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1

Coffee prevents CCl 4 -induced liver cirrhosis in the rat  

Microsoft Academic Search

Purpose  Previous clinical observations suggested that coffee may have beneficial effects on the liver. In fact, an inverse relationship\\u000a between coffee consumption and liver cirrhosis has been reported in humans. However, the causative role of coffee has not\\u000a been established; therefore, the aim of this work was to study the effect of coffee in an experimental model of liver damage.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  In

Mario G. Moreno; Enrique Chávez; Liseth R. Aldaba-Muruato; José Segovia; Paula Vergara; Víctor Tsutsumi; Mineko Shibayama; Yadira Rivera-Espinoza; Pablo Muriel

2

FXR Regulates Liver Repair after CCl4-Induced Toxic Injury  

PubMed Central

Liver repair is key to resuming homeostasis and preventing fibrogenesis as well as other liver diseases. Farnesoid X receptor (FXR, NR1H4) is an emerging liver metabolic regulator and cell protector. Here we show that FXR is essential to promote liver repair after carbon tetrachloride (CCl4)-induced injury. Expression of hepatic FXR in wild-type mice was strongly suppressed by CCl4 treatment, and bile acid homeostasis was disrupted. Liver injury was induced in both wild-type and FXR?/? mice by CCl4, but FXR?/? mice had more severe defects in liver repair than wild-type mice. FXR?/? livers had a decreased peak of regenerative DNA synthesis and reduced induction of genes involved in liver regeneration. Moreover, FXR?/? mice displayed increased mortality and enhanced hepatocyte deaths. During the early stages of liver repair after CCl4 treatment, we observed overproduction of TNF? and a strong decrease of phosphorylation and DNA-binding activity of signal transducer and activator of transcription 3 in livers from FXR?/? mice. Exogenous expression of a constitutively active signal transducer and activator of transcription 3 protein in FXR?/? liver effectively reduced hepatocyte death and liver injury after CCl4 treatment. These results suggest that FXR is required to regulate normal liver repair by promoting regeneration and preventing cell death. PMID:20211986

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

2010-01-01

3

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

PubMed

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

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

2014-06-01

4

Hepatoprotective effect of manganese chloride against CCl4-induced liver injury in rats.  

PubMed

The aim of the present study is to evaluate the protective effect of manganese chloride against carbon tetrachloride (CCl4)-induced liver injury in rats. Manganese chloride (0.001, 0.01, 0.05 and 0.1 g/kg bw) was administered intragastrically for 28 consecutive days to male CCl4-treated rats. The hepatoprotective activity was assessed using various biochemical parameters such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), ?-glutamyltransferase (GGT) and superoxide dismutase (SOD). Histopathological changes in the liver of different groups were also studied. Administration of CCl4 increased the serum ALT, AST, ALP and GGT but decreased SOD levels in rats. Treatment with manganese chloride significantly attenuated these changes to nearly normal levels. The animals treated with manganese chloride have shown decreased necrotic zones and hepatocellular degeneration when compared to the liver exposed to CCl4 intoxication alone. Thus, the histopathological studies also supported the protective effect of manganese chloride. Therefore, the results of this study suggest that manganese chloride exerts hepatoprotection via promoting antioxidative properties against CCl4-induced oxidative liver damage. PMID:24037643

Eidi, Akram; Mortazavi, Pejman; Behzadi, Khodabakhsh; Rohani, Ali Haeri; Safi, Shahabeddin

2013-11-01

5

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

PubMed Central

Platelet-rich plasma (PRP) has been of great concern to the scientists and doctors who are involved in wound healing and regenerative medicine which focuses on repairing and replacing damaged cells and tissues. Growth factors of platelet-rich plasma are cost-effective, available, and is more stable than recombinant human growth factors. Given these valuable properties, we decided to assess the effect of PRP on CCl4-induced hepatotoxicity on rats. The rats received CCl4 (1?mL/kg, i.p. 1?:?1 in olive oil) twice per week for 8 weeks. Five weeks after CCl4 injection, the rats also received PRP (0.5?mL/kg, s.c.) two days a week for three weeks. Twenty-four hours after last CCl4 injection, the animals bled and their livers dissected for biochemical and histopathological studies. Blood analysis was performed to evaluate enzyme activity. The results showed that PRP itself was not toxic for liver and could protect the liver from CCl4-induced histological damages and attenuated oxidative stress by increase in glutathione content and decrease in lipid peroxidative marker of liver tissue. The results of the present study lend support to our beliefs in hepatoprotective effects of PRP. PMID:24707405

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

2014-01-01

6

Inhibitory effect of TCCE on CCl4-induced overexpression of IL-6 in acute liver injury.  

PubMed

Terminalia catappa L. leaves have been shown to protect against acute liver injury produced by some hepatotoxicants, but the active components and mechanisms are not clear. This study was designed to characterize the protective effects of the chloroform fraction of the ethanol extract of T. catappa leaves (TCCE) against carbon tetrachloride (CCl4)-induced hepatotoxicity in mice, and analyze the changes in expression level of interleukin-6 (IL-6) in the process. It was found that TCCE pretreatment (10 or 30 mg/kg, ig) protected mice from CCl4 toxicity, as evidenced by the reversed alterations in serum alanine aminotransferase (sALT) and serum aspartate aminotransferase (sAST) activities. Additionally liver tissues were subjected to RT-PCR, Western blot and immunohistochemistry to analyze changes in IL-6 expression. It was found that TCCE markedly suppressed the CCl4-induced over-transcription of IL-6 gene. Consistent with the result, the expression of IL-6 protein was also blocked by TCCE in CCl4-stimulated mice, especially in the area around central vein on liver tissue section. In conclusion, TCCE is effective in protecting mice from the hepatotoxicity produced by CCl4, and the mechanisms underlying its protective effects may be related to the inhibition on the overexpression of IL-6 mainly around terminal hepatic vein. PMID:15514851

Gao, Jing; Dou, Huan; Tang, Xin-Hui; Xu, Li-Zhi; Fan, Yi-Mei; Zhao, Xiao-Ning

2004-11-01

7

Adiponectin Agonist ADP355 Attenuates CCl4-Induced Liver Fibrosis in Mice  

PubMed Central

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

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

2014-01-01

8

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 Franca, Maria Eduarda Rocha; Rodrigues, Gabriel Barros; Barbosa, Karla Patricia Sousa; Nunes, Ana Karolina Santana; Pastor, Andre Filipe; Oliveira, Anne Gabrielle Vasconcelos; Oliveira, Wilma Helena; Luna, Rayana Leal Almeida; Peixoto, Christina Alves

2014-01-01

9

Hepatoprotective effect of rooibos tea (Aspalathus linearis) on CCl4-induced liver damage in rats.  

PubMed

Hepatoprotective properties of rooibos tea (Aspalathus linearis) were investigated in a rat model of liver injury induced by carbon tetrachloride (CCl(4)). Rooibos tea, like N-acetyl-L-cysteine which was used for the comparison, showed histological regression of steatosis and cirrhosis in the liver tissue with a significant inhibition of the increase of liver tissue concentrations of malondialdehyde, triacylglycerols and cholesterol. Simultaneously, rooibos tea significantly suppressed mainly the increase in plasma activities of aminotransferases (ALT, AST), alkaline phosphatase and billirubin concentrations, which are considered as markers of liver functional state. The antifibrotic effect in the experimental model of hepatic cirrhosis of rats suggests the use of rooibos tea as a plant hepatoprotector in the diet of patients with hepatopathies. PMID:12899659

Ulicná, O; Greksák, M; Vancová, O; Zlatos, L; Galbavý, S; Bozek, P; Nakano, M

2003-01-01

10

Evaluation of the protective potential of Artemisia maritima extract on acetaminophen- and CCl4-induced liver damage.  

PubMed

The hepatoprotective activity of the aqueous-methanolic extract of Artemisia maritima was investigated against acetaminophen (paracetamol, 4-hydroxy acetanilide)- and carbon tetrachloride (CCl4)-induced hepatic damage. Acetaminophen produced 100% mortality at the dose of 1 g/kg in mice, while pretreatment of animals with the plant extract (500 mg/kg) reduced the death rate to 20%. Acetaminophen at the dose of 640 mg/kg produced liver damage in rats as manifested by the significant (P < 0.001) rise in serum levels of glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT) to 1529 +/- 172 I.U./l and 904 +/- 116 I.U./l (n = 10), respectively, compared to respective control values of 87 +/- 12 I.U./l and 31 +/- 5 I.U./l. Pretreatment of rats with the plant extract (500 mg/kg) lowered significantly (P < 0.001) the respective serum GOT and GPT levels to 112 +/- 10 I.U./l and 47 +/- 11 I.U./l. Similarly, a hepatotoxic dose of CCl4 (1.5 ml/kg, orally) raised significantly (P < 0.01) the serum GOT and GPT levels to 463 +/- 122 I.U./l and 366 +/- 58 I.U./l (n = 10), respectively, compared to respective control values of 92 +/- 18 I.U./l and 35 +/- 9 I.U./l. The same dose of plant extract (500 mg/kg) was able to prevent significantly (P < 0.01) the CCl4-induced rise in serum transaminases and the estimated values of GOT and GPT were 105 +/- 29 I.U./l and 53 +/- 17 I.U./l, respectively. Moreover, it prevented CCl4-induced prolongation in pentobarbital sleeping time confirming hepatoprotectivity and validates the traditional use of this plant against liver damage. PMID:7564420

Janbaz, K H; Gilani, A H

1995-06-23

11

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

PubMed Central

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

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

2014-01-01

12

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

PubMed

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

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

2013-03-01

13

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

14

Recovery of the Cell Cycle Inhibition in CCl4-Induced Cirrhosis by the Adenosine Derivative IFC-305  

PubMed Central

Introduction. Cirrhosis is a chronic degenerative illness characterized by changes in normal liver architecture, failure of hepatic function, and impairment of proliferative activity. The aim of this study is to know how IFC-305 compound induces proliferation of the liver during reversion of cirrhosis. Methods. Once cirrhosis has been installed by CCl4 treatment for 10 weeks in male Wistar rats, they were divided into four groups: two received saline and two received the compound; all were euthanized at 5 and 10 weeks of treatment. Liver homogenate, mitochondria, and nucleus were used to measure cyclins, CDKs, and cell cycle regulatory proteins PCNA, pRb, p53, E2F, p21, p27, HGF, liver ATP, and mitochondrial function. Results. Diminution and small changes were observed in the studied proteins in the cirrhotic animals without treatment. The IFC-305-treated rats showed a clear increase in most of the proteins studied mainly in PCNA and CDK6, and a marked increased in ATP and mitochondrial function. Discussion/Conclusion. IFC-305 induces a recovery of the cell cycle inhibition promoting recovery of DNA damage through the action of PCNA and p53. The increase in energy and preservation of mitochondrial function contribute to recovering the proliferative function. PMID:23056951

Chagoya de Sanchez, Victoria; Martinez-Perez, Lidia; Hernandez-Munoz, Rolando; Velasco-Loyden, Gabriela

2012-01-01

15

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

PubMed Central

Background/Aims The Wnt/?-catenin signaling pathway has been reported to play an important role in liver fibrosis. This study was designed to investigate whether mesoderm-specific transcript homologue (Mest), a strong negative regulator of Wnt/?-catenin signaling, could inhibit liver fibrosis. Methods pcDNA-Mest was transfected into hepatic stellate cells (HSCs) and rats. Rats were randomly divided into four groups: normal group (normal saline), treatment group (pcDNA-Mest+CCl4), control group (pcDNA-neo+CCl4), and model group (normal saline+CCl4). Changes in liver pathology were evaluated by hematoxylin and eosin and Masson's trichrome staining. The levels of alanine transaminase, aspartate transaminase, lactic dehygrogenase, hyaluronic acid, and laminin in the serum and hydroxyproline in the liver were detected by biochemical examination and radioimmunoassay, respectively. The expression and distribution of ?-catenin, ?-smooth muscle actin (?-SMA), Smad3, and tissue inhibitor of metalloproteinase type I were determined, and the viability of the HSCs was tested. Results Our data demonstrate that Mest alleviated CCl4-induced collagen deposition in liver tissue and improved the condition of the liver in rats. Mest also significantly reduced the expression and distribution of ?-catenin, ?-SMA and Smad3 both in vivo and in vitro, in addition to the viability of HSCs in vitro. Conclusions We found that Mest attenuates liver fibrosis by repressing ?-catenin expression, which provides a new therapeutic approach for treating liver fibrosis. PMID:24827625

Li, Wenting; Zhu, Chuanlong; Li, Yi

2014-01-01

16

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

PubMed

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

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

2013-05-01

17

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

18

Curcumin Protects against CCl4-Induced Liver Fibrosis in Rats by Inhibiting HIF-1? Through an ERK-Dependent Pathway.  

PubMed

The ERK/HIF-1? signaling pathway is believed to play an important role in the genesis of progressive fibrosis. An increasing expression of HIF-1? and ERK accompanies CCl4-induced liver fibrosis in rats. Curcumin is verified to have antifibrotic effects in several kinds of liver fibrosis models. There is no specific evidence illustrating a connection between curcumin and the HIF-1?/ERK pathway in rat liver fibrosis induced by CCl4. In this study, liver fibrosis was induced by CCl4 in treated rats. The data demonstrated that curcumin was able to attenuate liver fibrosis and inhibit the proliferation of HSC. Moreover, curcumin could remarkably elevate the hepatic function by decreasing serum levels of ALT, AST and ALP, and increasing levels of ALB, TP and ?-SMA, Col III mRNA expression. Meanwhile, ECM status could also be reflected by curcumin treatment. The alleviation with curcumin treatment was associated with inhibition of HIF-1? and phosphor-ERK. This study indicates that curcumin alleviates fibrosis by reducing the expression of HIF-1? partly through the ERK pathway. PMID:25407718

Zhao, Yanling; Ma, Xiao; Wang, Jiabo; He, Xuan; Hu, Yan; Zhang, Ping; Wang, Ruilin; Li, Ruisheng; Gong, Man; Luo, Shengqiang; Xiao, Xiaohe

2014-01-01

19

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

PubMed Central

Objective: to investigate the hepatoprotective potential of ether insoluble phenolic components of n-butanol fraction (EPC-BF) of flaxseed against CCl4 -induced liver damage in rats. Materials and Methods: Hepatotoxicity was induced to Wistar rats by administration of 0.2% CCl4 in olive oil (8 mL/kg, i.p.) on the seventh day of treatment. Hepatoprotective potential of EPC-BF at doses, 250 and 500 mg/kg, p.o. was assessed through biochemical and histological parameters. Results: EPC-BF and silymarin pretreated animal groups showed significantly decreased activities of Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and level of total bilirubin, elevated by CCl4 intoxication. Hepatic lipid peroxidation elevated by CCl4 intoxication were also found to be alleviated at almost normal level in the EPC-BF and silymarin pretreated groups. Histological studies supported the biochemical findings and treatment of EPC-BF at doses 250 and 500 mg/kg, p.o. was found to be effective in restoring CCl4 -induced hepatic damage. However, EPC-BF did not show dose-dependent hepatoprotective potential. EPC-BF depicted maximum protection against CCl4 -induced hepatic damage at lower dose 250 mg/kg than higher dose (500 mg/ kg). Conclusion: EPC-BF possesses the significant hepatoprotective activity against CCl4 induced liver damage, which could be mediated through increase in antioxidant defenses. PMID:22923966

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

2012-01-01

20

CX3CL1-CX3CR1 interaction prevents CCl4-induced liver inflammation and fibrosis  

PubMed Central

Chronic liver disease is associated with hepatocyte injury, inflammation and fibrosis, in which chemokines and chemokine receptors are key factors for the migration of inflammatory cells including macrophages and non-inflammatory cells such as hepatic stellate cells (HSCs). The expression of CX3CR1 and its ligand CX3CL1 (Fractalkine) is upregulated in chronic liver diseases, such as chronic hepatitis C. However, the precise role of CX3CR1 in the liver is still unclear. Here we investigated the role of the CX3CL1-CX3CR1 interaction in a carbon tetrachloride (CCl4)-induced liver inflammation and fibrosis model. CX3CR1 is dominantly expressed on Kupffer cells in the liver. In contrast, the main source of CX3CL1 is HSC. Mice deficient in CX3CR1 showed a significant increase of inflammatory cell recruitment and cytokine production, including TNF-?, MCP-1, MIP-1? and RANTES after CCl4 treatment compared to WT mice, suggesting that CX3CR1 signaling prevents liver inflammation. Kupffer cells in CX3CR1-deficient mice after CCl4 treatment had increased expression of TNF-? and TGF-?, and reduced expression of the anti-inflammatory markers IL-10 and arginase-1. Co-culture experiments showed that HSCs had significantly greater activation by Kupffer cells from CCl4-treated CX3CR1-deficient mice compared to those from WT mice. Indeed, augmented fibrosis was observed in CX3CR1-deficient mice compared to WT mice after CCl4 treatment. Finally, CX3CL1 treatment induced the expression of IL-10 and arginase-1 in WT cultured Kupffer cells through CX3CR1, which in turn suppress HSC activation. In conclusion, CX3CL1-CX3CR1 interaction inhibits inflammatory properties in Kupffer cells/macrophages resulting in decreased liver inflammation and fibrosis. PMID:20683935

Aoyama, Tomonori; Inokuchi, Sayaka; Brenner, David A.; Seki, Ekihiro

2010-01-01

21

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

22

Protection of CCl4-Induced Liver and Kidney Damage by Phenolic Compounds in Leaf Extracts of Cnestis ferruginea (de Candolle)  

PubMed Central

Background: The chemoprevention of chemically-induced hepatotoxicity is a crucial means of minimizing susceptibility to hepatic carcinogenesis and plants remain a rich source of anti-hepatotoxicants with antioxidant properties. Objective: The protective role of defatted-methanol (MECF) and ethyl acetate fractions (EF), obtained from Leaves of Cnestis ferruginea in rats induced with carbon tetrachloride (CCl4) toxicity was investigated. Materials and Methods: Adult male Wistar rats were orally administered MECF or EF (125 – 500 mg/kg bwt/5mL) or silymarin (25 mg/kg bwt/5 mL) separately for three days before intervention with an intraperitoneal dose of CCl4. Biomarkers of liver and kidney toxicity as well as Ca2+ regulation were evaluated. Results: Pre-treatment with MECF and EF significantly (P < 0.05) decreased the activities of serum alanine and aspartate aminotransferases, levels of urea, creatinine and cholesterol. A significantly (P < 0.05) enhanced Ca2+ -ATPase activity and lowered levels of membrane cholesterol: Phospholipid ratio were observed in liver microsomes of pre-treated as compared to CCl4 -only treated rats. Rat liver superoxide dismutase activity was enhanced by 125 mg/kg and 250 mg/kg of EF and MECF, while decreases were observed at 500 mg/kg. MECF and EF, like silymarin, attenuated CCl4 -induced hepatotoxicity, microsomal membrane Ca2+ -ATPase inactivation and renal dysfunction. Phytochemistry of MECF revealed the presence of anthraquinones, cardiac and flavone glycosides, tannins and trihydroxyl phenol. Conclusion: These findings suggest that the mechanism of hepatoprotection elicited by MECF and EF, involve its antioxidative properties and regulation of Ca2+ homeostasis. PMID:24497738

Rahmat, Adisa A.; Dar, Farooq Ahsana; Choudhary, Iqbal M.

2014-01-01

23

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

PubMed Central

Objective The antioxidant effects of aqueous root bark, stem bark and leaves of Vitex doniana (V. doniana) were evaluated in carbon tetrachloride (CCl4) induced liver damage and non induced liver damage albino rats. Methods A total of 60 albino rats (36 induced liver damage and 24 non induced liver damage) were assigned into liver damage and non liver damage groups of 6 rats in a group. The animals in the CCl4 induced liver damage groups, were induced by intraperitoneal injection with a single dose of CCl4 (148 mg·ml?1·kg?1 body weight) as a 1:1 (v/v) solution in olive oil and were fasted for 36 h before the subsequent treatment with aqueous root bark, stem bark and leaves extracts of V. doniana and vitamin E as standard drug (100 mg/kg body weighy per day) for 21 d, while the animals in the non induced groups were only treated with the daily oral administration of these extracts at the same dose. The administration of CCl4 was done once a week for a period of three weeks. Results The liver of CCl4 induced not treated group showed that the induction with CCl4, significantly (P<0.05) increased thiobarbituric acid reactive substance (TBARS) and significantly (P<0.05) decreased superoxide dismutase (SOD) and catalase (CAT). However there was no significant (P>0.05) difference between TBARS, SOD and CAT in the liver of the induced treated groups and normal control group. In the kidney, TBARS showed no significant (P>0.05) difference between the normal and the induced groups, SOD was significantly (P<0.05) reduced in the CCl4 group compared to standard drug and normal control groups, CAT was significantly (P<0.05) increased in root and vitamin E groups when compared to induced not treated group. The studies also showed that when the extracts were administered to normal animals, there was no significant (P>0.05) change in the liver and kidney level of TBARS, SOD and CAT compared with the normal control except in the kidney of animals treated with stem extract where TBARS was significantly (P<0.05) lowered compared to control group. Conclusion The result of the present study suggests that application of V. doniana plant would play an important role in increasing the antioxidant effect and reducing the oxidative damage that formed both in liver and in kidney tissues. However stem bark has potential to improve renal function in normal rats. PMID:23646304

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

2013-01-01

24

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

PubMed Central

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

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

2013-01-01

25

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

26

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

PubMed

Activation of spermine/spermidine-N(1)-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 (CCl(4)). The expression and activity of SSAT increase in the liver subsequent to CCl(4) administration. Furthermore, the early liver injury after CCl(4) 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 CCl(4). 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 CCl(4)-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

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

2012-09-01

27

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

PubMed

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

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

2014-06-01

28

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

PubMed Central

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

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

2012-01-01

29

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

30

Effect of low-molecular-weight heparin on the commitment of bone marrow cells to liver sinusoidal endothelial cells in CCl 4-induced liver injury  

Microsoft Academic Search

Background\\/aimsRecently liver regeneration by bone marrow transplantation has been proposed as an alternative source of functional liver cells. We investigate commitment of bone marrow cells (BMCs) to liver regeneration and the effect of dalteparin sodium (DS) on regeneration of the damaged liver caused by carbon tetrachloride (CCl4) administration in the mice.

Nobuko Serizawa; Yoshiyuki Takei; Hironao Okubo; Shunhei Yamasina; Nobuyuki Enomoto; Nobuhiro Sato

2006-01-01

31

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

PubMed Central

Background Hydrogen sulfide (H2S) displays vasodilative, anti-oxidative, anti-inflammatory and cytoprotective activities. Impaired production of H2S contributes to the increased intrahepatic resistance in cirrhotic livers. The study aimed to investigate the roles of H2S in carbon tetrachloride (CCl4)-induced hepatotoxicity, cirrhosis and portal hypertension. Methods and Findings Sodium hydrosulfide (NaHS), a donor of H2S, and DL-propargylglycine (PAG), an irreversible inhibitor of cystathionine ?-lyase (CSE), were applied to the rats to investigate the effects of H2S on CCl4-induced acute hepatotoxicity, cirrhosis and portal hypertension by measuring serum levels of H2S, hepatic H2S producing activity and CSE expression, liver function, activity of cytochrome P450 (CYP) 2E1, oxidative and inflammatory parameters, liver fibrosis and portal pressure. CCl4 significantly reduced serum levels of H2S, hepatic H2S production and CSE expression. NaHS attenuated CCl4-induced acute hepatotoxicity by supplementing exogenous H2S, which displayed anti-oxidative activities and inhibited the CYP2E1 activity. NaHS protected liver function, attenuated liver fibrosis, inhibited inflammation, and reduced the portal pressure, evidenced by the alterations of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), hyaluronic acid (HA), albumin, tumor necrosis factor (TNF)-?, interleukin (IL)-1?, IL-6 and soluble intercellular adhesion molecule (ICAM)-1, liver histology, hepatic hydroxyproline content and ?-smooth muscle actin (SMA) expression. PAG showed opposing effects to NaHS on most of the above parameters. Conclusions Exogenous H2S attenuates CCl4-induced hepatotoxicity, liver cirrhosis and portal hypertension by its multiple functions including anti-oxidation, anti-inflammation, cytoprotection and anti-fibrosis, indicating that targeting H2S may present a promising approach, particularly for its prophylactic effects, against liver cirrhosis and portal hypertension. PMID:22022478

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

2011-01-01

32

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

Microsoft Academic Search

BackgroundHydrogen sulfide (H2S) displays vasodilative, anti-oxidative, anti-inflammatory and cytoprotective activities. Impaired production of H2S contributes to the increased intrahepatic resistance in cirrhotic livers. The study aimed to investigate the roles of H2S in carbon tetrachloride (CCl4)-induced hepatotoxicity, cirrhosis and portal hypertension.Methods and FindingsSodium hydrosulfide (NaHS), a donor of H2S, and DL-propargylglycine (PAG), an irreversible inhibitor of cystathionine ?-lyase (CSE), were

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

2011-01-01

33

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

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

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

36

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

37

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

PubMed

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 (CCl(4))-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

38

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

PubMed

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

Verma, Nitin; Khosa, R L

2010-04-01

39

[Liver cirrhosis--procoagulant stasis].  

PubMed

Abnormal hemostasis tests and bleeding are often associated in liver cirrhosis. In these patients the balance between hypo- and hypercoagulation status is more fragile than in healthy people. In the hemostatic abnormalities associated with chronic liver disease are two main chategory factors: favoring hemorrage and favoring thrombosis. The main factors that favoring hemorrage are: low platelet count, impaired platelet function, decreased levels coagulation factors (II, V, VII, IX, X, XI), quantitative and qualitative abnormalities of fibrinogen, vitamin K defiency, low levels of trombin activable fibrinolisis inhibitor, activat plasminogenic tisular. The factors favoring thrombosis are elevated levels of factors VIII and von Willebrand, decreased levels of protein C, protein S, antithrombin, decreased levels of plasminogen. Traditionally it was thought that arterial and venous thrombosis is rare events in cirrhotic patients but recent studies have indicated that thrombotic complications can paradoxically occur even if clinically an increased risk of hemorrhage is considered. Treatment of venous thrombosis in patients with cirrhosis using routine anticoagulation with heparin and vitamin K antagonists has been described but with a high level of bleeding complications. So, based on the limited data available, AASLD guidelines stated no recommendations for or against the use of anticoagulation in cirrhotic patients with portal thrombosis. Although abnormal hemostasis tests and bleeding are often associated in patients with chronic liver disease it is a relatively poor correlation between hemorrhagic risk and routine diagnostic tests of hemostasis. Management of bleeding complications in liver cirrhosis varies and no general guidelines are available. The main therapeutic strategies are: red cell concentrate, plasma, platelet concentrate, recombinant factor VIIa, factor concentrates, desmopressin, antifibrynolitic agents, thrombopoietin receptor agonists, antibiotics. Clinical studies examining safety and efficacy of the various products for the different bleedeing or trombotic complications of liver cirrhosis need to be initiaded. PMID:22046771

Prelipcean, Cristina Cijevschi; Fierbinteanu-Braticevici, Carmen; Drug, V L; L?c?tu?u, Cristina; Mihai, B; Mihai, C?t?lina

2011-01-01

40

Oxymatrine improves intestinal epithelial barrier function involving NF-?B-mediated signaling pathway in CCl4-induced cirrhotic rats.  

PubMed

Accumulating evidence suggests that intestinal epithelial barrier dysfunction plays an important role in the pathogenesis of hepatic cirrhosis and its complications such as gastrointestinal injury and hepatic encephalopathy. To date, there is no cure for cirrhosis-associated intestinal mucosal lesion and ulcer. This study aimed to investigate the effect of oxymatrine on intestinal epithelial barrier function and the underlying mechanism in carbon tetrachloride (CCl4)-induced cirrhotic rats. Thirty CCl4-induced cirrhotic rats were randomly divided into treatment group, which received oxymatrine treatment (63 mg/kg), and non-treatment group, which received the same dose of 5% glucose solution (vehicle). The blank group (n?=?10 healthy rats) received no treatment. Terminal ileal samples were collected for histopathological examination. The expression level of nuclear factor-?B (NF-?B) p65 in ileal tissue was evaluated by immunohistochemistry. The gene and protein expression levels of tumor necrosis factor-? (TNF-?) and interleukin 6 (IL-6) in ileal tissues were analyzed by reverse-transcriptase polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Additionally, plasma endotoxin level was determined. In comparison to the blank group, a significant alteration in the morphology of intestinal mucosal villi in the non-treatment group was observed. The intestinal mucosal villi were atrophic, shorter, and fractured, and inflammatory cells were infiltrated into the lamina propria and muscular layer. Besides, serious swell of villi and loose structure of mucous membrane were observed. Oxymatrine reversed the CCl4-induced histological changes and restored intestinal barrier integrity. Moreover, oxymatrine reduced the protein expression level of NF-?B p65, TNF-?, and IL-6, which were elevated in the vehicle-treated group. In addition, the serum endotoxin level was significantly decreased after oxymatrine treatment in CCl4-induced cirrhotic rats. The results indicate that oxymatrine improves intestinal barrier function via NF-?B-mediated signaling pathway and may be used as a new protecting agent for cirrhosis-associated intestinal mucosal damage. PMID:25171482

Wen, Jian-Bo; Zhu, Fang-Qing; Chen, Wei-Guo; Jiang, Li-Ping; Chen, Jie; Hu, Zhao-Peng; Huang, Yong-Jian; Zhou, Zhi-Wei; Wang, Gui-Liang; Lin, Hao; Zhou, Shu-Feng

2014-01-01

41

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

PubMed

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

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

2014-03-01

42

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 ...

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 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

45

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

E-print Network

Abstract: 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.

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

2011-01-01

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

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

PubMed Central

Background Carissa opaca (Apocynaceae) leaves possess antioxidant activity and hepatoprotective effects, and so may provide a possible therapeutic alternative in hepatic disorders. The effect produced by methanolic extract of Carissa opaca leaves (MCL) was investigated on CCl4-induced liver damages in rat. Methods 30 rats were divided into five groups of six animals of each, having free access to food and water ad libitum. Group I (control) was given olive oil and DMSO, while group II, III and IV were injected intraperitoneally with CCl4 (0.5 ml/kg) as a 20% (v/v) solution in olive oil twice a week for 8 weeks. Animals of group II received only CCl4. Rats of group III were given MCL intragastrically at a dose of 200 mg/kg bw while that of group IV received silymarin at a dose of 50 mg/kg bw twice a week for 8 weeks. However, animals of group V received MCL only at a dose of 200 mg/kg bw twice a week for 8 weeks. The activities of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and ?-glutamyltransferase (?-GT) were determined in serum. Catalase (CAT), peroxidase (POD), superoxide dismutase (SOD), glutathione-S-transferase (GST), glutathione peroxidase (GSH-Px), glutathione reductase (GSR) and quinone reductase (QR) activity was measured in liver homogenates. Lipid peroxidation (thiobarbituric acid reactive substances; TBARS), glutathione (GSH) and hydrogen peroxide (H2O2) concentration was also assessed in liver homogenates. Phytochemicals in MCL were determined through qualitative and high performance liquid chromatography (HPLC) analysis. Results Hepatotoxicity induced with CCl4 was evidenced by significant increase in lipid peroxidation (TBARS) and H2O2 level, serum activities of AST, ALT, ALP, LDH and ?-GT. Level of GSH determined in liver was significantly reduced, as were the activities of antioxidant enzymes; CAT, POD, SOD, GSH-Px, GSR, GST and QR. On cirrhotic animals treated with CCl4, histological studies showed centrilobular necrosis and infiltration of lymphocytes. MCL (200 mg/kg bw) and silymarin (50 mg/kg bw) co-treatment prevented all the changes observed with CCl4-treated rats. The phytochemical analysis of MCL indicated the presence of flavonoids, tannins, alkaloids, phlobatannins, terpenoids, coumarins, anthraquinones, and cardiac glycosides. Isoquercetin, hyperoside, vitexin, myricetin and kaempherol was determined in MCL. Conclusion These results indicate that MCL has a significant protective effect against CCl4 induced hepatotoxicity in rat, which may be due to its antioxidant and membrane stabilizing properties. PMID:21699742

2011-01-01

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

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

50

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

PubMed

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; Park, Kun-Young

2013-08-01

51

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

PubMed

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

Esmaeili, Mohammad Ali; Alilou, Mostafa

2014-06-01

52

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

53

Glycyrrhizic acid attenuates CCl4-induced hepatocyte apoptosis in rats via a p53-mediated pathway  

PubMed Central

AIM: To investigate the effect of glycyrrhizic acid (GA) on carbon tetrachloride (CCl4)-induced hepatocyte apoptosis in rats via a p53-dependent mitochondrial pathway. METHODS: Forty-five male Sprague-Dawley rats were randomly and equally divided into three groups, the control group, the CCl4 group, and the GA treatment group. To induce liver fibrosis in this model, rats were given a subcutaneous injection of a 40% solution of CCl4 in olive oil at a dose of 0.3 mL/100 g body weight biweekly for 8 wk, while controls received the same isovolumetric dose of olive oil by hypodermic injection, with an initial double-dose injection. In the GA group, rats were also treated with a 40% solution of CCl4 plus 0.2% GA solution in double distilled water by the intraperitoneal injection of 3 mL per rat three times a week from the first week following previously published methods, with modifications. Controls were given the same isovolumetric dose of double distilled water. Liver function parameters, such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined. Pathologic changes in the liver were detected by hematoxylin and eosin staining. Collagen fibers were evaluated by Sirius red staining. Hepatocyte apoptosis was investigated using the terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphosphate nick end labeling (TUNEL) assay and the cleaved caspase-3 immunohistochemistry assay. The expression levels of p53 and apoptosis-related proteins were evaluated by immunohistochemistry or Western blotting analysis. RESULTS: After 8 wk of treatment, GA significantly reduced serum activity of ALT (from 526.7 ± 57.2 to 342 ± 44.8, P < 0.05) and AST (from 640 ± 33.7 to 462.8 ± 30.6, P < 0.05), attenuated the changes in liver histopathology and reduced the staging score (from 3.53 ± 0.74 to 3.00 ± 0.76, P < 0.05) in CCl4-treated rats. GA markedly reduced the positive area of Sirius red and the ratio of the hepatic fibrotic region (from 7.87% ± 0.66% to 3.68% ± 0.32%, P < 0.05) compared with the CCl4 group. GA also decreased the expression level of cleaved caspase-3 compared to the CCl4 group. TUNEL assay indicated that GA significantly diminished the number of TUNEL-positive cells compared with the CCl4 group (P < 0.05). GA treatment clearly decreased the level of p53 (P < 0.05) detected by immunohistochemistry and Western blotting analysis. Compared with the CCl4 group, we also found that GA reduced the Bax/Bcl-2 ratio (P < 0.05), the expression of cleaved caspase-3 (P < 0.05), cleaved caspase-9 (P < 0.05), and inhibited cytochrome C and second mitochondria-derived activator of caspases (Smac) release from mitochondria to cytoplasm, i.e., GA reduced the expression level of Smac, which inhibited c-IAP1 activity (P < 0.05), ultimately inhibiting the activity of caspase-3, according to Western blotting analysis. As a result, GA suppressed activation of the caspase cascades and prevented hepatocyte apoptosis. CONCLUSION: GA can inhibit CCl4-induced hepatocyte apoptosis via a p53-dependent mitochondrial pathway to retard the progress of liver fibrosis in rats. PMID:23840116

Guo, Xiao-Ling; Liang, Bo; Wang, Xue-Wei; Fan, Fu-Gang; Jin, Jing; Lan, Rui; Yang, Jing-Hui; Wang, Xiao-Chun; Jin, Lei; Cao, Qin

2013-01-01

54

[Bacterial infections in liver cirrhosis].  

PubMed

Bacterial infections are well described complications of cirrhosis that greatly increase mortality rates. Two factors play important roles in the development of bacterial infections in these patients: the severity of liver disease and gastrointestinal haemorrhage. The most common infections are spontaneous bacterial peritonitis, urinary tract infections, pneumonia and sepsis. Gram-negative and gram-positive bacteria are equal causative organisms. For primary prophylaxis, short-term antibiotic treatment (oral norfloxacin or ciprofloxacin) is indicated in cirrhotic patients (with or without ascites) admitted with gastrointestinal haemorrhage (variceal or non-variceal). Administration of norfloxacin is advisable for hospitalized patients with low ascitic protein even without gastrointestinal haemorrhage. The first choice in empirical treatment of spontaneous bacterial peritonitis is the iv. III. generation cephalosporin; which can be switched for a targeted antibiotic regime based on the result of the culture. The duration of therapy is 5-8 days. Amoxicillin/clavulanic acid and fluoroquinolones--patients not on prior quinolone prophylaxis--were shown to be as effective and safe as cefotaxime. In patients with evidence of improvement, iv. antibiotics can be switched safely to oral antibiotics after 2 days. In case of renal dysfunction, iv albumin should also be administered. Long-term antibiotic prophylaxis is recommended in patients who have recovered from an episode of spontaneous bacterial peritonitis (secondary prevention). For "selective intestinal decontamination", poorly absorbed oral norfloxacin is the preferred schedule. Oral ciprofloxacin or levofloxacin (added gram positive spectrum) all the more are reasonable alternatives. Trimethoprim/sulfamethoxazole is only for patients who are intolerant to quinolones. Prophylaxis is indefinite until disappearance of ascites, transplant or death. Long-term prophylaxis is currently not recommended for patients without previous spontaneous bacterial peritonitis episode, not even when refractory ascites or low ascites protein content is present. PMID:17344166

Papp, Mária; Farkas, Anikó; Udvardy, Miklós; Tornai, István

2007-03-01

55

Transplanted Human Amniotic Membrane-Derived Mesenchymal Stem Cells Ameliorate Carbon Tetrachloride-Induced Liver Cirrhosis in Mouse  

PubMed Central

Background Human amniotic membrane-derived mesenchymal stem cells (hAMCs) have the potential to reduce heart and lung fibrosis, but whether could reduce liver fibrosis remains largely unknown. Methodology/Principal Findings Hepatic cirrhosis model was established by infusion of CCl4 (1 ml/kg body weight twice a week for 8 weeks) in immunocompetent C57Bl/6J mice. hAMCs, isolated from term delivered placenta, were infused into the spleen at 4 weeks after mice were challenged with CCl4. Control mice received only saline infusion. Animals were sacrificed at 4 weeks post-transplantation. Blood analysis was performed to evaluate alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Histological analysis of the livers for fibrosis, hepatic stellate cells activation, hepatocyte apoptosis, proliferation and senescence were performed. The donor cell engraftment was assessed using immunofluorescence and polymerase chain reaction. The areas of hepatic fibrosis were reduced (6.2%±2.1 vs. control 9.6%±1.7, p<0.05) and liver function parameters (ALT 539.6±545.1 U/dl, AST 589.7±342.8 U/dl,vs. control ALT 139.1±138.3 U/dl, p<0.05 and AST 212.3±110.7 U/dl, p<0.01) were markedly ameliorated in the hAMCs group compared to control group. The transplantation of hAMCs into liver-fibrotic mice suppressed activation of hepatic stellate cells, decreased hepatocyte apoptosis and promoted liver regeneration. More interesting, hepatocyte senescence was depressed significantly in hAMCs group compared to control group. Immunofluorescence and polymerase chain reaction revealed that hAMCs engraftment into host livers and expressed the hepatocyte-specific markers, human albumin and ?-fetoproteinran. Conclusions/Significance The transplantation of hAMCs significantly decreased the fibrosis formation and progression of CCl4-induced cirrhosis, providing a new approach for the treatment of fibrotic liver disease. PMID:21326862

Zhang, DingGuo; Jiang, MinYue; Miao, DengShun

2011-01-01

56

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

Microsoft Academic Search

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

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

2007-01-01

57

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

58

[Nutritional care for patients with liver cirrhosis].  

