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Sample records for ccl4-induced liver cirrhosis

  1. Role of estrogen receptor β selective agonist in ameliorating portal hypertension in rats with CCl4-induced liver cirrhosis

    PubMed Central

    Zhang, Cheng-Gang; Zhang, Bin; Deng, Wen-Sheng; Duan, Ming; Chen, Wei; Wu, Zhi-Yong

    2016-01-01

    AIM: To investigate the role of diarylpropionitrile (DPN), a selective agonist of estrogen receptor β (ERβ), in liver cirrhosis with portal hypertension (PHT) and isolated hepatic stellate cells (HSCs). METHODS: Female Sprague-Dawley rats were ovariectomized (OVX), and liver cirrhosis with PHT was induced by CCl4 injection. DPN and PHTPP, the selective ERβ agonist and antagonist, were used as drug interventions. Liver fibrosis was assessed by hematoxylin and eosin (HE) and Masson’s trichrome staining and by analyzing smooth muscle actin expression. Hemodynamic parameters were determined in vivo using colored microspheres technique. Protein expression and phosphorylation were determined by immunohistochemical staining and Western blot analysis. Messenger RNA levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). Collagen gel contraction assay was performed using gel lattices containing HSCs treated with DPN, PHTPP, or Y-27632 prior to ET-1 addition. RESULTS: Treatment with DPN in vivo greatly lowered portal pressure and improved hemodynamic parameters without affecting mean arterial pressure, which was associated with the attenuation of liver fibrosis and intrahepatic vascular resistance (IHVR). In CCl4-treated rat livers, DPN significantly decreased the expression of RhoA and ROCK II, and even suppressed ROCK II activity. Moreover, DPN remarkedly increased the levels of endothelial nitric oxide synthase (eNOS) and phosphorylated eNOS, and promoted the activities of protein kinase G (PKG), which is an NO effector in the liver. Furthermore, DPN reduced the contractility of activated HSCs in the 3-dimensional stress-relaxed collagen lattices, and decreased the ROCK II activity in activated HSCs. Finally, in vivo/in vitro experiments demonstrated that MLC activity was inhibited by DPN. CONCLUSION: For OVX rats with liver cirrhosis, DPN suppressed liver RhoA/ROCK signal, facilitated NO/PKG pathways, and decreased IHVR, giving rise to reduced portal pressure. Therefore, DPN represents a relevant treatment choice against PHT in cirrhotic patients, especially postmenopausal women. PMID:27182159

  2. Protective effect of wedelolactone against CCl4-induced acute liver injury in mice.

    PubMed

    Lu, Yang; Hu, DongMei; Ma, ShanBo; Zhao, Xian; Wang, Shan; Wei, Guo; Wang, XiFang; Wen, AiDong; Wang, JingWen

    2016-05-01

    Eclipta, a traditional Chinese medicine, has been used to treat liver disease for centuries. However, the chemical basis and biological mechanisms of Eclipta remain elusive. The current study aims to investigate the hepatoprotective effect of wedelolactone (WEL), a major coumarin in Eclipta, using C57BL/6 mice with carbon tetrachloride CCl4-induced acute liver injury (ALI). Our data showed that WEL markedly decreased the CCl4-induced elevation of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, and improved hepatic histopathology changes. WEL also significantly decreased the content of MDA in liver tissues, meanwhile increased the activities of antioxidant enzymes SOD and GSH-Px. In addition, WEL reduced the protein expression of TNF-α, IL-1β and IL-6, as well as mRNA expression. Western blot results revealed that WEL repressed phosphorylation of extracellular signal-regulated kinase (ERK) and translocation of NF-κB p65 from cytoplasm to nucleus and enhanced the phosphorylation of c-Jun. N-terminal kinase (JNK). Moreover, results showed that WEL significantly inhibited CCl4-induced hepatocytes apoptosis, markedly suppressed the down-regulation of Bax and active Caspase-3 expression and accelerated the expression of Bcl-2. Overall, the findings indicate that WEL exhibits a protective effect against CCl4-induced ALI in mice by enhancing the antioxidative defense system, suppressing the inflammatory response and cell apoptosis of liver. PMID:26921731

  3. Parboiled Germinated Brown Rice Protects Against CCl4-Induced Oxidative Stress and Liver Injury in Rats.

    PubMed

    Wunjuntuk, Kansuda; Kettawan, Aikkarach; Charoenkiatkul, Somsri; Rungruang, Thanaporn

    2016-01-01

    Parboiled germinated brown rice (PGBR) of Khao Dawk Mali 105 variety was produced by steaming germinated paddy rice, which is well-known for its nutrients and bioactive compounds. In this study we determined the in vivo antioxidant and hepatoprotective effects of PGBR in carbon tetrachloride (CCl4)-induced oxidative stress in rats. Male Sprague-Dawley rats, (weight 200-250?g) were randomly divided into (1) control, (2) CCl4, (3) white rice (WR)+CCl4, (4) brown rice (BR)+CCl4, and (5) PGBR+CCl4 groups. PGBR, BR, and WR diets were produced by replacing corn starch in the AIN76A diet with cooked PGBR, BR, and WR powders, respectively. All rats except the control group were gavaged with 50% CCl4 in olive oil (v/v, 1?mL/kg) twice a week for 8 weeks. CCl4-treated rats exhibited significant liver injury, lipid peroxidation, protein oxidation, and DNA damage, as well as obvious changes to liver histopathology compared to control. In addition, CCl4 treatment decreased the activities of CYP2E1 and antioxidant enzymes: glutathione S-transferase, glutathione peroxidase, superoxide dismutase and catalase, and glutathione (GSH) content. However, the PGBR+CCl4 group exhibited less liver injury, lipid peroxidation, protein oxidation, and DNA damage, as well as better antioxidant enzyme activities and GSH content. Furthermore, PGBR inhibited degradation of CYP2E1 in CCl4-induced decrease of CYP2E1 activity. These data suggest that PGBR may prevent CCl4-induced liver oxidative stress and injury through enhancement of the antioxidant capacities, which may be due to complex actions of various bioactive compounds, including phenolic acids, ?-oryzanol, tocotrienol, and GABA. PMID:26075965

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

    PubMed

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

    2014-06-01

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

  5. 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

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

    PubMed

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

    PubMed Central

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

    2014-01-01

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

  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. PMID:15514851

  9. Resolvin D1 attenuates CCl4-induced acute liver injury involving up-regulation of HO-1 in mice.

    PubMed

    Chen, Xiahong; Gong, Xia; Jiang, Rong; Wang, Bin; Kuang, Ge; Li, Ke; Wan, Jingyuan

    2016-04-01

    Acute hepatic failure involves in excessive oxidative stress and inflammatory responses, leading to a high mortality due to lacking effective therapy. Resolvin D1 (RvD1), an endogenous lipid mediator derived from polyunsaturated fatty acids, has been shown anti-inflammatory and anti-oxidative actions, however, whether RvD1 has protective effects on hepatic failure remains elusive. In this study, the roles and molecular mechanisms of RvD1 were explored in carbon tetrachloride (CCl4)-induced acute liver injury. Our results showed that RvD1 protected mice against CCl4-induced hepatic damage, as evaluated by reduced aminotransferase activities and malondialdehyde content, elevated glutathione and superoxide dismutase activities, and alleviated hepatic pathological damage. Moreover, RvD1 significantly attenuated serum tumor necrosis factor-α and interleukin-6 levels as well as hepatic myeloperoxidase activity, whereas enhanced serum IL-10 level in CCl4-administered mice. Further, RvD1 markedly up-regulated the expression and activity of heme oxygenase-1 (HO-1). However, inhibition of HO-1 activity reversed the protective effects of RvD1 on CCl4-induced liver injury. These results suggest that RvD1 could effectively prevent CCl4-induced liver injury by inhibition of oxidative stress and inflammation, and the underlying mechanism may be related to up-regulation of HO-1. PMID:26630551

  10. Adiponectin agonist ADP355 attenuates CCl4-induced liver fibrosis in mice.

    PubMed

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

    2014-01-01

    Liver fibrosis is a growing global health problem characterized by excess deposition of fibrillar collagen, and activation of hepatic stellate cells (HSCs). Adiponectin is known to possess anti-fibrotic properties; however a high physiological concentration and multiple forms circulating in blood prohibit clinical use. Recently, an adiponectin-like small synthetic peptide agonist (ADP355: H-DAsn-Ile-Pro-Nva-Leu-Tyr-DSer-Phe-Ala-DSer-NH2) was synthesized for the treatment of murine breast cancer. The present study was designed to evaluate the efficacy of ADP355 as an anti-fibrotic agent in the in vivo carbon tetrachloride (CCl4)-induced liver fibrosis model. Liver fibrosis was induced in eight-week old male C57BL/6J mice by CCl4-gavage every other day for four weeks before injection of a nanoparticle-conjugated with ADP355 (nano-ADP355). Control gold nanoparticles and nano-ADP355 were administered by intraperitoneal injection for two weeks along with CCl4-gavage. All mice were sacrificed after 6 weeks, and serum and liver tissue were collected for biochemical, histopathologic and molecular analyses. Biochemical studies suggested ADP355 treatment attenuates liver fibrosis, determined by reduction of serum aspartate aminotransferase (AST), alanine aminotransferase ALT) and hydroxyproline. Histopathology revealed chronic CCl4-treatment results in significant fibrosis, while ADP355 treatment induced significantly reversed fibrosis. Key markers for fibrogenesis-α-smooth muscle actin (α-SMA), transforming growth factor-beta1 (TGF-β1), connective tissue growth factor (CTGF), and the tissue inhibitor of metalloproteinase I (TIMP1) were also markedly attenuated. Conversely, liver lysates from ADP355 treated mice increased phosphorylation of both endothelial nitric oxide synthase (eNOS) and AMPK while AKT phosphorylation was diminished. These findings suggest ADP355 is a potent anti-fibrotic agent that can be an effective intervention against liver fibrosis. PMID:25310107

  11. Adiponectin Agonist ADP355 Attenuates CCl4-Induced Liver Fibrosis in Mice

    PubMed Central

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

    2014-01-01

    Liver fibrosis is a growing global health problem characterized by excess deposition of fibrillar collagen, and activation of hepatic stellate cells (HSCs). Adiponectin is known to possess anti-fibrotic properties; however a high physiological concentration and multiple forms circulating in blood prohibit clinical use. Recently, an adiponectin-like small synthetic peptide agonist (ADP355: H-DAsn-Ile-Pro-Nva-Leu-Tyr-DSer-Phe-Ala-DSer-NH2) was synthesized for the treatment of murine breast cancer. The present study was designed to evaluate the efficacy of ADP355 as an anti-fibrotic agent in the in vivo carbon tetrachloride (CCl4)-induced liver fibrosis model. Liver fibrosis was induced in eight-week old male C57BL/6J mice by CCl4-gavage every other day for four weeks before injection of a nanoparticle-conjugated with ADP355 (nano-ADP355). Control gold nanoparticles and nano-ADP355 were administered by intraperitoneal injection for two weeks along with CCl4-gavage. All mice were sacrificed after 6 weeks, and serum and liver tissue were collected for biochemical, histopathologic and molecular analyses. Biochemical studies suggested ADP355 treatment attenuates liver fibrosis, determined by reduction of serum aspartate aminotransferase (AST), alanine aminotransferase ALT) and hydroxyproline. Histopathology revealed chronic CCl4-treatment results in significant fibrosis, while ADP355 treatment induced significantly reversed fibrosis. Key markers for fibrogenesis–α-smooth muscle actin (α-SMA), transforming growth factor-beta1 (TGF-β1), connective tissue growth factor (CTGF), and the tissue inhibitor of metalloproteinase I (TIMP1) were also markedly attenuated. Conversely, liver lysates from ADP355 treated mice increased phosphorylation of both endothelial nitric oxide synthase (eNOS) and AMPK while AKT phosphorylation was diminished. These findings suggest ADP355 is a potent anti-fibrotic agent that can be an effective intervention against liver fibrosis. PMID:25310107

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

    PubMed Central

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

    2014-01-01

    This study investigated the anti-inflammatory effects of DEC on the CCl4-induced hepatotoxicity in C57BL/6 mice. Chronic inflammation was induced by i.p. administration of CCl4 0.5 μL/g of body weight through two injections a week for 6 weeks. DEC (50 mg/kg) was administered by gavage for 12 days before finishing the CCl4 induction. Histological analyses of the DEC-treated group exhibited reduced inflammatory process and prevented liver necrosis and fibrosis. Immunohistochemical and immunofluorescence analyses of the DEC-treated group showed reduced COX-2, IL1β, MDA, TGF-β, and αSMA immunopositivity, besides exhibiting decreased IL1β, COX-2, NFκB, IFNγ, and TGFβ expressions in the western blot analysis. The DEC group enhanced significantly the IL-10 expression. The reduction of hepatic injury in the DEC-treated group was confirmed by the COX-2 and iNOS mRNA expression levels. Based on the results of the present study, DEC can be used as a potential anti-inflammatory drug for chronic hepatic inflammation. PMID:25374445

  13. Oligonol Ameliorates CCl4-Induced Liver Injury in Rats via the NF-Kappa B and MAPK Signaling Pathways

    PubMed Central

    Bak, Jeonghyeon; Je, Nam Kyung; Chung, Hae Young; Yokozawa, Takako; Yoon, Sik; Moon, Jeon-Ok

    2016-01-01

    Oxidative stress is thought to be a key risk factor in the development of hepatic diseases. Blocking or retarding the reactions of oxidation and the inflammatory process by antioxidants could be a promising therapeutic intervention for prevention or treatment of liver injuries. Oligonol is a low molecular weight polyphenol containing catechin-type monomers and oligomers derived from lychee fruit. In this study, we investigated the anti-inflammatory effect of oligonol on carbon tetrachloride- (CCl4-) induced acute hepatic injury in rats. Oral administration of oligonol (10 or 50 mg/kg) reduced CCl4-induced abnormalities in liver histology and serum AST and serum ALT levels. Oligonol treatment attenuated the CCl4-induced production of inflammatory mediators, including TNF-α, IL-1β, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) mRNA levels. Western blot analysis showed that oligonol suppressed proinflammatory nuclear factor-kappa B (NF-κB) p65 activation, phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK), and p38 mitogen-activated protein kinases (MAPKs) as well as Akt. Oligonol exhibited strong antioxidative activity in vitro and in vivo, and hepatoprotective activity against t-butyl hydroperoxide-induced HepG2 cells. Taken together, oligonol showed antioxidative and anti-inflammatory effects in CCl4-intoxicated rats by inhibiting oxidative stress and NF-κB activation via blockade of the activation of upstream kinases including MAPKs and Akt. PMID:26798422

  14. 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

  15. 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

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

    PubMed

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

    2013-03-01

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

  17. 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

  18. Hepatoprotective effect of manual acupuncture at acupoint GB34 against CCl4-induced chronic liver damage in rats

    PubMed Central

    Yim, Yun-Kyoung; Lee, Hyun; Hong, Kwon-Eui; Kim, Young-Il; Lee, Byung-Ryul; Kim, Tae-Han; Yi, Ji-Young

    2006-01-01

    AIM: To investigate the hepatoprotective effect of manual acupuncture at Yanglingquan (GB34) on CCl4-induced chronic liver damage in rats. METHODS: Rats were injected intraperitoneally with CCl4 (1 mL/kg) and treated with manual acupuncture using reinforcing manipulation techniques at left GB34 (Yanglingquan) 3 times a week for 10 wk. A non-acupoint in left gluteal area was selected as a sham point. To estimate the hepatoprotective effect of manual acupuncture at GB34, measurement of liver index, biochemical assays including serum ALT, AST, ALP and total cholesterol, histological analysis and blood cell counts were conducted. RESULTS: Manual acupuncture at GB34 reduced the liver index, serum ALT, AST, ALP and total cholesterol levels as compared with the control group and the sham acupuncture group. It also increased and normalized the populations of WBC and lymphocytes. CONCLUSION: Manual acupuncture with reinforcing manipulation techniques at left GB34 reduces liver toxicity, protects liver function and liver tissue, and normalizes immune activity in CCl4-intoxicated rats. PMID:16610030

  19. 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

    2015-01-01

    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. PMID:26213907

  20. 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

  1. Comparative Evaluation of Hepatoprotective Activities of Geniposide, Crocins and Crocetin by CCl4-Induced liver Injury in Mice

    PubMed Central

    Chen, Ping; Chen, Yang; Wang, Yarong; Cai, Shining; Deng, Liang; Liu, Jia; Zhang, Hao

    2016-01-01

    Iridoid glycosides (mainly geniposide) and crocetin derivatives (crocins) are the two major active constituents in Gardenia jasminoides Ellis. In the present study, geniposide, crocins, crocin-1 and crocetin were separated from gardenia chromatographically. Then, mice were orally administrated with geniposide (400 mg/kg b.w.), crocins (400 mg/kg b.w.), crocin-1 (400 mg/kg b.w.) and crocetin (140 mg/kg b.w.) once daily for 7 days with CCl4. Hepatoprotective properties were evaluated by biochemical parameters: Administration of geniposide, crocins, crocin-1and crocetin significantly lowered serum alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP) levels in CCl4-treated mice. The reduced glutathione (GSH) levels and antioxidant enzymes (SOD and CAT) activities were also increased by geniposide, crocins, crocin-1 and crocetin. Histopathological examination of livers showed that these components reduced deformability, irregular arrangement and rupture of hepatocyte in CCl4-treated mice. These biochemical results and liver histopathological assessment demonstrated that geniposide, crocetin derivatives and crocetin show comparative beneficial effects on CCl4-induced liver damage via induction of antioxidant defense. Therefore, contents of geniposide and crocetin derivatives should be both considered for hepatoprotective efficacy of Gardenia jasminoides Ellis. PMID:26902084

  2. Comparative Evaluation of Hepatoprotective Activities of Geniposide, Crocins and Crocetin by CCl4-Induced liver Injury in Mice.

    PubMed

    Chen, Ping; Chen, Yang; Wang, Yarong; Cai, Shining; Deng, Liang; Liu, Jia; Zhang, Hao

    2016-03-01

    Iridoid glycosides (mainly geniposide) and crocetin derivatives (crocins) are the two major active constituents in Gardenia jasminoides Ellis. In the present study, geniposide, crocins, crocin-1 and crocetin were separated from gardenia chromatographically. Then, mice were orally administrated with geniposide (400 mg/kg b.w.), crocins (400 mg/kg b.w.), crocin-1 (400 mg/kg b.w.) and crocetin (140 mg/kg b.w.) once daily for 7 days with CCl4. Hepatoprotective properties were evaluated by biochemical parameters: Administration of geniposide, crocins, crocin-1and crocetin significantlylowered serum alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP) levels in CCl4-treated mice. The reduced glutathione (GSH) levels and antioxidant enzymes (SOD and CAT) activities were also increased by geniposide, crocins, crocin-1 and crocetin. Histopathological examination of livers showed that these components reduced deformability, irregular arrangement and rupture of hepatocyte in CCl4-treated mice. These biochemical results and liver histopathological assessment demonstrated that geniposide, crocetin derivatives and crocetin show comparative beneficialeffects on CCl4-induced liver damage via induction of antioxidant defense. Therefore, contents of geniposide and crocetin derivatives should be both considered for hepatoprotective efficacyof Gardenia jasminoides Ellis. PMID:26902084

  3. [Effects of Hemerocallis citrine baroni flavonids on CCl4-induced liver fibrosis of rats].

    PubMed

    Shen, Nan; Huang, Xiao-dong; Li, Zhi-wei; Wang, Yan-chun; Qi, Ling; An, Ying; Liu, Ting-ting

    2015-05-01

    This study is designed to explore the possible effects of Hemerocallis citrina baroni flavonids (HCBF) on liver fibrosis induced by CCl4 in rats. The liver fibrosis model was induced by CCl4, and HCBF were administered by gastric perfusion at 25 and 50 mg x kg(-1) qd for 50 days, while the contents of alanine transaminase (ALT), aspartate aminotransferase (AST), gamma glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), superoxide dismutase (SOD), maleic dialdehyde (MDA) and transforming growth factor-β1 (TGF-β1) were measured and the contents of PINP were measured in liver tissue, and the expression of TGF-β1 were observed by immunohistochemisty and Western blot. The pathological changes of liver tissue were examined by HE. The results showed that HCBF (25, 50 mg x kg(-1)) improved the liver function significantly through reducing the level of ALT, AST, GGT and ALP (P < 0.05 or P < 0.01), and increasing the content of SOD (P < 0.01), while reducing the content of MDA (P < 0.05 or P < 0.01), the expression of TGF-β1 (P < 0.05) and the content of PINP (P < 0.05). The results suggest that HCBF (25, 50 mg x kg(-1)) may inhibit the liver injury induced by CCl4 by decreasing the oxidative stress. PMID:26234134

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

    PubMed Central

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

    2012-01-01

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

  5. Optical diagnosis of the progression and reversal of CCl4-induced liver injury in rodent model using minimally invasive autofluorescence spectroscopy.

    PubMed

    Nazeer, Shaiju S; Sandhyamani, S; Jayasree, Ramapurath S

    2015-06-01

    Worldwide, liver cancer is the fifth most common cancer in men and seventh most common cancer in women. Intoxicant-induced liver injury is one of the major causes for severe structural damage with fibrosis and functional derangement of the liver leading to cancer in its later stages. This report focuses on the minimally invasive autofluorescence spectroscopic (AFS) studies on intoxicant, carbon tetrachloride (CCl4)-induced liver damage in a rodent model. Different stages of liver damage, including the reversed stage, on stoppage of the intoxicant are examined. Emission from prominent fluorophores, such as collagen, nicotinamide adenine dinucleotide (NADH), and flavin adenine dinucleotide (FAD), and variations in redox ratio have been studied. A direct correlation between the severity of the disease and the levels of collagen and redox ratio was observed. On withdrawal of the intoxicant, a gradual reversal of the disease to normal conditions was observed as indicated by the decrease in collagen levels and redox ratio. Multivariate statistical techniques and principal component analysis followed by linear discriminant analysis (PC-LDA) were used to develop diagnostic algorithms for distinguishing different stages of the liver disease based on spectral features. The PC-LDA modeling on a minimally invasive AFS dataset yielded diagnostic sensitivities of 93%, 87% and 87% and specificities of 90%, 98% and 98% for pairwise classification among normal, fibrosis, cirrhosis and reversal conditions. We conclude that AFS along with PC-LDA algorithm has the potential for rapid and accurate minimally invasive diagnosis and detection of structural changes due to liver injury resulting from various intoxicants. PMID:25853289

  6. 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

  7. A novel fluorinated stilbene exerts hepatoprotective properties in CCl(4)-induced acute liver damage.

    PubMed

    Rivera, Horacio; Morales-Ríos, Martha S; Bautista, Wendy; Shibayama, Mineko; Tsutsumi, Víctor; Muriel, Pablo; Pérez-Álvarez, Víctor

    2011-10-01

    There has been a recently increase in the development of novel stilbene-based compounds with in vitro anti-inflamatory properties. For this study, we synthesized and evaluated the anti-inflammatory properties of 2 fluorinated stilbenes on carbon tetrachloride (CCl₄)-induced acute liver damage. To achieve this, CCl₄ (4 g·kg(-1), per os) was administered to male Wistar rats, followed by either 2-fluoro-4'-methoxystilbene (FME) or 2,3-difluoro-4'-methoxystilbene (DFME) (10 mg·kg(-1), per os). We found that although both of the latter compounds prevented cholestatic damage (γ-glutamyl transpeptidase activity), only DFME showed partial but consistent results in the prevention of necrosis, as assessed by both alanine aminotransferase activity and histological analysis. Since inflammatory responses are mediated by cytokines, mainly tumour necrosis factor α (TNF-α), we used the Western blot technique to determine the action of FME and DFME on the expression level of this cytokine. The observed increase in the level of TNF-α caused by CCl₄ administration was only prevented by treatment with DFME, in agreement with our biochemical findings. This result was confirmed by measuring interleukin-6 (IL-6) levels, since the expression of this protein depends on the level of TNF-α. In this case, DFME completely blocked the CCl₄-induced increase of IL-6. Our results suggest that DFME possesses greater anti-inflammatory properties in vivo than FME. DFME constitutes a possible therapeutic agent for liver disease and could serve as a template for structure optimization. PMID:21923234

  8. 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

  9. Evaluation of the effectiveness of Piper cubeba extract in the amelioration of CCl4-induced liver injuries and oxidative damage in the rodent model.

    PubMed

    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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  12. 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

  13. 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

  14. Cannabinoid receptors are involved in the protective effect of a novel curcumin derivative C66 against CCl4-induced liver fibrosis.

    PubMed

    Huang, Si-Si; Chen, Da-Zhi; Wu, He; Chen, Rui-Cong; Du, Shan-Jie; Dong, Jia-Jia; Liang, Guang; Xu, Lan-Man; Wang, Xiao-Dong; Yang, Yong-Ping; Yu, Zhen-Ping; Feng, Wen-Ke; Chen, Yong-Ping

    2016-05-15

    Liver fibrosis is one of the major causes of morbidity and mortality worldwide and lacks efficient therapy. Recent studies suggest the curcumin protects liver from fibrosis. However, curcumin itself is in low bioavailable concentration when administered orally, and the protective mechanism remains poorly understood. The current study aimed to investigate whether a more stable derivative of curcumin, C66, protects against CCl4-inudced liver fibrosis and examine the underlying mechanism involving cannabinoid receptor (CB receptor). At a dose lower than curcumin itself, C66 displayed a superior anti-fibrotic effect. C66 significantly reduced collagen deposition, pro-inflammatory cytokine expression, and liver enzyme activities. Mechanistic study revealed that C66 treatment decreased CCl4-induced cannabinoid receptor 1 (CB1 receptor) expression and increased cannabinoid receptor 2 (CB2 receptor) expression, along with an inhibition of JNK/NF-κB-mediated inflammatory signaling. In conclusion, this curcumin derivative attenuates liver fibrosis likely involving a CB/JNK/NF-κB-mediated pathway. PMID:26945822

  15. 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 NK cells. CMCS partially reverses ASGM-1-induced depletion of hepatic NK cells. PMID:26592510

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

    PubMed

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

    2014-12-01

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

  17. Comparison of the Treatment Efficiency of Bone Marrow-Derived Mesenchymal Stem Cell Transplantation via Tail and Portal Veins in CCl4-Induced Mouse Liver Fibrosis

    PubMed Central

    Truong, Nhung Hai; Nguyen, Nam Hai; Le, Trinh Van; Vu, Ngoc Bich; Huynh, Nghia; Nguyen, Thanh Van; Le, Huy Minh; Phan, Ngoc Kim

    2016-01-01

    Because of self-renewal, strong proliferation in vitro, abundant sources for isolation, and a high differentiation capacity, mesenchymal stem cells are suggested to be potentially therapeutic for liver fibrosis/cirrhosis. In this study, we evaluated the treatment effects of mouse bone marrow-derived mesenchymal stem cells (BM-MSCs) on mouse liver cirrhosis induced by carbon tetrachloride. Portal and tail vein transplantations were examined to evaluate the effects of different injection routes on the liver cirrhosis model at 21 days after transplantation. BM-MSCs transplantation reduced aspartate aminotransferase/alanine aminotransferase levels at 21 days after injection. Furthermore, BM-MSCs induced positive changes in serum bilirubin and albumin and downregulated expression of integrins (600- to 7000-fold), transforming growth factor, and procollagen-α1 compared with the control group. Interestingly, both injection routes ameliorated inflammation and liver cirrhosis scores. All mice in treatment groups had reduced inflammation scores and no cirrhosis. In conclusion, transplantation of BM-MSCs via tail or portal veins ameliorates liver cirrhosis in mice. Notably, there were no differences in treatment effects between tail and portal vein administrations. In consideration of safety, we suggest transfusion of bone marrow-derived mesenchymal stem cells via a peripheral vein as a potential method for liver fibrosis treatment. PMID:26839564

  18. Liver cirrhosis.

    PubMed Central

    Williams, E. J.; Iredale, J. P.

    1998-01-01

    Liver fibrosis and its related complications continue to represent a significant worldwide healthcare burden. Over the past decade there has been considerable improvement in our understanding of the cellular mechanisms and pathophysiology underlying hepatic fibrosis. This greater insight into the relevant basic sciences may lead to the development of novel treatment strategies designed to block the fibrogenic cascade or even enhance matrix degradation. In addition, there have been significant advances in the management of the complications of cirrhosis, with specific treatments now available for some conditions. Perhaps most notably, liver transplantation is now a highly successful treatment for end-stage liver disease and should be considered in all patients with chronic liver disease. PMID:9683971

  19. 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. PMID:26551763

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

    PubMed Central

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

    2012-01-01

    Metabolomics has been frequently used in pharmacodynamic studies, especially those on traditional Chinese medicine (TCM). Radix Paeoniae Alba and Radix Paeoniae Rubra are popularly used in TCM, and both have hepatoprotective effects. In this study, a CCl4-induced acute liver injury rat model was established and confirmed by the observed serum aminotransferase activities. The metabolomics approach was applied to study the influence of Radix Paeoniae Alba and Radix Paeoniae Rubra on the metabolic changes in rats with acute liver injury. The partial least-squares-discriminant analysis (PLS-DA) of rat serum and their ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) fingerprints allowed discrimination of controlled, acute liver injury-model rats after administration of the two types of TCMs. The time-dependent PLS-DA plots showed that the changes in the metabolic patterns of the rats, which were administered with the TCMs, had stabilized within 2 h after they received the intraperitoneal CCl4 injection. The results indicated the protective effect of TCMs against liver injury. Several potential biomarkers were detected and identified, which included creatine, deoxycholic acid, choline, 5-methylenetetrahydrofolate, folic acid, and glycocholic acid. The physiological significance of these metabolic changes was discussed. PMID:23203085

  1. Inhibition of MAPK and NF-κB signaling pathways alleviate carbon tetrachloride (CCl4)-induced liver fibrosis in Toll-like receptor 5 (TLR5) deficiency mice.

    PubMed

    Shu, Ming; Huang, Dan-Dan; Hung, Zuo-An; Hu, Xiao-Rong; Zhang, Shun

    2016-02-26

    Current researches showed that TLR family plays an important role in liver fibrosis, yet the molecular mechanism by which this occurs is not fully explained. In this study, we investigated the role of TLR5 in carbon tetrachloride-induced liver fibrosis, and further examined wether TLR5 knockout attenuated tetrachloride-induced liver fibrosis by inhibiting hepatic stellate cells activation via modulating NF-κB and MAPK signaling pathways. Our results found that carbon tetrachloride induced liver function injury in WT mice with a inflammatory responses through the activation of NF-κB and MAPK signaling pathways, resulting in hepatic stellate cells activation. In contrast, TLR5 deficiency mice after carbon tetrachloride administration reduced NF-κB and MAPK signaling pathways activation, which down regulated hepatic stellate cells activation. In addition, alpha smooth muscle-actin as marker of hepatic stellate cells further indicated that TLR5 knockout mice have a lower collagen accumulation in liver tissue than WT mice after carbon tetrachloride administration, resulting in inhibition of NF-κB and MAPK signaling pathways activation. Moreover, in vitro experiment of hepatic stellate cells challenged with LPS or TGF-β, further indicated that NF-κB and MAPK were involved in liver fibrosis development, leading to α-SMA expression and inflammation infiltration. However, cells from TLR5(-)(/-) may weaken phosphorylation levels of signal pathways, finally suppress progress of collagen accumulation and inflammatory responses. These results suggest a new therapeutic approach or target to protect against fibrosis caused by chronic liver diseases. PMID:26845355

  2. Epigenetic Alterations of IL-6/STAT3 Signaling by Placental Stem Cells Promote Hepatic Regeneration in a Rat Model with CCl4-induced Liver Injury

    PubMed Central

    Jung, Jieun; Moon, Ji Wook; Choi, Jong-Ho; Lee, Yong Woo; Park, Sun-Hwa; Kim, Gi Jin

    2015-01-01

    Background Human chorionic plate-derived mesenchymal stem cells (CP-MSCs) isolated from the placenta have been reported to demonstrate therapeutic effects in animal models of liver injury; however, the underlying epigenetic mechanism of this effect has not been elucidated. Thus, we investigated whether CP-MSCs influence epigenetic processes during regeneration of the injured liver. Methods CP-MSCs were engrafted into a carbon tetrachloride (CCl4)-injured rat model through direct transplantation into the liver (DTX), intrasplenic transplantation (STX), and intravenous transplantation via the tail vein (TTX). Non-transplanted (NTX) rats were maintained as sham controls. Liver tissues were analyzed after transplantation using immunohistochemistry, western blot analysis, and quantitative methylation-specific polymerase chain reaction. Proliferation and human interleukin-6 (hIL-6) enzyme-linked immunosorbent assays were performed using CCl4-treated hepatic cells that were co-cultured with CP-MSCs. Results The Ki67 labeling index, cell cyclins, albumin, IL-6, and gp130 levels were elevated in the CP-MSC transplantation groups. The concentration of hIL-6 in supernatants and the proliferation of CCl4-treated rat hepatic cells were enhanced by co-culturing with CP-MSCs (p<0.05), while the methylation of IL-6/IL-6R and STAT3 by CP-MSC transplantation decreased. Conclusion These results suggest that administration of CP-MSCs promotes IL-6/STAT3 signaling by decreasing the methylation of the IL-6/SATA3 promoters and thus inducing the proliferation of hepatic cells in a CCl4-injured liver rat model. These data advance our understanding of the therapeutic mechanisms in injured livers, and can facilitate the development of cell-based therapies using placenta-derived stem cells. PMID:26019757

  3. Pathogenesis of liver cirrhosis

    PubMed Central

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

    2014-01-01

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

  4. [Complications of liver cirrhosis].

    PubMed

    Wittenburg, H; Tennert, U; Berg, T

    2011-09-01

    The occurrence of complications increases the mortality in patients with cirrhosis of the liver. Therefore, early detection and treatment of complications of cirrhosis is of major importance. Following diagnosis of cirrhosis, a screening gastroscopy detects esophageal varices. Primary prevention of variceal bleeding can be initiated with β-receptor antagonists or variceal band ligation. With the first episode of ascites or the manifestation of other complications of cirrhosis such as hepatic encephalopathy and hepatorenal syndrome, a paracentesis excludes spontaneous bacterial peritonitis. Hepatorenal syndrome can be treated with a combination of vasopressors and albumine. Furthermore, occurrence of complications in patients with cirrhosis of the liver should prompt the evaluation of an indication for liver transplantation. PMID:21611819

  5. [Epistemology of liver cirrhosis].

    TOXLINE Toxicology Bibliographic Information

    Coppo M; Borghi A

    1990-04-01

    Critical considerations are expressed on scientific approach to liver cirrhosis, a nosological entity based on both analytical inquiry and long term observation of a large number of cirrhotic patients. The main points taken into consideration are: the etiopathogenesis of cirrhosis; a systematic of diagnostic elements; some preventional aspects of the disease and of its major sequelae. In the histogenetical analysis, the following steps are identified and analysed: a) hepatocellular death (necrosis), b) inflammatory process, c) fibrosis, d) hepatocellular regeneration and disorganized vascular architecture as a consequence of nodular regeneration. The hepatotoxic action of the three most studied and widespread etiologic agents of cirrhosis, alcohol, HBV, iron, is also considered. Finally, as a last pathogenetic step and peculiar to liver cirrhosis, the complex vascular rearrangement that leads to a relative increase of the liver blood flow is analysed. Clinical experience suggests a distinction between active and inactive liver cirrhosis. In the former we find a chronic active hepatitis associated with nodular regeneration and subsequent compensatory blood flow rearrangement. No signs of chronic active hepatitis can be found in the latter which is characterized by irreversible alteration of the liver architecture, reduction of the liver function and hemodynamic rearrangement (portal and arterial). Both nosologic entities can be either clinically characterized or not by symptoms of the major sequelae and complications of cirrhosis. On the basis of the clinical experience, among the complications of cirrhosis spontaneous bacterial peritonitis, gastrointestinal bleeding, hepatorenal syndrome and hepatocarcinoma appear to have a great prognostic value. Association between hepatocarcinoma and liver cirrhosis, which seems to be independent of single etiologic factors of cirrhosis itself, also has a great reliance.(ABSTRACT TRUNCATED AT 250 WORDS)

  6. [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. PMID:23628170

  7. 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

  8. 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. PMID:25807561

  9. 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

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

    PubMed

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

    2014-04-01

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

  11. 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

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

    PubMed

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

    2012-07-01

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

  13. Gastrointestinal dysfunction in liver cirrhosis

    PubMed Central

    Kalaitzakis, Evangelos

    2014-01-01

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

  14. 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

  15. Arrhythmia risk in liver cirrhosis

    PubMed Central

    Mozos, Ioana

    2015-01-01

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

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

    PubMed Central

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

    2012-01-01

    The burden of liver disease in Egypt is exceptionally high due to the highest prevalence of hepatitis C virus (HCV) resulting in rising rates of hepatocellular carcinoma (HCC). The aim of the current study was to determine the isoflavones in soy and to evaluate the protective role of soy against CCl4-induced liver damage in rats. Four experimental groups were treated for 8 weeks and included the control group, soy-supplemented diet (20% w/w) group, the group treated orally with CCl4 (100 mg/kg bw) twice a week, and the group fed soy-supplemented diet and treated with CCl4. Blood and liver tissue samples were collected for biochemical analyses and histological examination. The results indicated that protein content was 45.8% and the total isoflavones recorded 167.3 mg/100 g soy. Treatment with CCl4 resulted in a significant biochemical changes in serum liver tissue accompanied with severe oxidative stress and histological changes. Supplementation with soy succeeded to restore the elevation of liver enzymes activities and improved serum biochemical parameters. Moreover, soy supplementation improved the antioxidant enzymes, decreased lipid peroxidation, and improved the histological picture of the liver tissue. It could be concluded that soy-protein-enriched isoflavones may be a promising agent against liver diseases. PMID:22530140

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

    PubMed

    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

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

    PubMed Central

    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. PMID:23533498

  19. 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

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed Central

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

    2014-01-01

    Background: Nowadays attention to use herbs such as cornelian cherry (Cornus mas) is increasing, which contains high levels of antioxidants and anthocyanins. Cornus mas fruits have been used for gastrointestinal and excretory disorders for many years in traditional medicine, also may improve liver and kidney functions, and have protective effects such as anti-allergic, antidiabetic, antibacterial, antimicrobial, antihistamine and antimalarial properties. Objectives: The aim of this study was to investigate protective effects of Cornus mas fruits extract on serum biomarkers in CCl4-induced hepatotoxicity in male rats. Materials and Methods: Hepatotoxicity was induced by administration of carbon tetrachloride (1 mL/kg i.p.) in 1:1 dilution with olive oil. To evaluate the effect of Cornus mas fruits extract on disease progression, serum marker enzymes, serum total protein and albumin and liver lipid peroxidation were determined in CCl4-induced hepatotoxicity. Results: Oral administration of Cornus mas fruits extract to rats for 14 days provided a significant (P < 0.05) hepatoprotection by decreasing elevated serum level of enzymes, total serum protein, albumin and liver lipid peroxidation content. Conclusions: Cornus mas fruit extract effect may be due to including some antioxidant components, which caused membrane stabilizing and normalization of fluctuated biochemical profiles induced by CCl4 exposure. Our results validated the traditional use of Cornus mas in the treatment of liver disorders. PMID:24829584

  2. 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. PMID:25015447

  3. Portal vein thrombosis in liver cirrhosis

    PubMed Central

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

    2014-01-01

    Portal vein thrombosis (PVT) is considered to be a frequent complication of liver cirrhosis. However, unlike PVT in patients without cirrhosis, very few data are available on the natural history and management of PVT in cirrhosis, despite its association with potentially life-threatening conditions, such as gastroesophageal bleeding and acute intestinal ischemia. Moreover, no consensus regarding PVT in cirrhosis exists. Suggested causes of PVT in cirrhosis include reduced portal blood flow velocity, multiple congenital or acquired thrombophilic factors, inherited or acquired conditions, and derangement of liver architecture. However, the understanding of PVT in cirrhosis is incomplete. In addition, information on the management of PVT in cirrhosis is inadequate. The aims of this review are to: (1) assemble data on the physiopathological mechanism, clinical findings, diagnosis and management of PVT in cirrhosis; (2) describe the principal factors most frequently involved in PVT development; and (3) summarize the recent knowledge concerning diagnostic and therapeutic procedures. PMID:24575165

  4. 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. PMID:23964314

  5. Cholecystectomy in Patients with Liver Cirrhosis

    PubMed Central

    Sadr-Azodi, Omid

    2015-01-01

    Background. The aim of this population-based study was to describe characteristics of patients with liver cirrhosis undergoing cholecystectomy and evaluate the risk for perioperative and postoperative complications during the 30-day postoperative period. Method. All laparoscopic and open cholecystectomy procedures registered between 2006 and 2011 in the Swedish Registry for Gallstone Surgery and ERCP (GallRiks) were included. Patients with liver cirrhosis were identified by linking data to the Swedish National Patient Registry (NPR). Results. Of 62,488 patients undergoing cholecystectomy, 77 (0.12%) had cirrhosis, of which 29 patients (37.7%) had decompensated cirrhosis. Patients with cirrhosis were older and had more often gallstone complications at the time for surgery. Postoperative complications were registered in 13 (16.9%) patients with liver cirrhosis and in 5,738 (9.2%) patients in the noncirrhotic group (P < 0.05). Univariable analysis showed that patients with liver cirrhosis are more likely to receive postoperative blood transfusion (OR = 4.4, CI 1.08–18.0, P < 0.05) and antibiotic treatment >1 day (OR = 2.3, CI 1.11–4.84, P < 0.05) than noncirrhotic patients. Conclusion. Patients with cirrhosis undergoing cholecystectomy have a higher incidence of postoperative complications than patients without cirrhosis. However, cholecystectomy is safe and if presented with adequate indication, surgery should not be delayed due to fears of surgical complications. PMID:26788053

  6. The protective effects of Masson pine pollen aqueous extract on CCl4-induced oxidative damage of human hepatic cells

    PubMed Central

    Jin, Xueyuan; Cong, Tao; Zhao, Lin; Ma, Long; Li, Reisheng; Zhao, Ping; Guo, Changjiang

    2015-01-01

    Objective: We observed the effects of Masson pine pollen aqueous extracts (MPPAE) on CCl4-induced oxidative damage of the human hepatic cell line L-02. Methods: We created an in vitro model of oxidative liver damage by treating L-02 human hepatic cells with 40 mmol/L CCl4. Effects of different concentrations of MPPAE on cell proliferation, morphology, and change of functional indexes were observed after addition of CCl4. Results: CCl4 was toxic to proliferation, cell morphology, and functionality of hepatic cells. It decreased proliferation by 29.3-38.4% and increased AST and ALT activities by 22.3% and 99.2%, respectively. The oxidative stress also disrupted hepatic cell growth and induced pyknosis. Although MPPAE did not prevent decreased proliferation of L-02 cells, the treatment alleviated some CCl4-induced cell morphology changes and inhibited the abnormal rise of ALT (39.8%-70.1%) and AST (14.75-27.25%) activities in a dose dependent manner. A high dose of MPPAE (400 mg/L) ameliorated nucleus deformation to an almost normal appearance. Conclusions: According to our in vitro model, MPPAE specifically prevented the changes in cell morphology and functional injury caused by CCL4 treatment; however, it offered limited protection against damage-induced reduction of proliferation. PMID:26770368

  7. 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. PMID:26742763

  8. 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 7.87% ± 0.66% to 3.68% ± 0.32%, P < 0.05) compared with the CCl4 group. GA also decreased the expression level of cleaved caspase-3 compared to the CCl4 group. TUNEL assay indicated that GA significantly diminished the number of TUNEL-positive cells compared with the CCl4 group (P < 0.05). GA treatment clearly decreased the level of p53 (P < 0.05) detected by immunohistochemistry and Western blotting analysis. Compared with the CCl4 group, we also found that GA reduced the Bax/Bcl-2 ratio (P < 0.05), the expression of cleaved caspase-3 (P < 0.05), cleaved caspase-9 (P < 0.05), and inhibited cytochrome C and second mitochondria-derived activator of caspases (Smac) release from mitochondria to cytoplasm, i.e., GA reduced the expression level of Smac, which inhibited c-IAP1 activity (P < 0.05), ultimately inhibiting the activity of caspase-3, according to Western blotting analysis. As a result, GA suppressed activation of the caspase cascades and prevented hepatocyte apoptosis. CONCLUSION: GA can inhibit CCl4-induced hepatocyte apoptosis via a p53-dependent mitochondrial pathway to retard the progress of liver fibrosis in rats. PMID:23840116

  9. 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. PMID:26902361

  10. 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

  11. Inflammasome activation in decompensated liver cirrhosis

    PubMed Central

    González-Navajas, José M

    2016-01-01

    Inflammation participates in the pathogenesis of many liver diseases, including liver cirrhosis. Certain inflammatory citokines, such as interleukin (IL)-1β and IL-18, are produced after the activation of a multiprotein complex known as the inflammasome. Activation of the inflammasome has been documented in several liver diseases, but its role in the development and progression of liver cirrhosis or the complications associated with this disease is still largely unknown. We have recently studied the impact of the inflammasome in the sterile inflammatory response that takes place in the ascitic fluid of patients with decompensated cirrhosis, providing evidence that activation of the absent in melanoma 2 (AIM2) inflammasome is an important response in these patients. Ascitic fluid-derived macrophages were able to mount a very robust AIM2-mediated response even in the absence of a priming signal, which is usually required for the full activation of all the inflammasomes. In addition, high level of inflammasome activation in these patients was associated with a higher degree of liver disease and an increased incidence of spontaneous bacterial peritonitis. These results may help explain the exacerbated inflammatory response that usually occurs in patients with decompensated cirrhosis in the absence of detectable infections. Thus, inflammasomes should be considered as possible therapeutic targets in sterile inflammatory complications in patients with cirrhosis. PMID:26855691

  12. 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. PMID:26626635

  13. 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 ...

