Science.gov

Sample records for ccl4-induced liver cirrhosis

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

    PubMed

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

    2010-04-01

    Rosmarinus officinalis (Lamiaceae) possesses antioxidant activity and hepatoprotective effects, and so may provide a possible therapeutic alternative for chronic liver disease. The effect produced by a methanolic extract of Rosmarinus officinalis on CCl(4)-induced liver cirrhosis in rats was investigated using both prevention and reversion models. Over the course of the development of cirrhosis, the increased enzymatic activities of gamma-glutamyl transpeptidase and alanine aminotransferase, and the rise in bilirubin levels caused by CCl(4) administration, were prevented by Rosmarinus officinalis co-administration. When the cirrhosis by oxidative stress was evaluated as an increase on liver lipoperoxidation, total lipid peroxides, nitric oxide in serum, and loss of erythrocyte plasma membrane stability, R. officinalis was shown to prevent such alterations. On cirrhotic animals treated with CCl(4), histological studies showed massive necrosis, periportal inflammation and fibrosis which were modified by R. officinalis. These benefits on experimental cirrhosis suggest a potential therapeutic use for R. officinalis as an alternative for liver cirrhosis. PMID:19827016

  2. Estrogen reduces CCL4- induced liver fibrosis in rats

    PubMed Central

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

    2002-01-01

    AIM: Chronic liver diseases, such as fibrosis or cirrhosis, are more common in men than in women. This gender difference may be related to the effects of sex hormones on the liver. The aim of the present work was to investigate the effects of estrogen on CCL4-induced fibrosis of the liver in rats. METHODS: Liver fibrosis was induced in male, female and ovariectomized rats by CCL4 administration. All the groups were treated with estradiol (1 mg/kg) twice weekly. And tamoxifen was given to male fibrosis model. At the end of 8 wk, all the rats were killed to study serum indicators and the livers. RESULTS: Estradiol treatment reduced aspartate aminotransferase (AST), alanine aminotransferase (ALT), hyaluronic acid (HA) and type IV collagen (CIV) in sera, suppressed hepatic collagen content, decreased the areas of hepatic stellate cells (HSC) positive for ?-smooth muscle actin (?-SMA), and lowered the synthesis of hepatic type I collagen significantly in both sexes and ovariectomy fibrotic rats induced by CCL4 administration. Whereas, tamoxifen had the opposite effect. The fibrotic response of the female liver to CCL4 treatment was significantly weaker than that of male liver. CONCLUSION: Estradiol reduces CCL4-induced hepatic fibrosis in rats. The antifibrogenic role of estrogen in the liver may be one reason for the sex associated differences in the progression from hepatic fibrosis to cirrhosis. PMID:12378635

  3. 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–?-smooth muscle actin (?-SMA), transforming growth factor-beta1 (TGF-?1), connective tissue growth factor (CTGF), and the tissue inhibitor of metalloproteinase I (TIMP1) were also markedly attenuated. Conversely, liver lysates from ADP355 treated mice increased phosphorylation of both endothelial nitric oxide synthase (eNOS) and AMPK while AKT phosphorylation was diminished. These findings suggest ADP355 is a potent anti-fibrotic agent that can be an effective intervention against liver fibrosis. PMID:25310107

  4. 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-?-smooth muscle actin (?-SMA), transforming growth factor-beta1 (TGF-?1), connective tissue growth factor (CTGF), and the tissue inhibitor of metalloproteinase I (TIMP1) were also markedly attenuated. Conversely, liver lysates from ADP355 treated mice increased phosphorylation of both endothelial nitric oxide synthase (eNOS) and AMPK while AKT phosphorylation was diminished. These findings suggest ADP355 is a potent anti-fibrotic agent that can be an effective intervention against liver fibrosis. PMID:25310107

  5. 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-?, TGF-?1, 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

  6. Reactive oxygen species in the progression of CCl4-induced liver injury.

    PubMed

    Sipes, I G; el Sisi, A E; Sim, W W; Mobley, S A; Earnest, D L

    1991-01-01

    Pretreatment of rats with large doses of vitamin A (retinol) dramatically increased the hepatotoxicity of carbon tetrachloride (CCl4). Experiments were performed to elucidate the mechanism of this potentiation. Hypervitaminosis A was produced by oral administration of retinol, 250,000 IU/kg for seven days. CCl4 was then administered at a dose of 0.15 ml/kg, ip. This large dose of vitamin A did not enhance the biotransformation of CCl4, but did produce a 4-fold increase in CCl4-induced lipid peroxidation, as assessed by ethane exhalation. Because vitamin A has been shown to activate macrophages, it was hypothesized that this increased lipid peroxidation and liver injury resulted from the release of reactive oxygen species from activated Kupffer cells. By using a chemiluminescence assay, an enhanced release of free radicals was detected in Kupffer cells isolated from vitamin A pretreated rats. In addition, Kupffer cells from vitamin A pretreated rats displayed enhanced phagocytic activity in vitro, towards sheep red blood cells. In vivo, vitamin A pretreated rats cleared carbon particles from the blood 2-3 times faster than non-pretreated rats. In vivo administration of superoxide dismutase (SOD) 2 hr after CCl4 exposure did not influence CCl4 toxicity in control rats but did block the enhanced ethane exhalation and also the potentiation of CCl4 liver injury in vitamin A treated rats. Administration of methyl palmitate, an inhibitor of Kupffer cell function, did not inhibit CCl4 toxicity in control rats, but did effectively block enhanced ethane exhalation and potentiation of CCl4 injury in vitamin A treated rats. We conclude that potentiation of CCl4 hepatotoxicity by hypervitaminosis A is mediated in part by reactive oxygen species released from activated Kupffer cells. PMID:2069020

  7. 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

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

    PubMed Central

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

    2014-01-01

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

  9. 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 ?-smooth muscle actin (?-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 ?-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

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

    PubMed

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

    2014-09-01

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

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

    PubMed

    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, ?-GGT, ALP, total bilirubin, LDH, and total protein. Meanwhile, in vivo antioxidant activities as LPO, NP-SH, and CAT were measured in rat liver as well as mRNA expression of cytokines such as TNF?, IL-6, and IL-10 and stress related genes iNOS and HO-1 were determined by RT-PCR. The extent of liver damage was also analyzed through histopathological observations. Results. Treatment with PCEE significantly and dose dependently prevented drug induced increase in serum levels of hepatic enzymes. Furthermore, PCEE significantly reduced the lipid peroxidation in the liver tissue and restored activities of defense antioxidant enzymes NP-SH and CAT towards normal levels. The administration of PCEE significantly downregulated the CCl4-induced proinflammatory cytokines TNF? and IL-6 mRNA expression in dose dependent manner, while it upregulated the IL-10 and induced hepatoprotective effect by downregulating mRNA expression of iNOS and HO-1 gene. PMID:25654097

  12. Antioxidant Properties of Proanthocyanidins Attenuate Carbon Tetrachloride (CCl4)–Induced Steatosis and Liver Injury in Rats via CYP2E1 Regulation

    PubMed Central

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

    2014-01-01

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

  13. Changes in expression of the albumin, fibronectin and type I procollagen genes in CCl4-induced liver fibrosis: effect of pyridoxol L,2-pyrrolidon-5 carboxylate.

    PubMed

    Arosio, B; Santambrogio, D; Gagliano, N; Annoni, G

    1993-12-01

    The protective activity of pyridoxol L,2-pyrrolidon-5 carboxylate (metadoxine) was investigated in a rat model of carbon tetrachloride (CCL4)-induced hepatic fibrosis. After 6 weeks of CCl4 treatment, the animals developed fibrosis and inflammation of the liver while those treated with CCl4 + metadoxine had less severe lesions (P < 0.05). Since in liver fibroplasia there are quantitative changes of the extracellular matrix components and almost invariably a decrease in albumin synthesis, we have also investigated by Northern blot analysis the expression of the cellular fibronectin, pro-alpha 2(I)collagen and albumin genes. There were striking increases in fibronectin and pro-alpha 2(I)collagen mRNA contents in the livers of CCL4-treated animals and these enhancements were less evident in the metadoxine-treated rats. In contrast, albumin mRNA levels, almost identical in control and metadoxine-treated rats, were lower in the CCl4-treated animals. These data suggest that metadoxine might slow the development of CCl4-mediated liver fibrosis. PMID:7512265

  14. Tonsil-derived Mesenchymal Stem Cells Ameliorate CCl4induced Liver Fibrosis in Mice via Autophagy Activation

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2005-04-01

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

  16. NF-?B 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-?B as well as inhibits the release of proinflammatory cytokine TNF-? and IL-1?. The results suggest that MIL has a significant hepatoprotective activity which might be due to the presence of phytochemicals namely analogues of ferulic acid and other phytochemicals which together may suppress the inflammatory signaling pathways and promote hepatoprotective activity against CCl4 intoxicated liver damage. PMID:25445959

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

    PubMed

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

    2006-11-01

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

  18. Protective effect of Indigofera oblongifolia in CCl4-induced hepatotoxicity.

    PubMed

    Shahjahan, M; Vani, G; Devi, C S Shyamala

    2005-01-01

    The present study aimed at assessing the protective effect of Indigofera oblongifolia on carbon tetrachloride (CCl4-induced hepatotoxicity. Hepatotoxicity was induced in male Wistar rats using CCl4 (1 mL/day at an interval of 72 hours). CCl4-induced animals were treated with I. oblongifolia at different doses. Hepatoprotection was assessed from activities of marker enzymes in serum and antioxidant status in the liver after an experimental period of 10 days. The activities of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and lactate dehydrogenase were significantly (P < .001) increased in serum of CCl4-induced animals when compared with control animals. Antioxidant status was significantly lowered in CCl4-treated animals with a significant (P < .001) increase in the levels of lipid peroxides [thiobarbituric acid-reactive substances (TBARS)], significantly lower levels of glutathione (GSH), and lowered activities of superoxide dismutase (SOD), catalase (CAT), and GSH peroxidase (GPx). The protective effect of I. oblongifolia was evident from lowering of levels of marker enzymes in serum and maintenance of antioxidant status in the liver as seen from lowered levels of TBARS, increased levels of GSH, and increased activities of SOD, CAT, and GPx. These results show the protective effect of I. oblongifolia and suggest the antioxidant property of the extract. PMID:16117622

  19. 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

  20. 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??M, 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 ?-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

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. Cirrhosis

    MedlinePLUS

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

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

    PubMed Central

    2011-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  9. 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 ...

  10. Vitamin D and melatonin protect the cell's viability and ameliorate the CCl4 induced cytotoxicity in HepG2 and Hep3B hepatoma cell lines.

    PubMed

    Özerkan, Dil?ad; Özsoy, Nesrin; Y?lmaz, Erkan

    2015-12-01

    Carbon tetrachloride (CCl4) is widely used to induce liver toxicity in in vitro/in vivo models. Lipid peroxidation (LPO) begins with toxicity and affects cell viability. Recently, the beneficial effects of melatonin and Vitamin D on cell proliferation in human normal and cancer cells were found. This study was planned to evaluate antioxidant and cytoprotective activity of melatonin and Vitamin D in CCl4 induced cytotoxicity in HepG2 and Hep3B hepatoma cell lines. Based on the cytotoxicity assay, melatonin and Vitamin D were evaluated for cytotoprotective potential against CCl4 induced toxicity in HepG2 and Hep3B liver cell lines by monitoring cell viability, LPO and glutathione (GSH) level. Different dosages of CCl4 (0.1, 0.2, 0.3 and 0.4 % v/v) were applied to HepG2 and Hep3B cells in order to determine the most toxic dosage of it in a time dependent manner. The same experiments were repeated with exogenously applied melatonin (MEL) and Vitamin D to groups treated with/without CCL4. Cell viability was determined with MTT measurements at the 2nd, 24th and 48th h. GSH content and Malondialdehyde levels were measured from the cell lysates. As a result, both melatonin and Vitamin D administration during CCl4 exposure protected liver cells from CCl4 induced cell damage. Increase in LPO and decrease in GSH were found in the CCl4 groups of both cells. Contrary to these results administration of MEL and Vitamin D on cells exhibited results similar to the control groups. Therefore, melatonin and Vitamin D might be a promising therapeutic agent in several toxic hepatic diseases. PMID:24997582

  11. Protective effects of polydatin against CCl4-induced injury to primarily cultured rat hepatocytes

    PubMed Central

    Huang, Zhao-Sheng; Wang, Zong-Wei; Liu, Ming-Ping; Zhong, Shi-Qing; Li, Qiao-Mei; Rong, Xiang-Lu

    1999-01-01

    AIM To investigate the protective effects of polydatin (PD) against injury to primarily cultured rat hepatocytes induced by CCl4. METHODS Rat hepatocytes were separated by methods of liver infusion in vivo and cultured medium (7.5 × 105 cells/mL). Two mL or 0.2 mL was added into 24-well or 96-well plates respectively. Twenty-four hours after cell preculture, PD at concentrations of 10-7 mol/L-10-4 mol/L was added into each plate. At the same time injury to hepatocytes was induced by adding 10 mmol/L-CCl4. Then, 0.1 mL or 1 mL-culture solution was removed from the 96-well or 24-well plates at 6 h, 12 h, 24 h and 48 h after CCl4 intox-ication respectively for the determination of GPT, GSH and MDA. At 48 h, the survivability of rat hepatocytes was assayed by the MTT colormetric method. RESULTS After CCl4 challenge, the release of GPT and the form ation of MDA in rat hepatocytes markedly increased and maintained at a high level in 48 h, whereas PD with different concentrations could markedly inhibit this elevation with 10-5 mol/L PD having the strongest effects and inhibiting rate was over 50%. PD could also im-prove the decreased content of GSH caused by CCl4 in accordance with the doses used. CCl4 ev-idently decreased the he patocyte survivability from 91.0% ± 7.9% to 35.4% ± 3.8%. On the other hand, PD at 10-7 mol/L-10-4 mol/L could reverse this change and improve t he cell survival rates to 56.1% ± 5.2%, 65.8% ± 5.0%, 88.7% ± 6.8% and 75.2% ± 7.3%, respectively. CONCLUSION PD at 10-7 mol/L-10-4 mol/L could protect primarily cultured rat hepatocytes against CCl4 induced injury. PMID:11819383

  12. Neurologic Manifestations of Chronic Liver Disease and Liver Cirrhosis.

    PubMed

    Sureka, Binit; Bansal, Kalpana; Patidar, Yashwant; Rajesh, S; Mukund, Amar; Arora, Ankur

    2015-01-01

    The normal functioning of brain is intimately as well as intricately interrelated with normal functioning of the liver. Liver plays a critical role of not only providing vital nutrients to the brain but also of detoxifying the splanchnic blood. Compromised liver function leads to insufficient detoxification thus allowing neurotoxins (such as ammonia, manganese, and other chemicals) to enter the cerebral circulation. In addition, portosystemic shunts, which are common accompaniments of advanced liver disease, facilitate free passage of neurotoxins into the cerebral circulation. The problem is compounded further by additional variables such as gastrointestinal tract bleeding, malnutrition, and concurrent renal failure, which are often associated with liver cirrhosis. Neurologic damage in chronic liver disease and liver cirrhosis seems to be multifactorial primarily attributable to the following: brain accumulation of ammonia, manganese, and lactate; altered permeability of the blood-brain barrier; recruitment of monocytes after microglial activation; and neuroinflammation, that is, direct effects of circulating systemic proinflammatory cytokines such as tumor necrosis factor, IL-1?, and IL-6. Radiologist should be aware of the conundrum of neurologic complications that can be encountered in liver disease, which include hepatic encephalopathy, hepatocerebral degeneration, hepatic myelopathy, cirrhosis-related parkinsonism, cerebral infections, hemorrhage, and osmotic demyelination. In addition, neurologic complications can be exclusive to certain disorders, for example, Wilson disease, alcoholism (Wernicke encephalopathy, alcoholic cerebellar degeneration, Marchiafava-Bignami disease, etc). Radiologist should be aware of their varied clinical presentation and radiological appearances as the diagnosis is not always straightforward. PMID:25908229

  13. 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

  14. 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

  15. New prognostic markers in liver cirrhosis.

    PubMed

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

    2015-05-28

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-11-01

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

  17. 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

  18. 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)-? and interleukin (IL)-1? levels, and receptor for advanced glycation end-products (RAGE) and nuclear factor (NF)?B-p65 immunocontent] were investigated. Our findings demonstrated that Peel, PPP and FPP (200 or 400 mg/kg) daily administration by oral gavage for 30 days conferred a significant protection against CCl4-induced antioxidant enzymes activation and, most importantly, oxidative damage to lipids and proteins as well as blocked induction of inflammatory mediators such as TNF-?, IL-1?, RAGE and NF?B. This antioxidant/anti-inflammatory effect seems to be associated with the abundance of carotenoids and polyphenols present in peach-derived products, which are enriched in fresh-fruit-derived preparations (Peel and FPP) but are also present in PPP. The Syrup - which was the least enriched in antioxidants - displayed no protective effect in our experiments. These effects cumulated in decreased levels of transaminases and lactate dehydrogenase leakage into serum and maintenance of organ architecture. Therefore, the herein presented results show evidence that supplementation with peach products may be protective against organ damage caused by oxidative stress, being interesting candidates for production of antioxidant-enriched functional foods. PMID:25287815

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

    PubMed Central

    2012-01-01

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

  20. 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

  1. 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

  2. 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.

  3. Failure of hypoxic pulmonary vasoconstriction in patients with liver cirrhosis

    PubMed Central

    Daoud, Fuheid S.; Reeves, John T.; Schaefer, John W.

    1972-01-01

    The combination of arterial hypoxemia and low pulmonary vascular resistance in patients with liver cirrhosis is unexplained. Pulmonary microcirculatory dilation, but not gross arterio-venous shunts, has been the usual postmortem finding in patients with liver cirrhosis. When 10 patients with alcoholic liver cirrhosis breathed 10% oxygen in nitrogen, they failed to increase their pulmonary vascular resistance. However, four patients with functional murmurs, three patients with hyperkinetic heart syndrome, six patients with normal pulmonary artery pressures and intracardiac left to right shunts, and five patients with renal failure and anemia all increased their pulmonary vascular resistances when they breathed 10% oxygen in nitrogen. These findings suggested that in liver cirrhosis the normal regulating mechanism (hypoxic vasoconstriction) of the pulmonary circulation may be impaired, resulting in failure of the lung to match perfusion with ventilation. PMID:5057127

  4. 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

  5. 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, ?-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

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

    PubMed

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

    2012-11-01

    Phyllanthus amarus (PA) is commonly used in traditional medicine for hepatoprotectivity. The major limitation is that, treatment requires a large quantity of herbal extract for a longer duration. Aim of the present study was to encapsulate ethanolic plant extract for sustained release of constituents in intestine and facilitate maximum absorption. The efficacy was compared for the hepatoprotective activity of nanoencapsulated ethanolic extract of P. amarus (NPA) and PA in carbon tetrachloride (CCl4) induced hepatotoxic male rats. Based on total phenol content (TPC), the loading efficiency of nanocapsules was 89% (pH 7.0) and optimum concentration was 2:18 (mg/mL) for plant extract: olive oil. Scanning electron microscopy (SEM) showed a spherical morphology, photon correlation spectroscopy (PCS) identified mean particle diameter as 213 nm and Fourier transform infrared spectroscopy (FT-IR) revealed that the phytoconstituents were stable. An oral dose of NPA (20 mg/kg body wt.) showed a better hepatoprotective activity than PA (100 mg/kg body wt.) and also repeated dose oral toxicity proved to be safe. These biochemical assessments were supported by rat biopsy examinations. In conclusion, the nanoemulsification method may be applied for poor water-soluble ethanolic herbal extracts to reduce the dosage and time. PMID:23305029

  7. 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

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

    PubMed

    Khan, Muhammad Rashid; Younus, Tahira

    2011-10-01

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

  9. 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

  10. Changing trends of hospitalisation of liver cirrhosis in Beijing, China

    PubMed Central

    Bao, Xiao-Yuan; Xu, Bei-Bei; Fang, Kai; Li, Yan; Hu, Yong-Hua; Yu, Guo-Pei

    2015-01-01

    Objective To examine if the hospitalisation trends of liver cirrhosis are changing with the changes of risk factors of the disease in China. Design Secondary analysis of hospitalisation records in the 31 top-ranking hospitals in Beijing. Results Between 2006 and 2010, hospitalisation from viral hepatitis cirrhosis (VHC) decreased by 10% (95% CI=5–14%, p<0.001), but non-viral hepatitis cirrhosis (NVHC) and alcoholic cirrhosis (AC) increased by 35% (26–46%, p<0.001) and 33% (19%– 47%, p<0.001), respectively. The age patterns of hospitalisation varied with different types of liver cirrhosis. The hospitalisation risks for patients with VHC and AC were significantly high in the age groups 40–49 and 50–59?years, but risks for those with NHVC were high in all age groups of 40?years or above. Overall male-to-female hospitalisation ratios for VHC, NVHC and AC were 2.71, 1.14 and 59.9, respectively. The sex ratio became smaller with time from 2006 to 2010 in hospitalised patients with VHC, but it substantially increased in those with NVHC during the same period. Conclusions Hospitalisation rates for liver cirrhosis in Beijing are changing with time. The changes of viral hepatitis infection and alcohol consumption in the general population may cause these changes. PMID:26629359

  11. 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

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

    E-print Network

    Clemmer, David E.

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

  13. Influence of unrecorded alcohol consumption on liver cirrhosis mortality

    PubMed Central

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

    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

  14. Management of portal vein thrombosis in liver cirrhosis.

    PubMed

    Qi, Xingshun; Han, Guohong; Fan, Daiming

    2014-07-01

    Portal vein thrombosis (PVT) is a fairly common complication of liver cirrhosis. Importantly, occlusive PVT might influence the prognosis of patients with cirrhosis. Evidence from a randomized controlled trial has shown that anticoagulation can prevent the occurrence of PVT in patients with cirrhosis without prior PVT. Evidence from several case series has also demonstrated that anticoagulation can achieve portal vein recanalization in patients with cirrhosis and PVT. Early initiation of anticoagulation therapy and absence of previous portal hypertensive bleeding might be positively associated with a high rate of portal vein recanalization after anticoagulation. However, the possibility of spontaneous resolution of partial PVT questions the necessity of anticoagulation for the treatment of partial PVT. In addition, a relatively low recanalization rate of complete PVT after anticoagulation therapy suggests its limited usefulness in patients with complete PVT. Successful insertion of a transjugular intrahepatic portosystemic shunt (TIPS) not only recanalizes the thrombosed portal vein, but also relieves the symptomatic portal hypertension. However, the technical difficulty of TIPS potentially limits its widespread application, and the risk and benefits should be fully balanced. Notably, current recommendations regarding the management of PVT in liver cirrhosis are insufficient owing to low-quality evidence. PMID:24686266

  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. Non invasive tools for the diagnosis of liver cirrhosis.

    PubMed

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

    2014-12-28

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

  17. Ultrasonography in predicting and screening liver cirrhosis in children: A preliminary study

    PubMed Central

    Zhu, Jia-An; Hu, Bing

    2003-01-01

    AIM: To evaluate the value of ultrasonography in predicting and screening liver cirrhosis in children. METHODS: Twenty-eight children with liver cirrhosis of various etiologies were examined by routine ultrasonography. A percutaneous liver biopsy guided by ultrasound was also performed on each patient, and the results of liver biopsy and ultrasonography were compared. RESULTS: When compared with the biopsy results, ultrasonography in combination of clinical and laboratory findings gave accurate diagnoses of children liver cirrhosis. Although ultrasound imaging of children with liver cirrhosis revealed abnormal characteristics, these images were not specific to this disease, thus reinforcing the necessity of ultrasound-guided liver biopsy in the diagnosis of children liver cirrhosis. CONCLUSION: Ultrasonography is reliable in the diagnosis of children liver cirrhosis, and its usefulness should be stressed in the screening and follow-up of high-risk pediatric patients. PMID:14562409

  18. Prevention of carbon tetrachloride (CCl4)-induced toxicity in testes of rats treated with Physalis peruviana L. fruit.