PubMed

The liver is an important organ with specific functions that influence directly on the nutritional and physiological status of every person. At the presence of any illness or injury in this organ, liver cirrhosis is always its final phase. In this pathology, patients present carbohydrate utilization and storage diminishment, as well as protein and fat catabolism increase. This situation, plus a low ingest and a bad nutrient absorption, results in a high prevalence of malnutrition. Many studies prove the importance of an opportune nutritional treatment in these patients, bringing general benefits and improving their quality of life. It's important to considerate the possible nutritional risks and deficiencies that could appear in the course of the cirrhosis to take opportune actions. The nutritional assessment and treatment is transcendental both in compensated phase (without complications) and in decompensated phase (with complications) of the illness. PMID:24528340

Aceves-Martins, Magaly

2014-01-01

59

Primary biliary cirrhosis and liver transplantation  

PubMed Central

Summary Primary biliary cirrhosis (PBC) is an immune-mediated chronic progressive inflammatory liver disease, predominantly affecting middle-aged women, characterized by the presence of antimitochondrial antibodies (AMAs), which can lead to liver failure. Genetic contributions, environmental factors including chemical and infectious xenobiotics, autoimmunity and loss of tolerance have been aggressively investigated in the pathogenesis of PBC, however, the actual impact of these factors is still controversial. Survival of PBC patients has been largely improved with the widespread use of ursodeoxycholic acid (UDCA), however, one third of patients still do not respond to the treatment and proceed to liver cirrhosis, requiring liver transplantation as a last resort for cure. The outcome of liver transplantation is excellent with 5- and 10-year survival rates around 80% and 70%, respectively, while along with long survival, the recurrence of the disease has become an important outcome after liver transplantation. Prevalence rates of recurrent PBC rage widely between 1% and 35%, and seem to increase with longer follow-up. Center-specific issues, especially the use of protocol biopsy, affect the variety of incidence, yet, recurrence itself does not affect patient and graft survival at present, and retransplantation due to recurrent disease is extremely rare. With a longer follow-up, recurrent disease could have an impact on patient and graft survival.

Akamatsu, Nobuhisa; Sugawara, Yasuhiko

2012-01-01

60

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

61

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

62

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

PubMed Central

Rationale Lack of an experimental model of portopulmonary hypertension (POPH) has been a major obstacle in understanding of pathophysiological mechanisms underlying the disease. Objective We investigated the effects of CCl4-mediated cirrhosis on the pulmonary vasculature, as an initial step towards an improved understanding of POPH. Methods And Results Male C57BL/6 mice received intraperitoneal injection of either sterile olive oil or CCl4 3 times/week for 12 weeks. Cirrhosis and portal hypertension were confirmed by evidence of bridging fibrosis and nodule formation in CCl4-treated liver determined by trichrome/picrosirius red staining and an increase in spleen weight/body weight ratio, respectively. Staining for the oxidative stress marker, 4-hydroxynonenal (4-HNE), was strong in the liver but was absent in the lung, suggesting that CCl4 did not directly induce oxidative injury in the lung. Pulmonary acceleration time (PAT) and the ratio of PAT/pulmonary ejection time (PET) measured by echocardiography were significantly decreased in cirrhotic mice. Increase in right ventricle (RV) weight/body weight as well as in the weight ratio of RV/(left ventricle + septum) further demonstrated the presence of pathological changes in the pulmonary circulation in these mice. Histological examination revealed that lungs of cirrhotic mice have excessive accumulation of perivascular collagen and thickening of the media of the pulmonary artery. Conclusion Collectively, our data demonstrate that chronic CCl4 treatment induces pathological changes in pulmonary circulation in cirrhotic mice. We propose that this murine cirrhotic model provides an exceptional tool for future studies of the molecular mechanisms mediating pulmonary vascular diseases associated with cirrhosis and for evaluation of novel therapeutic interventions. PMID:24763616

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

2014-01-01

63

Prescribing Medications in Patients with Decompensated Liver Cirrhosis  

PubMed Central

Patients with decompensated liver cirrhosis have various serious complications which require multiple drugs for therapeutic or prophylactic use. Majority of the drugs are primarily metabolized and excreted by hepatobiliary system; hence, liver cell necrosis contributes to impaired drug handling in liver failure while portosystemic shunt can alter drug action in cirrhosis. Hence, in order to decide drug dosing in liver failure, 3 important factors need to be considered (1) pharmacokinetic alterations of drugs, (2) pharmacodynamic alteration of drugs, and (3) increased susceptibility of patients to adverse events particularly hepatotoxicity. Though there is no predictable test which can be used to determine drug dosage in patients with decompensated liver cirrhosis, drugs with first pass metabolism require reduction in oral dosages, for high clearance drugs both loading and maintenance dosages need adjustment, for low clearance drugs maintenance dose needs adjustment, whenever possible measuring drug level in the blood and monitoring of adverse events frequently should be done. No evidence-based guidelines exist for the use of medication in patients' with liver cirrhosis. There are hardly any prospective studies on the safety of drugs in cirrhotic patients. According to the experts opinion, most of the drugs can be used safely in patients with cirrhosis, but drug-induced hepatotoxicity may be poorly tolerated by patients with cirrhosis; hence, potential hepatotoxins should be avoided in patients with liver cirrhosis. Potentially hepatotoxic drugs may be used in patients with liver cirrhosis based on the clinical needs and when there are no alternatives available. Caveat for the prescribing medications in patients with cirrhosis the drug dosing should be individualized depending on a number of factors like nutritional status, renal function, adherence, and drug interaction. Monitoring of the liver function at frequent intervals is highly recommended. PMID:21994861

Amarapurkar, Deepak N.

2011-01-01

64

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

65

The DEN and CCl4 -Induced Mouse Model of Fibrosis and Inflammation-Associated Hepatocellular Carcinoma.  

PubMed

Human hepatocellular carcinoma (HCC) develops most often as a complication of fibrosis or cirrhosis. While most human studies of HCC provide crucial insights into the molecular signatures of HCC, seldom do they address the etiology of HCC. Mouse models are essential tools for investigating the pathogenesis of HCC; however, the overwhelming majority of cancer models in rodents do not feature liver fibrosis. Detailed in this unit is a protocol for an experimental mouse model of HCC that arises in association with advanced liver fibrosis. The disease model is induced by a single injection of N-nitrosodiethylamine (DEN) followed by repeated administration of carbon tetrachloride (CCl4 ). A dramatic potentiation of liver tumor incidence is observed following administration of DEN and CCl4 , with100% of mice developing liver tumors at 5 months of age. This model can be employed for studying the molecular mechanisms of fibrogenesis and HCC development, and in cancer hazard/chemotherapy testing of drug candidates. Curr. Protoc. Pharmacol. 66:14.30.1-14.30.10. © 2014 by John Wiley & Sons, Inc. PMID:25181010

Uehara, Takeki; Pogribny, Igor P; Rusyn, Ivan

2014-01-01

66

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

67

Management of Coagulopathy in Patients with Decompensated Liver Cirrhosis  

PubMed Central

Patients with decompensated liver cirrhosis have significantly impaired synthetic function. Many proteins involved in the coagulation process are synthesized in the liver. Routinely performed tests of the coagulation are abnormal in patients with decompensated liver cirrhosis. This has led to the widespread belief that decompensated liver cirrhosis is prototype of acquired hemorrhagic coagulopathy. If prothrombin time is prolonged more than 3 seconds over control, invasive procedures like liver biopsy, splenoportogram, percutaneous cholangiography, or surgery were associated with increased risk of bleeding, and coagulopathy should be corrected with infusion of fresh frozen plasma. These practices were without any scientific evidence and were associated with significant hazards of fresh frozen plasma transfusion. Now, it is realized that coagulation is a complex process involving the interaction of procoagulation and anticoagulation factors and the fibrinolytic system. As there is reduction in both anti and procoagulant factors, global tests of coagulation are normal in patients with acute and chronic liver disease indicating that coagulopathy in liver disease is more of a myth than a reality. In the last few years, surgical techniques have substantially improved, and complex procedures like liver transplantation can be done without the use of blood or blood products. Patients with liver cirrhosis may also be at increased risk of thrombosis. In this paper, we will discuss coagulopathy, increased risk of thrombosis, and their management in decompensated liver cirrhosis. PMID:22164337

Amarapurkar, Pooja D.; Amarapurkar, Deepak N.

2011-01-01

68

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

PubMed Central

Background Rutin is a polyphenolic natural flavonoid which possesses antioxidant and anticancer activity. In the present study the hepatoprotective effect of rutin was evaluated against carbon tetrachloride (CCl4)-induced liver injuries in rats. Methods and materials 24 Sprague–Dawley male rats were equally divided into 4 groups for the assessment of hepatoprotective potential of rutin. Rats of group I (control) received only vehicles; 1 ml/kg bw of saline (0.85%) and olive oil (3 ml/kg) and had free access to food and water. Rats of group II, III and IV were treated with CCl4 (30% in olive oil, 3 ml/kg bw) via the intraperitoneal route twice a week for four weeks. The rutin at the doses of 50 and 70 mg/kg were administered intragastrically after 48 h of CCl4 treatment to group III and IV, respectively. Protective effect of rutin on serum enzyme level, lipid profile, activities of antioxidant enzymes and molecular markers were calculated in CCl4-induced hepatotoxicity in rat. Results Rutin showed significant protection with the depletion of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transpeptidase (?-GT) in serum as was raised by the induction of CCl4. Concentration of serum triglycerides, total cholesterol and low density lipoproteins was increased while high-density lipoprotein was decreased with rutin in a dose dependent manner. Activity level of endogenous liver antioxidant enzymes; catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSHpx), glutathione-S-transferase (GST) and glutathione reductase (GSR) and glutathione (GSH) contents were increased while lipid peroxidation (TBARS) was decreased dose dependently with rutin. Moreover, increase in DNA fragmentation and oxo8dG damages while decrease in p53 and CYP 2E1 expression induced with CCl4 was restored with the treatment of rutin. Conclusion From these results, it is suggested that rutin possesses hepatoprotective properties. PMID:23043521

2012-01-01

69

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

70

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

71

Report: 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

72

Introducing an Optimal Liver Allocation System for Liver Cirrhosis Patients  

PubMed Central

Background Liver transplantation (LT) is the only treatment option for patients with advanced liver disease. Currently, liver donation to these patients, considering priorities, is based on the Model for End-Stage Liver Disease (MELD). MELD score is a tool for predicting the risk of mortality in patients with advanced liver disease. However, few studies have so far been conducted in Iran on the efficacy of MELD score of these patients. Objectives This study reviews the present status of the MELD score and introduces a new model for optimal prediction of the risk of mortality in Iranian patients with advanced liver disease. Patients and Methods Data required were collected from 305 patients with advanced liver disease who enrolled in a waiting list (WL) in Imam Khomeini Hospital from May 2008 to May 2009. All of the patients were followed up for at least 3 years until they died or underwent LT. Cox regression analysis was applied to select the factors affecting their mortality. Survival curves were plotted. Wilcoxson test and receiver operating characteristics curves for survival predictive model were used to compare the scores. All calculations were performed with the SPSS (version 13.0) and R softwares. Results During the study, 71 (23.3%) patients died due to liver cirrhosis and 43 (14.1%) underwent LT. Viral Hepatitis (43.7%) is the most common cause of end-stage liver disease among Iranian patients. A new model (NMELD) was proposed with the use of the natural logarithms of two blood serum variables (total bilirubin and albumin) and the patients' age (year) by applying the Cox model: NMELD = 10 × (0.736 × ln (bilirubin) – 1.312 × ln (albumin) + 0.025 × age + 1.776) Conclusions The results of the Wilcoxon test showed that there is a significant difference between the usual MELD and our proposed NMELD scores (P < 0.001). Receiver operating characteristics curve for survival predictive model indicated that the NMELD score is more efficient compared with the MELD score in predicting the risk of mortality. Since serum creatinine was not significant in NMELD score, further studies to clarify this issue are suggested. PMID:24098306

Abolghasemi, Jamileh; Eshraghian, Mohammad Reza; Nasiri Toosi, Mohsen; Mahmoodi, Mahmood; Rahimi Foroushani, Abbas

2013-01-01

73

Altered Liver Morphology After Portal Vein Thrombosis: Not Always Cirrhosis  

Microsoft Academic Search

The macroscopic appearance of the liver after primary portal vein thrombosis often mimics cirrhosis, despite the absence of\\u000a bridging fibrosis at histology. The purpose of this study was to describe unique morphologic changes of the liver after portal\\u000a venous thrombosis. A retrospective review was performed to find patients with portal vein thrombosis and a corresponding noncirrhotic\\u000a liver biopsy. The CT

Mitchell E. Tublin; Alexander J. Towbin; Michael P. Federle; Michael A. Nalesnik

2008-01-01

74

Suspected azathioprine induced liver cirrhosis: an unusual side effect  

PubMed Central

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

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

2014-01-01

75

Oxidative Stress and Pulmonary Changes in Experimental Liver Cirrhosis  

PubMed Central

The use of carbon tetrachloride (CCl4) in rats is an experimental model of hepatic tissue damage; which leads to fibrosis, and at the long term, cirrhosis. Cirrhosis is the consequence of progressive continued liver damage, it may be reversible when the damaging noxae have been withdrawn. The aim of this study is to evaluate the changes caused by cirrhosis in lung and liver, through the experimental model of intraperitoneal CCI4 administration. We used 18 male Wistar rats divided into three groups: control (CO) and two groups divided by the time of cirrhosis induction by CCI4: G1 (11 weeks), G2 (16 weeks). We found significant increase of transaminase levels and lipid peroxidation (TBARS) in liver and lung tissue and also increased antioxidant enzymes SOD and CAT, as well as the expression of TNF-? and IL-1? in the lung of cirrhotic animals. We observed changes in gas exchange in both cirrhotic groups. We can conclude that our model reproduces a model of liver cirrhosis, which causes alterations in the pulmonary system that leads to changes in gas exchange and size of pulmonary vessels. PMID:23316268

Salatti Ferrari, Renata; da Rosa, Darlan Pase; Forgiarini, Luiz Felipe; Bona, Silvia; Simoes Dias, Alexandre; Marroni, Norma Possa

2012-01-01

76

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

77

Detection of Novel Biomarkers of Liver Cirrhosis by Proteomic Analysis  

PubMed Central

Hepatic cirrhosis is a life-threatening disease arising from different chronic liver disorders. One major cause for hepatic cirrhosis is chronic hepatitis C. Chronic hepatitis C is characterized by a highly variable clinical course, with at least 20% developing liver cirrhosis within 40 years. Only liver biopsy allows a reliable evaluation of the course of hepatitis C by grading inflammation and staging fibrosis, and thus serum biomarkers for hepatic fibrosis with high sensitivity and specificity are needed. To identify new candidate biomarkers for hepatic fibrosis, we performed a proteomic approach of microdissected cirrhotic septa and liver parenchyma cells. In cirrhotic septa, we detected an increasing expression of cell structure associated proteins, including actin, prolyl 4-hydroxylase, tropomyosin, calponin, transgelin, and human microfibril–associated protein 4 (MFAP-4). Tropomyosin, calponin, and transgelin reflect a contribution of activated stellate cells/myofibroblasts to chronic liver injury. The expression of tropomyosin, transgelin, and MFAP-4, an extracellular matrix associated protein, were further evaluated by immunohistochemistry. Tropomyosin and MFAP-4 demonstrated high serum levels in patients with hepatic cirrhosis of different causes. Conclusion A quantitative analysis of MFAP-4 serum levels in a large number of patients showed MFAP-4 as novel candidate biomarker with high diagnostic accuracy for prediction of nondiseased liver versus cirrhosis [area under receiver operating characteristic curve (AUC) = 0.97, P < 0.0001] as well as stage 0 versus stage 4 fibrosis (AUC = 0.84, P < 0.0001), and stages 0 to 3 versus stage 4 fibrosis (AUC = 0.76, P < 0.0001). PMID:19177598

Molleken, Christian; Sitek, Barbara; Henkel, Corinna; Poschmann, Gereon; Sipos, Bence; Wiese, Sebastian; Warscheid, Bettina; Broelsch, Christoph; Reiser, Markus; Friedman, Scott L.; Torn?e, Ida; Schlosser, Anders; Kloppel, Gunter; Schmiegel, Wolff; Meyer, Helmut E.; Holmskov, Uffe; Stuhler, Kai

2010-01-01

78

Alpha 1-antitrypsin deficiency and liver cirrhosis in adults.  

PubMed

Although cirrhosis of the liver caused by alpha 1-antitrypsin deficiency is not uncommon in children, only a few cases have been described in adults. We have seen three such patients--one man and two women, ranging in age from 57 to 66 years. These cases show the wide spectrum of this genetically influenced disease. PMID:3871255

Sassaris, M P; Trinkl, W; Meka, R; Gonzales, P; Torres, O; Leach, R; Hunter, F M

1985-01-01

79

Influence of unrecorded alcohol consumption on liver cirrhosis mortality.  

PubMed

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

2014-06-21

80

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

National Technical Information Service (NTIS)

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

R. Geiger

1983-01-01

81

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

82

Primary biliary cirrhosis in the era of liver transplantation.  

PubMed

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

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

2014-01-01

83

Spectral CT: Preliminary Studies in the Liver Cirrhosis  

PubMed Central

Objective To investigate the value of spectral CT imaging in the diagnosis and classification of liver cirrhosis during the arterial phase (AP) and portal venous phase (PVP). Materials and Methods Thirty-eight patients with liver cirrhosis (Child-Pugh class A/B/C: n = 10/14/14), and 43 patients with healthy livers, participated in this study. The researchers used abdominal spectral CT imaging during AP and PVP. Iodine concentration, derived from the iodine-based material-decomposition image and the iodine concentration ratio (ICratio) between AP and PVP, were obtained. Statistical analyses {two-sample t test, One-factor analysis of variance, and area under the receiver operating characteristic curve (A [z])} were performed. Results The mean normalized iodine concentration (NIC) (0.5 ± 0.12) during PVP in the control group was significantly higher than that in the study group (0.4 ± 0.10 on average, 0.4 ± 0.08 for Class A, 0.4 ± 0.15 for Class B, and 0.4 ± 0.06 for Class C) (All p < 0.05). Within the cirrhotic liver group, the mean NIC for Class C during the AP (0.1 ± 0.05) was significantly higher than NICs for Classes A (0.1 ± 0.06) and B (0.1 ± 0.03) (Both p < 0.05). The ICratio in the study group (0.4 ± 0.15), especially for Class C (0.5 ± 0.14), was higher than that in the control group (0.3 ± 0.15) (p < 0.05).The combination of NIC and ICratio showed high sensitivity and specificity for differentiating healthy liver from cirrhotic liver, especially in Class C cirrhotic liver. Conclusion Spectral CT Provides a quantitative method with which to analyze the cirrhotic liver, and shows the potential value in the classification of liver cirrhosis. PMID:22778565

Lv, Peijie; Lin, Xiaozhu; Gao, Jianbo

2012-01-01

84

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

85

Failure of liver cirrhosis induction by thioacetamide in Nagase analbuminaemic rats  

Microsoft Academic Search

Summary Repeated administration of thioacetamide (TA), either intraperitoneally or in drinking water, produced liver cirrhosis in normal Sprague-Dawley rats (SDR) with signi® cant histological alterations similar to those observed in human cirrhosis. In the present study, we evaluated the ability of TA to induce liver cirrhosis in mutant Nagase analbuminaemic SDR. Thioacetamide was administered either intraperitoneally up to 4 months

Pascale David; Eliane Alexandre; Marie-Pierre Chenard-Neu; Philippe Wolf; Daniel Jaeck; Lysiane Richert

2002-01-01

86

[Volume retention in heart failure, nephrotic syndrome, and liver cirrhosis].  

PubMed

Volume retention in heart failure, nephrotic syndrome, and liver cirrhosis reflects pathological changes in homeostatic mechanisms that regulate the extracellular volume (sympathetic activity, renin-angiotensin-aldosterone system [RAAS], natriuretic peptides) and plasma osmolality (antidiuretic hormone [ADH]). In heart failure and liver cirrhosis, these changes are induced by a reduction of the effective circulating volume, which is the part of the extracellular fluid that is within the arterial system and effectively perfusing the tissues. This reduction in the effective circulating volume is caused by reduced cardiac output (heart failure), or by splanchnic vasodilatation with arterial underfilling (liver cirrhosis). In both cases, baroreceptors in both the carotid sinuses and in the glomerular afferent arterioles upregulate RAAS- and sympathetic activity, resulting in systemic vasoconstriction and renal sodium (and volume) retention. More severe reductions in the effective circulating volume may additionally stimulate ADH release, thus increasing the reabsorption of free water with subsequent hyponatriemia. In nephrotic syndrome, volume retention results either directly from the primary renal disease, which induces renal sodium and volume retention ("overfilling"), or indirectly from the reduced plasma oncotic pressure due to hypoalbuminemia, which induces a fluid shift from the intravascular to the interstitial space ("underfilling") with subsequent acitivation of baroreceptors and secondary sodium and volume retention. PMID:17009041

Heine, G H; Sester, U; Köhler, H

2006-11-01

87

Stage of cirrhosis predicts the risk of liver-related death in patients with low model for End-Stage liver disease scores and cirrhosis awaiting liver transplantation.  

PubMed

The Model for End-Stage Liver Disease (MELD) score has reduced predictive ability in patients with cirrhosis and MELD scores???20. We aimed to assess whether a 5-stage clinical model could identify liver transplantation (LT) candidates with low MELD scores who are at increased risk for death. We conducted a case-control study of subjects with cirrhosis and MELD scores???20 who were awaiting LT at a single academic medical center between February 2002 and May 2011. Conditional logistic regression was used to evaluate the risk of liver-related death according to the cirrhosis stage. We identified 41 case subjects who died from liver-related causes with MELD scores???20 within 90 days of death while they were waiting for LT. The cases were matched with up to 3 controls (66 controls in all) on the basis of the listing year, age, sex, liver disease etiology, presence of hepatocellular carcinoma, and MELD score. The cirrhosis stage was assessed for all subjects: (1) no varices or ascites, (2) varices, (3) variceal bleeding, (4) ascites, and (5) ascites and variceal bleeding. The MELD scores were similar for cases and controls. Clinical states contributing to death in cases were: sepsis 49%, spontaneous bacterial peritonitis 15%, variceal bleeding 24%, and hepatorenal syndrome 22%. In a univariate analysis, variceal bleeding [odds ratio (OR)?=?5.6, P?=?0.003], albumin (OR?=?0.5, P?=?0.041), an increasing cirrhosis stage (P?=?0.003), reaching cirrhosis stage 2, 3, or 4 versus lower stages (OR?=?3.6, P?=?0.048; OR?=?7.4, P?liver-related death. In a multivariate model including the cirrhosis stage, albumin, sodium, and hepatic encephalopathy, an increasing cirrhosis stage (P?=?0.010) was independently associated with liver-related death. In conclusion, assessing the cirrhosis stage in patients with low MELD scores awaiting LT may help to select candidates for more aggressive monitoring or for living or extended criteria donation. Liver Transpl 20:1193-1201, 2014. © 2014 AASLD. PMID:24916539

Wedd, Joel; Bambha, Kiran M; Stotts, Matt; Laskey, Heather; Colmenero, Jordi; Gralla, Jane; Biggins, Scott W

2014-10-01

88

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

EPA Science Inventory

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

89

Hepatoprotective potential of aqueous extract of Butea monosperma against CCl 4 induced damage in rats  

Microsoft Academic Search

Aqueous extract of flowers of Butea monosperma (Fabaceae) was evaluated at different dose levels (200, 400, 800mg\\/kg, p.o.) for its protective efficacy against CCl4 (1.5ml\\/kg i.p.) induced acute liver injury to validate its use in traditional medicines. The CCl4 administration altered various biochemical parameters, including serum transaminases, protein, albumin, hepatic lipid peroxidation, reduced glutathione and total protein levels, which were

Neetu Sharma; Sangeeta Shukla

2011-01-01

90

Hepatoprotective potential of aqueous extract of Butea monosperma against CCl(4) induced damage in rats.  

PubMed

Aqueous extract of flowers of Butea monosperma (Fabaceae) was evaluated at different dose levels (200, 400, 800 mg/kg, p.o.) for its protective efficacy against CCl(4) (1.5 ml/kg i.p.) induced acute liver injury to validate its use in traditional medicines. The CCl(4) administration altered various biochemical parameters, including serum transaminases, protein, albumin, hepatic lipid peroxidation, reduced glutathione and total protein levels, which were restored towards control by therapy of B. monosperma Adenosine triphosphatase and glucose-6-phosphatase activity in the liver were decreased significantly in CCl(4) treated animals. Therapy of B. monosperma showed its protective effect on biochemical and histopathological alterations at all the three doses in dose dependent manner. B. monosperma extract possess modulatory effect on drug metabolizing enzymes as it significantly decreased the hexobarbitone induced sleep time and increased excretory capacity of liver which was measured by BSP retention. Histological studies also supported the biochemical finding and maximum improvement in the histoarchitecture was seen at higher dose of BM extract. PMID:20561774

Sharma, Neetu; Shukla, Sangeeta

2011-11-01

91

Emergency liver transplant in patient with Child-Pugh class C cirrhosis and strangulated umbilical hernia.  

PubMed

The authors report the case of a patient who presented with small bowel obstruction while awaiting liver transplant for Child-Pugh class C cirrhosis. He underwent emergency liver transplant with resection of the small bowel after the obstruction did not improve with conservative management. The authors believe this is the first case of successful emergency liver transplant with resection of the small bowel in a patient with decompensated Child-Pugh class C liver cirrhosis and strangulated umbilical hernia. This case suggests the possibility of improved outcomes of emergency hernia repair in patients with liver cirrhosis when small bowel resection is combined with liver transplant. PMID:23190414

Chaudhary, Abhideep; Daga, Sachin; Goyal, Neerav; Ramaswamy, Vasudevan Karisangal; Agarwal, Shaleen; Pareek, Shishir; Ray, Ramdip; Wadhawan, Manav; Gupta, Subash

2013-02-01

92

DNA ploidy of liver biopsies from patients with liver cirrhosis and hepatocellular carcinoma: a flow cytometric analysis  

Microsoft Academic Search

Flow cytometric DNA analysis was used to assess cellular kinetics of needle liver biopsies from patients with liver cirrhosis and hepatocellular carcinoma (HCC). An abnormal DNA content was shown in 44.5% of liver cirrhosis cases and in 78.6% of tumor sites. The number of proliferating cells (S+G2M%) was significantly increased in cirrhotic liver (P<0.05). Dysplasia was found in 66% of

Abdelfattah M Attallah; Ashraf A Tabll; Samia F Salem; Mohamed El-Sadany; Talaat A Ibrahim; Sanaa Osman; Ibrahem M El-Dosoky

1999-01-01

93

Evaluation of hepatoprotective effects of Helminthostachys zeylanica (L.) Hook against carbon tetrachloride-induced liver damage in Wistar rats  

Microsoft Academic Search

The rhizomes of Helminthostachys zeylanica (L.) are used by the Kattunaikan tribe of Kerala, for the treatment of various hepatic disorders. In the present study, the effect of the methanolic extract of Helminthostachys zeylanica rhizomes on carbon tetrachloride (CCl4)-induced liver damage in Wistar rats was studied. The results showed that significant hepatoprotective effect was obtained against CCl4-induced liver damage, by

S. R. Suja; P. G. Latha; P. Pushpangadan; S. Rajasekharan

2004-01-01

94

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

95

Bile salt secretion in cirrhosis of the liver  

PubMed Central

Secretion of bile salts into the duodenum was studied in eight normal subjects, in 10 patients with cirrhosis, and in two cholecystectomized subjects. Duodenal juice was aspirated continuously through a double-lumen tube during an unstimulated period, after an intravenous injection of pancreozymin/cholecystokinin, and during a continuous intravenous infusion of secretin given at a rate of 3 units per kilogram body weight per hour. Precautions were taken to try to ensure quantitative recovery during the studies, and recovery of an infused nonabsorbable marker was greater than 80% in all subjects. Secretin induced a flow of a greater volume of juice in the cirrhotic patients than in the normal group (49 to 57 ml per 10 minutes compared with 28 to 49 ml per 10 minutes). This change may have resulted from a higher effective dose of secretin if it is assumed that the cirrhotic liver fails to catabolize secretin. The bile acid response to pancreozymin/cholecystokinin followed by secretin in the cirrhotic subjects resembled that seen in patients after cholecystectomy in whom pancreozymin/cholecystokinin induces only a slight increase in bile salt output but in whom the output of bile salts during rest and secretin stimulation is markedly greater than normal. This response in cirrhosis is probably best interpreted as due to impaired function of the gallbladder. The total amount of bile salt liberated over the two hours of the test in the cirrhotic patients was similar to normal The concentration of bile salt after pancreozymin/cholecystokinin was less than in normal subjects, but similar to that in cholecystectomized patients. It is unlikely therefore that deficient output or concentration of bile salt can be held responsible for steatorrhea in cirrhosis. There was a marked decrease in the deoxycholate conjugates and a reduction in the glycine: taurine ratio in the bile of cirrhotic patients. The former change may reflect a change in bacterial flora and the latter a defect in hepatic conjugating mechanisms. ImagesFig. 6 PMID:5441881

Turnberg, Leslie A.; Grahame, Gordon

1970-01-01

96

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

97

Osteoporosis in primary biliary cirrhosis of the liver  

PubMed Central

Osteoporosis is a metabolic bone disease associated with a reduction in bone mass and deterioration of bone architecture, leading to increased fragility and subsequent low-trauma fractures in the vertebral column, hip, forearm and other bones. In literature, metabolic bone diseases such as osteoporosis and osteomalacia have been recognised as a complication of chronic liver disease, although the mechanisms of this association remain unclear. An increasing body of research data indicates a strong relationship between osteoporosis and primary biliary cirrhosis (PBC), which mainly results from early diagnosis of the disease, usually when it is still asymptomatic. The incidence of osteoporosis in PBC ranges from 20% to 44% and increases with the progression of the disease. Similarly, the incidence of bone fractures is high in this group of patients (10–20%). In this article, current knowledge on risk factors, pathogenesis, diagnosis and treatment of osteoporosis in PBC is reviewed. PMID:25061487

Raszeja-Wyszomirska, Joanna

2014-01-01

98

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

Microsoft Academic Search

The present study is aiming at evaluating the hepatoprotective and antioxidant effects of Glycyrrhiza glabra extract (2.5, 5 and 10 ?g\\/ml) on the carbon tetrachloride (CCl4)-induced carp hepatocyte damage in vitro. Glycyrrhiza glabra extract was added to the carp primary hepatocytes before (pre-treatment), after (post-treatment) and both before and after\\u000a (pre- and post-treatment) the incubation of the hepatocytes with CCl4. CCl4

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

2011-01-01

99

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

Microsoft Academic Search

Summary Two female breast cancer patients who received combined tamoxifen and tegafur as postsurgical adjuvant therapy developed severe hepatotoxicity after being treated for three and eight months, respectively. Shortly after the cessation of the treatment, routine liver tests showed gradual recovery, but liver biopsies revealed chronic active hepatitis in one patient and liver cirrhosis in the other. Four and five

Shigeo Maruyama; Chisato Hirayama; Juro Abe; Jun Tanaka; Katsuaki Matsui

1995-01-01

100

Clinical denouement and mutation analysis of patients with cystic fibrosis undergoing liver transplantation for biliary cirrhosis  

Microsoft Academic Search

Objective: To describe the clinical characteristics of patients with cystic fibrosis considered for liver transplantation and the clinical outcome after transplantation. Methods: Patient charts were reviewed. Mutation analysis was performed on blood or liver tissue samples with a panel of 17 mutations. Results: Eight patients (five girls) with cystic fibrosis have undergone orthotopic liver transplantation for biliary cirrhosis. Mean age

David R. Mack; Monica D. Traystman; John L. Colombo; Paul H. Sammut; Stuart S. Kaufman; Jon A. Vanderhoof; Dean L. Antonson; Rodney S. Markin; Byers W. Shaw; Alan N. Langnas

1995-01-01

101

Development of a New Animal Model of Liver Cirrhosis in Swine  

Microsoft Academic Search

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

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

2009-01-01

102

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

103

Noninvasive diagnosis of liver cirrhosis using DNA sequencer–based total serum protein glycomics  

Microsoft Academic Search

We applied our 'clinical glycomics' technology, based on DNA sequencer\\/fragment analyzers, to generate profiles of serum protein N-glycans of liver disease patients. This technology yielded a biomarker that distinguished compensated cirrhotic from noncirrhotic chronic liver disease patients, with 79% sensitivity and 86% specificity (100% sensitivity and specificity for decompensated cirrhosis). In combination with the clinical chemistry–based Fibrotest biomarker, compensated cirrhosis

Hans Van Vlierberghe; Annelies Van Hecke; Wouter Laroy; Joris Delanghe; Nico Callewaert; Roland Contreras

2004-01-01

104

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

105

Temporal expression of hepatic inducible nitric oxide synthase in liver cirrhosis  

PubMed Central

AIM: Nitric oxide (NO) has been implicated in the pathogenesis of liver cirrhosis. We have found inducible nitric oxide synthase (iNOS) can be induced in hepatocytes of cirrhotic liver. This study further investigated the temporal expression and activity of hepatic iNOS in cirrhosis development. METHODS: Cirrhosis was induced in rats by chronic bile duct ligation (BDL). At different time points after the operation, samples were collected to examine NO concentration, liver function, and morphological changes. Hepatocytes were isolated for determination of iNOS mRNA, protein and enzymatic activity. RESULTS: Histological examination showed early cirrhosis 1-2 wk after BDL, with advanced cirrhosis at 3-4 wk. Bilirubin increased dramatically 3 d after BDL, but decreased by 47% on d 14. Three weeks after BDL, it elevated again. Systemic NO concentration did not increase significantly until 4 wk after BDL, when ascites developed. Hepatocyte iNOS mRNA expression was identified 3 d after BDL, and enhanced with time to 3 wk, but reduced thereafter. iNOS protein showed a similar pattern to mRNA expression. iNOS activity decreased from d 3 to d 7, but increased again thereafter till d 21. CONCLUSION: Hepatic iNOS can be induced in the early stage, which increases with time as cirrhosis develops. Its enzymatic activity is significantly correlated with protein expression and histological alterations of the liver, but not with systemic NO levels, nor with absolute values of liver function markers. PMID:15637745

Wei, Chang-Li; Hon, Wei-Min; Lee, Kang-Hoe; Khoo, Hoon-Eng

2005-01-01

106

Liver transplantation for jejunoileal bypass–associated cirrhosis: Allograft histology in the setting of an intact bypassed limb  

Microsoft Academic Search

Jejunoileal bypass (JIB) is a well known cause of steatohepatitis, which may, on occasion, progress to cirrhosis and require liver transplantation. We report 3 patients who underwent orthotopic liver transplantation (OLT) for steatohepatitic cirrhosis secondary to JIB in which the JIB was left intact. All 3 patients have demonstrated recurrent steatosis in the graft after liver transplantation. In two of

SM D'Souza-Gburek; KP Batts; GA Nikias; RH Wiesner; RA Krom

1997-01-01

107

Abdominal imaging can misdiagnose submassive hepatic necrosis as cirrhosis in acute liver failure.  

