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Sample records for ccl4-induced liver cirrhosis

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

    PubMed

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

    2010-04-01

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

  2. Bacterial translocation aggravates CCl4-induced liver cirrhosis by regulating CD4+ T cells in rats

    PubMed Central

    Shi, Haiyan; Lv, Longxian; Cao, Hongcui; Lu, Haifeng; Zhou, Ning; Yang, Jiezuan; Jiang, Haiyin; Dong, Huihui; Hu, Xinjun; Yu, Wei; Jiang, Xiawei; Zheng, Beiwen; Li, Lanjuan

    2017-01-01

    Bacterial translocation (BT) is thought to play an important role in the development of liver cirrhosis, but the mechanisms have not been fully explored. This study aims to investigate the distribution of Treg (CD3+CD4+CD25+Foxp3+), Th17 (CD3+CD4+IL-17+), and Th1 (CD3+CD4+IFN-γ+) cells in the intestinal lamina propria, liver and blood and to explore their relationships with BT. Cirrhotic rats with ascites were induced by CCl4. We found that there were lower levels of total protein and albumin, lower albumin/globulin ratio, lower body weight and higher spleen weight and ascites volume in cirrhotic rats with than without BT. We found that BT may cause increase of Treg cells in the proximal small intestine and decrease of Th17 cells in the whole intestine and blood in cirrhotic rats. It may also aggravate the CCl4-induced decrease in Th1 cells in the whole intestine, liver, caecum, and blood and the CCl4-induced increase in Th17 cells in the liver and Tregs in the distal small intestine, colon, and liver. Our data suggest that BT may aggravate liver injury and decrease liver function via an interaction with CD4+ T Cells. The results of this study may be helpful for the development of new treatments for liver cirrhosis. PMID:28134306

  3. Sulfasalazine prevents the increase in TGF-β, COX-2, nuclear NFκB translocation and fibrosis in CCl4-induced liver cirrhosis in the rat.

    PubMed

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

    2012-09-01

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

  4. Non-invasive evaluation of liver stiffness after splenectomy in rabbits with CCl4-induced liver fibrosis

    PubMed Central

    Wang, Ming-Jun; Ling, Wen-Wu; Wang, Hong; Meng, Ling-Wei; Cai, He; Peng, Bing

    2016-01-01

    AIM To investigate the diagnostic performance of liver stiffness measurement (LSM) by elastography point quantification (ElastPQ) in animal models and determine the longitudinal changes in liver stiffness by ElastPQ after splenectomy at different stages of fibrosis. METHODS Liver stiffness was measured in sixty-eight rabbits with CCl4-induced liver fibrosis at different stages and eight healthy control rabbits by ElastPQ. Liver biopsies and blood samples were obtained at scheduled time points to assess liver function and degree of fibrosis. Thirty-one rabbits with complete data that underwent splenectomy at different stages of liver fibrosis were then included for dynamic monitoring of changes in liver stiffness by ElastPQ and liver function according to blood tests. RESULTS LSM by ElastPQ was significantly correlated with histologic fibrosis stage (r = 0.85, P < 0.001). The optimal cutoff values by ElastPQ were 11.27, 14.89, and 18.21 kPa for predicting minimal fibrosis, moderate fibrosis, and cirrhosis, respectively. Longitudinal monitoring of the changes in liver stiffness by ElastPQ showed that early splenectomy (especially F1) may delay liver fibrosis progression. CONCLUSION ElastPQ is an available, convenient, objective and non-invasive technique for assessing liver stiffness in rabbits with CCl4-induced liver fibrosis. In addition, liver stiffness measurements using ElastPQ can dynamically monitor the changes in liver stiffness in rabbit models, and in patients, after splenectomy. PMID:28028365

  5. Mechanism investigation of dioscin against CCl4-induced acute liver damage in mice.

    PubMed

    Lu, Binan; Xu, Yousong; Xu, Lina; Cong, Xiaonan; Yin, Lianhong; Li, Hua; Peng, Jinyong

    2012-09-01

    The mechanisms of the ameliorating effects of dioscin against CCl(4) induced acute liver damage are investigated in this study. Dioscin significantly inhibited (p<0.01) the increases of serum ALT and AST activities compared with the CCl(4)-treated animals. The hepatic lipid peroxidation formation and, concentrations of TNF-α and IL-6 were also decreased. Liver histopathologic studies and a DNA laddering assay indicated that dioscin protected hepatocytes against CCl(4)-induced apoptosis and necrosis. Furthermore, dioscin decreased the protein expressions of Fas/FasL, increased Bcl-2/Bax ratio, inhibited the release of cytochrome c from mitochondrion to cytosol and attenuated CCl(4)-induced caspase-3 and -8 activities. The expressions of ICAM-1, vimentin, prohibitin, HGF, c-MET and GSTA1 were also regulated by dioscin and iNOS was also involved in the effects of this agent. These protective effects against CCl(4) induced acute liver damage might be through inhibiting lipid peroxidation, inflammatory cytokines, necrosis and apoptosis, and dioscin shows promise for development toward the treatment of acute chemically mediated liver injury.

  6. Protective Role of Grape Seed Proanthocyanidins Against Ccl4 Induced Acute Liver Injury in Mice

    PubMed Central

    Zou, Jinfa; Qi, Fengjie; Ye, Liping; Yao, Suyan

    2016-01-01

    Background We investigated the effect of grape seed proanthocyanidins (GSPs) on carbon tetrachloride (CCl4)-induced acute liver injury. Material/Methods Sixty SPF KM mice were randomly divided into 6 groups: the control group, CCl4-model group, bifendate group (DDB group), and low-, moderate-, and high-dose GSP groups. The following parameters were measured: serum levels of alanine aminotransferase (ALT); aspartate aminotransferase (AST); tumor necrosis factor (TNF)-α; interleukin-6 (IL-6); high-mobility group box (HMGB)-1; body weight; liver, spleen, and thymus indexes; superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity; HMGB1 mRNA; malondialdehyde (MDA) content; hepatocyte proliferation; and changes in liver histology. Results Compared to the CCl4-model group, decreases in liver index and increases in thymus index significantly increased SOD and GSH-Px activities and reduced MDA content, and higher hepatocyte proliferative activity was found in all GSP dose groups and the DDB group (all P<0.001). Compared with the CCl4-model group, serum TNF-α and IL-6 levels and HMGB 1 mRNA and protein expressions decreased significantly in the high GSP dose group (all P<0.05). Conclusions Our results provide strong evidence that administration of GSPs might confer significant protection against CCl4-induced acute liver injury in mice. PMID:26986029

  7. Hepatoprotective Effect of Low Doses of Caffeine on CCl4-Induced Liver Damage in Rats.

    PubMed

    Cachón, Andrés Uc; Quintal-Novelo, Carlos; Medina-Escobedo, Gilberto; Castro-Aguilar, Gaspar; Moo-Puc, Rosa E

    2017-03-04

    Several studies have shown the hepatoprotective effect of the consumption of coffee and tea, which is mainly attributed to caffeine. Many experimental studies have demonstrated this effect; however, these studies used high caffeine doses that are not related to human consumption. The aim of this study was to evaluate the hepatoprotective effect of low doses of caffeine on carbon tetrachloride (CCl4)-treated rats. Low doses of caffeine (CAFF) 5 and 10 mg/kg (CAFF5 and CAFF10) were evaluated in chronic liver damage induced by CCl4 (0.75 mL/kg) in rats. CAFF treatment was administered once a day and CCl4 administration was twice weekly for 10 weeks. Liver function tests (biochemical markers) and functional (sleeping time) and histological (hematoxylin-eosin and Masson trichrome stains) parameters were carried out at the end of damage treatment. Daily treatments of CAFF5 and CAFF10 exhibited a hepatoprotective effect supported by a decrease of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (AP) serum activities and bilirubin serum levels compared with control and also restored serum albumin levels and liver glutathione (GSH). Moreover, CAFF prevented CCl4-induced prolongation in pentobarbital sleeping time and a decrease of liver fibrosis and cell death. Our results demonstrated that low doses of CAFF exert a hepatoprotective effect against CCl4 -induced liver damage in rats.

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

    PubMed

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

    2004-11-01

    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.

  9. MicroRNA Expression Profiling in CCl4-Induced Liver Fibrosis of Mus musculus

    PubMed Central

    Hyun, Jeongeun; Park, Jungwook; Wang, Sihyung; Kim, Jieun; Lee, Hyun-Hee; Seo, Young-Su; Jung, Youngmi

    2016-01-01

    Liver fibrosis is a major pathological feature of chronic liver diseases, including liver cancer. MicroRNAs (miRNAs), small noncoding RNAs, regulate gene expression posttranscriptionally and play important roles in various kinds of diseases; however, miRNA-associated hepatic fibrogenesis and its acting mechanisms are poorly investigated. Therefore, we performed an miRNA microarray in the fibrotic livers of Mus musculus treated with carbon-tetrachloride (CCl4) and analyzed the biological functions engaged by the target genes of differentially-expressed miRNAs through gene ontology (GO) and in-depth pathway enrichment analysis. Herein, we found that four miRNAs were upregulated and four miRNAs were downregulated more than two-fold in CCl4-treated livers compared to a control liver. Eight miRNAs were predicted to target a total of 4079 genes. GO analysis revealed that those target genes were located in various cellular compartments, including cytoplasm, nucleolus and cell surface, and they were involved in protein-protein or protein-DNA bindings, which influence the signal transductions and gene transcription. Furthermore, pathway enrichment analysis demonstrated that the 72 subspecialized signaling pathways were associated with CCl4-induced liver fibrosis and were mostly classified into metabolic function-related pathways. These results suggest that CCl4 induces liver fibrosis by disrupting the metabolic pathways. In conclusion, we presented several miRNAs and their biological processes that might be important in the progression of liver fibrosis; these findings help increase the understanding of liver fibrogenesis and provide novel ideas for further studies of the role of miRNAs in liver fibrosis. PMID:27322257

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

    PubMed

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

    2015-01-01

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

  11. Protective effect of Trillium tschonoskii saponin on CCl4-induced acute liver injury of rats through apoptosis inhibition.

    PubMed

    Wu, Hao; Qiu, Yong; Shu, Ziyang; Zhang, Xu; Li, Renpeng; Liu, Su; Chen, Longquan; Liu, Hong; Chen, Ning

    2016-12-01

    To explore hepatoprotective role and underlying mechanisms of Trillium tschonoskii Maxim (TTM), 36 rats were randomly divided into control, CCl4-induced liver injury model, and biphenyl dimethyl dicarboxylate (DDB) and low-, moderate-, and high-dose TTM treatment groups. After CCl4-induced model establishment, the rats from DDB and TTM groups were administrated with DDB at 0.2 g/kg per day and TTM at 0.1, 0.5, and 1.0 g/kg per day, while the rats from control and model groups were administrated with saline. After 5 days of treatments, all rats were sacrificed for determining serum ALT and AST levels and liver index, examining histopathological changes in liver through HE and TUNEL staining, and evaluating TNF-α and IL-6 mRNA expression by real-time PCR, and caspase-3, Bcl-2, and Bax expression by Western blot. Results indicated that CCl4 could induce acute liver injury and abnormal liver function in rats with obvious hepatomegaly, increased liver index, high ALT and AST levels, up-regulated TNF-α and IL-6, and overexpressed Bax and caspase-3. However, DDB and TTM could execute protective role in CCl4-induced liver injury in rats through reducing ALT and AST levels, rescuing hepatomegaly, down-regulating inflammatory factors and inhibiting hepatocyte apoptosis in a dose-dependent manner. Therefore, TTM has obvious protective role in CCl4-induced liver injury of rats through inhibiting hepatocyte apoptosis.

  12. Collagen-binding vascular endothelial growth factor attenuates CCl4-induced liver fibrosis in mice

    PubMed Central

    Wu, Kangkang; Huang, Rui; Wu, Hongyan; Liu, Yong; Yang, Chenchen; Cao, Shufeng; Hou, Xianglin; Chen, Bing; Dai, Jianwu; Wu, Chao

    2016-01-01

    Vascular endothelial growth factor (VEGF) serves an important role in promoting angiogenesis and tissue regeneration. However, the lack of an effective delivery system that can target this growth factor to the injured site reduces its therapeutic efficacy. Therefore, in the current study, collagen-binding VEGF was constructed by fusing a collagen-binding domain (CBD) to the N-terminal of native VEGF. The CBD-VEGF can specifically bind to collagen which is the major component of the extracellular matrix in fibrotic liver. The anti-fibrotic effects of this novel material were investigated by the carbon tetrachloride (CCl4)-induced liver fibrotic mouse model. Mice were injected with CCl4 intraperitoneally to induce liver fibrosis. CBD-VEGF was injected directly into the liver tissue of mice. The liver tissues were stained with hematoxylin and eosin for general observation or with Masson's trichrome staining for detection of collagen deposition. The hepatic stellate cell activation, blood vessel formation and hepatocyte proliferation were measured by immunohistochemical staining for α-smooth muscle actin, CD31 and Ki67 in the liver tissue. The fluorescent TUNEL assay was performed to evaluate the hepatocyte apoptosis. The present study identified that the CBD-VEGF injection could significantly promote vascularization of the liver tissue of fibrotic mice and attenuate liver fibrosis. Furthermore, hepatocyte apoptosis and hepatic stellate cell activation were attenuated by CBD-VEGF treatment. CBD-VEGF treatment could additionally promote hepatocyte regeneration in the liver tissue of fibrotic mice. Thus, it was suggested that CBD-VEGF may be used as a novel therapeutic intervention for liver fibrosis. PMID:27748931

  13. The Deficiency of Indoleamine 2,3-Dioxygenase Aggravates the CCl4-Induced Liver Fibrosis in Mice

    PubMed Central

    Ogiso, Hideyuki; Ito, Hiroyasu; Ando, Tatsuya; Arioka, Yuko; Kanbe, Ayumu; Ando, Kazuki; Ishikawa, Tetsuya; Saito, Kuniaki; Hara, Akira; Moriwaki, Hisataka; Shimizu, Masahito; Seishima, Mitsuru

    2016-01-01

    In the present study, we examined the role of indoleamine 2,3-dioxygenase (IDO) in the development of CCl4-induced hepatic fibrosis. The liver fibrosis induced by repetitive administration with CCl4 was aggravated in IDO-KO mice compared to WT mice. In IDO-KO mice treated with CCl4, the number of several inflammatory cells and the expression of pro-inflammatory cytokines increased in the liver. In the results, activated hepatic stellate cells (HSCs) and fibrogenic factors on HSCs increased after repetitive CCl4 administration in IDO-KO mice compared to WT mice. Moreover, the treatment with l-tryptophan aggravated the CCl4-induced hepatic fibrosis in WT mice. Our findings demonstrated that the IDO deficiency enhanced the inflammation in the liver and aggravated liver fibrosis in repetitive CCl4-treated mice. PMID:27598994

  14. Effects of platelet-rich plasma on liver regeneration in CCl4-induced hepatotoxicity model.

    PubMed

    Mafi, Afsaneh; Dehghani, Farzaneh; Moghadam, Abbas; Noorafshan, Ali; Vojdani, Zahra; Talaei-Khozani, Tahereh

    2016-12-01

    Numerous bioactive growth factors and cytokines in platelet-rich plasma (PRP) have recently made it an attractive biomaterial for therapeutic purposes. These growth factors have the potential to regenerate the injured tissues. The aim of this study was to investigate the therapeutic effects of PRP in hepatotoxic animal model. Hepatotoxicity was induced in rats by oral administration of 4 mL/kg/week of CCl4 diluted 1:1 in corn oil for 10 weeks. To confirm the hepatotoxicity, 24 h after the last CCl4 administration, blood samples were collected via cardiac puncture to assess the serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, albumin, total protein, and total bilirubin. Twenty-four hours after blood collection, the experimental animals received a single injection of PRP (1 mL) via the anterior mesenteric vein. One week later, all biochemical tests were performed again, and the rats were scarified and their livers were removed, prepared histologically, and stained. The stereological analyses were performed to evaluate the effects of PRP on histopathological features of CCl4-treated livers. The results were compared statistically with the corresponding control and CCl4+normal saline (NS)-treated animals. A significant decrease in the number and volume of hepatocytes (p = 0.01), and also a reduction in the volume of sinusoids (p = 0.001) and connective tissue (p = 0.04), were observed in the PRP-treated animals compared with the CCl4+NS-treated ones. Our findings demonstrated that application of PRP had beneficial effects on CCl4-induced fibrosis; however, it had detrimental effects on the total number of hepatocytes and the volume of hepatocytes and sinusoidal spaces.

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

    PubMed

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

    2003-01-01

    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.

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

    PubMed Central

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

    2014-01-01

    Objective To evaluate the hepatocurative effects of aqueous root bark, stem bark and leaves of Vitex doniana in carbon tetrachloride (CCl4) induced liver damage and non induced liver damage albino rats. Methods A total of 60 albino rats (36 induced liver damage and 24 non induced liver damage) were assigned into liver damage and non liver damage groups of 6 rats in a group. The animals in the CCl4 induced liver damage groups, were induced by intraperitoneal injection with a single dose of CCl4 (1 mL/kg body weight) as a 1:1(v/v) solution in olive oil and were fasted for 36 h before the subsequent treatment with aqueous root bark, stem bark and leaves extracts of Vitex doniana and vitamin E as standard drug (100 mg/kg body weight per day) for 21 d, while the animals in the non induced groups were only treated with the daily oral administration of these extracts at the same dose. The administration of CCl4 was done once a week for a period of 3 weeks. Results There was significant (P<0.05) increase in concentration of all liver marker enzymes, alanine aminotransferase, aspartate aminotransferase and alkaline aminotransferase (ALT, AST and ALP) and significant (P<0.05) decrease in albumin in the CCl4 induced liver damage control when compared to the normal control. The extracts caused a significant (P<0.05) reduction in the serum activities of liver marker enzymes (ALT, AST and ALP) and a significant (P<0.05) increase in albumin of all the induced treated groups. Only stem bark extract and vitamin E significantly (P<0.05) increased total protein. All the extracts significantly (P<0.05) lowered serum creatinine whereas only root bark extract significantly (P<0.05) lowered serum level of urea in the rats with CCl4 induced liver damage. Conclusion Hepatocurative study shows that all the plant parts (root bark, stem bark and leaves) possess significant hepatocurative properties among other therapeutic values justifying their use in folklore medicine. PMID:25182950

  17. Tyrosine kinase inhibitor BIBF1120 ameliorates inflammation, angiogenesis and fibrosis in CCl4-induced liver fibrogenesis mouse model

    PubMed Central

    Öztürk Akcora, Büsra; Storm, Gert; Prakash, Jai; Bansal, Ruchi

    2017-01-01

    Hepatic fibrosis, a progressive chronic disease mainly caused by hepatitis viral infections, alcohol abuse or metabolic syndrome leading to liver dysfunction and is the growing cause of mortality worldwide. Tyrosine kinase inhibitor BIBF1120 (Nintedanib) has been evaluated in clinical trials for idiopathic pulmonary fibrosis and advanced Hepatocellular carcinoma, but has not been explored for liver fibrosis yet. In this study, we aimed to investigate the therapeutic effects and mechanism of BIBF1120 in liver fibrogenesis. The effects of BIBF1120 were evaluated in TGFβ-activated mouse 3T3 fibroblasts, LX2 cells, primary human hepatic stellate cells (HSCs) and CCl4-induced liver fibrogenesis mouse model. Fibroblasts-conditioned medium studies were performed to assess the paracrine effects on macrophages and endothelial cells. In-vitro in TGFβ-activated fibroblasts, BIBF1120 significantly inhibited expression of major fibrotic parameters, wound-healing and contractility. In vivo in CCl4-induced acute liver injury model, post-disease BIBF1120 administration significantly attenuated collagen accumulation and HSC activation. Interestingly, BIBF1120 drastically inhibited intrahepatic inflammation and angiogenesis. To further elucidate the mechanism of action, 3T3-conditioned medium studies demonstrated increased 3T3-mediated macrophage chemotaxis and endothelial cells tube formation and activation, which was significantly decreased by BIBF1120. These results suggests that BIBF1120 can be a potential therapeutic approach for the treatment of liver fibrosis. PMID:28291245

  18. Studies on protective effect of DA-9601, Artemisia asiatica extract, on acetaminophen- and CCl4-induced liver damage in rats.

    PubMed

    Ryu, B K; Ahn, B O; Oh, T Y; Kim, S H; Kim, W B; Lee, E B

    1998-10-01

    The hepatoprotective effect of DA-9601, a quality-controlled extract of Artemisia asiatica, on liver damage induced by acetaminophen (APAP) and carbon tetrachloride (CCl4) was investigated by means of serum-biochemical, hepatic-biochemical, and histopathological examinations. Doses of DA-9601 (10, 30, or 100 mg/kg) were administered intragastrically to each rat on three consecutive days i.e. 48 h, 24 h and 2 h before a single administration of APAP (640 mg/kg, i.p.) or CCl4 (2 ml/kg, p.o.). Four h and 24 h after hepatotoxin treatment, the animals were sacrificed for evaluation of liver damage. Pretreatment of DA-9601 reduced the elevation of serum ALT, AST, LDH and histopathological changes such as centrilobular necrosis, vacuolar degeneration and inflammatory cell infiltration dose-dependently. DA-9601 also prevented APAP- and CCl4-induced hepatic glutathione (GSH) depletion and CCl4-induced increase of hepatic malondialdehyde (MDA), a parameter of lipid peroxidation, in a dose-dependent manner. These findings suggest that pretreatment with DA-9601 may reduce chemically induced liver injury by complex mechanisms which involve prevention of lipid peroxidation and preservation of hepatic GSH.

  19. Free Radical-Scavenging, Anti-Inflammatory/Anti-Fibrotic and Hepatoprotective Actions of Taurine and Silymarin against CCl4 Induced Rat Liver Damage

    PubMed Central

    Abdel-Moneim, Ashraf M.; Al-Kahtani, Mohammed A.; El-Kersh, Mohamed A.; Al-Omair, Mohammed A.

    2015-01-01

    The present study aims to investigate the hepatoprotective effect of taurine (TAU) alone or in combination with silymarin (SIL) on CCl4-induced liver damage. Twenty five male rats were randomized into 5 groups: normal control (vehicle treated), toxin control (CCl4 treated), CCl4+TAU, CCl4+SIL and CCl4+TAU+SIL. CCl4 provoked significant increases in the levels of hepatic TBARS, NO and NOS compared to control group, but the levels of endogenous antioxidants such as SOD, GPx, GR, GST and GSH were significantly decreased. Serum pro-inflammatory and fibrogenic cytokines including TNF-α, TGF-β1, IL-6, leptin and resistin were increased while the anti-inflammatory (adiponectin) cytokine was decreased in all treated rats. Our results also showed that CCl4 induced an increase in liver injury parameters like serum ALT, AST, ALP, GGT and bilirubin. In addition, a significant increase in liver tissue hydroxyproline (a major component of collagen) was detected in rats exposed to CCl4. Moreover, the concentrations of serum TG, TC, HDL-C, LDL-C, VLDL-C and FFA were significantly increased by CCl4. Both TAU and SIL (i.e., antioxidants) post-treatments were effectively able to relieve most of the above mentioned imbalances. However, the combination therapy was more effective than single applications in reducing TBARS levels, NO production, hydroxyproline content in fibrotic liver and the activity of serum GGT. Combined treatment (but not TAU- or SIL-alone) was also able to effectively prevent CCl4-induced decrease in adiponectin serum levels. Of note, the combined post-treatment with TAU+SIL (but not monotherapy) normalized serum FFA in CCl4-treated rats. The biochemical results were confirmed by histological and ultrastructural changes as compared to CCl4-poisoned rats. Therefore, on the basis of our work, TAU may be used in combination with SIL as an additional adjunct therapy to cure liver diseases such as fibrosis, cirrhosis and viral hepatitis. PMID:26659465

  20. Study on the effects of blueberry treatment on histone acetylation modification of CCl4-induced liver disease in rats.

    PubMed

    Zhan, W; Liao, X; Tian, T; Yu, L; Liu, X; Li, B; Liu, J; Han, B; Xie, R J; Ji, Q H; Yang, Q

    2017-02-16

    The objective of this study was to investigate the effects of blueberry treatment on histone acetylation modification of carbon tetrachloride (CCl4)-induced liver disease in rats. Laboratory rats were randomly divided into control, hepatic fibrosis, blueberry treatment, blueberry intervention, and natural recovery groups. Rats in the model groups were treated with CCl4 administered subcutaneously at 4- and 8-week intervals, and then executed. Both the 4- and 8-week treatment groups were treated with blueberry juice for 8 weeks, and then executed after 12 and 16 weeks, respectively. Following the experiment, four liver function and hepatic fibrosis indices were measured. Liver index was calculated, hematoxylin-eosin staining was conducted, and H3K9, H3K14, and H3K18 expressions were evaluated among the nuclear proteins of the liver tissues. No differences in alanine transaminase were noted between the control and intervention groups, but significant differences were detected among the model, treatment, and natural recovery groups (P < 0.01). Significant differences were also observed in aspartate transaminase, hyaluronic acid, and collagen IV among the model, treatment, intervention, and natural recovery groups (P < 0.01, P < 0.01, P < 0.01). Liver index, and H3K9 and H3K14 expression were significantly different among the model groups (P < 0.05 and P < 0.01), whereas H3K18 expression was dramatically different among model, treatment, intervention, and natural recovery groups (P < 0.01). Following blueberry treatment, rat liver function and hepatic fibrosis improved, potentially indicating that blueberry components could regulate histone acetylation and improve liver pathologic changes in rats with CCl4-induced disease.

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

    PubMed Central

    2010-01-01

    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

  2. Accelerated CCl4-Induced Liver Fibrosis in Hjv-/- Mice, Associated with an Oxidative Burst and Precocious Profibrogenic Gene Expression

    PubMed Central

    Sebastiani, Giada; Gkouvatsos, Kostas; Maffettone, Carmen; Busatto, Graziella; Guido, Maria; Pantopoulos, Kostas

    2011-01-01

    Hereditary hemochromatosis is commonly associated with liver fibrosis. Likewise, hepatic iron overload secondary to chronic liver diseases aggravates liver injury. To uncover underlying molecular mechanisms, hemochromatotic hemojuvelin knockout (Hjv-/-) mice and wild type (wt) controls were intoxicated with CCl4. Hjv-/- mice developed earlier (by 2-4 weeks) and more acute liver damage, reflected in dramatic levels of serum transaminases and ferritin and the development of severe coagulative necrosis and fibrosis. These responses were associated with an oxidative burst and early upregulation of mRNAs encoding α1-(I)-collagen, the profibrogenic cytokines TGF-β1, endothelin-1 and PDGF and, notably, the iron-regulatory hormone hepcidin. Hence, CCl4-induced liver fibrogenesis was exacerbated and progressed precociously in Hjv−/− animals. Even though livers of naïve Hjv−/− mice were devoid of apparent pathology, they exhibited oxidative stress and immunoreactivity towards α-SMA antibodies, a marker of hepatic stellate cells activation. Furthermore, they expressed significantly higher (2–3 fold vs. wt, p<0.05) levels of α1-(I)-collagen, TGF-β1, endothelin-1 and PDGF mRNAs, indicative of early fibrogenesis. Our data suggest that hepatic iron overload in parenchymal cells promotes oxidative stress and triggers premature profibrogenic gene expression, contributing to accelerated onset and precipitous progression of liver fibrogenesis. PMID:21966437

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

    PubMed Central

    Chagoya de Sánchez, Victoria; Martínez-Pérez, Lidia; Hernández-Muñoz, Rolando; Velasco-Loyden, Gabriela

    2012-01-01

    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

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

    PubMed

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

    2013-05-01

    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.

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

    PubMed Central

    2013-01-01

    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

  6. Hepatocyte Growth Factor Mediates the Antifibrogenic Action of Ocimum bacilicum Essential Oil against CCl4-Induced Liver Fibrosis in Rats.

    PubMed

    Ogaly, Hanan A; Eltablawy, Nadia A; El-Behairy, Adel M; El-Hindi, Hatim; Abd-Elsalam, Reham M

    2015-07-23

    The current investigation aimed to evaluate the antifibrogenic potential of Ocimum basilicum essential oil (OBE) and further to explore some of its underlying mechanisms. Three groups of rats were used: group I (control), group II (CCl4 model) and group III (OBE-treated) received CCl4 and OBE 2 weeks after the start of CCl4 administration. Oxidative damage was assessed by the measurement of MDA, NO, SOD, CAT, GSH and total antioxidant capacity (TAC). Liver fibrosis was assessed histopathologically by Masson's trichrome staining and α-smooth muscle actin (α-SMA) immunostaining. Expression of hepatocyte growth factor (HGF) and cytochrome P450 (CYP2EI isoform) was estimated using real-time PCR and immunohistochemistry. OBE successfully attenuated liver injury, as shown by histopathology, decreased serum transaminases and improved oxidative status of the liver. Reduced collagen deposition and α-SMA immuopositive cells indicated an abrogation of hepatic stellate cell activation by OBE. Furthermore, OBE was highly effective in stimulating HGF mRNA and protein expression and inhibiting CCl4-induced CYP2E1 down-regulation. The mechanism of antifibrogenic action of OBE is hypothesized to proceed via scavenging free radicals and activating liver regeneration by induction of HGF. These data suggest the use of OBE as a complementary treatment in liver fibrosis.

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

    PubMed

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

    2014-09-05

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

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

    PubMed

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

    2011-01-01

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

  9. Antioxidant Activity of The Ancient Herb, Holy Basil in CCl4-Induced Liver Injury in Rats

    PubMed Central

    Ponnusam, Yuvaraj; Louis, Therasilin; Madhavachandran, V; Kumar, Suresh; Thoprani, Neelam; Hamblin, Michael R; Lakshmanan, Shanmugamurthy

    2015-01-01

    An herbal preparation called “holy basil plus herbal powder” (HBPP) containing Ocimum santum, Withania somnifera, Pongamia pinnata, Plumbago indica, Emblica officinalis and Curcuma longa was investigated as an antioxidant and hepatoprotective agent. The antioxidant activity of HBPP was investigated in rats with liver injury induced by oral administration of carbon tetrachloride:olive oil (1:1). HBPP was administered orally at 500 mg/kg daily for 7 days before. HBPP exhibited statistically significant antioxidant activity, as shown by increased levels of glutathione peroxidase (GPX), glutathione S-transferase (GST), glutathione reductase (GRD), superoxide dismutase (SOD) and catalase (CAT) and decreased level of lipid peroxidation (LPO). HBPP performed equally well as silymarin, a well-established antioxidant preparation used to protect against liver injury. PMID:26925464

  10. Glutamine inhibits CCl4 induced liver fibrosis in mice and TGF-β1 mediated epithelial-mesenchymal transition in mouse hepatocytes.

    PubMed

    Shrestha, Nirajan; Chand, Lokendra; Han, Myung Kwan; Lee, Seung Ok; Kim, Chan Young; Jeong, Yeon Jun

    2016-07-01

    Glutamine, traditionally a non-essential amino acid, now has been considered as essential in serious illness and injury. It is a major precursor for glutathione synthesis. However, the anti-fibrotic effect of glutamine and its molecular mechanism in experimental liver fibrosis have not been explored. In the present study we aimed to examine the potential role of glutamine in carbon tetrachloride (CCl4) induced liver fibrosis and TGF-β1 mediated epithelial mesenchymal transition (EMT) and apoptosis in mouse hepatocytes. Liver fibrosis was induced by intraperitoneal injection of CCl4 three times a week for 10 weeks. Glutamine treatment effectively attenuated liver injury and oxidative stress. Collagen content was significantly decreased in liver sections of glutamine treated mice compared to CCl4 model mice. Furthermore, glutamine decreased expression level of α-SMA and TGF-β in liver tissue. Our in vitro study showed that TGF-β1 treatment in hepatocytes resulted in loss of E-cadherin and increased expression of mesenchymal markers and EMT related transcription factor. In addition, TGF-β1 increased the expression of apoptotic markers. However, glutamine interestingly suppressed TGF-β1 mediated EMT and apoptosis. In conclusion, our results suggest that glutamine ameliorates CCl4 induced liver fibrosis and suppresses TGF-β1 induced EMT progression and apoptosis.

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

    PubMed Central

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

    2015-01-01

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

  12. Hepatoprotective activity of petroleum ether, diethyl ether, and methanol extract of Scoparia dulcis L. against CCl4-induced acute liver injury in mice

    PubMed Central

    Praveen, T.K.; Dharmaraj, S.; Bajaj, Jitendra; Dhanabal, S.P.; Manimaran, S.; Nanjan, M.J.; Razdan, Rema

    2009-01-01

    Objectives: The present study was aimed at assessing the hepatoprotective activity of 1:1:1 petroleum ether, diethyl ether, and methanol (PDM) extract of Scoparia dulcis L. against carbon tetrachloride-induced acute liver injury in mice. Materials and Methods: The PDM extract (50, 200, and 800 mg/kg, p.o.) and standard, silymarin (100 mg/kg, p.o) were tested for their antihepatotoxic activity against CCl4-induced acute liver injury in mice. The hepatoprotective activity was evaluated by measuring aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and total proteins in serum, glycogen, lipid peroxides, superoxide dismutase, and glutathione reductase levels in liver homogenate and by histopathological analysis of the liver tissue. In addition, the extract was also evaluated for its in vitro antioxidant activity using 1, 1-Diphenyl-2-picrylhydrazyl scavenging assay. Results: The extract at the dose of 800 mg/kg, p.o., significantly prevented CCl4-induced changes in the serum and liver biochemistry (P < 0.05) and changes in liver histopathology. The above results are comparable to standard, silymarin (100 mg/kg, p.o.). In the in vitro 1, 1-diphenyl-2-picrylhydrazyl scavenging assay, the extract showed good free radical scavenging potential (IC 50 38.9 ± 1.0 μg/ml). Conclusions: The results of the study indicate that the PDM extract of Scoparia dulcis L. possesses potential hepatoprotective activity, which may be attributed to its free radical scavenging potential, due to the terpenoid constituents. PMID:20442817

  13. 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

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

    2011-01-01

    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

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

    PubMed Central

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

    2012-01-01

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

  15. Tonsil-derived mesenchymal stem cells ameliorate CCl4-induced liver fibrosis in mice via autophagy activation.

    PubMed

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

    2015-02-27

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

  16. Balance between oxidative damage and proliferative potential in an experimental rat model of CCl4-induced cirrhosis: protective role of adenosine administration.

    PubMed

    Hernández-Muñoz, R; Díaz-Muñoz, M; López, V; López-Barrera, F; Yáñez, L; Vidrio, S; Aranda-Fraustro, A; Chagoya de Sánchez, V

    1997-11-01

    Oxidative stress and its consequent lipid peroxidation (LP) exert harmful effects, which have been currently involved in the generation of carbon tetrachloride-induced cirrhosis. However, the recent report that "physiological" LP can be associated with liver regeneration (LR) makes it necessary to discriminate between oxidative stress-induced and LR-associated LP. In rats rendered cirrhotic by continuous CCl4 administration for 4 weeks, moderate cell necrosis and fine fatty infiltration were found. The histological abnormalities were accompanied by increased LP, mainly accounted for by the microsomal and cytosolic fractions and evidence of oxidative stress (decreased hepatic glutathione content and changes in xanthine oxidase and pentose phosphate pathway activities). After 8 weeks, a micronodular cirrhosis developed, but oxidative stress was greatly attenuated, only persisting in the enhanced LP confined to microsomes. Simultaneous administration of adenosine, a reliable hepatoprotector that readily prevents the onset of liver fibrosis, was able to block the oxidative stress induced by the long-term CCl4 treatment but elicited a selective subcellular distribution of increased LP, similar to that found during LR. The adenosine-induced changes in liver LP (mainly in the nuclear fraction) correlated with an increased activity of thymidine kinase. Therefore, data suggest that adenosine-mediated preservation of energy availability and mitochondrial function could participate in preventing the onset of oxidative stress in cirrhotic rats. The latter could induce a successful liver recovery, curtailing the sequence of events leading to fibrogenesis.

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

    PubMed

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

    2005-04-01

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

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

    PubMed

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

    2012-07-01

    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.

  19. Cultured Mycelium Cordyceps sinensis allevi¬ates CCl4-induced liver inflammation and fibrosis in mice by activating hepatic natural killer cells

    PubMed Central

    Peng, Yuan; Huang, Kai; Shen, Li; Tao, Yan-yan; Liu, Cheng-hai

    2016-01-01

    Aim: Recent evidence shows that cultured mycelium Cordyceps sinensis (CMCS) effectively protects against liver fibrosis in mice. Here, we investigated whether the anti-fibrotic action of CMCS was related to its regulation of the activity of hepatic natural killer (NK) cells in CCl4-treated mice. Methods: C57BL/6 mice were injected with 10% CCl4 (2 mL/kg, ip) 3 times per week for 4 weeks, and received CMCS (120 mg·kg−1·d−1, ig) during this period. In another part of experiments, the mice were also injected with an NK cell-deleting antibody ASGM-1 (20 μg, ip) 5 times in the first 3 weeks. After the mice were sacrificed, serum liver function, and liver inflammation, hydroxyproline content and collagen deposition were assessed. The numbers of hepatic NK cells and expression of NKG2D (activation receptor of NK cells) on isolated liver lymphocytes were analyzed using flow cytometry. Desmin expression and cell apoptosis in liver tissues were studied using desmin staining and TUNEL assay, respectively. The levels of α-SMA, TGF-β, RAE-1δ and RAE-1ε in liver tissues were determined by RT-qPCR. Results: In CCl4-treated mice, CMCS administration significantly improved liver function, attenuated liver inflammation and fibrosis, and increased the numbers of hepatic NK cells and expression level of NKG2D on hepatic NK cells. Furthermore, CMCS administration significantly decreased desmin expression in liver tissues, and increased TUNEL staining adjacent to hepatic stellate cells. Injection with NK cell-deleting ASGM-1 not only diminished the numbers of hepatic NK cells, but also greatly accelerated liver inflammation and fibrosis in CCl4-treated mice. In CCl4-treated mice with NK cell depletion, CMCS administration decelerated the rate of liver fibrosis development, and mildly upregulated the numbers of hepatic NK cells but without changing NKG2D expression. Conclusion: CMCS allevi¬ates CCl4-induced liver inflammation and fibrosis via promoting activation of hepatic

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

    PubMed

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

    2006-11-01

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

  1. Preventative effects of prostaglandin E1 in combination with iodized olive oil on liver fibrosis after transcatheter arterial chemoembolization in a rabbit model of CCl4-induced liver fibrosis.

    PubMed

    Jin, Shuqiang; Cao, Haili; Wang, Kaibing; Li, Ying; Bai, Bin

    2015-06-01

    To explore the preventative effects of prostaglandin E1 (PGE1) on a rabbit model of CCl4-induced liver fibrosis after transcatheter arterial chemoembolization (TACE), we generated a rabbit model of CCl4-induced liver fibrosis by treatment with 40% CCl4 in iodized olive oil for 16 weeks. Body mass and serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total protein (TP), albumin (ALB), albumin:globulin ratio (A:G), total bilirubin (TBIL), and direct bilirubin (DBIL) were measured. After TACE, the levels of hyaluronic acid (HA), procollagen III (PC III), laminin (LN), and collagen IV (IV-C) were measured, and the severity of liver fibrosis as well as the morphology of liver tissues were determined. Body mass in the model group was significantly decreased from 10 to 16 weeks, and the serum levels of ALT, AST, TP, TBIL, and DBIL levels were significantly increased while the model was being generated; the levels of ALB and A:G were significantly decreased. After TACE, serum levels of HA, PC III, and LN in the group injected with 1.0 mL iodized olive oil (Group B) were higher than in the group that were injected with 1.0 mL iodized olive oil + 0.2 mL PGE1 (Group C), whereas the serum levels of IV-C were lower. The severity of liver fibrosis was ameliorated in Group C. The combination of PGE1 and iodized olive oil prevented the development of liver fibrosis following TACE.

  2. Anti-inflammatory and hepatoprotective effects of glycyrrhetinic acid on CCl4-induced damage in precision-cut liver slices from Jian carp (Cyprinus carpio var. jian) through inhibition of the nf-kƁ pathway.

    PubMed

    Cao, Liping; Ding, Weidong; Jia, Rui; Du, Jingliang; Wang, Tao; Zhang, Chunyun; Gu, Zhengyan; Yin, Guojun

    2017-03-10

    In order to evaluate the antioxidant and anti-inflammatory effects of glycyrrhetinic acid (GA) on carbon tetrachloride (CCl4)-induced damage in precision-cut liver slices (PCLS) from Jian carp (Cyprinus carpio. Jian), an acute liver damage model was established in this study. The viability of PCLS, levels of anti-oxidases in liver homogenates, expression of inflammation-related genes including nuclear factor-κB (nf-κB)/c-rel, inducible nitric oxide synthase (inos), interleukin-1β (il-1β), interleukin-6 (il-6) and interleukin-8 (il-8), and protein levels of (nf-κB)/c-rel in liver tissues were measured. The results showed that pretreatment of PCLS with GA at 5 and 10 μg/mL for 6 h significantly inhibited the cytotoxicity of CCl4. GA attenuated CCl4-induced oxidative stress in PCLS through promoting the recovery of superoxide dismutase (SOD) and glutathione (GSH) levels, and inhibiting malondialdehyde (MDA) synthesis. In inflammatory response, GA at both 5 and 10 μg/mL significantly inhibited the increase in mRNA levels of inflammatory cytokines including nf-kƁ/c-rel, inos, il-1β, il-6 and il-8, and the protein level of Nf-kƁ/C-rel induced by CCl4. Furthermore, treatment with pyrrolyl dithiocarbamate (PDTC, 4 μg/mL), an inhibitor of nuclear transcription factor nf-kB, significantly inhibited nf-kB levels, and transcription of downstream cytokines inos, il-1β, il-6 and il-8, also the viability of PCLS was significantly increased. These results indicated that GA suppressed inflammation and reduced cytotoxicity by inhibiting the nf-kƁ signaling pathway, and plays a role in liver protection.

  3. Protective Effect of Zingiber Officinale against CCl4-Induced Liver Fibrosis Is Mediated through Downregulating the TGF-β1/Smad3 and NF-ĸB/IĸB Pathways.

    PubMed

    Hasan, Iman H; El-Desouky, M A; Hozayen, Walaa G; Abd el Aziz, Ghada M

    2016-01-01

    No ideal hepatoprotective agents are available in modern medicine to effectively prevent liver disorders. In this study, we aimed at evaluating the potential of Zingiber officinale in the regression of liver fibrosis and its underlining mechanism of action. To induce liver fibrosis, male Wistar rats received CCl4 (2 ml/kg/2 times/week; i.p.), with and without 300 or 600 mg/kg Z. officinale extract daily through oral gavage. To assess the protective effect of Z. officinale, liver function parameters, histopathology, inflammatory markers and gene expression of transforming growth factor-beta 1 (TGF-β1)/Smad3 and nuclear factor-kappa B (NF-ĸB)/IĸB pathways were analyzed. Results demonstrate that Z. officinale extract markedly prevented liver injury as evident by the decreased liver marker enzymes. Concurrent administration of Z. officinale significantly protected against the CCl4-induced inflammation as showed by the decreased pro-inflammatory cytokine levels as well as the downregulation of the NF-ĸB)/IĸB and TGF-β1/Smad3 pathways in CCl4-administered rats. In conclusion, our study provides evidence that the protective effect of Z. officinale against rat liver fibrosis could be explained through its ability to modulate the TGF-β1/Smad3 and NF-ĸB)/IĸB signaling pathways.

  4. JNK1 and JNK2 regulate α-SMA in hepatic stellate cells during CCl4 -induced fibrosis in the rat liver.

    PubMed

    Hong, Il-Hwa; Park, Sang-Joon; Goo, Moon-Jung; Lee, Hye-Rim; Park, Jin-Kyu; Ki, Mi-Ran; Kim, Sang-Hyeob; Lee, Eun-Mi; Kim, Ah-Young; Jeong, Kyu-Shik

    2013-10-01

    Following liver injuries, hepatic stellate cells (HSCs) express α-SMA. Mitogen activated protein kinase (MAPK) signaling pathways mediate α-SMA expression in distinct cell types. However, the regulation of α-SMA expression by MAPKs in HSCs has been rarely studied. We aimed to study the role of MAPKs in the activation of HSCs during liver fibrosis. Liver fibrosis of rats was induced by carbon tetrachloride. HSC-T6 cells, murine embryonic fibroblasts, JNK1(-/-) and JNK2(-/-) cells were used for in vitro studies. Immunohistochemistry and immunoblot analysis were used. We have found that the expression of JNK and α-SMA co-localized in HSCs during liver fibrosis, but ERK and p38 expressed in macrophages. The expression of α-SMA was up-regulated by JNK1 and JNK2 in non-stress condition. Under TGF-β stimulation, however, the level α-SMA expression was increased by only JNK1, but not significantly changed by JNK2. We suggest that JNKs are responsible for α-SMA regulation, and especially JNK1 has a major role in up-regulation of α-SMA expression in HSCs under stress condition induced by TGF-β during liver fibrosis.

  5. Methanolic Extract of Dill Leaves Inhibits AGEs Formation and Shows Potential Hepatoprotective Effects in CCl4 Induced Liver Toxicity in Rat.

    PubMed

    Oshaghi, Ebrahim Abbasi; Khodadadi, Iraj; Mirzaei, Fatemeh; Khazaei, Mozafar; Tavilani, Heidar; Goodarzi, Mohammad Taghi

    2017-01-01

    The research was aimed at evaluating the antiglycation, antioxidant, and hepatoprotective properties of methanolic extract of Anethum graveolens (dill). The antioxidant properties, photochemical characteristics, and antiglycation effects of dill extract were measured. Carbon tetrachloride-induced hepatotoxic rats were used to show the hepatoprotective activity of dill leaves. Different concentration of dill extract (0.032, 0.065, 0.125, 0.25, 0.5, and 1 mg/mL) showed potential antioxidant ability. The extract of dill leaves significantly reduced AGEs formation and also fructosamine and protein carbonyl levels in rats' liver. Thiol groups' oxidation, amyloid cross-β, and protein fragmentation (P < 0.001) significantly reduced in treated rats. Liver damage markers significantly reduced in dill-treated animals (P < 0.05). Dill with potential antioxidant, antiglycation, and hepatoprotective effects can be suggested for treatment of diabetes complications.

  6. Methanolic Extract of Dill Leaves Inhibits AGEs Formation and Shows Potential Hepatoprotective Effects in CCl4 Induced Liver Toxicity in Rat

    PubMed Central

    Khodadadi, Iraj; Mirzaei, Fatemeh; Khazaei, Mozafar; Tavilani, Heidar

    2017-01-01

    The research was aimed at evaluating the antiglycation, antioxidant, and hepatoprotective properties of methanolic extract of Anethum graveolens (dill). The antioxidant properties, photochemical characteristics, and antiglycation effects of dill extract were measured. Carbon tetrachloride-induced hepatotoxic rats were used to show the hepatoprotective activity of dill leaves. Different concentration of dill extract (0.032, 0.065, 0.125, 0.25, 0.5, and 1 mg/mL) showed potential antioxidant ability. The extract of dill leaves significantly reduced AGEs formation and also fructosamine and protein carbonyl levels in rats' liver. Thiol groups' oxidation, amyloid cross-β, and protein fragmentation (P < 0.001) significantly reduced in treated rats. Liver damage markers significantly reduced in dill-treated animals (P < 0.05). Dill with potential antioxidant, antiglycation, and hepatoprotective effects can be suggested for treatment of diabetes complications. PMID:28182107

  7. The Effects of Taoren-Honghua Herb Pair on Pathological Microvessel and Angiogenesis-Associated Signaling Pathway in Mice Model of CCl4-Induced Chronic Liver Disease

    PubMed Central

    Xi, Shengyan; Yue, Lifeng; Shi, Mengmeng; Peng, Ying; Xu, Yangxinzi; Wang, Xinrong; Li, Qian; Kang, Zhijun; Li, Hanjing; Wang, Yanhui

    2016-01-01

    Chronic liver disease is one of the most common diseases that threaten human health. Effective treatment is still lacking in western medicine. Semen Persicae (Taoren) and Flos Carthami (Honghua) are known to relieve acute hepatic injury and inflammation, improve microcirculation, and reduce tissue fiber. The aim of our study is to investigate the potential mechanisms of Taoren-Honghua Herb Pair (THHP) in murine model of chronic liver disease caused by Carbon Tetrachloride (CCl4). Mice were randomly divided into seven groups: (1) blank, (2) model, (3) control (colchicine, 0.1 mg/kg), (4) THHP (5.53, 2.67, and 1.33 g/kg), and (5) Tao Hong Siwu Decoction (THSWD) (8.50 g/kg). Histological change and microvessels density were examined by microscopy. Hepatic function, serum fibrosis related factors, and hepatic vascular endothelial growth factor (VEGF) were measured with ELISA. VEGF, kinase insert domain-containing receptor (KDR), Flt-1, and Akt mRNA expression in hepatic tissue were determined with PCR. Tissues of Akt, pAkt, KDR, and Flt-1 were measured with western blotting. Data from this study showed that THHP improved hepatic function and restrained the hepatic inflammation and fibrosis. Its role in inhibiting pathological angiogenesis and hepatic fibrogenesis may be through affecting the angiogenesis-associated VEGF and its upstream and downstream signaling pathways. PMID:27293456

  8. Pathogenesis of liver cirrhosis.

    PubMed

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

    2014-06-21

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

  9. An ω-3-enriched diet alone does not attenuate CCl4-induced hepatic fibrosis.

    PubMed

    Harris, Todd R; Kodani, Sean; Yang, Jun; Imai, Denise M; Hammock, Bruce D

    2016-12-01

    Exposure to the halogenated hydrocarbon carbon tetrachloride (CCl4) leads to hepatic lipid peroxidation, inflammation and fibrosis. Dietary supplementation of ω-3 fatty acids has been increasingly advocated as being generally anti-inflammatory, though its effect in models of liver fibrosis is mixed. This raises the question of whether diets high in ω-3 fatty acids will result in a greater sensitivity or resistance to liver fibrosis as a result of environmental toxicants like CCl4. In this study, we fed CCl4-treated mice a high ω-3 diet (using a mix of docosahexaenoic acid and eicosapentaenoic acid ethyl esters). We also co-administered an inhibitor of soluble epoxide hydrolase, 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), which has been shown to boost anti-inflammatory epoxy fatty acids that are produced from both ω-3 and ω-6 dietary lipids. We showed that soluble epoxide inhibitors reduced CCl4-induced liver fibrosis. Three major results were obtained. First, the ω-3-enriched diet did not attenuate CCl4-induced liver fibrosis as judged by collagen deposition and collagen mRNA expression. Second, the ω-3-enriched diet raised hepatic tissue levels of several inflammatory lipoxygenase metabolites and prostaglandins, including PGE2. Third, treatment with TPPU in drinking water in conjunction with the ω-3-enriched diet resulted in a reduction in liver fibrosis compared to all other groups. Taken together, these results indicate that dietary ω-3 supplementation alone did not attenuate CCl4-induced liver fibrosis. Additionally, oxylipin signaling molecules may play role in the CCl4-induced liver fibrosis in the high ω-3 diet groups.

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

    PubMed

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

    2014-02-01

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

  11. Protective effects of L-carnosine on CCl4 -induced hepatic injury in rats.

    PubMed

    Alsheblak, Mehyar Mohammad; Elsherbiny, Nehal M; El-Karef, Amro; El-Shishtawy, Mamdouh M

    2016-03-01

    The present study was undertaken to investigate the possible protective effect of L-carnosine (CAR), an endogenous dipeptide of alanine and histidine, on carbon tetrachloride (CCl4)-induced hepatic injury. Liver injury was induced in male Sprague-Dawley rats by intraperitoneal (i.p.) injections of CCl4, twice weekly for six weeks. CAR was administered to rats daily, at dose of 250 mg/kg, i.p. At the end of six weeks, blood and liver tissue specimens were collected. Results show that CAR treatment attenuated the hepatic morphological changes, necroinflammation and fibrosis induced by CCl4, as indicated by hepatic histopathology scoring. In addition, CAR treatment significantly reduced the CCl4-induced elevation of liver-injury parameters in serum. CAR treatment also combatted oxidative stress; possibly by restoring hepatic nuclear factor erythroid 2-related factor 2 (Nrf-2) levels. Moreover, CAR treatment prevented the activation of hepatic stellate cells (HSCs), as indicated by reduced α-smooth muscle actin (α-SMA) expression in the liver, and decreased hepatic inflammation as demonstrated by a reduction in hepatic tumor necrosis factor-α (TNF-α) and restoration of interleukin-10 (IL-10) levels. In conclusion, CCl4-induced hepatic injury was alleviated by CAR treatment. The results suggest that these beneficial, protective effects are due, at least in part, to its anti-oxidant, anti-inflammatory and anti-fibrotic activities.

  12. Plumbagin Ameliorates CCl4-Induced Hepatic Fibrosis in Rats via the Epidermal Growth Factor Receptor Signaling Pathway

    PubMed Central

    Chen, Si; Chen, Yi; Chen, Bi; Cai, Yi-jing; Zou, Zhuo-lin; Wang, Jin-guo; Lin, Zhuo; Wang, Xiao-dong; Fu, Li-yun; Hu, Yao-ren; Chen, Yong-ping; Chen, Da-zhi

    2015-01-01

    Epidermal growth factor (EGF) and its signaling molecules, EGFreceptor (EGFR) and signal transducer and activator of transcription factor 3 (STAT3), have been considered to play a role in liver fibrosis and cirrhosis. Plumbagin (PL) is an extracted component from the plant and has been used to treat different kinds of cancer. However, its role in regulation of EGFR and STAT3 during liver fibrosis has not been investigated. In this study, the effects of PL on the regulation of EGFR and STAT3 were investigated in carbon tetrachloride (CCl4) induced liver fibrosis and hepatic stellate cells (HSC-T6). PL significantly attenuated liver injury and fibrosis in CCl4 treated rats. At concentrations of 2 to 6 μM, PL did not induce significant cytotoxicity of HSC-T6 cells. Moreover, PL reduced phosphorylation of EGFR and STAT3 in both fibrotic liver and heparin-binding EGF-like growth factor (HB-EGF) treated HSC-T6 cells. Furthermore, PL reduced the expression of α-SMA, EGFR, and STAT3 in both fibrotic liver and HB-EGF treated HSC-T6 cells. In conclusion, plumbagin could ameliorate the development of hepatic fibrosis through its downregulation of EGFR and STAT3 in the liver, especially in hepatic stellate cells. PMID:26550019

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

    PubMed Central

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

    2015-01-01

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

  14. Chicory (Cichorium intybus L.) root extract regulates the oxidative status and antioxidant gene transcripts in CCl4-induced hepatotoxicity.

    PubMed

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

    2015-01-01

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

  15. [Diabetes in liver cirrhosis].

    PubMed

    García-Compeán, Diego; Jáquez-Quintana, Joel O; González-González, José A; Lavalle-González, Fernando J; Villarreal-Pérez, Jesús Z; Maldonado-Garza, Hector J

    2013-01-01

    The prevalence of overt diabetes mellitus (DM) in liver cirrhosis is about 30%. However, DM or impaired glucose tolerance can be observed in 90% after an oral glucose tolerance test in patients with normal fasting plasma glucose. Type 2 DM may produce cirrhosis, whereas DM may be a complication of cirrhosis. The latter is known as «hepatogenous diabetes». Overt and subclinical DM is associated with liver complications and death in cirrhotic patients. Treating diabetes is difficult in cirrhotic patients because of the metabolic impairments due to liver disease and because the most appropriate pharmacologic treatment has not been defined. It is also unknown if glycemic control with hypoglycemic agents has any impact on the course of the liver disease.

  16. Ameliorative effects of 7-methylcoumarin and 7-methoxycoumarin against CCl4-induced hepatotoxicity in rats.

    PubMed

    Sancheti, Sandesh; Sancheti, Shruti; Seo, Sung-Yum

    2013-01-01

    The available conventional remedies for the treatment of drug-induced liver diseases are highly inadequate and possess serious adverse effects; therefore, the development of new, effective drugs is considered necessary. This article explores the hepatoprotective and antioxidant potential of 7-methylcoumarin (MC) and 7-methoxycoumarin (MOC) in CCl(4)-induced hepatotoxicity in rats. MC and MOC individually, at doses of 50 and 100 mg/kg body weight, were administered orally once-daily for 7 days. The hepatoprotective activity was assessed using various biochemical parameters, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum bilirubin (TB), total protein (TP), and albumin (TA). Serum antioxidant enzyme [e.g., superoxide dismutase (SOD) and catalase (CAT)] levels were determined. Also, thiobarbituric-acid-related substances (TBARS) levels, along with histopathological studies of liver tissue, were scrutinized. Pretreatment with MC and MOC significantly decreased ALT, AST, and TB in the serum of CCl(4)-induced liver damaged rats in a dose-dependent manner. TA and TP levels in the serum were also restored significantly in all presupplemented MC and MOC groups. In addition, oxidative stress induced by CCl(4) was prevented significantly; thereby, increasing SOD and CAT levels and decreasing TBARS levels in liver homogenates. Histopathological studies revealed the ameliorative natures of both the compounds. This study demonstrates the strong hepatoprotective activity of MC and MOC, which could be attributed to their potent antioxidant effects.

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

    PubMed

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

    2012-01-01

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

  18. Ameliorative effect of Grewia tenax (Forssk) fiori fruit extract on CCl(4)-induced oxidative stress and hepatotoxicity in rats.

    PubMed

    Al-Said, Mansour S; Mothana, Ramzi A; Al-Sohaibani, Mohammed O; Rafatullah, Syed

    2011-01-01

    The ethanol extract of Grewia tenax (GTE) fruit was tested for possible efficacy against carbon tetrachloride (CCl(4)) induced liver toxicity in Wistar albino rats. GTE at doses of 250 and 500 mg/kg were administered orally to CCl(4)-treated rats. Acute toxicity test and sleeping time determination were done with mice. The results showed that oral administration of GTE for 3 wk to rats significantly reduced the CCl(4)-induced elevated levels of serum glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, gamma-glutamyl transferase, alkaline phosphatase, bilirubin, cholesterol, high-density lipoproteins, low-density lipoproteins, very low density lipoproteins, and triglycerides. Moreover, it was found that the treatment with GTE significantly elevated the hemoglobin level in serum and increased the nonprotein sulfhydryl and total protein contents in the liver tissue, and a significant diminution was observed in the CCl(4)-induced elevated levels of malondialdehyde in the liver tissue. The biochemical findings were supported by an evaluation with liver histopathology. Pentobarbital-induced prolongation of narcolepsy in mice was shortened significantly by the extract. The observed hepatoprotective effect is believed to occur due to antioxidant properties of the contents of G. tenax extract, which may provide a new drug to be used for fighting liver diseases and it validates its folkloric use in anemic and other conditions.

  19. 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

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

    2014-01-01

    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

  20. Cirrhosis

    MedlinePlus

    Liver cirrhosis; Chronic liver disease; End-stage liver disease; Liver failure - cirrhosis; Ascites - cirrhosis ... Cirrhosis is the end result of chronic liver damage caused by ... liver disease in the United States are: Hepatitis B or hepatitis ...

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

    PubMed

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

    2008-09-01

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

  2. Hepatoprotective effect against CCl4-induced acute liver damage in mice and High-performance liquid chromatography mass spectrometric method for analysis of the constituents of extract of Rubus crataegifolius.