    PubMed

    Abdel Moneim, Ahmed E

    2014-08-21

    Treatment of rats with carbon tetrachloride (CCl4; 2 ml/kg body weight) once a week for 12 weeks caused a significant decrease in serum levels of testosterone, luteinizing hormone, and follicle-stimulating hormone. These decreases in sex hormones were reduced with Physalis peruviana L. (Cape gooseberry) juice supplementation. In addition, testicular activity of antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione-S-transferase suppressed with CCl4 were elevated after P. peruviana juice supplements. P. peruviana juice supplementation significantly increased the testicular glutathione and significantly decreased the level of lipid peroxidation and the nitric oxide production compared with the CCl4 group. In addition, the decline in the activity of antioxidant enzymes after CCl4 was ameliorated by P. peruviana. Moreover, degeneration of germ and Leydig cells along with deformities in spermatogenesis induced after CCl4 injections were prevented with the supplementation of P. peruviana juice. Furthermore, P. peruviana juice attenuated CCl4-induced apoptosis in testes tissue by inhibition of caspase-3 activity. The results clearly demonstrate that P. peruviana juice augments the antioxidants defense mechanism against CCl4-induced reproductive toxicity and provides evidence that the juice may have a therapeutic role in free radical-mediated diseases and infertility. PMID:25147302

  19. Factor analysis of the biochemical markers related to liver cirrhosis

    PubMed Central

    Kim, Hyun-Jin; Lee, Hae-Kag; Cho, Jae-Hwan

    2015-01-01

    Objectives: The purpose of this study was to find the correlations between biochemical study and liver cirrhosis. Methods: The patients had liver biopsy to check the degree of their liver fibrosis, from August 2013 to August 2014 at the current medical center. In order to find the etiology of hepatitis, a research was done on gender, age, weight, and biochemical study through the investigation of subjects’ medical record and medical history. For biochemical study, we examined hemoglobin, platelets, albumin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, gamma-glutamyl transferase (GGT), prothrombin time (PT), and international normalised ratio (INR). We also analyzed the factors that are related to liver cirrhosis. Results: As a result, the patients at liver cirrhosis F?2 stage showed 0.973, which is higher than the patients at FO stage with 0.943. F?2 stage of hemoglobin was 0.544, which is lower than FO stage of hemoglobin with 0.817. Platelet count in F?2 stage was 0.417, which is higher than FO stage with 0.074. For Albumin, F?2 stage was 0.155 when F0 stage was 0.135. ATS’s F?2 stage was 0.665, which is 6 times higher than FO stage with 0.100. Moreover, in the case of GGT, F?2 stage was higher with 0.492 than FO stage with 0.078. Conclusions: In conclusion, it was confirmed that there is an increase in liver cirrhosis in the following general characteristics and biochemical factors: increase of age, increase of GGT, decrease of albumin, increase of the total bilirubin, and growth of INR (International Normalized Ratio).

  20. 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

  1. 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

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

    PubMed

    Prystupa, Andrzej; Kici?ski, Pawe?; Sak, Jaros?aw; Boguszewska-Czubara, Anna; Toru?-Jurkowska, Anna; Za?uska, Wojciech

    2015-01-01

    Background. The aim of the study was to assess the activity of interleukin-1?, 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-1?, 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-1? 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

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

    PubMed Central

    Prystupa, Andrzej; Kici?ski, Pawe?; Sak, Jaros?aw; Boguszewska-Czubara, Anna; Toru?-Jurkowska, Anna; Za?uska, Wojciech

    2015-01-01

    Background. The aim of the study was to assess the activity of interleukin-1?, 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-1?, 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-1? 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

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

    EPA Science Inventory

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

  5. 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

  6. 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 ?U/mL. The intra and interassay variation coefficients were < 4% and < 10%, respectively. The normal values were between 2 and 17 ?U/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

  7. 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

  8. [Recent advances in the treatment of decompensated liver cirrhosis].

    PubMed

    Moriwaki, H; Kato, M; Murase, M; Muto, Y

    1994-01-01

    Comprehensive care is required to treat decompensated liver cirrhosis. Fischer's solution and lactulose are usually administered to the patients with hepatic encephalopathy, and improve 98% of those with chronic recurrent type hepatic coma. Benzodiazepine receptor antagonist may be effective to prevent "sensitized brain" in cirrhotics. As to ascites, bed rest, administration of diuretics and albumin infusion improve 88% of the patients. Autoinfusion of filtered and concentrated ascites shows 40% efficacy in patients with ascites, which does not respond to conventional therapy, but is not effective when plasma total bilirubin level is higher than 10 mg/dl. To prevent the development of liver failure in cirrhotic, oral supplementation with branched-chain amino acids is particularly important, in addition to administration of lactulose and prevention of major gastrointestinal bleeding by histamin H2 receptor antagonist and sclerotherapy of esophageal varices. PMID:8114292

  9. Increased prevalence of intestinal inflammation in patients with liver cirrhosis

    PubMed Central

    Saitoh, Osamu; Sugi, Kazunori; Kojima, Keishi; Matsumoto, Hisashi; Nakagawa, Ken; Kayazawa, Masanobu; Tanaka, Seigou; Teranishi, Tsutomu; Hirata, Ichiro; Katsu, Ken-ichi

    1999-01-01

    AIM: To investigate the pathophysiology of the digestive tract in patients with liver cirrhosis. METHODS: In 42 cirrhotic patients and 20 control subjects, the following fecal proteins were measured by enzyme-linked immunosorbent assay: albumin (Alb), transferrin (Tf), and ?1-antitrypsin (?1-AT) as a marker for intestinal protein loss, hemoglobin (Hb) for bleeding, PMN-elastase for intestinal inflammation, and secretory IgA for intestinal immunity. RESULTS: The fecal concentrations of Hb, Alb, Tf, ?1-AT, an d PMN-elastase were increased in 13 (31%), 8 (19%), 10 (24%), 6 (14%), and 11 (26%) cases among 42 patients, respectively. Fecal concentration of secretory IgA was decreased in 7 (17%) of 42 patients. However, these fecal concentrations were not related to the severity or etiology of liver cirrhosis. The serum Alb level was significantly decreased in patients with intestinal protein loss compared to that in patients without intestinal protein loss. CONCLUSION: These findings suggest that: ? besides the well-known pathological conditions, such as bleeding and protein loss, intestinal inflammation and decreased intestinal immunity are found in cirrhotic patients; ? intestinal protein loss contributes to hypoalbuminemia in cirrhotic patients, and ? intestinal inflammation should not be over looked in cirrhotic patients, since it may contribute to or cause intestinal protein loss and other various path ological conditions. PMID:11819475

  10. 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

  11. Hepatoprotective effects of polysaccharide isolated from Agaricus bisporus industrial wastewater against CCl4-induced hepatic injury in mice.

    PubMed

    Huang, Jiafu; Ou, Yixin; Yew, Tai Wai David; Liu, Jingna; Leng, Bo; Lin, Zhichao; Su, Yi; Zhuang, Yuanhong; Lin, Jiaofen; Li, Xiumin; Xue, Yu; Pan, Yutian

    2016-01-01

    During the industrial production of canned mushroom (Agaricus bisporus), a large quantity of wastewater is produced. In this study, the wastewater generated during the canning of mushroom was analyzed. From this wastewater, four polysaccharide components (Abnp1001, Abnp1002, Abap1001, and Abap1002) with hepatic-protective activity were isolated by ultrafiltration, DEAE cellulose-52 chromatography and Sephadex G-200 size-exclusion chromatography. Results of ultraviolet spectra analysis and molecular weight determination showed that Abnp1001, Abnp1002, Abap1001 and Abap1002 were uniform with average molecular weights of 336, 12.8, 330 and 15.8kDa, respectively. The monosaccharide composition analysis using gas chromatography (GC) showed that the four fractions were heteropolysaccharides and mainly composed of glucose. Fourier transform-infrared (FT-IR) analysis showed that the isolated fractions were all composed of ?-glycoside linkages. Additionally, the potential hepatoprotective activities of these polysaccharides against CCl4-induced hepatic injury in mice were studied. Notably, Abnp1002 and Abap1002 could lower the alanine aminotransferase (ALT) and aspartate aminotransferase (AST) concentrations in serum in a dose dependent manner and reduce the hepatocellular degeneration and necrosis, as well as inflammatory infiltration. These results indicate that these two polysaccharides had protective effects on acute hepatic injury induced by CCl4 in mice and suggest that the polysaccharides extracted from A. bisporus industrial wastewater might have potential in therapeutics of acute hepatic injury. PMID:26454111

  12. 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

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

    PubMed

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

    2014-12-01

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

  14. 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

  15. Nerve growth factor involvement in liver cirrhosis and hepatocellular carcinoma

    PubMed Central

    Rasi, Guido; Serafino, Annalucia; Bellis, Lia; Lonardo, Maria Teresa; Andreola, Federica; Zonfrillo, Manuela; Vennarecci, Giovanni; Pierimarchi, Pasquale; Vallebona, Paola Sinibaldi; Ettorre, Giuseppe Maria; Santoro, Eugenio; Puoti, Claudio

    2007-01-01

    AIM: To define NGF (nerve growth factor) and its high-affinity receptor trkANGF presence and distribution in fibrotic liver and in HCC, and to verify if NGF might have a role in fibrosis and HCC. METHODS: Intracellular distribution of NGF and trkANGF were assessed by immunohistochemistry and immuno-electron microscopy in liver specimens from HCC, cirrhosis or both. ELISA was used to measure circulating NGF levels. RESULTS: NGF and trkANGF were highly expressed in HCC tissue, mainly localized in hepatocytes, endothelial and some Kupffer cells. In the cirrhotic part of the liver they were also markedly expressed in bile ducts epithelial and spindle-shaped cells. Surprisingly, in cirrhotic tissue from patients without HCC, both NGF and trkANGF were negative. NGF serum levels in cirrhotic and/or HCC patient were up to 25-fold higher than in controls. CONCLUSION: NGF was only detected in liver tissue with HCC present. Intracellular distribution suggests paracrine and autocrine mechanisms of action. Better definition of mechanisms may allow for therapeutic and diagnostic/prognostic use of NGF. PMID:17854142

  16. Prevalence of spontaneous bacterial peritonitis in liver cirrhosis with ascites

    PubMed Central

    Oladimeji, Ajayi Akande; Temi, Adegun Patrick; Adekunle, Ajayi Ebenezer; Taiwo, Raimi Hassan; Ayokunle, Dada Samuel

    2013-01-01

    Introduction Spontaneous bacterial peritonitis (SBP) is a common bacterial infection in patients with cirrhosis and ascites requiring prompt recognition and treatment. The aim of this study was to determine the prevalence, and characteristics of SBP among in-patients with cirrhosis and ascites seen at our facility. Methods Thirty one patients with liver cirrhosis and ascites who were admitted into the Medical ward of the Ekiti State University Teaching Hospital (EKSUTH), Ado-Ekiti, Nigeria from August 2009 to July 2010 were retrospectively studied. All the patients had abdominal paracentesis done within 48 hours of admission under aseptic condition and the data obtained were analyzed. Results The mean age of the studied population was 62±9 years (age range 43-78 years). Of the 21 that developed SPB, culture positive SBP was present in 66.7% (14/21) while CNNA was found in 33.3% (7/21). The prevalence of MNB was 26% (8/31) in this study. Of those with SBP, 93% had monomicrobial infection with aerobic Gram negative bacilli being responsible in 66.7% of the cases with E.coli (70%) being the predominant organism followed by Klebsiella species. Gram positive organisms accounted for 33.3% with Streptococcal species (60%) being the predominant organism followed by Staphylococcus aureus (40%). Patients with SBP had significantly lower platelet count when compared with those without SBP, p < 0.05. Also, international normalization ratio (INR) was significantly higher in those patients with SBP compared with those without SBP, p < 0.05. The poor prognostic indicators found in this study were; low ascitic protein, hepatic encephalopathy, coagulopathy, renal dysfunction (creatinine >2mg/dl) and leukocytosis (p < 0.05). Conclusion It is therefore imperative to do diagnostic abdominal paracentesis for cell count and culture in any patient with onset of ascites or cirrhotic patients with ascites and suggestive symptoms compatible or suggestive of SBP. PMID:24255734

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

    PubMed Central

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

    2014-01-01

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

  18. Immune complex type glomerulonephritis in cirrhosis of the liver.

    PubMed Central

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

    1975-01-01

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

  19. 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.

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

    PubMed Central

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

    2015-01-01

    Kallistatin, which protects organs and cells against inflammation, fibrosis and oxidative stress, is mainly synthesized and secreted in liver. However, its relationship to human liver disease remains unclear. The purpose of this study was to explore the relationship between serum kallistatin and clinical evidence of both cirrhosis and hepatocellular carcinoma (HCC), and to determine if serum kallistatin levels could be used as a diagnostic indicator of hepatic health status, especially human liver cirrhosis (LC). Our cohort consisted of 115 patients with clinically proven liver fibrosis (LF), LC, or HCC by liver biopsies, and 31 healthy controls (CON). Serum kallistatin levels were quantified by ELISA. Results of the present study demonstrated that irrespective of the underlying etiology, serum kallistatin levels were significantly lower in the LF/LC group when compared with the CON group. A decrease in serum kallistatin levels appeared to reflect the extent of cirrhosis, with the lowest levels associated with higher grades of cirrhosis. Patients with LC had a noticeable correlation between serum kallistatin levels and other serum biochemical indicators. The area under the curve (AUC) for LC, viral liver cirrhosis (VLC) and alcoholic liver cirrhosis (ALC) was 0.845, 0.757 and 0.931, respectively. In conclusion, our findings demonstrated that kallistatin, a plasma protein produced by the liver, can be a useful and reliable diagnostic indicator of hepatic health status, especially for LC. PMID:26579446

  1. 1H Magnetic Resonance Spectroscopy Predicts Hepatocellular Carcinoma in a Subset of Patients With Liver Cirrhosis

    PubMed Central

    Wang, Dan; Li, Yuehua

    2015-01-01

    Abstract The goal of this study was to investigate the utility of 1H magnetic resonance spectroscopy (1H-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 1H-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?cirrhosis group and the control and HCC groups (all P?cirrhosis groups, the control and HCC groups, and the cirrhosis and HCC groups (all P?liver cirrhosis secondary to chronic hepatitis B and HCC. Thus, 1H-MRS may be helpful in monitoring HCC and liver cirrhosis development. PMID:26166077

  2. 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

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

    PubMed Central

    Wong, Grace Lai-Hung; Espinosa, Wendell Zaragoza

    2015-01-01

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

  4. Serum MicroRNA-122 Predicts Survival in Patients with Liver Cirrhosis

    PubMed Central

    Waidmann, Oliver; Köberle, Verena; Brunner, Friederike; Zeuzem, Stefan

    2012-01-01

    Background Liver cirrhosis is associated with high morbidity and mortality. MicroRNAs (miRs) circulating in the blood are an emerging new class of biomarkers. In particular, the serum level of the liver-specific miR-122 might be a clinically useful new parameter in patients with acute or chronic liver disease. Aim Here we investigated if the serum level of miR-122 might be a prognostic parameter in patients with liver cirrhosis. Methods 107 patients with liver cirrhosis in the test cohort and 143 patients in the validation cohort were prospectively enrolled into the present study. RNA was extracted from the sera obtained at the time of study enrollment and the level of miR-122 was assessed. Serum miR-122 levels were assessed by quantitative reverse-transcription PCR (RT-PCR) and were compared to overall survival time and to different complications of liver cirrhosis. Results Serum miR-122 levels were reduced in patients with hepatic decompensation in comparison to patients with compensated liver disease. Patients with ascites, spontaneous bacterial peritonitis and hepatorenal syndrome had significantly lower miR-122 levels than patients without these complications. Multivariate Cox regression analysis revealed that the miR-122 serum levels were associated with survival independently from the MELD score, sex and age. Conclusions Serum miR-122 is a new independent marker for prediction of survival of patients with liver cirrhosis. PMID:23029162

  5. 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

  6. Synthesis of platelet-activating factor and its receptor expression in Kupffer cells in rat carbon tetrachloride-induced cirrhosis

    PubMed Central

    Lu, Yin-Ying; Wang, Chun-Ping; Zhou, Lin; Chen, Yan; Su, Shu-Hui; Feng, Yong-Yi; Yang, Yong-Ping

    2008-01-01

    AIM: To determine the platelet-activating factor (PAF) synthesis and its receptor expression in Kupffer cells in rat carbon tetrachloride-induced cirrhosis. METHODS: Kupffer cells, isolated from the livers of control and CCl4-induced cirrhotic rats, were placed in serum-free medium overnight. PAF saturation binding, ET-1 saturation and competition binding were assayed. ET-1 induced PAF synthesis, mRNA expression of PAF, preproendothelin-1, endothelin A (ETA) and endothelin B (ETB) receptors were also determined. RESULTS: A two-fold increase of PAF synthesis (1.42 ± 0.14 vs 0.66 ± 0.04 pg/?g DNA) and a 1.48-fold increase of membrane-bound PAF (1.02 ± 0.06 vs 0.69 ± 0.07 pg/?g DNA) were observed in activated Kupffer cells of cirrhotic rats. The application of ET-1 to Kupffer cells induced PAF synthesis in a concentration-dependent manner in both cirrhotic and normal rats via ETB receptor, but PAF synthesis in the activated Kupffer cells was more effective than that in the normal Kupffer cells. In activated Kupffer cells, PAF receptor expression and PAF binding capacity were markedly enhanced. Activated Kupffer cells raised the [125I]-ET-1 binding capacity, but changed neither the affinity of the receptors, nor the expression of ETA receptor. CONCLUSION: Kupffer cells in the course of CCl4-induced cirrhosis are the main source of increased PAF. ET-1 is involved endogenously in stimulating the PAF synthesis in activated Kupffer cells via ETB receptor by paracrine. ETA receptor did not appear in activated Kupffer cells, which may exacerbate the hepatic and extrahepatic complications of cirrhosis. PMID:18205269

  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. 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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

    Background: Cirrhosis is one of the most severe liver complications, with multiple etiologies. The torque teno virus (TTV), also known as transfusion transmitted virus, which has a high incidence in the world population, is one of the possible increasing risk factors in patients with idiopathic fulminant hepatitis and cryptogenic cirrhosis. Objectives: The aim of this study was to evaluate solitary and co-infection with TTV, in patients with cryptogenic and determined cause of cirrhosis. Patients and Methods: In this cross-sectional study, 200 liver transplant patients were consecutively recruited between years 2007 and 2011. Patients were classified, based on recognition of the etiology of cirrhosis to determined (n = 81) and cryptogenic (n = 119) patient groups. The existence of TTV infection was analyzed, using a semi-nested polymerase chain reaction method. The presence of hepatitis B virus (HBV) infective markers, including HBV DNA, hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), hepatitis B core antibody (HBcAb), and hepatitis B e antibody (HBeAb), was evaluated using qualitative polymerase chain reaction and enzyme linked immunosorbent assay protocols, respectively. Results: The TTV infection was found in 37 of 200 (18.5%) and 53 of 200 (26.5%) plasma and tissue samples of studied liver transplanted patients, respectively. The TTV genomic DNA was found in 32 (26.9%) and 28 (23.5%) of 119 liver tissue and plasma samples of transplanted patients with cryptogenic cirrhosis, respectively. The genomic DNA of TTV was also diagnosed in 21 (25.9%) and nine (11.1%) of the 81 liver tissue and plasma samples of patients with determined cirrhosis, respectively. Significant associations were found between TTV infection with HBV molecular and immunologic infective markers, in liver transplanted patients, with determined and cryptogenic cirrhosis. Conclusions: The diagnosis of the high frequency of solitary TTV and co-infection with HBV, in both liver transplanted patients with cryptogenic and determined cirrhosis, emphasized on the importance of TTV infection in the development of cirrhosis, especially in the cases of cryptogenic ones, prompting for further studies the confirm this agent in the etiology of determined cirrhosis. PMID:26504468

  11. Hrd1 suppresses Nrf2-mediated cellular protection during liver cirrhosis

    PubMed Central

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

    2014-01-01

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

  12. 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.