PubMed

Patients with acute liver failure (ALF) can be listed status I for liver transplantation (LT) whereas patients with cirrhosis must follow the MELD scoring system. Liver imaging can mistakenly diagnose submassive hepatic necrosis in ALF as cirrhosis. The purpose of our study was to assess the accuracy of ultrasound (US) and computed tomography (CT) in distinguishing cirrhosis from ALF. All patients listed for ALF and transplanted during the study period were included. Controls were age- and gender-matched cirrhotic patients who underwent LT during the same period. Abdominal US or CT scans obtained on all patients were independently reviewed by three blinded abdominal radiologists. Explants from all patients were reviewed by two blinded pathologists, and histological diagnosis was correlated with radiological diagnosis. Forty-one patients with ALF and 42 patients with cirrhosis were analyzed. Univariate and multivariate analyses both revealed overall accuracy of 85% for ultrasound and 93% for CT. US and CT scans both provide high levels of accuracy in terms of discriminating ALF from cirrhosis but measures taken to determine whether a patient has ALF vs. cirrhosis needs to approach 100% accuracy. Thus, imaging studies alone should not definitively diagnosis one etiology of liver failure over the other. PMID:23647426

Kim, Andrew I; Han, Steven-Huy; Tran, Doan-Trang; Sullivan, Peggy; Lassman, Charles; Raman, Steve; Zimmerman, Peter; Chin, Eva E

2013-01-01

108

Distinct cellular responses differentiating alcohol- and hepatitis C virus-induced liver cirrhosis  

Microsoft Academic Search

BACKGROUND: Little is known at the molecular level concerning the differences and\\/or similarities between alcohol and hepatitis C virus induced liver disease. Global transcriptional profiling using oligonucleotide microarrays was therefore performed on liver biopsies from patients with cirrhosis caused by either chronic alcohol consumption or chronic hepatitis C virus (HCV). RESULTS: Global gene expression patterns varied significantly depending upon etiology

Sharon L Lederer; Kathie-Anne Walters; Sean Proll; Bryan Paeper; Shahar Robinzon; Loreto Boix; Nelson Fausto; Jordi Bruix; Michael G Katze

2006-01-01

109

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

Microsoft Academic Search

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

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

2008-01-01

110

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

111

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

PubMed

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

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

2013-10-01

112

N-glycomic changes in hepatocellular carcinoma patients with liver cirrhosis induced by hepatitis B virus  

Microsoft Academic Search

We evaluated the use of blood serum N-glycan fingerprinting as a tool for the diagnosis of hepatocellular carcinoma (HCC) in patients with cirrhosis induced by hepatitis B virus (HBV). A group of 450 HBV-infected patients with liver fibrosis or cirrhosis with or without HCC were studied. HCC was diagnosed by -fetoprotein (AFP) analysis, ultrasonography, and\\/or computed tomography and was studied

Xue-En Liu; Liesbeth Desmyter; Chun-Fang Gao; Wouter Laroy; Sylviane Dewaele; Valerie Vanhooren; Ling Wang; Hui Zhuang; Nico Callewaert; Claude Libert; Roland Contreras; Cuiying Chen

2007-01-01

113

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

PubMed Central

Chronic liver injury leads to fibrosis, cirrhosis, and loss of liver function. Liver cirrhosis is the 12th leading cause of death in the United States, and it is the primary risk factor for developing liver cancer. Fibrosis and cirrhosis result from activation of hepatic stellate cells (HSCs), which are the primary collagen producing cell type in the liver. Here, we show that platelet-derived growth factor receptor ? (PDGFR?) is expressed by human HSCs, and PDGFR? expression is elevated in human liver disease. Using a green fluorescent protein (GFP) reporter mouse strain, we evaluated the role of PDGFR? in liver disease in mice and found that mouse HSCs express PDGFR? and expression is upregulated during carbon tetrachloride (CCl4) induced liver injury and fibrosis injection. This fibrotic response is reduced in Pdgfr? heterozygous mice, consistent with the hypothesis that liver fibrosis requires upregulation and activation of PDGFR?. These results indicate that Pdgfr? expression is important in the fibrotic response to liver injury in humans and mice, and suggest that blocking PDGFR?–specific signaling pathways in HSCs may provide therapeutic benefit for patients with chronic liver disease. PMID:24667490

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

2014-01-01

114

Hrd1 suppresses Nrf2-mediated cellular protection during liver cirrhosis  

PubMed Central

Increased endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) are the salient features of end-stage liver diseases. Using liver tissues from liver cirrhosis patients, we observed up-regulation of the XBP1–Hrd1 arm of the ER stress response pathway and down-regulation of the Nrf2-mediated antioxidant response pathway. We further confirmed this negative regulation of Nrf2 by Hrd1 using Hrd1 conditional knockout mice. Down-regulation of Nrf2 was a surprising result, since the high levels of ROS should have inactivated Keap1, the primary ubiquitin ligase regulating Nrf2 levels. Here, we identified Hrd1 as a novel E3 ubiquitin ligase responsible for compromised Nrf2 response during liver cirrhosis. In cirrhotic livers, activation of the XBP1–Hrd1 arm of ER stress transcriptionally up-regulated Hrd1, resulting in enhanced Nrf2 ubiquitylation and degradation and attenuation of the Nrf2 signaling pathway. Our study reveals not only the convergence of ER and oxidative stress response pathways but also the pathological importance of this cross-talk in liver cirrhosis. Finally, we showed the therapeutic importance of targeting Hrd1, rather than Keap1, to prevent Nrf2 loss and suppress liver cirrhosis. PMID:24636985

Wu, Tongde; Zhao, Fei; Gao, Beixue; Tan, Can; Yagishita, Naoko; Nakajima, Toshihiro; Wong, Pak K.; Chapman, Eli; Fang, Deyu; Zhang, Donna D.

2014-01-01

115

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

PubMed

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

Vogt, M; Gitzelmann, R; Allemann, J

1980-11-22

116

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

117

Liver cirrhosis in cystic fibrosis--therapeutic implications and long term follow up.  

PubMed Central

Experience gained from liver studies in 450 patients with cystic fibrosis, seen in a 38 year period from 1964 to 1992, is surveyed. Of these, 31 (7%) showed findings that indicated multilobular cirrhosis. There was a slight but not significant male predominance: 19 males against 12 females. Liver disease had its onset during childhood in most cases. The natural course of liver disease and of cirrhosis is protracted. All patients were routinely evaluated by way of: (i) clinical examination, (ii) biochemical studies and specifically estimation of transaminases and gamma glutamyltransferase, and (iii) liver imaging, ultrasonography, and computed tomography. The study aimed to detect early liver disease, that is multilobular cirrhosis and its complications, with a view to optimal introduction of treatment with ursodeoxycholic acid as this drug shows promise for preventing or stabilising the cirrhotic process. Effects of surgical treatment on portal hypertension are surveyed. These include portacaval shunting, partial splenectomy (considered the procedure of choice), liver transplant in the event of liver failure, or a triple transplant (liver, lungs, and heart) if necessary. One triple transplant was successfully performed in a boy of 10 years with a 2 year follow up. Images PMID:8280210

Feigelson, J; Anagnostopoulos, C; Poquet, M; Pecau, Y; Munck, A; Navarro, J

1993-01-01

118

Zinc supplementation in experimental liver cirrhosis: a morphological, structural and ultrastructural study.  

PubMed Central

Zinc treatment in liver cirrhosis is known to prevent a number of clinical symptoms. Previous studies have also indicated that Zn has a protective effect on the development of the clinical, biochemical and morphological manifestations of hepatic injury if administered simultaneously with the noxious agent. In this study, the protective effects of zinc treatment against the development of liver cirrhosis have been tested in cirrhotic rats treated by intragastric administration of CCl4. The development of morphological lesions has been investigated by means of standardized and comparable techniques, LM, TEM, SEM, microvascular casts and measurements of liver collagen content by colorimetric determination in paraffin embedded sections. LM and EM observations showed typical morphological features of cirrhosis in all CCl4 treated rats. In the same group of animals, the microvascular casts showed the development of the typical 'perinodular' branching and the various anastomoses of pre and post-sinusoidal vessels. Colorimetric evaluation has shown a significant increase in collagen content after CCl4 treatment. Qualitative and quantitative data of livers of CCl4 treated rats supplemented or not with zinc were significantly similar. In conclusion, zinc treatment influences biochemical parameters, but not the morphology of liver cirrhosis. Images Figure 1 Figure 2 Figure 3 PMID:8217781

Gaudio, E.; Pannarale, L.; Franchitto, A.; Riggio, O.

1993-01-01

119

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

120

Pulmonary vascular dilatation and diffusion-dependent impairment of gas exchange in liver cirrhosis  

Microsoft Academic Search

To test the hypothesis that diffusion-limitation for oxygen is due to abnormal vascular dilatation and significantly contributes to the arterial hypox- aemia of liver cirrhosis requires an experimental approach that detects both dif- fusion-limitation for oxygen and the presence of abnormal dilatation of pulmonary vessels exposed to alveolar gas. We therefore studied the gas exchange of a 64 year old

A. B. H. Crawford; J. Regnis; L. Laks; P. Donnelly; L. A. Engel; I. H. Young

1995-01-01

121

Enhanced external counterpulsation: a new technique to augment renal function in liver cirrhosis  

Microsoft Academic Search

Background. Advanced liver cirrhosis is characterized by cardiovascular changes, such as low arterial blood pressure, peripheral vasodilation and renal vasocon- striction. As a consequence, renal hypoperfusion, impaired diuresis and natriuresis and eventual hepato- renal syndrome may ensue. Previous studies using head-out water immersion to increase central blood volume have demonstrated the functional nature of the renal abnormalities. Enhanced external counter-

Dierk Werner; Peter Tragner; Andrea Wawer; Heiner Porst; Werner G. Daniel; Peter Gross

2005-01-01

122

Doppler Ultrasound of Hepatic and System Hemodynamics in Patients with Alcoholic Liver Cirrhosis  

Microsoft Academic Search

Objective The progression of liver cirrhosis eventually increases cardiac output, while blood pressure and systemic vascular resistance\\u000a are reduced. A complex behavior of portal hemodynamic to hepatic artery and system circulation has not yet been presented.\\u000a There is a lack in knowledge about the correlation of local and systemic circulation parameters to the degree of liver failure,\\u000a with respect to

Zekanovic Drazen; Ljubicic Neven; Boban Marko; Nikolic Marko; Delic-Brkljacic Diana; Gacina Petar; Klarin Ivo; Turcinov Jadranko

2010-01-01

123

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

PubMed Central

Plasminogen activator inhibitor-1 (PAI-1) is an acute phase protein that has been shown to play a role in experimental fibrosis caused by bile duct ligation (BDL) in mice. However, its role in more severe models of hepatic fibrosis (e.g., carbon tetrachloride; CCl4) has not been determined and is important for extrapolation to human disease. Wild-type or PAI-1 knockout mice were administered CCl4 (1 ml/kg body wt ip) 2×/wk for 4 wk. Plasma (e.g., transaminase activity) and histological (e.g., Sirius red staining) indexes of liver damage and fibrosis were evaluated. Proliferation and apoptosis were assessed by PCNA and TdT-mediated dUTP nick-end labeling (TUNEL) staining, respectively, as well as by indexes of cell cycle (e.g., p53, cyclin D1). In contrast to previous studies with BDL, hepatic fibrosis was enhanced in PAI-1?/? mice after chronic CCl4 administration. Indeed, all indexes of liver damage were elevated in PAI-1?/? mice compared with wild-type mice. This enhanced liver damage correlated with impaired hepatocyte proliferation. A similar effect on proliferation was observed after one bolus dose of CCl4, without concomitant increases in liver damage. Under these conditions, a decrease in phospho-p38, coupled with elevated p53 protein, was observed; these results suggest impaired proliferation and a potential G1/S cell cycle arrest in PAI-1?/? mice. These data suggest that PAI-1 may play multiple roles in chronic liver diseases, both protective and damaging, the latter mediated by its influence on inflammation and fibrosis and the former via helping maintain hepatocyte division after an injury. PMID:20203062

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

2010-01-01

124

Successful off-pump pericardiectomy and coronary artery bypass in liver cirrhosis.  

PubMed

Cardiopulmonary bypass can be detrimental to patients with hepatic cirrhosis. Pericardiectomy performed on the beating heart is an effective treatment for pericardial constriction. Off-pump coronary artery bypass grafting is becoming firmly established as a surgical option for myocardial ischemia associated with multivessel disease. A single-stage operation combining both procedures without utilizing cardiopulmonary bypass has not been reported. This provided excellent surgical outcome for a patient with the dual pathology and coexisting liver cirrhosis. The off-pump approach should be considered in such a high-risk scenario. PMID:15854097

Tang, Augustine T M; Karski, Jacek; Cusimano, Robert J

2005-01-01

125

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

126

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

127

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

128

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

129

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.

Kim, Kyung-Hyun; Park, Kwan-Kyu

2014-01-01

130

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

131

Increased expression of claudin-1 and claudin-7 in liver cirrhosis and hepatocellular carcinoma.  

PubMed

Claudins have been reported to be differentially regulated in malignancies and implicated in the process of carcinogenesis and tumor progression. Claudin-1 has been described as key factor in the entry of hepatitis C virus (HCV) into hepatocytes and as promoter of epithelial-mesenchymal transition in liver cells. The objective of the current study was to characterize claudin expression in hepatocellular carcinoma (HCC) as well as HCC-surrounding and normal liver samples with respect to cirrhosis and HCV infection. Expression of claudin-1, -2, -3, -4, and -7 was measured by morphometric analysis of immunohistochemistry, and Western blotting in 30 HCCs with 30 corresponding non-tumorous tissues and 6 normal livers. Claudin-1 and -7 protein expression was found significantly elevated in cirrhosis when compared with non-cirrhotic liver. HCCs developed in cirrhotic livers showed even higher expression of claudin-1 contrary to decreased claudin-7 expression when compared with cirrhosis. With reference to HCV status, HCCs or surrounding livers of HCV-infected samples did not show significant alterations in claudin expression when compared with HCV-negative specimens. Cirrhotic transformation associates with elevated claudin-1 and -7 expressions in both non-tumorous liver and HCC. The fact that no significant differences in claudin expression were found regarding HCV-positivity in our sample set suggests that HCV infection alone does not induce a major increase in the total amount of its entry co-factor claudin-1. Increased expression of claudin-1 seems to be a consequence of cirrhotic transformation and might contribute to a more effective HCV entry and malignant transformation. PMID:24696415

Holczbauer, Ágnes; Gyöngyösi, Benedek; Lotz, Gábor; Törzsök, Péter; Kaposi-Novák, Pál; Szijártó, Attila; Tátrai, Péter; Kupcsulik, Péter; Schaff, Zsuzsa; Kiss, András

2014-07-01

132

[Rupture of ileal varices in a type C liver cirrhosis patient: a case report].  

PubMed

A 74-year-old woman was admitted to our hospital with recurrent massive lower gastrointestinal bleeding. She had a history of type C liver cirrhosis and appendectomy, and had undergone endoscopic ligation of esophageal varices one year before. Three-dimensional CTA revealed ileal varices in the right lower quadrant of the abdomen. Superior mesenteric arteriography demonstrated varices at the corresponding area and collateral veins from the superior mesenteric vein to the right ovarian vein. Ileal varices were diagnosed and ileal resection was performed. At surgery, exposed vessels were present at the mucosal surface of the resected specimen and they were thought to be the origin of hemorrhage. In conclusion, bleeding from small intestinal varices, though uncommon, should be considered when the origin of melena is unidentified in a patient with liver cirrhosis. PMID:19654470

Suzuki, Takahisa; Murayama, Mutsumi; Shinoda, Masataka; Takashi, Hitomi; Uchiyama, Isako; Morise, Kazuhiro; Usami, Akihisa; Tsuji, Hideki; Haruki, Nobuhiro; Tashiro, Kazuhiro; Ando, Takafumi; Goto, Hidemi

2009-08-01

133

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

PubMed Central

BACKGROUND Liver cirrhosis is one of the major causes of hospitalization and mortality in children. A wide spectrum of disorders including developmental abnormalities, infections, metabolic and genetic disorders can lead to liver cirrhosis in pediatric patients. Determination of its etiology is important for treatment, prevention of progressive liver damage, family counseling and prioritizing liver transplantation. The aim of this study is to evaluate causes of liver cirrhosis in children in Southern Iran. METHODS We included all cirrhotic children aged less than 18 years who referred to an outpatient pediatric gastroenterology clinic affiliated with Shiraz University of Medical Sciences between March 2009 and September 2010 in this cross-sectional study. The etiology of cirrhosis was determined according to clinical findings, laboratory tests, imaging studies such as ultrasonography or computed tomography scan, hepatobiliary scintigraphy and histopathologic examination of the liver biopsy. Cirrhosis with unknown etiology was considered as cryptogenic. RESULTS A total of 106 cirrhotic children aged between 5 months to 18 years with a mean age of 8.24 ± 6.12 years that included 60 boys (56.6%) and 46 girls (43.4%) were enrolled in the study. The most common causes of liver cirrhosis were Wilson disease (n=22; 20.7%), biliary atresia (n=19; 17.9%), and cryptogenic cirrhosis (n=14; 13.2%). Other causes were autoimmune hepatitis (n=12; 11.3%), idiopathic neonatal hepatitis (n=10; 9.4%), hepatorenal tyrosinemia (n=9; 8.5%), glycogen storage disease (n=6; 5.7%), and progressive familial intrahepatic cholestasis (n=4; 3.8%). CONCLUSION Considering the most common etiology of liver cirrhosis in children in this part of Iran we suggest testing for Wilson disease in all cirrhotic children. PMID:24829669

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

2013-01-01

134

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

135

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

PubMed

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

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

1995-12-01

136

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

137

Liver cirrhosis and hepatocellular carcinoma in hepatic vena cava disease, a liver disease caused by obstruction of inferior vena cava  

Microsoft Academic Search

Purpose  Hepatic vena cava disease (HVD), a form of Budd-Chiari syndrome, is caused by the obstruction of hepatic portion of the inferior\\u000a vena cava. It is a chronic disease characterized by the development of liver cirrhosis (LC) and hepatocellular carcinoma (HCC).\\u000a As HVD occurred in areas with high incidence of hepatitis B virus (HBV) infection and some patients tested HBsAg positive,

Santosh Man Shrestha

2009-01-01

138

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

Microsoft Academic Search

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

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

2009-01-01

139

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

Microsoft Academic Search

Background  Health service databases of administrative type can be a useful tool for the study of progression of a disease, but the data\\u000a reported in such sources could be affected by misclassifications of some patients' real disease states at the time. Aim of\\u000a this work was to estimate the transition probabilities through the different degenerative phases of liver cirrhosis using\\u000a health

Nicola Bartolomeo; Paolo Trerotoli; Gabriella Serio

2011-01-01

140

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

Microsoft Academic Search

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

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

1979-01-01

141

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

142

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

143

A rare cause of hypoxia in a patient with liver cirrhosis  

PubMed Central

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

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

2012-01-01

144

[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

145

Favorable outcome of primary liver transplantation in children with cirrhosis and hepatocellular carcinoma.  

PubMed

The outcome of HCC after transplantation (OLT) in children is not well known. Unfavorable features based on adult reports may lead to contraindicate OLT even in children. We reviewed a cohort of children with cirrhosis and HCC to evaluate their outcome after primary transplantation. We considered children with cirrhosis and HCC who had a primary OLT. We retrospectively recorded demographic, medical and surgical features, and MC as predictors of outcome. Among 456 children transplanted in the last 15 yr, 10 (2%), median age at diagnosis 1.8 yr (range 0.5-7.2), had HCC in biliary atresia (3), BSEP deficiency (3), tyrosinemia type 1 (2), complications of choledocal cyst and glycogen storage disease type IV (1 each). At HCC discovery, median AFP was 2322 ng/mL (3-35,000), high or rising in 9/10 patients. Six patients were outside the MC. Median time on the waiting list was 38 days (1-152). Two patients died from early complications of OLT. In the other eight patients, there was no tumor recurrence after a median follow-up of four yr. Children with cirrhosis may develop HCC at a very young age. The outcome appears excellent even outside MC. Primary liver transplantation is advisable for children with cirrhosis, HCC, and no extrahepatic disease. PMID:21797955

Romano, Fabrizio; Stroppa, Paola; Bravi, Michela; Casotti, Valeria; Lucianetti, Alessandro; Guizzetti, Michela; Sonzogni, Aurelio; Colledan, Michele; D'Antiga, Lorenzo

2011-09-01

146

Liver Allograft Its Use in Chronic Active Hepatitis With Macronodular Cirrhosis, Hepatitis B Surface Antigen  

PubMed Central

A patient suffering from chronic active hepatitis with macronodular cirrhosis, positive for hepatitis B surface antigen (HB,Ag), was treated with an orthoiopic liver allograft. The HB, antigenemia, as measured with several precipltation tests and by complement fixation, became negative after transplantation and remained so for about 2½ months. During the interval, very low Iters of the antigen were detectable by, radioimmunoassay. At about three months after transplantation, she had an attack of acute hepatitis, at which time HB,Ag became detectable by all tests. She recovered, but progressive liver disease developed during the remaining 1½ years of her life. She died of disseminaled nocardiosis and candidiasis with deteriorating hepatic function. The homograft at autopsy, showed no evidence of rejection, but was the site of chronic active liver disease, although of a different pathologic pattern than that affecting her native liver. The differences in histology may reflect the influence of chronic Immunosuppression on the features of chronic active hepatitis. PMID:365134

Corman, Jarques L.; Putnam, Charles W.; Iwatsuki, Shunzaburo; Redeker, Allan G.; Porter, K. A.; Peters, Robert L.; Schroter, Gerhard; Starzl, Thomas E.

2010-01-01

147

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

PubMed

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

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

2013-10-01

148

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

Przybylkowski, Adam; Gromadzka, Grazyna; Chabik, Grzegorz; Wierzchowska, Agata; Litwin, Tomasz; Czlonkowska, Anna

2014-01-01

149

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

PubMed Central

Purpose To investigate whether histogram analysis of the hepatobiliary phase on gadoxetate enhanced-MRI could be used as a quantitative index for determination of liver cirrhosis. Materials and Methods A total of 63 patients [26 in a normal liver function (NLF) group and 37 in a cirrhotic group] underwent gadoxetate-enhanced MRI, and hepatobiliary phase images were obtained at 20 minutes after contrast injection. The signal intensity of the hepatic parenchyma was measured at four different regions of interest (ROI) of the liver, avoiding vessels and bile ducts. Standard deviation (SD), coefficient of variation (CV), and corrected CV were calculated on the histograms at the ROIs. The distributions of CVs calculated from the ROI histogram were examined and statistical analysis was carried out. Results The CV value was 0.041±0.009 (mean CV±SD) in the NLF group, while that of cirrhotic group was 0.071±0.020. There were statistically significant differences in the CVs and corrected CV values between the NLF and cirrhotic groups (p<0.001). The most accurate cut-off value among CVs for distinguishing normal from cirrhotic group was 0.052 (sensitivity 83.8% and specificity 88.5%). There was no statistically significant differences in SD between NLF and cirrhotic groups (p=0.307). Conclusion The CV of histograms of the hepatobiliary phase on gadoxetate-enhanced MRI may be useful as a quantitative value for determining the presence of liver cirrhosis. PMID:24719131

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

2014-01-01

150

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

PubMed Central

AIM: To determine if subclinical abnormal glucose tolerance (SAGT) has influence on survival of non-diabetic patients with liver cirrhosis. METHODS: In total, 100 patients with compensated liver cirrhosis and normal fasting plasma glucose were included. Fasting plasma insulin (FPI) levels were measured, and oral glucose tolerance test (OGTT) was performed. According to OGTT results two groups of patients were formed: those with normal glucose tolerance (NGT) and those with SAGT. Patients were followed every three months. The mean follow-up was 932 d (range of 180-1925). Survival was analyzed by the Kaplan-Meyer method, and predictive factors of death were analyzed using the Cox proportional hazard regression model. RESULTS: Of the included patients, 30 showed NGT and 70 SAGT. Groups were significantly different only in age, INR, FPI and HOMA2-IR. Patients with SAGT showed lower 5-year cumulated survival than NGT patients (31.7% vs 71.6%, P = 0.02). Differences in survival were significant only after 3 years of follow-up. SAGT, Child-Pugh B, and high Child-Pugh and Model for End-Stage Liver Disease (MELD) scores were independent predictors of death. The causes of death in 90.3% of cases were due to complications related to liver disease. CONCLUSION: SAGT was associated with lower survival. SAGT, Child-Pugh B, and high Child-Pugh and MELD scores were independent negative predictors of survival. PMID:24944496

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

2014-01-01

151

Defect of Fc receptors and phenotypical changes in sinusoidal endothelial cells in human liver cirrhosis.  

PubMed Central

To analyze the pathological changes occurring in Fc receptors (FcRs) in sinusoidal endothelial cells (SECs) in chronic liver diseases, we first characterized immunohistochemically the SEC FcRs by using monoclonal antibodies (MAbs) to FcRs and then investigated the distribution of the SEC FcRs by using peroxidase-antiperoxidase IgG complexes as a ligand on frozen sections. MAb 2E1 to FcRII reacted with SECs in a similar manner to peroxidase-antiperoxidase IgG and blocked the peroxidase-antiperoxidase IgG binding to SECs, whereas MAbs 3G8 and Leu-11b to FcRIII did not. FcRs in normal liver were found along the sinusoidal walls, except for those in the outer periportal zones, but FcRs in chronic active hepatitis and cirrhosis were intermittently or focally absent. The lengths of the FcR-positive portion of sinusoids in unit areas were respectively about 54% and 76% of the normal values in active and inactive cirrhosis. Where FcRs were absent, the MAbs CD36, CD31, and EN4 revealed the presence of sinusoids and, in active cirrhosis, frequently the thickening of liver cell plates. The FcR-negative SECs in the outer periportal zones of normal livers were different from the SECs of other sites in the presence of PAL-E antigen and a rich amount of EN4 antigen, though these sinusoids possessed Kupffer cells and no perisinusoidal deposition of laminin. The FcR-negative SECs in liver diseases occasionally presented the character of ordinary blood vessels, viz., PAL-E antigen, CD34 antigen, and a deficiency of Kupffer cells, regardless of perisinusoidal laminin deposition. However, they preserved the character of normally FcR-possessing SECs, viz., CD36 antigen, and a small amount of EN4 and CD31 antigens. These findings indicate that the outer-periportal SECs in normal livers are phenotypically different from other SECs and that the SECs in diseased livers frequently undergo phenotypical changes, including loss of FcRs, regardless of perisinusoidal laminin deposition, i.e., capillarization of the sinusoids. These phenotypical changes in SECs may reduce the capacity of FcR-mediated IgG-IC metabolism in diseased livers. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 PMID:7686339

Muro, H.; Shirasawa, H.; Kosugi, I.; Nakamura, S.

1993-01-01

152

Hepatocellular carcinoma after sustained virologic response in hepatitis C patients without cirrhosis on a pre-treatment liver biopsy  

PubMed Central

Among hepatitis C patients, lack of cirrhosis and sustained virologic response reduce the risk of hepatocellular carcinoma. Japanese studies document multiple cases of hepatocellular carcinoma among these patients, but only one case has been reported outside of Asia. We identified five patients with hepatitis C in our university-based hepatology practice who developed hepatocellular carcinoma despite sustained virologic response and lack of cirrhosis on their pre-treatment liver biopsy. At the time of hepatocellular carcinoma diagnosis, two remained noncirrhotic, one had clearly progressed to cirrhosis, and two lacked repeat histology. We present these patients in a case series format and discuss several important implications of their cases. Physicians often base screening and treatment decisions on an initial liver biopsy performed years prior. Because fibrosis may advance, and because sustained virologic response and lack of cirrhosis do not fully protect against hepatocellular carcinoma, future study should further evaluate the risk of hepatocellular carcinoma among hepatitis C patients after SVR. PMID:19212213

Sewell, Justin L.; Stick, Kristine M.; Monto, Alexander

2009-01-01

153

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

154

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

PubMed Central

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

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

2012-01-01

155

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

156

[A case of cryptococcal meningitis mimicking hepatic encephalopathy in a patient with liver cirrhosis caused by chronic hepatitis C].  

PubMed

Cryptococcus neoformans, an encapsulated fungus, is an important opportunistic pathogen that can cause meningitis in im-munocompromised patients. Since patients with cryptococcemia have high mortality, it is essential to make an early diagnosis and promptly initiate antifungal therapy. However, it is often very difficult to differentiate between cryptococcal meningitis and hepatic encephalopathy in patients with liver cirrhosis, and there is delay in making the diagnosis. Therefore, these patients have a particularly grave prognosis and consequently many patients die before culture results become available. In one study, starting antifungal therapy within 48 hours of the blood culture was associated with improved survival, but patients with liver cirrhosis were significantly less likely to receive antifungal therapy within 48 hours compared to those without liver cirrhosis. Recently, the authors experience a case of a 68-year-old woman with liver cirrhosis who presented with fever and a drowsy mental status. She had a previous history of having been admitted for infection-associated hepatic encephlopathy. Cryptococcal meningitis and cryptococcemia were diagnosed by spinal puncture and culture of cerebrospinal fluid. In spite of adequate treatment, the patient developed multi-system organ failure and eventually expired. Herein, we report a case of cryptococcal meningitis mimicking hepatic encephalopathy in a patient with liver cirrhosis. (Korean J Gastroenterol 2014;64:294-297). PMID:25420740

Choi, Hye Mi; Jung, Gum Mo; Lee, Woong Ki; Lee, Hyeuk Soo; Kim, Byung Sun; Seong, Choong Sil; Yoon, So Hee; Cho, Yong Keun

2014-11-25

157

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

158

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

PubMed

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

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

2014-01-01

159

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

PubMed Central

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

Toshikuni, Nobuyuki; Arisawa, Tomiyasu; Tsutsumi, Mikihiro

2014-01-01

160

A proteomic strategy to identify novel serum biomarkers for liver cirrhosis and hepatocellular cancer in individuals with fatty liver disease  

PubMed Central

Background Non-alcoholic fatty liver disease (NAFLD) has a prevalence of over 20% in Western societies. Affected individuals are at risk of developing both cirrhosis and hepatocellular cancer (HCC). Presently there is no cost effective population based means of identifying cirrhotic individuals and even if there were, our ability to perform HCC surveillance in the at risk group is inadequate. We have performed a pilot proteomic study to assess this as a strategy for serum biomarker detection. Methods 2D Gel electrophoresis was performed on immune depleted sera from 3 groups of patients, namely those with (1) pre-cirrhotic NAFLD (2) cirrhotic NAFLD and (3) cirrhotic NAFLD with co-existing HCC. Five spots differentiating at least one of these three groups were characterised by mass spectroscopy. An ELISA assay was optimised and a cross sectional study assessing one of these serum spots was performed on serum from 45 patients with steatohepatitis related cirrhosis and HCC and compared to 77 patients with histologically staged steatohepatitis. Results Four of the spots identified were apolipoprotein isoforms, the pattern of which was able to differentiate the three groups. The 5th spot, seen in the serum of cirrhotic individuals and more markedly in those with HCC, was identified as CD5 antigen like (CD5L). By ELISA assay, although CD5L was markedly elevated in a number of cirrhotic individuals with HCC, its overall ability to distinguish non-cancer from cancer individuals as determined by AUC ROC analysis was poor. However, serum CD5L was dramatically increased, independently of age, sex, and the presence of necroinflammation, in the serum of individuals with NAFLD cirrhosis relative to those with pre-cirrhotic disease. Conclusion This novel proteomic strategy has identified a number of candidate biomarkers which may have benefit in the surveillance and diagnosis of individuals with chronic liver disease and/or HCC. PMID:19656391

2009-01-01

161

Effects of silymarin in alcoholic patients with cirrhosis of the liver: results of a controlled, double-blind, randomized and multicenter trial  

Microsoft Academic Search

Background\\/Aims: Silymarin has protective effects in different experimental conditions, but its efficacy in human liver cirrhosis has not been completely established. Therefore, this study was carried out to determine the effect of silymarin in alcoholics with liver cirrhosis with respect to survival and clinical and laboratory changes.Methods: From February 1986 to June 1989, we enrolled 200 alcoholics with histologically or

Albert Parés; Ramón Planas; Miguel Torres; Joan Caballería; Josep M. Viver; Doroteo Acero; Juliá Panés; Joaquim Rigau; Justiniano Santos; Joan Rodés

1998-01-01

162

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

163

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

164

Minimal Hepatic Encephalopathy in Patients with Cirrhosis by Measuring Liver Stiffness and Hepatic Venous Pressure Gradient  

PubMed Central

Background/Aim: Transient elastography (TE) of liver and hepatic venous pressure gradient (HVPG) allows accurate prediction of cirrhosis and its complications in patients with chronic liver disease. There is no study on prediction of minimal hepatic encephalopathy (MHE) using TE and HVPG in patients with cirrhosis. Patients and Methods: Consecutive cirrhotic patients who never had an episode of hepatic encephalopathy (HE) were enrolled. All patients were assessed by psychometry (number connection test (NCT-A and B), digit symbol test (DST), serial dot test (SDT), line tracing test (LTT)), critical flicker frequency test (CFF), TE by FibroScan and HVPG. MHE was diagnosed if there were two or more abnormal psychometry tests (± 2 SD controls). Results: 150 patients with cirrhosis who underwent HVPG were screened; 91 patients (61%, age 44.0 ± 11.4 years, M:F:75:16, Child's A:B:C 18:54:19) met the inclusion criteria. Fifty three (58%) patients had MHE (Child A (7/18, 39%), Child B (32/54, 59%) and Child C (14/19, 74%)). There was no significant difference between alanine aminotranferease (ALT), aspartate aminotransferase (AST) and total bilirubin level in patients with MHE versus non MHE. Patients with MHE had significantly lower CFF than non MHE patients (38.4 ± 3.0 vs. 40.2 ± 2.2 Hz, P = 0.002). TE and HVPG in patients with MHE did not significantly differ from patients with no MHE (30.9 ± 17.2 vs. 29.8 ± 18.2 KPas, P = 0.78; and 13.6 ± 2.7 vs. 13.6 ± 3.2 mmHg, P = 0.90, respectively).There was significant correlation of TE with Child's score (0.25, P = 0.01), MELD (0.40, P = 0.001) and HVPG (0.72, P = 0.001) while no correlation with psychometric tests, CFF and MHE. Conclusion: TE by FibroScan and HVPG cannot predict minimal hepatic encephalopathy in patients with cirrhosis. PMID:23006459

Sharma, Praveen; Kumar, Ashish

2012-01-01

165

Survival of patients with alcoholic and cryptogenic cirrhosis without liver transplantation: a single center retrospective study  

PubMed Central

Background There is no recent data addressing the long term survival of cirrhosis patients without transplantation, but with the availability of optimal pharmacological and endoscopic therapies. We compared the long term transplant free survival of alcoholic (AC) and cryptogenic (CC) cirrhosis patients in a setting where liver transplantation was, until very recently, not available. AC and CC patient details were extracted from our database, maintained since 1995. For those who had not attended clinics within the past 4 weeks, the patient or families were contacted to obtain survival status. If deceased, cause of death was ascertained from death certificates and patient records. Survival was compared using Kaplan-Meier curves. Results Complete details were available in 549/651 (84.3%) patients (AC 306, CC 243). Mean follow up duration (SD) (months) was 29.9 (32.6). 82/96 deaths (85.4%) among AC and 80/94 deaths (85.1%) among CC were liver related. Multivariate analysis showed age at diagnosis and Child’s class predicted overall survival among all groups. The median survival in Child’s class B and C were 53.5 and 25.3 months respectively. Survival was similar among AC and CC. Among AC survival was improved by abstinence [HR = 0.63 (95% CI: 0.40-1.00)] and was worse with diabetes [HR=1.59 (95% CI: 1.02- 2.48)] irrespective of alcohol status. Conclusions The overall survival of AC was similar to CC. Death in both groups were predominantly liver related, and was predicated by age at diagnosis and Child class. Among AC, presence of diabetes and non-abstinence from alcohol were independent predictors for poor survival. PMID:23198995

2012-01-01

166

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

167

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

PubMed

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

Seo, Yeon Seok; Shah, Vijay H

2012-12-01

168

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

169

Disease-specific health-related quality of life and its determinants in liver cirrhosis patients in Lithuania  

PubMed Central

AIM: To evaluate disease-specific quality of life (QOL) in liver cirrhosis patients and to compare it with those of a healthy population. Also an important objective was to assess whether QOL in liver cirrhosis patients differs by age and gender, by type and severity of disease. METHODS: The case group of 131 liver cirrhosis patients was selected. The control group of 262 was enrolled from a healthy population according to the scheme of case-control study. Clinical, demographic, laboratory data were collected. QOL was measured with a specific chronic liver disease questionnaire (CLDQ), which was translated and validated in Lithuanian. QOL scores were compared between groups by age, gender, type and severity of disease. Cronbach’s alpha statistics calculation was used for evaluation of internal consistency reliability. Student’s t test or ANOVA were used for evaluation hypothesis about probability equation. RESULTS: QOL was significantly lower in liver cirrhosis patients than in healthy population (59.5 ± 18.3 vs 85.3 ± 12.3, P < 0.001). The significant QOL differences between case and control groups were observed in domains of worry and abdominal symptoms, the smaller differences-in emotional functions and systematic symptom domains. Significantly worse QOL was in observed patients with increased clinical severity of the disease measured by Child-Pugh class. Age, gender and etiology of disease had an insignificant effect on QOL in cirrhotic patients. CONCLUSION: QOL was significantly impaired in all CLDQ domains in liver cirrhosis patients. Increase in severity of disease was the major factor associated with poorer QOL. PMID:17203522

Sumskiene, Jolanta; Sumskas, Linas; Petrauskas, Dalius; Kupcinskas, Limas

2006-01-01

170

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

171

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

172

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

PubMed

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

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

2014-01-01

173

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

174

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

175

Gastric ischemia after epinephrine injection in a patient with liver cirrhosis  

PubMed Central

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

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

2013-01-01

176

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

PubMed Central

This study looked at the possible association between alcohol abuse and free radical mediated oxidative injury by examining the presence of oxidative damage, as monitored by erythrocyte malonildialdehyde and plasma lipid hydroperoxides, in patients with liver cirrhosis and different lifetime daily alcohol intake. All patients with an alcohol intake above 100 g/day (ALC) showed concentrations of malonildialdehyde and lipid hydroperoxide on average four to fivefold higher than cirrhotic patients with alcohol intake below 100 g/day (NAC) or healthy controls. Further subgrouping of ALC patients showed that those with alcohol intake ranging between 100 and 200 g/day (ALC1) had malonildialdehyde and lipid hydroperoxide concentrations significantly lower than those with an intake higher than 200 g/day (ALC2). These differences were not related to the extent of liver injury or to the liver derangement as assessed by Child's classification. The increase in lipid peroxidation markers in ALC cirrhotic patients was associated with a decrease in, respectively, plasma alpha-tocopherol and erythrocyte glutathione concentrations. Significant differences were also seen between ALC1 and ALC2 groups in plasma alpha-tocopherol, but not in erythrocyte glutathione concentrations. The concentrations of alpha-tocopherol and glutathione in the blood of NAC patients were in contrast not substantially different from those of healthy controls. The close association between oxidative damage and alcohol abuse suggested that free radical intermediates produced during ethanol metabolism might be responsible for causing oxidative damage. PMID:7828989

Clot, P; Tabone, M; Arico, S; Albano, E

1994-01-01

177

Mechanisms of fibrogenesis in liver cirrhosis: The molecular aspects of epithelial-mesenchymal transition  

PubMed Central

Liver injuries are repaired by fibrosis and regeneration. The cause of fibrosis and diminished regeneration, especially in liver cirrhosis, is still unknown. Epithelial-mesenchymal transition (EMT) has been found to be associated with liver fibrosis. The possibility that EMT could contribute to hepatic fibrogenesis reinforced the concept that activated hepatic stellate cells are not the only key players in the hepatic fibrogenic process and that other cell types, either hepatic or bone marrow-derived cells could contribute to this process. Following an initial enthusiasm for the discovery of this novel pathway in fibrogenesis, more recent research has started to cast serious doubts upon the real relevance of this phenomenon in human fibrogenetic disorders. The debate on the authenticity of EMT or on its contribution to the fibrogenic process has become very animated. The overall result is a general confusion on the meaning and on the definition of several key aspects. The aim of this article is to describe how EMT participates to hepatic fibrosis and discuss the evidence of supporting this possibility in order to reach reasonable and useful conclusions. PMID:24799989

Lee, Sun-Jae; Kim, Kyung-Hyun; Park, Kwan-Kyu

2014-01-01

178

Mechanisms of fibrogenesis in liver cirrhosis: The molecular aspects of epithelial-mesenchymal transition.  