    PubMed

    Sun, Yongjiao; Jia, Lingyun; Huang, Zhanbo; Wang, Jing; Lu, Jincai; Li, Jing

    2017-03-21

    This study is an attempt to evaluate the hepatoprotective activity of Rubus Crataegifolius against carbon tetrachloride-induced liver injury in mice. 70% ethanolic, ethyl acetate and n-BuOH extract of R. crataegifolius were administered daily for 14 days in experimental animals before they were treated with CCl4. The hepatoprotective activity of the extracts in this study was compared with the reference drug silymarin. A high-performance liquid chromatography mass spectrometric (HPLC-EIS-MS/MS) method was developed for the determination of the constituents of the extracts. According to the data of HPLC-EIS-MS/MS, the chemical structures of the largely 14 constituents of R. crataegifolius were identified online without time-consuming isolation. Ethyl acetate extracts of R. crataegifolius showed strong antioxidant activities and significant protective effect against acute hepatotoxicity induced by CCl4. According to the data of HPLC-EIS-MS/MS, Oleanic acid, Phlorizin dehydrate and Quercetin-3-rhamnoside are considered as the main hepatoprotective factor in ethyl acetate extract.

  3. Preventive activity of banana peel polyphenols on CCl4-induced experimental hepatic injury in Kunming mice

    PubMed Central

    WANG, RUI; FENG, XIA; ZHU, KAI; ZHAO, XIN; SUO, HUAYI

    2016-01-01

    The aim of the present study was to evaluate the preventive effects of banana peel polyphenols (BPPs) against hepatic injury. Mice were divide into normal, control, 100 mg/kg and 200 mg/kg banana peel polyphenol and silymarin groups. All the mice except normal mice were induced with hepatic damage using CCl4. The serum and tissue levels of mice were determined by a kit and the tissues were further examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. BPPs reduced the serum levels of aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase in a CCl4-induced mouse model of hepatic injury. Furthermore, BPPs reduced the levels of malondialdehyde and triglyceride, while increasing glutathione levels in the serum and liver tissues of mice. In addition, the effects of 200 mg/kg treatment were more evident, and these effects were comparable to those of the drug silymarin. Serum levels of the cytokines, interleukin (IL)-6, IL-12, tumor necrosis factor (TNF)-α and interferon-γ, were reduced in the mice treated with BPPs compared with injury control group mice, and these levels were comparable to those of the normal and silymarin-treated groups. Histopathological examination indicated that BPPs were able to reduce the extent of CCl4-induced liver tissue injury and protect the liver cells. Furthermore, the mRNA and protein expression levels of the inflammation-associated factors cyclooxygenase-2, nitric oxide synthase, TNF-α and IL-1β were reduced in mice treated with BPPs compared with the control group mice. Mice that received 200 mg/kg BPP exhibited reduced expression levels of these factors compared with mice that received 100 mg/kg BPP. In conclusion, the results of the present study suggested that BPPs exert a good preventive effect against hepatic injury. PMID:27168833

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

    PubMed

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

    2014-03-01

    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.

  5. In vitro differentiated hepatic oval-like cells enhance hepatic regeneration in CCl4 -induced hepatic injury.

    PubMed

    Awan, Sana Javaid; Baig, Maria Tayyab; Yaqub, Faiza; Tayyeb, Asima; Ali, Gibran

    2017-01-01

    Hepatic oval cells are likely to be activated during advanced stage of liver fibrosis to reconstruct damaged hepatic tissue. However, their scarcity, difficulties in isolation, and in vitro expansion hampered their transplantation in fibrotic liver. This study was aimed to investigate the repair potential of in vitro differentiated hepatic oval-like cells in CCl4 -induced liver fibrosis. BMSCs and oval cells were isolated and characterized from C57BL/6 GFP(+) mice. BMSCs were differentiated into oval cells by preconditioning with HGF, EGF, SCF, and LIF and analyzed for the oval cells-specific genes. Efficiency of oval cells to reduce hepatocyte injury was studied by determining cell viability, release of LDH, and biochemical tests in a co-culture system. Further, in vivo repair potential of differentiated oval cells was determined in CCl4 -induced fibrotic model by gene expression analysis, biochemical tests, mason trichrome, and Sirius red staining. Differentiated oval cells expressed hepatic oval cells-specific markers AFP, ALB, CK8, CK18, CK19. These differentiated cells when co-cultured with injured hepatocytes showed significant hepato-protection as measured by reduction in apoptosis, LDH release, and improvement in liver functions. Transplantation of differentiated oval cells like cells in fibrotic livers exhibited enhanced homing, reduced liver fibrosis, and improved liver functions by augmenting hepatic microenvironment by improved liver functions. This preconditioning strategy to differentiate BMSCs into oval cell leads to improved survival and homing of transplanted cells. In addition, reduction in fibrosis and functional improvement in mice with CCl4 -induced liver fibrosis was achieved.

  6. Reversal of liver cirrhosis in autoimmune hepatitis.

    PubMed

    Shah, Anish M; Malhotra, Ashish; Kothari, Shivangi; Baddoura, Walid; Depasquale, Joseph; Spira, Robert

    2011-01-01

    Liver cirrhosis is generally considered irreversible but there are reports in which there is documented reversal of fibrosis/cirrhosis in various clinical conditions like Wilson's disease, hemochromatosis, primary biliary cirrhosis and autoimmune hepatitis. The subgroup of patients with autoimmune hepatitis that will have reversal of cirrhosis is not known. We present two cases with documented liver cirrhosis that had reversal of cirrhosis after treatment with immunosuppressive agents. We postulate that patients presenting with acute hepatitis and no other fibrogenic factors have higher chances of reversal of liver cirrhosis as compared to those presenting as chronic liver injury.

  7. The Effect of rhCygb on CCl4-Induced Hepatic Fibrogenesis in Rat

    PubMed Central

    Li, Zhen; Wei, Wei; Chen, Bohong; Cai, Gaotai; Li, Xin; Wang, Ping; Tang, Jinping; Dong, Wenqi

    2016-01-01

    This study aims to investigate whether the use of recombinant human cytoglobin (rhCygb) impact on hepatic fibrogenesis caused by CCl4. SD (n = 150) rats were randomly divided into three groups of normal, CCl4 model and rhCygb groups. After model establishment, rats in rhCygb groups were administered daily with rhCygb (2 mg/kg, s.c.). Histological lesions were staged according to metavir. Serum parameters including ALT, AST, HA, LN, Col III and Col IV were determined. The liver proteins were separated by 2-DE and identified. As a result, the stage of hepatic damage and liver fibrosis in rhCygb groups were significantly milder than that in CCl4 model groups. Meanwhile, rhCygb dramatically reversed serum levels of ALT and AST, and also markedly decreased the liver fibrosis markers levels of LN, HA, Col III and Col IV. In 2-DE, 33 proteins among three groups with the same changing tendency in normal and rhCygb treated groups compared with CCl4 model group were identified. GO analysis showed that several identified proteins involved in oxidative stress pathway. The study provides new insights and data for administration of rhCygb reversing CCl4-induced liver fibrosis suggesting that rhCygb might be used in the treatment of liver fibrosis. PMID:27006085

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

    PubMed

    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

    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 β -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.

  9. A New Oleanolic Acid Derivative against CCl4-Induced Hepatic Fibrosis in Rats

    PubMed Central

    Xiang, Hongjun; Han, Yaotian; Zhang, Yuzhong; Yan, Wenqiang; Xu, Bing; Chu, Fuhao; Xie, Tianxin; Jia, Menglu; Yan, Mengmeng; Zhao, Rui; Wang, Penglong; Lei, Haimin

    2017-01-01

    A novel hepatoprotective oleanolic acid derivative, 3-oxours-oleana-9(11), 12-dien-28-oic acid (Oxy-Di-OA), has been reported. In previous studies, we found that Oxy-Di-OA presented the anti-HBV (Hepatitis B Virus) activity (IC50 = 3.13 µg/mL). Remarkably, it is superior to lamivudine in the inhibition of the rebound of the viral replication rate. Furthermore, Oxy-Di-OA showed good performance of anti-HBV activity in vivo. Some studies showed that liver fibrosis may affiliate with HBV gene mutations. In addition, the anti-hepatic fibrosis activity of Oxy-Di-OA has not been studied. Therefore, we evaluated the protective effect of Oxy-Di-OA against carbon tetrachloride (CCl4)-induced liver injury in rats. Daily intraperitoneally administration of Oxy-Di-OA prevented the development of CCl4-induced liver fibrosis, which was evidenced by histological study and immunohistochemical analysis. The entire experimental protocol lasted nine weeks. Oxy-Di-OA significantly suppressed the increases of plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels (p < 0.05). Furthermore, Oxy-Di-OA could prevent expression of transforming growth factor β1 (TGF-β1). It is worth noting that the high-dose group Oxy-Di-OA is superior to bifendate in elevating hepatic function. Compared to the model group, Oxy-Di-OA in the high-dose group and low-dose group can significantly reduce the liver and spleen indices (p < 0.05). The acute toxicity test showed that LD50 and a 95% confidence interval (CIs) value of Oxy-Di-OA were 714.83 mg/kg and 639.73–798.73 mg/kg via intraperitoneal injection in mice, respectively. The LD50 value of Oxy-Di-OA exceeded 2000 mg/kg via gavage in mice. In addition, a simple and rapid high performance liquid chromatography-ultraviolet (HPLC-UV) method was developed and validated to study the pharmacokinetic characteristics of the compound. After single-dose oral administration, time to reach peak concentration of Oxy-Di-OA (Cmax = 8.18

  10. Cirrhosis and Liver Disease in Latina Women

    MedlinePlus

    ... Home > Minority Women's Health > Latinas Minority Women's Health Cirrhosis and liver disease Health conditions common in Latinas: More information on cirrhosis and liver disease in English Más recursos en ...

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

    PubMed

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

    2014-07-01

    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.

  12. FR-167653, a selective p38 MAPK inhibitor, exerts salutary effect on liver cirrhosis through downregulation of Runx2.

    PubMed

    Hattori, Shinji; Dhar, Dipok K; Hara, Nobumasa; Tonomoto, Yasuhito; Onoda, Toshinao; Ono, Takashi; Yamanoi, Akira; Tachibana, Mitsuo; Tsuchiya, Mikako; Nagasue, Naofumi

    2007-06-01

    Liver cirrhosis remains a difficult-to-treat disease with a substantial morbidity and mortality rate. There is an emerging body of data purporting a pivotal role of the activated p38 mitogen-activated protein kinase (MAPK) in the process of cirrhosis. Several anticirrhotic agents have been developed over the past few years, and most of them exert their effects by indirectly inhibiting the p38 pathway. Effect of a selective p38 inhibitor is yet to be reported. In this study, we evaluated the salutary effect of FR-167653 (FR), a selective p38 inhibitor, in a carbon tetrachloride (CCl(4))-induced rat cirrhotic model. Twenty rats were assigned into four groups: Sham, olive oil only; Control, CCl(4) in olive oil; FR50, FR 50 mg/kg/day and CCl(4); and FR100, FR 100 mg/kg/day and CCl(4). FR dose-dependently inhibited activation of p38 and had an ameliorating effect on cirrhosis formation. Significant dose-dependent reduction in alpha-smooth muscle actin immunostaining and hydroxyproline content of the liver was noticed in the FR-treated rats. Also densitometric analysis showed a significant reduction in azan-stained area in the FR-treated rats. These fibrotic changes were observed in the myofibroblasts including the hepatic stellate cells and portal fibroblasts. mRNA expression of runt-related protein 2 (Runx2), a profibrogenic transcription factor, was significantly low in FR-treated livers, indicating that Runx2 might be a key downstream regulator of the p38 pathway. A similar reduction in expression of Smad4 and tissue inhibitor of metalloproteinase-1 was noticed in the FR-treated rats. In conclusion, FR treatment exerted a significant beneficial effect in a CCl(4)-induced rat cirrhotic model. The ameliorating effect of FR could be partially attributable to an inhibition of the Smad4/p38/Runx2 axis in the cirrhotic liver.

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

    PubMed

    Zhao, Xin; Song, Jia-Le; Kil, Jeung-Ha; Park, Kun-Young

    2013-08-01

    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)-γ, and tumor necrosis factor (TNF)-α. 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-α, and IL-1β in rat liver tissues. Bamboo salt induced a significant decrease (~80%) in mRNA and protein expression levels of COX-2, iNOS, TNF-α, and IL-1β, compared with the other salts. Thus, we found that baked bamboo salt preparations could prevent CCl4-induced hepatic damage in vivo.

  14. Biochemical and molecular modulation of CCl4-induced peripheral and central damage by Tilia americana var. mexicanaextracts.

    PubMed

    Coballase-Urrutia, Elvia; Cárdenas-Rodríguez, Noemí; González-García, María Carolina; Núñez-Ramírez, Eithan; Floriano-Sánchez, Esaú; González-Trujano, María Eva; Fernández-Rojas, Berenice; Pedraza-Chaverrí, José; Montesinos-Correa, Hortencia; Rivera-Espinosa, Liliana; Sampieri, Aristides Iii; Carmona-Aparicio, Liliana

    2017-03-01

    Around the world, species from the genus Tilia are commonly used because of their peripheral and central medicinal effects; they are prepared as teas and used as tranquilizing, anticonvulsant, and analgesic agents. In this study, we provide evidence of the protective effects of organic and aqueous extracts (100 mg/kg, i.p.) obtained from the leaves of Tilia americana var. mexicana on CCl4-induced liver and brain damage in the rat. Protection was observed in the liver and brain (cerebellum, cortex and cerebral hemispheres) by measuring the activity of antioxidant enzymes and levels of malondialdehyde (MDA) using spectrophotometric methods. Biochemical parameters were also assessed in serum samples from the CCl4-treated rats. The T. americana var. mexicana leaf extracts provided significant protection against CCl4-induced peripheral and central damage by increasing the activity of antioxidant enzymes, diminishing lipid peroxidation, and preventing alterations in biochemical serum parameters, such as the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), γ-globulin (γ-GLOB), serum albumin (ALB), total bilirubin (BB), creatinine (CREA) and creatine kinase (CK), relative to the control group. Additionally, we correlated gene expression with antioxidant activity in the experimental groups treated with the organic and aqueous Tilia extracts and observed a non-statistically significant positive correlation. Our results provide evidence of the underlying biomedical properties of T. americana var. mexicana that confer its neuro- and hepatoprotective effects.

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

    PubMed Central

    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

    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 α-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 μmol/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 α-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

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

    PubMed Central

    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

    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

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

    PubMed Central

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

    2012-01-01

    Aim This investigation aimed to assess the hepatoprotective effect of saponin fraction isolated from the fruit pericarp of Sapindus mukorossi on carbon tetrachloride (CCl4)-induced hepatotoxicity. Methods Fruit of S. mukorossi was collected and authenticated, and dried pericarp powder subjected to extraction with cold ethanol (70%) by maceration followed by isolation of total saponin fraction. Hepatoprotective activity was demonstrated in the CCl4-damaged primary monolayer culture. In in vivo studies, pretreatment with total saponin fraction (50,100 and 150 mg/kg per os once a day for 4 days before CCl4 introduction and continued afterward for 3 days) attenuated the CCl4-induced acute increase in serum glutamic pyruvic transaminase, serum glutamic oxaloacetic transaminase, and alkaline phosphatase activities and considerably reduced histopathological alterations. Further, saponin fraction reduced thiopentone-induced (4 mg/kg, intraperitoneal) sleeping time in rats. Results Saponin fraction pretreatment improves bromsulphalein clearance and also increases cellular viability. Saponin administration replenished depleted hepatic glutathione and superoxide dismutase by improving the antioxidant status of the liver and liver function enzymes. These effects substantiate protection of cellular phospholipids from peroxidative damage induced by highly reactive toxic intermediate radicals formed during biotransformation of CCl4. Conclusion The above findings lead to the conclusion that the saponin fraction of S. mukorossi has a protective capability both in vitro on primary hepatocyte cultures and in vivo in a rat model of CCl4-mediated liver injury. Hence, we suggest that the inclusion of this S. mukorossi fruit pericarp in the management of liver disorders is justified. PMID:22888266

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

    PubMed Central

    2012-01-01

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

  19. Liver progenitor cells-mediated liver regeneration in liver cirrhosis.

    PubMed

    Shang, Haitao; Wang, Zhijun; Song, Yuhu

    2016-05-01

    Cirrhosis is defined as the histological development of regenerative nodules surrounded by fibrous bands in response to chronic liver injury. In cirrhotic liver where hepatocytes proliferation is compromised, liver progenitor cells (LPCs) are activated and then differentiated into hepatocytes and cholangiocytes, leading to the generation of regenerative nodules and functional restoration. Here, we summarize and discuss recent findings on the mechanisms underlying LPCs-mediated regeneration in liver cirrhosis. Firstly, we provide recent research on the mechanism underlying LPCs activation in severe or chronic liver injury. Secondly, we present new and exciting data on exploring the origin of LPCs, which reveal that the hepatocytes give rise to duct-like progenitors that then differentiate back into hepatocytes in chronic liver injury or liver cirrhosis. Finally, we highlight recent findings from the literature exploring the role of LPCs niche in directing the behavior and fate of LPCs. This remarkable insight into the cellular and molecular mechanisms of LPCs-mediated regeneration in liver cirrhosis will provide a basis for translating this knowledge into clinical application.

  20. Efficiency of Cell Therapy in Liver Cirrhosis.

    PubMed

    Shevela, E Ya; Starostina, N M; Pal'tsev, A I; Shipunov, M V; Zheltova, O I; Meledina, I V; Khvan, L A; Leplina, O Yu; Ostanin, A A; Chernykh, E R; Kozlov, V A

    2016-02-01

    We studied safety and clinical efficacy of transplantation of autologous bone marrow cell in complex therapy of 158 patients with chronic hepatitis and cirrhosis of the liver. The efficiency of cell therapy was assessed in 12 months after single injection of the cells. The positive response (alleviation of liver cirrhosis or stabilization of the pathological process) was observed in 70% cases. The efficacy of therapy correlated with the severity and etiology of the disease and was maximum in patients with Child-Pugh class A (in 82.5% cases) and class B liver cirrhosis (in 79% cases); in patients with class C liver cirrhosis, the positive response was achieved in 42.5% cases. In 39 patients, ultrasonic examination performed in 3 years after transplantation revealed no focal lesions or ectopic ossification foci.

  1. Effects of Rhus tripartitum fruit extract on CCl4-induced hepatotoxicity and cisplatin-induced nephrotoxicity in rats.

    PubMed

    Tlili, Nizar; Feriani, Anouar; Allagui, Mohamed Salah; Saadoui, Ezzeddine; Khaldi, Abdelhamid; Nasri, Nizar

    2016-08-01

    Rhus tripartitum D.C., Anacardiaceae, has traditionally been used in Tunisia against many illnesses. The present study investigates, for the first time, the protective effects of the methanol extract of Rhus tripartitum fruit (MERT) against CCl4-induced hepatotoxicity and cisplatin-induced nephrotoxicty in Wistar rats. ALT, AST, LDH, GGT, creatinin, urea, and uric acid levels were studied. The changes in antioxidant parameters such as malondialdehyde (MDA) and protein carbonyl contents were also determined. The increased levels of MDA (30.97 and 11.50 nmol MDA/mg protein in liver and kidney, respectively) and protein carbonyls (13.4 and 17.95 nmol/mg protein in liver and kidney, respectively) were attenuated by MERT pretreatment (19.35 and 6.1 nmol MDA/mg protein and 9.15 and 12 nmol/mg protein in liver and kidney, respectively). The MERT pretreatment significantly reduced the increased biochemical parameters of liver and kidney caused by CCl4 and cisplatin treatment. The histopathologic observation showed that MERT pretreatment restores the altered tissues. The observed results could be due to the high phenolic content and to MERT's important antioxidant potential. This study supports the hepatoprotective and nephroprotective effects of R. tripartitum.

  2. Cirrhosis and autoimmune liver disease: Current understanding

    PubMed Central

    Liberal, Rodrigo; Grant, Charlotte R

    2016-01-01

    Primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) constitute the classic autoimmune liver diseases (AILDs). While AIH target the hepatocytes, in PBC and PSC the targets of the autoimmune attack are the biliary epithelial cells. Persistent liver injury, associated with chronic AILD, leads to un-resolving inflammation, cell proliferation and the deposition of extracellular matrix proteins by hepatic stellate cells and portal myofibroblasts. Liver cirrhosis, and the resultant loss of normal liver function, inevitably ensues. Patients with cirrhosis have higher risks or morbidity and mortality, and that in the decompensated phase, complications of portal hypertension and/or liver dysfunction lead to rapid deterioration. Accurate diagnosis and monitoring of cirrhosis is, therefore of upmost importance. Liver biopsy is currently the gold standard technique, but highly promising non-invasive methodology is under development. Liver transplantation (LT) is an effective therapeutic option for the management of end-stage liver disease secondary to AIH, PBC and PSC. LT is indicated for AILD patients who have progressed to end-stage chronic liver disease or developed intractable symptoms or hepatic malignancy; in addition, LT may also be indicated for patients presenting with acute liver disease due to AIH who do not respond to steroids. PMID:27729952

  3. Protective Effect of Aframomum melegueta phenolics Against CCl4-Induced Rat Hepatocytes Damage; Role of Apoptosis and Pro-inflammatory Cytokines inhibition

    PubMed Central

    El-Halawany, Ali M.; Dine, Riham Salah El; El Sayed, Nesrine S.; Hattori, Masao

    2014-01-01

    Aframomum melegueta is a commonly used African spice. Through a hepatoprotective bioassay-guided isolation, the chloroform fraction of A.melegueta seeds yielded one new diarylheptanoid named 3-(S)-acetyl-1-(4′-hydroxy-3′, 5′-di methoxyphenyl)-7-(3″,4″, 5″-trihydroxyphenyl)heptane (1), and two new hydroxyphenylalkanones, [8]-dehydrogingerdione (2) and [6]-dehydroparadol (3), in addition to six known compounds (4–9). The hepatoprotective effect of A. melegueta methanol extract, sub-fractions and isolated compounds was investigated using carbon tetrachloride (CCl4)-induced liver injury in a rat hepatocytes model. The methanol, chloroform extracts and compounds 1, 5, 8 and 9 of A. melegueta significantly inhibited the elevated serum alanine aminotransferase (ALT), thiobarbituric acid reactive substances (TBARS), tumor necrosis factor (TNFα), interleukin-1beta (Il-1β), caspase3 and 9 and enhanced the reduced liver glutathione (GSH) level caused by CCl4 intoxication. These results indicate that A.melegueta extracts, and isolated compounds play a protective role in CCl4 induced acute liver injury which might be due to elevated antioxidative defense potentials, suppressed inflammatory responses and apoptosis of liver tissue. PMID:25077538

  4. Liver surgery in cirrhosis and portal hypertension.

    PubMed

    Hackl, Christina; Schlitt, Hans J; Renner, Philipp; Lang, Sven A

    2016-03-07

    The prevalence of hepatic cirrhosis in Europe and the United States, currently 250 patients per 100000 inhabitants, is steadily increasing. Thus, we observe a significant increase in patients with cirrhosis and portal hypertension needing liver resections for primary or metastatic lesions. However, extended liver resections in patients with underlying hepatic cirrhosis and portal hypertension still represent a medical challenge in regard to perioperative morbidity, surgical management and postoperative outcome. The Barcelona Clinic Liver Cancer classification recommends to restrict curative liver resections for hepatocellular carcinoma in cirrhotic patients to early tumor stages in patients with Child A cirrhosis not showing portal hypertension. However, during the last two decades, relevant improvements in preoperative diagnostic, perioperative hepatologic and intensive care management as well as in surgical techniques during hepatic resections have rendered even extended liver resections in higher-degree cirrhotic patients with portal hypertension possible. However, there are few standard indications for hepatic resections in cirrhotic patients and risk stratifications have to be performed in an interdisciplinary setting for each individual patient. We here review the indications, the preoperative risk-stratifications, the morbidity and the mortality of extended resections for primary and metastatic lesions in cirrhotic livers. Furthermore, we provide a review of literature on perioperative management in cirrhotic patients needing extrahepatic abdominal surgery and an overview of surgical options in the treatment of hepatic cirrhosis.

  5. Liver surgery in cirrhosis and portal hypertension

    PubMed Central

    Hackl, Christina; Schlitt, Hans J; Renner, Philipp; Lang, Sven A

    2016-01-01

    The prevalence of hepatic cirrhosis in Europe and the United States, currently 250 patients per 100000 inhabitants, is steadily increasing. Thus, we observe a significant increase in patients with cirrhosis and portal hypertension needing liver resections for primary or metastatic lesions. However, extended liver resections in patients with underlying hepatic cirrhosis and portal hypertension still represent a medical challenge in regard to perioperative morbidity, surgical management and postoperative outcome. The Barcelona Clinic Liver Cancer classification recommends to restrict curative liver resections for hepatocellular carcinoma in cirrhotic patients to early tumor stages in patients with Child A cirrhosis not showing portal hypertension. However, during the last two decades, relevant improvements in preoperative diagnostic, perioperative hepatologic and intensive care management as well as in surgical techniques during hepatic resections have rendered even extended liver resections in higher-degree cirrhotic patients with portal hypertension possible. However, there are few standard indications for hepatic resections in cirrhotic patients and risk stratifications have to be performed in an interdisciplinary setting for each individual patient. We here review the indications, the preoperative risk-stratifications, the morbidity and the mortality of extended resections for primary and metastatic lesions in cirrhotic livers. Furthermore, we provide a review of literature on perioperative management in cirrhotic patients needing extrahepatic abdominal surgery and an overview of surgical options in the treatment of hepatic cirrhosis. PMID:26973411

  6. [PRIMARY BILIARY LIVER CIRRHOSIS: MODERN CONCEPTS].

    PubMed

    Tsimmerman, Ya S

    2015-01-01

    Modern data on primary biliary liver cirrhosis are presented including the definition, prevalence, possible etiological factors, and detailed description of pathogenesis (autoimmune mechanisms, intrahepatic cholestasis, hereditary predisposition, environmental factors) and clinical picture. Also considered are complications and concomitant diseases, methods of laboratory, instrumental and morphological diagnostics, approaches to medicamental treatment and its effectiveness, indications for liver transplantation.

  7. Effect of schisandrin B and sesamin mixture on CCl(4)-induced hepatic oxidative stress in rats.

    PubMed

    Chang, Chia-Yu; Chen, Ya-Ling; Yang, Suh-Ching; Huang, Guan-Cheng; Tsi, Daniel; Huang, Chi-Chang; Chen, Jiun-Rong; Li, Joe-Sharg

    2009-02-01

    To study the effects of schisandrin B and sesamin mixture on carbon tetrachloride (CCl(4))-induced hepatic oxidative stress in male Sprague-Dawley rats. The rats were randomly assigned to five groups: control group (olive oil injection), CCl(4) group (CCl(4) injection), silymarin group (CCl(4) injection combined with supplementation of silymarin, 7.5 mg/kg/day), low dose group (CCl(4) injection combined with supplementation of schisandrin B and sesamin mixture at a low dose, 43 mg/kg/day) and high dose group (CCl(4) injection combined with the supplementation of schisandrin B and sesamin mixture at a high dose, 215 mg/kg/day). The hepatic superoxide dismutase and glutathione peroxidase activities of rats in the low dose and high dose groups were increased significantly compared with those in the CCl(4) group. The hepatic reduced glutathione concentration in the silymarin, low dose and high dose groups were increased significantly (48%, 45% and 53%, respectively) when compared with those of the CCl(4) group. In addition, the concentration of glutathione in the erythrocytes of the low dose group was significantly higher than the CCl(4) group by 25%. These results suggest that the schisandrin B-sesamin mixture exerted a hepatoprotective effect by improving the antioxidative capacity in rats under CCl(4)-induced hepatic oxidative stress.

  8. The role of zinc in liver cirrhosis.

    PubMed

    Grüngreiff, Kurt; Reinhold, Dirk; Wedemeyer, Heiner

    2016-01-01

    Zinc is an essential trace element playing fundamental roles in cellular metabolism. It acts mostly by binding a wide range of proteins, thus affecting a broad spectrum of biological processes, which include cell division, growth and differentiation. Zinc is critical to a large number of structural proteins, enzymatic processes, and transcription factors. Zinc deficiency can result in a spectrum of clinical manifestations, such as poor of appetite, loss of body hair, altered taste and smell, testicular atrophy, cerebral and immune dysfunction, and diminished drug elimination capacity. These are common symptoms in patients with chronic liver diseases, especially liver cirrhosis. The liver is the main organ responsible for the zinc metabolism which can be affected by liver diseases. On the other hand, zinc deficiency may alter hepatocyte functions and also immune responses in inflammatory liver diseases. Liver cirrhosis represents the most advanced stage of chronic liver diseases and is the common outcome of chronic liver injury. It is associated with energy malnutrition, with numerous metabolic disorders, such as hypoalbuminemia, with imbalance between branched-chain amino acids and aromatic amino acids, and with reduced zinc serum concentrations. All these processes can influence the clinical outcome of patients, such ascites, hepatic encephalopathy and hepatocellular carcinoma. In the present review, we summarize the emerging evidence on the pitoval role of zinc in the pathogenesis of liver cirrhosis.

  9. Therapeutic Effect of Losartan, an Angiotensin II Type 1 Receptor Antagonist, on CCl4-Induced Skeletal Muscle Injury

    PubMed Central

    Hwang, Ok-Kyung; Park, Jin-Kyu; Lee, Eun-Joo; Lee, Eun-Mi; Kim, Ah-Young; Jeong, Kyu-Shik

    2016-01-01

    TGF-β1 is known to inhibit muscle regeneration after muscle injury. However, it is unknown if high systemic levels of TGF-β can affect the muscle regeneration process. In the present study, we demonstrated the effect of a CCl4 intra-peritoneal injection and losartan (an angiotensin II type 1 receptor antagonist) on skeletal muscle (gastrocnemius muscle) injury and regeneration. Male C57BL/6 mice were grouped randomly as follows: control (n = 7), CCl4-treatment group (n = 7), and CCl4 + losartan treatment group (n = 7). After CCl4 treatment for a 16-week period, the animals were sacrificed and analyzed. The expression of dystrophin significantly decreased in the muscle tissues of the control group, as compared with that of the CCl4 + losartan group (p < 0.01). p(phospho)-Smad2/3 expression significantly increased in the muscles of the control group compared to that in the CCl4 + losartan group (p < 0.01). The expressions of Pax7, MyoD, and myogenin increased in skeletal muscles of the CCl4 + losartan group compared to the corresponding levels in the control group (p < 0.01). We hypothesize that systemically elevated TGF-β1 as a result of CCl4-induced liver injury causes skeletal muscle injury, while losartan promotes muscle repair from injury via blockade of TGF-β1 signaling. PMID:26867195

  10. Camel milk and bee honey regulate profibrotic cytokine gene transcripts in liver cirrhosis induced by carbon tetrachloride.

    PubMed

    Sadek, Kadry; Beltagy, Doha; Saleh, Ebeed; Abouelkhair, Reham

    2016-05-30

    The lack of studies regarding the mechanism of the protective effects of camel milk and bee honey against hepatotoxic compounds led us to perform this study. Thirty-six male rats were divided into two main groups. The first group (n = 9) comprised control non-cirrhotic rats. The rats of the second group (n = 27) were administered carbon tetrachloride (CCl4) by intraperitoneal injection to induce liver cirrhosis. The cirrhotic rats were then divided into three equal subgroups, each comprising nine animals, as follows: (i) cirrhotic rats, (ii) cirrhotic rats treated with camel milk, and (iii) cirrhotic rats treated with camel milk and bee honey. The present findings revealed that CCl4 elevated the activities of liver enzymes, blood glucose levels, non-esterified fatty acids (NEFA) in the serum and glycogen content in the liver. On the other hand, CCl4 significantly decreased phosphorylase activity in the liver tissue and significantly increased carbohydrate intolerance and insulin resistance index (HOMA-IR). Moreover, CCl4 induced a significant increase in oxidative stress, along with increased expression of the profibrotic cytokine genes TNF-α and TGF-β. However, camel milk either alone or in combination with bee honey ameliorated these toxic actions. The antioxidant properties of these protective agents and their effects of downregulating certain procirrhotic cytokine gene transcripts underlie this protection.

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

    PubMed Central

    2012-01-01

    Background Launaea procumbens (L.) is traditionally used in the treatment of various human ailments including pulmonary damages. The present study was arranged to evaluate the role of Launaea procumbens methanol extract (LME) against carbon tetrachloride (CCl4) induced oxidative pulmonary damages in rat. Methods 36 Sprague–Dawley male rats (170-180 g) were randomly divided into 06 groups. After a week of acclamization, group I was remained untreated while group II was given olive oil intraperitoneally (i.p.) and dimethyl sulfoxide (DMSO) orally, groups III, IV, V and VI were administered CCl4, 3 ml/kg body weight (30% in olive oil i.p.). Groups IV, V were treated with 100 mg/kg, 200 mg/kg of LME whereas group VI was administered with 50 mg/kg body weight of rutin (RT) after 48 h of CCl4 treatment for four weeks. Antioxidant profile in lungs were evaluated by estimating the activities of antioxidant enzymes; catalase (CAT), peroxidase (POD), superoxide dismutase (SOD), glutathione-S-transferase (GST), glutathione reductase (GSR), glutathione peroxidase (GSH-Px), quinone reductase (QR) and reduced glutathione (GSH). CCl4-induced lipid peroxidation was determined by measuring the level of thiobarbituric acid reactive substances (TBARS) with conjugation of deoxyribonucleic acid (DNA) damages, argyrophilic nucleolar organizer regions (AgNORs) counts and histopathology. Results Administration of CCl4 for 6 weeks significantly (p < 0.01) reduced the activities of antioxidant enzymes and GSH concentration while increased TBARS contents and DNA damages in lung samples. Co-treatment of LME and rutin restored the activities of antioxidant enzymes and GSH contents. Changes in TBARS concentration and DNA fragmentation were significantly (p < 0.01) decreased with the treatment of LME and rutin in lung. Changes induced with CCl4 in histopathology of lungs were significantly reduced with co-treatment of LME and rutin. Conclusion Results of present study

  12. Cirrhosis

    MedlinePlus

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

  13. [Nutritional support in patients with liver cirrhosis].

    PubMed

    Rivera Irigoin, Robin; Abilés, Jimena

    2012-10-01

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

  14. Isorhamnetin-3-O-galactoside Protects against CCl4-Induced Hepatic Injury in Mice.

    PubMed

    Kim, Dong-Wook; Cho, Hong-Ik; Kim, Kang-Min; Kim, So-Jin; Choi, Jae Sue; Kim, Yeong Shik; Lee, Sun-Mee

    2012-07-01

    This study was performed to examine the hepatoprotective effect of isorhamnetin-3-O-galactoside, a flavonoid glycoside isolated from Artemisia capillaris Thunberg (Compositae), against carbon tetrachloride (CCl4)-induced hepatic injury. Mice were treated intraperitoneally with vehicle or isorhamnetin-3-O-galactoside (50, 100, and 200 mg/kg) 30 min before and 2 h after CCl4 (20 μl/kg) injection. Serum aminotransferase activities and hepatic level of malondialdehyde were significantly higher after CCl4 treatment, and these increases were attenuated by isorhamnetin-3-O-galactoside. CCl4 markedly increased serum tumor necrosis factor-α level, which was reduced by isorhamnetin-3-O-galactoside. The levels of inducible nitric oxide synthase (iNOS), cyclooxygenase- 2 (COX-2), and heme oxygenase-1 (HO-1) protein and their mRNA expression levels were significantly increased after CCl4 injection. The levels of HO-1 protein and mRNA expression levels were augmented by isorhamnetin-3-O-galactoside, while isorhamnetin- 3-O-galactoside attenuated the increases in iNOS and COX-2 protein and mRNA expression levels. CCl4 increased the level of phosphorylated c-Jun N-terminal kinase, extracellular signal-regulated kinase and p38, and isorhamnetin-3-O-galactoside reduced these increases. The nuclear translocation of nuclear factor kappa B (NF-κB), activating protein-1, and nuclear factor erythroid 2-related factor 2 (Nrf2) were signifi cantly increased after CCl4 administration. Isorhamnetin-3-O-galactoside attenuated the increases of NF-κB and c-Jun nuclear translocation, while it augmented the nuclear level of Nrf2. These results suggest that isorhamnetin-3-O-galactoside ameliorates CCl4-induced hepatic damage by enhancing the anti-oxidative defense system and reducing the inflammatory signaling pathways.

  15. Protective Effect of Gallotannin-Enriched Extract Isolated from Galla Rhois against CCl4-Induced Hepatotoxicity in ICR Mice

    PubMed Central

    Go, Jun; Kim, Ji Eun; Koh, Eun Kyoung; Song, Sung Hwa; Sung, Ji Eun; Lee, Hyun Ah; Lee, Young Hee; Lim, Yong; Hong, Jin Tae; Hwang, Dae Youn

    2016-01-01

    To investigate the toxicity, protective effects, and action mechanism of gallotannin-enriched extracts isolated from Galla Rhois (GEGR) against carbon tetrachloride (CCl4)-induced hepatotoxicity in Institute for Cancer Research (ICR) mice, alterations in serum biochemical indicators, histopathological structure, antioxidative status, hepatic apoptosis-related proteins, and liver fibrosis regulating factors were measured in mice pretreated with GEGR for five days before CCl4 injection. The GEGR/CCl4 treated group showed decreased levels of three serum marker enzymes (ALP, AST, and ALT) representing liver toxicity, although LDH levels remained constant. Necrotic area indicating hepatic cell death significantly inhibited, while malondialdehyde (MDA) concentration and superoxide dismutase (SOD) expression were dramatically recovered in the GEGR preadministrated group. In mechanism analyses of GEGR, the formation of active caspase-3 and enhancement of Bax/Bcl-2 expression was effectively inhibited in the GEGR/CCl4 treated group. The level of pro-inflammatory cytokines, TNF-α and IL-6, as well as the phosphorylation of p38 and JNK in the TNF-α downstream signaling pathway was rapidly recovered in the GEGR/CCl4 treated group, while anti-inflammatory cytokine (IL-10) increased slightly in the same group. Furthermore, the GEGR/CCl4 treated group showed a significant decrease in collagen accumulation results from alleviation of MMP-2 expression, TGF-β1 secretion and the phosphorylation of Smad2/3. Taken together, these results suggest that GEGR may induce remarkable protective effects against hepatic injury induced by CCl4 treatment through upregulation of the anti-inflammatory and antioxidant system. PMID:26907337

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

    NASA Astrophysics Data System (ADS)

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

    2015-11-01

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

  17. Cardiovascular dysfunction in patients with liver cirrhosis

    PubMed Central

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

    2015-01-01

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

  18. [Nutritional care for patients with liver cirrhosis].

    PubMed

    Aceves-Martins, Magaly

    2014-02-01

    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.

  19. Nanoemulsified ethanolic extract of Pyllanthus amarus Schum & Thonn ameliorates CCl4 induced hepatotoxicity in Wistar rats.

    PubMed

    Deepa, V; Sridhar, R; Goparaju, A; Reddy, P Neelakanta; Murthy, P Balakrishna

    2012-11-01

    Phyllanthus amarus (PA) is commonly used in traditional medicine for hepatoprotectivity. The major limitation is that, treatment requires a large quantity of herbal extract for a longer duration. Aim of the present study was to encapsulate ethanolic plant extract for sustained release of constituents in intestine and facilitate maximum absorption. The efficacy was compared for the hepatoprotective activity of nanoencapsulated ethanolic extract of P. amarus (NPA) and PA in carbon tetrachloride (CCl4) induced hepatotoxic male rats. Based on total phenol content (TPC), the loading efficiency of nanocapsules was 89% (pH 7.0) and optimum concentration was 2:18 (mg/mL) for plant extract: olive oil. Scanning electron microscopy (SEM) showed a spherical morphology, photon correlation spectroscopy (PCS) identified mean particle diameter as 213 nm and Fourier transform infrared spectroscopy (FT-IR) revealed that the phytoconstituents were stable. An oral dose of NPA (20 mg/kg body wt.) showed a better hepatoprotective activity than PA (100 mg/kg body wt.) and also repeated dose oral toxicity proved to be safe. These biochemical assessments were supported by rat biopsy examinations. In conclusion, the nanoemulsification method may be applied for poor water-soluble ethanolic herbal extracts to reduce the dosage and time.

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

    PubMed Central

    2014-01-01

    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

  1. FastStats: Chronic Liver Disease and Cirrhosis

    MedlinePlus

    ... Submit What's this? Submit Button NCHS Home Chronic Liver Disease and Cirrhosis Recommend on Facebook Tweet Share ... Services Administration American Association for the Study of Liver Diseases American Liver Foundation Get Email Updates To ...

  2. Nutrition in cirrhosis and chronic liver disease.

    PubMed

    Juakiem, Wassem; Torres, Dawn M; Harrison, Stephen A

    2014-02-01

    Nutrition has not been a primary focus of many medical conditions despite its importance in the development and the severity of these diseases. This is certainly the case with nutrition and end-stage liver disease despite the well-established association of nutritional deficiencies and increased rates of complications and mortality in cirrhosis. This review provides an overview of nutrition in chronic liver disease with an emphasis on its pathogenesis as well as ways to assess nutritional status and intervene in an effort to improve nutrition.

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

    PubMed Central

    2012-01-01

    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 (γ-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

  4. [Endotoxinaemia in liver cirrhosis (author's transl)].

    PubMed

    Nilius, R; Bernhardt, H; Zipprich, B; Knoke, M

    1980-01-01

    23 patients with liver cirrhosis of diverse etiology and of different activity levels and grades of compensation of the portal circulation were examined with regard to the systemic endotoxinaemia. The endotoxin was determined using the Limulus-Amoebocyte-Lysat-test. Endotoxin was traceable in the venous blood of 7 out of 23 patients (= 30,4%). No relation was found between endotoxaemia and the activity or grade of severity of liver cirrhosis; nor were there any accumulation of endotoxinaemia in patients with collateral circulation or portal decompensation. Consequently, as a result of our findings, the prognostic value of the symptom endotoxinaemia remains debatable, then endotoxinaemia does not always mean endotoxicosis. Particularly high immunoglobulin concentration and low albumin values in serum of endotoxin-positive cirrhotics indicate a "spillovet" of antigen substances and also of endotoxines in the body circulation resulting from insufficiency of the liver-RHS. Parallel analysis of microbian small bowel flora in 10 patients indicate that coli-dysbiosis appears to play a role in the development of systemic endoxinaemia, although the latter was also traceable in borderline cases of eubiosis/dysbiosis. Our findings strengthen the view that it is not possible to simply translate the findings in animals on to human liver diseases. Quite a number of the mechanisms being discussed are still with uncleared details and they give only a blurred picture of the pathophysiology of endotoxinaemia.

  5. A Mechanistic Pharmacokinetic Model for Liver Transporter Substrates Under Liver Cirrhosis Conditions

    PubMed Central

    Li, R; Barton, HA; Maurer, TS

    2015-01-01

    Liver cirrhosis is a disease characterized by the loss of functional liver mass. Physiologically based pharmacokinetic (PBPK) modeling was applied to interpret and predict how the interplay among physiological changes in cirrhosis affects pharmacokinetics. However, previous PBPK models under cirrhotic conditions were developed for permeable cytochrome P450 substrates and do not directly apply to substrates of liver transporters. This study characterizes a PBPK model for liver transporter substrates in relation to the severity of liver cirrhosis. A published PBPK model structure for liver transporter substrates under healthy conditions and the physiological changes for cirrhosis are combined to simulate pharmacokinetics of liver transporter substrates in patients with mild and moderate cirrhosis. The simulated pharmacokinetics under liver cirrhosis reasonably approximate observations. This analysis includes meta-analysis to obtain system-dependent parameters in cirrhosis patients and a top-down approach to improve understanding of the effect of cirrhosis on transporter-mediated drug disposition under cirrhotic conditions. PMID:26225262

  6. Cancer and liver cirrhosis: implications on prognosis and management

    PubMed Central

    Pinter, Matthias; Trauner, Michael; Peck-Radosavljevic, Markus; Sieghart, Wolfgang

    2016-01-01

    Liver cirrhosis, the end-stage of every chronic liver disease, is not only the major risk factor for the development of hepatocellular carcinoma but also a limiting factor for anticancer therapy of liver and non-hepatic malignancies. Liver cirrhosis may limit surgical and interventional approaches to cancer treatment, influence pharmacokinetics of anticancer drugs, increase side effects of chemotherapy, render patients susceptible for hepatotoxicity, and ultimately result in a competitive risk for morbidity and mortality. In this review, we provide a concise overview about the impact of liver cirrhosis on the management and prognosis of patients with primary liver cancer or non-hepatic malignancies. PMID:27843598

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

    PubMed

    Khan, Muhammad Rashid; Younus, Tahira

    2011-10-01

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

  8. Group IVA phospholipase A(2) deficiency prevents CCl4-induced hepatic cell death through the enhancement of autophagy.

    PubMed

    Ishihara, Keiichi; Kanai, Shiho; Tanaka, Kikuko; Kawashita, Eri; Akiba, Satoshi

    2016-02-26

    Group IVA phospholipase A2 (IVA-PLA2), which generates arachidonate, plays a role in inflammation. IVA-PLA2-deficiency reduced hepatotoxicity and hepatocyte cell death in mice that received a single dose of carbon tetrachloride (CCl4) without any inhibitory effects on CCl4-induced lipid peroxidation. An immunoblot analysis of extracts from wild-type mouse- and IVA-PLA2 KO mouse-derived primary hepatocytes that transiently expressed microtubule-associated protein 1 light chain 3B (LC3) revealed a higher amount of LC3-II, a typical index of autophagosome formation, in IVA-PLA2-deficient cells, suggesting the enhancement of constitutive autophagy. IVA-PLA2 may promote CCl4-induced cell death through the suppression of constitutive autophagy in hepatocytes.

  9. Liver Cirrhosis: Evaluation, Nutritional Status, and Prognosis.

    PubMed

    Nishikawa, Hiroki; Osaki, Yukio

    2015-01-01

    The liver is the major organ for the metabolism of three major nutrients: protein, fat, and carbohydrate. Chronic hepatitis C virus infection is the major cause of chronic liver disease. Liver cirrhosis (LC) results from different mechanisms of liver injury that lead to necroinflammation and fibrosis. LC has been seen to be not a single disease entity but one that can be graded into distinct clinical stages related to clinical outcome. Several noninvasive methods have been developed for assessing liver fibrosis and these methods have been used for predicting prognosis in patients with LC. On the other hand, subjects with LC often have protein-energy malnutrition (PEM) and poor physical activity. These conditions often result in sarcopenia, which is the loss of skeletal muscle volume and increased muscle weakness. Recent studies have demonstrated that PEM and sarcopenia are predictive factors for poorer survival in patients with LC. Based on these backgrounds, several methods for evaluating nutritional status in patients with chronic liver disease have been developed and they have been preferably used in the clinical field practice. In this review, we will summarize the current knowledge in the field of LC from the viewpoints of diagnostic method, nutritional status, and clinical outcomes.

  10. Herbal supplement attenuation of cardiac fibrosis in rats with CCl₄-induced liver cirrhosis.

    PubMed

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

    2014-02-28

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

  11. New prognostic markers in liver cirrhosis

    PubMed Central

    Di Martino, Vincent; Weil, Delphine; Cervoni, Jean-Paul; Thevenot, Thierry

    2015-01-01

    Determining the prognosis of cirrhotic patients is not an easy task. Prognostic scores, like Child-Pugh and Model of End-stage Liver Disease scores, are commonly used by hepatologists, but do not always reflect superimposed events that may strongly influence the prognosis. Among them, bacterial intestinal translocation is a key phenomenon for the development of cirrhosis-related complications. Several biological variables (C-reactive protein, serum free cortisol, copeptin, von Willebrand factor antigen) are surrogates of “inflammatory stress” and have recently been identified as potential prognostic markers in cirrhotic patients. Most of these above mentioned markers were investigated in pilot studies with sometimes a modest sample size but allow us to catch a glimpse of the pathophysiological mechanisms leading to the worsening of cirrhosis. These new data should generate further well-designed studies to better assess the benefit for liver function of preventing intestinal bacterial translocation and microvascular thrombosis. The control of infection is vital and among all actors of immunity, vitamin D also appears to act as an anti-infective agent and therefore has probably a prognostic value. PMID:26019739

  12. New prognostic markers in liver cirrhosis.

    PubMed

    Di Martino, Vincent; Weil, Delphine; Cervoni, Jean-Paul; Thevenot, Thierry

    2015-05-28

    Determining the prognosis of cirrhotic patients is not an easy task. Prognostic scores, like Child-Pugh and Model of End-stage Liver Disease scores, are commonly used by hepatologists, but do not always reflect superimposed events that may strongly influence the prognosis. Among them, bacterial intestinal translocation is a key phenomenon for the development of cirrhosis-related complications. Several biological variables (C-reactive protein, serum free cortisol, copeptin, von Willebrand factor antigen) are surrogates of "inflammatory stress" and have recently been identified as potential prognostic markers in cirrhotic patients. Most of these above mentioned markers were investigated in pilot studies with sometimes a modest sample size but allow us to catch a glimpse of the pathophysiological mechanisms leading to the worsening of cirrhosis. These new data should generate further well-designed studies to better assess the benefit for liver function of preventing intestinal bacterial translocation and microvascular thrombosis. The control of infection is vital and among all actors of immunity, vitamin D also appears to act as an anti-infective agent and therefore has probably a prognostic value.

  13. [Nutrition in liver cirrhosis: diagnostic aspects and treatment].

    PubMed

    Gundling, F; Schepp, W

    2008-04-01

    Malnutrition is very common in patients with liver cirrhosis and includes especially protein-calorie malnutrition. The pathophysiological reasons vary and are caused by metabolic modifications and characteristics of enteral absorption and digestion cause by the cirrhosis. Malnutrition contributes to overall mortality and complication rate of the chronic liver disease. An adequate daily energy and protein supply should be ensured in patients with liver cirrhosis, which is higher than that in the normal population, because of higher amino-acid turnover. Ascites may benefit from daily low-salt fluid intake. Nutritional substitution of vitamins and trace elements is indicated when symptoms of deficiency occur.

  14. Virus-related liver cirrhosis: molecular basis and therapeutic options.

    PubMed

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

    2014-06-07

    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-α 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-α 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.

  15. Unilateral pleural effusion without ascites in liver cirrhosis

    SciTech Connect

    Faiyaz, U.; Goyal, P.C.

    1983-09-01

    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.

  16. The antioxidative and hepatoprotective effects comparison of Chinese angelica polysaccharide(CAP)and selenizing CAP (sCAP) in CCl4 induced hepatic injury mice.

    PubMed

    Gao, Zhenzhen; Zhang, Chao; Tian, Weijun; Liu, Kuanhui; Hou, Ranran; Yue, Chanjuan; Wu, Yi; Wang, Deyun; Liu, Jiaguo; Hu, Yuanliang; Yang, Ying

    2017-04-01

    Chinese angelica polysaccharides (CAP) and selenizing CAP (sCAP) were prepared and identified through FTIR and SEM observation. Their antioxidant activities in vitro and hepatoprotective effects in vivo were compared by free radical-scavenging tests or with CCl4-induced hepatic injury model mice. The results showed that for DPPH radical, superoxide anion and hydroxyl radical, the scavenging capabilities of sCAP were significantly stronger than those of CAP. In hepatic injury model mice, sCAP could significantly reduce ALT, AST and ALP contents and raised TP content in serum, significantly reduce MDA and ROS contents and raised SOD and T-AOC activities in liver homogenate in comparison with CAP; obviously relieve the pathological changes of liver and significantly inhibit the expressions of p-ERK, p-JNK and p-p38 protein as compared with those in model control group. These results indicate that selenylation modification can enhance the antioxidant and hepatoprotective actions of Chinese angelica polysaccharide. A action mechanism of sCAP is suppressing the protein expression of MAPK signaling pathway.

  17. Gut microbiota and host metabolism in liver cirrhosis

    PubMed Central

    Usami, Makoto; Miyoshi, Makoto; Yamashita, Hayato

    2015-01-01

    The gut microbiota has the capacity to produce a diverse range of compounds that play a major role in regulating the activity of distal organs and the liver is strategically positioned downstream of the gut. Gut microbiota linked compounds such as short chain fatty acids, bile acids, choline metabolites, indole derivatives, vitamins, polyamines, lipids, neurotransmitters and neuroactive compounds, and hypothalamic-pituitary-adrenal axis hormones have many biological functions. This review focuses on the gut microbiota and host metabolism in liver cirrhosis. Dysbiosis in liver cirrhosis causes serious complications, such as bacteremia and hepatic encephalopathy, accompanied by small intestinal bacterial overgrowth and increased intestinal permeability. Gut dysbiosis in cirrhosis and intervention with probiotics and synbiotics in a clinical setting is reviewed and evaluated. Recent studies have revealed the relationship between gut microbiota and host metabolism in chronic metabolic liver disease, especially, non-alcoholic fatty liver disease, alcoholic liver disease, and with the gut microbiota metabolic interactions in dysbiosis related metabolic diseases such as diabetes and obesity. Recently, our understanding of the relationship between the gut and liver and how this regulates systemic metabolic changes in liver cirrhosis has increased. The serum lipid levels of phospholipids, free fatty acids, polyunsaturated fatty acids, especially, eicosapentaenoic acid, arachidonic acid, and docosahexaenoic acid have significant correlations with specific fecal flora in liver cirrhosis. Many clinical and experimental reports support the relationship between fatty acid metabolism and gut-microbiota. Various blood metabolome such as cytokines, amino acids, and vitamins are correlated with gut microbiota in probiotics-treated liver cirrhosis patients. The future evaluation of the gut-microbiota-liver metabolic network and the intervention of these relationships using probiotics

  18. Gut microbiota and host metabolism in liver cirrhosis.

    PubMed

    Usami, Makoto; Miyoshi, Makoto; Yamashita, Hayato

    2015-11-07

    The gut microbiota has the capacity to produce a diverse range of compounds that play a major role in regulating the activity of distal organs and the liver is strategically positioned downstream of the gut. Gut microbiota linked compounds such as short chain fatty acids, bile acids, choline metabolites, indole derivatives, vitamins, polyamines, lipids, neurotransmitters and neuroactive compounds, and hypothalamic-pituitary-adrenal axis hormones have many biological functions. This review focuses on the gut microbiota and host metabolism in liver cirrhosis. Dysbiosis in liver cirrhosis causes serious complications, such as bacteremia and hepatic encephalopathy, accompanied by small intestinal bacterial overgrowth and increased intestinal permeability. Gut dysbiosis in cirrhosis and intervention with probiotics and synbiotics in a clinical setting is reviewed and evaluated. Recent studies have revealed the relationship between gut microbiota and host metabolism in chronic metabolic liver disease, especially, non-alcoholic fatty liver disease, alcoholic liver disease, and with the gut microbiota metabolic interactions in dysbiosis related metabolic diseases such as diabetes and obesity. Recently, our understanding of the relationship between the gut and liver and how this regulates systemic metabolic changes in liver cirrhosis has increased. The serum lipid levels of phospholipids, free fatty acids, polyunsaturated fatty acids, especially, eicosapentaenoic acid, arachidonic acid, and docosahexaenoic acid have significant correlations with specific fecal flora in liver cirrhosis. Many clinical and experimental reports support the relationship between fatty acid metabolism and gut-microbiota. Various blood metabolome such as cytokines, amino acids, and vitamins are correlated with gut microbiota in probiotics-treated liver cirrhosis patients. The future evaluation of the gut-microbiota-liver metabolic network and the intervention of these relationships using probiotics

  19. Management of coagulopathy in patients with decompensated liver cirrhosis.

    PubMed

    Amarapurkar, Pooja D; Amarapurkar, Deepak N

    2011-01-01

    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.

  20. [Activity of antioxidant enzymes in patients with liver cirrhosis].

    PubMed

    Czeczot, Hanna; Scibior, Dorota; Skrzycki, Michał; Podsiad, Małgorzata

    2006-01-01

    The aim of our studies was the estimation of activities of antioxidant enzymes in patients with liver cirrhosis. We investigated activities of superoxide dismutases (CuZnSOD, MnSOD), catalase (CAT), selenium dependent GSH peroxidase (Se-GSH-Px), selenium independent GSH peroxidase (non-Se-GSH-Px), GSH-S-transferase (GST), GSH reductase (GSHR) and the level ofreduced gutathione (GSH) in cirrhotic and healthy liver tissues. The activities of CuZnSOD, MnSOD, CAT and GSH-dependent enzymes (except GSHR) were found to be lower in cirrhotic tissue compared to healthy liver. Those changes were associated with decrease of GSH level in cirrhotic tissue compared with control liver tissue. Our results show that antioxidant barrier in liver cirrhosis is impaired. It is associated with decrease of glutathione level and changes of activities of antioxidant enzymes (SOD, CAT, GSHPx, GST, GSHR) in liver cirrhosis compared with healthy liver.

  1. Periodontal disease and liver cirrhosis: A systematic review

    PubMed Central

    2015-01-01

    Objectives: Studies suggest that periodontal disease, a source of subclinical and persistent infection, may be associated with various systemic conditions, including liver cirrhosis. The aim of this study was to examine the literature and determine the relationship between periodontal disease and liver cirrhosis and to identify opportunities and directions for future research in this area. Methods: A systematic review of English articles in the PubMed, EMBASE, and Scopus databases was conducted using search terms including ‘liver cirrhosis’, ‘end-stage liver disease’, ‘liver diseases’, ‘oral health’, ‘periodontal disease’, ‘mouth disease’, ‘gingivitis’, and ‘periodontitis’. Results: Thirteen studies published between 1981 and 2014 were found to include data on oral health and periodontal disease in cirrhotic patients. Studies indicated an increased incidence of periodontal disease in patients with liver cirrhosis, measured with several different periodontal indices. The reported prevalence of periodontal disease in cirrhosis patients ranged from 25.0% to 68.75% in four studies and apical periodontitis was found in 49%–79% of the patients. One study found that mortality was lower among patients who underwent dental treatment versus non-treated patients. Another study suggested an association between periodontal disease and the progression of liver cirrhosis, but data are sparse and conflicting as to whether periodontal disease is correlated to cirrhosis aetiology and severity. Conclusion: Despite the clinical reality of periodontal disease in liver cirrhosis patients, there are few published studies. Before clinical implications can be addressed, more data on the prevalence of and correlation between periodontal disease and liver cirrhosis aetiology, duration, and progression are needed. PMID:26770799

  2. Biomechanics and functionality of hepatocytes in liver cirrhosis.

    PubMed

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

    2014-06-27

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

  3. Beta-Adrenergic Receptor 1 Selective Antagonism Inhibits Norepinephrine-Mediated TNF-Alpha Downregulation in Experimental Liver Cirrhosis

    PubMed Central

    Zapater, Pedro; Gómez-Hurtado, Isabel; Peiró, Gloria; González-Navajas, José Manuel; García, Irma; Giménez, Paula; Moratalla, Alba; Such, José; Francés, Rubén

    2012-01-01

    Background Bacterial translocation is a frequent event in cirrhosis leading to an increased inflammatory response. Splanchnic adrenergic system hyperactivation has been related with increased bacterial translocation. We aim at evaluating the interacting mechanism between hepatic norepinephrine and inflammation during liver damage in the presence of bacterial-DNA. Animals and Methods Forty-six mice were included in a 16-week protocol of CCl4-induced cirrhosis. Laparotomies were performed at weeks 6, 10, 13 and 16. A second set of forty mice injected with a single intraperitoneal dose of CCl4 was treated with saline, 6-hydroxidopamine, Nebivolol or Butoxamine. After 5 days, mice received E. coli-DNA intraperitoneally. Laparotomies were performed 24 hours later. Liver bacterial-DNA, norepinephrine, TNF-alpha, IL-6 and beta-adrenergic receptor levels were measured. Results Bacterial-DNA translocation was more frequent in CCl4-treated animals compared with controls, and increased as fibrosis progressed. Liver norepinephrine and pro-inflammatory cytokines were significantly higher in mice with vs without bacterial-DNA (319.7±120.6 vs 120.7±68.6 pg/g for norepinephrine, 38.4±6.1 vs 29.7±4.2 pg/g for TNF-alpha, 41.8±7.4 vs 28.7±4.3 pg/g for IL-6). Only beta-adrenergic receptor-1 was significantly increased in treated vs control animals (34.6±7.3 vs 12.5±5.3, p = 0.01) and correlated with TNF-alpha, IL-6 and norepinephrine hepatic levels in animals with bacterial-DNA. In the second set of mice, cytokine levels were increased in 6-hydroxidopamine and Nebivolol (beta-adrenergic receptor-1 antagonist) treated mice compared with saline. Butoxamine (beta-adrenergic receptor-2 antagonist) didn’t inhibit liver norepinephrine modulation of pro-inflammatory cytokines. Conclusions Beta-adrenergic receptor-1 mediates liver norepinephrine modulation of the pro-inflammatory response in CCl4-treated mice with bacterial-DNA. PMID:22916250

  4. Clinico-hemato-biochemical profile of dogs with liver cirrhosis

    PubMed Central

    Elhiblu, M. A.; Dua, K.; Mohindroo, J.; Mahajan, S. K.; Sood, N. K.; Dhaliwal, P. S.