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

    PubMed Central

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

    2000-01-01

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

  14. 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-? (TNF-?) in the plasma, and TNF-?, 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-? in the plasma, and TNF-?, 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

  15. 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

  16. 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

  17. Resveratrol attenuates the progress of liver fibrosis via the Akt/nuclear factor-?B pathways.

    PubMed

    Zhang, Hui; Sun, Qingfeng; Xu, Tingyan; Hong, Liang; Fu, Rongquan; Wu, Jinguo; Ding, Jiguang

    2016-01-01

    Liver fibrosis is a wound-healing response to chronic liver injury that results in the accumulation of extracellular matrix proteins. It eventually leads to cirrhosis of the liver and liver failure, and it is a critical threat to the health and lives of patients with chronic liver diseases. No effective treatment is currently available. Resveratrol is a polyphenol with antioxidant, anti?cancer and anti?inflammatory properties. It has been reported that resveratrol prevents liver fibrosis, possibly by inhibiting NF??B activation. The present study investigated the mechanisms by which resveratrol prevented liver fibrosis, focusing on the possible involvement of the NF??B pathway. Mice with carbon tetrachloride (CCl4)?induced liver fibrosis were treated with various concentrations of resveratrol. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and tumor necrosis factor (TNF)?? were detected by ELISAs. Expression of ??smooth muscle actin (??SMA), collagen I, inhibitor of NF??B (I?B) and NF??B were detected by western blot analysis. In addition, the present study examined the effects of resveratrol on the expression of fibrosis markers in LX?2 cells. Western blot analysis was further used to detect the levels of Akt and phosphorylated Akt, as well as the nuclear levels of I?B, phosphorylated I?B and NF??B p65. The expression of ??SMA in resveratrol?treated LX?2 cells was detected by immunofluorescence and flow cytometry, which demonstrated that resveratrol decreased the expression of ??SMA in LX?2 cells. Resveratrol also decreased CCl4?induced upregulation of serum AST, ALT, TNF??, ??SMA and collagen I. Finally, resveratrol prevented the activation of NF??B and Akt. The results of the present study therefore indicated that resveratrol attenuates liver fibrosis via the Akt/NF-?B pathways. PMID:26530037

  18. Endogenous carbon monoxide downregulates hepatic cystathionine-?-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-?-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

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

    PubMed Central

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

    2015-01-01

    Background: Chronic hepatitis B virus (HBV) infection has a broad spectrum of manifestation, ranging from silent carrier state to advanced cirrhosis and hepatocellular carcinoma. The persistence of HBV DNA in serum and hepatocytes of the cirrhotic patient could be detected by molecular techniques in spite of negative HBV serologic markers. Objectives: This case-control study was designed to evaluate the prevalence of occult HBV infection (OBI) in patients with cryptogenic liver cirrhosis in comparison with healthy subjects. Patients and Methods: Of 165 patients with liver cirrhosis, 50 consecutive patients with cryptogenic cirrhosis and 80 healthy individual without any risk factors as a control group were enrolled in this study. Their sera were tested for HBV DNA using nested PCR method. Results: Of 50 patients with cryptogenic cirrhotic, 36 (72%) were male. The mean age of patients was 53.34 ± 14.73 years; 80 healthy subjects were selected as control group with mean age of 32.65 ± 8.51 years; 7 (14%) of the patients with cryptogenic cirrhosis showed positive HBV DNA by PCR, while HBV DNA was negative for the control group (P = 0.0001); 4 (57%) cases with positive HBV shown by PCR were negative for anti-HBc and anti-HBs tests. The mean level of transaminases was significantly higher in patients with cirrhosis. There were no significant differences in demographic parameters, transaminases level and degree of hepatic failure among cirrhotic patients with and without OBI. Conclusions: The prevalence of OBI was relatively high in patients with cryptogenic cirrhosis. OBI was found among the patients above 40 years old. Prospective cohort studies are needed to evaluate the clinical significance of OBI. PMID:25861432

  20. Multiresistant bacterial infections in liver cirrhosis: Clinical impact and new empirical antibiotic treatment policies

    PubMed Central

    Acevedo, Juan

    2015-01-01

    Recently, important changes have been reported regarding the epidemiology of bacterial infections in liver cirrhosis. There is an emergence of multiresistant bacteria in many European countries and also worldwide, including the United States and South Korea. The classic empirical antibiotic treatment (third-generation cephalosporins, e.g., ceftriaxone, cefotaxime or amoxicillin-clavulanic acid) is still effective in infections acquired in the community, but its failure rate in hospital acquired infections and in some health-care associated infections is high enough to ban its use in these settings. The current editorial focuses on the different epidemiology of bacterial infections in cirrhosis across countries and on its therapeutic implications. PMID:25954474

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

    PubMed Central

    2012-01-01

    Background Interleukin-22 (IL-22), recently identified as a crucial parameter of pathology in experimental liver damage, may determine survival in clinical end-stage liver disease. Systematic analysis of serum IL-22 in relation to morbidity and mortality of patients with advanced liver cirrhosis has not been performed so far. Methods This is a prospective cohort study including 120 liver cirrhosis patients and 40 healthy donors to analyze systemic levels of IL-22 in relation to survival and hepatic complications. Results A total of 71% of patients displayed liver cirrhosis-related complications at study inclusion. A total of 23% of the patients died during a mean follow-up of 196 ± 165 days. Systemic IL-22 was detectable in 74% of patients but only in 10% of healthy donors (P < 0.001). Elevated levels of IL-22 were associated with ascites (P = 0.006), hepatorenal syndrome (P < 0.0001), and spontaneous bacterial peritonitis (P = 0.001). Patients with elevated IL-22 (>18 pg/ml, n = 57) showed significantly reduced survival compared to patients with regular (?18 pg/ml) levels of IL-22 (321 days versus 526 days, P = 0.003). Other factors associated with reduced overall survival were high CRP (?2.9 mg/dl, P = 0.005, hazard ratio (HR) 0.314, confidence interval (CI) (0.141 to 0.702)), elevated serum creatinine (P = 0.05, HR 0.453, CI (0.203 to 1.012)), presence of liver-related complications (P = 0.028, HR 0.258, CI (0.077 to 0.862)), model of end stage liver disease (MELD) score ?20 (P = 0.017, HR 0.364, CI (0.159 to 0.835)) and age (P = 0.011, HR 0.955, CI (0.922 to 0.989)). Adjusted multivariate Cox proportional-hazards analysis identified elevated systemic IL-22 levels as independent predictors of reduced survival (P = 0.007, HR 0.218, CI (0.072 to 0.662)). Conclusions In patients with liver cirrhosis, elevated systemic IL-22 levels are predictive for reduced survival independently from age, liver-related complications, CRP, creatinine and the MELD score. Thus, processes that lead to a rise in systemic interleukin-22 may be relevant for prognosis of advanced liver cirrhosis. PMID:22967278

  2. Spontaneous Bacterial Peritonitis and Henoch-Schönlein Purpura in a Patient with Liver Cirrhosis

    PubMed Central

    Gupta, Neil; Kim, Joyce; Njei, Basile

    2015-01-01

    Henoch-Schönlein purpura (HSP) is a small vessel systemic vasculitis, predominantly affecting children, characterized by a tetrad of manifestations, specifically palpable purpura, arthralgia, abdominal pain, and renal disease. HSP in the adult population is rare, and no case has been described of HSP in liver cirrhosis with spontaneous bacterial peritonitis (SBP). We present the case of a 58-year-old male with liver cirrhosis, who was subsequently diagnosed with SBP and later HSP. In this patient, the diagnosis of HSP was demonstrated clinically by his palpable purpura, diarrhea, hematuria, and abdominal pain and confirmed pathologically by his renal and skin biopsies demonstrating leukocytoclastic vasculitis and IgA complexes. We believe that this is an example of altered IgA processing in cirrhosis leading to the development of IgA immune complexes and ultimately HSP. The patient additionally had SBP, which may have increased his risk for developing HSP given antigen processing by mucosa-associated lymphoid tissues leading to immune complex deposition, which may not have been effectively cleared in the context of his liver disease. The patient unfortunately died of gastrointestinal hemorrhage, which is unclear to be due to his underlying cirrhosis or a gastrointestinal manifestation of HSP itself. PMID:26064127

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

    PubMed Central

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

    2012-01-01

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

  4. 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.

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

    PubMed

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

    2013-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  7. 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.

  8. 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.

  9. 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.

  10. An evaluation of long-term outcomes after liver transplantation for cryptogenic cirrhosis.

    PubMed

    Heneghan, Michael A; Zolfino, Teresa; Muiesan, Paolo; Portmann, Bernard C; Rela, Mohammed; Heaton, Nigel D; O'grady, John G

    2003-09-01

    Patients with cryptogenic cirrhosis (CC) comprise a significant proportion of liver transplant recipients. Poor outcome after transplantation has been reported by some centers, with fibrosis occurring in a significant proportion of patients. Outcome of 46 patients with CC who underwent transplantation between 1989 and 1999 at King's College Hospital London were compared with time-matched recipients who underwent transplantation for hepatitis C virus (HCV) cirrhosis (n = 58) and patients with alcohol-related cirrhosis (AC, n = 53) during the same time period. Mean follow-up was 46 +/- 37 months for CC patients, 41 +/- 31 months for AC patients, and 49 +/- 31 months for HCV patients. No protocol liver biopsy specimens were obtained, and biopsies were performed only for investigation of biochemical abnormalities. Acute cellular rejection occurred in 30% of CC, 26% of AC, and 37% of HCV patients (P = NS). Overall patient and graft survival at 1 year was 85% and 80% for CC patients, 87% and 81% for AC patients, and 91% and 82% for patients with HCV (P = NS). Five-year patient and graft survival was 81% and 77% for CC patients, 60% and 48% for AC patients, and 79% and 57% for HCV patients (Log rank; P =.369). Twenty-two percent of CC patients had inflammation on last evaluable liver biopsy, compared with 25% of patients who underwent transplantation for AC and 68% of patients who underwent transplantation for HCV. No patient who underwent transplantation for CC had histologic evidence of cirrhosis on last evaluable biopsy, compared with 2% of patients who underwent transplantation for AC and 16% of patients who underwent transplantation for HCV (Chi-squared = 13.053, P =.0015). These results suggest that CC is a favorable indication for OLT and that although a proportion of patients develop inflammation in the liver allograft, this does not result in significant graft dysfunction or loss. PMID:12942453

  11. 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.

  12. 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.

  13. Lipid peroxidation in thioacetamide-induced macronodular rat liver cirrhosis.

    PubMed

    Müller, D; Sommer, M; Kretzschmar, M; Zimmermann, T; Buko, V U; Lukivskaya, O; Dargel, R

    1991-01-01

    Microsomes and isolated hepatocytes from thioacetamide (TAA)-induced macronodularly cirrhotic rat livers were analysed for their susceptibility to unstimulated and stimulated lipid peroxidation measured as malondialdehyde (MDA) formation. In microsomes from TAA-induced macronodularly cirrhotic livers the MDA production stimulated either by ascorbate-iron or by ADP-iron in a NADPH-regenerating system was decreased. Hepatic microsomes from TAA-treated rats exhibited a reduced cytochrome P450 content and lowered activities of ethylmorphine N-demethylase, ethoxycoumarin O-deethylase and epoxide hydrolase. Besides this, the microsomal fatty acid pattern of phosphatidylcholine and phosphatidylethanolamine was significantly changed after 6 months of TAA administration. The 18:2/20:4 ratio of phospholipid fatty acids was markedly increased. In contrast to the microsomes, in isolated hepatocytes from macronodularly cirrhotic livers the iron- and ascorbate-iron-stimulated MDA formation was increased. The hepatocellular GSH content was unaffected by TAA pretreatment, whereas the GSSG content exhibited a significant increase, thus leading to a pronounced reduction of the GSH/GSSG ratio. The calcium channel blocker verapamil (200 microM), known to be able to scavenge OH' radicals produced by the Fenton reaction, revealed an inhibitory effect on ascorbate-iron- and ADP-iron-stimulated lipid peroxidation in hepatocytes from normal as well as TAA-treated livers which is attributed to its antioxidative properties. In summary, lipid peroxidation is altered in TAA-induced macronodularly cirrhotic rat livers. Furthermore, the data clearly show that isolated microsomes and parenchymal cells prepared from cirrhotic livers react differently to prooxidant stimuli. PMID:2053847

  14. 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 (2004–2011) 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 (52±11 vs. 49±11 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

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

    PubMed Central

    Garbuzenko, Dmitry Victorovich

    2015-01-01

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

  16. 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

  17. 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.

  18. 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

  19. 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.

  20. 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

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

    PubMed Central

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

    2014-01-01

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

  2. 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

  3. 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

  4. Correction of altered plasma amino acid pattern in cirrhosis of the liver by somatostatin.

    PubMed Central

    Limberg, B; Kommerell, B

    1984-01-01

    The purpose of our study was to evaluate the effect of somatostatin (500 microgram/h intravenously) upon insulin, c-peptide, glucagon and plasma amino acids concentrations in patients with and without cirrhosis of the liver. The typical plasma amino acid pattern in cirrhosis is characterised by increased concentrations of the aromatic amino acids and decreased concentrations of the branched chain amino acids and of alanine and glycine. After administration of somatostatin insulin, c-peptide and glucagon concentrations decreased and those of the branched chain amino acids in both groups increased; in addition in patients with cirrhosis the plasma concentrations of threonine, serine, glycine, alanine, lysine, and arginine increased also. Infusion of somatostatin plus insulin in patients with cirrhosis succeeded in preventing the increase in the branched chain amino acid concentrations, while the infusion of somatostatin plus glucagon decreased threonine, serine, glycine, alinine, phenylalanine, tyrosine, lysine and arginine concentrations. It is therefore suggested that the effect of somatostatin on the plasma amino acids may be because of the reduction of insulin and glucagon concentrations; however, other effects of somatostatin cannot be excluded at present. PMID:6149982

  5. 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

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

    PubMed Central

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

    2014-01-01

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

  7. 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.

  8. 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

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

    PubMed

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

    2016-01-01

    Hepatocellular adenoma is considered to occur exclusively in non-fibrotic livers. It is a heterogeneous entity and a molecular classification is now widely accepted. The most frequent hepatocellular adenoma subtype, namely inflammatory adenoma, harbor somatic activating mutations of genes involved in the interleukin-6 pathway that lead to high C-reactive protein and serum amyloid A expression. The aim of our study was to investigate a series of benign hepatocellular neoplasms developed on cirrhotic livers and characterized by an unequivocal histological diagnosis. We performed a clinical, pathological, and molecular study of 10 benign hepatocellular neoplasms developed in three patients with cirrhosis. Markers allowing hepatocellular adenoma classification were assessed by quantitative real-time PCR and immunohistochemistry. Samples were sequenced for CTNNB1, HNF1A, IL6ST, GNAS, STAT3, and TERT (promoter) mutations. A control series of 32 classical macronodules developed in cirrhosis related to various etiologies was screened by immunohistochemistry and gene sequencing. The three patients had cirrhosis related to metabolic syndrome and/or alcohol intake; two had a single tumor, while the third developed more than 30 lesions. Microscopic examination showed well-differentiated neoplasms sharing features with inflammatory adenoma including inflammatory infiltrates, sinusoidal dilatation, and dystrophic vessels. Sequencing revealed classical hotspot somatic mutations (IL6ST, n=8; STAT3, n=1; and GNAS, n=1) known to be responsible for IL-6/JAK/STAT pathway activation. Two classical high-grade macronodules demonstrated high serum amyloid A and/or C-reactive protein expression, without gene mutations. Altogether, our findings support the existence of rare inflammatory adenoma developed in cirrhosis. PMID:26516697

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

    PubMed Central

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

    2012-01-01

    Background & aims Minimal hepatic encephalopathy (MHE) has significant impact on future clinical outcomes, such as occurrence of overt HE (OHE) and survival in patients of cirrhosis. In the absence of a ‘gold standard’, psychometric hepatic encephalopathy score (PHES) is widely used for the diagnosis of MHE. This cross-sectional and prospective study was carried out to determine the usefulness of inhibitory control test (ICT) for the diagnosis of MHE. Methods One hundred and two patients with cirrhosis and without a history of OHE were enrolled in to the study and were subjected to PHES and ICT. MHE was diagnosed when the PHES was ? ?5. ICT was considered abnormal when the numbers of ICT lures were more than 14. Results Forty-one (40.2%) patients had MHE. There were 40 patients with normal PHES and ICT, 32 with abnormal PHES and ICT, 9 with abnormal PHES and normal ICT, and 21 with abnormal ICT and normal PHES score. ICT had 78% sensitivity and 65.6% specificity and an area-under-the-curve value of 0.735 (95% CI = 0.632–0.830) for the diagnosis of MHE. In patients with cirrhosis, ICT did not correlate with severity of liver disease as measured by CTP score (r = 0.044, P = 0.658) and MELD score (r = 0.176, P = 0.077). ICT did not predict survival as well as PHES; while 6 (11.3%) patients died among those who had altered ICT compared to 4 (8.2%) patients who did not have altered ICT (P = 0.74), 8 (19.5%) patients died among those who had altered PHES compared to 2 (3.3%) patients who did not have altered PHES (P = 0.013). Conclusion ICT is not as useful as PHES in diagnosing MHE in patients with cirrhosis of the liver. It does not correlate with disease severity and predict survival as well as PHES. PMID:25755452

  11. Primary biliary cirrhosis

    MedlinePLUS

    Primary biliary cirrhosis is irritation and swelling (inflammation) of the bile ducts of the liver. This blocks the flow ... ducts in the liver is not known. However, primary biliary cirrhosis is an autoimmune disorder. That means your body's ...

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

    PubMed

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

    2015-05-01

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

  13. 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.

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. Prediction of Esophageal Variceal Bleeding in Liver Cirrhosis: Is There a Role for Hemostatic Factors?

    PubMed

    Barrera, Francisco; Zúñiga, Pamela; Arrese, Marco

    2015-07-01

    Variceal bleeding is a frequent and ominous complication of liver cirrhosis. Fortunately, primary prophylaxis with ? blockers or esophageal band ligation effectively reduces the risk of variceal bleeding and its associated mortality. Periodic endoscopic surveillance of esophageal varices (EV) is currently recommended in every patient with cirrhosis for early detection of EV and initiation of primary variceal bleeding prophylaxis is indicated for high-risk patients. During the last decades several noninvasive tests have emerged, aiming to facilitate access, reduce cost, and avoid unnecessary risk associated with endoscopic EV surveillance. In addition, several hemostatic abnormalities have been described in cirrhosis, and their role in variceal bleeding pathogenesis is yet to be defined. In this article, we review and critically analyze the accuracy of noninvasive EV predictors and utility of hemostatic factors to predict individual variceal bleeding risk. In addition, we summarize available data regarding the therapeutic role of hemostatic factors in primary prevention of variceal bleeding and early recurrence after an initial episode of variceal hemorrhage. PMID:26049066

  20. 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

  1. Non-alcoholic steatohepatitis-related liver cirrhosis is increasing in China: A ten-year retrospective study

    PubMed Central

    Xiong, Ji; Wang, Jun; Huang, Juan; Sun, Wenjing; Wang, Jun; Chen, Dongfeng

    2015-01-01

    OBJECTIVE: Little is known about metabolic factors in cirrhotic patients in China. Therefore, we aimed to quantify the prevalence of both metabolic factors and non-alcoholic steatohepatitis-related liver cirrhosis in China. METHODS: The medical records of 1,582 patients diagnosed with liver cirrhosis from June 2003 to July 2013 at Daping Hospital (Chongqing, China) were retrospectively reviewed through a computer-generated search. RESULTS: Serum hepatitis B virus surface antigen was present in 1,083 (68.5%) patients, and hepatitis B was found to be the only etiological factor in 938 (59.3%) of all patients. Obesity, diabetes mellitus, and arterial hypertension were observed in 229 (14.5%), 159 (10.1%), and 129 (8.2%) patients, respectively. From 2012-2013, the proportion of non-alcoholic steatohepatitis-related liver cirrhosis increased to 3.2%, whereas the average proportion of non-alcoholic steatohepatitis-related liver cirrhosis in the previous ten years was 1.9%. The incidence of hepatocellular carcinoma was much higher in males than in females (6.3% vs. 3.7%, respectively, p=0.036). Obesity and diabetes mellitus did not significantly increase the incidence of hepatocellular carcinoma in the whole cirrhotic group. The presence of hepatitis B virus was the only risk factor for hepatocellular carcinoma in cirrhotic patients (p<0.001). CONCLUSIONS: Although hepatitis B virus remains the main etiology of liver cirrhosis in China, steatohepatitis-related liver cirrhosis is increasing in frequency. Hepatitis B virus was the sole significant risk factor for hepatocellular carcinoma in the whole cirrhotic group in the present study, in contrast to obesity and diabetes mellitus, for which only a trend of increased hepatocellular carcinoma was found. PMID:26247669

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

    PubMed

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

    2014-03-01

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

  3. 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

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

    PubMed Central

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

    2015-01-01

    Liver cirrhosis (LC) is a chronic illness caused by inflammatory responses and progressive fibrosis. Globally, the most common causes of chronic liver disease include persistent alcohol abuse, followed by viral hepatitis infections and nonalcoholic fatty liver disease. However, regardless of the etiological factors, the susceptibility and degree of liver damage may be influenced by genetic polymorphisms that are associated with distinct ethnic and cultural backgrounds. Consequently, metabolic genes are influenced by variable environmental lifestyle factors, such as diet, physical inactivity, and emotional stress, which are associated with regional differences among populations. This Topic Highlight will focus on the genetic and environmental factors that may influence the metabolism of alcohol and nutrients in the setting of distinct etiologies of liver disease. The interaction between genes and environment in the current-day admixed population, Mestizo and Native Mexican, will be described. Additionally, genes involved in immune regulation, insulin sensitivity, oxidative stress and extracellular matrix deposition may modulate the degree of severity. In conclusion, LC is a complex disease. The onset, progression, and clinical outcome of LC among the Mexican population are influenced by specific genetic and environmental factors. Among these are an admixed genome with a heterogenic distribution of European, Amerindian and African ancestry; a high score of alcohol consumption; viral infections; a hepatopathogenic diet; and a high prevalence of obesity. The variance in risk factors among populations suggests that intervention strategies directed towards the prevention and management of LC should be tailored according to such population-based features. PMID:26556986

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

    Feld, Jordan J.; Lavoie, Élise G.; Michel, Fausther; 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

  7. Primary liver carcinoma and liver cirrhosis in atomic bomb survivors, Hiroshima and Nagasaki, 1961-75, with special reference to hepatitis B surface antigen

    SciTech Connect

    Asano, M.; Kato, H.; Yoshimoto, K.; Seyama, S.; Itakura, H.; Hamada, T.; Iijima, S.

    1982-12-01

    During 1961-75, 128 cases of primary liver carcinoma (PLC) in the Radiation Effects Research Foundation life-span study extended sample and 301 cases of liver cirrhosis in the pathology study sample were observed. The presence of hepatitis B surface antigen (HBsAg) was assessed in all of the cases with the use of orcein and aldehyde fuchsin stains and was confirmed by the immunofluorescence technique. The incidence of PLC was two times higher in Nagasaki than in Hiroshima, which was statistically significant, but little difference was noted in the prevalence of cirrhosis in the two cities. Findings that might possibly explain the higher PLC incidence in Nagasaki were 1) the 2.3 times higher presence in Nagasaki than in Hiroshima of HBsAg in the livers of subjects without liver disease and 2) the two times higher prevalence in Nagasaki than in Hiroshima of cirrhosis with PLC. We believe that the higher incidence of PLC in Nagasaki is attributable to hepatitis B virus infection, although other factors (e.g., immunologic competence affected by radiation) cannot be excluded. In both cities, a suggestive relationship of radiation dose to cirrhosis prevalence, but not to PCL prevalence, was noted. To clarify possible radiation effects on cirrhosis prevalence, further follow-up of the populations of these two cities is necessary.

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

  9. A patient with Simpson-Golabi-Behmel syndrome, biliary cirrhosis and successful liver transplantation.

    PubMed

    Jedraszak, Guillaume; Girard, Muriel; Mellos, Antonio; Djeddi, Djamal-Dine; Chardot, Christophe; Vanrenterghem, Audrey; Moizard, Marie-Pierre; Gondry, Jean; Sevestre, Henri; Mathieu-Dramard, Michele; Lacaille, Florence; Demeer, Benedicte

    2014-03-01

    Simpson-Golabi-Behmel syndrome type 1 (SGBS1) -OMIM 312870- is a rare X-linked inherited overgrowth syndrome caused by a loss of function mutation in the GPC3 gene. Affected patients present a variable phenotype with pre- and post-natal macrosomia, distinctive facial dysmorphism, organomegaly, and multiple congenital anomalies. Intellectual disability is not constant. About 10% of patients have an increased risk of developing embryonic tumors in early childhood. Only one case of biliary disease has been described so far. GPC3 is localized on Xq26. It encodes for glypican 3, a heparan sulfate proteoglycan, which among its different known roles, negatively regulates liver regeneration and hepatocyte proliferation. This report concerns a male with a SGBS1, carrier of a GPC3 pathogenic mutation, and neonatal liver disease, who developed an early biliary cirrhosis. Together with the associated risk of cancer and developmental delay, liver transplantation was discussed and then successfully performed at the age of 19 months. A hypothesis on the role of GPC3 in the patient's liver disease is also proposed. PMID:24357529

  10. Green tea polyphenol decreases the severity of portosystemic collaterals and mesenteric angiogenesis in rats with liver cirrhosis.

    PubMed

    Hsu, Shao-Jung; Wang, Sun-Sang; Hsin, I-Fang; Lee, Fa-Yauh; Huang, Hui-Chun; Huo, Teh-Ia; Lee, Wen-Shin; Lin, Han-Chieh; Lee, Shou-Dong

    2014-05-01

    Abnormal angiogenesis in liver cirrhosis often leads to severe complications such as variceal haemorrhage and encephalopathy. Furthermore, splanchnic angiogenesis elevates portal pressure, in which angiogenic factors play pivotal roles. GTP (green tea polyphenol) extracted from Camellia sinensis has anti-angiogenic properties, but the effects on the parameters described above in cirrhosis have not been investigated. The aim of the present study was to determine the effects of GTP in cirrhosis and to investigate the underlying mechanism. Liver cirrhosis was induced in Spraque-Dawley rats by common BDL (bile duct ligation). They randomly received GTP or DW (distilled water, vehicle) for 28 days, then haemodynamic parameters, portosystemic shunting, mesenteric window vascular density, intrahepatic angiogenesis, liver fibrosis, plasma VEGF (vascular endothelial growth factor) concentration, mesenteric angiogenic factor and receptor protein expression, and serum and mesenteric oxidative stress parameters were assessed. Compared with the DW group, GTP significantly decreased portosystemic shunting, liver fibrosis, intrahepatic angiogenesis, mesenteric window vascular density, VEGF concentration and down-regulated the mesenteric HIF (hypoxia-inducible factor)-1?, VEGF and phospho-Akt expression. In conclusion, GTP ameliorates the severity of portosystemic shunting and mesenteric angiogenesis via the suppression of HIF-1?, Akt activation and VEGF. GTP appears to be an appropriate agent in controlling portal hypertension-related complications via anti-angiogenesis. PMID:24063570

  11. What I Need to Know about Cirrhosis

    MedlinePLUS

    ... URL Español What I need to know about Cirrhosis Page Content On this page: What is cirrhosis? ... Pronunciation Guide For More Information Acknowledgments What is cirrhosis? Cirrhosis * is scarring of the liver. Scar tissue ...