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

    PubMed

    Rivera Irigoin, Robin; Abils, 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. PMID:22657567

  15. Bloodstream infections in patients with liver cirrhosis.

    PubMed

    Bartoletti, Michele; Giannella, Maddalena; Lewis, Russell Edward; Viale, Pierluigi

    2016-04-01

    Bloodstream infections are a serious complication in patients with liver cirrhosis. Dysregulated intestinal bacterial translocation is the predominant pathophysiological mechanism of infections in this setting. For this reason enteric Gram-negative bacteria are commonly encountered as the first etiological cause of infection. However, through the years, the improvement in the management of cirrhosis, the recourse to invasive procedures and the global spread of multidrug resistant pathogens have importantly changed the current epidemiology. Bloodstream infections in cirrhotic patients are characterized by high mortality rate and complications including metastatic infections, infective endocarditis, and endotipsitis (or transjugular intrahepatic portosystemic shunt-related infection). For this reason early identification of patients at risk for mortality and appropriated therapeutic management is mandatory. Liver cirrhosis can significantly change the pharmacokinetic behavior of antimicrobials. In fact hypoproteinaemia, ascitis and third space expansion and impairment of renal function can be translated in an unpredictable drug exposure. PMID:26864729

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

    PubMed

    Jaswal, Amita; Shukla, Sangeeta

    2015-01-01

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

  17. Cirrhosis

    MedlinePlus

    ... over 10 to 12 years can lead to alcoholic cirrhosis. 4 Nonalcoholic fatty liver disease (NAFLD) and ... 6, 2014. O'Shea RS, Dasarathy S, McCullough AJ. Alcoholic liver disease. Hepatology. 2010;51(1):307–328. ...

  18. Primary biliary cirrhosis and liver transplantation

    PubMed Central

    Akamatsu, Nobuhisa; Sugawara, Yasuhiko

    2012-01-01

    Summary Primary biliary cirrhosis (PBC) is an immune-mediated chronic progressive inflammatory liver disease, predominantly affecting middle-aged women, characterized by the presence of antimitochondrial antibodies (AMAs), which can lead to liver failure. Genetic contributions, environmental factors including chemical and infectious xenobiotics, autoimmunity and loss of tolerance have been aggressively investigated in the pathogenesis of PBC, however, the actual impact of these factors is still controversial. Survival of PBC patients has been largely improved with the widespread use of ursodeoxycholic acid (UDCA), however, one third of patients still do not respond to the treatment and proceed to liver cirrhosis, requiring liver transplantation as a last resort for cure. The outcome of liver transplantation is excellent with 5- and 10-year survival rates around 80% and 70%, respectively, while along with long survival, the recurrence of the disease has become an important outcome after liver transplantation. Prevalence rates of recurrent PBC rage widely between 1% and 35%, and seem to increase with longer follow-up. Center-specific issues, especially the use of protocol biopsy, affect the variety of incidence, yet, recurrence itself does not affect patient and graft survival at present, and retransplantation due to recurrent disease is extremely rare. With a longer follow-up, recurrent disease could have an impact on patient and graft survival. PMID:25343075

  19. 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

  20. Telomere shortening as genetic risk factor of liver cirrhosis.

    PubMed

    Carulli, Lucia

    2015-01-14

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

  1. N-acetylcysteine protects against liver injure induced by carbon tetrachloride via activation of the Nrf2/HO-1 pathway

    PubMed Central

    Cai, Zhaobin; Lou, Qi; Wang, Fugen; Li, Er; Sun, Jingjing; Fang, Hongying; Xi, Jianjun; Ju, Liping

    2015-01-01

    Chronic liver injury is an important clinical problem which eventually leads to cirrhosis, hepatocellular carcinoma and end-stage liver failure. It is well known that cell damage induced by reactive oxygen species (ROS) is an important mechanism of hepatocyte injure. N-acetylcysteine (NAC), a precursor of glutathione (GSH), is well-known role as the antidote to acetaminophen toxicity in clinic. NAC is now being utilized more widely in the clinical setting for non-acetaminophen (APAP) related causes of liver injure. However, the mechanisms underlying its beneficial effects are poorly defined. Thus, Aim of the present study was to investigate potential hepatic protective role of NAC and to delineate its mechanism of action against carbon tetrachloride (CCl4)-induced liver injury in models of rat. Our results showed that the alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities as well as malondialdehyde (MDA) contents decreased significantly in CCl4-induced rats with NAC treatment. GSH content and superoxide dismutase (SOD) activities remarkably increased in the NAC groups compared with those in CCl4-induced group. Treatment with NAC had been shown to an increase in nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) mRNA levels. In conclusion, these results suggested that NAC upregulated HO-1 through the activation of Nrf2 pathway and protected rat against CCl4-induced liver injure. The results of this study provided pharmacological evidence to support the clinical application of NAC. PMID:26339453

  2. 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

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

    PubMed Central

    ZHAO, XIN

    2013-01-01

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

  4. 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

  5. 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. PMID:26494949

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

    PubMed Central

    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. PMID:26494949

  7. 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.

  8. 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

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

    PubMed

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

    2014-12-01

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

  10. 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

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

    PubMed Central

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

    2014-01-01

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

  12. 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

  13. Virus-related liver cirrhosis: Molecular basis and therapeutic options

    PubMed Central

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

    2014-01-01

    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. PMID:24914367

  14. 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.

  15. Gut microbiota and host metabolism in liver cirrhosis.

    PubMed

    Usami, Makoto; Miyoshi, Makoto; Yamashita, Hayato

    2015-11-01

    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, synbiotics, and prebiotics, with sufficient nutrition could aid the development of treatments and prevention for liver cirrhosis patients. PMID:26556989

  16. 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, synbiotics, and prebiotics, with sufficient nutrition could aid the development of treatments and prevention for liver cirrhosis patients. PMID:26556989

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

    PubMed

    Zaib, Sania; Khan, Muhammad Rashid

    2014-11-01

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

  18. Group IVA phospholipase A2 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. PMID:26850849

  19. Ameliorative action of cyanobacterial phycoerythrin on CCl(4)-induced toxicity in rats.

    PubMed

    Soni, Badrish; Visavadiya, Nishant P; Madamwar, Datta

    2008-06-01

    Carbon tetrachloride (CCl(4)) is largely used as solvent in chemical industries. Carbon tetrachloride is also well known for hepatic and renal toxic actions. The in vivo metabolism of carbon tetrachloride to trichloromethyl (CCl(3)) and peroxy trichloromethyl (OOCCl(3)) radicals has been extensively reported to cause acute liver damage like cirrhosis, steatosis and necrosis. We have evaluated protective action of purified cyanobacterial phycoerythrin (C-PE) on carbon tetrachloride-induced hepatic and renal toxicity in male rats. Rats were orally treated with 25 and 50mg/kg BW of C-PE along with CCl(4) (50% CCl(4), 0.5 ml/kg BW, intraperitoneally) for 28 consecutive days. Results demonstrated that C-PE dose-responsively ameliorates CCl(4)-toxicity by significantly decreasing (P<0.05) organs weight, aminotransferases, alkaline phosphatase, glucose, lipid profile, creatinine, uric acid and malondialdehyde (MDA) concentrations with rise in body weight, food intake, hemoglobin, protein, bilirubin and FRAP values. Neither C-PE nor CCl(4) influenced on serum minerals. Hepatic and renal tissues showed significant decline (P<0.05) in malondialdehyde, lipid hydroperoxides and conjugated dienes with rise in SOD, catalase, GPx, GSH, vitamin-E and vitamin-C levels. Presently observed pharmacological effect on CCl(4) toxicity were from tetrapyrrole molecule and to some extent bilirubin biotransformations, as well as metabolic (dietary protein) actions of C-PE. PMID:18440118

  20. Serum levels of cytokines in alcoholic liver cirrhosis and pancreatitis.

    PubMed

    Szuster-Ciesielska, A; Daniluk, J; Kandefer-Zerszeń, M

    2000-01-01

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

  1. 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 in dogs. PMID:27047120

  2. 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

  3. Molecular prognostic prediction in liver cirrhosis

    PubMed Central

    Goossens, Nicolas; Nakagawa, Shigeki; Hoshida, Yujin

    2015-01-01

    The natural history of cirrhosis varies and therefore prognostic prediction is critical given the sizable patient population. A variety of clinical prognostic indicators have been developed and enable patient risk stratification although their performance is somewhat limited especially within relatively earlier stage of disease. Molecular prognostic indicators are expected to refine the prediction, and potentially link a subset of patients with molecular targeted interventions that counteract poor prognosis. Here we overview clinical and molecular prognostic indicators in the literature, and discuss critical issues to successfully define, evaluate, and deploy prognostic indicators as clinical scores or tests. The use of liver biopsy has been diminishing due to sampling variability on fibrosis assessment and emergence of imaging- or lab test-based fibrosis assessment methods. However, recent rapid developments of genomics technologies and selective molecular targeted agents has highlighted the need for biopsy tissue specimen to explore and establish molecular information-guided personalized/stratified clinical care, and eventually achieve “precision medicine”. PMID:26420954

  4. [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. PMID:24309482

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

    PubMed

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

    2014-01-01

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

  6. Primary hyperoxaluria complicated with liver cirrhosis: A case report.

    PubMed

    Kogiso, Tomomi; Tokushige, Katsutoshi; Hashimoto, Etsuko; Miyakata, Chiharu; Taniai, Makiko; Torii, Nobuyuki; Omori, Akiko; Kotera, Yoshihito; Egawa, Hiroto; Yamamoto, Masakazu; Nagata, Masao; Shiratori, Keiko

    2015-12-01

    Primary hyperoxaluria (PH) is a rare, autosomal recessive disorder characterized by overproduction of oxalate caused by a deficiency in a hepatic enzyme. The excess oxalate combines with calcium in the kidneys to form deposits of calcium oxalate, which can lead to nephrocalcinosis and renal failure. PH type 1 (PH1), the most common form of this disease, is caused by a deficiency of the liver-specific enzyme alanine/glyoxylate aminotransferase (AGT). Liver transplantation is performed as a definitive therapy for PH to correct the enzyme defect. Usually, liver depositions are limited and liver function is normal without fibrosis. Here, we report an adult case of liver cirrhosis caused by PH1. A 28-year-old woman was admitted to our hospital under suspicion of PH1 and the presence of nephrocalcinosis. The patient had suffered from kidney stone recurrences from 17 years of age, and was initiated on hemodialysis due to renal failure at the age of 27 years. The serum level of oxalic acid was high, whereas the AGT level in the liver tissue was decreased. Thus, the patient was definitively diagnosed with PH1. Although she had normal liver function, surface nodularity and splenomegaly were detected by computed tomography, suggesting liver cirrhosis. The native liver showed micronodular cirrhosis and portal fibrosis. Several arterioles were filled with rhomboid and polyhedral refractile oxalate crystals and various portal tracts showed these crystals. Our case suggests that long-term oxalosis can lead to liver cirrhosis; thus, PH should be considered one of the causes of liver cirrhosis. PMID:25594663

  7. Oxidative Stress and Pulmonary Changes in Experimental Liver Cirrhosis

    PubMed Central

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

    2012-01-01

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

  8. Management of thrombocytopenia due to liver cirrhosis: A review

    PubMed Central

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

    2014-01-01

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

  9. Laparoscopic liver resection for hepatocellular carcinoma in patients with cirrhosis

    PubMed Central

    Lo, Chung Mau

    2015-01-01

    Liver resection for patients with cirrhosis remains a challenging operation. The presence of thrombocytopenia and portal hypertension could lead to severe bleeding during hepatectomy. The enthusiasm of laparoscopic hepatectomy has been growing and many studies have reported their initial favorable results for patients with hepatocellular carcinoma (HCC). The advancement in technology, better understanding of the use of pneumoperitoneum pressure and more experience accumulated make laparoscopic liver resection for patients with cirrhosis possible. Favorable outcome may be achieved if the patients are carefully selected and carried out in high volume centers. PMID:26734625

  10. 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

    2014-09-01

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

  11. Serum cytokine levels in alcohol-related liver cirrhosis.

    PubMed

    Daniluk, J; Szuster-Ciesielska, A; Drabko, J; Kandefer-Szerszeń, M

    2001-01-01

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

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

    PubMed

    Raj, Sreena; Gothandam, K M

    2014-05-01

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

  13. 4-Phenylbutyric acid regulates CCl4-induced acute hepatic dyslipidemia in a mouse model: A mechanism-based PK/PD study.

    PubMed

    Lee, Hwa Young; Marahatta, Anu; Bhandary, Bidur; Kim, Hyung-Ryong; Chae, Han-Jung

    2016-04-15

    Endoplasmic reticulum (ER) stress and associated protein aggregation are closely associated with human diseases, including alterations in hepatic lipid metabolism. Inhibition of ER stress can have a significant effect on the prevention of hepatic dyslipidemia. Here, we studied the role of 4-phenylbutyric acid (4-PBA), a chemical chaperone, on ER stress-induced hepatic lipid accumulation. We studied ER stress induction following CCl4 exposure and delineated mechanisms of the CCl4-induced ER stress response in liver tissue from mice. CCl4 affected the formation of disulfide bonds through excessive hyper-oxidation of protein disulfide isomerase (PDI). Increased complex formation between PDI and its client proteins persisted in CCl4-exposed samples. Conversely, 4-PBA inhibited ER stress via secretion of apolipoprotein B and prevention of hepatic lipid accumulation. We also studied the mechanism-based pharmacokinetic and pharmacodynamic profiles and identified the ER stress-related proteins GRP78 and CHOP, along with plasma apolipoprotein B and triglyceride levels, as novel biomarkers of ER stress-induced hepatic lipid accumulation. ER stress and its clinical relevance for therapeutic approaches were well correlated with the activity of the ER stress regulator 4-PBA, which may be a promising drug candidate for the treatment of hepatic lipid accumulation, such as hepatic steatosis. PMID:26948310

  14. Influence of unrecorded alcohol consumption on liver cirrhosis mortality

    PubMed Central

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

    2014-01-01

    Unrecorded alcohol includes illegally distributed alcohol as well as homemade or surrogate alcohol which is unintended for consumption by humans (e.g., cosmetics containing alcohol). The highest unrecorded alcohol consumption occurs in Eastern Europe and some of these countries have an over proportional liver cirrhosis mortality. Compounds besides ethanol have been hypothesized as being responsible for this observation. On the other hand, chemical investigations were unable to prove that unrecorded alcohol regularly contains contaminants above toxicological thresholds. However, illegally produced spirits regularly contain higher percentages of alcohol (above 45% by volume), but for considerably less costs compared with licit beverages, potentially causing more problematic patterns of drinking. In this review, it is investigated whether patterns of drinking rather than product composition can explain the liver cirrhosis mortality rates. Statistical examination of World Health Organization country data shows that the originally detected correlation of the percentage of unrecorded alcohol consumption and liver cirrhosis mortality rates disappears when the data is adjusted for the prevalence of heavy episodic drinking. It may be concluded that there is currently a lack of data to demonstrate causality between the composition of illicit spirits (e.g., higher levels of certain contaminants in home-produced products) and liver toxicity on a population scale. Exceptions may be cases of poisoning with antiseptic liquids containing compounds such as polyhexamethyleneguanidine, which were reported to be consumed as surrogate alcohol in Russia, leading to an outbreak of acute cholestatic liver injury, histologically different from conventional alcoholic liver disease. PMID:24966592

  15. 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

  16. Painful muscle cramps. A symptom of liver cirrhosis?

    PubMed

    Konikoff, F; Theodor, E

    1986-12-01

    We found an 88% incidence of painful muscle cramps in 33 patients with cirrhosis, as compared to 21% in a matched population without liver disease. The cramps were characterized by severe pain, occurred in calf muscles several times a week (mainly at rest or during sleep), and lasted for a few minutes. No definite etiological factor could be found and the underlying pathophysiology remains obscure, as in most other types of muscle cramps. However, the strikingly high incidence and uniformity of the phenomenon may justify the inclusion of painful muscle cramps among the recognized symptoms of cirrhosis. PMID:3805668

  17. Vibrio vulnificus infection and liver cirrhosis: a potentially lethal combination.

    PubMed

    Nazir, Salik; Brown, Krysta; Shin, Ann Kyungwohn; Donato, Anthony A

    2016-01-01

    We present a case of a 40-year-old man with decompensated alcoholic liver cirrhosis presenting with atraumatic cellulitis of one extremity and severe sepsis that rapidly progressed to compartment syndrome despite broad-spectrum antibiotics. Local cultures following debridement revealed Vibrio vulnificus, and subsequent history revealed consumption of raw oysters 48 h before presentation. Our case points out the unique susceptibility of those with cirrhosis and elevated iron saturation to Vibrio septicaemia, as well as the rapidity and severity of the disease progression. PMID:27151052

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

    PubMed

    Desai, Archita P; Reau, Nancy

    2016-02-01

    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. PMID:26782133

  19. 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. PMID:24359651

  20. 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

  1. Hepatoprotective effects of polyprenols from Ginkgo biloba L. leaves on CCl4-induced hepatotoxicity in rats.

    PubMed

    Yang, Lan; Wang, Cheng-zhang; Ye, Jian-zhong; Li, Hai-tao

    2011-09-01

    The hepatoprotective effects of polyprenols from Ginkgo biloba L. leaves were evaluated against carbon tetrachloride induced hepatic damage in Sprague-Dawley rats. The elevated levels of serum ALT, AST, ALP, ALB, TP, HA, LN, TG, and CHO were restored towards normalization significantly by GBP in a dose dependent manner. The biochemical observations were supplemented with histopathological examination of rat liver sections. Meanwhile, GBP also produced a significant and dose-dependent reversal of CCl(4)-diminished activity of the antioxidant enzymes and reduced CCl(4)-elevated level of MDA. In general, the effects of GBP were not significantly different from those of the standard drug Essentiale. PMID:21596107

  2. Repeat Liver Resection for Hepatocellular Carcinoma Complicating Primary Biliary Cirrhosis

    PubMed Central

    Mochizuki, Susumu; Nakayama, Hisashi; Higaki, Tokio; Okubo, Takao; Midorikawa, Yutaka; Moriguchi, Masamichi; Aramaki, Osamu; Yamazaki, Shintaro; Sugitani, Masahiko; Takayama, Tadatoshi

    2013-01-01

    The incidence of hepatocellular carcinoma (HCC) complicating primary biliary cirrhosis (PBC) is between 0.7% and 16%. Repeat liver resection for recurrent HCC complicating PBC is not usually performed and not published because this approach is not generally applicable due to liver dysfunction. We applied repeat liver resection for these diseases. Three patients were diagnosed with PBC. The first HCC was noted at a mean of 6 years (4–17 years) after diagnosis of PBC. The second HCC occurred at a mean of 2.5 years (0.4–3 years) after the first surgery. All patients were treated with curative resection on first and second surgery. The mean overall survival time after the first liver resection was 46 months. Repeat liver resection for recurrent HCC complicating PBC is an option and may improve the outcome. PMID:24229035

  3. 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

  4. Experimental liver cirrhosis induced by alcohol and iron.

    PubMed Central

    Tsukamoto, H; Horne, W; Kamimura, S; Niemelä, O; Parkkila, S; Ylä-Herttuala, S; Brittenham, G M

    1995-01-01

    To determine if alcoholic liver fibrogenesis is exacerbated by dietary iron supplementation, carbonyl iron (0.25% wt/vol) was intragastrically infused with or without ethanol to rats for 16 wk. Carbonyl iron had no effect on blood alcohol concentration, hepatic biochemical measurements, or liver histology in control animals. In both ethanol-fed and control rats, the supplementation produced a two- to threefold increase in the mean hepatic non-heme iron concentration but it remained within or near the range found in normal human subjects. As previously shown, the concentrations of liver malondialdehyde (MDA), liver 4-hydroxynonenal (4HNE), and serum aminotransferases (ALT, AST) were significantly elevated by ethanol infusion alone. The addition of iron supplementation to ethanol resulted in a further twofold increment in mean MDA, 4HNE, ALT, and AST. On histological examination, focal fibrosis was found < 30% of the rats fed ethanol alone. In animals given both ethanol and iron, fibrosis was present in all, with a diffuse central-central bridging pattern in 60%, and two animals (17%) developed micronodular cirrhosis. The iron-potentiated alcoholic liver fibrogenesis was closely associated with intense and diffuse immunostaining for MDA and 4HNE adduct epitopes in the livers. Furthermore, in these animals, accentuated increases in procollagen alpha 1(I) and TGF beta 1 mRNA levels were found in both liver tissues and freshly isolated hepatic stellate cells, perisinusoidal cells believed to be a major source of extracellular matrices in liver fibrosis. The dietary iron supplementation to intragastric ethanol infusion exacerbates hepatocyte damage, promotes liver fibrogenesis, and produces evident cirrhosis in some animals. These results provide evidence for a critical role of iron and iron-catalyzed oxidant stress in progression of alcoholic liver disease. Images PMID:7615836

  5. 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

  6. 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. PMID:26159280

  7. Liver cirrhosis and liver cancer. A study of their relationship in 2563 autopsies.

    PubMed

    Melato, M; Sasso, F; Zanconati, F

    1993-03-01

    A sample of 2,563 cases of liver cirrhosis diagnosed among 26,879 autopsies performed consecutively in the years 1976/85 was considered in order to study the morphologic feature of the liver cirrhosis and their relationship with primary liver cancer (PLC) outbreak. The study showed that age of patients affected by cirrhosis is a significant risk factor for PLC. In fact, in the 10 years considered, the observed mean annual increase of age at death of the cirrhotic patients was associated with an increase in PLC cases. This may be explained as a well known consequence of the conversion of micronodular type of cirrhosis to mixed and macronodular ones (for which cancer complication is more frequent) but also as a statistically significant higher risk of PLC in the older group of patients affected by micronodular cirrhosis. The older age of cirrhotic patients at death observed in the last few years in the Trieste area is probably correlated to a general European trend: our results, although relative to a restricted geographic area, seem to be of interest in order to identify better the patients at risk of PLC among those affected by cirrhosis. PMID:8388716

  8. 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

  9. Protective effects of Carissa opaca fruits against CCl4-induced oxidative kidney lipid peroxidation and trauma in rat

    PubMed Central

    Sahreen, Sumaira; Khan, Muhammad Rashid; Khan, Rahmat Ali; Alkreathy, Huda Mohammad

    2015-01-01

    Background Carbon tetrachloride (CCl4) is a potent nephrotoxin, as it causes acute as well as chronic toxicity in kidneys. Therefore, this study was carried out to assess the pharmacological potential of different fractions of Carissa opaca fruits on CCl4-induced oxidative trauma in the kidney. Methods The parameters studied in this respect were the kidney function tests viz, serum profile, urine profile, genotoxicity, characteristic morphological findings, and antioxidant enzymatic level of kidneys. Result The protective effects of various fractions of C. opaca fruits against CCl4 administration were reviewed by rat renal function alterations. Chronic toxicity caused by 8-week treatment of CCl4 to the rats significantly decreased the pH level, activities of antioxidant enzymes, and glutathione contents, whereas a significant increase was found in the case of specific gravity, red blood cells, white blood cells, level of urea, and lipid peroxidation in comparison to control group. Administration of various fractions of C. opaca fruit with CCl4 showed protective ability against CCl4 intoxication by restoring the urine profile, activities of antioxidant enzymes, and lipid peroxidation in rat. CCl4 induction in rats also caused DNA fragmentation and glomerular atrophy by means of dilation, disappearance of Bowmen's space, congestion in the capillary loops, dilation in renal tubules, and foamy look of epithelial cells of tubular region, which were restored by co-admiration of various fractions of C. opaca. Conclusion Results revealed that the methanolic fractions of C. opaca are the most potent and helpful in kidney trauma. PMID:26350293

  10. Postreperfusion syndrome during liver transplantation for cirrhosis: outcome and predictors.

    PubMed

    Paugam-Burtz, Catherine; Kavafyan, Juliette; Merckx, Paul; Dahmani, Souhayl; Sommacale, Daniel; Ramsay, Michael; Belghiti, Jacques; Mantz, Jean

    2009-05-01

    During orthotopic liver transplantation (OLT), a marked decrease in blood pressure following unclamping of the portal vein and liver reperfusion is frequently observed and is termed postreperfusion syndrome (PRS). The predictive factors and clinical consequences of PRS are not fully understood. The goal of this study was to identify predictors of PRS and morbidity/mortality associated with its occurrence during OLT in patients with cirrhosis. During a 3-year period, all consecutive OLT procedures performed in patients with cirrhosis were studied. Exclusion criteria were OLT for acute liver failure, early retransplantation, combined liver/kidney transplantation, and living-donor related transplantation. PRS was defined as a decrease in the mean arterial pressure of more than 30% of the value observed in the anhepatic stage, for more than 1 minute during the first 5 minutes after reperfusion of the graft. Transplantation was performed with preservation of the inferior vena cava with or without temporary portocaval shunt. Associations between PRS and donor and recipient demographic data, recipient operative and postoperative outcomes were tested with bivariate statistics. Independent predictors of PRS were determined in multivariable logistic regression analysis. Of the 75 patients included in the study, 20 patients (25%) developed PRS. In a multivariable analysis, absence of a portocaval shunt [odds ratio (95% confidence interval) = 4.42 (1.18-17.6)] and duration of cold ischemia [odds ratio (95% confidence interval) = 1.34 (1.07-1.72)] were independent predictors of PRS. Patients who experienced PRS displayed more postoperative renal failure and lower early (<15 days after OLT) survival (80% versus 96%; P = 0.04). In conclusion, the absence of portocaval shunt and the duration of cold ischemia were independent predictors of intraoperative PRS. PRS was associated with significant adverse postoperative outcome. These results provide realistic clinical targets to improve patient outcome after OLT for cirrhosis. PMID:19399736

  11. Plasma betatrophin levels in patients with liver cirrhosis

    PubMed Central

    Arias-Loste, Maria Teresa; García-Unzueta, Maria Teresa; Llerena, Susana; Iruzubieta, Paula; Puente, Angela; Cabezas, Joaquín; Alonso, Carmen; Cuadrado, Antonio; Amado, José Antonio; Crespo, Javier; Fábrega, Emilio

    2015-01-01

    AIM: To investigate the plasma levels of betatrophin in patients with cirrhosis. METHODS: Forty patients diagnosed at the clinic with liver cirrhosis according to biological, ultrasonographic, or histological criteria were included. The severity of cirrhosis was classified according to Pugh’s modification of Child’s classification and MELD score. Insulin resistance (IR) was assessed by the Homeostasis Model Assessment. A total of 20 patients showed a MELD score higher than 14. The control group consisted in 15 sex-and aged-matched subjects. Fasting blood samples were obtained for subsequent analysis. Serum insulin was determined by Liaison automated immune chemiluminiscence assay (DiaSorin S.p.A.) using a sandwich assay. The sensitivity of the assay was 0.2 μU/mL. The intra and interassay variation coefficients were < 4% and < 10%, respectively. The normal values were between 2 and 17 μU/mL. Human active betatrophin was analyzed by specific quantitative sandwich ELISA (Aviscera Bioscience®). The sensitivity of the assay was 0.4 ng/mL, and the intra and interassay reproducibility were < 6% and < 10%, respectively. RESULTS: Plasma betatrophin levels were significantly increased in patients with cirrhosis compared with those in healthy subjects (P = 0.0001). Betatrophin levels were also associated with disease severity, being higher in Child-Pugh C patients compared to Child-Pugh B (P < 0.0005) and in patients who displayed a MELD score higher than 14 points compared to patients with lower punctuation (P = 0.01). In addition, we found a positive correlation between plasma betatrophin levels and the severity of cirrhosis according to Child-Pugh classification (r = 0.53; P < 0.01) or MELD score (r = 0.45; P < 0.01). In the overall cohort, a moderate correlation between serum betatrophin and plasmatic bilirrubin (r = 0.39; P < 0.01) has been observed, as well as an inverse correlation between betatrophin and albumin (r = -0.41; P < 0.01) or prothrombin time (r = -0.44; P <0.01). Moreover, insulin resistance was observed in 82.5% of the cirrhotic patients. In this group of patients, betatrophin levels were significantly higher than those in the group of patients without IR (P < 0.05). CONCLUSION: Plasma betatrophin is increased in patients with cirrhosis. This increase is related to the severity of cirrhosis, as well as with the emergence of insulin resistance. PMID:26457026

  12. Stage of cirrhosis predicts the risk of liver-related death in patients with low Model for End-Stage Liver Disease scores and cirrhosis awaiting liver transplantation.

    PubMed

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

    2014-10-01

    The Model for End-Stage Liver Disease (MELD) score has reduced predictive ability in patients with cirrhosis and MELD scores ≤ 20. We aimed to assess whether a 5-stage clinical model could identify liver transplantation (LT) candidates with low MELD scores who are at increased risk for death. We conducted a case-control study of subjects with cirrhosis and MELD scores ≤ 20 who were awaiting LT at a single academic medical center between February 2002 and May 2011. Conditional logistic regression was used to evaluate the risk of liver-related death according to the cirrhosis stage. We identified 41 case subjects who died from liver-related causes with MELD scores ≤ 20 within 90 days of death while they were waiting for LT. The cases were matched with up to 3 controls (66 controls in all) on the basis of the listing year, age, sex, liver disease etiology, presence of hepatocellular carcinoma, and MELD score. The cirrhosis stage was assessed for all subjects: (1) no varices or ascites, (2) varices, (3) variceal bleeding, (4) ascites, and (5) ascites and variceal bleeding. The MELD scores were similar for cases and controls. Clinical states contributing to death in cases were: sepsis 49%, spontaneous bacterial peritonitis 15%, variceal bleeding 24%, and hepatorenal syndrome 22%. In a univariate analysis, variceal bleeding [odds ratio (OR) = 5.6, P = 0.003], albumin (OR = 0.5, P = 0.041), an increasing cirrhosis stage (P = 0.003), reaching cirrhosis stage 2, 3, or 4 versus lower stages (OR = 3.6, P = 0.048; OR = 7.4, P < 0.001; and OR = 4.1, P = 0.008), a sodium level < 135 mmol/L (OR = 3.4, P = 0.006), and hepatic encephalopathy (OR = 2.3, P = 0.082) were associated with liver-related death. In a multivariate model including the cirrhosis stage, albumin, sodium, and hepatic encephalopathy, an increasing cirrhosis stage (P = 0.010) was independently associated with liver-related death. In conclusion, assessing the cirrhosis stage in patients with low MELD scores awaiting LT may help to select candidates for more aggressive monitoring or for living or extended criteria donation. PMID:24916539

  13. 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

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

    PubMed

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

    2013-02-01

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

  15. Liver Cancer: Connections with Obesity, Fatty Liver, and Cirrhosis.

    PubMed

    Marengo, Andrea; Rosso, Chiara; Bugianesi, Elisabetta

    2016-01-14

    The burden of hepatocellular carcinoma (HCC), the most common form of liver cancer, is steadily growing because obesity, type 2 diabetes, and nonalcoholic fatty liver disease (NAFLD) are replacing viral- and alcohol-related liver disease as major pathogenic promoters. The most worrisome aspects of these new risk factors are their large spread in the general population and their link with HCC arising in noncirrhotic livers. HCC may be the presenting feature of an asymptomatic nonalcoholic steatohepatitis (NASH), the progressive form of NAFLD. The HCC risk connected to metabolic factors has been underestimated so far, and a poorer surveillance has prevented an adequate treatment. Systemic and hepatic molecular mechanisms involved in obesity- and NAFLD-induced hepatocarcinogenesis as well as potential early markers of HCC are being extensively investigated. This review summarizes current evidence linking obesity, NAFLD and liver cancer, discusses its clinical impact and describes the main mechanisms underlying this complex relationship. PMID:26473416

  16. 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

  17. Non-invasive diagnosis of liver fibrosis and cirrhosis

    PubMed Central

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

    2015-01-01

    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. PMID:26556987

  18. 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

  19. THE IMMUNOPATHOLOGY OF LIVER GRANULOMAS IN PRIMARY BILIARY CIRRHOSIS

    PubMed Central

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

    2013-01-01

    Liver granuloma are recognized as specific histological features in primary biliary cirrhosis but their significance remains enigmatic. Similarly, there are limited data on the impact of hyper-IgM on granulomas while in both cases a role of B cells has been hypothesized. The present study investigates a significant number of tissue samples from PBC and control livers as well as other granulomatous diseases to investigate the representation of dendritic cells and the role of IgM in PBC-associated granulomas. We demonstrate that the classical cellular marker for dendritc cells CD11c is highly expressed in hepatic granulomas from PBC liver samples, along with markers of immature dendritic cells, i.e. CD11b, low MHC II, IL-23 and CCR7 and CD83 expression, and C1q high expression. PBC patients with granulomas had significantly higher serum IgM levels and PBC granulomas were surrounded by B and plasma cells. Using ad in vitro approach we further demonstrate that IgM inhibits LPS-induced maturation of myeloid dendritic cells, as well as LPS-induced activation of NF-κB and the expression of proinflammatory cytokines such as TNF-α, IL-12, and IFN-β. In conclusion, we propose that immature dendritic cells are key factors in liver granulomas and that the commonly observed hyper-IgM may contribute to their appearance in patients with PBC. PMID:22727562

  20. 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

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

    PubMed Central

    Chang, Ji Hong; Song, Kijun

    2012-01-01

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

  2. 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

  3. 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

  4. Resistant ascites in alcoholic liver cirrhosis: course and prognosis.

    PubMed

    Capone, R R; Buhac, I; Kohberger, R C; Balint, J A

    1978-10-01

    A group of 29 patients with decompensated cirrhosis of the liver who retained a large amount of ascites under a hospital regimen during two months or longer was identified. The prognosis for this selected group of patients, while grave [during continuous hospitalization 11 out of 29 patients (= 38%) died], is not without hope: 18 patients (62%) improved and could be discharged from the hospital. Their further course was influenced by resumption of alcohol usage. Five of 11 (45.4%) who resumed drinking died due to hepatic causes within 10 months. Of the remaining six only one lost his ascites. Those who abstained (7 patients) remained alive for an average follow-up of 33 months and all lost their ascites. Alcohol resumption significantly decreased both survival (P less than 0.05) and ascites resorption (P less than 0.0015). Continued abstinence from alcohol may thus obviate the need for surgical measures to relieve ascites in these patients. PMID:717345

  5. 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.