    2015-01-01

    Aim: The aim of this study was to determine the relevant tools in the diagnosis of liver cirrhosis in dogs. Material and Methods: A total of 140 dogs presented at Veterinary Teaching Hospital, Guru Angad Dev Veterinary and Animal Sciences University, Ludhiana, showing clinical signs of hepatic insufficiency were subjected to clinico-hemato biochemical, urological, ultrasonographic (USG), and USG guided fine-needle biopsy examinations by standard methods. On the basis of these results, 6 dogs out of 140 dogs were found to be suffering from liver cirrhosis. Six clinically healthy dogs constituted the control group. Results: The dogs suffering from liver cirrhosis manifested inappetence, halitosis, abdominal distension, weight loss, melena, icterus, anemia, and neutrophilic leukocytosis with the left shift. Levels of hemoglobin, lymphocytes, packed cell volume, mean corpuscular volume, mean corpuscular Hb (MCH), and platelet count were significantly lower in liver cirrhosis group than control group while total leukocyte count, neutrophils, and MCH concentration were significantly higher. Glucose, total protein, albumin, A/G ratio, and fibrinogen were significantly lower, and creatinine, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, prothrombin time, and APTT were significantly higher than the control values. Ultrasound revealed diffuse increase in echogenicity with rounded and irregular liver margins. Cytological examination of the ascitic fluid and fine-needle aspiration biopsy of liver was not fruitful in the diagnosis of liver cirrhosis. Conclusions: Liver cirrhosis causes clinical and hemo-biochemical alterations, which require special consideration when treating diseased animals. USG, diffuse increase in echogenicity of liver, rounding and irregularity of liver margins and microhepatica were the consistent findings. It is suggested that USG along with hemo-biochemical alterations may be used as a diagnostic tool for liver cirrhosis

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

    PubMed

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

    2014-07-01

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

  6. Vitamin K status in cystic fibrosis patients with liver cirrhosis.

    PubMed

    Krzyżanowska, Patrycja; Drzymała-Czyż, Sławomira; Pogorzelski, Andrzej; Duś-Żuchowska, Monika; Skorupa, Wojciech; Bober, Lyudmyla; Sapiejka, Ewa; Oralewska, Beata; Rohovyk, Nataliya; Moczko, Jerzy; Nowak, Jan; Wenska-Chyży, Ewa; Rachel, Marta; Lisowska, Aleksandra; Walkowiak, Jarosław

    2017-01-23

    The available data on the influence of liver cirrhosis on vitamin K status in CF patients is scarce. Therefore, the aims of the present study were to assess the prevalence of vitamin K deficiency in cirrhotic CF subjects and to determine whether it correlates with liver cirrhosis. The study group comprised of 27 CF patients with and 63 without liver cirrhosis. Vitamin K status was assessed using prothrombin induced by vitamin K absence (PIVKA-II) and the percentage of undercarboxylated osteocalcin (u-OC). PIVKA-II concentrations were higher in cirrhotic than in non-cirrhotic CF patients (median [1st-3rd quartile]: 3.2ng/ml [1.0-10.0] vs. 1.3ng/ml [0.2-2.6], p=0.0029). However, the differences in u-OC percentages between the studied groups did not reach the level of significance (49.4% [7.0-73.8] vs. 8.0% [2.6-59.1], p=0.0501). Based on multiple linear regression analysis the dose of vitamin K and F508del mutation were potentially defined as determinants of vitamin K deficiency. Liver cirrhosis was not documented to be an independent risk factor. In CF patients with liver cirrhosis vitamin K deficiency is not only more frequent, but also more severe. However, not liver cirrhosis, but the presence of a F508del CFTR mutation constitutes an independent risk factor for vitamin K deficiency.

  7. Prediction of liver cirrhosis, using diagnostic imaging tools

    PubMed Central

    Yeom, Suk Keu; Lee, Chang Hee; Cha, Sang Hoon; Park, Cheol Min

    2015-01-01

    Early diagnosis of liver cirrhosis is important. Ultrasound-guided liver biopsy is the gold standard for diagnosis of liver cirrhosis. However, its invasiveness and sampling bias limit the applicability of the method. Basic imaging for the diagnosis of liver cirrhosis has developed over the last few decades, enabling early detection of morphological changes of the liver by ultrasonography (US), computed tomography, and magnetic resonance imaging (MRI). They are also accurate diagnostic methods for advanced liver cirrhosis, for which early diagnosis is difficult. There are a number of ways to compensate for this difficulty, including texture analysis to more closely identify the homogeneity of hepatic parenchyma, elastography to measure the stiffness and elasticity of the liver, and perfusion studies to determine the blood flow volume, transit time, and velocity. Amongst these methods, elastography using US and MRI was found to be slightly easier, faster, and able to provide an accurate diagnosis. Early diagnosis of liver cirrhosis using MRI or US elastography is therefore a realistic alternative, but further research is still needed. PMID:26301049

  8. Genetic markers in alcoholic liver cirrhosis.

    PubMed

    Lareu, M V; Alvarez-Prechous, A; Pardiñas, C; Concheiro, L; Carracedo, A

    1992-01-01

    11 genetic markers were typed in 157 individuals suffering from alcoholic cirrhosis, and compared with a random sample of healthy individuals. No significant differences were found for transferrin, specific group component, orosomucoid, esterase D, phosphogluconate dehydrogenase and adenylate kinase. Strong associations between alcoholic cirrhosis and alpha-1-antitrypsin PI*Z allele, haptoglobin HP*1 allele and acid phosphatase ACP AC phenotype were observed. The biological significance of these associations and their relationships with the development of alcoholic cirrhosis are also discussed.

  9. [Pain management in patients with liver cirrhosis].

    PubMed

    Ojeda, Antonio; Moreno, Luis A

    2014-01-01

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

  10. Factors predicting early postoperative liver cirrhosis-related complications after lung cancer surgery in patients with liver cirrhosis.

    PubMed

    Iwata, Takashi; Inoue, Kiyotoshi; Nishiyama, Noritoshi; Nagano, Koshi; Izumi, Nobuhiro; Tsukioka, Takuma; Hanada, Shoji; Suehiro, Shigefumi

    2007-12-01

    We aimed to determine the factors predicting liver cirrhosis-related complications in the early postoperative period after lung cancer surgery in patients with liver cirrhosis. We retrospectively reviewed the medical records of patients who underwent curative surgery for primary lung cancer in our institute from January 1990 to March 2007, finding 37 cases with comorbid liver cirrhosis. These patients were divided into two groups, according to whether liver failure, bleeding, and critical infection had occurred postoperatively. Various clinical parameters were analyzed statistically between the bigeminal groups. Liver cirrhosis-related complications occurred in seven of the 37 patients (18.9%). Transient liver failure occurred in two patients (5.4%) after pulmonary resection. Acute intrathoracic bleeding occurred in four cases (10.8%). Two patients died (5.4%) in both cases due to sepsis. Preoperative total bilirubin (P<0.05), and indocyanine green retention rate at 15 min (P<0.05) were significantly higher in patients with liver failure. Only serum value of total bilirubin was an independent risk factor (P<0.05) by multivariate analysis. In predicting death from infection, only preoperative nutritional status was a significant risk factor (P<0.05). To avoid postoperative cirrhosis-related complications, preoperative preparation to improve their liver function and nutrition status is essential.

  11. Nutritional assessment and treatment of patients with liver cirrhosis.

    PubMed

    Moctezuma-Velázquez, Carlos; García-Juárez, Ignacio; Soto-Solís, Rodrigo; Hernández-Cortés, Juan; Torre, Aldo

    2013-01-01

    Prevalence of chronic liver diseases, including liver cirrhosis, is increasing worldwide. The nutritional state assessment in these patients is complicated, and besides anthropometry is based on several other tools in order to be more accurate. Specific dietary recommendations are needed in patients with chronic liver diseases in order to help prevent and treat liver decompensation because malnutrition is an independent predictor of mortality. This review focuses on essential aspects in the nutritional assessment of cirrhotic patients and some general recommendations for their treatment.

  12. Occult endocrine dysfunction in patients with cirrhosis of liver

    PubMed Central

    Kumar, K. V. S. Hari; Pawah, A. K.; Manrai, Manish

    2016-01-01

    Background: Liver dysfunction leads to endocrine disturbance due to the alteration in protein metabolism or synthesis. We studied the presence of occult endocrine dysfunction in liver cirrhosis and compared the same with underlying etiology. Materials and Methods: We evaluated thirty patients with liver cirrhosis in this cross-sectional, observational study. All subjects were assessed for pituitary, thyroid, adrenal, and gonadal function. The patients were divided into Group 1 (cirrhosis, n = 30) and Group 2 (controls, n = 15) and the data were analyzed with appropriate statistical tests. Results: The study participants (20 males, 10 females) had a mean age of 54.5 ± 12.4 years and duration of the cirrhosis 5.1 ± 2.7 years. Four patients were in Child Class A, 11 and 15 patients were in Child Classes B and C, respectively. Eleven out of thirty patients (37%) had endocrine disorders, that include subclinical hypothyroidism (n = 3), primary hypothyroidism (n = 1), Sick Euthyroid syndrome (n = 3), central hypothyroidism (n = 2), secondary hypogonadism (n = 3) and growth hormone deficiency in three patients. Two patients had partial hypopituitarism and one patient had complete hypopituitarism. Conclusion: Occult endocrine dysfunction of thyroid and gonadal axes is common in patients with cirrhosis of the liver. The hormonal abnormalities are not different based on the etiology of the cirrhosis. PMID:28217586

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

    PubMed

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

    2013-12-01

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

  14. Probiotics in Nonalcoholic Fatty Liver Disease, Nonalcoholic Steatohepatitis, and Cirrhosis.

    PubMed

    Qamar, Amir A

    2015-01-01

    With the growing epidemic of obesity, the incidence of both nonalcoholic fatty liver disease (NAFL) and nonalcoholic steatohepatitis (NASH) is increasing. The intestinal microbiota differs between individuals who are obese or have normal body mass indices. Animal studies have shown increased intestinal permeability in NAFL, NASH, and cirrhosis. This increases the risk of oxidative and inflammatory injury to the liver from intestinal microbacteria. It may also increase the risk of fatty acid injury and fatty deposition. Bacterial translocation is associated with increased portal hypertension and hepatic encephalopathy in cirrhosis. By preventing bacterial adhesion and translocation, probiotics may have a role in the management of patients with NAFL, NASH, and cirrhosis. Multiple small studies have suggested that probiotics improve some of the clinical markers of activity in patients with NAFL and NASH. Controlled studies have also shown improved outcomes in patients with cirrhosis who were treated with probiotics.

  15. Hepatoprotection by freshwater clam extract against CCl4-induced hepatic damage in rats.

    PubMed

    Hsu, Chin-Lin; Hsu, Chien-Chen; Yen, Gow-Chin

    2010-01-01

    Freshwater clam is traditionally used as a food and has been mentioned in ancient books to have a hepatoprotective effect. The hepatoprotective effect of freshwater clam extract was evaluated in the model of chronic hepatic fibrosis induced by carbon tetrachloride (CCl4). Male Sprague-Dawley rats were orally treated with freshwater clam extract (0.3, 0.6 and 1.5 g/kg of bw) or silymarin (0.2 g/kg of bw) along with the administration of CCl4 (0.5 ml/rat, 20% CCl4 in olive oil) for eight consecutive weeks. Blood samples were collected for assaying serum biochemical parameters. The livers were excised for evaluating peroxidation products and antioxidant substances, as well as the activities of antioxidant enzymes. Pathological histology was also performed. The data showed that supplementation of freshwater clam extract (0.6 g/kg bw) significantly reduced the serum levels of alanine aminotransferase and aspartate aminotransferase in rats treated with CCl4, and also decreased the thiobarbituric acid reactive substances, hydroxyproline and excessive inflammation in the livers of CCl4-treated rats. Histopathological analysis of the liver showed that freshwater clam extract (0.6 g/kg bw) markedly reduced the injury score of the fibrosis induced by CCl4 in rats. The data suggest that oral administration with freshwater clam extract might provide a novel and alternative approach for treating chronic liver failure.

  16. Management of thrombocytopenia due to liver cirrhosis: a review.

    PubMed

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

    2014-03-14

    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.

  17. Effect of Cichorium Glandulosum Extracts on CCl4-Induced Hepatic Fibrosis

    PubMed Central

    Qin, Dongmei; Wen, Zhiping; Nie, Yaru; Yao, Guangmin

    2013-01-01

    Background: Cichorium glandulosum (CG), which is a Compositae family plant, is a commonly used traditional Uighur medicine capable of cleansing liver and being cholagogue, strengthening stomach, promoting digestion, inducing diuresis and reducing edema. Objectives: To study the liver and spleen indices, the levels of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and the histopathological changes. Materials and Methods: Rats were intragastrically administered with the extracts of a traditional Uighur medicine Cichorium glandulosum (CG). The expressions of FN, Smard3 IGFBPrPl and TGF-β1 were detected. Results: The liver and spleen indices of the CG-V group were significantly lower than those of the model group (P < 0.01). The hepatic fibrosis symptoms of the CG-V and CG-VII groups were significantly relieved, and more FN, Smard3 and IGFBPrPl were expressed than those in the normal group. The expressions of FN, Smard3 and TGF-β1 in all treatment groups were significantly higher than those in the normal group, and the expressions in the CG-V and CG-VII groups were significantly different from those in the model group (P < 0.05). Compared with the normal group, the apoptotic index of the model group was significantly higher, but the indices of the CG-V and CG-VII groups were significantly lower than that of the model group (P < 0.01). Conclusions: The extracts of CG probably exerted protective effects by influencing the TGF-β/Smads signal transduction pathway. PMID:24693382

  18. Evidence-based clinical practice guidelines for liver cirrhosis 2015.

    PubMed

    Fukui, Hiroshi; Saito, Hidetsugu; Ueno, Yoshiyuki; Uto, Hirofumi; Obara, Katsutoshi; Sakaida, Isao; Shibuya, Akitaka; Seike, Masataka; Nagoshi, Sumiko; Segawa, Makoto; Tsubouchi, Hirohito; Moriwaki, Hisataka; Kato, Akinobu; Hashimoto, Etsuko; Michitaka, Kojiro; Murawaki, Toshikazu; Sugano, Kentaro; Watanabe, Mamoru; Shimosegawa, Tooru

    2016-07-01

    The Japanese Society of Gastroenterology revised the evidence-based clinical practice guidelines for liver cirrhosis in 2015. Eighty-three clinical questions were selected, and a literature search was performed for the clinical questions with use of the MEDLINE, Cochrane, and Igaku Chuo Zasshi databases for the period between 1983 and June 2012. Manual searching of the latest important literature was added until August 2015. The guidelines were developed with use of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. This digest version in English introduces selected clinical questions and statements related to the management of liver cirrhosis and its complications. Branched-chain amino acids relieve hypoalbuminemia and hepatic encephalopathy and improve quality of life. Nucleoside analogues and peginterferon plus ribavirin combination therapy improve the prognosis of patients with hepatitis B virus related liver cirrhosis and hepatitis C related compensated liver cirrhosis, respectively, although the latter therapy may be replaced by direct-acting antivirals. For liver cirrhosis caused by primary biliary cirrhosis and active autoimmune hepatitis, urosodeoxycholic acid and steroid are recommended, respectively. The most adequate modalities for the management of variceal bleeding are the endoscopic injection sclerotherapy for esophageal varices and the balloon-occluded retrograde transvenous obliteration following endoscopic obturation with cyanoacrylate for gastric varices. Beta-blockers are useful for primary prophylaxis of esophageal variceal bleeding. The V2 receptor antagonist tolvaptan is a useful add-on therapy in careful diuretic therapy for ascites. Albumin infusion is useful for the prevention of paracentesis-induced circulatory disturbance and renal failure. In addition to disaccharides, the nonabsorbable antibiotic rifaximin is useful for the management of encephalopathy. Anticoagulation therapy is proposed for

  19. Alterations of the human gut microbiome in liver cirrhosis.

    PubMed

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

    2014-09-04

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

  20. Intestinal permeability in a patient with liver cirrhosis

    PubMed Central

    Aguirre Valadez, Jonathan Manuel; Rivera-Espinosa, Liliana; Méndez-Guerrero, Osvely; Chávez-Pacheco, Juan Luis; García Juárez, Ignacio; Torre, Aldo

    2016-01-01

    Liver cirrhosis is a worldwide public health problem, and patients with this disease are at high risk of developing complications, bacterial translocation from the intestinal lumen to the mesenteric nodes, and systemic circulation, resulting in the development of severe complications related to high mortality rate. The intestinal barrier is a structure with a physical and biochemical activity to maintain balance between the external environment, including bacteria and their products, and the internal environment. Patients with liver cirrhosis develop a series of alterations in different components of the intestinal barrier directly associated with the severity of liver disease that finally increased intestinal permeability. A “leaky gut” is an effect produced by damaged intestinal barrier; alterations in the function of tight junction proteins are related to bacterial translocation and their products. Instead, increasing serum proinflammatory cytokines and hemodynamics modification, which results in the appearance of complications of liver cirrhosis such as hepatic encephalopathy, variceal hemorrhage, bacterial spontaneous peritonitis, and hepatorenal syndrome. The intestinal microbiota plays a fundamental role in maintaining the proper function of the intestinal barrier; bacterial overgrowth and dysbiosis are two phenomena often present in people with liver cirrhosis favoring bacterial translocation. Increased intestinal permeability has an important role in the genesis of these complications, and treating it could be the base for prevention and partial treatment of these complications. PMID:27920543

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

    PubMed Central

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

    2010-01-01

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

  2. Reversal of liver cirrhosis: current evidence and expectations

    PubMed Central

    Jung, Young Kul; Yim, Hyung Joon

    2017-01-01

    In the past, liver cirrhosis was considered an irreversible phenomenon. However, many experimental data have provided evidence of the reversibility of liver fibrosis. Moreover, multiple clinical studies have also shown regression of fibrosis and reversal of cirrhosis on repeated biopsy samples. As various etiologies are associated with liver fibrosis via integrated signaling pathways, a comprehensive understanding of the pathobiology of hepatic fibrogenesis is critical for improving clinical outcomes. Hepatic stellate cells play a central role in hepatic fibrogenesis upon their activation from a quiescent state. Collagen and other extracellular material components from activated hepatic stellate cells are deposited on, and damage, the liver parenchyma and vascular structures. Hence, inactivation of hepatic stellate cells can lead to enhancement of fibrolytic activity and could be a potential target of antifibrotic therapy. In this regard, continued efforts have been made to develop better treatments for underlying liver diseases and antifibrotic agents in multiple clinical and therapeutic trials; the best results may be expected with the integration of such evidence. In this article, we present the underlying mechanisms of fibrosis, current experimental and clinical evidence of the reversibility of liver fibrosis/cirrhosis, and new agents with therapeutic potential for liver fibrosis. PMID:28171717

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

    PubMed Central

    2012-01-01

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

  4. Non invasive tools for the diagnosis of liver cirrhosis

    PubMed Central

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

    2014-01-01

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

  5. Non invasive tools for the diagnosis of liver cirrhosis.

    PubMed

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

    2014-12-28

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

  6. The Burden of Rehospitalization for Patients With Liver Cirrhosis.

    PubMed

    Desai, Archita P; Reau, Nancy

    2016-01-01

    Advanced liver disease is becoming more prevalent in the United States. This increase has been attributed largely to the growing epidemic of nonalcoholic fatty liver disease and an aging population infected with hepatitis C. Complications of cirrhosis are a major cause of hospital admissions and readmissions. It is important to target efforts for preventing rehospitalization toward patients with cirrhosis who are at the highest risk for readmission, such as those who have high Model for End-Stage Liver Disease scores, are at risk for fluid/electrolyte abnormalities or overt hepatic encephalopathy recurrence, and those who have comorbid conditions (e.g. diabetes). The heart failure management paradigm may provide valuable insights for managing patients with cirrhosis, given the extensive research on preventing hospital readmission and improving health care utilization in this subpopulation. As quality measures related to hospital readmissions for cirrhosis and its complications are adopted by the Centers for Medicare & Medicaid Services and private payers in the future, understanding drivers of hospital readmissions and health care utilization in this vulnerable population are key to improving quality measure performance.

  7. Primary biliary cirrhosis in the era of liver transplantation.

    PubMed

    Raczyńska, Joanna; Habior, Andrzej; Pączek, Leszek; Foroncewicz, Bartosz; Pawełas, Andrzej; Mucha, Krzysztof

    2014-09-29

    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.

  8. Non-invasive evaluation of liver cirrhosis using ultrasound.

    PubMed

    Goyal, N; Jain, N; Rachapalli, V; Cochlin, D L; Robinson, M

    2009-11-01

    Ultrasound (US) is essential in both assessment of the potentially cirrhotic liver and surveillance of selected patients with chronic hepatitis as liver biopsy can be misleading or inaccurate in up to 25% of cases. Various techniques are already in routine use, such as grey-scale imaging, Doppler US, and contrast-enhanced US (CEUS), while newer techniques such as elastography and hepatic vein transit time (HVTT) have the potential to exclude patients without significant fibrosis or cirrhosis; however, they are operator dependent and require specific software. Grey-scale imaging may demonstrate changes, such as volume redistribution, capsule nodularity, parenchymal nodularity, and echotexture changes. The Doppler findings in the hepatic and portal veins, hepatic artery, and varices allow assessment of liver cirrhosis. However, the operator needs to be aware of limitations of these techniques. Low mechanical index CEUS plays an important role in the assessment of complications of cirrhosis, such as hepatocellular carcinoma and portal vein thrombus. Optimized US technique is crucial for accurate diagnosis of the cirrhotic liver and its complications.

  9. Neurosurgical procedures in patients with liver cirrhosis: A review

    PubMed Central

    Chen, Ching-Chang; Huang, Yin-Cheng; Yeh, Chun-Nan

    2015-01-01

    Liver cirrhosis, a devastating liver fibrosis caused by hepatitis/inflammation or tumors, is a major comorbid factor in known surgery fields, such as cardiovascular and abdominal surgeries. It is important to review possible comorbid results in neurosurgical procedures in cirrhotic patients. In the reviewed literature, Child-Pugh and model for end-stage liver disease scores are commonly used in the assessment of surgical risks for cirrhotic patients undergoing abdominal, cardiovascular or neurosurgical procedures. The major categories of neurosurgery are traumatic brain injury (TBI), spontaneous intracranial hemorrhage (SICH), brain tumors, and spinal instrumentation procedures. TBI was reported with surgical mortality as high as 34.5% and a complication rate of 87.2%. For SICH, mortality ranged from 22.7% to 47.0%, while complications were reported to be 43.2%. Less is discussed in brain tumor patients; still the postoperative hemorrhage rate approached 26.7%. In spinal fusion instrumentation procedures, the complication rate was as high as 41.0%. Preoperative assessment and correction could possibly decrease complications such as hemorrhage, wound infection and other cirrhosis-related complications (renal, pulmonary, ascites and encephalopathy). In this study, we reviewed the neurosurgical-related literature with regard to liver cirrhosis as a prognostic factor influencing neurosurgical outcomes. PMID:26413225

  10. Iliopsoas muscle hematoma secondary to alcoholic liver cirrhosis.

    PubMed

    Yamashita, Suguru; Tanaka, Nobutaka; Nomura, Yukihiro; Miyahara, Takuya; Furuya, Takatoshi

    2012-09-01

    Iliopsoas muscle hematoma in a patient with alcoholic liver cirrhosis is rarely seen, however it has a high mortality. Thus we should cautiously make a diagnosis and treatment. This is the case of a 60-year-old male. He had a 15-year history of alcoholic liver disease and emphysema. He presented with low back pain after a fall that had happened 2 months before. Due to persistent back pain, he went to see a local physician who, after detailed examination, suspected rupture of bilateral common iliac artery aneurysms and transferred the patient to our hospital. The same presumptive diagnosis was made, and on this basis, an aortic bifemoral Y-graft was implanted. He developed aspiration pneumonia and hepatic and renal dysfunction postoperatively, which led to multiple organ failure and subsequent in-hospital death on postoperative day 62. This was believed to be a case of iliopsoas muscle hematoma developed in a patient with liver cirrhosis, and considering it was a case with poor surgical risk, a conservative treatment option such as transcatheter arterial embolization should also have been considered. Although iliopsoas muscle hematoma with alcoholic liver cirrhosis is rare, an appropriate treatment plan should be determined on a case-by-case basis despite its poor prognosis.

  11. Nursing Assessment Tool for People With Liver Cirrhosis

    PubMed Central

    Reis, Renata Karina; da Silva, Patrícia Costa dos Santos; Silva, Ana Elisa Bauer de Camargo; Atila, Elisabeth

    2016-01-01

    The aim of this study was to describe the process of developing a nursing assessment tool for hospitalized adult patients with liver cirrhosis. A descriptive study was carried out in three stages. First, we conducted a literature review to develop a data collection tool on the basis of the Conceptual Model of Wanda Horta. Second, the data collection tool was assessed through an expert panel. Third, we conducted the pilot testing in hospitalized patients. Most of the comments offered by the panel members were accepted to improve the tool. The final version was in the form of a questionnaire with open-closed questions. The panel members concluded that the tool was useful for accurate nursing diagnosis. Horta's Conceptual Model assisted with the development of this data collection tool to help nurses identify accurate nursing diagnosis in hospitalized patients with liver cirrhosis. We hope that the tool can be used by all nurses in clinical practice. PMID:26425862

  12. Increased Autophagy Markers Are Associated with Ductular Reaction during the Development of Cirrhosis.

    PubMed

    Hung, Tzu-Min; Yuan, Ray-Hwang; Huang, Wei-Pang; Chen, Yu-Hsuan; Lin, Yu-Chun; Lin, Chih-Wen; Lai, Hong-Shiee; Lee, Po-Huang

    2015-09-01

    Autophagy is a regulatory pathway in liver fibrosis. We investigated the roles of autophagy in human cirrhotic livers. Cirrhotic and noncirrhotic liver tissues were obtained from patients with hepatocellular carcinoma, and liver tissues from live donors served as control. Patients with cirrhotic livers had significantly increased levels of various essential autophagy-related genes compared with noncirrhotic livers. In addition, colocalization of autophagy marker microtubule-associated protein 1 light chain 3B (LC3B) with lysosome-associated membrane protein-1, increased levels of lysosome-associated membrane protein-2, and increased maturation of lysosomal cathepsin D were observed in cirrhotic livers. By using dual-immunofluorescence staining, we demonstrated that increased LC3B was located mainly in the cytokeratin 19-labeled ductular reaction (DR) in human cirrhotic livers and in an experimental cirrhosis induced by 2-acetylaminofluorene (AAF) with carbon tetrachloride (CCl4), indicating a conserved response to chronic liver damage. Furthermore, an AAF/CCl4-mediated increase in DR and fibrosis were attenuated after chloroquine treatment, suggesting that the autophagy-lysosome pathway was essential for AAF/CCl4-induced DR-fibrosis. In conclusion, we demonstrated that increased autophagy marker positively correlated with DR during the development of cirrhosis. Therefore, targeting autophagy may hold therapeutic value for liver cirrhosis.

  13. [Basics of nutrition in cirrhosis of the liver].

    PubMed

    Mörk, H

    2007-04-26

    Liver cirrhosis is associated with complex metabolic disorders, and regularly leads to a catabolic state. Catabolism, malassimilation, but also loss of protein and, frequently, malnutrition, are the main reasons underlying reduced the nutritional status frequently encountered in these patients. This promotes such complications as ascites, diabetes mellitus, encephalopathy, infections and the hepatorenal syndrome. Dietary therapy individually tailored to the course of the disease provides the often increased energy requirement, while also serving to prevent and treat complications.

  14. Mobilization of hematopoietic progenitor cells in patients with liver cirrhosis

    PubMed Central

    Gehling, Ursula M; Willems, Marc; Schlagner, Kathleen; Benndorf, Ralf A; Dandri, Maura; Petersen, Jörg; Sterneck, Martina; Pollok, Joerg-Matthias; Hossfeld, Dieter K; Rogiers, Xavier

    2010-01-01

    AIM: To test the hypothesis that liver cirrhosis is associated with mobilization of hematopoietic progenitor cells. METHODS: Peripheral blood samples from 72 patients with liver cirrhosis of varying etiology were analyzed by flow cytometry. Identified progenitor cell subsets were immunoselected and used for functional assays in vitro. Plasma levels of stromal cell-derived factor-1 (SDF-1) were measured using an enzyme linked immunosorbent assay. RESULTS: Progenitor cells with a CD133+/CD45+/CD14+ phenotype were observed in 61% of the patients. Between 1% and 26% of the peripheral blood mononuclear cells (MNCs) displayed this phenotype. Furthermore, a distinct population of c-kit+ progenitor cells (between 1% and 38 % of the MNCs) could be detected in 91% of the patients. Additionally, 18% of the patients showed a population of progenitor cells (between 1% and 68% of the MNCs) that was characterized by expression of breast cancer resistance protein-1. Further phenotypic analysis disclosed that the circulating precursors expressed CXC chemokine receptor 4, the receptor for SDF-1. In line with this finding, elevated plasma levels of SDF-1 were present in all patients and were found to correlate with the number of mobilized CD133+ progenitor cells. CONCLUSION: These data indicate that in humans, liver cirrhosis leads to recruitment of various populations of hematopoietic progenitor cells that display markers of intrahepatic progenitor cells. PMID:20066741

  15. Tolvaptan for the treatment of liver cirrhosis oedema.

    PubMed

    Sakaida, Isao

    2014-07-01

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

  16. Protein-protein interaction network analysis of cirrhosis liver disease

    PubMed Central

    Safaei, Akram; Rezaei Tavirani, Mostafa; Arefi Oskouei, Afsaneh; Zamanian Azodi, Mona; Mohebbi, Seyed Reza; Nikzamir, Abdol Rahim

    2016-01-01

    Aim: Evaluation of biological characteristics of 13 identified proteins of patients with cirrhotic liver disease is the main aim of this research. Background: In clinical usage, liver biopsy remains the gold standard for diagnosis of hepatic fibrosis. Evaluation and confirmation of liver fibrosis stages and severity of chronic diseases require a precise and noninvasive biomarkers. Since the early detection of cirrhosis is a clinical problem, achieving a sensitive, specific and predictive novel method based on biomarkers is an important task. Methods: Essential analysis, such as gene ontology (GO) enrichment and protein-protein interactions (PPI) was undergone EXPASy, STRING Database and DAVID Bioinformatics Resources query. Results: Based on GO analysis, most of proteins are located in the endoplasmic reticulum lumen, intracellular organelle lumen, membrane-enclosed lumen, and extracellular region. The relevant molecular functions are actin binding, metal ion binding, cation binding and ion binding. Cell adhesion, biological adhesion, cellular amino acid derivative, metabolic process and homeostatic process are the related processes. Protein-protein interaction network analysis introduced five proteins (fibroblast growth factor receptor 4, tropomyosin 4, tropomyosin 2 (beta), lectin, Lectin galactoside-binding soluble 3 binding protein and apolipoprotein A-I) as hub and bottleneck proteins. Conclusion: Our result indicates that regulation of lipid metabolism and cell survival are important biological processes involved in cirrhosis disease. More investigation of above mentioned proteins will provide a better understanding of cirrhosis disease. PMID:27099671

  17. [Chronic Budd-Chiari syndrome can cause liver cirrhosis].

    PubMed

    Karlsen, Stine; Nielsen, Dennis Tønner; Grønbæk, Henning

    2012-06-11

    Budd-Chiari syndrome (BCS) is a rare disease defined by congestive hepatopathy with obstruction of the hepatic venous outflow tract. Classical symptoms and signs include ascites, hepatomegaly, abdominal pain and various degrees of liver dysfunction. BCS is predominantly caused by thrombosis, malformations and venous compression. We present a case, in which BCS was the cause of liver cirrhosis complicated with refractory ascites and which can be misinterpreted as hepatocellular carcinoma nodules. The diagnosis was confirmed during the transjugular intrahepatic portosystemic shunt procedure with successful vascular stenting resolving the ascites formation.

  18. Does pressure cause liver cirrhosis? The sinusoidal pressure hypothesis

    PubMed Central

    Mueller, Sebastian

    2016-01-01

    Independent of their etiology, all chronic liver diseases ultimately lead to liver cirrhosis, which is a major health problem worldwide. The underlying molecular mechanisms are still poorly understood and no efficient treatment strategies are available. This paper introduces the sinusoidal pressure hypothesis (SPH), which identifies an elevated sinusoidal pressure (SP) as cause of fibrosis. SPH has been mainly derived from recent studies on liver stiffness. So far, pressure changes have been exclusively seen as a consequence of cirrhosis. According to the SPH, however, an elevated SP is the major upstream event that initiates fibrosis via biomechanic signaling by stretching of perisinusoidal cells such as hepatic stellate cells or fibroblasts (SPH part I: initiation). Fibrosis progression is determined by the degree and time of elevated SP. The SPH predicts that the degree of extracellular matrix eventually matches SP with critical thresholds > 12 mmHg and > 4 wk. Elevated arterial flow and final arterialization of the cirrhotic liver represents the self-perpetuating key event exposing the low-pressure-organ to pathologically high pressures (SPH part II: perpetuation). It also defines the “point of no return” where fibrosis progression becomes irreversible. The SPH is able to explain the macroscopic changes of cirrhotic livers and the uniform fibrotic response to various etiologies. It also opens up new views on the role of fat and disease mechanisms in other organs. The novel concept will hopefully stimulate the search for new treatment strategies. PMID:28082801

  19. Hyponatremia in Patients with Cirrhosis of the Liver

    PubMed Central

    Bernardi, Mauro; Ricci, Carmen Serena; Santi, Luca

    2014-01-01

    Hyponatremia is common in cirrhosis. It mostly occurs in an advanced stage of the disease and is associated with complications and increased mortality. Either hypovolemic or, more commonly, hypervolemic hyponatremia can be seen in cirrhosis. Impaired renal sodium handling due to renal hypoperfusion and increased arginine-vasopressin secretion secondary to reduced effective volemia due to peripheral arterial vasodilation represent the main mechanisms leading to dilutional hyponatremia in this setting. Patients with cirrhosis usually develop slowly progressing hyponatremia. In different clinical contexts, it is associated with neurological manifestations due to increased brain water content, where the intensity is often magnified by concomitant hyperammonemia leading to hepatic encephalopathy. Severe hyponatremia requiring hypertonic saline infusion is rare in cirrhosis. The management of asymptomatic or mildly symptomatic hyponatremia mainly rely on the identification and treatment of precipitating factors. However, sustained resolution of hyponatremia is often difficult to achieve. V2 receptor blockade by Vaptans is certainly effective, but their long-term safety, especially when associated to diuretics given to control ascites, has not been established as yet. As in other conditions, a rapid correction of long-standing hyponatremia can lead to irreversible brain damage. The liver transplant setting represents a condition at high risk for the occurrence of such complications. PMID:26237020

  20. Challenges and Management of Liver Cirrhosis: Practical Issues in the Therapy of Patients with Cirrhosis due to NAFLD and NASH.

    PubMed

    Traussnigg, Stefan; Kienbacher, Christian; Halilbasic, Emina; Rechling, Christian; Kazemi-Shirazi, Lili; Hofer, Harald; Munda, Petra; Trauner, Michael

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome and comprises a liver disease spectrum ranging from steatosis to nonalcoholic steatohepatitis (NASH) with risk of progression to liver cirrhosis and hepatocellular carcinoma (HCC). Associated metabolic conditions and comorbidities such as obesity, diabetes and cardiovascular diseases are common and require concerted management. Adiponutrin (PNPLA3) variants may help to identify NAFLD patients at higher risk for liver disease progression towards advanced fibrosis and HCC. The therapeutic options in NAFLD/NASH include lifestyle modification, pharmacological treatment, bariatric surgery for patients with morbid obesity and treatment of complications of liver cirrhosis and HCC, including liver transplantation. Insulin sensitizers and antioxidative treatment strategies with vitamin E are among the best-established pharmacological approaches, but both drugs have long-term safety issues and there is limited evidence in cirrhotic patients. Treatment of concomitant/underlying metabolic conditions with statins or metformin may also have beneficial effects on portal hypertension, complications of liver cirrhosis and HCC prevention. The bile acid receptor FXR may be a promising novel therapeutic target for the treatment of NAFLD/NASH, fibrosis and portal hypertension, but the prognostic implications of associated changes in low- and high-density lipoprotein cholesterol require further studies. Morbidly obese NASH patients can benefit from bariatric surgery which may reduce liver fibrosis but carries a risk of decompensation in patients with advanced liver cirrhosis. When carefully selected, patients with NASH cirrhosis undergoing liver transplantation have a good outcome. This review summarizes recent progress in the management of patients with liver cirrhosis due to NASH.

  1. Pharmacokinetics of metoclopramide in patients with liver cirrhosis.

    PubMed Central

    Magueur, E; Hagege, H; Attali, P; Singlas, E; Etienne, J P; Taburet, A M

    1991-01-01

    The pharmacokinetics of metoclopramide were investigated after intravenous and oral administration in eight patients with severe alcoholic cirrhosis and in eight healthy volunteers. As a consequence of a 50% lower clearance (0.16 +/- 0.07 vs 0.34 +/- 0.09 l h-1 kg-1, plasma drug concentrations and the half-life of metoclopramide were greater in patients following both routes of drug administration. Volume of distribution (3.1 +/- 0.8 vs 3.4 +/- 1.2 l kg-1) and absolute bioavailability (79 +/- 19 vs 84 +/- 15%) were similar in the two groups. The adverse effects of metoclopramide observed in patients with marked hepatic impairment are likely to result from increased accumulation of the drug as a result of impaired clearance. Consequently a reduction in dose of 50% is recommended in patients with severe liver cirrhosis. PMID:2049236

  2. Liver transplantation for hepatic cirrhosis in cystic fibrosis.

    PubMed Central

    Noble-Jamieson, G; Barnes, N; Jamieson, N; Friend, P; Calne, R

    1996-01-01

    About 10% of children with CF develop hepatic cirrhosis and progressive portal hypertension. As the portal hypertension worsens these children are likely to develop serious variceal bleeding and other complications including malnutrition and a decline in respiratory function. Indices of lung function may fall as much as 50% in a year and chest infections may require frequent admissions to hospital. The respiratory symptoms are often attributed to CF related lung disease and affected children may therefore be considered unsuitable for liver transplantation. We propose a simple scoring system which can help to select patients who should be referred for assessment of liver transplantation. After careful assessment and preparation children with lung function indices as low as 30% predicted can have a successful outcome after liver transplantation. With good graft function portal hypertension is relieved and absorption, nutrition and respiratory function all improve. The improved quality of life of these children is remarkable. PMID:8778448

  3. Doxazosin Treatment Attenuates Carbon Tetrachloride-Induced Liver Fibrosis in Hamsters through a Decrease in Transforming Growth Factor β Secretion

    PubMed Central

    Muñoz-Ortega, Martin Humberto; Llamas-Ramírez, Raúl Wiliberto; Romero-Delgadillo, Norma Isabel; Elías-Flores, Tania Guadalupe; de Jesus Tavares-Rodríguez, Edgar; del Rosario Campos-Esparza, María; Cervantes-García, Daniel; Muñoz-Fernández, Luis; Gerardo-Rodríguez, Martin; Ventura-Juárez, Javier

    2016-01-01

    Background/Aims The development of therapeutic strategies for the treatment of cirrhosis has become an important focus for basic and clinical researchers. Adrenergic receptor antagonists have been evaluated as antifibrotic drugs in rodent models of carbon tetrachloride (CCl4)-induced cirrhosis. The aim of the present study was to evaluate the effects of carvedilol and doxazosin on fibrosis/cirrhosis in a hamster animal model. Methods Cirrhotic-induced hamsters were treated by daily administration of carvedilol and doxazosin for 6 weeks. Hepatic function and histological evaluation were conducted by measuring biochemical markers, including total bilirubin, aspartate aminotransferase, alanine aminotransferase and albumin, and liver tissue slices. Additionally, transforming growth factor β (TGF-β) immunohistochemistry was analyzed. Results Biochemical markers revealed that hepatic function was restored after treatment with doxazosin and carvedilol. Histological evaluation showed a decrease in collagen type I deposits and TGF-β-secreting cells. Conclusions Taken together, these results suggest that the decrease in collagen type I following treatment with doxazosin or carvedilol is achieved by decreasing the profibrotic activities of TGF-β via the blockage of α1- and β-adrenergic receptor. Consequently, a diminution of fibrotic tissue in the CCl4-induced model of cirrhosis is achieved. PMID:26573293

  4. Coding and non-coding gene regulatory networks underlie the immune response in liver cirrhosis

    PubMed Central

    Zhang, Xueming; Huang, Yongming; Yang, Zhengpeng; Zhang, Yuguo; Zhang, Weihui; Gao, Zu-hua; Xue, Dongbo

    2017-01-01

    Liver cirrhosis is recognized as being the consequence of immune-mediated hepatocyte damage and repair processes. However, the regulation of these immune responses underlying liver cirrhosis has not been elucidated. In this study, we used GEO datasets and bioinformatics methods to established coding and non-coding gene regulatory networks including transcription factor-/lncRNA-microRNA-mRNA, and competing endogenous RNA interaction networks. Our results identified 2224 mRNAs, 70 lncRNAs and 46 microRNAs were differentially expressed in liver cirrhosis. The transcription factor -/lncRNA- microRNA-mRNA network we uncovered that results in immune-mediated liver cirrhosis is comprised of 5 core microRNAs (e.g., miR-203; miR-219-5p), 3 transcription factors (i.e., FOXP3, ETS1 and FOS) and 7 lncRNAs (e.g., ENTS00000671336, ENST00000575137). The competing endogenous RNA interaction network we identified includes a complex immune response regulatory subnetwork that controls the entire liver cirrhosis network. Additionally, we found 10 overlapping GO terms shared by both liver cirrhosis and hepatocellular carcinoma including “immune response” as well. Interestingly, the overlapping differentially expressed genes in liver cirrhosis and hepatocellular carcinoma were enriched in immune response-related functional terms. In summary, a complex gene regulatory network underlying immune response processes may play an important role in the development and progression of liver cirrhosis, and its development into hepatocellular carcinoma. PMID:28355233

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

    PubMed

    Fukui, Hiroshi

    2015-03-27

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

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

    PubMed Central

    Fukui, Hiroshi

    2015-01-01

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

  7. Concentrations of fetuin-A, osteoprotegerin and α-Klotho in patients with alcoholic liver cirrhosis

    PubMed Central

    Prystupa, Andrzej; Dąbrowska, Anna; Sak, Jarosław Jerzy; Tarach, Jerzy; Toruń-Jurkowska, Anna; Lachowska-Kotowska, Patrycja; Dzida, Grzegorz

    2016-01-01

    The aim of the present study was to evaluate the concentrations of fetuin-A, osteoprotegerin (OPG) and α-Klotho protein in patients with alcoholic cirrhosis at different stages of the disease, and to demonstrate that fetuin-A, osteoprotegin and α-Klotho may be used as markers of the severity of cirrhosis. A total of 54 patients with alcoholic liver cirrhosis treated in various hospitals in the Lublin region of Poland were randomly enrolled. The control group consisted of 18 healthy individuals without liver disease, who did not drink alcohol. Serum levels of fetuin-A, OPG and α-Klotho were measured by ELISA kits. Levels of fetuin-A were significantly reduced in patients with alcoholic liver cirrhosis compared with the control group. OPG levels were higher in patients with alcoholic liver cirrhosis than in the controls, whereas the levels of α-Klotho were comparable in the cirrhosis and control groups. No statistically significant differences in the concentrations of fetuin-A, OPG and α-Klotho protein were demonstrated according to type of liver cirrhosis. The findings of the present study revealed a significant negative correlation between the level of α-Klotho protein and C-reactive protein in the patients with alcoholic liver cirrhosis. Concentrations of fetuin-A were lower, whereas those of OPG were higher, in the alcoholic liver cirrhosis group compared with the control group. Fetuin-A, OPG and α-Klotho may not be good indicators of liver cirrhosis severity. In conclusion, fetuin-A and OPG may be used in the diagnosis of liver cirrhosis. PMID:27882180

  8. Liver transplantation for hepatic cirrhosis in cystic fibrosis.

    PubMed Central

    Noble-Jamieson, G; Valente, J; Barnes, N D; Friend, P J; Jamieson, N V; Rasmussen, A; Calne, R Y

    1994-01-01

    Five children with cystic fibrosis complicated by hepatic cirrhosis received liver grafts. They all had portal hypertension with varices and three had variceal bleeding; respiratory function was only moderately impaired, but four were colonised with pseudomonas and one with aspergillus. Liver transplantation was well tolerated and there was no increase in respiratory or other early postoperative complications. Four of the children were fully well from 14 to 35 months after transplantation; the most recently transplanted had problems from a biliary stricture. In spite of the need for immunosuppression there was no increase in infection and respiratory function improved or remained stable. Once the children were stabilised after transplantation their nutrition and general health were greatly improved. PMID:7979532

  9. Impact of a CXCL12/CXCR4 Antagonist in Bleomycin (BLM) Induced Pulmonary Fibrosis and Carbon Tetrachloride (CCl4) Induced Hepatic Fibrosis in Mice

    PubMed Central

    Chow, Leola N.; Schreiner, Petra; Ng, Betina Y. Y.; Lo, Bernard; Hughes, Michael R.; Scott, R. Wilder; Gusti, Vionarica; Lecour, Samantha; Simonson, Eric; Manisali, Irina; Barta, Ingrid; McNagny, Kelly M.; Crawford, Jason; Webb, Murray; Underhill, T. Michael

    2016-01-01

    Modulation of chemokine CXCL12 and its receptor CXCR4 has been implicated in attenuation of bleomycin (BLM)-induced pulmonary fibrosis and carbon tetrachloride (CCl4)-induced hepatic injury. In pulmonary fibrosis, published reports suggest that collagen production in the injured lung is derived from fibrocytes recruited from the circulation in response to release of pulmonary CXCL12. Conversely, in hepatic fibrosis, resident hepatic stellate cells (HSC), the key cell type in progression of fibrosis, upregulate CXCR4 expression in response to activation. Further, CXCL12 induces HSC proliferation and subsequent production of collagen I. In the current study, we evaluated AMD070, an orally bioavailable inhibitor of CXCL12/CXCR4 in alleviating BLM-induced pulmonary and CCl4-induced hepatic fibrosis in mice. Similar to other CXCR4 antagonists, treatment with AMD070 significantly increased leukocyte mobilization. However, in these two models of fibrosis, AMD070 had a negligible impact on extracellular matrix deposition. Interestingly, our results indicated that CXCL12/CXCR4 signaling has a role in improving mortality associated with BLM induced pulmonary injury, likely through dampening an early inflammatory response and/or vascular leakage. Together, these findings indicate that the CXCL12-CXCR4 signaling axis is not an effective target for reducing fibrosis. PMID:26998906

  10. Impact of a CXCL12/CXCR4 Antagonist in Bleomycin (BLM) Induced Pulmonary Fibrosis and Carbon Tetrachloride (CCl4) Induced Hepatic Fibrosis in Mice.

    PubMed

    Chow, Leola N; Schreiner, Petra; Ng, Betina Y Y; Lo, Bernard; Hughes, Michael R; Scott, R Wilder; Gusti, Vionarica; Lecour, Samantha; Simonson, Eric; Manisali, Irina; Barta, Ingrid; McNagny, Kelly M; Crawford, Jason; Webb, Murray; Underhill, T Michael

    2016-01-01

    Modulation of chemokine CXCL12 and its receptor CXCR4 has been implicated in attenuation of bleomycin (BLM)-induced pulmonary fibrosis and carbon tetrachloride (CCl4)-induced hepatic injury. In pulmonary fibrosis, published reports suggest that collagen production in the injured lung is derived from fibrocytes recruited from the circulation in response to release of pulmonary CXCL12. Conversely, in hepatic fibrosis, resident hepatic stellate cells (HSC), the key cell type in progression of fibrosis, upregulate CXCR4 expression in response to activation. Further, CXCL12 induces HSC proliferation and subsequent production of collagen I. In the current study, we evaluated AMD070, an orally bioavailable inhibitor of CXCL12/CXCR4 in alleviating BLM-induced pulmonary and CCl4-induced hepatic fibrosis in mice. Similar to other CXCR4 antagonists, treatment with AMD070 significantly increased leukocyte mobilization. However, in these two models of fibrosis, AMD070 had a negligible impact on extracellular matrix deposition. Interestingly, our results indicated that CXCL12/CXCR4 signaling has a role in improving mortality associated with BLM induced pulmonary injury, likely through dampening an early inflammatory response and/or vascular leakage. Together, these findings indicate that the CXCL12-CXCR4 signaling axis is not an effective target for reducing fibrosis.

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

    PubMed

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

    2010-05-01

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

  12. alpha 2-Plasmin inhibitor metabolism in patients with liver cirrhosis.

    PubMed

    Knot, E A; Drijfhout, H R; ten Cate, J W; de Jong, E; Iburg, A H; Kahlé, L H; Grijm, R

    1985-03-01

    We describe the metabolism of purified human alpha 2-plasmin inhibitor in patients with liver cirrhosis to determine whether low plasma concentrations of alpha 2-plasmin inhibitor are the result of impaired synthesis or increased catabolism or both. A kinetic study was performed with 131I-alpha 2-plasmin inhibitor as a sensitive parameter of fibrinolysis in 14 patients with histologically proved liver cirrhosis compared with six healthy control subjects. Eight patients had macronodular cirrhosis (with positive hepatitis B surface antigen), and six had micronodular cirrhosis as a result of alcohol abuse. None of the patients had clinical signs of ascites, and in all the disease was stabilized. alpha 2-Plasmin inhibitor levels biologically and immunologically measured were decreased in all patients. Ten microCi 131I-alpha 2PI was injected intravenously, the disappearance of plasma radioactivity was measured, and turnover data were calculated according to the function x(t) = A1e-alpha 1t + A2e-alpha 2t + Be-beta t. Mean (+/- SD) turnover data in the control subjects were plasma radioactivity half-life 60.1 +/- 5.3 hours, fractional catabolic rate constant of the plasma pool 0.0318 +/- 0.0106 hr-1, and absolute catabolic (synthetic) rate constant 2.10 +/- 0.60 mg/kg/day. The alpha 1-phase was 1.26 +/- 0.23, and the transcapillary influx constant (k2,1) was 0.974 +/- 0.109 hr-1. In the patients, plasma radioactivity half-life was 58.7 +/- 12.09 hr, and fractional catabolic rate constant of the plasma pool 0.0283 +/- 0.0043 hr-1. The alpha 1-phase 4.74 +/- 6.48 and the transcapillary influx (k2,1) 3.08 +/- 3.9 hr-1 were both significantly increased compared with control values (p less than 0.05 and p less than 0.05, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

  13. Outcomes of abdominal surgery in patients with liver cirrhosis

    PubMed Central

    Lopez-Delgado, Juan C; Ballus, Josep; Esteve, Francisco; Betancur-Zambrano, Nelson L; Corral-Velez, Vicente; Mañez, Rafael; Betbese, Antoni J; Roncal, Joan A; Javierre, Casimiro

    2016-01-01

    Patients suffering from liver cirrhosis (LC) frequently require non-hepatic abdominal surgery, even before liver transplantation. LC is an important risk factor itself for surgery, due to the higher than average associated morbidity and mortality. This high surgical risk occurs because of the pathophysiology of liver disease itself and to the presence of contributing factors, such as coagulopathy, poor nutritional status, adaptive immune dysfunction, cirrhotic cardiomyopathy, and renal and pulmonary dysfunction, which all lead to poor outcomes. Careful evaluation of these factors and the degree of liver disease can help to reduce the development of complications both during and after abdominal surgery. In the emergency setting, with the presence of decompensated LC, alcoholic hepatitis, severe/advanced LC, and significant extrahepatic organ dysfunction conservative management is preferred. A multidisciplinary, individualized, and specialized approach can improve outcomes; preoperative optimization after risk stratification and careful management are mandatory before surgery. Laparoscopic techniques can also improve outcomes. We review the impact of LC on surgical outcome in non-hepatic abdominal surgeries required in this cirrhotic population before, during, and after surgery. PMID:26973406

  14. Outcomes of abdominal surgery in patients with liver cirrhosis.

    PubMed

    Lopez-Delgado, Juan C; Ballus, Josep; Esteve, Francisco; Betancur-Zambrano, Nelson L; Corral-Velez, Vicente; Mañez, Rafael; Betbese, Antoni J; Roncal, Joan A; Javierre, Casimiro

    2016-03-07

    Patients suffering from liver cirrhosis (LC) frequently require non-hepatic abdominal surgery, even before liver transplantation. LC is an important risk factor itself for surgery, due to the higher than average associated morbidity and mortality. This high surgical risk occurs because of the pathophysiology of liver disease itself and to the presence of contributing factors, such as coagulopathy, poor nutritional status, adaptive immune dysfunction, cirrhotic cardiomyopathy, and renal and pulmonary dysfunction, which all lead to poor outcomes. Careful evaluation of these factors and the degree of liver disease can help to reduce the development of complications both during and after abdominal surgery. In the emergency setting, with the presence of decompensated LC, alcoholic hepatitis, severe/advanced LC, and significant extrahepatic organ dysfunction conservative management is preferred. A multidisciplinary, individualized, and specialized approach can improve outcomes; preoperative optimization after risk stratification and careful management are mandatory before surgery. Laparoscopic techniques can also improve outcomes. We review the impact of LC on surgical outcome in non-hepatic abdominal surgeries required in this cirrhotic population before, during, and after surgery.

  15. Non-invasive diagnosis of liver fibrosis and cirrhosis.

    PubMed

    Lurie, Yoav; Webb, Muriel; Cytter-Kuint, Ruth; Shteingart, Shimon; Lederkremer, Gerardo Z

    2015-11-07

    The evaluation and follow up of liver fibrosis and cirrhosis have been traditionally performed by liver biopsy. However, during the last 20 years, it has become evident that this "gold-standard" is imperfect; even according to its proponents, it is only "the best" among available methods. Attempts at uncovering non-invasive diagnostic tools have yielded multiple scores, formulae, and imaging modalities. All are better tolerated, safer, more acceptable to the patient, and can be repeated essentially as often as required. Most are much less expensive than liver biopsy. Consequently, their use is growing, and in some countries the number of biopsies performed, at least for routine evaluation of hepatitis B and C, has declined sharply. However, the accuracy and diagnostic value of most, if not all, of these methods remains controversial. In this review for the practicing physician, we analyze established and novel biomarkers and physical techniques. We may be witnessing in recent years the beginning of the end of the first phase for the development of non-invasive markers. Early evidence suggests that they might be at least as good as liver biopsy. Novel experimental markers and imaging techniques could produce a dramatic change in diagnosis in the near future.

  16. Differential Sympathetic Vasomotor Activation Induced by Liver Cirrhosis in Rats

    PubMed Central

    Bergamaschi, Cássia T.; Campos, Ruy R.

    2016-01-01

    We tested the hypothesis that there is a topographical sympathetic activation in rats submitted to experimental cirrhosis. Baseline renal (rSNA) and splanchnic (sSNA) sympathetic nerve activities were evaluated in anesthetized rats. In addition, we evaluated main arterial pressure (MAP), heart rate (HR), and baroreceptor reflex sensitivity (BRS). Cirrhotic Wistar rats were obtained by bile duct ligation (BDL). MAP and HR were measured in conscious rats, and cardiac BRS was assessed by changes in blood pressure induced by increasing doses of phenylephrine or sodium nitroprusside. The BRS and baseline for the control of sSNA and rSNA were also evaluated in urethane-anesthetized rats. Cirrhotic rats had increased baseline sSNA (BDL, 102 vs control, 58 spikes/s; p<0.05), but no baseline changes in the rSNA compared to controls. These data were accompanied by increased splanchnic BRS (p<0.05) and decreased cardiac (p<0.05) and renal BRS (p<0.05). Furthermore, BDL rats had reduced basal MAP (BDL, 93 vs control, 101 mmHg; p<0.05) accompanied by increased HR (BDL, 378 vs control, 356; p<0.05). Our data have shown topographical sympathetic activation in rats submitted to experimental cirrhosis. The BDL group had increased baseline sSNA, independent of dysfunction in the BRS and no changes in baseline rSNA. However, an impairment of rSNA and HR control by arterial baroreceptor was noted. We suggest that arterial baroreceptor impairment of rSNA and HR is an early marker of cardiovascular dysfunction related to liver cirrhosis and probably a major mechanism leading to sympathoexcitation in decompensated phase. PMID:27055088

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

    PubMed Central

    Kowalczyk, Wojciech; Krasuska-Sławińska, Ewa; Dądalski, Maciej; Kostewicz, Krzysztof; Pawłowska, Joanna

    2014-01-01

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

  18. Behavior of Oxidative Stress Markers in Alcoholic Liver Cirrhosis Patients

    PubMed Central

    Galicia-Moreno, Marina; Rosique-Oramas, Dorothy; Medina-Avila, Zaira; Álvarez-Torres, Tania; Falcón, Dalia; Higuera-de la tijera, Fátima; Béjar, Yadira L.; Cordero-Pérez, Paula; Muñoz-Espinosa, Linda; Pérez-Hernández, José Luis; Kershenobich, David

    2016-01-01

    Alcohol is the most socially accepted addictive substance worldwide, and its metabolism is related with oxidative stress generation. The aim of this work was to evaluate the role of oxidative stress in alcoholic liver cirrhosis (ALC). This study included 187 patients divided into two groups: ALC, classified according to Child-Pugh score, and a control group. We determined the levels of reduced and oxidized glutathione (GSH and GSSG) and the GSH/GSSG ratio by an enzymatic method in blood. Also, protein carbonyl and malondialdehyde (MDA) content were estimated in serum. MDA levels increased in proportion to the severity of damage, whereas the GSH and GSSG levels decreased and increased, respectively, at different stages of cirrhosis. There were no differences in the GSH/GSSG ratio and carbonylated protein content between groups. We also evaluated whether the active consumption of or abstinence from alcoholic beverages affected the behavior of these oxidative markers and only found differences in the MDA, GSH, and GSSG determination and the GSH/GSSG ratio. Our results suggest that alcoholic cirrhotic subjects have an increase in oxidative stress in the early stages of disease severity and that abstinence from alcohol consumption favors the major antioxidant endogen: GSH in patients with advanced disease severity. PMID:28074118

  19. Amiodarone-Induced Cirrhosis of Liver: What Predicts Mortality?

    PubMed Central

    Hussain, Nasir

    2013-01-01

    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

  20. Behavior of Oxidative Stress Markers in Alcoholic Liver Cirrhosis Patients.

    PubMed

    Galicia-Moreno, Marina; Rosique-Oramas, Dorothy; Medina-Avila, Zaira; Álvarez-Torres, Tania; Falcón, Dalia; Higuera-de la Tijera, Fátima; Béjar, Yadira L; Cordero-Pérez, Paula; Muñoz-Espinosa, Linda; Pérez-Hernández, José Luis; Kershenobich, David; Gutierrez-Reyes, Gabriela

    2016-01-01

    Alcohol is the most socially accepted addictive substance worldwide, and its metabolism is related with oxidative stress generation. The aim of this work was to evaluate the role of oxidative stress in alcoholic liver cirrhosis (ALC). This study included 187 patients divided into two groups: ALC, classified according to Child-Pugh score, and a control group. We determined the levels of reduced and oxidized glutathione (GSH and GSSG) and the GSH/GSSG ratio by an enzymatic method in blood. Also, protein carbonyl and malondialdehyde (MDA) content were estimated in serum. MDA levels increased in proportion to the severity of damage, whereas the GSH and GSSG levels decreased and increased, respectively, at different stages of cirrhosis. There were no differences in the GSH/GSSG ratio and carbonylated protein content between groups. We also evaluated whether the active consumption of or abstinence from alcoholic beverages affected the behavior of these oxidative markers and only found differences in the MDA, GSH, and GSSG determination and the GSH/GSSG ratio. Our results suggest that alcoholic cirrhotic subjects have an increase in oxidative stress in the early stages of disease severity and that abstinence from alcohol consumption favors the major antioxidant endogen: GSH in patients with advanced disease severity.