  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. 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

  14. Effect of branched chain amino acid infusions on body protein metabolism in cirrhosis of liver.

    PubMed Central

    Wright, P D; Holdsworth, J D; Dionigi, P; Clague, M B; James, O F

    1986-01-01

    Thirty seven patients with established cirrhosis of the liver were subjected to measurement of body protein metabolism using L-(1-14C) labelled leucine as a tracer. The effects of disease severity and those of solutions containing 0%, 16%, 35%, 53%, and 100% branched chain amino acids were evaluated. Significant increases in protein synthesis were noted with solutions containing 35%, 53%, and 100% branched chain amino acids, but in patients receiving 100% branched chain amino acids without additional essential amino acid supplement the increase in synthesis was matched by a significant increase in protein breakdown. Protein balance was thus improved only in patients receiving 35% and 53% branched chain amino acids. It was concluded that the high increase in protein breakdown in patients receiving 100% branched chain amino acids was undesirable, and such a solution should not be recommended for clinical use. PMID:3539714

  15. Neutrophil Gelatinase Associated Lipocalin (NGAL) – a biomarker of renal dysfunction in patients with liver cirrhosis: Do we have enough proof?

    PubMed Central

    Firu, SG; Streba, CT; Firu, D; Tache, DE; Rogoveanu, I

    2015-01-01

    Rationale. Renal dysfunction has a serious impact on the natural evolution of liver cirrhosis. Treatment and prognosis may be improved if an early diagnosis could be established, and specific therapeutic interventions would be applied. Although RIFLE and AKIN classifications have been successfully implemented in the clinical practice of Nephrology and Intensive Care Units, these did not provide major improvements in patients with liver cirrhosis. In the last decade, various biomarkers of kidney injury have been assessed, and Neutrophil Gelatinase-Associated Lipocalin (NGAL) is one of the most promising and most studied novel biomarker. Objective. To offer a brief evaluation on current data on the utility of this biomarker in patients with liver cirrhosis. Methods and results. We have searched through current literature and analyzed all significant full text articles on this topic. Discussions. NGAL and other new kidney injury molecules may be useful in patients with liver cirrhosis, particularly in identifying structural kidney dysfunction, but larger validation studies to confirm this observation are needed. Abbreviations: ADQI = Acute Dialysis Quality Initiative, AKI = acute kidney injury, AKIN = Acute Kidney Injury Network, ATN = acute tubular necrosis, CKD = chronic kidney disease, Cys C = cystatin C, GFR = glomerular filtration rate, HRS = hepatorenal syndrome, IAC = International Ascites Club, IL-18 = interleukin-18, KIM-1 = kidney injury molecule-1, L-FABP = liver-type fatty acid-binding protein, LT = liver transplantation, MDRD6 = Modification of Diet in Renal Disease 6, NAG = N-acetyl-?-D-glucosaminidase, NGAL = Neutrophil Gelatinase-Associated Lipocalin, pi-GST = pi-glutathione S-transferase, PRA = prerenal azotemia, RBP = retinol binding protein, RRT = renal replacement therapies, SCr = serum creatinine, SLKT = simultaneous liver and kidney transplant, UO = urine output, ?-GT = ?-glutamyl transpeptidase PMID:26361506

  16. Efficacy and safety of tauroursodeoxycholic acid in the treatment of liver cirrhosis: a double-blind randomized controlled trial.

    PubMed

    Pan, Xiao-li; Zhao, Li; Li, Liang; Li, Ai-hua; Ye, Jin; Yang, Ling; Xu, Ke-shu; Hou, Xiao-hua

    2013-04-01

    No direct comparison of tauroursodeoxycholic acid (TUDCA) and ursodeoxycholic acid (UDCA) has yet been carried out in the treatment of liver cirrhosis in China. We designed a double-blind randomized trial to evaluate the potential therapeutic efficacy of TUDCA in liver cirrhosis, using UDCA as parallel control. The enrolled 23 patients with liver cirrhosis were randomly divided into TUDCA group (n=12) and UDCA group (n=11), and given TUDCA and UDCA respectively at the daily dose of 750 mg, in a randomly assigned sequence for a 6-month period. Clinical, biochemical and histological features, and liver ultrasonographic findings were evaluated before and after the study. According to the inclusion criteria, 18 patients were included in the final analysis, including 9 cases in both two groups. Serum ALT, AST and ALP levels in TUDCA group and AST levels in UDCA group were significantly reduced as compared with baseline (P<0.05). Serum albumin levels were significantly increased in both TUDCA and UDCA groups (P<0.05). Serum markers for liver fibrosis were slightly decreased with the difference being not significant in either group. Only one patient in TUDCA group had significantly histological relief. Both treatments were well tolerated and no patient complained of side effects. It is suggested that TUDCA therapy is safe and appears to be more effective than UDCA in the treatment of liver cirrhosis, particularly in the improvement of the biochemical expression. However, both drugs exert no effect on the serum markers for liver fibrosis during 6-month treatment. PMID:23592128

  17. Hepatic progenitor cells in human liver cirrhosis: Immunohistochemical, electron microscopic and immunofluorencence confocal microscopic findings

    PubMed Central

    Xiao, Jia-Cheng; Jin, Xiao-Long; Ruck, Peter; Adam, Anne; Kaiserling, Edwin

    2004-01-01

    AIM: To investigate whether hepatic progenitor cells (HPC), that reveal the features of oval cells in rodents and small epithelial cells (SEC) in certain human liver disease, were also found in human liver cirrhosis (HLC). METHODS: Surgical liver specimens from 20 cases of hepatitis B virus-positive HLC (15 cases containing hepatocellular carcinoma) were investigated by light microscopic immunohistochemistry (LM-IHC). Among them specimens from 15 cases were investigated by electron microscopy (EM) and those from 5 cases by immunofluorencence confocal laser scanning microscopy (ICLSM). Antibodies against cytokeratin 7 and albumin were used and single and/or double labelling were performed respectively. RESULTS: LM-IHC showed that at the margins of regenerating nodules and in the fibrous septae, a small number of cells in the proliferating bile ductules were positive for CK7 and albumin. At the EM level these HPC were morphologically similar to the SEC described previously, and also similar to the oval cells seen in experimental hepatocarcinogenesis. They were characterized by their small size, oval shape, a high nucleus/cytoplasm ratio, a low organelle content in cytoplasm, and existence of tonofilaments and intercellular junctions. ICLSM revealed that HPC expressed both cytokeratin 7 and albumin. CONCLUSION: HPC with ultrastructural and immunophenotypical features of oval cells, i.e., hepatic stem cell-like cells as noted in other liver diseases, were found in HLC. These findings further support the hypothesis that bipotent hepatic stem cells, that may give rise to biliary epithelial cells and hepatocytes, exist in human livers. PMID:15069727

  18. Clinical significance of aflatoxin, mutant P53 gene and sIL-2 receptor in liver cirrhosis and hepatocellular carcinoma.

    PubMed

    El-Shanawani, Faten M; Abdel-Hadi, Afaf A; Abu Zikri, Nadia B; Ismail, Alaa; El-Ansary, Mahmoud; El-Raai, Ahmed

    2006-04-01

    The incidence of hepatocellular carcinoma (HCC) varies widely worldwide. Chronic infection with hepatitis B virus (HBV) and exposure to aflatoxins in foodstuffs are the main risk factors. AAG to AGT transversion at codon 249 of the P53 gene arg-ser (249ser) has been identified as a hotspot, reflecting DNA damage caused by aflatoxin B1 metabolites in HCC. Because HBV infection is often endemic in high aflatoxin exposure areas, it is still not clear whether HBV acts as a con-founder or as a synergistic partner in the development of the 249ser P53 mutation. Serum levels of soluble interleukin 2 receptor (sIL-2R) correlated with the progression of liver cirrhosis independently of its etiology. This fact may reflect the stimulation of T-lymphocytes, monocytes and macrophages in liver cirrhosis. The inter-relationship among aflatoxin exposure, HBV & HCV infections, P53 & sIL-2R in patients with liver cirrhosis and hepatocellular carcinoma was studied. The results revealed significant increase in serum levels of mutant P53, sIL-2R and aflatoxin B1 in patients with cirrhosis and those with HCC compared to the controls. HCC patients showed levels of all the three parameters significantly higher than both cirrhotics and controls (P<0.001). Correlations were found between serum aflatoxin B1, mutant P53 and sIL-2R in HCC group. The results were discussed. PMID:16605112

  19. 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 ...

  20. 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

  1. 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 ?g/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/?L) 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

  2. 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

  3. 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

  4. 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

  5. Increased expression of 78 kD glucose-regulated protein promotes cardiomyocyte apoptosis in a rat model of liver cirrhosis

    PubMed Central

    Zhang, Lili; Zhang, Huiying; Lv, Minli; Jia, Jiantao; Fan, Yimin; Tian, Xiaoxia; Li, Xujiong; Li, Baohong; Ji, Jingquan; Wang, Limin; Zhao, Zhongfu; Han, Dewu; Ji, Cheng

    2015-01-01

    Aims: This study was to investigate the role and underlying mechanism of 78 kD glucose-regulated protein (GRP78) in cardiomyocyte apoptosis in a rat model of liver cirrhosis. Methods: A rat model of liver cirrhosis was established with multiple pathogenic factors. A total of 42 male SD rats were randomly divided into the liver cirrhosis group and control group. Cardiac structure analysis was performed to assess alterations in cardiac structure. Cardiomyocytes apoptosis was detected by TdT-mediated dUTP nick end labeling method. Expression of GRP78, CCAAT/enhancer-binding protein homologous protein (CHOP), caspase-12, nuclear factor kappa-light-chain-enhancer of activated B cells p65 subunit (NF-?B p65) and B cell lymphoma-2 (Bcl-2) was detected by immunohistochemical staining. Results: The ratios of left ventricular wall thickness to heart weight and heart weight to body weight were significantly increased with the progression of liver cirrhosis (P < 0.05). Apoptosis index of cardiomyocytes was significantly increased with the progression of liver cirrhosis (P < 0.05). The expression levels of GRP78, CHOP and caspase-12 were significantly increased in the progression of liver cirrhosis (P < 0.05). The expression levels of NF-?B p65 and Bcl-2 were highest in the 4-wk liver cirrhosis, and they were decreased in the 6-wk and 8-wk in the progression of liver cirrhosis. GRP78 expression levels were positively correlated with apoptosis index, CHOP and caspase-12 expression levels (P < 0.05). CHOP expression levels were negatively correlated with NF-?B p65 and Bcl-2 expression levels (P < 0.05). Conclusion: Increased expression of GRP78 promotes cardiomyocyte apoptosis in rats with cirrhotic cardiomyopathy. PMID:26464674

  6. 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 ?-1-acid glycoprotein) of blood plasma from patients at different stages of liver cirrhosis by the fluorescent probe method. We used the hydrophobic fluorescent probes anionic 8-anilinonaphthalene-1-sulfonate, which interacts in blood plasma mainly with albumin; cationic Quinaldine red, which interacts with ?-1-acid glycoprotein; and neutral Nile red, which redistributes between lipoproteins and albumin in whole blood plasma. We show that the binding ability of albumin and ?-1-acid glycoprotein to negatively charged and positively charged hydrophobic metabolites, respectively, increases in the compensation stage of liver cirrhosis. As the pathology process deepens and transitions into the decompensation stage, the transport abilities of albumin and ?-1-acid glycoprotein decrease whereas the binding ability of lipoproteins remains high.

  7. 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.

  8. 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-in?ammatory drugs (NSAIDs) are best avoided because of risk of renal impairment, hepatorenal syndrome, and gastrointestinal hemorrhage. Most opioids can have deleterious effects in patients with cirrhosis. They have an increased risk of toxicity and hepatic encephalopathy. They should be administrated with lower and less frequent dosing in these patients and be avoided in patients with a history of encephalopathy or addiction to any substance. Conclusions: No evidence-based guidelines exist on the use of analgesics in patients with liver disease and cirrhosis. As a result pain management in these patients generates considerable misconception among health care professionals, leading under-treatment of pain in this population. Providing concrete guidelines toward the administration of these agents will lead to more efficient and safer pain management in this setting. PMID:25477978

  9. 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??g/mL). This study showed hepatoprotective effect of ERZO. PMID:24396831

  10. Optical biopsy of liver fibrosis by use of multiphoton microscopy

    NASA Astrophysics Data System (ADS)

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

    2004-11-01

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

  11. 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

  12. Hepatocellular carcinoma and liver cirrhosis TP53 mutation analysis reflects a moderate dietary exposure to aflatoxins in Espírito Santo State, Brazil.

    PubMed

    de Carvalho, Fernanda Magri; de Almeida Pereira, Thiago; Gonçalves, Patrícia Lofego; Jarske, Robson Dettmann; Pereira, Fausto Edmundo Lima; Louro, Iuri Drumond

    2013-08-01

    The close relationship between aflatoxins and 249ser TP53 gene mutation (AGG to AGT, Arg to Ser) in hepatocellular carcinoma (HCC) makes this mutation an indirect indicator of dietary contamination with this toxin. We have examined the prevalence of codon 249 TP53 mutation in 41 HCC and 74 liver cirrhosis (without HCC) cases diagnosed at the HUCAM University Hospital in Vitoria, Espírito Santo State, Brazil. DNA was extracted from paraffin sections and from plasma. The mutation was detected by DNA amplification, followed by restriction endonuclease digestion and confirmed by direct sequencing. DNA restriction showed 249ser mutation in 16 HCC and 13 liver cirrhosis, but sequencing confirmed mutations in only 6 HCC and 1 liver cirrhosis. In addition, sequencing revealed 4 patients with mutations at codon 250 (250ser and 250leu) in HCC cases. The prevalence of TP53 mutation was 10/41 (24.3%) in HCC and 1/74 (1.4%) in liver cirrhosis. No relationship between the presence of mutations and the etiology of HCC was observed. TP53 exon 7 mutations, which are related to aflatoxins exposure, were found at 14.6% (249ser), 7.3% (250leu) and 2.4% (250ser) in 41 cases of HCC and 1.4% in 74 liver cirrhosis (without HCC) cases, suggesting a moderate dietary exposure to aflatoxins in the Espírito Santo State, Brazil. PMID:23649769

  13. 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

  14. Association between D-dimer level and portal venous system thrombosis in liver cirrhosis: a retrospective observational study

    PubMed Central

    Dai, Junna; Qi, Xingshun; Peng, Ying; Hou, Yue; Chen, Jiang; Li, Hongyu; Guo, Xiaozhong

    2015-01-01

    Objective: This study aimed to explore the association between D-dimer levels and presence of portal venous system thrombosis (PVST) in liver cirrhosis. Methods: All consecutive patients with a diagnosis of liver cirrhosis who underwent D-dimer test were retrospectively enrolled. Normal reference range of D-dimer level was 0-0.3 µg/mL. PVST was diagnosed on the basis of contrast-enhanced computed tomography and/or magnetic resonance imaging scans. Results: Of the 66 included patients, 24 were diagnosed with PVST. Mean D-dimer level was 0.51±0.72 µg/mL (range: 0.10-3.44). Mean D-dimer level was not significantly different between PVST and non-PVST groups (0.68±0.93 µg/mL versus 0.41±0.56 µg/mL, P=0.146). Area under the receiver operating curve for D-dimer level for predicting the presence of PVT was 0.606 (95% confidence interval: 0.478-0.724, P=0.1393). The optimal cut-off value for D-dimer was 0.22 with a sensitivity of 58.3% and a specificity of 69.0%. The subgroup analyses of patients without splenectomy or those with different Child-Pugh classes demonstrated no significant difference in the D-dimer level between PVST and non-PVST groups. Conclusion: D-dimer might not be useful to identify the presence of PVST in liver cirrhosis. However, given the retrospective nature of this study, further well-designed prospective study should be necessary to confirm this finding. PMID:26629017

  15. Mechanism of insulin resistance in human liver cirrhosis. Evidence of a combined receptor and postreceptor defect.

    PubMed Central

    Cavallo-Perin, P; Cassader, M; Bozzo, C; Bruno, A; Nuccio, P; Dall'Omo, A M; Marucci, M; Pagano, G

    1985-01-01

    Insulin resistance in liver cirrhosis may depend on either reduced sensitivity (receptor defect) and/or reduced response to insulin (postreceptor defect). To clarify the mechanism of such resistance, a [3H]glucose infusion (0.2 microCi/min) was performed for 120 min before and during a euglycemic clamp at approximately 100, 1,000, and 10,000 microU/ml steady state plasma insulin concentration in 18 compensated cirrhotics with portal hypertension and impaired glucose tolerance, and 18 healthy volunteers with no family history of diabetes, matched for sex, age, and weight. Mean fasting plasma insulin (29.2 +/- 3.4 SEM vs. 14.8 +/- 1.1 microU/ml) was significantly higher (P less than 0.001) in cirrhotics, while fasting plasma glucose was much the same in the two groups. Glucose use (milligrams per kilogram per minute) was significantly lower in cirrhotics at all three steady state plasma insulin levels: 3.04 +/- 0.34 vs. 7.72 +/- 0.61 (P less than 0.001) at approximately 100; 6.05 +/- 1.07 vs. 11.45 +/- 1.24 (P less than 0.001) at approximately 1,000; and 11.69 +/- 0.69 vs. 14.13 +/- 0.74 (P less than 0.05) at approximately 10,000 microU/ml. Mean plasma C-peptide was significantly higher in cirrhotics both basally and during the steady states (P less than 0.001); it was completely suppressed at approximately 10,000 microU/ml in controls and only 57.5% of the baseline in cirrhotics. Endogenous glucose production (milligrams per kilogram per minute) was much the same in the two groups in the fasting state and almost entirely suppressed in the controls (0.10 +/- 0.05 vs. 0.48 +/- 0.11, P less than 0.001) at approximately 100 microU/ml; at approximately 1,000 microU/ml a residual glucose production, 0.07 +/- 0.05, was observed in the cirrhotics only. In addition, insulin binding and 3-ortho-methyl-glucose transport were studied in vitro in six cirrhotics and six controls. Insulin binding to circulating monocytes and isolated adipocytes was significantly lower (P less than 0.025) in cirrhotics in all insulin concentration studies. Glucose transport values on isolated adipocytes were significantly lower in cirrhotics both basally (P less than 0.001) and at maximal insulin concentration (P less than 0.05). These results suggest that insulin resistance in human cirrhosis is more dependent on depressed peripheral glucose use than on increased endogenous glucose production, and that a combined receptor and postreceptor defect in insulin action on target cells seems to be present. PMID:3889056

  16. Hepatic silicosis, cirrhosis, and liver tumors in mice and hamsters: studies of transforming growth factor beta expression.

    PubMed

    Williams, A O; Knapton, A D

    1996-05-01

    Hepatic silicosis, cirrhosis, liver cell adenoma, and carcinomas developed in nude mice (NCr-Nu) given quartz by the subcutaneous and intraperitoneal routes. Syrian golden hamsters (15:16 EHS:cr) given quartz by both routes developed extensive fibrosis and cirrhosis and had higher morbidity and mortality rates after 3 months. Crystalline silica (quartz) induces fibrosis, adenomas, and carcinomas in the lungs of Fisher 344 rats, but certain strains of mice and hamsters are resistant to quartz-induced pulmonary carcinogenesis. Pulmonary fibrosis, however, is minimal in mice and absent in hamsters who received quartz intratracheally. To determine whether species differences are due to organ-specific rather than species-specific factors, susceptibility of the liver to quartz toxicity was investigated in nude mice and hamsters. The present study shows that the differential manifestations of quartz toxicity by these rodent species are dependent on factors that are organ-specific rather than host-specific. At 3 months, hepatocytes in mice were immunostained with intracellular transforming growth factor (TGF) beta 1 (LC 1-30) but not with TGF-beta 1 latency-associated peptide (LAP) protein (266-278); at 12 months, hepatocytes were immunostained with TGF-beta 1 LAP (266-278) but not with TGF-beta 1 (LC1-30). The hepatocytes of hamsters at 3 months showed immunoreactivities to TGF-beta 1 LAP (266-278) and TGF-beta 1 (LC1-30); immunostaining to TGF-beta 1 (LC1-30) was detected in nonparenchymal cells. Extracellular TGF-beta 1 (CC1-30) was detected in the silicotic granulomas and fibrous tissue in livers of both species. Quartz-induced liver carcinoma did not express TGF-beta 1 LAP (266-278) and LC (1-30) proteins, but these were detected in the cells of the adenoma in the same liver. Control animals showed no hepatic lesions nor immunoreactivity to TGF-beta 1. The spatial and temporal patterns of expression of TGF-beta 1, TGF-beta 2, TGF-beta receptor type II messenger RNAs (mRNAs), and TGF-beta 1 proteins in the different hepatic lesions suggests that TGF-beta isoforms may play a role in the pathogenesis of quartz-induced fibrosis, cirrhosis, liver cell adenoma, and carcinoma. PMID:8621163

  17. Plasma levels of substance P in liver cirrhosis: relationship to the activation of vasopressor systems and urinary sodium excretion.

    PubMed

    Fernández-Rodriguez, C M; Prieto, J; Quiroga, J; Zozoya, J M; Andrade, A; Núñez, M; Sangro, B; Penas, J

    1995-01-01

    The mediators of the hyperdynamic circulation of liver cirrhosis are not well characterized. Substance P is a potent vasodilatory peptide produced by the enteric nervous system and partly cleared by the liver. In this work we have investigated the plasma levels of substance P and their relationship to the hemodynamic, neurohormonal, and renal function changes occurring in patients with cirrhosis. Seven healthy subjects (control group), 7 cirrhotic patients without ascites (group I), and 24 cirrhotic patients with ascites (group II) were studied. Cardiac output (CO), femoral blood flow (FBF), blood volume (BV), femoral arteriovenous difference of oxygen content (Ca-v O2), plasma renin activity (PRA), plasma aldosterone concentration (PAC), and plasma norepinephrine (NE) were determined. Five patients underwent trans-jugular intrahepatic porto-systemic stent shunt (TIPSS) because of refractory ascites. Immunoreactive substance P (irSP) was measured by radioimmunoassay after plasma extraction. irSP was higher in ascitic patients than in healthy controls (P < .01) and directly correlated with PRA, PAC, plasma NE, and Pugh's score and was inversely correlated with urinary sodium excretion, glomerular filtration rate, and Ca-v O2. No differences were observed between portal and peripheral vein irSP concentration. TIPSS placement induced a decrease in portal pressure and an increase in CO but circulating irSP remained unchanged. Our data show that circulating irSP is increased in decompensated cirrhotic patients and may be involved in the pathogenesis of the hemodynamic changes of cirrhosis. Alleviation of portal hypertension did not result in decreased plasma levels of this vasodilatory substance. PMID:7528711

  18. Recurrence of primary biliary cirrhosis and development of autoimmune hepatitis after liver transplant: A blind histologic study

    PubMed Central

    Hytiroglou, Prodromos; Gutierrez, Julio A.; Freni, Maria; Odin, Joseph A.; Stanca, Carmen M.; Merati, Sukma; Schiano, Thomas D.; Branch, Andrea D.; Thung, Swan N.

