between tumor mass and normal tissue. These results suggest that OD may have antiproliferative activity, inhibition of metastasis, and apoptotic effects in chemically induced HCC model and can have the potential use for clinical application as anticancer drug of the herbal extract. PMID:25852766

Sunwoo, Yun-Young; Lee, Jin-Hee; Jung, Ho Yong; Jung, Yu Jin; Park, Moon-Seo; Chung, Yong-An; Maeng, Lee-So; Han, Young-Min; Shin, Hak Soo; Lee, Jisoo; Park, Sang In

2015-01-01

253

Oldenlandia diffusa Promotes Antiproliferative and Apoptotic Effects in a Rat Hepatocellular Carcinoma with Liver Cirrhosis  

PubMed Central

Oldenlandia diffusa (OD) is commonly used with various diseases such as cancer, arthritis, and autoimmune disease. Liver cirrhosis is a predominant risk factor for hepatocellular carcinoma (HCC). Here, we show that the therapeutic effect of OD, which was investigated both in vitro and chemically, induced HCC model. OD significantly enhanced apoptosis and antiproliferative activity and reduced migration ability of HCC cells. In vivo, OD was treated twice a day for 28 days after confirmed HCC model through 2-[18F]-fluoro-2-deoxy-D-glucose (18F-FDG) imaging. The survival in OD treated groups was shown to have a greater therapeutic effect than the control group. 28 days after OD treatment, OD treated groups resulted in a significant reduction in tumor number, size, 18F-FDG uptake, and serum levels such as alanine transaminase, aspartate transaminase, and alkaline phosphate compared to the control group. Also, proliferated cells in tumor sites by OD were reduced compared to the control group. Furthermore, several rats in OD treated group survived over 60 days and liver morphology of these rats showed the difference between tumor mass and normal tissue. These results suggest that OD may have antiproliferative activity, inhibition of metastasis, and apoptotic effects in chemically induced HCC model and can have the potential use for clinical application as anticancer drug of the herbal extract. PMID:25852766

Sunwoo, Yun-Young; Lee, Jin-Hee; Jung, Ho Yong; Jung, Yu Jin; Park, Moon-Seo; Chung, Yong-An; Maeng, Lee-So; Han, Young-Min; Shin, Hak Soo; Lee, Jisoo; Park, Sang In

2015-01-01

254

Identification of Helicobacter pylori and Other Helicobacter Species by PCR, Hybridization, and Partial DNA Sequencing in Human Liver Samples from Patients with Primary Sclerosing Cholangitis or Primary Biliary Cirrhosis  

Microsoft Academic Search

Helicobacter pylori was identified in human liver tissue by PCR, hybridization, and partial DNA sequencing. Liver biopsies were obtained from patients with primary sclerosing cholangitis (n 5 12), primary biliary cirrhosis (n 5 12), and noncholestatic liver cirrhosis (n 5 13) and (as controls) normal livers (n 5 10). PCR analyses were carried out using primers for the Helicobacter genus,

HANS-OLOF NILSSON; JALAL TANEERA; MARIA CASTEDAL; ELISABETH GLATZ; ROLF OLSSON; TORKEL WADSTROM

255

Association between Portal Vein Thrombosis and Survival in Non-Liver-Transplant Patients with Liver Cirrhosis: A Systematic Review of the Literature  

PubMed Central

A systematic review of the literature was performed to analyze the association between portal vein thrombosis (PVT) and survival in non-liver-transplant patients with liver cirrhosis. PubMed, EMBASE, and Cochrane Library databases were searched for all relevant papers which evaluated the prognostic value of PVT in predicting the survival of liver cirrhosis. Meta-analyses were not conducted because the ways of data expression and lengths of follow-up were heterogeneous among studies. Overall, 13 papers were included. The 5-day, 6-week, and 1-year mortality were investigated in 1, 3, and 1 studies, respectively; and all of them were not significantly different between cirrhotic patient with and without PVT. By comparison, the 3-year mortality was reported in 1 study; and it was significantly increased by the presence of PVT. The overall mortality was analyzed in 5 studies; and the association with overall mortality and PVT was significant in 4 studies, but not in another one. However, as for the cirrhotic patients undergoing surgical or interventional shunts, the overall mortality was not significantly associated with the presence of PVT in 4 studies. In conclusion, the presence of PVT might be associated with the long-term mortality in non-liver-transplant patients with liver cirrhosis, but not with the short-term mortality.

Dai, Junna; Yang, Man; Ren, Weirong; Jia, Jia; Guo, Xiaozhong

2015-01-01

256

Enhanced synthesis and reduced metabolism of endothelin-1 (ET1) by hepatocytes - an important mechanism of increased endogenous levels of ET1 in liver cirrhosis  

Microsoft Academic Search

Background\\/Aims: Hepatic concentration of endothelin-1 (ET-1) is increased in human and experimental liver cirrhosis. Because of its potent actions in the liver, ET-1 has been suggested to play an important role in the pathophysiology of cirrhosis. Since hepatocytes are the major cell type to metabolize ET-1, we investigated whether their reduced capacity to degrade ET-1 is a mechanism of its

Ruhul H Kuddus; Michael A Nalesnik; Vladimir M Subbotin; Abdul S Rao; Chandrashekhar R Gandhi

2000-01-01

257

Estimation of the binding ability of main transport proteins of blood plasma with liver cirrhosis by the fluorescent probe method  

NASA Astrophysics Data System (ADS)

We present results from an investigation of the binding ability of the main transport proteins (albumin, lipoproteins, and ?-1-acid glycoprotein) of blood plasma from patients at different stages of liver cirrhosis by the fluorescent probe method. We used the hydrophobic fluorescent probes anionic 8-anilinonaphthalene-1-sulfonate, which interacts in blood plasma mainly with albumin; cationic Quinaldine red, which interacts with ?-1-acid glycoprotein; and neutral Nile red, which redistributes between lipoproteins and albumin in whole blood plasma. We show that the binding ability of albumin and ?-1-acid glycoprotein to negatively charged and positively charged hydrophobic metabolites, respectively, increases in the compensation stage of liver cirrhosis. As the pathology process deepens and transitions into the decompensation stage, the transport abilities of albumin and ?-1-acid glycoprotein decrease whereas the binding ability of lipoproteins remains high.

Korolenko, E. A.; Korolik, E. V.; Korolik, A. K.; Kirkovskii, V. V.

2007-07-01

258

Hyponatremia in cirrhosis and end-stage liver disease: treatment with the vasopressin V?-receptor antagonist tolvaptan.  

PubMed

Hyponatremia is common in patients with cirrhosis and portal hypertension, and is characterized by excessive renal retention of water relative to sodium due to reduced solute-free water clearance. The primary cause is increased release of arginine vasopressin. Hyponatremia is associated with increased mortality in cirrhotic patients, those with end-stage liver disease (ESLD) on transplant waiting lists, and, in some studies, posttransplantation patients. Clinical evidence suggests that adding serum sodium to model for ESLD (MELD) scoring identifies patients in greatest need of liver transplantation by improving waiting list mortality prediction. Hyponatremia is also associated with numerous complications in liver disease patients, including severe ascites, hepatic encephalopathy, infectious complications, renal impairment, increased severity of liver disease in cirrhosis, and increased hospital stay and neurologic/infectious complications posttransplant. Vasopressin receptor antagonists, which act to increase free water excretion (aquaresis) and thereby increase serum sodium concentration, have been evaluated in patients with hypervolemic hyponatremia (including cirrhosis and heart failure) and euvolemic hyponatremia (SIADH). Tolvaptan, a selective vasopressin V(2)-receptor antagonist, is the only oral agent in this class approved for raising sodium levels in hypervolemic and euvolemic hyponatremia. The SALT trials showed that tolvaptan treatment rapidly and effectively resolved hyponatremia in these settings, including cirrhosis, and it has been shown that this agent can be safely and effectively used in long-term treatment. Fluid restriction should be avoided during the first 24 h of treatment to prevent overly rapid correction of hyponatremia, and tolvaptan should not be used in patients who cannot sense/respond to thirst, anuric patients, hypovolemic patients, and/or those requiring urgent intervention to raise serum sodium acutely. PMID:22732834

Gaglio, Paul; Marfo, Kwaku; Chiodo, Joseph

2012-11-01

259

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

260

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. PMID:25624735

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

261

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

262

Symptoms and distress among patients with liver cirrhosis but without hepatocellular carcinoma in Taiwan.  

PubMed

A cross-sectional study design was used to assess the items and frequency of physical symptoms and psychological distress among patients with liver cirrhosis (LC) but without hepatocellular carcinoma. Inpatients with LC were recruited from a medical center in northern Taiwan. Informants were asked to describe their frequency of symptoms and distress at 2 weeks before admission. During August 2008 and July 2009, 49 patients participated. The symptoms and distress were moderate, with a mean of 3.9 and 4.2 of 7, respectively. The mean ranking of subscales from the highest to lowest was abdominal symptoms, fatigue, fluid retention, loss of appetite, systemic symptoms, decreased attention, and bleeding. Symptoms and distress were significantly correlated (r = .59). The total scores of symptoms and distress were not associated with causes of the disease (p = .7644, p = .8548, respectively), disease severity (p = .7203, p = .3354, respectively), disease duration (p = .5820, p = .8184, respectively), or previous admission (p = .3094, p = .7365, respectively), but decreased attention was significantly associated with disease severity (p = .0317) and systemic symptoms were significantly associated with disease duration (p = .0267). The study found that physical symptoms and psychological distress are multidimensional and highly correlated. Our findings can be used to develop a symptom management program to relieve discomfort and indirectly improve the quality of life for individuals with LC. PMID:24476834

Tsai, Li-Hung; Lin, Chang-Ming; Chiang, Shu-Chen; Chen, Chia-Ling; Lan, Su-Jane; See, Lai-Chu

2014-01-01

263

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

264

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;92(1):135-50" DOI : 10.1038/labinvest.2011.143 #12;Chobert MN et al Abstract Hepatic fibrosis, the major

Boyer, Edmond

265

The Therapeutic Use of Analgesics in Patients With Liver Cirrhosis: A Literature Review and Evidence-Based Recommendations  

PubMed Central

Context: Pain management in cirrhotic patients is a major clinical challenge for medical professionals. Unfortunately there are no concrete guidelines available regarding the administration of analgesics in patients with liver cirrhosis. In this review we aimed to summarize the available literature and suggest appropriate evidence-based recommendations regarding to administration of these drugs. Evidence Acquisition: An indexed MEDLINE search was conducted in July 2014, using keywords “analgesics”, “hepatic impairment”, “cirrhosis”, “acetaminophen or paracetamol”, “NSAIDs or nonsteroidal anti-inflammatory drugs”, “opioid” for the period of 2004 to 2014. All randomized clinical trials, case series, case report and meta-analysis studies with the above mentioned contents were included in review process. In addition, unpublished information from the Food and Drug Administration are included as well. Results: Paracetamol is safe in patients with chronic liver disease but a reduced dose of 2-3 g/d is recommended for long-term use. Non-steroidal anti-in?ammatory drugs (NSAIDs) are best avoided because of risk of renal impairment, hepatorenal syndrome, and gastrointestinal hemorrhage. Most opioids can have deleterious effects in patients with cirrhosis. They have an increased risk of toxicity and hepatic encephalopathy. They should be administrated with lower and less frequent dosing in these patients and be avoided in patients with a history of encephalopathy or addiction to any substance. Conclusions: No evidence-based guidelines exist on the use of analgesics in patients with liver disease and cirrhosis. As a result pain management in these patients generates considerable misconception among health care professionals, leading under-treatment of pain in this population. Providing concrete guidelines toward the administration of these agents will lead to more efficient and safer pain management in this setting. PMID:25477978

Imani, Farnad; Motavaf, Mahsa; Safari, Saeid; Alavian, Seyed Moayed

2014-01-01

266

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

267

Serum amyloid A and C-reactive protein positive nodule in alcoholic liver cirrhosis, hard to make definite diagnosis.  

PubMed

We describe a case of serum amyloid A (SAA) and C-reactive protein (CRP) positive nodule detected by immunohistochemical analysis in a 37-year-old woman with alcohol-related cirrhosis. Imaging studies at first admission pointed to hepatocellular carcinoma (HCC), a dysplastic nodule, an inflammatory pseudotumor or focal nodular hyperplasia (FNH). Ultrasonography-guided biopsy in Segment 2 showed minimal atypical changes, except for a slight increase in cell density and micronodular cirrhosis in the non-nodular portion. gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging carried out after a year and a half revealed hypervascularity in the arterial phase and isointensity in the hepatobiliary phase. Three years thereafter, however, the imaging displayed a change from isointensity to a defect in the hepatobiliary phase, and the nodule demonstrated minimal histological atypia. Immunohistochemical staining of the nodule was positive for SAA, CRP, liver fatty acid-binding protein and glutamine synthetase, but negative for ?-catenin, heat shock protein 70 and Glypican 3. Organic anion transporter (OATP)8 staining was weaker in the nodule than in the non-nodular portion of the alcohol-related micronodular cirrhosis. The nodule was diagnosed as an SAA and CRP positive nodule, and HCC was ruled out. Despite the change from isointensity to a defect in the hepatobiliary phase, no evidence of HCC was found in the biopsy specimen. The change may be explained more by the weak OATP8 staining compared with that of alcohol-related liver cirrhosis than by malignant transformation into HCC. PMID:23607539

Kim, Soo Ryang; Kondo, Fukuo; Otono, Yumi; Imoto, Susumu; Ando, Kenji; Hirakawa, Makoto; Fukuda, Katsumi; Sasaki, Madoka; Kim, Soo Ki; Komaki, Takamitsu; Tsuchida, Shinobu; Kobayashi, Sawako; Matsuoka, Toshiyuki; Kudo, Masatoshi

2014-05-01

268

Alterations in Arterial Blood Parameters in Patients with Liver Cirrhosis and Ascites  