PubMed

Liver injuries are repaired by fibrosis and regeneration. The cause of fibrosis and diminished regeneration, especially in liver cirrhosis, is still unknown. Epithelial-mesenchymal transition (EMT) has been found to be associated with liver fibrosis. The possibility that EMT could contribute to hepatic fibrogenesis reinforced the concept that activated hepatic stellate cells are not the only key players in the hepatic fibrogenic process and that other cell types, either hepatic or bone marrow-derived cells could contribute to this process. Following an initial enthusiasm for the discovery of this novel pathway in fibrogenesis, more recent research has started to cast serious doubts upon the real relevance of this phenomenon in human fibrogenetic disorders. The debate on the authenticity of EMT or on its contribution to the fibrogenic process has become very animated. The overall result is a general confusion on the meaning and on the definition of several key aspects. The aim of this article is to describe how EMT participates to hepatic fibrosis and discuss the evidence of supporting this possibility in order to reach reasonable and useful conclusions. PMID:24799989

Lee, Sun-Jae; Kim, Kyung-Hyun; Park, Kwan-Kyu

2014-04-27

179

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

180

Cancer biomarker profiling in patients with chronic hepatitis C virus, liver cirrhosis and hepatocellular carcinoma.  

PubMed

The detection and diagnosis of hepatocellular carcinoma (HCC) at an early stage may significantly affect the prognosis of HCC patients. Thus, it is necessary to always identify novel putative markers for improving diagnosis. Hepatocarcinogenesis correlates with pathological hepatic angiogenesis. However, each tumor-induced angio-genetic process is influenced by the microenvironment through several pro- and anti-angiogenic factors released from tumor cells, tumor-associated inflammatory cells and/or from the extracellular matrix, and modulated by various signal pathways. In this study, we evaluated the profiling of angiogenic factors using Bio-Plex Pro™ Human Cancer Biomarker Panel 1, a 16-plex magnetic bead-based assay, in sera of patients with chronic hepatitis C (CHC) virus, liver cirrhosis (LC) and HCC. Our results demonstrated: i) high levels of hepatocyte growth factor (HGF) and prolactin only in LC and HCC patients, ii) high levels of soluble human epidermal growth factor receptor?2 (sHER-2/neu; ErbB-2), sIL-6Ra, leptin (LEP) and platelet endothelial cell adhesion molecule?1 (PECAM-1) in CHC, LC and HCC patients and iii) that sIL-6R correlated with the fibrosis stage in CHC patients, with Child?Pugh score in those patients with LC and with tumor size in those patients with HCC, confirming that this protein may be used as a predictor of liver damage and of inflammatory process leading to fibrosis, cirrhosis, and subsequently to cancer. Moreover, an interactomic study conducted using the Ingenuity Pathway Analysis (IPA) software proved the existence of a correlation between 5 significant proteins [ErbB-2, sIL-6Ra, prolactin (PRL), HGF and LEP] which are involved in the same metabolic pathways. PMID:23564159

Costantini, Susan; Capone, Francesca; Maio, Patrizia; Guerriero, Eliana; Colonna, Giovanni; Izzo, Francesco; Castello, Giuseppe

2013-06-01

181

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

182

Glycyrrhizinate reduces portal hypertension in isolated perfused rat livers with chronic hepatitis  

PubMed Central

AIM: To investigate the effects of diammonium glycyrrhizinate (Gly) on portal hypertension (PHT) in isolated portal perfused rat liver (IPPRL) with carbon tetrachloride (CCl4)-induced chronic hepatitis. METHODS: PHT model was replicated with CCl4 in rats for 84 d. Model was identified by measuring the ascetic amounts, hepatic function, portal pressure in vivo, splenic index, and pathological alterations. Inducible nitric oxide synthase (iNOS) in liver was assessed by immunohistochemistry. IPPRLs were performed at d0, d28, d56, and d84. After phenylephrine-induced constriction, Gly was geometrically used to reduce PHT. Gly action was expressed as median effective concentration (EC50) and area under the curve (AUC). Underlying mechanism was exploited by linear correlation between AUC values of Gly and existed iNOS in portal triads. RESULTS: PHT model was confirmed with ascites, splenomegaly, serum biomarkers of hepatic injury, and elevated portal pressure. Pathological findings had shown normal hepatic structure at d0, degenerations at d28, fibrosis at d56, cirrhosis at d84 in PHT rats. Pseudo lobule ratios decreased and collagen ratios increased progressively along with PHT development. Gly does dose-dependently reduce PHT in IPPRLs with CCl4-induced chronic hepatitis. Gly potencies were increased gradually along with PHT development, characterized with its EC50 at 2.80 × 10-10, 3.03 × 10-11, 3.77 × 10-11 and 4.65×10-11 mol/L at d0, d28, d56 and d84, respectively. Existed iNOS was located at hepatocyte at d0, stellate cells at d28, stellate cells and macrophages at d56, and macrophages in portal triads at d84. Macrophages infiltrated more into portal triads and expressed more iNOS along with PHT development. AUC values of Gly were positively correlated with existed iNOS levels in portal triads. CONCLUSION: Gly reduces indirectly PHT in IPPRL with CCl4-induced chronic hepatitis. The underlying mechanisms may relate to rescue NO bioavailability from macrophage-derived peroxynitrite in portal triads. PMID:24106408

Zhao, Xin; Deng, Bo; Xu, Xue-Yan; Yang, Shi-Jun; Zhang, Tao; Song, Yi-Jun; Liu, Xiao-Ting; Wang, Yue-Qi; Cai, Da-Yong

2013-01-01

183

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

E-print Network

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

Boyer, Edmond

184

An unusual hyperplastic hepatocellular nodule in a patient with hepatitis C virus-related liver cirrhosis.  

PubMed

Recent advances in diagnostic imaging techniques have increased the likelihood of detecting novel nodular lesions of the liver. We report here a case of unusual hyperplastic hepatocellular tumor found in a 70-yr-old woman with hepatitis C virus-related cirrhosis. A mass was incidentally detected in the right lobe by abdominal ultrasonography and confirmed by computed axial tomography (CT). Magnetic resonance imaging demonstrated that the tumor had hyperintense signal with a small hypointense region in the center and a thin, hypointense rim on T1-weighted image and a hypointense signal on T2-weighted image. CT during hepatic arteriography showed that the tumor was hypodense with a central hyperdense region, whereas CT during arterial portography revealed that the tumor was isodense and surrounded by a thin circular hypodense band with a central hypodense region. These radiographic findings suggested a diagnosis of dysplastic nodule with malignant foci of hepatocellular carcinoma. The patient underwent tumor resection. Macroscopically, the tumor, 45 x 45 x 30 mm in size, was encapsulated and had a central stellate-like scar with radiating septa. Histological examination showed a hyperplastic hepatocellular tumor without cellular, nuclear or structural atypia. The central fibrous scar contained abundant small, artery-like and vein-like vessels, whereas there were no normal portal triads but rather several portal tract-like structures lacking bile ducts in the parenchyma of the tumor. Some of the portal tract-like structures were composed of artery-like and vein-like vessels, and the others possessed vein-like vessels only. There were no bile ducts in the tumor. The nontumorous liver tissue had evidence of macronodular cirrhosis. Finally, this tumor was regarded as an unusual type of hyperplastic hepatocellular nodule encountered in cirrhotic liver, characterized by the presence of central stellate-like fibrosis and the lack of bile ducts. Although the pathogenesis of the hyperplastic lesion is unclear, it may represent a focal regenerative hepatocellular response to localized circulatory disorder. PMID:9860435

Kageyama, F; Kobayashi, Y; Kawasaki, T; Nakamura, H; Baba, S; Nakamura, S; Nakashima, O; Kojiro, M

1998-12-01

185

Comparative proteomics study on liver mitochondria of primary biliary cirrhosis mouse model  

PubMed Central

Background Primary biliary cirrhosis (PBC) is a liver specific chronic disease with unclear pathogenesis, especially for the early stage molecular events. The mitochondrion is a multi-functional organelle associated with various diseases including PBC. The purpose of this study was to discover the alterations in the mitochondria proteome using an early stage PBC mouse model for revealing the possible pathogenesis mechanisms in the early stages of PBC. Methods Mouse model of early stage of PBC was constructed by consecutive administration of poly I:C. Mitochondria of mouse models and controls were purified and comparative proteomics was performed by iTRAQ technology. Then, differentially expressed proteins were validated by western blotting. Results In total 354 proteins that satisfied the criteria for comparative proteomics study were identified. Of them, nine proteins were downregulated and 20 were up-regulated in liver mitochondria of PBC mouse model. Most differentially expressed proteins are associated with oxidation-reduction and lipid metabolism, and some are involved in the biosynthesis of steroid hormone and primary bile acid. Interestingly, four proteins (HCDH, CPT I, DECR, ECHDC2) involved in the fatty acid beta-oxidation were all upregulated. Conclusions iTRAQ is a powerful tool for comparative proteomics study of PBC mouse model and differentially expressed proteins in mitochondria proteome of PBC mouse model provide insights for the pathogenesis mechanism at early stage of PBC. PMID:23586776

2013-01-01

186

Polymorphism of alcohol dehydrogenase, alcohol and aldehyde dehydrogenase activities: implication in alcoholic cirrhosis in white patients. The French Group for Research on Alcohol and Liver.  

PubMed

Two types of factors can theoretically modulate alcohol metabolism toward increased acetaldehyde production. These factors are the following: (a) individual, genetically determined isoenzymes with distinct catalytic properties, and (b) modifications of enzyme activity induced by alcohol itself or liver damage. To investigate the respective roles of these factors in white individuals, we studied the alcohol dehydrogenase phenotype, together with liver alcohol dehydrogenase and aldehyde dehydrogenase activities, in 161 patients. Patients with alcoholic cirrhosis (n = 31) were compared with three types of controls: patients with nonalcoholic cirrhosis (n = 25) and excessive (n = 62) and moderate drinkers (n = 43) without liver disease. No association between alcohol dehydrogenase-3 phenotype and alcoholic cirrhosis was found. The prevalence of atypical alcohol dehydrogenase in the four groups was less than 1%. Patients with cirrhosis, regardless of its cause, had significantly lower alcohol dehydrogenase activity than the patients without cirrhosis (p less than 0.05 and p less than 0.01 vs. excessive and moderate drinkers, respectively). Among the noncirrhotic patients, alcohol dehydrogenase activity was significantly lower in the excessive drinkers than in the moderate drinkers (p less than 0.001). Aldehyde dehydrogenase activity was not different between cirrhosis-free excessive and moderate drinkers; in contrast, compared with these two groups, it was significantly lower in the two cirrhosis groups (p less than 0.01). These results suggest that no phenotypic pattern of alcohol dehydrogenase-3 associated with alcoholic cirrhosis in white patients exists, that liver alcohol dehydrogenase activity falls as a consequence of both alcohol abuse and cirrhosis and that liver aldehyde dehydrogenase activity is unaffected by alcohol abuse and only falls after the onset of cirrhosis. PMID:1592339

Poupon, R E; Nalpas, B; Coutelle, C; Fleury, B; Couzigou, P; Higueret, D

1992-06-01

187

Pulmonary vascular dilatation and diffusion-dependent impairment of gas exchange in liver cirrhosis.  

PubMed

To test the hypothesis that diffusion-limitation for oxygen is due to abnormal vascular dilatation and significantly contributes to the arterial hypoxaemia of liver cirrhosis requires an experimental approach that detects both diffusion-limitation for oxygen and the presence of abnormal dilatation of pulmonary vessels exposed to alveolar gas. We therefore studied the gas exchange of a 64 year old man with alcoholic liver cirrhosis and severe resting arterial hypoxaemia (arterial oxygen tension (Pa,O2) 7.5 kPa) whilst breathing air and 100% O2 using conventional blood gas (CBG) analysis, the multiple inert gas elimination technique (MIGET) and whole body scintigraphy (WBS) following the i.v. administration of radiolabelled boli of macroaggregates with a minimum diameter of 15 microM. During air breathing, there was a consistently positive difference between the arterial oxygen tension predicted by MIGET and that actually measured (P-M Pa,O2, average 0.9 kPa). During O2 breathing, P-M Pa,O2 became negative, (average -12.2 kPa), and shunt estimated by the O2 method (% of Q') was consistently less than that measured by MIGET. Whereas both O2 method and MIGET estimates of shunt never exceeded 25%, the WBS shunt was 40%, indicating that a substantial fraction of cardiac output flowed through abnormally dilated pulmonary vessels, some of which were exposed to alveolar gas and, hence, participated in gas exchange. Although our observations pertain to one subject, we believe they provide the most convincing in vivo evidence to date that abnormal dilatation of interalveolar vessels may, per se, result in a significant diffusion impairment for O2. Furthermore, in view of the consistently negative P-M Pa,O2 observed during oxygen breathing, we speculate that such abnormal vascular dilatation may also have produced a significant diffusive impairment of one or more of the less soluble inert gases used in the MIGET analysis. PMID:8666095

Crawford, A B; Regnis, J; Laks, L; Donnelly, P; Engel, L A; Young, I H

1995-12-01

188

Hyperreninemic hypoaldosteronism syndrome, plasma concentrations of interleukin-6 and outcome in critically ill patients with liver cirrhosis  

Microsoft Academic Search

Objective  To investigate the relation between the adrenal production of gluco- and mineralocorticoids, the inflammatory status and the\\u000a outcome in critically ill patients with liver cirrhosis.\\u000a \\u000a \\u000a \\u000a Design  Prospective descriptive study.\\u000a \\u000a \\u000a \\u000a Setting  Medical intensive care unit (ICU) in a university hospital.\\u000a \\u000a \\u000a \\u000a Patients  Fifty consecutive patients with liver cirrhosis.\\u000a \\u000a \\u000a \\u000a Interventions  A corticotropin stimulation test within 12?h following ICU admission. Plasma cortisol concentration was measured before and\\u000a after the test.

Damien du Cheyron; Bruno Bouchet; Brigitte Cauquelin; Damien Guillotin; Michel Ramakers; Cédric Daubin; Jean-Jacques Ballet; Pierre Charbonneau

2008-01-01

189

A case of liver cirrhosis with chylous ascites and multiple cystic dilatation of the abdominal lymphatic system.  

PubMed

A 51-year-old male suffering from abdominal distension and diagnosed by laparoscopic and histological examination as a liver cirrhosis patient, had a chylous ascites with a negative Gordon test. The content of chylomicron in ascites decreased by restriction of dietary fat, although the ascites retention was resistant to salt restriction, diuretics and intravenous re-infusion of ascites. Lymphangiography revealed dysplasia of the retroperitoneal lymphatic system and dilatation of the thoracic duct. Main autopsy findings were liver cirrhosis (post-necrotic type) without malignancy and marked cystic dilatations of the lymphatic duct. The lymph congestion in the intestine was more remarkable in the subserosal space and the leakage of the chyle into the abdominal cavity was also proved by histological examination. PMID:7203372

Watanabe, M; Taketa, K; Yonei, J; Kubota, M; Nagashima, H; Akamutsu, K; Awai, M

1980-10-01

190

Genetic variations in bile acid homeostasis are not overrepresented in alcoholic cirrhosis compared to patients with heavy alcohol abuse and absent liver disease.  

PubMed

Increased serum bile salt levels have been associated to a single-nucleotide polymorphism in the bile salt export pump (BSEP; ABCB11) in several acquired cholestatic liver diseases but there is little evidence in alcoholic liver disease (ALD). Furthermore, a crosstalk between vitamin D and bile acid synthesis has recently been discovered. Whether this crosstalk has an influence on the course of ALD is unclear to date. Our aim was to analyse the role of genetic polymorphisms in BSEP and the vitamin D receptor gene (NR1I1) on the emergence of cirrhosis in patients with ALD. Therefore, 511 alcoholic patients (131 with cirrhosis and 380 without cirrhosis) underwent ABCB11 genotyping (rs2287622). Of these, 321 (131 with cirrhosis and 190 without cirrhosis) were also tested for NR1I1 polymorphisms (bat-haplotype: BsmI rs1544410, ApaI rs7975232 and TaqI rs731236). Frequencies of ABCB11 and NR1I1 genotypes and haplotypes were compared between alcoholic patients with and without cirrhosis and correlated to serum bile salt, bilirubin and aspartate aminotransferase levels in those with cirrhosis. Frequencies of ABCB11 and NR1I1 genotypes and haplotypes did not differ between the two subgroups and no significant association between genotypes/haplotypes and liver function tests could be determined for neither polymorphism. We conclude that ABCB11 and NR1I1 polymorphisms are obviously not associated with development of cirrhosis in patients with ALD. PMID:22522591

Many, Natalie; Stickel, Felix; Schmitt, Johannes; Stieger, Bruno; Soyka, Michael; Frei, Pascal; Götze, Oliver; Müllhaupt, Beat; Geier, Andreas

2012-09-01

191

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

Microsoft Academic Search

BACKGROUND: The exogenous administration of Insulin-like Growth Factor-I (IGF-I) induces hepatoprotective and antifibrogenic actions in experimental liver cirrhosis. To better understand the possible pathways behind the beneficial effect of IGF-I, the aim of this work was to investigate severe parameters involved in oxidative damage in hepatic tissue from cirrhotic animals treated with IGF-I (2 ?g. 100 g-1. day-1). Iron and

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

2005-01-01

192

Transplanted Human Amniotic Membrane-Derived Mesenchymal Stem Cells Ameliorate Carbon Tetrachloride-Induced Liver Cirrhosis in Mouse  

Microsoft Academic Search

BackgroundHuman amniotic membrane-derived mesenchymal stem cells (hAMCs) have the potential to reduce heart and lung fibrosis, but whether could reduce liver fibrosis remains largely unknown.Methodology\\/Principal FindingsHepatic cirrhosis model was established by infusion of CCl4 (1 ml\\/kg body weight twice a week for 8 weeks) in immunocompetent C57Bl\\/6J mice. hAMCs, isolated from term delivered placenta, were infused into the spleen at

Dingguo Zhang; Minyue Jiang; Dengshun Miao; Syed Aziz

2011-01-01

193

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

194

E3 Ubiquitin Ligase Synoviolin Is Involved in Liver Fibrogenesis  

PubMed Central

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

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

2010-01-01

195

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

PubMed Central

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

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

2013-01-01

196

Natural History of Portal Hypertensive Gastropathy in Patients With Liver Cirrhosis  

Microsoft Academic Search

Background & Aims: The clinical importance of portal hypertensive gastropathy (PHG) as a source of gastrointestinal bleeding in patients with cirrhosis is poorly defined. We investigated the natural history of this condition in a large series of patients. Methods: All patients with cirrhosis seen at 7 hospitals during June and July 1992 were followed up with clinical and endoscopic examinations

2000-01-01

197

Transplanted hepatocytes engraft, survive, and proliferate in the liver of rats with carbon tetrachloride-induced cirrhosis.  

PubMed

Repopulation of the cirrhotic liver with disease-resistant hepatocytes could offer novel therapies, as well as systems for biological studies. Establishing whether transplanted hepatocytes can engraft, survive, and proliferate in the cirrhotic liver is a critical demonstration. Dipeptidyl peptidase IV-deficient F344 rats were used to localize transplanted hepatocytes isolated from the liver of syngeneic normal F344 rats. Cirrhosis was induced by administration of carbon tetrachloride with phenobarbitone and these drugs were withdrawn prior to cell transplantation. Cirrhotic rats showed characteristic hepatic histology, as well as significant portosystemic shunting. When hepatocytes were transplanted via the spleen, cells were distributed immediately in periportal areas, fibrous septa, and regenerative nodules of the cirrhotic liver. Although some transplanted cells translocated into pulmonary capillaries, this was not deleterious. At 1 week, transplanted cells were fully integrated in the liver parenchyma, along with expression of glucose-6-phosphatase and glycogen as reporters of hepatic function. Transplanted cells proliferated in the liver of cirrhotic animals and survived indefinitely. At 1 year, transplanted hepatocytes formed large clusters containing several-fold more cells than normal control animals, which was in agreement with increased cell turnover in the cirrhotic rat liver. The findings indicate that the cirrhotic liver can be repopulated with functionally intact hepatocytes that are capable of proliferating. Liver repopulation using disease-resistant hepatocytes will be applicable in chronic conditions, such as viral hepatitis or Wilson's disease. PMID:10767723

Gagandeep, S; Rajvanshi, P; Sokhi, R P; Slehria, S; Palestro, C J; Bhargava, K K; Gupta, S

2000-05-01

198

Long-term treatment with cisapride and antibiotics in liver cirrhosis: effect on small intestinal motility, bacterial overgrowth, and liver function  

Microsoft Academic Search

OBJECTIVES:Altered small-bowel motility, lengthening of the orocecal transit time, and small-intestinal bacterial overgrowth have been described in patients with liver cirrhosis. These changes might be related to the progressive course and poor prognosis of the disease. We investigated the effect of a long-term treatment with cisapride and an antibiotic regimen on small-intestinal motor activity, orocecal transit time, bacterial overgrowth, and

Ana Maria Madrid; Carmen Hurtado; Mauricio Venegas; Francisco Cumsille; Carlos Defilippi

2001-01-01

199

In Vivo Evaluation of Ethanolic Extract of Zingiber officinale Rhizomes for Its Protective Effect against Liver Cirrhosis  

PubMed Central

Zingiber officinale is a traditional medicine against various disorders including liver diseases.The aim of this study was to assess the hepatoprotective activity of the ethanolic extract of rhizomes of Z. officinale (ERZO) against thioacetamide-induced hepatotoxicity in rats. Five groups of male Sprague Dawley have been used. In group 1 rats received intraperitoneal (i.p.) injection of normal saline while groups 2–5 received thioacetamide (TAA, 200?mg/kg; i.p.) for induction of liver cirrhosis, thrice weekly for eight weeks. Group 3 received 50?mg/kg of silymarin. The rats in groups 4 and 5 received 250 and 500?mg/kg of ERZO (dissolved in 10% Tween), respectively. Hepatic damage was assessed grossly and microscopically for all of the groups. Results confirmed the induction of liver cirrhosis in group 2 whilst administration of silymarin or ERZO significantly reduced the impact of thioacetamide toxicity. These groups decreased fibrosis of the liver tissues. Immunohistochemistry assessment against proliferating cell nuclear antigen did not show remarkable proliferation in the ERZO-treated rats when compared with group 2. Moreover, factions of the ERZO extract were tested on Hep-G2 cells and showed antiproliferative activity (IC50 38–60??g/mL). This study showed hepatoprotective effect of ERZO. PMID:24396831

Abdulaziz Bardi, Daleya; Halabi, Mohammed Farouq; Abdullah, Nor Azizan; Rouhollahi, Elham

2013-01-01

200

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

201

A discriminant score based on four routine laboratory blood tests for accurate diagnosis of severe fibrosis and\\/or liver cirrhosis in Egyptian patients with chronic hepatitis C  

Microsoft Academic Search

Liver biopsy is still recommended in most patients with chronic hepatitis C (CHC). Due to its limitations and risks, the use of non-invasive blood biomarkers has been suggested for predicting liver cirrhosis in these patients. Here, we analyzed a panel of routine blood biochemical and hematological markers of 455 Egyptians (272 males and 183 females aged 26–67 years; mean age

Abdelfattah M. Attallah; Gamal E. Shiha; Mohamed M. Omran; Khaled R. Zalata

2006-01-01

202

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

203

Increased activated natural killer T cells in the liver of patients with advanced stage primary biliary cirrhosis.  

PubMed

Although growing evidence suggests a major role for T cells in the pathogenesis of primary biliary cirrhosis (PBC), the roles of natural killer (NK) and natural killer T (NKT) cells, which predominate in the liver, in the pathogenesis of PBC remain unclear. We investigated the status of NK and NKT cells in the liver and peripheral blood samples obtained from 11 patients with asymptomatic PBC diagnosed as stage I or II (early PBC) and 7 patients with symptomatic PBC who underwent liver transplantation (advanced PBC) using flow cytometry and immunohistochemical staining. The proportions of NK and NKT cells were significantly decreased in the liver of patients with early PBC compared with normal donors. However, the proportion of CD56+ NKT cells was increased in the liver of patients with advanced PBC. Moreover, the proportion of activated Fas ligand (FasL)-positive NKT cells was significantly increased in the liver of patients with advanced PBC compared with early PBC (P=0.013). We also found increased expression of FasL on lymphocytes infiltrating around the injured bile duct in advanced PBC using immunohistochemical staining. Our results suggest that activated NKT cells may contribute to the biliary epithelial cell death resulting in the progression of PBC. PMID:24759184

Aso-Ishimoto, Yuiko; Yamagiwa, Satoshi; Ichida, Takafumi; Miyakawa, Ryoko; Tomiyama, Chikako; Sato, Yoshinobu; Watanabe, Hisami; Aoyagi, Yutaka

2014-01-01

204

Characteristic gene expression profiles in the progression from liver cirrhosis to carcinoma induced by diethylnitrosamine in a rat model  

PubMed Central

Background Liver cancr is a heterogeneous disease in terms of etiology, biologic and clinical behavior. Very little is known about how many genes concur at the molecular level of tumor development, progression and aggressiveness. To explore the key genes involved in the development of liver cancer, we established a rat model induced by diethylnitrosamine to investigate the gene expression profiles of liver tissues during the transition to cirrhosis and carcinoma. Methods A rat model of liver cancer induced by diethylnitrosamine was established. The cirrhotic tissue, the dysplasia nodules, the early cancerous nodules and the cancerous nodules from the rats with lung metastasis were chosen to compare with liver tissue of normal rats to investigate the differential expression genes between them. Affymetrix GeneChip Rat 230 2.0 arrays were used throughout. The real-time quantity PCR was used to verify the expression of some differential expression genes in tissues. Results The pathological changes that occurred in the livers of diethylnitrosamine-treated rats included non-specific injury, fibrosis and cirrhosis, dysplastic nodules, early cancerous nodules and metastasis. There are 349 upregulated and 345 downregulated genes sharing among the above chosen tissues when compared with liver tissue of normal rats. The deregulated genes play various roles in diverse processes such as metabolism, transport, cell proliferation, apoptosis, cell adhesion, angiogenesis and so on. Among which, 41 upregulated and 27 downregulated genes are associated with inflammatory response, immune response and oxidative stress. Twenty-four genes associated with glutathione metabolism majorly participating oxidative stress were deregulated in the development of liver cancer. There were 19 members belong to CYP450 family downregulated, except CYP2C40 upregulated. Conclusion In this study, we provide the global gene expression profiles during the development and progression of liver cancer in rats. The data obtained from the gene expression profiles will allow us to acquire insights into the molecular mechanisms of hepatocarcinogenesis and identify specific genes (or gene products) that can be used for early molecular diagnosis, risk analysis, prognosis prediction, and development of new therapies. PMID:19638242

Liu, Yue-Fang; Zha, Bin-Shan; Zhang, Hui-Lin; Zhu, Xiao-Jing; Li, Yu-Hua; Zhu, Jin; Guan, Xiao-Hong; Feng, Zhen-Qing; Zhang, Jian-Ping

2009-01-01

205

Major Histocompatibility Class II Pathway Is Not Required for the Development of Nonalcoholic Fatty Liver Disease in Mice  

PubMed Central

Single-nucleotide polymorphisms within major histocompatibility class II (MHC II) genes have been associated with an increased risk of drug-induced liver injury. However, it has never been addressed whether the MHC II pathway plays an important role in the development of nonalcoholic fatty liver disease, the most common form of liver disease. We used a mouse model that has a complete knockdown of genes in the MHC II pathway (MHCII?/?). Firstly we studied the effect of high-fat diet-induced hepatic inflammation in these mice. Secondly we studied the development of carbon-tetra-chloride- (CCl4-) induced hepatic cirrhosis. After the high-fat diet, both groups developed obesity and hepatic steatosis with a similar degree of hepatic inflammation, suggesting no impact of the knockdown of MHC II on high-fat diet-induced inflammation in mice. In the second study, we confirmed that the CCl4 injection significantly upregulated the MHC II genes in wild-type mice. The CCl4 treatment significantly induced genes related to the fibrosis formation in wild-type mice, whereas this was lower in MHCII?/? mice. The liver histology, however, showed no detectable difference between groups, suggesting that the MHC II pathway is not required for the development of hepatic fibrosis induced by CCl4. PMID:23710178

Willemin, Gilles; Roger, Catherine; Bauduret, Armelle; Minehira, Kaori

2013-01-01

206

Two classifiers based on serum peptide pattern for prediction of HBV-induced liver cirrhosis using MALDI-TOF MS.  

PubMed

Chronic infection with hepatitis B virus (HBV) is associated with the majority of cases of liver cirrhosis (LC) in China. Although liver biopsy is the reference method for evaluation of cirrhosis, it is an invasive procedure with inherent risk. The aim of this study is to discover novel noninvasive specific serum biomarkers for the diagnosis of HBV-induced LC. We performed bead fractionation/MALDI-TOF MS analysis on sera from patients with LC. Thirteen feature peaks which had optimal discriminatory performance were obtained by using support-vector-machine-(SVM-) based strategy. Based on the previous results, five supervised machine learning methods were employed to construct classifiers that discriminated proteomic spectra of patients with HBV-induced LC from those of controls. Here, we describe two novel methods for prediction of HBV-induced LC, termed LC-NB and LC-MLP, respectively. We obtained a sensitivity of 90.9%, a specificity of 94.9%, and overall accuracy of 93.8% on an independent test set. Comparisons with the existing methods showed that LC-NB and LC-MLP held better accuracy. Our study suggests that potential serum biomarkers can be determined for discriminating LC and non-LC cohorts by using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. These two classifiers could be used for clinical practice in HBV-induced LC assessment. PMID:23509784

Cao, Yuan; He, Kun; Cheng, Ming; Si, Hai-Yan; Zhang, He-Lin; Song, Wei; Li, Ai-Ling; Hu, Cheng-Jin; Wang, Na

2013-01-01

207

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

PubMed Central

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

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

1977-01-01

208

Primary biliary cirrhosis  

Microsoft Academic Search

Primary biliary cirrhosis (PBC) is an immune-mediated chronic cholestatic liver disease with a slowly progressive course.\\u000a Without treatment, most patients eventually develop fibrosis and cirrhosis of the liver and may need liver transplantation\\u000a in the late stage of disease. PBC primarily affects women (female preponderance 9–10:1) with a prevalence of up to 1 in 1,000\\u000a women over 40 years of age.

Simon Hohenester; Ronald P. J. Oude-Elferink; Ulrich Beuers

2009-01-01

209

Primary biliary cirrhosis  

Microsoft Academic Search

Primary biliary cirrhosis (PBC) is an immune-mediated chronic cholestatic liver disease with a slowly progressive course. Without treatment, most patients eventually develop fibrosis and cirrhosis of the liver and may need liver transplantation in the late stage of disease. PBC primarily affects women (female preponderance 9-10:1) with a prevalence of up to 1 in 1,000 women over 40 years of

S. Hohenester; R. P. J. Oude-Elferink; U. Beuers

2009-01-01

210

Assessment of Clinical Signs of Liver Cirrhosis Using T1 Mapping on Gd-EOB-DTPA-Enhanced 3T MRI  

PubMed Central

Objectives To assess the differences between normal and cirrhotic livers by means of T1 mapping of liver parenchyma on gadoxetic acid (Gd-EOB-DTPA)-enhanced 3 Tesla (3T) MR imaging (MRI). Methods 162 patients with normal (n = 96) and cirrhotic livers (n = 66; Child-Pugh class A, n = 30; B, n = 28; C, n = 8) underwent Gd-EOB-DTPA-enhanced 3T MRI. To obtain T1 maps, two TurboFLASH sequences (TI = 400 ms and 1000 ms) before and 20 min after Gd-EOB-DTPA administration were acquired. T1 relaxation times of the liver and the reduction rate between pre- and post-contrast enhancement images were measured. Results The T1 relaxation times for Gd-EOB-DTPA-enhanced MRI showed significant differences between patients with normal liver function and patients with Child-Pugh class A, B, and C (p < 0.001). The T1 relaxation times showed a constant significant increase from Child-Pugh class A up to class C (Child-Pugh class A, 335 ms ± 80 ms; B, 431 ms ± 75 ms; C, 557 ms ± 99 ms; Child-Pugh A to B, p < 0.001; Child-Pugh A to C, p < 0.001; Child-Pugh B to C, p < 0.001) and a constant decrease of the reduction rate of T1 relaxation times (Child-Pugh class A, 57.1% ± 8.8%; B, 44.3% ± 10.2%, C, 29.9% ± 6.9%; Child-Pugh A to B, p < 0.001; Child-Pugh A to C,p < 0.001; Child-Pugh B to C, p < 0.001). Conclusion Gd-EOB-DTPA-enhanced T1 mapping of the liver parenchyma may present a useful method for determining severity of liver cirrhosis. PMID:24392025

Haimerl, Michael; Verloh, Niklas; Zeman, Florian; Fellner, Claudia; Muller-Wille, Rene; Schreyer, Andreas G.; Stroszczynski, Christian; Wiggermann, Philipp

2013-01-01

211

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

212

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

213

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

214

One-month mortality rate after liver transplantation for parenchymal cirrhosis: analysis of risk factors in a ten year period.  

PubMed

Accurate prediction of short-term survival rate after liver transplantation is one way of selecting recipients and should improve organ allocation. We observed, during the first ten years of our program a striking decline in postoperative mortality with time, a well known observation in Europe as well as in the United States. In 65 adults with parenchymal cirrhosis having received a liver transplant between 1984 and 1994, we examined the possible influence of various preoperative risk factors on one-month mortality rate which was 13.8% in this series. Univariate analysis led to the identification of five significant risk factors: date of transplantation, low serum sodium, previous history of jaundice, ascites and encephalopathy. In the final multivariate analysis however, the date of transplantation emerged as the sole predictive factor of early mortality rate. Therefore, factors such as pretransplantation state of the patient and poor hepatic reserve are counterbalanced by the improvement of surgical skill and other technical aspects, as well as by better perioperative management which have all contributed to the improved results of liver transplantation with time. PMID:10692766

Eskinazi, R; Bourgeois, N; Le Moine, O; Vereerstraeten, P; Van de Stad, J; Gelin, M; Adler, M

1999-01-01

215

LIVER TRANSPLANTATION IN A RANDOMIZED CONTROLLED TRIAL OF EMERGENCY TREATMENT OF ACUTELY BLEEDING ESOPHAGEAL VARICES IN CIRRHOSIS  

PubMed Central

Background Bleeding esophageal varices (BEV) in cirrhosis has been considered an indication for liver transplantation (LT). This issue was examined in a randomized controlled trial (RCT) of unselected, consecutive patients with advanced cirrhosis and BEV that compared endoscopic sclerotherapy (EST) (n=106) to emergency direct portacaval shunt (EPCS) (n=105). Methods Diagnostic workup and treatment were initiated within 8 hours. Patients were evaluated for LT on admission and repeatedly thereafter. 96% underwent over 10 years of regular follow-up. The analysis was supplemented by 1300 unrandomized cirrhotic patients who previously underwent portacaval shunt (PCS) with 100% follow-up. Results In the RCT, long-term bleeding control was 100% following EPCS, only 20% following EST. 3, 5, 10, and 15-year survival rates were 75%, 73%, 46%, and 46% following EPCS, compared to 44%, 21%, 9%, and 9% following EST (p<0.001). Only 13 RCT patients (6%) were ultimately referred for LT mainly because of progressive liver failure; only 7 (3%) were approved for LT and only 4 (2%) underwent LT. 1- and 5-year LT survival rates were 0.68% and 0, compared to 81% and 73% after EPCS. In the 1300 unrandomized PCS patients. 50 (3.8%) were referred and 19 (1.5%) underwent LT. Five-year survival rate was 53% compared to 72% for all 1300 patients. Conclusions If bleeding is permanently controlled, as occurred invariably following EPCS, cirrhotic patients with BEV seldom require LT. PCS is effective first-line and long-term treatment. Should LT be required in patients with PCS, although technically more demanding, numerous studies have shown that PCS does not increase mortality or complications. EST is not effective emergency or long-term therapy. PMID:21168637

Orloff, Marshall J.; Isenberg, Jon I.; Wheeler, Henry O.; Haynes, Kevin S.; Jinich-Brook, Horacio; Rapier, Roderick; Vaida, Florin; Hye, Robert J.; Orloff, Susan L.

2010-01-01

216

Impact of Rifaximin on the Frequency and Characteristics of Spontaneous Bacterial Peritonitis in Patients with Liver Cirrhosis and Ascites  

PubMed Central

Background Rifaximin is a non-absorbable antibiotic used to prevent relapses of hepatic encephalopathy which may also be a candidate for prophylaxis of spontaneous bacterial peritonitis (SBP). Aim To detect the impact of rifaximin on the occurrence and characteristics of SBP. Methods We prospectively studied all hospitalized patients that underwent a diagnostic paracentesis in our department from March 2012 to April 2013 for SBP and recorded all clinical data including type of SBP prophylaxis, prior use of rifaximin, concomitant complications of cirrhosis, as well as laboratory results and bacteriological findings. Patients were divided into the following three groups: no antibiotic prophylaxis, prophylaxis with rifaximin or with systemically absorbed antibiotic prophylaxis. Results Our study cohort comprised 152 patients with advanced liver cirrhosis, 32 of whom developed SBP during the study period. As expected, our study groups differed regarding a history of hepatic encephalopathy and SBP before inclusion into the study. None of the 17 patients on systemic antibiotic prophylaxis developed SBP while 8/27 patients on rifaximin and 24/108 without prophylaxis had SBP (p?=?0.02 and p?=?0.04 versus systemic antibiotics, respectively). In general, episodes of SBP were similar for patients treated with rifaximin and those without any prophylaxis. However, Escherichia coli and enterococci were dominant in the ascites of patients without any prophylaxis, while mostly klebsiella species were recovered from the ascites samples in the rifaximin group. Conclusion Rifaximin pretreatment did not lead to a reduction of SBP occurrence in hospitalized patients with advanced liver disease. However, the bacterial species causing SBP were changed by rifaximin. PMID:24714550

Lutz, Philipp; Parcina, Marijo; Bekeredjian-Ding, Isabelle; Nischalke, Hans Dieter; Nattermann, Jacob; Sauerbruch, Tilman; Hoerauf, Achim; Strassburg, Christian P.; Spengler, Ulrich

2014-01-01

217

Testosterone in the management of cirrhosis of the liver--a controlled study.  

PubMed

The results of the controlled study covering 21 cases of decompensated hepatic cirrhosis are repoted. Nine controls received conventional therapy with diuretics and vitamin supplement. Testosteron 100 mg intramuscularly, on alternate days for four weeks, was administered to 12 others, in addition to the conventional therapy. Patients in the testosterone group responded with reduction in ascites and pedal edema together with a subjective feeling of improvement. Serum albumin rose at the end of the four weeks while globulin fell in those that received the hormone. The difference in respect of both serum albumin and globulin in the testosterone group became statistically significant at the end of four weeks. PMID:350213

Puliyel, M M; Vyas, G P; Mehta, G S

1977-12-01

218

HEMOGLOBIN PRODUCTION FACTORS IN THE HUMAN LIVER : ANEMIAS, HYPOPROTEINEMIA, CIRRHOSIS, PIGMENT ABNORMALITIES, AND PREGANCY.  