  6. Osteoporosis in primary biliary cirrhosis of the liver

    PubMed Central

    Raszeja-Wyszomirska, Joanna

    2014-01-01

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

  7. Brain Natriuretic Peptide in Liver Cirrhosis and Fatty Liver: Correlation with Cardiac Performance

    PubMed Central

    Metwaly, Amna; khalik, Ashraf Abdel; Nasr, Fatma Mohammad; Sabry, Amal Ismail; Gouda, Mohamed Fathy; Hassan, Mona

    2016-01-01

    Objective The aims of the present study were to assess the serum BNP level in patients with post hepatitis C liver cirrhosis and patients with fatty liver and to determine the correlation between BNP and the severity of liver disease and cardiac performance. Methods The study was conducted on 140 subjects subdivided into 3 groups: group 1 included 60 patients having post hepatitis C virus (HCV) liver cirrhosis; group 2 included 60 patients with nonalcoholic fatty liver disease (NAFLD); and group 3 included 20 healthy volunteers serving as a control group. All patients and volunteers were subjected to full physical examinations, laboratory evaluation of hemoglobin percent, liver and renal function tests, serum electrolytes, cholesterol, triglyceride, HBs antigen, HCV antibody and serum BNP levels, ECG, abdominal ultrasonography, and echocardiography. Results There was a significant increase in the BNP level in cirrhotic patients compared to the other two groups (p = 0.000), and it was correlated with the severity of liver disease assigned as Child’s classification (p = 0.000). Also, there was a significant increase in the BNP level in cirrhotic patients with decompensation components compared to those without decompensation components (p = 0.000), history of hepatic encephalopathy (p = 0.000), history of variceal bleeding (p = 0.000), history of spontaneous bacterial peritonitis (p = 0.000), presence of ascites (p = 0.000) and portal vein diameter > 11 mm in abdominal ultrasound (p = 0.000), and prolonged QTc interval in ECG (p = 0.011). There was a significant increase in serum BNP in patients with cirrhosis with the following echocardiographic findings: IVST > 11 mm, PWT > 11 mm, LA diameter > 40 mm, EF% < 54%, and E/A ratio < 1 compared to those without these echocardiographic findings (p = 0.000). Conclusion BNP level increases in post hepatitis C cirrhotic patients and tends to decrease in fatty liver disease patients, and it is correlated with both the severity of liver disease and the morpho-functional cardiac changes. Given the ever-increasing prevalence of liver cirrhosis and fatty liver disease worldwide, it is important to understand the benefits and limitations of BNP as a heart failure biomarker in hepatic patients, where the relationship between BNP level and myocardial function is complex and is altered by the liver disease. PMID:27054009

  8. Panhypopituitarism due to Absence of the Pituitary Stalk: A Rare Aetiology of Liver Cirrhosis

    PubMed Central

    Gonzalez Rozas, Marta; Hernanz Roman, Lidia; Gonzalez, Diego Gonzalez; Pérez-Castrillón, José Luis

    2016-01-01

    Studies have established a relationship between hypothalamic-pituitary dysfunction and the onset of liver damage, which may occasionally progress to cirrhosis. Patients with hypopituitarism can develop a metabolic syndrome-like phenotype. Insulin resistance is the main pathophysiological axis of metabolic syndrome and is the causal factor in the development of nonalcoholic fatty liver disease (NAFLD). We present the case of a young patient with liver cirrhosis of unknown aetiology that was finally attributed to panhypopituitarism. PMID:27213061

  9. A study of carbohydrate metabolism in postnecrotic cirrhosis liver.

    PubMed

    Yeung, R T; Wang, C C

    1974-11-01

    Intravenous glucose tolerance, insulin tolerance, tolbutamide, and glucagon tests were carried out in 21 patients with postnecrotic cirrhosis. Based arbitrarily on the bromsulphthalein retention they were divided into group A, nine patients with less impaired liver function, and group B, 12 patients with greater impairment of liver function. Intravenous glucose and insulin tolerances were reduced in both groups. The hypoglycaemic effect of tolbutamide was similar in the controls and in both groups of cirrhotic patients but this was achieved at higher plasma insulin levels in group B indicating resistance of the liver to the effect of endogenous insulin. The blood glucose response to glucagon was markedly impaired in group B patients which is consistent with this hypothesis. In contrast to the insulin response to glucose and tolbutamide, the insulin response to glucagon was reduced in the cirrhotic patients. Fasting human growth hormone and free fatty acid levels were elevated in both groups but they were not considered to be important factors in the production of insulin resistance. PMID:4455570

  10. Liver cirrhosis due to autoimmune hepatitis combined with systemic sclerosis.

    PubMed

    You, Byung Chul; Jeong, Soung Won; Jang, Jae Young; Goo, So Mi; Kim, Sang Gyune; Kim, Young Seok; Jeon, Chan Hong; Jeen, Yoon Mi

    2012-01-01

    Systemic sclerosis (SSc) is a chronic systemic disease that affects the skin, lungs, heart, gastrointestinal tract, kidneys, and musculoskeletal system. Although up to 90% of patients with scleroderma have been estimated to have gastrointestinal involvement, liver disease has been reported only rarely. A 51-year-old woman was hospitalized due to esophageal variceal bleeding. Her serum was positive for anti-nuclear antibody and anti-centromere antibody. Sclerodactyly was noted on both hands, and she had recently developed Raynaud's syndrome. Punch biopsy of the hand showed hyperkeratosis, regular acanthosis, and increased basal pigmentation in the epidermis, and thick pale collagenous bundles in the dermis. Liver biopsy showed chronic active hepatitis with bridging fibrosis. Consequently, she was diagnosed with liver cirrhosis due to autoimmune hepatitis (AIH) combined with SSc. AIH had subsided after administration of prednisolone at 40 mg per day. She received 5-10 mg/day of prednisolone as an outpatient, and her condition has remained stable. Patients with either AIH or SSc should be monitored for further development of concurrent autoimmune diseases. The early diagnosis of AIH combined with SSc will be helpful in achieving optimal management. PMID:22289955

  11. Serum selenium concentration in patients with liver cirrhosis and hepatocellular carcinoma.

    PubMed

    Buljevac, M; Romić, Z; Vucelić, B; Banić, M; Krznarić, Z; Plesko, S

    1996-01-01

    The aim of the study was to investigate the serum selenium concentration in patients with liver cirrhosis and hepatocellular carcinoma. A total of 59 patients, 49 with liver cirrhosis and 10 with liver cirrhosis and coexistent hepatocellular carcinoma, as well as 202 healthy volunteers entered the study. In the patients with liver cirrhosis and in those with liver cirrhosis and coexistent hepatocellular carcinoma, serum selenium concentrations were significantly lower (39.28 +/- 13.99 and 42.00 +/- 10.59 g/L, respectively), when compared to the group of healthy volunteers (66. 79 +/- 9.13 g/L) (p < 0.001). There was no significant difference in serum selenium concentrations between the two patient groups. In the group of patients with liver cirrhosis positive correlation was found between serum selenium and albumin concentrations, and negative correlation between serum selenium and bilirubin (p < 0.05 and p < 0.01, respectively). There was no correlation of serum selenium concentration with fibrinogen and prothrombin time. Results of the study suggested the possible important nutritive and protective role of selenium in the patients with liver cirrhosis and coexistent hepatocellular carcinoma, as well as the potential need of selenium supplementation in these patients. PMID:8776109

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

    PubMed Central

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

    2014-01-01

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

  13. 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. PMID:26408009

  14. Liver cirrhosis: changes of Doppler waveform of hepatic veins.

    PubMed

    Bolondi, L; Li Bassi, S; Gaiani, S; Zironi, G; Benzi, G; Santi, V; Barbara, L

    1991-02-01

    The authors compared the Doppler ultrasonographic pattern of hepatic veins (HVs) in a group of 60 patients affected by liver cirrhosis and in 65 healthy subjects comparable for sex and age to (a) detect possible differences in HV waveform in the two groups and (b) investigate the relationship of these differences with the severity of the disease (according to Child-Pugh classification) and the modifications of systemic hemodynamics. The waveform of HVs was arbitrarily classified into three patterns: HV0, a normal waveform; HV1, lower oscillations without the reversed phase; and HV2, completely flat waveform. The resistivity index of the superior mesenteric artery, reflecting the peripheral splanchnic impedance and the hyperdynamic circulation, was also measured in a subgroup of 45 cirrhotic patients. The waveform of HVs in all healthy subjects corresponded to the HV0 pattern. Among cirrhotic patients, HV0 was found in 30 (50%), HV1 in 19 (31.7%), and HV2 in 11 (81.3%). The severity of functional impairment was greatest in the HV2 group and least in the HV0 group. This was significantly correlated with the decrease of the resistivity index in the superior mesenteric artery in the subgroup of 45 patients. Changes in the normal HV waveform could be considered a useful adjunctive tool for the noninvasive evaluation of liver disease. The pathophysiology of these changes in HV blood flow is still unclear. The significant correlation with the severity of the disease and with the decrease of splanchnic resistances indicates that these changes in the HV waveform occur in the presence of marked rearrangements of liver tissue and of hyperdynamic systemic circulation. PMID:1987617

  15. Pathogenesis and treatment of liver fibrosis in alcoholics: 1996 update.

    PubMed

    Lieber, C S

    1997-01-01

    Fibrosis is a common end stage for most chronic liver diseases. It results from an imbalance between collagen production and degradation. One promising approach for prevention and treatment is the stimulation of collagenolytic processes. In nonhuman primates it was found that polyenylphosphatidylcholine (PPC), extracted from soybeans, protects against alcohol-induced fibrosis and cirrhosis and prevents the associated hepatic phosphatidylcholine (PC) depletion by increasing 18:2-containing PC species; it also attenuates the transformation of lipocytes into collagen-producing transitional cells. Furthermore, it increases collagen breakdown, as shown in cultured lipocytes enriched with pure dilinoleoyl PC (18:2-18:2 PC), the main PC species present in the extract, which may be the active ingredient. Since PC appears to promote the breakdown of collagen, there is reasonable hope that this treatment may affect not only the progression of the disease, but may also reverse preexisting fibrosis, as demonstrated for CCl4-induced cirrhosis in the rat. Therefore, PPC may be useful for the management of fibrosis of alcoholic and nonalcoholic etiologies as well. S-Adenosylmethionine opposes CCl4-induced fibrosis and can affect some of the consequences of the ethanol-induced oxidative stress in experimental animals and in man. Anti-inflammatory medications (corticosteroids, colchicine) are also being used and agents that interfere with collagen synthesis, such as inhibitors of prolyl-4-hydroxylase and antioxidants, are being tested. PMID:9101129

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

    PubMed

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

    2014-06-01

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

  17. 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. PMID:26998906

  18. 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

  19. Nutrition and exercise in the management of liver cirrhosis

    PubMed Central

    Toshikuni, Nobuyuki; Arisawa, Tomiyasu; Tsutsumi, Mikihiro

    2014-01-01

    Liver cirrhosis (LC) patients often have protein-energy malnutrition (PEM) and decreased physical activity. These conditions often lead to sarcopenia, which is the loss of skeletal muscle volume and increased muscle weakness. Recent studies have demonstrated that PEM and sarcopenia are predictors for poor survival in LC patients. Nutrition and exercise management can improve PEM and sarcopenia in those patients. Nutrition management includes sufficient dietary intake and improved nutrient metabolism. With the current high prevalence of obesity, the number of obese LC patients has increased, and restriction of excessive caloric intake without the exacerbation of impaired nutrient metabolism is required for such patients. Branched chain amino acids are good candidates for supplemental nutrients for both obese and non-obese LC patients. Exercise management can increase skeletal muscle volume and strength and improve insulin resistance; however, nutritional status and LC complications should be assessed before an exercise management regimen is implemented in LC patients. The establishment of optimal exercise regimens for LC patients is currently required. In this review, we describe nutritional status and its clinical impact on the outcomes of LC patients and discuss general nutrition and exercise management in LC patients. PMID:24966599

  20. 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. PMID:24966599

  1. 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

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

    PubMed Central

    Gonalves, Patricia Lofego; da Penha Zago-Gomes, Maria; Marques, Carla Couzi; Mendona, Ana Tereza; Gonalves, 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 53.212.6 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

  3. Regression of esophageal varices during entecavir treatment in patients with hepatitis-B-virus-related liver cirrhosis

    PubMed Central

    Jwa, Hye Young; Cho, Yoo-Kyung; Choi, Eun Kwang; Kim, Heung Up; Song, Hyun Joo; Na, Soo-Young; Boo, Sun-Jin; Jeong, Seung Uk; Kim, Bong Soo; Lee, Byoung-Wook; Song, Byung-Cheol

    2016-01-01

    Recent studies suggest that liver cirrhosis is reversible after administering oral nucleos(t)ide analogue therapy to patients with hepatitis B virus (HBV) infection. However, few studies have addressed whether esophageal varices can regress after such therapy. We report a case of complete regression of esophageal varices during entecavir therapy in patients with HBV-related liver cirrhosis, suggesting that complications of liver cirrhosis such as esophageal varices can regress after the long-term suppression of HBV replication. PMID:27044771

  4. Proinflammatory Cytokines (IL-1α, IL-6) and Hepatocyte Growth Factor in Patients with Alcoholic Liver Cirrhosis

    PubMed Central

    Prystupa, Andrzej; Kiciński, Paweł; Sak, Jarosław; Boguszewska-Czubara, Anna; Toruń-Jurkowska, Anna; Załuska, Wojciech

    2015-01-01

    Background. The aim of the study was to assess the activity of interleukin-1α, interleukin-6, and hepatocyte growth factor protein (HGF) in serum of patients with alcoholic liver cirrhosis. Materials and Methods. Sixty patients with alcoholic liver cirrhosis treated in various hospitals were randomly enrolled. The stage of cirrhosis was assessed according to the Child-Turcotte-Pugh scoring system. The control group consisted of ten healthy persons without liver disease, who did not drink alcohol. Additionally, the group of alcoholics without liver cirrhosis was included in the study. The activity of interleukin-1α, interleukin-6, and HGF in blood plasma of patients and controls was measured using the sandwich enzyme immunoassay technique with commercially available quantitative ELISA test kits. Results. Higher concentrations of HGF protein were demonstrated in patients with Child class B and Child class C liver cirrhosis, compared to controls and alcoholics without liver cirrhosis. Moreover, significantly higher concentrations of HGF protein were found in patients with Child class C liver cirrhosis compared to patients with Child class A liver cirrhosis (p < 0.05). The concentrations of interleukin-1α in patients with Child class B and Child class C liver cirrhosis were significantly higher in comparison with controls. Significantly higher concentrations of interleukin-6 were demonstrated in Child class C, compared to Child class A. PMID:26448742

  5. Bleeding complications in critically ill patients with liver cirrhosis

    PubMed Central

    Cho, Jaeyoung; Choi, Sun Mi; Yu, Su Jong; Park, Young Sik; Lee, Chang-Hoon; Lee, Sang-Min; Yim, Jae-Joon; Yoo, Chul-Gyu; Kim, Young Whan; Han, Sung Koo; Lee, Jinwoo

    2016-01-01

    Background/Aims: Patients with liver cirrhosis (LC) are at risk for critical events leading to Intensive Care Unit (ICU) admission. Coagulopathy in cirrhotic patients is complex and can lead to bleeding as well as thrombosis. The aim of this study was to investigate bleeding complications in critically ill patients with LC admitted to a medical ICU (MICU). Methods: All adult patients admitted to our MICU with a diagnosis of LC from January 2006 to December 2012 were retrospectively assessed. Patients with major bleeding at the time of MICU admission were excluded from the analysis. Results: A total of 205 patients were included in the analysis. The median patient age was 62 years, and 69.3% of the patients were male. The most common reason for MICU admission was acute respiratory failure (45.4%), followed by sepsis (27.3%). Major bleeding occurred in 25 patients (12.2%). The gastrointestinal tract was the most common site of bleeding (64%), followed by the respiratory tract (20%). In a multivariate analysis, a low platelet count at MICU admission (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.97 to 0.99) and sepsis (OR, 8.35; 95% CI, 1.04 to 67.05) were independent risk factors for major bleeding. The ICU fatality rate was significantly greater among patients with major bleeding (84.0% vs. 58.9%, respectively; p = 0.015). Conclusions: Major bleeding occurred in 12.2% of critically ill cirrhotic patients admitted to the MICU. A low platelet count at MICU admission and sepsis were associated with an increased risk of major bleeding during the MICU stay. Further study is needed to better understand hemostasis in critically ill patients with LC. PMID:26805633

  6. 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. PMID:26833199

  7. 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.

  8. Challenges and Management of Liver Cirrhosis: Pathophysiology of Renal Dysfunction in Cirrhosis.

    PubMed

    Solà, Elsa; Ginès, Pere

    2015-01-01

    Kidney dysfunction is a common complication of patients with advanced cirrhosis and is associated with poor prognosis. Patients with advanced cirrhosis show circulatory dysfunction characterized by reduced systemic vascular resistance due to splanchnic arterial vasodilation, which is caused by portal hypertension. The progressive reduction in systemic vascular resistance leads to effective arterial hypovolemia. In order to maintain arterial pressure within normal limits in this setting, there is activation of systemic vasoconstrictor systems, including the renin-angiotensin-aldosterone system, sympathetic nervous system and, in late stages, nonosmotic hypersecretion of vasopressin. Although these systems have positive effects in maintaining arterial pressure, they have a negative influence on kidney function, leading to the retention of sodium and solute-free water, and in late stages of the disease an intense kidney vasoconstriction develops, leading to decrease of the glomerular filtration rate and the development of hepatorenal syndrome (HRS). Moreover, bacterial translocation and the existence of a systemic inflammatory state in patients with advanced cirrhosis may play a role in the impairment of circulatory function. HRS is a unique cause of kidney failure of functional origin that develops in patients with cirrhosis. However, besides HRS, patients with cirrhosis may develop kidney failure due to other causes, including bacterial infections, prerenal kidney failure, shock, use of nephrotoxic drugs or intrinsic kidney diseases. Considering the existence of circulatory dysfunction and some degree of kidney vasoconstriction, patients with advanced cirrhosis have fragile kidney function and are susceptible to easily developing kidney failure associated with other complications of the disease, particularly bacterial infections and gastrointestinal bleeding. PMID:26159270

  9. 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

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

    PubMed

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

    2013-10-01

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

  11. Short report: effect of ranitidine on duodenal ulcer healing in patients with cirrhosis of the liver.

    PubMed

    Ljubicic, W; Bilić, A; Roić, D

    1993-04-01

    The effect of ranitidine (300 mg daily) on the healing of acute duodenal ulcer was investigated in patients with and without cirrhosis of the liver. Of the 109 patients who entered the study, two patients from each group were excluded. Healing rates after 4 and 8 weeks were significantly different between patients with cirrhosis and controls (4- and 8-week healing rates in cirrhotics and non-cirrhotics: 49 and 69%, and 71 and 91%, respectively). This study demonstrates that duodenal ulcer healing is delayed in patients with cirrhosis. PMID:8485276

  12. Alcohol consumption and the risk of developing liver cirrhosis: implications for future research.

    PubMed

    Parrish, K M; Higuchi, S; Dufour, M C

    1991-01-01

    Studies of the association of alcohol consumption and liver cirrhosis were reviewed, focusing on possible biases of study design. Daily alcohol consumption (as opposed to intermittent binge drinking), amount of alcohol consumed, longer duration of alcohol abuse, and being female were associated with the increased risk of cirrhosis. Follow-up studies reviewed failed to take full advantage of the study design and added little information to existing literature. Retrospective studies were relatively free of bias and are valuable tools in estimating the risk of cirrhosis. Future research needs to take the following variables into consideration: better ascertainment of alcohol consumption, consumption patterns, changes in alcohol consumption, gender, and body weight. PMID:1821289

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

    PubMed

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

    2016-06-01

    The metabolic loading is heavier in liver especially when injured or inflammation. San Huang Shel Shin Tang (SHSST) was an old traditional herbal decoction, which composed with Rheum officinale Baill, Scutellaria baicalnsis Geprgi and Coptis chinensis Franch (1:1:2 in weight), can provide a liver protection effects. We used a beta-cyclodextrin (β-CD) drug modification method in reduce of the necessary dose of the SHSST. As the results, the FAS-FADD expressions leaded apoptosis in CCl4 intraperitoneal (IP) injection induced acute liver injury in rats. Silymarin, baicalein, SHSST, and SHSST β-CD complex (SHSSTc) pretreatments protected liver through the decreasing of the expressions of FAS-FADD and downstream caspase-3 and caspase-8. Particularly, SHSSTc (30 mg/kg day) treatment enhanced cell survival pathway activation through the PI3K, Akt and Bad phosphorylation. Compared with SHSST as well as silymarin and baicalein, SHSSTc provided a magnificent liver protection effect, especially in survival pathway activation/TUNEL-apoptotic cell reduction/serum cholesterol level suppression. All these data suggested that β-CD complex modified the SHSST and promoted the bioavailability and liver protection effects. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 663-670, 2016. PMID:25447754

  14. Cirrhosis

    MedlinePlus

    ... weight loss Nausea or belly pain Small, red spider-like blood vessels on the skin As liver ... result of too much fluid Reddened palms Red spider-like blood vessels on the skin Small testicles ...

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

    PubMed Central

    Turunen, U; Malkamäki, M; Valtonen, V V; Larinkaŕi, U; Pikkarainen, P; Salaspuro, M P; Mäkelä, P H

    1981-01-01

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

  16. 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). PMID:27017731

  17. The Safety and Benefit of Statins in Liver Cirrhosis: a Review.

    PubMed

    Souk, K; Al-Badri, M; Azar, S T

    2015-11-01

    Dyslipidemia is a primary, major risk factor for coronary artery disease CAD. The prevalence of dyslipidemia had decreased over the past 30 years, which may in part be explained by the steady increase in the use of lipid-lowering drug therapy, especially statins. Cardiovascular risk has been shown to be greater in liver disease (20% in the liver cirrhosis vs. 12% in the general population), where statins can play an important role as a primary and secondary prevention for CAD. Given patients with chronic liver disease, especially liver cirrhosis are at risk of decreased hepatic clearance, there is concern that this patient population may be at higher risk for complications from statin therapy. Several retrospective studies showed that statin use in chronic liver disease and cirrhosis is safe, and even it was associated with lower mortality and lower rate of hepatic decompensation. This review discusses the safety and the different mechanisms where statins can decrease the rate of complications in liver cirrhosis, including portal hypertension, sepsis and the incidence of hepatocellular carcinoma. PMID:26600051

  18. 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

  19. Genetics Home Reference: cryptogenic cirrhosis

    MedlinePlus

    ... Liver Disease/Cirrhosis Johns Hopkins Medicine: Nonalcoholic Fatty Liver Disease Merck Manual Professional Version: Cirrhosis Patient Support and Advocacy Resources (3 links) American Liver Foundation: ...

  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 ? 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. Stem Cells 2016;34:135-147. PMID:26389810

  1. 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.

  2. Serum and intestinal secretory IgA in alcoholic cirrhosis of the liver.

    PubMed Central

    Pelletier, G; Briantais, M J; Buffet, C; Pillot, J; Etienne, J P

    1982-01-01

    Serum and intestinal secretory IgA (sIgA) were investigated in control subjects and patients with alcoholic cirrhosis of the liver. Intestinal secretions were sampled by intraluminal perfusion with a balloon catheter. Monomeric IgA and sIgA were assayed by reversed radial immunodiffusion and nephelometry after separation by Ultrogel column filtration. High levels of serum sIgA were found only in patients with severe cirrhosis accompanied by jaundice. The intestinal rate of secretion of sIgA measured in these patients was significantly lower than that observed in either controls or the patients with compensated cirrhosis. Such an intestinal sIgA deficiency, which could be explained either by a fall in small intestinal immunocyte synthesis or by a defect in the transenterocyte transport system, could be partially responsible for the high incidence of intestinal infection observed in severe cirrhosis. PMID:7076021

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

    PubMed

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

    2009-08-01

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

  4. Non-invasive diagnosis of liver cirrhosis: a comparison between four discriminant functions.

    PubMed

    Corrao, G; Carle, F; Valenti, M; Aricò, S; Galatola, G; Tabone, M; Di Orio, F

    1993-01-01

    We assessed the performance of 4 methods of discriminant analysis using as independent variables the age and 16 serum tests, for correctly identifying patients with liver cirrhosis among hospitalized patients affected by chronic liver disease without signs of liver failure; 290 patients entered this study: on the basis of laparoscopy with or without liver biopsy, 152 patients had a diagnosis of liver cirrhosis and 138 were classified as chronic hepatitic patients. Due to the non-multinormal distribution of the variables used and to the unequality of the variance-covariance matrices, we compared the following 4 methods: linear discriminant function, quadratic discriminant function, non-parametric discriminant function and logistic regression. The Receiver Operating Characteristic (ROC) analysis was used to compare diagnostic ability of the assessed methods: the quadratic discriminant function was the best performing method. The predictive ability of this function was compared to that reported for percutaneous liver biopsy, showing that this simple statistical method using age and biochemical tests can efficiently identify liver cirrhosis in the setting of chronic liver disease, reducing the need for invasive diagnostic procedures. PMID:8493390

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

    PubMed Central

    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. PMID:26107182

  6. 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. PMID:26107182

  7. 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/AIMSAlcoholic 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.?METHODSThe results for 53patients transplanted for alcoholic cirrhosis between 1989and 1994were compared with those for 48patients 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.?RESULTSRecovery 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%.?CONCLUSIONThe 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

  8. 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

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

    PubMed Central

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

    2012-01-01

    Background. Experimental research in hepatology has focused on developing traditional medicines into potential pharmacological solutions aimed at protecting liver from cirrhosis. Along the same line, this study investigated the effects of ethanol-based extract from a traditional medicine plant Boesenbergia rotunda (BR) on liver cirrhosis. Methodology/Results. The BR extract was tested for toxicity on 3 groups of rats subjected to vehicle (10% Tween 20, 5 mL/kg) and 2g/kg and 5g/kg doses of the extract, respectively. Next, experiments were conducted on a rat model of cirrhosis induced by thioacetamide injection. The rats were divided into five groups and, respectively, administered orally with 10% Tween-20 (5 mL/kg) (normal control group), 10% Tween-20 (5 mL/kg) (cirrhosis control group), 50 mg/kg of silymarin (reference control group), and 250 mg/kg and 500 mg/kg of BR extract (experimental groups) daily for 8 weeks. The rats in normal group were intraperitoneally injected with sterile distilled water (1 mL/kg) 3 times/week, and those in the remaining groups were injected intraperitoneally with thioacetamide (200 mg/kg) thrice weekly. At the end of the 8 weeks, the animals were sacrificed and samples were collected for comprehensive histopathological, coagulation profile and biochemical evaluations. Also, the antioxidant activity of the BR extract was determined and compared with that of silymarin. Data from the acute toxicity tests showed that the extract was safe to use. Histological analysis of the livers of the rats in cirrhosis control group revealed uniform coarse granules on their surfaces, hepatocytic necrosis, and lymphocytes infiltration. But, the surfaces morphologically looked much smoother and the cell damage was much lesser in those livers from the normal control, silymarin and BR-treated groups. In the high-dose BR treatment group, the livers of the rats exhibited nearly normal looking lobular architecture, minimal inflammation, and minimal hepatocyte damage, the levels of the serum biomarkers and liver enzymes read nearly normal, and these results were all comparable to those observed or quantified from the normal and silymarin-treated groups. The BR extract had the antioxidant activity about half of what was recorded for silymarin. Conclusion. The progression of the liver cirrhosis can be intervened using the ethanol-based BR extract, and the liver's status quo of property, structure, and function can be preserved. This capability of the extract warrants further studies exploring the significance of its pharmacologic potential in successfully treating the liver cirrhosis in humans. PMID:22988470

  10. Hemostatic balance in patients with liver cirrhosis: Report of a consensus conference.

    PubMed

    2016-05-01

    Patients with cirrhosis present with hemostatic alterations secondary to reduced availability of pro-coagulant and anti-coagulant factors. The net effect of these changes is a rebalanced hemostatic system. The Italian Association of the Study of the Liver (AISF) and the Italian Society of Internal Medicine (SIMI) promoted a consensus conference on the hemostatic balance in patients with cirrhosis. The consensus process started with the review of the literature by a scientific board of experts and ended with a formal consensus meeting in Rome in December 2014. The statements were graded according to quality of evidence and strength of recommendations, and approved by an independent jury. The statements presented here highlight strengths and weaknesses of current laboratory tests to assess bleeding and thrombotic risk in cirrhotic patients, the pathophysiology of hemostatic perturbations in this condition, and outline the optimal management of bleeding and thrombosis in patients with liver cirrhosis. PMID:27012444

  11. Non-invasive diagnostic and prognostic evaluation of liver cirrhosis and portal hypertension.

    PubMed

    Berzigotti, Annalisa; Ashkenazi, Eyal; Reverter, Enric; Abraldes, Juan G; Bosch, Jaime

    2011-01-01

    Cirrhosis is the final stage of most of chronic liver diseases, and is almost invariably complicated by portal hypertension, which is the most important cause of morbidity and mortality in these patients. This review will focus on the non-invasive methods currently used in clinical practice for diagnosing liver cirrhosis and portal hypertension. The first-line techniques include physical examination, laboratory parameters, transient elastography and Doppler-US. More sophisticated imaging methods which are less commonly employed are CT scan and MRI, and new technologies which are currently under evaluation are MR elastography and acoustic radiation force imaging (ARFI). Even if none of them can replace the invasive measurement of hepatic venous pressure gradient and the endoscopic screening of gastroesophageal varices, they notably facilitate the clinical management of patients with cirrhosis and portal hypertension, and provide valuable prognostic information. PMID:22045398

  12. 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

  13. 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

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

    PubMed Central

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

    2015-01-01

    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. PMID:26139982

  15. 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. PMID:26139982

  16. Impaired Gut-Liver-Brain Axis in Patients with Cirrhosis.

    PubMed

    Ahluwalia, Vishwadeep; Betrapally, Naga S; Hylemon, Phillip B; White, Melanie B; Gillevet, Patrick M; Unser, Ariel B; Fagan, Andrew; Daita, Kalyani; Heuman, Douglas M; Zhou, Huiping; Sikaroodi, Masoumeh; Bajaj, Jasmohan S

    2016-01-01

    Cirrhosis is associated with brain dysfunction known as hepatic encephalopathy (HE). The mechanisms behind HE are unclear although hyperammonemia and systemic inflammation through gut dysbiosis have been proposed. We aimed to define the individual contribution of specific gut bacterial taxa towards astrocytic and neuronal changes in brain function using multi-modal MRI in patients with cirrhosis. 187 subjects (40 controls, 147 cirrhotic; 87 with HE) underwent systemic inflammatory assessment, cognitive testing, stool microbiota analysis and brain MRI analysis. MR spectroscopy (MRS) changes of increased Glutamate/glutamine, reduced myo-inositol and choline are hyperammonemia-associated astrocytic changes, while diffusion tensor imaging (DTI) demonstrates changes in neuronal integrity and edema. Linkages between cognition, MRI parameters and gut microbiota were compared between groups. We found that HE patients had a significantly worse cognitive performance, systemic inflammation, dysbiosis and hyperammonemia compared to controls and cirrhotics without HE. Specific microbial families (autochthonous taxa negatively and Enterobacteriaceae positively) correlated with MR spectroscopy and hyperammonemia-associated astrocytic changes. On the other hand Porphyromonadaceae, were only correlated with neuronal changes on DTI without linkages with ammonia. We conclude that specific gut microbial taxa are related to neuronal and astrocytic consequences of cirrhosis-associated brain dysfunction. PMID:27225869

  17. Analysis of Serum Haptoglobin Fucosylation in Hepatocellular Carcinoma and Liver Cirrhosis of Different Etiologies

    PubMed Central

    2015-01-01

    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 ?L 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. PMID:24807840

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

    PubMed Central

    2010-01-01

    Background Domestic dogs and cats are very well known to develop chronic hepatic diseases, including hepatic lipidosis and cirrhosis. Ultrasonographic examination is extensively used to detect them. However, there are still few reports on the use of the ultrasound B-mode scan in correlation with histological findings to evaluate diffuse hepatic changes in rodents, which represent the most important animal group used in experimental models of liver diseases. The purpose of this study was to determine the reliability of ultrasound findings in the assessment of fatty liver disease and cirrhosis when compared to histological results in Wistar rats by following up a murine model of chronic hepatic disease. Results Forty Wistar rats (30 treated, 10 controls) were included. Liver injury was induced by dual exposure to CCl4 and ethanol for 4, 8 and 15 weeks. Liver echogenicity, its correlation to the right renal cortex echogenicity, measurement of portal vein diameter (PVD) and the presence of ascites were evaluated and compared to histological findings of hepatic steatosis and cirrhosis. Liver echogenicity correlated to hepatic steatosis when it was greater or equal to the right renal cortex echogenicity, with a sensitivity of 90%, specificity of 100%, positive and negative predictive values of 100% and 76.9% respectively, and accuracy of 92.5%. Findings of heterogeneous liver echogenicity and irregular surface correlated to liver cirrhosis with a sensitivity of 70.6%, specificity of 100%, positive and negative predictive values of 100% and 82.1% respectively, and accuracy of 87.5%. PVD was significantly increased in both steatotic and cirrhotic rats; however, the later had greater diameters. PVD cut-off point separating steatosis from cirrhosis was 2.1 mm (sensitivity of 100% and specificity of 90.5%). One third of cirrhotic rats presented with ascites. Conclusion The use of ultrasound imaging in the follow-up of murine diffuse liver disease models is feasible and efficient, especially when the studied parameters are used in combination. The potential implication of this study is to provide a non-invasive method that allows follow-up studies of fatty liver disease and cirrhosis of individual rats for pre-clinical drug or cell based therapies. PMID:20113491

  19. Of liver, whisky and plants: a requiem for colchicine in alcoholic cirrhosis?

    PubMed

    Lonardo, Amedeo; Loria, Paola

    2002-04-01

    Colchicine decreases liver fibrosis in experimental and human disease, but a meta-analysis recently concluded that colchicine should not be used for liver fibrosis or cirrhosis irrespective of the aetiology. In this issue, Cortez-Pinto et al. confirm such negative conclusions in their series of 55 outpatients with biopsy-proven alcoholic cirrhosis followed for a median of 3.5 years. Although well tolerated, colchicine did not affect either the annual incidence rate of complications or liver function tests. Current treatment of alcoholic cirrhosis includes correction of nutritional deficiencies, exogenous administration of antioxidants (notably S-adenosylmethionine and polyenylphosphatidylcholine), and liver transplantation. In the future, preventive/therapeutic strategies will include campaigns to decrease alcohol abuse aimed at subjects genetically prone to develop alcoholic liver injury, prevention of liver fibrosis via inhibition of the Na+/H+ exchange, stimulation of apoptosis of stellate cells, antagonism of cytokines involved in liver injury, degradation of extracellular matrix, and reversal of ethanol-induced inflammatory and fibrotic changes via increased nitric oxide levels. On the grounds that it renders the hepatocyte more vulnerable to necrosis, steatosis has a key role in the pathogenesis of alcoholic and non-alcoholic liver disease. Conditions associated with insulin resistance have been recognized as risk factors for chronic liver disease and hepatocellular carcinoma in the alcoholic. This suggests that, through steatosis, insulin resistance could be a co-factor of alcoholic liver disease. Were such a hypothesis confirmed, it would unify our view of the pathogenesis of alcoholic and non-alcoholic liver disease, with all its inherent therapeutic implications. PMID:11943945

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

    PubMed Central

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

    2008-01-01

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

  1. Increased risk of benign prostatic enlargement among patients with liver cirrhosis: a nationwide population-based study.

    PubMed

    Chung, Shiu-Dong; Lin, Herng-Ching

    2011-01-01

    There have been several post mortem studies focusing on the association between liver cirrhosis and benign prostate hyperplasia; however, the results are controversial. The aim of this study was to estimate the risk of benign prostatic enlargement during a 5-year follow-up period following a liver cirrhosis diagnosis, using nationwide population-based data and a retrospective cohort design. We used the "Longitudinal Health Insurance Database," derived from the Taiwan National Health Insurance program. The study cohort comprised 661 patients who had received treatment for liver cirrhosis between 1997 and 2001; the comparison cohort was composed of 3305 randomly selected patients. Stratified Cox proportional hazard regressions were performed as a means of comparing the 5-year benign prostatic enlargement survival rate for the 2 cohorts. Of the sampled patients, 808 patients (20.4%) developed benign prostatic enlargement during the follow-up period (ie, 163 individuals from the study cohort [24.7% of the patients with liver cirrhosis] and 645 individuals from the comparison cohort [19.5% of comparison cohort patients]). The log-rank test indicated that patients with liver cirrhosis had significantly lower 5-year benign prostatic enlargement-free survival rates than the controls (P < .001). The adjusted hazard ratios for benign prostatic enlargement following diagnosis with liver cirrhosis were 1.41 during the 5-year follow-up period. We conclude that the risk for benign prostatic enlargement increased after a diagnosis of liver cirrhosis. Further studies are needed to identify the underlying pathophysiology. PMID:20798385

  2. Decompensated Liver Cirrhosis Presenting as a Spontaneous Left-Sided Bacterial Empyema

    PubMed Central

    Nathoo, Sunina

    2016-01-01

    Decompensation of cirrhosis presents with ascites, encephalopathy, variceal bleeding, or spontaneous bacterial peritonitis. Infrequently, decompensation can result from spontaneous bacterial empyema. A 38-year-old man presented with fevers, chills, and dyspnea. Labs were significant for leukocytosis, transaminitis, and coagulopathy. Imaging showed liver cirrhosis with ascites and a left pleural effusion. Treatment of the effusion consisted of chest tube drainage and antibiotics. Spontaneous bacterial empyema was diagnosed after pleural fluid cultures were positive for Escherichia coli. Our case demonstrates that spontaneous bacterial empyemas can be left-sided, and the first sign of decompensation.

  3. Genetic diseases that predispose to early liver cirrhosis.

    PubMed

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

    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

  4. 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

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

    PubMed Central

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

    2010-01-01

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

  6. Differential Kinetics of Coagulation Factors and Natural Anticoagulants in Patients with Liver Cirrhosis: Potential Clinical Implications

    PubMed Central

    Tischendorf, Michael; Miesbach, Wolfgang; Chattah, Umer; Chattah, Zenab; Maier, Sebastian; Welsch, Christoph; Zeuzem, Stefan; Lange, Christian M.

    2016-01-01

    Background Advanced liver diseases are associated with profound alterations of the coagulation system increasing the risk not only of bleeding, but also of thromboembolic complications. A recent milestone study has shown that prophylactic anticoagulation in liver cirrhosis patients results in a reduced frequency of hepatic decompensation. Yet, INR measurement, one of the most widely applied tests to assess liver function, only inaccurately predicts the risk of hepatic decompensation related to alterations of the coagulation system. To assess the relationship between selected coagulation factors / natural anticoagulants with INR, MELD score, and hepatic decompensation, we performed the present pilot study. A total number of 92 patients with various stages of liver cirrhosis were included and prospectively followed for at least 6 months. We found that important natural anticoagulants, namely antithrombin and protein C, as well as factor XI (which may also serve as an anticoagulant) decreased earlier and by a larger magnitude than one would expect from classical coagulation test results. The correlation between these factors and INR was only moderate. Importantly, reduced plasma activities of natural anticoagulants but not INR or MELD score were independent predictors of hepatic encephalopathy (P = 0.013 and 0.003 for antithrombin and protein C, respectively). Conclusion In patients with liver cirrhosis plasma activities of several natural anticoagulants are earlier and stronger affected than routine coagulation tests. Reduced activities of natural anticoagulants may be predictive for the development of hepatic encephalopathy. PMID:27171213

  7. Serum Liver Fibrosis Markers for Predicting the Presence of Gastroesophageal Varices in Liver Cirrhosis: A Retrospective Cross-Sectional Study

    PubMed Central

    Li, Hongyu; Chen, Jiang; Xia, Chunlian; Peng, Ying; Dai, Junna; Hou, Yue; Deng, Han; Li, Jing; Guo, Xiaozhong

    2015-01-01

    Background and Aims. A retrospective cross-sectional study was conducted to evaluate the role of hyaluronic acid (HA), laminin (LN), amino-terminal propeptide of type III procollagen (PIIINP), and collagen IV (CIV) in predicting the presence of gastroesophageal varices (GEVs) in patients with liver cirrhosis. Methods. We enrolled 118 patients with liver cirrhosis who underwent the tests for the four serum liver fibrosis markers and upper gastrointestinal endoscopy at the same admissions. The predictive values of the four serum liver fibrosis markers were evaluated by the areas under the receiving operator characteristics curves (AUROCs) with 95% confidence intervals (CIs). Results. The prevalence of GEVs was 88% (104/118). The AUROCs for HA, LN, PIIINP, and CIV levels in predicting the presence of GEVs were 0.553 (95% CI: 0.458 to 0.644, P = 0.5668), 0.490 (95% CI: 0.397 to 0.584, P = 0.9065), 0.622 (95% CI: 0.528 to 0.710, P = 0.1099), and 0.560 (95% CI: 0.466 to 0.652, P = 0.4909). The PIIINP level at a cut-off value of 31.25 had a sensitivity of 73.1% and a specificity of 57.1%. Conclusions. The present study did not recommend HA, LN, PIIINP, and CIV levels to evaluate the presence of GEVs in liver cirrhosis. PMID:26770190

  8. Liver myofibroblasts regulate the phenotype and function of monocytes through soluble factors in cirrhosis

    PubMed Central

    ZHANG, MIN; WANG, FENG-LAN; ZHU, JIAN-YUN; ZHENG, YU-BAO; ZHAO, QI-YI; GU, YU-RONG; ZHANG, QI; CHONG, YU-TIAN; GAO, ZHI-LIANG

    2013-01-01

    The ability of lymphocytes and macrophage-derived cytokines and chemokines to modulate the activation of stromal cells during immune responses is well-documented, but few studies have investigated whether liver myofibroblasts shape the phenotype and function of monocytes in liver disease. In the present study, Kupffer cells were demonstrated to be activated in the inflamed livers of patients with cirrhosis and be in close contact with liver myofibroblasts. The Kupffer cells from cirrhotic livers expressed significantly elevated levels of PD-L1 (also termed B7-H1), TLR4, CD80, CD32 and CD64 relative to those from normal livers. Consistent with this finding, the expression of these surface molecules was significantly upregulated in monocytes following exposure to liver myofibroblasts originating from inflamed livers. Accordingly, the liver myofibroblast-exposed monocytes exhibited a significant increase in dextran endocytosis. These data reveal that bidirectional interactions between liver myofibroblasts and Kupffer cells may function as an ‘amplification loop’ to enhance inflammation further in the liver. Liver myofibroblasts are central in the pathogenesis of liver diseases and should be considered as targets for the rational design of effective immune-based anti-inflammation therapies. Furthermore, it was also demonstrated that skin fibroblasts were as effective as liver myofibroblasts at inducing monocyte activation, suggesting that fibroblasts, which are numerous in the body, may represent an underrated cell population that is actively involved in immunomodulatory functions. PMID:23251256

  9. 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.

  10. 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. PMID:26166077

  11. Relation between severity of liver disease and renal oxygen consumption in patients with cirrhosis

    PubMed Central

    Gadano, A; Moreau, R; Heller, J; Chagneau, C; Vachiery, F; Trombino, C; Elman, A; Denie, C; Valla, D; Lebrec, D

    1999-01-01

    BACKGROUND—Worsening cirrhosis may lead to increased renal O2 metabolism caused by activation of neurohumoral antinatriuretic substances.
AIMS—To evaluate the relation between the severity of liver disease, sodium excretion, and neurohumoral antinatriuretic substances on the one hand and renal O2 metabolism on the other in patients with cirrhosis.
METHODS—Renal O2 consumption and haemodynamics as well as plasma concentrations of noradrenaline, renin, and aldosterone were measured. Investigations were performed in 14 patients with Pugh's grade A, 43 with grade B, and 29 with grade C liver disease.
RESULTS—Renal O2 consumption significantly increased with the severity of cirrhosis (grade A, 8.9 (1.6); grade B, 15.5 (1.3); grade C, 18.0 (1.5) ml/min/m2). Plasma concentrations of noradrenaline, renin, and aldosterone significantly increased while mean arterial presssure and systemic vascular resistance significantly decreased with the severity of the disease. A significant inverse correlation was found between renal O2 consumption and sodium excretion. A significant direct correlation was found between plasma levels of noradrenaline and aldosterone on the one hand and renal O2 consumption on the other. Renal blood flow and the glomerular filtration rate did not differ significantly between patients with grade C and grade A or B disease.
CONCLUSIONS—This study shows for the first time that, in patients with cirrhosis, worsening of the disease is associated with an increase in renal O2 consumption. The results suggest that increased renal O2 consumption is due to renal tubular sodium retention caused by increased levels of neurohumoral antinatriuretic substances. This neurohumoral activation is related to cirrhosis induced vasodilation.


Keywords: antinatriuretic hormones; cirrhosis; kidney; haemodynamics; O2 consumption; sodium retention PMID:10369714

  12. 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

  13. Liver transplantation for hepatitis B and C virus-related cirrhosis: mid-term results.

    PubMed

    Manzia, T M; Di Paolo, D; Sforza, D; Toti, L; Angelico, R; Brega, A; Angelico, M; Tisone, G

    2010-05-01

    Hepatitis C virus (HCV) recurrence after orthotopic liver transplantation (OLT) is almost universal; cirrhosis develops in up to 30% of cases. Currently there is interest in the midterm outcomes of HCV patients with concomitant hepatitis B virus (HBV) infection among OLT recipients. We therefore retrospectively analyzed our database of patients who underwent OLT for HCV-HBV-related cirrhosis. Between April 1992 and December 2008, 350 patients underwent OLT, including 20 (5.7%) transplanted for HBV-HCV cirrhosis. We assessed patient and graft survivals at 1 and 5 years, as well as the progression of fibrosis. Protocol liver biopsies were available yearly after OLT. The survival curves were analyzed by the Kaplan-Meier approach and chronic hepatitis evaluated according to the Ishak scoring system. At a median follow-up of 68.4 +/- 53 months, the 1- and 5-year patient and graft survival rates were 80% and 70%, respectively. The 5-year fibrosis progression rate was 0.17 +/- 0.08 units of fibrosis. The only patient who developed histologic cirrhosis within 10 years of follow-up showed a lamivudine-resistant HBV recurrence. Patients transplanted for HBV-HCV coinfection showed a lower fibrosis progression rate compared with HCV monoinfected subjects. PMID:20534261

  14. Clinical value of real-time elastography quantitative parameters in evaluating the stage of liver fibrosis and cirrhosis

    PubMed Central

    GE, LAN; SHI, BAOMIN; SONG, YE; LI, YUAN; WANG, SHUO; WANG, XIUYAN

    2015-01-01

    The aim of the present study was to assess the value of real-time elastography (RTE) quantitative parameters, namely the liver fibrosis (LF) index and the ratio of blue area (%AREA), in evaluating the stage of liver fibrosis. RTE quantitative analysis software was used to examine 120 patients with chronic hepatitis in order to obtain the values for 12 quantitative parameters from the elastic images. The diagnostic performance of two such parameters, the LF index and %AREA, were assessed with a receiver operating characteristic (ROC) curve to determine the optimal diagnostic cut-off values for liver cirrhosis and fibrosis. A good correlation was observed between the LF index and %AREA with the fibrosis stage. The areas under the ROC curve for the LF index were 0.985 for the diagnosis of liver cirrhosis and 0.790 for liver fibrosis. With regard to %AREA, the areas under the ROC curve for the diagnosis of liver cirrhosis and fibrosis were 0.963 and 0.770, respectively. An LF index of >3.25 and a %AREA of >28.83 for the diagnosis of cirrhosis stage resulted in sensitivity values of 100 and 100%, specificity values of 88.9 and 85.9% and accuracy values of 90.8 and 88.3%, respectively. The LF index and %AREA parameters exhibited higher reliability in the diagnosis of liver cirrhosis compared with the diagnosis of the liver fibrosis stage. However, the two parameters possessed a similar efficacy in the diagnosis of liver cirrhosis and the stage of liver fibrosis. Therefore, the quantitative RTE parameters of the LF index and %AREA may be clinically applicable as reliable indices for the early diagnosis of liver cirrhosis, without the requirement of an invasive procedure. PMID:26622426

  15. 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.