PubMed Central

In cirrhotic patients, in addition to hepatocytes and Kuppfer cells dysfunction circulatory anatomic shunt and ventilation/perfusion (VA/ Q) ratio abnormalities can induce decrease in partial pressure of oxygen in arterial blood (PaO2), in oxygen saturation of hemoglobin (SaO2) as well as various acid-base disturbances. We studied 49 cases of liver cirrhosis (LC) with ascites compared to 50 normal controls. Causes were: posthepatic 37 (75.51%), alcoholic 7 (14.24%), cardiac 2 (4.08%), and cryptogenic 3 (6.12%). Complications were: upper gastrointestinal bleeding 24 (48.97), hepatic encephalopathy 20 (40.81%), gastritis 28 (57.14%), hepatoma 5 (10.2%), renal hepatic syndrome 2 (4.01%), HbsAg (+) 24 (48.97%), and hepatic pleural effusions 7 (14.28%). Average PaO2 and SaO2 were 75.2 mmHg and 94.5 mmHg, respectively, compared to 94.2 mmHg and 97.1 mmHg of the control group, respectively (p value in both PaO2 and SaO2 was p<0.01). Respiratory alkalosis, metabolic alkalosis, metabolic acidosis, respiratory acidosis and metabolic acidosis with respiratory alkalosis were acid-base disturbances observed. In conclusion, portopulmonary shunt, intrapulmonary arteriovenous shunt and VA/Q inequality can induce a decrease in PaO2 and SaO2 as well as various acid-base disturbances. As a result, pulmonary resistance is impaired and patients more likely succumb to infections and adult respiratory distress syndrome. PMID:17396160

Charalabopoulos, Konstantinos; Peschos, Dimitrios; Zoganas, Leonidas; Bablekos, George; Golias, Christos; Charalabopoulos, Alexander; Stagikas, Dimitrios; Karakosta, Angi; Papathanasopoulos, Athanasios; Karachalios, George; Batistatou, Anna

2007-01-01

269

Chemical pleurodesis for the management of refractory hepatic hydrothorax in patients with decompensated liver cirrhosis  

PubMed Central

Background/Aims Hepatic hydrothorax in patients with decompensated liver cirrhosis is a challenging problem. Treatment with diuretics and intermittent thoracentesis can be effective in selected patients. However, there are few effective therapeutic options in patients who are intolerant of these therapies. This study investigated the clinical usefulness of chemical pleurodesis with or without video-assisted thoracoscopic surgery (VATS) for patients with refractory hepatic hydrothorax. Methods Eleven consecutive patients with refractory hepatic hydrothorax who underwent chemical pleurodesis with or without VATS between July 2007 and February 2011 were enrolled in this study. The medical records and radiologic imagings of these patients were thoroughly reviewed. Results The median number of chemical pleurodesis sessions performed was 3 (range: 2-10). Successful pleurodesis was achieved in 8 of the 11 patients (72.7%), 5 (62.5%) of whom remained asymptomatic and hydrothorax free for a median follow-up of 16 weeks (range: 2-52 weeks). Complications were low-grade fever/leukocytosis (n=11, 100%), pneumonia (n=1, 9.1%), pneumothorax (n=4, 36.4%), azotemia/acute renal failure (n=6, 54.6%), and hepatic encephalopathy (n=4, 36.4%). Five patients were suspected as having procedure-related mortality (45.5%) due to the occurrence of acute renal failure with hepatic failure. The overall survival was significantly longer in the success group than in the non-success group. Conclusions Although chemical pleurodesis may improve the clinical symptoms and the radiologic findings in as many as 72.7% of patients with refractory hepatic hydrothorax, a significantly high prevalence of procedure-related morbidity and mortality hinders the routine application of this procedure for such patients. PMID:22310793

Lee, Woo Jin; Park, Jung Ho; Park, Dong Il; Cho, Yong Kyun; Sohn, Chong Il; Jeon, Woo Kyu; Kim, Byung Ik

2011-01-01

270

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

271

Effects of bone marrow-derived mesenchymal stem cells transplanted via the portal vein or tail vein on liver injury in rats with liver cirrhosis  

PubMed Central

The aim of the present study was to compare the effects of bone marrow-derived mesenchymal stem cells (BMSCs) transplanted via the portal vein or tail vein on liver injury in rats with liver cirrhosis. BMSCs were isolated from rat bone marrow and labeled with green fluorescent protein (GFP). Then, the labeled BMSCs were injected into rats with liver injury via the portal vein or tail vein. Two weeks after transplantation, three rats in each group were sacrificed to test the distribution of GFP in the liver and the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and albumin. Six weeks later, the remaining rats were sacrificed, and serum ALT, AST, albumin, hyaluronic acid (HA), laminin (LN) and procollagen type III (PC-III) levels were measured. The expression of albumin in the liver was analyzed by immunohistochemistry. Two weeks after BMSC transplantation, GFP-positive cells were detected in the livers of rats with BMSCs transplanted via the portal vein and tail vein. Compared with pre-transplantation levels, the ALT levels of the groups with BMSC transplantation via the portal vein and tail vein were significantly decreased after two and six weeks of BMSC transplantation (P<0.05), whereas the AST and albumin levels were not significantly different at two weeks after BMSC transplantation in the two groups (all P>0.05). However, the AST and albumin levels were significantly reduced at six weeks after BMSC transplantation (all P<0.05). At six weeks after BMSC transplantation, the serum HA, LN and PC-III levels in rats transplanted with BMSCs via the portal vein or tail vein had decreased significantly (all P<0.05), as compared with the levels prior to BMSC transplantation. BMSCs transplanted via the portal vein and tail vein achieved similar improvements in liver function in rats with liver cirrhosis, which suggests that peripheral venous administration is a convenient and effective route for BMSC transplantation. PMID:25780424

SONG, YING-MING; LIAN, CHANG-HONG; WU, CHENG-SONG; JI, AI-FANG; XIANG, JUAN-JUAN; WANG, XIAO-YAN

2015-01-01

272

Hemodynamic response to propranolol in patients with recurrent hepatitis C virus-related cirrhosis after liver transplantation: a case-control study.  

PubMed

Cirrhosis recurrence is frequent after orthotopic liver transplantation for hepatitis C virus (HCV). Because transplantation causes liver denervation, we hypothesized that the response to propranolol might differ in transplant patients versus nontransplant patients with cirrhosis and portal hypertension. Twenty-one patients with cirrhosis recurrence after orthotopic liver transplantation with portal hypertension were compared to 20 nontransplant patients with cirrhosis, HCV, and portal hypertension, and they were matched by sex, age, presence of varices, and Child-Pugh score. The patients underwent systemic and hepatic hemodynamic measurements at the baseline and 20 minutes after intravenous propranolol (0.15 mg/kg). At the baseline, the transplant patients with cirrhosis had a lower hepatic venous pressure gradient (HVPG) than the nontransplant patients with cirrhosis (14.8?±?2.9 versus 17.3?±?4.4 mm Hg, P?=?0.03) but a higher mean arterial pressure (MAP; 100.3?±?12.3 versus 91.8?±?11.6 mm Hg, P?=?0.04) and higher systemic vascular resistance (2253?±?573 versus 1883?±?525 dyn/second/cm(-5) , P?=?0.03). There were no differences in the cardiac index (CI). Propranolol significantly decreased HVPG to similar extents in transplant patients and nontransplant patients with cirrhosis (-14.1%?±?8.0% versus -16.9%?±?9.5%, P?>?0.99). MAP tended to increase in transplant patients with cirrhosis, whereas it slightly decreased in nontransplant patients (5.1%?±?14.2% versus -4.8%?±?6.4%, P?=?0.007); however, the reduction in CI was less marked in transplant patients with cirrhosis (-18.6%?±?7.6% versus -26.9%?±?9.0%, P?=?0.005). In conclusion, patients with HCV-related cirrhosis and portal hypertension after orthotopic liver transplantation have lower baseline HVPG values but similar HVPG responses to propranolol infusions in comparison with nontransplant patients with cirrhosis. In contrast to nontransplant patients, propranolol increases the systemic vascular resistance and arterial pressure in transplant patients with cirrhosis and attenuates the fall in CI. PMID:23408436

Schepis, Filippo; Vukotic, Ranka; Berzigotti, Annalisa; Carrión, José A; Forns, Xavier; Abraldes, Juan G; García-Valdecasas, Juan-Carlos; Navasa, Miguel; García-Pagán, Juan-Carlos; Bosch, Jaime

2013-04-01

273

Serum and urinary nitrate levels in liver cirrhosis: endotoxemia, renal function and hyperdynamic circulation  

Microsoft Academic Search

Background\\/Aims: The relationship between nitric oxide production, endotoxemia, renal function and hyperdynamic circulatory syndrome has not been yet investigated in patients with cirrhosis.Methods: Serum and urine nitrate, endotoxemia and cardiac index were measured in 59 patients with cirrhosis.Results: Patients with a tense ascites had higher serum nitrate levels than health control subjects (39±7 vs 19±4 ?mol\\/l, p<0.01). Patients with mild

Bernard Campillo; Phuong Nhi Bories; Christophe Benvenuti; Catherine Dupeyron

1996-01-01

274

Prophylactic endoscopic sclerotherapy of oesophageal varices in liver cirrhosis. A multicentre prospective controlled randomised trial in Vienna.  

PubMed Central

The effect of prophylactic treatment of oesophageal varices by endoscopic injection sclerotherapy before the first episode of variceal haemorrhage was studied in patients with cirrhosis in a prospective, randomised and controlled multicentre trial. From February 1984 to March 1987 patients with liver cirrhosis and large varices (stage III-IV according to Paquet) were treated and followed up. The sample comprised 87 patients: 45 in the prophylactic treatment and 42 in the control group. After excluding drop outs, 41 patients were treated in each group. Twenty nine per cent of patients in the sclerotherapy group and 34% in the control group had a variceal haemorrhage during the period of observation. There was no significant difference in the distributions of the bleeding free intervals between the sclerotherapy and the control groups. During the follow up period 24% of patients in the sclerotherapy group and 46% in the control group died. The distribution of survival times indicates a tendency towards longer survival of patients with prophylactic sclerotherapy, particularly in those with alcoholic cirrhosis. PMID:2666282

Pötzi, R; Bauer, P; Reichel, W; Kerstan, E; Renner, F; Gangl, A

1989-01-01

275

[Small unilocular hepatocellular carcinoma (0 < 5 cm) in patients with liver cirrhosis. Early diagnosis, surgical indications, resection and prognosis].  

PubMed

In 151 (17.5%) of 861 patients with liver cirrhosis regularly screened by sonography and determination of alpha-fetoprotein a hepatocellular carcinoma (HCC) was detected. Diagnosis was verified by sonographically guided fine needle puncture and exceptionally by laparoscopy and direct puncture. In 34 patients (22.5%) selection criteria for operation were a tumour diameter under 5 cm, no central localisation in the liver and at least 5 mm distant from the main structures; furthermore multilocular HCC and intra- and extrahepatic metastases were contraindications. Additionally Child-Pugh-classification should be A + B and urea synthesis rate 6 g per day. 27 patients (80%) had esophagogastric varices seen at endoscopy and 20 (59%) had bleeding episodes from varices managed endoscopically or surgically. Types of surgical resections were segmentectomy [17], bisegmentectomy [10] and oncologically defined wedge resections [7] using controlled hypotension and interrupted occlusion of the hepatoduodenal ligament. 4 patients (11.8%) died within 30 days of liver failure [3] and sepsis [1]. All patients could be followed up for eleven years: 18 patients died after 1.5-10 years of liver failure, tumour recurrence or second tumour and a cause not associated with HCC, 12 patients are living. Kaplan-Meier survival curves show that survival at 5 years is 50% and at 10 years 34%. The main indicators for a good prognosis were clinically the HBsAG-activity, the Child-Pugh-classification and the application of autologous blood, pathologic-anatomically the classification and grading and histologically the absence of vascular invasion, absence of satellites and a number of mitoses under 7 in the visual field. For tumour recurrence dysplasia is of positive influence.--Liver resection remains the most widely used therapeutic option for treatment of HCC in cirrhosis. The early and long-term results can be improved by early diagnosis, strict selection of patients for operation and the use of well defined clinical, pathological and histological criteria. PMID:10960974

Paquet, K J; Lazar, A; Heine, W P; Jachmann-Jahn, V

2000-01-01

276

Embryonic hepatocyte transplantation for hepatic cirrhosis: Efficacy and mechanism of action  

PubMed Central

AIM: To investigate the efficacy and mechanism of action of allogeneic embryonic hepatocyte transplantation for the treatment of hepatic cirrhosis. METHODS: Rat embryonic hepatocytes were characterized by examining cell markers. Wistar rats with CCl4-induced cirrhosis were randomly divided into two groups: a model group receiving continuous CCl4, and a cell transplantation group receiving continuous CCl4 and transplanted with embryonic fluorescent-labeled hepatocytes. In addition, a normal control group was composed of healthy rats. All rats were sacrificed after 2 wk following the initiation of the cell transplant. Ultrasound, pathological analyses and serum biochemical tests were used to evaluate the efficacy of embryonic hepatocyte transplantation. To analyze the recovery status of cirrhotic hepatocytes and the signaling pathways influenced by embryonic hepatocyte transplantation, real-time polymerase chain reaction was performed to examine the mRNA expression of stellate activation-associated protein (STAP), c-myb, ? smooth muscle actin (?-SMA) and endothelin-1 (ET-1). Western blotting and immunohistochemistry were employed to detect ?-SMA and ET-1 protein expression in hepatic tissues. RESULTS: Gross morphological, ultrasound and histopathological examinations, serum biochemical tests and radioimmunoassays demonstrated that hepatic cirrhosis was successfully established in the Wistar rats. Stem cell factor receptor (c-kit), hepatocyte growth factor receptor (c-Met), Nestin, ? fetal protein, albumin and cytokeratin19 markers were observed in the rat embryonic hepatocytes. Following embryonic hepatocyte transplantation, there was a significant reversal in the gross appearance, ultrasound findings, histopathological properties, and serum biochemical parameters of the rat liver. In addition, after the activation of hepatic stellate cells and STAP signaling, ?-SMA, c-myb and ET-1 mRNA levels became significantly lower than in the untreated cirrhotic group (P < 0.05). These levels, however, were not statistically different from those of the normal healthy group. Immunohistochemical staining and Western blot analyses revealed that ?-SMA and ET-1 protein expression levels in the transplantation group were significantly lower than in the untreated cirrhotic group, but being not statistically different from the normal group. CONCLUSION: Transplantation of embryonic hepatocytes in rats has therapeutic effects on cirrhosis. The described treatment may significantly reduce the expression of STAP and ET-1. PMID:22294837

Bin, Wen-Ting; Ma, Li-Mei; Xu, Qing; Shi, Xiao-Lin

2012-01-01

277

Twelve potential fibrosis markers to differentiate mild liver fibrosis from cirrhosis in patients infected with chronic hepatitis C genotype 1.  