PubMed

Human liver tissue has been assayed to determine the amount of hemoglobin production factors in normal and abnormal states. Standardized dogs made anemic by blood removal have been used in this biological assay. Normal animal liver as control is rated as 100 per cent. Normal human liver tissue as compared with the normal animal control contains more of these hemoglobin production factors-a biological assay ratio of 120 to 160 per cent. Infections, acute and chronic, do not appear to modify these values, the concentration of hemoglobin-producing factors falling within the normal range. Pernicious anemia and aplastic anemia both show large liver stores of hemoglobin-producing factors-a biological assay ratio of 200 to 240 per cent. Therapy in pernicious anemia reduces these liver stores as new red cells are formed. Secondary anemia presents a low normal or subnormal liver store of hemoglobin-producing factors-an assay of 60 to 130 per cent. Hemochromatosis, erythroblastic anemia, and hemolytic icterus in spite of large iron deposits in the liver usually show a biological assay which is normal or close to normal. Polycythemia shows low reserve stores of hemoglobin-producing factors. Leukemias present a wide range of values discussed above. Hypoproteinemia almost always is associated with low reserve stores of hemoglobin-producing factors in the liver-biological assays of 60 to 80 per cent. Hypoproteinemia means a depletion of body protein reserve stores including the labile protein liver reserves-a strong indication that the prehemoglobin material (or globin) is related to these liver stores. Pregnancy, eclampsia, and lactation all may present subnormal liver stores of hemoglobin-producing factors. Exhaustion of protein stores lowers the barrier to infection and renders the liver very susceptible to many toxic substances. It should not be difficult to correct hypoproteinemia under these conditions and thus relieve the patient of a real hazard. PMID:19871236

Whipple, G H; Robscheit-Robbins, F S

1942-09-01

219

Stability of cirrhotic systemic hemodynamics ensures sufficient splanchnic blood flow after living-donor liver transplantation in adult recipients with liver cirrhosis  

PubMed Central

AIM: To investigate the correlation between systemic hemodynamics and splanchnic circulation in recipients with cirrhosis undergoing living-donor liver transplantation (LDLT), and to clarify how systemic hemodynamics impact on local graft circulation after LDLT. METHODS: Systemic hemodynamics, indocyanine green (ICG) elimination rate (KICG) and splanchnic circulation were simultaneously and non-invasively investigated by pulse dye densitometry (PDD) and ultrasound. Accurate estimators of optimal systemic hyperdynamics after LDLT [i.e., balance of cardiac output (CO) to blood volume (BV) and mean transit time (MTT), defined as the time required for half the administered ICG to pass through an attached PDD sensor in the first circulation] were also measured. Thirty recipients with cirrhosis were divided into two groups based on clinical outcomes corresponding to postoperative graft function. RESULTS: Cirrhotic systemic hyperdynamics characterized by high CO, expanded BV and low total peripheral resistance (TPR) were observed before LDLT. TPR reflecting cirrhotic vascular alterations was slowly restored after LDLT in both groups. Although no significant temporal differences in TPR were detected between the two groups, CO/BV and MTT differed significantly. Recipients with good outcomes showed persistent cirrhotic systemic hyperdynamics after LDLT, whereas recipients with poor outcomes presented with unstable cirrhotic systemic hyperdynamics and severely decreased KICG. Systemic hyperdynamic disorders after LDLT impacted on portal venous flow but not hepatic arterial flow. CONCLUSION: We conclude that subtle systemic hyperdynamics disorders impact on splanchnic circulation, and that an imbalance between CO and BV decreases portal venous flow, which results in critical outcomes. PMID:17990357

Hori, Tomohide; Yagi, Shintaro; Iida, Taku; Taniguchi, Kentaro; Yamagiwa, Kentaro; Yamamoto, Chiduru; Hasegawa, Takashi; Yamakado, Koichiro; Kato, Takuma; Saito, Kanako; Wang, Linan; Torii, Mie; Hori, Yukinobu; Takeda, Kan; Maruyama, Kazuo; Uemoto, Shinji

2007-01-01

220

The long-term effects of splenectomy and subsequent interferon therapy in patients with HCV-related liver cirrhosis.  

PubMed

Partial splenic embolization (PSE) or splenectomy is widely performed to increase platelet counts for interferon (IFN) therapy. The aim of the present study was to evaluate the long-term effects of splenectomy and subsequent IFN therapy in patients with hepatitis C virus (HCV)-related liver cirrhosis (LC). The present study included 19 patients with HCV-related LC who underwent splenectomy for thrombo-cytopenia caused by hypersplenism. IFN therapy was performed in all 19 patients. The effects of splenectomy and subsequent IFN therapy on peripheral blood counts, liver function, carcinogenesis and survival rates were evaluated. Splenectomy was safely performed in all patients without major complications with the exception of portal thrombosis, which, however, it did not affect liver function when treated appropriately. Thrombocytopenia improved and IFN therapy could be performed in all the patients. A sustained virological response (SVR) was not observed in patients with genotype 1 although it was observed in 75% of patients with genotype 2. Due to severe side effects, five patients did not undergo scheduled IFN therapy. Over 5 years, the mean platelet number increased from 5.2 x 10(4) to 16.8 x 10(4)/mm3 (P<0.01) and liver function improved following splenectomy (albumin, Alb: 3.5?3.8 g/dl; total bilirubin, T-Bil: 1.0?0.7 mg/dl; prothrombin time, PT: 74.1?97.7%; total cholesterol; T-cho: 140?168 mg/dl; P<0.05). Hepatocellular carcinoma (HCC) occurred in only one patient during long?term observation and follow?up of the patients not presenting with HCC at entry. The results of the present study demonstrate that splenectomy followed by interferon therapy could be beneficial in patients with HCV-related LC. PMID:24336960

Inagaki, Yuji; Sugimoto, Kazushi; Shiraki, Katsuya; Tameda, Masahiko; Kusagawa, Satoko; Nojiri, Keiichiro; Ogura, Suguru; Yamamoto, Norihiko; Takei, Yoshiyuki; Ito, Masaaki; Mizuno, Shugo; Usui, Masanobu; Sakurai, Hiroyuki; Isaji, Shuji

2014-02-01

221

Mini-Mental State Examination in patients with hepatic encephalopathy and liver cirrhosis: a prospective, quantified electroencephalography study  

PubMed Central

Background Mini-Mental State Examination (MMSE) is one of the most commonly used methods in the assessment of cognitive mental status. MMSE has been used in hepatology but its usefulness in the evaluation of hepatic encephalopathy (HE) has never been properly assessed. The aim of the study was to investigate the value of MMSE in detection of HE in patients with cirrhosis. Methods One hundred and one consecutive patients with liver cirrhosis underwent neurological examination, MMSE and electroencephalography (EEG). Spectral analysis of EEG was done with calculation of mean dominant frequency (MDF) and relative power of delta, theta, alpha and beta rhythms. Minimal HE was diagnosed in patients with normal neurological status and alterations in spectral EEG. Statistical analysis included Fisher’s exact and Anova analysis. Categorical data were compared using Levene’s test for equality of variances. Correlation-coefficient analysis was performed by the Pearson’s r or Z-test, as needed. Tests performance was assessed by the calculating the area under the ROC curve (AUC) and evaluating its difference from reference area (AUC=0.5). A p value <0.05 was considered statistically significant. Results Overt HE was identified in 49 (48.5%) and minimal HE in 22 (21.8%) patients. Although there were significant correlations between both severity of liver disease (Child-Pugh classification), overt HE (West-Haven criteria) and various MMSE items, MDF showed no correlation with any of MMSE items as well as MMSE summary score. MMSE (score and items) did not discriminate patients without HE and minimal HE. The only significant differences between patients without HE and with overt HE were seen in respect of MMSE score (p<0.02), orientation to place (p<0.003), repetition (p<0.01) and complex commands-understanding (p<0.02). Test performance analysis has shown that MMSE has no value as a prediction method in determining minimal HE and in respect of overt HE has a sensitivity of 63% and specificity of 52% by a cut-off level at 27.5 points to diagnose overt HE. Conclusions In conclusion, although MMSE score and single items are altered in patients with overt HE, MMSE has no value in the assessment of minimal HE. Because MMSE could be impaired in several cognitive dysfunctions, more specific test should be used for measuring HE. PMID:23815160

2013-01-01

222

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

PubMed Central

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

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

2013-01-01

223

Prevention of hepatocellular carcinoma recurrence with alpha-interferon after liver resection in HCV cirrhosis.  

PubMed

Tumor recurrence after resection of hepatocellular carcinoma (HCC) can occur early (<2 years) or late (>2 years) as metastases or de novo tumors. Interferon (IFN) has the potential for chemoprevention against hepatitis C virus (HCV)-related cirrhosis. A predetermined group of 150 HCV RNA-positive patients undergoing resection of early- to intermediate-stage HCC was stratified into 80 HCV-pure (hepatitis B anticore antibody [anti-HBc]-negative) and 70 mixed HCV+hepatitis B virus (HBV) (anti-HBc-positive) groups, then randomized to IFN-alpha (3 million units 3 times every week for 48 weeks [n = 76]) versus control (n = 74). The primary end point was recurrence-free survival (RFS); secondary end points were disease-specific and overall survival. Intention-to-treat and subgroup analysis on adherent patients were conducted. Treatment effects on early/late recurrences were assessed using multiple Cox regression analysis. No patient experienced life-threatening adverse events. There were 28 adherent patients (37%). After 45 months of median follow-up, overall survival was 58.5%, and no significant difference in RFS was detectable between the two study arms (24.3% vs. 5.8%; P = .49). HCC recurred in 100 patients (48 IFN-treated, 52 controls), with a 50% reduction in late recurrence rate in the treatment arm. HCC multiplicity and vascular invasion were significantly related to recurrence (P = .01 and .0003). After viral status stratification, while no treatment effect was apparent in the mixed HCV+HBV population and on early recurrences (72 events), there was a significant benefit on late recurrences (28 events) in HCV-pure patients adherent to treatment (HR: 0.3; 95% CI: 0.09-0.9; P = .04). In conclusion, IFN does not affect overall prevention of HCC recurrence after resection, but it may reduce late recurrence in HCV-pure patients receiving effective treatment. PMID:17133492

Mazzaferro, Vincenzo; Romito, Raffaele; Schiavo, Marcello; Mariani, Luigi; Camerini, Tiziana; Bhoori, Sherrie; Capussotti, Lorenzo; Calise, Fulvio; Pellicci, Riccardo; Belli, Giulio; Tagger, Alessandro; Colombo, Massimo; Bonino, Ferruccio; Majno, Pietro; Llovet, Josep M

2006-12-01

224

Application of a new histological staging and grading system for primary biliary cirrhosis to liver biopsy specimens: Interobserver agreement.  

PubMed

Recently the authors proposed a new staging and grading system for primary biliary cirrhosis (PBC) that takes into account necroinflammatory activity and histological heterogeneity. Herein is proposed a convenient version of this system. Scores for fibrosis, bile duct loss, and chronic cholestasis were combined for staging: stage 1, total score of 0; stage 2, score 1-3; stage 3, score 4-6; and stage 4, score 7-9. Cholangitis activity (CA) and hepatitis activity (HA) were graded as CA0-3, and HA0-3, respectively. Analysis of interobserver agreement was then conducted. Digital images of 62 needle liver biopsy specimens of PBC were recorded as virtual slides on DVDs that were sent to 28 pathologists, including five located overseas. All participants were able to apply this version in all 62 cases. For staging, kappa was 0.385 (fair agreement) and the concordance rate was 63.9%. For necroinflammatory activity, the kappa and concordance rate were 0.110 (slight agreement) and 36.9% for CA, and 0.197 (slight agreement) and 47% for HA, respectively. In conclusion, this new staging and grading system for PBC seems to be more convenient and practical than those used at present, but more instruction and guidance are recommended for the grading of necroinflammatory activity in practice. PMID:20403042

Nakanuma, Yasuni; Zen, Yoh; Harada, Kenichi; Sasaki, Motoko; Nonomura, Akitaka; Uehara, Takeshi; Sano, Kenji; Kondo, Fukuo; Fukusato, Toshio; Tsuneyama, Koichi; Ito, Masahiro; Wakasa, Kenichi; Nomoto, Minoru; Minato, Hiroshi; Haga, Hironori; Kage, Masayoshi; Yano, Hirohisa; Haratake, Joji; Aishima, Shinichi; Masuda, Tomoyuki; Aoyama, Hajime; Miyakawa-Hayashino, Aya; Matsumoto, Toshiharu; Sanefuji, Hayato; Ojima, Hidenori; Chen, Tse-Ching; Yu, Eunsil; Kim, Ji-Hun; Park, Young Nyun; Tsui, Wilson

2010-03-01

225

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

226

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 ( ...

227

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

228

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

PubMed

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

229

Increased Risk of Hepatocellular Carcinoma and Liver Cirrhosis in Vinyl Chloride Workers: Synergistic Effect of Occupational Exposure with Alcohol Intake  

PubMed Central

Hepatocellular carcinoma (HCC) and liver cirrhosis (LC) are not well-established vinyl chloride monomer (VCM)–induced diseases. Our aim was to appraise the role of VCM, alcohol intake, and viral hepatitis infection, and their interactions, in the etiology of HCC and LC. Thirteen cases of HCC and 40 cases of LC were separately compared with 139 referents without chronic liver diseases or cancer in a case–referent study nested in a cohort of 1,658 VCM workers. The odds ratios (ORs) and the 95% confidence intervals (CIs) were estimated by common methods and by fitting models of logistic regression. We used Rothman’s synergy index (S) to evaluate interactions. By holding the confounding factors constant at logistic regression analysis, each extra increase of 1,000 ppm × years of VCM cumulative exposure was found to increase the risk of HCC by 71% (OR = 1.71; 95% CI, 1.28–2.44) and the risk of LC by 37% (OR = 1.37; 95% CI, 1.13–1.69). The joint effect of VCM exposure above 2,500 ppm × years and alcohol intake above 60 g/day resulted in ORs of 409 (95% CI, 19.6–8,553) for HCC and 752 (95% CI, 55.3–10,248) for LC; both S indexes suggested a synergistic effect. The joint effect of VCM exposure above 2,500 ppm × years and viral hepatitis infection was 210 (95% CI, 7.13–6,203) for HCC and 80.5 (95% CI, 3.67–1,763) for LC; both S indexes suggested an additive effect. In conclusion, according to our findings, VCM exposure appears to be an independent risk factor for HCC and LC interacting synergistically with alcohol consumption and additively with viral hepatitis infection. PMID:15289165

Mastrangelo, Giuseppe; Fedeli, Ugo; Fadda, Emanuela; Valentini, Flavio; Agnesi, Roberto; Magarotto, Giancarlo; Marchì, Teresio; Buda, Andrea; Pinzani, Massimo; Martines, Diego

2004-01-01

230

Next-Generation Sequence Analysis of Genes Associated with Obesity and Nonalcoholic Fatty Liver Disease-Related Cirrhosis in Extreme Obesity  

PubMed Central

Objectives Genome-wide association studies (GWAS) have led to the identification of single nucleotide polymorphisms in or near several loci that are associated with the risk of obesity and nonalcoholic fatty liver disease (NAFLD). We hypothesized that missense variants in GWAS and related candidate genes may underlie cases of extreme obesity and NAFLD-related cirrhosis, an extreme manifestation of NAFLD. Methods We performed whole-exome sequencing on 6 Caucasian patients with extreme obesity [mean body mass index (BMI) 84.4] and 4 obese Caucasian patients (mean BMI 57.0) with NAFLD-related cirrhosis. Results Sequence analysis was performed on 24 replicated GWAS and selected candidate obesity genes and 5 loci associated with NAFLD. No missense variants were identified in 19 of the 29 genes analyzed, although all patients carried at least 2 missense variants in the remaining genes without excess homozygosity. One patient with extreme obesity carried 2 novel damaging mutations in BBS1 and was homozygous for benign and damaging MC3R variants. In addition, 1 patient with NAFLD-related cirrhosis was compound heterozygous for rare damaging mutations in PNPLA3. Conclusions These results indicate that analyzing candidate loci previously identified by GWAS analyses using whole-exome sequencing is an effective strategy to identify potentially causative missense variants underlying extreme obesity and NAFLD-related cirrhosis. PMID:24081230

Gerhard, Glenn S.; Chu, Xin; Wood, G. Craig; Gerhard, Genevieve M.; Benotti, Peter; Petrick, Anthony T.; Gabrielsen, Jon; Strodel, William E.; Still, Christopher D.; Argyropoulosa, George

2014-01-01

231

Hepatic synthesis and clearance of components of the fibrinolytic system in healthy volunteers and in patients with different stages of liver cirrhosis.  

PubMed

We determined plasma levels of tissue-type plasminogen activator (t-PA) antigen, urokinase-type plasminogen activator (u-PA) antigen, and activity of the fast acting inhibitor of plasminogen activator (PAI-1) in patients with different stages of liver cirrhosis (Child A, B, and C) and in age and sex-matched healthy controls to investigate the contribution of the liver to the metabolism of these main components of the fibrinolytic system. For control purposes routine clotting parameters were also determined. In patients with the most severe form of liver cirrhosis (Child C) t-PA antigen levels were significantly elevated as compared to patients with Child A or Child B (p less than 0.05) or to controls (p less than 0.01). Furthermore, Child C patients exhibited significantly decreased PAI-1 plasma levels (p less than 0.05) as compared to controls. We were not able to demonstrate, however, any significant correlation between liver function and u-PA plasma levels. Furthermore, t-PA antigen and albumin plasma levels were negatively correlated (r = 0.48; p = 0.0015) and t-PA antigen and bilirubin were positively correlated (r = 0.46; p = 0.0022) thus indicating that the liver is mainly involved in the clearance of t-PA antigen. PAI-1 activity, however, seems to depend partially on synthesis by the liver as demonstrated by a positive correlation between PAI-1 and albumin (r = 0.33; p = 0.037). These physiologic liver functions are both progressively attenuated in severe liver damage and an increase of t-PA plasma levels and a decrease of PAI-1 might contribute to the higher fibrinolytic tendency observed in those patients. PMID:1910213

Huber, K; Kirchheimer, J C; Korninger, C; Binder, B R

1991-06-01

232

Detecting patients with cirrhosis in primary care.  

PubMed

Cirrhosis is a condition that arises as a result of chronic liver damage, typically over many years. It is characterised by fibrosis and nodularity of the liver parenchyma. Cirrhosis interferes with the normal functions of the liver, reducing its ability to produce proteins, which can lead to coagulopathy, low serum albumin and raised bilirubin. The incidence of cirrhosis is rising in the UK, this can primarily be attributed to increasing levels of alcohol consumption and obesity. Mortality from cirrhosis is also rising. Common causes of chronic liver disease include alcohol, non-alcoholic fatty liver disease and chronic viral hepatitis. Nearly half of patients with cirrhosis are asymptomatic. As a result the condition may only be discovered incidentally as a result of abnormalities in liver function tests or imaging of the abdomen performed for other reasons. Alternatively patients may present with signs and symptoms of the complications of cirrhosis e.g. jaundice, ascites, variceal bleeding, hepatic encephalopathy or hepatocellular carcinoma. Detecting patients with cirrhosis in primary care usually relies on identifying common risk factors. Currently, there are no standard criteria for the investigation of patients with suspected cirrhosis. If a patient is suspected of having cirrhosis, most GPs will arrange for blood tests and an ultrasound of the liver to be performed. The gold standard test for the diagnosis of cirrhosis remains a liver biopsy. Staging of liver fibrosis is an important predictor of prognosis and is necessary to guide management. PMID:25211789

Keane, Margaret G; Lai, Cindy; Pereira, Stephen P

2014-01-01

233

Protective effects of Ephedra pachyclada extract on mouse models of carbon tetrachloride- induced chronic and acute liver failure.  

PubMed

Inflammation and oxidation are two important factors in the pathogenesis of liver. Ephedra pachyclada (EP) is a traditional medical herb that has anti-inflammatory and anti-oxidant activities. During this study, anti-oxidant activities of the EP extract was measured in vitro by 2,2'- diphenyl-1-picrylhydrazyl (DPPH) and ?-Carotene bleaching assays. Then, we examined possible in vivo hepatoprotective effects of EP extract on mouse models of carbon tetrachloride (CCl4)-induced chronic and acute liver failure. To produce mouse models of chronic and acute liver injuries, male SW1 mice were interaperitoneally injected with 1ml/kg body weight (bw) CCl4 biweekly for 42 days and a single dose of 2ml/kg bw, respectively. In the experimental groups, mouse models were treated with low (140mg/kg bw) and high (1400mg/kg bw) doses of the EP extract. Olive oil and water treated mice were considered as controls during model derivation and EP extract treatment respectively. The results showed the antioxidant activity of EP extract and a significant reduction of all parameters of CCl4-induced liver injury such as relative liver weight, necrosis, fibrosis, inflammation, and serum aspartate transaminase (AST) and alanine aminotransferase (ALT) in mouse models of acute and chronic liver injury treated with EP extract. Therefore, EP induces its hepatoprotective effects probably by suppressing oxidative stress and inhibit inflammation in the liver and is able to protect the liver against CCl4-induced acute and chronic injuries. PMID:24388354

Ghasemi, Marzieh; Azarnia, Mahnaz; Jamali, Mansoor; Mirabolghasemi, Ghadireh; Nazarian, Shahram; Naghizadeh, Mohammad Mehdi; Rajabi, Majid; Tahamtani, Yaser

2014-02-01

234

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

235

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

236

Hepatoprotective effect and its possible mechanism of Coptidis rhizoma aqueous extract on carbon tetrachloride-induced chronic liver hepatotoxicity in rats  

Microsoft Academic Search

Ethnopharmacological relevanceCoptidis rhizoma is traditionally used for heat-clearing and toxic-scavenging and it belongs to liver meridian in Chinese medicine practice. Clinically, Coptidis rhizoma can be used for hepatic and biliary disorders, yet details in the therapies of liver diseases and underlying mechanism(s) remain unclear. Our previous study demonstrated that Coptidis rhizoma aqueous extract (CRAE) against CCl4-induced acute liver damage was

Yibin Feng; Ning Wang; Xingshen Ye; Huangyun Li; Yigang Feng; Fan Cheung; Tadashi Nagamatsu

237

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

PubMed Central

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

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

2013-01-01

238

Silybin exerts antioxidant effects and induces mitochondrial biogenesis in liver of rat with secondary biliary cirrhosis.  

PubMed

The accumulation of toxic hydrophobic bile acids in hepatocytes, observed during chronic cholestasis, induces substantial modification in the redox state and in mitochondrial functions. Recent reports have suggested a significant role of impaired lipid metabolism in the progression of chronic cholestasis. In this work we report that changes observed in the expression of the lipogenic enzymes acetyl-CoA carboxylase and fatty acid synthase were associated with a decrease in the activity of citrate carrier (CIC), a protein of the inner mitochondrial membrane closely related to hepatic lipogenesis. We also verified that the impairment of citrate transport was dependent on modification of the phospholipid composition of the mitochondrial membrane and on cardiolipin oxidation. Silybin, an extract of silymarin with antioxidant and anti-inflammatory properties, prevented mitochondrial reactive oxygen species (ROS) production, cardiolipin oxidation, and CIC failure in cirrhotic livers but did not affect the expression of lipogenic enzymes. Moreover, supplementation of silybin was also associated with mitochondrial biogenesis. In conclusion, we demonstrate that chronic cholestasis induces cardiolipin oxidation that in turn impairs mitochondrial function and further promotes ROS production. The capacity of silybin to limit mitochondrial failure is part of its hepatoprotective property. PMID:24819445

Serviddio, Gaetano; Bellanti, Francesco; Stanca, Eleonora; Lunetti, Paola; Blonda, Maria; Tamborra, Rosanna; Siculella, Luisa; Vendemiale, Gianluigi; Capobianco, Loredana; Giudetti, Anna Maria

2014-08-01

239

Protective effect of Panax ginseng against serum biochemical changes and apoptosis in liver of rats treated with carbon tetrachloride (CCl4).  

PubMed

The purpose of this study was to investigate possible beneficial effects of Panax ginseng (PG) on carbon tetrachloride (CCl(4))-induced acute hepatotoxicity in rats. CCl(4) challenge elevated serum enzyme activities of liver and some biochemical parameters, but these effects were prevented by the pretreatment of rats with PG. Histologically, a great amount of mononuclear cells infiltration, necrotic cells and few fibroblasts were observed in liver of CCl(4) group. Also, CD68(+) and caspase-3 staining cells were diffused in both lobular and portal areas. However, PG pretreatment had a little influence on the number of caspase-3 immunopositive staining cells in the liver, but CD68(+) staining areas were significantly decreased in the PG+CCl(4) when compared to CCl(4) group. We conclude that PG treatment may play a protective role by enhancing liver enzyme activities and recovering biochemical parameters, and improving the changes in histological structure against CCl(4)-induced liver damages in rats. PMID:21880419

Karakus, Emre; Karadeniz, Ali; Simsek, Nejdet; Can, Ismail; Kara, Adem; Yildirim, Serap; Kalkan, Yildiray; Kisa, Fikrullah

2011-11-15

240

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

241

Aminotriazole attenuated carbon tetrachloride-induced oxidative liver injury in mice.  

PubMed

Carbon tetrachloride (CCl(4)) has been used extensively to study xenobiotic-induced oxidative liver injury. Catalase (CAT) is a major antioxidant enzyme while aminotriazole (ATZ) is commonly used as a CAT inhibitor. In the present study, the effects of ATZ on CCl(4)-induced liver injury were investigated. Our experimental data showed that pretreatment with ATZ significantly decreased CCl(4)-induced elevation of serum aspartate transaminase (AST) and alanine transaminase (ALT) and improved hepatic histopathological abnormality. ATZ dose-dependently inhibited the activity of CAT, but it reduced the content of H(2)O(2) and the levels of malondialdehyde (MDA) in liver tissues. ATZ decreased plasma level of pro-inflammatory cytokines (TNF-? and IL-6) and reduced hepatic levels of myeloperoxidase (MPO). In addition, posttreatment with ATZ also decreased the level of ALT and AST. These data indicated that ATZ effectively alleviated CCl(4)-induced oxidative liver damage. These findings suggested that ATZ might have potential value in preventing oxidative liver injury. PMID:22687551

Deng, Xinyu; Wu, Kunwei; Wan, Jingyuan; Li, Longjiang; Jiang, Rong; Jia, Mengying; Jing, Yuping; Zhang, Li

2012-09-01

242

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

243

Treatment of HBV-related cirrhosis.  

PubMed

The goal of antiviral therapy in HBV cirrhotic patients is to prevent progression of the disease to decompensated cirrhosis, end-stage liver disease, hepatocellular carcinoma and death. This goal can be achieved if HBV replication can be suppressed, leading to biochemical remission, histological improvement and prevention of complications. If finite treatment with pegylated interferon is not contraindicated in compensated cirrhosis, long-term treatment with nucleoside/nucleotide analogues is recommended in patients with HBV-related cirrhosis, especially in decompensated cirrhosis. Patients with cirrhosis require careful monitoring to detect resistance and prevent flares, and also to screen for hepatocellular carcinoma, portal hypertension and liver failure. PMID:19485793

Vallet-Pichard, Anais; Mallet, Vincent; Costentin, Charlotte E; Pol, Stanislas

2009-06-01

244

Autoimmune Liver Diseases in Canterbury, New Zealand.  

E-print Network

??Autoimmune hepatitis (AIH), primary sclerosing cholangitis (PSC) and primary biliary cirrhosis (PBC) are progressive autoimmune liver diseases (AiLD) that can lead to liver cirrhosis, hepatic… (more)

Ngu, Jing Hieng

2013-01-01

245

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

246

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

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

2014-01-01

247

Prognosis of histological cirrhosis in type 1 autoimmune hepatitis  

Microsoft Academic Search

BACKGROUND & AIMS: Cirrhosis connotes irreversible damage to the liver and shortened life expectancy. The aim of this study was to evaluate the impact of cirrhosis on treatment response and survival in type 1 autoimmune hepatitis. METHODS: One hundred twenty-eight patients were evaluated for histological cirrhosis. Response to treatment, predictors for cirrhosis, and outcomes were determined. RESULTS: Thirty-seven patients (29%)

SK Roberts; TM Therneau; AJ Czaja

1996-01-01

248

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

249

Quantitation and karyometry of cerebral neuroglia and endothelial cells in liver cirrhosis and in the hepatosplenic schistosomiasis mansoni  

Microsoft Academic Search

A morphological, karyometric, and quantitative study of cerebral neuroglia and endothelial cells of blood capillaries was done in cirrhotic and in hepatosplenic schistosomotic human autopsied cases. Cluster analysis applied to them revealed three subgroups (cirrhosis and schistosomiasis polar groups and one intermediate). The comparison of these three groups with a control revealed increased numbers of astrocytes, oligodendrocytes and endothelial cells,

G. Brasileiro-Filho; R. C. Guimaraes; J. E. H. Pittella

1989-01-01

250

High Serum Levels of HDV RNA Are Predictors of Cirrhosis and Liver Cancer in Patients with Chronic Hepatitis Delta  

PubMed Central

Chronic infection with the hepatitis delta virus (HDV) is a risk factor for cirrhosis and hepatocellular carcinoma (HCC), but little is known whether the outcome of hepatitis is predicted by serum markers of HDV and hepatitis B virus (HBV) infection. The aim of the study was to investigate these correlations in 193 patients with chronic HDV infection who had been followed up for a median of 9.5 years (4.8–19.3). HDV-RNA was first measured by qualitative in-house nested RT-PCR and quantified by in-house real-time PCR. HDV RNA levels only appeared significantly associated to HCC (univariate analysis: OR 1.32, 95% CI 1.02–1.71; p?=?0.037; multivariate analysis: OR 1.42, 95% CI 1.04–1.95; p?=?0.03). In non-cirrhotics at first presentation (n?=?105), HDV RNA levels were associated with progression to cirrhosis (univariate analysis: OR?=?1.57, 95% CI 1.20–2.05, p<0.001; multivariate analysis: OR?=?1.60, 95% CI 1.20–2.12, p?=?0.007) and development of HCC (univariate analysis: OR?=?1.66, 95% CI 1.04–2.65, p?=?0.033; multivariate analysis: OR?=?1.88, 95% CI 1.11–3.19, p?=?0.019). ROC analysis showed that approximately 600,000 HDV RNA copies/mL was the optimal cut-off value in our cohort of patients for discriminating the development of cirrhosis. High levels of HDV viremia in non-cirrhotic patients are associated with a considerable likelihood of progression to cirrhosis and the development of HCC. Once cirrhosis has developed, the role of HDV replication as a predictor of a negative outcome lessens. PMID:24658127

Romeo, Raffaella; Foglieni, Barbara; Casazza, Giovanni; Spreafico, Marta; Colombo, Massimo; Prati, Daniele

2014-01-01

251

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

PubMed Central

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

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

2014-01-01

252

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.

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

253

Total body dual X-ray absorptiometry is a good measure of both fat mass and fat-free mass in liver cirrhosis compared to "gold-standard" techniques. Melbourne Liver Group.  

PubMed

Liver cirrhosis is a condition in which overnutrition, edema, and undernutrition can coexist simultaneously, or successively, over a period of time, giving rise to alterations in body composition, as well as systemic and multiorgan manifestations. We undertook a cross-sectional study of body composition in 198 adult patients with liver cirrhosis (140 males, mean age 53.6, range 31-85 years; and 58 females, mean age 58.4, range 36-79 years). The patients had cirrhosis of differing etiology and different stages of severity. They were gathered from seven different hospital clinics in the city of Melbourne, Australia, but all the body composition measurements were performed in one body composition laboratory. A variety of body composition techniques were used to identify which commonly available ones could best assess both fat-free mass and fat mass relative to a criterion "gold-standard" method available in a specialist laboratory. A gold-standard fat-free mass (FFMGS) was defined as the sum of total body protein, measured by in vivo neutron activation analysis (IVNA), plus total body water, measured by D2O dilution, plus bone mineral content, measured by dual X-ray absorptiometry (DXA). A gold-standard fat mass (FATGS) was defined as the difference between body weight and FFMGS. "Usual" fat mass and fat-free mass were defined by different techniques including DXA, anthropometry (ANT), single-frequency bioelectrical impedance (SFBIA), multiple-frequency bioelectrical impedance spectroscopy (MFBIA), and whole body gamma counting (TBK). The FFMGS was overhydrated in both sexes, relative to the usual value of 0.73, but women were significantly overhydrated compared to men. Relative to the gold-standard deuterium oxide dilution method for measuring total body water, SFBIA slightly overestimated TBW, whereas MFBIA slightly underestimated TBW, with both methods having wide limits of agreement for any single estimate. In comparing FFM to FFMGS, only DXA showed a small negative bias, in both males and females, with modest limits of agreement for any single estimate. All other methods showed a large negative bias (ANT, SFBIA, and MFBIA) or a large positive bias (TBK) relative to FFMGS, with wide limits of agreement. In comparing FAT with the FATGS, only DXA showed a small positive bias, in both males and females, with modest limits of agreement for any single estimate. All other methods showed a large positive bias (ANT, SFBIA, and MFBIA) or a large negative bias (TBK) relative to FATGS, with wide limits of agreement. In cirrhosis, DXA is a good and widely available method to assess both fat mass and fat-free mass. However, it cannot give information about the quality of the FFM, particularly its water content. The bedside methods of anthropometry and bioelectrical impedance, both SFBIA and MFBIA, are poor methods of measuring body composition in patients with liver cirrhosis, whereas whole body gamma counting, although not widely available, also significantly differs from the gold-standard method of assessment of fat-free mass and fat mass in liver cirrhosis. PMID:10865710

Strauss, B J; Gibson, P R; Stroud, D B; Borovnicar, D J; Xiong, D W; Keogh, J

2000-05-01

254

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

PubMed

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

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

2014-04-01

255

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

256

The Etiology Mystery in Primary Biliary Cirrhosis  

Microsoft Academic Search

The etiology of primary biliary cirrhosis remains largely unknown despite numerous lines of evidence that have been recently proposed or supported. Primary biliary cirrhosis is a chronic cholestatic liver disease for which an autoimmune pathogenesis is widely accepted, mostly based on the presence of autoantibodies and autoreactive T cells. Cumulatively, association and twin studies suggest that both a susceptible genetic

Carlo Selmi; M. Eric Gershwin

2010-01-01

257

Alcoholic liver disease. Parenchyma to stroma relationship in fibrosis and cirrhosis as revealed by three-dimensional reconstruction and immunohistochemistry.  

PubMed Central

Severe ethanol-induced liver damage is characterized by fibrous dissociation of liver cell plates leading to many apparently isolated hepatocytes. Three-dimensional reconstruction, however, revealed hepatocytes that were surrounded by connective tissue as endpoints of "parenchymal pillars" or in association with liver cell plates and bile ductules. Double immunofluorescence studies displayed the expression of cytokeratin (CK) 7 in bile ducts, including bile ductules, but also in some hepatocytes still organized in liver cell plates. The other bile duct, typical CK, namely CK 19, was only detectable in few hepatocytes. However, the expression of CK 7 and/or CK 19 was less frequent in hepatocytes that were closely associated with bile ductules. CK 7 and CK 19 were also found in some, but not all, Mallory bodies. These observations indicate that the expression of these two CKs is neither related to a transformation of hepatocytes to bile duct-like structures ("ductal metaplasia") nor to the formation of Mallory bodies. Furthermore, double immunofluorescence studies revealed small groups of hepatocytes and bile ductules that were encircled by basement membrane material, thus suggesting the formation of "secretory units." Images Figure 1 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 13 Figure 14 PMID:1378697

Dinges, H. P.; Zatloukal, K.; Denk, H.; Smolle, J.; Mair, S.

1992-01-01

258

Pharmacokinetics of sildenafil and its metabolite, N-desmethylsildenafil, in rats with liver cirrhosis and diabetes mellitus, alone and in combination.  

PubMed

Pharmacokinetics of sildenafil and its metabolite, N-desmethylsildenafil, in humans and rats with liver cirrhosis (LC) and diabetes mellitus (DM), alone and in combination (LCD) did not seem to be reported. Sildenafil was administered intravenously (10 mg/kg) and orally (20 mg/kg) to control, LC, DM, and LCD rats. Expression of intestinal CYP isozymes in those rats was also measured. In LC, DM, and LCD rats, the areas under the curve (AUCs) of intravenous sildenafil were significantly greater (by 195%, 54.2%, and 127%, respectively) than controls. In LC and LCD rats, AUCs of oral sildenafil were significantly greater (3010% and 2030%, respectively) than controls. In LC, DM, and LCD rats, significantly greater AUCs of intravenous sildenafil were due to the slower hepatic extraction of sildenafil (because of decrease in the protein expression of hepatic CYP2C11 and 3A subfamily in LC and LCD rats, and CYP2C11 in DM rats). In LC and LCD rats, greater magnitude of increase in AUCs of oral sildenafil than those after the intravenous administration could be mainly due to the decrease in the intestinal extraction of sildenafil (because of decrease in the protein expression of intestinal CYP2C11 in LC and LCD rats). PMID:21070144

Ahn, C Y; Bae, S K; Bae, S H; Kang, H E; Kim, S H; Lee, M G; Shin, W G

2011-02-01

259

Management of Ascites in Cirrhosis  

Microsoft Academic Search

The term ascites is derived from the Greek word askos referring to a bag or sack. Ascites are defined as the pathologic accumulation of fluid within the peritoneal cavity. Cirrhosis of the liver is the most common cause of ascites and accounts for almost 85% of all cases of ascites (1). Numerous other disorders, however, including malignancy, cardiac failure, pancreatitis,

Arun J. Sanyal

260

A Ribosomal S-6 Kinase-Mediated Signal to C/EBP-? Is Critical for the Development of Liver Fibrosis  

PubMed Central

Background In response to liver injury, hepatic stellate cell (HSC) activation causes excessive liver fibrosis. Here we show that activation of RSK and phosphorylation of C/EBP? on Thr217 in activated HSC is critical for the progression of liver fibrosis. Methodology/Principal Findings Chronic treatment with the hepatotoxin CCl4 induced severe liver fibrosis in C/EBP?+/+ mice but not in mice expressing C/EBP?-Ala217, a non-phosphorylatable RSK-inhibitory transgene. C/EBP?-Ala217 was present within the death receptor complex II, with active caspase 8, and induced apoptosis of activated HSC. The C/EBP?-Ala217 peptides directly stimulated caspase 8 activation in a cell-free system. C/EBP?+/+ mice with CCl4-induced severe liver fibrosis, while continuing on CCl4, were treated with a cell permeant RSK-inhibitory peptide for 4 or 8 weeks. The peptide inhibited RSK activation, stimulating apoptosis of HSC, preventing progression and inducing regression of liver fibrosis. We found a similar activation of RSK and phosphorylation of human C/EBP? on Thr266 (human phosphoacceptor) in activated HSC in patients with severe liver fibrosis but not in normal livers, suggesting that this pathway may also be relevant in human liver fibrosis. Conclusions/Significance These data indicate that the RSK-C/EBP? phosphorylation pathway is critical for the development of liver fibrosis and suggest a potential therapeutic target. PMID:18159255

Buck, Martina; Chojkier, Mario

2007-01-01

261

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

262

A novel mechanism of abnormal hematological indices in liver cirrhosis: bone marrow endothelial cell dysfunction caused by humoral inhibitor affects the hematopoietic function of bone marrow.  