  1. UDP-glucuronosyltransferase 1A7 polymorphisms are associated with liver cirrhosis.

    PubMed

    Tang, Kung-Sheng; Lee, Chuan-Mo; Teng, Hsiu-Chen; Huang, May-Jen; Huang, Ching-Shan

    2008-02-15

    Variations in the UDP-glucuronosyltransferase (UGT) 1A7 gene have been found to be related to the development of hepatocellular carcinoma (HCC). Since the pathogenesis of liver cirrhosis is not dissimilar to that of HCC, we hypothesized that UGT1A7 genetic polymorphisms may be associated with liver cirrhosis. PCR-restriction fragment length polymorphism was utilized to determine UGT for 1A7 genotypes for the 159 patients with liver cirrhosis and 263 gender/age matched controls. Simple logistic regression analysis revealed that significant risk factors for liver cirrhosis were (1) hepatitis B virus (HBV) infection, (2) hepatitis C virus (HCV) infection, (3) HBV infection plus HCV infection and (4) low-activity UGT1A7 genotypes. The results of further multivariate logistic regression confirmed these associations. Interaction of low-activity UGT1A7 genotypes and HBV (or HCV) infection produced an additive effect upon the risk for the development of liver cirrhosis [observed odds ratio (OR) (54.59) greater than the expected OR (18.05)]. UGT1A7 low/low genotype was also related to advanced liver cirrhosis (Child-Pugh classes C and/or B) (OR=7.50, P=0.009). This study demonstrates the novel findings that carriage of low-activity UGT1A7 genotypes represents a risk factor for the development and functional severity of liver cirrhosis.

  2. Terahertz spectroscopy of liver cirrhosis: investigating the origin of contrast

    NASA Astrophysics Data System (ADS)

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

    2010-12-01

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

  3. The immunopathology of liver granulomas in primary biliary cirrhosis.

    PubMed

    You, Zhengrui; Wang, Qixia; Bian, Zhaolian; Liu, Yuan; Han, Xiaofeng; Peng, Yanshen; Shen, Lei; Chen, Xiaoyu; Qiu, Dekai; Selmi, Carlo; Gershwin, M Eric; Ma, Xiong

    2012-09-01

    Liver granulomas and elevated serum IgM are commonly observed in patients with primary biliary cirrhosis (PBC) but their pathogenetic significance remains largely unknown. To address this issue we performed an extensive immunostaining and colocalization study of markers associated with dendritic cells and IgM in a large cohort of tissue samples from PBC and control livers as well as from non-hepatic granulomatous diseases. First, the classical dendritic cell CD11c marker is highly expressed and more sensitive than classical hematoxylin-eosin staining in detecting granulomas associated with PBC and other conditions. Second, PBC cases with CD11c-positive granulomas have significantly higher serum IgM levels and earlier disease stages. Third, granulomas from PBC and other diseases demonstrate markers of dendritic cell immaturity, i.e. CD11b, reduced MHC II, IL-23, CCR7 and CD83 expression, and elevated C1q expression. Lastly, B cells and IgM-positive plasma cells are largely represented around PBC granulomas along with macrophages. In conclusion, our comprehensive immunohistochemical study suggests that dendritic cells are key to the pathogenesis of granulomas, regardless of their origin. More specifically, PBC liver granulomas may result from the interaction between immature dendritic cells and IgM.

  4. Kallistatin, a new and reliable biomarker for the diagnosis of liver cirrhosis.

    PubMed

    Cheng, Zhiyun; Lv, Yinghui; Pang, Suqiu; Bai, Ruyu; Wang, Mingxi; Lin, Shuyu; Xu, Tianwen; Spalding, Duncan; Habib, Nagy; Xu, Ruian

    2015-05-01

    Kallistatin, which protects organs and cells against inflammation, fibrosis and oxidative stress, is mainly synthesized and secreted in liver. However, its relationship to human liver disease remains unclear. The purpose of this study was to explore the relationship between serum kallistatin and clinical evidence of both cirrhosis and hepatocellular carcinoma (HCC), and to determine if serum kallistatin levels could be used as a diagnostic indicator of hepatic health status, especially human liver cirrhosis (LC). Our cohort consisted of 115 patients with clinically proven liver fibrosis (LF), LC, or HCC by liver biopsies, and 31 healthy controls (CON). Serum kallistatin levels were quantified by ELISA. Results of the present study demonstrated that irrespective of the underlying etiology, serum kallistatin levels were significantly lower in the LF/LC group when compared with the CON group. A decrease in serum kallistatin levels appeared to reflect the extent of cirrhosis, with the lowest levels associated with higher grades of cirrhosis. Patients with LC had a noticeable correlation between serum kallistatin levels and other serum biochemical indicators. The area under the curve (AUC) for LC, viral liver cirrhosis (VLC) and alcoholic liver cirrhosis (ALC) was 0.845, 0.757 and 0.931, respectively. In conclusion, our findings demonstrated that kallistatin, a plasma protein produced by the liver, can be a useful and reliable diagnostic indicator of hepatic health status, especially for LC.

  5. Liver cirrhosis in selected autoimmune diseases: a nationwide cohort study in Taiwan.

    PubMed

    Tung, Chien-Hsueh; Lai, Ning-Seng; Lu, Ming-Chi; Lee, Ching-Chih

    2016-02-01

    The association between autoimmune diseases and liver cirrhosis has rarely been explored in Asian populations, an endemic area of viral hepatitis. The aim of this study was to investigate the comparative risk of liver cirrhosis among a group of selective autoimmune diseases in Taiwanese patients and to identify groups of high risk. This retrospective study was a nationwide, population-based study and used Taiwan's National Health Insurance Research Database. A total of 29,856 patients with definite diagnosis of selected autoimmune diseases (Registry of Taiwan Catastrophic Illness Database, ACR classification) at the starting time point of January 1, 2005, were enrolled in this study. After tracked for a 5-year period, the endpoints were diagnosis of liver cirrhosis (in accordance with International Classification of Diseases, Ninth Revision, Clinical Modification, ICD-9-CM codes 571). The control group was composed of other patients in the same database and consisted of randomly selected 753,495 sex- and age-matched non-autoimmune disease patients. The Cox proportional hazard regression model was used to calculate the risk of liver cirrhosis after adjusting for certain variables such as comorbidity, living area, and socioeconomic status. Among the patients with selected autoimmune diseases, 1987 liver cirrhosis were observed. Patients with psoriasis had a significantly increased risk of liver cirrhosis (HR 1.87, 95 % CI 1.25-2.81) than control group without psoriasis. The risk of liver cirrhosis was significantly lower in patients with rheumatoid arthritis (HR 0.29, 95 % CI 0.19-0.44). There is a gradient of risk of liver cirrhosis among the autoimmune diseases; the specific risks need to be investigated on the basis of hypotheses. Conventional immunosuppressive drug administration should be carefully implemented by regular monitoring of liver condition in order to avoid causing an adverse effect of chronic liver fibrosis.

  6. Transketolase-TPP-effect in chronic alcoholics with various degrees of liver cirrhosis.

    PubMed

    Somogyi, J C; Kopp, P M; Filippini, L; Monnat, A

    1980-01-01

    A re-investigation of the use of the transketolase-TPP-effect for the assessment of the thiamine status of chronic alcoholics with various degrees of liver cirrhosis was carried out on 36 alcoholics. The extent of the liver damage in these patients was established by clinical examinations and biochemical tests. Fourteen persons showed no significant hepatic abnormalities, 5 patients had compensated liver cirrhosis, 7 slightly decompensated, and 10 patients suffered from severely decompensated liver cirrhosis. This investigation shows that the transketolase-TPP-effect is also present in patients even with severe liver cirrhosis and that a decrease of the TPP-effect can be observed after oral thiamine administration in these subjects. The TPP-effect of patients with compensated liver cirrhosis was markedly smaller than that of the subjects with slightly or severely decompensated cirrhosis. Accordingly a relationship exists between the TPP-effect and the degree of liver damage. No other correlations however could be established in this respect.

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

    PubMed

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

    2015-05-01

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

  8. [Metabolic disturbances in liver cirrhosis (part 1)--hepatic osteopathy and malnutrition].

    PubMed

    Gundling, F; Seidl, H; Löffler, N; Strassen, I; Schepp, W

    2009-11-01

    Medical treatment of patients with liver cirrhosis consists mainly of symptomatic therapy of associated complications. Apart from the classical complications of cirrhosis, e. g. ascites, portal hypertension or hepatic encephalopathy, other frequent complications are neglected in everyday medicine. The incidence of metabolic disturbances seems to be similar to the prevalence of classical complications of liver cirrhosis, such as portal hypertension or ascites. Osteoporosis is an important manifestation of hepatic osteopathy, especially in chronic cholestatic diseases and in candidates for liver transplantation, which necessitates timely adequate diagnostic test (e. g. osteodensitometry) and treatment (pre-emptive and causal). Malnutrition, especially when related to protein- and energy supply, is very common in patients with liver cirrhosis and has prognostic significance regarding mortality and complication rates. A sufficient daily energy and protein supply should be ensured, one which is higher than that for the normal population. Additional substitution of vitamins and trace elements is indicated when symptoms of deficiency became apparent.

  9. Torsion of the gallbladder, localized in right subphrenic space in a patient with liver cirrhosis.

    PubMed

    Maruyama, Yuichiro; Tanaka, Yuya; Yasunaga, Masafumi; Ogata, Kei; Tanaka, Hiroyuki; Akagi, Yoshito; Okuda, Koji

    2015-12-01

    We report a case of torsion of the gallbladder displaced under the right subphrenic space in a patient with liver cirrhosis. An 82-year-old Japanese woman was admitted to our hospital for acute pain in the right upper quadrant. Clinical features suggested gallbladder torsion. She was under treatment for hepatitis C virus-related cirrhosis at our hospital. Abdominal CT showed the swollen fundus and body of the gallbladder under the right subphrenic space. Emergency laparoscopic cholecystectomy was performed. Intraoperative findings included a grossly necrotic gallbladder in the right subphrenic space with 360° clockwise torsion, together with liver cirrhosis and localized peritonitis. The clinical features and imaging findings in this rare case of misplaced gallbladder in right subphrenic space resembled those described in typical strangulated gallbladder. The displacement was probably related to right liver lobe atrophy associated with liver cirrhosis. Appropriate diagnosis and prompt surgical treatment are essential for a positive outcome.

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

    PubMed Central

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

    2012-01-01

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

  11. Serum Liver Fibrosis Markers in the Prognosis of Liver Cirrhosis: A Prospective Observational Study.

    PubMed

    Qi, Xingshun; Liu, Xu; Zhang, Yongguo; Hou, Yue; Ren, Linan; Wu, Chunyan; Chen, Jiang; Xia, Chunlian; Zhao, Jiajun; Wang, Di; Zhang, Yanlin; Zhang, Xia; Lin, Hao; Wang, Hezhi; Wang, Jinling; Cui, Zhongmin; Li, Xueyan; Deng, Han; Hou, Feifei; Peng, Ying; Wang, Xueying; Shao, Xiaodong; Li, Hongyu; Guo, Xiaozhong

    2016-08-02

    BACKGROUND The prognostic role of serum liver fibrosis markers in cirrhotic patients remains unclear. We performed a prospective observational study to evaluate the effect of amino-terminal pro-peptide of type III pro-collagen (PIIINP), collagen IV (CIV), laminin (LN), and hyaluronic acid (HA) on the prognosis of liver cirrhosis. MATERIAL AND METHODS All patients who were diagnosed with liver cirrhosis and admitted to our department were prospectively enrolled. PIIINP, CIV, LN, and HA levels were tested. RESULTS Overall, 108 cirrhotic patients were included. Correlation analysis demonstrated that CIV (coefficient r: 0.658, p<0.001; coefficient r: 0.368, p<0.001), LN (coefficient r: 0.450, p<0.001; coefficient r: 0.343, p<0.001), and HA (coefficient r: 0.325, p=0.001; coefficient r: 0.282, p=0.004) levels, but not PIIINP level (coefficient r: 0.081, p=0.414; coefficient r: 0.090, p=0.363), significantly correlated with Child-Pugh and MELD scores. Logistic regression analysis demonstrated that HA (odds ratio=1.00003, 95% confidence interval [CI]=1.000004-1.000056, p=0.022) was significantly associated with the 6-month mortality. Receiver operating characteristics analysis demonstrated that the area under the curve (AUC) of HA for predicting the 6-month mortality was 0.612 (95%CI=0.508-0.709, p=0.1531). CONCLUSIONS CIV, LN, and HA levels were significantly associated with the severity of liver dysfunction, but might be inappropriate for the prognostic assessment of liver cirrhosis.

  12. Personalized management of cirrhosis by non-invasive tests of liver fibrosis

    PubMed Central

    Wong, Grace Lai-Hung; Espinosa, Wendell Zaragoza

    2015-01-01

    Owing to the high prevalence of various chronic liver diseases, cirrhosis is one of the leading causes of morbidity and mortality worldwide. In recent years, the development of non-invasive tests of fibrosis allows accurate diagnosis of cirrhosis and reduces the need for liver biopsy. In this review, we discuss the application of these non-invasive tests beyond the diagnosis of cirrhosis. In particular, their role in the selection of patients for hepatocellular carcinoma surveillance and varices screening is highlighted. PMID:26523265

  13. A comparison of the accuracy of peritoneoscopy and liver biopsy in the diagnosis of cirrhosis

    PubMed Central

    Bruguera, M.; Bordas, J. M.; Mas, P.; Rodes, J.

    1974-01-01

    The accuracy of peritoneoscopy and liver biopsy in the diagnosis of hepatic cirrhosis was compared in 473 consecutive patients submitted to both procedures. One hundred and fifty-two of them had cirrhosis diagnosed by one or both methods. There was 73% agreement between the two procedures. `Apparent' false-negative results were 17·7% for peritoneoscopy and 9·3% for liver biopsy. The incidence of false-negative results in the diagnosis of cirrhosis can be reduced by combining both procedures. PMID:4279817

  14. Skeletal muscle myopenia in mice model of bile duct ligation and carbon tetrachloride-induced liver cirrhosis.

    PubMed

    Giusto, Michela; Barberi, Laura; Di Sario, Francesca; Rizzuto, Emanuele; Nicoletti, Carmine; Ascenzi, Francesca; Renzi, Anastasia; Caporaso, Nicola; D'Argenio, Giuseppe; Gaudio, Eugenio; Musarò, Antonio; Merli, Manuela

    2017-04-01

    Skeletal muscle myopathy is universal in cirrhotic patients, however, little is known about the main mechanisms involved. The study aims to investigate skeletal muscle morphological, histological, and functional modifications in experimental models of cirrhosis and the principal molecular pathways responsible for skeletal muscle myopathy. Cirrhosis was induced by bile duct ligation (BDL) and carbon tetrachloride (CCl4) administration in mice. Control animals (CTR) underwent bile duct exposure or vehicle administration only. At sacrifice, peripheral muscles were dissected and weighed. Contractile properties of extensor digitorum longus (EDL) were studied in vitro. Muscle samples were used for histological and molecular analysis. Quadriceps muscle histology revealed a significant reduction in cross-sectional area of muscle and muscle fibers in cirrhotic mice with respect to CTR. Kinetic properties of EDL in both BDL and CCl4 were reduced with respect to CTR; BDL mice also showed a reduction in muscle force and a decrease in the resistance to fatigue. Increase in myostatin expression associated with a decrease in AKT-mTOR expressions was observed in BDL mice, together with an increase in LC3 protein levels. Upregulation of the proinflammatory citochines TNF-a and IL6 and an increased expression of NF-kB and MuRF-1 were observed in CCl4 mice. In conclusion, skeletal muscle myopenia was present in experimental models of BDL and CCl4-induced cirrhosis. Moreover, reduction in protein synthesis and activation of protein degradation were the main mechanisms responsible for myopenia in BDL mice, while activation of ubiquitin-pathway through inflammatory cytokines seems to be the main potential mechanism involved in CCl4 mice.

  15. Baculovirus-mediated interferon alleviates dimethylnitrosamine-induced liver cirrhosis symptoms in a murine model.

    PubMed

    Nishibe, Y; Kaneko, H; Suzuki, H; Abe, T; Matsuura, Y; Takaku, H

    2008-07-01

    The wild-type baculovirus Autographa californica multiple nuclear polyhedrosis virus (AcMNPV) infects a range of mammalian cell types in vitro but does not replicate in these cells. The current study investigated the in vivo effect of AcMNPV in the mouse model of liver cirrhosis induced by the mutagen dimethylnitrosamine. Intraperitoneal injection of AcMNPV induced an immune response. The baculovirus was taken up by the liver and spleen where it suppressed liver injury and fibrosis through the induction of interferons. This study presents the first evidence of the feasibility of using baculovirus to treat liver cirrhosis.

  16. Learning to Diagnose Cirrhosis with Liver Capsule Guided Ultrasound Image Classification

    PubMed Central

    Liu, Xiang; Song, Jia Lin; Wang, Shuo Hong; Zhao, Jing Wen; Chen, Yan Qiu

    2017-01-01

    This paper proposes a computer-aided cirrhosis diagnosis system to diagnose cirrhosis based on ultrasound images. We first propose a method to extract a liver capsule on an ultrasound image, then, based on the extracted liver capsule, we fine-tune a deep convolutional neural network (CNN) model to extract features from the image patches cropped around the liver capsules. Finally, a trained support vector machine (SVM) classifier is applied to classify the sample into normal or abnormal cases. Experimental results show that the proposed method can effectively extract the liver capsules and accurately classify the ultrasound images. PMID:28098774

  17. Expression of antisense of microRNA-26a-5p in mesenchymal stem cells increases their therapeutic effects against cirrhosis

    PubMed Central

    Chen, Li; Zeng, Wenhuan; Yang, Bo; Cui, Xiang; Feng, Cong; Wang, Lili; Wang, Hao; Zhou, Xuan; Li, Peng; Lv, Faqin; Li, Tanshi

    2017-01-01

    Hepatocyte growth factor (HGF) is a potent mitogen for mature hepatocytes, and has been shown to prevent cirrhosis during liver regeneration. Transplantation of mesenchymal stem cells (MSCs) reduces the development of cirrhosis after liver injury. However, the production and secretion of transplanted MSCs in liver were not studied yet. Here we found that the MSCs expressed low levels of HGF protein, but surprisingly high levels of HGF mRNA. Further investigation using bioinformatics analyses and luciferase reporter assay showed that MSCs expressed high levels of microRNA-26a-5p (miR-26a-5p), which targeted 3’-UTR of HGF mRNA to inhibit its protein translation. In vivo, miR-26a-5p-depleted MSCs were transplanted into mice with carbon tetrachloride (CCl4)-induced cirrhosis. We found that suppression of miR-26a-5p in MSCs further ameliorated the severity of liver fibrosis, reduced the portal hypertension and sodium retention, compared to transplantation of control MSCs. Hence, our study suggests that suppression of miR-26a-5p in MSCs may improve their therapeutic effects against cirrhosis through increasing HGF production. PMID:28386375

  18. Pharmacokinetics of oral brotizolam in patients with liver cirrhosis

    PubMed Central

    Jochemsen, Roeline; Joeres, R. P.; Wesselman, J. G. J.; Richter, E.; Breimer, D. D.

    1983-01-01

    1 Disposition of oral brotizolam (0.5 mg) was studied in male patients with liver cirrhosis (patients) and in other patients (control) matched for age, weight, smoking and drinking habits. 2 Absorption of brotizolam was relatively rapid in both groups with a median peak time (range) of 1.0 (0.5-2.0) h. Peak concentrations were also similar with median values of 7.1 (3.2-10.7) ng/ml in patients and 9.4 (2.9-19.0 ng/ml) in controls. 3 Elimination half-life was longer in patients than in controls. The median values were 12.8 (9.4-25) h and 6.9 (4.4-8.4) h respectively (P < 0.01). In two patients hardly any drug elimination was observed, indicating severe impairment of drug metabolizing activity. The prolongation of the elimination half-life was likely to be due to a decrease in clearance (45 ml/min in patients compared with 64 ml/min in controls), and an increase in volume of distribution (0.62 l/kg and 0.39 l/kg respectively). 4 Median values of protein unbound fraction of brotizolam were 9.2 (7.8-10.4)% in controls and 12.4 (10.4-18.9)% in patients. Clearance of unbound drug was 612 ml/min and 380 ml/min respectively. PMID:6661377

  19. Nutrition and exercise in the management of liver cirrhosis.

    PubMed

    Toshikuni, Nobuyuki; Arisawa, Tomiyasu; Tsutsumi, Mikihiro

    2014-06-21

    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.

  20. Telomere Dysfunction in Nonalcoholic Fatty Liver Disease and Cryptogenic Cirrhosis.

    PubMed

    Laish, Ido; Mannasse-Green, Batya; Hadary, Ruth; Biron-Shental, Tal; Konikoff, Fred M; Amiel, Aliza; Kitay-Cohen, Yona

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) and cryptogenic cirrhosis (CC) are considered preneoplastic conditions that might progress to hepatocellular carcinoma. We evaluated parameters of telomere dysfunction in these patient groups to study the correlation between telomere length and the progression of NAFLD. We analyzed peripheral lymphocytes from 22 patients with NAFLD, 20 patients with CC, and 20 healthy, age-matched controls. Telomere length was analyzed using quantitative fluorescence in situ hybridization, and cellular senescence was evaluated by the percentage of cells with senescence-associated heterochromatin foci. The expression of telomerase reverse transcriptase (hTERT) mRNA was measured using polymerase chain reaction, and telomere capture (TC) was assessed with 2 Cytocell probes, 15qter and 13qter. Shorter telomere length and increased cellular senescence was demonstrated in patients with NAFLD, compared to the CC patients and healthy controls. While hTERT mRNA was significantly decreased, TC was increased in CC patients, compared to the NAFLD group and healthy individuals. Thus, there is a correlation between hTERT mRNA expression and telomere length in patients with NAFLD, which might be related to associated metabolic disorders and the risk of malignant transformation. Patients with CC, on the contrary, elongate their telomeres through the TC mechanism.

  1. Rectal administration of 13N-ammonia in cirrhosis of the liver.

    PubMed

    Hazenberg, H J; Gips, C H; Beekhuis, H; Vaalburg, W

    1976-01-01

    13N-ammonia, applied rectally, after absorption and transportation visualises the liver. After release of 13N-aminoacids and 13N-urea by the liver, 13N-activity can be measured over other organs. In patients with porta-systemic shunts, 13N-ammonia will appear in the systemic circulation as well. In 16 controls and 26 patients with cirrhosis, activities were measured for 20 minutes over liver, spleen, heart, lungs and forearm. In all subjects, the liver was visualised within a minute, in some patients with cirrhosis faintly, however. Release by the liver of 13N-ammonia metabolites started within a few minutes. Liver/heart activity ratios proved to be more discriminating between the control- and the cirrhosis group than liver/lung and liver/spleen ratios. In the control group, the 20 minutes' liver/heart ratio was most suitable for determining the normal range. The lower normal level was found to be 2.25. Fourteen of the 26 patients with cirrhosis had a normal, 12 an abnormally low 20 minutes' liver/heart ratio.

  2. Beyond "cirrhosis": a proposal from the International Liver Pathology Study Group.

    PubMed

    Hytiroglou, Prodromos; Snover, Dale C; Alves, Venancio; Balabaud, Charles; Bhathal, Prithi S; Bioulac-Sage, Paulette; Crawford, James M; Dhillon, Amar P; Ferrell, Linda; Guido, Maria; Nakanuma, Yasuni; Paradis, Valerie; Quaglia, Alberto; Theise, Neil D; Thung, Swan N; Tsui, Wilson M S; van Leeuwen, Dirk J

    2012-01-01

    "Cirrhosis" is a morphologic term that has been used for almost 200 years to denote the end stage of a variety of chronic liver diseases. The term implies a condition with adverse prognosis due to the well-known complications of portal hypertension, hepatocellular carcinoma, and liver failure. However, recent advances in the diagnosis and treatment of chronic liver diseases have changed the natural history of cirrhosis significantly. This consensus document by the International Liver Pathology Study Group challenges the usefulness of the word cirrhosis in modern medicine and suggests that this is an appropriate time to consider discontinuing the use of this term. The role of pathologists should evolve to the diagnosis of advanced stage of chronic liver disease, with emphasis on etiology, grade of activity, features suggestive of progression or regression, presence of other diseases, and risk factors for malignancy, within the perspective of an integrated clinicopathologic assessment.

  3. Etiology of liver cirrhosis in Brazil: chronic alcoholism and hepatitis viruses in liver cirrhosis diagnosed in the state of Espírito Santo

    PubMed Central

    Gonçalves, Patricia Lofego; da Penha Zago-Gomes, Maria; Marques, Carla Couzi; Mendonça, Ana Tereza; Gonçalves, Carlos Sandoval; Pereira, Fausto Edmundo Lima

    2013-01-01

    OBJECTIVES: To report the etiology of liver cirrhosis cases diagnosed at the University Hospital in Vitoria, Espirito Santo, Brazil. METHODS: The medical charts of patients with liver cirrhosis who presented to the University Hospital in Vitoria were reviewed. Chronic alcoholism and the presence of hepatitis B or C infections (HBV and HCV, respectively) were pursued in all cases. RESULTS: The sample consisted of 1,516 cases (male:female ratio 3.5:1, aged 53.2±12.6 years). The following main etiological factors were observed: chronic alcoholism alone (39.7%), chronic alcoholism in association with HBV or HCV (16.1%), HCV alone (14.5%) and in association with alcoholism (8.6%) (total, 23.1%), and HBV alone (13.1%) and in association with alcoholism (7.5%, total 20.6%). The remaining etiologies included cryptogenic cases (9.8%) and other causes (6.0%). The mean patient age was lower and the male-to-female ratio was higher in the cirrhosis cases that were associated with alcoholism or HBV compared with other causes. Intravenous drug abuse and a history of surgery or blood transfusion were significantly associated with HCV infection. Hepatocellular carcinoma was present at the time of diagnosis in 15.4% of cases. Chronic alcoholism associated with HCV infection was significantly associated (p<0.001) with reduced age (at the time of cirrhosis diagnosis) and increased prevalence of hepatocellular carcinoma (p = 0.052). CONCLUSION: Alcoholism, HCV and HBV are the main factors associated with liver cirrhosis in the state of Espirito Santo. Chronic alcoholism associated with HCV infection reduced the age of patients at the time of liver cirrhosis diagnosis. PMID:23644846

  4. Human umbilical cord mesenchymal stem cells improve liver function and ascites in decompensated liver cirrhosis patients.

    PubMed

    Zhang, Zheng; Lin, Hu; Shi, Ming; Xu, Ruonan; Fu, Junliang; Lv, Jiyun; Chen, Liming; Lv, Sa; Li, Yuanyuan; Yu, Shuangjie; Geng, Hua; Jin, Lei; Lau, George K K; Wang, Fu-Sheng

    2012-03-01

    Decompensated liver cirrhosis (LC), a life-threatening complication of chronic liver disease, is one of the major indications for liver transplantation. Recently, mesenchymal stem cell (MSC) transfusion has been shown to lead to the regression of liver fibrosis in mice and humans. This study examined the safety and efficacy of umbilical cord-derived MSC (UC-MSC) in patients with decompensated LC. A total of 45 chronic hepatitis B patients with decompensated LC, including 30 patients receiving UC-MSC transfusion, and 15 patients receiving saline as the control, were recruited; clinical parameters were detected during a 1-year follow-up period. No significant side-effects and complications were observed in either group. There was a significant reduction in the volume of ascites in patients treated with UC-MSC transfusion compared with controls (P < 0.05). UC-MSC therapy also significantly improved liver function, as indicated by the increase of serum albumin levels, decrease in total serum bilirubin levels, and decrease in the sodium model for end-stage liver disease scores. UC-MSC transfusion is clinically safe and could improve liver function and reduce ascites in patients with decompensated LC. UC-MSC transfusion, therefore, might present a novel therapeutic approach for patients with decompensated LC.

  5. Body mass index and risk of liver cirrhosis in middle aged UK women: prospective study

    PubMed Central

    Balkwill, Angela; Reeves, Gillian; Beral, Valerie

    2010-01-01

    Objective To determine the relation between body mass index (BMI) and liver cirrhosis and the contribution that BMI and alcohol consumption make to the incidence of liver cirrhosis in middle aged women in the UK. Design Prospective cohort study (Million Women Study). Setting Women recruited from 1996 to 2001 in NHS breast screening centres and followed by record linkage to routinely collected information on hospital admissions and deaths. Participants 1 230 662 women (mean age 56 years at recruitment) followed for an average of 6.2 years. Main outcome measures Relative risk and absolute risk of first hospital admission with or death from liver cirrhosis adjusted for age, recruitment region, alcohol consumption, smoking, socioeconomic status, and physical activity. Results 1811 women had a first hospital admission with or died from liver cirrhosis during follow-up. Among women with a BMI of 22.5 or above, increasing BMI was associated with an increased incidence of liver cirrhosis: the adjusted relative risk of cirrhosis increased by 28% (relative risk 1.28, 95% confidence interval 1.19 to 1.38; P<0.001) for every 5 unit increase in BMI. Although the relative increase in the risk of liver cirrhosis per 5 unit increase in BMI did not differ significantly according to the amount of alcohol consumed, the absolute risk did. Among women who reported drinking less than 70 g alcohol per week, the absolute risk of liver cirrhosis per 1000 women over five years was 0.8 (0.7 to 0.9) for those with a BMI between 22.5 and 25 and 1.0 (0.9 to 1.2) for those with a BMI of 30 or more. Among women who reported drinking 150 g alcohol or more per week, the corresponding figures were 2.7 (2.1 to 3.4) and 5.0 (3.8 to 6.6). Conclusions Excess body weight increases the incidence of liver cirrhosis. In middle aged women in the UK, an estimated 17% of incident or fatal liver cirrhosis is attributable to excess body weight. This compares with an estimated 42% attributable to alcohol

  6. Increased Th17 cells contribute to disease progression in patients with HBV-associated liver cirrhosis.

    PubMed

    Sun, H Q; Zhang, J Y; Zhang, H; Zou, Z S; Wang, F S; Jia, J H

    2012-06-01

    T helper (Th) 17 cells have been demonstrated to participate in the pathogenesis of HBV-associated liver damage. However, little is known regarding the immunopathogenic role of liver fibrosis in patients with HBV-associated liver cirrhosis. The aims of this study were to evaluate whether Th17 cells are related to disease progression in patients and to explore the possible mechanisms. The frequencies of circulating Th17 cells were analysed in 78 patients with hepatitis B and cirrhosis (Child A: 34; Child B: 22; Child C 22) and matched controls. Liver samples were collected from 13 patients with HBV-associated cirrhosis, 23 patients with chronic hepatitis B and 12 healthy controls for immunohistochemical analysis. IL-17 receptor expression was studied on liver biopsies and in human hepatic stellate cells as well as their response to recombinant IL-17 by flow cytometry. Patients with hepatitis B-associated cirrhosis with more severe disease displayed significant increases in peripheral numbers of Th17 cells as well as in IL-17 plasma levels. The increased intrahepatic IL-17(+) cells correlated positively with fibrotic staging scores and clinical progression from CHB to cirrhosis. Moreover, many IL-17(+) cells were located in fibrotic areas in the liver of patients with cirrhosis. In vitro, IL-17 together with IL-17-activated monocytes, could promote the activation of stellate cells, which, in turn, aggravated liver fibrosis and the inflammatory response. In summary, increased peripheral and intrahepatic Th17 cells are enriched in patients with hepatitis B and cirrhosis and contribute further to the severity of disease progression through induction of stellate cell activation.

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

    PubMed

    Montano-Loza, A J

    2013-06-01

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

  8. Hepatoprotective effect of Maytenus robusta Reiss extract on CCl4-induced hepatotoxicity in mice and HepG2 cells.

    PubMed

    Thiesen, Liliani Carolini; da Silva, Luisa Mota; Santin, José Roberto; Bresolin, Tania Mari Bellé; de Andrade, Sérgio Faloni; Amorim, Clarissa de Medeiros; Merlin, Lidia; de Freitas, Rilton Alves; Niero, Rivaldo; Netz, Daisy Janice Aguilar

    2017-03-08

    We investigated the hepatoprotective effect of methanolic extract from Maytenus robusta leaves in mice and HepG2 cells. The administration of CCl4 in mice promoted a deep destruction of the histological lobular structure and increased the alanine aminotransferase (ALT) serum levels by 46.25% compared with the control group (p < 0.05). The M. robusta extract reduced the hepatic histological changes and normalization the ALT levels. The antioxidant effect of M. robusta in liver tissue promoted the reduction in 31.5% on lipoperoxides levels (p < 0.05), increased by 101.5% the reduced glutathione content (p < 0.05) and increased the activity of superoxide dismutase, catalase, and glutathione-S-transferase by 21.3% (p < 0.05), 49.3% (p < 0.05), and 27.6% (p < 0.05), respectively, compared with the vehicle group. Moreover, the extract reduced hepatic inflammation by diminishing myeloperoxidase activity, TNF and interleukin-6 levels by 29.4% (p < 0.05), 46.1% (p < 0.01), and 59.5% (p < 0.0001), respectively, compared with the vehicle group. The viability of HepG2 cells after incubation with CCl4 was 29.56± 3.07%, whereas the extract (300 μg/mL) restored the viability to 65.27± 8.75% and aspartate aminotransferase levels to 41.82 ± 4.41 U/L. The extract scavenged DPPH (IC50 = 14.44 μg/mL) and ABTS (IC50 = 3.00 μg/mL) radicals and did not produce acute toxicity in mice at 2000 mg/kg. In conclusion, was confirmed the hepatoprotective potential of M. robusta by its antioxidant effects.

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

    PubMed

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

    2011-03-01

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

  10. [Routes of resorption of peritoneal fluid in the diaphragm in liver cirrhosis (morphologic study)].

    PubMed

    Khoroshaev, V A; Vorozheĭkin, V M; Baĭbekov, I M

    1991-01-01

    The diaphragm peritoneum from 12 operated patients and 34 patients who died from liver cirrhosis with or without ascites was studied by means of light microscopy and electron transmission and scanning microscopy. Considerable lesions are found in the peritoneum: cuboidization of mesothelial cells, basal membrane thickening, dilation of stomata, lymphatic lacunae and collectors lumina. Liver cirrhosis with ascites is frequently followed by lymphatic vessels thrombosis and firm attachment of the diaphragm to the liver resulting in the inhibition of the ascitic liquid elimination. Thus both the enhancement of liquid transudation into the abdominal cavity and the disturbance of the drainage function of the diaphragm peritoneum take place.

  11. Gut-liver axis: an immune link between celiac disease and primary biliary cirrhosis.

    PubMed

    Volta, Umberto; Caio, Giacomo; Tovoli, Francesco; De Giorgio, Roberto

    2013-03-01

    The association between celiac disease and primary biliary cirrhosis is well established. The breakdown of gut-liver axis equilibrium plays a central role in the development of immune disorders involving the small bowel and liver. In celiac disease, immunologically active molecules generated from the cross-linking between tissue transglutaminase and food/bacterial antigens reach the liver through the portal circulation owing to the increased intestinal permeability. A molecular mimicry between bacterial antigens and the pyruvate dehydrogenase E2 component, recognized by antimitochondrial autoantibodies, may have a role in primary biliary cirrhosis pathogenesis. An aberrant intestinal T lymphocyte homing to the liver may contribute to trigger immune hepatic damage. Both celiac disease and primary biliary cirrhosis share several features, including a higher prevalence in females, autoimmune comorbidities and specific autoantibodies. Reciprocal screening for both diseases is recommended, as an early diagnosis with the appropriate treatment can improve the outcome of these patients.

  12. Inhibition of Experimental Liver Cirrhosis in Mice by Telomerase Gene Delivery

    NASA Astrophysics Data System (ADS)

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

    2000-02-01

    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.

  13. Alteration of liver glycopatterns during cirrhosis and tumor progression induced by HBV.

    PubMed

    Qin, Yannan; Zhong, Yaogang; Ma, Tianran; Wu, Fei; Wu, Haoxiang; Yu, Hanjie; Huang, Chen; Li, Zheng

    2016-04-01

    The incidence of hepatocellular carcinoma (HCC) is closely correlated with hepatitis B virus (HBV)-induced liver cirrhosis. Structural changes in the glycans of serum and tissue proteins are reliable indicators of liver damage. However, little is known about the alteration of liver glycopatterns during cirrhosis and tumor progression induced by HBV infection. This study compared the differential expression of liver glycopatterns in 7 sets of normal pericarcinomatous tissues (PCTs), cirrhotic, and tumor tissues from patients with liver cirrhosis and HCC induced by HBV using lectin microarrays. Fluorescence-based lectin histochemistry and lectin blotting were further utilized to validate and assess the expression and distribution of certain glycans in 9 sets of corresponding liver tissue sections. Eight lectins (e.g., Jacalin and AAL) revealed significant difference in cirrhotic tissues versus PCTs. Eleven lectins (e.g., EEL and SJA) showed significant alteration during cirrhotic and tumor progression. The expression of Galα1-3(Fucα1-2)Gal (EEL) and fucosyltransferase 1 was mainly increasing in the cytoplasm of hepatocytes during PCTs-cirrhotic-tumor tissues progression, while the expression of T antigen (ACA and PNA) was decreased sharply in cytoplasm of tumor hepatocytes. Understanding the precision alteration of liver glycopatterns related to the development of hepatitis, cirrhosis, and tumor induced by HBV infection may help elucidate the molecular mechanisms underlying the progression of chronic liver diseases and develop new antineoplastic therapeutic strategies.

  14. The Synthetic Triterpenoid RTA 405 (CDDO-EA) Halts Progression of Liver Fibrosis and Reduces Hepatocellular Carcinoma Size Resulting in Increased Survival in an Experimental Model of Chronic Liver Injury

    PubMed Central

    Getachew, Yonas; Cusimano, Frank A.; Gopal, Purva; Reisman, Scott A.; Shay, Jerry W.

    2016-01-01

    Patients with cirrhosis have an increased risk of developing liver cancer and a higher rate of mortality. Cirrhosis currently has no known cure, and patients may benefit from new agents aimed at alleviating their complications and slowing down the rate of disease progression. Therefore, the effects of the orally bioavailable synthetic triterpenoid 2-cyano-3,12-dioxooleana- 1,9(11)-dien-28-oate-ethyl amide (CDDO-EA, RTA 405), which has potent antioxidative and antiinflammatory properties, was evaluated in a chronic carbon tetrachloride (CCl4)-induced model of liver cirrhosis and hepatocellular carcinoma (HCC). Mice were injected with CCl4 (to induce fibrosis and cirrhosis) or placebo biweekly for 12 weeks followed by CDDO-EA in the diet for 18 weeks with continued biweekly injections of CCl4. Chronic CCl4 administration resulted in cirrhosis, ascites, and HCC formation, associated with increased serum transforming growth factor-β1, hepatic hydroxyproline content, and increased serum bilirubin. CDDO-EA, whose administration commenced after establishment of liver fibrosis, decreased liver fibrosis progression, serum bilirubin, ascites, and HCC formation and markedly increased overall survival. CDDO-EA also attenuated -TNFα (tumor necrosis factor-α), α-SMA (alpha smooth muscle actin), augmented -IL-10 levels, and improved histologic and serologic markers of fibrosis. Conclusions: CDDO-EA mitigates the progression of liver fibrosis induced by chronic CCl4 administration, which is associated with the induction of antifibrogenic genes and suppression of profibrogenic genes. PMID:26443840

  15. Role of Chymase in the Development of Liver Cirrhosis and Its Complications: Experimental and Human Data

    PubMed Central

    Sansoè, Giovanni; Aragno, Manuela; Mastrocola, Raffaella; Mengozzi, Giulio; Novo, Erica; Parola, Maurizio

    2016-01-01

    Background Tissue Angiotensin II (Ang-II), produced through local non ACE-dependent pathways, stimulates liver fibrogenesis, renal vasoconstriction and sodium retention. Aim To highlight chymase-dependent pathway of Ang-II production in liver and kidney during cirrhosis development. Methods Liver histology, portal pressure, liver and kidney function, and hormonal status were investigated in rat liver cirrhosis induced through 13 weeks of CCl4, with or without chymase inhibitor SF2809E, administered between 4th and 13th CCl4 weeks; liver and kidney chymase immunolocation and Ang-II content were assessed. Chymase immunohistochemistry was also assessed in normal and cirrhotic human liver, and chymase mRNA transcripts were measured in human HepG2 cells and activated hepatic stellate cells (HSC/MFs) in vitro. Results Rats receiving both CCl4 and SF2809E showed liver fibrotic septa focally linking portal tracts but no cirrhosis, as compared to ascitic cirrhotic rats receiving CCl4. SF2809E reduced portal pressure, plasma bilirubin, tissue content of Ang-II, plasma renin activity, norepinephrine and vasopressin, and increased glomerular filtration rate, water clearance, urinary sodium excretion. Chymase tissue content was increased and detected in α-SMA-positive liver myofibroblasts and in kidney tubular cells of cirrhotic rats. In human cirrhosis, chymase was located in hepatocytes of regenerative nodules. Human HepG2 cells and HSC/MFs responded to TGF-β1 by up-regulating chymase mRNA transcription. Conclusions Chymase, through synthesis of Ang-II and other mediators, plays a role in the derangement of liver and kidney function in chronic liver diseases. In human cirrhosis, chymase is well-represented and apt to become a future target of pharmacological treatment. PMID:27637026

  16. Autologous Stem Cells Transplantation in Egyptian Patients with Liver Cirrhosis on Top of Hepatitis C Virus

    PubMed Central

    Al Tayeb, Hoda; El Dorry, Ahmed; Amer, Nehad; Mowafy, Nadia; Zimaity, Maha; Bayoumy, Essam; Saleh, Shereen A.

    2015-01-01

    Background and Objectives Use of pluripotent stem cells is an ideal solution for liver insufficiencies. This work aims is to evaluate the safety and feasibility of autologous stem cells transplantation (SCT) in Egyptian patients of liver cirrhosis on top of hepatitis C virus (HCV). Subjects and Results 20 patients with HCV induced liver cirrhosis were divided into 2 groups. Group I: included 10 patients with liver cirrhosis Child score ≥9, for whom autologous stem cell transplantation was done using granulocyte colony stimulating factor (G-CSF) for stem cells mobilization. Separation and collection of the peripheral blood stem cells was done by leukapheresis. G-CSF mobilized peripheral blood mononuclear cells (G-CSF PB-MNCs) were counted by flow cytometry. Stem cell injection into the hepatic artery was done. Group II: included 10 patients with HCV induced liver cirrhosis as a control group. Follow up and comparison between both groups were done over a follow up period of 6 months. The procedure was well tolerated. Mobilization was successful and the total number of G-CSF PB-MNCs in the harvests ranged from 25×106 to 191×106. There was improvement in the quality of life, serum albumin, total bilirubin, liver enzymes and the Child-Pugh score of group I over the first two-three months after the procedure. Conclusion SCT in HCV induced liver cirrhosis is a safe procedure. It can improve the quality of life and hepatic functions transiently with no effect on the life expectancy or the fate of the liver cirrhosis. PMID:26634069

  17. Association Between TT Virus Infection and Cirrhosis in Liver Transplant Patients

    PubMed Central

    Kazemi, Mohammad Javad; Yaghobi, Ramin; Iravani Saadi, Mahdiyar; Geramizadeh, Bita; Moayedi, Javad

    2015-01-01

    Background: Cirrhosis is one of the most severe liver complications, with multiple etiologies. The torque teno virus (TTV), also known as transfusion transmitted virus, which has a high incidence in the world population, is one of the possible increasing risk factors in patients with idiopathic fulminant hepatitis and cryptogenic cirrhosis. Objectives: The aim of this study was to evaluate solitary and co-infection with TTV, in patients with cryptogenic and determined cause of cirrhosis. Patients and Methods: In this cross-sectional study, 200 liver transplant patients were consecutively recruited between years 2007 and 2011. Patients were classified, based on recognition of the etiology of cirrhosis to determined (n = 81) and cryptogenic (n = 119) patient groups. The existence of TTV infection was analyzed, using a semi-nested polymerase chain reaction method. The presence of hepatitis B virus (HBV) infective markers, including HBV DNA, hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), hepatitis B core antibody (HBcAb), and hepatitis B e antibody (HBeAb), was evaluated using qualitative polymerase chain reaction and enzyme linked immunosorbent assay protocols, respectively. Results: The TTV infection was found in 37 of 200 (18.5%) and 53 of 200 (26.5%) plasma and tissue samples of studied liver transplanted patients, respectively. The TTV genomic DNA was found in 32 (26.9%) and 28 (23.5%) of 119 liver tissue and plasma samples of transplanted patients with cryptogenic cirrhosis, respectively. The genomic DNA of TTV was also diagnosed in 21 (25.9%) and nine (11.1%) of the 81 liver tissue and plasma samples of patients with determined cirrhosis, respectively. Significant associations were found between TTV infection with HBV molecular and immunologic infective markers, in liver transplanted patients, with determined and cryptogenic cirrhosis. Conclusions: The diagnosis of the high frequency of solitary TTV and co-infection with HBV, in both liver

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

    PubMed Central

    Prystupa, Andrzej; Szpetnar, Maria; Boguszewska-Czubara, Anna; Grzybowski, Andrzej; Sak, Jarosław; Załuska, Wojciech

    2015-01-01

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

  19. Association between interleukin-10 gene promoter polymorphisms and susceptibility to liver cirrhosis.

    PubMed

    Yao, Lanjie; Xing, Shuli; Fu, Xueqin; Song, Hongjie; Wang, Zhendong; Tang, Jianrong; Zhao, Yongjing

    2015-01-01

    We conducted a case-control study to investigate the association between three common SNPs in IL-10 gene (rs1800896, rs1800871 and rs1800872) and the development of liver cirrhosis in a Chinese population. Between January 2013 and December 2014, a total of 318 patients with liver cirrhosis and 318 health control subjects were enrolled into our study. The IL-10 rs1800896, rs1800871 and rs1800872 polymorphisms were analyzed using polymerase chain reaction (PCR) coupled with restriction fragment length polymorphism (RFLP). By multivariate logistic regression analysis, we found that individuals with the AA genotype and GA+AA genotype of IL-10 rs1800896 were more likely to have an increased risk of liver cirrhosis when compared with the GG genotype, and the ORs (95% CI) for the AA genotype and GA+AA genotype were 2.04 (1.20-3.50) and 1.41 (1.02-1.96), respectively. We found that the GA+AA genotype of IL-10 rs1800896 had higher risk of liver cirrhosis in individuals with chronic hepatitis B when compared with the GG genotype (OR = 1.95, 95% CI = 1.01-3.59). In conclusion, we found that IL-10 rs1800896 polymorphism was correlated with an increased risk of liver cirrhosis, especially in individuals with chronic hepatitis B.

  20. Molecular and Cellular Functions Distinguish Superior Therapeutic Efficiency of Bone Marrow CD45 Cells Over Mesenchymal Stem Cells in Liver Cirrhosis.

    PubMed

    Baligar, Prakash; Mukherjee, Snehasish; Kochat, Veena; Rastogi, Archana; Mukhopadhyay, Asok

    2016-01-01

    Liver fibrosis is strongly associated with chronic inflammation. As an alternative to conventional treatments for fibrosis, mesenchymal stem cells (MSCs) therapy is found to be attractive due to its immunomodulatory functions. However, low survival rate and profibrogenic properties of MSCs remain the major concerns, leading to skepticism in many investigators. Here, we have asked the question whether bone marrow (BM)-derived CD45 cells is the better candidate than MSCs to treat fibrosis, if so, what are the molecular mechanisms that make such distinction. Using CCl4 -induced liver fibrosis mouse model of a Metavir fibrosis score 3, we showed that BM-CD45 cells have better antifibrotic effect than adipose-derived (AD)-MSCs. In fact, our study revealed that antifibrotic potential of CD45 cells are compromised by the presence of MSCs. This difference was apparently due to significantly high level expressions of matrix metalloproteinases-9 and 13, and the suppression of hepatic stellate cells' (HpSCs) activation in the CD45 cells transplantation group. Mechanism dissection studied in vitro supported the above opposing results and revealed that CD45 cell-secreted FasL induced apoptotic death of activated HpSCs. Further analyses suggest that MSC-secreted transforming growth factor β and insulin-like growth factor-1 promoted myofibroblastic differentiation of HpSCs and their proliferation. Additionally, the transplantation of CD45 cells led to functional improvement of the liver through repair and regeneration. Thus, BM-derived CD45 cells appear as a superior candidate for the treatment of liver fibrosis due to structural and functional improvement of CCl4 -induced fibrotic liver, which were much lower in case of AD-MSC therapy.

  1. Association of Fasciola hepatica Infection with Liver Fibrosis, Cirrhosis, and Cancer: A Systematic Review

    PubMed Central

    Machicado, Claudia; Machicado, Jorge D.; Maco, Vicente; Terashima, Angelica; Marcos, Luis A.

    2016-01-01

    Background Fascioliasis has been sporadically associated with chronic liver disease on previous studies. In order to describe the current evidence, we carried out a systematic review to assess the association between fascioliasis with liver fibrosis, cirrhosis and cancer. Methodology and Principal Findings A systematic search of electronic databases (PubMed, LILACS, Scopus, Embase, Cochrane, and Scielo) was conducted from June to July 2015 and yielded 1,557 published studies. Among 21 studies that met inclusion and exclusion criteria, 12 studies explored the association of F. hepatica with liver fibrosis, 4 with liver cirrhosis, and 5 with cancer. Globally these studies suggested the ability of F. hepatica to promote liver fibrosis and cirrhosis. The role of F. hepatica in cancer is unknown. Given the heterogeneity of the studies, a meta-analysis could not be performed. Conclusions Future high-quality studies are needed to determine the role of F. hepatica on the development of liver fibrosis, liver cirrhosis, and cancer in humans. PMID:27681524

  2. NATIVE VALVE ENDOCARDITIS CAUSED BY METHICILLIN-RESISTANT STAPHYLOCOCCUS EPIDERMIDIS IN A PATIENT WITH ADVANCED LIVER CIRRHOSIS.

    PubMed

    Cavrić, Gordana; Ilić, Diana; Njers, Kristina; Prkacin, Ingrid; Hamp, Dubravka Bartolek

    2015-12-01

    We present a case of a 50-year-old man with advanced liver cirrhosis and native valve infective endocarditis caused by methicillin-resistant Staphylococcus epidermidis. Bacterial infections are one of the most common complications of liver cirrhosis, but reports of infective endocarditis in patients with liver cirrhosis are relatively rare. Because of vulnerability of patients with advanced cirrhosis for developing infections, it is necessary to pay attention to the pathogens that are sometimes considered contamination and actively seek for the seat of infection, even in less expected areas (e.g., native heart valves without a history of heart disease).

  3. Molecular Mechanisms Involved in the Interaction Effects of Alcohol and Hepatitis C Virus in Liver Cirrhosis

    PubMed Central

    Mas, Valeria R; Fassnacht, Ryan; Archer, Kellie J; Maluf, Daniel

    2010-01-01

    The mechanisms by which alcohol consumption accelerates liver disease in patients with chronic hepatitis C virus (HCV) are not well understood. To identify the characteristics of molecular pathways affected by alcohol in HCV patients, we fit probe-set level linear models that included the additive effects as well as the interaction between alcohol and HCV. The study included liver tissue samples from 78 patients, 23 (29.5%) with HCV-cirrhosis, 13 (16.7%) with alcohol-cirrhosis, 23 (29.5%) with HCV/alcohol cirrhosis and 19 (24.4%) with no liver disease (no HCV/no alcohol group). We performed gene-expression profiling by using microarrays. Probe-set expression summaries were calculated by using the robust multiarray average. Probe-set level linear models were fit where probe-set expression was modeled by HCV status, alcohol status, and the interaction between HCV and alcohol. We found that 2172 probe sets (1895 genes) were differentially expressed between HCV cirrhosis versus alcoholic cirrhosis groups. Genes involved in the virus response and the immune response were the more important upregulated genes in HCV cirrhosis. Genes involved in apoptosis regulation were also overexpressed in HCV cirrhosis. Genes of the cytochrome P450 superfamily of enzymes were upregulated in alcoholic cirrhosis, and 1230 probe sets (1051 genes) had a significant interaction estimate. Cell death and cellular growth and proliferation were affected by the interaction between HCV and alcohol. Immune response and response to the virus genes were downregulated in HCV-alcohol interaction (interaction term alcohol*HCV). Alcohol*HCV in the cirrhotic tissues resulted in a strong negative regulation of the apoptosis pattern with concomitant positive regulation of cellular division and proliferation. PMID:20386865

  4. Liver Cirrhosis/Severe Fibrosis Is a Risk Factor for Anastomotic Leakage after Colorectal Surgery

    PubMed Central

    Hofmann, Irina; Willi, Niels; Stickel, Felix

    2016-01-01

    Purpose. Liver cirrhosis associated with high perioperative morbidity/mortality. This retrospective study determines whether liver cirrhosis represents a risk factor for anastomotic leakage after colonic anastomosis or not. Methods. Based on a prospective database with all consecutive colorectal resections performed at the authors' institution from 07/2002 to 07/2012 (n = 2104) all colonic and rectal anastomoses were identified (n = 1875). A temporary loop ileostomy was constructed in 257 cases (13.7%) either due to Mannheimer Peritonitis-Index > 29 or rectal anastomosis below 6 cm from the anal verge. More than one-third of the patients (n = 691) had postoperative contrast enema, either at the occasion of another study or prior to closure of ileostomy. The presence of liver cirrhosis and the development of anastomotic leakage were assessed by chart review. Results. The overall anastomotic leakage rate was 2.7% (50/1875). In patients with cirrhosis/severe fibrosis, the anastomotic leakage rate was 12.5% (3/24), while it was only 2.5% (47/1851) in those without (p = 0.024). The difference remained statistically significant after correction for confounding factors by multivariate analysis. Conclusion. Patients with liver cirrhosis/severe fibrosis have an increased risk of leakage after colonic anastomosis. PMID:28105046

  5. [Polymorphism of ornithine decarboxylase antizyme inhibitor 1 gene is associated with liver cirrhosis in Chinese hepatitis B patients].

    PubMed

    Peng, Li-Jun; Guo, Jin-Sheng; Zhang, Zhe; Shi, Hong; Wang, Jian; Friedman, Scott L; Sninsky, John J; Wang, Ji-Yao

    2011-03-01

    A cirrhosis risk score (CRS) comprised of single nucleotide polymorphisms (SNPs) in seven genes that predicts the risk of cirrhosis in Caucasian hepatitis C has been reported. The present study was to evaluate the association of 11 separate but related SNPs and the CRS with cirrhosis risk in Chinese hepatitis B patients. A total of 563 Chinese subjects with persistent HBV infection (349 with evident liver cirrhosis and 214 without cirrhosis clinically or pathologically) were studied. The candidate SNPs were detected with a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) method. The allele frequency and genotype distribution of each polymorphism as well as the CRS value within the cirrhosis and non-cirrhosis subjects were compared. The rs2679757 polymorphism of the antizyme inhibitor 1 (AZIN1) gene was associated with the risk of cirrhosis (x2 = 6.79, P = 0.03, odds ratio for GG+AG versus AA = 1.63, 95% confidence interval = 1.13-2.35). A gene variant (rs886277) in the transient receptor potential cation channel subfamily M, member 5 gene (TRPM5) was associated with liver cirrhosis, but did not reach statistical significance (x2 = 5.77, P = 0.06). Two SNPs (rs4986791, rs62522600) are not polymorphic in Chinese. Genotype frequencies of other SNPs were not different between the cirrhosis and non-cirrhosis groups. The overall CRS values were not different between the cirrhotic and non-cirrhotic groups (median value 0.57 versus 0.62, Z = -1.05, P = 0.29). SNP rs2679757 in the AZIN1 gene is associated with the risk of HBV-related liver cirrhosis in Chinese. The CRS for Caucasian population has limited applicability for predicting liver cirrhosis in Chinese hepatitis B patients. SNPs associated with cirrhosis prognosis in hepatitis B patients and liver diseases with other etiologies warrant further clinical validation.

  6. Hepatocyte growth factor: a regenerative drug for acute hepatitis and liver cirrhosis.

    PubMed

    Mizuno, Shinya; Nakamura, Toshikazu

    2007-03-01

    Liver cirrhosis is a major cause of morbidity worldwide and is characterized by the loss of hepatocytes with interstitial fibrosis. In this review, we discuss the potential uses of hepatocyte growth factor for treating hepatic diseases, focusing on the molecular mechanisms whereby hepatocyte growth factor reverses liver cirrhosis. Hepatic myofibroblasts play a central role in the development of liver cirrhosis, while myofibroblasts acquire c-Met. Using a rat model of liver cirrhosis, we recently delineated the direct effect of hepatocyte growth factor toward myofibroblasts: the induction of apoptotic cell death associated with matrix degradation, the inhibition of overproliferation and the suppression of transforming growth factor-beta1 production in myofibroblasts. Hepatocyte growth factor elicits mitogenic, anti-apoptotic and anti-inflammatory functions in hepatocytes, therefore contributing to reversing liver dysfunction. Considering the insufficient production of hepatocyte growth factor is responsible for the manifestation of chronic hepatitis, supplementation with or reinduction of hepatocyte growth factor represents a new strategy for attenuating intractable liver diseases.

  7. [Protein catabolism and malnutrition in liver cirrhosis - impact of oral nutritional therapy].