    2011-01-01

    Aim This long-term study aimed to evaluate recurrence and evolution of primary biliary cirrhosis (PBC) after orthotopic liver transplantation (OLT). Methods We reviewed “blindly” allograft biopsy specimens of women who underwent transplantation for PBC (n = 84), and women who received a transplant for chronic hepatitis C virus infection (CHCV) (n = 108). All needle liver biopsy specimens obtained more than 6 months post-OLT were examined, including 83 specimens from 44 PBC patients and 152 specimens from 58 CHCV patients. Results Granulomatous destructive cholangitis was found in five biopsies from four PBC patients (P = 0.0048). Non-necrotizing epithelioid cell granulomas were present in four biopsies from four PBC patients, and in two biopsies from one CHCV patient. Piecemeal necrosis (P = 0.0002), lobular necroinflammatory activity (P < 0.0001), steatosis (P < 0.0001) and fibrosis (P < 0.0001) were more prevalent in CHCV patients than PBC patients. Four PBC patients developed histologic evidence of autoimmune hepatitis (AIH), at a mean time of 3.66 years post-OLT. One of these patients had histologic features of AIH/PBC overlap syndrome. All four patients developed bridging fibrosis (n = 2) or cirrhosis (n = 2). No other PBC patient had evidence of cirrhosis after OLT. Conclusions Histologic findings indicative of recurrent PBC were present in 15.9% of the PBC patients undergoing biopsy in this series. However, this group of patients did not suffer significant bile duct loss or fibrosis, as compared to the control group, suggesting that recurrent PBC is a mild or slowly progressive disease. Histologic evidence of AIH was observed in allograft biopsies of some PBC patients. PMID:19207586

  19. Using Ultrasonic Transient Elastometry (FibroScan) to Predict Esophageal Varices in Patients with Viral Liver Cirrhosis.

    PubMed

    Hu, Zhongwei; Li, Yuyuan; Li, Chuo; Huang, Chunming; Ou, Zhitao; Guo, Jiawei; Luo, Hongbin; Tang, Xiaoping

    2015-06-01

    The correlation between liver stiffness (LS), measured by ultrasonic transient elastometry (FibroScan), and the presence and severity of esophageal varices (EV) in patients with viral cirrhosis of the liver has not been well documented to date. The study described here investigated the value of using FibroScan to predict EV. Patients with cirrhosis (200 patients: 167 cases caused by hepatitis B virus and 33 cases caused by hepatitis C virus) underwent both upper gastrointestinal endoscopy and FibroScan. Demographic, clinical, biochemical and endoscopic data and FibroScan-obtained LS parameters were collected. The mean LS value in patients with EV (33.2 kPa) was significantly higher than the mean LS value in patients without EV (18.6 kPa) (p < 0.05). The mean LS value in patients with grade 2 and 3 EV (38.3 kPa) was significantly higher than that in patients with grade 1 EV (24.8 kPa) (p < 0.05). Overall, FibroScan was 86.4% sensitive and 72.2% specific in predicting the presence of EV, with an area under the receiver operating characteristic curve (AUROC) of 0.84. The sensitivity and specificity for the patients with grade 2 or 3 EV were 84% and 73% (AUROC = 0.86). When FibroScan was combined with platelet count, the overall sensitivity and specificity of prediction increased to 84% and 80% (AUROC = 0.88), respectively, and 84% and 75% (AUROC = 0.89), respectively, in patients with grade 2 and 3 EV. FibroScan alone or combined with platelet count might predict the presence and severity of EV in patients with hepatitis B or C-related viral cirrhosis. PMID:25817781

  20. 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

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

    PubMed Central

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

    2014-01-01

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

  2. Helicobacter pylori infection in patients with liver cirrhosis: facts and fictions.

    PubMed

    Zullo, A; Hassan, C; Morini, S

    2003-03-01

    Helicobacter pylori infection could play a role in different clinical alterations observed in cirrhosis, from gastroduodenal lesions to hepatic encephalopathy. Although its prevalence in cirrhotics is similar to that in controls, H. pylori infection is responsible for the increased prevalence of peptic ulcer observed in these patients. The ammonia production by H. pylori urease does not seem to increase blood ammonia levels during cirrhosis, indicating that its role in hepatic encephalopathy could be marginalized in clinical practice. Dual and triple therapies have been shown to be equally effective for H. pylori eradication in these patients. PMID:12779075

  3. 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

  4. 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.

  5. 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

  6. In recurrent primary biliary cirrhosis after liver transplantation, biliary epithelial cells show increased expression of mitochondrial proteins.

    PubMed

    Sasaki, Motoko; Hsu, Maylee; Yeh, Matthew M; Nakanuma, Yasuni

    2015-10-01

    In biliary epithelial lesions in primary biliary cirrhosis (PBC), mitochondrial proteins associated with deregulated autophagy are abnormally expressed. We examined whether this could be used as a diagnostic marker for end-stage PBC and recurrent PBC after liver transplantation. We examined the expression of the mitochondrial protein pyruvate dehydrogenase complex-E2 component and cytochrome c oxidase, subunit I (CCO), the autophagy-related marker microtubule-associated protein-light chain 3 (LC3), and p62/sequestosome-1 and the senescence markers p16(Ink4a) and p21(WAF1/Cip1) in small bile ducts and bile ductules in explanted livers from patients with PBC (n?=?20) in comparison with liver tissue from control patients (n?=?21) and post-transplant samples including recurrent PBC and cellular rejection (n?=?28). Intense granular expression of mitochondrial proteins was significantly more frequent in small bile ducts in explanted livers with PBC than in control livers (p?liver transplantation. PMID:26259963

  7. Opposite effects of sleep deprivation on the continuous reaction times in patients with liver cirrhosis and normal persons.

    PubMed

    Lauridsen, Mette Munk; Frøjk, Jesper; de Muckadell, Ove B Schaffalitzky; Vilstrup, Hendrik

    2014-09-01

    The continuous reaction times (CRT) method describes arousal functions. Reaction time instability in a patient with liver disease indicates covert hepatic encephalopathy (cHE). The effects of sleep deprivation are unknown although cirrhosis patients frequently suffer from sleep disorders. The aim of this study was to determine if sleep deprivation influences the CRT test. Eighteen cirrhosis patients and 27 healthy persons were tested when rested and after one night's sleep deprivation. The patients filled out validated sleep quality questionnaires. Seven patients (38%) had unstable reaction times (a CRTindex?cirrhosis patients, sleep disturbances do not lead to 'falsely' slowed and unstable reaction times. In contrast, the acute sleep deprivation slowed and destabilized the reaction times of the healthy participants. This may have negative consequences for decision-making. PMID:25008562

  8. The PNPLA3 rs738409 148M/M Genotype Is a Risk Factor for Liver Cancer in Alcoholic Cirrhosis but Shows No or Weak Association in Hepatitis C Cirrhosis

    PubMed Central

    Luda, Carolin; Berg, Thomas; Müller, Tobias; Grünhage, Frank; Lammert, Frank; Coenen, Martin; Krämer, Benjamin; Körner, Christian; Vidovic, Natascha; Oldenburg, Johannes; Nattermann, Jacob; Sauerbruch, Tilman; Spengler, Ulrich

    2011-01-01

    Background An isoleucine>methionine mutation at position 148 in the PNPLA3 gene (p.I148M, rs738409) has recently been identified as a susceptibility factor for liver damage in steatohepatitis. Here, we studied whether the PNPLA3 rs738409 polymorphism also affects predisposition to hepatocellular carcinoma (HCC). Methods We compared distributions of PNPLA3 genotypes in 80 and 81 Caucasian patients with alcoholic and hepatitis C virus (HCV)-associated HCC to 80 and 81 age- and sex-matched patients with alcohol-related and HCV-related cirrhosis without HCC, respectively. PNPLA3 genotypes in 190 healthy individuals from the same population served as reference. Potential confounders obesity, diabetes, HCV genotype and HBV co-infection were controlled by univariate and multivariate logistic regression with forward variable selection. Results PNPLA3 genotypes were in Hardy-Weinberg equilibrium for all study groups. The frequency of the 148M allele was significantly (p<0.001) increased in alcoholic cirrhosis with (53.7%) and without HCC (36.2%) but was not different between healthy controls (22.9%) and patients with cirrhosis (25.3%; p?=?0.545) and HCC (30.2%; p?=?0.071) due to hepatitis C. HCC risk was highest in 148M/M homozygous patients with alcoholic liver disease (odds ratio (OR) 16.8 versus healthy controls; 95% confidence interval (CI) 6.68–42.43, p<0.001). Finally, multivariate regression confirmed 148M/M homozygosity (OR 2.8; 95%-CI: 1.24–6.42; p?=?0.013) as HCC risk factor in alcoholic cirrhosis. In HCV-related cirrhosis only HCV genotype 1 was confirmed as a HCC risk factor (OR 4.2; 95%-CI: 1.50–11.52; p?=?0.006). Conclusion The PNPLA3 148M variant is a prominent risk factor for HCC in patients with alcoholic cirrhosis, while its effects are negligible in patients with cirrhosis due to HCV. This polymorphism provides an useful tool to identify individuals with particularly high HCC risk in patients with alcoholic liver disease that should be taken into account in future HCC prevention studies. PMID:22087248

  9. 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

  10. 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

  11. Ginkgo biloba extract mitigates liver fibrosis and apoptosis by regulating p38 MAPK, NF-?B/I?B?, 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-?Bp65 via inhibition of I?B? 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/I?B? 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/I?B? signaling pathways (inhibiting inflammation and HSCs activation) and 2) the Bcl-2/Bax signaling pathway (inhibiting the apoptosis of hepatocytes). PMID:26664050

  12. HIV and HHV-8 negative primary effusion lymphoma in a patient with hepatitis C virus-related liver cirrhosis.

    PubMed

    Paner, Gladell P; Jensen, Joanne; Foreman, Kimberly E; Reyes, Cesar V

    2003-10-01

    Primary effusion lymphoma (PEL) or body cavity-based lymphoma (BCBL) is a unique subgroup of B-cell lymphomas that exhibits exclusive or dominant involvement of serous body cavities without a detectable tumor mass. We present a case of a PEL/BCBL that exclusively involved the peritoneal cavity of a 58-year-old immunocompetent male with hepatitis C virus (HCV)-related liver cirrhosis. The lymphoma cells were large, highly atypical and expressed CD19, CD20, CD22, CD10, HLA-DR, and CD45 with kappa light chain restriction. Unlike typical PEL/BCBL, human herpesvirus type 8/Kaposi sarcoma herpes virus (HHV-8/KSHV) genomic sequence was not present in the lymphoma cells and there was no serologic evidence of human immunodeficiency virus (HIV) infection. This is the fourth reported case of HHV-8 negative, HIV negative PEL/BCBL in a patient with associated HCV-related cirrhosis and review of these cases showed some consistent clinicopathological features, i.e. exclusive involvement of the peritoneal cavity and phenotypic expression of B-cell associated antigens in contrast to the generally null phenotype PEL/BCBL. The occurrence of these cases suggests that HCV may play an etiological role in a subcategory of PEL/BCBL not associated with HHV-8. PMID:14692539

  13. 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

  14. 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

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

    PubMed Central

    2013-01-01

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

  16. 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 ?(65)Cu was observed within the cirrhosis population and ?(65)Cu seems to be linked to the severity of the disease. Patients with end-stage liver disease showed a significantly lighter serum Cu isotopic composition. Many clinical parameters used for the diagnosis and monitoring of liver diseases, i.e. the levels of aspartate aminotransferase, De Ritis ratio, prothrombin and international normalized ratio, albumin, bilirubin, Na and C-reactive protein, correlate well with the ?(65)Cu values, as did the ceruloplasmin level and the ceruloplasmin/Cu concentration ratio. The isotopic composition of serum Cu appears to reveal the synthetic and hepatocellular function of the liver synergistically with inflammation and fluid retention in the cohort studied. A relevant relationship was also observed between ?(65)Cu and scores of mortality risk, such as the Model for End-stage Liver Disease (MELD) and MELD-Na. Thus, the isotopic composition of serum Cu shows potential as a new approach for the prognosis of liver disease, and although further investigation is required, for evaluation of the mortality risk in end-stage liver disease and prioritization of liver transplants. PMID:25644127

  17. Pattern analysis of serum alpha-fetoprotein in the early diagnosis of hepatocellular carcinoma in liver cirrhosis.

    PubMed

    Arrigoni, A; Andriulli, A; Gindro, T; Piantino, P; Capussotti, L; Rizzetto, M

    1988-01-01

    In a surveillance program for hepatocellular carcinoma (HCC), serum alpha-fetoprotein (AFP) was determined every 4 months in 164 patients with liver cirrhosis. Ultrasonography (US) was performed yearly or as dictated by abnormal AFP levels. During a follow-up of 32.5 +/- 20.8 months HCC was identified by US in 16 patients. In 9 of them the AFP levels rose steadily over 4 months, increasing 7, 8 and 12 months in 3 cases before the lesion became detectable by US. In 4 patients tumors developed despite persistently normal AFP levels. Nine more patients showed abnormal fluctuations of AFP but HCC was not detected. AFP sensitivity was higher at a low cut-off point (40 ng/ml) while specificity of the test appeared higher at the 200 ng/ml cut-off point. An AFP value rising steeply over a few months appeared more reliable than a fixed preset threshold in indicating carcinomatous transformation. Screening for AFP can be expected to uncover about 3/4 of HCC developing in cirrhotics with few false-positive reactions. The test may have a unique role in identifying a subset of liver tumors whose early expression is AFP production. PMID:2466093

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

    PubMed

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

    2012-01-01

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

  19. Platelet count combined with right liver volume and spleen volume measured by magnetic resonance imaging for identifying cirrhosis and esophageal varices

    PubMed Central

    Chen, Xiao-Li; Chen, Tian-Wu; Zhang, Xiao-Ming; Li, Zhen-Lin; Zeng, Nan-Lin; Zhou, Ping; Li, Hang; Ren, Jing; Xu, Guo-Hui; Hu, Jia-Ni

    2015-01-01

    AIM: To determine whether the combination of platelet count (PLT) with spleen volume parameters and right liver volume (RV) measured by magnetic resonance imaging (MRI) could predict the Child-Pugh class of liver cirrhosis and esophageal varices (EV). METHODS: Two hundred and five cirrhotic patients with hepatitis B and 40 healthy volunteers underwent abdominal triphasic-enhancement MRI and laboratory examination of PLT in 109/L. Cirrhotic patients underwent endoscopy for detecting EV. Spleen maximal width (W), thickness (T) and length (L) in mm together with spleen volume (SV) and RV in mm3 were measured by MRI, and spleen volume index (SI) in mm3 was obtained by W × T × L. SV/PLT, SI/PLT and RV × PLT/SV (RVPS) were calculated and statistically analyzed to assess cirrhosis and EV. RESULTS: SV/PLT (r = 0.676) and SI/PLT (r = 0.707) increased, and PLT (r = -0.626) and RVPS (r = -0.802) decreased with the progress of Child-Pugh class (P < 0.001 for all). All parameters could determine the presence of cirrhosis, distinguish between each class of Child-Pugh class, and identify the presence of EV [the areas under the curve (AUCs) = 0.661-0.973]. Among parameters, RVPS could best determine presence and each class of cirrhosis with AUCs of 0.973 and 0.740-0.853, respectively; and SV/PLT could best identify EV with an AUC of 0.782. CONCLUSION: The combination of PLT with SV and RV could predict Child-Pugh class of liver cirrhosis and identify the presence of esophageal varices. PMID:26401083

  20. ESI-LC-MS Method for Haptoglobin Fucosylation Analysis in Hepatocellular Carcinoma and Liver Cirrhosis.

    PubMed

    Zhang, Yiwei; Zhu, Jianhui; Yin, Haidi; Marrero, Jorge; Zhang, Xin-Xiang; Lubman, David M

    2015-12-01

    A method for the detection of fucosylated glycans from haptoglobin in patient serum has been developed that provides enhanced sensitivity. The workflow involves isolation of the haptoglobin using an HPLC-based affinity column followed by glycan removal, extraction, and desialylation. The fucosylated glycans are then derivatized by Meladrazine, which significantly enhances the detection of the glycans in electrospray ionization. The separation of the derivatized glycans in a HILIC column shows that eight glycans from haptoglobin can be detected using less than 1 ?L of a serum sample, with excellent reproducibility and quantitation, where without derivatization the glycans could not be detected. The ratio of the fucosylated peaks to their corresponding nonfucosylated forms shows that the fucosylated glycans are upregulated in the case of hepatocellular carcinoma (HCC) samples versus cirrhosis samples, where the relatively low abundance bifucosylated tetra-antennary form can be detected and may be a particularly good marker for HCC. PMID:26503433

  1. Ascites: A Common Problem in People with Cirrhosis

    MedlinePLUS

    ... Cirrhosis Ascites: A Common Problem in People with Cirrhosis Basics Resources Overview Accumulation of fluid in the ... called ascites. Ascites is common in people with cirrhosis and it usually develops when the liver is ...

  2. Mechanism of protective effect of phyllanthin against carbon tetrachloride-induced hepatotoxicity and experimental liver fibrosis in mice.

    PubMed

    Krithika, Rajesh; Jyothilakshmi, Vasavan; Prashantha, Karunakar; Verma, Ramtej J

    2015-11-01

    Chronic injury to liver triggers synthesis of extracellular matrix components resulting in progressive fibrosis and eventually cirrhosis. Transforming growth factor-?1 (TGF-?1) transduces its signal by binding to TGF-? type 1 receptor kinase or activin like kinase (ALK5) receptor and mediates hepatic fibrosis by increasing the transcription of downstream entities such as collagen via Smad2 and Smad3. The present study was carried out to investigate the mechanism by which phyllanthin, a hepatoprotective lignin isolated from the plant Phyllanthus amarus (P. amarus) exerts its anti-fibrotic effect. The inhibitory role of phyllanthin on ALK5 was first analyzed using molecular docking experiments. Phyllanthin was found to effectively bind to serine (Ser) 280 at the active site of ALK5 by forming hydrogen bonds. The in vivo protective effect of phyllanthin against carbon tetrachloride (CCl4)-induced hepatic fibrosis was established by studying the protein expressions of TGF-?1, ALK5 and Smad2 and 3 and by determining various biochemical and histopathological parameters. Phyllanthin was found to exert its anti-fibrotic effect by down-regulating TGF signaling pathway via ALK5 and Smad2 and 3 inhibition. PMID:26337812

  3. Primary biliary cirrhosis.

    PubMed

    Carey, Elizabeth J; Ali, Ahmad H; Lindor, Keith D

    2015-10-17

    Primary biliary cirrhosis is a chronic cholestatic liver disease characterised by destruction of small intrahepatic bile ducts, leading to fibrosis and potential cirrhosis through resulting complications. The serological hallmark of primary biliary cirrhosis is the antimitochondrial antibody, a highly disease-specific antibody identified in about 95% of patients with primary biliary cirrhosis. These patients usually have fatigue and pruritus, both of which occur independently of disease severity. The typical course of primary biliary cirrhosis has changed substantially with the introduöction of ursodeoxycholic acid (UDCA). Several randomised placebo-controlled studies have shown that UDCA improves transplant-free survival in primary biliary cirrhosis. However, about 40% of patients do not have a biochemical response to UDCA and would benefit from new therapies. Liver transplantation is a life-saving surgery with excellent outcomes for those with decompensated cirrhosis. Meanwhile, research on nuclear receptor hormones has led to the development of exciting new potential treatments. This Seminar will review the current understanding of the epidemiology, pathogenesis, and natural history of primary biliary cirrhosis, discuss management of the disease and its sequelae, and introduce research on new therapeutic options. PMID:26364546

  4. Effect of nadolol on liver haemodynamics and function in patients with cirrhosis.

    PubMed Central

    Merkel, C; Sacerdoti, D; Finucci, G F; Zuin, R; Bazzerla, G; Bolognesi, M; Gatta, A

    1986-01-01

    Beta-adrenoceptor blockers used in the medical management of portal hypertension decrease liver blood flow. The sporadic onset of hepatic encephalopathy during propranolol treatment was ascribed to this decrease. The aim of the present study was to evaluate the effect of chronic treatment with nadolol on liver blood flow and liver function. Nadolol, a non-cardioselective beta-adrenoceptor blocker, has been reported to be as powerful as propranolol in decreasing portal pressure. Before and after 1 month of treatment with nadolol at a dose reducing heart rate by 25%, in 15 cirrhotic patients with portal hypertension, the following parameters were determined: hepatic venous pressure gradient, hepatic blood flow, galactose eliminating capacity, aminopyrine metabolic activity, ICG clearance and intrinsic hepatic clearance. Hepatic venous pressure gradient and hepatic blood flow were decreased by nadolol. However liver function was not affected by the drug. We conclude that, despite a lowered hepatic blood flow, liver function is not affected by 1 month of nadolol treatment. PMID:3741719

  5. 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, Child–Pugh 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 0.31–3.92). The PT, APTT, and PLT levels were comparable between the 2 groups both before and after infusion (P?>?0.05). Incremental analyses showed that Child–Pugh 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

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

    PubMed Central

    2013-01-01

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

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

    PubMed

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

    1998-01-01

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

  8. Severe hepatic encephalopathy in a patient with liver cirrhosis after administration of angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker combination therapy: a case report

    PubMed Central

    2010-01-01

    Introduction A combination therapy of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers has been used to control proteinuria, following initial demonstration of its efficacy. However, recently concerns about the safety of this therapy have emerged, prompting several authors to urge for caution in its use. In the following case report, we describe the occurrence of a serious and unexpected adverse drug reaction after administration of a combination of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers to a patient with nephrotic syndrome and liver cirrhosis with severe portal hypertension. Case presentation We administered this combination therapy to a 40-year-old Caucasian man with liver cirrhosis in our Hepatology Clinic, given the concomitant presence of glomerulopathy associated with severe proteinuria. While the administration of one single drug appeared to be well-tolerated, our patient developed severe acute encephalopathy after the addition of the second one. Discontinuation of the therapy led to the disappearance of the side-effect. A tentative rechallenge with the same drug combination led to a second episode of acute severe encephalopathy. Conclusion We speculate that this adverse reaction may be directly related to the effect of angiotensin II on the excretion of blood ammonia. Therefore, we suggest that patients with liver cirrhosis and portal hypertension are at risk of developing clinically relevant encephalopathy when angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker combination therapy is administered, thus indicating the need for a careful clinical follow-up. In addition, the incidence of this serious side-effect should be rigorously evaluated in all patients with liver cirrhosis administered with this common treatment combination. PMID:20482828

  9. Liver transplantation for hepatocellular carcinoma on cirrhosis: Strategies to avoid tumor recurrence

    PubMed Central

    Vivarelli, Marco; Risaliti, Andrea

    2011-01-01

    Hepatocellular carcinoma (HCC) is one of the most frequent neoplasms worldwide and in most cases it is associated with chronic liver disease. Liver transplantation (LT) is potentially the optimal treatment for those patients with HCC who have a poor functional hepatic reserve due to their underlying chronic liver disease. However, due to the limited availability of donors, only those patients whose oncologic profile is favorable can be considered for LT. Despite the careful selection of candidates based on strict rules, 10 to 20% of liver transplant recipients who have HCC in the native cirrhotic liver develop tumor recurrence after transplantation. The selection criteria presently employed to minimize the risk of recurrence are based on gross tumor characteristics defined by imaging techniques; unfortunately, the accuracy of imaging is far from being optimal. Furthermore, microscopic tumor features that are strictly linked with prognosis can not be assessed prior to transplantation. Pre-transplantation tumor downstaging may allow transplantation in patients initially outside the selection criteria and seems to improve the prognosis; it also provides information on tumor biology. The main peculiarity of the transplantation setting, when this is compared with other modalities of treatment, is the need for pharmacological immunosuppression: this is based on drugs that have been demonstrated to increase the risk of tumor development. As HCC is an aggressive malignancy, immunosuppression has to be handled carefully in patients who have HCC at the time of transplantation and new categories of immunosuppressive agents should be considered. Adjuvant chemotherapy following transplantation has failed to show any significant advantage. The aim of the present study is to review the possible strategies to avoid recurrence of HCC after liver transplantation based on the current clinical evidence and the more recent developments and to discuss possible future directions. PMID:22147974

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

    PubMed Central

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

    2014-01-01

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

  11. Sclerosing encapsulating peritonitis (abdominal cocoon) associated with liver cirrhosis and diffuse large B-cell lymphoma: autopsy case.