PubMed

Abnormal hematological indices (HIs), a complication of liver cirrhosis (LC), present difficulties in the treatment of LC and pose a serious threat to the survival of patients. LC is a dynamic wound-healing process that occurs in response to repeated liver injury and is a chronic disorder associated with changes in various organs and tissues. It has been reported that humoral inhibitor in the formation of LC could affect the hematogenic functions of bone marrow (BM) by acting on erythroid differentiation. This indicates that the BM microenvironment is affected by humoral inhibitor in LC. Bone marrow endothelial cells (BMECs) are very important components of the BM microenvironment that function as the cytoskeleton to support the adhesion of hematopoietic stem cells (HSCs). In addition, they can secrete cytokines, which have important functions in regulating positioning, homing, proliferation, differentiation and other functions of HSCs on the BM microenvironment. These functions of BMECs may be affected due to direct contact with blood and long-term exposure to an environment with humoral inhibitor in the presence of LC. Multiple studies have shown that during the formation of LC, hepatic sinusoid endothelial cells were damaged and secreted cytokines and matrix proteins. Moreover, these cytokines and matrix proteins were involved in the formation and development of LC. Similar in function to mature-stage BM, liver at the embryonic stage also functions as a type of hematogenic organ. With similar anatomical position and functions to that of hepatic sinusoid endothelial cells, BMECs may undergo similar changes and impair hematogenic function of BM. More importantly, we found even more convincing evidence in that the humoral inhibitor in LC could lead to the ultrastructural damage of BMECs that were positively related to the degree of severity of LC. Therefore, we hypothesise the existence of a novel mechanism for abnormal HIs in LC: the continuous humoral inhibitor may lead to abnormal cytokine secretion of BMECs and attenuate their supporting functions, and such alterations of BMECs may lead to BM microenvironment disorder and dysfunction of HSCs, finally causing abnormal HIs. PMID:24388557

Gao, Bo; Li, Zhi-tuo; Xue, Dong-bo; Zhang, Wei-hui

2014-03-01

263

Clinical outcomes of balloon-occluded retrograde transvenous obliteration for the treatment of gastric variceal hemorrhage in Korean patients with liver cirrhosis: a retrospective multicenter study  

PubMed Central

Background/Aims This study evaluated the clinical outcomes of balloon-occluded retrograde transvenous obliteration (BRTO) for the treatment of hemorrhage from gastric varices (GV) in Korean patients with liver cirrhosis (LC). Methods We retrospectively analyzed data from 183 LC patients who underwent BRTO for GV bleeding in 6 university-based hospitals between January 2001 and December 2010. Results Of the 183 enrolled patients, 49 patients had Child-Pugh (CP) class A LC, 105 had CP class B, and 30 had CP class C at the time of BRTO. BRTO was successfully performed in 177 patients (96.7%). Procedure-related complications (e.g., pulmonary thromboembolism and renal infarction) occurred in eight patients (4.4%). Among 151 patients who underwent follow-up examinations of GV, 79 patients (52.3%) achieved eradication of GV, and 110 patients (72.8%) exhibited marked shrinkage of the treated GV to grade 0 or I. Meanwhile, new-appearance or aggravation of esophageal varices (EV) occurred in 54 out of 136 patients who underwent follow-up endoscopy (41.2%). During the 36.0±29.2 months (mean±SD) of follow-up, 39 patients rebled (hemorrhage from GV in 7, EV in 18, nonvariceal origin in 4, and unknown in 10 patients). The estimated 3-year rebleeding-free rate was 74.8%, and multivariate analysis showed that CP class C was associated with rebleeding (odds ratio, 2.404; 95% confidence-interval, 1.013-5.704; P=0.047). Conclusions BRTO can be performed safely and effectively for the treatment of GV bleeding. However, aggravation of EV or bleeding from EV is not uncommon after BRTO; thus, periodic endoscopy to follow-up of EV with or without prophylactic treatment might be necessary in LC patients undergoing BRTO. PMID:23323252

Jang, Se Young; Kim, Go Heun; Park, Soo Young; Cho, Chang Min; Tak, Won Young; Kim, Jeong Han; Choe, Won Hyeok; Kwon, So Young; Lee, Jae Myeong; Kim, Sang Gyune; Kim, Dae Yong; Kim, Young Seok; Lee, Se-Ok; Min, Yang Won; Lee, Joon Hyeok; Paik, Seung Woon; Yoo, Byung Chul; Lim, Jae Wan; Kim, Hong Joo; Cho, Yong Kyun; Sohn, Joo Hyun; Jeong, Jae Yoon; Lee, Yu Hwa; Kim, Tae Yeob

2012-01-01

264

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

265

Yellow tea is more potent than other types of tea in suppressing liver toxicity induced by carbon tetrachloride in rats.  

PubMed

The present study compared the effects of six Chinese teas categorized by their production process: green, white, yellow, oolong, black and pu-erh teas, on carbon tetrachloride (CCl4)-induced liver injury. Wistar rats were given ad libitum the Chinese teas prepared according to the home-style methods for 1 week, and then intraperitoneally injected with CCl4 (1 mg/kg body weight) or olive oil as a vehicle. The yellow tea significantly ameliorated the increase in the activity of the alanine- and aspartate-aminotransferases in plasma. Thus, the drinking of yellow tea may contribute to protection against liver injury. PMID:17444574

Hashimoto, Takashi; Goto, Miho; Sakakibara, Hiroyuki; Oi, Naomi; Okamoto, Mayumi; Kanazawa, Kazuki

2007-07-01

266

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

267

Distinct Distribution Pattern of Hepatitis B Virus Genotype C and D in Liver Tissue and Serum of Dual Genotype Infected Liver Cirrhosis and Hepatocellular Carcinoma Patients  

PubMed Central

Aims The impact of co-infection of several hepatitis B virus (HBV) genotypes on the clinical outcome remains controversial. This study has for the first time investigated the distribution of HBV genotypes in the serum and in the intrahepatic tissue of liver cirrhotic (LC) and hepatocellular carcinoma (HCC) patients from India. In addition, the genotype-genotype interplay and plausible mechanism of development of HCC has also been explored. Methods The assessment of HBV genotypes was performed by nested PCR using either surface or HBx specific primers from both the circulating virus in the serum and replicative virus that includes covalently closed circular DNA (cccDNA) and relaxed circular DNA (rcDNA) of HBV from the intrahepatic tissue. The integrated virus within the host chromosome was genotyped by Alu-PCR method. Each PCR products were cloned and sequences of five randomly selected clones were subsequently analysed. Results HBV/genotype D was detected in the serum of all LC and HCC patients whereas the sequences of the replicative HBV DNA (cccDNA and rcDNA) from the intrahepatic tissue of the same patients revealed the presence of both HBV/genotype C and D. The sequences of the integrated viruses exhibited the solo presence of HBV/genotype C in the majority of LC and HCC tissues while both HBV/genotype C and D clones were found in few patients in which HBV/genotype C was predominated. Moreover, compared to HBV/genotype D, genotype C had higher propensity to generate double strand breaks, ER stress and reactive oxygen species and it had also showed higher cellular homologous-recombination efficiency that engendered more chromosomal rearrangements, which ultimately led to development of HCC. Conclusions Our study highlights the necessity of routine analysis of HBV genotype from the liver tissue of each chronic HBV infected patient in clinical practice to understand the disease prognosis and also to select therapeutic strategy. PMID:25032957

Datta, Somenath; Roychoudhury, Shrabasti; Ghosh, Alip; Dasgupta, Debanjali; Ghosh, Amit; Chakraborty, Bidhan; Roy, Sukanta; Gupta, Subash; Santra, Amal Kumar; Datta, Simanti; Das, Kausik; Dhali, Gopal Krishna; Chowdhury, Abhijit; Banerjee, Soma

2014-01-01

268

Protective effects of total flavonoids of Bidens pilosa L. (TFB) on animal liver injury and liver fibrosis.  

PubMed

The hepatoprotective effects of total flavonoids of Bidens pilosa L. (TFB), a traditional Chinese medicine were evaluated in carbon tetrachloride (CCl(4))-induced liver injury in mice and rats. Total flavonoids of Bidens pilosa L. (25, 50 and 100mg/kg) were administered via gavage daily for 10 days to CCl(4)-treated mice as well as TFB (30, 60 and 90mg/kg) administered for 6 weeks to CCl(4)-treated rats. Liver index (liver weight/body weight), serum levels of transaminases (alanine aminotransferase, ALT and aspartate aminotransferase, AST), hepatic malondialdehyde (MDA) content, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were evaluated following the 10 days treatment in mice. In addition histopathologic changes and nuclear factor-kappaB (NF-kappaB) expression of the liver were detected with hematoxylin-eosin (HE) and immunohistochemistry methods, respectively. The results showed that TFB (50 and 100mg/kg) effectively reduced the CCl(4)-induced elevated liver index, serum ALT, AST levels, hepatic MDA content, and restored hepatic SOD, GSH-Px activities in acute liver injury mice. TFB (60 and 90mg/kg) treatment significantly inhibited NF-kappaB activation in liver fibrosis of rats. The histopathological analysis suggested that TFB reduced the degree of liver injury in mice and severity of liver fibrosis in rats. These results suggested that TFB had a protective and therapeutic effect on animal liver injury, which might be associated with its antioxidant properties and inhibition of NF-kappaB activation. PMID:18313245

Yuan, Li-Ping; Chen, Fei-Hu; Ling, Lu; Dou, Peng-Fei; Bo, Hu; Zhong, Ming-Mei; Xia, Li-Juan

2008-03-28

269

Propofol Attenuates Toxic Oxidative Stress by CCl4 in Liver Mitochondria and Blood in Rat  

PubMed Central

Anti-oxidant effects of propofol (2, 6-diisopropylphenol) were evaluated agains carbon tetrachloridet CCl4 -induced oxidative stress in rat liver. 30 male rats were equally divided in to 6 groups (5 rats each). Group I (control), while Group II was given CCl4 (3 mL /Kg/day, IP). Animals of Groups III received only propofol (10 mg/Kg/day, IP). Group IV was given propofol+ CCl4. Group V was administered vitamin E (alpha-tocopherol acetate 15 mg/Kg/day, SC) .Animals of Group VII received alpha-tocopherol acetate + CCl4 once daily for two weeks. After treatment, blood and liver mitochondria were isolated. Anti-oxidant enzymes activity such as glutathione peroxidase (GPx), superoxide dismutase (SOD) and oxidative stress marker such as reduced glutathione (GSH) and lipid peroxidation (LPO) concentration were measured. Oxidative stress induced with CCl4 in liver mitochondria was evident by a significant increase in enzymatic activities of GPx, SOD, and LPO and decreased of GSH and vailability of mitochondria. Propofol and vitamin E restored CCl4-induced changes in GSH, GPx, SOD and LPO in blood and liver mitochondria. CCl4 decreased viability of mitochondria that was recovered by propofol and vitamin E. It is concluded that oxidative damage is the mechanism of toxicity of CCl4 in the mitochondria that can be recovered by propofol comparable to vitamin E. PMID:24734078

Ranjbar, Akram; Sharifzadeh, Mohammad; Karimi, Jamshid; Tavilani, Heidar; Baeeri, Maryam; Heidary shayesteh, Tavakol; Abdollahi, Mohammad

2014-01-01

270

Emerging Therapies for Liver Fibrosis  

Microsoft Academic Search

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

Andrew J. Fowell; John P. Iredale

2006-01-01

271

Peculiar characteristics of portal-hepatic hemodynamics of alcoholic cirrhosis  

PubMed Central

Alcohol-related cirrhosis is a consequence of heavy and prolonged drinking. Similarly to patients with cirrhosis of other etiologies, patients with alcoholic cirrhosis develop portal hypertension and the hepatic, splanchnic and systemic hemodynamic alterations that follow. However, in alcoholic cirrhosis, some specific features can be observed. Compared to viral cirrhosis, in alcohol-related cirrhosis sinusoidal pressure is generally higher, hepatic venous pressure gradient reflects portal pressure better, the portal flow perfusing the liver is reduced despite an increase in liver weight, the prevalence of reversal portal blood flow is higher, a patent paraumbilical vein is a more common finding and signs of hyperdynamic circulations, such as an increased cardiac output and decreased systemic vascular resistance, are more pronounced. Moreover, alcohol consumption can acutely increase portal pressure and portal-collateral blood flow. Alcoholic cardiomyopathy, another pathological consequence of prolonged alcohol misuse, may contribute to the hemodynamic changes occurring in alcohol-related cirrhosis. The aim of this review was to assess the portal-hepatic changes that occur in alcohol-related cirrhosis, focusing on the differences observed in comparison with patients with viral cirrhosis. The knowledge of the specific characteristics of this pathological condition can be helpful in the management of portal hypertension and its complications in patients with alcohol-related cirrhosis. PMID:25009370

Bolognesi, Massimo; Verardo, Alberto; Di Pascoli, Marco

2014-01-01

272

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

PubMed Central

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

2013-01-01

273

FTY720, a sphingosine-1 phosphate receptor modulator, improves liver fibrosis in a mouse model by impairing the motility of bone marrow-derived mesenchymal stem cells.  

PubMed

FTY720 is a novel immunosuppressant that modulates sphingosine 1-phosphate (S1P) receptors for the treatment of several diseases. Several hallmarks of liver fibrosis are influenced by S1P, and the interference of S1P signaling by treatment with FTY720 results in beneficial effects in various animal models of fibrosis. However, whether these treatment strategies suppress liver fibrosis progression is incompletely understood. Here, we investigated the effects and mechanisms by which FTY720 improves liver fibrosis in the carbon tetrachloride (CCl4)-induced mouse model. FTY720 treatment significantly attenuated the expression of fibrotic markers in the injured liver of both wild-type and SCID-beige mice. The migration of bone marrow-derived mesenchymal stem cells (BMSCs) to circulation, and subsequently the injured liver, was suppressed by FTY720. Furthermore, in vitro, phosphorylated-FTY720 blocked the migration of BMSCs mediated by S1P. Thus, FTY720 is an effective therapy for liver fibrosis via the suppression of BMSC migration in the CCl4-induced mouse model. PMID:24682874

Kong, Yaxian; Wang, Hong; Wang, Shuling; Tang, Na

2014-08-01

274

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

PubMed Central

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

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

2011-01-01

275

Jejunal microvilli atrophy and reduced nutrient transport in rats with advanced liver cirrhosis: improvement by Insulin-like Growth Factor I  

Microsoft Academic Search

BACKGROUND: Previous results have shown that in rats with non-ascitic cirrhosis there is an altered transport of sugars and amino acids associated with elongated microvilli. These alterations returned to normal with the administration of Insulin-Like Growth Factor-I (IGF-I). The aims of this study were to explore the evolution of these alterations and analyse the effect of IGF-I in rats with

Inma Castilla-Cortázar; María Pascual; Elena Urdaneta; Javier Pardo; Juan Enrique Puche; Bárbara Vivas; Amelia Díaz-Casares; María García; Matías Díaz-Sánchez; Isabel Varela-Nieto; Alberto Castilla; Salvador González-Barón

2004-01-01

276

Post-treatment of Ganoderma lucidum reduced liver fibrosis induced by thioacetamide in mice.  

PubMed

The present study was aimed at assessing the effects of Ganoderma lucidum extract (GLE) on an established liver fibrosis model with reference to the previously reported hepatoprotective effect of GLE against CCl(4)-induced fibrosis in rats. Repeated administration of thioacetamide (TAA) for 12 weeks to mice induced liver fibrosis. Treatment with GLE after the induction of liver fibrosis decreased the hepatic hydroxyproline content and improved liver histology. RT-qPCR analysis showed that GLE treatment reduced the mRNA expression of collagen (alpha1)(I), smooth muscle alpha-actin, tissue inhibitor of metalloproteinase 1 and metalloproteinase-13. In addition, the TAA-induced decrease in total collagenase activity was reversed by GLE treatment. In conclusion, oral administration of GLE reversed TAA-induced liver fibrosis, the mechanism of which might be related to the enhancement of collagenase activity. PMID:19621343

Wu, Yueh-Wern; Fang, Hsun-Lang; Lin, Wen-Chuan

2010-04-01

277

Direct and indirect evidence for the reversibility of cirrhosis.  

PubMed

The aim of this study was to assess the reversibility of cirrhosis after therapy in a large series of patients with cirrhosis from various etiologies. We performed a retrospective study of 113 patients with biopsy-proven cirrhosis who underwent specific therapy and follow-up biopsies. Two pathologists performed blinded analyses of indirect biochemical and morphological signs of cirrhosis. Fourteen (12.4%) of the 113 cirrhotic patients had biopsy-proven disappearance of cirrhosis, defined as a decrease of 2 or greater in their METAVIR fibrosis score: 8 were related to hepatitis C virus, 3 to hepatitis B virus, and 3 to autoimmune cirrhosis. Necro-inflammatory activity decreased from 2.4 +/- 0.65 to 0.85 +/- 0.9 (P = .004), and fibrosis from 4 to 1.7 +/- 0.61 (P = .001). Prothrombin time (n = 1), platelet count (n = 2), serum albumin level (n = 2), and ultrasound abnormalities (n = 6) normalized in patients who had initial abnormalities. Hyaluronic acid and procollagen type III serum level decreased in all. In the 11 patients with regression of viral cirrhosis, 2 were nonresponders and 9 were responders, including 2 relapsers. The 3 patients with regressive autoimmune cirrhosis were complete responders to immunosupressive therapy. Using repeated liver biopsies, clinicobiochemical, radiologic, and endoscopic tests, we provide evidence for potential reversibility of cirrhosis after long-lasting suppression of the necro-inflammatory activity of liver disease. PMID:16997354

Serpaggi, Jeanne; Carnot, Françoise; Nalpas, Bertrand; Canioni, Danièle; Guéchot, Jérôme; Lebray, Pascal; Vallet-Pichard, Anaïs; Fontaine, Hélène; Bedossa, Pierre; Pol, Stanislas

2006-12-01

278

Continuous blood pressure monitoring in cirrhosis  

Microsoft Academic Search

Background\\/Aims: Low arterial blood pressure is recognised as a distinctive factor in the hyperdynamic circulation in cirrhosis. 24-hour monitoring of the blood pressure and heart rate has recently revealed a reduced circadian variation with relation to liver function. However, associations with other clinical and haemodynamic characteristics have not been investigated and the aim of the present study was to identify

Søren Møller; Erik Christensen; Jens H. Henriksen

1997-01-01

279

Human C1 inhibitor attenuates liver ischemia-reperfusion injury and promotes liver regeneration.  

PubMed

Liver ischemia-reperfusion injury (IRI) is a well-known cause of morbidity and mortality after liver transplantation (LT). Activation of the complement system contributes to the pathogenesis of IRI. Effective treatment strategies aimed at reducing hepatic IRI and accelerating liver regeneration could offer major benefits in LT. Herein, we investigated the effect of C1-esterase inhibitor (human) [C1-INH] on IRI and liver regeneration. Mice were subjected to 60-min partial IRI, with or without 70% partial hepatectomy, or CCl4-induced acute liver failure. Before liver injury, the animals were pretreated with intravenous C1-INH or normal saline. Liver IRI was evaluated using serum levels of alanine aminotransferase, serum interleukin-6, and histopathology. Liver samples were stained for specific markers of regeneration (5-bromo-2'-deoxyuridine [BrdU] staining and proliferating cell nuclear antigen [PCNA]). Histology, serum interleukin-6, and alanine aminotransferase release revealed that C1-INH treatment attenuated liver injury compared with controls. Improved animal survival and increased number of BrdU- and PCNA-positive cells were observed in C1-INH-treated animals which underwent IRI + partial hepatectomy or CCl4 injection compared with control group. These data indicate that complement plays a key role in IRI and liver regeneration. C1-INH represents a potential therapeutic strategy to reduce IRI and promote regeneration in LT. PMID:24433870

Saidi, Reza F; Rajeshkumar, Barur; Shariftabrizi, Ahmad; Dresser, Karen; Walter, Otto

2014-04-01

280

Promotion of Liver Regeneration/Repair by Farnesoid X Receptor in Both Liver and Intestine  

PubMed Central

FXR is a member of the nuclear receptor superfamily and is the primary bile acid receptor. We previously showed that FXR was required for the promotion of liver regeneration/repair after physical resection or liver injury. However, the mechanism by which FXR promotes liver regeneration/repair is still unclear. Here we showed that both hepatic-FXR and intestine-FXR contributed to promoting liver regeneration/repair after either 70% partial hepatectomy or CCl4-induced liver injury. Hepatic FXR, but not intestine FXR, is required for the induction of Foxm1b gene expression in liver during liver regeneration/repair. In contrast, intestine FXR is activated to induce FGF15 expression in intestine after liver damage. Ectopic expression of FGF15 was able to rescue the defective liver regeneration/repair in intestine-specific FXR null mice. Conclusion These results demonstrate that, in addition to the cell-autonomous effect of hepatic FXR, the endocrine FGF15 pathway activated by FXR in intestine also participates in the promotion of liver regeneration/repair. PMID:22711662

Zhang, Lisheng; Wang, Yan-Dong; Chen, Wei-Dong; Wang, Xichun; Lou, Guiyu; Liu, Nian; Lin, Min; Forman, Barry M.; Huang, Wendong

2012-01-01

281

Cirrhosis of undefined pathogenesis: absence of evidence for unknown viruses or autoimmune processes.  

PubMed

To examine whether unknown viruses or autoimmune processes contribute to the development of cryptogenic liver disease, we studied 48 patients undergoing liver transplantation who had non-A, non-B cirrhosis; non-blood-borne cirrhosis of unknown etiology; or autoimmune cirrhosis. After the diagnosis of hepatitis C virus infection was established by the presence of viral antibodies or viral RNA, patients were reclassified into three groups: hepatitis C virus infection, autoimmune cirrhosis and cryptogenic cirrhosis. Explant histological appearance, incidence of posttransplant hepatitis and immunological features were compared in the three groups. Thirty-one percent of patients had neither hepatitis C virus infection nor classical autoimmune cirrhosis and were classified as having cryptogenic cirrhosis. Unlike histological appearance in hepatitis C virus infection but similar to that in autoimmune cirrhosis, explant histological appearance of cryptogenic cirrhosis showed inactive cirrhosis with little inflammation. After transplantation, histological hepatitis of the allograft was demonstrated in 44% of patients with hepatitis C infection but in no patient with autoimmune or cryptogenic cirrhosis. The autoimmune score, developed from clinical criteria associated with autoimmune liver disease, was significantly lower in cryptogenic cirrhosis and hepatitis C virus infection than in autoimmune cirrhosis. Autoantibodies--including antinuclear antibodies, smooth muscle antibodies and liver-kidney microsomal antibodies--were not commonly present in serum of patients with cryptogenic cirrhosis, whereas antibodies to soluble liver antigens were found with increased frequency in this entity. We conclude that in many patients with liver disease, no pathogenesis can be identified.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8386693

Greeve, M; Ferrell, L; Kim, M; Combs, C; Roberts, J; Ascher, N; Wright, T L

1993-04-01

282

Antioxidant Activity and Hepatoprotective Potential of Black Seed, Honey and Silymarin on Experimental Liver Injuries Induced by CCl4 in Rats  

NASA Astrophysics Data System (ADS)

The possible antioxidant activity and hepatoprotective potential of black seed honey and silymarin on CCl4 induced liver injuries in rats was investigated. Fifty male rats were used in this study and divided into five groups, 10 rats each. Group 1 served as a control; group 2 injected 1 mL kg-1 day-1 CCl4 intraperitoneally 3 times a week for 4 week, groups 3, 4 and 5 subjected to the same injection of CCl4 and co-treatment with black seed, honey and silymarin (50 mg kg-1 b.wt.), respectively, daily by stomach tube for 4 weeks. Blood and tissue samples were taken for biochemical and histopathological studies. The results revealed that CCl4 administration caused significant elevations in the levels of MDA, NO, MMP-2, AST and ALT. Histopathological observations showed severe damage in the liver. Its fibrotic areas were measured using Image Analyzer. Combined treatment with CCl4 and black seed, honey and silymarin showed marked improvement in antioxidant status and in histopathological findings as well as reductions in the fibrotic areas. These results concluded that black seed, honey and silymarin have protective characteristics against CCl4-induced rat liver injury through potentiation of antioxidant capacity of liver cells and prevention of oxidative stress that accompanied with CCl4 hepatotoxicity. The protective effect was higher in silymarin followed by black seed then honey.

Khadr, Mona E.; Mahdy, Karam A.; El-Shamy, Karima A.; Morsy, Fatma A.; El-Zayat, Salwa R.; Abd-Allah, Azza A.

283

Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells Alleviate Liver Fibrosis  

PubMed Central

Mesenchymal stem cells (MSCs) have been considered as an attractive tool for the therapy of diseases. Exosomes excreted from MSCs can reduce myocardial ischemia/reperfusion damage and protect against acute tubular injury. However, whether MSC-derived exosomes can relieve liver fibrosis and its mechanism remain unknown. Previous work showed that human umbilical cord-MSCs (hucMSCs) transplanted into acutely injured and fibrotic livers could restore liver function and improve liver fibrosis. In this study, it was found that transplantation of exosomes derived from hucMSC (hucMSC-Ex) reduced the surface fibrous capsules and got their textures soft, alleviated hepatic inflammation and collagen deposition in carbon tetrachloride (CCl4)-induced fibrotic liver. hucMSC-Ex also significantly recovered serum aspartate aminotransferase (AST) activity, decreased collagen type I and III, transforming growth factor (TGF)-?1 and phosphorylation Smad2 expression in vivo. In further experiments, we found that epithelial-to-mesenchymal transition (EMT)-associated markers E-cadherin-positive cells increased and N-cadherin- and vimentin-positive cells decreased after hucMSC-Ex transplantation. Furthermore, the human liver cell line HL7702 underwent typical EMT after induction with recombinant human TGF-?1, and then hucMSC-Ex treatment reversed spindle-shaped and EMT-associated markers expression in vitro. Taken together, these results suggest that hucMSC-Ex could ameliorate CCl4-induced liver fibrosis by inhibiting EMT and protecting hepatocytes. This provides a novel approach for the treatment of fibrotic liver disease. PMID:23002959

Li, Tingfen; Yan, Yongmin; Wang, Bingying; Zhang, Xu; Shen, Li; Wang, Mei; Zhou, Ying; Zhu, Wei; Li, Wei

2013-01-01

284

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

PubMed Central

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

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

2014-01-01

285

Hepatitis C Virus Network Based Classification of Hepatocellular Cirrhosis and Carcinoma  

E-print Network

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

Huang, Tao

286

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

PubMed

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

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

2012-08-01

287

Primary biliary cirrhosis associated with membranous glomerulonephritis.  

PubMed

A 33-year-old woman was admitted to our department for evaluation of liver dysfunction and proteinuria. A liver biopsy specimen showed ductular proliferation and moderate portal fibrosis indicating stage II primary biliary cirrhosis. A renal biopsy specimen showed mild to moderate mesangial cell proliferation without crescent formation or interstitial nephritis. Immunofluorescent staining revealed deposition of immunoglobulin G (IgG), third component of complement (C3), and Clq on glomerular basement membranes. The findings indicated stage I membranous glomerulonephritis. Administration of ursodesoxycholic acid together with prednisolone, azathioprine, and dipyridamole decreased proteinuria and improved cholestatic liver dysfunction. PMID:10052737

Goto, T; Komatsu, M; Fujii, T; Ohshima, S; Nakane, K; Yoneyama, K; Shibuya, T; Meng, X W; Masamune, O; Imai, H

1999-01-01

288

Liver  

E-print Network

Lipids in liver wet and dry matter, liver moist and dry matter and their relationships were investigated based on species, sex and age in cows, buffaloes, sheep and goats. Mean percentage of lipids in liver wet and dry matter and liver dry matter in cows were 3.60%, 1.10%, 29.70%, and for buffaloes were 5.30%, 1.55%, 29.20%, sheep 3.00%, 0.83%, 27.90%, and goats 2.910%, 1.55 % and 28.40%, respectively. The highest and lowest percentage of lipids in liver wet and dry matter was observed in buffaloes and sheep, and for the liver dry matter was recorded in cows and sheep, respectively. Analyses showed significant differences in liver parameters among ruminants (p liver parameters. In overall 15.00 % of buffaloes and 3.50 % of cows showed over 10.00 % lipids in liver, while none of small ruminants appeared to have over 6.00 % lipids in liver. There was no correlation between liver lipid and liver dry matter. In conclusion mean percentage of lipid in liver dry matter in small ruminants was less than large ruminants. Liver dry matter was high in cows and low in sheep. Mean differences in liver parameters was significant, while the age and sex of the

Aligholi Ramin; Shahram Nozad; Babak Jelodari; Ghazaleh Ashtab; Zohreh Eftekhari; Sina Ramin; Key Words

2011-01-01

289

Hepatic and splanchnic nitric oxide activity in patients with cirrhosis  

Microsoft Academic Search

BACKGROUNDIn animal models of cirrhosis, altered activity of nitric oxide (NO) has been implicated in the pathogenesis of increased intrahepatic portal vascular resistance and abnormal mesenteric vasodilatation.AIMSTo investigate NO activity in the liver and splanchnic vascular bed of patients with cirrhosis.METHODSActivity of the calcium dependent constitutive and calcium independent inducible isoforms of NO synthase (cNOS and iNOS, respectively) was assayed

A I Sarela; F M A Mihaimeed; J J Batten; B R Davidson; R T Mathie

1999-01-01

290

Icaritin ameliorates carbon tetrachloride-induced acute liver injury mainly because of the antioxidative function through estrogen-like effects.  

PubMed

To investigate the effects of icaritin, an active ingredient extracted from Epimedium Sagittatum (Sieb. et Zucc.), on CCl4-induced liver injury and its possible mechanisms. Hepatocytes isolated from Sprague-Dawley male rats were treated with 3 mmol/L CCl4 for 24 h to induce acute liver cell injury, then icaritin (0.1, 1, 10, 100 ?mol/L, respectively) was administrated to the cells, and estrogen receptor antagonist ICI182,780 (1 ?mol/L) was co-treated with 10 ?mol/L icaritin. Biochemical parameters (alanine aminotransferase (ALT), aspartate aminotransferase (AST), malondialdehyde (MDA), and superoxide dismutase (SOD)) and cell apoptosis were detected to evaluate the injury degree. Protein expressions of Bax, Bcl-2, liver fatty acid-binding protein (L-FABP), and peroxisome proliferator-activated receptor-? (PPAR-?) as well as reactive oxygen species (ROS) generation were determined by western blot. Icaritin alleviated CCl4-induced liver cell injury in a concentration-dependent manner and 10 ?mol/L was the optimal concentration. Icaritin (10 ?mol/L) significantly reduced activities of ALT, AST in cell culture medium and MDA level of the impaired liver cells, but increased the intercellular SOD activity. The apoptotic rate of the impaired liver cells was also decreased by icaritin (10 ?mol/L) treatment. Icaritin might exert antioxidative and anti-apoptotic functions via estrogen-like effect, as the ratio of Bcl-2/Bax was significantly increased, while protein expressions of L-FABP and PPAR-? were markedly increased, and this function was blocked by the estrogen receptor antagonist ICI182,780 efficiently. Icaritin may be a promising drug candidate for acute liver injury benefiting from the antioxidative and anti-apoptotic functions via estrogen-like effect. PMID:25148823

Liu, Peng; Jin, Xiang; Lv, Hao; Li, Jing; Xu, Wen; Qian, Hai-Hua; Yin, Zhengfeng

2014-12-01

291

Antioxidant and hepatoprotective activity of punicalagin and punicalin on carbon tetrachloride-induced liver damage in rats.  

PubMed

Punicalagin and punicalin, isolated from the leaves of Terminalia catappa L., are used to treat dermatitis and hepatitis. Both compounds have strong antioxidative activity. The antihepatotoxic activity of punicalagin and punicalin on carbon tetrachloride (CCl4)-induced toxicity in the rat liver was evaluated. Levels of serum glutamate-oxalate-transaminase and glutamate-pyruvate-trans-aminase were increased by administration of CCl4 and reduced by drug treatment. Histological changes around the liver central vein and oxidation damage induced by CCl4 also benefited from drug treatment. The results show that both punicalagin and punicalin have anti-hepatotoxic activity but that the larger dose of punicalin induced liver damage. Thus even if tannins have strong antioxidant activity at very small doses, treatment with a larger dose will induce cell damage. PMID:9720629

Lin, C C; Hsu, Y F; Lin, T C; Hsu, F L; Hsu, H Y

1998-07-01

292

Therapeutic potential of morin against liver fibrosis in rats: modulation of oxidative stress, cytokine production and nuclear factor kappa B.  

PubMed

Therapeutic potential of morin, a member of flavonoid family, against carbon tetrachloride (CCl4)-induced liver fibrosis in rats was investigated and compared with that of silymarin. Results show that treatment with morin (30 mg/kg/day) revealed attenuation in liver index and serum biomarkers of liver function that were enhanced by chronic CCl4 intoxication. Further, morin inhibited the elevated levels of malondialdehyde and nitric oxide and restored hepatic reduced glutathione to its normal level. The increased production of hepatic hydroxyproline content by CCl4 was markedly decreased by administration of morin. In addition, treatment with morin significantly attenuated the inflammatory responses caused by CCl4 as evident by the decreased hepatic tumor necrosis factor-alpha (TNF-?) level, immunohistochemical expressions of inducible nitric oxide synthase and nuclear factor kappa B. Collectively, this study indicates that morin possesses antifibrotic effect in the CCl4 model of fibrosis via reducing oxidative stress, inflammatory responses and fibrogenic markers. PMID:24583409

Heeba, Gehan H; Mahmoud, Magda E

2014-03-01

293

Improving Survival in Decompensated Cirrhosis  

PubMed Central

Mortality in cirrhosis is consequent of decompensation, only treatment being timely liver transplantation. Organ allocation is prioritized for the sickest patients based on Model for End Stage Liver Disease (MELD) score. In order to improve survival in patients with high MELD score it is imperative to preserve them in suitable condition till transplantation. Here we examine means to prolong life in high MELD score patients till a suitable liver is available. We specially emphasize protection of airways by avoidance of sedatives, avoidance of Bilevel Positive Airway Pressure, elective intubation in grade III or higher encephalopathy, maintaining a low threshold for intubation with lesser grades of encephalopathy when undergoing upper endoscopy or colonoscopy as pre transplant evaluation or transferring patient to a transplant center. Consider post-pyloric tube feeding in encephalopathy to maintain muscle mass and minimize risk of aspiration. In non intubated and well controlled encephalopathy, frequent physical mobility by active and passive exercises are recommended. When renal replacement therapy is needed, night-time Continuous Veno-Venous Hemodialysis may be useful in keeping the daytime free for mobility. Sparing and judicious use of steroids needs to be borne in mind in treatment of ARDS and acute hepatitis from alcohol or autoimmune process. PMID:22811919

Mukerji, Amar Nath; Patel, Vishal; Jain, Ashokkumar

2012-01-01

294

Improving survival in decompensated cirrhosis.  

PubMed

Mortality in cirrhosis is consequent of decompensation, only treatment being timely liver transplantation. Organ allocation is prioritized for the sickest patients based on Model for End Stage Liver Disease (MELD) score. In order to improve survival in patients with high MELD score it is imperative to preserve them in suitable condition till transplantation. Here we examine means to prolong life in high MELD score patients till a suitable liver is available. We specially emphasize protection of airways by avoidance of sedatives, avoidance of Bilevel Positive Airway Pressure, elective intubation in grade III or higher encephalopathy, maintaining a low threshold for intubation with lesser grades of encephalopathy when undergoing upper endoscopy or colonoscopy as pre transplant evaluation or transferring patient to a transplant center. Consider post-pyloric tube feeding in encephalopathy to maintain muscle mass and minimize risk of aspiration. In non intubated and well controlled encephalopathy, frequent physical mobility by active and passive exercises are recommended. When renal replacement therapy is needed, night-time Continuous Veno-Venous Hemodialysis may be useful in keeping the daytime free for mobility. Sparing and judicious use of steroids needs to be borne in mind in treatment of ARDS and acute hepatitis from alcohol or autoimmune process. PMID:22811919

Mukerji, Amar Nath; Patel, Vishal; Jain, Ashokkumar

2012-01-01

295

Effects of proinflammatory cytokines on rat organic anion transporters during toxic liver injury and cholestasis.  

PubMed

Hepatobiliary transporters are down-regulated in toxic and cholestatic liver injury. Cytokines such as tumor necrosis factor alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta) are attributed to mediate this regulation, but their particular contribution in vivo is still unknown. Thus, we studied the molecular mechanisms by which Ntcp, Oatp1, Oatp2, and Mrp2 are regulated by proinflammatory cytokines during liver injury. Rats were injected intraperitoneally with either carbon tetrachloride or endotoxin. Inactivation of TNF-alpha and IL-1 beta was achieved by repetitive intraperitoneal injection of etanercept and anakinra, respectively. Messenger RNA (mRNA) levels of transporters and binding activities as well as nuclear protein levels of Ntcp, Oatp2, and Mrp2 transactivators were determined 20 to 24 hours later. In contrast to IL-1 beta, TNF-alpha inactivation alone fully prevented down-regulation of Ntcp, Oatp1, and Oatp2 mRNA as well as reduced binding activity of hepatocyte nuclear factor 1 (HNF-1) in CCl(4)-induced toxic injury. In endotoxemia, down-regulation of Mrp2, and partially in case of Ntcp, could be prevented by IL-1 beta but not TNF-alpha blockade. However, inactivation of either cytokine led to preservation of HNF1 and partially of retinoid X receptor/retinoic acid receptor (RXR/RAR) binding activity. No effect of anticytokines was seen on pregnane X receptor (PXR) and constitutive androstane receptor (CAR) binding activity as well as nuclear protein mass. In conclusion, TNF-alpha represents the master cytokine responsible for HNF1-dependent down-regulation of Ntcp, Oatp1, and Oatp2 in CCl(4)-induced toxic liver injury. IL-1 beta predominates in a complex signaling network of Ntcp and Mrp2 regulation in cholestatic liver injury. In contrast to in vitro studies, HNF1 and RXR/RAR-independent mechanisms appear to be more important in regulation of Mrp2 and Ntcp gene expression in endotoxemia. PMID:12883478

Geier, Andreas; Dietrich, Christoph G; Voigt, Sebastian; Kim, Suk-Kyum; Gerloff, Thomas; Kullak-Ublick, Gerd A; Lorenzen, Johann; Matern, Siegfried; Gartung, Carsten

2003-08-01

296

Antitubercular therapy in patients with cirrhosis: challenges and options.  