    PubMed

    Norman, K; Valentini, L; Lochs, H; Pirlich, M

    2010-07-01

    Malnutrition with loss of muscle is common in patients with liver cirrhosis and has negative impact on morbidity and mortality. The aetiology of malnutrition is multifactorial and includes inflammation, early onset of gluconeogenesis due to impaired glycogen storage and sometimes hypermetabolism. Reduced nutritional intake, however, plays the most important role in the pathogenesis of malnutrition. There is, however, ample evidence that nutritional intake and therapy are inadequate in liver cirrhosis although studies have clearly shown that dietary counselling and nutritional therapy with oral supplements improve intake in these patients. Protein requirement is considered to be increased in liver cirrhosis and high protein intake has been shown to be well tolerated and associated with an improvement of liver function and nutritional status. Protein intolerance on the other hand is uncommon and hepatic encephalopathy can thus rarely be attributed to high protein consumption. Recommendations for general protein restriction must therefore be considered obsolete and rather a risk factor for an impaired clinical outcome. Furthermore, the administration of late evening meals is highly beneficial in patients with liver disease since the rapid onset of the overnight catabolic state is counteracted. The serum concentration of branched-chain amino acids (BCAA) is decreased in patients with liver cirrhosis and long-term supplementation of BCAA has been shown to improve nutritional status and prolong event-free survival and quality of life.

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

    PubMed Central

    2013-01-01

    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-β1 and TNF-α 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

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

    PubMed

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

    2015-04-01

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

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

    NASA Astrophysics Data System (ADS)

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

    1990-04-01

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

  11. Cirrhosis - discharge

    MedlinePlus

    ... this page: //medlineplus.gov/ency/patientinstructions/000290.htm Cirrhosis - discharge To use the sharing features on this page, please enable JavaScript. You have cirrhosis of the liver. Scar tissue forms and your ...

  12. Concise review: Interferon-free treatment of hepatitis C virus-associated cirrhosis and liver graft infection

    PubMed Central

    Weiler, Nina; Zeuzem, Stefan; Welker, Martin-Walter

    2016-01-01

    Chronic hepatitis C is a major reason for development of cirrhosis and hepatocellular carcinoma and a leading cause for liver transplantation. The development of direct-acting antiviral agents lead to (pegylated) interferon-alfa free antiviral therapy regimens with a remarkable increase in sustained virologic response (SVR) rates and opened therapeutic options for patients with advanced cirrhosis and liver graft recipients. This concise review gives an overview about most current prospective trials and cohort analyses for treatment of patients with liver cirrhosis and liver graft recipients. In patients with compensated cirrhosis Child-Pugh-Turcotte (CTP) class A, all approved agents are safe and SVR rates do not significantly differ from patients without cirrhosis in general. In patients with decompensated cirrhosis CTP class B or C, daclastasvir, ledipasvir, velpatasvir, and sofosbuvir are approved, and SVR rates higher than 90% can be achieved. Especially for patients with a model of end stage liver disease score higher than 15 and therefore eligible for liver transplantation, data is scarce. Reported SVR rates in patients with cirrhosis CTP class C are lower compared to patients with a less severe liver disease. In liver transplant recipients with a maximum of CTP class A, SVR rates are comparable to patients without LT. Patients with decompensated graft cirrhosis should be treated on an individual basis. PMID:27895394

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

    PubMed

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

    2014-06-01

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

  14. [Studies on the mechanism of elevation of serum PIVKA-II levels in alcoholic liver cirrhosis].

    PubMed

    Sakizono, Kenji; Oita, Tatsuo; Eto, Masaaki; Bito, Sanae; Takegawa, Hiroshi; Kasakura, Shinpei

    2002-03-01

    We measured serum PIVKA-II concentrations in 18 patients with alcoholic liver cirrhosis. Alcoholic liver disease was diagnosed by the history of ethanol intake of more than 900 ml/day for over 10 years. Liver cirrhosis was diagnosed histologically. Infections with hepatitis B and C viruses were ruled out by assaying serum virus markers. No tumor was detected in liver by ultrasonography and computed tomography during observation period. None of the patients studied were positive for alpafetoprotein (AFP). Eight out of 18 (44.4%) patients with alcoholic liver cirrhosis showed elevated serum PIVKA-II levels. In contrast, only eight out of 93 (8.6%) patients with nonalcholic liver cirrhosis had elevated serum PIVKA-II levels. PIVKA-II is well known as a tumor marker of hepatocellular carcinoma (HCC). The rates of positive PIVKA-II found in alcoholic liver cirrhosis approached its rates in HCC. However, the time course for the elevation of serum PIVKA-II levels was different each other in alcoholic liver cirrhosis and HCC. In HCC, serum PIVKA-II "levels" continued to elevate until therapy. In contrast, its elevation was transient and its levels returned to baseline in alcoholic liver cirrhosis. The values of ALT (GPT), gamma-GTP, and ALP correlated poorly with serum PIVKA-II levels in patients with alcoholic liver cirrhosis. To investigate the mechanism by which elevation of serum PIVKA-II levels in patients with alcoholic liver cirrhosis occurred, we studied the effect of vitamin K on production of PIVKA-II and AFP by hepatocytes. Hepatocytes(Alexander PLC/PRF/F cell line) were cultured in the presence of various concentrations of vitamin K (Kaytwo, Eisai, Tokyo). Vitamin K had no effect on AFP production. In contrast, PIVKA-II production was inhibited by addition of vitamin K in a dose dependent manner. Moreover, elevation of serum PIVKA-II levels in patients with alcoholic liver cirrhosis was suppressed by administration of vitamin K (Kaytwo) to these patients. Taken

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

    PubMed Central

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

    2000-01-01

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

  16. Enhanced expression of glucose-regulated protein 78 correlates with malondialdehyde levels during the formation of liver cirrhosis in rats

    PubMed Central

    ZHANG, YUN; ZHANG, HUIYING; ZHAO, ZHONGFU; LV, MINLI; JIA, JIANTAO; ZHANG, LILI; TIAN, XIAOXIA; CHEN, YUNXIA; LI, BAOHONG; LIU, MINGSHE; HAN, DEWU; JI, CHENG

    2015-01-01

    The aim of the present study was to explore the role of glucose-regulated protein 78 (GRP78) in the development of liver cirrhosis promoted by intestinal endotoxemia in rats. Fifty-one male Wistar rats were randomly divided into the liver cirrhosis 4-week, 6-week and 8-week groups and the normal control group at each time point. Liver cirrhosis was induced by employing multiple pathogenic factors in the rats. Blood and liver tissues were collected. The levels of alanine aminotransferase (ALT), homocysteine, endotoxin and tumor necrosis factor-α (TNF-α) in the plasma, and TNF-α, malondialdehyde (MDA) and procollagen type III peptide (PIIIP) in the liver tissues were determined. The mRNA and protein expression levels of GRP78 in the liver were detected using reverse transcription-quantitative polymerase chain reaction and immunohistochemistry. Morphological changes were observed through hematoxylin and eosin and van Gieson staining of the liver. Liver cirrhosis caused marked histopathological changes to the livers of the rats. Following significant increases in the levels of ALT, homocysteine, endotoxin and TNF-α in the plasma, and TNF-α, MDA and PIIIP in the liver tissues of all experimental groups with the progression of liver cirrhosis, the mRNA and protein expression levels of GRP78 also gradually increased. In addition, correlation analysis indicated that the enhanced expression of GRP78 correlated with the MDA levels of the rats during the formation of liver cirrhosis. PMID:26668603

  17. Circulating Lipids Are Associated with Alcoholic Liver Cirrhosis and Represent Potential Biomarkers for Risk Assessment.

    PubMed

    Meikle, Peter J; Mundra, Piyushkumar A; Wong, Gerard; Rahman, Khairunnessa; Huynh, Kevin; Barlow, Christopher K; Duly, Alastair M P; Haber, Paul S; Whitfield, John B; Seth, Devanshi

    2015-01-01

    Liver disease is the greatest cause of death related to alcohol and a major public health problem. While excessive alcohol intake results in hepatosteatosis in most individuals, this can progress in some to more severe forms of liver disease including fibrosis and cirrhosis. An ongoing challenge in the management of alcoholic liver disease is the identification of liver injury early in the disease process such that intervention strategies can prevent serious long term outcomes. Given that excessive alcohol consumption results in dysregulation of lipid metabolism we applied lipid profiling technology to characterise and compare serum lipid profiles from excessive chronic drinkers with no liver disease to those with advanced alcoholic cirrhosis. In a cohort of 59 excessive drinkers (31 with liver cirrhosis and 28 with no evidence of liver disease) we used electrospray ionisation tandem mass spectrometry to measure over 300 individual lipid species in serum, including species of the major phospholipid, sphingolipid, glycerolipid and sterol classes. Six of the 25 lipid classes and subclasses were significantly associated with alcoholic liver cirrhosis; these included dihexosylceramide, trihexosylceramide, alkylphosphatidylcholine, lysoalkylphosphatidylcholine, phosphatidylinositol and free cholesterol. Multivariate classification models created with only clinical characteristics gave an optimal model with an AUC of 0.847 and an accuracy of 79.7%. The addition of lipid measurements to the clinical characteristics resulted in models of improved performance with an AUC of 0.892 and accuracy of 81.8%. The gain in AUC and accuracy of the combined models highlight the potential of serum lipids as markers of liver injury in alcoholic liver disease.

  18. Alcoholic cirrhosis is a good indication for liver transplantation, even for cases of recidivism

    PubMed Central

    Pageaux, G; Michel, J; Coste, V; Perney, P; Possoz, P; Perrigault, P; Navarro, F; Fabre, J; Domergue, J; Blanc, P; Larrey, D

    1999-01-01

    BACKGROUND/AIMS—Alcoholic cirrhosis remains a controversial indication for liver transplantation, mainly because of ethical considerations related to the shortage of donor livers. The aim of this study was to review experience to date, focusing on survival rates and complications, and the effect of alcohol relapse on outcome and alterations in marital and socioprofessional status.
METHODS—The results for 53 patients transplanted for alcoholic cirrhosis between 1989 and 1994 were compared with those for 48 patients transplanted for non-alcoholic liver disease. The following variables were analysed: survival, rejection, infection, cancer, retransplantation, employment and marital status, alcoholic recurrence. The same variables were compared between alcohol relapsers and non-relapsers.
RESULTS—Recovery of employment was the only significantly different variable between alcoholic (30%) and non-alcoholic patients (60%). Two factors influenced survival in the absence of alcohol recidivism: age and abstinence before transplantation. For all other variables, there were no differences between alcoholic and non-alcoholic patients, and, within the alcoholic group, between relapsers and non-relapsers. The recidivism rate was 32%.
CONCLUSION—The data indicate that liver transplantation is justified for alcoholic cirrhosis, even in cases of recidivism, which did no affect survival and compliance with the immunosuppressive regimen. These good results should help in educating the general population about alcoholic disease.


Keywords: liver; transplantation; alcohol; cirrhosis PMID:10446113

  19. Genotyping diagnosis of alpha-1 antitrypsin deficiency in Saudi adults with liver cirrhosis

    PubMed Central

    Al-Jameil, Noura; Hassan, Amina A.; Buhairan, Ahlam; Hassanato, Rana; Isac, Sree R.; Al-Otaiby, Maram; Al-Maarik, Basmah; Al-Ajeyan, Iman

    2017-01-01

    Abstract The acute phase protein alpha-1 antitrypsin (AAT) is mainly produced in liver cells. AAT deficiency affects the lungs and liver. We conducted a case-control study to define a valuable method for the proper diagnosis of alpha-1 antitrypsin deficiency (AATD), as well as the association of liver cirrhosis with AATD in Saudi adults. Blood samples from 300 liver cirrhosis patients and 400 controls were analyzed according to serum AAT concentration, phenotyping, and genotyping. Nephelometry was used for AAT quantification, isoelectric focusing electrophoresis was used for phenotyping detection, and real-time PCR was used for genotyping to determine the Z and S deficiency alleles. This study highlights the accuracy of using genotyping in addition to AAT quantification, since this technique has proven to be successful in the diagnosis of AATD for 100% of our cases. A significant deviation in AAT genotypes frequencies from the Hardy–Weinberg equilibrium in the adult cirrhosis group occurred due to a higher observed frequency than expected for the Pi ZZ homozygous genotype. Pi ZZ in adults may be considered as the risk factor for liver cirrhosis. However, we could not establish this relationship for heterozygous AATD genotypes (such as Pi MZ and Pi SZ). PMID:28178162

  20. Biliary liver cirrhosis secondary to cystic fibrosis: a rare indication for liver transplantation.

    PubMed

    Sańko-Resmer, J; Paczek, L; Wyzgał, J; Ziółkowski, J; Ciszek, M; Alsharabi, A; Grzelak, I; Paluszkiewicz, R; Patkowski, W; Krawczyk, M

    2006-01-01

    As more effective therapies prolong the lives of patients with cystic fibrosis, there are now more patients in this population diagnosed with liver diseases. Secondary biliary cirrhosis is not a rare complication of mucoviscidosis. It is diagnosed in 20% of patients with mucoviscidosis; in 2% it is accompanied by portal hypertension. On average patients with portal hypertension and its complications are 12 years old. Liver transplantation is an accepted method of treatment for children with cystic fibrosis and portal hypertension. It eliminates the cause of the portal hypertension, decreases life-threatening medical conditions, and improves their nutritional status and quality of life. Despite immunosuppressive treatment they do not seem to beat increased risk of upper respiratory tract infections. On the contrary improved respiratory function and status are generally observed. We present our first case of orthotopic liver transplantation performed in a 29-year-old man with cystic fibrosis. The donor was a 42-year-old woman who died of a ruptured cerebral aneurysm. The surgery was performed in September 2004. The patient received immunosuppression based on steroids, basiliximab, tacrolimus, and mycophenolic acid due to renal insufficiency. Antibiotic (meropenem) and antiviral prophylaxis (gancyclovir) were used. A 6-month period of observation confirmed the clinical data from the pediatric population-a good prognosis with improved nutritional status, respiratory function, and quality of life.

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

    PubMed Central

    McCormack, Lucas; Capitanich, Pablo; Quiñonez, Emilio

    2008-01-01

    Background data The prevalence of steatosis and hepatitis-related liver cirrhosis is dramatically increasing together worldwide. Cirrhosis and, more recently, steatosis are recognized as a clinically important feature that influences patient morbidity and mortality after hepatic resection when compared with patients with healthy liver. Objective To review present knowledge regarding how the presence of cirrhosis or steatosis can influence postoperative outcome after liver resection. Methods A critical review of the English literature was performed to provide data concerning postoperative outcome of patients presenting injured livers who required hepatectomy. Results In clinical studies, the presence of steatosis impaired postoperative outcome regardless the severity and quality of the hepatic fat. A great improvement in postoperative outcome has been achieved using modern and multidisciplinary preoperative workup in cirrhotic patients. Due to the lack of a proper classification for morbidity and a clear definition of hepatic failure in the literature, the comparison between different studies is very limited. Although, many surgical strategies have been developed to protect injured liver surgery, no one have gained worldwide acceptance. Conclusion Surgeons should take the presence of underlying injured livers into account when planning the extent and type of hepatic surgery. Preoperative and perioperative interventions should be considered to minimize the additional damage. Further randomized trials should focus on the evaluation of novel preoperative strategies to minimize risk in these patients. Each referral liver center should have the commitment to report all deaths related to postoperative hepatic failure and to use a common classification system for postoperative complications. PMID:18439273

  2. Endogenous carbon monoxide downregulates hepatic cystathionine-γ-lyase in rats with liver cirrhosis

    PubMed Central

    GUO, SHI-BIN; DUAN, ZHI-JUN; WANG, QIU-MING; ZHOU, QIN; LI, QING; SUN, XIAO-YU

    2015-01-01

    The aim of the present study was to investigate the effect of endogenous carbon monoxide (CO) on the hydrogen sulfide/cystathionine-γ-lyase (H2S/CSE) pathway in cirrhotic rat livers. The rats were allocated at random into four groups: Sham, cirrhosis, cobalt protoporphyrin (CoPP) and zinc protoporphyrin IX (ZnPP). The expression of hepatic CSE mRNA was evaluated using a quantitative polymerase chain reaction, while CSE protein expression was determined using immunohistochemical analysis. Hematoxylin and eosin staining was performed for the histological evaluation of liver fibrosis. The levels of H2S, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL) and carboxyhemoglobin (COHb) in the arterial blood were determined, in addition to the portal vein pressure. The mRNA and protein expression levels of hepatic CSE and the serum levels of H2S were significantly decreased in the cirrhosis group compared with those in the sham group (P<0.05). Compared with the cirrhosis group, rats in the ZnPP group had significantly lower levels of serum ALT, AST and TBIL, arterial COHb and hepatic fibrosis, while hepatic CSE expression and the production of H2S were significantly increased (P<0.05). The CoPP group exhibited decreased hepatic CSE expression and H2S production, but aggravated hepatic function and fibrosis (P<0.05). In conclusion, the H2S/CSE pathway is involved in the formation of liver cirrhosis and serves a crucial function in protecting liver cells against the progression of liver fibrosis. Endogenous CO downregulates hepatic CSE mRNA and protein expression and the production of H2S in rats with liver cirrhosis. PMID:26668593

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-12-07

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

  5. [Action of DDPH in the interventional treatment of portal hypertension induced by liver cirrhosis in rabbits].

    PubMed

    Qian, J; Feng, G; Liang, H

    1998-01-01

    To explore a new way of utilizing intervential treatment to effectively decrease the portal hypertension, the animal models of liver cirrhosis accompanying portal hypertension were set up by intraportal vein injection of suspensions of Bletilla striata to 10 rabbits by means of prospective investigational method. The catheter filled with heparin solution was remained in theportal vein for infusion of drugs. Three weeks later, DDPH solution was injected into the portal vein via the catheter to determine its effect of decreasing portal vein pressure and its influence of peripheral blood pressure and heart rate. At the same time, other 10 rabbits with liver cirrhosis associated with portal hypertension were subjected to the injection of DDPH solution via the ear vein served as control group. The results showed that administration of DDPH by portal vein could rapidly, safely and effectively decrease the portal hypertenive pressure without side effects and partially reverse liver cirrhosis, as compared with injection of DDPH via peripheral veins. It was concluded that DDPH exerted its alpha 1-adrenoceptor blocking and calcium antagonistic effects, thereby significantly reduce the portal hypertension. Injection of DDPH via portal vein is a completely new and relaible method for the treatment of liver cirrhosis with portal hypertension.

  6. Impact of muscle wasting on survival in patients with liver cirrhosis.

    PubMed

    Kalafateli, Maria; Konstantakis, Christos; Thomopoulos, Konstantinos; Triantos, Christos

    2015-06-28

    Muscle wasting is defined as the progressive and generalized loss of muscle mass. Muscle depletion is a common feature of chronic liver disease found in approximately 40% of patients with cirrhosis. Its etiology is multifactorial subsequent to liver failure and its prevalence increases along with disease severity. Cross-sectional analytic morphometry using computed tomography (CT) scan or magnetic resonance imaging are considered by consensus the gold standards to assess muscle size in cirrhosis for research purposes because they are not biased by fluid accumulation. Several studies have assessed the impact of muscle wasting on overall survival of patients in the waiting list for liver transplantation and there is a general agreement that decreased muscle size assessed by CT scan is an independent predictor for mortality in cirrhosis. It has been proposed that the addition of cross-sectional muscle area into the Model for End-stage Liver Disease can increase its prognostic performance. Nevertheless, the use of CT scan in assessing muscle size is inappropriate for routine clinical practice and an alternative cost-effective, easy to use and accurate tool should be developed. In conclusion, muscle wasting has a detrimental impact on survival of patients with cirrhosis and, thus, it remains to be elucidated if nutritional interventions and exercise could improve muscle wasting and, subsequently, survival in this setting.

  7. Gallbladder contractility in liver cirrhosis: comparative study in patients with and without gallbladder stones.

    PubMed

    Acalovschi, Monica; Dumitrascu, Dan L; Nicoara, Cezar D

    2004-01-01

    An increased prevalence of gallstones was demonstrated in patients with liver cirhosis, higher in the advanced stages of the disease. Some studies have found impaired emptying of the gallbladder in cirrhotic patients. Our aim here was to investigate gallbladder emptying in cirrhotic patients with and without gallstones to find out whether emptying is further impaired in the presence of gallstones. The study group comprised 24 patients with liver cirrhosis and gallstones, 8 in each Child class. The controls were represented by 18 cirrhotic patients without gallstones, 6 in each Child class. Fasting gallbladder volume was calculated by ultrasound using the ellipsoid formula. Gallbladder emptying was evaluated for 90 min after ingestion of a solid-liquid meal (14 g fat, 425 kcal), by assessing minimal residual volume, gallbladder ejection fraction, and area under emptying curve at 15-min intervals. Statistical analysis was performed using the two-tailed Students' t test and Pearson's correlation coefficient. In controls, gallbladder fasting and residual volumes increased with the severity of cirrhosis, but gallbladder emptying did not change significantly. In cirrhotics with gallstones, gallbladder emptying decreased in Child C compared with Child A class patients and, also, compared to Child C controls. The number or size of gallstones, as well as the thickness of the gallbladder wall, did not correlate with gallbladder emptying parameters. Gallbladder contractility is impaired in patients with liver cirrhosis and gallstones. Hypomotility is proportional to the severity of liver disease. Gallbladder hypomotility might contribute to the increased gallstone formation in patients with advanced cirrhosis.

  8. Analysis of serum haptoglobin fucosylation in hepatocellular carcinoma and liver cirrhosis of different etiologies.

    PubMed

    Zhu, Jianhui; Lin, Zhenxin; Wu, Jing; Yin, Haidi; Dai, Jianliang; Feng, Ziding; Marrero, Jorge; Lubman, David M

    2014-06-06

    We have developed herein a quantitative mass spectrometry-based approach to analyze the etiology-related alterations in fucosylation degree of serum haptoglobin in patients with liver cirrhosis and hepatocellular carcinoma (HCC). The three most common etiologies, including infection with hepatitis B virus (HBV), infection with hepatitis C virus (HCV), and heavy alcohol consumption (ALC), were investigated. Only 10 μL of serum was used in this assay in which haptoglobin was immunoprecipitated using a monoclonal antibody. The N-glycans of haptoglobin were released with PNGase F, desialylated, and permethylated prior to MALDI-QIT-TOF MS analysis. In total, N-glycan profiles derived from 104 individual patient samples were quantified (14 healthy controls, 40 cirrhosis, and 50 HCCs). A unique pattern of bifucosylated tetra-antennary glycan, with both core and antennary fucosylation, was identified in HCC patients. Quantitative analysis indicated that the increased fucosylation degree was highly associated with HBV- and ALC-related HCC patients compared to that of the corresponding cirrhosis patients. Notably, the bifucosylation degree was distinctly increased in HCC patients versus that in cirrhosis of all etiologies. The elevated bifucosylation degree of haptoglobin can discriminate early stage HCC patients from cirrhosis in each etiologic category, which may be used to provide a potential marker for early detection and to predict HCC in patients with cirrhosis.

  9. Acute kidney injury in liver cirrhosis: new definition and application

    PubMed Central

    Wong, Florence

    2016-01-01

    The traditional diagnostic criteria of renal dysfunction in cirrhosis are a 50% increase in serum creatinine (SCr) with a final value above 1.5 mg/dL. This means that patients with milder degrees of renal dysfunction are not being diagnosed, and therefore not offered timely treatment. The International Ascites Club in 2015 adapted the term acute kidney injury (AKI) to represent acute renal dysfunction in cirrhosis, and defined it by an increase in SCr of 0.3 mg/dL (26.4 µmoL/L) in <48 hours, or a 50% increase in SCr from a baseline within ≤3 months. The severity of AKI is described by stages, with stage 1 represented by these minimal changes, while stages 2 and 3 AKI by 2-fold and 3-fold increases in SCr respectively. Hepatorenal syndrome (HRS), renamed AKI-HRS, is defined by stage 2 or 3 AKI that fulfils all other diagnostic criteria of HRS. Various studies in the past few years have indicated that these new diagnostic criteria are valid in the prediction of prognosis for patients with cirrhosis and AKI. The future in AKI diagnosis may include further refinements such as inclusion of biomarkers that can identify susceptibility for AKI, differentiating the various prototypes of AKI, or track its progression. PMID:27987536

  10. Acute kidney injury in liver cirrhosis: new definition and application.

    PubMed

    Wong, Florence

    2016-12-01

    The traditional diagnostic criteria of renal dysfunction in cirrhosis are a 50% increase in serum creatinine (SCr) with a final value above 1.5 mg/dL. This means that patients with milder degrees of renal dysfunction are not being diagnosed, and therefore not offered timely treatment. The International Ascites Club in 2015 adapted the term acute kidney injury (AKI) to represent acute renal dysfunction in cirrhosis, and defined it by an increase in SCr of 0.3 mg/dL (26.4 µmoL/L) in <48 hours, or a 50% increase in SCr from a baseline within ≤3 months. The severity of AKI is described by stages, with stage 1 represented by these minimal changes, while stages 2 and 3 AKI by 2-fold and 3-fold increases in SCr respectively. Hepatorenal syndrome (HRS), renamed AKI-HRS, is defined by stage 2 or 3 AKI that fulfils all other diagnostic criteria of HRS. Various studies in the past few years have indicated that these new diagnostic criteria are valid in the prediction of prognosis for patients with cirrhosis and AKI. The future in AKI diagnosis may include further refinements such as inclusion of biomarkers that can identify susceptibility for AKI, differentiating the various prototypes of AKI, or track its progression.

  11. Elevated renin levels in patients with liver cirrhosis and hepatocellular carcinoma.

    PubMed

    Lotfy, Mahmoud; El-Kenawy, Ayman El-Meghawry; Abdel-Aziz, Mohamed M; El-Kady, Ibrahim; Talaat, Ayman

    2010-01-01

    Liver fibrosis is the common consequence of chronic liver injury of any etiology, disrupting the normal architecture,and causing hepatocellular dysfunction and portal hypertension. Since the renin-angiotensin system (RAS) may be involved in chronic liver diseases, in the present study we assayed renin levels using ELISA in groups of Egyptian patients with liver cirrhosis (N=32) and hepatocellular carcinoma (HCC) (N=67), for comparison with twenty five healthy controls. The results showed significant differences between the control and liver cirrhosis patients (P<0.001) and also the controls and HCC patients (P<0.001), without significant variation between the patient groups. Furthermore, in HCC patients, it was found that the renin levels negatively correlated with serum albumin and prothrombin time (P=0.003 for each) and positively with α-fetoprotein (P=0.04). Thus, it is concluded that renin levels are elevated in patients with liver cirrhosis and HCC and suitable medical intervention should be placed for management of such alteration. Moreover, further studies are warranted to explore its prognostic significance.

  12. Correlation of serum liver fibrosis markers with severity of liver dysfunction in liver cirrhosis: a retrospective cross-sectional study

    PubMed Central

    Zhu, Cuihong; Qi, Xingshun; Li, Hongyu; Peng, Ying; Dai, Junna; Chen, Jiang; Xia, Chunlian; Hou, Yue; Zhang, Wenwen; Guo, Xiaozhong

    2015-01-01

    Hyaluronic acid (HA), laminin (LN), amino-terminal pro-peptide of type III pro-collagen (PIIINP), and collagen IV (CIV) are four major serum markers of liver fibrosis. This retrospective cross-sectional study aimed to evaluate the correlations of the four serum markers with the severity of liver dysfunction in cirrhotic patients. Between January 2013 and June 2014, a total of 228 patients with a clinical diagnosis with liver cirrhosis and without malignancy underwent the tests of HA, LN, PIIINP, and CIV levels. Laboratory data were collected. Child-Pugh and model for the end-stage of liver diseases (MELD) scores were calculated. Of them, 32%, 40%, and 18% had Child-Pugh class A, B, and C, respectively. MELD score was 7.58±0.50. HA (coefficient r: 0.1612, P=0.0203), LN (coefficient r: 0.2445, P=0.0004), and CIV (coefficient r: 0.2361, P=0.0006) levels significantly correlated with Child-Pugh score, but not PIIINP level. Additionally, LN (coefficient r: 0.2588, P=0.0002) and CIV (coefficient r: 0.1795, P=0.0108) levels significantly correlated with MELD score, but not HA or PIIINP level. In conclusions, HA, LN, and CIV levels might be positively associated with the severity of liver dysfunction in cirrhotic patients. However, given a relatively weak correlation between them, our findings should be cautiously interpreted and further validated. PMID:26131195

  13. Nutrient intakes, nutritional patterns and the risk of liver cirrhosis: an explorative case-control study.

    PubMed

    Corrao, Giovanni; Zambon, Antonella; Bagnardi, Vinccnzo; Aricò, Sarino; Loguercio, Carmelina; D'Amicis, Amleto

    2004-01-01

    Several experimental studies have suggested that specific nutrients might play a role on the risk of liver damage. Nevertheless, few epidemiological studies have evaluated the role of diet on the risk of symptomatic liver cirrhosis, giving contradictory results. To evaluate the role of the intake of nutritional factors and dietary patterns on the risk of symptomatic liver cirrhosis and to examine their combined action with alcohol consumption we used data from the Italian Study on Liver Cirrhosis Determinants project. From 1994 to 1998 all the consecutive cirrhotic inpatients admitted to 19 Italian collaborative hospitals for signs of liver decompensation in whom the diagnosis of liver cirrhosis was made for the first time (259 cases) and one or two gender, age and area of residence matched individuals (416 controls) were recruited. Data on lifetime alcohol intake, usual consumption of 191 food items and on markers of hepatitis B and C viral infection were collected. The analysis of principal components identified a nutritional pattern positively correlated with vegetable and fruit intakes and negatively with animal and no-fruit sugar products. With respect to abstainers, relative risks in consumers of use < or = 25 and > or = 51 g/day of alcohol increased from 0.4 [95% confidence interval 0.0, 5.9] to 9.3 [1.3, 69.0] and from 2.1 [1.1, 4.2] to 18.1 [2.8, 118.3] for the lowest and the highest value of this nutritional pattern, respectively. Diet might therefore modulate the damaging effect of alcohol on the liver.

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

    PubMed Central

    2012-01-01

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

  15. Dobutamine stress echocardiography for evaluating cirrhotic cardiomyopathy in liver cirrhosis

    PubMed Central

    Kim, Moon Young; Won, Chan Sik; Park, Hong Jun; Jeon, Hyo Keun; Hong, Hyun Il; Kim, Jae Woo; Kim, Hyun Soo; Kwon, Sang Ok; Kim, Jang Young; Yoo, Byung Su; Lee, Seung Hwan

    2010-01-01

    Background/Aims The blunted ventricular systolic and diastolic contractile responses to physical and pharmacological stress in cirrhosis are termed cirrhotic cardiomyopathy (CCM). CCM has been known to involve multiple defects in the β-adrenergic signaling pathway. The aim of this study was to determine whether cirrhotic patients have blunted cardiac responses to catecholamine stimulation through dobutamine stress echocardiography (DSE). Methods Seventy-one cirrhotic patients with normal left ventricular (LV) chamber size and ejection fraction were enrolled. The LV systolic and diastolic functions were evaluated by two-dimensional and Doppler echocardiography at rest and during peak dobutamine infusion (40 µg/kg/min). An abnormal response was defined as a decrease of less than 10% in LV end-diastolic volume, a decrease of less than 20% in end-systolic volume, and an increase of less than 10% in LV ejection fraction (EF) at peak dobutamine infusion, based on previously used criteria. The early/late diastolic flow (E/A) ratio and diastolic parameters were also measured. Results A blunted LV response to dobutamine was observed in 18 of 71 cirrhotic patients (25.4%). The baseline EF was significantly higher in 18 patients with a blunted DSE response than that of those with a normal DSE response (P<0.05). The baseline and peak E/A ratios, which are common diastolic dysfunction markers, were higher in the cirrhosis group than in the control group (P<0.001). No adverse events associated with DSE were observed. Conclusions Blunted cardiac responses to dobutamine stimulation, which are implicated in defects in the β-adrenergic signaling pathway, might contribute to the pathogenesis of CCM in patients with cirrhosis. PMID:21415581

  16. Factors associated with significant liver necroinflammation in chronic hepatitis B patients with cirrhosis

    PubMed Central

    Chen, Sheng-Sen; Yu, Kang-Kang; Ling, Qing-Xia; Huang, Chong; Li, Ning; Zheng, Jian-Ming; Bao, Su-Xia; Cheng, Qi; Zhu, Meng-Qi; Chen, Ming-Quan

    2016-01-01

    We determined the association between various clinical parameters and significant liver necroinflammation in patients with chronic hepatitis B (CHB) related cirrhosis. Two hundred patients with CHB related cirrhosis were recruited in the final analysis. Clinical laboratory values and characteristics were obtained from the medical record. We performed analyses of the relationships between independent variables and significant liver necroinflammation by using binary logistic regression analysis and discriminant analysis. Significant liver necroinflammation (grade≥2) was found in 58.0% (80/138) of antiviral therapy patients and 48.4% (30/62) of non antiviral therapy patients respectively. Also, there were some significant differences in serum hepatitis B surface antigen (HBsAg), serum hepatitis B e antigen (HBeAg) and serum hepatitis B virus (HBV) DNA between antiviral therapy and non antiviral therapy patients. After that, aspartate aminotransferase (AST), total bilirubin (TBIL), total bile acid (TBA), prothrombin time (PT), aspartate aminotransferase to platelet ratio index (APRI) and serum HBV DNA were confirmed as independent predictors of significant liver necroinflammation in CHB patients with cirrhosis by univariate analysis and multivariate analysis (p = 0.002, 0.044, 0.001, 0.014, 0.01 and 0.02 respectively). Finally, receiver operating characteristic (ROC) curve analysis and discriminant analysis validated that these six variables together have strong predictive power to evaluate significant liver necroinflammation. PMID:27615602

  17. Genetic Diseases That Predispose to Early Liver Cirrhosis

    PubMed Central

    Liguori, Renato

    2014-01-01

    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

  18. 1H Magnetic Resonance Spectroscopy Predicts Hepatocellular Carcinoma in a Subset of Patients With Liver Cirrhosis: A Randomized Trial.

    PubMed

    Wang, Dan; Li, Yuehua

    2015-07-01

    The goal of this study was to investigate the utility of H magnetic resonance spectroscopy (H-MRS) to quantify the differences in liver metabolites. Magnetic resonance spectroscopy was used as a means of predicting the probability of developing hepatocellular carcinoma (HCC) in patients with liver cirrhosis secondary to chronic hepatitis B.This study included 20 healthy volunteers, 20 patients with liver cirrhosis secondary to chronic hepatitis B (cirrhosis group), and 20 patients with small HCC secondary to cirrhosis liver parenchyma (HCC group). All patients underwent routine MRI and H-MRS scanning. LCModel software was used to quantify Cho (Choline), Lip (lipid), and Cho/Lip in the 3 groups, and a one-way ANOVA was used to compare the differences in these metabolites between groups.Choline levels were significantly different between the control and HCC group and between the cirrhosis group and the HCC group (all P < 0.001). There was also a significant difference in Lip levels between the control and cirrhosis group and the control and HCC groups (all P < 0.001). There were also differences in Cho/Lip between the control and cirrhosis groups, the control and HCC groups, and the cirrhosis and HCC groups (all P < 0.001).H-MRS followed by the analysis with LCModel can be used to measure changes in hepatic metabolite levels in patients with liver cirrhosis secondary to chronic hepatitis B and HCC. Thus, H-MRS may be helpful in monitoring HCC and liver cirrhosis development.

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

    PubMed Central

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

    2013-01-01

    Hepatic cirrhosis is the clinical and pathologic result of a multifactorial chronic liver injury. It is well known that cirrhosis is the origin of multiple extrahepatic abdominal complications and a markedly increased risk of hepatocellular carcinoma (HCC). This tumor is the sixth most common malignancy worldwide and the third most common cause of cancer related death. With the rising incidence of HCC worldwide, awareness of the evolution of cirrhotic nodules into malignancy is critical for an early detection and treatment. Adequate imaging protocol selection with dynamic multiphase Multidetector Computed Tomography (MDCT) and reformatted images is crucial to differentiate and categorize the hepatic nodular dysplasia. Knowledge of the typical and less common extrahepatic abdominal manifestations is essential for accurately assessing patients with known or suspected hepatic disease. The objective of this paper is to illustrate the imaging spectrum of intra- and extrahepatic abdominal manifestations of hepatic cirrhosis seen on MDCT. PMID:23986608

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

    SciTech Connect

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

    1981-11-01

    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.

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

    PubMed Central

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

    2000-01-01

    We describe a patient with liver cirrhosis who presented with erosive oral and cutaneous lichen planus (LP) and incidentally was found simultaneously to have thymoma and hepatoma. We support the notion forwarded earlier that LP and chronic liver disease is more than a mere coincidence and that there is a non-coincidental association between LP and thymoma. We believe this is also the first reported case in the English Literature of coexistence of the three condition LP, thymoma and hepatoma complicating liver disease. PMID:22977389

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

    PubMed Central

    Kim, Kyung-Hyun; Park, Kwan-Kyu

    2014-01-01

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

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

    PubMed

    Kim, Kyung-Hyun; Park, Kwan-Kyu

    2014-10-28

    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.

  4. Body Posture Angle Affects the Physiological Indices of Patients With Liver Cirrhosis Ascites.

    PubMed

    Hsu, Wen-chuan; Ho, Lun-hui; Lin, Mei-hsiang; Chiu, Hsiu-ling

    2016-01-01

    The study objective was to compare the effect of different angles of lying positions on the physiological indices of patients with cirrhosis ascites. Chronic liver disease and cirrhosis were ranked 9th among the top 10 causes of death. Ascites is the most common cirrhosis comorbidity. Body posture can affect pulmonary ventilation and arterial oxygen partial pressure, making it an important clinical nursing intervention significantly affecting patient recovery. This was a quasi-experimental study design. From a medical center in Taiwan, 252 patients with cirrhosis ascites were recruited. Subjects were randomly divided into three groups by bed angle: 15°, 30°, and 45°. Physiological indices were measured at 5, 10, 15, 20, 25, and 30 minutes to determine any changes in heart rate, respiration rate, and oxygenation saturation. Data analysis included descriptive statistics and the generalized estimating equation for statistical analysis with significance set at α= 0.05. After controlling for confounding variables, the three groups differed significantly in heart rate at 20, 25, and 30 minutes, oxygenation saturations at 15 and 20 minutes, and respiration rate at 5 and 10 minutes (α< 0.05). Body posture can affect pulmonary ventilation and arterial oxygen partial pressure and is thus an important clinical nursing intervention that significantly affects the recovery of patients. When caring for patients with cirrhosis ascites, nurses should help patients to choose the most comfortable angle for them with no particular restrictions. Our results can be used to guide nurses in making a plan for health education and nursing that improves the quality of care for patients with chronic liver disease and cirrhosis patients with ascites.

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

    PubMed

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

    2015-02-21

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

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

    PubMed Central

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

    2012-01-01

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

  7. Platelet count increase following phlebotomy in iron overloaded patients with liver cirrhosis.

    PubMed

    Franchini, Massimo

    2003-08-01

    Thrombocytopenia is a frequent hematological complication in patients with liver cirrhosis, but its pathogenesis is not clearly understood. We evaluated the effect of iron depletion by phlebotomy on platelet count in 62 consecutive iron overloaded patients with liver cirrhosis and thrombocytopenia. After a median follow-up of 30.2 months we observed a significant increase of platelet count in all patients (from mean baseline levels of 110.1 up to 168.22109/l at the end of follow-up, P<0.001) with platelet count normalization in 42 of them (67.7%). In addition, we observed a significant improvement of serum ALT levels (from pretreatment mean values of 126.7 up to 59.7 U/l at the end of follow-up, P<0.001) along with the reduction of serum ferritin levels and transferrin saturation during phlebotomy. Different pathogenetic mechanisms involving both humoral (erythropoietin and thrombopoietin, TPO) and physical (portal hypertension and hypersplenism) factors are here discussed to explain the platelet count increase following phlebotomy. Our results show that phlebotomy is effective not only in lowering iron overload, but also in improving liver function and thrombocytopenia in patients with liver cirrhosis.

  8. Peripheral blood monocytes from patients with HBV related decompensated liver cirrhosis can differentiate into functional hepatocytes.

    PubMed

    Yan, Li; Han, Ying; Wang, Jingbo; Liu, Jingmei; Hong, Liu; Fan, Daiming

    2007-11-01

    Peripheral blood monocytes (PBMCs) have the potential to differentiate into various progenitor cells. Here we have investigated the differentiation potential of PBMCs derived from patients with HBV related decompensated liver cirrhosis into hepatocyte-like cells. In our clinical trial, the PBMCs from 2 patients were mobilized by the recombinant human granulocyte colony stimulating factor, followed by leukapheresis and transplantation of PBMCs. PBMCs, induced by recombinant human hepatocyte growth factors, were identified by the expression of hepatocyte markers and specific biological functions with biochemical assays in vitro. Patients showed a lasting clinical amelioration for more than one year after transplantation, and hepatocyte-like cells were identified by expressing liver specific genes, synthesizing albumin, urea, aspirate transaminase, and glycogen, which were all similar to the human normal hepatic cell line QZG. Our results clearly demonstrated that mobilized PBMCs from patients with HBV related decompensated liver cirrhosis could differentiate into functional hepatocyte-like cells, indicating the possibility of autologous cell transplantation for treating patients with HBV related decompensated liver cirrhosis.

  9. Portal-systemic encephalopathy in two patients without liver cirrhosis and portal hypertension.

    PubMed

    K C, Sudhamshu; Matsutani, Shoichi; Maruyama, Hitoshi; Fukamachi, Tadahiro; Nomoto, Hiromasa; Akiike, Taro; Ebara, Masaaki; Saisho, Hiromitsu

    2002-06-01

    The portal-systemic venous shunt is uncommon in patients without portal hypertension. We present two cases of portal-systemic encephalopathy due to extrahepatic shunt without liver cirrhosis and portal hypertension. Two women in their seventies were admitted to our hospital because of recurrent episodes of altered sensorium, drowsiness, slurred speech, disorientation, asterexis and high blood ammonia levels. There was no history of abdominal surgery or abdominal trauma. Clinical examination revealed no signs of portal hypertension or stigmata of chronic liver diseases. Brain CT and MRI scanning were unremarkable except for a high intensity signal in the basal ganglia on T1 weighted MRI images. Laboratory tests were almost normal except for the hyperammonemia occurring on several occasions. There was no evidence of liver cirrhosis by imaging. However, color Doppler showed an extra-hepatic shunt in both patients and pulsed Doppler showed decreased velocity and volume of the portal venous flow. These sonographic findings were confirmed during percutaneous transhepatic portography (PTP). Portal pressures measured during PTP were 9 and 11 mmHg. Needle biopsy ruled out idiopathic portal hypertension and liver cirrhosis. The diagnosis was portal systemic encephalopathy due to extra-hepatic portosystemic venous shunting. Both patients were treated by embolization of the shunting vessel with metallic coils.

  10. Splenectomy Causes 10-Fold Increased Risk of Portal Venous System Thrombosis in Liver Cirrhosis Patients.

    PubMed

    Qi, Xingshun; Han, Guohong; Ye, Chun; Zhang, Yongguo; Dai, Junna; Peng, Ying; Deng, Han; Li, Jing; Hou, Feifei; Ning, Zheng; Zhao, Jiancheng; Zhang, Xintong; Wang, Ran; Guo, Xiaozhong

    2016-07-19

    BACKGROUND Portal venous system thrombosis (PVST) is a life-threatening complication of liver cirrhosis. We conducted a retrospective study to comprehensively analyze the prevalence and risk factors of PVST in liver cirrhosis. MATERIAL AND METHODS All cirrhotic patients without malignancy admitted between June 2012 and December 2013 were eligible if they underwent contrast-enhanced CT or MRI scans. Independent predictors of PVST in liver cirrhosis were calculated in multivariate analyses. Subgroup analyses were performed according to the severity of PVST (any PVST, main portal vein [MPV] thrombosis >50%, and clinically significant PVST) and splenectomy. Odds ratios (ORs) and 95% confidence intervals (CIs) were reported. RESULTS Overall, 113 cirrhotic patients were enrolled. The prevalence of PVST was 16.8% (19/113). Splenectomy (any PVST: OR=11.494, 95%CI=2.152-61.395; MPV thrombosis >50%: OR=29.987, 95%CI=3.247-276.949; clinically significant PVST: OR=40.415, 95%CI=3.895-419.295) and higher hemoglobin (any PVST: OR=0.974, 95%CI=0.953-0.996; MPV thrombosis >50%: OR=0.936, 95%CI=0.895-0.980; clinically significant PVST: OR=0.935, 95%CI=0.891-0.982) were the independent predictors of PVST. The prevalence of PVST was 13.3% (14/105) after excluding splenectomy. Higher hemoglobin was the only independent predictor of MPV thrombosis >50% (OR=0.952, 95%CI=0.909-0.997). No independent predictors of any PVST or clinically significant PVST were identified in multivariate analyses. Additionally, PVST patients who underwent splenectomy had a significantly higher proportion of clinically significant PVST but lower MELD score than those who did not undergo splenectomy. In all analyses, the in-hospital mortality was not significantly different between cirrhotic patient with and without PVST. CONCLUSIONS Splenectomy may increase by at least 10-fold the risk of PVST in liver cirrhosis independent of severity of liver dysfunction.

  11. Hyperammonemia Is Associated with Increasing Severity of Both Liver Cirrhosis and Hepatic Encephalopathy

    PubMed Central

    Ayub, Maimoona; Khan, Wazir Mohammad

    2016-01-01

    Background. Hyperammonemia resulting from chronic liver disease (CLD) can potentially challenge and damage any organ system of the body, particularly the brain. However, there is still some controversy regarding the diagnostic or prognostic values of serum ammonia in patients with over hepatic encephalopathy, especially in the setting of acute-on-chronic or chronic liver failure. Moreover, the association of serum ammonia with worsening Child-Pugh grade of liver cirrhosis has not been studied. Objective. This study was conducted to solve the controversy regarding the association between hyperammonemia and cirrhosis, especially hepatic encephalopathy in chronically failed liver. Material and Methods. In this study, 171 cirrhotic patients had their serum ammonia measured and analyzed by SPSS version 16. Chi-squared test and one-way ANOVA were applied. Results. The study had 110 male and 61 female participants. The mean age of all the participants in years was 42.33 ± 7.60. The mean duration (years) of CLD was 10.15 ± 3.53 while the mean Child-Pugh (CP) score was 8.84 ± 3.30. Chronic viral hepatitis alone was responsible for 71.3% of the cases. Moreover, 86.5% of participants had hepatic encephalopathy (HE). The frequency of hyperammonemia was 67.3%, more frequent in males (N = 81, z-score = 2.4, and P < 0.05) than in females (N = 34, z-score = 2.4, and P < 0.05), and had a statistically significant relationship with increasing CP grade of cirrhosis (χ2(2) = 27.46, P < 0.001, Phi = 0.40, and P < 0.001). Furthermore, serum ammonia level was higher in patients with hepatic encephalopathy than in those without it; P < 0.001. Conclusion. Hyperammonemia is associated with both increasing Child-Pugh grade of liver cirrhosis and hepatic encephalopathy. PMID:27847646

  12. Determinants of hepatic function in liver cirrhosis in the rat. Multivariate analysis.

    PubMed Central

    Reichen, J; Egger, B; Ohara, N; Zeltner, T B; Zysset, T; Zimmermann, A

    1988-01-01

    We investigated the determinants of hepatic clearance functions in a rat model of liver cirrhosis induced by phenobarbital/CCl4. Aminopyrine N-demethylation (ABT), galactose elimination (GBT), and serum bile acids (SBA) were determined in vivo. The livers were then characterized hemodynamically: intrahepatic shunting (IHS) was determined by microspheres and sinusoidal capillarization by measuring the extravascular albumin space (EVA) by a multiple indicator dilution technique. The intrinsic clearance was determined by assaying the activity of the rate-limiting enzymes in vitro. Hepatocellular volume (HCV) was measured by morphometry. ABT and SBA, but not GBT, differentiated cirrhotic from normal liver. IHS ranged from normal to 10%; all cirrhotic livers showed evidence of sinusoidal capillarization (reduced EVA). The cirrhotic livers showed a bimodal distribution of HCV, HCV being decreased in 50% of the cirrhotic livers. Multivariate analysis showed EVA and portal flow to be the main determinants of microsomal (ABT) and cytosolic (GBT) clearance function; SBA, by contrast, were determined solely by IHS. We conclude that sinusoidal capillarization is the main determinant of hepatic clearance, while serum bile acids reflect intrahepatic shunting. These findings emphasize the importance of alterations of hepatic nutritional flow to explain reduced clearance function in cirrhosis of the liver. PMID:3198765

  13. The molecular basis of susceptibility to infection in liver cirrhosis.

    PubMed

    Chavez-Tapia, Norberto C; Torre-Delgadillo, Aldo; Tellez-Avila, Felix I; Uribe, Misael

    2007-01-01

    There is much clinical evidence of a relationship between infectious disease and chronic liver disease. The consequences of this adverse association have been described and advances in the treatment and prophylaxis of infectious disease have had an important effect on the management of patients with chronic liver disease. The association between infectious disease and chronic liver disease involves altered cytokine production, cellular immunity, and vascular response. However, there is little information on the mechanisms underlying these phenomena. In this report, we review the mechanistic basis of this common association.

  14. Factors Influencing Surveillance for Hepatocellular Carcinoma in Patients with Liver Cirrhosis

    PubMed Central

    Ahmed Mohammed, Hager A.; Yang, Ju Dong; Giama, Nasra H.; Choi, Jonggi; Ali, Hawa M.; Mara, Kristin C.; Harmsen, William S.; Wiesner, Russell H.; Leise, Michael D.; Therneau, Terry M.; Roberts, Lewis R.

    2017-01-01

    Objective Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related mortality worldwide, and a rising cause of cancer mortality in the U.S. Liver cirrhosis is the major risk factor for HCC. Surveillance of persons with cirrhosis facilitates early detection and improves outcomes. We assessed the surveillance rate for HCC within a major academic health system and identified factors influencing surveillance. Patients and Methods We examined the surveillance rate for HCC using liver ultrasound, CT, or MRI, and factors influencing surveillance in a cohort of 369 Minnesota residents with cirrhosis seen at the Mayo Clinic between 2007 and 2009. Results Ninety-three percent of cirrhosis patients received at least one surveillance study, but only 14% received the recommended uninterrupted semiannual surveillance. Thirty percent received ≥75% of recommended surveillance, and 59% received ≥50% of recommended surveillance. Factors increasing surveillance included gastroenterology or hepatology specialist visits (p < 0.0001), advanced liver disease as assessed by hepatic encephalopathy (p = 0.0008), and comorbid illness as assessed by diabetes mellitus (p = 0.02). Age, sex, race, residence, cirrhosis etiology, or number of primary care visits did not significantly affect the rate of surveillance. Conclusions While the rate of surveillance in a major academic health system was higher than reported in other studies, surveillance was heavily dependent on visits to a subspecialist. This suggests a major and urgent national need to improve identification of individuals at risk for HCC in the primary care setting and the initiation and maintenance of surveillance by primary care practitioners. PMID:28275579

  15. Systemic hemodynamics in advanced cirrhosis: Concerns during perioperative period of liver transplantation

    PubMed Central

    Hori, Tomohide; Ogura, Yasuhiro; Onishi, Yasuharu; Kamei, Hideya; Kurata, Nobuhiko; Kainuma, Motoshi; Takahashi, Hideo; Suzuki, Shogo; Ichikawa, Takashi; Mizuno, Shoko; Aoyama, Tadashi; Ishida, Yuki; Hirai, Takahiro; Hayashi, Tomoko; Hasegawa, Kazuko; Takeichi, Hiromu; Ota, Atsunobu; Kodera, Yasuhiro; Sugimoto, Hiroyuki; Iida, Taku; Yagi, Shintaro; Taniguchi, Kentaro; Uemoto, Shinji

    2016-01-01

    Advanced liver cirrhosis is usually accompanied by portal hypertension. Long-term portal hypertension results in various vascular alterations. The systemic hemodynamic state in patients with cirrhosis is termed a hyperdynamic state. This peculiar hemodynamic state is characterized by an expanded blood volume, high cardiac output, and low total peripheral resistance. Vascular alterations do not disappear even long after liver transplantation (LT), and recipients with cirrhosis exhibit a persistent systemic hyperdynamic state even after LT. Stability of optimal systemic hemodynamics is indispensable for adequate portal venous flow (PVF) and successful LT, and reliable parameters for optimal systemic hemodynamics and adequate PVF are required. Even a subtle disorder in systemic hemodynamics is precisely indicated by the balance between cardiac output and blood volume. The indocyanine green (ICG) kinetics reflect the patient’s functional hepatocytes and effective PVF, and PVF is a major determinant of the ICG elimination constant (kICG) in the well-preserved allograft. The kICG value is useful to set the optimal PVF during living-donor LT and to evaluate adequate PVF after LT. Perioperative management has a large influence on the postoperative course and outcome; therefore, key points and unexpected pitfalls for intensive management are herein summarized. Transplant physicians should fully understand the peculiar systemic hemodynamic behavior in LT recipients with cirrhosis and recognize the critical importance of PVF after LT. PMID:27660671

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

    SciTech Connect

    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

    (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.

  17. A liver cirrhosis classification on B-mode ultrasound images by the use of higher order local autocorrelation features

    NASA Astrophysics Data System (ADS)

    Sasaki, Kenya; Mitani, Yoshihiro; Fujita, Yusuke; Hamamoto, Yoshihiko; Sakaida, Isao

    2017-02-01

    In this paper, in order to classify liver cirrhosis on regions of interest (ROIs) images from B-mode ultrasound images, we have proposed to use the higher order local autocorrelation (HLAC) features. In a previous study, we tried to classify liver cirrhosis by using a Gabor filter based approach. However, the classification performance of the Gabor feature was poor from our preliminary experimental results. In order accurately to classify liver cirrhosis, we examined to use the HLAC features for liver cirrhosis classification. The experimental results show the effectiveness of HLAC features compared with the Gabor feature. Furthermore, by using a binary image made by an adaptive thresholding method, the classification performance of HLAC features has improved.

  18. Expression of leptin and leptin receptor during the development of liver fibrosis and cirrhosis.

    PubMed

    Otte, C; Otte, J-M; Strodthoff, D; Bornstein, S R; Fölsch, U R; Mönig, H; Kloehn, S

    2004-01-01

    Leptin is involved in the regulation of food intake and is mainly secreted by adipocytes. Major secretagogues are cytokines such as TNF-alpha or IL-1. Leptin in turn upregulates inflammatory immune responses. Elevated leptin serum levels have been detected in patients with liver cirrhosis, a disease frequently associated with elevated levels of circulating cytokines as well as hypermetabolism and altered body weight. Recently, leptin has been detected in activated hepatic stellate cells in vitro and an involvement of leptin in liver fibrogenisis has been suggested. The current study was designed to further clarify the role of leptin in liver disease by characterizing leptin and leptin receptor expression in the development and onset of experimental liver fibrosis. Liver fibrosis and cirrhosis was induced in rats by use of phenobarbitone and increasing doses of CCl (4). Leptin and leptin receptor mRNA expression was determined by semiquantitative RT-PCR, protein expression by Western blot analysis and localization of leptin and its receptor by immunohistochemistry. Normal liver tissue does not express leptin, but leptin receptor mRNA. Increasing levels of leptin mRNA were detected in fibrotic and cirrhotic livers correlated to the degree of fibrosis. Leptin receptor mRNA expression was not significantly altered in damaged livers. Increasing levels of leptin were detected in fibrotic and cirrhotic livers, whereas protein expression of the receptor remained unchanged. Throughout different stages of liver fibrosis, leptin immunoreactivity was localized in activated hepatic stellate cells only, whereas immunoreactivity for the receptor was mainly seen on hepatocytes. In conclusion, leptin is expressed at increasing levels in activated hepatic stellate cells in vivo, which may therefore be a source of increased leptin tissue and serum levels contributing to the pathophysiology and morphological changes of chronic liver disease.

  19. Primary biliary cirrhosis

    MedlinePlus

    ... medlineplus.gov/ency/article/000282.htm Primary biliary cirrhosis To use the sharing features on this page, ... and leads to scarring of the liver called cirrhosis. This is called biliary cirrhosis. Causes The cause ...

  20. [Gender difference of clinical features in Japanese patients with alcoholic liver cirrhosis].

    PubMed

    Kawashima, Osamu; Ohata, Mitsuru; Sakamoto, Kazuhiko; Hashimoto, Kenichi; Nakajima, Hisato; Yamauchi, Masayoshi

    2003-02-01

    Gender difference of alcohol intake and laboratory data was investigated in 165 Japanese patients with alcoholic liver cirrhosis. Mean age of first drinking and habitual drinking were higher in female. Duration of drinking was shorter in female. Although cumulative alcohol intake was larger in male, mean daily alcohol intake did not differ in both gender. Moreover, daily alcohol intake adjusted to body weight was significantly larger in female. Body mass index, serum levels of total protein, albumin and cholinesterase were significantly decreased in female. Platelet counts on admission did not differ in both gender. However, it was significantly increased in female after one month abstinence. C reactive protein, ammonia and serum levels of total bilirubin were significantly higher in female as compared to male. In conclusion, female alcoholics seems to progress to liver cirrhosis earlier because of high daily alcohol intake adjusted to body weight, poor nutritional condition and inflammation caused by endotoxin.

  1. Multiple Brain Abscesses Due to Aspergillus Fumigatus in a Patient With Liver Cirrhosis: A Case Report.

    PubMed

    Tang, Hung-Jen; Liu, Wei-Lun; Chang, Tsung Chain; Li, Ming-Chi; Ko, Wen-Chien; Wu, Chi-Jung; Chuang, Yin-Ching; Lai, Chih-Cheng

    2016-03-01

    Invasive cerebral aspergillosis always developed in immunocompromised host. Early diagnosis may save life in this critical condition; however, it is difficult to reach. Herein, we presented an unusual case of invasive cerebral aspergillosis in a cirrhotic patient. A 47-year-old man presented with progressive deterioration of consciousness for three days. The patient had a history of alcoholic liver cirrhosis, Child-Pugh class C. Magnetic resonance imaging (MRI) of brain showed multi-focal parenchymal lesions, which was consistent with multiple brain abscesses. The diagnosis of invasive cerebral aspergillosis was made by molecular based laboratory methods including Aspergillus galactomannan antigen assay and oligonucleotide array. Despite treatment with the antifungal agent, Amphotericin B, the patient died at the ninth day of hospitalization. Our findings suggest that liver cirrhosis can be one of risk factors of invasive cerebral aspergillosis, and support the diagnosing usefulness of MRI, Aspergillus galactomannan antigen assay, and oligonucleotide array.

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

    SciTech Connect

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

    1981-08-01

    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.

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

    NASA Astrophysics Data System (ADS)

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

    1992-04-01

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

  4. Acute-on-chronic liver failure: A new syndrome that will re-classify cirrhosis.

    PubMed

    Arroyo, Vicente; Moreau, Richard; Jalan, Rajiv; Ginès, Pere

    2015-04-01

    Acute-on-chronic liver failure (ACLF) is a recently recognized syndrome characterized by acute decompensation (AD) of cirrhosis and organ/system failure(s) (organ failure: liver, kidney, brain, coagulation, circulation and/or respiration) and extremely poor survival (28-day mortality rate 30-40%). ACLF occurs in relatively young patients. It is especially frequent in alcoholic- and untreated hepatitis B associated-cirrhosis, in addition it is related to bacterial infections and active alcoholism, although in 40% of cases no precipitating event can be identified. It may develop at any time during the course of the disease in the patient (from compensated to long-standing cirrhosis). The development of ACLF occurs in the setting of a systemic inflammation, the severity of which correlates with the number of organ failures and mortality. Systemic inflammation may cause ACLF through complex mechanisms including an exaggerated inflammatory response and systemic oxidative stress to pathogen- or danger/damage-associated molecular patterns (immunopathology) and/or alteration of tissue homeostasis to inflammation caused either by the pathogen itself or through a dysfunction of tissue tolerance. A scoring system composed of three scores (CLIF-C OFs, CLIF-C AD, and CLIF-C ACLFs) specifically designed for patients with AD, with and without ACLF, allows a step-wise algorithm for a rational indication of therapy. The management of ACLF should be carried out in enhanced or intensive care units. Current therapeutic measures comprise the treatment for associated complications, organ failures support and liver transplantation.