  16. Multiple Brain Abscesses Due to Aspergillus Fumigatus in a Patient With Liver Cirrhosis

    PubMed Central

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

    2016-01-01

    Abstract 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. PMID:26945363

  17. 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. PMID:26945363

  18. Uncommon cause of acute encephalopathy in liver cirrhosis.

    PubMed

    Dieuvil, Monique; Malaty, John

    2016-01-01

    A 49-year-old woman with a medical history of alcoholic cirrhosis status post-transjugular intrahepatic portosystemic shunt (post-TIPS) in 2012, and ongoing alcohol abuse, presented to the hospital, with haematuria. CT intravenous pyelogram (IVP) was normal except for 'a large intrahepatic cystic mass adjacent to the TIPS, causing intrahepatic biliary duct dilation'. The patient also presented with acute encephalopathy, jaundice, right upper quadrant abdominal pain and hyperbilirubinaemia (total bilirubin of 8.1 mg/dL with direct bilirubin of 3.0 mg/dL). She remained encephalopathic despite adequate treatment for alcohol withdrawal, hepatic encephalopathy and enterococcus urinary tract infection. MRI of the abdomen later confirmed presence of an obstructing biloma. The biloma, drained by CT-guided percutaneous drains, demonstrated an Escherichia coli and ESBL Klebsiella infection. The patient's encephalopathy completely resolved after treatment of the infected biloma. With adequate drainage, her hyperbilirubinaemia resolved to her post-TIPS baseline (total bilirubin of 3.7 mg/dL with direct bilirubin of 3.3 mg/dL). PMID:27194673

  19. Laparoscopic liver resection for hepatocellular carcinoma with cirrhosis in a single institution

    PubMed Central

    Wakabayashi, Go; Nitta, Hiroyuki; Hasegawa, Yasushi; Katagiri, Hirokatsu; Takeda, Daiki; Makabe, Kenji; Sasaki, Akira

    2015-01-01

    Background In a statement by the second International Consensus Conference for Laparoscopic Liver Resection (LLR), minor LLR was confirmed to be a standard surgical practice, as it has become adopted by an increasing proportion of surgeons. However, it is unclear whether this applies to the more complex group of patients suffering from cirrhosis. Therefore, the aim of this retrospective study was to compare the feasibility and safety of LLR for hepatocellular carcinoma (HCC) between non-liver cirrhosis (NLC) patients and liver cirrhosis (LC) patients at a single high-volume laparoscopy center. Methods From the beginning of 2000 to the end of 2013, open liver resection (OLR) was performed in 99 HCC patients, and LLR was in 118. The HCC patients who underwent LLR were divided into NLC-LLR (n=60) and LC-LLR (n=58) groups, and we compare the short-term outcomes between them. Results There was no significant difference in the incidence of blood loss and transfusion requirements between the NLC-LLR group and the LC-LLR group, although wedge resection was mainly performed in the LC-LLR group. There was no significant difference in the complication rate between the two groups, and the remarkable finding was that there was a significantly lower incidence of postoperative ascites in the LC-LLR group than in the NLC-LLR group. Conclusions According to our experience, it appears that LLR for selected HCC patients with cirrhosis is a feasible and promising procedure that is associated with less blood loss and fewer postoperative complications, especially the incidence of postoperative ascites. Further investigations are clearly warranted. PMID:26734624

  20. 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.

  1. 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.

  2. Laparoscopic splenectomy for hypersplenism secondary to liver cirrhosis and portal hypertension

    PubMed Central

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

    2014-01-01

    Since the first laparoscopic splenectomy (LS) was reported in 1991, LS has become the gold standard for the removal of normal to moderately enlarged spleens in benign conditions. Compared with open splenectomy, fewer postsurgical complications and better postoperative recovery have been observed, but LS is contraindicated for hypersplenism secondary to liver cirrhosis in many institutions owing to technical difficulties associated with splenomegaly, well-developed collateral circulation, and increased risk of bleeding. With the improvements of laparoscopic technique, the concept is changing. This article aims to give an overview of the latest development in laparoscopic splenectomy for hypersplenism secondary to liver cirrhosis and portal hypertension. Despite a lack of randomized controlled trial, the publications obtained have shown that with meticulous surgical techniques and advanced instruments, LS is a technically feasible, safe, and effective procedure for hypersplenism secondary to cirrhosis and portal hypertension and contributes to decreased blood loss, shorter hospital stay, and less impairment of liver function. It is recommended that the dilated short gastric vessels and other enlarged collateral circulation surrounding the spleen be divided with the LigaSure vessel sealing equipment, and the splenic artery and vein be transected en bloc with the application of the endovascular stapler. To support the clinical evidence, further randomized controlled trials about this topic are necessary. PMID:24914339

  3. The Economic Burden of Liver Cirrhosis in Iran: a Cost of Illness Study

    PubMed Central

    AKBARI SARI, Ali; KAZEMI KARYANI, Ali; ALAVIAN, Seyed Moayed; ARAB, Mohamad; ROSTAMI GHOLMOHAMADI, Fateme; REZAEI, Satar

    2015-01-01

    Background: According to importance of cirrhosis of the liver and the lack of information about the economic burden of the disease, we performed this study to estimate the economic burden of liver Cirrhosis in Iran in 2011. Methods: The cost-of-illness method, based on the human capital theory, has been used. Both direct and indirect costs have been estimated using a prevalence approach and bottom-up method. The inpatient and outpatient records were investigated for obtaining the medical costs. Also, a questionnaire was used for collection the other data such as transportation costs, out of pocket payment and times of inpatients, etc. Costs consisted of expenditures which happened during March 2011 to February 2012 and the perspective of the study was Iranian society. Results: The total cost of the disease was 2014.5 billion Rials (USD164.32 million). Direct and indirect costs were 1384.16 and 630.4 billion Rials (86.7% and 11.3% of the total cost), respectively. Cost due to premature death was USD 38.66 million, included 23.52% of the total cost and 75% of indirect cost. Conclusion: Liver Cirrhosis impose enormous economic burden on Iranian society. Policymakers should therefore take this into consideration and according to available health resources provide services and facilities for the prevention and treatment of the disease. PMID:26056670

  4. 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.

  5. Diabetes Mellitus Predicts Occurrence of Cirrhosis and Hepatocellular Cancer in Alcoholic Liver and Non-alcoholic Fatty Liver Diseases

    PubMed Central

    Raff, Evan J.; Kakati, Donny; Bloomer, Joseph R.; Shoreibah, Mohamed; Rasheed, Khalid; Singal, Ashwani K.

    2015-01-01

    Background and Aims Alcohol abuse and nonalcoholic fatty liver disease (NAFLD) are common causes of liver disease. Diabetes mellitus (DM) is a common comorbidity among NAFLD patients. We performed this study with the specific aim to examine the impact of DM on progression of alcoholic liver disease (ALD) liver and NAFLD. Methods Medical charts of 480 patients with ALD or NAFLD (20042011) managed at a tertiary center were retrospectively reviewed. NAFLD was diagnosed based on exclusion of other causes of liver disease and alcohol use of <10 g/d. ALD was diagnosed based on alcohol use of >40 g/d in women or >60 g/d in men for >5 years. Results Of 480 patients (307 NAFLD), 200 diabetics differed from nondiabetics for: age (5211 vs. 4911 years; p=0.004); male gender (48% vs. 57%; p=0.03); metabolic syndrome (49% vs. 30%; p=0.0002); NAFLD (80% vs. 56%; p<0.0001); cirrhosis (70% vs. 59%; p=0.005); and hepatocellular carcinoma (HCC; 8% vs. 3%; p=0.009). Over a 3 year median follow-up period, diabetics relative to nondiabetics had a higher probability to develop cirrhosis (60% vs. 41%; p=0.022) and HCC (27% vs. 10%; p=0.045). There was a trend for increased development of hepatic encephalopathy in diabetics compared to nondiabetics (55% vs. 39%; p=0.053), and there was no difference between the two groups in survival or other liver disease complications. Conclusions DM increased risk for cirrhosis and HCC among patients with ALD and NAFLD. Prospective studies with longer follow-up periods are needed to examine the impact of DM on survival and the role of aggressive HCC screening in diabetic cirrhotics. PMID:26356325

  6. 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

  7. Association of Serum Level of Growth Differentiation Factor 15 with Liver Cirrhosis and Hepatocellular Carcinoma

    PubMed Central

    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. PMID:25996938

  8. Impact of hyponatremia on frequency of complications in patients with decompensated liver cirrhosis

    PubMed Central

    Barakat, Ashraf Abd El-Khalik; Metwaly, Amna Ahmed; Nasr, Fatma Mohammad; El-Ghannam, Maged; El-Talkawy, Mohamed Darwish; taleb, Hoda Abu

    2015-01-01

    Introduction Hyponatremia is common in cirrhosis. The relationship between hyponatremia and severity of cirrhosis is evidenced by its close association with the occurrence of complications, the prevalence of hepatic encephalopathy, hepatorenal syndrome, spontaneous bacterial peritonitis, refectory ascites, and hepatic hydrothorax. The aim of this study was assess the impact of hyponatremia on the occurrence of both liver-related complications and the hemodynamic cardiovascular dysfunction. Methods This prospective study was conducted in 2015 on 74 patients with liver cirrhosis. The patients were from the Gastroenterology and Hepatology Department of Theodor Bilharz Research Institute in Giza, Egypt. The patients were divided into three groups according to their serum level of sodium. Group 1 included 30 patients with serum sodium >135 meq/L, group 2 included 24 patients with serum sodium between135 and 125 meq/L, and group 3 included 20 patients with serum sodium <125 meq/L. For each of the patients, we conducted aclinical examination, laboratory investigations, chest X-ray, ECG, abdominal sonar, and echocardiography. Results Hyponatremia was found in 59.46% of our cirrhotic patients, and they showed significantly increased Model for End-Stage Liver Disease (MELD) score, MELD-Na score, QTc interval, Pulmonary vascular resistance (PVR) and inferior vena cava (IVC) collapsibility, and decreased SVR and IVC diameter. Also hepatic encephalopathy, ascites, renal failure, infectious complications, and pleural effusion were significantly more common in hyponatremic cirrhotic patients. Conclusion In cirrhosis, hyponatremia is more common in severe cardiovascular dysfunction and associated with increased risk of hepatic encephalopathy, ascites, illness severity scores, renal failure, infectious complications, and pleural effusion. We recommend selective oral administration of vasopressin V2-receptor antagonist, tolvaptan, which acts to increase the excretion of free water, thereby resolving hypervolemic hyponatremia and may have the potential to improve outcomes in these patients. PMID:26516441

  9. Hepatic stem cells: A viable approach for the treatment of liver cirrhosis.

    PubMed

    Habeeb, Md Aejaz; Vishwakarma, Sandeep Kumar; Bardia, Avinash; Khan, Aleem Ahmed

    2015-06-26

    Liver cirrhosis is characterized by distortion of liver architecture, necrosis of hepatocytes and regenerative nodules formation leading to cirrhosis. Various types of cell sources have been used for the management and treatment of decompensated liver cirrhosis. Knowledge of stem cells has offered a new dimension for regenerative therapy and has been considered as one of the potential adjuvant treatment modality in patients with end stage liver diseases (ESLD). Human fetal hepatic progenitor cells are less immunogenic than adult ones. They are highly propagative and challenging to cryopreservation. In our earlier studies we have demonstrated that fetuses at 10-18 wk of gestation age contain a large number of actively dividing hepatic stem and progenitor cells which possess bi-potent nature having potential to differentiate into bile duct cells and mature hepatocytes. Hepatic stem cell therapy for the treatment of ESLD is in their early stage of the translation. The emerging technology of decellularization and recellularization might offer a significant platform for developing bioengineered personalized livers to come over the scarcity of desired number of donor organs for the treatment of ESLD. Despite these significant advancements long-term tracking of stem cells in human is the most important subject nowadays in order to answer several unsettles issues regarding the route of delivery, the choice of stem cell type(s), the cell number and the time-point of cell delivery for the treatment in a chronic setting. Answering to these questions will further contribute to the development of safer, noninvasive, and repeatable imaging modalities that could discover better cell therapeutic approaches from bench to bed-side. Combinatorial approach of decellularization and nanotechnology could pave a way towards the better understanding in determination of cell fate post-transplantation. PMID:26131316

  10. Hepatic stem cells: A viable approach for the treatment of liver cirrhosis

    PubMed Central

    Habeeb, Md Aejaz; Vishwakarma, Sandeep Kumar; Bardia, Avinash; Khan, Aleem Ahmed

    2015-01-01

    Liver cirrhosis is characterized by distortion of liver architecture, necrosis of hepatocytes and regenerative nodules formation leading to cirrhosis. Various types of cell sources have been used for the management and treatment of decompensated liver cirrhosis. Knowledge of stem cells has offered a new dimension for regenerative therapy and has been considered as one of the potential adjuvant treatment modality in patients with end stage liver diseases (ESLD). Human fetal hepatic progenitor cells are less immunogenic than adult ones. They are highly propagative and challenging to cryopreservation. In our earlier studies we have demonstrated that fetuses at 10-18 wk of gestation age contain a large number of actively dividing hepatic stem and progenitor cells which possess bi-potent nature having potential to differentiate into bile duct cells and mature hepatocytes. Hepatic stem cell therapy for the treatment of ESLD is in their early stage of the translation. The emerging technology of decellularization and recellularization might offer a significant platform for developing bioengineered personalized livers to come over the scarcity of desired number of donor organs for the treatment of ESLD. Despite these significant advancements long-term tracking of stem cells in human is the most important subject nowadays in order to answer several unsettles issues regarding the route of delivery, the choice of stem cell type(s), the cell number and the time-point of cell delivery for the treatment in a chronic setting. Answering to these questions will further contribute to the development of safer, noninvasive, and repeatable imaging modalities that could discover better cell therapeutic approaches from bench to bed-side. Combinatorial approach of decellularization and nanotechnology could pave a way towards the better understanding in determination of cell fate post-transplantation. PMID:26131316

  11. Should we give thromboprophylaxis to patients with liver cirrhosis and coagulopathy?

    PubMed Central

    Senzolo, Marco; Sartori, Maria Teresa; Lisman, Ton

    2009-01-01

    Patients with liver cirrhosis are characterized by decreased synthesis of both pro- and anticoagulant factors, and recently there has been evidence of normal generation of thrombin resulting in a near normal haemostatic balance. Although it is generally recognized that bleeding is the most common clinical manifestation as a result of decreased platelet function and number, diminished clotting factors and excessive fibrinolysis, hypercoagulability may play an under recognized but important role in many aspects of chronic liver disease. In fact, they can encounter thrombotic complications such as portal vein thrombosis, occlusion of small intrahepatic vein branches and deep vein thrombosis (DVT). In particular, patients with cirrhosis appear to have a higher incidence of unprovoked DVT and pulmonary embolism (PE) compared with the general population. In dedicated studies, the incidence of DVT/PE ranges from 0.5% to 1.9%, similar to patients without comorbidities, but lower than patients with other chronic diseases (i.e, renal or heart disease). Surprisingly, standard coagulation laboratory parameters are not associated with a risk of developing DVT/PE; however, with multivariate analysis, serum albumin level was independently associated with the occurrence of thrombosis. Moreover, patients with chronic liver disease share the same risk factors as the general population for DVT/PE, and specifically, liver resection can unbalance the haemostatic equilibrium towards a hypercoagulable state. Current guidelines on antithrombotic prophylaxis do not specifically comment on the cirrhotic population as a result of the perceived risk of bleeding complications but the cirrhotic patient should not be considered as an auto-anticoagulated patient. Therefore, thromboprophylaxis should be recommended in patients with liver cirrhosis at least when exposed to high-risk conditions for thrombotic complications. Low molecular weight heparins (LWMHs) seem to be relatively safe in this group of patients; however, when important risk factors for bleeding are present, graduated compression stockings or intermittent pneumatic compression should be considered. PMID:19816608

  12. Hepatic hydrothorax without ascites as the first sign of liver cirrhosis.

    PubMed

    Kim, Jung Soo; Kim, Cheol-Woo; Nam, Hae-Seong; Cho, Jae Hwa; Ryu, Jeong-Seon; Lee, Hong Lyeol

    2016-03-01

    A 60-year-old woman without a history of liver diseases, but with a history of regular alcohol consumption, presented with a right-sided transudative pleural effusion. Neither parenchymal lung lesion nor pleural thickening was seen on a chest computed tomography. On abdominal ultrasonography, the liver size and contour were normal, and ascites was not noted. Despite performing imaging and laboratory studies, we could not find a cause of the pleural effusion. Thus, due to her history of regular alcohol consumption, we decided to measure liver stiffness using a transient elastography (Fibroscan(®), Echosens(TM), Paris, France), which showed a value of 35.3 kPa suggestive of liver cirrhosis. An intraperitoneal injection of a radioisotope demonstrated the transdiaphragmatic flow of fluid from peritoneal cavity to pleural cavity. The diagnosis was confirmed as hepatic hydrothorax. Management consisting of restricted salt and water intake with diuretics resulted in resolution of the hepatic hydrothorax. PMID:26839695

  13. 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.

  14. 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

  15. Pulse Diagnosis Signals Analysis of Fatty Liver Disease and Cirrhosis Patients by Using Machine Learning

    PubMed Central

    Youhua, Yu; Dawei, Huang; Bin, Xu; Jia, Liu; Tongda, Li; Liyuan, Xue; Zengyu, Shan; Yanping, Chen; Jia, Wang

    2015-01-01

    Objective. To compare the signals of pulse diagnosis of fatty liver disease (FLD) patients and cirrhosis patients. Methods. After collecting the pulse waves of patients with fatty liver disease, cirrhosis patients, and healthy volunteers, we do pretreatment and parameters extracting based on harmonic fitting, modeling, and identification by unsupervised learning Principal Component Analysis (PCA) and supervised learning Least squares Regression (LS) and Least Absolute Shrinkage and Selection Operator (LASSO) with cross-validation step by step for analysis. Results. There is significant difference between the pulse diagnosis signals of healthy volunteers and patients with FLD and cirrhosis, and the result was confirmed by 3 analysis methods. The identification accuracy of the 1st principal component is about 75% without any classification formation by PCA, and supervised learning's accuracy (LS and LASSO) was even more than 93% when 7 parameters were used and was 84% when only 2 parameters were used. Conclusion. The method we built in this study based on the combination of unsupervised learning PCA and supervised learning LS and LASSO might offer some confidence for the realization of computer-aided diagnosis by pulse diagnosis in TCM. In addition, this study might offer some important evidence for the science of pulse diagnosis in TCM clinical diagnosis.

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

    PubMed

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

    2013-04-01

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

  17. Copeptin as an Indicator of Hemodynamic Derangement and Prognosis in Liver Cirrhosis

    PubMed Central

    Chiang, Fang W. T.; Laleman, Wim; van der Reijden, Johan J.; van Duijn, Wim; Nevens, Frederik; Wolterbeek, Ron; van Hoek, Bart; Verspaget, Hein W.; Coenraad, Minneke J.

    2015-01-01

    Background Advanced liver cirrhosis is associated with systemic hemodynamic derangement leading to the development of severe complications associated with increased mortality. Copeptin is a stable cleavage product of the precursor of arginine vasopressin, a key-regulator in hemodynamic homeostasis. Copeptin is currently considered a reliable prognostic marker in a wide variety of diseases other than cirrhosis. The present study aimed to assess copeptin, both experimentally and clinically, as a potential biomarker of hemodynamic derangement and to evaluate its prognostic significance in cirrhosis. Materials and Methods Two studies were executed: 1) in 18 thioacetamide-induced cirrhotic rats and 5 control rats, plasma copeptin and hemodynamic measurements were performed, 2) in 61 cirrhotic patients, serum copeptin concentration was measured in samples collected at time of registration at the waiting list for liver transplantation. In 46 patients, also a second copeptin measurement was performed during follow-up while registered at the waiting list for liver transplantation. To determine the association of serum copeptin and clinical data with outcome, Cox proportional hazard regression analysis and Kaplan Meier analysis were performed. Results Plasma copeptin concentration was significantly higher in cirrhotic rats than in controls (1.6 ± 0.5 vs. 0.9 ± 0.1 pmol/L, p< 0.01) and was negatively correlated to the mean arterial blood pressure (r = -0.574, p = 0.013). In cirrhotic patients, serum copeptin concentration was high [11.0 (5.2–24.0) pmol/L] and increased significantly during the time of registration at the waiting list for liver transplantation. MELD and MELD-sodium score were significantly correlated to serum copeptin [MELD: (r = 0.33, p = 0.01), MELD-sodium: (r = 0.29, p = 0.02)], also at time of the second copeptin measurement [MELD and MELD-sodium: r = 0.39, p< 0.01]. In cirrhotic humans, serum copeptin concentration was significantly associated with outcome, independently of the MELD and MELD-sodium score. Patients with a low serum copeptin concentration at time of registration at the liver transplant waiting list had significantly better transplant-free survival rates at 3, 6 and 12 months of follow-up as compared to those with a high serum copeptin concentration (Log-rank: p< 0.01, p< 0.01 and p = 0.02 respectively). Conclusions Circulating copeptin levels are elevated in rats and humans with cirrhosis. Copeptin is independently associated with outcome in cirrhotic patients awaiting liver transplantation. PMID:26378453

  18. Influence of antibiotic-regimens on intensive-care unit-mortality and liver-cirrhosis as risk factor

    PubMed Central

    Friedrich-Rust, Mireen; Wanger, Beate; Heupel, Florian; Filmann, Natalie; Brodt, Reinhard; Kempf, Volkhard AJ; Kessel, Johanna; Wichelhaus, Thomas A; Herrmann, Eva; Zeuzem, Stefan; Bojunga, Joerg

    2016-01-01

    AIM: To assess the rate of infection, appropriateness of antimicrobial-therapy and mortality on intensive care unit (ICU). Special focus was drawn on patients with liver cirrhosis. METHODS: The study was approved by the local ethical committee. All patients admitted to the Internal Medicine-ICU between April 1, 2007 and December 31, 2009 were included. Data were extracted retrospectively from all patients using patient charts and electronic documentations on infection, microbiological laboratory reports, diagnosis and therapy. Due to the large hepatology department and liver transplantation center, special interest was on the subgroup of patients with liver cirrhosis. The primary statistical-endpoint was the evaluation of the influence of appropriate versus inappropriate antimicrobial-therapy on in-hospital-mortality. RESULTS: Charts of 1979 patients were available. The overall infection-rate was 53%. Multiresistant-bacteria were present in 23% of patients with infection and were associated with increased mortality (P < 0.000001). Patients with infection had significantly increased in-hospital-mortality (34% vs 17%, P < 0.000001). Only 9% of patients with infection received inappropriate initial antimicrobial-therapy, no influence on mortality was observed. Independent risk-factors for in-hospital-mortality were the presence of septic-shock, prior chemotherapy for malignoma and infection with Pseudomonas spp. Infection and mortality-rate among 175 patients with liver-cirrhosis was significantly higher than in patients without liver-cirrhosis. Infection increased mortality 2.24-fold in patients with cirrhosis. Patients with liver cirrhosis were at an increased risk to receive inappropriate initial antimicrobial therapy. CONCLUSION: The results of the present study report the successful implementation of early-goal-directed therapy. Liver cirrhosis patients are at increased risk of infection, mortality and to receive inappropriate therapy. Increasing burden are multiresistant-bacteria. PMID:27122670

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

    PubMed Central

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

    2014-01-01

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

  20. 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.

  1. An MLP Classifier for Prediction of HBV-Induced Liver Cirrhosis Using Routinely Available Clinical Parameters

    PubMed Central

    Hu, Zhi-De; Liu, Xiao-Fei; Deng, An-Mei

    2013-01-01

    Background. Liver cirrhosis (LC) is the final stage of most of chronic liver diseases and is almost caused by chronic hepatitis B (CHB) in China. Liver biopsy is the reference method for the evaluation of liver cirrhosis. However, it is an invasive procedure with inherent risk. The aim of this study was to construct a new classifier based on the routine clinical markers for the prediction of HBV-induced LC. Subjects and Methods. We collected routine clinical parameters from 124 LC patients with CHB and 115 with CHB. Training set (n = 120) and test set (n = 119) were built for model construction and evaluation, respectively. Results. We describe a new classifier, MLP, for prediction of LC with CHB. MLP was built with seven routinely available clinical parameters, including age, ALT, AST, PT, PLT, HGB, and RDW. With optimal cutoff, we obtained a sensitivity of 95.2%, a specificity of 84.2%, and an overall accuracy of 89.9% on an independent test set, which were superior to those of FIB-4 and APRI. Conclusions. Our study suggests that the MLP classifier can be implemented for discriminating LC and non-LC cohorts by using machine learning method based on the routine available clinical parameters. It could be used for clinical practice in HBV-induced LC assessment. PMID:24302810

  2. 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. PMID:27044760

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

    PubMed Central

    Moreau, Richard

    2016-01-01

    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. PMID:27044760

  4. Curative Effects of Fuzheng Huayu on Liver Fibrosis and Cirrhosis: A Meta-Analysis

    PubMed Central

    Dong, Shu; Chen, Qi-Long; Su, Shi-Bing

    2015-01-01

    The Fuzheng Huayu (FZHY) formula is being used in antiliver fibrosis treatment in China. For systemic evaluation of the curative effects of FZHY on liver fibrosis and cirrhosis progress, a total of 1392 subjects (714 cases and 678 controls) were found to be eligible for meta-analysis in this study. Standard mean differences (SMDs) with 95% confidence interval (CI) were calculated for changes between FZHY groups and controls by employing fixed effects or random effects model. In the overall analysis, alanine transaminase (ALT) (P = 0.003, SMD = −0.87, 95% CI: −1.46 to −0.29), total bilirubin (TBil) (P = 0.001, SMD = −1.30, 95% CI: −2.10 to −0.50), hyaluronic acid (HA) (P = 0.000, SMD = −0.94, 95% CI: −1.30 to −0.58), laminin (LN) (P = 0.000, SMD = −0.80, 95% CI: −1.20 to −0.41), type III procollagen (PC-III) (P = 0.000, SMD = −1.27, 95% CI: −1.93 to −0.60), and type IV procollagen (IV-C) (P = 0.000, SMD = −0.78, 95% CI: −1.05 to −0.51) were decreased after FZHY treatment; however, albumin (ALB) was increased (P = 0.037, SMD = 1.10, 95% CI: 0.07 to 2.12) significantly. Furthermore, the Child-Pugh score was reduced significantly and the life quality was improved after FZHY treatment in cirrhosis patients. The results of this meta-analysis indicated that FZHY effectively improves the liver function, alleviates hepatic fibrosis, decreases Child-Pugh score, and relieves TCM symptoms caused by liver dysfunction, indicating that FZHY may contribute to the alleviation of liver fibrosis and cirrhosis. PMID:26221168

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

    PubMed

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

    1993-01-01

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

  6. NT Pro BNP Plasma Level and Atrial Volume Are Linked to the Severity of Liver Cirrhosis

    PubMed Central

    Licata, Anna; Corrao, Salvatore; Petta, Salvatore; Genco, Chiara; Cardillo, Mauro; Calvaruso, Vincenza; Cabibbo, Giuseppe; Massenti, Fatima; Cammà, Calogero; Licata, Giuseppe; Craxì, Antonio

    2013-01-01

    Background and Aims Plasma levels of NT-pro-BNP, a natriuretic peptide precursor, are raised in the presence of fluid retention of cardiac origin and can be used as markers of cardiac dysfunction. Recent studies showed high levels of NT pro BNP in patients with cirrhosis. We assessed NT pro-BNP and other parameters of cardiac dysfunction in patients with cirrhosis, with or without ascites, in order to determine whether the behaviour of NT pro BNP is linked to the stage of liver disease or to secondary cardiac dysfunction. Methods Fifty eight consecutive hospitalized patients mostly with viral or NAFLD-related cirrhosis were studied. All underwent abdominal ultrasound and upper GI endoscopy. Cardiac morpho-functional changes were evaluated by echocardiography and NT-pro-BNP plasma levels determined upon admission. Twenty-eight hypertensive patients, without evidence of liver disease served as controls. Results Fifty eight cirrhotic patients (72% men) with a median age of 62 years (11% with mild arterial hypertension and 31% with type 2 diabetes) had a normal renal function (mean creatinine 0.9 mg/dl, range 0.7–1.06). As compared to controls, cirrhotic patients had higher NT pro-BNP plasma levels (365.2±365.2 vs 70.8±70.6 pg/ml; p<0.001). Left atrial volume (LAV) (61.8±26.3 vs 43.5±14.1 ml; p = 0.001), and left ventricular ejection fraction (62.7±6.9 vs. 65.5±4%,; p = 0.05) were also altered in cirrhotic patients that in controls. Patients with F2-F3 oesophageal varices as compared to F0/F1, showed higher e' velocity (0.91±0.23 vs 0.66±0.19 m/s, p<0.001), and accordingly a higher E/A ratio (1.21±0.46 vs 0.89±0.33 m/s., p = 0.006). Conclusion NT-pro-BNP plasma levels are increased proportionally to the stage of chronic liver disease. Advanced cirrhosis and high NT-pro-BNP levels are significantly associated to increased LAV and to signs of cardiac diastolic dysfunction. NT pro-BNP levels could hence be an useful prognostic indicators of early decompensation of cirrhosis. PMID:23940514

  7. Assessment of the fecal lactobacilli population in patients with hepatitis B virus-related decompensated cirrhosis and hepatitis B cirrhosis treated with liver transplant.

    PubMed

    Wu, Zhong-Wen; Lu, Hai-Feng; Wu, Jianping; Zuo, Jian; Chen, Ping; Sheng, Ji-Fang; Zheng, Shu-Sen; Li, Lan-Juan

    2012-05-01

    This study aims to provide an overview of the diversity of intestinal Lactobacillus among Chinese patients with hepatitis B virus (HBV)-related decompensated cirrhosis and who received liver transplant for hepatitis B cirrhosis. Fecal samples were collected from 38 healthy volunteers, 61 patients with HBV-related decompensated cirrhosis (group LC) and 74 patients who had liver transplant for hepatitis B cirrhosis (group LT). Quantitative polymerase chain reaction technology with species-specific primers was applied to investigate lactobacilli 16S rDNA in crude DNA, extracted from fecal samples. Software package Statistical Package for the Social Sciences and Palaeontological Statistics for Windows was used to analyze the data. Lactobacilli population of the two patient groups was different from the healthy control subjects, principal differences being marked decrease in the population of Lactobacillus rhamnosus (p < 0.001 for both patient groups) and reduction in the frequency of Lactobacillus fermentus (p < 0.001 for group LC and p < 0.01 for group LT). Our findings on the frequency of lactobacilli population suggested decreased diversity in groups LC and LT (compared with the healthy controls (p < 0.001 and p < 0.01, respectively)). Patients tended to have less complex fecal lactobacilli composition than the healthy controls, especially in the group LC. PMID:21965156

  8. 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.

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  11. 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. PMID:25737646

  12. 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

  13. An orthotopic mouse model of hepatocellular carcinoma with underlying liver cirrhosis.

    PubMed

    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

    2015-08-01

    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(-/-)Stk3(F/-) (also known as Mst1(-/-)Mst2(F/-); F indicates a floxed allele) mice, and it results in the development of HCC tumors (hepatocarcinogenesis) concomitantly with liver cirrhosis. PMID:26203823

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-11-27

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

  16. Efficacy of Radiofrequency Ablation of Hepatocellular Carcinoma Associated with Chronic Liver Disease without Cirrhosis

    PubMed Central

    Salmi, Andrea; Turrini, Renato; Lanzani, Giovanna; Savio, Antonella; Anglani, Livio

    2008-01-01

    Background. Hepatocellular carcinoma is one of the leading causes of death for compensated chronic liver disease. Aim. The evaluation of technical success as primary ablation rate, local tumor progression, safety, and long­-term patients outcome of radiofrequency ablation in single (less than 3.5 cm in diameter) or multiple nodules (up to 3, sized less than 3 cm) of hepatocellular carcinoma associated to chronic liver disease without cirrhosis. Materials and Methods. 25 consecutive patients, mainly chronic hepatitis C, with surgical unresectable hepatocellular carcinoma due to comorbidity or tumor location recruited from a local sonographic screening, were treated. Results. Primary ablation was obtained in 96% of patients (24 out of 25) and in 93 % of nodules (27 out of 29). 1, 3, and 5-year local tumor progression rates after treatment were 4, 14, and 14%. Survival rates at 1,3, and 5-year were 92, 72, and 64%. No treatment-related deaths and severe complications were recorded. Conclusions. Radiofrequency ablation is effective with 96% of primary ablation with few tumoral recurrence and limited morbidity in patients with hepatocellular carcinoma associated with chronic liver disease without cirrhosis, it could represent a valid alternative treatment whenever surgical therapy is not safe. PMID:18974861

  17. 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

  18. Portal vein thrombosis in liver cirrhosis - the added value of contrast enhanced ultrasonography.

    PubMed

    Danila, Mirela; Sporea, Ioan; Popescu, Alina; Șirli, Roxana

    2016-06-01

    Portal vein thrombosis (PVT) is a frequent complication of liver cirrhosis and its prevalence increases with the severity of liver disease. Patients with liver cirrhosis and hepatocellular carcinoma may have either malignant or blunt (benign) PVT. In these patients, the diagnosis and characterization of PVT is important for the prognosis and further treatment. Ultrasound (US) is the modality of choice for the diagnosis of PVT. The features of PVT on B-mode (gray-scale) US include: dilatation of the portal vein, visualization of the thrombus and, in chronic PVT- cavernous transformation. Sensitivity of US in the diagnosis of PVT is improved by the use of Doppler US and of ultrasound contrast agents. In the latter years, contrast enhanced ultrasound (CEUS) showed high sensitivity in the differential diagnosis between benign and malignant PVT and could be the diagnostic method of choice for the characterization of PVT. Blunt thrombi are avascular and will not enhance during CEUS examination, while a hyperenhancement pattern of the portal thrombus in the arterial phase, with "wash out" in the portal or late phase is typical for malignant PVT. PMID:27239658

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

    Hadano, Yoshiro; Iwata, Hiroyoshi

    2013-01-01

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

  1. 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. PMID:8329968

  2. 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

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

    PubMed Central

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

    2013-01-01

    Background Occult hepatitis C virus (HCV) infection is a new entity described by the presence of HCV-RNA in liver biopsy and/or peripheral blood mononuclear cell (PBMC) specimens, and undetectable levels or absence of HCV-RNA and in the absence or presence of anti HCV antibodies in plasma by current laboratory methods. Objectives To evaluate the detection of HCV-RNA in PBMC specimens of the liver transplant candidates with cryptogenic cirrhosis by reverse transcriptase-nested polymerase chain reaction (RT-nested PCR). Patients and Methods From November 2007 to March 2013, 45 patients from Liver Transplant Center of Imam Khomeini Hospital, Tehran, were enrolled in this cross sectional study. PBMC specimens were separated from the peripheral blood sample. After extraction of RNA from plasma and PBMC specimens, HCV-RNA status was tested by RT-nested PCR. The 5′-untranslated region (5′-UTR) genotyping of HCV-RNA amplified from PBMC specimens was performed by a standard methodology with the INNO-LiPATM HCV II kit. The PCR products of 5′-UTR were sequenced after cloning into the pJET1.2 / blunt cloning vector. Results Of 45 patients, 4 (8.9% [95% CI: 4.4-15.6]) had detectable genomic HCV-RNA in their PBMC specimens. HCV genotypes were determined in the PBMCs of these subjects showed that 2 (50.0%) subjects with occult HCV infection had HCV subtype 3a, and 2 (50.0%) had HCV subtype 1b. Conclusions This study found that 8.9 % of the Iranian candidates for liver transplant with cryptogenic cirrhosis had occult HCV infection. Therefore, designing prospective studies focusing on the diagnosis of occult HCV infection in these subjects prior to liver transplantation could be valuable. PMID:24082889

  4. Worldwide patterns and trends in mortality from liver cirrhosis, 1955 to 1990.

    PubMed

    La Vecchia, C; Levi, F; Lucchini, F; Franceschi, S; Negri, E

    1994-11-01

    Trends in mortality rates for liver cirrhosis between 1955 and 1990 have been analyzed for 38 countries (two from North America, six from Latin America, five from Asia, 23 from Europe, and Australia and New Zealand) on the basis of official death certification data derived from the World Health Organization database. Chile and Mexico had exceedingly high rates (around 60/100,000 males and 15/100,000 females in the late 1980s), while in Canada, the United States, and Latin American countries that provided data, cirrhosis death rates were between 5 and 17/100,000 males and 3 and 5/100,000 females over the same calendar period. The pattern of trends was, however, similar in all American countries, with some increase between the 1950s and the 1970s, and declines thereafter. A similar trend was observed in Japanese males, whose rate was 13.6 in 1990. Conversely, cirrhosis mortality declined steadily from 8.0 to 4.6 in Japanese females. Appreciable downward trends were observed in Hong Kong and Singapore, whereas mortality increased in Thailand. In Europe, in the late 1950s, the highest rates were registered in Portugal (33.6/100,000 males and 14.6/100,000 females), followed by France (31.8/100,000 males and 14.1/100,000 females), Austria, Italy, Spain, and Germany. Most of these countries, however, after some further rise up to the 1970s, showed reversal of the trends over most recent years. Thus, in the late 1980s or early 1990s, only Austria, Italy, and Portugal had cirrhosis mortality around 30/100,000 males and 10/100,000 females. Britain, Ireland, and Nordic countries started from much lower values (2 to 4/100,000 males), but showed some, although discontinuous, upward trend.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7804504

  5. 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

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

    PubMed Central

    2013-01-01

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

  7. Allocation of patients with liver cirrhosis and organ failure to intensive care: Systematic review and a proposal for clinical practice

    PubMed Central

    Lindvig, Katrine Prier; Teisner, Ane Søgaard; Kjeldsen, Jens; Strøm, Thomas; Toft, Palle; Furhmann, Valentin; Krag, Aleksander

    2015-01-01

    AIM: To propose an allocation system of patients with liver cirrhosis to intensive care unit (ICU), and developed a decision tool for clinical practice. METHODS: A systematic review of the literature was performed in PubMed, MEDLINE and EMBASE databases. The search includes studies on hospitalized patients with cirrhosis and organ failure, or acute on chronic liver failure and/or intensive care therapy. RESULTS: The initial search identified 660 potentially relevant articles. Ultimately, five articles were selected; two cohort studies and three reviews were found eligible. The literature on this topic is scarce and no studies specifically address allocation of patients with liver cirrhosis to ICU. Throughout the literature, there is consensus that selection criteria for ICU admission should be developed and validated for this group of patients and multidisciplinary approach is mandatory. Based on current available data we developed an algorithm, to determine if a patient is candidate to intensive care if needed, based on three scoring systems: premorbid Child-Pugh Score, Model of End stage Liver Disease score and the liver specific Sequential Organ Failure Assessment score. CONCLUSION: There are no established systems for allocation of patients with liver cirrhosis to the ICU and no evidence-based recommendations can be made. PMID:26269687

  8. Should surveillance for liver cancer be modified in hepatitis C patients after treatment-related cirrhosis regression?

    PubMed

    D'Ambrosio, Roberta; Colombo, Massimo

    2016-06-01

    Surveillance of hepatocellular carcinoma (HCC) with abdominal ultrasound (US) is recommended for patients with advanced liver fibrosis because of hepatitis C virus (HCV) infections who achieve a sustained virological response (SVR) to antiviral therapy. HCC, in fact, may still develop following SVR as a consequence of long-standing carcinogenic activity of either HCV or hepatic fibrosis, whereas HCC risk in non-viraemic patients may also be driven by cofactors like alcohol abuse or diabetes. This explains the debate on whether surveillance for HCC should be continued in patients with documented cirrhosis regression following a SVR too. While regression of cirrhosis was documented to occur in a majority of patients with compensated cirrhosis 5 years after an SVR to interferon, it should be noted that this clinical benefit could be the consequence of treating a selected population with well-compensated liver disease who in fact were interferon able. This may not be the case for most real-life patients with advanced cirrhosis receiving direct antivirals, in whom liver fibrosis may have reached a point of no-return thus potentially preventing the recovery of a normal liver architecture following SVR. Both invasive and non-invasive tools have suboptimal diagnostic accuracy for fibrosis regression in non-viraemic patients, and this prompts to follow international societies' recommendation to perform surveillance in patients with advanced liver fibrosis achieving a SVR, independently on liver histology outcome. PMID:26936383

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

    PubMed Central

    2009-01-01

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

  10. Prospective study of profile of hepatic osteodystrophy in patients with non-choleastatic liver cirrhosis and impact of bisphosphonate supplementation

    PubMed Central

    Bansal, Rinkesh Kumar; Kumar, Mandhir; Kumar, Ashish

    2015-01-01

    Background and objectives Patients with liver cirrhosis are more prone to develop reduced bone mineral density (BMD), i.e. hepatic osteodystrophy (HOD). There are few data on the prevalence of HOD in the Indian population and its treatment. We aimed to determine the prevalence of HOD, factors associated with it and the impact of bisphosphonates on BMD in patients with liver cirrhosis. Patients and methods Consecutive patients with liver cirrhosis admitted at Sir Ganga Ram Hospital, New Delhi, between August 2012 and July 2013 were enrolled. Patients with chronic kidney disease, hyperparathyroidism and those on steroids were excluded. BMD was measured by dual-energy X-ray absorptiometry (DEXA) at the lumbar spine and femoral neck. Osteopenia and osteoporosis were defined according to WHO criteria. Ibandronic acid 150 mg per day orally for six months was given to patients with osteoporosis and DEXA scan repeated. Results A total of 215 patients (males 179, 83%) with a mean age of 50.9 ± 11 years were enrolled in this study. Prevalence of HOD was found to be 66% (142/215). On multivariate analysis BMI, TLC, total serum bilirubin and transient elastography values were found to be independently associated with HOD. All the patients with osteoporosis (n = 47) were treated with ibandronic acid as per protocol. Treated patients had significant improvement in DEXA scans after six months as compared to baseline. Conclusions HOD was seen in two-thirds of patients with liver cirrhosis. Higher liver stiffness as determined by transient elastography is significantly associated with HOD. Severity scores of liver disease (CTP and MELD) and etiology of liver cirrhosis did not determine HOD. Ibandronic acid is a safe drug that showed significant improvement in BMD in patients with liver disease along with osteoporosis. PMID:26966526

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

    PubMed Central

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

    2001-01-01

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

  12. The effectiveness of the treatment of octreotide on chylous ascites after liver cirrhosis.

    PubMed

    Zhou, Dong Xun; Zhou, Hua Bang; Wang, Qing; Zou, Shan Shan; Wang, Hao; Hu, He Ping

    2009-08-01

    Octreotide is a crucial drug used for treating patients with chylous ascites; however, there have been few reports related to octreotide that are being used in cirrhotic patients. Thus, this thesis is designed to determine the effects of octreotide on patients with chylous ascites after liver cirrhosis. Eight patients were diagnosed with chylous ascites, on the basis of laboratory findings on ascites samples, between January 2003 and May 2008. Octreotide was given to the six patients, while the remaining two were treated as a control. All patients had persistent peritoneal drainage with the quantity and quality of the drainage fluid observed once every other day. All the necessary care was individually given to the patients during the therapy. All patients properly received combined therapy including a low-fat and low-sodium diet, and diuretic and peritoneal drainage. The volume of the peritoneal drainage was reduced to zero in one of the six patients who received octreotide therapy, while the other five had the drainage volumes decreased from 2,000 to 50 ml with a clear appearance and negative qualitative analysis of chyle. For those two patients who did not receive octreotide therapy, the conditions of peritoneal drainage seldom changed both from the qualitative and quantitative aspects. In conclusion, Octreotide, along with combined therapy, can rapidly relieve portal hypertension and reduce triglyceride levels in ascites. It appears to be an effective therapy available for the treatment of chylous ascites caused by liver cirrhosis. PMID:19051030

  13. Genetic polymorphism in alcohol dehydrogenase 2 (ADH2) gene and alcoholic liver cirrhosis risk

    PubMed Central

    He, Lei; Deng, Tao; Luo, He-Sheng

    2015-01-01

    The alcohol dehydrogenase 2 (ADH2) gene has been implicated in the development of alcoholic liver cirrhosis (ALC). However, the results are inconsistent. In this study, a meta-analysis was performed to assess the associations between the ADH2 polymorphism and the risk of ALC. Relevant studies were retrieved by searching PubMed, Web of Science, CNKI, Wanfang and VIP databases up to January 10, 2015. The pooled odds ratio (OR) with a 95% confidence interval (CI) was calculated using the fixed- or random effects model. A total of 21 case-control studies included 1812 cases and 3468 controls were included. Overall, the ADH2 polymorphism was associated with a decreased risk of ALC in all four genetic models (dominant model: OR=0.56, 95% CI: 0.38-0.83; recessive model: OR=0.59, 95% CI: 0.39-0.91; *1/*2 vs. *1/*1: OR=0.58, 95% CI: 0.40-0.85; *2/*2 vs *1/*1: OR=0.35, 95% CI: 0.16-0.75). Besides, in stratification analysis by ethnicity, similar results were observed in Asian populations, however, we detected no association in Caucasian populations under recessive and homozygote comparison model. The pooled evidence suggests that ADH2 polymorphism may be an important protective factor for alcoholic liver cirrhosis, especially for Asians. PMID:26221330

  14. I drink for my liver, Doc: emerging evidence that coffee prevents cirrhosis.

    PubMed

    Feld, Jordan J; Lavoie, Élise G; Fausther, Michel; Dranoff, Jonathan A

    2015-01-01

    Evidence demonstrating that regular ingestion of coffee has salutary effects on patients with chronic liver disease is accumulating rapidly. Specifically, it appears that coffee ingestion can slow the progression of liver fibrosis, preventing cirrhosis and hepatocellular carcinoma (HCC). This should excite clinicians and scientists alike, since these observations, if true, would create effective, testable hypotheses that should lead to improved understanding on fibrosis pathogenesis and thus may generate novel pharmacologic treatments of patients with chronic liver disease. This review is designed to examine the relevant clinical and epidemiological data in critical fashion and to examine the putative pharmacological effects of coffee relevant to the pathogenesis of liver fibrosis and cirrhosis. We hope that this will inspire relevant critical analyses, especially among "coffee skeptics". Of note, one major assumption made by this review is that the bulk of the effects of coffee consumption are mediated by caffeine, rather than by other chemical constituents of coffee. Our rationales for this assumption are threefold: first, caffeine's effects on adenosinergic signaling provide testable hypotheses; second, although there are  myriad chemical constituents of coffee, they are present in very low concentrations, and perhaps more importantly, vary greatly between coffee products and production methods (it is important to note that we do not dismiss the "botanical" hypothesis here; rather, we do not emphasize it at present due to the limitations of the studies examined); lastly, some (but not all) observational studies have examined both coffee and non-coffee caffeine consumption and found consistent effects, and when examined, no benefit to decaffeinated coffee has been observed. Further, in the interval since we examined this phenomenon last, further evidence has accumulated supporting caffeine as the effector molecule for coffee's salutary effects. PMID:25977756

  15. I drink for my liver, Doc: emerging evidence that coffee prevents cirrhosis

    PubMed Central

    Feld, Jordan J.; Lavoie, Élise G.; Fausther, Michel; Dranoff, Jonathan A.