    PubMed

    Yamada, Sohsuke; Tanimoto, Akihide; Matsuki, Yasumasa; Hisada, Yuji; Sasaguri, Yasuyuki

    2009-09-01

    A case of sclerosing encapsulating peritonitis (SEP) associated with liver cirrhosis (LC) and complicated by diffuse large B-cell lymphoma (DLBCL) is reported herein. A 49-year-old Japanese man had undergone peritoneo-venous shunt against refractory ascites due to hepatitis C virus-positive uncompensated LC for 2 years. After he received a diagnosis of DLBCL of the left neck lymph node 3 months before his death, palliative care was given because of his poor general condition. He developed severe abdominal distention and pain over 1 week and was found to have marked ascites and whole bowel lumped together on abdominal CT. At autopsy, the peritoneum was covered with a thick white membrane and the bowel could not be distinguished, which was macroscopically characterized by a cocoon-like appearance. Histology indicated a proliferation of diffusely thickened or hyalinized fibrocollagenous tissue in the entire peritoneum with a slight chronic inflammatory infiltrate and without remarkable change of mucosa. A diagnosis of SEP, also known as abdominal cocoon, was established based on these features. Additionally, in the abdominal cavity, a large amount of serous ascites and multiple peritoneal nodules or masses involved by DLBCL were recognized. To the authors' knowledge this is the first case report of SEP associated with LC and complicated by the invasion of DLBCL in the abdominal cavity. PMID:19712139

  12. 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-?B). Finally, carvedilol significantly reduced liver fibrosis markers including hydroxyproline, collagen accumulation, and the expression of the hepatic stellate cell (HSC) activation marker; alpha smooth muscle actin. In conclusion, the present study provides evidences for the promising antifibrotic effects of carvedilol that can be explained by amelioration of oxidative stress through mainly, replenishment of GSH, restoration of antioxidant enzyme activities and reduction of lipid peroxides as well as amelioration of inflammation and fibrosis by decreasing collagen accumulation, acute phase protein level, NF-?B expression and finally HSC activation. -- Highlights: ? Carvedilol is a beta blocker with antioxidant and antifibrotic properties. ? It restores GSH and antioxidant enzyme activities and reduces lipid peroxidation. ? It ameliorates inflammation and nuclear factor kappa-B expression. ? It ameliorates fibrosis by decreasing collagen accumulation and HSC activation.

  13. 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.

  14. 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

  15. 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

  16. Predictive value of the efficacy of tolvaptan in liver cirrhosis patients using free water clearance

    PubMed Central

    MIYAAKI, HISAMITSU; NAKAMURA, YUTAKA; ICHIKAWA, TATSUKI; TAURA, NAOTA; MIUMA, SATOSHI; SHIBATA, HIDETAKA; HONDA, TAKUYA; NAKAO, KAZUHIKO

    2015-01-01

    Tolvaptan, an arginine vasopressin V2 antagonist, is available for patients with refractory ascites. Free water clearance was evaluated as a predictor of tolvaptan efficacy. Twenty-one patients with refractory ascites were enrolled in the present study. Liver function test, renal function test, urine volume, free water clearance and osmotic pressure were measured at baseline (day 0) and for each dose of tolvaptan (1.875, 3.75 and 7.5 mg), and compared for efficacy. Tolvaptan increased urine volume and free water clearance decreased osmotic pressure at each dose of tolvaptan, compared to pretreatment levels. Compared to baseline, an increased volume of free water clearance at 1.875 mg of tolvaptan showed a significant correlation with body weight reduction (r=0.480 and P=0.028). Any factors (age, liver function test and renal function test) at pretreatment showed no significant correlation with body weight reduction. An increased volume of urine and osmotic pressure at each dose was not significantly correlated with the tolvaptan effect. Compared to baseline, an increased volume of free water clearance at 1.875 mg of tolvaptan in responders was significantly increased, compared to non-responders (270±241 ml/day: 27±257 ml/day; P=0.042). In conclusion, an increased volume of free water clearance on day 1 was significantly associated with body weight reduction. Free water clearance could be a simple and useful marker for the prediction of tolvaptan efficacy. PMID:26623035

  17. 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

  18. Efficacy and Safety of Faldaprevir, Deleobuvir, and Ribavirin in Treatment-Naive Patients with Chronic Hepatitis C Virus Infection and Advanced Liver Fibrosis or Cirrhosis

    PubMed Central

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

    2014-01-01

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

  19. 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

  20. American Liver Foundation

    MedlinePLUS

    Resources Liver Disease Information Select Info Center Alagille Syndrome Alcohol-Related Liver Disease Alpha-1 Antitrypsin Deficiency Autoimmune Hepatitis Benign Liver Tumors Biliary Atresia Cirrhosis ...

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

    PubMed Central

    Farr, Maryjane; Schulze, Paul Christian

    2014-01-01

    Patients with end-stage liver disease in need of liver transplantation increasingly are older with a greater burden of cardiac disease and other co-morbidities, which may increase perioperative risk and adversely affect long-term prognosis. Cirrhosis of any etiology manifests hemodynamically as a state of low systemic vascular resistance, with high peripheral, but low central blood volume, leading to a state of neurohormonal activation and high cardiac output, which may adversely affect cardiac reserve under extreme perioperative stress, aptly termed cirrhosis-associated or cirrhotic cardiomyopathy. Evidence of asymptomatic cirrhotic cardiomyopathy may be found in subtle electrocardiographic and echocardiographic changes, but may progress to severe heart failure under the demands of bleeding and transfusions, vasopressors, rebounding peripheral vascular resistance, withdrawal of cardioprotective beta-blockers and mineralocorticoid antagonists, exacerbated by sepsis or systemic inflammatory response syndrome. This review will add to the current body of literature on cirrhotic cardiomyopathy by focusing on the role of advanced echocardiographic imaging techniques, cardiac biomarkers, and advanced heart failure therapies available to manage patients with cirrhotic cardiomyopathy while waiting for liver transplant and during the perioperative period. PMID:25657603

  2. 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

  3. 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.

  4. 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.

  5. Alcoholic liver disease

    MedlinePLUS

    Liver disease due to alcohol; Cirrhosis or hepatitis - alcoholic; Laennec's cirrhosis ... Alcoholic liver disease occurs after years of heavy drinking. The heavy drinking could be every day, or just a ...

  6. EVALUATION OF ANTIVIRAL THERAPY TREATMENT FOR LIVER CIRRHOSIS CAUSED BY CHRONIC HEPATITIS C AND HEPATITIS C BY 31P-MRS, BASED ON METABOLITE DETECTION.

    PubMed

    Gu, J S; Sun, R R; Shen, S; Yu, Z J

    2015-01-01

    This study discusses the application of magnetic resonance spectrum (MRS) to evaluate the efficacy of antiviral therapy in the treatment of liver cirrhosis caused by chronic hepatitis C and hepatitis C, based on metabolite detection. A total of 54 patients with liver cirrhosis caused by chronic hepatitis C and hepatitis C were selected and divided into treatment group and control group. 31P-MRS imaging was carried out on patients in the two groups both before receiving antiviral treatment and 6 months after treatment to compare the change of metabolite ratio (PE+PC)/(GPE+GPC). It was revealed that no statistically significant difference was found in the comparison of (PC+PE)/(GPC+GPE) ratio in the two groups before treatment, but the difference was found 6 months after treatment; ratio of (PC+PE)/ (GPC+GPE) in the treatment group distinctly decreased 6 months after treatment compared to before treatment, with a statistically significant difference, while the control group had no remarkable change or statistical significance. Moreover, 32 patients were found with sustained virus response to antiviral therapy. Of these, 25 patients possessed a decreased ratio of (PC+PE)/ (GPC+GPE), 4 remained without change and 3 had a slightly increased ratio after antiviral treatment. Of 12 patients with no response, 1 had a decreased ratio of (PC+PE)/ (GPC+GPE), 2 remained without change and 9 had a slightly increased ratio. The differences were all statistically significant in comparison of the two groups. 31P-MRS is thought to be effective for evaluating the efficacy of antiviral therapy through non-invasive detection of liver energy metabolism. PMID:26122235

  7. PAI-1 4G-4G and MTHFR 677TT in non-hepatitis C virus/hepatitis B virus-related liver cirrhosis

    PubMed Central

    Pasta, Linda; Pasta, Francesca

    2015-01-01

    AIM: To evaluate the different roles of thrombophilia in patients with and without viral etiology. The thrombophilic genetic factors (THRGFs), PAI-1 4G-4G, MTHFR 677TT, V Leiden 506Q and prothrombin 20210A, were studied as risk factors in 1079 patients with liver cirrhosis (LC), enrolled from January 2000 to January 2014. METHODS: All Caucasian LC patients consecutively observed in a fourteen-year period were included; the presence of portal vein thrombosis (PVT) and Budd Chiari syndrome (BCS) was registered. The differences between the proportions of each THRGF with regard to the presence or absence of viral etiology and the frequencies of the THRGF genotypes with those predicted in a population by the Hardy-Weinberg equilibrium were registered. RESULTS: Four hundred and seventeen/one thousand and seventy-six patients (38.6%) showed thrombophilia: 217 PAI-1 4G-4G, 176 MTHFR C677TT, 71 V Leiden factor and 41 prothrombin G20210 A, 84 with more than 1 THRGF; 350 presented with no viral liver cirrhosis (NVLC) and 729 with, called viral liver cirrhosis (VLC), of whom 56 patients were hepatitis C virus + hepatitis B virus. PAI-1 4G-4G, MTHFR C677TT, the presence of at least one TRHGF and the presence of > 1 THRGF, were statistically more frequent in patients with NVLC vs patients with VLC: All ?2 > 3.85 and P < 0.05. Patients with PVT and/or BCS with at least one TRHGF were 189/352 (53.7%). The Hardy-Weinberg of PAI-1 and MTHFR 677 genotypes deviated from that expected from a population in equilibrium in patients with NVLC (respectively ?2 = 39.3; P < 0.000 and ?2 = 27.94; P < 0.05), whereas the equilibrium was respected in VLC. CONCLUSION: MTHFR 677TT was nearly twofold and PAI-1 4G-4G more than threefold more frequently found in NVLC vs patients with VLC; the Hardy-Weinberg equilibrium of these two polymorphisms confirms this data in NVLC. We suggest that PAI-1 4G-4G and MTHFR 677TT could be considered as factors of fibrosis and thrombosis mechanisms, increasing the inflammation response, and causing the hepatic fibrosis and augmented intrahepatic vascular resistance typical of LC. PAI-1 4G-4G and MTHFR 677TT screening of LC patients could be useful, mainly in those with NVLC, to identify patients in which new drug therapies based on the attenuation of the hepatic stellate cells activation or other mechanisms could be more easily evaluated. PMID:26689658

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

    PubMed

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

    2013-11-01

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

  9. New insight into the role of NT-proBNP in alcoholic liver cirrhosis as a noninvasive marker of esophageal varices

    PubMed Central

    Ljubi?i?, Neven; Gomer?i?, Marija; Zekanovi?, Dražen; Bodroži?-, Tomislava; Džaki?; ?uzel, Ana

    2012-01-01

    Aim To investigate the association between plasma concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and formation of esophageal varices. Methods Thirty-five patients with alcoholic cirrhosis were divided into three groups according to the Child-Pugh classification: grade A (n?=?11, 32%), B (n?=?12, 34%), and C (n?=?12, 34%). System hemodynamic parameters were measured using sphygmomanometry, electrocardiography, and echocardiography. NT-proBNP was analyzed by using an electrochemiluminiscence sandwich immunoassay. Results The presence of esophageal varices was associated with a higher serum NT-proBNP level, with a cut-off value of >101 pg/mL (sensitivity, 87.60% and specificity, 72.73%; P?liver cirrhosis. In cirrhotic patients, NT-proBNP value >101 pg/mL was shown to be a valuable noninvasive parameter in predicting the presence of varices. PMID:22911531

  10. Hemodynamic Effects of the Non-Peptidic Angiotensin-(1-7) Agonist AVE0991 in Liver Cirrhosis

    PubMed Central

    Schierwagen, Robert; Grace, Josephine; Haltenhof, Tom; Uschner, Frank E.; Strassburg, Christian P.; Sauerbruch, Tilman; Walther, Thomas; Angus, Peter W.; Trebicka, Jonel

    2015-01-01

    Background & Aims Although in cirrhosis with portal hypertension levels of the vasoconstrictor angiotensin II are increased, this is accompanied by increased production of angiotensin (Ang)-(1–7), the endogenous ligand of the Mas receptor (MasR), which blunts hepatic fibrosis and decreases hepatic vascular resistance. Therefore, we investigated the effects of the non-peptidic Ang-(1–7) agonist, AVE0991, in experimental cirrhosis. Methods Cirrhosis was induced by bile duct ligation (BDL) or carbon tetrachloride (CCl4) intoxication. The coloured microsphere technique assessed portal and systemic hemodynamic effects of AVE0991 in vivo. Hepatic expression of eNOS, p-eNOS, iNOS, JAK2, ROCK and p-Moesin were analyzed by western blots. Activities of ACE and ACE2 were investigated fluorometrically. Moreover, fibrosis was assessed in BDL rats receiving AVE0991. Results In vivo, AVE0991 decreased portal pressure (PP) in both rat models of cirrhosis. Importantly, systemic effects were not observed. The hepatic effects of AVE0991 were based on upregulation of vasodilating pathways involving p-eNOS and iNOS, as well as by downregulation of the vasoconstrictive pathways (ROCK, p-Moesin). Short-term treatment with AVE0991 decreased the activity of ACE2, long-term treatment did not affect hepatic fibrosis in BDL rats. Conclusions The non-peptidic agonist of Ang-(1–7), AVE0991, decreases portal pressure without influencing systemic pressure. Thus, although it does not inhibit fibrosis, AVE0991 may represent a promising new therapeutic strategy for lowering portal pressure. PMID:26406236

  11. Carbon tetrachloride-induced liver injury in the rabbit.

    PubMed Central

    Bernacchi, A. S.; de Castro, C. R.; de Ferreyra, E. C.; Villarruel, M. C.; Fernández, G.; de Fenos, O. M.; Castro, J. A.

    1983-01-01

    CCl4 administration to rabbits leads to early destruction of liver microsomal cytochrome P-450, to depression of glucose 6 phosphatase, to ultrastructurally revealable alterations and to an intense necrosis and fat accumulation in liver. Despite the known resistance of rabbit liver microsomes to lipid peroxidation, CCl4 administration to rabbits promoted lipid peroxidation of their liver microsomal lipids as revealable by the diene hyperconjugation technique, at periods of time from 1 to 12 h. Nevertheless, the intensity of this process is not equivalent to that occurring in rat liver microsomes, since the arachidonic acid content of rabbit liver microsomal lipids does not decrease at either 6 or 24 h after CCl4 administration. Rabbit liver is able to activate CCl4 to reactive metabolites that bind covalently to lipids. Relevance of covalent binding of CCl4 reactive metabolites and CCl4-promoted lipid peroxidation to CCl4-induced rabbit liver injury is analysed. Images Fig. 1 Fig. 2 PMID:6309207

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

    PubMed Central

    Nilsson, Hans-Olof; Taneera, Jalal; Castedal, Maria; Glatz, Elisabeth; Olsson, Rolf; Wadström, Torkel

    2000-01-01

    Helicobacter pylori was identified in human liver tissue by PCR, hybridization, and partial DNA sequencing. Liver biopsies were obtained from patients with primary sclerosing cholangitis (n = 12), primary biliary cirrhosis (n = 12), and noncholestatic liver cirrhosis (n = 13) and (as controls) normal livers (n = 10). PCR analyses were carried out using primers for the Helicobacter genus, Helicobacter pylori (the gene encoding a species-specific 26-kDa protein and the 16S rRNA), Helicobacter bilis, Helicobacter pullorum, and Helicobacter hepaticus. Samples from patients with primary biliary cirrhosis and primary sclerosing cholangitis (11 and 9 samples, respectively) were positive by PCR with Helicobacter genus-specific primers. Of these 20 samples, 8 were positive with the 16S rRNA primer and 9 were positive with the 26-kDa protein primer of H. pylori. These nine latter samples were also positive by Southern blot hybridization for the amplified 26-kDa fragment, and four of those were verified to be H. pylori by partial 16S rDNA sequencing. None of the samples reacted with primers for H. bilis, H. pullorum, or H. hepaticus. None of the normal livers had positive results in the Helicobacter genus PCR assay, and only one patient in the noncholestatic liver cirrhosis group, a young boy who at reexamination showed histological features suggesting primary sclerosing cholangitis, had a positive result in the same assay. Helicobacter positivity was thus significantly more common in patients with cholestatic diseases (20 of 24) than in patients with noncholestatic diseases and normal controls (1 of 23) (P = <0.00001). Patients positive for Helicobacter genus had significantly higher values of alkaline phosphatases and prothrombin complex than Helicobacter-negative patients (P = 0.0001 and P = 0.0003, respectively). Among primary sclerosing cholangitis patients, Helicobacter genus PCR positivity was weakly associated with ulcerative colitis (P = 0.05). Significant differences related to blood group or HLA status were not found. PMID:10698999

  13. Heating improves poor compliance with branched chain amino acid-rich supplementation in patients with liver cirrhosis: A before-after pilot study.

    PubMed

    Itou, Minoru; Kawaguchi, Takumi; Taniguchi, Eitaro; Shiraishi, Satomi; Ibi, Ryoko; Mutou, Michiko; Okada, Teruyo; Uchida, Yuki; Otsuka, Momoka; Oriishi, Tetsuharu; Tanaka, Suiko; Takakura, Machiko; Mitsuyama, Keiichi; Tsuruta, Osamu; Sata, Michio

    2009-01-01

    Although branched chain amino acid (BCAA) supplementation improves malnutrition in cirrhotic patients, patient compliance with the administration of BCAA-rich supplements is poor due to their bitter taste. Since temperature is an important factor affecting taste, we examined the effect of heating on the stability of BCAAs and on the compliance of patients with liver cirrhosis with BCAA-rich supplement administration. A thermal denaturation test was first conducted, in which the BCAA-rich supplement Aminoleban® EN was heated to 37, 60, or 80°C for 30 or 60 min. The concentration of three amino acids, L-valine, L-leucine and L-isoleucine, was subsequently measured. The nutritional status of the cirrhotic patients was also evaluted. Patients presenting liver failure with a Child-Pugh class of A (n=2), B (n=2) or C (n=2) were hospitalized at Kurume University Hospital. Six patients with liver cirrhosis (HCV, n=3; HBV, n=1; alcohol, n=2) were enrolled. Venous blood samples were drawn in the morning after a 12-h overnight fast. The BCAA-rich supplement was administered to patients at room temperature (25°C) or heat loaded at 60°C for 10 min, with the temperature maintained above 45°C. Each patient was interviewed by a nationally registered dietitian regarding food consumption and intake of the BCAA-rich supplement immediately after each meal. Nutritional status was evaluated according to serum albumin levels, blood hemoglobin, prothrombin time and total lymphocyte count. No significant decrease was noted in valine, leucine or isoleucine levels following the heating of the BCAAs to 80°C. The caloric intake of the BCAA-rich supplement was significantly higher with administration after heating to 60°C, compared to caloric intake with administration at 25°C. In addition, heating of the BCAA-rich supplement significantly increased blood lymphocyte counts. In conclusion, heating did not affect the stability of the BCAAs, and may improve compliance with BCAA-rich supplement administration. As a result, the nutritional status of cirrhotic patients may be improved. PMID:21475931

  14. One-Year Mortality after Traumatic Brain Injury in Liver Cirrhosis Patients—A Ten-Year Population-Based Study

    PubMed Central

    Cheng, Chieh-Yang; Ho, Chung-Han; Wang, Che-Chuan; Liang, Fu-Wen; Wang, Jhi-Joung; Chio, Chung-Ching; Chang, Chin-Hung; Kuo, Jinn-Rung

    2015-01-01

    Abstract This study investigated the 1-year mortality of patients who underwent brain surgery following traumatic brain injury (TBI) who also had alcoholic and/or nonalcoholic liver cirrhosis (LC) using a nationwide database in Taiwan. A longitudinal cohort study matched by propensity score with age, gender, length of ICU stay, HTN, DM, MI, stroke, HF, renal diseases, and year of TBI diagnosis in TBI patients with alcoholic and/or nonalcoholic LC and TBI patients without LC was conducted using the National Health Insurance Research Database in Taiwan between January 1997 and December 2007. The main outcome studied was 1-year mortality. In total, 7296 subjects (2432 TBI patients with LC and 4864 TBI patients without LC) were enrolled in this study. The main findings were (1) TBI patients with LC had a higher 1-year mortality (52.18% vs 30.61%) and a 1.75-fold increased risk of mortality (95% CI 1.61–1.90) compared with non-LC TBI patients, (2) renal diseases and HF are risk factors, but hypertension could be a protective factor in cirrhotic TBI patients, and (3) TBI patients with non-alcoholic LC and the coexistence of alcoholic and nonalcoholic LC had higher 1-year mortality compared with TBI patients with alcoholic cirrhosis. This study showed that patients with LC who have undergone brain surgery might have higher risk of 1-year mortality than those without LC. In addition, nonalcoholic and the coexistence of alcoholic and nonalcoholic LC show higher 1-year mortality risk than alcoholic in TBI patients with LC, especially in those with comorbidities of hypertension, diabetes mellitus, and stroke. PMID:26448001

  15. Heparin Saline Versus Normal Saline for Flushing and Locking Peripheral Venous Catheters in Decompensated Liver Cirrhosis Patients: A Randomized Controlled Trial.

    PubMed

    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

    2015-08-01

    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, Child-Pugh 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 0.31-3.92). The PT, APTT, and PLT levels were comparable between the 2 groups both before and after infusion (P?>?0.05). Incremental analyses showed that Child-Pugh 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

  16. Diagnostic Accuracy of APRI, AAR, FIB-4, FI, King, Lok, Forns, and FibroIndex Scores in Predicting the Presence of Esophageal Varices in Liver Cirrhosis

    PubMed Central

    Deng, Han; Qi, Xingshun; Guo, Xiaozhong

    2015-01-01

    Abstract Aspartate aminotransferase-to-platelet ratio (APRI), aspartate aminotransferase-to-alanine aminotransferase ratio (AAR), FIB-4, FI, King, Lok, Forns, and FibroIndex scores may be simple and convenient noninvasive diagnostic tests, because they are based on the regular laboratory tests and demographic data. This study aimed to systematically evaluate their diagnostic accuracy for the prediction of varices in liver cirrhosis. All relevant papers were searched via PubMed, EMBASE, CNKI, and Wanfang databases. The area under the summary receiver operating characteristic curve (AUSROC), sensitivity, specificity, positive and negative likelihood ratio (PLR and NLR), and diagnostic odds ratio (DOR) were calculated. Overall, 12, 4, 5, 0, 0, 4, 3, and 1 paper was identified to explore the diagnostic accuracy of APRI, AAR, FIB-4, FI, King, Lok, Forns, and FibroIndex scores, respectively. The AUSROCs of APRI, AAR, FIB-4, Lok, and Forns scores for the prediction of varices were 0.6774, 0.7275, 0.7755, 0.7885, and 0.7517, respectively; and those for the prediction of large varices were 0.7278, 0.7448, 0.7095, 0.7264, and 0.6530, respectively. The diagnostic threshold effects of FIB-4 and Forns scores for the prediction of varices were statistically significant. The sensitivities/specificities/PLRs/NLRs/DORs of APRI, AAR, and Lok scores for the prediction of varices were 0.60/0.67/1.77/0.58/3.13, 0.64/0.63/1.97/0.54/4.18, and 0.74/0.68/2.34/0.40/5.76, respectively. The sensitivities/specificities/PLRs/NLRs/DORs of APRI, AAR, FIB-4, Lok, and Forns scores for the prediction of large varices were 0.65/0.66/2.15/0.47/4.97, 0.68/0.58/2.07/0.54/3.93, 0.62/0.64/2.02/0.56/3.57, 0.78/0.63/2.09/0.37/5.55, and 0.65/0.61/1.62/0.59/2.75, respectively. APRI, AAR, FIB-4, Lok, and Forns scores had low to moderate diagnostic accuracy in predicting the presence of varices in liver cirrhosis. PMID:26496312

  17. Renal dysfunction in cirrhosis

    PubMed Central

    Urrunaga, Nathalie H.; Mindikoglu, Ayse L.; Rockey, Don C.