  5. Contemporary concepts of the medical therapy of portal hypertension under liver cirrhosis

    PubMed Central

    Garbuzenko, Dmitry Victorovich

    2015-01-01

    Severe complications of liver cirrhosis are mostly related to portal hypertension. At the base of the pathogenesis of portal hypertension is the increase in hepatic vascular resistance to portal blood flow with subsequent development of hyperdynamic circulation, which, despite of the formation of collateral circulation, promotes progression of portal hypertension. An important role in its pathogenesis is played by the rearrangement of vascular bed and angiogenesis. As a result, strategic directions of the therapy of portal hypertension under liver cirrhosis include selectively decreasing hepatic vascular resistance with preserving or increasing portal blood flow, and correcting hyperdynamic circulation and pathological angiogenesis, while striving to reduce the hepatic venous pressure gradient to less than 12 mmHg or 20% of the baseline. Over the last years, substantial progress in understanding the pathophysiological mechanisms of hemodynamic disorders under liver cirrhosis has resulted in the development of new drugs for their correction. Although the majority of them have so far been investigated only in animal experiments, as well as at the molecular and cellular level, it might be expected that the introduction of the new methods in clinical practice will increase the efficacy of the conservative approach to the prophylaxis and treatment of portal hypertension complications. The purpose of the review is to describe the known methods of portal hypertension pharmacotherapy and discuss the drugs that may affect the basic pathogenetic mechanisms of its development. PMID:26034348

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

    SciTech Connect

    Angelico, M.; Alvaro, D.; Cantafora, A.; Masella, R.; Gaudio, E.; Gandin, C.; Ginanni Corradini, S.; Ariosto, F.; Riggio, O.; Capocaccia, L. )

    1991-07-01

    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.

  7. The Prescription Pattern of Acetaminophen and Non-Steroidal Anti-Inflammatory Drugs in Patients with Liver Cirrhosis.

    PubMed

    Hong, Young Mi; Yoon, Ki Tae; Heo, Jeong; Woo, Hyun Young; Lim, Won; An, Dae Seong; Han, Jun Hee; Cho, Mong

    2016-10-01

    Analgesics, known to be hepatotoxic drugs, are frequently prescribed to patients with liver cirrhosis who are prone to drug-induced liver injury. No guidelines are available regarding the prescription of analgesics in these patients. Therefore, we aimed to evaluate the prescription pattern of most frequently used analgesics in patients with cirrhosis. We assessed the prescription pattern of acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs) in patients with liver cirrhosis registered in Health Insurance Review Assessment Service database between January 1, 2012 and December 31, 2012. A total of 125,505 patients with liver cirrhosis were registered from January 1, 2012 to December 31, 2012. Of that group, 50,798 (40.5%) patients claimed reimbursement for at least one prescription for acetaminophen or NSAIDs during the one year follow-up period. Overall, NSAIDs (82.7%) were more prescribed than acetaminophen (64.5%). NSAIDs were more prescribed than acetaminophen even in decompensated cirrhosis compared with compensated cirrhosis (71.5% vs. 68.8%, P value < 0.001). There was a marked difference in prescription preference between acetaminophen and NSAIDs among physicians. Internists more frequently prescribed acetaminophen than NSAIDs compared to other physicians (50.9% vs. 76.2%, P < 0.001). Gastroenterologists more frequently prescribed acetaminophen over NSAIDs compared to other internists (80.9% vs. 51.2%, P < 0.001). Analgesics were prescribed in 40.5% of patients with cirrhosis. NSAIDs were more frequently prescribed although they should be avoided. The prescription pattern of analgesics were different significantly among physicians in patients with liver cirrhosis. The harmful effects of NSAIDs in patients with cirrhosis should be reminded to all physicians prescribing analgesics.

  8. The Prescription Pattern of Acetaminophen and Non-Steroidal Anti-Inflammatory Drugs in Patients with Liver Cirrhosis

    PubMed Central

    2016-01-01

    Analgesics, known to be hepatotoxic drugs, are frequently prescribed to patients with liver cirrhosis who are prone to drug-induced liver injury. No guidelines are available regarding the prescription of analgesics in these patients. Therefore, we aimed to evaluate the prescription pattern of most frequently used analgesics in patients with cirrhosis. We assessed the prescription pattern of acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs) in patients with liver cirrhosis registered in Health Insurance Review Assessment Service database between January 1, 2012 and December 31, 2012. A total of 125,505 patients with liver cirrhosis were registered from January 1, 2012 to December 31, 2012. Of that group, 50,798 (40.5%) patients claimed reimbursement for at least one prescription for acetaminophen or NSAIDs during the one year follow-up period. Overall, NSAIDs (82.7%) were more prescribed than acetaminophen (64.5%). NSAIDs were more prescribed than acetaminophen even in decompensated cirrhosis compared with compensated cirrhosis (71.5% vs. 68.8%, P value < 0.001). There was a marked difference in prescription preference between acetaminophen and NSAIDs among physicians. Internists more frequently prescribed acetaminophen than NSAIDs compared to other physicians (50.9% vs. 76.2%, P < 0.001). Gastroenterologists more frequently prescribed acetaminophen over NSAIDs compared to other internists (80.9% vs. 51.2%, P < 0.001). Analgesics were prescribed in 40.5% of patients with cirrhosis. NSAIDs were more frequently prescribed although they should be avoided. The prescription pattern of analgesics were different significantly among physicians in patients with liver cirrhosis. The harmful effects of NSAIDs in patients with cirrhosis should be reminded to all physicians prescribing analgesics. PMID:27550489

  9. Hepatoprotective Effects of Chinese Medicine Herbs Decoction on Liver Cirrhosis in Rats

    PubMed Central

    Lim, Tong-Hye; Nor-Amdan, Nur-Asyura

    2017-01-01

    Hepatoprotective and curative activities of aqueous extract of decoction containing 10 Chinese medicinal herbs (HPE-XA-08) were evaluated in Sprague–Dawley albino rats with liver damage induced by thioacetamide (TAA). These activities were assessed by investigating the liver enzymes level and also histopathology investigation. Increases in alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) levels were observed in rats with cirrhotic liver. No significant alterations of the liver enzymes were observed following treatment with HPE-XA-08. Histopathology examination of rats treated with HPE-XA-08 at 250 mg/kg body weight, however, exhibited moderate liver protective effects. Reduced extracellular matrix (ECM) proteins within the hepatocytes were noted in comparison to the cirrhotic liver. The curative effects of HPE-XA-08 were observed with marked decrease in the level of ALP (more than 3x) and level of GGT (more than 2x) in cirrhotic rat treated with 600 mg/kg body weight HPE-XA-08 in comparison to cirrhotic rat treated with just water diluent. Reversion of cirrhotic liver to normal liver condition in rats treated with HPE-XA-08 was observed. Results from the present study suggest that HPE-XA-08 treatment assisted in the protection from liver cirrhosis and improved the recovery of cirrhotic liver. PMID:28280515

  10. Serum Concentrations of Selected Heavy Metals in Patients with Alcoholic Liver Cirrhosis from the Lublin Region in Eastern Poland.

    PubMed

    Prystupa, Andrzej; Błażewicz, Anna; Kiciński, Paweł; Sak, Jarosław J; Niedziałek, Jarosław; Załuska, Wojciech

    2016-06-13

    According to the WHO report, alcohol is the third most significant health risk factor for the global population. There are contrary reports about heavy metals concentrations in patients with alcoholic liver cirrhosis. The aim of this study was to investigate serum concentrations of selected heavy metals in patients with alcoholic liver cirrhosis living in the eastern part of Poland according to cirrhosis stage. The participants came from various hospitals of the Lublin region were enrolled. The study group included 46 male and 16 female patients. The control group consisted of 18 healthy individuals without liver disease. High Performance Ion Chromatography was used to determine the concentrations of metal ions (Cd, Zn, Cu, Ni, Co, Mn, and Pb) in serum samples. The concentrations of copper, zinc, nickel, and cobalt were found to be significantly lower in patients with alcoholic liver cirrhosis compared to the control group. The serum concentration of cadmium was significantly higher in patients with advanced alcoholic liver cirrhosis compared to the control group. We hypothesize that disorders of metabolism of heavy metals seem to be the outcome of impaired digestion and absorption, which are common in cirrhosis, improper diet, environmental and occupational exposure.

  11. Serum Concentrations of Selected Heavy Metals in Patients with Alcoholic Liver Cirrhosis from the Lublin Region in Eastern Poland

    PubMed Central

    Prystupa, Andrzej; Błażewicz, Anna; Kiciński, Paweł; Sak, Jarosław J.; Niedziałek, Jarosław; Załuska, Wojciech

    2016-01-01

    According to the WHO report, alcohol is the third most significant health risk factor for the global population. There are contrary reports about heavy metals concentrations in patients with alcoholic liver cirrhosis. The aim of this study was to investigate serum concentrations of selected heavy metals in patients with alcoholic liver cirrhosis living in the eastern part of Poland according to cirrhosis stage. The participants came from various hospitals of the Lublin region were enrolled. The study group included 46 male and 16 female patients. The control group consisted of 18 healthy individuals without liver disease. High Performance Ion Chromatography was used to determine the concentrations of metal ions (Cd, Zn, Cu, Ni, Co, Mn, and Pb) in serum samples. The concentrations of copper, zinc, nickel, and cobalt were found to be significantly lower in patients with alcoholic liver cirrhosis compared to the control group. The serum concentration of cadmium was significantly higher in patients with advanced alcoholic liver cirrhosis compared to the control group. We hypothesize that disorders of metabolism of heavy metals seem to be the outcome of impaired digestion and absorption, which are common in cirrhosis, improper diet, environmental and occupational exposure. PMID:27304961

  12. Nanoparticle Based Delivery of Quercetin for the Treatment of Carbon Tetrachloride Mediated Liver Cirrhosis in Rats.

    PubMed

    Verma, Shashi Kant; Rastogil, Shweta; Arora, Indu; Javed, Kalim; Akhtar, Mohd; Samim, Mohd

    2016-02-01

    Liver fibrosis is the common response to chronic liver injury and ultimately leads to cirrhosis. There is a pressing need in the pharmaceutical industry to develop efficient well-targeted drug delivery systems, which are lacking to date. This study was designed to investigate the efficacy of a nanoquercetin NQ; i.e., quercetin encapsulated in PAG (p-aminophenyl-1-thio-β-D-galactopryranoside)-coated NIPAAM (N-isopropyl acrylamide) nanopolymer in liver compared with naked quercetin (Q) using a carbon tetrachloride (CCl₄)-mediated liver cirrhosis model. NQ was more effective at restoring liver membrane integrity as indicated by significantly reduced serum markers, including Alanine Transaminase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) and Lactate Dehydrogenase (LDH), compared with naked Q. The findings of reduced collagen and histopathology also show that the NQ effects were much better than those of naked Q. Biochemical parameters, including antioxidant defense enzymes, also provide supporting evidence. Furthermore, the decrease in NF-κB and NOS-2 expression in the NQ-treated groups was also much stronger than in the naked Q-treated group. Thus, the data clearly suggest that NQ not only provides significant hepatoprotection compared with naked Q, but it also substantially lowered the required concentration (1,000 to 10,000-fold lower) by increasing the bioavailability.

  13. Association of serum level of growth differentiation factor 15 with liver cirrhosis and hepatocellular carcinoma.

    PubMed

    Liu, Xiuying; Chi, Xiumei; Gong, Qiaoling; Gao, Lei; Niu, Yuqiang; Chi, Xiaojing; Cheng, Min; Si, Youhui; Wang, Maorong; Zhong, Jin; Niu, Junqi; Yang, Wei

    2015-01-01

    Hepatocellular carcinoma (HCC) and liver cirrhosis are associated with high mortality worldwide. Currently, alpha-fetoprotein (AFP) is used as a standard serum marker for the detection of HCC, but its sensitivity and specificity are unsatisfactory, and optimal diagnostic markers for cirrhosis are lacking. We previously reported that growth differentiation factor 15 (GDF15) was significantly induced in HCV-infected hepatocytes. This study aimed to investigate GDF15 expression and its correlation with hepatitis virus-related liver diseases. A total of 412 patients with various liver diseases were studied. Healthy and Mycobacterium tuberculosis-infected subjects were included as controls. Serum and tissue GDF15 levels were measured. Serum GDF15 levels were significantly increased in patients with HCC (6.66±0.67 ng/mL, p<0.0001) and cirrhosis (6.51±1.47 ng/mL, p<0.0001) compared with healthy controls (0.31±0.01 ng/mL), though the GDF15 levels in HBV and HCV carriers were moderately elevated (1.34±0.19 ng/mL and 2.13±0.53 ng/mL, respectively). Compared with HBV or HCV carriers, GDF15 had a sensitivity of 63.1% and a specificity of 86.6% at the optimal cut-off point of 2.463 ng/mL in patients with liver cirrhosis or HCC. In HCC patients, the area under the receiver operating curve was 0.84 for GDF15 and 0.76 for AFP, but 0.91 for the combined GDF15 and AFP. Serum GDF15 levels did not significantly differ between the high-AFP and low-AFP groups. GDF15 protein expression in HCC was significantly higher than that in the corresponding adjacent paracarcinomatous tissue and normal liver. Using a combination of GDF15 and AFP will improve the sensitivity and specificity of HCC diagnosis. Further research and the clinical implementation of serum GDF15 measurement as a biomarker for HCC and cirrhosis are recommended.

  14. Circulating vascular endothelial growth factor and its soluble receptors in patients with liver cirrhosis: possible association with hepatic function impairment.

    PubMed

    Jaroszewicz, Jerzy; Januszkiewicz, Marcin; Flisiak, Robert; Rogalska, Magdalena; Kalinowska, Alicja; Wierzbicka, Iwona

    2008-10-01

    Recent studies provided in vivo evidences of an increased angiogenesis in animal model of portal hypertension and cirrhosis which was linked to increased expression of vascular endothelial growth factor. The aim of study was to evaluate the plasma concentration of VEGF and its receptors in liver cirrhosis and the possible association with the degree of liver insufficiency. Methods. Vascular endothelial growth factor (VEGF) and its soluble receptors: sVEGF-R1, sVEGF-R2 were measured in plasma of 78 patients with liver cirrhosis by ELISA. Results. The significant increase of plasma VEGF and sVEGF-R1 was observed in liver cirrhosis compared to healthy individuals (153.1+/-51.9 vs. 46.8+/-4.1pg/mL, P<0.05; 279.8+/-34.3 vs. 105.1+/-5.9pg/mL, P<0.001, respectively). Plasma VEGF and foremost sVEGF R1 showed significant associations with biochemical indices of liver function. Among clinical parameters, only ascites revealed significant association with plasma VEGR and sVEGF-R1. VEGF and sVEGF-R1 were increased respectively to the degree of liver insufficiency. It was demonstrated through a significant positive correlation with Child-Pugh score and MELD classification. In conclusion, our study suggests that serum VEGF and VEGF-R1 may reflect the hepatic function impairment in liver cirrhosis and seems to be associated with portal hypertension symptoms.

  15. Clinical efficacy of tolvaptan for treatment of refractory ascites in liver cirrhosis patients

    PubMed Central

    Zhang, Xin; Wang, Shu-Zhen; Zheng, Jun-Fu; Zhao, Wen-Min; Li, Peng; Fan, Chun-Lei; Li, Bing; Dong, Pei-Ling; Li, Lei; Ding, Hui-Guo

    2014-01-01

    AIM: To evaluate the efficacy and safety of tolvaptan to treat refractory ascites in decompensated liver cirrhosis patients with or without further complications, such as hepatorenal syndrome and/or hepatocellular carcinoma. METHODS: Thirty-nine patients (mean age 55 years, males: 32) with decompensated liver cirrhosis and refractory ascites were enrolled. All patients received a combination of tolvaptan (15 mg/d for 5-14 d) and diuretics (40-80 mg/d of furosemide and 80-160 mg/d of spironolactone). The etiology of cirrhosis included hepatitis B (69.2%), hepatitis C (7.7%) and alcohol-induced (23.1%). Changes in the urine excretion volume, abdominal circumference and edema were assessed. The serum sodium levels were also measured, and adverse events were recorded. A follow-up assessment was conducted 1 mo after treatment with tolvaptan. RESULTS: Tolvaptan increased the mean urine excretion volume (1969.2 ± 355.55 mL vs 3410.3 ± 974.1 mL, P < 0.001), and 89.7% of patients showed improvements in their ascites, 46.2% of whom showed significant improvements. The overall efficacy of tolvaptan in all patients was 89.7%; the efficacies in patients with hepatocellular carcinoma and hepatorenal syndrome were 84.2% and 77.8%, respectively. The incidence of hyponatremia was 53.8%. In patients with hyponatremia, the serum sodium levels increased after tolvaptan treatment (from 128.1 ± 4.22 mEq/L vs 133.1 ± 3.8 mEq/L, P < 0.001). Only mild drug-related adverse events, including thirst and dry mouth, were observed. CONCLUSION: Tolvaptan is a promising aquaretic for the treatment of refractory ascites in patients with decompensated liver cirrhosis. PMID:25170228

  16. Prevalence of Iron deficiency anemia in children with liver cirrhosis: A cross-sectional study

    PubMed Central

    Zareifar, Soheila; Dehghani, Seyed Mohsen; Rahanjam, Najmeh; Farahmand Far, Mohammad Reza

    2015-01-01

    Background: Among the many complications reported for cirrhosis, iron deficiency anemia (IDA) has attracted much attention. This type of anemia, in contrast to other types of anemia, is easy to treat prophylactically, but if left untreated can lead to a poor quality of life. The aim of this study was to estimate the hemoglobin and serum iron levels among patients with liver cirrhosis for the early diagnosis of IDA and to avoid unnecessary testing and iron supplementation. Subjects and Methods: In this cross-sectional study, 88 children diagnosed with cirrhosis were included, and the values of hemoglobin, serum iron levels and relationship between serum iron (SI), total iron-binding capacity (TIBC), prothrombine time (PT), international normalization ratio (INR), total and direct bilirubin and hepatic enzymes were estimated using paired t test, Mann-Whitney, Chi-square and Kruskal-Wallis tests. Results: Forty-six (52.3%) of 88 children were girls and 42 (47.7%) were boys. Forty-eight (54.5%) patients had anemia and 8 (9%) had iron deficiency anemia (5 boys, 5.6%, and 3 girls, 3.4%). No relationships were observed between iron deficiency anemia and the patient’s age or gender, whereas there was a relationship between iron deficiency and severity and duration of the disease, although the correlation was not statistically significant. Conclusion: The high frequency of iron deficiency anemia in children with cirrhosis (9%) suggests that timely screening should be used for early diagnosis and treatment. PMID:26261697

  17. Identification of circulating CD90+ CD73+ cells in cirrhosis of liver

    PubMed Central

    Sasikala, Mitnala; Surya, Pugazhelthi; Radhika, Gaddipati; Kumar, Pondugala Pavan; Rao, Mekala Subba; Mukherjee, Rathindra Mohan; Rao, Padaki Nagaraja; Reddy, D Nageshwar

    2011-01-01

    AIM: To identify circulating CD90+ CD73+ CD45- cells and evaluate their in vitro proliferating abilities. METHODS: Patients with cirrhosis (n = 43), and healthy volunteers (n = 40) were recruited to the study. Mononuclear cells were isolated and cultured from the peripheral blood of controls and cirrhosis patients. Fibroblast-like cells that appeared in cultures were analyzed for morphological features, enumerated by flow cytometry and confirmed by immunocytochemistry (ICC). Colony forming efficiency (CFE) of these cells was assessed and expressed as a percentage. RESULTS: In comparison to healthy volunteers, cells obtained from cirrhotic patients showed a significant increase (P < 0.001) in the percentage of CD90+ CD73+ CD45- cells in culture. Cultured cells also showed 10 fold increases in CFE. Flow cytometry and ICC confirmed that the proliferating cells expressed CD90+ CD73+ in the cultures from cirrhosis patients. CONCLUSION: These results indicate the presence of circulating CD90+ CD73+ CD45- cells in patients with liver cirrhosis that have the potential to proliferate at a higher rate. PMID:21860671

  18. Sparse reconstruction of liver cirrhosis from monocular mini-laparoscopic sequences

    NASA Astrophysics Data System (ADS)

    Marcinczak, Jan Marek; Painer, Sven; Grigat, Rolf-Rainer

    2015-03-01

    Mini-laparoscopy is a technique which is used by clinicians to inspect the liver surface with ultra-thin laparoscopes. However, so far no quantitative measures based on mini-laparoscopic sequences are possible. This paper presents a Structure from Motion (SfM) based methodology to do 3D reconstruction of liver cirrhosis from mini-laparoscopic videos. The approach combines state-of-the-art tracking, pose estimation, outlier rejection and global optimization to obtain a sparse reconstruction of the cirrhotic liver surface. Specular reflection segmentation is included into the reconstruction framework to increase the robustness of the reconstruction. The presented approach is evaluated on 15 endoscopic sequences using three cirrhotic liver phantoms. The median reconstruction accuracy ranges from 0.3 mm to 1 mm.

  19. Serum Catecholamines and Dysautonomia in Diabetic Gastroparesis and Liver Cirrhosis

    PubMed Central

    Aslam, Naeem; Kedar, Archana; Nagarajarao, Harsha S.; Reddy, Kartika; Rashed, Hani; Cutts, Teresa; Riely, Caroline; Abell, Thomas L.

    2016-01-01

    Background Plasma catecholamine influences autonomic function and control, but there are few reports correlating them. In this study, 47 individuals (mean age, 38 years) were studied: 19 diabetes mellitus (DM) patients with gastroparesis, 16 with liver disease and 12 control subjects. Methods Noninvasive autonomic function was assessed for sympathetic adrenergic functions as peripheral vasoconstriction in response to cold stress test and postural adjustment ratio (PAR) and cholinergic function as Valsalva ratio, represented by change in R-R intervals. Measurements were compared by analysis of variance and Spearman’s correlation, and results were reported as mean ± standard error. Results Plasma norepinephrine (1902.7 ± 263.3; P = 0.001) and epinephrine (224.5 ± 66.5; P = 0.008) levels, as well as plasma dopamine levels (861.3 ± 381.7), and total plasma catecholamine levels were highest for patients with liver disease, who also had significant negative correlation between norepinephrine level and vasoconstriction (P = 0.01; r = −0.5), PAR1 (P = 0.01; r = −0.5), sympathetic adrenergic functions (P = 0.005; r = −0.6), total autonomic index (P = 0.01–0.5) and total autonomic function (P = 0.01; r = −0.2) and also negative correlation between epinephrine plasma level and total autonomic function (P = 0.04; r = 0.4). DM patients were next highest in norepinephrine level (133.26 ± 7.43), but lowest for plasma catecholamine; a positive correlation between dopamine level and PAR1 (P = 0.008; r = 0.6) was also seen in this group. Plasma dopamine levels and spider score correlated negatively (P = 0.04; r = −0.5) and total plasma catecholamine positively with encephalopathy (P = 0.04; r = 0.5) in patients with liver disease. Conclusions Plasma catecholamine levels correlated with adrenergic functions in control subjects and patients with DM and liver disease, with no significant correlation seen for cholinergic function. PMID:26181082

  20. Case Report of Cirrhosis following Yttrium-90 Radioembolization for Pancreatic Neuroendocrine Liver Metastases

    PubMed Central

    Loree, Jonathan M.; Hiruki, Tadaaki; Kennecke, Hagen F.

    2016-01-01

    Background Management options for pancreatic neuroendocrine tumors (pNETs) metastatic to the liver include surgical, ablative, cytotoxic, and radioisotope approaches. One potential local treatment option includes selective internal radiotherapy utilizing yttrium-90 (90Y) microspheres. 90Y has also been used in the treatment of hepatocellular carcinoma and tumors metastatic to the liver. It appears to be well tolerated; however, there is no randomized controlled trial reporting long-term toxicities. Previous retrospective reports have described biliary damage as a potential complication of therapy with 90Y and chemoembolization; however, the long-term sequelae of 90Y treatment are poorly understood. Case Presentation We present the case of a 65-year-old Caucasian woman who suffered biliary damage following 90Y administration for metastatic pNETs and subsequently developed cirrhosis. Given the timeline of her various treatments and the lack of any other identifiable etiology for her cirrhosis, we believe this to be a potential long-term complication of 90Y therapy. Conclusion This case provides pathologic confirmation of cirrhosis as a potential long-term sequela of 90Y treatment. This long-term risk needs to be considered when sequencing therapy for patients with neuroendocrine tumors who have a good prognosis. There are now several other systemic and ablative treatment options available to these patients, and long-term complications must be considered during treatment. PMID:26933423

  1. Diagnostic accuracy of APRI, FIB-4 and Forns for the detection of liver cirrhosis in HIV/HCV-coinfected patients.

    PubMed

    Merli, Marco; Galli, Laura; Castagna, Antonella; Salpietro, Stefania; Gianotti, Nicola; Messina, Emanuela; Poli, Andrea; Morsica, Giulia; Bagaglio, Sabrina; Cernuschi, Massimo; Bigoloni, Alba; Uberti-Foppa, Caterina; Lazzarin, Adriano; Hasson, Hamid

    2016-04-01

    We determined the diagnostic accuracy and optimal cut off of three indirect fibrosis biomarkers (APRI, FIB-4, Forns) compared with liver stiffness (LS) for the detection of liver cirrhosis in HIV/HCV-coinfected patients. An observational retrospective study on HIV/HCV-coinfected patients with concomitant LS measurement and APRI, FIB-4 and Forns was performed. The presence of liver cirrhosis was defined as a LS ≥13 KPa. The diagnostic accuracy and optimal cut-off values, compared with LS categorization (<13 vs ≥13 KPa), were determined by receiver operating characteristics (ROC) curves. The study sample included 646 patients. The area-under-the ROC curve (95% confidence interval) for the detection of liver cirrhosis were 0.84 (0.81-0.88), 0.87 (0.84-0.91) and 0.87 (0.84-0.90) for APRI, FIB-4 and Forns, respectively. According to the optimal cut off values for liver cirrhosis (≥0.97 for APRI, ≥2.02 for FIB-4 and ≥7.8 for Forns), 80%, 80% and 82% of subjects were correctly classified by the three indirect fibrosis biomarkers, respectively. Misclassifications were mostly due to false positive cases. The study suggests that indirect fibrosis biomarkers can help clinicians to exclude liver cirrhosis in the management of HIV/HCV co-infected patients, reducing the frequency of more expensive or invasive assessments.

  2. 3-Dimensional liver volume assessment in patients with hepatitis B virus-related liver cirrhosis during long-term oral nucleos(t)ide analogues therapy

    PubMed Central

    Lee, Chang Hun; Kim, In Hee; Moon, Jin Chang; Seo, Seung Young; Kim, Seong Hun; Kim, Sang Wook; Lee, Seung Ok; Lee, Soo Teik; Kim, Dae Ghon; Yang, Jae Do; Yu, Hee Chul

    2017-01-01

    AIM To assess the effect of long-term oral nucleos(t)ide analogues (NUCs) therapy on liver volume change in patients with suppress hepatitis B virus (HBV)-related liver cirrhosis. METHODS We reviewed the data of naïve patients with HBV-related liver cirrhosis, who had taken oral NUCs therapy, between 2003 and 2007 at Chonbuk University Hospital. We analyzed two consecutive sets of abdominal computerized tomography scans-one at the time of treatment initiation and another at the second-year follow-up. Liver volume was calculated by 3-dimensional liver extraction volumetry program. RESULTS A total of 55 patients (34 males) were included. There was 114.3 mL ± 167.8 mL (12.9% ± 17.9%) of increase in liver volume during the two years of NUCs therapy (993.8 mL ± 242.8 mL at baseline vs 1108.1 mL ± 263.3 mL at two-year follow-up, P < 0.001). The ratio of the measured baseline liver volume to the estimated standard liver volume was improved from 70.8% to 78.0%. An increase in liver volume was shown not only in patients with compensated cirrhosis (P = 0.046) but also in those with decompensated cirrhosis (P < 0.001). Significant factors for volume increases were Child-Turcotte-Pugh grade and model for end-stage liver disease score improvement without virological breakthrough. In multiple linear regression analysis, delta albumin and delta alanine aminotransferase levels showed a significant association with the increase in liver volume (P = 0.002 and 0.005, respectively). CONCLUSION Long-term oral NUCs therapy in patients with HBV-related liver cirrhosis lead to significant increase in liver volume assessed with 3-dimensional liver extraction volumetry program. PMID:28127203

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

    PubMed

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

    2013-10-01

    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.

  4. Influence of smoking on caffeine elimination in healthy volunteers and in patients with alcoholic liver cirrhosis.

    PubMed

    Joeres, R; Klinker, H; Heusler, H; Epping, J; Zilly, W; Richter, E

    1988-01-01

    The effect of smoking on caffeine elimination was measured in 7 healthy volunteers and in 18 smoking and in 30 nonsmoking patients with alcoholic liver cirrhosis following oral application of 366 mg caffeine. In an intraindividual experiment in smoking health probands, caffeine clearance decreased from 118 +/- 33 to 77 +/- 22 ml per min (p less than 0.05) after abstaining cigarette smoking for 3 weeks. In a control group without liver disease (8 smokers, 15 nonsmokers), we found a caffeine clearance of 114 +/- 40 ml per min in smokers and 64 +/- 20 in nonsmokers (p less than 0.05). Smoking and nonsmoking patients with alcoholic liver cirrhosis did not differ with respect to clinical and laboratory data and hexobarbitone elimination. However, caffeine clearance was 63 +/- 63 ml per min in smoking patients compared to 34 +/- 49 ml per min in nonsmokers (p less than 0.05). Fasting plasma concentrations of caffeine were higher in nonsmokers (5.1 +/- 6.2 micrograms per ml) than in smokers (2.1 +/- 4.5 micrograms per ml, p less than 0.05). We conclude that smoking habits have to be taken into account if caffeine is used as a model compound for measuring quantitative liver function.

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

    SciTech Connect

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

    1984-08-01

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

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

    PubMed

    Acalovschi, Monica

    2014-06-21

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

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

    PubMed

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

    2012-06-01

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

  8. Acute-on-chronic liver failure: a new syndrome in cirrhosis.

    PubMed

    Moreau, Richard

    2016-03-01

    Patients with cirrhosis who are hospitalized for an acute decompensation (AD) and also have organ failure(s) are at high risk of short-term death. These patients have a syndrome called Acute-on-Chronic Liver Failure (ACLF). ACLF is now considered as a new syndrome that it is distinct from "mere" AD not only because of the presence of organ failure(s) and high short-term mortality but also because of younger age, higher prevalence of alcoholic etiology of cirrhosis, higher prevalence of some precipitants (such as bacterial infections, active alcoholism), and more intense systemic inflammatory response. ACLF is a new syndrome also because severe sepsis or severe alcoholic hepatitis do not account for 100% of the observed cases; in fact, almost 50% of the cases are of "unknown" origin. In other words, severe sepsis, severe alcoholic hepatitis and ACLF of "unknown origin" are subcategories of the syndrome.

  9. [Peptic ulcer disease in liver cirrhosis: role of Helicobacter pylori infection and therapeutic approach].

    PubMed

    Mitrică, Dana; Constantinescu, R; Drug, V L; Stanciu, C

    2011-01-01

    Peptic ulcer has frequently been associated with liver cirrhosis. The death rate for peptic ulcer in cirrhotics has been reported to be five times higher than in general population. The underlying mechanisms are poorly understood. Different factors have been claimed to be involved, such as alterations in serum gastrin level, gastric acid secretions, mucosal blood flow and decreased prostaglandin production in gastric mucosa. Moreover, Helicobacter pylori infection, when accurately assessed, is detectable in most peptic ulcer cirrhotics. Since the H. pylori infection strongly correlates with peptic ulcer in general population, it is necessary to clarify the role of H. pylori in the pathogenesis of peptic ulcer in cirrhosis before eradication can be proposed as a preventive measure.

  10. Inflammatory hepatocellular adenomas developed in the setting of chronic liver disease and cirrhosis.

    PubMed

    Calderaro, Julien; Nault, Jean C; Balabaud, Charles; Couchy, Gabrielle; Saint-Paul, Marie-Christine; Azoulay, Daniel; Mehdaoui, Dalila; Luciani, Alain; Zafrani, Elie S; Bioulac-Sage, Paulette; Zucman-Rossi, Jessica

    2016-01-01

    Hepatocellular adenoma is considered to occur exclusively in non-fibrotic livers. It is a heterogeneous entity and a molecular classification is now widely accepted. The most frequent hepatocellular adenoma subtype, namely inflammatory adenoma, harbor somatic activating mutations of genes involved in the interleukin-6 pathway that lead to high C-reactive protein and serum amyloid A expression. The aim of our study was to investigate a series of benign hepatocellular neoplasms developed on cirrhotic livers and characterized by an unequivocal histological diagnosis. We performed a clinical, pathological, and molecular study of 10 benign hepatocellular neoplasms developed in three patients with cirrhosis. Markers allowing hepatocellular adenoma classification were assessed by quantitative real-time PCR and immunohistochemistry. Samples were sequenced for CTNNB1, HNF1A, IL6ST, GNAS, STAT3, and TERT (promoter) mutations. A control series of 32 classical macronodules developed in cirrhosis related to various etiologies was screened by immunohistochemistry and gene sequencing. The three patients had cirrhosis related to metabolic syndrome and/or alcohol intake; two had a single tumor, while the third developed more than 30 lesions. Microscopic examination showed well-differentiated neoplasms sharing features with inflammatory adenoma including inflammatory infiltrates, sinusoidal dilatation, and dystrophic vessels. Sequencing revealed classical hotspot somatic mutations (IL6ST, n=8; STAT3, n=1; and GNAS, n=1) known to be responsible for IL-6/JAK/STAT pathway activation. Two classical high-grade macronodules demonstrated high serum amyloid A and/or C-reactive protein expression, without gene mutations. Altogether, our findings support the existence of rare inflammatory adenoma developed in cirrhosis.

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

    PubMed Central

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

    2008-01-01

    AIM: To study the possible association between chronic pancreatitis (CP) and liver cirrhosis (LC) of alcoholic etiology, after excluding any other causes. METHODS: One hundred and forty consecutive alcoholic patients were subdivided into three groups: CP (n = 53), LC (n = 57), and asymptomatic alcoholic (n = 30). Clinical, biochemical and morphological characteristics, Child-Pugh index, indocyanine green test, and fecal pancreatic elastase-1 test were assessed. RESULTS: In patients with cirrhosis, major clinical manifestations of CP such as pancreatic pain and steatorrhea, as well as imaging alterations of CP such as calcifications, duct dilation and pseudocysts were absent; insulin-dependent diabetes was present in 5.3% of cases, and elastase-1 test was altered in only 7%, and severely altered in none. In patients with CP, clinical characteristics of cirrhosis such as ascites, encephalopathy and gastrointestinal hemorrhage were present in one case, Child-Pugh grade > A in 5.7%, and altered indocyanine green test in 1.9% cases. In asymptomatic alcoholism, there was only a non-coincident alteration of elastase-1 test and indocyanine test in 14.8% and 10%, respectively, but other characteristics of cirrhosis or CP were absent. An inverse correlation (r = -0.746) between elastase-1 test and indocyanine test was found in alcoholic patients. CONCLUSION: There is a scarce coincidence in clinical and morphological alterations among patients with CP or LC of alcoholic etiology, but an inverse correlation between pancreatic and liver function tests. These findings support that these alcoholic diseases evolve in a different manner and have different etiopathogenesis. PMID:18985807

  12. The role of exosomes in hepatitis, liver cirrhosis and hepatocellular carcinoma.

    PubMed

    Shen, Jiliang; Huang, Chiung-Kuei; Yu, Hong; Shen, Bo; Zhang, Yaping; Liang, Yuelong; Li, Zheyong; Feng, Xu; Zhao, Jie; Duan, Lian; Cai, Xiujun

    2017-02-22

    Exosomes are small vesicles that were initially thought to be a mechanism for discarding unneeded membrane proteins from reticulocytes. Their mediation of intercellular communication appears to be associated with several biological functions. Current studies have shown that most mammalian cells undergo the process of exosome formation and utilize exosome-mediated cell communication. Exosomes contain various microRNAs, mRNAs and proteins. They have been reported to mediate multiple functions, such as antigen presentation, immune escape and tumour progression. This concise review highlights the findings regarding the roles of exosomes in liver diseases, particularly hepatitis B, hepatitis C, liver cirrhosis and hepatocellular carcinoma. However, further elucidation of the contributions of exosomes to intercellular information transmission is needed. The potential medical applications of exosomes in liver diseases seem practical and will depend on the ingenuity of future investigators and their insights into exosome-mediated biological processes.

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

    PubMed

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

    2014-11-01

    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.

  14. Automatic seed selection for segmentation of liver cirrhosis in laparoscopic sequences

    NASA Astrophysics Data System (ADS)

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

    2014-03-01

    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.

  15. Antifibrotic effect of edaravone in rat liver cirrhosis induced by dimethylnitrosamine.

    PubMed

    Tanaka, Hiroto; Ueda, Hiroki; Fukuchi, Hiroko; Ichinose, Masakazu

    2009-09-01

    Edaravone (EDA), a newly synthesized free radical scavenger, has shown excellent results in the treatment of stroke. An overproduction of reactive oxygen species (ROS) causing oxidative DNA damage has been accounted as a major factor causing liver injury and fibrosis. Therefore, we examined its effect of EDA in rat model of liver cirrhosis induced by dimethylnitrosamine (DMN). Ten rats (DMN-group) were injected intraperitoneally with DMN (10 microg/g body weight) alone and another ten rats (EDA-group) were injected intraperitoneally with EDA (10 mg/kg body weight) 2 h after being injected with DMN. Both groups underwent their injection regimen three times a week for 4 weeks, after which the rats were sacrificed and their liver tissue sections were stained with Azan-Mallory for quantitative analyses of fibrosis development, using soft imaging and a previously published scoring system. Additionally, these sections were immunohistochemically stained using an antibody against alpha-smooth muscle actin (alpha-SMA). The total-bililubin in the EDA-group was found to be lower than that in the DMN-group. Quantitive analysis of liver fibrosis showed that the fibrotic area of the EDA-group was significantly smaller than that of the DMN-group. Additionally, the number of alpha-SMA positive cells in the EDA-group were significantly lower than that in the DMN-group. This study showed that EDA reduces liver fibrosis in a rat of cirrhosis induced by DMN. These data suggest that the reduction of liver fibrosis by EDA may be induced by the suppression of activated hepatic stellate cells.

  16. [Clinical features of liver cirrhosis complicated by portal vein thrombosis and related risk factors].

    PubMed

    Lin, G S; Xu, Q; Zhao, S Y; Zhang, Y X

    2016-07-20

    Objective: To investigate the clinical features of patients with liver cirrhosis complicated by portal vein thrombosis (PVT) and related risk factors. Methods: A total of 65 patients with liver cirrhosis complicated by PVT who were diagnosed and treated from June 2013 to June 2015 were enrolled as PVT group, and 70 cirrhotic patients without PVT were enrolled as controls (non-PVT group). The data collected included general information, results of laboratory examination, imaging findings, clinical manifestations, and complications. The clinical features were compared between the two groups, and related risk factors were screened out. Results: There were no significant differences between the PVT group and non-PVT group in age, sex, nation, etiology, white blood cell count, platelet count, international normalized ratio, activated partial thromboplastin time, fibrinogen, serum creatinine, total bilirubin, and the diameter of the splenic vein (all P > 0.05), while between these two groups, there were significant differences in D-dimer (1.87±1.45 mg/ml vs 0.55±0.58 mg/ml, P < 0.05), fibrinogen degradation product (FDP) level (18.57±19.46 μg/ml vs 5.45±6.00 μg/ml, P < 0.05), hemoglobin (99.32±26.73 g/L vs 112.64±25.03 g/L, P < 0.05), albumin (28.51±5.19 g/L vs 33.07±7.94 g/L, P < 0.05), the diameter of the portal vein (12.53±2.70 mm vs 11.17±1.79 mm, P < 0.05), spleen thickness (5.12±0.95 cm vs 4.56±0.83 cm, P < 0.05), spleen length (15.35±3.21 cm vs 13.86±2.82 cm, P < 0.05), and Child-Pugh score (7.66±2.06 vs 6.93±1.87, P < 0.05). The two groups showed no significant differences in diarrhea, ileus, hepatorenal syndrome, and hepatic encephalopathy (P > 0.05), but showed significant differences in abdominal pain (18 vs 7 cases, P < 0.05), fever (17 vs 4 cases, P < 0.05), esophageal variceal bleeding (22 vs 9 cases, P < 0.05), and spontaneous peritonitis (24 vs 12 cases, P < 0.05). D-dimer (OR = 4.290, P < 0.000) and mean platelet volume (OR = 1.294, P

  17. Diagnosis of liver cancer and cirrhosis by the fluorescence spectra of blood and urine.

    PubMed

    AlSalhi, M; Al Mehmadi, A M; Abdo, Ayman Assad; Prasad, S; Masilamani, V

    2012-08-01

    Liver cancer or hepato cellular carcinoma (HCC) is a serious malady with only 10% survival rate and is fatal next only to pancreatic cancer. This disease is conventionally detected and diagnosed by ultra sound, CT or MRI scans which are quite expensive. Also the discrimination between cirrhosis and HCC, by these imaging techniques, is poor. The conventional tissue biopsy is quite invasive and painful. In the new diagnostic procedure presented in this paper we have obtained fluorescence emission spectra with excitation at 400 nm and the synchronous emission spectra (Δλ = 10 nm) for a set of blood and urine samples (Normal control N = 25, Liver Malfunction N = 58). Based on the ratio fluorometric parameters, all the three liver maladies (minor inflammation like Hepatitis C, serious diseases like Cirrhosis and hepatoma) could be detected and discriminated with an accuracy of about 80%. Hence this inexpensive, non invasive, optical technique may have significant impact in screening, diagnosis and also prognosis of HCC in large segment of people in the populous Asian countries.

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

    PubMed Central

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

    2014-01-01

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

  19. An orthotopic mouse model of hepatocellular carcinoma with underlying liver cirrhosis

    PubMed Central

    Reiberger, Thomas; Chen, Yunching; Ramjiawan, Rakesh R; Hato, Tai; Fan, Christopher; Samuel, Rekha; Roberge, Sylvie; Huang, Peigen; Lauwers, Gregory Y; Zhu, Andrew X; Bardeesy, Nabeel; Jain, Rakesh K; Duda, Dan G

    2016-01-01

    Subcutaneous xenografts have been used for decades to study hepatocellular carcinoma (HCC). These models do not reproduce the specific pathophysiological features of HCCs, which occur in cirrhotic livers that show pronounced necroinflammation, abnormal angiogenesis and extensive fibrosis. As these features are crucial for studying the role of the pathologic host microenvironment in tumor initiation, progression and treatment response, alternative HCC models are desirable. Here we describe a syngeneic orthotopic HCC model in immunocompetent mice with liver cirrhosis induced by carbon tetrachloride (CCl4) that recapitulates key features of human HCC. Induction of substantial hepatic fibrosis requires 12 weeks of CCl4 administration. Intrahepatic implantation of mouse HCC cell lines requires 30 min per mouse. Tumor growth varies by tumor cell line and mouse strain used. Alternatively, tumors can be induced in a genetically engineered mouse model. In this setting, CCl4 is administered for 12 weeks after tail-vein injection of Cre-expressing adenovirus (adeno-Cre) in Stk4−/−Stk3F/− (also known as Mst1−/−Mst2F/−; F indicates a floxed allele) mice, and it results in the development of HCC tumors (hepatocarcinogenesis) concomitantly with liver cirrhosis. PMID:26203823

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

    PubMed

    Al-Attar, Atef M; Shawush, Nessreen A

    2015-03-01

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

  1. Risk Factors for Portal Vein Thrombosis in Patients With Cirrhosis Awaiting Liver Transplantation in Shiraz, Iran

    PubMed Central

    Bagheri Lankarani, Kamran; Homayon, Katayon; Motevalli, Dorna; Heidari, Seyed Taghi; Alavian, Seyed Moayed; Malek-Hosseini, Seyed Ali

    2015-01-01

    Background: Portal vein thrombosis is a fairly common and potentially life-threatening complication in patients with liver cirrhosis. The risk factors for portal vein thrombosis in these patients are still not fully understood. Objectives: This study aimed to investigate the associations between various risk factors in cirrhotic patients and the development of portal vein thrombosis. Patients and Methods: In this case-control study performed at the Shiraz organ transplantation center, Iran, we studied 219 patients (> 18 years old) with liver cirrhosis, who were awaiting liver transplants in our unit, from November 2010 to May 2011. The patients were evaluated by history, physical examination, and laboratory tests, including factor V Leiden, prothrombin gene mutation, Janus Kinase 2 (JAK2) mutation, and serum levels of protein C, protein S, antithrombin III, homocysteine, factor VIII, and anticardiolipin antibodies. Results: There was no statistically significant difference in the assessed hypercoagulable states between patients with or without portal vein thrombosis. A history of previous variceal bleeding with subsequent endoscopic treatment in patients with portal vein thrombosis was significantly higher than in those without it (P = 0.013, OR: 2.526, 95% CI: 1.200 - 5.317). Conclusions: In our population of cirrhotic patients, treatment of variceal bleeding predisposed the patients to portal vein thrombosis, but hypercoagulable disorders by themselves were not associated with portal vein thrombosis. PMID:26977162

  2. Efficient liver repopulation of transplanted hepatocyte prevents cirrhosis in a rat model of hereditary tyrosinemia type I

    PubMed Central

    Zhang, Ludi; Shao, Yanjiao; Li, Lu; Tian, Feng; Cen, Jin; Chen, Xiaotao; Hu, Dan; Zhou, Yan; Xie, Weifen; Zheng, Yunwen; Ji, Yuan; Liu, Mingyao; Li, Dali; Hui, Lijian

    2016-01-01

    Hereditary tyrosinemia type I (HT1) is caused by a deficiency in the enzyme fumarylacetoacetate hydrolase (Fah). Fah-deficient mice and pigs are phenotypically analogous to human HT1, but do not recapitulate all the chronic features of the human disorder, especially liver fibrosis and cirrhosis. Rats as an important model organism for biomedical research have many advantages over other animal models. Genome engineering in rats is limited till the availability of new gene editing technologies. Using the recently developed CRISPR/Cas9 technique, we generated Fah−/− rats. The Fah−/− rats faithfully represented major phenotypic and biochemical manifestations of human HT1, including hypertyrosinemia, liver failure, and renal tubular damage. More importantly, the Fah−/− rats developed remarkable liver fibrosis and cirrhosis, which have not been observed in Fah mutant mice or pigs. Transplantation of wild-type hepatocytes rescued the Fah−/− rats from impending death. Moreover, the highly efficient repopulation of hepatocytes in Fah−/− livers prevented the progression of liver fibrosis to cirrhosis and in turn restored liver architecture. These results indicate that Fah−/− rats may be used as an animal model of HT1 with liver cirrhosis. Furthermore, Fah−/− rats may be used as a tool in studying hepatocyte transplantation and a bioreactor for the expansion of hepatocytes. PMID:27510266

  3. Portal vein thrombosis relevance on liver cirrhosis: Italian Venous Thrombotic Events Registry.

    PubMed

    Violi, Francesco; Corazza, Roberto Gino; Caldwell, Stephen Hugh; Perticone, Francesco; Gatta, Angelo; Angelico, Mario; Farcomeni, Alessio; Masotti, Michela; Napoleone, Laura; Vestri, Annarita; Raparelli, Valeria; Basili, Stefania

    2016-12-01

    Portal vein thrombosis may occur in cirrhosis; nevertheless, its prevalence, and predictors are still elusive. To investigate this issue, the Italian Society of Internal Medicine undertook the "Portal vein thrombosis Relevance On Liver cirrhosis: Italian Venous thrombotic Events Registry" (PRO-LIVER). This prospective multicenter study includes consecutive cirrhotic patients undergoing Doppler ultrasound examination of the portal area to evaluate the prevalence and incidence of portal vein thrombosis over a 2-year scheduled follow-up. Seven hundred and fifty-three (68 % men; 64 ± 12 years) patients were included in the present analysis. Fifty percent of the cases were cirrhotic outpatients. Viral (44 %) etiology was predominant. Around half of the patients had a mild-severity disease according to the Child-Pugh score; hepatocellular carcinoma was present in 20 %. The prevalence of ultrasound-detected portal vein thrombosis was 17 % (n = 126); it was asymptomatic in 43 % of the cases. Notably, more than half of the portal vein thrombosis patients (n = 81) were not treated with anticoagulant therapy. Logistic step-forward multivariate analysis demonstrated that previous portal vein thrombosis (p < 0.001), Child-Pugh Class B + C (p < 0.001), hepatocellular carcinoma (p = 0.01), previous upper gastrointestinal bleeding (p = 0.030) and older age (p = 0.012) were independently associated with portal vein thrombosis. Portal vein thrombosis is a frequent complication of cirrhosis, particularly in patients with moderate-severe liver failure. The apparent undertreatment of patients with portal vein thrombosis is a matter of concern and debate, which should be addressed by planning interventional trials especially with newer oral anticoagulants. Clinicaltrials.gov identifier NCT01470547.

  4. Identification and localization of xylose-binding proteins as potential biomarkers for liver fibrosis/cirrhosis.

    PubMed

    Zhong, Yaogang; Sun, Xiu-Xuan; Zhang, Peixin; Qin, Xinmin; Chen, Wentian; Guo, Yonghong; Jia, Zhansheng; Bian, Huijie; Li, Zheng

    2016-02-01

    In our recent study, we found that the expression levels of total xylose-binding proteins (XBPs) were up-regulated significantly in activated hepatic stellate cells (HSCs); however, the denomination, distribution, and function of the XBPs were uncharted. Herein, 70 XBPs from activated HSCs and 64 XBPs from quiescent HSCs were isolated, identified and annotated. A total of 30 XBPs were up-regulated (all fold change ≥ 1.5, p ≤ 0.05) and 14 XBPs were down-regulated (all fold change ≤ 0.67, p ≤ 0.05) in the activated HSCs. The XBPs were localized at the cytoplasm and cytoplasmic membrane in HSCs and cirrhotic liver tissues by cy/histochemistry. The XBPs (i.e. PDIA6 and CFL2) responsible for the regulation of protein binding were up-regulated and those responsible for the regulation of catalytic activity (i.e. TUBB and MX1) were up-regulated in the activated HSCs. 2 candidates (i.e. PDIA6 and APOA1) were then selected for further verification in the sera of patients with HBV-induced chronic hepatitis/cirrhosis using western blotting and serum microarrays. PDIA6 showed a higher discrimination (Area Under Curves, AUCs = 0.8985, p < 0.0001) relative to APOA1 (AUCs = 0.8738, p < 0.0001) in the sera of patients as biomarker candidate. In conclusion, the precision alteration of the XBPs associated with pathological changes in HSCs during liver fibrosis/cirrhosis may provide pivotal information needed to discover potential glycan-binding protein-related biomarkers for diagnosis of liver fibrosis/cirrhosis and for development of new anti-fibrotic strategies.

  5. Isorhamnetin attenuates liver fibrosis by inhibiting TGF-β/Smad signaling and relieving oxidative stress.

    PubMed

    Yang, Ji Hye; Kim, Sang Chan; Kim, Kyu Min; Jang, Chang Ho; Cho, Sam Seok; Kim, Seung Jung; Ku, Sae Kwang; Cho, Il Je; Ki, Sung Hwan

    2016-07-15

    Hepatic fibrosis is considered integral to the progression of chronic liver diseases, leading to the development of cirrhosis and hepatocellular carcinoma. Activation of hepatic stellate cells (HSCs) is the dominant event in hepatic fibrogenesis. We investigated the ability of isorhamnetin, the 3'-O-methylated metabolite of quercetin, to protect against hepatic fibrosis in vitro and in vivo. Isorhamnetin inhibited transforming growth factor (TGF)-β1-induced expression of α-smooth muscle actin (α-SMA), plasminogen activator inhibitor-1 (PAI-1), and collagen in primary murine HSCs and LX-2 cells. The TGF-β1- or Smad-induced luciferase reporter activity of Smad binding elements was significantly decreased by isorhamnetin with a concomitant decrease in Smad2/3 phosphorylation. Isorhamnetin increased the nuclear translocation of Nrf2 in HSCs and increased antioxidant response element reporter gene activity. Furthermore, isorhamnetin blocked TGF-β1-induced reactive oxygen species production. The specific role of Nrf2 in isorhamnetin-mediated suppression of PAI-1 and phosphorylated Smad3 was verified using a siRNA against Nrf2. To examine the anti-fibrotic effect of isorhamnetin in vivo, liver fibrosis was induced by CCl4 in mice. Isorhamnetin significantly prevented CCl4-induced increases in serum alanine transaminase and aspartate transaminase levels, and caused histopathological changes characterized by decreases in hepatic degeneration, inflammatory cell infiltration, and collagen accumulation. Moreover, isorhamnetin markedly decreased the expression of phosphorylated Smad3, TGF-β1, α-SMA, and PAI-1. Isorhamnetin attenuated the CCl4-induced increase in the number of 4-hydroxynonenal and nitrotyrosine-positive cells, and prevented glutathione depletion. We propose that isorhamnetin inhibits the TGF-β/Smad signaling pathway and relieves oxidative stress, thus inhibiting HSC activation and preventing liver fibrosis.

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

    PubMed

    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

    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 (μg/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.

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

    PubMed Central

    2012-01-01

    Background Gastrointestinal dysmotility may be involved in the development of bacterial translocation and infection in patients with liver cirrhosis. The aim of the present study was to describe gastric, small intestinal and colorectal motility and transit in patients with liver cirrhosis and portal hypertension using a magnet-based Motility Tracking System (MTS-1) and standard radiopaque markers. Methods We included 15 patients with liver cirrhosis (8 Child-Pugh A, 6 Child-Pugh B, and 1 Child-Pugh C) and portal hypertension (11 males, median age 54 years (range 38–73), median hepatic venous pressure gradient 18 mmHg (range 12–37)), and 18 healthy controls (8 males, median age 58 years (range 34–64)). The gastric emptying time and small intestinal motility were evaluated by MTS-1, and the total gastrointestinal transit time was assessed by radiopaque markers and abdominal radiographs. Results The velocity through the proximal small intestine was significantly higher in cirrhotic patients (median 1.27 metres (m)/hour, range 0.82–2.68) than in the healthy controls (median 1.00 m/hour, range 0.46–1.88) (p = 0.03). Likewise, the magnet travelled significantly longer in both fast (p = 0.04) and slow movements (p = 0.05) in the patient group. There was no significant difference in either gastric emptying time—23 minutes (range 5–131) in patients and 29 minutes (range 10.5–182) in healthy controls (p = 0.43)—or total gastrointestinal transit time—1.6 days (range 0.5–2.9) in patients and 2.0 days (range 1.0–3.9) in healthy controls (p = 0.33). No correlation was observed between the hepatic venous pressure gradient and the velocity of the magnet through the small intestine. Conclusion Patients with liver cirrhosis and portal hypertension demonstrated faster-than-normal transit through the proximal small intestine. This may be due to an overactive bowel, as suggested by previous studies. PMID:23216853

  8. Mortality and rebleeding following variceal haemorrhage in liver cirrhosis and periportal fibrosis

    PubMed Central

    Mohammed, Sara Elfadil Abbas; Abdo, Abdelmunem Eltayeb; Mudawi, Hatim Mohamed Yousif

    2016-01-01

    AIM To investigate mortality and rebleeding rate and identify associated risk factors at 6 wk and 5 d following acute variceal haemorrhage in patients with liver cirrhosis and schistosomal periportal fibrosis. METHODS This is a prospective study conducted during the period from March to December 2014. Patients with portal hypertension presenting with acute variceal haemorrhage secondary to either liver cirrhosis (group A) or schistosomal periportal fibroses (group B) presenting within 24 h of the onset of the bleeding were enrolled in the study and followed for a period of 6 wk. Analysis of data was done by Microsoft Excel and comparison between groups was done by Statistical Package of Social Sciences version 20 to calculate means and find the levels of statistical differences and define the mortality rates, the P value of < 0.05 was considered to be significant. RESULTS A total of 94 patients were enrolled in the study. Thirty-two patients (34%) had liver cirrhosis (group A) and 62 (66%) patients had periportal fibrosis (group B). Mortality: The 6-wk and 5-d mortality were 53% and 16% respectively in group A compared to 10% and 0% in group B (P value < 0.000 and < 0.004). In group A; a Child-Turcotte-Pugh class C and rebleeding within 5 d were significantly associated with 5-d mortality (P value < 0.029 and < 0.049 respectively) and Child- Turcotte-Pugh class C was also a significant risk factor for 6-wk mortality (P value < 0.018). In group B; mortality was significantly associated with rebleeding within the 6-wk follow-up period and requirement for blood transfusion on admission (P value < 0.005 and < 0.049). Rebleeding: The 6-wk and 5-d rebleeding rate in group A were 56% and 25% respectively compared to 32% and 3% in group B (P value < 0.015 and < 0.002). Clinical presentation with encephalopathy was a significant risk factor for 5 d rebleeding in group A (P value < 0.005) while grade III periportal fibrosis and requirement for blood transfusion on admission

  9. AISF-SIMTI position paper: the appropriate use of albumin in patients with liver cirrhosis

    PubMed Central

    Caraceni, Paolo; Angeli, Paolo; Prati, Daniele; Bernardi, Mauro; Liumbruno, Giancarlo M.; Bennardello, Francesco; Piccoli, Pierluigi; Velati, Claudio

    2016-01-01

    The use of human albumin is common in hepatology since international scientific societies support its administration to treat or prevent severe complications of cirrhosis, such as the prevention of post-paracentesis circulatory dysfunction after large-volume paracentesis and renal failure induced by spontaneous bacterial peritonitis, and the treatment of hepatorenal syndrome in association with vasoconstrictors. However, these indications are often disregarded, mainly because the high cost of human albumin leads health authorities and hospital administrations to restrict its use. On the other hand, physicians often prescribe human albumin in patients with advanced cirrhosis for indications that are not supported by solid scientific evidence and/or are still under investigation in clinical trials. In order to implement appropriate prescription of human albumin and to avoid its futile use, the Italian Association for the Study of the Liver (AISF) and the Italian Society of Transfusion Medicine and Immunohaematology (SIMTI) nominated a panel of experts, who reviewed the available clinical literature and produced practical clinical recommendations for the use of human albumin in patients with cirrhosis. PMID:26820615

  10. Liver cirrhosis deaths within occupations and industries in the California occupational mortality study.

    PubMed

    Leigh, J P; Jiang, W Y

    1993-06-01

    Mortality rates were drawn from the California Occupational Mortality Study (COMS) to analyze liver cirrhosis deaths within occupations and industries from 1979 to 1981. Age-adjusted Standardized Mortality Rates (SMRs) were made available by the State of California for separate analyses of women, men, blacks and whites. Rankings of occupations with narrow confidence intervals were strikingly similar for blacks and whites. Within occupations, the highest female SMRs were for waitresses, telephone operators, cosmetologists, dress makers, hospital orderlies, textile workers, and laborers. The lowest female SMRs were for skilled crafts workers and teachers. High male occupations included water transportation workers, bartenders, loggers, laborers, roofers, construction workers, farm workers, iron workers, and painters. Low male occupations included teachers, physicians and dentists, managers, factory supervisors, business sales workers, heavy equipment operators, and other professionals. High female industries included eating and drinking places, laundry/dry cleaning, nursing and personal care facilities, aerospace, beauty shops, and entertainment. Low female industries included wholesale trades and education. High male industries included water transportation, military, guard services, eating and drinking places, iron and steel mills, and railroads. Low male industries included research/engineering labs, education, and computer manufacturing. This study was descriptive. It remains unknown whether certain jobs cause excessive drinking and cirrhosis, or whether people who are prone to develop cirrhosis select certain jobs.