    2015-01-01

    Evidence demonstrating that regular ingestion of coffee has salutary effects on patients with chronic liver disease is accumulating rapidly. Specifically, it appears that coffee ingestion can slow the progression of liver fibrosis, preventing cirrhosis and hepatocellular carcinoma (HCC). This should excite clinicians and scientists alike, since these observations, if true, would create effective, testable hypotheses that should lead to improved understanding on fibrosis pathogenesis and thus may generate novel pharmacologic treatments of patients with chronic liver disease. This review is designed to examine the relevant clinical and epidemiological data in critical fashion and to examine the putative pharmacological effects of coffee relevant to the pathogenesis of liver fibrosis and cirrhosis. We hope that this will inspire relevant critical analyses, especially among “coffee skeptics”. Of note, one major assumption made by this review is that the bulk of the effects of coffee consumption are mediated by caffeine, rather than by other chemical constituents of coffee. Our rationales for this assumption are threefold: first, caffeine’s effects on adenosinergic signaling provide testable hypotheses; second, although there are  myriad chemical constituents of coffee, they are present in very low concentrations, and perhaps more importantly, vary greatly between coffee products and production methods (it is important to note that we do not dismiss the “botanical” hypothesis here; rather, we do not emphasize it at present due to the limitations of the studies examined); lastly, some (but not all) observational studies have examined both coffee and non-coffee caffeine consumption and found consistent effects, and when examined, no benefit to decaffeinated coffee has been observed. Further, in the interval since we examined this phenomenon last, further evidence has accumulated supporting caffeine as the effector molecule for coffee’s salutary effects. PMID:25977756

  16. 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

  17. Genetic, metabolic and environmental factors involved in the development of liver cirrhosis in Mexico.

    PubMed

    Ramos-Lopez, Omar; Martinez-Lopez, Erika; Roman, Sonia; Fierro, Nora A; Panduro, Arturo

    2015-11-01

    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

  18. 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

  19. Portal Hypertension in Patients with Liver Cirrhosis: Diagnostic Accuracy of Spleen Stiffness.

    PubMed

    Takuma, Yoshitaka; Nouso, Kazuhiro; Morimoto, Youichi; Tomokuni, Junko; Sahara, Akiko; Takabatake, Hiroyuki; Matsueda, Kazuhiro; Yamamoto, Hiroshi

    2016-05-01

    Purpose To evaluate the accuracy of spleen stiffness (SS) and liver stiffness (LS) measured by using acoustic radiation force impulse imaging in the diagnosis of portal hypertension in patients with liver cirrhosis, with the hepatic venous pressure gradient (HVPG) as a reference standard. Materials and Methods Institutional review board approval and informed consent were obtained for this prospective single-center study. From February 2012 to August 2013, 60 patients with liver cirrhosis (mean age, 70.8 years; age range, 34-88 years; 34 men, 26 women) with HVPG, LS, and SS measurements and gastrointestinal endoscopy and laboratory data were included if they met the following criteria: no recent episodes of gastrointestinal bleeding, no history of splenectomy, no history of partial splenic embolization, no history of β-blocker therapy, and absence of portal thrombosis. The efficacy of the parameters for the evaluation of portal hypertension was analyzed by using the Spearman rank-order correlation coefficient and receiver operating characteristic (ROC) curve analysis. Results The correlation coefficient between SS and HVPG (r = 0.876) was significantly better than that between LS and HVPG (r = 0.609, P < .0001). The areas under the ROC curve of SS for the identification of clinically important portal hypertension (HVPG ≥ 10 mm Hg), severe portal hypertension (HVPG ≥ 12 mm Hg), esophageal varices (EVs), and high-risk EVs were significantly higher (0.943, 0.963, 0.937, and 0.955, respectively) than those of LS, spleen diameter, platelet count, and platelet count to spleen diameter ratio (P < .05 for all). SS could be used to accurately rule out the presence of clinically important portal hypertension, severe portal hypertension, EVs, and high-risk EVs (negative likelihood ratios, 0.051, 0.056, 0.054, and 0.074, respectively). Conclusion SS is reliable and has better diagnostic performance than LS for identifying portal hypertension in liver cirrhosis. (©) RSNA, 2015 Online supplemental material is available for this article. PMID:26588019

  20. 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.

  1. Tyrosine kinase inhibitors improve parenchymal findings of liver cirrhosis in a patient exhibiting concomitant hepatocellular carcinoma and renal cell cancer

    PubMed Central

    KUS, TULAY; AKTAS, GOKMEN; SEVINC, ALPER; OKTAY, CEMIL; KALENDER, MEHMET EMIN; CAMCI, CELALETDIN

    2016-01-01

    Hepatocellular carcinoma (HCC) and renal cell cancer (RCC) are malignancies, which are chemotherapy resistant and fatal at the advanced stages. Previously developed tyrosine kinase inhibitors are used in the treatment of advanced stage disease. In the present case study, a patient using sunitinib for stage IV RCC presented with HCC following 2 years of treatment. A patient who exhibited Child-Pugh class C cirrhosis initially, exhibited a marked improvement of hepatocellular parenchyma findings following treatment with sunitinib. Sunitinib is suggested to have preventive effects on the pathogenesis of liver fibrosis and cirrhosis in vitro, via an anti-vascular endothelial growth factor and anti-platelet-derived growth factor mechanism. However, no clinical supportive study has been performed until now. Improvement of liver functions may be explained in this manner. Therefore, investigations are required with different doses of sunitinib and other tyrosine kinase inhibitors in order to evaluate the efficacy on treatment of cirrhosis progression. PMID:26893877

  2. 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

  3. Association of sustained virologic response with reduced progression to liver cirrhosis in elderly patients with chronic hepatitis C

    PubMed Central

    Tseng, Chih-Wei; Chang, Ting-Tsung; Tzeng, Shinn-Jia; Hsieh, Yu-Hsi; Hung, Tsung-Hsing; Huang, Hsiang-Ting; Wu, Shu-Fen; Tseng, Kuo-Chih

    2016-01-01

    Objective We studied the effect of sustained virologic response (SVR) after treatment with pegylated-interferon (PEG-IFN) plus ribavirin on the development of liver cirrhosis in elderly patients with chronic hepatitis C (CHC). Patients and methods This retrospective study enrolled 145 elderly CHC patients (aged ≥65 years) who were treatment-naïve and were treated with PEG-IFN plus ribavirin for 6 months between January 2005 and December 2011. Abdominal sonography was performed and liver biochemistry was studied at baseline, at the end of treatment, and every 3–6 months thereafter. The development of liver cirrhosis and related complications was evaluated at the follow-ups. The aspartate aminotransferase-to-platelet ratio index was used as a noninvasive maker for fibrosis. Results The mean patient age was 69.1±3.3 years, and the average follow-up time was 5.5 years (standard deviation: 2.5 years, range: 1.1–12.3 years). Ninety-five patients (65.5%) achieved SVR, and 26 (17.9%) discontinued treatment. Twenty-seven patients (18.6%) developed liver cirrhosis after treatment. Patients without SVR had significantly greater risk of liver cirrhosis than those with SVR (hazard ratio [HR]: 3.39, 95% confidence interval [CI]: 1.312–8.761, P=0.012). The difference in 3-year cumulative incidence of liver cirrhosis was 24.8% greater for patients without SVR (35.2%, 95% CI: 13.0–57.5, P=0.012) compared with those with SVR (10.4%, 95% CI: 3.1–17.7). There was a trend of a higher baseline aspartate aminotransferase-to-platelet ratio index score in patients who progressed to liver cirrhosis compared with those who did not progress (2.1±1.2 vs 1.6±1.3, P=0.055), but the difference failed to reach significance by Cox regression (adjusted HR: 1.285, 95% CI: 0.921–1.791, P=0.14). Conclusion An SVR following PEG-IFN combination treatment can reduce the risk of liver cirrhosis in elderly CHC patients. PMID:27051280

  4. Necrotizing Fasciitis Among Patients With Liver Cirrhosis in Texas, 2001 - 2010: A Population-Based Cohort Study

    PubMed Central

    Oud, Lavi; Watkins, Phillip

    2016-01-01

    Background Liver cirrhosis is a risk factor for necrotizing fasciitis (NF), and is associated with markedly worse outcomes than for NF among non-cirrhosis patients. Only limited, mostly single-center, data were reported to date on the epidemiology, clinical features, resource utilization and outcomes of NF among patients with cirrhosis. Methods We studied a population-based cohort of adult hospitalizations associated with cirrhosis, who had a diagnosis of NF during the years 2001 - 2010, using the Texas Inpatient Public Use Data File. The annual volume of NF hospitalizations was benchmarked against all annual hospitalizations with a diagnosis of cirrhosis. The patterns of demographics, chronic comorbidities, evolving organ failure, resource utilization and outcomes were examined. Results There were 371,745 hospitalizations associated with liver cirrhosis, with 381 NF hospitalizations during study period. The annual volume of NF hospitalizations rose 7.9%/year (P = 0.0287), while its incidence among cirrhosis-associated hospitalizations remained unchanged (P = 0.2955). Non-cirrhosis comorbidities were reported in 69.6% and ICU care was required in 67.2% of NF hospitalization. The key changes noted between 2001 - 2003 and 2008 - 2010 among NF hospitalizations included rising mean (SD) Deyo-Charlson index 2.4 (1.5) vs. 3.9 (2.4) (P < 0.0001), development of ≥ 3 organ failures in 9.1% vs. 39.8% (P < 0.0001), and discharge to long-term care facilities 7.8% vs. 21.1% (P = 0.0204). Hospital mortality was unchanged (26% vs. 33.1%; P = 0.3659). Inflation-adjusted total hospital charges did not change (P = 0.1025) during study period. Conclusions The present cohort of NF associated with liver cirrhosis is the largest reported to date. A rising annual volume of NF events matched a corresponding increase in cirrhosis-associated hospitalizations. There was increasing burden of chronic comorbidity and rising severity of illness, with a majority of patients requiring ICU care. Case fatality was high and there has been increasing residual morbidity among hospital survivors. The observed findings warrant further study in other populations. PMID:26767076

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

    PubMed Central

    Nowosławski, Adam; Krawczyński, Krzysztof; Brzosko, Witold J.; Madaliński, Kazimierz

    1972-01-01

    In a significant percentage of examined cases of fulminant hepatitis, subacute hepatitis, chronic aggressive hepatitis, liver cirrhosis and chronic persistent hepatitis, Australia (hepatitis-associated) antigen (Au HAA) was identified in the liver and in extrahepatic locations. The several immunofluorescent patterns of Au HAA localization in hepatocytes strongly suggested various stages of Au HAA accumulation and release. Deposits of a mixture of immunoglobulins G and M and occasionally β1C-globulin were found in the cytoplasm of Au HAA containing hepatocytes, on their plasma membranes, on or in the nuclei, in the cytoplasm of Kupffer cells and, rarely, in the sinusoids. The accompanying tissue changes were hepatocellular degeneration and necrosis. These intra- and extracellular complexes of Au HAA and immunoglobulins displayed strong affinity for guinea pig complement in the immunohistochemical complement fixation reaction. When tested by immunodiffusion in agar, IgG dissociated from these complexes by potassium thiocyanate (KSCN) treatment showed anti-Au HAA specificity. In fulminant hepatitis neither Au HAA nor immunoglobulins and complement were found in the liver. In chronic aggressive hepatitis and subacute hepatitis the amount of the Au HAA immune complexes identified in the liver was approximately inversely proportional to the extent and severity of the parenchymal lesions. In liver cirrhosis and chronic persistent hepatitis there was a positive correlation between the amount of the Au HAA immune complexes found in the liver and the degree of hepatocellular damage. The deposits of Au HAA, identified in extrahepatic locations including germinal centers of lymph nodes and spleen, kidney glomeruli and blood vessel walls, were as a rule accompanied by deposits of IgG, IgM, β1C-globulin and fibrin. All these deposits showed strong affinity for guinea pig complement in the immunohistochemical reaction of complement fixation. Germinal center activation, chronic membraneous glomerulonephritis, panarteritis and simple arteriolar hyalinosis were found at sites of localization of these deposits. ImagesFig 21Fig 22Fig 23Fig 24Fig 1Fig 2Fig 3Fig 4Fig 5Fig 6Fig 25Fig 26Fig 27Fig 28Fig 29Fig 7Fig 8Fig 9Fig 10Fig 11Fig 12Fig 13Fig 14Fig 15Fig 16Fig 17Fig 18Fig 19Fig 20 PMID:4628111

  6. 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. PMID:25755099

  7. 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

  8. A profile of volatile organic compounds in exhaled air as a potential non-invasive biomarker for liver cirrhosis.

    PubMed

    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

  9. 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 liver, as well as those in the mesenteric vascular circulation. Translational implications of recent research and the future directions that it points to are also highlighted. PMID:24911462

  10. 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 as those in the mesenteric vascular circulation. Translational implications of recent research and the future directions that it points to are also highlighted. PMID:24911462

  11. Inflammation: A novel target of current therapies for hepatic encephalopathy in liver cirrhosis

    PubMed Central

    Luo, Ming; Guo, Jian-Yang; Cao, Wu-Kui

    2015-01-01

    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. PMID:26557005

  12. Inflammation: A novel target of current therapies for hepatic encephalopathy in liver cirrhosis.

    PubMed

    Luo, Ming; Guo, Jian-Yang; Cao, Wu-Kui

    2015-11-01

    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. PMID:26557005

  13. State-of-the-art imaging of liver fibrosis and cirrhosis: A comprehensive review of current applications and future perspectives

    PubMed Central

    Huber, Adrian; Ebner, Lukas; Heverhagen, Johannes T.; Christe, Andreas

    2015-01-01

    Objective The purpose of this article is to provide a comprehensive overview of imaging findings in patients with hepatic fibrosis and cirrhosis; and to describe which radiological/clinical modality is best for staging hepatic fibrosis. Conclusion MR elastography (MRE) appears to be the most reliable method for grading liver fibrosis, although the CT fibrosis score derived from the combination of caudate-to-right-lobe ratio and the diameters of the liver veins significantly correlates with the stage of fibrosis. PMID:26937441

  14. 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

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

    PubMed Central

    2014-01-01

    Background Although cardiovascular disease is thouht to be common in cirrhosis, there are no systematic investigations on the prevalence of electrocardiographic (ECG) abnormalities in these patients and data on the occurrence of post-transplant cardiac events in comparison with the general population are lacking. We aimed to study the prevalence and predictors of ECG abnormalities in patients with cirrhosis undergoing liver transplantation and to define the risk of cardiac events post-transplant compared to the general population. Methods Cirrhotic patients undergoing first-time liver transplantation between 1999–2007 were retrospectively enrolled. ECGs at pre-transplant evaluation were reviewed using the Minnesota classification and compared to healthy controls. Standardized incidence ratios for post-transplant cardiac events were calculated. Results 234 patients with cirrhosis were included, 186 with an available ECG (36% with alcoholic and 24% with viral cirrhosis; mean follow-up 4 years). Cirrhotics had a prolonged QTc interval, a Q wave, abnormal QRS axis deviation, ST segment depression and a pathologic T wave more frequently compared to controls (p < 0.05 for all). Arterial hypertension, older age, cirrhosis severity and etiology were related to ECG abnormalities. Compared to the general Swedish population, patients were 14 times more likely to suffer a cardiac event post-transplant (p < 0.001). A prolonged QTc interval and Q wave were related to post-transplant cardiac events (p < 0.05 for all). Conclusions Pre-transplant ECG abnormalities are common in cirrhosis and are associated with cardiovascular risk factors and cirrhosis severity and etiology. Post-transplant cardiac events are more common than in the general population. PMID:24708568

  16. 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 from the reduction of thioacetamide-induced toxicity, normalizing reactive oxygen species levels, inhibiting cellular proliferation, and inducing apoptosis in HepG2 cells. PMID:25280007

  17. Cirrhosis and Portal Hypertension

    MedlinePlus

    MENU Return to Web version Cirrhosis and Portal Hypertension Overview What is cirrhosis? In people who have ... lead to coma and death. What is portal hypertension? Normally, blood is carried to the liver by ...

  18. Excretion of [24-14C] glycochenodeoxycholate-3-sulphate in patients with liver cirrhosis.

    PubMed

    Hedenborg, G; Norman, A; Wisén, O

    1989-02-01

    [24-14C] glycochenodeoxycholate-3-sulphate (GCDC-3S) was given intravenously to seven patients with liver cirrhosis and the elimination of the isotope from blood and the isotope excretion in urine and faeces followed. The bile acid conjugates in serum and urine were separated by HPLC and the change in specific activity in isolated conjugates determined. [24-14C] GCDC-3S was rapidly eliminated either by urinary excretion or faecal excretion and the half-life of the labelled conjugates varied between 76-198 min. No deamination or desulphation of the isotope occurred prior to urinary excretion. Only small amounts of GCDC-3S excreted in bile were absorbed from the intestine, as no isotope was recovered in other bile acid conjugates in serum. PMID:2727614

  19. 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. PMID:23467463

  20. [Plasma amino acids in patients with liver cirrhosis treated with lactulose].

    PubMed

    Giardina, M G; Matarazzo, M; Prantera, T; Verre, C; De Marco, F

    1984-12-30

    The altered plasma amino acid pattern (i.e. increased levels of aromatic amino acids and decreased levels of branched chain amino acids) is a characteristic feature of cirrhotic patients. Recently it has been proved that an increased net degradation of BCAA is positively correlated to the plasma NH3 level, strongly suggesting that these amino acids are molecularly involved in glutamine synthesis to detoxify ammonia in skeletal muscle. Lactulose, a synthetic, nonabsorbable disaccharide, is believed to actively promote excretion of ammonia from the body by causing it to be trapped in the acidified fecal stream and making it unavailable for absorption. Therefore therapy with lactulose could determine an increase of BCAA. The present study was undertaken to examine plasma amino acid pattern of ten patients with liver cirrhosis before and after lactulose therapy. No statistically significant changes of amino acids were observed. PMID:6529509

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    1994-01-01

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

  3. Effect of artesunate supplementation on bacterial translocation and dysbiosis of gut microbiota in rats with liver cirrhosis

    PubMed Central

    Chen, Yun-Xia; Lai, Li-Na; Zhang, Hui-Ying; Bi, Yang-Hui; Meng, Li; Li, Xu-Jiong; Tian, Xiao-Xia; Wang, Li-Min; Fan, Yi-Min; Zhao, Zhong-Fu; Han, De-Wu; Ji, Cheng

    2016-01-01

    AIM: To evaluate the effect of artesunate (AS) supplementation on bacterial translocation (BT) and gut microbiota in a rat model of liver cirrhosis. METHODS: Fifty-four male Sprague-Dawley rats were randomly divided into a normal control group (N), a liver cirrhosis group (M) and a liver cirrhosis group intervened with AS (MA). Each group was sampled at 4, 6 and 8 wk. Liver cirrhosis was induced by injection of carbon tetrachloride (CCl4), intragastric administration of 10% ethanol, and feeding a high fat diet. Rats in the MA group were intragastrically administered with AS (25 mg/kg body weight, once daily). Injuries of the liver and intestinal mucosa were assessed by hematoxylin-eosin or Masson’s trichrome staining. Liver index was calculated as a ratio of the organ weight (g) to body weight (g). The gut microbiota was examined by automated ribosomal intergenic-spacer analysis of fecal DNA. BT was assessed by standard microbiological techniques in the blood, mesenteric lymph nodes (MLNs), liver, spleen, and kidney. RESULTS: Compared to group N, the body weight was reduced significantly in groups M and MA due to the development of liver cirrhosis over the period of 8 wk. The body weight was higher in group MA than in group M. The liver indices were significantly elevated at 4, 6 and 8 wk in groups M and MA compared to group N. AS supplementation partially decreased the liver indices in group MA. Marked histopathologic changes in the liver and small intestinal mucosa in group M were observed, which were alleviated in group MA. Levels of pro-inflammatory interleukin-6 and tumor necrosis factor-α were significantly elevated at 8 wk in ileal homogenates in group M compared to group N, which were decreased after AS supplementation in group MA. The dysbiosis of gut microbiota indicated by the mean diversity (Shannon index) and mean similarity (Sorenson index) was severe as the liver cirrhosis developed, and AS supplementation had an apparent intervention effect on the dysbiosis of gut microbiota at 4 wk. The occurrence of BT was increased in the liver of group M compared to that of group N. AS supplementation reduced BT in group MA at 8 wk. BT also occurred in the MLNs, spleen, and kidney, which was reduced by AS supplementation. BT was not detected in the blood in any group. CONCLUSION: Dysbiosis of gut microbiota, injury of intestinal mucosal barrier and BT occurred as liver cirrhosis progressed, which might enhance inflammation and aggravate liver injury. AS may have other non-antimalarial effects that modulate gut microbiota, inhibit BT and alleviate inflammation, resulting in a reduction in CCl4, alcohol and high fat-caused damages to the liver and intestine. PMID:26973391

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

    PubMed Central

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

    2015-01-01

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

  5. Autologous mobilized peripheral blood CD34+ cell infusion in non-viral decompensated liver cirrhosis

    PubMed Central

    Sharma, Mithun; Rao, Padaki Nagaraja; Sasikala, Mitnala; Kuncharam, Mamata Reddy; Reddy, Chimpa; Gokak, Vardaraj; Raju, BPSS; Singh, Jagdeesh R; Nag, Piyal; Reddy, D Nageshwar

    2015-01-01

    AIM: To study the effect of mobilized peripheral blood autologous CD34 positive (CD34+) cell infusion in patients with non-viral decompensated cirrhosis. METHODS: Cirrhotic patients of non-viral etiology were divided into 2 groups based on their willingness to be listed for deceased donor liver transplant (DDLT) (control, n = 23) or to receive autologous CD34+ cell infusion through the hepatic artery (study group, n = 22). Patients in the study group were admitted to hospital and received granulocyte colony stimulating factor injections 520 μg/d for 3 consecutive days to mobilize CD34+ cells from the bone marrow. On day 4, leukapheresis was done and CD34+ cells were isolated using CliniMAC magnetic cell sorter. The isolated CD34+ cells were infused into the hepatic artery under radiological guidance. The patients were discharged within 48 h. The control group received standard of care treatment for liver cirrhosis and were worked up for DDLT as per protocol of the institute. Both groups were followed up every week for 4 wk and then every month for 3 mo. RESULTS: In the control and the study group, the cause of cirrhosis was cryptogenic in 18 (78.2%) and 16 (72.72%) and alcohol related in 5 (21.7%) and 6 (27.27%), respectively. The mean day 3 cell count (cells/μL) was 27.00 ± 20.43 with a viability of 81.84 ± 11.99%. and purity of 80%-90%. Primary end point analysis revealed that at 4 wk, the mean serum albumin in the study group increased significantly (2.83 ± 0.36 vs 2.43 ± 0.42, P = 0.001) when compared with controls. This improvement in albumin was, however, not sustained at 3 mo. However, at the end of 3 mo there was a statistically significant improvement in serum creatinine in the study group (0.96 ± 0.33 vs 1.42 ± 0.70, P = 0.01) which translated into a significant improvement in the Model for End-Stage Liver Disease score (15.75 ± 5.13 vs 19.94 ± 6.68, P = 0.04). On statistical analysis of secondary end points, the transplant free survival at the end of 1 mo and 3 mo did not show any significant difference (P = 0.60) when compared to the control group. There was no improvement in aspartate transaminase, alanine transaminase, and bilirubin at any point in the study population. There was no mortality benefit in the study group. The procedure was safe with no procedural or treatment related complications. CONCLUSION: Autologous CD 34+ cell infusion is safe and effectively improves liver function in the short term and may serve as a bridge to liver transplantation. PMID:26109814

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

    PubMed Central

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

    2015-01-01

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

  7. Direct antiviral agent treatment of decompensated hepatitis C virus-induced liver cirrhosis

    PubMed Central

    Ohkoshi, Shogo; Hirono, Haruka; Yamagiwa, Satoshi

    2015-01-01

    Recently, direct antiviral agents (DAAs) have been increasingly used for the treatment of chronic hepatitis C virus (HCV) infections, replacing interferon-based regimens that have severe adverse effects and low tolerability. The constant supply of new DAAs makes shorter treatment periods with enhanced safety possible. The efficacy of DAAs for treatment of compensated liver cirrhosis (LC) is not less than that for treatment of non-cirrhotic conditions. These clinical advantages have been useful in pre- and post-liver transplantation (LT) settings. Moreover, DAAs can be used to treat decompensated HCV-induced LC in elderly patients or those with severe complications otherwise having poor prognosis. Although encouraging clinical data are beginning to appear, the actual efficacy of DAAs for suppressing disease progression, allowing delisting for LT and, most importantly, improving prognosis of patients with decompensated HCV-LC remains unknown. Case-control studies to examine the short- or long-term effects of DAAs for treatment of decompensated HCV-LC are urgently need. PMID:26558145

  8. Cellular immune function and liver damage in post-hepatitic cirrhosis

    PubMed Central

    Feng, Zhi-Jie; Niu, Ran-Ming; Ren, Xi-Ling; Yao, Xi-Xian

    1997-01-01

    AIM: To study cellular immune function in patients with post-hepatitic cirrhosis (PHC) and its relationship with different types of liver damage. METHODS: Fifty-one patients with PHC, including 20 cases of Child-Pugh class A, 18 of class B, 13 of class C and 22 normal subjects as controls were studied. After peripheral blood mononuclear cells were isolated by Ficoll-Hypaque gradient centrifugation, lymphocyte transformation (LT) test, IL-2 activity and NK cell activity were measured by the 3H-TdR incorporation technique. RESULTS: Changes of LT stimulation index (SI), IL-2 activity (SI) and NK cell activity (%) in patients with PHC were significantly decreased compared with in the healthy controls (18.1 ± 13.0 vs 34.9 ± 21.7, P < 0.01; 8.1 ± 6.0 vs 13.6 ± 5.8, P < 0.01; 40.3 ± 21.7 vs 61.3 ± 20.5, P < 0.01; respectively). The defects of cellular immune function were closely related to Child-Pugh classification. The values in class C were much lower than those in B and A (P < 0.01) and those in B were lower than those in A (P < 0.05). CONCLUSION: Defective cellular immune functions in patients with PHC are connected with the degree of liver damage. PMID:27006578

  9. Systemic vascular resistance and fluid status in patients with decompensated liver cirrhosis with or without functional renal failure in Egypt

    PubMed Central

    Barakat, Ashraf Abd El-Khalik; Nasr, Fatma Mohammad; Metwaly, Amna Ahmed; El-Ghannam, Maged

    2015-01-01

    Background: Functional renal failure and cardiovascular dysfunction are common complications of liver cirrhosis. This study aimed to evaluate cardiac performance, systemic vascular resistance (SVR) and fluid status in patients with decompensated liver cirrhosis either with or without functional renal failure. Methods: Sixty patients diagnosed as having decompensated liver cirrhosis were divided into two groups. Group 1 included 30 patients with decompensated liver cirrhosis with ascites and with creatinine values ≤ 1.5 mg/dl. Group 2 included 30 azotemic decompensated cirrhotic patients with diagnostic criteria of hepatorenal syndrome (HRS). Also, 20 healthy subjects, of matched age and sex to the Group 1 and Group 2 patients, were included in the study as the control group. All patients and normal controls were subjected to clinical examination, laboratory evaluation, ECG, abdominal ultrasonography and echocardiographic studies. Results: The echocardiographic and ECG data showed significant increase in LAD (P<0.01, P<0.01), AoD (P<0.05, P<0.01), interventricular septum thickness (IVST) (P<0.01, P<0.01), posterior wall thickness (PWT) (P<0.01, P<0.01), EDD (P<0.01, P<0.01), ESD (P<0.05, P<0.01), left ventricular (LV) mass (P<0.01, P<0.01), and Corrected QT (QTc) (P<0.01, P<0.01) interval with significant decrease in SVR (P<0.01, P<0.01). Additionally, there was significant decrease in IVC diameter in both patients groups compared to the control group (P<0.01, P<0.01). Conclusion: Patients with decompensated liver cirrhosis have low SVR, and Doppler echocardiography provides an easy noninvasive tool to assess this finding. Also, these patients demonstrate small inferior vena cava (IVC) diameter with normal collapsibility, which indicates low effective plasma volume. Measuring IVC diameter and collapsibility are of value in the prediction of intravascular fluid status in liver cirrhosis. This is especially true with renal dysfunction. Early addition of oral vasoconstrictors in decompensated patients may correct the SVR and circulatory dysfunction and hinder HRS occurrence. PMID:26396731

  10. MELD score and serum sodium in the prediction of survival of patients with cirrhosis awaiting liver transplantation

    PubMed Central

    Londoño, Maria‐Carlota; Cárdenas, Andrés; Guevara, Mónica; Quintó, Llorenç; de las Heras, Dara; Navasa, Miguel; Rimola, Antoni; Garcia‐Valdecasas, Juan‐Carlos; Arroyo, Vicente; Ginès, Pere

    2007-01-01

    Background/Aims Serum sodium predicts prognosis in cirrhosis and may improve the prognostic accuracy of the model for end‐stage liver disease (MELD) score, but the available information is limited. The aim of the present study was to assess the prognostic value of serum sodium in the prediction of survival at 3 and 12 months after listing in patients with cirrhosis awaiting liver transplantation, and to compare its predictive value with that of the MELD score. Patients and methods 308 consecutive patients with cirrhosis listed for transplantation during a 5‐year period were included in the study. The end‐point was survival at 3 and 12 months before transplantation. Variables obtained at the time of listing were analysed for prognostic value using multivariable analysis. Accuracy of prognostic variables was analysed by receiver operating characteristic (ROC) curves. Results The MELD score and serum sodium concentration were the only independent predictors of survival at 3 and 12 months after listing. Low serum sodium was associated with an increased risk of death in all subpopulations of patients with cirrhosis categorised according to the major complication developed before listing. The area under the ROC curves for serum sodium and MELD score was not significantly different both at 3 months (0.83 vs 0.79, respectively) and at 12 months (0.70 vs 0.77, respectively). The addition of serum sodium did not significantly improve the accuracy of the MELD score in the prediction of survival at 3 and 12 months. Conclusion In patients with cirrhosis awaiting liver transplantation, serum sodium and MELD were found to be independent predictors of survival. Larger studies are needed to determine whether the addition of serum sodium to MELD can improve its prognostic accuracy. PMID:17452425

  11. 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.

  12. Hepatocyte proliferation rate is a powerful parameter for predicting hepatocellular carcinoma development in liver cirrhosis.

    PubMed Central

    Borzio, M; Trerè, D; Borzio, F; Ferrari, A R; Bruno, S; Roncalli, M; Colloredo, G; Leandro, G; Oliveri, F; Derenzini, M

    1998-01-01

    AIMS: A sound predictive test is lacking for the identification of cirrhotic patients at high risk of developing hepatocellular carcinoma. The present study evaluates the measurement of hepatocyte expression of silver stained nucleolar organiser region (AgNOR) proteins as a risk factor for the development of hepatocellular carcinoma in cirrhosis. METHODS: Liver biopsies from 176 cirrhotic patients included in a follow up surveillance programme for hepatocellular carcinoma development were evaluated prospectively for hepatocyte AgNOR protein quantity. The follow up programme consisted of clinical and biochemical assessment every three months, and ultrasound scanning and serum alpha-fetoprotein (alpha FP) assessment every six months. Histological sections from the needle biopsies performed at enrollment were stained selectively for AgNOR proteins and the percentage of hepatocytes with an AgNOR protein area > or = 7 micron 2, indicative of a proliferative state (AgNOR proliferation index (AgNOR-PI)), was measured. RESULTS: During the mean (SD) follow up time of 65.5 (36.29) months (range, 12-143; median, 67), hepatocellular carcinoma was diagnosed in 48 of 176 patients (27.3%). The AgNOR-PI of the whole series ranged from 0% to 5% (median, 0.9%), and was significantly higher in patients with liver cell dysplasia and hepatitis B surface antigen (HBsAg) positivity (p < 0.0001 and p = 0.0002, respectively). The 176 patients were divided into two groups according to their AgNOR-PI scores; a cut off value of 2.5% defined by the receiver operating characteristic curve and the Youden index was used. Forty two patients were included in the high AgNOR-PI (< 2.5%) group, and 134 patients the low AgNOR-PI (< 2.5%) group. In the high AgNOR-PI group, 25 of 42 patients developed hepatocellular carcinoma, in contrast to only 23 of 134 patients (17.2%) in the group with a low AgNOR-PI (p < 0.0001). Hepatocellular carcinoma development was also significantly more frequent in patients with liver cell dysplasia and HBsAg positivity. Multivariate analysis using AgNOR-PI, liver cell dysplasia, HBsAg positivity, and hepatitis C virus (HCV) infection as covariates demonstrated that the AgNOR-PI parameter was the only significant predictor of hepatocellular carcinoma development. CONCLUSIONS: These results demonstrate that a high hepatocyte proliferation rate is a major risk factor for hepatocellular carcinoma development in the cirrhotic liver. Therefore, the evaluation of the hepatocyte proliferation rate is very important to identify patients requiring a more strict follow up programme for early diagnosis of hepatocellular carcinoma. PMID:9713593

  13. 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 of ex vivo and in vivo hepatotoxicity and oxidative damage. This further suggests its therapeutic value in various liver diseases. However, isolations of the active principles, their mechanisms of action, and other therapeutic contributions remain to be addressed. PMID:27059702

  14. Is there any vindication for low dose nonselective β-blocker medication in patients with liver cirrhosis?

    PubMed Central

    Kim, Tae Wan; Chon, Chang Uk; Won, Hyun Sun; Park, Jung Ho; Park, Dong Il; Cho, Yong Kyun; Sohn, Chong Il; Jeon, Woo Kyu; Kim, Byung Ik

    2012-01-01

    Background/Aims Nonselective β-blockers (NSBBs), such as propranolol, reportedly exert a pleiotropic effect in liver cirrhosis. A previous report suggested that survival was higher in patients receiving adjusted doses of NSBBs than in ligation patients. This study investigated whether low-dose NSBB medication has beneficial effects in patients with liver cirrhosis, especially in terms of overall survival. Methods We retrospectively studied 273 cirrhotic patients (199 males; age 53.6±10.2 years, mean±SD) who visited our institution between March 2003 and December 2007; follow-up data were collected until June 2011. Among them, 138 patients were given a low-dose NSBB (BB group: propranolol, 20-60 mg/day), and the remaining 135 patients were not given an NSBB (NBB group). Both groups were stratified randomly according to Child-Turcotte-Pugh (CTP) classification and age. Results The causes of liver cirrhosis were alcohol (n=109, 39.9%), hepatitis B virus (n=125, 45.8%), hepatitis C virus (n=20, 7.3%), and cryptogenic (n=19, 7.0%). The CTP classes were distributed as follows: A, n=116, 42.5%; B, n=126, 46.2%; and C, n=31, 11.4%. Neither the overall survival (P=0.133) nor the hepatocellular carcinoma (HCC)-free survival (P=0.910) differed significantly between the BB and NBB groups [probability of overall survival at 4 years: 75.1% (95% CI=67.7-82.5%) and 81.2% (95% CI=74.4-88.0%), respectively; P=0.236]. In addition, the delta CTP score did not differ significantly between the two groups. Conclusions Use of low-dose NSBB medication in patients with liver cirrhosis is not indicated in terms of overall and HCC-free survival. PMID:22893871

  15. The Role of Fas/Fas Ligand System in the Pathogenesis of Liver Cirrhosis and Hepatocellular Carcinoma

    PubMed Central

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

    2012-01-01

    Background The Fas receptor/ligand system including soluble forms is the most important apoptotic initiator in the liver. Dysregulation of this pathway may contribute to abnormal cell proliferation and cell death and is regarded as one of the mechanisms preventing the immune system from rejecting the tumor cells. Objectives To analyze the role of Fas system Fas/ Fas ligand (Fas/ FasL) in the multi-step process of hepatic fibrosis/carcinogenesis, and to use of the serum markers as possible candidate biomarkers for early detection of hepatocellular carcinoma (HCC). Patients and Methods Ninety patients were enrolled: 30 cases of chronic hepatitis C (CHC) without cirrhosis, 30 cases of CHC with liver cirrhosis, and 30 cases of HCC and hepatitis V virus (HCV) infection. Ten wedge liver biopsies, taken during laparoscopic cholecystectomy, were served as normal controls. Serum soluble Fas (sFas) levels were measured using ELISA technique; Fas and FasL proteins were detected in hepatic tissue by indirect Immuno-histochemical technique (IHC); electron microscopic (EM) and immune electron microscopic examinations were performed for detection of Fas expression on lymphocytes. Results Hepatic expression of both Fas and FasL as well as expression of Fas on separated lymphocytes were significantly increased in the diseased groups (P < 0. 01) compared to the control specimens. The highest expression was noticed in CHC specimens, particularly with the necro-inflammatory activity and advancement of the fibrosis. The sFas in cirrhotic patients and HCC were significantly higher than that in normal controls and CHC without cirrhosis group (P < 0.01). Conclusions Apoptosis and the Fas system were significantly involved in the process of converting liver cirrhosis into hepatocellular carcinoma. Down-regulation of Fas expression, up regulation of FasL expression in hepatocytes, and elevation of serum sFas levels were important in tumor evasion from immune surveillance, and in hepatic carcinogenesis. PMID:23300494

  16. Methotrexate is not associated with increased liver cirrhosis in a population-based cohort of rheumatoid arthritis patients with chronic hepatitis B

    PubMed Central

    Tang, Kuo-Tung; Hung, Wei-Ting; Chen, Yi-Hsing; Lin, Ching-Heng; Chen, Der-Yuan

    2016-01-01

    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. PMID:26928373

  17. 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

    2016-01-01

    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. PMID:26928373

  18. 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

  19. LYVE-1 is not restricted to the lymph vessels: expression in normal liver blood sinusoids and down-regulation in human liver cancer and cirrhosis.

    PubMed

    Mouta Carreira, C; Nasser, S M; di Tomaso, E; Padera, T P; Boucher, Y; Tomarev, S I; Jain, R K

    2001-11-15

    Lymphatic vessel endothelial hyaluronan receptor (LYVE)-1 is thought to be restricted to lymph vessels and has been used as such to show that tumor lymphangiogenesis occurs on overexpression of lymphangiogenic factors in mouse tumor models. However, these studies have not yet been corroborated in human tumors. Here we show, first, that LYVE-1 is not exclusive to the lymph vessels. Indeed, LYVE-1 is also present in normal hepatic blood sinusoidal endothelial cells in mice and humans. Surprisingly, LYVE-1 is absent from the angiogenic blood vessels of human liver tumors and only weakly present in the microcirculation of regenerative hepatic nodules in cirrhosis, though both vessels are largely derived from the liver sinusoids. Second, we propose a novel approach to identify lymphatics in human and murine liver. By combining LYVE-1 and Prox 1 (a transcription factor) immunohistochemistry, we demonstrate that lymphatics are abundant in cirrhosis. In contrast, in human hepatocellular carcinoma and liver metastases, they are restricted to the tumor margin and surrounding liver. The absence of intratumor lymphatics in hepatocellular carcinomas and liver metastases may impair molecular and cellular transport in these tumors. Finally, the presence of LYVE-1 in liver sinusoidal endothelia suggests that LYVE-1 has functions beyond the lymph vascular system. PMID:11719431

  20. 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

  1. Sorafenib Prevents Escape from Host Immunity in Liver Cirrhosis Patients with Advanced Hepatocellular Carcinoma

    PubMed Central

    Nagai, Hidenari; Mukozu, Takanori; Matsui, Daigo; Kanekawa, Takenori; Kanayama, Masahiro; Wakui, Noritaka; Momiyama, Kouichi; Shinohara, Mie; Iida, Kazunari; Ishii, Koji; Igarashi, Yoshinori; Sumino, Yasukiyo

    2012-01-01

    Purpose. It has been reported that Th2 cytokines downregulate antitumor immunity, while activation of type T cells promotes antitumor immunity. The aim of this paper was to evaluate host immunity in liver cirrhosis (LC) patients with advanced hepatocellular carcinoma (aHCC) receiving sorafenib therapy. Methods. Forty-five adult Japanese LC patients received sorafenib for aHCC between 2009 and 2011 at our hospital. Sorafenib was administered at a dose of 200–800 mg/day for 4 weeks. Blood samples were collected before and after treatment. Results. Eleven patients were treated with sorafenib at 200 mg/day (200 group), 27 patients received sorafenib at 400 mg/day (400 group), and 7 patients were given sorafenib at 800 mg/day (800 group). There was no significant change in the percentage of Th1 cells after treatment in any group. However, the percentages of Th2 cells and regulatory T cells were significantly decreased after treatment in the 400 group and 800 group compared with before treatment, although there was no significant change after treatment in the 200 group. Conclusions. These results indicate that treatment with sorafenib might induce Th1 dominance and prevent the escape of tumor cells from the host immune system in LC patients with aHCC. PMID:22666283

  2. 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.