PubMed

Information about the stage of liver fibrosis is important for managing patients with chronic hepatitis C (CHC). The aim of this study was to evaluate 12 plasma markers for differentiating no/mild liver fibrosis from cirrhosis among patients with CHC genotype 1. Transient elastography was used to assess the stage of fibrosis for the patients included in the study. Forty patients were included (21 cirrhotic). Plasma levels of tumor necrosis factor-? (TNF-?), interleukin 8 (IL-8), interferon-? inducible protein-10 (IP-10), monocyte chemotactic protein-1 (MCP-1), soluble urokinase-type plasminogen activator (suPAR), monokine induced by ?-interferon (MIG), human hepatocyte growth factor (HGF), insulin, interleukin 6 (IL-6), interleukin 1-? (IL-1?), leptin, and nerve growth factor (NGF) were analyzed. Concentrations of TNF-? (median 15.0 vs. 25.1 pg/ml, area under the receiver operating characteristic curve [AUC] 0.91), IL-8 (48.7 vs. 103.3 pg/ml, AUC 0.85), IP-10 (176 vs. 566 pg/ml, AUC 0.83), MCP-1 (449 vs. 735 pg/ml, AUC 0.78), suPAR (3.5 vs. 5.2 ng/ml, AUC 0.78), MIG (100 vs. 152 pg/ml, AUC 0.75), and HGF (3.69 vs. 5.58 ng/ml, AUC 0.71) were significantly higher in patients with cirrhosis. In conclusion, several of the investigated markers showed promise for differentiating cirrhosis from no/mild fibrosis among patients with CHC genotype 1. PMID:21229279

Andersen, E S; Ruhwald, M; Moessner, B; Christensen, P B; Andersen, O; Eugen-Olsen, J; Weis, N

2011-06-01

278

High interleukin-6 serum levels and increased production by leucocytes in alcoholic liver cirrhosis. Correlation with IgA serum levels and lymphokines production.  

PubMed Central

Hypergammaglobulinaemia and enhanced serum IgA levels are common in alcoholic liver cirrhosis. Interleukin-6 (IL-6), which is identical to B cell differentiation factor BSF2 and is implicated in various autoimmune diseases, has been studied in patients with alcoholic liver cirrhosis. Increased serum levels and spontaneous or induced production of IL-6 by peripheral blood monoclonal cells have been found. IL-6 production correlates closely with IgA serum levels and negatively with impaired interleukin-2 and interferon gamma production. This abnormality could be related to overproduction of immunoglobulins and immune disturbances observed in this disease. PMID:2505958

Deviere, J; Content, J; Denys, C; Vandenbussche, P; Schandene, L; Wybran, J; Dupont, E

1989-01-01

279

Effectiveness of ibopamine in the management of ascitic liver cirrhosis--a controlled study v placebo and frusemide.  

PubMed Central

1 Thirty in-patients of both sexes suffering from ascitic liver cirrhosis were divided into three groups treated with (a) a placebo, (b) ibopamine (SB 7505, a new oral dopaminergic drug) and (c) frusemide, for 10 days. 2 Body weight decreased with both frusemide and ibopamine, diuresis and urinary excretion of Na+ and Cl- increased with both drugs; whereas urinary excretion of K+ increased only with frusemide. 3 An important difference between the frusemide and ibopamine treatment was encountered in creatinine clearance, which increased only with ibopamine, and in blood uric acid which increased only with frusemide. 4 The antidiuretic hormone (ADH) in the plasma of cirrhotic patients was lower than the sensitivity limit of the radioimmunoassay method, whereas in a group of healthy subjects it could be clearly measured. 5 The treatments did not affect systolic or diastolic blood pressure, heart rate, or a series of haematochemical parameters. 6 The increase in diuresis and creatinine clearance and the very good tolerability encountered with ibopamine highlight this new oral dopamine agonist as a useful drug in the management of liver cirrhosis. PMID:7041934

Melloni, G F; Minoja, G M; Melloni, R; Piatto, E; Scarazzati, E; Bauer, R; Ghirardi, P

1981-01-01

280

Staging of liver fibrosis or cirrhosis: The role of hepatic venous pressure gradient measurement  

PubMed Central

Liver fibrosis is a common histological change of chronic liver injury and it is closely related with portal hypertension which is hemodynamic complication of chronic liver disease. Currently, liver fibrosis has been known as a reversible dynamic process in previous literatures. Although liver biopsy is a gold standard for assessing the stage of liver fibrosis, it may not completely represent the stage of liver fibrosis because of sampling error or semi-quantative measurement. Recent evidences suggested that histologic, clinical, hemodynamic, and biologic features are closely associated in patients with chronic liver disease. Hepatic venous pressure gradient (HVPG) measurement has been known as a modality to evaluate the portal pressure. The HVPG measurement has been used clinically for fibrosis diagnosis, risk stratification, preoperative screening for liver resection, monitoring the efficacy of medical treatments, and assessing the prognosis of liver fibrosis. Therefore, the HVPG measurement can be used to monitor areas the chronic liver disease but also other important areas of chronic liver disease.

Suk, Ki Tae; Kim, Dong Joon

2015-01-01

281

Optical biopsy of liver fibrosis by use of multiphoton microscopy  

NASA Astrophysics Data System (ADS)

We demonstrate the application of multiphoton microscopy in diagnosing toxin- CCl4 - induced liver fibrosis in mice. Although hepatocyte autofluorescence does not vary significantly, different degrees of necrosis and stellate cell proliferation at necrotic sites in livers with fibrosis (ex vivo) can be detected easily from multiphoton-induced autofluorescence images by use of 780-nm excitation. Our result suggests that multiphoton microscopy can be developed into an effective technique for the detection and diagnosis of liver fibrosis in vivo.

Lee, Hsuan-Shu; Liu, Yuan; Chen, Hsiao-Ching; Chiou, Ling-Ling; Huang, Guan-Tarn; Lo, Wen; Dong, Chen-Yuan

2004-11-01

282

Rapid “Breath-Print” of Liver Cirrhosis by Proton Transfer Reaction Time-of-Flight Mass Spectrometry. A Pilot Study.  

PubMed Central

The aim of the present work was to test the potential of Proton Transfer Reaction Time-of-Flight Mass Spectrometry (PTR-ToF-MS) in the diagnosis of liver cirrhosis and the assessment of disease severity by direct analysis of exhaled breath. Twenty-six volunteers have been enrolled in this study: 12 patients (M/F 8/4, mean age 70.5 years, min-max 42–80 years) with liver cirrhosis of different etiologies and at different severity of disease and 14 healthy subjects (M/F 5/9, mean age 52.3 years, min-max 35–77 years). Real time breath analysis was performed on fasting subjects using a buffered end-tidal on-line sampler directly coupled to a PTR-ToF-MS. Twelve volatile organic compounds (VOCs) resulted significantly differently in cirrhotic patients (CP) compared to healthy controls (CTRL): four ketones (2-butanone, 2- or 3- pentanone, C8-ketone, C9-ketone), two terpenes (monoterpene, monoterpene related), four sulphur or nitrogen compounds (sulfoxide-compound, S-compound, NS-compound, N-compound) and two alcohols (heptadienol, methanol). Seven VOCs (2-butanone, C8-ketone, a monoterpene, 2,4-heptadienol and three compounds containing N, S or NS) resulted significantly differently in compensate cirrhotic patients (Child-Pugh A; CP-A) and decompensated cirrhotic subjects (Child-Pugh B+C; CP-B+C). ROC (Receiver Operating Characteristic) analysis was performed considering three contrast groups: CP vs CTRL, CP-A vs CTRL and CP-A vs CP-B+C. In these comparisons monoterpene and N-compound showed the best diagnostic performance. Conclusions Breath analysis by PTR-ToF-MS was able to distinguish cirrhotic patients from healthy subjects and to discriminate those with well compensated liver disease from those at more advanced severity stage. A breath-print of liver cirrhosis was assessed for the first time. PMID:23573204

Morisco, Filomena; Aprea, Eugenio; Lembo, Vincenzo; Fogliano, Vincenzo; Vitaglione, Paola; Mazzone, Giovanna; Cappellin, Luca; Gasperi, Flavia; Masone, Stefania; De Palma, Giovanni Domenico; Marmo, Riccardo; Caporaso, Nicola; Biasioli, Franco

2013-01-01

283

Transplantation of Autologous Mesenchymal Stem Cells for End-Stage Liver Cirrhosis: A Meta-Analysis Based on Seven Controlled Trials  

PubMed Central

Background. The bone marrow-derived mesenchymal stem cells (BM-MSCs) have demonstrated great potential as regenerative medicine in different therapeutic applications. This study aims to pool previous controlled clinical trials to make an update assessment of the effectiveness of BM-MSC transplantation on end-stage liver cirrhosis. Methods. Relevant studies published between January 1990 and June 2014 were searched among Pubmed, Embase, and ClinicalTrial.gov. A meta-analysis was performed to assess the effect of BM-MSCs on liver function indicators, including Models of End-Stage Liver Disease (MELD) score, serum albumin (g/L), total bilirubin (mg/dl), Prothrombin concentration (%), and alanine aminotransferase (ALT) (U/L). Results. BM-MSCs therapy could significantly improve liver function in patients with end-stage liver cirrhosis, in terms of MELD score, serum albumin, total bilirubin, and prothrombin concentration, at least during the half year after transplantation. Conclusions. Due to BM-MSCs' immunomodulatory functions and the potential to differentiate into hepatocytes, they are a promising therapeutic agent to liver cirrhosis. Considering currently available evidence, this therapy is relatively safe and effective in improving liver function. However, how different variables should be controlled to optimize the therapeutic effect is still not clear. Thus, future mechanism studies and clinical trials are required for this optimization.

Ma, Xiang-Rui; Tang, Ya-Ling; Xuan, Ming; Chang, Zheng; Wang, Xiao-Yi; Liang, Xin-Hua

2015-01-01

284

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

285

Molecular identification of bacterial 16S ribosomal RNA gene in liver tissue of primary biliary cirrhosis: Is Propionibacterium acnes involved in granuloma formation?  

Microsoft Academic Search

The etiopathogenesis of primary biliary cirrhosis (PBC) remains speculative. Epithelioid granulomas are often found in the vicinity of damaged interlobular bile ducts in PBC, raising the possibility of a reaction to microbial materials. In this study, we tried to detect and identify bacterial DNA within granulomatous lesions in PBC. Using liver sections from 9 patients with PBC and 13 control

Kenichi Harada; Koichi Tsuneyama; Yoshiko Sudo; Shinji Masuda; Yasuni Nakanuma

2001-01-01

286

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

287

[Two case reports of septic shock due to Vibrio vulnificus with liver cirrhosis].  

PubMed

We have recently experienced a case of Vibrio vulnificus septicemia which occurred in a patient with hepatic cirrhosis, and as we were able to give early antibiotic treatment, the patient survived. We would like to report this case here together with another case experienced 2 years ago. Case 1 was a 58-year-old male who was attending our hospital as an outpatient for hepatic cirrhosis. At 5:30 pm on August 8, 1987, he consumed abalone and giant clam and at 9 pm complained of high fever with shaking chills. He was admitted to our department as an emergency case. Cefoperazone was administered resulting in a decline of fever on the following day. During the course of treatment he fell transiently into pre-DIC, but due mainly to the administration of antibiotics his condition was subsided. Case 2 was a 53-year-old male who was under medical care in our hospital for grave hepatic cirrhosis. On October 11, 1985, he consumed sushi and two days later suffered chills and pyrexia. A blood culture revealed Vibrio vulnificus. His condition improved transiently with administration of Cefazolin, but oliguria, hypotension and ascites occurred subsequently, and finally the patient died on the 22nd day. PMID:2501432

Tateyama, M; Higa, M; Kakazu, T; Miyagi, M; Shikiya, K; Arakaki, T; Kaneshima, H; Irabu, Y; Shimoji, K; Kitsukawa, K

1989-02-01

288

Primary biliary cirrhosis  

MedlinePLUS

... Saunders Elsevier; 2011:chap 158. Angulo P, Lindor KD. Primary biliary cirrhosis. In: Feldman M, Friedman LS, ... Clin Liver Dis . 2008;12:277-288. Lindor KD, Gershwin ME, Poupon R, Kaplan M, et al. ...

289

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

290

Isotopic analysis of Cu in blood serum by multi-collector ICP-mass spectrometry: a new approach for the diagnosis and prognosis of liver cirrhosis?  

PubMed

The isotopic composition of blood serum Cu has been investigated as a potential parameter for the diagnosis and prognosis of liver cirrhosis. Serum samples from supposedly healthy women (reference population) and from a group of female patients suffering from liver cirrhosis of different etiologies were analysed. The procedure for isolation of serum Cu and the measurement protocol for its isotopic analysis by multi-collector inductively coupled plasma-mass spectrometry (MC-ICP-MS) were evaluated. Significant differences in the isotopic composition of Cu were observed between the reference population and the patients. A wide spread in ?(65)Cu was observed within the cirrhosis population and ?(65)Cu seems to be linked to the severity of the disease. Patients with end-stage liver disease showed a significantly lighter serum Cu isotopic composition. Many clinical parameters used for the diagnosis and monitoring of liver diseases, i.e. the levels of aspartate aminotransferase, De Ritis ratio, prothrombin and international normalized ratio, albumin, bilirubin, Na and C-reactive protein, correlate well with the ?(65)Cu values, as did the ceruloplasmin level and the ceruloplasmin/Cu concentration ratio. The isotopic composition of serum Cu appears to reveal the synthetic and hepatocellular function of the liver synergistically with inflammation and fluid retention in the cohort studied. A relevant relationship was also observed between ?(65)Cu and scores of mortality risk, such as the Model for End-stage Liver Disease (MELD) and MELD-Na. Thus, the isotopic composition of serum Cu shows potential as a new approach for the prognosis of liver disease, and although further investigation is required, for evaluation of the mortality risk in end-stage liver disease and prioritization of liver transplants. PMID:25644127

Costas-Rodríguez, Marta; Anoshkina, Yulia; Lauwens, Sara; Van Vlierberghe, Hans; Delanghe, Joris; Vanhaecke, Frank

2015-03-11

291

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

292

Quantitative Assessment of the Presence and Severity of Cirrhosis in Patients with Hepatitis B Using Right Liver Lobe Volume and Spleen Size Measured at Magnetic Resonance Imaging  

PubMed Central

Objective To determine whether right liver lobe volume (RV) and spleen size measured utilizing magnetic resonance (MR) imaging could identify the presence and severity of cirrhosis in patients with hepatitis B. Methods Two hundred and five consecutive patients with clinically confirmed diagnosis of cirrhosis due to hepatitis B and 40 healthy control individuals were enrolled in this study and underwent abdominal triphasic enhanced scans using MR imaging. Spleen maximal width (W), thickness (T) and length (L), together with RV and spleen volume (SV), were measured utilizing MR imaging. Spleen multidimensional index (SI) was obtained by multiplying previously acquired parameters W×T×L. Then statistical assessment was performed to evaluate the ability of these parameters, including RV, SV, RV/SV and SI, to identify the presence of cirrhosis and define Child-Pugh class of this disease. Results SV and SI tended to increase (r?=?0.557 and 0.622, respectively; all P<0.001), and RV and RV/SV tended to decrease (r?=??0.749 and ?0.699, respectively; all P<0.001) with increasing Child-Pugh class of cirrhosis. All the parameters, including RV, SV, RV/SV and SI, might be the indicators used to discriminate the patients with liver cirrhosis from the control group, and to distinguish these patients between Child-Pugh class A and B, between B and C, and between A and C (area under receiver operating characteristic curve [AUC]?=?0.609–0.975, all P<0.05). Among these parameters, RV/SV was the best noninvasive factor for the discrimination of liver cirrhosis between Child-Pugh class A and B (AUC?=?0.725), between A and C (AUC?=?0.975), and between B and C (AUC?=?0.876), while SI was the best variable to distinguish the cirrhosis patients from the control group (AUC?=?0.960, P<0.05). Conclusion RV/SV should be used to identify the severity of cirrhosis, while SI can be recommended to determine the presence of this disease. PMID:24594920

Wu, Jian-lin

2014-01-01

293

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

294

Aflatoxin-induced TP53 R249S mutation in hepatocellular carcinoma in Thailand: association with tumors developing in the absence of liver cirrhosis.  