    2015-01-01

    Purpose of review Renal dysfunction causes significant morbidity in cirrhotic patients. Diagnosis is challenging because it is based on serum creatinine, which is used to calculate estimated glomerular filtration rate, which itself is not an ideal measure of renal function in patients with cirrhosis. Finding the exact cause of renal injury in patients with cirrhosis remains problematic due to the limitations of the current diagnostic tests. The purpose of this review is to highlight studies used to diagnose renal dysfunction in patients with renal dysfunction and review current treatments. Recent findings New diagnostic criteria and classification of renal dysfunction, especially for acute kidney injury (AKI), have been proposed in hopes of optimizing treatment and improving outcomes. New biomarkers that help to differentiate structural from functional AKI in cirrhotic patients have been developed, but require further investigation. Vasoconstrictors are the most commonly recommended treatment of hepatorenal syndrome (HRS). Given the high mortality in patients with type 1 HRS, all patients with HRS should be evaluated for liver transplantation. When renal dysfunction is considered irreversible, combined liver–kidney transplantation is advised. Summary Development of new biomarkers to differentiate the different types of AKI in cirrhosis holds promise. Early intervention in cirrhotic patients with renal dysfunction offers the best hope of improving outcomes. PMID:25763790

  18. Hepatitis C in Special Patient Cohorts: New Opportunities in Decompensated Liver Cirrhosis, End-Stage Renal Disease and Transplant Medicine

    PubMed Central

    Hüsing, Anna; Kabar, Iyad; Schmidt, Hartmut H.; Heinzow, Hauke S.

    2015-01-01

    Worldwide, hepatitis C virus (HCV) is a common infection. Due to new antiviral approaches and the approval of direct-acting antiviral agents (DAA), HCV therapy has become more comfortable. Nevertheless, there are special patient groups, in whom treatment of HCV is still challenging. Due to only few data available, tolerability and efficacy of DAAs in special patient cohorts still remain unclear. Such special patient cohorts comprise HCV in patients with decompensated liver disease (Child-Pugh Class B or C), patients with chronic kidney disease, and patients on waiting lists to renal/liver transplantation or those with HCV recurrence after liver transplantation. HCV infection in these patient cohorts has been shown to be associated with increased morbidity and mortality and may lead to reduced graft survival after transplantation. Successful eradication of HCV results in a better outcome concerning liver-related complications and in a better clinical outcome of these patients. In this review, we analyze available data and results from recently published literature and provide an overview of current recommendations of HCV-therapy regimen in these special patient cohorts. PMID:26251895

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

    PubMed

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

    2007-07-01

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

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

    PubMed Central

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

    2015-01-01

    Indoleamine 2,3-dioxygenase (IDO) is an immunoregulatory enzyme. It plays a key role in various malignancies, infection and autoimmune diseases. IDO induces immunosuppression through the depletion of tryptophan and its downstream metabolites. Hepatitis C virus (HCV) has infected more than 12 million individuals in Pakistan. The aim of the present study was to assess the expression and activity of IDO in HCV-infected patients. The functional enzymatic activity of IDO was measured by colorimetric assay. Serum samples from 100 HCV-infected patients were taken to examine IDO activity and samples from 100 healthy volunteers were used as controls. Liver sections from patients with HCV (n=35) and healthy controls (n=5) were used for immunohistochemical studies. Immunohistochemical analysis revealed that IDO was overexpressed in 28 of 35 (80%) cirrhotic liver samples, whereas 5 of 35 (14.2%) cases presented moderate and 2 of 35 (5.7%) cases presented mild expression of IDO. The enzymatic activity of IDO was significantly higher in the serum samples of HCV-infected patients as compared with those in the control. These data indicate that the expression of IDO correlated with the pathogenesis of disease. In summary, it is suggested that the high expression of IDO in the progressively cirrhotic livers of HCV-infected patients might contribute to the development of hepatocellular carcinoma. IDO may characterize a novel therapeutic target against HCV. PMID:25667650

  1. Non-invasive diagnosis of advanced fibrosis and cirrhosis

    PubMed Central

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

    2014-01-01

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

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

    SciTech Connect

    Caturelli, Eugenio; Biasini, Elisabetta; Bartolucci, Francesca; Facciorusso, Domenico; Decembrino, Francesco; Attino, Vito; Bisceglia, Michele

    2002-08-15

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

  3. Incidence, risk factors and outcome of de novo tumors in liver transplant recipients focusing on alcoholic cirrhosis

    PubMed Central

    Jiménez-Romero, Carlos; Justo-Alonso, Iago; Cambra-Molero, Félix; Calvo-Pulido, Jorge; García-Sesma, Álvaro; Abradelo-Usera, Manuel; Caso-Maestro, Oscar; Manrique-Municio, Alejandro

    2015-01-01

    Orthotopic liver transplantation (OLT) is an established life-saving procedure for alcoholic cirrhotic (AC) patients, but the incidence of de novo tumors ranges between 2.6% and 15.7% and is significantly increased in comparison with patients who undergo OLT for other etiologies. Tobacco, a known carcinogen, has been reported to be between 52% and 83.3% in AC patients before OLT. Other risk factors that contribute to the development of malignancies are dose-dependent immunosuppression, advanced age, viral infections, sun exposure, and premalignant lesions (inflammatory bowel disease, Barrett’s esophagus). A significantly more frequent incidence of upper aerodigestive (UAD) tract, lung, skin, and kidney-bladder tumors has been found in OLT recipients for AC in comparison with other etiologies. Liver transplant recipients who develop de novo non-skin tumors have a decreased long-term survival rate compared with controls. This significantly lower survival rate is more evident in AC recipients who develop UAD tract or lung tumors after OLT mainly because the diagnosis is usually performed at an advanced stage. All transplant candidates, especially AC patients, should be encouraged to cease smoking and alcohol consumption in the pre- and post-OLT periods, use skin protection, avoid sun exposure and over-immunosuppression, and have a yearly otopharyngolaryngeal exploration and chest computed tomography scan in order to prevent or reduce the incidence of de novo malignancies. Although still under investigation, substitution of calcineurin inhibitors for sirolimus or everolimus may reduce the incidence of de novo tumors after OLT. PMID:25954477

  4. Real-time two-dimensional shear wave ultrasound elastography of the liver is a reliable predictor of clinical outcomes and the presence of esophageal varices in patients with compensated liver cirrhosis

    PubMed Central

    Grgurevi?, Ivica; Bokun, Tomislav; Mustapi?, Sanda; Trkulja, Vladimir; Heinzl, Renata; Bani?, Marko; Puljiz, Željko; Lukši?, Boris; Kujundži?, Milan

    2015-01-01

    Aim Primary: to evaluate predictivity of liver stiffness (LS), spleen stiffness (SS), and their ratio assessed by real-time 2D shear wave elastography (RT-2D-SWE) for adverse outcomes (hepatic decompensation, hepatocellular carcinoma or death; “event”) in compensated liver cirrhosis (LC) patients. Secondary: to evaluate ability of these measures to discriminate between cirrhotic patients with/without esophageal varices (EV). Methods Predictivity of LS, SS, and LS/SS was assessed in a retrospectively analyzed cohort of compensated LC patients (follow-up cohort) and through comparison with incident patients with decompensated cirrhosis (DC) (cross-sectional cohort). Both cohorts were used to evaluate diagnostic properties regarding EV. Results In the follow-up cohort (n?=?44) 18 patients (40.9%) experienced an “event” over a median period of 28 months. LS?21.5 kPa at baseline was independently associated with 3.4-fold (95% confidence interval [CI] 1.16-10.4, P?=?0.026) higher risk of event. Association between SS and outcomes was weaker (P?=?0.056), while there was no association between LS/SS ratio and outcomes. Patients with DC (n?=?43) had higher LS (35.3 vs 18.3 kPa, adjusted difference 65%, 95% CI 43%-90%; P?

  5. Successful and Safe Long-Term Standard Antiviral Therapy in a Patient with “Explosive” Immune Response in Course of HCV-Related Liver Cirrhosis

    PubMed Central

    Conca, Paolo; Cafaro, Giovanni; De Renzo, Amalia; Coppola, Antonio; Cimino, Ernesto; Tarantino, Giovanni

    2015-01-01

    Hepatitis C virus (HCV) has been recognized to be both a hepato- and lymphotropic virus. HCV lymphotropism represents an essential detail in the pathogenesis of virus-related autoimmune and lymphoproliferative disorders, ranging from clonal expansion of B-cells with organ and non-organ-specific autoantibody production up to overt non-Hodgkin’s lymphoma along a continuous step-by-step model of B-cell lymphomagenesis, where the intermediated mixed cryoglobulinemia could be considered as a stage of suppressible antigen-driven lymphoproliferation. The HCV long-lasting extrahepatic replicative state generates an abnormal systemic immunological response, including rheumatoid factor (RF) and cryo- and non-cryoprecipitable immune complexes, as well as clinical manifestations, comprising dermatitis, polyarthralgias and arthritis, pulmonary disease, aplastic anemia, glomerulonephritis and vasculitis. The mechanism of these extra-hepatic disorders is thought of as linked to immune complex disease, but their pathogenesis is poorly clarified. Immune-suppressive treatment could induce high-level hepatitis C viremia and impair hepatic disease. We report a female patient, whose chronic HCV-related liver cirrhosis with associated explosive, but oligosymptomatic lymphoproliferative immune response, i.e., RF beyond three thousand times the upper of normal range (unr), type II cryoglobulinemia with cryocrit 40% and monoclonal gammopathy IgM-k, has been successfully and safely treated by long-lasting (sixty-six months) combined antiviral therapy (pegylated interferon alfa and ribavirin), at moderate and tapering dose regimen, prolonged for nearly 24 months after the first viral suppression. At the last follow-up (fifty-one months), the patient was showing very-long term antiviral response, progressive decline of secondary immune activation and absence of significant side-effects. Further research is required to fully verify the real impact on therapeutic choice/regimen. PMID:26101866

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

    PubMed Central

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

    2014-01-01

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

  7. Alleviation of Carbon-Tetrachloride-Induced Liver Injury and Fibrosis by Betaine Supplementation in Chickens

    PubMed Central

    Tsai, Meng-Tsz; Chen, Ching-Yi; Pan, Yu-Hui; Wang, Siou-Huei; Mersmann, Harry J.; Ding, Shih-Torng

    2015-01-01

    Betaine is a food component with well-reported hepatoprotection effects. However, the effects and mechanisms of betaine on liver fibrosis development are still insufficient. Because metabolic functions of chicken and human liver is similar, we established a chicken model with carbon Tetrachloride- (CCl4-) induced fibrosis for studying antifibrotic effect of betaine in vivo and in vitro. Two-week-old male chicks were supplemented with betaine (1%, w/v) in drinking water for 2 weeks prior to the initiation of CCl4 treatment (i.p.) until sacrifice. Primary chicken hepatocytes were treated with CCl4 and betaine to mimic the in vivo supplementation. The supplementation of betaine significantly alleviated liver fibrosis development along with the inhibition of lipid peroxidation, hepatic inflammation cytokine, and transforming growth factor-?1 expression levels. These inhibitive effects were also accompanied with the attenuation of hepatic stellate cell activation. Furthermore, our in vitro studies confirmed that betaine provides antioxidant capacity for attenuating the hepatocyte necrosis by CCl4. Altogether, our results highlight the antioxidant ability of betaine, which alleviates CCl4-induced fibrogenesis process along with the suppression of hepatic stellate cells activation. Since betaine is a natural compound without toxicity, we suggest betaine can be used as a potent nutritional or therapeutic factor for reducing liver fibrosis. PMID:26491462

  8. Cirrhosis in children and adolescents: An overview

    PubMed Central

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

    2015-01-01

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

  9. Primary biliary cirrhosis

    PubMed Central

    Kumagi, Teru; Heathcote, E Jenny

    2008-01-01

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

  10. Effects of 18?-glycyrrhizin on TGF-?1/Smad signaling pathway in rats with carbon tetrachloride-induced liver fibrosis

    PubMed Central

    Qu, Ying; Zong, Lei; Xu, Mingyi; Dong, Yuwei; Lu, Lungen

    2015-01-01

    Background: Glycyrrhizin has various pharmacological effects including hepato-protection. This study aimed to investigate the potential mechanism underlying the protective effects of 18?-glycyrrhizin (18?-GL) in rats with carbon tetrachloride (CCl4) induced liver fibrosis. Methods: Male Sprague-Dawley (SD) rats were randomly divided into control group, fibrosis group, 25 mg/kg 18?-GL group and 12.5 mg/kg 18?-GL group. Rats in experimental groups were subcutaneously injected with 40% CCl4 twice weekly for 8 weeks. Immunohistochemical examination was carried out to detect the protein expressions of collagen I, collagen III, TGF-?1, p-Smad2, p-Smad3, Smad 7 and SP-1, in the liver, and the mRNA and protein expressions of these genes were determined in the liver by real time PCR and Western blot assay, respectively. Results: 18?-GL ameliorated histological changes and significantly suppressed collagen deposition. 18?-GL significantly decreased the mRNA expressions of TGF-?1, Smad2, Smad3 and SP-1 in the liver. Immunohistochemical staining revealed that TGF-?1, p-Smad2, p-Smad3 and SP-1 expressions reduced following 18?-GL therapy. Western blot assay showed p-Smad2, p-Smad3, smad2 and smad3 expressions decreased after 18?-GL treatment. The mRNA and protein expression of Smad7 remained unchanged. Conclusion: 18?-GL is able to attenuate CCl4 induced liver fibrosis in rat. PMID:25973013

  11. Hepatic encephalopathy in alcoholic cirrhosis.

    PubMed

    Butterworth, Roger F

    2014-01-01

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

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

    PubMed Central

    2013-01-01

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

  13. Management options in decompensated cirrhosis

    PubMed Central

    Shah, Neeral L; Banaei, Yasmin Pourkazemi; Hojnowski, Kristen L; Cornella, Scott L

    2015-01-01

    Chronic injury to the liver from a variety of different sources can result in irreversible scarring of the liver, known as cirrhosis. Cirrhosis is a major cause of morbidity and mortality in the USA, and according to the Centers for Disease Control and Prevention was responsible for 31,903 deaths in 2010 alone. It is thus of the utmost importance to appropriately manage these patients in the inpatient and outpatient setting to improve morbidity and mortality. In this review, we address four major areas of cirrhosis management: outpatient management of portal hypertension with decompensation, hepatic encephalopathy, hepatorenal syndrome, and bleeding/coagulation issues. Outpatient management covers recommendations for health care maintenance and screening. Hepatic encephalopathy encompasses a brief review of pathophysiology, treatment in the acute setting, and long-term prevention. Hepatorenal syndrome is discussed in regards to pathophysiology and treatment in the hospital setting. Finally, a discussion of the assessment of coagulation profiles in cirrhosis and recommendations for bleeding and thrombosis complications is included. These topics are not all encompassing with regard to this complicated population, but rather an overview of a few medical problems that are commonly encountered in their care. PMID:26203291

  14. Association Between Catalase Gene Polymorphisms and Risk of Chronic Hepatitis B, Hepatitis B Virus-Related Liver Cirrhosis and Hepatocellular Carcinoma in Guangxi Population

    PubMed Central

    Liu, Yanqiong; Xie, Li; Zhao, Jiangyang; Huang, Xiuli; Song, Liuying; Luo, Jingrong; Ma, Liping; Li, Shan; Qin, Xue

    2015-01-01

    Abstract Reactive oxygen species (ROS) play critical roles in hepatocarcinogenesis. The catalase (CAT) enzyme is involved in the repair of ROS. Therefore, we investigate the association between CAT gene polymorphisms and the risk of hepatocellular carcinoma (HCC). A total of 715 subjects were divided into 4 groups: 111 chronic hepatitis B (CHB) patients, 90 hepatitis B virus (HBV)-related liver cirrhosis (LC) patients, 266 HBV-HCC patients, and 248 healthy controls. The polymerase chain reaction-restriction fragment length polymorphism strategy was used to detect CAT gene rs1001179, rs769217, and rs7943316 polymorphisms. Binary logistic regression analyses adjusting for sex, age, ethnicity, smoking and alcohol consumption, and body mass index suggested that subjects carrying the rs769217 T allele were at marginally increased risk of CHB, LC, and HCC, with adjusted odds ratios (ORs) of 1.51 (95% confidence interval [CI]?=?1.04–2.20, P?=?0.029), 1.48 (95% CI?=?1.03–2.14, P?=?0.035), and 1.51 (95% CI?=?1.14–1.98, P?=?0.004), respectively. Similarly, those individuals carrying the rs769217 TT genotype had a moderately increased risk of CHB, LC, and HCC, with adjusted ORs of 2.11 (95% CI?=?1.05–4.22, P?=?0.035), 2.00 (95% CI, 1.01–3.95, P?=?0.047), and 1.93 (95% CI?=?1.14–3.28, P?=?0.015), respectively. Moreover, subjects carrying the rs769217 CT genotype and at least 1 copy of the T allele (dominant model) were 1.78 times and 1.83 times more likely to develop HCC, respectively (OR?=?1.78, 95% CI?=?1.16–2.73, P?=?0.009 and OR?=?1.83, 95% CI?=?1.23–2.71, P?=?0.003). This association between CAT rs769217 T alleles and HCC risk is significantly strengthened among men, nonsmokers, nondrinkers, and among individuals <50 years of age. Furthermore, we found 1 high-risk haplotype GTA for CHB (OR?=?1.45, 95% CI?=?1.05–2.01) and 1 protective haplotype GCA for HCC risk (OR?=?0.67, 95% CI?=?0.52–0.87). We did not found any significant difference in CAT rs1001179 and rs7943316 polymorphisms between controls and cases. Our findings suggest that the CAT rs769217 T allele is associated with increased risk of CHB, HBV-LC, and HBV-HCC in Guangxi population. PMID:25837767

  15. Further exploration of MRI techniques for liver T1rho quantification.

    PubMed

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

    2013-12-01

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

  16. Inflammatory status in human hepatic cirrhosis.

    PubMed

    Martínez-Esparza, María; Tristán-Manzano, María; Ruiz-Alcaraz, Antonio J; García-Peñarrubia, Pilar

    2015-11-01

    This review focuses on new findings about the inflammatory status involved in the development of human liver cirrhosis induced by the two main causes, hepatitis C virus (HCV) infection and chronic alcohol abuse, avoiding results obtained from animal models. When liver is faced to a persistent and/or intense local damage the maintained inflammatory response gives rise to a progressive replacement of normal hepatic tissue by non-functional fibrotic scar. The imbalance between tissue regeneration and fibrosis will determine the outcome toward health recovery or hepatic cirrhosis. In all cases progression toward liver cirrhosis is caused by a dysregulation of mechanisms that govern the balance between activation/homeostasis of the immune system. Detecting differences between the inflammatory status in HCV-induced vs alcohol-induced cirrhosis could be useful to identify specific targets for preventive and therapeutic intervention in each case. Thus, although survival of patients with alcoholic cirrhosis seems to be similar to that of patients with HCV-related cirrhosis (HCV-C), there are important differences in the altered cellular and molecular mechanisms implicated in the progression toward human liver cirrhosis. The predominant features of HCV-C are more related with those that allow viral evasion of the immune defenses, especially although not exclusively, inhibition of interferons secretion, natural killer cells activation and T cell-mediated cytotoxicity. On the contrary, the inflammatory status of alcohol-induced cirrhosis is determined by the combined effect of direct hepatotoxicity of ethanol metabolites and increases of the intestinal permeability, allowing bacteria and bacterial products translocation, into the portal circulation, mesenteric lymph nodes and peritoneal cavity. This phenomenon generates a stronger pro-inflammatory response compared with HCV-related cirrhosis. Hence, therapeutic intervention in HCV-related cirrhosis must be mainly focused to counteract HCV-immune system evasion, while in the case of alcohol-induced cirrhosis it must try to break the inflammatory loop established at the gut-mesenteric lymph nodes-peritoneal-systemic axis. PMID:26556984

  17. Inflammatory status in human hepatic cirrhosis

    PubMed Central

    Martínez-Esparza, María; Tristán-Manzano, María; Ruiz-Alcaraz, Antonio J; García-Peñarrubia, Pilar

    2015-01-01

    This review focuses on new findings about the inflammatory status involved in the development of human liver cirrhosis induced by the two main causes, hepatitis C virus (HCV) infection and chronic alcohol abuse, avoiding results obtained from animal models. When liver is faced to a persistent and/or intense local damage the maintained inflammatory response gives rise to a progressive replacement of normal hepatic tissue by non-functional fibrotic scar. The imbalance between tissue regeneration and fibrosis will determine the outcome toward health recovery or hepatic cirrhosis. In all cases progression toward liver cirrhosis is caused by a dysregulation of mechanisms that govern the balance between activation/homeostasis of the immune system. Detecting differences between the inflammatory status in HCV-induced vs alcohol-induced cirrhosis could be useful to identify specific targets for preventive and therapeutic intervention in each case. Thus, although survival of patients with alcoholic cirrhosis seems to be similar to that of patients with HCV-related cirrhosis (HCV-C), there are important differences in the altered cellular and molecular mechanisms implicated in the progression toward human liver cirrhosis. The predominant features of HCV-C are more related with those that allow viral evasion of the immune defenses, especially although not exclusively, inhibition of interferons secretion, natural killer cells activation and T cell-mediated cytotoxicity. On the contrary, the inflammatory status of alcohol-induced cirrhosis is determined by the combined effect of direct hepatotoxicity of ethanol metabolites and increases of the intestinal permeability, allowing bacteria and bacterial products translocation, into the portal circulation, mesenteric lymph nodes and peritoneal cavity. This phenomenon generates a stronger pro-inflammatory response compared with HCV-related cirrhosis. Hence, therapeutic intervention in HCV-related cirrhosis must be mainly focused to counteract HCV-immune system evasion, while in the case of alcohol-induced cirrhosis it must try to break the inflammatory loop established at the gut-mesenteric lymph nodes-peritoneal-systemic axis. PMID:26556984

  18. Proangiogenic factors in the development of HCC in alcoholic cirrhosis.

    PubMed

    Machado, Mariana V; Cortez-Pinto, Helena

    2015-09-01

    Alcoholic liver disease, the most common cause of liver cirrhosis, is associated with an increased risk for hepatocellular carcinoma. Angiogenic factors have been implicated in pathophysiology of cirrhosis, and of hepatocellular carcinoma, and in particular of alcoholic liver cirrhosis, due to alcohol induced hypoxia associated with increased hepatic oxygen consumption. In one study, it was found that among genetic polymorphisms in proangiogenic factors, KDR and VEFGA may confer an increased risk of HCC, in patients with ALD. There is need of further studies of the proangiogenic factors in HCC, in order to help us define their use as prognostic markers and also as markers of response to treatment. PMID:26193870

  19. Autoimmune liver disease panel

    MedlinePLUS

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

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

    NASA Astrophysics Data System (ADS)

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

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

  1. The Current Economic Burden of Cirrhosis

    PubMed Central

    Duncan, Christopher W.; Schiff, Eugene R.