  3. 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. PMID:15889562

  4. Absorption of a nutrient solution in chronic alcoholics without nutrient deficiencies and liver cirrhosis.

    PubMed

    Pfeiffer, A; Schmidt, T; Vidon, N; Pehl, C; Kaess, H

    1992-12-01

    Duodenal and jejunal absorption of a nutrient solution at two different caloric loads (1.32 and 3.96 kcal/min = 5.6 and 16.8 kJ/min) was compared in chronic alcoholics without malnutrition, liver cirrhosis, obvious small-bowel dysfunction, and exocrine pancreatic insufficiency and in an age-matched control group, by means of the intestinal perfusion technique. In chronic alcoholics duodenal net absorption of water (p < 0.025), sodium (p < 0.02), potassium (p < 0.005), total nitrogen (p < 0.02), carbohydrates (p < 0.05), and lipids (p < 0.05) was lower than in controls when both caloric loads were administered, but jejunal absorption rates were not decreased. Biliopancreatic secretion did not differ between alcoholics and controls. Higher serum protein leakage in alcoholics was indicated by an increased (p < 0.01) duodenal alpha 1-antitrypsin clearance under low caloric load infusion. It is concluded that the absorptive function of the duodenum is impaired in alcoholics, whereas the upper jejunum is not affected. PMID:1475618

  5. 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-HBV vectors for liver-specific gene therapy, including and perhaps particularly for HBV-related disease. PMID:23301066

  6. Child–Pugh Versus MELD Score for the Assessment of Prognosis in Liver Cirrhosis

    PubMed Central

    Peng, Ying; Qi, Xingshun; Guo, Xiaozhong

    2016-01-01

    Abstract Child–Pugh and MELD scores have been widely used for the assessment of prognosis in liver cirrhosis. A systematic review and meta-analysis aimed to compare the discriminative ability of Child–Pugh versus MELD score to assess the prognosis of cirrhotic patients. PubMed and EMBASE databases were searched. The statistical results were summarized from every individual study. The summary areas under receiver operating characteristic curves, sensitivities, specificities, positive and negative likelihood ratios, and diagnostic odds ratios were also calculated. Of the 1095 papers initially identified, 119 were eligible for the systematic review. Study population was heterogeneous among studies. They included 269 comparisons, of which 44 favored MELD score, 16 favored Child–Pugh score, 99 did not find any significant difference between them, and 110 did not report the statistical significance. Forty-two papers were further included in the meta-analysis. In patients with acute-on-chronic liver failure, Child–Pugh score had a higher sensitivity and a lower specificity than MELD score. In patients admitted to ICU, MELD score had a smaller negative likelihood ratio and a higher sensitivity than Child–Pugh score. In patients undergoing surgery, Child–Pugh score had a higher specificity than MELD score. In other subgroup analyses, Child–Pugh and MELD scores had statistically similar discriminative abilities or could not be compared due to the presence of significant diagnostic threshold effects. Although Child–Pugh and MELD scores had similar prognostic values in most of cases, their benefits might be heterogeneous in some specific conditions. The indications for Child–Pugh and MELD scores should be further identified. PMID:26937922

  7. Effect of Chronic Alcohol Ingestion on Bone Mineral Density in Males without Liver Cirrhosis

    PubMed Central

    Kim, Mi Jin; Shim, Myung Suk; Kim, Moon Kyu; Lee, Yeon; Shin, Young Goo; Chung, Choon Hee; Kwon, Sang Ok

    2003-01-01

    Background: Osteoporosis in men is an important public health problem. Because of the tendency of the numbers of the elderly population to increase, and age-specific incidence of fractures, it is inevitable that the health burden due to fractures will increase. Chronic alcoholism is associated with other risk factors, such as poor nutrition, leanness, liver disease, malabsorption, vitamin D deficiency, hypogonadism, hemosiderosis, parathyroid dysfunction and tobacco use, and these may contribute to the pathogenesis of bone disease related to alcoholism. Chronic alcohol intake may reduce bone density, but can also increase bone density. It is well established that liver disease also induces bone density changes, thus it is difficult to distinguish the role of liver disease from that of alcohol itself in the bone alterations occurring in patients with chronic alcohol consumption. Chronic male alcoholics, not having liver cirrhosis were studied to assess the effect of chronic alcohol consumption on their bone mineral density. Methods: The study subjects comprised of 18 chronic heavy drinkers of more than 40 g of alcohol per day for at least 3 years and 18 age-matched controls who drank less than 20 g of alcohol per day. The serum and urinary parameters of bone and mineral metabolism were determined. The bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry at four axial sites (lumbar spine, femoral neck, Ward’s triangle and trochanter). Results: The alcoholic and control patients drank an average of 97.6 g and 7.2 g of alcohol per day. Osteocalcin, a marker of bone formation, was slightly decreased in alcoholic patients, and deoxypyridinoline, a marker of bone resorption, was slightly increased, but the difference was not statistically significant (p>0.05). There were no differences between the two groups in the levels of free testosterone, estradiol, 25(OH) vitamin D and parathyroid hormone. The Ward’s triangle and trochanter BMDs of the femur were significantly lower in the alcoholics than the controls, and lumbar spine BMD was decreased in proportion to the total alcohol intake in the alcoholics (r=−0.625, p=0.01). Conclusion: We suggest that chronic alcohol consumption induces low bone density in the femur Ward’s triangle and trochanter. There was also a significant inverse correlation between the lumbar spine BMD and the total amount of alcohol consumed. Large scaled randomized and prospective studies are needed to clarify the pathogenesis of alcohol-induced osteoporosis. PMID:14619387

  8. 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

  9. 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. PMID:25214398

  10. 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

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

    PubMed

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

    2014-05-01

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

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

    PubMed Central

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

    2011-01-01

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

  13. Liver cirrhosis in hepatic vena cava syndrome (or membranous obstruction of inferior vena cava)

    PubMed Central

    Shrestha, Santosh Man

    2015-01-01

    Hepatic vena cava syndrome (HVCS) also known as membranous obstruction of inferior vena cava reported mainly from Asia and Africa is an important cause of hepatic venous outflow obstruction (HVOO) that is complicated by high incidence of liver cirrhosis (LC) and moderate to high incidence of hepatocellular carcinoma (HCC). In the past the disease was considered congenital and was included under Budd-Chiari syndrome (BCS). HVCS is a chronic disease common in developing countries, the onset of which is related to poor hygienic living condition. The initial lesion in the disease is a bacterial infection induced localized thrombophlebitis in hepatic portion of inferior vena cava at the site where hepatic veins open which on resolution transforms into stenosis, membrane or thick obstruction, and is followed by development of cavo-caval collateral anastomosis. The disease is characterized by long asymptomatic period and recurrent acute exacerbations (AE) precipitated by clinical or subclinical bacterial infection. AE is managed with prolonged oral antibiotic. Development of LC and HCC in HVCS is related to the severity and frequency of AEs and not to the duration of the disease or the type or severity of the caval obstruction. HVOO that develops during severe acute stage or AE is a pre-cirrhotic condition. Primary BCS on the other hand is a rare disease related to prothrombotic disorders reported mainly among Caucasians that clinically manifest as acute, subacute disease or as fulminant hepatic failure; and is managed with life-long anticoagulation, porto-systemic shunt/endovascular angioplasty and stent or liver transplantation. As epidemiology, etiology and natural history of HVCS are different from classical BCS, it is here, recognized as a separate disease entity, a third primary cause of HVOO after sinusoidal obstruction syndrome and BCS. Understanding of the natural history has made early diagnosis of HVCS possible. This paper describes epidemiology, natural history and diagnosis of HVCS and discusses the pathogenesis of LC in the disease and mentions distinctive clinical features of HVCS related LC. PMID:25937864

  14. Liver iron is predictive of death in alcoholic cirrhosis: a multivariate study of 229consecutive patients with alcoholic and/or hepatitis C virus cirrhosis: a prospective follow up study

    PubMed Central

    Ganne-Carrie, N; Christidis, C; Chastang, C; Ziol, M; Chapel, F; Imbert-Bismut, F; Trinchet, J; Guettier, C; Beaugrand, M

    2000-01-01

    BACKGROUND/AIMSA study was undertaken of liver biopsy samples from 229consecutive patients with alcoholic or hepatitis C virus related cirrhosis who were prospectively followed until January 1996to evaluate the influence of liver iron content on survival and the occurrence of hepatocellular carcinoma.?METHODSHepatic iron content was measured with a validated semiquantitative score, and its predictive value for survival and the occurrence of hepatocellular carcinoma was assessed.?RESULTS130 patients had detectable iron at enrolment. During follow up (57(28) months), 95patients died and 39patients developed hepatocellular carcinoma. No significant relation was found between hepatic iron and the occurrence of hepatocellular carcinoma. Conversely, the presence of iron was predictive of death in alcoholic patients (p=0.007) by the log rank test but not in patients with hepatitis C virus related (p=0.71) or mixed (p=0.98) cirrhosis. The predictive value of hepatic iron content in patients with alcoholic cirrhosis was confirmed by the Cox model using either a binary coding (p=0.009; relative risk=2.27; 95% confidence interval 1.2to 4.19) or the continuous values (p=0.002).?CONCLUSIONSThese results suggest that hepatic iron enhances liver lesions caused by alcohol but not those caused by hepatitis C virus.???Keywords: cirrhosis; liver; iron; survival; hepatocellular carcinoma; alcohol PMID:10644325

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

    PubMed Central

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

    2015-01-01

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

  16. Epidemiology, Risk Factors, and In-Hospital Mortality of Venous Thromboembolism in Liver Cirrhosis: A Single-Center Retrospective Observational Study.

    PubMed

    Zhang, Xintong; Qi, Xingshun; De Stefano, Valerio; Hou, Feifei; Ning, Zheng; Zhao, Jiancheng; Peng, Ying; Li, Jing; Deng, Han; Li, Hongyu; Guo, Xiaozhong

    2016-01-01

    BACKGROUND Risk of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), may be increased in liver cirrhosis. We conducted a single-center study to explore the epidemiology, risk factors, and in-hospital mortality of VTE in Chinese patients with liver cirrhosis. MATERIAL AND METHODS All patients with liver cirrhosis who were consecutively admitted to our hospital between January 2011 and December 2013 were retrospectively included. RESULTS Of 2006 patients with liver cirrhosis included, 9 patients were diagnosed with or developed VTE during hospitalization, including 5 patients with a previous history of DVT, 1 patient with either a previous history of DVT or new onset of PE, and 3 patients with new onset of VTE (PE, n=1; DVT, n=2). Risk factors for VTE included a significantly higher proportion of hypertension and significantly higher red blood cells, hemoglobin, alanine aminotransferase, aspartate aminotransferase, prothrombin time (PT), international normalized ratio (INR), D-dimer, and Child-Pugh scores. The in-hospital mortality was significantly higher in patients with VTE than those without VTE (33.3% [3/9] versus 3.4% [67/1997], P<0.001). CONCLUSIONS VTE was observed in 0.4% of patients with liver cirrhosis during hospitalization and it significantly increased the in-hospital mortality. Elevated PT/INR aggravated the risk of VTE. PMID:27009380

  17. Epidemiology, Risk Factors, and In-Hospital Mortality of Venous Thromboembolism in Liver Cirrhosis: A Single-Center Retrospective Observational Study

    PubMed Central

    Zhang, Xintong; Qi, Xingshun; De Stefano, Valerio; Hou, Feifei; Ning, Zheng; Zhao, Jiancheng; Peng, Ying; Li, Jing; Deng, Han; Li, Hongyu; Guo, Xiaozhong

    2016-01-01

    Background Risk of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), may be increased in liver cirrhosis. We conducted a single-center study to explore the epidemiology, risk factors, and in-hospital mortality of VTE in Chinese patients with liver cirrhosis. Material/Methods All patients with liver cirrhosis who were consecutively admitted to our hospital between January 2011 and December 2013 were retrospectively included. Results Of 2006 patients with liver cirrhosis included, 9 patients were diagnosed with or developed VTE during hospitalization, including 5 patients with a previous history of DVT, 1 patient with either a previous history of DVT or new onset of PE, and 3 patients with new onset of VTE (PE, n=1; DVT, n=2). Risk factors for VTE included a significantly higher proportion of hypertension and significantly higher red blood cells, hemoglobin, alanine aminotransferase, aspartate aminotransferase, prothrombin time (PT), international normalized ratio (INR), D-dimer, and Child-Pugh scores. The in-hospital mortality was significantly higher in patients with VTE than those without VTE (33.3% [3/9] versus 3.4% [67/1997], P<0.001). Conclusions VTE was observed in 0.4% of patients with liver cirrhosis during hospitalization and it significantly increased the in-hospital mortality. Elevated PT/INR aggravated the risk of VTE. PMID:27009380

  18. Effect of variations in treatment regimen and liver cirrhosis on exposure to benzodiazepines during treatment of alcohol withdrawal syndrome

    PubMed Central

    Gershkovich, Pavel; Wasan, Kishor M; Ribeyre, Charles; Ibrahim, Fady; McNeill, John H

    2015-01-01

    Purpose: Benzodiazepines (BDZs) are the drugs of choice to prevent the symptoms of alcohol withdrawal syndrome (AWS). Various treatment protocols are published and have been shown to be effective in both office-managed and facility-managed treatment of AWS. The aim of this scientific commentary is to demonstrate the differences in the expected exposure to BDZs during AWS treatment using different treatment regimens available in the literature, in patients with or without alcoholic liver cirrhosis. Methods: Diazepam and lorazepam AWS protocols were examined and reviewed in the literature, and blood plasma levels were examined and compared, respectively. Results: Considerable variation in the blood levels with the different dosing schedules was found. Because the drugs are metabolized differently, we have also shown that liver disease affects the blood levels of diazepam, but not of lorazepam. Conclusions: Differences in treatment regimens, the choice of BDZ, as well as the presence of liver cirrhosis can substantially alter the exposure of patients to drugs used for AWS treatment. Outpatient treatment of AWS has been shown to be relatively safe and effective for the treatment of AWS but patients should be carefully monitored. PMID:26322116

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

    PubMed Central

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

    2014-01-01

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

  20. The natural history of cirrhosis from parenteral nutrition-associated liver disease after resolution of cholestasis with parenteral fish oil therapy

    PubMed Central

    Nandivada, Prathima; Chang, Melissa I.; Potemkin, Alexis K.; Carlson, Sarah J.; Cowan, Eileen; O’loughlin, Alison A.; Mitchell, Paul D.; Gura, Kathleen M.; Puder, Mark

    2014-01-01

    Objective To determine the natural history of cirrhosis from parenteral nutrition-associated liver disease (PNALD) after resolution of cholestasis with fish oil (FO) therapy Background Historically, cirrhosis from PNALD resulted in end-stage liver disease (ESLD), often requiring transplantation for survival. With FO therapy, most children now experience resolution of cholestasis and rarely progress to ESLD. However, outcomes for cirrhosis after resolution of cholestasis are unknown and patients continue to be considered for liver/multivisceral transplantation. Methods Prospectively collected data was reviewed for children with cirrhosis due to PNALD who had resolution of cholestasis after treatment with FO from 2004 to 2012. Outcomes evaluated included need for liver/multivisceral transplantation, mortality, and the clinical progression of liver disease. Results Fifty-one patients with cirrhosis from PNALD were identified, with 76% demonstrating resolution of cholestasis after FO therapy. The mean direct bilirubin decreased from 6.4 ± 4 mg/dL to 0.2 ± 0.1 mg/dL (p <0.001) 12 months after resolution of cholestasis, with a mean time to resolution of 74 days. None of the patients required transplantation or died from ESLD. Pediatric End-Stage Liver Disease (PELD) scores decreased from 16 ± 4.6 to −1.2 ± 4.6, 12 months after resolution of cholestasis (p <0.001). In children who remained PN-dependent, the PELD score remained normal throughout the follow-up period. Conclusions Cirrhosis from PNALD may be stable rather than progressive once cholestasis resolves with FO therapy. Furthermore, these patients may not require transplantation and show no clinical evidence of liver disease progression, even when persistently PN-dependent. PMID:24374535

  1. Autoantibodies against complement receptor 1 (CD35) in SLE, liver cirrhosis and HIV-infected patients.

    PubMed

    Sadallah, S; Hess, C; Trendelenburg, M; Vedeler, C; Lopez-Trascasa, M; Schifferli, J A

    2003-01-01

    The acquired loss of CR1 (CD35) on erythrocytes in specific autoimmune diseases and chronic infections may be due to autoAb against CR1. An ELISA using rCR1 was established to measure antiCR1 IgG autoAb. Plasma containing alloAb to polymorphism on CR1 (Knops blood group Ab) reacted strongly against rCR1 and were used as positive controls. AntiCR1 Ab was found in 3/90 (3.5%) plasma samples from healthy blood donors. The binding of these Ab was not inhibited by high salt concentrations. AntiCR1 Ab were present in the IgG fractions of plasma, and they bound to rCR1 on Western Blot. Affinity chromatography on rCR1-sepharose depleted the plasma of antiCR1, and the acid-eluted fractions contained the antiCR1 Ab. An increased frequency of antiCR1 autoAb was found in patients with SLE (36/78; 46%), liver cirrhosis (15/41; 36%), HIV infection (23/76; 30%) (all P < 0.0001), and in patients with anticardiolipin Ab (4/21; 19%, P < 0.01) multiple sclerosis (7/50; 14%, P < 0.02), and myeloma (autoAb (8/56; 14%, P < 0.02), but not in those with acute poststreptococcal glomerulonephritis (1:32; 3%). Because C1q binds to CR1, antiC1q Ab were analysed in the same patients. There was no correlation between levels of antiC1q and antiCR1 autoAb. In HIV patients, levels of antiCR1 did not correlate with low CR1 levels expressed on erythrocytes or soluble CR1 in plasma. The binding of antiCR1 autoAb to rCR1 fixed on ELISA plates was not inhibited by soluble rCR1 or by human erythrocyte CR1, in contrast to alloAb and one SLE serum, which induced partial blockade. Thus, antiCR1 autoAb recognize mostly CR1 epitope(s) not present on the native molecule, suggesting that they are not directly involved in the loss of CR1. Rather antiCR1 autoAb might indicate a specific immune response to denatured CR1. PMID:12519402

  2. 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. PMID:26563125

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

    PubMed Central

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

    2009-01-01

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

  4. Influence of Genetic Polymorphisms of Tumor Necrosis Factor Alpha and Interleukin 10 Genes on the Risk of Liver Cirrhosis in HIV-HCV Coinfected Patients

    PubMed Central

    Corchado, Sara; Márquez, Mercedes; Montes de Oca, Montserrat; Romero-Cores, Paula; Fernández-Gutiérrez, Clotilde; Girón-González, José-Antonio

    2013-01-01

    Objective Analysis of the contribution of genetic (single nucleotide polymorphisms (SNP) at position -238 and -308 of the tumor necrosis factor alpha (TNF-α) and -592 of the interleukin-10 (IL-10) promotor genes) and of classical factors (age, alcohol, immunodepression, antirretroviral therapy) on the risk of liver cirrhosis in human immunodeficiency (HIV)-hepatitis C (HCV) virus coinfected patients. Patients and Methods Ninety one HIV-HCV coinfected patients (50 of them with chronic hepatitis and 41 with liver cirrhosis) and 55 healthy controls were studied. Demographic, risk factors for the HIV-HCV infection, HIV-related (CD4+ T cell count, antiretroviral therapy, HIV viral load) and HCV-related (serum ALT concentration, HCV viral load, HCV genotype) characteristics and polymorphisms at position -238 and -308 of the tumor necrosis factor alfa (TNF- α) and -592 of the interleukin-10 (IL-10) promotor genes were studied. Results Evolution time of the infection was 21 years in both patients’ groups (chronic hepatitis and liver cirrhosis). The group of patients with liver cirrhosis shows a lower CD4+ T cell count at the inclusion in the study (but not at diagnosis of HIV infection), a higher percentage of individuals with previous alcohol abuse, and a higher proportion of patients with the genotype GG at position -238 of the TNF-α promotor gene; polymorphism at -592 of the IL-10 promotor gene approaches to statistical significance. Serum concentrations of profibrogenic transforming growth factor beta1 were significantly higher in healthy controls with genotype GG at -238 TNF-α promotor gene. The linear regression analysis demonstrates that the genotype GG at -238 TNF-α promotor gene was the independent factor associated to liver cirrhosis. Conclusion It is stressed the importance of immunogenetic factors (TNF-α polymorphism at -238 position), above other factors previously accepted (age, gender, alcohol, immunodepression), on the evolution to liver cirrhosis among HIV-infected patients with established chronic HCV infections. PMID:23840511

  5. Dynamical Regulation Analysis Identifies Molecular Mechanisms of Fuzheng-Huayu Formula against Hepatitis B-Caused Liver Cirrhosis

    PubMed Central

    Chen, Qi-Long; Lu, Yi-Yu; Peng, Jing-Hua; Dong, Shu; Wei, Bin; Song, Ya-Nan; Zhou, Qian-Mei; Zhang, Hui; Liu, Ping; Su, Shi-Bing

    2015-01-01

    Fuzheng-Huayu (FZHY) tablet was formulated based on Chinese medicine theory in treating liver fibrosis. A clinical trial has indicated that FZHY can against hepatitis B-caused liver cirrhosis (HBC), but the underlying mechanism of FZHY efficacy is unclear. Here, we report that miRNA expression levels are remarkably changed when FZHY formula was used in HBC patient's treatment as a paradigm of trials. Then, we functionally characterize the significant impact of potential kernel miRNAs by miRNA-target network analysis. Enrichment analysis show that the FZHY formula dramatically effecting the molecular regulated module in HBC. Thus, we infer that FZHY plays a critical function in HBC treatment process and directly regulated many important pathways, including but not limited to cell cycle, p53 signaling pathway, and TGF-? signaling pathway, suggesting a new strategy for investigating the molecular mechanism of FZHY treatment. PMID:26221171

  6. Successful management of complex open heart surgery in a patient with Child-Pugh class C liver cirrhosis: report of a case.

    PubMed

    Kubota, Yasuhiko; Sakaguchi, Taichi; Miyagawa, Shigeru; Nishi, Hiroyuki; Yoshikawa, Yasushi; Fukushima, Satsuki; Saito, Shunsuke; Sawa, Yoshiki

    2013-03-01

    Open heart surgery in patients with Child-Pugh class C liver cirrhosis has a high mortality rate and is generally considered to be contraindicated. A patient with liver cirrhosis (Child-Pugh class C) underwent mandatory complex open heart surgery due to severe heart failure. The perioperative management, including the prophylactic use of intraaortic balloon pumping to increase the hepatic blood flow and the early initiation of continuous veno-venous hemodialysis to avoid hepatic congestion, enabled the patient to survive. PMID:22975800

  7. MicroRNA panels as disease biomarkers distinguishing hepatitis B virus infection caused hepatitis and liver cirrhosis.

    PubMed

    Jin, Bo-Xun; Zhang, Yong-Hong; Jin, Wen-Jing; Sun, Xiang-Ying; Qiao, Gui-Fang; Wei, Ying-Ying; Sun, Li-Bo; Zhang, Wei-Hong; Li, Ning

    2015-01-01

    An important unresolved clinical issue is to distinguish hepatitis B virus (HBV) infection caused chronic hepatitis and their corresponding liver cirrhosis (LC). Recent research suggests that circulating microRNAs are useful biomarkers for a wide array of diseases. We analyzed microRNA profiles in the plasmas of a total of 495 chronic hepatitis B (CHB) patients, LC patients and healthy donors and identified 10 miRNAs that were differentially expressed between CHB and LC patients. Our logistic models show that three panels of miRNAs have promising diagnostic performances in discriminating CHB from LC. Blinded tests were subsequently conducted to evaluate the diagnostic performances in clinical practice and a sensitivity of 85% and specificity of 70% have been achieved in separating CHB from LC pateints. The expression levels of some circulating miRNAs were significantly correlated with HBV DNA load and liver function, such as prothrombin activity (PTA) and levels of alanin aminotransferase (ALT), albumin (ALB) and cholinesterase (CHE). Our results provide important information for developing novel diagnostic tools for distinguishing chronic HBV hepatitis and their corresponding cirrhosis. PMID:26456479

  8. MicroRNA panels as disease biomarkers distinguishing hepatitis B virus infection caused hepatitis and liver cirrhosis

    PubMed Central

    Jin, Bo-Xun; Zhang, Yong-Hong; Jin, Wen-Jing; Sun, Xiang-Ying; Qiao, Gui-Fang; Wei, Ying-Ying; Sun, Li-Bo; Zhang, Wei-Hong; Li, Ning

    2015-01-01

    An important unresolved clinical issue is to distinguish hepatitis B virus (HBV) infection caused chronic hepatitis and their corresponding liver cirrhosis (LC). Recent research suggests that circulating microRNAs are useful biomarkers for a wide array of diseases. We analyzed microRNA profiles in the plasmas of a total of 495 chronic hepatitis B (CHB) patients, LC patients and healthy donors and identified 10 miRNAs that were differentially expressed between CHB and LC patients. Our logistic models show that three panels of miRNAs have promising diagnostic performances in discriminating CHB from LC. Blinded tests were subsequently conducted to evaluate the diagnostic performances in clinical practice and a sensitivity of 85% and specificity of 70% have been achieved in separating CHB from LC pateints. The expression levels of some circulating miRNAs were significantly correlated with HBV DNA load and liver function, such as prothrombin activity (PTA) and levels of alanin aminotransferase (ALT), albumin (ALB) and cholinesterase (CHE). Our results provide important information for developing novel diagnostic tools for distinguishing chronic HBV hepatitis and their corresponding cirrhosis. PMID:26456479

  9. Tracking of transplanted mesenchymal stem cells labeled with fluorescent magnetic nanoparticle in liver cirrhosis rat model with 3-T MRI.

    PubMed

    Kim, Tae Hee; Kim, Jai Keun; Shim, Wooyoung; Kim, Sun Yong; Park, Tae Jun; Jung, Jae Yeon

    2010-09-01

    In vivo visualization of transplanted stem cells with noninvasive technique is essential for the monitoring of cell implantation, homing and differentiation. At present, superparamagnetic iron oxide (SPIO) is most commonly used for cell labeling. However, stem cells lack phagocytic capacity and transfection agent is required for sufficient internalization of SPIO for cellular imaging. However, the potential hazards of transfection agents are not fully investigated. Instead of SPIO, we used commercially available new tagging material, fluorescent magnetic nanoparticle (MNP) containing rhodamine B isothiocyanate within a silica shell (Biterials, Seoul, Korea). This tagging material does not require transfection agents for the cell labeling. In addition to that, the core of this MNP is composed of ferrite and the inner portion of silica shell contains fluorescent materials, therefore, it has both magnetic and optical features. This study was designed to track intrasplenically injected bone marrow mesenchymal stem cells (MSCs) labeled with fluorescent MNP in liver cirrhosis rat model with 3-T magnetic resonance equipment. We compared magnetic resonance imaging (MRI) of livers in rats which were injected with non-labeled stem cells or labeled stem cells with MNP or SPIO. We found that the respective liver-to-muscle contrast-to-noise ratios at 3 and 5 h after MNP or SPIO-labeled stem cell injection was significantly lower than that of pre-injection and non-labeled group. There was no significant difference between MNP-labeled group and SPIO-labeled group. We can effectively detect intrasplenically injected MNP-labeled MSCs in an experimental rat model of liver cirrhosis with 3-T MRI. PMID:20663626

  10. Adenoviral delivery of truncated MMP-8 fused with the hepatocyte growth factor mutant 1K1 ameliorates liver cirrhosis and promotes hepatocyte proliferation

    PubMed Central

    Liu, Jinghua; Li, Jianbo; Fu, Weiwei; Tang, Jiacheng; Feng, Xu; Chen, Jiang; Liang, Yuelong; Jin, Ren’an; Xie, Anyong; Cai, Xiujun

    2015-01-01

    Liver cirrhosis is a chronic liver disease caused by chronic liver injury, which activates hepatic stellate cells (HSCs) and the secretion of extracellular matrix (ECM). Cirrhosis accounts for an extensive level of morbidity and mortality worldwide, largely due to lack of effective treatment options. In this study, we have constructed a fusion protein containing matrix metal-loproteinase 8 (MMP-8) and the human growth factor mutant 1K1 (designated cMMP8-1K1) and delivered it into hepatocytes and in vivo and in cell culture via intravenous injection of fusion protein-harboring adenovirus. In doing so, we found that the cMMP8-1K1 fusion protein promotes the proliferation of hepatocytes, likely resulting from the combined inhibition of type I collagen secretion and the degradation of the ECM in the HSCs. This fusion protein was also observed to ameliorate liver cirrhosis in our mouse model. These changes appear to be linked to changes in downstream gene expression. Taken together, these results suggest a possible strategy for the treatment of liver cirrhosis and additional work is warranted. PMID:26527860

  11. The relationship between internally deposited alpha-particle radiation and subsite-specific liver cancer and liver cirrhosis: an analysis of published data.

    PubMed

    Sharp, Gerald B

    2002-12-01

    Chronic exposure to high LET radiation has been shown to cause liver cancer in humans based on studies of patients who received Thorotrast, a colloidal suspension of thorium dioxide formerly used as a radiological contrast agent, and on studies of Russian nuclear weapons workers exposed to internally ingested plutonium. Risk estimates for these exposures and specific subtypes of liver cancer have not been previously reported. Combining published data with tumor registry data pertinent to the Thorotrast cohorts in Germany, Denmark, Portugal, and Japan and to Russian workers, we generally found significantly elevated risks of three major histologic types of liver tumors: hepatocellular carcinoma (HCC), cholangiocarcinoma (CC), and hemangiosarcoma (HS) for Thorotrast exposures. In contrast, HS was the only liver tumor significantly associated with the lower alpha-particle doses experienced by the Russian workers. Excess cases per 1,000 persons exposed to Thorotrast were similar for the three liver cancer subtypes but lower for plutonium exposure. Odds ratios (OR) of HS and CC for Thorotrast were from 26 to 789 and from 1 to 31 times higher than those for HCC, respectively. ORs of liver cirrhosis for Thorotrast exposure ranged from 2.7 (95% confidence interval (CI): 2.2-3.4) to 6.7 (5.1-8.7). PMID:12674201

  12. Chlordecone potentiates hepatic fibrosis in chronic liver injury induced by carbon tetrachloride in mice.

    PubMed

    Tabet, Elise; Genet, Valentine; Tiaho, François; Lucas-Clerc, Catherine; Gelu-Simeon, Moana; Piquet-Pellorce, Claire; Samson, Michel

    2016-07-25

    Chronic liver damage due to viral or chemical agents leads to a repair process resulting in hepatic fibrosis. Fibrosis may lead to cirrhosis, which may progress to liver cancer or a loss of liver function, with an associated risk of liver failure and death. Chlordecone is a chlorinated pesticide used in the 1990s. It is not itself hepatotoxic, but its metabolism in the liver triggers hepatomegaly and potentiates hepatotoxic agents. Chlordecone is now banned, but it persists in soil and water, resulting in an ongoing public health problem in the Caribbean area. We assessed the probable impact of chlordecone on the progression of liver fibrosis in the population of contaminated areas, by developing a mouse model of chronic co-exposure to chlordecone and a hepatotoxic agent, carbon tetrachloride (CCl4). After repeated administrations of chlordecone and CCl4 by gavage over a 12-week period, we checked for liver damage in the exposed mice, by determining serum liver transaminase (AST, ALT) levels, histological examinations of the liver and measuring the expression of genes encoding extracellular matrix components. The co-exposure of mice to CCl4 and chlordecone resulted in significant increases in ALT and AST levels. Chlordecone also increased expression of the Col1A2, MMP-2, TIMP-1 and PAI-1 genes in CCl4-treated mice. Finally, we demonstrated, by quantifying areas of collagen deposition and alpha-SMA gene expression, that chlordecone potentiated the hepatic fibrosis induced by CCl4. In conclusion, our data suggest that chlordecone potentiates hepatic fibrosis in mice with CCl4-induced chronic liver injury. PMID:26853152

  13. Repair of liver mediated by adult mouse liver neuro-glia antigen 2-positive progenitor cell transplantation in a mouse model of cirrhosis.

    PubMed

    Zhang, Hongyu; Siegel, Christopher T; Shuai, Ling; Lai, Jiejuan; Zeng, Linli; Zhang, Yujun; Lai, Xiangdong; Bie, Ping; Bai, Lianhua

    2016-01-01

    NG2-expressing cells are a population of periportal vascular stem/progenitors (MLpvNG2(+) cells) that were isolated from healthy adult mouse liver by using a "Percoll-Plate-Wait" procedure. We demonstrated that isolated cells are able to restore liver function after transplantation into a cirrhotic liver, and co-localized with the pericyte marker (immunohistochemistry: PDGFR-β) and CK19. Cells were positive for: stem cell (Sca-1, CD133, Dlk) and liver stem cell markers (EpCAM, CD14, CD24, CD49f); and negative for: hematopoietic (CD34, CD45) and endothelial markers (CD31, vWf, von Willebrand factor). Cells were transplanted (1 × 10(6) cells) in mice with diethylnitrosamine-induced cirrhosis at week 6. Cells showed increased hepatic associated gene expression of alpha-fetoprotein (AFP), Albumin (Alb), Glucose-6-phosphatase (G6Pc), SRY (sex determining region Y)-box 9 (Sox9), hepatic nuclear factors (HNF1a, HNF1β, HNF3β, HNF4α, HNF6, Epithelial cell adhesion molecule (EpCAM), Leucine-rich repeated-containing G-protein coupled receptor 5-positive (Lgr5) and Tyrosine aminotransferase (TAT). Cells showed decreased fibrogenesis, hepatic stellate cell infiltration, Kupffer cells and inflammatory cytokines. Liver function markers improved. In a cirrhotic liver environment, cells could differentiate into hepatic lineages. In addition, grafted MLpvNG2(+) cells could mobilize endogenous stem/progenitors to participate in liver repair. These results suggest that MLpvNG2(+) cells may be novel adult liver progenitors that participate in liver regeneration. PMID:26905303

  14. Repair of liver mediated by adult mouse liver neuro-glia antigen 2-positive progenitor cell transplantation in a mouse model of cirrhosis

    PubMed Central

    Zhang, Hongyu; Siegel, Christopher T.; Shuai, Ling; Lai, Jiejuan; Zeng, Linli; Zhang, Yujun; Lai, Xiangdong; Bie, Ping; Bai, Lianhua

    2016-01-01

    NG2-expressing cells are a population of periportal vascular stem/progenitors (MLpvNG2+ cells) that were isolated from healthy adult mouse liver by using a “Percoll-Plate-Wait” procedure. We demonstrated that isolated cells are able to restore liver function after transplantation into a cirrhotic liver, and co-localized with the pericyte marker (immunohistochemistry: PDGFR-β) and CK19. Cells were positive for: stem cell (Sca-1, CD133, Dlk) and liver stem cell markers (EpCAM, CD14, CD24, CD49f); and negative for: hematopoietic (CD34, CD45) and endothelial markers (CD31, vWf, von Willebrand factor). Cells were transplanted (1 × 106 cells) in mice with diethylnitrosamine-induced cirrhosis at week 6. Cells showed increased hepatic associated gene expression of alpha-fetoprotein (AFP), Albumin (Alb), Glucose-6-phosphatase (G6Pc), SRY (sex determining region Y)-box 9 (Sox9), hepatic nuclear factors (HNF1a, HNF1β, HNF3β, HNF4α, HNF6, Epithelial cell adhesion molecule (EpCAM), Leucine-rich repeated-containing G-protein coupled receptor 5-positive (Lgr5) and Tyrosine aminotransferase (TAT). Cells showed decreased fibrogenesis, hepatic stellate cell infiltration, Kupffer cells and inflammatory cytokines. Liver function markers improved. In a cirrhotic liver environment, cells could differentiate into hepatic lineages. In addition, grafted MLpvNG2+ cells could mobilize endogenous stem/progenitors to participate in liver repair. These results suggest that MLpvNG2+ cells may be novel adult liver progenitors that participate in liver regeneration. PMID:26905303

  15. Evaluation of Serum Cystatin C as a Marker of Early Renal Impairment in Patients with Liver Cirrhosis

    PubMed Central

    Omar, Mahmoud; Abdel-Razek, Wael; Abo-Raia, Gamal; Assem, Medhat; El-Azab, Gasser

    2015-01-01

    Background. Serum cystatin C (CysC) was proposed as an effective reflection of the glomerular filtration rate (GFR). However, its role in patients with liver cirrhosis has not been extensively verified especially in the detection of early RI. Patients and Methods. Seventy consecutive potential candidates for living donor liver transplantation with serum creatinine (Cr) <1.5 mg/dL were included. CysC, Cr, and estimated GFR [creatinine clearance (CCr), Cockcroft-Gault formula (C-G), MDRD equations with 4 and 6 variables, CKD-EPI-Cr, CKD-EPI-CysC, and CKD-EPI-Cr-CysC] were all correlated to isotopic GFR. Early RI was defined as GFR of 60–89 mL/min/1.73 m2. Results. Patients were 25.7% and 74.3% Child-Pugh classes B and C, respectively. GFR was ≥90, 60–89, and 30–59 mL/min/1.73 m2 in 31.4%, 64.3%, and 4.3% of the patients, respectively. All markers and equations, except C-G, were significantly correlated to GFR with CKD-EPI-Cr-CysC formula having the highest correlation (r = 0.474) and the largest area under the ROC curve (0.808) for discriminating early RI. At a cutoff value of 1.2 mg/L, CysC was 89.6% sensitive and 63.6% specific in detecting early RI. Conclusion. In patients with liver cirrhosis, CysC and CysC-based equations showed the highest significant correlation to GFR and were measures that best discriminated early RI. PMID:26550493

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

    PubMed Central

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

    2014-01-01

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

  17. Liver cirrhosis grading Child-Pugh class B: a Goliath to challenge in laparoscopic liver resection?—prior experience and matched comparisons

    PubMed Central

    Liang, Xiao; Yu, Tunan; Liang, Yuelong; Jing, Renan; Jiang, Wenbing; Li, Jianbo; Ying, Hanning

    2015-01-01

    Background Laparoscopic hepatectomy (LH) is highly difficult in the background of liver cirrhosis. In this case series, we aimed to summarize our prior experience of LH in liver cirrhosis grading Child-Pugh class B. Methods In the LH database of Sir Run Run Shaw Hospital in Zhejiang, China, patients who were pathologically diagnosed with cirrhosis and graded as Child-Pugh class B or C were reviewed. Results Five patients grading Child B were included. There was no Child C case in our LH database. For included cases, median blood loss (BL) was 800 (range, 240-1,000) mL, median operative time was 135 (range, 80-170) minutes, and median length of hospital stay was 9 (range, 7-15) days. Forty percent (2/5) of patients was converted to open. The postoperative complication (PC) rate was 20.0% (1/5). When these Child B cases were compared with Child A cases undergoing LH, there was no statistical significance in BL, complication rate, operative time, open rate and hospital stay (HS) (P>0.05). This finding was confirmed by two ways of matched comparisons (a 1:2 comparison based on age and gender, and a 1:1 propensity score matching). Conclusions Although relevant literatures had suggested feasibility of LH in cirrhotic cases grading Child A, this study was the first one to discuss the value of LH in Child B cases. Our prior experience showed that in selected patients, LH in Child B patients had the potential to be as safe as in Child A cases. The efficacy of LH in Child C patients needs further exploration. PMID:26734623

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

    NASA Astrophysics Data System (ADS)

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

    2014-03-01

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

  19. Multimodality therapy and liver transplantation in patients with cirrhosis and hepatocellular carcinoma: 6 years, single-center experience.