PubMed

Primary Liver Cancer (PLC) is the leading cause of death by cancer among males in Thailand and the 3(rd) among females. Most cases are hepatocellular carcinoma (HCC) but cholangiocarcinomas represent between 4 and 80% of liver cancers depending upon geographic area. Most HCC are associated with chronic infection by Hepatitis B Virus while a G ? T mutation at codon 249 of the TP53 gene, R249S, specific for exposure to aflatoxin, is detected in tumors for up to 30% of cases. We have used Short Oligonucleotide Mass Analysis (SOMA) to quantify free circulating R249S-mutated DNA in plasma using blood specimens collected in a hospital case:control study. Plasma R249S-mutated DNA was detectable at low concentrations (? 67 copies/mL) in 53 to 64% of patients with primary liver cancer or chronic liver disease and in 19% of controls. 44% of patients with HCC and no evidence of cirrhosis had plasma concentrations of R249S-mutated DNA ? 150 copies/mL, compared to 21% in patients with both HCC and cirrhosis, 22% in patients with cholangiocarcinoma, 12% in patients with non-cancer chronic liver disease and 3% of subjects in the reference group. Thus, plasma concentrations of R249S-mutated DNA ? 150 copies/mL tended to be more common in patients with HCC developing without pre-existing cirrhosis (p = 0.027). Overall, these results support the preferential occurrence of R249S-mutated DNA in HCC developing in the absence of cirrhosis in a context of HBV chronic infection. PMID:22675488

Villar, Stephanie; Ortiz-Cuaran, Sandra; Abedi-Ardekani, Behnoush; Gouas, Doriane; Nogueira da Costa, Andre; Plymoth, Amelie; Khuhaprema, Thiravud; Kalalak, Anant; Sangrajrang, Suleeporn; Friesen, Marlin D; Groopman, John D; Hainaut, Pierre

2012-01-01

295

Platelet-Activating Factor Involvement in Thioacetamide-Induced Experimental Liver Fibrosis and Cirrhosis  

Microsoft Academic Search

Platelet-activating factor (PAF) is a potent lipid inflammatory mediator acting on cells through its specific receptor. Plasma\\u000a PAF-acetylhydrolase (PAF-AH) is the main enzyme that inactivates PAF in blood, participating in its homeostasis. The objective\\u000a of this study was to investigate the involvement of PAF in the liver fibrotic process using an experimental animal model.\\u000a Liver fibrosis was induced in adult

Haralabos C. Karantonis; Georgios Gribilas; Ioannis Stamoulis; Constantinos Giaginis; Chara Spiliopoulou; Gregorios Kouraklis; Constantinos Demopoulos; Stamatios E. Theocharis

2010-01-01

296

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 ( ...

297

Personality disorder as a contraindication for liver transplantation in alcoholic cirrhosis.  

PubMed

Severe personality disorder has been proposed as a contraindication for liver transplantation. Seventy-three subjects with alcoholic-related liver disease were evaluated for personality disorder and followed for 6 months. The subjects with severe personality disorder had higher rates of divorce, higher rates of comorbid drug abuse or dependence, lower Weschler Adult Inventory Scale IQ estimates, and higher scores on indicators of emotional impairment. Personality disorder was not associated with a higher rate of return to alcohol use during the follow-up period. Three subjects with personality disorder underwent liver transplantation without behavioral or substance abuse complications. This study does not support routine exclusion of subjects based solely on a diagnosis of a severe personality disorder. PMID:9819950

Yates, W R; LaBrecque, D R; Pfab, D

1998-01-01

298

Augmented utilization of branched-chain amino acids by skeletal muscle in decompensated liver cirrhosis in special relation to ammonia detoxication  

Microsoft Academic Search

Summary  Femoral arterio-venous (A-V) differences of blood free amino acids and plasma ammonia (NH3) were simultaneously determined after an overnight fast in 16 patients with decompensated liver cirrhosis in the absence\\u000a and presence of encephalopathy, as compared with those in 8 control subjects. In spite of increased releases of phenylalanine\\u000a (Phe) and tyrosine (Tyr) from the peripheral tissue, releases of isoleucine

Masanori Hayashi; Hiroo Ohnishi; Yasuhiko Kawade; Yasutoshi Muto; Yoshiyata Takahashi

1981-01-01

299

T-lymphocyte subsets in liver tissues of patients with primary biliary cirrhosis (PBC), patients with primary sclerosing cholangitis (PSC), and normal controls  

Microsoft Academic Search

T lymphocytes infiltrating hepatic tissues were typed and enumerated in liver biopsies of patients with primary biliary cirrhosis (PBC), patients with primary sclerosing cholangitis (PSC), and normal controls using monoclonal antibodies and the avidin-biotin-immunoperoxidase technique. The peripheral blood mononuclear cells were studied also by flow cytometry. In PBC, T lymphocytes were decreased (PPP<0.001) in the number of T8+ cells. The

Lusheng Si; Theresa L. Whiteside; Robert R. Schade; Thomas E. Starzl; DAVID H. VAN THIEL

1984-01-01

300

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

301

Severe recurrent hepatitis C after liver retransplantation for hepatitis C virus–related graft cirrhosis  

Microsoft Academic Search

An increase in the number of hepatitis C virus (HCV)-infected transplant recipients at need for repeated liver transplantation is anticipated. To date, there is a certain reluctance to accept these patients because of an increased organ shortage, early reports suggesting a poor outcome, and uncertainty regarding the natural history of recurrent hepatitis C in the second graft. The aim of

Marina Berenguer; Mart??n Prieto; Antonio Palau; José M. Rayón; Domingo Carrasco; F-Xavier López-Labrador; Rosalba Moreno; José Mir; Joaqu??n Berenguer

2003-01-01

302

Septic shock and necrotizing fasciitis due to Aeromonas hydrophila after chemotherapy in a patient with mantle cell lymphoma accompanied by liver cirrhosis.  

PubMed

A 78-year-old man with liver cirrhosis was admitted to our hospital because of persistent diarrhea and abdominal pain. Colonoscopy revealed erosions and submucosal tumors in portions of the sigmoid colon and rectum, which were diagnosed as mantle cell lymphoma with biopsy. After chemotherapy consisting of vincristine and prednisone, he developed Aeromonas hydrophila septicemia, resulting in septic shock and necrotizing fasciitis despite prescribing antimicrobial agents to which this organism was susceptible. Whenever we intend to treat patients with hematological malignancies and an underlying chronic liver disease, we must keep this bacterium in mind. PMID:25744046

Tanaka, Masaru; Watanabe, Naoki; Aota, Yasuo; Ando, Jun; Gotoh, Akihiko; Komatsu, Norio

2014-12-01

303

Selection of a TIPS stent for management of portal hypertension in liver cirrhosis: An evidence-based review  

PubMed Central

Nowadays, transjugular intrahepatic portosystemic shunt (TIPS) has become a mainstay treatment option for the management of portal hypertension-related complications in liver cirrhosis. Accumulated evidence has shown that its indications are being gradually expanded. Notwithstanding, less attention has been paid for the selection of an appropriate stent during a TIPS procedure. Herein, we attempt to review the current evidence regarding the diameter, type, brand, and position of TIPS stents. Several following recommendations may be considered in the clinical practice: (1) a 10-mm stent may be more effective than an 8-mm stent for the management of portal hypertension, and may be superior to a 12-mm stent for the improvement of survival and shunt patency; (2) covered stents are superior to bare stents for reducing the development of shunt dysfunction; (3) if available, Viatorr stent-grafts may be recommended due to a higher rate of shunt patency; and (4) the placement of a TIPS stent in the left portal vein branch may be more reasonable for decreasing the development of hepatic encephalopathy. However, given relatively low quality of evidence, prospective well-designed studies should be warranted to further confirm these recommendations. PMID:24914368

Qi, Xing-Shun; Bai, Ming; Yang, Zhi-Ping; Fan, Dai-Ming

2014-01-01

304

Deficient Serum Bactericidal Activity Against Escherichia Coli in Patients with Cirrhosis of the Liver  

PubMed Central

The serum bactericidal activity (SBA) of cirrhotic patients was compared with that of normal individuals using the release of 51Cr from radiolabeled Escherichia coli as the assay method. 80% (22/27) of patients were found to have deficient SBA against at least one of three smooth, serum-sensitive test strains of E. coli. Cirrhotic patients were found to have normal levels of serum lysozyme. Although some patients were mildly hypocomplementemic, this abnormality did not correlate with the presence of a bactericidal defect. Bactericidal antibody in normal and cirrhotics' sera was limited to the immunoglobulin (Ig)M class. Purified IgM from patients with deficient SBA against E. coli 0111 had lower concentrations of bactericidal antibody for that E. coli than did IgM from normal sera; the calculated bactericidal activity of total serum IgM was also lower. The bactericidal defect in cirrhotic serum could be completely corrected by either human antiserum to the homologous strain of E. coli or by purified, normal human IgM. However, because higher concentrations of IgM were required to restore normal SBA to a cirrhotic's serum than to agammaglobulinemic serum, there may be an inhibitor of bactericidal antibody in addition to a deficiency of bactericidal IgM antibody to E. coli in the serum of patients with cirrhosis. The bactericidal activity of the alternative complement pathway was also assessed. Sera from cirrhotic patients had no deficit in SBA attributable to the alternative complement pathway. In fact, in some, the activity of the alternative complement pathway was supernormal, compensating in part for the deficit in IgM-mediated SBA. PMID:376551

Fierer, Joshua; Finley, Fred

1979-01-01

305

Function of interleukin-17 and ?35 in the blood of patients with hepatitis B-related liver cirrhosis  

PubMed Central

Intrahepatic T helper (Th)17 cytokine and serum interleukin (IL)-17 levels in patients with hepatitis B are positively correlated with the progression of liver cirrhosis (LC). IL-35 can significantly inhibit the differentiation of Th17 cells and the synthesis of IL-17. The present study aimed to investigate the function and expression of IL-17 and IL-35 in the blood of patients with hepatitis B-related LC. The levels of IL-17 and IL-35 in the peripheral blood of 30 patients with chronic hepatitis B (CHB), 79 with LC, 14 with chronic severe hepatitis B (CSHB), and 20 normal controls were detected by ELISA. Quantitative polymerase chain reaction was used to evaluate Epstein-Barr virus-induced gene 3 (EBI3), forkhead box (FOX)P3 and IL-17 mRNA expression levels in peripheral blood mononuclear cells (PBMCs). Western blotting was used to determine protein expression. The liver function of patients and normal controls was measured. EBI3, IL-17 and FOXP3 mRNA expression levels in PBMCs from patients with LC, CHB and CSHB were higher than those in cells from the controls. IL-17 mRNA levels differed significantly according to the Child-Pugh classification and exhibited an upward trend over time in contrast to a downward trend for EBI3 and FOXP3 mRNA. The changes in protein expression in the peripheral blood were consistent with the changes in mRNA expression. Serum IL-17 levels were positively correlated with total bilirubin (TBIL), alanine aminotransferase (ALT) and Child-Pugh grade, and were negatively correlated with albumin. These observed differences were significant. Serum IL-35 levels were negatively correlated with albumin, but not with Child-Pugh grade, ALT and TBIL. IL-17 and IL-35 may be critically involved in the pathogenesis of hepatitis B-related LC. PMID:25323532

SHI, MIN; WEI, JUE; DONG, JINBIN; MENG, WENYING; MA, JIALI; WANG, TING; WANG, NA; WANG, YUGANG

2015-01-01

306

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

307

Hepatoprotective activity of Haridradi ghrita on carbon tetrachloride-induced liver damage in rats.  

PubMed

Haridradi ghrita, a ghee based polyherbal formulation, (50, 100, 200 and 300 mg/kg) significantly lowered marker enzymes (SGPT, SGOT, ALP) and bilirubin in serum and liver peroxide, superoxide dismutase and catalase in liver homogenate following CCl4 (0.7 ml/kg, ip) toxicity. The protective effect was further supported by reversal of CCl4 induced histological changes. The results demonstrate significant hepatoprotective action of H. ghrita in CCl4 damaged rats. PMID:15320500

Satturwar, P M; Fulzele, S V; Joshi, S B; Dorle, A K

2003-12-01

308

Day-night variations in thyroid stimulating hormone and its relation with clinical status and metabolic parameters in patients with cirrhosis of the liver.  