  11. Volatile Biomarkers in Breath Associated With Liver Cirrhosis — Comparisons of Pre- and Post-liver Transplant Breath Samples

    PubMed Central

    Fernández del Río, R.; O'Hara, M.E.; Holt, A.; Pemberton, P.; Shah, T.; Whitehouse, T.; Mayhew, C.A.

    2015-01-01

    Background The burden of liver disease in the UK has risen dramatically and there is a need for improved diagnostics. Aims To determine which breath volatiles are associated with the cirrhotic liver and hence diagnostically useful. Methods A two-stage biomarker discovery procedure was used. Alveolar breath samples of 31 patients with cirrhosis and 30 healthy controls were mass spectrometrically analysed and compared (stage 1). 12 of these patients had their breath analysed after liver transplant (stage 2). Five patients were followed longitudinally as in-patients in the post-transplant period. Results Seven volatiles were elevated in the breath of patients versus controls. Of these, five showed statistically significant decrease post-transplant: limonene, methanol, 2-pentanone, 2-butanone and carbon disulfide. On an individual basis limonene has the best diagnostic capability (the area under a receiver operating characteristic curve (AUROC) is 0.91), but this is improved by combining methanol, 2-pentanone and limonene (AUROC curve 0.95). Following transplant, limonene shows wash-out characteristics. Conclusions Limonene, methanol and 2-pentanone are breath markers for a cirrhotic liver. This study raises the potential to investigate these volatiles as markers for early-stage liver disease. By monitoring the wash-out of limonene following transplant, graft liver function can be non-invasively assessed. PMID:26501124

  12. Renal dysfunction in liver cirrhosis: renal duplex Doppler US vs. scintigraphy for early identification.

    PubMed

    Al-Kareemy, E A; Sobh, M A; Muhammad, A M; Mostafa, M M; Saber, R A

    1998-01-01

    A diagnostic tool to detect early renal dysfunction before it becomes irreversible would be useful in cirrhosis. This study was carried out to evaluate the role of Doppler sonography and Tc-99m DTPA renography in the detection of early renal dysfunction in patients with different grades of liver cirrhosis. Renal arteries of 43 patients with cirrhosis and normal renal function tests were compared with 15 age and gender matched normal subjects as a control group using colour Doppler sonography and Tc-99m DTPA scintigraphy. The patients were categorized into three groups, A (14), B (14) and C (15), according to a modified Child's classification that assesses the severity of liver cirrhosis. Doppler results revealed a highly significant increase in both the pulsatility and resistive indices in groups B and C compared with either group A patients or control subjects and in group C compared with group B (P < 0.001) in the main renal arteries as well as in the interlobar and arcuate arteries. Insignificant differences were observed between group A and controls (PI: control 0.96+/-0.08, group A 0.95+/-0.07, group B 1.26+/-0.06, group C 1.48+/-0.06; RI: control 0.57+/-0.02, group A 0.58+/-0.02, group B 0.66+/-0.01, group C 0.72+/-0.02). Abnormal renograms in the form of delayed appearance (34+/-14.6 s), diminished blood flow bilaterally with prolonged secretory (12+/-4.5 min) and excretory phases (> 30 min) and poor response to intravenous frusemide were only observed in group C patients. Radionuclide computed glomerular filtration rate was within the normal range in patients of group A (81+/-9.5 ml/min) and group B (78+/-8.4 ml/min) and reduced only in patients of group C (34+/-14.5 ml/min). Thus Doppler sonography can detect an increase in renal vascular resistance in patients with moderately severe cirrhosis (Child grade B) when renography was normal. We conclude that Doppler sonography can be used for earlier identification of cirrhotic patients with a higher risk of

  13. Safety of ERCP in patients with liver cirrhosis: a national database study

    PubMed Central

    Navaneethan, Udayakumar; Njei, Basile; Zhu, Xiang; Kommaraju, Kiran; Parsi, Mansour A.; Varadarajulu, Shyam

    2017-01-01

    Background and aims Given the limited data on the safety of endoscopic retrograde cholangiopancreatography (ERCP) in patients with liver cirrhosis, we attempted to evaluate this question using a large national database. Methods We conducted a matched case – control study using the 2010 National Inpatient Sample database in which four non-cirrhotic controls were matched randomly for every cirrhotic patient from the same 10-year age group. We compared adverse events and safety of inpatient ERCP between patients with (n = 3228) and without liver cirrhosis (controls, n = 12 912). Results Of the 3228 cirrhotic patients, 2603 (80.6 %) had decompensated and 625 (19.4 %) had compensated disease. Post-procedure bleeding (2.1 % vs. 1.2 %, P < 0.01) was higher in patients compared to controls. On multivariable analysis, decompensated cirrhosis (adjusted odds ratio [aOR], 2.7; 95 % confidence interval [CI], 2.2 – 3.2), compensated cirrhosis (aOR 2.2; 95 %CI 1.2 – 3.9), therapeutic ERCPs (aOR 1.4; 95 % CI 1.2 – 2.1), and biliary sphincterotomy (aOR 1.6; 95 %CI 1.1 – 2.1) were independently associated with increased risk of post-procedure bleeding. Performing ERCPs in large (aOR 0.5; 95 %CI 0.4 – 0.6) and medium (aOR 0.7; 95 %CI 0.6 – 0.9) sized hospitals was associated with a decreased risk of post-procedure bleeding. Biliary sphincterotomy (aOR 1.7; 95 %CI 1.2 – 2.3) and therapeutic ERCPs (aOR 1.1; 95 %CI 1.1 – 1.3) increased the risk of post-ERCP pancreatitis, and pancreatic stent placement was associated with a decreased risk of post-ERCP pancreatitis (aOR 0.8; 95 %CI 0.7 – 0.9). Conclusions Cirrhosis (both compensated and decompensated), performing therapeutic ERCPs and biliary sphincterotomy increase the risk of post-procedure bleeding. Performing ERCPs in large and medium sized hospitals may improve outcomes. PMID:28393104

  14. Effective control of relapsing disseminated intravascular coagulation in a patient with decompensated liver cirrhosis by recombinant soluble thrombomodulin.

    PubMed

    Hasebe, Takumu; Sawada, Koji; Nakajima, Shunsuke; Maeda, Shigeaki; Abe, Masami; Suzuki, Yasuaki; Ohtake, Takaaki; Hasebe, Chitomi; Fujiya, Mikihiro; Kohgo, Yutaka

    2014-01-01

    A 70-year-old Japanese man was hospitalized for expanding purpura and chronic disseminated intravascular coagulation (DIC) caused by decompensated liver cirrhosis. As there are no effective treatments for chronic DIC caused by liver cirrhosis, we decided to administer recombinant human soluble thrombomodulin (rhsTM) after he provided informed consent. The DIC was rapidly improved; however, the purpura and coagulopathy recurred after two months, and repeated rhsTM treatments were required. The rhsTM treatment sufficiently controlled the coagulopathy for two years, without any complications, including bleeding. This is the first report demonstrating that rhsTM can be administered safely and repeatedly to a patient with decompensated liver cirrhosis, and that it appears to be associated with a favorable outcome.

  15. Repeated intravenous injection of recombinant human hepatocyte growth factor ameliorates liver cirrhosis but causes albuminuria in rats.

    PubMed

    Kusumoto, Kazunori; Ido, Akio; Moriuchi, Akihiro; Katsura, Toshiya; Kim, Ildeok; Takahama, Yuka; Numata, Masatsugu; Kodama, Mayumi; Hasuike, Satoru; Nagata, Kenji; Uto, Hirofumi; Inui, Ken-Ichi; Tsubouchi, Hirohito

    2006-03-01

    Hepatocyte growth factor (HGF) is a promising agent for the treatment of liver cirrhosis because of its mitogenic and anti-fibrotic effects. We investigated the effect of recombinant human HGF (rh-HGF) on cirrhosis development; its pharmacokinetics and nephrotoxicity in rats with liver cirrhosis induced by 4-week treatment with dimethylnitrosamine (DMN). rh-HGF (0.3 mg/kg) was intravenously administered to rats once a day for 4 weeks in parallel with DMN treatment or twice a day for the last 2 weeks of DMN treatment. Repeated doses of rh-HGF increased the liver weight and serum albumin, and reduced serum ALT. The development of hepatic fibrosis was inhibited more efficiently by extended low-dose treatment with rh-HGF. In cirrhotic rats, serum levels of rh-HGF increased and clearance was decreased, leading to an increase in the area under the plasma-concentration time curve and a decrease in the steady-state volume of distribution. Repeated doses of rh-HGF led to increased urinary albumin excretion, but no rh-HGF-treated animals developed increased serum creatinine levels. Urinary albumin excretion returned to baseline after the cessation of rh-HGF. These results suggest that extended treatment with rh-HGF is required for the attenuation of cirrhosis, and repeated doses of rh-HGF cause adverse effects in extra-hepatic organs. These issues must be resolved before the widespread application of rh-HGF in the treatment of liver cirrhosis.

  16. Mueller matrix microscope: a quantitative tool to facilitate detections and fibrosis scorings of liver cirrhosis and cancer tissues.

    PubMed

    Wang, Ye; He, Honghui; Chang, Jintao; He, Chao; Liu, Shaoxiong; Li, Migao; Zeng, Nan; Wu, Jian; Ma, Hui

    2016-07-01

    Today the increasing cancer incidence rate is becoming one of the biggest threats to human health.Among all types of cancers, liver cancer ranks in the top five in both frequency and mortality rate all over the world. During the development of liver cancer, fibrosis often evolves as part of a healing process in response to liver damage, resulting in cirrhosis of liver tissues. In a previous study, we applied the Mueller matrix microscope to pathological liver tissue samples and found that both the Mueller matrix polar decomposition (MMPD) and Mueller matrix transformation (MMT) parameters are closely related to the fibrous microstructures. In this paper,we take this one step further to quantitatively facilitate the fibrosis detections and scorings of pathological liver tissue samples in different stages from cirrhosis to cancer using the Mueller matrix microscope. The experimental results of MMPD and MMT parameters for the fibrotic liver tissue samples in different stages are measured and analyzed. We also conduct Monte Carlo simulations based on the sphere birefringence model to examine in detail the influence of structural changes in different fibrosis stages on the imaging parameters. Both the experimental and simulated results indicate that the polarized light microscope and transformed Mueller matrix parameter scan provide additional quantitative information helpful for fibrosis detections and scorings of liver cirrhosis and cancers. Therefore, the polarized light microscope and transformed Mueller matrix parameters have a good application prospect in liver cancer diagnosis.

  17. Mueller matrix microscope: a quantitative tool to facilitate detections and fibrosis scorings of liver cirrhosis and cancer tissues

    NASA Astrophysics Data System (ADS)

    Wang, Ye; He, Honghui; Chang, Jintao; He, Chao; Liu, Shaoxiong; Li, Migao; Zeng, Nan; Wu, Jian; Ma, Hui

    2016-07-01

    Today the increasing cancer incidence rate is becoming one of the biggest threats to human health. Among all types of cancers, liver cancer ranks in the top five in both frequency and mortality rate all over the world. During the development of liver cancer, fibrosis often evolves as part of a healing process in response to liver damage, resulting in cirrhosis of liver tissues. In a previous study, we applied the Mueller matrix microscope to pathological liver tissue samples and found that both the Mueller matrix polar decomposition (MMPD) and Mueller matrix transformation (MMT) parameters are closely related to the fibrous microstructures. In this paper, we take this one step further to quantitatively facilitate the fibrosis detections and scorings of pathological liver tissue samples in different stages from cirrhosis to cancer using the Mueller matrix microscope. The experimental results of MMPD and MMT parameters for the fibrotic liver tissue samples in different stages are measured and analyzed. We also conduct Monte Carlo simulations based on the sphere birefringence model to examine in detail the influence of structural changes in different fibrosis stages on the imaging parameters. Both the experimental and simulated results indicate that the polarized light microscope and transformed Mueller matrix parameters can provide additional quantitative information helpful for fibrosis detections and scorings of liver cirrhosis and cancers. Therefore, the polarized light microscope and transformed Mueller matrix parameters have a good application prospect in liver cancer diagnosis.

  18. Dual-Functional Nanoparticles Targeting CXCR4 and Delivering Antiangiogenic siRNA Ameliorate Liver Fibrosis.

    PubMed

    Liu, Chun-Hung; Chan, Kun-Ming; Chiang, Tsaiyu; Liu, Jia-Yu; Chern, Guann-Gen; Hsu, Fu-Fei; Wu, Yu-Hsuan; Liu, Ya-Chi; Chen, Yunching

    2016-07-05

    The progression of liver fibrosis, an intrinsic response to chronic liver injury, is associated with hepatic hypoxia, angiogenesis, abnormal inflammation, and significant matrix deposition, leading to the development of cirrhosis and hepatocellular carcinoma (HCC). Due to the complex pathogenesis of liver fibrosis, antifibrotic drug development has faced the challenge of efficiently and specifically targeting multiple pathogenic mechanisms. Therefore, CXCR4-targeted nanoparticles (NPs) were formulated to deliver siRNAs against vascular endothelial growth factor (VEGF) into fibrotic livers to block angiogenesis during the progression of liver fibrosis. AMD3100, a CXCR4 antagonist that was incorporated into the NPs, served dual functions: it acted as a targeting moiety and suppressed the progression of fibrosis by inhibiting the proliferation and activation of hepatic stellate cells (HSCs). We demonstrated that CXCR4-targeted NPs could deliver VEGF siRNAs to fibrotic livers, decrease VEGF expression, suppress angiogenesis and normalize the distorted vessels in the fibrotic livers in the carbon tetrachloride (CCl4) induced mouse model. Moreover, blocking SDF-1α/CXCR4 by CXCR4-targeted NPs in combination with VEGF siRNA significantly prevented the progression of liver fibrosis in CCl4-treated mice. In conclusion, the multifunctional CXCR4-targeted NPs delivering VEGF siRNAs provide an effective antifibrotic therapeutic strategy.

  19. Free amino acids in plasma and skeletal muscle of patients with liver cirrhosis.

    PubMed

    Montanari, A; Simoni, I; Vallisa, D; Trifirò, A; Colla, R; Abbiati, R; Borghi, L; Novarini, A

    1988-01-01

    Free amino acids were measured under postabsorptive conditions in plasma and intracellular water of skeletal muscle obtained by needle biopsy in nine healthy controls and 14 subjects suffering from clinically stable liver cirrhosis. The aromatic amino acids phenylalanine and tyrosine in cirrhotics were elevated to the same extent in plasma and in muscle water. Branched-chain amino acids were uniformly reduced in plasma, but in muscle water only valine was significantly lower (222 +/- 92 mumoles per kg intracellular water vs. 368 +/- 82, p less than 0.001), while isoleucine (142 +/- 63 vs. 103 +/- 30), leucine (223 +/- 88 vs. 226 +/- 36) and branched-chain amino acids as a whole (589 +/- 186 vs. 681 +/- 88) were normal or elevated with an increased muscle:plasma ratio (3.12 +/- 2.03 vs. 1.41 +/- 0.37, p less than 0.05 for isoleucine; 3.00 +/- 1.28 vs. 1.85 +/- 0.27, p less than 0.025 for leucine; 2.24 +/- 0.64 vs. 1.69 +/- 0.13, p less than 0.05 for total branched-chain amino acids. Our data show that, in cirrhosis, plasma concentrations of branched-chain amino acids do not reflect their levels in muscle cellular water; only the intracellular pool of valine is severely depleted. This suggests that higher amounts of valine supplementation may be useful in nutritional treatment of liver cirrhosis. The elevated muscle:plasma gradients for branched-chain amino acids may result from abnormalities in their transport through muscle-plasma membrane.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. Treatment of patients with HBV-related decompensated cirrhosis and liver transplanted patients.

    PubMed

    Roche, Bruno; Samuel, Didier

    2013-08-01

    Antiviral therapy using newer nucleos(t)ide analogs with lower resistance rates could suppress hepatitis B virus (HBV) replication, improve liver function in patients with compensated or decompensated cirrhosis, delay or obviate liver transplantation in some patients, and reduce the risk of HBV recurrence. Some form of HBV prophylaxis needs to be continued indefinitely posttransplant. However, in patients with a low-risk of HBV recurrence it is possible to discontinue hepatitis B immunoglobulins and maintain long-term nucleos(t)ide analog therapy. Currently, treatment of posttransplantation hepatitis B is a less important clinical problem than it was historically because effective antiviral therapies exist to rescue patients who failed initial prophylaxis.

  1. [A case of Pasteurella multocida subsp. multocida septicemia due to cat bites in liver cirrhosis patient].

    PubMed

    Shimizu, T; Hasegawa, K; Mitsuhashi, Y; Kojima, S; Ishikawa, K; Hayashi, N; Sawada, T

    1995-11-01

    A 60-year-old male who had been suffering from liver cirrhosis was admitted to our hospital with high grade fever accompanied by right chest pain. Chest X-rays revealed a moderate amount of pleural fluid suggesting pleuritis. Multocida was isolated from the blood culture as well as the pleural fluid. Antibiotic therapy was initiated according to the drug susceptibility of the isolates. Ten days treatment was effective on the cessation of both septicemia and the clinical symptoms. Since the patient had been bitten several times by his own pet cats, their mouth swabs were taken for pathogenic investigations. Serotypes of the cats' isolates coincided with that of the patient's which consequently indicated the route of infection. P. multocida is a Gram negative coccobacillary organism that resides as normal flora in the oral cavity of animals, including dogs and cats. It has been originally known to be a causative agent for hemorrhagic septicemia in domestic animals. However, recently reports of P. multocida infections in man has been increasing due to the enlargement of pet populations. Although outbreaks of septicemia is rare, it occurs most often in immunologically compromised hosts, including patients with liver cirrhosis as in this case. Therefore, it is important to initiate an urgent antibiotic therapy in such cases. Overall, it is of utmost importance to instruct immunosuppressed patients to avoid excessive exposure to animals including pets.

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

    PubMed

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

    2013-12-01

    Sildenafil citrate is a phosphodiesterase-5 inhibitor, approved for the treatment of erectile dysfunction. It enhances nitric-oxide-induced vasodilatation and it promotes angiogenesis. A relationship between angiogenesis and hepatic fibrosis has long been speculated, where the 2 are believed to progress together. In this study, the ability of sildenafil (10 mg·(kg body mass)(-1), orally, once daily) to prevent and also reverse liver fibrosis/cirrhosis experimentally induced by thioacetamide injection (200 mg·kg(-1), intraperitoneal (i.p.), 3 times·week(-1)) in male Sprague-Dawley rats has been investigated. Sildenafil administration, either to prevent or to reverse liver fibrosis/cirrhosis significantly improved the estimated hepatic functions, reduced hepatic hydroxyproline and, in turn, hepatic collagen content, as well as reducing serum levels of the pro-fibrogenic mediator transforming growth factor β1. In co-ordination with such improvement, fibrosis grades declined and fibrosis retracted. Herein, the observed results provide evidence for the potential therapeutic efficacy of sildenafil as an antifibrotic agent.

  3. Regression of esophageal varices and splenomegaly in two patients with hepatitis-C-related liver cirrhosis after interferon and ribavirin combination therapy.

    PubMed

    Lee, Soon Jae; Cho, Yoo-Kyung; Na, Soo-Young; Choi, Eun Kwang; Boo, Sun Jin; Jeong, Seung Uk; Song, Hyung Joo; Kim, Heung Up; Kim, Bong Soo; Song, Byung-Cheol

    2016-09-01

    Some recent studies have found regression of liver cirrhosis after antiviral therapy in patients with hepatitis C virus (HCV)-related liver cirrhosis, but there have been no reports of complete regression of esophageal varices after interferon/peg-interferon and ribavirin combination therapy. We describe two cases of complete regression of esophageal varices and splenomegaly after interferon-alpha and ribavirin combination therapy in patients with HCV-related liver cirrhosis. Esophageal varices and splenomegaly regressed after 3 and 8 years of sustained virologic responses in cases 1 and 2, respectively. To our knowledge, this is the first study demonstrating that complications of liver cirrhosis, such as esophageal varices and splenomegaly, can regress after antiviral therapy in patients with HCV-related liver cirrhosis.

  4. Genetic, metabolic and environmental factors involved in the development of liver cirrhosis in Mexico

    PubMed Central

    Ramos-Lopez, Omar; Martinez-Lopez, Erika; Roman, Sonia; Fierro, Nora A; Panduro, Arturo

    2015-01-01

    Liver cirrhosis (LC) is a chronic illness caused by inflammatory responses and progressive fibrosis. Globally, the most common causes of chronic liver disease include persistent alcohol abuse, followed by viral hepatitis infections and nonalcoholic fatty liver disease. However, regardless of the etiological factors, the susceptibility and degree of liver damage may be influenced by genetic polymorphisms that are associated with distinct ethnic and cultural backgrounds. Consequently, metabolic genes are influenced by variable environmental lifestyle factors, such as diet, physical inactivity, and emotional stress, which are associated with regional differences among populations. This Topic Highlight will focus on the genetic and environmental factors that may influence the metabolism of alcohol and nutrients in the setting of distinct etiologies of liver disease. The interaction between genes and environment in the current-day admixed population, Mestizo and Native Mexican, will be described. Additionally, genes involved in immune regulation, insulin sensitivity, oxidative stress and extracellular matrix deposition may modulate the degree of severity. In conclusion, LC is a complex disease. The onset, progression, and clinical outcome of LC among the Mexican population are influenced by specific genetic and environmental factors. Among these are an admixed genome with a heterogenic distribution of European, Amerindian and African ancestry; a high score of alcohol consumption; viral infections; a hepatopathogenic diet; and a high prevalence of obesity. The variance in risk factors among populations suggests that intervention strategies directed towards the prevention and management of LC should be tailored according to such population-based features. PMID:26556986

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

    PubMed Central

    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

    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

  6. [Liver cirrhosis and encephalopathy: clinical and metabolic consequences and nutritional support].

    PubMed

    Mesejo, A; Juan, M; Serrano, A

    2008-05-01

    Cirrhosis represents the final stage of many chronic liver diseases and is associated to more or less pronounced hyponutrition, independently of the etiology, particularly at advanced stages. Its origin is multifactorial, with three factors contributing to it: a) limitation or decrease of intake; b) impairment in nutrients digestion or absorption; and c) the interference with nutrients metabolism. A poor nutritional status is associated with a poor survival prognosis. Whether caloric-protein malnourishment (CPM) is an independent predictor of mortality or only a marker of the severity of liver failure is subject to controversy. There is no consensus on which are the best diagnostic criteria for CPM in cirrhosis. Assessment of hyponutrition is extremely difficult since both the disease itself and the triggering or etiologic factors affect many of the parameters used. Metabolic impairments mimic a hypercatabolic state. These patients have decreased carbohydrate utilization and storage capacity and increased protein and fat catabolism leading to depletion of protein and lipid reserves. These abnormalities together with decreased nutrients intake and absorption are the bases for CPM. The most important metabolic impairment in patients with advanced liver disease is the change in amino acids metabolism. The plasma levels of branched amino acids (BAA) are decreased and of aromatic amino acids (AAA) are increased, which has therapeutic implications. Among the consequences of the structural impairments taking place in cirrhosis, we may highlight hepatic encephalopathy, defined as impaired central nervous system functioning that manifests as a series of neuropsychiatric, neuromuscular, and behavioral symptoms. These are due to the inability of the diseased liver to metabolize neurotoxins that accumulate in the brain affecting neurotransmitters and are attributed to the toxic effect of ammonium on the brain tissue. Nutritional therapy brings benefits in the different stages

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

    SciTech Connect

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

    1982-12-01

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

  8. Correlation of circulating TLR2/4 expression with CD3+/4+/8+ T cells and Treg cells in HBV-related liver cirrhosis.

    PubMed

    Lian, Jian-Qi; Wang, Xiao-Qin; Zhang, Ye; Huang, Chang-Xing; Bai, Xue-Fan

    2009-10-01

    Toll-like receptors (TLRs) 2 and 4 play a key role in chronic hepatitis B virus (HBV) infection. However, the role of TLRs in the pathogenesis of HBV-related liver cirrhosis and their regulation of the innate immune response of patients with liver cirrhosis remain unknown. To assess the contribution of TLR2/4 in HBV-related liver cirrhosis, we examined the expression of circulating TLR2 and TLR4 on peripheral blood mononuclear cells (PBMCs), CD4(+)CD25(+)CD127(low/-) Treg proportions, and CD3(+)/CD4(+)/CD8(+) T-cell counts in 30 liver cirrhosis patients, 21 chronic hepatitis B (CHB) patients, and 16 normal controls (NC). Furthermore, we analyzed the relationship between TLR2/4 expression and Treg proportions and T-cell counts. We show that the expression of TLR2 and TLR4 was significantly upregulated in patients with liver cirrhosis compared to NC. TLR4 expression was significantly increased in patients with liver cirrhosis compared to patients with CHB, and for TLR2 expression there were no differences between them. TLR4 expression showed a significant positive correlation with the frequency of Tregs in liver cirrhosis patients. TLR2 expression negatively correlated with CD3(+)/CD4(+)/CD8(+) T-cell counts and HBV viral load in patients with liver cirrhosis. These findings indicate that TLR may be involved in the pathogenesis of HBV-related liver cirrhosis, and may interact with Tregs and CD3(+)/CD4(+)/CD8(+) T cells in the immune response during HBV-related liver cirrhosis.

  9. Therapeutic efficacy of ethanolic extract of Aerva javanica aerial parts in the amelioration of CCl4-induced hepatotoxicity and oxidative damage in rats

    PubMed Central

    Arbab, Ahmed H.; Parvez, Mohammad K.; Al-Dosari, Mohammed S.; Al-Rehaily, Adnan J.; Ibrahim, Khalid E.; Alam, Perwez; Alsaid, Mansour S.; Rafatullah, Syed

    2016-01-01

    Background Liver diseases, the fifth most common cause of global death, can be metabolic, toxin-induced, or infective. Though approximately 35 Saudi medicinal plants are traditionally used to treat liver disorders, the hepatoprotective potential of Aerva javanica has not been explored. Objective To investigate the antioxidative and hepatoprotective effect of Aerva javanica. Design Total ethanol extract of A. javanica aerial parts was prepared and tested on DCFH-toxicated HepG2 cells ex vivo, and in CCl4-injured Wistar rats in vivo. MTT assay was used to determine cell viability and the serum biochemical markers of liver injury as well as histopathology was performed. In vitro 1,1-diphenyl-2-picrylhydrazyl and β-carotene free-radical scavenging assay and phytochemical screening of the extract were done. Furthermore, A. javanica total extract was standardized and validated by high-performance thin layer chromatographic method. Results MTT assay showed that, while DCFH-injured cells were recovered to ~56.7% by 100 µg/ml of the extract, a 200 µg/ml dose resulted in hepatocytes recovery by ~90.2%. Oral administration of the extract (100 and 200 mg/kg.bw/day) significantly normalized the serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, gamma-glutamyl transferase, alkaline phosphatase, bilirubin, cholesterol, high-density lipoprotein, low-density lipoprotein, very-low-density lipoprotein, triglyceride, and malondialdehyde levels, including tissue nonprotein sulfhydryl and total protein in CCl4-injured rats. In addition, the histopathology of dissected liver also revealed that A. javanica cured the tissue lesion compared to silymarin treatment. In vitro assays revealed strong free-radical scavenging ability of the extract and presence of alkaloids, flavonoids, tannins, sterols, and saponins where rutin, a well-known antioxidant flavonoid, was identified. Conclusions Our findings demonstrate the potential of A. javanica in the attenuation

  10. Neonatal Liver Failure and Congenital Cirrhosis due to Gestational Alloimmune Liver Disease: A Case Report and Literature Review

    PubMed Central

    Rostirola Guedes, Renata; Kieling, Carlos Oscar; Rossato Adami, Marina; Cerski, Carlos Thadeu Schmidt

    2017-01-01

    Neonatal liver failure (NLF) is a major cause of neonatal morbidity and mortality, presenting as acute liver failure and/or congenital cirrhosis. Many affected patients show antenatal signs of fetal injury. There are several causes of NLF and early diagnosis is mandatory to elucidate the etiology and determine a specific treatment or the best management strategy. Gestational alloimmune liver disease associated with neonatal hemochromatosis (GALD-NH) is a rare but potentially treatable cause of NLF. It should be considered in any neonate with fetal signs of disease and postnatal signs of liver failure with no other identifiable causes. GALD-NH is often diagnosed late and patients are therefore referred late to specialized centers, delaying treatment. This case highlights the consequences of late diagnosis and treatment of GALD-NH and emphasizes the importance of a high grade of suspicion of this disease in order to refer the patient to a specialized center soon enough to perform the appropriate treatment. PMID:28251010

  11. Gene regulations in HBV-related liver cirrhosis closely correlate with disease severity.

    PubMed

    Lee, Seram; Kim, Soyoun

    2007-09-30

    Liver cirrhosis (LC) is defined as comprising diffuse fibrosis and regenerating nodules of the liver. The biochemical and anatomical dysfunction in LC results from both reduced liver cell number and portal vascular derangement. Although several studies have investigated dysregulated genes in cirrhotic nodules, little is known about the genes implicated in the pathophysiologic change of LC or about their relationship with the degree of decompensation. Here, we applied cDNA microarray analysis using 38 HBsAg-positive LC specimens to identify the genes dysregulated in HBV-associated LC and to evaluate their relation to disease severity. Among 1063 known cancer- and apoptosis-related genes, we identified 104 genes that were significantly up- (44) or down- (60) regulated in LC. Interestingly, this subset of 104 genes was characteristically correlated with the degree of decompensation, called the Pugh-Child classification (20 Pugh-Child A, 10 Pugh-Child B, and 8 Pugh-Child C). Patient samples from Pugh-Child C exhibited a distinct pattern of gene expression relative to those of Pugh-Child A and B. Especially in Pugh-Child C, genes encoding hepatic proteins and metabolizing enzymes were significantly down-regulated, while genes encoding various molecules related to cell replication were up-regulated. Our results suggest that subsets of genes in liver cells correspond to the pathophysiologic change of LC according to disease severity and possibly to hepatocarcinogenesis.

  12. Ex vivo expansion of circulating CD34+ cells enhances the regenerative effect on rat liver cirrhosis

    PubMed Central

    Nakamura, Toru; Koga, Hironori; Iwamoto, Hideki; Tsutsumi, Victor; Imamura, Yasuko; Naitou, Masako; Masuda, Atsutaka; Ikezono, Yu; Abe, Mitsuhiko; Wada, Fumitaka; Sakaue, Takahiko; Ueno, Takato; Ii, Masaaki; Alev, Cantas; Kawamoto, Atsuhiko; Asahara, Takayuki; Torimura, Takuji

    2016-01-01

    Ex vivo expansion of autologous cells is indispensable for cell transplantation therapy of patients with liver cirrhosis. The aim of this study was to investigate the efficacy of human ex vivo-expanded CD34+ cells for treatment of cirrhotic rat liver. Recipient rats were intraperitoneally injected with CCl4 twice weekly for 3 weeks before administration of CD34+ cells. CCl4 was then re-administered twice weekly for 3 more weeks, and the rats were sacrificed. Saline, nonexpanded or expanded CD34+ cells were injected via the spleen. After 7 days, CD34+ cells were effectively expanded in a serum-free culture medium. Expanded CD34+ cells were also increasingly positive for cell surface markers of VE-cadherin, VEGF receptor-2, and Tie-2. The expression of proangiogenic growth factors and adhesion molecules in expanded CD34+ cells increased compared with nonexpanded CD34+ cells. Expanded CD34+ cell transplantation reduced liver fibrosis, with a decrease of αSMA+ cells. Assessments of hepatocyte and sinusoidal endothelial cell proliferative activity indicated the superior potency of expanded CD34+ cells over non-expanded CD34+ cells. The inhibition of integrin αvβ3 and αvβ5 disturbed the engraftment of transplanted CD34+ cells and aggravated liver fibrosis. These findings suggest that expanded CD34+ cells enhanced the preventive efficacy of cell transplantation in a cirrhotic model. PMID:27162932

  13. Ultrasound-guided percutaneous portal transplantation of peripheral blood monocytes in patients with liver cirrhosis

    PubMed Central

    Yu, Su Jong; Yoon, Jung-Hwan; Kim, Won; Lee, Jeong Min; Lee, Yun Bin; Cho, Yuri; Lee, Dong Hyeon; Lee, Minjong; Yoo, Jeong-Ju; Cho, Eun Ju; Lee, Jeong-Hoon; Kim, Yoon Jun; Kim, Chung Yong

    2017-01-01

    Background/Aims Liver transplantation offers the only definite cure for cirrhosis but lacking donors is problem. Stem cell therapy is attractive in this setting. In this study, we aimed to explore the safety and efficacy of ultrasound-guided percutaneous portal transplantation of peripheral blood monocyte cell (PBMC) in cirrhotic patients. Methods A total of nine decompensated cirrhotic patients were randomized into three groups: group 1 (n = 3) was control group, group 2 (n = 3) received granulocyte-colony stimulating factor (G-CSF) mobilization for 3 days, and group 3 (n = 3) received G-CSF mobilized PBMCs by leukapheresis and PBMC transplantation through ultrasound-guided percutaneous portal vein puncture. Liver function and clinical features were evaluated. Results At baseline, the Child-Turcotte-Pugh and the model for end-stage liver disease scores were comparable in study groups. Compared with group 1, there was a tendency to improve liver function in group 3 at 6 months after treatment. Treatment was tolerable and no complications were encountered related to the G-CSF mobilization or percutaneous portal administration of PBMCs. Imaging studies showed patent portal veins at the end of the study period. Conclusions Autologous PBMC transplantation through ultrasound-guided percutaneous portal vein puncture could be considered as a safe alternative treatment for decompensated cirrhotic patients. PMID:27044856

  14. Rectal 13N-ammonia test (13N-liver/heart ratio), hepatic sinusoidal pressure and prevailing portal flow direction in cirrhosis of the liver.

    PubMed

    Hazenberg, H J; Gips, C H; Beekhuis, H; Kruizinga, K

    1976-01-01

    The 20 minutes' liver/heart activity ratio after rectal administration of 13N-ammonia was abnormally low (less than 2.25) in 12 of 26 patients with cirrhosis of the liver. An abnormal conventional rectal arterial ammonia test (porta-systemic shunts), an abnormally low urea index (prevailing hepatofugal portal venous flow direction), marked portal hypertension (hepatic sinusoidal pressure greater than or equal to 8 mm Hg), ascites and extreme enlargement of the spleen occurred significantly more often in the patients with an abnormally low 13N-liver/heart ratio than in those with a ratio greater than or equal to 2.25. There was no correlation between the 13N-liver/heart ratio and absence or presence of oesophageal varices. The non-invasive rectal 13N-ammonia test appears to be an easy to perform, informative test in cirrhosis of the liver.

  15. Genetics Home Reference: cryptogenic cirrhosis

    MedlinePlus

    ... Understand Genetics Home Health Conditions cryptogenic cirrhosis cryptogenic cirrhosis Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Cryptogenic cirrhosis is a condition that impairs liver function. People ...

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

    PubMed

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

    2013-01-01

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

  17. Functional renal failure (FRF) in cirrhosis of the liver and liver carcinoma

    PubMed Central

    Vesin, P.; Traverso, H.

    1975-01-01

    The term ‘functional renal failure’ has been used to describe the renal failure developing in advanced cirrhosis in which tubular function and structure remain intact. It may develop spontaneously, in which case prognosis is poor, but may be secondary to gastro-intestinal haemorrhage or excessive use of diuretics, in which case correction of the precipitating factor leads to improvement in renal function. It is suggested that the renal failure is due to a reduction in effective circulating plasma volume. PMID:1234327

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

    PubMed

    Seo, Yeon Seok; Shah, Vijay H

    2012-12-01

    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.

  19. Green tea polyphenol decreases the severity of portosystemic collaterals and mesenteric angiogenesis in rats with liver cirrhosis.

    PubMed

    Hsu, Shao-Jung; Wang, Sun-Sang; Hsin, I-Fang; Lee, Fa-Yauh; Huang, Hui-Chun; Huo, Teh-Ia; Lee, Wen-Shin; Lin, Han-Chieh; Lee, Shou-Dong

    2014-05-01

    Abnormal angiogenesis in liver cirrhosis often leads to severe complications such as variceal haemorrhage and encephalopathy. Furthermore, splanchnic angiogenesis elevates portal pressure, in which angiogenic factors play pivotal roles. GTP (green tea polyphenol) extracted from Camellia sinensis has anti-angiogenic properties, but the effects on the parameters described above in cirrhosis have not been investigated. The aim of the present study was to determine the effects of GTP in cirrhosis and to investigate the underlying mechanism. Liver cirrhosis was induced in Spraque-Dawley rats by common BDL (bile duct ligation). They randomly received GTP or DW (distilled water, vehicle) for 28 days, then haemodynamic parameters, portosystemic shunting, mesenteric window vascular density, intrahepatic angiogenesis, liver fibrosis, plasma VEGF (vascular endothelial growth factor) concentration, mesenteric angiogenic factor and receptor protein expression, and serum and mesenteric oxidative stress parameters were assessed. Compared with the DW group, GTP significantly decreased portosystemic shunting, liver fibrosis, intrahepatic angiogenesis, mesenteric window vascular density, VEGF concentration and down-regulated the mesenteric HIF (hypoxia-inducible factor)-1α, VEGF and phospho-Akt expression. In conclusion, GTP ameliorates the severity of portosystemic shunting and mesenteric angiogenesis via the suppression of HIF-1α, Akt activation and VEGF. GTP appears to be an appropriate agent in controlling portal hypertension-related complications via anti-angiogenesis.

  20. A profile of volatile organic compounds in exhaled air as a potential non-invasive biomarker for liver cirrhosis

    PubMed Central

    Pijls, Kirsten E.; Smolinska, Agnieszka; Jonkers, Daisy M. A. E.; Dallinga, Jan W.; Masclee, Ad A. M.; Koek, Ger H.; van Schooten, Frederik-Jan

    2016-01-01

    Early diagnosis of liver cirrhosis may prevent progression and development of complications. Liver biopsy is the current standard, but is invasive and associated with morbidity. We aimed to identify exhaled volatiles within a heterogeneous group of chronic liver disease (CLD) patients that discriminates those with compensated cirrhosis (CIR) from those without cirrhosis, and compare this with serological markers. Breath samples were collected from 87 CLD and 34 CIR patients. Volatiles in exhaled air were measured by gas chromatography mass spectrometry. Discriminant Analysis was performed to identify the optimal panel of serological markers and VOCs for classifying our patients using a random training set of 27 CIR and 27 CLD patients. Two randomly selected independent internal validation sets and permutation test were used to validate the model. 5 serological markers were found to distinguish CIR and CLD patients with a sensitivity of 0.71 and specificity of 0.84. A set of 11 volatiles discriminated CIR from CLD patients with sensitivity of 0.83 and specificity of 0.87. Combining both did not further improve accuracy. A specific exhaled volatile profile can predict the presence of compensated cirrhosis among CLD patients with a higher accuracy than serological markers and can aid in reducing liver biopsies. PMID:26822454

  1. Anti-fibrotic Role of miR-214 in Thioacetamide-induced Liver Cirrhosis in Rats.

    PubMed

    Izawa, Takeshi; Horiuchi, Takashi; Atarashi, Machi; Kuwamura, Mitsuru; Yamate, Jyoji

    2015-08-01

    An increasing number of studies have focused on the role of microRNAs in liver fibrosis/cirrhosis. miR-214 has recently attracted more attention as a fibrosis-related factor; however, the molecular mechanisms in hepatic fibrogenesis remain largely unknown. Here, we investigate the pathological role of miR-214 during progression of liver cirrhosis in rats. Rats were injected intraperitoneally with thioacetamide at a dose of 100 mg/kg body weight, twice a week. The liver was collected at post first injection weeks 5, 10, 15, and 20. Hepatic expression of miR-214 was analyzed by real-time polymerase chain reaction, in situ hybridization, and laser microdissection. The effects of miR-214 overexpression were investigated by in vitro transfection using fibroblastic MT-9 cells. miR-214 was highly upregulated in the fibrotic area in parallel with the cirrhosis progression. miR-214 overexpression in MT-9 cells under transforming growth factor-β1 stimulation resulted in decreased cell number and increased expression of cleaved caspase 3 and decreased expression of α-smooth muscle actin, suggesting that miR-214 induces apoptosis and inhibits myofibroblast differentiation in fibroblastic cells under stimulation of fibrogenic factors. These data indicate an anti-fibrotic role of miR-214 in chemically induced liver fibrosis/cirrhosis.

  2. Aortic valve replacement for aortic stenosis with a small aortic annulus in a patient having Werner's syndrome and liver cirrhosis.

    PubMed

    Sogawa, M; Kasuya, S; Yamamoto, K; Koshika, M; Oguma, F; Hayashi, J

    2001-12-01

    Werner's syndrome is a rare genetic disease characterized by premature aging and scleroderma-like involvement of the skin. We report a case of aortic valve replacement for severely calcified aortic valve stenosis with a small annulus in a patient suffering from Werner's syndrome and liver cirrhosis

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

    PubMed

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

    2014-10-01

    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 β, 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

  4. Vascular pathobiology in chronic liver disease and cirrhosis – Current status and future directions

    PubMed Central

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

    2015-01-01

    Summary 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 β, 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

  5. Inflammation: A novel target of current therapies for hepatic encephalopathy in liver cirrhosis.

    PubMed

    Luo, Ming; Guo, Jian-Yang; Cao, Wu-Kui

    2015-11-07

    Hepatic encephalopathy (HE) is a severe neuropsychiatric syndrome that most commonly occurs in decompensated liver cirrhosis and incorporates a spectrum of manifestations that ranges from mild cognitive impairment to coma. Although the etiology of HE is not completely understood, it is believed that multiple underlying mechanisms are involved in the pathogenesis of HE, and one of the main factors is thought to be ammonia; however, the ammonia hypothesis in the pathogenesis of HE is incomplete. Recently, it has been increasingly demonstrated that inflammation, including systemic inflammation, neuroinflammation and endotoxemia, acts in concert with ammonia in the pathogenesis of HE in cirrhotic patients. Meanwhile, a good number of studies have found that current therapies for HE, such as lactulose, rifaximin, probiotics and the molecular adsorbent recirculating system, could inhibit different types of inflammation, thereby improving the neuropsychiatric manifestations and preventing the progression of HE in cirrhotic patients. The anti-inflammatory effects of these current therapies provide a novel therapeutic approach for cirrhotic patients with HE. The purpose of this review is to describe the inflammatory mechanisms behind the etiology of HE in cirrhosis and discuss the current therapies that target the inflammatory pathogenesis of HE.

  6. Evaluation of Aspartate Aminotransferase-to-Platelet Ratio Index as a Non-Invasive Marker for Liver Cirrhosis

    PubMed Central

    Tripathi, B.K.; Gupta, B.; Bhandari, Bharti; Jalan, Divesh

    2015-01-01

    Introduction Liver biopsy is considered as a gold standard for the diagnosis of cirrhosis. Till date there is no non-invasive marker to replace it. Aim To investigate the effectiveness of Aspartate aminotransferase-to-platelet ratio index (APRI) as a non-invasive marker for liver cirrhosis. Materials and Methods Fifty-one patients with cirrhosis, identified on USG abdomen were included in study. Platelet count and Aspartate aminotransferase (AST) were done using haematology automatic analyser and automatic HITACHI-912 Auto Analyser respectively. APRI was calculated for every patient using the formula {(AST / ULN) x 100}/platelet count (109/L). Predictive accuracy was evaluated with a receiver-operating characteristics (ROC) curve. Results APRI correctly classified 49 (96.1%) patients of cirrhosis with area under the ROC curve of 0.973 (95% CI) at cut-off 0.65 with negative predictive value (NPV) and Positive predictive value (PPV) of 96% and 96.1% respectively. The sensitivity and specificity of the test was found to be 96% and 96.1% respectively. Conclusion APRI could identify cirrhosis with high degree of accuracy in the studied patients. PMID:26672800

  7. Transforming growth factor-β genetic polymorphisms on development of liver cirrhosis in a meta-analysis.

    PubMed

    Wu, Xiao-Dan; Zeng, Kai; Gong, Can-Sheng; Chen, Jinhua; Chen, Yan-Qing

    2013-01-01

    Transforming growth factor-β (TGF-β) protein has been supposed to be a risk factor for liver cirrhosis; however, the associations between its genes (TGF-β -509C>T and +869T>C) and liver cirrhosis remained unclear. This study was to quantitatively analyze the correlations by using a meta-analysis. Pubmed, Embase, Wanfang databases were retrieved up to November 1st, 2011. Odds ratio (OR) and 95 % confidence interval (95 %CI) were used to demonstrate the strength of association, and P < 0.05 of Z test indicated statistical significance. Combined analyses were performed by using fixed or random-effect model, depending on between-study heterogeneity. Seven studies were for TGF-β -509C>T polymorphism, and eight studies were for +869T>C polymorphism. Combined results indicated that neither TGF-β -509C>T nor +869T>C polymorphisms were associated with risk of liver cirrhosis [OR (95 % CI): 0.79 (0.60-1.04) for CT vs. TT of -509C>T and 0.87 (0.68-1.12) for CT vs. CC of +869T>C], with no between-study heterogeneity. In addition, subgroups analyses still inferred that two polymorphisms were not associated with risk of liver cirrhosis for HBV-infected patients, Asians and for Population-based studies. This meta-analysis indicated that neither TGF-β -509C>T nor +869T>C polymorphisms were associated with risk of liver cirrhosis, regardless of HBV infection or not.

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

    PubMed Central

    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

    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

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

    PubMed

    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

    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

  10. Hematotesticular barrier is altered from early stages of liver cirrhosis: Effect of insulin-like growth factor 1

    PubMed Central

    Castilla-Cortázar, Inma; Diez, Nieves; García-Fernández, María; Puche, Juan Enrique; Diez-Caballero, Fernando; Quiroga, Jorge; Díaz-Sánchez, Matías; Castilla, Alberto; Casares, Amelia Díaz; Varela-Nieto, Isabel; Prieto, Jesús; González-Barón, Salvador

    2004-01-01

    AIM: The pathogenesis of hypogonadism in liver cirrhosis is not well understood. Previous results from our laboratory showed that IGF-1 deficiency might play a pathogenetic role in hypogonadism of cirrhosis. The administration of IGF-1 for a short period of time reverted the testicular atrophy associated with advanced experimental cirrhosis. The aim of this study was to establish the historical progression of the described alterations in the testes, explore testicular morphology, histopathology, cellular proliferation, integrity of testicular barrier and hypophyso-gonadal axis in rats with no ascitic cirrhosis. METHODS: Male Wistar rats with histologically-proven cirrhosis induced with carbon tetrachloride (CCl4) for 11 wk, were allocated into two groups (n = 12, each) to receive recombinant IGF-1 (2 μg/100 g.d, sc) for two weeks or vehicle. Healthy rats receiving vehicle were used as control group (n = 12). RESULTS: Compared to controls, rats with compensated cirrhosis showed a normal testicular size and weight and very few histopathological testicular abnormalities. However, these animals showed a significant diminution of cellular proliferation and a reduction of testicular transferrin expression. In addition, pituitary-gonadal axis was altered, with significant higher levels of FSH (P < 0.001 vs controls) and increased levels of LH in untreated cirrhotic animals. Interestingly, IGF-1 treatment normalized testicular transferrin expression and cellular proliferation and reduced serum levels of LH (P = ns vs controls, and P < 0.01 vs untreated cirrhotic group). CONCLUSION: The testicular barrier is altered from an early stage of cirrhosis, shown by a reduction of transferrin expression in Sertoli cells, a diminished cellular proliferation and an altered gonadal axis. The treatment with IGF-1 could be also useful in this initial stage of testicular disorder associated with compensated cirrhosis. PMID:15300898

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

    PubMed

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

    2015-04-01

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

  12. Effect of age and liver cirrhosis on the pharmacokinetics of nitrazepam

    PubMed Central

    Jochemsen, R.; Van Beusekom, B. R.; Spoelstra, P.; Janssens, A. R.; Breimer, D. D.

    1983-01-01

    1 The effect of age and liver cirrhosis on the pharmacokinetics of i.v. administered nitrazepam was studied in nine healthy relatively young subjects (age 22-49 years), eight healthy elderly (age 67-76 years) and 12 patients with alcoholic liver cirrhosis (age 39-66 years). 2 The elimination half-life of nitrazepam in the elderly subjects was longer than in the young ones but the difference did not reach statistical significance. Mean values (ranges) were 38 (26-64) h and 26 (19-31) h respectively. 3 The increase in elimination half-life was primarily due to an increase in volume of distribution, mean values (ranges) being 2.93 (1.96-5.33) l/kg and 1.89 (1.44-2.23) l/kg in the elderly and young groups respectively (P < 0.05). 4 The protein unbound fraction of nitrazepam tended to be higher in the elderly subjects, although the difference between the two age groups was not significant: 13.9 (11.5-15.4)% and 13.0 (11.0-15.9)% in elderly and young respectively. 5 Age had no effect on the clearance of total nitrazepam nor on the clearance of unbound nitrazepam (intrinsic clearance). Mean values (ranges) were 63 (50-87) ml/min and 489 (377-635) ml/min in the young and 64 (47-91) ml/min and 456 (348-652) ml/min in the elderly subjects respectively. 6 There were no significant differences in elimination half life, clearance and volume of distribution between patients with alcoholic liver cirrhosis and the total of healthy subjects of both age groups, mean values (ranges) being 31 (21-55) h, 59 (26-85) ml/min and 2.17 (1.57-3.22) l/kg respectively in patients and 31 (19-64) h, 63 (47-91) ml/min and 2.38 (1.44-5.33) l/kg in healthy subjects. 7 The protein unbound fraction of nitrazepam was substantially higher in the patient group: 18.9 (14.8-30.3)% as compared to 13.8 (11.0-15.9)% in the healthy subjects (P < 0.001). 8 Clearance calculated relative to unbound nitrazepam (intrinsic clearance) was significantly lower in the patient group: 320 (163-482) ml/min as compared to

  13. Postmortem diagnosis of "occult" Klinefelter syndrome in a patient with chronic renal disease and liver cirrhosis.

    PubMed

    Matsuoka, Kentaro; Orikasa, Hideki; Eyden, Brian; Yamazaki, Kazuto

    2002-03-01

    This report describes a patient not suspected of having Klinefelter syndrome during life but diagnosed with it following postmortem examination using fluorescent in situ hybridization (FISH) for sex chromosomes and hormone serum analysis. A 49-year-old Japanese man had a history of nephrosis, heavy alcohol consumption, diabetes mellitus, and liver cirrhosis and had been undergoing dialysis for 10 years. He died of ruptured esophageal varices. Autopsy revealed hypogonadism, suggesting Klinefelter syndrome. This was confirmed by FISH, which showed a mosaic 46XY, 47XXY karyotype, and by serum analysis, which revealed high luteinizing hormone and follicle-stimulating hormone and low testosterone levels. Autopsy also revealed a nodular, bilateral, testicular Leydig cell hyperplasia. This report illustrates the value of postmortem laboratory investigations, particularly FISH for sex chromosomes and serum hormone analysis, for the demonstration of clinically uncertain or "occult" Klinefelter syndrome.

  14. Gastric ischemia after epinephrine injection in a patient with liver cirrhosis

    PubMed Central

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

    2013-01-01

    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

  15. Transjugular intrahepatic portosystemic shunt in refractory chylothorax due to liver cirrhosis.

    PubMed

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

    2013-02-21

    A pleural effusion containing chylomicrons is termed chylothorax and results from leakage of lymph fluid into the pleural cavity. We report on the case of a 59-year-old woman with severe dyspnea due to a large chylothorax. She was known to have liver cirrhosis but no ascites. There was no history of trauma, cardiac function was normal and thorough diagnostic work-up did not reveal any signs of malignancy. In summary, no other etiology of the chylothorax than portal hypertension could be found. Therapy with diuretics as well as parenteral feeding failed to relieve symptoms. After a transjugular intrahepatic portosystemic shunt (TIPS) had successfully been placed, pleural effusion decreased considerably. Eight months later, TIPS revision had to be performed because of stenosis, resulting in remission from chylothorax. This case shows that even in the absence of ascites, chylothorax might be caused by portal hypertension and that TIPS can be an effective treatment option.

  16. Renal involvement in a syndrome of vasculitis complicating HBsAg negative cirrhosis of the liver.

    PubMed

    Montoliu, J; Darnell, A; Grau, J M; Torras, A; Revert, L

    1985-01-01

    Six HBsAg negative patients with cirrhosis of the liver (CL) presented with recurrent bouts of palpable purpura in the legs due to small vessel leucocytoclastic vasculitis. In addition, all patients had renal failure, proteinuria and microhaematuria. Renal biopsy disclosed either diffuse proliferative (3 cases) or focal necrotising glomerulonephritis with crescents (2 cases). One patient had IgM-IgG mixed cryoglobulinaemia (type II). Four patients died of complications of their CL. Hepatocellular carcinoma was found in 1 case. In the patient without renal biopsy renal function improved following steroids and cyclophosphamide. The pathogenesis of this syndrome of cutaneous vasculitis with severe glomerular involvement in CL is unknown but could be immune-complex mediated.

  17. Variables Associated With Inpatient and Outpatient Resource Utilization Among Medicare Beneficiaries With Nonalcoholic Fatty Liver Disease With or Without Cirrhosis

    PubMed Central

    Sayiner, Mehmet; Otgonsuren, Munkhzul; Cable, Rebecca; Younossi, Issah; Afendy, Mariam; Golabi, Pegah; Henry, Linda

    2017-01-01

    Background: Nonalcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver disease worldwide with tremendous clinical burden. The economic burden of NAFLD is not well studied. Goal: To assess the economic burden of NAFLD. Study: Medicare beneficiaries (January 1, 2010 to December 31, 2010) with NAFLD diagnosis by International Classification of Diseases, Ninth Revision codes in the absence of other liver diseases were selected. Inpatient and outpatient resource utilization parameters were total charges and total provider payments. NAFLD patients with compensated cirrhosis (CC) were compared with decompensated cirrhosis (DC). Results: A total of 976 inpatients and 4742 outpatients with NAFLD were included—87% were white, 36% male, 30% had cardiovascular disease (CVD) or metabolic syndrome conditions, and 12% had cirrhosis. For inpatients, median total hospital charge was $36,289. NAFLD patients with cirrhosis had higher charges and payments than noncirrhotic NAFLD patients ($61,151 vs. $33,863 and $18,804 vs. $10,146, P<0.001). Compared with CC, NAFLD patients with DC had higher charges and payments (P<0.02). For outpatients, median total charge was $9,011. NAFLD patients with cirrhosis had higher charges and payments than noncirrhotic NAFLD patients ($12,049 vs. $8,830 and $2,586 vs. $1,734, P<0.001). Compared with CC, DC patients had higher total charges ($15,187 vs. $10,379, P=0.04). In multivariate analysis, variables associated with increased inpatient resource utilization were inpatient mortality, DC, and CVD; for outpatients, having CVD, obesity, and hypertension (all P<0.001). Conclusions: NAFLD is associated with significant economic burden to Medicare. Presence of cirrhosis and CVD are associated with increased resource utilization. PMID:27332747

  18. Laparoscopic hepatectomy in a morbidly obese patient with liver cirrhosis: A case report

    PubMed Central

    Machairas, Nikolaos; Kostakis, Ioannis D.; Mantas, Dimitrios; Sotiropoulos, Georgios C.

    2017-01-01

    Cirrhotic patients constitute a high-risk population, and present a major challenge for the performance of minimally invasive laparoscopic resections due to difficulties in parenchymal transection. The present study describes the case of a 71-year-old morbidly obese male patient who was referred to our department with a hepatic mass identified on routine abdominal ultrasound. Abdominal computer tomography and magnetic resonance imaging confirmed a mass in segments V–VI of the liver, highly suspicious for HCC. The patient's past medical history additionally included non-alcoholic steatohepatitis, diabetes mellitus and arterial hypertension and myocardial infarction. The patient's body mass index was 45 kg/m2, and the American Society of Anesthesiologists' classification of preoperative risk was 3. The patient underwent laparoscopic resection of segments V–VI and cholecystectomy. Two years postoperatively, the patient remains disease-free and in excellent condition. To the best of our knowledge, this is the first report on laparoscopic liver resection for such a morbidly obese patient in the context of advanced liver cirrhosis.

  19. Nutritional status of patients with alcoholic cirrhosis undergoing liver transplantation: time trends and impact on survival.

    PubMed

    Singal, Ashwani K; Kamath, Patrick S; Francisco Ziller, Nickie; DiCecco, Sara; Shoreibah, M; Kremers, Walter; Charlton, Michael R; Heimbach, Julie K; Watt, Kymberly D; Shah, Vijay H

    2013-08-01

    Alcoholic cirrhotics evaluated for liver transplantation are frequently malnourished or obese. We analyzed alcoholic cirrhotics undergoing transplantation to examine time trends of nutrition/weight, transplant outcome, and effects of concomitant hepatitis C virus (HCV) and/or hepatocellular carcinoma (HCC). Nutrition and transplant outcomes were reviewed for alcoholic cirrhosis with/without HCV/HCC. Malnutrition was defined by subjective global assessment. Body mass index (BMI) classified obesity. A total of 261 patients receiving transplants were separated (1988-2000, 2001-2006, and 2007-2011) to generate similar size cohorts. Mean BMI for the whole cohort was 28 ± 6 with 68% classified as overweight/obese. Mean BMI did not vary among cohorts and was not affected by HCV/HCC. While prevalence of malnutrition did not vary among cohorts, it was lower in patients with HCV/HCC (P < 0.01). One-year graft/patient survival was 90% and not impacted by time period, HCV/HCC, or malnutrition after adjusting for demographics and model end-stage liver disease (MELD). Alcoholic cirrhotics undergoing transplantation are malnourished yet frequently overweight/obese. Among patients selected for transplantation, 1-year post-transplant graft/patient survival is excellent, have not changed over time, and do not vary by nutrition/BMI. Our findings support feasibility of liver transplantation for alcoholic cirrhotics with obesity and malnutrition.