    PubMed

    Maluf, D G; Stravitz, R T; Williams, B; Cotterell, A H; Mas, V R; Heuman, D; Luketic, V; Shiffman, M L; Sterling, R; Posner, M P; Fisher, R A

    2007-01-01

    The treatment of patients with cirrhosis and hepatocellular carcinoma (HCC) has improved dramatically over the past 10 years. We conducted a 6-year prospective study, using multimodality ablation therapy (MMT) combined with liver transplantation (LTx) for patients with cirrhosis and unresectable HCC. Subjects were classified as: group 1 (n = 35), intention to treat with MMT + LTx; group 2 (n = 16), contemporaneous LTx with "incidental" HCC on explants; group 3 (n = 94), MMT alone; and group 4 (n = 19), palliative care alone. MMT included trans-arterial chemo-embolization (54.4%), trans-arterial chemo-infusion (28.6%), and radio frequency ablation (17%). Group 1, with a mean wait time of 11.6 months pre-MELD era and 5.4 months post-MELD era, had a mean of 2.4 +/- 1.2 MMTs and achieved 1- 3-, and 5-year patient survivals of 100, 100, and 76%, respectively, which was not different from group 2 (incidental HCC), namely 93, 93, and 93%, respectively; or to a contemporaneous non-HCC LTx group: namely 84.3, 78.7, and 73.9%, respectively. Despite careful pretransplant HCC staging, 22.8% (8 of 35) group 1 subjects were understaged. Those subjects in group 1 with true T1-2 stage HCC achieved 100% cancer-free survival at 5 years. Only three cases of HCC recurrence occurred in our series, all of whom were understaged. Our data suggest that pretransplant MMT followed by timely LTx provides excellent disease-free survival at 5 years for patients with true T1-2 stage HCC and cirrhosis. Pretransplant HCC understaging contributes to posttransplant HCC recurrence after LTx. PMID:17275495

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

    PubMed

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

    2005-09-01

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

  1. PXR Mediated Protection against Liver Inflammation by Ginkgolide A in Tetrachloromethane Treated Mice

    PubMed Central

    Ye, Nanhui; Wang, Hang; Hong, Jing; Zhang, Tao; Lin, Chaotong; Meng, Chun

    2016-01-01

    The pregnane X receptor (PXR), a liver and intestine specific receptor,, has been reported to be related with the repression of inflammation as well as activation of cytochromosome P450 3A (CYP3A) expression. We examined the effect of PXR on tetrachloromethane (CCl4)-induced mouse liver inflammation in this work. Ginkgolide A, one main component of Ginkgo biloba extracts (GBE), activated PXR and enhanced PXR expression level, displayed both significant therapeutic effect and preventive effect against CCl4-induced mouse hepatitis. siRNA-mediated decrease of PXR expression significantly reduced the efficacy of Ginkgolide A in treating CCl4-induced inflammation in mice. Flavonoids, another important components of GBE, were shown anti-inflammatory effect in a different way from Ginkgolide A which might be independent on PXR because flavonoids significantly inhibited CYP3A11 activities in mice. The results indicated that anti-inflammatory effect of PXR might be mediated by enhancing transcription level of IκBα through binding of IκBα. Inhibition of NF-κB activity by NF-κB-specific suppressor IκBα is one of the potential mechanisms of Ginkgolide A against CCl4-induced liver inflammation. PMID:26759700

  2. Hepatoprotective effect of trimethylgallic acid esters against carbon tetrachloride-induced liver injury in rats.

    PubMed

    Sachdeva, Mamta; Chadha, Renu; Kumar, Anil; Karan, Maninder; Singh, Tejvir; Dhingra, Sameer

    2015-12-01

    Gallic acid and its derivatives are potential therapeutic agents for treating various oxidative stress mediated disorders. In the present study, we investigated the hepatoprotective effects of newly synthesized conjugated trimethylgallic acid (TMGA) esters against carbon tetrachloride (CCl4)-induced hepatotoxicity in rats. Animals were pre-treated with TMGA esters at their respective doses for 7 days against CCl4-induced hepatotoxicity. The histopathological changes were evaluated to find out degenerative fatty changes including vacuole formation, inflammation and tissue necrosis. Various biomarkers of oxidative stress (lipid peroxidation, glutathione levels, and endogenous antioxidant enzyme activities), liver enzymes (AST and ALT), triacylglycerol and cholesterol were evaluated. Pre-treatment with TMGA esters (MRG, MGG, MSG, and MUG at the dose of 28.71, 30.03, 31.35, 33.62 mg/kg/day), respectively reversed the CCl4-induced liver injury scores (reduced vacuole formation, inflammation and necrosis), biochemical parameters of plasma (increased AST, ALT, TG, and cholesterol), antioxidant enzymes (increased lipid peroxidation and nitrite levels; decreased glutathione levels, superoxide dismutase and catalase activities) in liver tissues and inflammatory surge (serum TNF-α) significantly. The study revealed that TMGA esters exerted hepatoprotective effects in CCl4-induced rats, specifically by modulating oxidative-nitrosative stress and inflammation. PMID:26742325

  3. PXR Mediated Protection against Liver Inflammation by Ginkgolide A in Tetrachloromethane Treated Mice.

    PubMed

    Ye, Nanhui; Wang, Hang; Hong, Jing; Zhang, Tao; Lin, Chaotong; Meng, Chun

    2016-01-01

    The pregnane X receptor (PXR), a liver and intestine specific receptor,, has been reported to be related with the repression of inflammation as well as activation of cytochromosome P450 3A (CYP3A) expression. We examined the effect of PXR on tetrachloromethane (CCl4)-induced mouse liver inflammation in this work. Ginkgolide A, one main component of Ginkgo biloba extracts (GBE), activated PXR and enhanced PXR expression level, displayed both significant therapeutic effect and preventive effect against CCl4-induced mouse hepatitis. siRNA-mediated decrease of PXR expression significantly reduced the efficacy of Ginkgolide A in treating CCl4-induced inflammation in mice. Flavonoids, another important components of GBE, were shown anti-inflammatory effect in a different way from Ginkgolide A which might be independent on PXR because flavonoids significantly inhibited CYP3A11 activities in mice. The results indicated that anti-inflammatory effect of PXR might be mediated by enhancing transcription level of IκBα through binding of IκBα. Inhibition of NF-κB activity by NF-κB-specific suppressor IκBα is one of the potential mechanisms of Ginkgolide A against CCl4-induced liver inflammation. PMID:26759700

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

    PubMed Central

    Suk, Ki Tae; Kim, Dong Joon

    2015-01-01

    Liver fibrosis is a common histological change of chronic liver injury and it is closely related with portal hypertension which is hemodynamic complication of chronic liver disease. Currently, liver fibrosis has been known as a reversible dynamic process in previous literatures. Although liver biopsy is a gold standard for assessing the stage of liver fibrosis, it may not completely represent the stage of liver fibrosis because of sampling error or semi-quantative measurement. Recent evidences suggested that histologic, clinical, hemodynamic, and biologic features are closely associated in patients with chronic liver disease. Hepatic venous pressure gradient (HVPG) measurement has been known as a modality to evaluate the portal pressure. The HVPG measurement has been used clinically for fibrosis diagnosis, risk stratification, preoperative screening for liver resection, monitoring the efficacy of medical treatments, and assessing the prognosis of liver fibrosis. Therefore, the HVPG measurement can be used to monitor areas the chronic liver disease but also other important areas of chronic liver disease. PMID:25848485

  5. The Levels of Ghrelin, Leptin, TNF-?, and IL-6 in Liver Cirrhosis and Hepatocellular Carcinoma due to HBV and HDV Infection

    PubMed Central

    Ataseven, Huseyin; Bahcecioglu, Ibrahim Halil; Kuzu, Nalan; Yalniz, Mehmet; Celebi, Selman; Erensoy, Ahmet; Ustundag, Bilal

    2006-01-01

    Background/Aim. Malnutrition, a common problem in liver cirrhosis and HCC, may readily deteriorate the clinical functions with resultant poor prognosis. Beside the hyper catabolic state frequently encountered in chronic liver disease and HCC, anorexia and reduced food intake also worsen the malnutrition. The recently discovered peptide hormone ghrelin acts as a counterpart of leptin in regulation of food intake and fat utilization. The aim of the present study was to investigate the ghrelin and leptin levels in cirrhosis and HCC due to hepatitis B and D viruses, and the association of ghrelin and leptin with TNF-?, IL-6 and the severity of the disease. Materials and methods. We measured serum ghrelin, leptin, TNF-?, and IL-6 levels using specific immunoassay in 45 patients (23 cirrhosis, 22 HCC) with HBV and/or HDV and in 25 control subjects. Results. In comparison to controls, serum ghrelin, TNF-?, and IL-6 levels were significantly higher in cirrhosis and HCC (P < .05), whereas serum leptin levels were found decreased (P < .05). There was a positive correlation between ghrelin and TNF-?, and a negative correlation between leptin and TNF-? (P < .05). Conclusion. In cirrhosis and HCC due to HBV or HDV, serum ghrelin levels were increased with a corresponding decrease in serum leptin concentrations, acting as a physiological counterpart of ghrelin. The increasing of ghrelin is more prominent in Child C cirrhosis and the level was correlated with TNF-?. The presence of nutritional and metabolic abnormalities, including malnutrition, in cirrhosis and HCC may, at least partly, elucidate high ghrelin and low leptin levels. PMID:17047295

  6. Direct targeting of risk factors significantly increases the detection of liver cirrhosis in primary care: a cross-sectional diagnostic study utilising transient elastography

    PubMed Central

    Harman, David J; Ryder, Stephen D; James, Martin W; Jelpke, Matthew; Ottey, Dominic S; Wilkes, Emilie A; Card, Timothy R; Aithal, Guruprasad P; Guha, Indra Neil

    2015-01-01

    Objectives To assess the feasibility of a novel diagnostic algorithm targeting patients with risk factors for chronic liver disease in a community setting. Design Prospective cross-sectional study. Setting Two primary care practices (adult patient population 10 479) in Nottingham, UK. Participants Adult patients (aged 18 years or over) fulfilling one or more selected risk factors for developing chronic liver disease: (1) hazardous alcohol use, (2) type 2 diabetes or (3) persistently elevated alanine aminotransferase (ALT) liver function enzyme with negative serology. Interventions A serial biomarker algorithm, using a simple blood-based marker (aspartate aminotransferase:ALT ratio for hazardous alcohol users, BARD score for other risk groups) and subsequently liver stiffness measurement using transient elastography (TE). Main outcome measures Diagnosis of clinically significant liver disease (defined as liver stiffness ≥8 kPa); definitive diagnosis of liver cirrhosis. Results We identified 920 patients with the defined risk factors of whom 504 patients agreed to undergo investigation. A normal blood biomarker was found in 62 patients (12.3%) who required no further investigation. Subsequently, 378 patients agreed to undergo TE, of whom 98 (26.8% of valid scans) had elevated liver stiffness. Importantly, 71/98 (72.4%) patients with elevated liver stiffness had normal liver enzymes and would be missed by traditional investigation algorithms. We identified 11 new patients with definite cirrhosis, representing a 140% increase in the number of diagnosed cases in this population. Conclusions A non-invasive liver investigation algorithm based in a community setting is feasible to implement. Targeting risk factors using a non-invasive biomarker approach identified a substantial number of patients with previously undetected cirrhosis. Trial registration number The diagnostic algorithm utilised for this study can be found on clinicaltrials.gov (NCT02037867), and is part of a continuing longitudinal cohort study. PMID:25941185

  7. Diagnostic Accuracy of APRI, AAR, FIB-4, FI, and King Scores for Diagnosis of Esophageal Varices in Liver Cirrhosis: A Retrospective Study.

    PubMed

    Deng, Han; Qi, Xingshun; Peng, Ying; Li, Jing; Li, Hongyu; Zhang, Yongguo; Liu, Xu; Sun, Xiaolin; Guo, Xiaozhong

    2015-01-01

    BACKGROUND Aspartate aminotransferase-to-platelet ratio index (APRI), aspartate aminotransferase-to-alanine aminotransferase ratio (AAR), FIB-4, fibrosis index (FI), and King scores might be alternatives to the use of upper gastrointestinal endoscopy for the diagnosis of esophageal varices (EVs) in liver cirrhosis. This study aimed to evaluate their diagnostic accuracy in predicting the presence and severity of EVs in liver cirrhosis. MATERIAL AND METHODS All patients who were consecutively admitted to our hospital and underwent upper gastrointestinal endoscopy between January 2012 and June 2014 were eligible for this retrospective study. Areas under curve (AUCs) were calculated. Subgroup analyses were performed according to the history of upper gastrointestinal bleeding (UGIB) and splenectomy. RESULTS A total of 650 patients with liver cirrhosis were included, and 81.4% of them had moderate-severe EVs. In the overall analysis, the AUCs of these non-invasive scores for predicting moderate-severe EVs and presence of any EVs were 0.506-0.6 and 0.539-0.612, respectively. In the subgroup analysis of patients without UGIB, their AUCs for predicting moderate-severe varices and presence of any EVs were 0.601-0.664 and 0.596-0.662, respectively. In the subgroup analysis of patients without UGIB or splenectomy, their AUCs for predicting moderate-severe varices and presence of any EVs were 0.627-0.69 and 0.607-0.692, respectively. CONCLUSIONS APRI, AAR, FIB-4, FI, and King scores had modest diagnostic accuracy of EVs in liver cirrhosis. They might not be able to replace the utility of upper gastrointestinal endoscopy for the diagnosis of EVs in liver cirrhosis. PMID:26687574

  8. Diagnostic Accuracy of APRI, AAR, FIB-4, FI, and King Scores for Diagnosis of Esophageal Varices in Liver Cirrhosis: A Retrospective Study

    PubMed Central

    Deng, Han; Qi, Xingshun; Peng, Ying; Li, Jing; Li, Hongyu; Zhang, Yongguo; Liu, Xu; Sun, Xiaolin; Guo, Xiaozhong

    2015-01-01

    Background Aspartate aminotransferase-to-platelet ratio index (APRI), aspartate aminotransferase-to-alanine aminotransferase ratio (AAR), FIB-4, fibrosis index (FI), and King scores might be alternatives to the use of upper gastrointestinal endoscopy for the diagnosis of esophageal varices (EVs) in liver cirrhosis. This study aimed to evaluate their diagnostic accuracy in predicting the presence and severity of EVs in liver cirrhosis. Material/Methods All patients who were consecutively admitted to our hospital and underwent upper gastrointestinal endoscopy between January 2012 and June 2014 were eligible for this retrospective study. Areas under curve (AUCs) were calculated. Subgroup analyses were performed according to the history of upper gastrointestinal bleeding (UGIB) and splenectomy. Results A total of 650 patients with liver cirrhosis were included, and 81.4% of them had moderate-severe EVs. In the overall analysis, the AUCs of these non-invasive scores for predicting moderate-severe EVs and presence of any EVs were 0.506–0.6 and 0.539–0.612, respectively. In the subgroup analysis of patients without UGIB, their AUCs for predicting moderate-severe varices and presence of any EVs were 0.601–0.664 and 0.596–0.662, respectively. In the subgroup analysis of patients without UGIB or splenectomy, their AUCs for predicting moderate-severe varices and presence of any EVs were 0.627–0.69 and 0.607–0.692, respectively. Conclusions APRI, AAR, FIB-4, FI, and King scores had modest diagnostic accuracy of EVs in liver cirrhosis. They might not be able to replace the utility of upper gastrointestinal endoscopy for the diagnosis of EVs in liver cirrhosis. PMID:26687574

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

    PubMed Central

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

    2014-01-01

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

  10. COMPARATIVE STUDY ON LIVER TRANSPLANTATION WITH AND WITHOUT HEPATOCELLULAR CARCINOMA WITH CIRRHOSIS: ANALYSIS OF MELD, WAITING TIME AND SURVIVAL

    PubMed Central

    de FREITAS, Alexandre Coutinho Teixeira; SHIGUIHARA, Rafael Shinmi; MONTEIRO, Ruan Teles; PAZETO, Thiago Linck; COELHO, Júlio Cezar Uili

    2016-01-01

    Background : Liver transplantation is the usual treatment for hepatocellular carcinoma. Aim: To analyze the MELD score, waiting time and three month and one year survival for liver transplantation in cirrhotic patients affected by hepatocellular carcinoma or not. Methods : This was a retrospective, observational and analytical study of 93 patients submitted to liver transplantation. Results : There were 28 hepatocellular carcinoma and 65 non-hepatocellular carcinoma patients with no differences related to age and sex distribution. The main causes of cirrhosis on hepatocellular carcinoma were hepatitis C virus (57.1%) and hepatitis B virus (28.5%), more frequent than non-hepatocellular carcinoma patients, which presented 27.7% and 4.6% respectively. The physiological and exception MELD score on hepatocellular carcinoma were 11.9 and 22.3 points. On non-hepatocellular carcinoma, it was 19.4 points, higher than the physiological MELD and lower than the exception MELD on hepatocellular carcinoma. The waiting time for transplantation was 96.2 days for neoplasia, shorter than the waiting time for non-neoplasia patients, which was 165.6 days. Three month and one year survival were 85.7% and 78.6% for neoplasia patients, similar to non-neoplasia, which were 77% and 75.4%. Conclusion: Hepatocellular carcinoma patients presented lower physiological MELD score, higher exception MELD score and shorter waiting time for transplantation when compared to non-hepatocellular carcinoma patients. Three month and one year survival were the same between the groups. PMID:27120734

  11. Immunohistochemical characterization of glial fibrillary acidic protein (GFAP)-expressing cells in a rat liver cirrhosis model induced by repeated injections of thioacetamide (TAA).

    PubMed

    Tennakoon, Anusha Hemamali; Izawa, Takeshi; Wijesundera, Kavindra Kumara; Murakami, Hiroshi; Katou-Ichikawa, Chisa; Tanaka, Miyuu; Golbar, Hossain M; Kuwamura, Mitsuru; Yamate, Jyoji

    2015-01-01

    Hepatic stellate cells, the principal fibrogenic cell type in the liver, are known to express the astrocyte marker glial fibrillary acidic protein (GFAP). However, the exact role of GFAP-expressing cells in liver fibrosis remains to be elucidated. In this study, cellular properties of GFAP-expressing cells were investigated in a rat model of liver cirrhosis. Six-week-old male F344 rats were injected intraperitoneally with thioacetamide (100 mg/kg BW, twice a week) and examined at post first injection weeks 5, 10, 15, 20 and 25. Appearance of GFAP-expressing myofibroblasts peaked at week 15, associated with fibrosis progression. The majority of GFAP-expressing myofibroblasts co-expressed vimentin, desmin and alpha-smooth muscle actin. Some GFAP-positive myofibroblasts co-expressed nestin (neural stem cell marker), while a few co-expressed A3 (mesenchymal stem cell marker) and Thy-1 (immature mesenchymal cell marker). A few GFAP expressing cells underwent both mitosis and apoptosis. These results indicate that there is a dynamic participation of GFAP-expressing myofibroblasts in rat liver cirrhosis, and that they are mainly derived from hepatic stellate cells, and partly from cells in the stem cell lineage. These findings, which were shown for the first time in detail, would be useful to understand the role of GFAP-expressing myofibroblasts in the pathogenesis of chemically induced liver cirrhosis. PMID:25446803

  12. [Liver cirrhosis mortality in Mexico. II. Excess mortality and pulque consumption].

    PubMed

    Narro-Robles, J; Gutiérrez-Avila, J H; López-Cervantes, M; Borges, G; Rosovsky, H

    1992-01-01

    Over the years high cirrhosis mortality rates have been reported in Mexico City and in the surrounding states (Hidalgo, Tlaxcala, Puebla and the State of Mexico); on the contrary, well defined areas, such as the northern states, have shown a considerably lower mortality rate. This situation may indicate that some factors such as the pattern of alcoholic intake and other environmental characteristics could explain this striking difference. To determine the role of alcohol, the availability and consumption of alcohol at regional and state level were compared with cirrhosis mortality rates. A high and statistically significant correlation was found with pulque availability and consumption (r = 72-92%, p less than 0.01) in all periods of time under examination. On the contrary, a statistically significant negative association was observed with beer consumption and a positive, but not significant correlation, with distilled alcoholic beverages. Infectious hepatitis incidence, prevalence of exclusive use of native languages (as an indirect index of ethnic background) and nutritional deficiencies were also studied as possible risk factors. Nutritional deficiencies and the prevalence of exclusive use of náhuatl and otomí languages were positively correlated. These results can be useful to conduct further epidemiological studies still needed to determine the etiologic role of pulque consumption as well as of the other risk factors. Nonetheless, the current data stress the need to implement public health programs to reduce alcohol consumption, especially pulque, and to minimize the impact of these risk factors in high mortality areas. PMID:1502659

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

    PubMed

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

    2015-03-01

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

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

    PubMed Central

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

    2014-01-01

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

  15. Invasive group B streptococcal infection in a patient with post splenectomy for hypersplenism secondary to liver cirrhosis and portal hypertension

    PubMed Central

    Okazaki, Tomoya; Hifumi, Toru; Manabe, Arisa; Matsumura, Hikari; Egawa, Satoshi; Hamaya, Hideyuki; Shinohara, Nastuyo; Takano, Koshiro; Shishido, Hajime; Abe, Yuko; Kawakita, Kenya; Hagiike, Masanobu; Kuroda, Yasuhiro

    2016-01-01

    BACKGROUND: Splenectomy in patients with liver cirrhosis (LC) is expected to become more common owing to its efficacy on portal hemodynamics. In this report we describe an alarming case of group B streptococcus (GBS) infection after splenectomy in a patient with LC. METHODS: A 72-year-old woman with a history of LC was admitted to our emergency department because of respiratory failure. The patient had received left lateral segmentectomy of the liver and splenectomy three months before admission. Pulmonary examination revealed significant wheezing during inspiration and expiration, but no crackles and stridor. Chest radiography and CT showed no infiltrates. A presumptive diagnosis of bronchial asthma caused by upper respiratory infection was made. Four days after admission, GBS infection was confirmed by blood culture and penicillin G was administered. Antibiotics were given intravenously for a total of 12 days. RESULTS: The patient was discharged on the 12th day after admission. CONCLUSIONS: Although efficacy of splenectomy in patients with LC has been reported, immune status should be evaluated for a longer period. Patients who have undergone splenectomy are highly susceptible to bacteria; moreover, LC itself is an independent risk factor for mortality in patients with sepsis. Since prophylaxis against GBS has not been established, immediate action should be taken. Emergency physicians should be aware of invasive GBS infection in the context of the critical risk factors related to splenectomy and LC, particularly the expected increase of splenectomy performed in LC patients. PMID:27006743

  16. Growth hormone response to thyrotropin-releasing hormone in liver cirrhosis: unique alteration in anterior pituitary responsiveness to hypothalamic hormones.

    PubMed

    Salerno, F; Cocchi, D; Lampertico, M; Manneschi, M; Monza, G; Müller, E E

    1982-09-01

    Patients with chronic liver diseases were evaluated for: 1) the ability of somatostatin to affect the thyrotropin-releasing hormone (TRH) induced growth hormone (GH) rise; 2) the competence of luteinizing-hormone releasing hormone (LH-RH) to release GH; 3) the non-specific releasing effect of TRH and LH-RH on other anterior pituitary (AP) hormones. In 6 patients, infusion of somatostatin (100 micrograms iv bolus + 375 micrograms i.v. infusion) completely abolished the TRH (400 micrograms i.v.)-induced GH rise; in none of 12 patients, of whom 7 were GH-responders to TRH, did LH-RH (100 micrograms i.v.) cause release of GH; 4) finally, LH-RH (12 patients) did not increase plasma prolactin (PRL) and TRH (7 patients) did not evoke a non-specific release of gonadotropins. It is concluded that: 1) abnormal GH-responsiveness to TRH is the unique alteration in AP responsiveness to hypothalamic hormones present in liver cirrhosis; 2) the mechanism(s) subserving the altered GH response to TRH is different from that underlying the TRH-induced GH rise present in another pathologic state i.e. acromegaly, a condition in which the effect of TRH escapes somatostatin suppression and LH-RH evokes GH and PRL release. PMID:6128295

  17. Ginkgo biloba extract mitigates liver fibrosis and apoptosis by regulating p38 MAPK, NF-κB/IκBα, and Bcl-2/Bax signaling

    PubMed Central

    Wang, Yuanyuan; Wang, Rong; Wang, Yujie; Peng, Ruqin; Wu, Yan; Yuan, Yongfang

    2015-01-01

    Background Liver fibrosis is the consequence of diverse liver injuries and can eventually develop into liver cirrhosis. Ginkgo biloba extract (GBE) is an extract from dried ginkgo leaves that has many pharmacological effects because of its various ingredients and has been shown to be hepatoprotective. Purpose and methods Aimed to investigate the underlying protective mechanisms of GBE on carbon tetrachloride (CCl4)-induced liver fibrosis in rats. Male Sprague Dawley rats were randomly divided into four groups: control group (C), model group (M), low-dose group (L), and high-dose group (H). Liver fibrosis was induced by CCl4 groups M, L, and H: group C was administered saline. In addition, GBE at different doses was used to treat groups L and H. Results The results of hematoxylin and eosin staining, Masson’s trichrome staining, a liver function index, and a liver fibrosis index showed that GBE application noticeably mitigated fibrosis and improved the function of the liver. The western blotting and immunohistochemistry analyses indicated that GBE reduced liver fibrosis not only by inhibiting p38 MAPK and NF-κBp65 via inhibition of IκBα degradation but also by inhibiting hepatocyte apoptosis via downregulation of Bax, upregulation of Bcl-2, and subsequent inhibition of caspase-3 activation. Inflammation-associated factors and hepatic stellate cell (HSC)-activation markers further demonstrated that GBE could effectively inhibit HSC activation and inflammation as a result of its regulation of p38 MAPK and nuclear factor-kappa B/IκBα signaling. Conclusion Our findings indicated a novel role for GBE in the treatment of liver fibrosis. The potential mechanisms may be associated with the following signaling pathways: 1) the p38 MAPK and nuclear factor-kappa B/IκBα signaling pathways (inhibiting inflammation and HSCs activation) and 2) the Bcl-2/Bax signaling pathway (inhibiting the apoptosis of hepatocytes). PMID:26664050

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

    PubMed Central

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

    2011-01-01

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

  19. Effect of Liver Damage and Hyperbaric Oxygenation on Glutamine Synthetase of Hepatocytes.

    PubMed

    Savilov, P N; Yakovlev, V N

    2016-01-01

    Activity of glutamine synthetase in the hepatocytes of healthy animals and animals with chronic CCl4-induced hepatitis was studied on white mature female rats after liver resection (15-20% of organ weight) and hyperbaric oxygenation (3 atm, 50 min, 3 times). Surgically operated left and non-operated middle lobes of the liver were analyzed on day 3 after liver resection and exposure to hyperbaric oxygenation. On day 65 of CCl4 poisoning, activity of glutamine synthetase decreased in both lobes and did not recover on day 3 after toxin cessation. Liver resection under conditions of CCl4-induced hepatitis restored reduced activity of glutamine synthetase in both liver lobes to the normal level. In healthy rats, the increase in glutamine synthetase activity after liver resection was found only in the middle lobe of the liver. Hyperbaric oxygenation enhanced the stimulatory effect of liver resection on glutamine synthetase activity in hepatocytes during chronic CCl4-induced hepatitis. In healthy animals with liver resection, activity of glutamine synthetase did not change after hyperbaric oxygenation, while normally oxygenation inhibited glutamine synthetase activity. PMID:26742742

  20. Transcatheter coil embolization of the inferior epigastric artery in a huge abdominal wall hematoma caused by paracentesis in a patient with liver cirrhosis

    PubMed Central

    Park, Yun Ji; Lee, Sang Yeon; Kim, Seong Hun; Kim, In Hee; Kim, Sang Wook

    2011-01-01

    Therapeutic paracentesis is considered to be a relatively safe procedure and is performed commonly for the control of massive ascites in patients with liver cirrhosis. The commonest puncture site, approximately 4 or 5 cm medial of left anterior superior iliac spine, can be located across the route of the inferior epigastric artery, which is one of the sites of potential massive bleeding. In a 46-year-old woman with liver cirrhosis and refractory ascites, a huge abdominal wall hematoma developed after therapeutic paracentesis. The patient was not stabilized by conservative treatment, and inferior epigastric artery injury was confirmed on angiography. Angiographic coil embolization of the inferior epigastric artery was conducted, after which the bleeding ceased and the hematoma stopped growing. This case indicates that physicians performing paracentesis should be aware of the possibility of inferior epigastric artery injury and consider early angiographic coil embolization when a life-threatening abdominal wall hematoma develops. PMID:22102392

  1. Early Detection of Hepatocellular Carcinoma: How to Screen and Follow up Patients with Liver Cirrhosis According to the GERMAN S3 Guideline?

    PubMed Central

    Plentz, Ruben R.; Malek, Nisar P.

    2015-01-01

    Hepatocellular carcinoma (HCC) is frequently detected in pre-existing liver cirrhosis, but can also develop without such pre-conditions. There is an increasing trend of HCC incidence worldwide. In patients with liver cirrhosis, HCC has become the leading cause of death. At diagnosis the tumor has very often reached an advanced stage and curative treatment options are missing. Thus, early diagnosis would help the patient and prevent increasing healthcare costs. In our review we will summarize the recommendations of the German S3 guideline for the early diagnosis of HCC and will discuss the current literature in this context. The reader will learn which diagnostic tools are available and in what order they can be usefully applied. Surveillance should be done with ultrasound by a skilled examiner, additional imaging at best with state-of-the-art dynamic magnetic resonance. PMID:26854167

  2. Heparin Saline Versus Normal Saline for Flushing and Locking Peripheral Venous Catheters in Decompensated Liver Cirrhosis Patients

    PubMed Central

    Wang, Rui; Zhang, Ming-Guang; Luo, Ou; He, Liu; Li, Jia-Xin; Tang, Yun-Jing; Luo, Yan-Li; Zhou, Min; Tang, Li; Zhang, Zong-Xia; Wu, Hao; Chen, Xin-Zu

    2015-01-01

    Abstract A prospective randomized, controlled, single-blinded trial to compare the effectiveness and safety of heparin saline (HS) to those of normal saline (NS) as flushing and locking solutions for peripheral venous catheter (PVC) in decompensated liver cirrhosis (DLC) patients. Patients with DLC at our institution between April 2012 and March 2013 were enrolled after obtaining informed consent. The patients were randomly allocated into 2 groups: the NS group received preservative-free 0.9% sodium chloride as the flushing and locking solution, while the HS group received HS (50?U/mL). PVC-related events and the duration of PVC maintenance were compared between the 2 groups. Moreover, the preinfusion and postinfusion levels of prothrombin time (PT), activated partial thromboplastin time (APTT), and platelet (PLT) were also compared. A total of 32 and 36 DLC patients in the NS (125 PVCs) and HS (65 PVCs) groups, respectively, were analyzed. Baseline characteristics, including gender, age, ChildPugh grade, PVC type and administration of anticoagulant, and irritant agents, were comparable between the 2 groups (P?>?0.05). The maintenance times of the HS and NS groups were 80.27??26.47 and 84.19??29.32?hours, respectively (P?=?0.397). Removal of PVC for abnormal reasons occurred in 30.7% and 22.4% of patients in the HS and NS groups (P?=?0.208). The PVC occlusion rates were 6.2% and 5.6% in the HS and NS groups, respectively (OR?=?1.11, 95% CI 0.313.92). The PT, APTT, and PLT levels were comparable between the 2 groups both before and after infusion (P?>?0.05). Incremental analyses showed that ChildPugh grade C might be a risk factor for the suppression of PLT in the HS group. We consider NS to be as effective as and safer than conventional HS for flushing and locking PVC in decompensated liver cirrhosis patients. PMID:26252305

  3. A lithium clearance study of sodium reabsorption at the proximal tubule in liver cirrhosis with ascites.

    PubMed

    Hattori, K; Yauchi, T; Minato, Y; Hasumura, Y; Takeuchi, J; Shiigai, T

    1989-10-01

    Since the reabsorption of lithium occurs almost exclusively in the proximal tubule and is associated with that of sodium, the fractional excretion of lithium (FELit) ws examined in 18 patients with cirrhosis in order to examine the reabsorption rate of sodium at the proximal tubule. As expected, the fractional excretion of sodium (FENa) was significantly lower in cirrhotic patients with ascites (0.43 +/- 0.10%, mean +/- SEM) than in cirrhotic patients without ascites (0.75 +/- 0.14%, P less than 0.05) and healthy controls (0.82 +/- 0.17%, P less than 0.05). By contrast, there was no significant difference in FELit among cirrhotic patients with ascites (16.7 +/- 2.0%), cirrhotic patients without ascites (15.4 +/- 2.0%) and controls (17.4 +/- 1.5%). It is unlikely, therefore, that in cirrhotic patients with ascites, the impaired sodium excretion is solely caused by the abnormal sodium reabsorption capacity of the proximal tubule. PMID:2806832

  4. Knowledge about non-invasive diagnostic tests for varices in liver cirrhosis: A questionnaire survey to the Gastroenterology Branch of the Liaoning Medical Association, China

    PubMed Central

    Qi, Xingshun; Guo, Xiaozhong; Li, Hongyu; Liu, Xu; Deng, Han

    2016-01-01

    Background and aims: Due to the invasiveness of upper gastrointestinal endoscopy, non-invasive diagnostic tests for varices in liver cirrhosis have been widely established by numerous studies. A questionnaire survey, which was aimed at understanding the current knowledge about non-invasive diagnostic tests for varices in liver cirrhosis, was distributed among the members of Gastroenterology Branch of the Liaoning Medical Association. Methods: A questionnaire assessing the knowledge about non-invasive diagnostic tests for varices was sent to 42 members who participated in the entire ninth committee. They were from 33 hospitals in 13 cities of Liaoning Province, China. Results: Overall, 97.6% (41/42) of participants responded to the questionnaire. A majority of participants were chief physicians (85.4%), had >20 years of experience in clinical work of digestive diseases (80.5%) and worked at tertiary hospitals (97.6%). In 46.3% of participants’ departments, there were >200 patients with liver cirrhosis and gastroesophageal varices admitted every year. In 90.2% of participants’ departments, upper gastrointestinal endoscopy was regularly employed for the diagnosis of gastroesophageal varices. Only six (15%) participants often used non-invasive diagnostic tests for varices in clinical practice. Thirty (75%) participants knew at least one non-invasive diagnostic test for varices. The knowledge of at least one non-invasive diagnostic test was significantly associated with the number of cirrhotic patients with varices (P = 0.038) or the regular use of gastrointestinal endoscopy to diagnose varices (P = 0.022). Conclusions: This questionnaire survey suggested that non-invasive diagnostic tests for varices in liver cirrhosis were rarely or never used in clinical practices in Liaoning Province, China. Reliable, non-invasive indexes should be further explored in a well-designed multi-center observational study. PMID:26159631

  5. Combined detection of liver stiffness and C-reactive protein in patients with hepatitis B virus-related liver cirrhosis, with and without hepatocellular carcinoma

    PubMed Central

    LIU, XIAO-YAN; MA, LI-NA; YAN, TING-TING; LU, ZHEN-HUI; TANG, YUAN-YUAN; LUO, XIA; DING, XIANG-CHUN

    2016-01-01

    The aim of the present study was to investigate the usefulness of combined detection of liver stiffness (LS) and serum C-reactive protein (CRP) level in patients with hepatitis B virus (HBV)-related liver cirrhosis (LC). A total of 156 cases of previously untreated patients with HBV-related LC were classified into the LC group [LC without hepatocellular carcinoma (HCC)] and the HCC group (LC with HCC). Comparative analyses of LS and serum CRP level were conducted between these two groups. LS values and serum CRP levels were found to be significantly higher in the HCC group compared with those in the LC group (P<0.01). The LS values and serum CRP levels were not significantly different between α-fetoprotein (AFP)-positive and -negative patients. A high LS value was a high-risk factor for HCC in patients with chronic hepatitis B. The CRP-positive rate was significantly higher in the HCC group compared with that in LC group in a subset of patients with high LS values (P<0.01). In conclusion, the combined detection of LS and serum CRP may complement the measurement of AFP in the diagnosis of HBV-related HCC, improve the identification of patients with AFP-negative HCC and help distinguish HCC from LC. PMID:27073669

  6. Clinical Implications of the Serum Apelin Level on Portal Hypertension and Prognosis of Liver Cirrhosis

    PubMed Central

    Lim, Yoo Li; Choi, Eunhee; Jang, Yoon Ok; Cho, Youn Zoo; Kang, Yong Seok; Baik, Soon Koo; Kwon, Sang Ok; Kim, Moon Young

    2016-01-01

    Background/Aims Levels of serum apelin (s-apelin), an endogenous ligand for angiotensin-like receptor 1, have been shown to be related to hepatic fibrosis and hemodynamic abnormalities in preclinical studies. We investigated the clinical implications of s-apelin as a noninvasive prognostic biomarker for chronic liver disease (CLD). Methods From January 2009 to December 2012, 215 CLD patients were enrolled and underwent clinical data collection, hepatic venous pressure gradient (HVPG) measurement, and liver biopsy. s-apelin was detected with a human total apelin enzyme-linked immunosorbent assay kit. All patients were prospectively observed during the median follow-up period of 23.0±12.9 months for decompensation and mortality. Results A total of 42 patients (19.5%) died during the follow-up period. s-apelin was significantly correlated with measurements of liver stiffness (R2=0.263, p<0.001) and collagen proportional area (R2=0.213, p<0.001) measured from liver biopsy tissue and HVPG (R2=0.356, p<0.001). In a multivariate analysis using a Cox regression hazard model, s-apelin was a weakly significant predictor of decompensation (hazard ratio [HR], 1.002; p<0.001) and mortality (HR, 1.003; p<0.001). Conclusions s-apelin showed a significant relationship with CLD severity. However, its significance as a noninvasive biomarker for disease severity and prognosis was weak. PMID:25963087

  7. [The significance of low levels of total proteins, albumins, globulins and complement factors in ascitic fluid and the development of spontaneous bacterial peritonitis in patients with liver cirrhosis].

    PubMed

    Ljubicić, N; Bilić, A; Babić, Z; Roić, D; Banić, M

    1992-01-01

    Spontaneous bacterial peritonitis is one of the most common complications of ascitic fluid in patients with liver cirrhosis. The aim of this study was to investigate the role of total protein, albumin, globulin and complement ascitic fluid concentrations in development of spontaneous bacterial peritonitis in patients with liver cirrhosis. In patients with liver cirrhosis and spontaneous bacterial peritonitis (n = 8) the ascitic fluid total protein, albumin and globulin concentrations were significantly lower than in patients with sterile ascites (n = 11) (p < 0.01). The ascitic fluid complement C3 and C4 concentrations were significantly lower in patients with spontaneous bacterial peritonitis than in patients with sterile ascites (9.1 +/- 3.1 mg/dL to 22.9 +/- 17.4 mg/dL, p < 0.01; 3.8 +/- 5.9 mg/dL to 8.2 +/- 5.9 mg/dL, p < 0.01, respectively). The ascites total protein, albumin, globulin and complement concentrations in cirrhotic patients with spontaneous bacterial peritonitis were significantly lower than in patients with sterile ascites demonstrating the importance of those factors in ascitic fluid defense against secondary bacterial infection. PMID:1343119

  8. Characteristics, Diagnosis and Prognosis of Acute-on-Chronic Liver Failure in Cirrhosis Associated to Hepatitis B.

    PubMed Central

    Li, Hai; Chen, Liu-Ying; Zhang, Nan-nan; Li, Shu-Ting; Zeng, Bo; Pavesi, Marco; Amorós, Àlex; Mookerjee, Rajeshwar P; Xia, Qian; Xue, Feng; Ma, Xiong; Hua, Jing; Sheng, Li; Qiu, De-kai; Xie, Qing; Foster, Graham R; Dusheiko, Geoffrey; Moreau, Richard; Gines, Pere; Arroyo, Vicente; Jalan, Rajiv

    2016-01-01

    The diagnostic and prognostic criteria of acute-on-chronic liver failure (ACLF) were developed in patients with no Hepatitis B virus (HBV) cirrhosis (CANONIC study). The aims of this study were to evaluate whether the diagnostic (CLIF-C organ failure score; CLIF-C OFs) criteria can be used to classify patients; and the prognostic score (CLIF-C ACLF score) could be used to provide prognostic information in HBV cirrhotic patients with ACLF. 890 HBV associated cirrhotic patients with acute decompensation (AD) were enrolled. Using the CLIF-C OFs, 33.7% (300 patients) were diagnosed as ACLF. ACLF was more common in the younger patients and in those with no previous history of decompensation. The most common organ failures were ‘hepatic’ and ‘coagulation’. As in the CANONIC study, 90-day mortality was extremely low in the non-ACLF patients compared with ACLF patients (4.6% vs 50%, p < 0.0001). ACLF grade and white cell count, were independent predictors of mortality. CLIF-C ACLFs accurately predicted short-term mortality, significantly better than the MELDs and a disease specific score generated for the HBV patients. Current study indicates that ACLF is a clinically and pathophysiology distinct even in HBV patients. Consequently, diagnostic criteria, prognostic scores and probably the management of ACLF should base on similar principles. PMID:27146801

  9. Long-Term Outcomes of Living-Donor Liver Transplantation for Primary Biliary Cirrhosis: A Japanese Multicenter Study.

    PubMed

    Egawa, H; Sakisaka, S; Teramukai, S; Sakabayashi, S; Yamamoto, M; Umeshita, K; Uemoto, S

    2016-04-01

    The factors that influence long-term outcomes after living-donor liver transplantation (LDLT) for primary biliary cirrhosis (PBC) are not well known. Compared with deceased-donor transplantation, LDLT has an increased likelihood of a related donor and a decreased number of human leukocyte antigen (HLA) mismatches. To clarify the effects of donor relatedness and HLA mismatch on the outcomes after LDLT, we retrospectively analyzed 444 Japanese patients. Donors were blood relatives for 332 patients, spouses for 105, and "other" for 7. The number of HLA A-B-DR mismatches was none to two in 141, three in 123, and four to six in 106 patients. The 15-year survival rate was 52.6%, and PBC recurred in 65 patients. Recipient aged 61 years or older, HLA mismatches of four or more (maximum of six), graft:recipient weight ratio less than 0.8, and husband donor were adverse indicators of patient survival. IgM 554 mg/dL or greater, donor-recipient sex mismatch, and initial immunosuppression with cyclosporine were significant risks for PBC recurrence, which did not affect patient survival. In subgroup analysis, conversion to cyclosporine from tacrolimus within 1 year diminished recurrence. Prospective studies are needed to determine the influence of pregnancy-associated sensitization and to establish an optimal immunosuppressive regimen in LDLT patients. PMID:26731039

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

    PubMed

    2014-09-01

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

  11. Characteristics, Diagnosis and Prognosis of Acute-on-Chronic Liver Failure in Cirrhosis Associated to Hepatitis B.

    PubMed

    Li, Hai; Chen, Liu-Ying; Zhang, Nan-Nan; Li, Shu-Ting; Zeng, Bo; Pavesi, Marco; Amorós, Àlex; Mookerjee, Rajeshwar P; Xia, Qian; Xue, Feng; Ma, Xiong; Hua, Jing; Sheng, Li; Qiu, De-Kai; Xie, Qing; Foster, Graham R; Dusheiko, Geoffrey; Moreau, Richard; Gines, Pere; Arroyo, Vicente; Jalan, Rajiv

    2016-01-01

    The diagnostic and prognostic criteria of acute-on-chronic liver failure (ACLF) were developed in patients with no Hepatitis B virus (HBV) cirrhosis (CANONIC study). The aims of this study were to evaluate whether the diagnostic (CLIF-C organ failure score; CLIF-C OFs) criteria can be used to classify patients; and the prognostic score (CLIF-C ACLF score) could be used to provide prognostic information in HBV cirrhotic patients with ACLF. 890 HBV associated cirrhotic patients with acute decompensation (AD) were enrolled. Using the CLIF-C OFs, 33.7% (300 patients) were diagnosed as ACLF. ACLF was more common in the younger patients and in those with no previous history of decompensation. The most common organ failures were 'hepatic' and 'coagulation'. As in the CANONIC study, 90-day mortality was extremely low in the non-ACLF patients compared with ACLF patients (4.6% vs 50%, p < 0.0001). ACLF grade and white cell count, were independent predictors of mortality. CLIF-C ACLFs accurately predicted short-term mortality, significantly better than the MELDs and a disease specific score generated for the HBV patients. Current study indicates that ACLF is a clinically and pathophysiology distinct even in HBV patients. Consequently, diagnostic criteria, prognostic scores and probably the management of ACLF should base on similar principles. PMID:27146801

  12. A novel glycobiomarker, Wisteria floribunda agglutinin macrophage colony-stimulating factor receptor, for predicting carcinogenesis of liver cirrhosis.