PubMed

To investigate day-night variations in thyroid stimulating hormone (TSH) and its relation with clinical status and metabolic parameters in patients with cirrhosis. Forty-one patients with negative thyroid antibodies and normal thyroid function tests who were diagnosed with cirrhosis were included. Thirty-five age- and gender-matched healthy subjects were included in control group.TSH, fT3, and fT4 levels, which were measured both in the morning and late evening. The difference between nocturnal TSH and morning TSH (?TSH) were compared between groups. Relation between Child-Turcotte-Pugh, model for End-Stage Liver Disease (MELD) and MELD-Na scores and levels of thyroid hormones, ?TSH and serum sodium (Na) levels was investigated. Relation between ?TSH and clinical status and metabolic parameters was also evaluated. The mean morning fT3, nocturnal fT3, nocturnal TSH, and ?TSH levels were significantly lower, morning and nocturnal fT4 levels were higher in patients with cirrhosis (p < 0.001, p < 0.001, p = 0.004, p < 0.001, and p < 0.001).As the ROC analysis, day-night variation was detected to be impaired in the event that difference between nocturnal TSH level and morning TSH level was lower than 1 uIU/mL in patients with cirrhosis with a sensitivity of 92.7 % and specificity of 71.4 % (p < 0.001).A significant positive correlation was found between serum Na levels and fT3 in patients with cirrhosis (r = 0.479, p = 0.001), and a significant negative correlation was found between the severity of clinical status and low levels of fT3 in patients with cirrhosis (p < 0.001).Nocturnal TSH increase does not occur in cases of cirrhosis without known thyroid disease and with normal thyroid function tests, which may be an early finding of impaired thyroid functions in patients with cirrhosis. PMID:25063309

Atalay, Roni; Ersoy, Reyhan; Demirezer, Aylin Bolat; Ak?n, Fatma Ebru; Polat, Sefika Burcak; Cakir, Bekir; Ersoy, Osman

2015-04-01

309

Impairment of Response Inhibition Precedes Motor Alteration in the Early Stage of Liver Cirrhosis: A Behavioral and Electrophysiological Study  

Microsoft Academic Search

Abnormality in movement initiation may partially explain psychomotor delay of cirrhotic patients, even in the absence of overt hepatic encephalopathy (HE). Therefore, the aim of this study was to determine the mechanisms of psychomotor delay observed in patients with cirrhosis in the absence of overt HE. Fourteen patients with nonalcoholic cirrhosis and 12 healthy matched control subjects underwent the lateralized

Sami Schiff; Antonino Vallesi; Daniela Mapelli; Raffaele Orsato; Andrea Pellegrini; Carlo Umiltà; Angelo Gatta; Piero Amodio

2005-01-01

310

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

311

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

2015-02-01

312

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

313

Alcohol and liver cirrhosis mortality in the US: Comparison of methods for the analyses of time-series panel data models  

PubMed Central

Background To explore various model specifications in estimating relationships between liver cirrhosis mortality rates and per capita alcohol consumption in aggregate level cross-section time-series data. Methods Using series of liver cirrhosis mortality rates from 1950 to 2002 for 47 US states, the effects of alcohol consumption were estimated from pooled ARIMA models and four types of panel data models: GEE, GLS, fixed effect and multi-level models. Various specifications of error term structure under each type of model were also examined. Different approaches controlling for time trends and for using concurrent or accumulated consumption as predictors were also evaluated. Results When cirrhosis mortality was predicted by total alcohol, highly consistent estimates were found between ARIMA and panel data analyses, with an average overall effect of 0.07–0.09. Less consistent estimates were derived using spirits, beer and wine consumption as predictors. Conclusions When multiple geographic time series are combined as panel data, none of existent models could accommodate all sources of heterogeneity such that any type of panel model must employ some form of generalization. Different types of panel data models should thus be estimated to examine the robustness of findings. We also suggest cautious interpretation when beverage-specific volumes are used as predictors. PMID:21039632

Ye, Yu; Kerr, William C.

2010-01-01

314

Protective effect of potato peel extract against carbon tetrachloride-induced liver injury in rats.  

PubMed

Our earlier studies have shown that extracts derived from potato peel (PPE) are rich in polyphenols and possess strong antioxidant activity both in vitro and in vivo. The objective of the present study was to investigate its potential to offer protection against acute liver injury in rats. Rats pretreated with PPE (oral, 100mg/kgb.w./day for 7 days) were administered a single oral dose carbon tetrachloride (CCl(4), 3ml/kg b.w., 1:1 in groundnut oil) and sacrificed 8h of post-treatment. Hepatic damage was assessed by employing biochemical parameters (transaminase enzyme levels in plasma and liver [AST-aspartate transaminase; ALT-alanine transaminase, LDH-lactate dehydrogenase]). Further, markers of hepatic oxidative damage were measured in terms of malondialdehyde (MDA), enzymic antioxidants (CAT, SOT, GST, GPX) and GSH (reduced glutathione) levels. In addition, the CCl(4)-induced pathological changes in liver were evaluated by histopathological studies. Our results demonstrated that pretreatment of rats with PPE significantly prevented the increased activities of AST and ALT in serum, prevented the elevation of hepatic MDA formation as well as protected the liver from GSH depletion. PPE pretreatment also restored CCl(4)-induced altered antioxidant enzyme activities to control levels. The protective effect of PPE was further evident through the decreased histological alterations in liver. Our findings provide evidences to demonstrate that PPE pretreatment significantly offsets CCl(4)-induced liver injury in rats, which may be attributable to its strong antioxidant propensity. PMID:21791371

Singh, Nandita; Kamath, Vasudeva; Narasimhamurthy, K; Rajini, P S

2008-09-01

315

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

316

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; Bourlière, Marc; Buti, Maria; Stern, Jerry O; Gallivan, John-Paul; Voss, Florian; Sabo, John P; Böcher, Wulf; Mensa, Federico J

2015-02-01

317

Clinical outcomes of patients with liver cirrhosis who underwent curative surgery for gastric cancer: a retrospective multi-center study.  

PubMed

We investigated early postoperative morbidity, mortality, and long-term outcomes in patients with liver cirrhosis (LC) who had undergone curative surgery for gastric cancer. The medical records of patients with LC who had undergone radical gastrectomy for gastric adenocarcinoma between January 1996 and September 2006 were retrospectively reviewed. A total of 57 patients were enrolled in this study. Forty-six patients (81%) were classified into Child's class A. In 22 patients (39%) postoperative complications developed, the most common being ascites (23%), followed by wound infection and hepatic encephalopathy. Postoperative ascites occurred more frequently in patients with Child's class B or C than in those with class A (63.6% vs 13%, P = 0.001). Massive ascites developed in 4 patients, 3 of whom had Child's class B and underwent D2 lymph node (LN) dissection, and 1 of whom had Child's class C and a D1 LN dissection. Postoperative mortality occurred in 5 patients (9%), with a significantly higher mortality rate for patients with Child's class B or C than for those with class A (27.2% vs 4.3%, P = 0.045). With a median follow-up of 32 months, the estimated 5-year survival rate for all patients was 54%. Regardless of the tumor depth, overall survival was longer for patients with Child's class A than for those with Child's class B or C. These results demonstrated that radical gastrectomy with extended LN dissection is feasible in patients with compensated LC. For patients with moderate to severe hepatic dysfunction, however, D1 or less extensive LN dissection may be the more reasonable surgical procedure. PMID:17597403

Jang, Hyun Joo; Kim, Jung Han; Song, Hun Ho; Woo, Kyung Hee; Kim, Mi; Kae, Sea Hyub; Lee, Jin; Cho, Ji Wong; Kang, Jung Hun; Lee, Soon Il; Gong, Soo Jung; Lee, Jung Ae; Zang, Dae Young

2008-02-01

318

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

319

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

320

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

321

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

322

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 ...

323

Nonalcoholic Fatty Liver Disease: Portal Hypertension Due to Outflow Block in Patients without Cirrhosis.  

PubMed

Purpose To prospectively evaluate whether the characteristics of hepatic blood flow change during the early stages of fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). Materials and Methods All participants provided written informed consent, and the study protocols were approved by the institutional ethics committee. A total of 121 patients with NAFLD that was diagnosed at histologic examination were enrolled. Hepatic blood flow was measured by means of Doppler ultrasonography (US), and the ratio of arterial to portal blood flow (arterioportal ratio) was calculated. Elasticity of the spleen was measured by means of real-time tissue elastography. The elastic ratio was measured as the value in the small splenic vessel divided by the value of the splenic parenchyma. The arterioportal ratio and splenic elasticity were compared in patients with all stages of fibrosis (F0-F4) and with all levels of platelet counts. Correlations among the resistive index of the hepatic artery and that of the splenic artery, the fibrosis 4 index, hepatic elasticity, arterioportal ratio, splenic elasticity, and platelet counts were analyzed. Univariate and multivariate logistic regression analyses were performed. Correlations in patients with platelet counts greater than 200 000/?L also were analyzed. Results The mean ± standard deviation arterioportal ratio was significantly higher at fibrosis stage 2 (2.4 ± 0.6) than at fibrosis stage 0 (1.8 ± 0.4) in patients with NAFLD (P < .01). Increased splenic stiffness at earlier stages of fibrosis also was observed in patients with NAFLD (fibrosis stage 2, 4.4 ± 2.3; fibrosis stage 0, 3.2 ± 1.9; P < .05). In patients with NAFLD with platelet counts higher than 200 000/?L, pericellular fibrosis was the only significant predictor of hepatic hemodynamic change at multivariate analysis (odds ratio, 7.17; 95% confidence interval: 1.33, 57.13; P = .021). Conclusion Change in hepatic blood flow occurred during the earliest stage of hepatic fibrosis in patients with NAFLD because of outflow block in the sinusoidal area. © RSNA, 2014 Online supplemental material is available for this article. PMID:25302830

Hirooka, Masashi; Koizumi, Yohei; Miyake, Teruki; Ochi, Hironori; Tokumoto, Yoshio; Tada, Fujimasa; Matsuura, Bunzo; Abe, Masanori; Hiasa, Yoichi

2015-02-01

324

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. PMID:25657603

Farr, Maryjane; Schulze, Paul Christian

2014-01-01

325

A case report of massive vaginal variceal hemorrhage in a patient with cirrhosis secondary to nonalcoholic steatohepatitis unresolved even after successful liver transplantation.  

PubMed

Massive hemorrhage from vaginal varices in patients with cirrhosis and a previous hysterectomy can be life-threatening. In the few previous reports, the treatments have all included an initial local tamponade followed by interventional radiology procedures, transvenous intrahepatic portosystemic shunts, surgical shunt, or liver transplantation. A patient with cirrhosis secondary to nonalcoholic steatohepatitis developed massive vaginal variceal hemorrhage. Control of the bleeding was achieved initially with local tamponade. Upon admission to the intensive care unit, the patient was upgraded to urgent status on the liver transplant waiting list, which was performed on day 7. Due to a portal vein thrombosis, an interpositional vein graft to the superior mesenteric vein was required. Postoperatively despite a functional graft and normalization of coagulation system, the vaginal bleeding continued as the left-sided portal hypertension had not been decompressed by the liver transplantation. During a subsequent laparotomy, splenectomy and ligation of the inferior mesenteric vein were required to definitively control the vaginal variceal hemorrhage. The degree and anatomy of the portal hypertension play a crucial role in determining the proper course of management and treatment of vaginal varices in a cirrhotic patient. PMID:23267803

Chan, G; Taqi, A; Drage, M; Quan, D

2013-03-01

326

Child-Pugh versus MELD score for predicting the in-hospital mortality of acute upper gastrointestinal bleeding in liver cirrhosis  

PubMed Central

A retrospective study was conducted to compare the performance of Child-Pugh and Model for End-Stage Liver Diseases (MELD) scores for predicting the in-hospital mortality of acute upper gastrointestinal bleeding (UGIB) in patients with liver cirrhosis. A total of 145 patients with a diagnosis of liver cirrhosis and acute UGIB between July 2013 and June 2014 were retrospectively analyzed (male/female: 94/51; mean age: 56.77±11.33 years; Child-Pugh class A/B/C: 46/64/35; mean Child-Pugh score: 7.88±2.17; mean MELD score: 7.86±7.22). The in-hospital mortality was 8% (11/145). Areas under receiving-operator characteristics curve (AUROC) for predicting the in-hospital mortality were compared between MELD and Child-Pugh scores. AUROCs for predicting the in-hospital mortality for Child-Pugh and MELD scores were 0.796 (95% confidence interval [CI]: 0.721-0.858) and 0.810 (95% CI: 0.736-0.870), respectively. The discriminative ability was not significant different between the two scoring systems (P=0.7241). In conclusion, Child-Pugh and MELD scores were similar for predicting the in-hospital mortality of acute UGIB in cirrhotic patients. PMID:25785053

Peng, Ying; Qi, Xingshun; Dai, Junna; Li, Hongyu; Guo, Xiaozhong

2015-01-01

327

The effect of alcoholic cirrhosis on the activities of microsomal aldrin epoxidase, 7-ethoxycoumarin O-de-ethylase and epoxide hydrolase, and on the concentrations of reduced glutathione in human liver.  