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

    PubMed Central

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

    2014-01-01

    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

  1. Serum cell death biomarkers for prediction of liver fibrosis and poor prognosis in primary biliary cirrhosis.

    PubMed

    Sekiguchi, Tomohiro; Umemura, Takeji; Fujimori, Naoyuki; Shibata, Soichiro; Ichikawa, Yuki; Kimura, Takefumi; Joshita, Satoru; Komatsu, Michiharu; Matsumoto, Akihiro; Tanaka, Eiji; Ota, Masao

    2015-01-01

    The development of simple, noninvasive markers of liver fibrosis is urgently needed for primary biliary cirrhosis (PBC). This study examined the ability of several serum biomarkers of cell death to estimate fibrosis and prognosis in PBC. A cohort of 130 patients with biopsy-proven PBC and 90 healthy subjects were enrolled. We assessed the utility of the M30 ELISA, which detects caspase-cleaved cytokeratin-18 (CK-18) fragments and is representative of apoptotic cell death, as well as the M65 and newly developed M65 Epideath (M65ED) ELISAs, which detect total CK-18 as indicators of overall cell death, in predicting clinically relevant fibrosis stage. All 3 cell death biomarkers were significantly higher in patients with PBC than in healthy controls and were significantly correlated with fibrosis stage. The areas under the receiver operating characteristic curve for the M65 and M65ED assays for differentiation among significant fibrosis, severe fibrosis, and cirrhosis were 0.66 and 0.76, 0.66 and 0.73, and 0.74 and 0.82, respectively. In multivariate analysis, high M65ED (hazard ratio 6.13; 95% confidence interval 1.18-31.69; P = 0.031) and severe fibrosis (hazard ratio 7.45; 95% confidence interval 1.82-30.51; P = 0.005) were independently associated with liver-related death, transplantation, or decompensation. High serum M65ED was also significantly associated with poor outcome in PBC (log-rank test; P = 0.001). Noninvasive cell death biomarkers appear to be clinically useful in predicting fibrosis in PBC. Moreover, the M65ED assay may represent a new surrogate marker of adverse disease outcome.

  2. A new definition of sarcopenia in patients with cirrhosis undergoing liver transplantation.

    PubMed

    Golse, Nicolas; Bucur, Petru Octav; Ciacio, Oriana; Pittau, Gabriella; Sa Cunha, Antonio; Adam, René; Castaing, Denis; Antonini, Teresa; Coilly, Audrey; Samuel, Didier; Cherqui, Daniel; Vibert, Eric

    2017-02-01

    Although sarcopenia is a common complication of cirrhosis, its diagnosis remains nonconsensual: computed tomography (CT) scan determinations vary and no cutoff values have been established in cirrhotic populations undergoing liver transplantation (LT). Our aim was to compare the accuracy of the most widely used measurement techniques and to establish useful cutoffs in the setting of LT. From the 440 patients transplanted between January 2008 and May 2011 in our tertiary center, we selected 256 patients with cirrhosis for whom a recent CT scan was available during the 4 months prior to LT. We measured different muscle indexes: psoas muscle area (PMA), PMA normalized by height or body surface area (BSA), and the third lumbar vertebra skeletal muscle index (L3SMI). Receiver operating characteristic curves were evaluated and prognostic factors for post-LT 1-year survival were then analyzed. PMA offered better accuracy (area under the curve [AUC] = 0.753) than L3SMI (AUC = 0.707) and PMA/BSA (AUC = 0.732), and the same accuracy as PMA/squared height. So, for its accuracy and simplicity of use, the PMA index was used for the remainder of the analysis and to define sarcopenia. In men, the better cutoff value for PMA was 1561 mm(2) (Se = 94%, Sp = 57%), whereas in women, it was 1464 mm(2) (Se = 52%, Sp = 91%). A PMA lower than these values defined sarcopenia in patients with cirrhosis awaiting LT. One- and 5-year overall survival rates were significantly poorer in the sarcopenic group (n = 57) than in the nonsarcopenic group (n = 199), at 59% versus 94% and 54% versus 80%, respectively (P < 0.001). In conclusion, pre-LT PMA is a simple tool to assess sarcopenia. We established sex-specific cutoff values (1561 mm(2) in men, 1464 mm(2) in women) in a cirrhotic population and showed that 1-year survival was significantly poorer in sarcopenic patients. Liver Transplantation 23 143-154 2017 AASLD.

  3. Effect of undifferentiated versus hepatogenic partially differentiated mesenchymal stem cells on hepatic and cognitive functions in liver cirrhosis

    PubMed Central

    Elberry, Dalia Azmy; Amin, Shaimaa Nasr; Esmail, Reham Shehab El Nemr; Rashed, Laila Ahmed; Gamal, Maha Mohamed

    2016-01-01

    Liver cirrhosis is the outcome of chronic liver injury. The current study aimed to investigate the therapeutic effect of undifferentiated mesenchymal stem cells versus in vitro partially differentiated mesenchymal stem cells on liver cirrhosis and hepatic encephalopathy. 50 adult male albino rats constituted the animal model and were divided into the following groups: control, thioacetamide, undifferentiated mesenchymal stem cells and hepatocyte growth factor-differentiated mesenchymal stem cells groups. Cognitive assessment was achieved by open field test and Y-maze task. We measured serum alanine aminotransferase, albumin and transforming growth factor-beta1, gene expression of α-smooth muscle actin, matrix metalloprotein-2, its tissue inhibitor and apoptotic markers: Bax and Bcl2, brain glial fibrillary acidic protein, synaptophysin, and dopaminergic receptors. PMID:28337098

  4. Immunohistochemical evidence of disease recurrence after liver transplantation for primary biliary cirrhosis.

    PubMed

    Van de Water, J; Gerson, L B; Ferrell, L D; Lake, J R; Coppel, R L; Batts, K P; Wiesner, R H; Gershwin, M E

    1996-11-01

    Whether primary biliary cirrhosis (PBC) recurs after liver transplantation has remained an interesting and controversial issue; rejection, viral hepatitis, and drug effects all may mimic recurrent PBC histologically and biochemically. Furthermore, reliable clinical criteria for PBC recurrence are lacking. In this study, the issue of disease recurrence using a well-characterized monoclonal antibody (MAb), C355.1, that reacts with the immunodominant mitochondrial autoantigen of PBC (pyruvate dehydrogenase complex [PDC-E2]) was addressed. When used in an immunohistochemical assay, C355.1 produces intense apical staining of bile duct epithelium specifically in liver sections of patients with PBC and may be the earliest known marker of PBC. Immunohistochemical and histological analysis of serial liver biopsy specimens of 67 patients pre- and post-orthotopic liver transplantation (OLT), including 38 patients with PBC and 29 non-PBC liver disease controls, was performed. Sections were stained with MAb C355.1 or the control MAb C315 and analyzed to determine whether there was a recurrence of apical reactivity in the bile ducts of the posttransplantation biopsy specimens. The immunohistochemical staining was correlated with the histological findings and serum biochemistries at the time of the biopsy. Our data indicate that a significant number of patients who underwent transplantation for PBC (28 of 38) but not controls (0 of 29) develop a staining pattern of liver bile duct epithelium with MAb C355.1 that is indistinguishable from the pretransplantation pattern. Of the 28 patients with this apical staining pattern, 8 were characterized histologically as possible recurrent PBC, 2 as chronic rejection, 2 as acute rejection, 9 as nonspecific changes, 4 as normal or near normal, and 3 had other histological changes. Only 50% of the patients with apical C355.1 staining had liver enzyme levels suggestive of cholestasis. Thus, there appears to be immunohistochemical evidence that

  5. Evaluating the safety and dosing of drugs in patients with liver cirrhosis by literature review and expert opinion

    PubMed Central

    Weersink, Rianne A; Bouma, Margriet; Burger, David M; Drenth, Joost P H; Hunfeld, Nicole G M; Kranenborg, Minke; Monster-Simons, Margje H; van Putten, Sandra A W; Metselaar, Herold J; Taxis, Katja; Borgsteede, Sander D

    2016-01-01

    Introduction Liver cirrhosis can have a major impact on drug pharmacokinetics and pharmacodynamics. Patients with cirrhosis often suffer from potentially preventable adverse drug reactions. Guidelines on safe prescribing for these patients are lacking. The aim of this study is to develop a systematic method for evaluating the safety and optimal dosage of drugs in patients with liver cirrhosis. Methods and analysis For each drug, a six-step evaluation process will be followed. (1) Available evidence on the pharmacokinetics and safety of a drug in patients with liver cirrhosis will be collected from the Summary of Product Characteristics (SmPC) and a systematic literature review will be performed. (2) Data regarding two outcomes, namely pharmacokinetics and safety, will be extracted and presented in a standardised assessment report. (3) A safety classification and dosage suggestion will be proposed for each drug. (4) An expert panel will discuss the validity and clinical relevance of this suggested advice. (5) Advices will be implemented in all relevant Clinical Decision Support Systems in the Netherlands and published on a website for patients and healthcare professionals. (6) The continuity of the advices will be guaranteed by a yearly check of new literature and comments on the advices. This protocol will be applied in the evaluation of a selection of drugs: (A) drugs used to treat (complications of) liver cirrhosis, and (B) drugs frequently prescribed to the general population. Ethics and dissemination Since this study does not directly involve human participants, it does not require ethical clearance. Besides implementation on a website and in clinical decision support systems, we aim to publish the generated advices of one or two drug classes in a peer-reviewed journal and at conference meetings. PMID:27733414

  6. Potential therapeutic application of intravenous autologous bone marrow infusion in patients with alcoholic liver cirrhosis.

    PubMed

    Saito, Takafumi; Okumoto, Kazuo; Haga, Hiroaki; Nishise, Yuko; Ishii, Rika; Sato, Chikako; Watanabe, Hisayoshi; Okada, Akio; Ikeda, Motoki; Togashi, Hitoshi; Ishikawa, Tsuyoshi; Terai, Shuji; Sakaida, Isao; Kawata, Sumio

    2011-09-01

    The present study was conducted to evaluate the application and efficacy of autologous bone marrow infusion (ABMi) for improvement of liver function in patients with alcoholic liver cirrhosis (ALC). Five subjects and 5 control patients with ALC who had abstained from alcohol intake for 24 weeks before the study were enrolled. Autologous bone marrow cells were washed and injected intravenously, and the changes in serum liver function parameters, and the level of the type IV collagen 7S domain as a marker of fibrosis, were monitored for 24 weeks. The distribution of activated bone marrow was assessed by indium-111-chloride bone marrow scintigraphy. The number of cells infused was 8.0±7.3×10(9) (mean±standard error). The serum levels of albumin and total protein and the prothrombin time were significantly higher during the follow-up period after ABMi than during the observation period in treated patients, whereas no such changes were observed in the controls. In the patients who received ABMi, the Child-Pugh score decreased in all 3 who were classified as class B; the serum levels of type IV collagen 7S domain improved in 4 of the 5 patients; and bone marrow scintigraphy demonstrated an increase of indium-111-chloride uptake in 3 of the 4 patients tested. ABMi for patients with ALC helps improve liver function parameters in comparison with observation during abstinence and ameliorates the degree of fibrosis in terms of serum markers and bone marrow activation in most cases.

  7. [Nutritional assessment in cirrhosis].

    PubMed

    Buyse, S; Durand, F; Joly, F

    2008-03-01

    The liver plays a key role in the metabolism of nutrients. Therefore, liver failure is often associated with malnutrition. It is well-established that malnutrition is an independent prognostic factor in patients with cirrhosis and liver failure. Since standard anthropometric and biological indexes are associated with liver dysfunction, nutritional assessment is difficult in patients with cirrhosis. In this review, we explain the various causes and mechanisms leading to malnutrition in cirrhosis. We also describe reliable methods used to assess the nutritional condition of these patients. Finally, we stress the importance of nutritional care in cirrhosis and liver dysfunction, describing its specific characteristics and indications.

  8. Cardiopulmonary response to exercise in patients with liver cirrhosis and impaired pulmonary gas exchange.

    PubMed

    Lemyze, Malcolm; Dharancy, Sébastien; Nevière, Remy; Wallaert, Benoît

    2011-10-01

    Maximal exercise capacity and pulmonary gas exchange are both commonly impaired in liver cirrhosis. Apart from rare cases of hepatopulmonary syndrome, it is still unknown whether these moderate pulmonary gas exchange abnormalities can alter aerobic capacity of cirrhotic patients. Resting pulmonary function tests and symptom-limited cardiopulmonary exercise testing were prospectively investigated in 30 patients with liver cirrhosis exhibiting a widened alveolar-arterial oxygen gradient (P(A-a)O(2) > 30 mm Hg at peak exercise) without pulmonary vascular dilatations at contrast-enhanced echocardiography. Data were compared with those of 30 normoxemic cirrhotic controls (matched for age, gender, body mass index, etiology and severity of liver disease, smoking habits, hemoglobin level, and beta-blocker therapy). Resting cardiopulmonary parameters were within normal range in both groups except carbon monoxide lung transfer (TLCO, 60.4 ± 2.9 vs 74.3 ± 2.8% in controls, p = 0.0004) and P(A-a)O(2) (28.8 ± 2 vs 15.3 ± 2 mm Hg in controls, p < 0.0001). Cirrhotics with impaired gas exchange during exercise exhibited a significant reduction in maximal oxygen uptake (VO(2)max, 1.18 ± 0.07 (53% predicted) vs 1.41 ± 0.07 L/min (62% predicted), p = 0.004), a higher ventilation level at ventilatory threshold (V(E)/VO(2), 39.2 ± 1.5 vs 35.3 ± 1.5, p = 0.01) without ventilatory limitation, and a greater dead space to tidal volume ratio (V(D)/V(T)max, 0.32 ± 0.01 vs 0.25 ± 0.01, p = 0.01). VO(2)max correlates negatively with V(D)/V(T)max (r(2) = 0.36; p < 0.0001). There were no differences in cardiac or metabolic response to exercise between groups. Taken together these findings suggest that clinically undetectable pulmonary vascular disorders can slightly contribute to further reduce exercise capacity of cirrhotic patients.

  9. High circulating D-dimers are associated with ascites and hepatocellular carcinoma in liver cirrhosis

    PubMed Central

    Spadaro, Aldo; Tortorella, Vincenza; Morace, Carmela; Fortiguerra, Agostino; Composto, Paola; Bonfiglio, Caterina; Alibrandi, Angela; Luigiano, Carmelo; Caro, Giuseppe De; Ajello, Antonino; Ferraù, Oscar; Freni, Maria Antonietta

    2008-01-01

    AIM: To measure plasma D-dimer levels in cirrhotic patients with and without ascites, assessing the effect of ascites resolution in D-dimer concentration. METHODS: Seventy consecutive cirrhotic patients (M = 44, F = 26, mean age 65 years, SD ± 13), observed from October 2005 to March 2006 were enrolled. Circulating D-dimer levels were measured using a latex-enhanced, immunoturbidimetric test. In patients with ascites (n = 42) the test was repeated after ascites resolution. RESULTS: Ascites was present in 42 patients (group A) and absent in 28 (group B). Group A patients had more advanced liver disease. Hepatocellular carcinoma (HCC) was diagnosed in 14 patients and was more frequent in group B. Above normal range D-dimers were found in 45/70 patients. High D-dimers were more frequent in group A than in group B (P = 0.001). High D-dimers were associated with presence of HCC (P = 0.048) only in group B. After ascites resolution, obtained in all patients, mean D-dimer values decreased in those 34 patients with high basal levels (P = 0.007), returning to normal in 17. CONCLUSION: In patients with liver cirrhosis, ascites and HCC are the main factors associated with increased fibrinolytic activity. PMID:18330946

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

    PubMed Central

    2011-01-01

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

  11. A method for estimating alcohol-related liver cirrhosis mortality in Japan.

    PubMed

    Parrish, K M; Higuchi, S; Muramatsu, T; Stinson, F S; Harford, T C

    1991-12-01

    In Japan, per capita alcohol consumption increased sharply during the post World War II period followed by an increase in cirrhosis mortality. The prevalence of alcoholic cirrhosis among hospitalized patients also increased, from 11% in 1969 to 18% in 1985. Despite an increase in the percentage of drinkers among young women, over 80% of women in Japan are still abstainers or light drinkers. Thus, female cirrhosis mortality rates can be used as a proxy measure of non-alcohol-related cirrhosis mortality rates to estimate alcohol-related cirrhosis deaths among Japanese men. Employing this method, we conclude that two-thirds of cirrhosis deaths among men between 24 and 85 years of age and half of all cirrhosis deaths were attributable to alcohol. Two factors are probably responsible for the differences in proportional morbidity and proportional mortality of alcohol-related cirrhosis: differences in survival rates between alcoholic and non-alcoholic cirrhosis patients and detection bias toward post-hepatic cirrhosis. The synergistic effect of alcohol on viral hepatitis may in part explain excess cirrhosis deaths among Japanese men.

  12. The impacts of liver cirrhosis on head and neck cancer patients undergoing microsurgical free tissue transfer: an evaluation of flap outcome and flap-related complications.

    PubMed

    Kao, Huang-Kai; Chang, Kai-Ping; Ching, Wei-Cheng; Tsao, Chung-Kan; Cheng, Ming-Huei; Wei, Fu-Chan

    2009-12-01

    Several authors have cited liver cirrhosis as a risk factor for surgery but no study performed statistical correlation between flap outcome and severity of liver cirrhosis in patients with head and neck cancer. We performed a retrospective analysis of 3108 patients who underwent free tissue transfer after head and neck cancer ablation between January 2000 and December 2008. Liver cirrhosis was identified in 62 patients. Forty-two patients (67.7%) were classified as having Child's class A cirrhosis, seventeen (27.4%) as having class B, and three (4.9%) as having class C cirrhosis. The overall complete flap survival rate was 90.3% (56/62). The flap-related complications of patients with Child's class A, B, and C were 38.1% (16/42), 47.1% (8/17), and 100% (3/3), respectively and showed no significant difference between these three groups (p=0.2758). The rate of postoperative neck hematoma was 14.5%; the risk of postoperative neck hematoma was significantly higher in patients with more advanced liver cirrhosis (p=0.0003). The recipient-site complications of patients with Child's class A cirrhosis, Child's class B, and Child's class C cirrhosis were 35.7%, 41.1%, and 66.6%, respectively, with no significant difference among the three groups. The statistical analysis demonstrated that diabetes mellitus is significantly associated with a negative prognosis for free flap reconstruction (p=0.0364). The flap survival rate and patency of microvascular anastomosis have no association with liver cirrhosis. To achieve a superior surgical outcome, preoperative optimization and a multidisciplinary team responsible for the evaluation and treatment of head and neck cancer patients with cirrhosis are necessary.

  13. The contribution of alcohol, thiamine deficiency and cirrhosis of the liver to cerebral cortical damage in alcoholics.

    PubMed

    Kril, J J

    1995-03-01

    The relative roles of alcohol toxicity, thiamine deficiency and cirrhosis of the liver in the pathogenesis of alcohol-related brain damage are unclear. Brain shrinkage and neuronal loss from four regions of the cortex was determined in 22 alcoholics with the Wernicke-Korsakoff Syndrome (WKS), cirrhosis of the liver or neither of these complications and compared to 22 age-matched non-alcoholic controls. Brain shrinkage was most marked in those alcoholics with WKS. Neuronal loss occurred only from the superior cortex and was of equal magnitude in all alcoholic subgroups. In an animal model of alcohol abuse and thiamine deficiency, neuronal loss from the cerebral cortex occurred in a time-dependent manner. Furthermore, those cells which contained the calcium-binding protein parvalbumin appeared to be preferentially damaged in this model.

  14. Metabolomic analysis of human cirrhosis, hepatocellular carcinoma, non-alcoholic fatty liver disease and non-alcoholic steatohepatitis diseases

    PubMed Central

    Safaei, Akram; Arefi Oskouie, Afsaneh; Mohebbi, Seyed Reza; Rezaei-Tavirani, Mostafa; Mahboubi, Mohammad; Peyvandi, Maryam; Okhovatian, Farshad; Zamanian-Azodi, Mona

    2016-01-01

    Metabolome analysis is used to evaluate the characteristics and interactions of low molecular weight metabolites under a specific set of conditions. In cirrhosis, hepatocellular carcinoma, non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatotic hepatitis (NASH) the liver does not function thoroughly due to long-term damage. Unfortunately the early detection of cirrhosis, HCC, NAFLD and NASH is a clinical problem and determining a sensitive, specific and predictive novel method based on biomarker discovery is an important task. On the other hand, metabolomics has been reported as a new and powerful technology in biomarker discovery and dynamic field that cause global comprehension of system biology. In this review, it has been collected a heterogeneous set of metabolomics published studies to discovery of biomarkers in researches to introduce diagnostic biomarkers for early detection and the choice of patient-specific therapies. PMID:27458508

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

    NASA Astrophysics Data System (ADS)

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

    2007-07-01

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

  16. Expression of glyoxalase-I is reduced in cirrhotic livers: A possible mechanism in the development of cirrhosis

    PubMed Central

    Hollenbach, Marcus; Thonig, Antje; Pohl, Sabine; Ripoll, Cristina; Michel, Maurice; Zipprich, Alexander

    2017-01-01

    Background High concentrations of methylglyoxal (MGO) cause cytotoxiticy via formation of advanced glycation endproducts (AGEs) and inflammation. MGO is detoxificated enzymatically by glyoxalase-I (Glo-I). The aim of this study was to analyze the role of Glo-I during the development of cirrhosis. Methods In primary hepatocytes, hepatic stellate cells (pHSC) and sinusoidal endothelial cells (pLSEC) from rats with early (CCl4 8wk) and advanced cirrhosis (CCl4 12wk) expression and activity of Glo-I were determined and compared to control. LPS stimulation (24h; 100ng/ml) of HSC was conducted in absence or presence of the partial Glo-I inhibitor ethyl pyruvate (EP) and the specific Glo-I inhibitor BrBzGSHCp2. MGO, inflammatory and fibrotic markers were measured by ELISA and Western blot. Additional rats were treated with CCl4 ± EP 40mg/kg b.w. i.p. from wk 8–12 and analyzed with sirius red staining and Western blot. Results Expression of Glo-I was significantly reduced in cirrhosis in whole liver and primary liver cells accompanied by elevated levels of MGO. Activity of Glo-I was reduced in cirrhotic pHSC and pLSEC. LPS induced increases of TNF-α, Nrf2, collagen-I, α-SMA, NF-kB and pERK of HSC were blunted by EP and BrBzGSHCp2. Treatment with EP during development of cirrhosis significantly decreased the amount of fibrosis (12wk CCl4: 33.3±7.3%; EP wk 8–12: 20.7±6.2%; p<0.001) as well as levels of α-SMA, TGF-β and NF-κB in vivo. Conclusions Our results show the importance of Glo-I as major detoxifying enzyme for MGO in cirrhosis. The reduced expression of Glo-I in cirrhosis demonstrates a possible explanation for increased inflammatory injury and suggests a “vicious circle” in liver disease. Blunting of the Glo-I activity decrease the amount of fibrosis in established cirrhosis and constitutes a novel target for antifibrotic therapy. PMID:28231326

  17. Methotrexate is not associated with increased liver cirrhosis in a population-based cohort of rheumatoid arthritis patients with chronic hepatitis C

    PubMed Central

    Tang, Kuo-Tung; Chen, Yi-Hsing; Lin, Ching-Heng; Chen, Der-Yuan

    2016-01-01

    A few studies have shown that methotrexate (MTX) use exacerbates liver fibrosis and even leads to liver cirrhosis in rheumatoid arthritis (RA) patients, although the risk is low compared to psoriatics. We therefore conducted a population-based cohort study to investigate the impact of long-term MTX use on the risk of chronic hepatitis C (CHC)-related cirrhosis among RA patients. We analyzed data from the National Health Insurance Research Database in Taiwan and identified 450 incident cases of RA among CHC patients (255 MTX users and 195 MTX non-users) from January 1, 1998 to December 31, 2007. After a median follow-up of more than 5 years since the diagnosis of CHC, a total of 55 (12%) patients developed liver cirrhosis. We did not find an increased risk of liver cirrhosis among CHC patients with long-term MTX use for RA. Furthermore, there was no occurrence of liver cirrhosis among the 43 MTX users with a cumulative dose ≧3 grams after 108 months of treatment. In conclusion, our data showed that long-term MTX use is not associated with an increased risk for liver cirrhosis among RA patients with CHC. However, these results should be interpreted with caution due to potential bias in the cohort. PMID:27609026

  18. Methotrexate is not associated with increased liver cirrhosis in a population-based cohort of rheumatoid arthritis patients with chronic hepatitis B.

    PubMed

    Tang, Kuo-Tung; Hung, Wei-Ting; Chen, Yi-Hsing; Lin, Ching-Heng; Chen, Der-Yuan

    2016-03-01

    A few studies showed that long-term methotrexate (MTX) use exacerbates liver fibrosis and even leads to liver cirrhosis in rheumatoid arthritis (RA) patients. We therefore conducted a population-based cohort study to investigate the impact of long-term MTX use on the risk of chronic hepatitis B (CHB)-related cirrhosis among RA patients. We analyzed data from the National Health Insurance Research Database in Taiwan and identified 631 incident cases of RA among CHB patients (358 MTX users and 273 MTX non-users) from January 1, 1998 to December 31, 2007. After a median follow-up of more than 6 years since the diagnosis of CHB, a total of 41 (6.5%) patients developed liver cirrhosis. We did not find an increased risk of liver cirrhosis among CHB patients with long-term MTX use for RA. Furthermore, there was no occurrence of liver cirrhosis among 56 MTX users with a cumulative dose ≧3 grams after 97 months' treatment. In conclusion, our data showed that long-term MTX use is not associated with an increased risk for liver cirrhosis among RA patients with CHB. However, interpretation of the results should be cautious due to potential bias in the cohort.

  19. Covered TIPS for secondary prophylaxis of variceal bleeding in liver cirrhosis

    PubMed Central

    Qi, Xingshun; Tian, Yulong; Zhang, Wei; Zhao, Haitao; Han, Guohong; Guo, Xiaozhong

    2016-01-01

    Abstract Background: In the era of bare stents, transjugular intrahepatic portosystemic shunt (TIPS) is the second-line choice of therapy for the prevention of variceal rebleeding in liver cirrhosis. In the era of covered stents, the role of TIPS should be re-evaluated. Aim: The aim of the study was to compare the outcomes of covered TIPS versus the traditional first-line therapy (i.e, drug plus endoscopic therapy) for the prevention of variceal rebleeding in liver cirrhosis. Methods: All relevant randomized controlled trials were searched via the PubMed, EMBASE, and Cochrane Library databases. Hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) and P values were calculated for the cumulative risk and overall risk, respectively. Heterogeneity among studies was also calculated. Results: Three of 111 retrieved papers were eligible. Among them, the proportion of patients who were switched from drug plus endoscopic therapy to TIPS was 16% to 25%. The risk of bias was relatively low in all included randomized controlled trials. Meta-analyses demonstrated that the covered TIPS group had a similar overall survival (HR = 0.84, 95% CI = 0.55–1.28, P = 0.41; OR = 1.00, 95% CI = 0.59–1.69, P = 0.99), a significantly lower risk of variceal rebleeding (HR = 0.30, 95% CI = 0.18–0.48, P < 0.00001; OR = 0.24, 95% CI = 0.12–0.46, P < 0.0001), and a similar risk of hepatic encephalopathy (HR = 1.35, 95% CI = 0.72–2.53, P = 0.36; OR = 1.28, 95% CI = 0.54–3.04, P = 0.57). In most of meta-analyses, the heterogeneity among studies was not statistically significant. Conclusions: Compared with drug plus endoscopic therapy, covered TIPS had a significant benefit of preventing from variceal rebleeding, but did not increase the overall survival or risk of hepatic encephalopathy. PMID:27977618

  20. [Spontaneous bacterial peritonitis in liver cirrhosis: optimization issues of prevention and treatment].

    PubMed

    Vinnitskaia, E V; Drozdov, V N; Petyrakov, A V; Sil'vestrova, S Iu; Brezgin, A G

    2012-01-01

    Research of features of a current of a spontaneous bacterial peritonitis (SBP) allows to allocate close interrelation between SBP, system inflammatory reaction and a sepsis to consider SBP, as one of stages in evolution of the difficult infectious process caused, as a rule, by resident flora, developing at patients with decompensated liver cirrhosis (LC), which demands timely preventive maintenance and adequate antibacterial therapy. In the present work therapy and preventive maintenance SBP questions are considered. In article the extensive review of the data of the literature and own supervision by efficiency of treatment SBP also is presented. For the purpose of optimization of pharmacotherapy of the sick LC, the complicated ascites, had been conducted pharmacokinetics research ciprofloxacin (CPF) according to dynamics of its maintenance in blood serum (BS) and ascitic fluid (AF) depending on presence and ascites size. Materials and methods. Researches are spent 18 sick decompensated liver cirrhosis (a class B and C on Ch-P), without signs SBP after unitary reception of 500 mg CPF per os on an empty stomach. All patients have been divided on two groups: I gr. (n = 10) with the expressed, intense ascites (> 10 1) and II gr. (n = 8) with the moderate, small ascites. Definition CPF in BS also was already carried out by a method of a highly effective liquid chromatography. On the basis of the received data for each patient counted the semidelucing period (T1/2), the area under pharmacokinetic curve (curve concentration - time) - (AUC), volume of distribution of a preparation (Avd), factor AUC(AF)\\MIC (size of the relation of the area under pharmacokinetic curve to its minimum inhibitive concentration). Results of research have shown that concentration levels (C) (CPF in BS and AF for the given concrete patient are at one level, showing thus distinctions in dynamic behavior. Average value AUC(AF)\\MIC (MIC - minimum inhibitive concentration) at patients II gr. has

  1. Bacteraemic pneumonia caused by Neisseria lactamica with reduced susceptibility to penicillin and ciprofloxacin in an adult with liver cirrhosis.

    PubMed

    Wang, Cheng-Yi; Chuang, Yu-Min; Teng, Lee-Jene; Lee, Li-Na; Yang, Pan-Chyr; Kuo, Sow-Hsong; Hsueh, Po-Ren

    2006-08-01

    This report presents a case of bacteraemic pneumonia caused by Neisseria lactamica in an adult patient with liver cirrhosis who was successfully treated with ceftriaxone. The isolate was confirmed as N. lactamica by analysis of a partial sequence of the 16S rRNA gene; it had reduced susceptibilities to penicillin (MIC 0.75 microg ml(-1)) and ciprofloxacin (MIC > or =0.5 mg l(-1)).

  2. Hyponatremia in cirrhosis and end-stage liver disease: treatment with the vasopressin V₂-receptor antagonist tolvaptan.

    PubMed

    Gaglio, Paul; Marfo, Kwaku; Chiodo, Joseph

    2012-11-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed Central

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

    2013-01-01

    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

  7. The correlation between cytopenia and esophageal varices in patients with liver cirrhosis.

    PubMed

    Gue, C S; Yap, C K; Ng, H S

    2004-12-01

    This retrospective study analysed the case records of 200 patients in the Department of Gastroenterology, Singapore General Hospital from February 2000 to January 2001 who had liver cirrhosis and underwent gastroscopy for the detection of varices. The aim of this study was to determine any relationship between leucopenia, thrombocytopenia and the occurrence of esophageal varices in a cirrhotic population. Our results showed that the diagnostic yield of varices grade 2 and 3 was 6.3% if platelet count was > 150,000/mm3, 25% if platelet count was 100,000 to 150,000/mm3, 38.9% if platelet count was 50,000-99,000/mm3 and 100% if platelet count was <50,000/mm3. Similarly, the diagnostic yield of varices grade 2 and 3 was 19.4% if total white count was > 4,000/mm3, 66.7% if total white count was 3,000- 4,000/mm3 and 94.8% if total white count was < 3,000/mm5. We conclude that thrombocytopenia and leucopenia can be used to stratify risk for occurrence of esophageal varices in cirrhotic patients and gastroscopy will have a high yield for varices when platelet count is < 150,000/mm3 or total white is < 4,000/mm.

  8. Treatment with zincum metallicum CH5 in patients with liver cirrhosis. Preliminary study.

    PubMed

    Bădulici, S; Chirulescu, Z; Chirilă, P; Chirilă, M; Roşca, A

    1994-01-01

    The zinc, an important enzymatic cofactor, is involved in many metabolic processes. Its deficiency might be due either to malabsorption or to excessive utilization. In the medical literature of the latest 10 years, zinc was considered to play a part in the immune processes. The authors of the present paper intend to study the zinc and immunoglobulin levels in various diseases, i.e., chronic progressive hepatitis, liver cirrhosis (LC), dermatitis, bronchial asthma. This preliminary investigation was carried out in 30 patients with LC in whom serum zinc values were assayed by atomic absorption spectrophotometry and the immunoglobulin levels were determined using the Mancini type simple radial immunodiffusion technique. All these patients presented considerable decrease of serum zinc concentration, the values ranging between 3.06 and 7.65 mumol/l as compared with 19.8 +/- 1.5 mumol/l in the controls, alongside with the increase of immunoglobulins G and M. In the patients treated with Zincum metallicum CH5 it was observed after about 30 days of treatment that the clinical state was considerably improved and IgG and IgM as well as serum zinc had resumed their normal values. This treatment should not be interrupted since in LC, without permanent additional supply, the serum zinc returns rapidly to the initial deficit or even lower.

  9. Altered potassium homeostasis in cirrhosis of the liver and Crohn's disease

    SciTech Connect

    Schober, O.; Bossaller, C.

    1984-01-01

    In the course of patients (pts) with cirrhosis of the liver (Ci) and Crohn's disease (CD) frequently noticed arrhythmias of the heart, weakness and adynamic ileus suggest alterations in the potassium (K) homeostasis. It is the purpose of the study to assess the role of Na/sup +/-K/sup +/ pump mechanism in intracellular and extracellular K homeostasis. Relative total body potassium (TBK), serum potassium (K-S), and the number of red blood cell ouabain binding sites (n-ATPase) was studied in 21 pts with Ci, 31 pts with CD and in 31 controls (C), all were not on digitalis. TBK was measured by equilibrium binding of H-3-ouabain. A significant reduction in TBK was accompanied by normal serum potassium levels, whereas the number of Na-K pumps is increased. The results support the suggestion that changes in TBK may regulate the synthesis of Na-K pump molecules. Secondary hyperaldosteronism and diarrhea e.g. may be responsible for chronic potassium depletion. The need for a nutritional support is discussed.

  10. Outcomes for recipients of liver transplantation for alpha-1-antitrypsin deficiency–related cirrhosis.

    PubMed

    Carey, Elizabeth J; Iyer, Vivek N; Nelson, Darlene R; Nguyen, Justin H; Krowka, Michael J

    2013-12-01

    Alpha-1-antitrypsin (AAT) deficiency is a rare genetic disease caused by an abnormal production of the serine protease inhibitor AAT. Liver transplantation (LT) cures cirrhosis caused by AAT deficiency and restores the normal production of AAT. There are few reports on the post-LT outcomes of patients with AAT deficiency. The aim of this study was to determine the characteristics and outcomes of patients undergoing LT for AAT deficiency at 3 large transplant centers. All patients undergoing LT at these 3 transplant centers from 1987 to 2012 for AAT deficiency (ZZ or SZ phenotype) were included. The most recent 50 patients with the MZ phenotype were also included for comparison. Data were collected retrospectively from internal databases and medical records. Seventy-three patients (50 with the ZZ phenotype and 23 with the SZ phenotype)underwent LT. The mean age was 52.8 years, and the majority of the patients (75.6%) were men. Before LT, serum AAT levels were lower for the ZZ patients versus the SZ patients (28.3 versus 58.0 mg/dL, P < 0.001). More than 40% of the SZ patients had an additional liver disease, whereas 8% in the ZZ group and 90% in the MZ group did. Before LT, there was no significant difference in pulmonary function between the ZZ and SZ groups. Seventeen patients (all with ZZ phenotype)had pulmonary function tests performed before and after LT. The forced expiratory volume in 1 second (FEV1) continued to decline for the majority. The 1-, 3-, 5-, and 10-year post-LT survival rates were 86%, 83%, 80%, and 72%, respectively, for the ZZ patients and 91%, 86%, 79%, and 79%, respectively, for the SZ patients. In conclusion, survival after LT for patients with ZZ or SZ AAT deficiency is excellent. Despite the normalization of AAT levels after LT, FEV1 continues to decline unexpectedly after LT in some ZZ and SZ patients.

  11. Liver Lobe Based Multi-Echo Gradient Recalled Echo T2*-Weighted Imaging in Chronic Hepatitis B-Related Cirrhosis: Association with the Presence and Child-Pugh Class of Cirrhosis

    PubMed Central

    Wang, Dan; Chen, Tian-wu; Zhang, Xiao-ming; Li, Jie; Zeng, Nan-lin; Li, Li; Tang, Yu-lian; Huang, Yu-cheng; Li, Rui; Chen, Fan; Chen, Yan-li

    2016-01-01

    Purpose To investigate whether liver lobe based T2* values measured on gradient recalled echo T2*-weighted imaging are associated with the presence and Child-Pugh class of hepatitis B-related cirrhosis. Methods Fifty-six patients with hepatitis B-related cirrhosis and 23 healthy control individuals were enrolled in this study and underwent upper abdominal T2*-weighted magnetic resonance imaging. T2* values of the left lateral lobe (LLL), left medial lobe (LML), right lobe (RL) and caudate lobe (CL) were measured on T2*-weighted imaging. Statistical analyses were performed to determine the association between liver lobe based T2* values and the presence and Child-Pugh class of cirrhosis. Results The T2* values of the LLL, LML and RL decreased with the progression of cirrhosis from Child-Pugh class A to C (r = -0.231, -0.223, and -0.395, respectively; all P < 0.05), except that of the CL (r = -0.181, P > 0.05). To a certain extent, Mann-Whitney U tests with Bonferroni correction for multigroup comparisons showed that the T2* values of the LLL, LML and RL could distinguish cirrhotic liver from healthy liver (all P < 0.05), whereas the T2* values of the CL could not (P > 0.05). Receiver operating characteristic analysis demonstrated that the T2* value of the RL could best distinguish cirrhosis from healthy liver, with an area under the receiver operating characteristic curve (AUC) of 0.713 among T2* values of the liver lobes, and that only the T2* value of the RL could distinguish Child-Pugh class C from A-B, with an AUC of 0.697 (all P < 0.05). Conclusion The T2* value of the RL can be associated with the presence and Child-Pugh class of hepatitis B-related cirrhosis. PMID:27171422

  12. Risk factors for hepatocellular carcinoma in cirrhosis due to nonalcoholic fatty liver disease: A multicenter, case-control study

    PubMed Central

    Corey, Kathleen E; Gawrieh, Samer; deLemos, Andrew S; Zheng, Hui; Scanga, Andrew E; Haglund, Jennifer W; Sanchez, Jorge; Danford, Christopher J; Comerford, Megan; Bossi, Krista; Munir, Samina; Chalasani, Naga; Wattacheril, Julia

    2017-01-01

    AIM To identify risk factors associated with hepatocellular carcinoma (HCC), describe tumor characteristics and treatments pursed for a cohort of individuals with nonalcoholic steatohepatitis (NASH) cirrhosis. METHODS We conducted a retrospective case-control study of a well-characterized cohort of patients among five liver transplant centers with NASH cirrhosis with (cases) and without HCC (controls). RESULTS Ninety-four cases and 150 controls were included. Cases were significantly more likely to be male than controls (67% vs 45%, P < 0.001) and of older age (61.9 years vs 58 years, P = 0.002). In addition, cases were more likely to have had complications of end stage liver disease (83% vs 71%, P = 0.032). On multivariate analysis, the strongest association with the presence of HCC were male gender (OR 4.3, 95%CI: 1.83-10.3, P = 0.001) and age (OR = 1.082, 95%CI: 1.03-1.13, P = 0.001). Hispanic ethnicity was associated with a decreased prevalence of HCC (OR = 0.3, 95%CI: 0.09-0.994, P = 0.048). HCC was predominantly in the form of a single lesion with regional lymph node(s) and distant metastasis in only 2.6% and 6.3%, respectively. Fifty-nine point three percent of individuals with HCC underwent locoregional therapy and 61.5% underwent liver transplantation for HCC. CONCLUSION Male gender, increased age and non-Hispanic ethnicity are associated with HCC in NASH cirrhosis. NASH cirrhosis associated HCC in this cohort was characterized by early stage disease at diagnosis and treatment with locoregional therapy and transplant. PMID:28321274

  13. Effects of ethanol and acetaldehyde load on erythrocyte deformability in healthy subjects and patients with liver cirrhosis.

    PubMed

    Shiraishi, Koichi; Tsuruya, Kota; Anzai, Kazuya; Arase, Yoshitaka; Hirose, Shunji; Kagawa, Tatehiro; Mine, Tetsuya; Matsuzaki, Shohei

    2015-02-01

    Alcohol intake leads to the distribution of alcohol and its metabolite, acetaldehyde throughout the blood and organs. Hepatic cirrhosis is associated with abnormal red blood cell morphology and function, particularly impaired red blood cell deformability. To investigate the effect of drinking on red blood cells in patients with hepatic cirrhosis, erythrocyte deformability was evaluated in response to alcohol and acetaldehyde tolerance. Erythrocyte deformability in 10 healthy and 15 cirrhotic subjects was examined by filterability of the red blood cells. Erythrocyte deformability decreased markedly in the cirrhosis group compared with the healthy group (p < 0.05). No significant change in erythrocyte deformability was observed in healthy or cirrhotic subjects due to ethanol 100 mM tolerance. Acetaldehyde tolerance elicited a significant decrease in erythrocyte deformability at 2 mM in the cirrhosis group (p < 0.05). Alcohol consumption in cirrhotic patients was suggested to worsen erythrocyte deformability and red blood cell function. Decreased erythrocyte deformability worsens microcirculation in the liver, resulting in more severe hepatic dysfunction.

  14. Identification and clinical significance of an elevated level of serum aminoacylase-1 autoantibody in patients with hepatitis B virus-related liver cirrhosis.

    PubMed

    He, Xiaomin; Hong, Yu; Wang, Xiaomei; Zhang, Xiaohong; Long, Jiang; Li, Hai; Zhang, Bei; Chen, Suhong; Liu, Qiqi; Li, Hongyi; Wang, Xiaoming; Ou, Xiaojuan; Huang, Jian

    2016-11-01

    Chronic hepatitis B (CHB) is prevalent worldwide and can develop into liver cirrhosis and liver carcinoma. Early discrimination of liver cirrhosis from chronic hepatitis is critical for effective treatment and optimal prognosis. The aim of the present study was to assess the diagnostic value of a panel of cellular proteins that can be recognized by autoantibodies in patient serum for hepatitis B virus (HBV)‑related liver cirrhosis. Twenty‑two candidate autoantigens screened using a serum proteomics assay in our previous study were assessed retrospectively in 443 participants, comprising 89 patients with HBV‑related liver cirrhosis, 89 patients with CHB, and 265 healthy controls. The levels of autoantibodies against the candidate autoantigens were measured by protein microarrays containing the candidate antigen proteins. Receiver operating characteristic (ROC) curves were used to calculate the diagnostic accuracy. The present study determined that seven of the 22 candidate autoantibodies differed significantly in serum level between HBV‑related liver cirrhosis and CHB (P<0.0001), with area under curve (AUC) values >0.7. The seven autoantibodies recognized aminoacylase‑1 (ACY1), histidine triad nucleotide‑binding protein 1, insulin‑like growth factor 2 mRNA‑binding protein 2, heat shock 70 kDa protein 6, peroxiredoxin 3, apoptosis‑inducing factor and regucalcin. Among these, the ACY1 autoantibody had the highest value for discriminating HBV‑related liver cirrhosis from CHB, with an AUC value of 0.872 (95% confidence interval: 0.810‑0.934, P<0.0001), sensitivity of 77.3% and specificity of 85.0%. In conclusion, with the elevated level in the disease progression of CHB, ACY1 autoantibody may be a valuable serum biomarker for discriminating HBV‑related liver cirrhosis from CHB.

  15. Effects of oral branched-chain amino acids on hepatic encephalopathy and outcome in patients with liver cirrhosis.

    PubMed

    Kawaguchi, Takumi; Taniguchi, Eitaro; Sata, Michio

    2013-10-01

    Branched-chain amino acids (BCAAs) constituting of valine, leucine, and isoleucine act as both substrates of proteins and as key regulators for various nutrient metabolisms. Patients with liver cirrhosis frequently lack sufficient BCAAs and therefore suffer from various metabolic disorders. Hepatic encephalopathy (HE) is a severe metabolic disorder with neurologic manifestations such as flapping tremors and coma in patients with liver cirrhosis. In addition, a mild form of HE known as minimal HE (MHE) is an important social issue because it occurs in up to 80% of patients with chronic liver disease and affects prognosis and activities of daily living, possibly resulting in falls and motor vehicle accidents. Although HE/MHE can be caused by various pathological conditions, including in an accumulation of mercaptans, short-chain fatty acids, and alterations in the gut flora, hyperammonemia has also been implicated in an important pathogenesis of HE/MHE. Besides urea cycle of liver, ammonia can be detoxified in the skeletal muscles by the amidation process for glutamine synthesis using BCAAs. Thus, BCAA supplementation may enhance detoxification of ammonia in skeletal muscle and may be a possible therapeutic strategy for HE/MHE. In this review, we summarize the clinical impacts of BCAA supplementation on HE/MHE and discuss possible mechanisms for a BCAA-induced improvement of HE/MHE. Furthermore, we present some modifications of oral BCAA therapy for improvement of efficacy in HE treatment. We also briefly describe pleiotropic benefits of BCAAs on life-threatening events and overall prognosis in patients with liver cirrhosis.

  16. De novo autoimmune hepatitis following liver transplantation for primary biliary cirrhosis: an unusual cause of late grafts dysfunction.

    PubMed

    Ennaifer, Rym; Ayadi, Hend; Romdhane, Haifa; Cheikh, Meriem; Mestiri, Hafedh; Khalfallah, Taher; Hadj, Najet Bel

    2015-01-01

    De novo autoimmune hepatitis (AIH) is a rare disorder first described in 1998. It occurs in patients who underwent liver transplantation for a different etiology. We present the case of a 56-year-old woman who was diagnosed with primary biliary cirrhosis and had liver transplantation for refractory pruritis. Seven years after transplantation, she presented alterations in the hepatic profile with hypertransaminasemia, elevated alkaline phosphatase and gamma-glutamyl-transferase. Her liver functions test also showed elevated IgG levels. Serum autoantibodies were negative except for antimitochondrial antibodies. Histological findings indicated features of AIH without bile duct damage or loss. She had a pretreatment AIH score of 13 points and a post treatment score of 15 points according to the International AIH Group. The patient was treated effectively with prednisolone and her liver function and globulin levels rapidly returned to normal.

  17. Diagnostic significance of nitrates and nitrites and L-arginine, in development of hepatorenal syndrome in patients with end stage alcoholic liver cirrhosis.

    PubMed

    Nickovic, Vanja; Kocic, Gordana; Bjelakovic, Goran; Pavlovic, Radmila; Stojanovic, Ivana; Katanic, Radoslav; Stojanovic, Svetlana; Djindjic, Boris

    2013-01-01

    Hepatorenal syndrome (HRS) represents a complication of the end-stage liver cirrhosis. The aim of the present study was to analyze concentrations of nitrates and nitrites (NO2 + NO3) and L-arginine in patients with liver cirrhosis and HRS as a possible predictive marker for the development of HRS. The research was performed in a group of 28 patients with cirrhosis and HRS, a group of 22 patients suffering from cirrhosis without HRS and a control group comprised of 42 healthy voluntary blood donors. In patients with end-stage alcoholic liver cirrhosis, with HRS, the concentrations of NO2 + NO3 increased and correlated with the degree of cirrhosis progression, compared to patients without HRS and significantly higher compared to the control group. The level of NO2 + NO3 was in a positive correlation with the degree of liver damage de Ritis coefficient (HRS = 0.72; cirrhosis: = 0.55; control = -0.10). Significant positive correlation was found between NO2 + NO3 concentration and inflammatory marker C-reactive protein (HRSC = 0.75; cirrhosis = 0.70, control = -0.25). The correlation between NO2 + NO3 concentration and creatinine concentration in patients with HRS was significantly higher compared to patients without HRS (HRS = 0.82; cirrhosis = 0.32; control = -0.25). By using binary regression analysis, on the basis of clinical criteria of HRS diagnosis, the strongest independent positive predictor for HRS development was NO2 + NO3, associated with 45.02 times higher incidence of HRS, compared to arginine (12.7 times higher incidence), creatinine (13.1 times higher incidence), and AST/ALT ratio (10.55 higher incidence of HRS). Since the determination of NO2 + NO3 represents a reliable and easily applicable method, it may be used as an early predictive marker for HRS development.

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

    PubMed

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

    2015-01-15

    1,25(OH)2D3, the active form of vitamin D, has an antiproliferative and antifibrotic effect on hepatic stellate cells. Our aim was to investigate the potential of 1,25(OH)2D3 to inhibit the development of liver fibrosis and to ameliorate established fibrosis in vivo. The antifibrotic effect of 1,25(OH)2D3 was investigated in a thioacetamide (TAA) model (as a preventive treatment and as a remedial treatment) and in a bile duct ligation model. In the preventive model, rats received simultaneously intraperitoneum injection of TAA and/or 1,25(OH)2D3 for 10 wk. In the remedial model, rats were treated with TAA for 10 wk and then received 1,25(OH)2D3 or saline for 8 wk. Fibrotic score was determined by Masson staining. Collagen I, α-smooth muscle actin (α-SMA), tissue inhibitor of metalloproteinase-1 (TIMP1), platelet-derived growth factor (PDGF), and transforming growth factor-β (TGF-β) expression were measured by Western blot analysis and real-time PCR. Hypercalemia was detected by chemistry measurements. Preventive treatment of 1,25(OH)2D3 significantly suppressed liver fibrosis both macroscopically and microscopically and significantly lowered the fibrotic score of the TAA + 1,25(OH)2D3 group compared with the TAA group. 1,25(OH)2D3 significantly inhibited expression of PDGF and TGF-β by ∼50% and suppressed the expression of collagen Iα1, TIMP1, and α-SMA by approximately three-, two-, and threefold, respectively. In contrast, 1,25(OH)2D3 was inefficient in amelioration of established liver fibrosis. Administration of 1,25(OH)2D3 to bile duct ligation rats led to a high mortality rate probably caused by hypercalcemia. We conclude that 1,25(OH)2D3 may be considered as a potential preventive treatment in an in vivo model but failed to ameliorate established cirrhosis.

  19. Alcoholic liver disease

    MedlinePlus

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

  20. The effect of short term treatment with probiotic VSL#3 on various clinical and biochemical parameters in patients with liver cirrhosis.

    PubMed

    Marlicz, W; Wunsch, E; Mydlowska, M; Milkiewicz, M; Serwin, K; Mularczyk, M; Milkiewicz, P; Raszeja-Wyszomirska, J

    2016-12-01

    The evidence is mounting that alterations of innate immunity and gut microbiota contribute to chronic liver disease and its complications. Modulation of intestinal microbiota is an emerging therapeutic strategy in hepatology. Probiotics through modulation of intestinal milieu have the potential to affect the course of liver disease. The data concerning the influence of probiotics on various plasma molecules and compounds involved in the pathogenesis of hyperdynamic circulatory state in liver cirrhosis is still not confluent and require further evaluation. In our study twenty patients with compensated and decompensated liver cirrhosis and ten healthy controls received probiotic VSL#3 daily for 28 days. Plasma levels of interleukin 6 (IL-6), vascular endothelial growth factor (VEGF), plasminogen activator inhibitor (PAI), macrophage inflammatory protein 3/α (MIP-3 α/CCL20), monocyte chemotactic protein-1α (MCP-1/CCL2), human myeloperoxidase (MPO), nitric oxide (NO), prostaglandins, thromboxane (TXB2) and big-endothelin were measured at baseline, day 14 and 28 of probiotic administration. The incidence of hepatic encephalopathy was assessed with critical flicker frequency. Changes in clinical, biochemical and microbiological parameters were evaluated. The stage of liver cirrhosis correlated with an increase in plasma levels of pro-inflammatory cytokines (IL-6) and chemotactic chemokines involved in immune cell trafficking (MIP-3α/CCL20). Probiotic administration in patients with liver cirrhosis led to modulation of plasma levels of several molecules and compounds measured (MIP-3α/CCL20, NO, big-endothelin, TXB2 and MPO). The grade of encephalopathy during the course of probiotic supplementation remained unaffected in both groups of patients. VSL#3 treatment was well tolerated and safe in patients with liver disease. In patients with compensated and decompensated liver cirrhosis, VSL#3 manipulates selected plasma molecules and compounds involved in hyperdynamic

  1. Smoking as a risk factor for autoimmune liver disease: what we can learn from primary biliary cirrhosis.

    PubMed

    Smyk, Daniel S; Rigopoulou, Eirini I; Muratori, Luigi; Burroughs, Andrew K; Bogdanos, Dimitrios P

    2012-01-01

    Primary biliary cirrhosis (PBC) is a cholestatic liver disease characterised by the immune-mediated destruction of biliary epithelial cells in small intrahepatic bile ducts. The disease is characterised by circulating anti-mitochondrial antibodies (AMA) as well as disease specific anti-nuclear antibodies (ANA), cholestatic liver biochemistry, and characteristic histology. The disease primarily affects middle-aged females, and its incidence is apparently increasing worldwide. Epidemiological studies have indicated several risk factors for the development of PBC, with family history of PBC, recurrent urinary tract infection, and smoking being the most widely cited. Smoking has been implicated as a risk factor in several autoimmune diseases, including the liver, by complex mechanisms involving the endocrine and immunological systems to name a few. Studies of smoking in liver disease have also shown that smoking may progress the disease towards fibrosis and subsequent cirrhosis. This review will examine the literature surrounding smoking as a risk factor for PBC, as well as a potential factor in the progression of fibrosis in PBC patients.

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

    PubMed Central

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

    2013-01-01

    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 μg/mL). This study showed hepatoprotective effect of ERZO. PMID:24396831

  3. Pharmacokinetics of omeprazole after intravenous and oral administration to rats with liver cirrhosis induced by dimethylnitrosamine.

    PubMed

    Lee, Dae Y; Lee, Inchul; Lee, Myung G

    2007-02-07

    The aim of this study is to report the pharmacokinetics of omeprazole after intravenous (20 mg/kg) and oral (40 mg/kg) administration to rats with liver cirrhosis induced by dimethylnitrosamine (cirrhotic rats) with respect to CYP isozyme changes. The expressions of CYP1A2 and 3A1 decreased in cirrhotic rats and omeprazole is reported to be mainly metabolized via CYP1A1/2, 2D1, and 3A1/2 in male Sprague-Dawley rats. Hence, the pharmacokinetics of omeprazole could be changed in cirrhotic rats. After intravenous administration to cirrhotic rats, the AUC (1180 microg min/ml versus 474 microg min/ml) and CL(NR) (17.4 ml/min/kg versus 42.3 ml/min/kg) of omeprazole were significantly greater and slower, respectively, than the controls. This could be due to decrease in the expressions of CYP1A2 and 3A1 in cirrhotic rats. The significantly slower CL(NR) could be supported by significantly slower in vitro CL(int) for the disappearance of omeprazole from hepatic microsomal study (0.102 ml/min/mg protein versus 0.144 ml/min/mg protein) and slower hepatic blood flow rate in cirrhotic rats. After oral administration to cirrhotic rats, the AUC difference was considerably greater (451% versus 149%) than that after intravenous administration, possibly due to decrease in intestinal first-pass effect of omeprazole in addition to decrease in hepatic metabolism of omeprazole in cirrhotic rats.

  4. Clinical characteristics of drug-induced liver injury and primary biliary cirrhosis

    PubMed Central

    Yang, Jun; Yu, Ya-Li; Jin, Yu; Zhang, Ying; Zheng, Chang-Qing

    2016-01-01

    AIM To summarize and compare the clinical characteristics of drug-induced liver injury (DILI) and primary biliary cirrhosis (PBC). METHODS A total of 124 patients with DILI and 116 patients with PBC treated at Shengjing Hospital Affiliated to China Medical University from 2005 to 2013 were included. Demographic data (sex and age), biochemical indexes (total protein, albumin, alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin, indirect bilirubin, alkaline phosphatase, and gamma glutamyltransferase), immunological indexes [immunoglobulin (Ig) A, IgG, IgM, antinuclear antibody, anti-smooth muscle antibody, anti-mitochondrial antibody, and anti-mitochondrial antibodies] and pathological findings were compared in PBC patients, untyped DILI patients and patients with different types of DILI (hepatocellular type, cholestatic type and mixed type). RESULTS There were significant differences in age and gender distribution between DILI patients and PBC patients. Biochemical indexes (except ALB), immunological indexes, positive rates of autoantibodies (except SMA), and number of cases of patients with different ANA titers (except the group at a titer of 1:10000) significantly differed between DILI patients and PBC patients. Biochemical indexes, immunological indexes, and positive rate of autoantibodies were not quite similar in different types of DILI. PBC was histologically characterized mainly by edematous degeneration of hepatocytes (n = 30), inflammatory cell infiltration around bile ducts (n = 29), and atypical hyperplasia of small bile ducts (n = 28). DILI manifested mainly as fatty degeneration of hepatocytes (n = 15) and spotty necrosis or loss of hepatocytes (n = 14). CONCLUSION Although DILI and PBC share some similar laboratory tests (biochemical and immunological indexes) and pathological findings, they also show some distinct characteristics, which are helpful to the differential diagnosis of the two diseases. PMID:27672278

  5. Differences in cognitive function between patients with viral and alcoholic compensated liver cirrhosis.

    PubMed

    Lee, Yunhyeong; Kim, Chulho; Suk, Ki Tae; Choi, Hui Chul; Bang, Chang Seok; Yoon, Jai Hoon; Baik, Gwang Ho; Kim, Dong Joon; Jang, Min Uk; Sohn, Jong Hee

    2016-04-01

    As alcohol induces change in frontal cortex primarily involved in cognition, cognitive function may be different between viral and alcoholic liver cirrhosis (LC). This study aimed to determine the differences of cognitive function between viral and alcoholic compensated LC. From October 2011 to March 2013, 80 patients (viral: 37; alcohol: 43) with compensated LC were prospectively enrolled. Neuropsychological functions including attention, language, visuospatial, verbal memory, visual memory, and frontal/executive function were evaluated between two groups and compared with age-matched normal group (n = 1000). Cumulative incidence rate of overt hepatic encephalopathy (HE) was calculated. In the comparison with normal group, both two groups showed decreased memory function, frontal/executive function, and Korea-Mini Mental Status Examination. In the analysis of two groups, memory function by Verbal Learning Test (recognition: 20.1 ± 3.6 and 17.8 ± 4.8, p = 0.022), visuospatial function by Ray-Complex Figure Copy Test (recognition: 19.0 ± 2.6 and 17.3 ± 4.0, p = 0.043), frontal/executive function by Controlled Oral Ward Association (semantic: 17.1 ± 6.9 and 12.7 ± 6.9, p = 0.004), and the Korea-Mini Mental Status Examination (27.5 ± 1.9 and 26.2 ± 3.1, p = 0.03) showed low scores in alcoholic compensated LC patients. The 1-, 2-, and 3-year cumulative incidence rates of overt HE were 23%, 26%, and 26% and 33%, 43%, and 49% in the viral and alcoholic compensated LC group, respectively (p = 0.033). Impaired memory and frontal lobe executive functions and early development of overt HE were more common in patients with alcoholic LC. For patients with alcoholic LC, more integrated tests for early detection of minimal HE and intensive treatment should be considered to prevent overt HE.

  6. The progressive elevation of alpha fetoprotein for the diagnosis of hepatocellular carcinoma in patients with liver cirrhosis

    PubMed Central

    Arrieta, Oscar; Cacho, Bernardo; Morales-Espinosa, Daniela; Ruelas-Villavicencio, Ana; Flores-Estrada, Diana; Hernández-Pedro, Norma

    2007-01-01

    Background Hepatocellular carcinoma is the most common cause of primary liver neoplasms and is one of the main causes of death in patients with liver cirrhosis. High Alpha fetoprotein serum levels have been found in 60–70% of patients with Hepatocellular carcinoma; nevertheless, there are other causes that increase this protein. Alpha fetoprotein levels ≥200 and 400 ng/mL in patients with an identifiable liver mass by imaging techniques are diagnostic of hepatocellular carcinoma with high specificity. Methods We analysed the sensitivi