    PubMed

    Iio, Etsuko; Ocho, Makoto; Togayachi, Akira; Nojima, Masanori; Kuno, Atsushi; Ikehara, Yuzuru; Hasegawa, Izumi; Yatsuhashi, Hiroshi; Yamasaki, Kazumi; Shimada, Noritomo; Ide, Tatsuya; Shinkai, Noboru; Nojiri, Shunske; Fujiwara, Kei; Joh, Takashi; Mizokami, Masashi; Narimatsu, Hisashi; Tanaka, Yasuhito

    2016-03-15

    Recently, we identified a novel liver fibrosis glycobiomarker, Wisteria floribunda agglutinin (WFA)-reactive colony stimulating factor 1 receptor (WFA(+) -CSF1R), using a glycoproteomics-based strategy. The aim of this study was to assess the value of measuring WFA(+) -CSF1R levels for the prognosis of carcinogenesis and outcome in liver cirrhosis (LC) patients with hepatitis C virus (HCV). WFA(+) -CSF1R and Total-CSF1R levels were measured in serum samples from 214 consecutive HCV-infected patients to evaluate their impact on carcinogenesis and the survival of LC patients. Serum WFA(+) -CSF1R levels were significantly higher in LC patients than chronic hepatitis (CH) patients (p < 0.001). The AUC of WFA(+) -CSF1R for predicting overall survival, calculated by time-dependent ROC analysis, was 0.691 and the HR (per 1-SD increase) was 1.80 (95% CI, 1.23-2.62, p < 0.001). Furthermore, the survival rate of LC patients with high WFA(+) -CSF1R levels (≥ 310 ng/ml) was significantly worse than those with lower levels (p < 0.01). The AUC of WFA(+) /total-CSF1R percentage (WFA(+) -CSF1R%) for predicting the cumulative carcinogenesis rate was 0.760, with an HR of 1.66 (95% CI 1.26-2.20, p < 0.001). In fact, the carcinogenesis rate was significantly higher in LC patients with a high WFA(+) -CSF1R% (≥ 35%, p = 0.006). Assessing serum levels of WFA(+) -CSF1R has diagnostic value for predicting carcinogenesis and the survival of LC patients. PMID:26437001

  13. Serum Markers of Epithelial Mesenchymal Transition as Predictors of HCV-induced Liver Fibrosis, Cirrhosis and Hepatocellular Carcinoma

    PubMed Central

    Zoheiry, Mona M; Hasan, Shaimaa AA; El-Ahwany, Eman; Nagy, Faten M; Taleb, Hoda Abu; Nosseir, Mona; Magdy, Mona; Meshaal, Safa; EL-Talkawy, Mohamed Darwish; Raafat, Inas

    2015-01-01

    Introduction Hepatitis C virus (HCV) is a major cause of chronic liver disease in Egypt, leading to hepatic fibrosis, liver cirrhosis (LC), and hepatocellular carcinoma (HCC). Liver fibrosis is characterized by excessive deposition of extracellular matrix (ECM). Newly-recognized pathogenic mechanisms point to the epithelial-mesenchymal transition (EMT) of hepatocytes to matrix synthesizing (myo-) fibroblasts. Transforming growth factor-beta (TGF-β1), bone morphogenic protein (BMP)-7, and connective tissue growth factor (CTGF) are biomarkers reflecting the EMT process. YKL-40 is a glycoprotein member of ECM and plays a role in cancer cell proliferation. The purpose of this study was to determine the serum biomarkers of EMT and its impact on the fibrogenic process and tumorigenesis in HCV-genotype 4 patients. Methods In this case-control study that was conducted in 2013–2014, 97 HCV-infected patients were subjected to clinical examination, laboratory investigations, and liver biopsy. According to the histopathologic examination, they were classified to F0 (14 cases), F1 (17 cases), F2 (15 cases), F3 (18 cases), F4 (22 cases), and HCC (11 cases). Fifteen age- and gender-matched subjects were included as normal controls. Serum levels of TGF-β1, BMP-7, CTGF, YKL-40 were assessed, and the TGF-β1/BMP-7 ratios were calculated. The data were analyzed by plotting the receiver operating characteristic curve (ROC), Pearson product-moment correlation coefficient, and Spearman’s rank correlation coefficient (Spearman’s rho). Results Serum levels of TGF-β1, BMP-7, CTGF, and YKL-40 were significantly increased in all patient groups compared to controls (p < 0.001). LC exhibited the highest CTGF level and YKL-40 was highest in HCC. The TGF-β1/ BMP-7 ratios reflected the progression of EMT from CHC to LC, however, there was no significant difference between LC and HCC. TGF-β1/ BMP-7 ratio is considered to reflect positive correlation with CTGF in LC group (r = 0.629; p < 0.03) and YKL-40 in HCC group (r = 0.504; p < 0.04). Conclusion Increased TGF-β1/BMP-7 ratio and CTGF levels reflect the rate of EMT and provide information about fibrogenic activity. Also, this ratio, in association with YKL-40, can be used to predict malignant transformation in HCV-genotype 4 Egyptian patients. PMID:26816590

  14. Hepatic Venous Waveform, Splenoportal and Damping Index in Liver Cirrhosis: Correlation with Child Pugh’s Score and Oesophageal Varices

    PubMed Central

    Antil, Neha; Mittal, Mahesh Kumar; Malik, Amita; Gupta, Bhupender; Thukral, Brij Bhushan

    2016-01-01

    Introduction Clinical assessment of chronic liver disease is done by Modified Child Pugh’s and Model for end-stage liver disease scoring system. Measurement of hepatic venous pressure gradient (HVPG) and Upper GI Endoscopy are considered the gold standards for measurement of portal hypertension in cirrhotics. There is a need for non-invasive evaluation of portal hypertension. Ultrasonography with colour and spectral Doppler evaluation may be an effective, rapid and inexpensive alternative. Aim To evaluate hepatic venous waveform, damping index, splenoportal index in patients of cirrhosis on Colour Doppler ultrasound, also predict severity of portal hypertension and presence of oesophageal varices. Materials and Methods Thirty patients of chronic liver disease were included in the study. Ultrasound and colour Doppler was done to look hepatic venous waveform pattern, Damping Index (DI), and Splenoportal Index (SPI). Contrast-enhanced Computed Tomography scan (CT) was done if renal function tests were normal, else endoscopy when the renal function tests were deranged to look for oesophageal varices. Results Twenty two (73.3%) patients had monophasic waveform. Biphasic and triphasic waveforms were seen in 4 (13.3%) cases. Twenty two patients (73.3%) had monophasic waveforms and majority of them were in class C. This distribution of hepatic vein waveform was statistically significantly with the Child Pugh’s class (p<0.05). Twenty patients (66.7%) had value of Damping index more than >0.6 where majority of patients (18) belonged to class C and 2 in class B. There was a positive correlation between Child Pugh’s total score and Damping index (r=0.614; p<0.05). There was weak positive correlation between splenoportal index and Child Pugh’s score (r=0.269; p=0.15). Conclusion Change in triphasic to monophasic waveform and DI >0.6 suggests severe liver dysfunction and is associated with severe portal hypertension. Hepatic venous waveform pressure changes, DI and SPI have no value in predicting presence of oesophageal varices. PMID:27042553

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

    SciTech Connect

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

    1984-05-01

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

  16. Future therapy of portal hypertension in liver cirrhosis – a guess

    PubMed Central

    Trebicka, Jonel

    2014-01-01

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

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

    PubMed

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

    2015-04-01

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

  18. Association of early age at establishment of chronic hepatitis B infection with persistent viral replication, liver cirrhosis and hepatocellular carcinoma: a systematic review.

    PubMed

    Shimakawa, Yusuke; Yan, Hong-Jing; Tsuchiya, Naho; Bottomley, Christian; Hall, Andrew J

    2013-01-01

    Age at infection with hepatitis B virus (HBV) is a known risk factor for chronic HBV infection. However, in addition, there is some evidence that early age at infection further increases the risk of primary liver cancer beyond its association with increased risk of chronic infection. This systematic review of observational studies assesses the association between age at initiation of chronic HBV infection and liver cirrhosis, hepatocellular carcinoma, and their predictors including indicators of ongoing viral replication and hepatic damage. The review includes birth order and maternal HBV serology as proxies for age at infection. Electronic searches in two English-language (Medline and Embase, until Jan 2012) and two Chinese-language (CNKI and SinoMed, until Sep 2012) databases without language restriction and manual search through reference lists identified 7,077 papers, of which 19 studies of 21 outcomes (8 primary liver cancer, 1 liver cirrhosis, 10 viral replication and 2 liver inflammation) are included. One study directly examined the age at infection in a longitudinal cohort, 12 assessed maternal sero-status and 6 investigated birth order. The direction of associations in all studies was in accordance with our hypothesis that earlier age at infection is associated with worse outcomes in addition to its effect of increasing the probability of chronic HBV infection. This has implications for the control of hepatitis B. PMID:23894479

  19. Nonalcoholic fatty liver disease and hepatic cirrhosis: Comparison with viral hepatitis-associated steatosis.

    PubMed

    Haga, Yuki; Kanda, Tatsuo; Sasaki, Reina; Nakamura, Masato; Nakamoto, Shingo; Yokosuka, Osamu

    2015-12-14

    Nonalcoholic fatty liver disease (NAFLD) including nonalcoholic steatohepatitis (NASH) is globally increasing and has become a world-wide health problem. Chronic infection with hepatitis B virus or hepatitis C virus (HCV) is associated with hepatic steatosis. Viral hepatitis-associated hepatic steatosis is often caused by metabolic syndrome including obesity, type 2 diabetes mellitus and/or dyslipidemia. It has been reported that HCV genotype 3 exerts direct metabolic effects that lead to hepatic steatosis. In this review, the differences between NAFLD/NASH and viral hepatitis-associated steatosis are discussed. PMID:26675364

  20. Nonalcoholic fatty liver disease and hepatic cirrhosis: Comparison with viral hepatitis-associated steatosis

    PubMed Central

    Haga, Yuki; Kanda, Tatsuo; Sasaki, Reina; Nakamura, Masato; Nakamoto, Shingo; Yokosuka, Osamu

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) including nonalcoholic steatohepatitis (NASH) is globally increasing and has become a world-wide health problem. Chronic infection with hepatitis B virus or hepatitis C virus (HCV) is associated with hepatic steatosis. Viral hepatitis-associated hepatic steatosis is often caused by metabolic syndrome including obesity, type 2 diabetes mellitus and/or dyslipidemia. It has been reported that HCV genotype 3 exerts direct metabolic effects that lead to hepatic steatosis. In this review, the differences between NAFLD/NASH and viral hepatitis-associated steatosis are discussed. PMID:26675364

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

    PubMed Central

    Ye, Yu; Kerr, William C.

    2010-01-01

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

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

    PubMed Central

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

    2015-01-01

    Zheng is the basic theory and essence of traditional Chinese medicine (TCM) in diagnosing diseases. However, there are no biological evidences to support TCM Zheng differentiation. In this study we elucidated the biological alteration of cirrhosis with TCM “Liver-Kidney Yin Deficiency (YX)” or “Dampness-Heat Internal Smoldering (SR)” Zheng and the potential of urine metabonomics in TCM Zheng differentiation. Differential metabolites contributing to the intergroup variation between healthy controls and liver cirrhosis patients were investigated, respectively, and mainly participated in energy metabolism, gut microbiota metabolism, oxidative stress, and bile acid metabolism. Three metabolites, aconitate, citrate, and 2-pentendioate, altered significantly in YX Zheng only, representing the abnormal energy metabolism. Contrarily, hippurate and 4-pyridinecarboxylate altered significantly in SR Zheng only, representing the abnormalities of gut microbiota metabolism. Moreover, there were significant differences between two TCM Zhengs in three metabolites, glycoursodeoxycholate, cortolone-3-glucuronide, and L-aspartyl-4-phosphate, among all differential metabolites. Metabonomic profiling, as a powerful approach, provides support to the understanding of biological mechanisms of TCM Zheng stratification. The altered urinary metabolites constitute a panel of reliable biological evidence for TCM Zheng differentiation in patients with posthepatitis B cirrhosis and may be used for the potential biomarkers of TCM Zheng stratification. PMID:25667596

  3. A novel type of selective immunoglobulin m deficiency in a patient with autoimmune liver cirrhosis with recurrent hepatocellular carcinoma: a case report and review of the literature.

    PubMed

    Arahata, Masahisa; Tajiri, Kazuto; Nomoto, Kazuhiro; Tsuneyama, Koichi; Minami, Shinji; Shimizu, Yukihiro

    2013-01-01

    A 64-year-old female with advanced liver cirrhosis who had never experienced severe infections presented in 2004 with general malaise. At the time, her serum showed low levels of immunoglobulin (Ig) M (11 mg/dl) with high levels of both IgG (2,942 mg/dl) and IgA (808 mg/dl). Because serum levels of IgG and IgA in previous cases of selective IgM deficiency were normal, this case could have a novel immunological mechanism. By 2006, serum IgM was undetectable (<5 mg/dl). Liver biopsy showed liver cirrhosis from autoimmune hepatitis. She had no other autoimmune diseases or hematological malignancies. She developed hepatocellular carcinoma (HCC) several times and died of liver failure. Immunological analyses performed before the first diagnosis of HCC showed polyclonal γ-globulin elevation, normal chromosome and normal gene rearrangement of immunoglobulin heavy chain Cµ. Peripheral blood showed low count B cells with few surface IgM-positive B lymphocytes, but the percentages of T cell subsets were normal. Expression of activation-induced cytidine deaminase (AID), which plays a critical role in immunoglobin class switching, was found to be overexpressed in the HCC tissue and B cells in bone marrow. This phenomenon could account for the clinical and immunological features of this case. In conclusion, we propose a novel type of selective IgM deficiency in association with the overexpression of AID. PMID:23257944

  4. Cost-effectiveness of non-invasive methods for assessment and monitoring of liver fibrosis and cirrhosis in patients with chronic liver disease: systematic review and economic evaluation.

    PubMed Central

    Crossan, Catriona; Tsochatzis, Emmanuel A; Longworth, Louise; Gurusamy, Kurinchi; Davidson, Brian; Rodríguez-Perálvarez, Manuel; Mantzoukis, Konstantinos; O'Brien, Julia; Thalassinos, Evangelos; Papastergiou, Vassilios; Burroughs, Andrew

    2015-01-01

    BACKGROUND Liver biopsy is the reference standard for diagnosing the extent of fibrosis in chronic liver disease; however, it is invasive, with the potential for serious complications. Alternatives to biopsy include non-invasive liver tests (NILTs); however, the cost-effectiveness of these needs to be established. OBJECTIVE To assess the diagnostic accuracy and cost-effectiveness of NILTs in patients with chronic liver disease. DATA SOURCES We searched various databases from 1998 to April 2012, recent conference proceedings and reference lists. METHODS We included studies that assessed the diagnostic accuracy of NILTs using liver biopsy as the reference standard. Diagnostic studies were assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Meta-analysis was conducted using the bivariate random-effects model with correlation between sensitivity and specificity (whenever possible). Decision models were used to evaluate the cost-effectiveness of the NILTs. Expected costs were estimated using a NHS perspective and health outcomes were measured as quality-adjusted life-years (QALYs). Markov models were developed to estimate long-term costs and QALYs following testing, and antiviral treatment where indicated, for chronic hepatitis B (HBV) and chronic hepatitis C (HCV). NILTs were compared with each other, sequential testing strategies, biopsy and strategies including no testing. For alcoholic liver disease (ALD), we assessed the cost-effectiveness of NILTs in the context of potentially increasing abstinence from alcohol. Owing to a lack of data and treatments specifically for fibrosis in patients with non-alcoholic fatty liver disease (NAFLD), the analysis was limited to an incremental cost per correct diagnosis. An analysis of NILTs to identify patients with cirrhosis for increased monitoring was also conducted. RESULTS Given a cost-effectiveness threshold of £20,000 per QALY, treating everyone with HCV without prior testing was cost-effective with an incremental cost-effectiveness ratio (ICER) of £9204. This was robust in most sensitivity analyses but sensitive to the extent of treatment benefit for patients with mild fibrosis. For HBV [hepatitis B e antigen (HBeAg)-negative)] this strategy had an ICER of £28,137, which was cost-effective only if the upper bound of the standard UK cost-effectiveness threshold range (£30,000) is acceptable. For HBeAg-positive disease, two NILTs applied sequentially (hyaluronic acid and magnetic resonance elastography) were cost-effective at a £20,000 threshold (ICER: £19,612); however, the results were highly uncertain, with several test strategies having similar expected outcomes and costs. For patients with ALD, liver biopsy was the cost-effective strategy, with an ICER of £822. LIMITATIONS A substantial number of tests had only one study from which diagnostic accuracy was derived; therefore, there is a high risk of bias. Most NILTs did not have validated cut-offs for diagnosis of specific fibrosis stages. The findings of the ALD model were dependent on assuptions about abstinence rates assumptions and the modelling approach for NAFLD was hindered by the lack of evidence on clinically effective treatments. CONCLUSIONS Treating everyone without NILTs is cost-effective for patients with HCV, but only for HBeAg-negative if the higher cost-effectiveness threshold is appropriate. For HBeAg-positive, two NILTs applied sequentially were cost-effective but highly uncertain. Further evidence for treatment effectiveness is required for ALD and NAFLD. STUDY REGISTRATION This study is registered as PROSPERO CRD42011001561. FUNDING The National Institute for Health Research Health Technology Assessment programme. PMID:25633908

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  7. The diagnostic value of neutrophil gelatinase-associated lipocalin and hepcidin in bacteria translocation of liver cirrhosis

    PubMed Central

    Zhang, Jiangguo; Gong, Fengyun; Li, Ling; Zhao, Manzhi; Wu, Zhuhua; Song, Jianxin

    2015-01-01

    Objective: Bacterial translocation (BT) or bacterial DNA (bactDNA) translocation is a critical pathogenesis mechanism of spontaneous bacterial peritonitis. Studies of BT or bactDNA translocation are limited in humans. Neutrophil gelatinase associated lipocalin (NGAL) can efficiently distinguish bacterial and nonbacterial ascites in ascitic patients. Hepcidin is a useful marker of bacterial infection in the late-onset sepsis. However, the relationship between NGAL, hepcidin and BT was still unclear. In present study, the levels of NGAL, hepcidin and their relationship with BT or bactDNA translocation were investigated. Material and methods: Weekly doses of carbon tetrachloride (CCl4) were given to induce liver cirrhosis in Sprague-Dawley rats. Trypticase (blood) soy agars were used to culture bacteria. BactDNA was sequenced by ABIPRISM 310 automated sequencer. The levels of NGAL and hepcidin were assessed by ELISA. Receiver operating characteristic (ROC) curve was used to determine the cut-off values and compare the diagnostic performance of NGAL and hepcidin. Results: 56 cirrhotic and 10 normal rats were included in this study. The levels of both two biomarkers were significantly higher in BT or bactDNA translocation group compared to non-translocation group. The area under ROC curve for the diagnosis of BT was 0.910 for serum NGAL, 0.858 for serum hepcidin and 0.940 for their combination, whereas that for the diagnosis of bactDNA translocation was 0.906 for NGAL, 0.779 for hepcidin and 0.950 for their combination, respectively. The combination of NGAL and hepcidin improved the ability to detect BT or bactDNA presence in MLNs and ascites. Conclusion: BT and the presence of bactDNA in MLNs were observed in a rat cirrhotic model. Serum NGAL and hepcidin can serve as sensitive and specific tests for diagnosis of BT or bactDNA translocation. NGAL in combination with hepcidin can improve the accuracy of diagnosis. PMID:26629169

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

    PubMed Central

    2012-01-01

    Background The roles of circulating endothelial progenitor cell (EPC) and mononuclear cell apoptosis (MCA) in liver cirrhosis (LC) patients are unknown. Moreover, vascular endothelial growth factor (VEGF) and stromal cell-derived factor (SDF)-1α are powerful endogenous substances enhancing EPC migration into circulation. We assessed the level and function of EPCs [CD31/CD34 (E1), KDR/CD34 (E2), CXCR4/CD34 (E3)], levels of MCA, VEGF and SDF-1α in circulation of LC patients. Methods Blood sample was prospectively collected once for assessing EPC level and function, MCA, and plasma levels of VEGF and SDF-1α using flow cytometry and enzyme-linked immunosorbent assay (ELISA), respectively, in 78 LC patients and 25 age- and gender-matched healthy controls. Results Number of EPCs (E1, E2, E3) was lower (all p < 0.0001), whereas SDF-1α level and MCA were higher (p < 0.001) in study patients compared with healthy controls. Number of EPCs (E2, E3) was higher but MCA was lower (all p < 0.05) in Child's class A compared with Child's class B and C patients, although no difference in VEGF and SDF-1α levels were noted among these patients. Chronic hepatitis B and esophageal varices bleeding were independently, whereas chronic hepatitis C, elevated aspartate aminotransferase (AST), and decompensated LC were inversely and independently correlated with circulating EPC level (all p < 0.03). Additionally, angiogenesis and transwell migratory ability of EPCs were reduced in LC patients than in controls (all p < 0.001). Conclusion The results of this study demonstrated that level, angiogenic capacity, and function of circulating EPCs were significantly reduced, whereas plasma levels of SDF-1α and circulating MCA were substantially enhanced in cirrhotic patients. PMID:22809449

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

    SciTech Connect

    Hamdy, Nadia; El-Demerdash, Ebtehal

    2012-06-15

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

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

    PubMed

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

    2015-01-01

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

  11. Combination of branched-chain amino acid and angiotensin-converting enzyme inhibitor improves liver fibrosis progression in patients with cirrhosis.

    PubMed

    Yoshiji, Hitoshi; Noguchi, Ryuichi; Ikenaka, Yasuhide; Kaji, Kosuke; Aihara, Yosuke; Douhara, Akitoshi; Yamao, Junichi; Toyohara, Masahisa; Mitoro, Akira; Sawai, Masayoshi; Yoshida, Motoyuki; Morioka, Chie; Fujimoto, Masao; Uemura, Masahito; Fukui, Hiroshi

    2012-02-01

    An effective therapeutic strategy for suppressing liver fibrosis should improve the overall prognosis of patients with chronic liver diseases. Although enormous efforts are ongoing to develop anti-fibrotic agents, no drugs have yet been approved as anti-fibrotic agents for humans. Insulin resistance (IR) is reportedly involved in the progression of liver fibrosis. The aim of the present study was to evaluate the effect of combination treatment with a clinically used branched-chain amino acid (BCAA) and an angiotensin-converting enzyme inhibitor (ACE-I) on several fibrotic indices in patients with liver cirrhosis under the condition of IR. BCAA granules (Livact; 12 g/day) and/or ACE-I (perindopril; 4 mg/day) were administered, and several indices were analyzed. A 48-month follow-up revealed that the combination treatment with BCAA and ACE-I markedly improved the progression of serum fibrosis markers, whereas single treatment with either BCAA or ACE-I did not exert these inhibitory effects. The plasma level of transforming growth factor-? was significantly attenuated almost in parallel with the suppression of serum fibrosis markers. Furthermore, the combined treatment with BCAA and ACE-I improved the serum albumin level and IR, which was evaluated using the homeostasis model assessment method for IR. Taken together, since both BCAA and ACE-I are widely used with safety in clinical practice, these results indicate that this combination therapy may represent a potential new future strategy against liver fibrosis development in patients with liver cirrhosis under the condition of IR. PMID:22089860

  12. Effect of cimetidine on the hepatic extraction of indocyanine green, the portal pressure and the systemic circulation in patients with cirrhosis of the liver.

    PubMed

    Herz, R; Rössle, M; Bonzel, T; Keller, E; Gerok, W

    1984-08-16

    The effect of cimetidine on hepatic and systemic haemodynamic parameters was studied in seven patients with portal hypertension due to alcohol-induced cirrhosis of the liver and in one patient with peliosis hepatis following oral contraceptive steroids. The intravenous administration of cimetidine (350 mg as bolus, followed by 2 mg/min over 60 min) reduced the hepatic extraction of continuously infused indocyanine green (ICG) by 27%; this was statistically significant (P less than 0.01). Since the ICG clearance, calculated independently of hepatic perfusion, was lowered by 19%, this effect seems to be mainly due to a reduced capacity of the liver to remove the dye from the blood, rather than due to changes in perfusion. Cimetidine did not influence the elevated portal pressure in the patients with cirrhosis, or the normal pressure in the patient with peliosis hepatis. No significant effect was observed on heart rate, mean arterial pressure, pulmonary artery pressure, pulmonary capillary pressure and cardiac output. These studies indicate that the reduction of the hepatic ICG extraction following cimetidine is more the result of an inhibited capacity of the liver to remove the dye than of changes in the hepatic perfusion or in the systemic circulation. PMID:6482311

  13. Hepatosplanchnic circulation in cirrhosis and sepsis

    PubMed Central

    Prin, Meghan; Bakker, Jan; Wagener, Gebhard

    2015-01-01

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

  14. Laparoscopic management of massive spontaneous external haemorrhage from the umbilical varix due to recanalisation of the paraumbilical vein in a patient with 'Child's Class A' liver cirrhosis.

    PubMed

    Zachariah, Sanoop K; Krishnankutty, Sreejith L; Raja, Nirmalan

    2012-04-01

    Spontaneous external haemorrhage from the umbilical varix is an extremely rare complication of portal hypertension. Bleeding is usually into the peritoneal cavity and the treatment involves urgent laparotomy and ligation of the bleeding varices. We describe a cirrhotic 38-year-old man who presented with spontaneous external haemorrhage from the umbilical varix which was successfully managed laparoscopically by in-situ distal clipping and proximal transcutaneous ligation of the recanalised paraumbilical veins. We therefore feel that laparoscopy can be safely and effectively employed to control external haemorrhage from the umbilical varix associated with liver cirrhosis. This novel technique can help avoid a laparotomy and also help preserve the umbilicus. PMID:22623827

  15. Treatment of HBV-related cirrhosis.

    PubMed

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

    2009-06-01

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

  16. Primary Biliary Cirrhosis

    MedlinePlus

    ... of liver cancer every 6 to 12 months. Health care providers use blood tests, ultrasound, or both to check for signs of ... make the diagnosis of primary biliary cirrhosis. A health care provider uses the test selectively when he or she is concerned that ...

  17. Laparoscopic liver resection for hepatitis B and C virus-related hepatocellular carcinoma in patients with Child B or C cirrhosis

    PubMed Central

    Brytska, Nataliya; Shehta, Ahmed; Yoon, Yoo-Seok; Cho, Jai Young; Choi, YoungRok

    2015-01-01

    Background The aim of this study was to evaluate the clinical and oncological outcomes after laparoscopic liver resection (LLR) in patients with hepatitis B and C virus-related hepatocellular carcinoma (HCC) with Child B or C cirrhosis. Methods Between January 2004 and December 2013, LLR was performed in 232 patients with HCC. Of these, 141 patients also had pathologically proven cirrhosis. Sixteen patients with hepatitis B and C virus-related HCC with Child B or C cirrhosis were included in the study. Thirteen (81.3%) patients had Child B disease and three (18.8%) patients had Child C disease. Results The median operation time was 215 min, the median estimated blood loss was 350 mL, and the median hospital stay was eight days. Three patients (18.8%) experienced complications after surgery. There was no postoperative mortality or reoperation. The mean follow-up period was 51.6 months. HCC recurred in eight (50%) patients: seven intrahepatic recurrences and one extrahepatic recurrence. The treatments for recurrence were laparoscopic reoperation in one (6.3%) patient, trans-catheter arterial chemo-embolization (TACE) in one (6.3%) patient, radiofrequency ablation (RFA) in one (6.3%) patient, and combined TACE and RFA in four (25%) patients. The five-year postoperative overall survival (OS) and disease-free survival (DFS) were 84.4% and 41.7%, respectively. Conclusions This study demonstrates that LLR can be safely used in patients with hepatitis B and C virus-related HCC and Child B or C cirrhosis, with acceptable survival outcomes. PMID:26734621

  18. Hepatoprotective efficacy of Sharbat-e-Deenar against carbon tetrachloride-induced liver damage.

    TOXLINE Toxicology Bibliographic Information

    Shakya AK; Saxena M; Sharma N; Shrivastava S; Shukla S

    2012-01-01

    This study was undertaken to evaluate the antioxidant and hepatoprotective efficacy of Sharbat-e-Deenar (SD) against carbon tetrachloride (CCl(4))-induced hepatic damage in a rat model. The antioxidant activity of SD was estimated by DPPH assay, H(2)O(2) assay, and total phenolic contents. SD therapy at doses of 1, 2, and 4 mL/kg, orally, was administered after CCl(4) intoxication (1.5 mL/kg, intraperitoneally for 48 hours) in experimental animals. Hexobarbitone sleep time and bromosulfophthalein retention time also were determined against CCl(4)-induced liver damage. Exposure to CCl(4) in experimental animals showed biochemical and histopathological deterioration in the liver. Treatment with SD showed a marked protection on biochemical parameters, that is, alanine transaminase, aspartate transaminase, albumin, and urea. SD therapy exhibited a protective effect by restoring the level of lipid peroxidation-reduced glutathione, adenosine triphosphate, and glucose-6-phosphatase (G-6-Pase). Treatment with SD significantly recovered the level of hexobarbitone sleep time and bromosulfophthalein retention time. DPPH and H(2)O(2) assays showed antioxidant properties in a dose-dependent manner. Histopathological observations of liver sections showed recovery in liver architecture after SD treatment. These results indicate that SD exerts a protective effect on CCl(4)-induced hepatotoxicity, which may be due to its antioxidant properties.

  19. Treat chronic hepatitis C virus infection in decompensated cirrhosis - pre- or post-liver transplantation? the ironic conundrum in the era of effective and well-tolerated therapy.

    PubMed

    Bunchorntavakul, C; Reddy, K Rajender

    2016-06-01

    The management of hepatitis C virus (HCV) infection in patients with decompensated cirrhosis has evolved dramatically over the past few years mainly due to the availability of all-oral antiviral regimens. The currently approved all-oral direct-acting antivirals (DAA) containing sofosbuvir, ledipasvir, daclatasvir and ribavirin, in various combinations, have shown to be safe and effective in patients with decompensated cirrhosis with sustained virological response (SVR) rates nearly comparable to those with well-compensated liver disease. Unique issues yet remain such as the challenges with renal insufficiency, tolerability of ribavirin and risk of further hepatic decompensation with a protease inhibitor-based regimen. While most patients who achieve SVR have demonstrated improvement in hepatic synthetic function over the short course of follow, the long-term beneficial effects are unknown. Further, the baseline predictors of improvement in hepatic function have not been well delineated and thus have left us in a quandary as to what we might expect with successful therapy and thus we are at a loss to well educate our patients. The major concern, in potential liver transplant candidates, is of unintended 'harm' by achieving SVR but without improvement in hepatic function to an extent where the patients might function well. As HCV therapies are as effective in liver transplant recipients, there is a growing sentiment in some of the transplant quarters that those with decompensated liver disease and awaiting liver transplant be treated for HCV after liver transplant. This strategy would thus eliminate any concern of leaving a patient in 'no person's' land by treating HCV successfully pretransplant but not to the point of functional normalcy, while also would maintain the risk of HCC. Yet a contrarian view would be that not all patients have access to liver transplantation (LT), cannot bear the cost, have comorbidities or contraindications to LT. While the debate continues, it is essential that we develop robust predictors of improvement in liver function so that we can carefully select our patients for therapy in the context of liver transplantation. PMID:27018088

  20. A Study of the Relationship between Serum Bile Acids and Propranolol Pharmacokinetics and Pharmacodynamics in Patients with Liver Cirrhosis and in Healthy Controls

    PubMed Central

    Buylaert, Mirabel; Tschöpl, Martin; Beuers, Ulrich; Drewe, Jürgen; Krähenbühl, Stephan

    2014-01-01

    The main objectives of the study were to determine the exposure and bioavailability of oral propranolol and to investigate their associations with serum bile acid concentration in patients with liver cirrhosis and in healthy controls. A further objective was to study the pharmacodynamics of propranolol. An open-label crossover study was performed to determine the pharmacokinetics and pharmacodynamics of propranolol after oral (40 mg) and intravenous (1 mg) administration as well as the concentration of total and individual fasting serum bile acids in 15 patients with liver cirrhosis and 5 healthy controls. After intravenous propranolol, patients showed a 1.8-fold increase in the area under the plasma concentration-time curve (AUC0–∞), a 1.8-fold increase in volume of distribution and a 3-fold increase in the elimination half-life (mean ± SEM: 641±100 vs. 205±43 minutes) compared to controls. After oral application, AUC0–∞ and elimination half-life of propranolol were increased 6- and 4-fold, respectively, and bioavailability 3-fold (83±8 vs. 27±9.2%). Maximal effects on blood pressure and heart rate occurred during the first 4 and first 2 hours, respectively, after intravenous and oral application in both patients and controls. Total serum bile acid concentrations were higher in patients than controls (42±11 vs. 2.7±0.3 µmol/L) and were linearly correlated with the serum chenodeoxycholic acid concentration. There was a linear correlation between the SBA concentration and propranolol oral AUC0–∞ in subjects not receiving interacting drugs (r2 = 0.73, n = 18). The bioavailability of and exposure to oral propranolol are increased in patients with cirrhosis. Fasting serum bile acid concentration may be helpful in predicting the exposure to oral propranolol in these patients. PMID:24906133

  1. l-Theanine prevents carbon tetrachloride-induced liver fibrosis via inhibition of nuclear factor κB and down-regulation of transforming growth factor β and connective tissue growth factor.

    PubMed

    Pérez-Vargas, J E; Zarco, N; Vergara, P; Shibayama, M; Segovia, J; Tsutsumi, V; Muriel, P

    2016-02-01

    Here we evaluated the ability of l-theanine in preventing experimental hepatic cirrhosis and investigated the roles of nuclear factor-κB (NF-κB) activation as well as transforming growth factor β (TGF-β) and connective tissue growth factor (CTGF) regulation. Experimental hepatic cirrhosis was established by the administration of carbon tetrachloride (CCl4) to rats (0.4 g/kg, intraperitoneally, three times per week, for 8 weeks), and at the same time, adding l-theanine (8.0 mg/kg) to the drinking water. Rats had ad libitum access to water and food throughout the treatment period. CCl4 treatment promoted NF-κB activation and increased the expression of both TGF-β and CTGF. CCl4 increased the serum activities of alanine aminotransferase and γ-glutamyl transpeptidase and the degree of lipid peroxidation, and it also induced a decrease in the glutathione and glutathione disulfide ratio. l-Theanine prevented increased expression of NF-κB and down-regulated the pro-inflammatory (interleukin (IL)-1β and IL-6) and profibrotic (TGF-β and CTGF) cytokines. Furthermore, the levels of messenger RNA encoding these proteins decreased in agreement with the expression levels. l-Theanine promoted the expression of the anti-inflammatory cytokine IL-10 and the fibrolytic enzyme metalloproteinase-13. Liver hydroxyproline contents and histopathological analysis demonstrated the anti-fibrotic effect of l-theanine. In conclusion, l-theanine prevents CCl4-induced experimental hepatic cirrhosis in rats by blocking the main pro-inflammatory and pro-fibrogenic signals. PMID:25852135

  2. Liver Cirrhosis and Diabetes Mellitus Are Risk Factors for Staphylococcus aureus Infection in Patients with Healthcare-Associated or Hospital-Acquired Pneumonia.

    PubMed

    Wu, Huang-Pin; Chu, Chien-Ming; Lin, Chun-Yao; Yu, Chung-Chieh; Hua, Chung-Ching; Yu, Teng-Jen; Liu, Yu-Chih

    2016-01-01

    Background. The risk factors for Staphylococcus aureus (S. aureus) pneumonia are not fully identified. The aim of this work was to find out the clinical characteristics associated with S. aureus infection in patients with healthcare-associated pneumonia (HCAP) and hospital-acquired pneumonia (HAP), which may be applicable for more appropriate selection of empiric antibiotic therapy. Methods. From July 2007 to June 2010, patients who were admitted to the intensive care unit with severe HCAP/HAP and severe sepsis were enrolled in this study. Lower respiratory tract sample was semiquantitatively cultured. Initial broad-spectrum antibiotics were chosen by Taiwan or American guidelines for pneumonia management. Standard bundle therapies were provided to all patients according to the guidelines of the Surviving Sepsis Campaign. Results. The most frequently isolated pathogens were Pseudomonas aeruginosa, S. aureus, Acinetobacter baumannii, Klebsiella pneumoniae, and Escherichia coli. Patients with positive isolation of S. aureus in culture had significantly higher history of liver cirrhosis and diabetes mellitus, with odds ratios of 3.098 and 1.899, respectively. The S. aureus pneumonia was not correlated with history of chronic obstructive pulmonary disease, hypertension, and hemodialysis. Conclusion. Liver cirrhosis and diabetes mellitus may be risk factors for S. aureus infection in patients with severe HCAP or HAP. PMID:26998356

  3. A case of liver cirrhosis due to hepatits C virus infection complicating giant anorectal varices treated with balloon-occluded retrograde transvenous obliteration.

    PubMed

    Watanabe, Kazuhiro; Imai, Yukinori; Takaya, Hiroaki; Nakazawa, Manabu; Chikayama, Taku; Ando, Satsuki; Mizuno, Yoshie; Sugawara, Kayoko; Nakamura, Yuuka; Saitoh, Eiko; Hamaoka, Kazuhiro; Motoya, Daisuke; Fujimori, Kenji; Inao, Mie; Nakayama, Nobuaki; Nagoshi, Sumiko; Mochida, Satoshi

    2011-02-01

    A 73-year-old man with liver cirrhosis due to hepatitis C virus infection was admitted to our hospital because of massive bleeding from external varices. Colonoscopic examination revealed that giant anorectal varices had developed between the anus and rectal ampulla, and had ruptured at the perianal site. On three-dimensional computed tomography imaging, the feeding and drainage vessels of the varices were identified as the inferior mesenteric vein and right inferior hemorrhoidal vein, respectively. Endoscopic therapies were not employed for the bleeding varices, because the blood flow volume of the feeding vessel was extremely large. Balloon-occluded retrograde transvenous obliteration (B-RTO) was therefore carried out through the drainage vessels. The variceal blood flow disappeared after B-RTO therapy, and the varices decreased in size with thrombus formation verified by colonoscopy. Bleeding from the external varices also ceased. B-RTO therapy may be an effective approach for giant anorectal varices presenting as a complication in liver cirrhosis patients in whom the main drainage vessels can be determined. PMID:26190616

  4. Liver Cirrhosis and Diabetes Mellitus Are Risk Factors for Staphylococcus aureus Infection in Patients with Healthcare-Associated or Hospital-Acquired Pneumonia

    PubMed Central

    Wu, Huang-Pin; Chu, Chien-Ming; Lin, Chun-Yao; Yu, Chung-Chieh; Hua, Chung-Ching; Yu, Teng-Jen; Liu, Yu-Chih

    2016-01-01

    Background. The risk factors for Staphylococcus aureus (S. aureus) pneumonia are not fully identified. The aim of this work was to find out the clinical characteristics associated with S. aureus infection in patients with healthcare-associated pneumonia (HCAP) and hospital-acquired pneumonia (HAP), which may be applicable for more appropriate selection of empiric antibiotic therapy. Methods. From July 2007 to June 2010, patients who were admitted to the intensive care unit with severe HCAP/HAP and severe sepsis were enrolled in this study. Lower respiratory tract sample was semiquantitatively cultured. Initial broad-spectrum antibiotics were chosen by Taiwan or American guidelines for pneumonia management. Standard bundle therapies were provided to all patients according to the guidelines of the Surviving Sepsis Campaign. Results. The most frequently isolated pathogens were Pseudomonas aeruginosa, S. aureus, Acinetobacter baumannii, Klebsiella pneumoniae, and Escherichia coli. Patients with positive isolation of S. aureus in culture had significantly higher history of liver cirrhosis and diabetes mellitus, with odds ratios of 3.098 and 1.899, respectively. The S. aureus pneumonia was not correlated with history of chronic obstructive pulmonary disease, hypertension, and hemodialysis. Conclusion. Liver cirrhosis and diabetes mellitus may be risk factors for S. aureus infection in patients with severe HCAP or HAP. PMID:26998356

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

    SciTech Connect

    Vasuri, Francesco; Capizzi, Elisa; Bellavista, Elena; Interdepartmental Center for Studies on Biophysics, Bioinformatics and Biocomplexity 'L. Galvani' , Bologna University ; Mishto, Michele; Interdepartmental Center for Studies on Biophysics, Bioinformatics and Biocomplexity 'L. Galvani' , Bologna University; Institute of Biochemistry, Medical Faculty Charite, Berlin ; Santoro, Aurelia; Interdepartmental Center for Studies on Biophysics, Bioinformatics and Biocomplexity 'L. Galvani' , Bologna University ; Fiorentino, Michelangelo; Capri, Miriam; Interdepartmental Center for Studies on Biophysics, Bioinformatics and Biocomplexity 'L. Galvani' , Bologna University ; Cescon, Matteo; Grazi, Gian Luca; Grigioni, Walter Franco; D'Errico-Grigioni, Antonia; Franceschi, Claudio; Interdepartmental Center for Studies on Biophysics, Bioinformatics and Biocomplexity 'L. Galvani' , Bologna University

    2010-06-25

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-12-01

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

  8. [The complex management of cirrhosis patients].

    PubMed

    Silvain, Christine

    2015-01-01

    All chronic liver diseases, whatever their causes, can lead to cirrhosis, when they evolve untreated for more than 10 to 20 years. The diagnosis of cirrhosis is based on the histology obtained from a liver biopsy, or on composite scores or elasticity. While these indirect tests are approved they are only reimbursed for viral hepatitis C associated or not with HIV. PMID:26144508

  9. Human albumin solution for patients with cirrhosis and acute on chronic liver failure: Beyond simple volume expansion.

    PubMed

    Valerio, Christopher; Theocharidou, Eleni; Davenport, Andrew; Agarwal, Banwari

    2016-03-01

    To provide an overview of the properties of human serum albumin (HSA), and to review the evidence for the use of human albumin solution (HAS) in critical illness, sepsis and cirrhosis. A MEDLINE search was performed using the terms "human albumin", "critical illness", "sepsis" and "cirrhosis". The references of retrieved articles were reviewed manually. Studies published between 1980 and 2014 were selected based on quality criteria. Data extraction was performed by all authors. HSA is the main plasma protein contributing greatly to its oncotic pressure. HSA demonstrates important binding properties for endogenous and exogenous toxins, drugs and drug metabolites that account for its anti-oxidant and anti-inflammatory properties. In disease states, hypoalbuminaemia is secondary to decreased HSA production, increased loss or transcapillary leakage into the interstitial space. HSA function can be also altered in disease with reduced albumin binding capacity and increased production of modified isoforms. HAS has been used as volume expander in critical illness, but received criticism due to cost and concerns regarding safety. More recent studies confirmed the safety of HAS, but failed to show any survival benefit compared to the cheaper crystalloid fluids, therefore limiting its use. On the contrary, in cirrhosis there is robust data to support the efficacy of HAS for the prevention of circulatory dysfunction post-large volume paracentesis and in the context of spontaneous bacterial peritonitis, and for the treatment of hepato-renal syndrome and hypervolaemic hyponatraemia. It is likely that not only the oncotic properties of HAS are beneficial in cirrhosis, but also its functional properties, as HAS replaces the dysfunctional HSA. The role of HAS as the resuscitation fluid of choice in critically ill patients with cirrhosis, beyond the established indications for HAS use, should be addressed in future studies. PMID:26981172

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

    PubMed Central

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

    2013-01-01

    The aim of the present work was to test the potential of Proton Transfer Reaction Time-of-Flight Mass Spectrometry (PTR-ToF-MS) in the diagnosis of liver cirrhosis and the assessment of disease severity by direct analysis of exhaled breath. Twenty-six volunteers have been enrolled in this study: 12 patients (M/F 8/4, mean age 70.5 years, min-max 42–80 years) with liver cirrhosis of different etiologies and at different severity of disease and