PubMed Central

Activities of the microsomal mono-oxygenases 7-ethoxycoumarin O-de-ethylase (EOC) and aldrin epoxidase (AE), together with microsomal epoxide hydrolase (EH) activity and concentrations of reduced glutathione (GSH) have been measured in liver from patients with alcoholic cirrhosis and in normals. Activities of both mono-oxygenases were significantly reduced in alcoholic cirrhosis. EOC activity (pmol 7-OH coumarin formed/mg microsomal protein/min) was 108.0 +/- 10.6 (n = 8) in normals and 60.9 +/- 11.6 (n = 8) in alcoholic cirrhosis (P less than 0.01). AE activity (pmol dieldrin formed/mg microsomal protein/min) was 58.9 +/- 9.5 (n = 11) in normal liver biopsies and 29.9 +/- 8.6 (n = 9) in alcoholic cirrhosis (P less than 0.05). Microsomal EH activity (nmol styrene glycol formed/mg microsomal protein/min) was similar in normals (39.2 +/- 4.4, n = 11) and alcoholic cirrhosis (40.5 +/- 9.1, n = 6). GSH concentrations (microgram GSH/g liver tissue) were lower (P less than 0.01) in alcoholic cirrhosis (792 +/- 73, n = 10) compared to normals (1182 +/- 76, n = 6). PMID:6603231

Woodhouse, K W; Williams, F M; Mutch, E; Wright, P; James, O F; Rawlins, M D

1983-01-01

328

Hepatosplanchnic circulation in cirrhosis and sepsis  

PubMed Central

Hepatosplanchnic circulation receives almost half of cardiac output and is essential to physiologic homeostasis. Liver cirrhosis is estimated to affect up to 1% of populations worldwide, including 1.5% to 3.3% of intensive care unit patients. Cirrhosis leads to hepatosplanchnic circulatory abnormalities and end-organ damage. Sepsis and cirrhosis result in similar circulatory changes and resultant multi-organ dysfunction. This review provides an overview of the hepatosplanchnic circulation in the healthy state and in cirrhosis, examines the signaling pathways that may play a role in the physiology of cirrhosis, discusses the physiology common to cirrhosis and sepsis, and reviews important issues in management. PMID:25759525

Prin, Meghan; Bakker, Jan; Wagener, Gebhard

2015-01-01

329

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

330

Hepatocyte growth factor incorporated chitosan nanoparticles augment the differentiation of stem cell into hepatocytes for the recovery of liver cirrhosis in mice  

PubMed Central

Background Short half-life and low levels of growth factors in the niche of injured microenvironment necessitates the exogenous and sustainable delivery of growth factors along with stem cells to augment the regeneration of injured tissues. Methods Here, recombinant human hepatocyte growth factor (HGF) was incorporated into chitosan nanoparticles (CNP) by ionic gelation method and studied for its morphological and physiological characteristics. Cirrhotic mice received either hematopoietic stem cells (HSC) or mesenchymal stemcells (MSC) with or without HGF incorporated chitosan nanoparticles (HGF-CNP) and saline as control. Biochemical, histological, immunostaining and gene expression assays were carried out using serum and liver tissue samples. One way analysis of variance was used for statics application Results Serum levels of selected liver protein and enzymes were significantly increased in the combination of MSC and HGF-CNP (MSC+HGF-CNP) treated group. Immunopositive staining for albumin (Alb) and cytokeratin 18 (CK18), and reverse transcription-polymerase chain reaction (RT-PCR) for Alb, alpha fetoprotein (AFP), CK18, cytokeratin 19 (CK19) ascertained that MSC-HGF-CNP treatment could be an effective combination to repopulate liver parenchymal cells in the liver cirrhosis. Zymogram and western blotting for matrix metalloproteinases 2 and 9 (MMP2 and MMP9) revealed that MMP2 actively involved in the fibrolysis of cirrhotic tissue. Immunostaining for alpha smooth muscle actin (?SMA) and type I collagen showed decreased expression in the MSC+HGF-CNP treatment. These results indicated that HGF-CNP enhanced the differentiation of stem cells into hepatocytes and supported the reversal of fibrolysis of extracellular matrix (ECM). Conclusion Bone marrow stem cells were isolated, characterized and transplanted in mice model. Biodegradable biopolymeric nanoparticles were prepared with the pleotrophic protein molecule and it worked well for the differentiation of stem cells, especially mesenchymal phenotypic cells. Transplantation of bone marrow MSC in combination with HGF-CNP could be an ideal approach for the treatment of liver cirrhosis. PMID:21526984

2011-01-01

331

Pulmonary Complications of Cirrhosis  

Microsoft Academic Search

Pulmonary vascular complications of liver disease comprise two distinct clinical entities: hepatopulmonary syndrome (HPS—microvascular\\u000a dilatation and angiogenesis) and portopulmonary hypertension (POPH—vasoconstriction and remodeling in resistance vessels).\\u000a These complications occur in similar pathophysiologic environments and may share pathogenic mechanisms. HPS is found in 15%\\u000a to 30% of patients with cirrhosis and its presence increases mortality and the risks of liver transplantation,

Rajan Kochar; Moises I. Nevah Rubin; Michael B. Fallon

2011-01-01

332

Hepatoprotective activity of carrot ( Daucus carota L.) against carbon tetrachloride intoxication in mouse liver  

Microsoft Academic Search

The effect of carrot extract on carbon tetrachloride (CCl4)-induced acute liver damage was evaluated. The increased serum enzyme levels (viz., glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, lactate dehydrogenase, alkaline phosphatase, sorbitol and glutamate dehydrogenase) by CCl4-induction were significantly lowered due to pretreatment with the extract. The extract also decreased the elevated serum bilirubin and urea content due to CCl4 administration.

Anupam Bishayee; Alok Sarkar; Malay Chatterjee

1995-01-01

333

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

334

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

335

Studies on immunoproteasome in human liver. Part I: Absence in fetuses, presence in normal subjects, and increased levels in chronic active hepatitis and cirrhosis  

SciTech Connect

Despite the central role of proteasomes in relevant physiological pathways and pathological processes, this topic is unexpectedly largely unexplored in human liver. Here we present data on the presence of proteasome and immunoproteasome in human livers from normal adults, fetuses and patients affected by major hepatic diseases such as cirrhosis and chronic active hepatitis. Immunohistochemistry for constitutive ({alpha}4 and {beta}1) and inducible (LMP2 and LMP7) proteasome subunits, and for the PA28{alpha}{beta} regulator, was performed in liver samples from 38 normal subjects, 6 fetuses, 2 pediatric cases, and 19 pathological cases (10 chronic active hepatitis and 9 cirrhosis). The immunohistochemical data have been validated and quantified by Western blotting analysis. The most striking result we found was the concomitant presence in hepatocyte cytoplasm of all healthy subjects, including the pediatric cases, of constitutive proteasome and immunoproteasome subunits, as well as PA28{alpha}{beta}. At variance, immunoproteasome was not present in hepatocytes from fetuses, while a strong cytoplasmic and nuclear positivity for LMP2 and LMP7 was found in pathological samples, directly correlated to the histopathological grade of inflammation. At variance from other organs such as the brain, immunoproteasome is present in livers from normal adult and pediatric cases, in apparent absence of pathological processes, suggesting the presence of a peculiar regulation of the proteasome/immunoproteasome system, likely related to the physiological stimuli derived from the gut microbiota after birth. Other inflammatory stimuli contribute in inducing high levels of immunoproteasome in pathological conditions, where its role deserve further attention.

Vasuri, Francesco; Capizzi, Elisa [Pathology Unit of the 'F. Addarii' Institute of Oncology, S.Orsola-Malpighi Hospital, Bologna University (Italy)] [Pathology Unit of the 'F. Addarii' Institute of Oncology, S.Orsola-Malpighi Hospital, Bologna University (Italy); Bellavista, Elena [Department of Experimental Pathology, Bologna University (Italy) [Department of Experimental Pathology, Bologna University (Italy); Interdepartmental Center for Studies on Biophysics, Bioinformatics and Biocomplexity 'L. Galvani' (CIG), Bologna University (Italy); Mishto, Michele [Department of Experimental Pathology, Bologna University (Italy) [Department of Experimental Pathology, Bologna University (Italy); Interdepartmental Center for Studies on Biophysics, Bioinformatics and Biocomplexity 'L. Galvani' (CIG), Bologna University (Italy); Institute of Biochemistry, Medical Faculty Charite, Berlin (Germany); Santoro, Aurelia [Department of Experimental Pathology, Bologna University (Italy) [Department of Experimental Pathology, Bologna University (Italy); Interdepartmental Center for Studies on Biophysics, Bioinformatics and Biocomplexity 'L. Galvani' (CIG), Bologna University (Italy); Fiorentino, Michelangelo [Pathology Unit of the 'F. Addarii' Institute of Oncology, S.Orsola-Malpighi Hospital, Bologna University (Italy)] [Pathology Unit of the 'F. Addarii' Institute of Oncology, S.Orsola-Malpighi Hospital, Bologna University (Italy); Capri, Miriam [Department of Experimental Pathology, Bologna University (Italy) [Department of Experimental Pathology, Bologna University (Italy); Interdepartmental Center for Studies on Biophysics, Bioinformatics and Biocomplexity 'L. Galvani' (CIG), Bologna University (Italy); Cescon, Matteo; Grazi, Gian Luca [Unit of General and Transplantation Surgery, S.Orsola-Malpighi Hospital, Bologna University (Italy)] [Unit of General and Transplantation Surgery, S.Orsola-Malpighi Hospital, Bologna University (Italy); Grigioni, Walter Franco; D'Errico-Grigioni, Antonia [Pathology Unit of the 'F. Addarii' Institute of Oncology, S.Orsola-Malpighi Hospital, Bologna University (Italy)] [Pathology Unit of the 'F. Addarii' Institute of Oncology, S.Orsola-Malpighi Hospital, Bologna University (Italy); Franceschi, Claudio, E-mail: claudio.franceschi@unibo.it [Department of Experimental Pathology, Bologna University (Italy) [Department of Experimental Pathology, Bologna University (Italy); Interdepartmental Center for Studies on Biophysics, Bioinformatics and Biocomplexity 'L. Galvani' (CIG), Bologna University (Italy)

2010-06-25

336

Healing and Preventive Effects of Calcium Alginate on Carbon Tetrachloride Induced Liver Injury in Rats  

PubMed Central

The purpose of this study was to investigate the pharmacological effects of calcium alginate on carbon tetrachloride (CCL4)-induced hepatotoxicity in rats. The study included two experiments. In the first experiment the animals were given daily CCL4 through gavage for 7 days and then 10, 50, or 250 mg/kg b.w. of calcium alginate for 21 days. The increased bilirubin level, enhanced alanine and aspartate aminotransferase activity in plasma and reduced liver glycogen content induced by CCL4 were partly normalized by alginate administration in a dose-dependent manner. In addition, alginate significantly improved CCL4-induced alterations of pro-oxidant and antioxidant biochemical parameters in liver and plasma compared to those of rats administered CCL4. In the second experiment the animals were given daily 10, 50 or 250 mg/kg b.w. of calcium alginate for 21 days before 7-day administration of CCL4. Pretreatment with alginate before CCL4 administration resulted in significantly inhibited increase of the blood enzymatic activities of alanine and aspartate aminotransferases and bilirubin level in a dose-dependent manner. Also, preliminary administration of alginate prevented elevation of lipid peroxidation products and reduction of liver glutathione content in rats given CCL4. These results suggest that calcium alginate exerts healing and preventive effects on CCL4-induced hepatotoxicity in rats.

Khotimchenko, Yuri S.; Khotimchenko, Maxim Y.

2004-01-01

337

Hepatitis Bs antibody in alcoholic cirrhosis  

Microsoft Academic Search

Sera from patients with chronic liver disease were tested for antibody against hepatitis B surface antigen by radioimmunoassay. The antibody was found in 25% of patients with alcoholic cirrhosis and in 52% when alcoholic cirrhosis was associated with portal hypertension, these results being significantly higher than in a matched control population. Other forms of chronic liver disease did not differ

P R Mills; T H Pennington; P Kay; R N MacSween; G Watkinson

1979-01-01

338

Senescent case of cholesterol ester storage disease that progressed to liver cirrhosis with a novel mutation (N250H) of lysosomal acid lipase gene.  

PubMed

The patient, a 69-year-old man, had a chief complaint of hepatomegaly. The liver was palpated four fingerbreadths below the costal margin, and the spleen was three fingerbreadths below the costal margin. There were no other abnormal findings. Laparoscopy showed that the liver resembled an orange-yellow crayon in appearance and was nodular. The pathological findings of the liver biopsy tissue were consistent with liver cirrhosis. Inside the fibrous septum was an apparent aggregation of enlarged macrophages that phagocytosed lipid components, as well as enlarged Kupffer cells that phagocytosed lipid droplets. Electron microscopy showed the lipid droplets to have a moth-eaten appearance. Using monocytes extracted from the peripheral blood, acid lipase activity was measured by fluorescence spectrometry using 4-methylumbelliferone palmitate as a substrate. This patient's human lysosomal acid lipase activity was 0.020?nM/min per 10(6) ?cells, corresponding to 5.9% of that in healthy subjects (0.332?±?0.066?nM/min per 10(6) ?cells). Cholesterol ester storage disease was therefore diagnosed. The acid lipase A base sequence obtained from leukocytes by direct sequencing was compared with a library. This patient had a point mutation of N250H/N250H in exon 7, a novel gene abnormality that has not previously been reported. PMID:23675960

Kojima, Seiichiro; Watanabe, Norihito; Takashimizu, Shinji; Kagawa, Tatehiro; Shiraishi, Koichi; Koizumi, Jun; Hirabayashi, Ken-Ichi; Ohkubo, Tomoichi; Kamiguchi, Hiroshi; Tsuda, Michio; Mine, Tetsuya

2013-12-01

339

Hispolon Protects against Acute Liver Damage in the Rat by Inhibiting Lipid Peroxidation, Proinflammatory Cytokine, and Oxidative Stress and Downregulating the Expressions of iNOS, COX-2, and MMP-9  

PubMed Central

The hepatoprotective potential of hispolon against carbon tetrachloride (CCl4)-induced liver damage was evaluated in preventive models in rats. Male rats were intraperitoneally treated with hispolon or silymarin once daily for 7 consecutive days. One hour after the final hispolon or silymarin treatment, the rats were injected with CCl4. Administration with hispolon or silymarin significantly decreased the alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in serum and increased the activities of superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), and glutathione (GSH) content and decreased the malondialdehyde (MDA) content in liver compared with CCl4-treated group. Liver histopathology also showed that hispolon reduced the incidence of liver lesions induced by CCl4. In addition, hispolon decreased nitric oxide (NO) production and tumor necrosis factor (TNF-?), inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) activation in CCl4-treated rats. We also examined the involvement of matrix metalloproteinase (MMP)-9 in the development of CCl4-induced liver damage in rats. Hispolon inhibited the expression of MMP-9 protein, indicating that MMP-9 played an important role in the development of CCl4-induced rat liver damage. Therefore, we speculate that hispolon protects rats from liver damage through their prophylactic redox balancing ability and anti-inflammation capacity. PMID:22013489

Huang, Guan-Jhong; Deng, Jeng-Shyan; Chiu, Chuan-Sung; Liao, Jung-Chun; Hsieh, Wen-Tsong; Sheu, Ming-Jyh; Wu, Chieh-Hsi

2012-01-01

340

Serum zinc value in patients with hepatitis virus-related chronic liver disease: association with the histological degree of liver fibrosis and with the severity of varices in compensated cirrhosis  

PubMed Central

The relationships between the serum mineral concentrations and the endoscopic findings of esophageal varices have been poorly investigated. In this study, we investigated hepatitis virus-positive patients who had undergone a liver biopsy (n = 576) and 75 patients with compensated cirrhosis in order to evaluate the association of the zinc value with the severity of liver fibrosis and esophageal varices. The mean zinc values decreased with the progression of fibrosis (METAVIR score; F0–1: 71.3 ± 11.3, F2: 68.9 ± 11.7, F3: 66.3 ± 11.8, F4: 63.9 ± 15.0). In the hepatitis virus-related compensated cirrhosis, the mean zinc value decreased with the severity of varices (patients without varices: 66.3 ± 12.6, patients with low-risk varices: 62.5 ± 13.7, patients with high-risk varices: 55.6 ± 13.0). The zinc value was significantly lower in patients with varices than in those without varices (59.3 ± 13.6 vs 66.3 ± 12.6, p<0.05). The zinc value was also significantly lower in the patients with a high risk of bleeding than in those with a low risk (55.6 ± 13.0 vs 64.6 ± 13.1, p<0.01). These findings suggest that the zinc value is not only an indicator of an abnormal metal metabolism, but is also a simple parameter associated with hepatitis virus-related various conditions, including the degree of liver fibrosis and the severity of esophageal varices in compensated cirrhosis. PMID:25320463

Iwata, Kazunari; Enomoto, Hirayuki; Nishiguchi, Shuhei; Aizawa, Nobuhiro; Sakai, Yoshiyuki; Iwata, Yoshinori; Tanaka, Hironori; Ikeda, Naoto; Takashima, Tomoyuki; Saito, Masaki; Imanishi, Hiroyasu; Iijima, Hiroko; Tsuda, Yasuhiro; Higuchi, Kazuhide

2014-01-01

341

[Spontaneous peritonitis induced by Campylobacter spp in patients with liver cirrhosis. Report of 2 cases and review of the literature].  