PubMed

Tuberculosis (TB) has been a human disease for centuries. Its frequency is increased manyfold in patients with liver cirrhosis. The gold standard of TB management is a 6-mo course of isoniazid, rifampicin, pyrazinamide and ethambutol. Although good results are seen with this treatment in general, the management of patients with underlying cirrhosis is a challenge. The underlying depressed immune response results in alterations in many diagnostic tests. The tests used for latent TB have many flaws in this group of patients. Three of four first-line antitubercular drugs are hepatotoxic and baseline liver function is often disrupted in patients with underlying cirrhosis. Frequency of hepatotoxicity is increased in patients with liver cirrhosis, frequently leading to severe liver failure. There are no established guidelines for the treatment of TB in relation to the severity of liver disease. There is no consensus on the frequency of liver function tests required or the cut-off used to define hepatotoxicity. No specific treatment exists for prevention or treatment of hepatotoxicity, making monitoring even more important. A high risk of multidrug-resistant TB is another major worry due to prolonged and interrupted treatment. PMID:24914337

Kumar, Naveen; Kedarisetty, Chandan Kumar; Kumar, Sachin; Khillan, Vikas; Sarin, Shiv Kumar

2014-05-21

297

Antitubercular therapy in patients with cirrhosis: Challenges and options  

PubMed Central

Tuberculosis (TB) has been a human disease for centuries. Its frequency is increased manyfold in patients with liver cirrhosis. The gold standard of TB management is a 6-mo course of isoniazid, rifampicin, pyrazinamide and ethambutol. Although good results are seen with this treatment in general, the management of patients with underlying cirrhosis is a challenge. The underlying depressed immune response results in alterations in many diagnostic tests. The tests used for latent TB have many flaws in this group of patients. Three of four first-line antitubercular drugs are hepatotoxic and baseline liver function is often disrupted in patients with underlying cirrhosis. Frequency of hepatotoxicity is increased in patients with liver cirrhosis, frequently leading to severe liver failure. There are no established guidelines for the treatment of TB in relation to the severity of liver disease. There is no consensus on the frequency of liver function tests required or the cut-off used to define hepatotoxicity. No specific treatment exists for prevention or treatment of hepatotoxicity, making monitoring even more important. A high risk of multidrug-resistant TB is another major worry due to prolonged and interrupted treatment. PMID:24914337

Kumar, Naveen; Kedarisetty, Chandan Kumar; Kumar, Sachin; Khillan, Vikas; Sarin, Shiv Kumar

2014-01-01

298

A case of Berardinelli-Seip syndrome presenting with cirrhosis.  

PubMed

Berardinelli-Seip congenital lipodystrophy (BSCL) is a rare autosomal recessive disorder of generalised lipoatrophy, characterised by the absence of functioning adipocytes, with lipid being stored in muscles, the liver and the pancreas. The usual presentation is in adulthood, with manifestations of insulin resistance, hypertriglyceridaemia and liver steatosis. Cirrhosis as the first presentation of BSCL in a young adult is rare. We describe a patient with BSCL presenting with cirrhosis. To the best of our knowledge this is the first case of BSCL reported in a Sri Lankan patient. PMID:24350312

Wimalaratna, H; Nandasiri, A S D

2013-01-01

299

Edible oils for liver protection: hepatoprotective potentiality of Moringa oleifera seed oil against chemical-induced hepatitis in rats.  

PubMed

In the present study, in vitro antioxidant, antioxidative stress and hepatoprotective activity of Moringa oleifera Lam. seed oil (Ben oil; BO) was evaluated against carbon tetrachloride (CCl(4) ) induced lipid peroxidation and hepatic damage in rats. The oil at 0.2 and 0.4 mL/rat was administered orally for 21 consecutive days. The substantially elevated serum enzymatic (GOT, GPT, ALP, GGT) and bilirubin levels were significantly restored towards normalization by the oil. There was a significant elevation in the level of malondialdehyde (MDA), non-protein sulfhydryl (NP-SH), and total protein (TP) contents in the liver tissue. The results obtained indicated that BO possesses potent hepatoprotective action against CCl(4) -induced hepatic damage by lowering liver marker enzymes, MDA concentration, and elevating NP-SH and TP levels in liver tissue. The biochemical observations were supplemented with histopathological examination of rat liver. The results of this study showed that treatment with Ben oil or silymarin (as a reference) appears to enhance the recovery from hepatic damage induced by CCl(4) . The pentobarbital induced narcolepsy prolongation in mice was retarded by the Ben oil. Acute toxicity test in mice showed no morbidity or mortality. In vitro DPPH radical scavenging and ?-carotene-linolic acid assay tests of the BO exhibited a moderate antioxidant activity in both tests used. The possible mechanism(s) of the liver protective activity of Ben oil activity may be due to free radical scavenging potential caused by the presence of antioxidant component(s) in the oil. Consequently, BO can be used as a therapeutic regime in treatment of some hepatic disorders. PMID:22757719

Al-Said, Mansour S; Mothana, Ramzi A; Al-Yahya, Mohammed A; Al-Blowi, Ali S; Al-Sohaibani, Mohammed; Ahmed, Atallah F; Rafatullah, Syed

2012-07-01

300

Antihepatoma and Liver Protective Potentials of Ganoderma Lucidum (?? Ling Zhi) Fermented in a Medium Containing Black Soybean (?? H?i D?u) and Astragalus Membranaceus (??? Sh?ng Hu?ng Q?)  

PubMed Central

The antihepatoma activity and liver protective function of the fermentation products (5 L fermenator) of Ganoderma lucidum (GL; ?? Ling Zhi) cultivated in a medium containing black soybean (BS; ?? H?i Dòu) and Astragalus membranaceus (AM; ??? Sh?ng Huáng Qí) at different fermentation temperatures were investigated in this study. Hep 3B cells pretreated with lovastatin were used to study the antihepatoma activity, and possible active components were analyzed by reverse-phase high-performance liquid chromatography. Carbon tetrachloride (CCl4)-induced primary rat hepatocyte injury was further used to evaluate the liver protective activity of the fermentation products. While all the GL broth filtrates do not inhibit the growth of Hep 3B cells, the ethanolic extract from GL-2 mycelia (GL-2-mE), cultivated in the medium containing BS (50 g/L) and AM (20 g/L) at 24°C for 11 days showed the best antihepatoma activity (IC50 26.6 ?g/mL) than the other ethanolic extracts from GL mycelia, GL fruiting body, BS, and AM did. The antihepatoma activities were correlated with some unknown active components in these samples. Furthermore, GL-2-mE (100 ?g/mL) without harmful effect on the growth of normal primary rat hepatocytes significantly maintained cell viability, reduced lactate dehydrogenase leakage, lowered lipid peroxidation, and increased glutathione peroxidase and glutathione S-transferase activities in the CCl4-induced damaged primary rat hepatocytes. PMID:24716165

Su, Zheng-Yuan; Sun Hwang, Lucy; Chiang, Been-Huang; Sheen, Lee-Yan

2013-01-01

301

Risk factors and outcome of bacterial infections in cirrhosis  

PubMed Central

Viable and non-viable pathological bacterial translocation promote a self-perpetuating circle of dysfunctional immune activation and systemic inflammation facilitating infections and organ failure in advanced cirrhosis. Bacterial infections and sepsis are now recognized as a distinct stage in the natural progression of chronic liver disease as they accelerate organ failure and contribute to the high mortality observed in decompensated cirrhosis. The increasing knowledge of structural, immunological and hemodynamic pathophysiology in advanced cirrhosis has not yet translated into significantly improved outcomes of bacterial infections over the last decades. Therefore, early identification of patients at the highest risk for developing infections and infection-related complications is required to tailor the currently available measures of surveillance, prophylaxis and therapy to the patients in need in order to improve the detrimental outcome of bacterial infections in cirrhosis. PMID:24627590

Bruns, Tony; Zimmermann, Henning W; Stallmach, Andreas

2014-01-01

302

Editorial:Clostridium difficile Infection: Yet Another Predictor of Poor Outcome in Cirrhosis  

Microsoft Academic Search

The development of Clostridium difficile infection in cirrhosis is predictive of death, independent of severity of liver disease. The main risk factors are the use of antibiotics and proton-pump inhibitors (PPIs). This is further evidence that supports the wise and cautious use of antibiotics in cirrhosis and suggests avoiding the use of PPIs in these patients except for indications of

Guadalupe Garcia-Tsao; Christina M Surawicz

2010-01-01

303

DOES INCREASED SPENDING ON ALCOHOLISM TREATMENT LEAD TO LOWER CIRRHOSIS DEATH RATES?  

Microsoft Academic Search

The purpose of this study was to see if recent changes in the funding of alcoholism programmes in the United States were related to changes in liver cirrhosis death rates. Data on per-capita spending, per-capita alcohol consumption and cirrhosis death rates were gathered from various sources for the years 1979 and 1989 for the 50 states and the District of

REGINALD G. SMART; ROBERT E. MANN; SEANG-LOOI LEE

304

Longitudinal variation in hepatitis C virus (HCV) viraemia and early course of HCV infection after liver transplantation for HCV cirrhosis: the role of different immunosuppressive regimens  

PubMed Central

BACKGROUND—The role of the type of immunosuppression in the natural history of post-transplant hepatitis C virus (HCV) infection is unclear.?AIMS—To evaluate the fluctuation of HCV viraemia and the early course of infection, and their relation to the type of immunosuppression in HCV transplant patients.?METHODS—In 47 HCV transplant patients, serum HCV RNA levels were determined pretransplant and at one and two weeks, and three and 12 months after transplant. Initial immunosuppression was triple (cyclosporin, azathioprine, prednisolone) in 31, double (cyclosporin, prednisolone) in five, and single (cyclosporin or tacrolimus) in 11 patients. Prednisolone was withdrawn at a median of six months.?RESULTS—At three months, HCV RNA levels were higher in patients with single than with triple or double initial therapy. At 12 months, HCV RNA levels correlated only with duration of prednisolone treatment and were relatively higher in patients with triple compared with single initial immunosuppression. A higher necroinflammatory activity at 12 months post-transplant was found in patients with post-transplant acute hepatitis compared with those without. Extent of fibrosis at 12 months was associated with the 12 month HCV RNA level and occurrence of post-transplant acute hepatitis.?CONCLUSIONS—HCV RNA levels at three months after transplant are higher in patients treated with single initial immunosuppressive therapy, but at 12 months are higher in patients with longer duration of steroid treatment. HCV viraemia at 12 months seems to be particularly important, as its levels are strongly correlated with the severity of fibrosis.???Keywords: HCV RNA; HCV genotype; grading score; staging score; immunosuppression; liver transplantation PMID:10446114

Papatheodoridis, G; Barton, S; Andrew, D; Clewley, G; Davies, S; Dhillon, A; Dusheiko, G; Davidson, B; Rolles, K; Burroughs, A

1999-01-01

305

Hepatoprotective effect of Phyllanthus in Taiwan on acute liver damage induced by carbon tetrachloride.  

PubMed

The effect of oral administration of Phyllanthus methanolic extracts (PME) (i.e. P. acidus, P. emblica, P. myrtifolius, P. multiflorus, P. amarus, P. debilis, P. embergeri, P. hookeri, P. tenellus, P. urinaria L.s. nudicarpus, P. urinaria L.s. urinaria) or gallic acid (GA) on the progression of acute liver damage induced by CCl(4) in rats was examined by morphological and biochemical methods. P. acidus, P. urinaria L.s. urinaria, GA at a dose of 0.5 g/kg, and P. emblica, P. urinaria L.s. nudicarpus at a dose of 1.0 g/kg attenuated CCl(4)-induced increase in serum glutamate-oxalate-transaminase (GOT). P. acidus, P. urinaria L.s. nudicarpus, P. urinaria L.s. urinaria, GA at a dose of 0.5 g/kg, and P. emblica, P. amarus, P. hookeri, P. tenellus at a dose of 1.0 g/kg attenuated CCl(4)-induced increase in serum glutamate-pyruvate-transaminase (GPT). Concurrently, P. acidus, P. multiflorus, P. embergeri, P. hookeri, P. tenellus and P. urinaria L.s. urinaria elevated the activity of liver reduced glutathione peroxidase (GSH-Px). Since the protective effects of P. acidus, P. emblica, P. myrtifolius, P. embergeri, P. urinaria L.s. nudicarpus, P. urinaria L.s. urinaria and GA correlate with a reduction in liver infiltration and focal necrosis observed using histological methods, these data demonstrate that P. acidus and P. urinaria L.s. urinaria are hepatoprotective and antioxidant agents. PMID:16710896

Lee, Chao-Ying; Peng, Wen-Huang; Cheng, Hao-Yuan; Chen, Fei-Na; Lai, Ming-Tsung; Chiu, Tai-Hui

2006-01-01

306

Reversibility of hepatitis C virus-related cirrhosis.  

PubMed

The aim of this retrospective study was to determine the potential reversibility of hepatitis C virus (HCV) cirrhosis with the combined antifibrotic effects of interferon-alpha and the increasing frequency of sustained virologic response. Sixty-four HCV-cirrhotic immunocompetent patients who underwent antiviral therapies (interferon-alpha with or without ribavirin) and pretreatment and posttreatment liver biopsies were included (group 1). Resolution of cirrhosis was defined as a decrease in the fibrosis score from 4 to 2 or less by the Metavir score after blinded analysis by 2 independent pathologists. An additional group of 4 HCV-infected dialysis patients (group 2) who had received antiviral treatment, among whom 3 underwent a combined renal and liver transplantation allowing the analysis of the whole liver, was also studied. In 5 (all stage Child A) of the 64 cirrhotic patients (7.8%), the final biopsy showed only F2 to portal and periportal fibrosis with rare fibrous septa without nodule formation. Four of these 5 were complete sustained responders (negative PCR and normal ALT), and 1 was a relapser. In group 2, reversibility of cirrhosis was observed in 3 of the 4 patients and was clearly shown in 2 patients by the analysis of the whole-liver examination at the time of the hepatectomy preceding the transplantation. In conclusion, long-lasting suppression of the necroinflammatory activity of liver disease and/or antifibrogenetic effects of interferon-alpha may allow regression of cirrhosis. PMID:14745732

Pol, Stanislas; Carnot, Françoise; Nalpas, Bertrand; Lagneau, Jean-Luc; Fontaine, Héléne; Serpaggi, Jeanne; Serfaty, Lawrence; Bedossa, Pierre; Bréchot, Christian

2004-01-01

307

Downregulation effects of beta-elemene on the levels of plasma endotoxin, serum TNF-alpha, and hepatic CD14 expression in rats with liver fibrosis.  

PubMed

It has been demonstrated that ?-elemene could protect against carbon tetrachloride (CCl(4))-induced liver fibrosis in our laboratory work, and the aim of this paper is to reveal the protective mechanisms of ?-elemene. The hepatic fibrosis experimental model was induced by the hypodermical injection of CCl(4) in Wistar male rats. ?-elemene was intraperitoneally administered into rats for 8 weeks (0.1 mL/100 g bodyweight per day), and plasma endotoxin content was assayed by biochemistry. The serum TNF-? level was detected using radioactive immunity. CD14 expression in rat livers was measured by immunohistochemistry and Western blot. The results showed that ?-elemene can downregulate the levels of plasma endotoxins, serum TNF-?, and hepatic CD14 expression in rats with liver fibrosis. ?-elemene plays an important role in downregulating the lipopolysaccharide signal transduction pathway, a significant pathway in hepatic fibrosis development. PMID:21681682

Liu, Jianguo; Zhang, Zhe; Gao, Jiechang; Xie, Jiwen; Yang, Lin; Hu, Shenjun

2011-03-01

308

Impact of cirrhosis on surgical outcome after pancreaticoduodenectomy  

PubMed Central

AIM: To elucidate surgical outcomes of pancreaticoduodenectomy (PD) in patients with liver cirrhosis. METHODS: We studied retrospectively all patients who underwent PD in our centre between January 2002 and December 2011. Group A comprised patients with cirrhotic livers, and Group B comprised patients with non-cirrhotic livers. The cirrhotic patients had Child-Pugh classes A and B (patient’s score less than 8). Preoperative demographic data, intra-operative data and postoperative details were collected. The primary outcome measure was hospital mortality rate. Secondary outcomes analysed included duration of the operation, postoperative hospital stay, postoperative morbidity and survival rate. RESULTS: Only 67/442 patients (15.2%) had cirrhotic livers. Intraoperative blood loss and blood transfusion were significantly higher in group A (P = 0.0001). The mean surgical time in group A was significantly longer than that in group B (P = 0.0001). Wound complications (P = 0.02), internal haemorrhage (P = 0.05), pancreatic fistula (P = 0.02) and hospital mortality (P = 0.0001) were significantly higher in the cirrhotic patients. Postoperative stay was significantly longer in group A (P = 0.03). The median survival was 19 mo in group A and 24 mo in group B. Portal hypertension (PHT) was present in 16/67 cases of cirrhosis (23.9%). The intraoperative blood loss and blood transfusion were significantly higher in patients with PHT (P = 0.001). Postoperative morbidity (0.07) and hospital mortality (P = 0.007) were higher in cirrhotic patients with PHT. CONCLUSION: Patients with periampullary tumours and well-compensated chronic liver disease should be routinely considered for PD at high volume centres with available expertise to manage liver cirrhosis. PD is associated with an increased risk of postoperative morbidity in patients with liver cirrhosis; therefore, it is only recommended in patients with Child A cirrhosis without portal hypertension. PMID:24222957

El Nakeeb, Ayman; Sultan, Ahmad M; Salah, Tarek; El Hemaly, Mohamed; Hamdy, Emad; Salem, Ali; Moneer, Ahmed; Said, Rami; AbuEleneen, Ahmed; Abu Zeid, Mostafa; Abdallah, Talaat; Abdel Wahab, Mohamed

2013-01-01

309

Gut microbiota-related complications in cirrhosis  

PubMed Central

Gut microbiota plays an important role in cirrhosis. The liver is constantly challenged with commensal bacteria and their products arriving through the portal vein in the so-called gut-liver axis. Bacterial translocation from the intestinal lumen through the intestinal wall and to mesenteric lymph nodes is facilitated by intestinal bacterial overgrowth, impairment in the permeability of the intestinal mucosal barrier, and deficiencies in local host immune defences. Deranged clearance of endogenous bacteria from portal and systemic circulation turns the gut into the major source of bacterial-related complications. Liver function may therefore be affected by alterations in the composition of the intestinal microbiota and a role for commensal flora has been evidenced in the pathogenesis of several complications arising in end-stage liver disease such as hepatic encephalopathy, splanchnic arterial vasodilatation and spontaneous bacterial peritonitis. The use of antibiotics is the main therapeutic pipeline in the management of these bacteria-related complications. However, other strategies aimed at preserving intestinal homeostasis through the use of pre-, pro- or symbiotic formulations are being studied in the last years. In this review, the role of intestinal microbiota in the development of the most frequent complications arising in cirrhosis and the different clinical and experimental studies conducted to prevent or improve these complications by modifying the gut microbiota composition are summarized.

Gomez-Hurtado, Isabel; Such, Jose; Sanz, Yolanda; Frances, Ruben

2014-01-01

310

Management and Treatment of Patients With Cirrhosis and Portal Hypertension: Recommendations From the Department of Veterans Affairs Hepatitis C Resource Center Program and the National Hepatitis C Program  

Microsoft Academic Search

Cirrhosis represents the end stage of any chronic liver disease. Hepatitis C and alcohol are currently the main causes of cirrhosis in the United States. Although initially cirrhosis is compensated, it eventually becomes decompensated, as defined by the presence of ascites, variceal hemorrhage, encephalopathy, and\\/or jaundice. These management recommendations are divided according to the status, compensated or decompensated, of the

Guadalupe Garcia-Tsao; Joseph Lim

2009-01-01

311

The Protective Effect of Glycyrrhetinic Acid on Carbon Tetrachloride-Induced Chronic Liver Fibrosis in Mice via Upregulation of Nrf2  

PubMed Central

This study was designed to investigate the potentially protective effects of glycyrrhetinic acid (GA) and the role of transcription factor nuclear factor-erythroid 2(NF-E2)-related factor 2 (Nrf2) signaling in the regulation of Carbon Tetrachloride (CCl4)-induced chronic liver fibrosis in mice. The potentially protective effects of GA on CCl4-induced chronic liver fibrosis in mice were depicted histologically and biochemically. Firstly, histopathological changes including regenerative nodules, inflammatory cell infiltration and fibrosis were induced by CCl4.Then, CCl4 administration caused a marked increase in the levels of serum aminotransferases (GOT, GPT), serum monoamine oxidase (MAO) and lipid peroxidation (MDA) as well as MAO in the mice liver homogenates. Also, decreased nuclear Nrf2 expression, mRNA levels of its target genes such as superoxide dismutase 3 (SOD3), catalase (CAT), glutathione peroxidase 2 (GPX2), and activity of cellular antioxidant enzymes were found after CCl4 exposure. All of these phenotypes were markedly reversed by the treatment of the mice with GA. In addition, GA exhibited the antioxidant effects in vitro by on FeCl2-ascorbate induced lipid peroxidation in mouse liver homogenates, and on DPPH scavenging activity. Taken together, these results suggested that GA can protect the liver from oxidative stress in mice, presumably through activating the nuclear translocation of Nrf2, enhancing the expression of its target genes and increasing the activity of the antioxidant enzymes. Therefore, GA may be an effective hepatoprotective agent and viable candidate for treating liver fibrosis and other oxidative stress-related diseases. PMID:23341968

Chen, Shaoru; Zou, Liyi; Li, Li; Wu, Tie

2013-01-01

312

The protective effect of glycyrrhetinic acid on carbon tetrachloride-induced chronic liver fibrosis in mice via upregulation of Nrf2.  

PubMed

This study was designed to investigate the potentially protective effects of glycyrrhetinic acid (GA) and the role of transcription factor nuclear factor-erythroid 2(NF-E2)-related factor 2 (Nrf2) signaling in the regulation of Carbon Tetrachloride (CCl(4))-induced chronic liver fibrosis in mice. The potentially protective effects of GA on CCl(4)-induced chronic liver fibrosis in mice were depicted histologically and biochemically. Firstly, histopathological changes including regenerative nodules, inflammatory cell infiltration and fibrosis were induced by CCl(4).Then, CCl(4) administration caused a marked increase in the levels of serum aminotransferases (GOT, GPT), serum monoamine oxidase (MAO) and lipid peroxidation (MDA) as well as MAO in the mice liver homogenates. Also, decreased nuclear Nrf2 expression, mRNA levels of its target genes such as superoxide dismutase 3 (SOD3), catalase (CAT), glutathione peroxidase 2 (GPX2), and activity of cellular antioxidant enzymes were found after CCl(4) exposure. All of these phenotypes were markedly reversed by the treatment of the mice with GA. In addition, GA exhibited the antioxidant effects in vitro by on FeCl(2)-ascorbate induced lipid peroxidation in mouse liver homogenates, and on DPPH scavenging activity. Taken together, these results suggested that GA can protect the liver from oxidative stress in mice, presumably through activating the nuclear translocation of Nrf2, enhancing the expression of its target genes and increasing the activity of the antioxidant enzymes. Therefore, GA may be an effective hepatoprotective agent and viable candidate for treating liver fibrosis and other oxidative stress-related diseases. PMID:23341968

Chen, Shaoru; Zou, Liyi; Li, Li; Wu, Tie

2013-01-01

313

An unusual case of aggressive systemic mastocytosis mimicking hepatic cirrhosis  

PubMed Central

Hepatic involvement in aggressive systemic mastocytosis (ASM) is relatively common, and the main clinical features of this disease include hepatomegaly, portal hypertension, ascites, and fibrosis. Cirrhosis is a rare ASM symptom. We report an ASM case that initially mimicked cirrhosis based on clinical and radiographic analyses. The portal tract was expanded by mononuclear in?ammatory cells, and an increase in collagen amount was observed in routine histological sections of the biopsied liver. A diagnosis of systemic mastocytosis (SM) was made after ancillary tests for mast cells using bone marrow aspirates. Extensive involvement of the liver and gastrointestinal tract was observed. Clinicians and pathologists need to consider ASM as a diagnosis or differential diagnosis in a clinical case of cirrhosis with unknown etiology. The diagnosis can be confirmed or disregarded by immunohistochemical staining and molecular analysis. PMID:25009756

Zhang, Xiao-Yang; Zhang, Wei-Hua

2014-01-01

314

Structural characterisation of algae Costaria costata fucoidan and its effects on CCl?-induced liver injury.  

PubMed

Fucoidan is a well-known natural product that is commonly found in brown algae and shows a variety of activities, including immunomodulation, antioxidation, and the combat of carcinogens. The fucoidan fractions of Costaria costata, a brown algae introduced from Japan and cultured in northern China, were studied. The fucoidan fractions were extracted, separated, and purified using a combinatorial procedure consisting of enzymolysis, ethanol precipitation, and DEAE and size-exclusion chromatographies. The fundamental characteristics of the four enriched fucoidan fractions (F1-F4), such as their sulphate content and monosaccharide composition, were investigated. FTIR and NMR spectroscopy were employed to further elucidate the structural features of the four fractions. It was found that the F1-F4 fractions all showed oxidative activity against hydroxyl radicals. The bioactive effects of the fucoidan fractions on CCl4-induced liver injury suggest their potential use as ingredients for functional foods or pharmaceuticals. PMID:24702942

Wang, Qiukuan; Song, Yuefan; He, Yunhai; Ren, Dandan; Kow, Felicia; Qiao, Zhiyong; Liu, Shu; Yu, Xingju

2014-07-17

315

The Cognitive Profile of Depressed Patients With Cirrhosis  

PubMed Central

Objective: To determine whether patients with cirrhosis and depressive symptoms have a different neuropsychological cognitive profile from patients with cirrhosis without depressive symptoms in order to show that cirrhosis may not be the only cause for cognitive decline in patients with cirrhosis. Method: Adult outpatients with a diagnosis of cirrhosis based on histologic findings and clinical characteristics, who did not have clinically overt hepatic encephalopathy and who were being treated in the advanced liver disease and liver transplant clinics, were recruited for the study from May 2003 to May 2006. Patients underwent neuropsychological testing and evaluation for depression using the Beck Depression Inventory-II (BDI-II). Age-adjusted standard neuropsychological domain scores were compared between depressed (BDI-II score ? 14) and nondepressed (BDI-II score < 14) patients. Results: Seventy-five subjects were included in the study. The 23 patients with depression were similar to the 52 nondepressed patients in level of education, age, and race; the laboratory parameters of international normalized ratio, bilirubin, creatinine, and albumin concentration; and Model for End-Stage Liver Disease scores. There was a higher percentage of women in the depressed group than in the nondepressed group, with a trend toward significance (52% vs 29%; P = .07). No etiology of liver disease was associated with depression. In linear regression analyses, decreases in cognitive function were associated with higher BDI-II scores for the domains of working memory (P = .026), with a trend toward significance for visual-perception (P = .056). Approximately 7% of the variability in working memory score was predicted using the BDI score. Conclusions: Depressive symptoms are associated with worsened cognitive function in cirrhosis. PMID:21977378

Enders, Felicity T. B.; Mitchell, Mary M.; Felmlee-Devine, Donna; Smith, Glenn E.

2011-01-01

316

Cytokine gene expression in cirrhotic and non-cirrhotic human liver  

Microsoft Academic Search

Background\\/Aims: In order to explore the role of cytokines in the pathogenesis of liver cirrhosis, we analyzed their gene expression in hepatic biopsies from patients with alcoholic liver cirrhosis, post-hepatitis C liver cirrhosis, and with idiopathic portal hypertension without cirrhosis.Methods: We assessed the gene expression of interleukins 1?, 2, 6, 8, and 10, as well as of tumor necrosis factor-?,

Luis Llorente; Yvonne Richaud-Patin; Natasha Alcocer-Castillejos; Rodrigo Ruiz-Soto; Miguel Angel Mercado; Hécto Orozco; Armando Gamboa-Domínguez; Jorge Alcocer-Varela

1996-01-01

317

Afferent mechanisms of sodium retention in cirrhosis and hepatorenal syndrome  

Microsoft Academic Search

Cirrhosis induces extra-cellular fluid volume expansion, which when the disease is advanced can be severe and poorly responsive to therapy. Prevention and\\/or effective therapy for cirrhotic edema requires understanding the stimulus that initiates and maintains sodium retention. Despite much study, this stimulus remains unknown. Work over the last several years has shown that signals originating in the liver can influence

Juan A Oliver; Elizabeth C Verna

2010-01-01

318

Cirrhosis-like radiological pattern in patients with breast cancer  

Microsoft Academic Search

Introduction  Hepatic toxicity of breast cancer therapy is well known, usually consisting of elevation in the serum levels of hepatic enzymes\\u000a or fatty infiltration of the liver. The chemotherapeutic agents most commonly linked to hepatotoxic effects are methotrexate,\\u000a anthracyclines, taxanes and cyclophosphamide. There are few reports of patients with liver metastasis having radiological\\u000a findings mimicking cirrhosis, both in the presence or

César Gómez Raposo; Andrés Redondo Sánchez; Félix Guerra-Gutiérrez; Beatriz Castelo Fernández; Silvia Gómez Senent; Enrique Espinosa Arranz; Beatriz Martínez Martínez; Pilar Zamora Auñón; Manuel González Barón

2008-01-01

319

Nonalcoholic Fatty Liver Disease: A Clinical Review  

Microsoft Academic Search

Nonalcoholic fatty liver disease may be the most common liver disease in the United States, with a high prevalence in the obese, type 2 diabetic population, and it is probably underestimated as a cause for cirrhosis. Clinicopathologically, it represents a wide spectrum of histologic abnormalities and clinical outcomes, ranging from benign hepatic steatosis to cirrhosis. Pathophysiologically, insulin resistance is thought

David A. Sass; Parke Chang; Kapil B. Chopra

2005-01-01

320

Polymyositis associated with primary biliary cirrhosis.  

PubMed

The coexistence of polymyositis (PM) and primary biliary cirrhosis (PBC) is rare; only nine cases have been described in English literature. We report a case of a 46-year-old woman presenting with these two autoimmune diseases. The diagnosis of PM was based on the symmetrical, proximal limb muscle weakness, elevated muscle enzymes and was confirmed with the electromyography and muscle biopsy. The diagnosis of PBC was based on the increased serum levels of alkaline phosphatase, gamma glutamyltransferase, IgM immunoglobulin, the presence of antimitochondrial antibodies and diagnostic liver biopsy. PMID:7641520

Boki, K A; Dourakis, S P

1995-05-01

321

Effect of alendronate sodium on the expression of mesenchymal-epithelial transition markers in mice with liver fibrosis  

PubMed Central

The aim of this study was to explore whether alendronate sodium regulates tissue remodeling by controlling the transforming growth factor (TGF)-?1-induced epithelial-mesenchymal transition (EMT) and bone morphogenetic protein (BMP)-7-induced mesenchymal-epithelial transition (MET) in CCl4-induced hepatic fibrosis in mice. A mouse model of CCl4-induced hepatic fibrosis was evaluated using the hematoxylin and eosin (HE) and Masson’s trichrome staining histological methods. The activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured using an automated biochemical analyzer. The expression of TGF-?1, ?-smooth muscle actin (?-SMA), BMP-7 and E-cadherin in the hepatic tissue was detected using immunohistochemistry. The mRNA and protein levels of TGF-?1, ?-SMA, BMP-7, fibroblast-specific protein 1 (FSP1), E-cadherin and N-cadherin were detected using RT-PCR and western blot analysis. Immunohistochemical and molecular biochemical examination revealed that alendronate sodium significantly arrested the progression of hepatic fibrosis. Alendronate sodium caused significant amelioration of liver injury and reduced the activities of serum ALT and AST (P<0.001). Furthermore, alendronate sodium markedly reduced TGF-?1 and ?-SMA mRNA expression and increased BMP-7 and E-cadherin in the mouse liver tissue (P<0.001). Alendronate sodium significantly arrested the progression of hepatic fibrosis. The underlying mechanism was associated with changes in the redox state, which remains variable in liver fibrosis, and depends on the balance between TGF-?/smad- and BMP-7-modulated mechanisms which regulate EMT and MET in multifunctional progenitors. PMID:23251277

BI, WAN-RONG; JIN, CAI-XIA; XU, GUO-TONG; YANG, CHANG-QING

2013-01-01

322

Prevention of Liver Fibrosis by Intrasplenic Injection of High-Density Cultured Bone Marrow Cells in a Rat Chronic Liver Injury Model  

PubMed Central

Endothelial progenitor cells (EPCs) from bone marrow have proven to be functional for the prevention of liver fibrosis in chronic liver injury. However, expansion of EPCs in culture is complicated and expansive. Previously, we have established a simple method that could enrich and expand EPCs by simple seeding bone marrow cells in high density dots. The purpose of this study is to evaluate whether cells derived from high-density (HD) culture of rat bone marrow cells could prevent the liver fibrosis in a chronic liver injury rat model, induced by carbon tetrachloride (CCl4). Flow cytometric analysis showed that cells from HD culture were enriched for EPCs, expressing high levels of EPC markers. Intrasplenic injection of HD cultured bone marrow cells in the CCl4-induced liver injury rat showed an enhanced antifibrogenic effect compared with animals treated with cells from regular-density culture. The antifibrogenic effect was demonstrated by biochemical and histological analysis 4 weeks post-transplantation. Furthermore, cells from HD culture likely worked through increasing neovascularization, stimulating liver cell proliferation, and suppressing pro-fibrogenic factor expression. HD culture, which is a simple and cost-effective procedure, could potentially be used to expand bone marrow cells for the treatment of liver fibrosis. PMID:25255097

Xu, Peng; Ai, Ai; Zhou, Guangdong; Liu, Wei; Cao, Yilin; Zhang, Wen Jie

2014-01-01

323

Was Beethoven's cirrhosis due to hemochromatosis?  

PubMed

Dr. Wagner's description of an advanced macronodular cirrhosis is compatible with end-stage liver disease due to a variety of causes. An alcoholic etiology seems more probable than chronic viral hepatitis since such a diagnosis might also account for the chronic pancreatitis, unless it was related to the cholelithiasis. However, Dr. Wagner's description favors a diagnosis of biliary pigment sludge related to hemolysis. Furthermore, the controversy over the extent of Beethoven's alcohol consumption and the absence of mention of pancreatic calcification weakens the case for an alcoholic etiology. On the other hand, Dr. Wagner's emphasis of bluish-green pigmentation of the liver, blackish pigmentation of the spleen, and an arteropathy of the hepatic vessels suggests the probability of hemochromatosis, which diagnosis is also in keeping with Beethoven's medical history. In this regard the composer's history of recurrent obscure abdominal pain, commencing in his third decade, is especially in keeping with hemochromatosis. As many as a third of patients present with recurrent abdominal pain, and eventually up to 40% of cases develop significant abdominal pain in the course of their disease. While some of these cases of abdominal pain have been attributed to hepatoma, ascites, pancreatitis, perisplenitis, or diabetic neuropathy, the majority remain ill-defined (32). Even so, the diagnosis of hemochromatosis remains unproved in the absence of a histological examination and measurement of hepatic iron concentration. It is proposed that the combined additive, toxic effects of alcohol and iron were the most likely cause of Beethoven's cirrhosis. PMID:7770648

Davies, P J

1995-01-01

324

MicroRNA in hepatic fibrosis and cirrhosis.  

PubMed

Hepatic fibrosis is caused by an imbalance between production and dissolution of extracellular matrix after chronic and inflmmatory injury, when hepatic stellate cells are stimulated to proliferate and secret extracellular matrix. The most common causes of liver fibrosis are chronic viral hepatitis B and C. Cirrhosis is the most advanced stage of fibrosis, which usually develop into hepatocellular carcinoma (HCC). microRNAs participate the pathogenesis of hepatic fibrosis and cirrhosis or even the onset of HCC. In this review, we will summarize the role of miRNA in the pathogenesis of viral hepatitis fibrosis, non-alcoholic steatohepatitis fibrosis, primary biliary cirrhosis and HCC onset, especially in the regulation of stellate cells. PMID:24896361

Xin, Xuan; Zhang, Yongxian; Liu, Xiaohong; Xin, Haixia; Cao, Yongcheng; Geng, Ming

2014-01-01

325

Hepatoprotective Activity of Capparis spinosa Root Bark Against CCl4 Induced Hepatic Damage in Mice  

Microsoft Academic Search

Many hepatoprotective herbal preparations have been recommended in alternative systems of medicine for the treatment of hepatic disorders. No systematic study has been done on protective efficacy of Capparis spinosa (Capparidaceae) to treat hepatic diseases. Protective action of C. spinosa ethanolic root bark extract was evaluated in this study in an animal model of hepatotoxicity, which was induced by carbon

Nasrin Aghel; Amir Mombeini

326

The role of granulomatous phlebitis and thrombosis in the pathogenesis of cirrhosis and portal hypertension in sarcoidosis  

Microsoft Academic Search

Sarcoidosis often involves the liver with mild elevation of serum enzymes and granulomas histologically. Rarely, chronic cholestasis, portal hypertension, cirrhosis, or nodular hyperplasia may be found. The pathogenesis of the portal hypertension and of the cirrhosis are not understood, in part because large samples of tissue have seldom been described. We describe the clinical and anatomic findings of four patients

F Moreno-Merlo; IR Wanless; K Shimamatsu; M Sherman; P Greig; D Chiasson

1997-01-01

327

Thrombin generation in patients with cirrhosis: the role of platelets.  

PubMed

Coagulation factor defects, thrombocytopenia, and thrombocytopathy are associated with cirrhosis. However, bleeding in patients who have cirrhosis does not entirely correlate with abnormal coagulation tests. Recently, it was shown that because of the concomitant abnormalities of the procoagulant and anticoagulant drives, thrombin generation in plasma patients with cirrhosis is normal when assessed with assays that include thrombomodulin (the main protein C activator). However, thrombin is also generated in vivo as a function of platelets, suggesting that thrombocytopenia and thrombocytopathy might affect thrombin generation in patients with cirrhosis. We addressed this issue using an assay that accounts for the contribution of plasma and platelets. The study showed that platelet-rich plasma with platelets adjusted by dilution of autologous platelet-rich into autologous platelet-poor plasma to a standard count (100 x 10(9)/L) generates as much thrombin in patients with cirrhosis as in controls (1,063 nmol/L vs. 1,167 nmol/L; P value not significant). When platelets were adjusted to correspond to whole-blood counts, patients with cirrhosis generated significantly less thrombin than controls (949 nmol/L vs. 1,239 nmol/L; P < .001). Furthermore, thrombin generation correlated with platelet numbers (rho = 0.50; P < .001). In addition, the amount of thrombin generated as a function of the whole-blood patients' platelet counts increased significantly when the numbers were adjusted to 100 x 10(9)/L (953 nmol/L vs.1,063 nmol/L; P < .001). In conclusion, severe thrombocytopenia may limit thrombin generation in patients with cirrhosis. These findings might justify platelet transfusion in patients with low platelet counts when they bleed spontaneously or before undergoing surgery or liver biopsy. Controlled clinical trials supporting this indication are warranted. PMID:16871542

Tripodi, Armando; Primignani, Massimo; Chantarangkul, Veena; Clerici, Marigrazia; Dell'Era, Alessandra; Fabris, Federica; Salerno, Francesco; Mannucci, Pier Mannuccio

2006-08-01

328

Cirrhosis and alcoholism as pathogenetic factors in pigment gallstone formation.  