PubMed

Campylobacter spp is not usual as the aetiology agent for spontaneous bacterial peritonitis. We report two cases of spontaneous peritonitis due to Campylobacter jejuni diagnosed in our hospital and review the literature trough MEDLINE data base. We found 13 cases of spontaneous peritonitis in which Campylobacter sp was isolated from ascitic fluid. The main characteristics of these cases were: the existence of an evolved alcoholic cirrhosis, a high positivity of blood cultures as well as a high relapse index and letality. PMID:11989076

Calonge Raventos, L; Len Abad, O; Bartolomé, R; Fernández de Sevilla, T

2002-01-01

342

Effect of simultaneous administration of glucagon and insulin on renal function in patients with liver cirrhosis and ascites  

Microsoft Academic Search

Summary  Since glucagon and insulin (G\\/I) have been suggested to be hepatotrophic substances, the effect of G\\/I infusion on the ability\\u000a to excrete water and sodium was tested in seven patients with cirrhosis and ascites (decompensated group), and compared with\\u000a that in seven cirrhotics without ascites (compensated group). A constant infusion of 1 U glucagon and 10 U regular insulin\\u000a over

Koji Hattori; Yasushi Hasumura; Jugoro Takeuchi

1984-01-01

343

Hepatocyte-Specific Ablation of PP2A Catalytic Subunit ? Attenuates Liver Fibrosis Progression via TGF-?1/Smad Signaling  

PubMed Central

Protein phosphatase 2A (PP2A), a family of the major serine/threonine phosphatases in cells, regulates many aspects of physiological processes. However, isoform-specific substrates and the biological role of each specific member of the PP2A family remain largely unknown. In this study, we investigated whether PP2A catalytic subunit C? (PP2Ac?) is involved in chronic hepatic injury and fibrosis. A hepatocyte-specific PP2Ac? ablation mice model was established to examine the effect of PP2Ac? on carbon tetrachloride- (CCl4-) induced chronic hepatic injury and fibrosis. Our results showed that PP2Ac? knockout mice were less susceptible to chronic CCl4-induced liver injury as evidenced by lower levels of serum alanine aminotransferase and aspartate aminotransferase, decreased hepatocyte proliferation, and increased rate of apoptotic removal of the injured hepatocytes. PP2Ac? knockout mice also displayed a lesser extent of liver fibrosis as a significant decrease in the proportion of ?-smooth muscle actin-expressing cells and collagen deposition was observed in their liver tissues. Furthermore, the levels of serum TGF-?1 and hepatocytic Smad phosphorylation were reduced in the PP2Ac? knockout mice. These data suggest that hepatocyte-specific ablation of PP2Ac? protects against CCl4-induced chronic hepatic injury and fibrogenesis and the protective effect is mediated at least partially through the impaired TGF-?1/Smad signaling. PMID:25710025

Tang, An; Chen, Lulu

2015-01-01

344

Hepatocyte-specific ablation of PP2A catalytic subunit ? attenuates liver fibrosis progression via TGF-?1/Smad signaling.  

PubMed

Protein phosphatase 2A (PP2A), a family of the major serine/threonine phosphatases in cells, regulates many aspects of physiological processes. However, isoform-specific substrates and the biological role of each specific member of the PP2A family remain largely unknown. In this study, we investigated whether PP2A catalytic subunit C? (PP2Ac?) is involved in chronic hepatic injury and fibrosis. A hepatocyte-specific PP2Ac? ablation mice model was established to examine the effect of PP2Ac? on carbon tetrachloride- (CCl4-) induced chronic hepatic injury and fibrosis. Our results showed that PP2Ac? knockout mice were less susceptible to chronic CCl4-induced liver injury as evidenced by lower levels of serum alanine aminotransferase and aspartate aminotransferase, decreased hepatocyte proliferation, and increased rate of apoptotic removal of the injured hepatocytes. PP2Ac? knockout mice also displayed a lesser extent of liver fibrosis as a significant decrease in the proportion of ?-smooth muscle actin-expressing cells and collagen deposition was observed in their liver tissues. Furthermore, the levels of serum TGF-?1 and hepatocytic Smad phosphorylation were reduced in the PP2Ac? knockout mice. These data suggest that hepatocyte-specific ablation of PP2Ac? protects against CCl4-induced chronic hepatic injury and fibrogenesis and the protective effect is mediated at least partially through the impaired TGF-?1/Smad signaling. PMID:25710025

Lu, Na; Liu, Yun; Tang, An; Chen, Lulu; Miao, Dengshun; Yuan, Xiaoqin

2015-01-01

345

Liver Facts  

MedlinePLUS

... Player. Common Diseases That May Lead to Transplantation Primary sclerosing cholangitis Acute hepatic necrosis Cirrhosis Metabolic diseases Portal hypertension Hepatitis (viral, autoimmune and idiopapathic) Liver tumors Biliary ...

346

Immune dysfunction in cirrhosis  

PubMed Central

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

2014-01-01

347

Opuntia ficus indica (L.) Mill. fruit juice protects liver from carbon tetrachloride-induced injury.  

PubMed

The protective effects of the juice of Opuntia ficus indica fruit (prickly pear) against carbon tetrachloride (CCl(4))-induced hepatotoxicity were examined in rats. The animals were treated orally with the juice (3 mL/rat) 2 h after administration of the hepatotoxic agent. Preventive effects were studied by giving the juice (3 mL/rat) for 9 consecutive days. On day 9 the rats received the hepatotoxic agent. Morphological and biochemical evaluations were carried out 24, 48 and 72 h after induction of the hepatic damage. Data show that O. ficus indica fruit juice administration exerts protective and curative effects against the CCl(4)-induced degenerative process in rat liver. Histology evaluation revealed a normal hepatic parenchyma at 48 h; the injury was fully restored after 72 h. Moreover, a significant reduction in CCl(4)-induced increase of GOT and GPT plasma levels is evident; these data are in agreement with the functional improvement of hepatocytes. O. ficus indica fruit juice contains many phenol compounds, ascorbic acid, betalains, betacyanins, and a flavonoid fraction, which consists mainly of rutin and isorhamnetin derivatives. Hepatoprotection may be related to the flavonoid fraction of the juice, but other compounds, such as vitamin C and betalains could, synergistically, counteract many degenerative processes by means of their antioxidant activity. PMID:16220574

Galati, E M; Mondello, M R; Lauriano, E R; Taviano, M F; Galluzzo, M; Miceli, N

2005-09-01

348

Protective effects of ethyl acetate fraction of Lawsonia inermis fruits extract against carbon tetrachloride-induced oxidative damage in rat liver.  

PubMed

This study aimed to investigate the antioxidant properties of different fractions obtained from the fruits of Lawsonia inermis, a widely used medicinal plant, against carbon tetrachloride (CCl4)-induced oxidative stress in rat liver. The results show that several fractions obtained from L. inermis fruits possessed important antioxidant activity. Among them, the ethyl acetate (EA) fraction showed the highest antioxidant activity. Then, EA fraction was selected for the purification of potential antioxidant compounds. The hepatoprotective effects of EA fraction and its most active constituent, gallic acid (GA), were evaluated against CCl4-induced hepatotoxicity in rats. CCl4 induced oxidative stress by a significant rise in serum marker enzymes. However, pretreatment of rats with EA fraction of fruits of L. inermis at a dose of 250 mg kg(-1) body weight and GA significantly lowered some serum biochemical parameters (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase) in treated rats. A significant reduction in hepatic thiobarbituric acid reactive substances and an increase in antioxidant enzymes namely superoxide dismutase, catalase, and glutathione peroxidase by treatment with plant extract and GA, against CCl4-treated rats, were observed. Histopathological examinations showed extensive liver injuries, characterized by extensive hepatocellular necrosis, vacuolization, and inflammatory cell infiltration. This potential antioxidant activity is comparable to those of the major purified antioxidant compound, GA. Based on these results, it was observed that fruits of L. inermis protect liver from oxidative stress induced by CCl4 and thus help in evaluation of traditional claim on this plant. PMID:24215067

Ben Hsouna, Anis; Mongi, Saoudi; Culioli, Gérald; Blache, Yves; Ghlissi, Zohra; Chaabane, Rim; El Feki, Abdelfattah; Jaoua, Samir; Trigui, Mohamed

2013-11-01

349

Hepatitis Bs antibody in alcoholic cirrhosis.  

PubMed Central

Sera from patients with chronic liver disease were tested for antibody against hepatitis B surface antigen by radioimmunoassay. The antibody was found in 25% of patients with alcoholic cirrhosis and in 52% when alcoholic cirrhosis was associated with portal hypertension, these results being significantly higher than in a matched control population. Other forms of chronic liver disease did not differ from the control population. Hepatitis B virus infection might be a factor in determining which alcoholic patients go on to develop chronic liver disease and cirrhosis. PMID:512037

Mills, P R; Pennington, T H; Kay, P; MacSween, R N; Watkinson, G

1979-01-01

350

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

351

[Protective action of kopsinine F against experimental liver injury in mice].  

PubMed

Kopsinine F is an indole alkaloid. The present studies show that prior oral administration of kopsinine F 150 mg/kg significantly protected mice from liver injuries induced by intraperitoneal injection of CCl4, thioacetamide and acetaminophen. The alkaloid also inhibited CCl4 induced lipid peroxidation (MDA formation) of liver microsomes and 14CCl4 covalent binding to lipids of liver microsomes in vitro. In addition, kopsinine F significanty induced hepatic microsomal cytochrome P-450 in mice. The results indicate that kopsinine F has hpatoeprotective activity in mice. PMID:2816370

Zhang, J; Liu, G T

1989-01-01

352

A new receipt for liver injury.  

PubMed

A new receipe consisting of Phyllanthus fraternus Webster, Eclipta alba and curcumin was prepared. The efficacy of this preparation was tested in carbontetrachloride (CCl(4)) induced fatty liver model in rats. This preparation was able to normalize the level of lipids accumulating in liver due to CCl(4) injury and it was also able to bring down elevated levels of serum bilirubin. Further, the decreased levels of serum triglycerides, pre B-lipoproteins and cholesterol in CCl(4) liver injured rats was raised after treatment with new preparation. Further, the decreased level of liver glycogen was also normalized. From these results, it can be inferred that the new receipe is able to offer protection against the liver injury caused by CCl(4) injection. PMID:22557595

Chandra, T; Sadique, J

1987-10-01

353

Management of patients with decompensated cirrhosis.  

PubMed

During the assessment of a patient with liver disease, finding the patient has decompensated cirrhosis, as defined by the presence of jaundice, ascites, variceal haemorrhage or hepatic encephalopathy, has major implications regarding management and prevention of cirrhosis-related complications, as well as consideration for a referral for liver transplantation evaluation. Prognosis is markedly worse in patients with decompensated compared with compensated cirrhosis. In general, any patient with decompensated cirrhosis should receive evaluation and medical care by a hepatologist. Since patients frequently present with more than one facet of liver decompensation, such cases pose a complex management challenge requiring input from a multidisciplinary team and close liaison with a liver transplant centre. PMID:25824076

Harrison, Phillip M

2015-04-01

354

A low steady HBsAg seroprevalence is associated with a low incidence of HBV-related liver cirrhosis and hepatocellular carcinoma in Mexico: a systematic review.  

PubMed

To address the relationship between hepatitis B virus (HBV) endemicity and HBV-related liver diseases in Mexico. Research literature reporting on HBsAg and antibody to hepatitis B core antigen (anti-HBc) prevalence in Mexican study groups were searched in NLM Gateway, PubMed, IMBIOMED, and others. Weighted mean prevalence (WMP) was calculated from the results of each study group. A total of 50 studies were analyzed. Three nationwide surveys revealed an HBsAg seroprevalence of less than 0.3%. Horizontal transmission of HBV infection occurred mainly by sexual activity and exposure to both contaminated surgical equipment and body fluids. High-risk groups exposed to these factors included healthcare workers, pregnant women, female sex workers, hemodialysis patients, and emergency department attendees with an HBsAg WMP ranging from 1.05% (95% confidence interval [CI], 0.68-1.43) to 14.3% (95% CI, 9.5-19.1). A higher prevalence of anti-HBc in adults than those younger than 20 years was associated with the main risk factors. Anti-HBc WMP ranged from 3.13% (95% CI, 3.01-3.24) in blood donors to 27.7% (95% CI, 21.6-33.9) in hemodialysis patients. A heterogeneous distribution of HBV infection was detected, mainly in native Mexican groups with a high anti-HBc WMP of 42.0% (95% CI, 39.5-44.3) but with a low HBsAg WMP of 2.9% (95% CI 2.08-3.75). Estimations of the Mexican population growth rate and main risk factors suggest that HBsAg seroprevalence has remained steady since 1974. A low HBsAg prevalence is related to the low incidence of HBV-related liver cirrhosis and hepatocellular carcinoma (HCC) previously reported in Mexico. PMID:19669360

Roman, Sonia; Panduro, Arturo; Aguilar-Gutierrez, Yadira; Maldonado, Montserrat; Vazquez-Vandyck, Maclovia; Martinez-Lopez, Erika; Ruiz-Madrigal, Bertha; Hernandez-Nazara, Zamira

2009-06-01

355

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 ãCD147 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

356

Hypercoagulability in patients with primary biliary cirrhosis and primary sclerosing cholangitis evaluated by thrombelastography  

Microsoft Academic Search

Background\\/Aims: Patients with primary biliary cirrhosis and primary sclerosing cholangitis survive variceal bleeding better than patients with alcoholic cirrhosis and have less bleeding at liver transplantation. Recently, patients with primary biliary cirrhosis have been found to have a higher incidence of thrombosis in the portal venous tree. We hypothesized that primary biliary cirrhosis and primary sclerosing cholangitis patients may be

Ziv Ben-Ari; Manos Panagou; David Patch; Steven Bates; Elsir Osman; John Pasi; Andrew Burroughs

1997-01-01

357

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

358

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

359

Monocyte function in cirrhosis.  