PubMed Central

The association of cirrhosis with pigment gallstones has been noted in numerous autopsy studies. However a direct relationship between alcoholism and pigment cholelithiasis has not been previously demonstrated. We have classified 123 cholecystectomy patients according to stone type and correlated the resulting categories with hepatic morphology, drinking history, and hematological data. Pigment stones were found in 79% of biopsy-verified cirrhotic patients but in only 26% of noncirrhotics. In patients without cirrhosis a positive history of alcoholism was found associated with pigment gallstones more often than with cholesterol or mixed stones (36% vs. 10%). Similarly, the mean red cell volume (MCV), a sensitive marker of alcoholism, was significantly increased in patients with pigment stones (93.6 mu 3 vs. 89.6 mu 3). We conclude that both cirrhosis and alcoholism predispose to pigment gallstone formation and that the effect of alcoholism may occur independent of cirrhosis. This suggests that the apparent association of cirrhosis with pigment stones may, in fact, result from a direct effect of long-term ethanol ingestion on red blood cells, liver, or bile. PMID:3977433

Schwesinger, W H; Kurtin, W E; Levine, B A; Page, C P

1985-01-01

329

Ductopenia related liver sarcoidosis.  

PubMed

Sarcoidosis is a systemic granulomatous disease which may involve many organs. In approximately 95% of patients there is liver involvement, with noncaseating hepatic granulomas occurring in 21 to 99% of patients with sarcoidosis. Liver involvement is usually asymptomatic and limited to mild to moderate abnormalities in liver biochemistry. The occurrence of jaundice in sarcoidosis is rare; extensive imaging procedures and the examination of liver biopsies permit a precise diagnostic. Ductopenia associated with sarcoidosis has been reported in less than 20 cases and can lead to biliary cirrhosis and liver- related death. We report here on a case of ductopenia-related sarcoidosis in which primary biliary cirrhosis and extrahepatic cholestasis have been carefully excluded. The patient follow up was 8 years. Although ursodesoxycholic acid appears to improve liver biochemistry it does not preclude the rapid occurrence of extensive fibrosis. A review of the literature of reported cases of ductopenia related to sarcoidosis is provided. PMID:22509431

Farouj, Nourr-Eddine; Cadranel, Jean-François D; Mofredj, Ali; Jouannaud, Vincent; Lahmiri, Maria; Lann, Pierre Le; Cazier, Alain

2011-06-27

330

Ductopenia related liver sarcoidosis  

PubMed Central

Sarcoidosis is a systemic granulomatous disease which may involve many organs. In approximately 95% of patients there is liver involvement, with noncaseating hepatic granulomas occurring in 21 to 99% of patients with sarcoidosis. Liver involvement is usually asymptomatic and limited to mild to moderate abnormalities in liver biochemistry. The occurrence of jaundice in sarcoidosis is rare; extensive imaging procedures and the examination of liver biopsies permit a precise diagnostic. Ductopenia associated with sarcoidosis has been reported in less than 20 cases and can lead to biliary cirrhosis and liver- related death. We report here on a case of ductopenia-related sarcoidosis in which primary biliary cirrhosis and extrahepatic cholestasis have been carefully excluded. The patient follow up was 8 years. Although ursodesoxycholic acid appears to improve liver biochemistry it does not preclude the rapid occurrence of extensive fibrosis. A review of the literature of reported cases of ductopenia related to sarcoidosis is provided. PMID:22509431

Farouj, Nourr-Eddine; Cadranel, Jean-François D; Mofredj, Ali; Jouannaud, Vincent; Lahmiri, Maria; Lann, Pierre Le; Cazier, Alain

2011-01-01

331

Hepatoprotective Effects of a Chinese Herbal Formula, Longyin Decoction, on Carbon-Tetrachloride-Induced Liver Injury in Chickens  

PubMed Central

The objective of this study is to establish poultry liver injury model induced by (CCl4) and seek effective hepatoprotective herbals for clinical application. Different doses of CCl4 dissolved in vegetable oil (1?:?1, V/V) were injected via pectoral muscle to induce acute liver injury model in chickens. An herbal formula, Longyin decoction, was prepared for hepatoprotection test on chicken acute liver injury models. The pathologic changes of the liver were observed, and the activities of ALT and AST were, respectively, detected to evaluate the hepatoprotective effects of Longyin decoction on chickens. The chicken acute liver injury model was successfully established by injecting CCl4 via pectoral muscle. The best dose of CCl4 inducing chicken liver injury was 4.0?mL/kg·BW (body weight). The results of qualitative determination by HPTLC showed that the components of Longyin decoction contained Gentian, Capillaries, Gardenia, and Bupleurum root. In the high-dose Longyin group and the middle-dose Longyin group, the pathological changes of the damaged liver were mitigated and the activities of ALT and AST in serum were reduced significantly. Longyin decoction has obvious hepatoprotective effect on acute liver injury induced by CCl4. PMID:23533478

Wang, Chunguang; Zhang, Tie; Cui, Xuemei; Li, Shuang; Zhao, Xinghua; Zhong, Xiuhui

2013-01-01

332

The protective effects of SA3443, a novel cyclic disulfide, on chronic liver injuries in rats.  

PubMed

The effects of (4R)-hexahydro-7,7-dimethyl-6-oxo-1,2,5-dithiazocine-4- carboxylic acid (SA3443), a novel cyclic disulfide compound, on the development of chronic liver injury were studied in rats, using two types of models, carbon tetrachloride (CCl4)-induced chronic liver injury and heterologous serum (swine serum)-induced liver fibrosis. SA3443 (30-100 mg/kg, p.o.) significantly suppressed increases in serum transaminase and alkaline phosphatase activity induced by CCl4-treatment for 10 weeks. This compound also inhibited increases in hepatic lipids and hydroxyproline content in CCl4-treated rats. In the histopathological studies, treatment with SA3443 resulted in a decrease in the degree of hepatic necrosis, fibrosis and steatosis. On the other hand, 8-weeks treatment with swine serum revealed hepatic fibrosis without appearance of necrosis or fatty accumulation. In this model, SA3443 (30 mg/kg, p.o.) reduced the hepatic hydroxyproline level, and diminished the formation of connective tissue in the liver. These findings indicate that SA3443 protects the liver against chronic liver injuries induced by CCl4 and heterogeneous serum. PMID:1744424

Ishida, N; Nakata, K; Takase, K; Tanaka, M; Mita, S

1991-09-01

333

Determination of DNA damage in experimental liver intoxication and role of N-acetyl cysteine.  

PubMed

The present study aimed at detecting DNA damage and fragmentation as well as histone acetylation depending on oxidative stress caused by CCl4 intoxication. Also, the protective role of N-acetyl cysteine, a precursor for GSH, in DNA damage is investigated. Sixty rats were used in this study. In order to induce liver toxicity, CCl4 in was dissolved in olive oil (1/1) and injected intraperitoneally as a single dose (2 ml/kg). N-acetyl cysteine application (intraperitoneal, 50 mg/kg/day) was started 3 days prior to CCl4 injection and continued during the experimental period. Control groups were given olive oil and N-acetyl cysteine. After 6 and 72 h of CCl4 injection, blood and liver tissue were taken under ether anesthesia. Nuclear extracts were prepared from liver. Changes in serum AST and ALT activities as well as MDA, TAS, and TOS levels showed that CCl4 caused lipid peroxidation and liver damage. However, lipid peroxidation and liver damage were reduced in the N-acetyl cysteine group. Increased levels in 8-hydroxy-2-deoxy guanosine and histone acetyltransferase activities, decreased histone deacetylase activities, and DNA breakage detected in nuclear extracts showed that CCl4 intoxication induces oxidative stress and apoptosis in rat liver. The results of the present study indicate that N-acetyl cysteine has a protective effect on CCl4-induced DNA damage. PMID:24819310

Aksit, Hasan; Bildik, Aysegül

2014-11-01

334

Focal ischemic necrosis in advanced biliary atresia cirrhosis.  

PubMed

This report correlates the clinical and biological findings, liver hemodynamics and histological features of focal INL in an infant with BA cirrhosis. An eight month old boy with BA, with previous successful porto-enterostomy, was admitted with signs of cholangitis and ascites. He was treated with antibiotics and diuretics with subsequent clinical improvement. Eight days later, while being fed with hyper-osmolar milk, he became febrile again: ASAT/ALAT climbed (9000/2300 IU/L), liver function deteriorated. Infectious work-up was negative. Liver-ultrasound showed reversed portal flow and a negative arterial diastolic flow. The patient recovered within five days under supportive treatment. A similar event recurred five days later. INL was suspected and semi-urgent living-related liver transplantation was performed, with uneventful post-operative course. Histology of the explanted liver showed extensive foci of INL of different ages. This report illustrates how the association of reversed portal and arterial diastolic flows, with subsequent liver hypoperfusion, may repeatedly cause foci of INL in BA cirrhosis, and lead to rapid progression to liver failure. Because of precarious hepatic blood supply in such patients, close monitoring of portal and diastolic arterial flows is recommended. PMID:18331537

Wildhaber, Barbara E; Rubbia-Brandt, Laura; Majno, Pietro; Mentha, Gilles; Schäppi, Michela G; Anooshiravani, Mehrak; Belli, Dominique; Chardot, Christophe

2008-06-01

335

Quantitative detection of cirrhosis: towards the development of computer-assisted detection method.  

PubMed

There are distinct morphologic features of cirrhosis on CT examinations; however, such impressions may be subtle or subjective. The purpose of this study is to build a computer-aided diagnosis (CAD) method to help radiologists with this diagnosis. One hundred sixty-seven abdominal CT examinations were randomly divided into training (n?=?88) and validation (n?=?79) sets. Livers were analyzed for morphological markers of cirrhosis and logistic regression models were created. Using the area under curve (AUC) for model performance, the best model had 0.89 for the training set and 0.85 for the validation set. For radiology reports, sensitivity of reporting cirrhosis was 0.45 and specificity 0.99. Using the predictive model adjunctively, radiologists' sensitivity increased to 0.63 and specificity slightly decreased to 0.97. This study demonstrates that quantifying morphological features in livers may be utilized for diagnosing cirrhosis and for developing a CAD method for it. PMID:24811859

Huhdanpaa, Hannu T; Zhang, Peng; Krishnamurthy, Venkataramu N; Douville, Chris; Enchakolody, Binu; Chou, Chris; Ethiraj, Sampathkumar; Wang, Stewart; Su, Grace L

2014-10-01

336

Hospitalization for variceal hemorrhage in an era with more prevalent cirrhosis  

PubMed Central

AIM: To examine hospitalization rates for variceal hemorrhage and relation to cause of cirrhosis during an era of increased cirrhosis prevalence. METHODS: We performed a retrospective review of patients with cirrhosis and gastroesophageal variceal hemorrhage who were admitted to a tertiary care referral center from 1998 to 2009. Subjects were classified according to the etiology of their liver disease: alcoholic cirrhosis and non-alcoholic cirrhosis. Rates of hospitalization for variceal bleeding were determined. Data were also collected on total hospital admissions per year and cirrhosis-related admissions per year over the same time period. These data were then compared and analyzed for trends in admission rates. RESULTS: Hospitalizations for cirrhosis significantly increased from 611 per 100000 admissions in 1998-2001 to 1232 per 100000 admissions in 2006-9 (P value for trend < 0.0001). This increase was seen in admissions for both alcoholic and non-alcoholic cirrhosis (P values for trend < 0.001 and < 0.0001 respectively). During the same time period, there were 243 admissions for gastroesophageal variceal bleeding (68% male, mean age 54.3 years, 62% alcoholic cirrhosis). Hospitalizations for gastroesophageal variceal bleeding significantly decreased from 96.6 per 100000 admissions for the time period 1998-2001 to 70.6 per 100000 admissions for the time period 2006-2009 (P value for trend = 0.01). There were significant reductions in variceal hemorrhage from non-alcoholic cirrhosis (41.6 per 100000 admissions in 1998-2001 to 19.7 per 100000 admissions in 2006-2009, P value for trend = 0.007). CONCLUSION: Hospitalizations for variceal hemorrhage have decreased, most notably in patients with non-alcoholic cirrhosis, and this may reflect broader use of strategies to prevent bleeding.

Lim, Nicholas; Desarno, Michael J; Lidofsky, Steven D; Ganguly, Eric

2014-01-01

337

Hepatoprotective effects of insulin-like growth factor I in rats with carbon tetrachloride-induced cirrhosis  

Microsoft Academic Search

BACKGROUND & AIMS: Bioavailability of insulin-like growth factor (IGF- I) is reduced in liver cirrhosis. The aim of this study was to analyze the effect of IGF-I on liver histopathology and function in experimental cirrhosis.METHODS: Rats received CCl4 inhalations for 11 or 30 weeks (protocols 1 and 2, respectively) and were treated with 2 microg x 100 g body wt(-1)

I Castilla-Cortazar; M Garcia; B Muguerza; J Quiroga; R Perez; S Santidrian; J Prieto

1997-01-01

338

[Chronic viral C hepatitis associated with primary biliary cirrhosis. Report of two cases].  

PubMed

Chronic viral hepatitis C is often associated with various autoimmune disorders. We report two patients infected by genotype 1b hepatitis C virus associated with primary biliary cirrhosis. These patients had anicteric cholestasis associated with cytolysis and positivity of M2 antimitochondrial antibodies at a titre of 1/200. Liver biopsy revealed chronic hepatitis in one case and histological pattern of primary biliary cirrhosis in the other. One patient was treated by antiviral therapy; the other only by ursodesoxycholic acid because of the association with hemolytic anemia. Association between primary biliary cirrhosis and chronic viral hepatitis C is uncommon and associated with diagnostic and therapeutic challenges. PMID:18835654

Mouelhi, L; Chaieb, M; Sfar, I; Debbeche, R; Trabelsi, S; Gorgi, Y; Najjar, T

2009-06-01

339

Detection of hepatitis B surface antigen in fixed tissues of patients with cirrhosis and hepatoma  

Microsoft Academic Search

HBsAg has been sought by light microscopy in liver specimens from patients with cirrhosis (79 cases) and hepatoma (99 cases). The study was carried out on fixed material using orcein staining, immunoperoxidase technique and indirect immunofluorescence. HBsAg was detected in the serum by radio-immunoassay (RIA) using Ausria II-125 in 38 patients with cirrhosis and in 36 with hepatoma. In the

G. Theodoropoulos; L. Nakopoulou; M. Repanti; N. Papacharalampous; K. Melissinos

1979-01-01

340

Protection from liver fibrosis by a peroxisome proliferator-activated receptor ? agonist.  

PubMed

Peroxisome proliferator-activated receptor delta (PPAR?), a member of the nuclear receptor family, is emerging as a key metabolic regulator with pleiotropic actions on various tissues including fat, skeletal muscle, and liver. Here we show that the PPAR? agonist KD3010, but not the well-validated GW501516, dramatically ameliorates liver injury induced by carbon tetrachloride (CCl(4)) injections. Deposition of extracellular matrix proteins was lower in the KD3010-treated group than in the vehicle- or GW501516-treated group. Interestingly, profibrogenic connective tissue growth factor was induced significantly by GW501516, but not by KD3010, following CCl(4) treatment. The hepatoprotective and antifibrotic effect of KD3010 was confirmed in a model of cholestasis-induced liver injury and fibrosis using bile duct ligation for 3 wk. Primary hepatocytes treated with KD3010 but not GW501516 were protected from starvation or CCl(4)-induced cell death, in part because of reduced reactive oxygen species production. In conclusion, our data demonstrate that an orally active PPAR? agonist has hepatoprotective and antifibrotic effects in animal models of liver fibrosis, suggesting a possible mechanistic and therapeutic approach in treating patients with chronic liver diseases. PMID:22538808

Iwaisako, Keiko; Haimerl, Michael; Paik, Yong-Han; Taura, Kojiro; Kodama, Yuzo; Sirlin, Claude; Yu, Elizabeth; Yu, Ruth T; Downes, Michael; Evans, Ronald M; Brenner, David A; Schnabl, Bernd

2012-05-22

341

Autonomic and sensory nerve dysfunction in primary biliary cirrhosis  

Microsoft Academic Search

AIM: Cardiovascular autonomic and peripheral sensory neuropathy is a known complication of chronic alcoholic and non-alcoholic liver diseases. We aimed to assess the prevalence and risk factors for peripheral sensory nerve and autonomic dysfunction using sensitive methods in patients with primary biliary cirrhosis (PBC). METHODS: Twenty-four AMA M2 positive female patients with clinical, biochemical and histological evidence of PBC and

Katalin Keresztes; Ildikó Istenes; Aniko Folhoffer; Peter L Lakatos; Andrea Horvath; Timea Csak; Peter Varga; Peter Kempler; Ferenc Szalay; Lakatos PL

342

Environmental Factors in Primary Biliary Cirrhosis  

PubMed Central

The etiology of the autoimmune liver disease primary biliary cirrhosis (PBC) remains largely unresolved, owing in large part to the complexity of interaction between environmental and genetic contributors underlying disease development. Observations of disease clustering, differences in geographical prevalence, and seasonality of diagnosis rates suggest the environmental component to PBC is strong, and epidemiological studies have consistently found cigarette smoking and history of urinary tract infection to be associated with PBC. Current evidence implicates molecular mimicry as a primary mechanism driving loss of tolerance and subsequent autoimmunity in PBC, yet other environmentally influenced disease processes are likely to be involved in pathogenesis. In this review, the authors provide an overview of current findings and touch on potential mechanisms behind the environmental component of PBC. PMID:25057950

Juran, Brian D.; Lazaridis, Konstantinos N.

2014-01-01

343

Coffee and liver diseases.  

PubMed

Coffee consumption is worldwide spread with few side effects. Interestingly, coffee intake has been inversely related to the serum enzyme activities gamma-glutamyltransferase, and alanine aminotransferase in studies performed in various countries. In addition, epidemiological results, taken together, indicate that coffee consumption is inversely related with hepatic cirrhosis; however, they cannot demonstrate a causative role of coffee with prevention of liver injury. Animal models and cell culture studies indicate that kahweol, diterpenes and cafestol (some coffee compounds) can function as blocking agents by modulating multiple enzymes involved in carcinogenic detoxification; these molecules also alter the xenotoxic metabolism by inducing the enzymes glutathione-S-transferase and inhibiting N-acetyltransferase. Drinking coffee has been associated with reduced risk of hepatic injury and cirrhosis, a major pathogenic step in the process of hepatocarcinogenesis, thus, the benefit that produces coffee consumption on hepatic cancer may be attributed to its inverse relation with cirrhosis, although allowance for clinical history of cirrhosis did not completely account for the inverse association. Therefore, it seems to be a continuum of the beneficial effect of coffee consumption on liver enzymes, cirrhosis and hepatocellular carcinoma. At present, it seems reasonable to propose experiments with animal models of liver damage and to test the effect of coffee, and/or isolated compounds of this beverage, not only to evaluate the possible causative role of coffee but also its action mechanism. Clinical prospective double blind studies are also needed. PMID:19825397

Muriel, Pablo; Arauz, Jonathan

2010-07-01

344

Influence of biliary cirrhosis on the detoxification and elimination of a food derived carcinogen  

PubMed Central

Background and aims: The liver is the central organ for the detoxification of numerous xenobiotics, including carcinogens. We studied the influence of cholestasis and biliary cirrhosis on the detoxification, elimination, and tissue distribution of a model compound and food derived carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Methods: Wistar rats were injected with 14C-PhIP into the portal vein one or six weeks after common bile duct ligation (CBDL). Bile flow was reconstituted, bile and urine were collected over 120 minutes, and metabolites were analysed using high performance liquid chromatograpy. Total tissue radioactivity levels in several organs as well as tissue bound (ethanol insoluble tissue fraction) radioactivity levels were determined. Results: Significant downregulation of the transport proteins multidrug resistance associated protein 2 and breast cancer resistance protein was observed in biliary cirrhosis. Biliary excretion of radioactivity was significantly reduced in cholestasis and biliary cirrhosis compared with controls (15 (2.9)% and 3.2 (1)% of the dose v 36.5 (2)%, respectively). Phase II metabolism was severely reduced in cirrhotic rats, resulting in a twofold increase in tissue radioactivity levels in the liver, kidney, and colon. Biliary cirrhosis increased tissue binding of reactive metabolites, as expressed in cpm/100 mg tissue in the liver and the colon (3267 (1218) v 1191 (429) in the liver, 3044 (1913) v 453 (253) in the colon). Conclusions: Biliary cirrhosis induced by CBDL causes impaired metabolism and elimination of PhIP, and leads to higher tissue levels of potentially genotoxic metabolites in the liver and colon of rats. These data may explain the increased incidence of hepatic and extrahepatic cancers in cholestasis and liver cirrhosis. PMID:15542527

Dietrich, C G; Geier, A; Wasmuth, H E; Matern, S; Gartung, C; de Waart, D R; Elferink, R P J O

2004-01-01

345

Effective protection of Terminalia catappa L. leaves from damage induced by carbon tetrachloride in liver mitochondria.  

PubMed

The protective effects of chloroform extracts of Terminalia catappa L. leaves (TCCE) on carbon tetrachloride (CCl4)-induced liver damage and the possible mechanisms involved in the protection were investigated in mice. We found that increases in the activity of serum aspartate aminotransferase and alanine aminotransferase and the level of liver lipid peroxidation (2.0-fold, 5.7-fold and 2.8-fold) induced by CCl4 were significantly inhibited by oral pretreatment with 20, 50 or 100 mg/kg of TCCE. Morphological observation further confirmed the hepatoprotective effects of TCCE. In addition, the disruption of mitochondrial membrane potential (14.8%), intramitochondrial Ca2+ overload (2.1-fold) and suppression of mitochondrial Ca2+-ATPase activity (42.0%) in the liver of CCl4-insulted mice were effectively prevented by pretreatment with TCCE. It can be concluded that TCCE have protective activities against liver mitochondrial damage induced by CCl4, which suggests a new mechanism of the hepatoprotective effects of TCCE. PMID:16169207

Tang, Xinhui; Gao, Jing; Wang, Yanping; Fan, Yi-Mei; Xu, Li-Zhi; Zhao, Xiao-Ning; Xu, Qiang; Qian, Zhong Ming

2006-03-01

346

Acute-on-chronic liver failure.  

PubMed

The Model for End-Stage Liver Disease (MELD) has been the single best predictor of outcome of the progression of cirrhosis. Acute-on-chronic liver failure (ACLF) has been proposed as an alternative path in the natural history of cirrhosis. ACLF occurs in patients with chronic liver disease and is characterized by a precipitating event, resulting in acute deterioration in liver function, multiorgan system failure, and high short-term mortality. In this review, the natural course of patients with ACLF, especially as it relates to management of cirrhotic patients on the transplant waiting list, and its impact on liver transplantation outcomes are defined. PMID:25017076

Asrani, Sumeet K; O'Leary, Jacqueline G

2014-08-01

347

Non-Alcoholic Fatty Liver Disease (NAFLD)  

MedlinePLUS

... to liver damage with scarring and cirrhosis. x Obesity x Diabetes x Insulin resistance x Hyperlipidemia NAFLD is estimated to occur in 10-40% of adults in the United States. NASH is present in 2 to 5 percent ...

348

Chronic liver disease: evaluation by magnetic resonance  

SciTech Connect

Magnetic resonance (MR) imaging distinguished hepatitis from fatty liver and cirrhosis in a woman with a history of alcohol abuse. Anatomic and physiologic manifestations of portal hypertension were also demonstrated by MR.

Stark, D.D.; Goldberg, H.I.; Moss, A.A.; Bass, N.M.

1984-01-01

349

The Effects of Poor Sleep Quality on Cognitive Function of Patients with Cirrhosis  

PubMed Central

Objectives: This study was conducted to assess the ill-defined relationship between sleep quality and multiple, specific domains of cognitive function in patients with cirrhosis. Methods: A comprehensive battery of neuropsychological tests (divided into six neurocognitive domains) and a standardized, validated measure of sleep quality (Pittsburgh Sleep Quality Index [PSQI]) were administered to patients with cirrhosis and without evidence of overt hepatic encephalopathy, recruited from liver transplant and advanced liver disease clinics (n = 34). An inflammatory bowel disease (IBD) control group (n = 23) was similarly recruited and evaluated to control for the secondary effect of a chronic illness on cognition. PSQI global and component scores were used to predict cognitive function in each neurocognitive domain, using linear regression Results: Global PSQI scores were significantly higher (indicating poorer sleep quality) in the cirrhosis group (median [range] = 10 [1-19]) than in IBD controls = 5 (1-14); p = 0.002). After controlling for age and education, short duration of sleep was associated with impaired memory for patients with cirrhosis; the use of soporific agents was associated with poor visual-perceptual function in patients with IBD. Conclusions: Poor sleep was associated with worsening of the already impaired cognitive function of patients with cirrhosis. Citation: Stewart CA; Auger R; Enders FTB; Felmlee-Devine D; Smith GE. The effects of poor sleep quality on cognitive function of patients with cirrhosis. J Clin Sleep Med 2014;10(1):21-26. PMID:24426816

Stewart, Charmaine A.; Auger, Robert; Enders, Felicity T. B.; Felmlee-Devine, Donna; Smith, Glenn E.

2014-01-01

350

New determinants of prognosis in bacterial infections in cirrhosis.  

PubMed

Despite major advances in the knowledge and management of liver diseases achieved in recent decades, decompensation of cirrhosis still carries a high burden of morbidity and mortality. Bacterial infections are one of the main causes of decompensation. It is very important for clinical management to be aware of the population with the highest risk of poor outcome. This review deals with the new determinants of prognosis in patients with cirrhosis and bacterial infections reported recently. Emergence of multiresistant bacteria has led to an increasing failure rate of the standard empirical antibiotic therapy recommended by international guidelines. Moreover, it has been recently reported that endothelial dysfunction is associated with the degree of liver dysfunction and, in infected patients, with the degree of sepsis. It has also been reported that relative adrenal insufficiency is frequent in the non-critically ill cirrhotic population and it is associated with a higher risk of developing infection, severe sepsis, hepatorenal syndrome and death. We advise a change in the standard empirical antibiotic therapy in patients with high risk for multiresistant infections and also to take into account endothelial and adrenal dysfunction in prognostic models in hospitalized patients with decompensated cirrhosis. PMID:24966596

Acevedo, Juan; Fernández, Javier

2014-06-21

351

Schistosomiasis of the liver  

Microsoft Academic Search

Schistosomiasis is an infection of trematodes, Schistosoma, causing periportal fibrosis and liver cirrhosis due to deposition of eggs in the small portal venules. In schistosomiasis\\u000a caused by S. mansoni, sonography shows echogenic thickening or fibrotic band along the portal veins. CT shows low-attenuation bands or rings around\\u000a the large portal vein branches in the central part of the liver with

Adonis Manzella; Kuni Ohtomo; Shuichi Monzawa; Jae Hoon Lim

352

Schistosomiasis of the liver  

Microsoft Academic Search

Schistosomiasis is an infection of trematodes, Schistosoma, causing periportal fibrosis and liver cirrhosis due to deposition of eggs in the small portal venules. In schistosomiasis\\u000a caused by S. mansoni, sonography shows echogenic thickening or fibrotic band along the portal veins. CT shows low-attenuation bands or rings around\\u000a the large portal vein branches in the central part of the liver with

Adonis Manzella; Kuni Ohtomo; Shuichi Monzawa; Jae Hoon Lim

2008-01-01

353

Liver transplantation and non-alcoholic fatty liver disease  

PubMed Central

Non-alcoholic fatty liver disease (NAFLD) is an important health problem worldwide. NAFLD encompasses a histological spectrum ranging from bland liver steatosis to severe steatohepatitis (nonalcoholic steatohepatitis, NASH) with the potential of progressing to cirrhosis and its associated morbidity and mortality. NAFLD is thought to be the hepatic manifestation of insulin resistance (or the metabolic syndrome); its prevalence is increasing worldwide in parallel with the obesity epidemic. In many developed countries, NAFLD is the most common cause of liver disease and NASH related cirrhosis is currently the third most common indication for liver transplantation. NASH related cirrhosis is anticipated to become the leading indication for liver transplantation within the next one or two decades. In this review, we discuss how liver transplantation is affected by NAFLD, specifically the following: (1) the increasing need for liver transplantation due to NASH; (2) the impact of the increasing prevalence of NAFLD in the general population on the quality of deceased and live donor livers available for transplantation; (3) the long term graft and patient outcomes after liver transplantation for NASH, and finally; and (4) the de novo occurrence of NAFLD/NASH after liver transplantation and its impact on graft and patient outcomes.

Zezos, Petros; Renner, Eberhard L

2014-01-01

354

Androgen receptor roles in hepatocellular carcinoma, cirrhosis, and hepatitis  

PubMed Central

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

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

2014-01-01

355

Serum prolactin in advanced chronic liver disease.  

PubMed

Hyperprolactinemia is a frequent endocrine disorder with well known harmful effects on the reproductive system and bone metabolism. Besides prolactinomas several drugs and disorders such as renal failure and hypothyroidism have been shown to cause hyperprolactinemia. Based on former studies, liver cirrhosis has also been suggested to cause hyperprolactinemia, while mechanisms have not been identified yet. In this study, we set out to investigate the prevalence and predictors of hyperprolactinemia in 178 patients with liver cirrhosis of different etio-logies. Eighteen out of 178 patients - 7 females and 11 males - displayed elevated serum pro-lactin levels. When patients were excluded who suffered from co-morbidities or took medication that are discussed to potentially interfere with prolactin metabolism, only 3 males displayed increased serum prolactin levels. Prolactin levels were similar in patients with liver cirrhosis of different etiologies. Our data suggest that hyperprolactinemia is not commonly found in patients with liver cirrhosis, but is mostly associated with intake of drugs or presence of comorbidites which are known to potentially cause hyperprolactinemia. We thus hypothesize that in contrast to former studies liver cirrhosis is not a common cause of hyperprolactinemia and that in the absence of co-morbidities or drugs that are known to potentially increase prolactin levels, marked hyperprolactinemia needs further investigation in patients with liver cirrhosis. PMID:24816831

Ress, C; Maeser, P-A; Tschoner, A; Loacker, L; Salzmann, K; Staudacher, G; Melmer, A; Zoller, H; Vogel, W; Griesmacher, A; Tilg, H; Graziadei, I; Kaser, S

2014-10-01

356

Hepatoprotective effects of Gentiana asclepiadea L. extracts against carbon tetrachloride induced liver injury in rats.  

PubMed

This study is an attempt to evaluate the hepatoprotective activity of Gentiana asclepiadea L. against carbon tetrachloride-induced liver injury in rats. Methanol extracts of aerial parts (GAA) and roots (GAR) of G. asclepiadea at doses of 100, 200, and 400mg/ kg b.w. were orally administered to Wistar rats once daily for 7 days before they were treated with CCl(4). The hepatoprotective activity of the extracts in this study was compared with the reference drug silymarin. In CCl(4) treated animals, GAA and GAR significantly decreased levels of serum transaminases, alkaline phosphatase and total bilirubin, and increased the level of total protein. Treatment with the extracts resulted in a significant increase in the levels of catalase, superoxide dismutase and reduced glutathione, accompanied with a marked reduction in the levels of malondialdehyde, as compared to CCl(4) treated group. The histopathological studies confirmed protective effects of extracts against CCl(4)-induced liver injuries. No genotoxicity was observed in liver cells after GAA treatment, while GAR showed only slight genotoxic effects by comet assay. Phytochemical analysis revealed the presence of sweroside, swertiamarin and gentiopicrin in high concentrations in both extracts. It could be concluded that the use of G. asclepiadea extracts in the treatment of chemical-induced hepatotoxicity. PMID:23146698

Mihailovi?, Vladimir; Mihailovi?, Mirjana; Uskokovi?, Aleksandra; Arambaši?, Jelena; Miši?, Danijela; Stankovi?, Vesna; Katani?, Jelena; Mladenovi?, Milan; Soluji?, Slavica; Mati?, Sanja

2013-02-01

357

In vitro and in vivo protective effects of proteoglycan isolated from mycelia of Ganoderma lucidum on carbon tetrachloride-induced liver injury  

PubMed Central

AIM: To investigate the possible mechanism of the protective effects of a bioactive fraction, Ganoderma lucidum proteoglycan (GLPG) isolated from Ganoderma lucidum mycelia, against carbon tetrachloride-induced liver injury. METHODS: A liver injury model was induced by carbon tetrachloride. Cytotoxicity was measured by MTT assay. The activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined with an automatic multifunction-biochemical analyzer and the levels of superoxide dismutase (SOD) and TNF-? were determined following the instructions of SOD kit and TNF radioimmunoassay kit. Liver sections were stained with hematoxylin and eosin (H&E) for histological evaluation and examined under light microscope. RESULTS: We found that GLPG can alleviate the L-02 liver cells injury induced by carbon tetrachloride (CCl4) through the measurements of ALT and AST activities and the administration of GLPG to L-02 cells did not display any toxicity. Furthermore, histological analysis of mice liver injury induced by CCl4 with or without GLPG pretreatment indicated that GLPG can significantly suppress the toxicity induced by CCl4 in mice liver. We also found that GLPG reduced TNF-? level induced by CCl4 in the plasma of mice, whereas increased SOD activity in the rat serum. CONCLUSION: GLPG has hepatic protective activity against CCl4-induced injury both in vitro and in vivo. The possible anti-hepatotoxic mechanisms may be related to the suppression of TNF-? level and the free radical scavenging activity. PMID:16552805

Yang, Xiao-Jun; Liu, Jing; Ye, Lin-Bai; Yang, Fan; Ye, Li; Gao, Jin-Rong; Wu, Zheng-Hui

2006-01-01

358

Incidence of hepatocellular carcinoma in HIV-infected patients with cirrhosis: a prospective study.  

PubMed

: This study assesses the incidence of hepatocellular carcinoma (HCC) in a prospective cohort of HIV-infected patients, the majority receiving antiretroviral therapy, with liver cirrhosis from different etiologies, enrolled between 2004 and 2005 with median follow-up of 5 years. We followed 371 patients, 25.6% with decompensated cirrhosis at baseline. The incidence rate of HCC was 6.72 per 1000 person-years [95% confidence interval (CI): 2.6 to 10.9]. There was a trend toward a higher cumulative probability of developing HCC at 6 years of follow-up (considering death and liver transplant as competing risks) in patients with decompensated versus compensated cirrhosis at baseline (6% vs. 2%, P < 0.06). PMID:24419065

Montes Ramírez, María Luisa; Miró, José M; Quereda, Carmen; Jou, Antoni; von Wichmann, Miguel Ángel; Berenguer, Juan; González-García, Juan J; Hernando, Asunción; Ortega, Enrique; Sanz, José; Arribas, José R

2014-01-01

359

Garlic oil and DDB, comprised in a pharmaceutical composition for the treatment of patients with viral hepatitis, prevents acute liver injuries potentiated by glutathione deficiency in rats.  

PubMed

A pharmaceutical composition PENNEL comprising garlic oil (GO) and dimethyl-4,4'-dimethoxy-5,6,5',6'-dimethylene dioxybiphenyl-2,2'-dicarboxylate (DDB) as ingredients active for phase II enzyme induction and liver protection, respectively, has been used as a curative preparation for patients with acute or chronic viral hepatitis. In spite of the wide clinical use of PENNEL in Asian and Middle Eastern countries, whether GO+DDB treatment synergistically protects the liver from injuries potentiated by GSH deficiency compared to the individual treatment has not been determined. This study investigated the effects of GO+DDB in comparison with each ingredient alone on chemical-induced liver injury potentiated by a GSH depleting agent. Rats that had been daily pretreated with GO+DDB, GO, DDB, ursodesoxycholic acid or silymarin for 6 days were exposed to buthionine sulfoximine (BSO) and then injected with a single dose of CCl4. The effects of the agents on acute liver toxicities induced by BSO, CCl4 or BSO+CCl4 were assessed by blood biochemistry and histopathology. GO+DDB pretreatment effectively prevented increases in plasma aminotransferases or lactate dehydrogenase activities in rats exposed to BSO+CCl4, compared to GO or DDB treatment alone. Whereas BSO potentiated CCl4-induced liver injuries as evidenced by elevations in central necrosis, hepatocyte degeneration and inflammation, pretreatment with GO+DDB abrogated BSO+CCl4-induced liver injuries more efficaciously than did that with GO or DDB. The hepatoprotective effect of GO+DDB was superior to that of ursodesoxycholic acid or silymarin. Also, blood biochemistry indicated that GO+DDB pretreatment prevented increases in plasma triglyceride contents in rats insulted with CCl4 or BSO+CCl4. The present study demonstrated that GO+DDB, when daily pretreated for six consecutive days, exerted synergistic protection of the liver from chemical-induced injury potentiated by the condition of GSH deficiency, and has additional advantages in lowering the plasma lipids. PMID:15950962

Park, Eun Young; Ki, Sung Hwan; Ko, Myong Sok; Kim, Choon Won; Lee, Min Ho; Lee, Young Sok; Kim, Sang Geon

2005-06-30

360

Interleukin6 Polymorphisms and Gender: Relationship with the Occurrence of Hepatocellular Carcinoma in Patients with End-Stage Liver Disease  

Microsoft Academic Search

Objective: To investigate whether interleukin-6 (IL-6) polymorphisms could be associated with the occurrence of hepatocellular carcinoma (HCC) in patients with liver cirrhosis and whether this influence could act synergistically with the gender of the patient. Methods: We studied 219 consecutive patients who underwent liver transplantation for liver cirrhosis. All total hepatectomy specimens were sectioned at intervals of 1 cm in

Edmondo Falleti; Carlo Fabris; Pierluigi Toniutto; Elisabetta Fontanini; Annarosa Cussigh; Davide Bitetto; Elisa Fumolo; Ezio Fornasiere; Walter Bragagnini; David J. Pinato; Rosalba Minisini; Mario Pirisi

2009-01-01

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