PubMed Central

Monocyte function has been studied in a total of 51 patients with biopsy-proven cirrhosis and 35 controls. There was significantly reduced monocyte spreading (p less than 0.05), chemotaxis (p less than 0.02), bacterial phagocytosis (p less than 0.05) and bacterial killing (p less than 0.02) in the cirrhotics compared to the controls. Monocytes from patients with cirrhosis produced significantly less of the lysosomal enzymes N-acetyl beta-glucosaminidase and beta-glucuronidase than those obtained from the controls (p less than 0.02). There was no significant difference in the number of monocytes obtained, the number of macrophage precursors, and the nitro-blue tetrazoline (NBT) reduction between the cirrhotic and the controls. The reduced function appeared to be mainly due to a circulating inhibitory factor and could be corrected by incubation of the cirrhotic cells in serum from control subjects. The response of monocytes from patients with cirrhosis did not differ from the controls in their response to added endotoxin or latex particles suggesting that they are capable of a normal response in the absence of the inhibitory factor. Paired specimens of portal and systemic serum were collected from patients with no evidence of liver disease undergoing vascular surgery. When added to normal human monocytes the portal serum caused a significant reduction in bacterial killing (p less than 0.02) and chemotaxis (p less than 0.05) compared to results obtained in the paired systemic serum. Mixing experiments suggests the presence of an active inhibitor in the portal serum. The results suggest that monocyte function is reduced in cirrhosis apparently due to a serum inhibitor which may have originated from the portal vein. The abnormalities may account in part for the increased susceptibility of these patients to infection. PMID:7119129

Holdstock, G; Leslie, B; Hill, S; Tanner, A; Wright, R

1982-01-01

360

BCAA-enriched snack improves nutritional state of cirrhosis  

Microsoft Academic Search

ObjectiveA late evening snack improves the catabolic state in patients with advanced liver cirrhosis. We tested whether long-term (3 mo) late evening snacking that included a branched-chain amino acid (BCAA)–enriched nutrient mixture produces a better nutritional state and better quality of life than ordinary food in patients with hepatitis C virus–positive liver cirrhosis.

Yutaka Nakaya; Kiwamu Okita; Kazuyuki Suzuki; Hisataka Moriwaki; Akinobu Kato; Yoshiyuki Miwa; Koichi Shiraishi; Hiroaki Okuda; Morikazu Onji; Hidenori Kanazawa; Hirohito Tsubouchi; Shinzo Kato; Masahiko Kaito; Akiharu Watanabe; Daiki Habu; Susumu Ito; Tomohisa Ishikawa; Naohiro Kawamura; Yasuyuki Arakawa

2007-01-01

361

Cirrhosis in children and adolescents: An overview.  

PubMed

Several conditions, especially chronic liver diseases, can lead to cirrhosis in children and adolescents. Most cases in clinical practice are caused by similar etiologies. In infants, cirrhosis is most often caused by biliary atresia and genetic-metabolic diseases, while in older children, it tends to result from autoimmune hepatitis, Wilson's disease, alpha-1-antitrypsin deficiency and primary sclerosing cholangitis. The symptoms of cirrhosis in children and adolescents are similar to those of adults. However, in pediatric patients, the first sign of cirrhosis is often poor weight gain. The complications of pediatric cirrhosis are similar to those observed in adult patients, and include gastrointestinal bleeding caused by gastroesophageal varices, ascites and spontaneous bacterial peritonitis. In pediatric patients, special attention should be paid to the nutritional alterations caused by cirrhosis, since children and adolescents have higher nutritional requirements for growth and development. Children and adolescents with chronic cholestasis are at risk for several nutritional deficiencies. Malnutrition can have severe consequences for both pre- and post-liver transplant patients. The treatment of cirrhosis-induced portal hypertension in children and adolescents is mostly based on methods developed for adults. The present article will review the diagnostic and differential diagnostic aspects of end-stage liver disease in children, as well as the major treatment options for this condition. PMID:25848466

Pinto, Raquel Borges; Schneider, Ana Claudia Reis; da Silveira, Themis Reverbel

2015-03-27

362

Cirrhosis in children and adolescents: An overview  

PubMed Central

Several conditions, especially chronic liver diseases, can lead to cirrhosis in children and adolescents. Most cases in clinical practice are caused by similar etiologies. In infants, cirrhosis is most often caused by biliary atresia and genetic-metabolic diseases, while in older children, it tends to result from autoimmune hepatitis, Wilson’s disease, alpha-1-antitrypsin deficiency and primary sclerosing cholangitis. The symptoms of cirrhosis in children and adolescents are similar to those of adults. However, in pediatric patients, the first sign of cirrhosis is often poor weight gain. The complications of pediatric cirrhosis are similar to those observed in adult patients, and include gastrointestinal bleeding caused by gastroesophageal varices, ascites and spontaneous bacterial peritonitis. In pediatric patients, special attention should be paid to the nutritional alterations caused by cirrhosis, since children and adolescents have higher nutritional requirements for growth and development. Children and adolescents with chronic cholestasis are at risk for several nutritional deficiencies. Malnutrition can have severe consequences for both pre- and post-liver transplant patients. The treatment of cirrhosis-induced portal hypertension in children and adolescents is mostly based on methods developed for adults. The present article will review the diagnostic and differential diagnostic aspects of end-stage liver disease in children, as well as the major treatment options for this condition. PMID:25848466

Pinto, Raquel Borges; Schneider, Ana Claudia Reis; da Silveira, Themis Reverbel

2015-01-01

363

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

364

Risk factors for naturally-occurring early-onset hepatocellular carcinoma in patients with HBV-associated liver cirrhosis in China  

PubMed Central

Aims: Early onset of hepatocellular carcinoma (HCC) (males and females under the age of 40 or 50 years old, respectively) has a significant prevalence and poor prognosis; however, few studies have reported the risk factors and development of HCC in such cases. Methods: In this study, we retrospectively analyzed clinical, laboratory and demographic data from 588 treatment-naïve HCC patients with hepatitis B virus (HBV)-associated liver cirrhosis (LC) and 708 age-matched HBV-associated LC patients as control in Beijing 302 Hospital. Results: 15.1% (89/588) of the HCC patients and 36.7% (181/708) of the LC patients were classified as early onset. Compared with age-matched LC controls, male gender (odds ratio (OR) = 2.09, P < 0.05), family history of HBV infection (OR = 2.45, P < 0.05) and alpha-fetoprotein (AFP) > 200 ng/ml (OR = 30.8, P < 0.05) were independent risk factors for early-onset HCC. Comparing late-onset LC controls, male gender (OR = 1.92, P < 0.05), age (OR = 1.04, P < 0.05), family history of HCC (OR = 2.06, P < 0.05), history of smoking (OR = 1.68, P < 0.05) and AFP > 200 ng/ml (OR = 12.0, P < 0.05) were associated with the development of naturally occurring HCC. Overall, male gender and AFP > 200 ng/ml is associated with HCC development across all ages, whereas a family history of HBV infection may identify younger HBV-associated LC patients at risk for HCC. Conclusion: Our data suggest that a family history of HBV infection is a unique risk factor for naturally-occurring early-onset HCC patients with HBV-associated LC, who should be considered for intensive screening programs. PMID:25785114

Li, Yuanyuan; Zhang, Zheng; Shi, Jianfei; Jin, Lei; Wang, Lifeng; Xu, Dongping; Wang, Fu-Sheng

2015-01-01

365

Impacts of human leukocyte antigen DQ genetic polymorphisms and their interactions with hepatitis B virus mutations on the risks of viral persistence, liver cirrhosis, and hepatocellular carcinoma.  

PubMed

Human leukocyte antigen (HLA)-DQ genetic polymorphisms have been associated with chronic hepatitis B virus (HBV) outcomes. We aimed to determine impacts of HLA-DQ polymorphisms and their interactions with HBV mutations on the risks of liver cirrhosis (LC) and hepatocellular carcinoma (HCC). rs2856718 (A>G) and rs9275319 (A>G) were genotyped in 1342 healthy controls, 327 HBV surface antigen (HBsAg) seroclearance subjects, 611 asymptomatic HBsAg carriers (ASCs), 1144 chronic hepatitis B (CHB) patients, 734 LC patients, and 1531 HCC patients using quantitative PCR. HBV mutations were detected by direct sequencing. Logistic regression analyses were utilized to assess the factors and/or multiplicative interactions significantly associated with liver diseases. rs9275319 variant genotypes were inversely associated with HBV persistence compared to HBV natural clearance subjects. rs2856718 variant genotypes significantly increased LC risk compared to ASCs plus CHB patients (GG vs. AA: odds ratio [OR], 1.52, 95% confidence interval [CI], 1.17-1.97 and AG+GG vs. AA: OR, 1.27; 95% CI, 1.04-1.54) and decreased HCC risk compared to HCC-free HBV-infected subjects (AG vs. AA: OR, 0.76; 95% CI, 0.65-0.89 and AG+GG vs. AA: OR, 0.78, 95% CI, 0.68-0.90). rs2856718 variant genotypes were significantly associated with an increased frequency of HBV A1726C mutation, a LC-risk, HCC-protective mutation, in genotype C. A rs9275319 variant genotype (GG) was significantly associated with an increased frequency of preS1 start codon mutation, an HCC-risk mutation, in genotype C. The interaction of rs2856718 AG+GG genotype with T1753V, a HCC-risk mutation, significantly reduced LC risk, with an OR of 0.26 (95% CI, 0.09-0.78); whereas the interaction of rs2856718 AG genotype with C1673T, a LC-risk mutation, significantly increased HCC risk, with an OR of 2.80 (95% CI, 1.02-7.66) in genotype C HBV-infected subjects. Conclusively, the HLA-DQ polymorphisms affect the risks of LC and HCC differently in chronic HBV-infected subjects, possibly via interacting with the HBV mutations. PMID:25281206

Ji, Xiaowei; Zhang, Qi; Li, Bin; Du, Yan; Yin, Jianhua; Liu, Wenbin; Zhang, Hongwei; Cao, Guangwen

2014-12-01

366

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

367

Evaluation of Alanine Transaminase and Hepatitis B Virus DNA to Predict Liver Cirrhosis in Hepatitis B e Antigen-Negative Chronic Hepatitis B Using Transient Elastography  

Microsoft Academic Search

BACKGROUND AND AIMS:We aimed to investigate the relationship between serum hepatitis B virus (HBV) DNA and alanine transaminase (ALT) levels and the risk of cirrhosis in a large cohort of hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) patients based on transient elastography.METHODS:We prospectively studied treatment-naive HBeAg-negative patients recruited based on territory-wide referrals. We defined possible cirrhosis and probable

Grace Lai-Hung Wong; Vincent Wai-Sun Wong; Paul Cheung-Lung Choi; Anthony Wing-Hung Chan; Angel Mei-Ling Chim; Karen Ka-Lam Yiu; Hoi-Yun Chan; Francis Ka-Leung Chan; Joseph Jao-Yao Sung; Henry Lik-Yuen Chan

2008-01-01

368

Hepatic encephalopathy in alcoholic cirrhosis.  

PubMed

Hepatic encephalopathy (HE) is a serious neuropsychiatric complication of cirrhosis in alcoholic patients that is characterized clinically by personality changes, sleep abnormalities, and impaired motor coordination, as well as cognitive dysfunction progressing to stupor and coma. Procedures used for diagnosis and grading of HE include neurologic assessment, electroencephalography, psychometric testing, and use of the critical flicker frequency test. Neuropathologically, HE in cirrhosis is principally a disorder of neuroglia characterized by Alzheimer type II astrocytosis and activation of microglia. However, thalamic and cerebellar neuronal pathologies have been noted as well as lesions to globus pallidus and substantia nigra, leading to a condition known as "parkinsonism in cirrhosis." Multiple mechanisms have been proposed to account for the pathogenesis of HE in cirrhosis, including the neurotoxic actions of ammonia and manganese (normally removed via the hepatobiliary route), impaired brain energy metabolism, central proinflammatory mechanisms, and alterations of both excitatory and inhibitory neurotransmission. Treatment of HE in cirrhosis continues to rely on ammonia-lowering strategies such as lactulose, antibiotics, probiotics and l-ornithine l-aspartate with nutritional management consisting of adequate (but not excessive) dietary protein and vitamin B1 supplements. l-DOPA may improve parkinsonian symptoms. Liver transplantation leads to recovery of central nervous system function in the majority of cases. PMID:25307598

Butterworth, Roger F

2014-01-01

369

Hepatoprotective effect of collagen peptides from cod skin against liver oxidative damage in vitro and in vivo.  

PubMed

The objective of this study was to investigate the hepatoprotective effect of cod skin collagen peptides (CSCP), isolated from fishing industrial by-products, in vitro and in vivo. Effect of CSCP on cell proliferation of normal and H2O2-damaged Chang liver cells was determined by MTT assay in vitro. Two animal models, CCl4-induced and acetaminophenum-induced acute hepatotoxicity, were established to assess the hepatoprotective effect of CSCP. Liver weight index, serum ALT and AST, antioxidant enzymes, and lipid peroxidation product were used as the markers of liver toxicity. The cell viability in the H2O2-treated Chang liver cells was remarkably increased when pretreated with CSCP from 100 to 1,000 µg/ml in a dose-dependent manner. CSCP pretreatment also alleviated the CCL4-induced liver index loss, while no marked changes were found in acetaminophenum-treated mice. Furthermore, CSCP pulled down serum ALT and AST level, increased the activities of SOD and CAT, and decreased MDA in both murine models of acute liver toxicity. Pretreatment with CSCP protected liver tissue against oxidative injure in vivo and in vitro. The underlying mechanism might involve enhancement in the activities of antioxidant enzymes and reduction in the lipid peroxidation. PMID:25344648

Han, Yantao; Xie, Jing; Gao, Hui; Xia, Yunqiu; Chen, Xuehong; Wang, Chunbo

2015-03-01

370