    2011-01-01

    Cirrhosis is a worldwide problem that is associated with a substantial economic burden. Hepatitis B virus (HBV) infection, hepatitis C virus (HCV) infection, and alcoholic liver disease are the main causes of cirrhosis, but cost-effective preventive strategies are only available for HBV infection. Treatment algorithms for HBV infection and HCV infection are numerous and may be economically advantageous, depending on the regimen utilized; however, effective treatment for alcoholic liver disease is lacking, with abstinence from alcohol consumption continuing to be the main treatment strategy. In addition, liver transplantation (the only cure for cirrhosis) continues to consume substantial economic resources despite a recent reduction in overall cost. More sensitive predictors of post-liver transplantation disability could reduce this cost by allowing interventions that would promote productivity and increase health-related quality of life after liver transplantation. This paper highlights recent publications that evaluate the cost-effectiveness of strategies that prevent or treat the main causes of cirrhosis as well as publications that assess the impact of quality of life on the overall cost burden of the disease. PMID:22298959

  2. Comorbidity in cirrhosis

    PubMed Central

    Jepsen, Peter

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  4. Liver Transplantation

    MedlinePLUS

    ... adults is cirrhosis. This is scarring of the liver, caused by injury or long-term disease. The most common reason in children is biliary atresia, a disease of the bile ducts. If you have a ... the new liver. NIH: National Institute of Diabetes and Digestive and ...

  5. Management before hepatectomy for hepatocellular carcinoma with cirrhosis

    PubMed Central

    Nakayama, Hisashi; Takayama, Tadatoshi

    2015-01-01

    The global distribution of hepatocellular carcinoma (HCC) varies markedly among regions, and patients in East Asia and Central Africa account for about 80% of all cases. The risk factors are hepatitis B, hepatitis C, alcohol, and etc. The risk of carcinogenesis further increases with progression to hepatic cirrhosis in all liver disorders. Radical treatment of HCC by liver resection without causing liver failure has been established as a safe approach through selection of an appropriate range of resection of the damaged liver. This background indicates that both evaluation of hepatic functional reserve and measures against concomitant diseases such as thrombocytopenia accompanying portal hypertension, prevention of rupture of esophageal varices, reliable control of ascites, and improvement of hypoalbuminemia are important issues in liver resection in patients with hepatic cirrhosis. We review the latest information on perioperative management of liver resection in HCC patients with hepatic cirrhosis. PMID:26380653

  6. Management before hepatectomy for hepatocellular carcinoma with cirrhosis.

    PubMed

    Nakayama, Hisashi; Takayama, Tadatoshi

    2015-09-18

    The global distribution of hepatocellular carcinoma (HCC) varies markedly among regions, and patients in East Asia and Central Africa account for about 80% of all cases. The risk factors are hepatitis B, hepatitis C, alcohol, and etc. The risk of carcinogenesis further increases with progression to hepatic cirrhosis in all liver disorders. Radical treatment of HCC by liver resection without causing liver failure has been established as a safe approach through selection of an appropriate range of resection of the damaged liver. This background indicates that both evaluation of hepatic functional reserve and measures against concomitant diseases such as thrombocytopenia accompanying portal hypertension, prevention of rupture of esophageal varices, reliable control of ascites, and improvement of hypoalbuminemia are important issues in liver resection in patients with hepatic cirrhosis. We review the latest information on perioperative management of liver resection in HCC patients with hepatic cirrhosis. PMID:26380653

  7. Role of systemic inflammation in cirrhosis: From pathogenesis to prognosis

    PubMed Central

    Dirchwolf, Melisa; Ruf, Andrés Eduardo

    2015-01-01

    The natural history of cirrhosis can be divided into an initial stage, known as compensated cirrhosis, and an advanced stage which encompasses both decompensated cirrhosis and acute-on-chronic liver failure (ACLF). The latter syndrome has been recently described as an acute deterioration of liver function in patients with cirrhosis, which is usually triggered by a precipitating event and results in the failure of one or more organs and high short-term mortality rates. Each stage is characterized by distinctive clinical manifestations and prognoses. One of the key elements involved in cirrhosis physiopathology is systemic inflammation, recently described as one of the components in the cirrhosis-associated immune dysfunction syndrome. This syndrome refers to the combination of immune deficiency and exacerbated inflammation that coexist during the course of cirrhosis and relates to the appearance of clinical complications. Since systemic inflammation is often difficult to assess in cirrhosis patients, new objective, reproducible and readily-available markers are needed in order to optimize prognosis and lengthen survival. Thus, surrogate serum markers and clinical parameters of systemic inflammation have been sought to improve disease follow-up and management, especially in decompensated cirrhosis and ACLF. Leukocyte counts (evaluated as total leukocytes, total eosinophils or neutrophil:lymphocyte ratio) and plasma levels of procalcitonin or C-reactive protein have been proposed as prognostic markers, each with advantages and shortcomings. Research and prospective randomized studies that validate these and other markers are clearly warranted. PMID:26261687

  8. Treating morbid obesity in cirrhosis: A quest of holy grail

    PubMed Central

    Kumar, Naveen; Choudhary, Narendra Singh

    2015-01-01

    The problem of obesity is increasing worldwide in epidemic proportions; the situation is similarly becoming more common in patients with cirrhosis which negatively affect the prognosis of disease and also makes liver transplantation difficult especially in the living donor liver transplantation setting where low graft to recipient weight ratio negatively affects survival. Treatment of obesity is difficult in cirrhosis due to difficulty in implementation of lifestyle measures, limited data on safety of anti-obesity drugs and high risk of surgery. Currently approved anti-obesity drugs have limited data in patients with cirrhosis. Bariatric surgery remains an option in selected compensated cirrhotic patients. Endoscopic interventions for obesity are emerging and are quite promising in patients with cirrhosis as these are minimally invasive. In present review, we briefly discuss various modalities of weight reduction in obese patients and their applicability in patients with cirrhosis. PMID:26668693

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

    PubMed

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

    2015-02-01

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

  10. Hyponatremia in cirrhosis: Pathophysiology and management

    PubMed Central

    John, Savio; Thuluvath, Paul J

    2015-01-01

    Hyponatremia is frequently seen in patients with ascites secondary to advanced cirrhosis and portal hypertension. The development of ascites in patients with cirrhosis is multi-factorial. Portal hypertension and the associated systemic vasodilation lead to activation of the sodium-retaining neurohumoral mechanisms which include the renin-angiotensin-aldosterone system, sympathetic nervous system and antidiuretic hormone (ADH). The net effect is the avid retention of sodium and water to compensate for the low effective circulatory volume resulting in the development of ascites. Although not apparent in the early stages of cirrhosis, the progression of cirrhosis and ascites leads to impairment of the kidneys to eliminate solute- free water. This leads to additional compensatory mechanisms including non-osmotic secretion of ADH, also known as arginine vasopressin, further worsening excess water retention and thereby hyponatremia. Hyponatremia is associated with increased morbidity and mortality in patients with cirrhosis, and is an important prognostic marker both before and after liver transplant. The management of hyponatremia in this setting is a challenge as conventional therapy for hyponatremia including fluid restriction and loop diuretics are frequently inefficacious. In this review, we discuss the pathophysiology and various treatment modalities, including selective vasopressin receptor antagonists, for the management of hyponatremia in patients with cirrhosis. PMID:25805925

  11. Hepatitis C Virus Network Based Classification of Hepatocellular Cirrhosis and Carcinoma

    E-print Network

    Huang, Tao

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

  12. Telmisartan prevents hepatic fibrosis and enzyme-altered lesions in liver cirrhosis rat induced by a choline-deficient L-amino acid-defined diet

    SciTech Connect

    Jin Haiyan; Yamamoto, Naoki; Uchida, Koichi; Terai, Shuji; Sakaida, Isao

    2007-12-28

    Rennin-angiotensin system is involved in liver fibrogenesis through activating hepatic stellate cells (HSCs). Telmisartan (Tel) is an angiotensin II type 1 receptor antagonist, could function as a selective peroxisome proliferator-activated receptor {gamma} activator. Here we studied the effect of Tel on liver fibrosis, pre-neoplastic lesions in vivo and primary HSCs in vitro. In vivo study, we used the choline-deficient L-amino acid-defined (CDAA)-diet induced rat NASH model. The rats were fed the CDAA diet for 8 weeks to induce liver fibrosis and pre-neoplastic lesions, and then co-administrated with Tel for another 10 weeks. Tel prevented liver fibrogenesis and pre-neoplastic lesions by down-regulating TGF{beta}1 and TIMP-1, 2 and increasing MMP-13 expression. Tel inhibited HSCs activation and proliferation. These results suggested that Tel could be a promising drug for NASH related liver fibrosis.

  13. Novel Serum Biomarker Candidates for Liver Fibrosis in Hepatitis C Patients

    E-print Network

    , and the result- ing wound-healing process can lead to liver fibrosis and the subsequent development of cirrhosis. One of the leading causes of hepatic fibrosis and cirrhosis is infection with the hepatitis C virus risk of developing liver fibrosis and cirrhosis. Of the patients with HCV-induced cirrhosis, 2%­5% de

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

    PubMed

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

    2014-12-01

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

  15. Expression of P53 and HSP70 in Chronic Hepatitis, Liver Cirrhosis, and Early and Advanced Hepatocellular Carcinoma Tissues and Their Diagnostic Value in Hepatocellular Carcinoma: An Immunohistochemical Study

    PubMed Central

    Wang, Zhi; Gou, Wenbin; Liu, Ming; Sang, Wei; Chu, Hui; Zhang, Wei

    2015-01-01

    Background Tumor protein (P53) and heat shock protein 70 (HSP70) play key roles in chronic liver diseases. This study aimed to characterize P53 and HSP70 expression in chronic hepatitis (CH), liver cirrhosis (LC), early and advanced HCC, and to analyze their diagnostic value in hepatocellular carcinoma (HCC). Material/Methods Immunohistochemical staining was conducted to evaluate the expression of P53 and HSP70 in 200 human liver tissue specimens, with advanced HCC (n=80), early HCC (n=30), CH (n=30), LC (n=30), and Controls (n=30). Results P53 expression levels were lower in LC than those of HCC, but remained on par with those of CH and Controls. HSP70 expression levels were higher in HCC than those of LC, CH, and Controls. The sensitivity and specificity for HCC diagnosis were: 50.9% and 98.9% for P53, and 78.2 and 77.8% for HSP70, respectively. The sensitivity and specificity of different combinations were: 95.5% and 85.5% with either P53 or HSP70 being positive, and 33.6% and 98.9% if both were positive. Among the differentiation stages marked low, intermediate, and high in HCC, the P53 positive rate was higher in the low than in the intermediate, which was higher than that in the high. HSP70 positive rate was higher in the low and the intermediate than in the high, but no obvious changes were found between the low and the intermediate. Conclusions P53 and HSP70 could be potential biomarkers for HCC diagnosis, and proper combinations of these 2 markers could improve diagnostic accuracy. PMID:26494212

  16. www.yalecancercenter.org Advances in Liver Cancer

    E-print Network

    O'Hern, Corey S.

    risk factors for liver cancers, cirrhosis being by far the most important risk factor cirrhosis as a precursor and actually most people with cholangiocarcinoma do not have cirrhosis. The one patients have cirrhosis and that can come from different things such as hepatitis B, hepatitis C, and from

  17. Diagnostic Accuracy of APRI, AAR, FIB-4, FI, King, Lok, Forns, and FibroIndex Scores in Predicting the Presence of Esophageal Varices in Liver Cirrhosis: A Systematic Review and Meta-Analysis.

    PubMed

    Deng, Han; Qi, Xingshun; Guo, Xiaozhong

    2015-10-01

    Aspartate aminotransferase-to-platelet ratio (APRI), aspartate aminotransferase-to-alanine aminotransferase ratio (AAR), FIB-4, FI, King, Lok, Forns, and FibroIndex scores may be simple and convenient noninvasive diagnostic tests, because they are based on the regular laboratory tests and demographic data. This study aimed to systematically evaluate their diagnostic accuracy for the prediction of varices in liver cirrhosis.All relevant papers were searched via PubMed, EMBASE, CNKI, and Wanfang databases. The area under the summary receiver operating characteristic curve (AUSROC), sensitivity, specificity, positive and negative likelihood ratio (PLR and NLR), and diagnostic odds ratio (DOR) were calculated.Overall, 12, 4, 5, 0, 0, 4, 3, and 1 paper was identified to explore the diagnostic accuracy of APRI, AAR, FIB-4, FI, King, Lok, Forns, and FibroIndex scores, respectively. The AUSROCs of APRI, AAR, FIB-4, Lok, and Forns scores for the prediction of varices were 0.6774, 0.7275, 0.7755, 0.7885, and 0.7517, respectively; and those for the prediction of large varices were 0.7278, 0.7448, 0.7095, 0.7264, and 0.6530, respectively. The diagnostic threshold effects of FIB-4 and Forns scores for the prediction of varices were statistically significant. The sensitivities/specificities/PLRs/NLRs/DORs of APRI, AAR, and Lok scores for the prediction of varices were 0.60/0.67/1.77/0.58/3.13, 0.64/0.63/1.97/0.54/4.18, and 0.74/0.68/2.34/0.40/5.76, respectively. The sensitivities/specificities/PLRs/NLRs/DORs of APRI, AAR, FIB-4, Lok, and Forns scores for the prediction of large varices were 0.65/0.66/2.15/0.47/4.97, 0.68/0.58/2.07/0.54/3.93, 0.62/0.64/2.02/0.56/3.57, 0.78/0.63/2.09/0.37/5.55, and 0.65/0.61/1.62/0.59/2.75, respectively.APRI, AAR, FIB-4, Lok, and Forns scores had low to moderate diagnostic accuracy in predicting the presence of varices in liver cirrhosis. PMID:26496312

  18. Therapeutic short hairpin RNA expression in the liver: viral targets and vectors

    E-print Network

    Kay, Mark A.

    people die annually from HBV-associated liver failure, end-stage cirrhosis or hepatocellular carcinoma and fibrogenesis, and ultimately progresses to cirrhosis, end-stage liver failure and HCC.11 Notably, the virus

  19. CD147 promotes liver fibrosis progression via VEGF-A/VEGFR2 signalling-mediated cross-talk between hepatocytes and sinusoidal endothelial cells.

    PubMed

    Yan, Zhaoyong; Qu, Kai; Zhang, Jing; Huang, Qichao; Qu, Ping; Xu, Xinsen; Yuan, Peng; Huang, Xiaojun; Shao, Yongping; Liu, Chang; Zhang, Hongxin; Xing, Jinliang

    2015-10-01

    Although previous evidence indicates close involvement of CD147 in the pathogenesis of liver fibrosis, the underlying molecular mechanisms and its therapeutic value remain largely unknown. In the present study, we investigated the biological roles of CD147 in liver fibrosis and assessed its therapeutic value as a target molecule in the CCl4-induced liver fibrosis mouse model. We found that CD147 was highly expressed in both hepatocytes and SECs (sinusoidal endothelial cells) in fibrotic liver tissues. Additionally, it was significantly associated with the fibrosis stage. TGF-?1 (transforming growth factor ?1) was found to be mainly responsible for the up-regulation of CD147. Bioinformatic and experimental data suggest a functional link between CD147 expression and VEGF-A (vascular endothelial growth factor A)/VEGR-2 (VEGF receptor 2) signalling-mediated angiogenesis in fibrotic liver tissues. Furthermore, we observed that the CD147-induced activation of the PI3K (phosphoinositide 3-kinase)/Akt signalling pathway promotes the production of VEGF-A in hepatocytes and expression of VEGFR-2 in SECs, which was found to enhance the angiogenic capability of SECs. Finally, our data indicate that blocking of CD147 using an mAb (monoclonal antibody) attenuated liver fibrosis progression via inhibition of VEGF-A/VEGFR-2 signalling and subsequent amelioration of microvascular abnormality in the CCl4-induced mouse model. Our findings suggest a novel functional mechanism that CD147 may promote liver fibrosis progression via inducing the VEGF-A/VEGFR-2 signalling pathway-mediated cross-talk between hepatocytes and SECs. New strategies based on the intervention of CD147 can be expected for prevention of liver fibrosis. PMID:26201021

  20. Influence of cirrhosis on lamotrigine pharmacokinetics

    PubMed Central

    Marcellin, P; de Bony, F; Garret, C; Altman, C; Boige, V; Castelnau, C; Laurent-Puig, P; Trinchet, J C; Rolan, P; Chen, C; Mamet, J P; Bidault, R

    2001-01-01

    Aims Lamotrigine, an antiepileptic drug, is cleared from the systemic circulation mainly by glucuronidation. The possibility of changes in the pharmacokinetics of lamotrigine in plasma owing to hepatic dysfunction has been evaluated. Methods Thirty-six subjects, including 24 patients with various degrees of liver cirrhosis and 12 healthy volunteers received a single 100 mg dose of lamotrgine. Blood samples were taken for 7 days in all subjects, except nine with severe cirrhosis, who had a 29 day blood sampling period. Results The pharmacokinetics of lamotrigine were comparable between the patients with moderate cirrhosis (corresponding to Child-Pugh grade A) and the healthy subjects. Plasma oral clearance mean ratios (90% confidence interval) in patients with severe cirrhosis without or with ascites (corresponding, respectively, to Child-Pugh grade B and C) to healthy subjects were, respectively, 60% (44%, 83%) and 36% (25%, 52%). Plasma half-life mean ratios (90% confidence interval) in these two patient groups to healthy subjects were, respectively, 204% (149%, 278%) and 287% (202%, 408%). Conclusions Lamotrigine administered as a single oral dose of 100 mg was well tolerated in all groups. Initial, escalation and maintenance doses should generally be reduced by approximately 50 or 75% in patients with Child-Pugh Grade B or C cirrhosis. Escalation and maintenance doses should be adjusted according to clinical response. PMID:11421997

  1. Angiogenesis and proliferation of bile duct enhances ischemic tolerance in rats with cirrhosis

    PubMed Central

    Zhang, Zhiqiang; Li, Zhennan; Zou, Chen; Zhang, Jingjing; Zhu, Yi; Miao, Yi

    2015-01-01

    Background/aims: Primary biliary cirrhosis (PBC), an autoimmune disease of the liver, is marked by slow progressive destruction of bile ducts. These patients with PBC often undergo orthotopic liver transplantation (OLT). Ischemic bile duct lesion (IBDL) is a major source of morbidity and even mortality after OLT. Cirrhosis of the liver has a higher tolerance to ischemia than a normal liver, but the mechanism remains unknown. Angiogenesis and proliferation of bile duct often responses in bile duct ischemia, which may enhance ischemic tolerance in patients with cirrhosis. Methodology: To test the hypothesis, a rat model with cirrhosis was established. Biochemical indexes of ischemic severity were measured including total bilirubin (TBIL) and direct bilirubin (DBIL). Immunohistochemical assay was performed for Ki67 (a biomarker for the proliferation of bile duct) and CD34 (a biomarker of angiogenesis). Results: The levels were lower for TBIL and DBIL in the bile duct from rat model with cirrhosis than that from a normal rat after ischemic surgery (P < 0.05). The levels were higher for Ki67 and CD34 from a rat model with cirrhosis than that from a normal rat after ischemic surgery (P < 0.05). Conclusions: The results suggest that a liver with cirrhosis has a better ischemic tolerance than a normal liver. Angiogenesis and proliferation of bile duct enhances ischemic tolerance in rats with cirrhosis. More research on the pathogenesis of IBDLs is needed for developing more specific preventive or therapeutic strategies. PMID:26550120

  2. Renal impairment in cirrhosis unrelated to hepatorenal syndrome

    PubMed Central

    Low, Gavin; Alexander, Graeme JM; Lomas, David J

    2015-01-01

    Renal impairment is common in liver disease and may occur as a consequence of the pathophysiological changes that underpin cirrhosis or secondary to a pre-existing unrelated insult. Nevertheless, the onset of renal impairment often portends a worsening prognosis. Hepatorenal syndrome remains one of the most recognized and reported causes of renal impairment in cirrhosis. However, other causes of renal impairment occur and can be classified into prerenal, intrinsic or postrenal, which are the subjects of the present review. PMID:25874649

  3. C-reactive protein and bacterial infection in cirrhosis

    PubMed Central

    Pieri, Giulia; Agarwal, Banwari; Burroughs, Andrew K.

    2014-01-01

    In the general population, C-reactive protein (CRP) level increases in the presence of acute or chronic inflammation and infections. In patients with cirrhosis, the basal level is higher than in patients without cirrhosis, due to chronic hepatic and other inflammation, but when infection occurs the more severe the underlying liver dysfunction, the lower the increase in CRP. Therefore, the predictive power of CRP for infection and prognosis is weak in patients with decompensated/advanced cirrhosis and in the intensive care setting. However, higher CRP and also persistently elevated CRP levels can help identify patients with a higher short-term risk of mortality. PMID:24733601

  4. Complications of cirrhosis. A 50 years flashback.

    PubMed

    Møller, Søren; Bendtsen, Flemming

    2015-06-01

    In patients with cirrhosis and portal hypertension, it is largely the frequency and severity of complications relating to the diseased liver, degree of portal hypertension and hemodynamic derangement that determine the prognosis. It can be considered as a multiple organ failure that apart from the liver involves the heart, lungs, kidneys, the immune systems and other organ systems. Progressive fibrosis of the liver and subsequent metabolic impairment leads to a systemic and splanchnic arteriolar vasodilatation. With the progression of the disease development of portal hypertension leads to formation of esophageal varices and ascites. The circulation becomes hyperdynamic with cardiac, pulmonary as well as renal consequences for dysfunction and reduced survival. Infections and a changed cardiac function known as cirrhotic cardiomyopathy may be involved in further aggravation of other complications such as renal failure precipitating the hepatorenal syndrome. Patients with end-stage liver disease and related complications as for example the hepatopulmonary syndrome can only radically be treated by liver transplantation. PMID:25881709

  5. Influence of cirrhosis in cardiac surgery outcomes

    PubMed Central

    Lopez-Delgado, Juan C; Esteve, Francisco; Javierre, Casimiro; Ventura, Josep L; Mañez, Rafael; Farrero, Elisabet; Torrado, Herminia; Rodríguez-Castro, David; Carrio, Maria L

    2015-01-01

    Liver cirrhosis has evolved an important risk factor for cardiac surgery due to the higher morbidity and mortality that these patients may suffer compared with general cardiac surgery population. The presence of contributing factors for a poor outcome, such as coagulopathy, a poor nutritional status, an adaptive immune dysfunction, a degree of cirrhotic cardiomyopathy, and a degree of renal and pulmonary dysfunction, have to be taken into account for surgical evaluation when cardiac surgery is needed, together with the degree of liver disease and its primary complications. The associated pathophysiological characteristics that liver cirrhosis represents have a great influence in the development of complications during cardiac surgery and the postoperative course. Despite the population of cirrhotic patients who are referred for cardiac surgery is small and recommendations come from small series, since liver cirrhotic patients have increased their chance of survival in the last 20 years due to the advances in their medical care, which includes liver transplantation, they have been increasingly considered for cardiac surgery. Indeed, there is an expected rise of cirrhotic patients within the cardiac surgical population due to the increasing rates of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis, especially in western countries. In consequence, a more specific approach is needed in the assessment of care of these patients if we want to improve their management. In this article, we review the pathophysiology and outcome prediction of cirrhotic patients who underwent cardiac surgery. PMID:25914775

  6. Hepatitis C cirrhosis: New perspectives for diagnosis and treatment

    PubMed Central

    Khullar, Vikas; Firpi, Roberto J

    2015-01-01

    Chronic hepatitis C infection is the leading cause of chronic liver disease, cirrhosis, hepatocellular carcinoma as well as the primary indication for liver transplantation in the United States. Despite recent advances in drugs for the treatment of hepatitis C, predictive models estimate the incidence of cirrhosis due to hepatitis C infection will to continue to rise for the next two decades. There is currently an immense interest in the treatment of patients with fibrosis and early-stage cirrhosis as treatment can lead to decrease in the rates of decompensated cirrhosis, hepatocellular carcinoma and need for liver transplantation in these patients. The goal of this paper is to provide clinicians and health care professionals further information about the treatment of patients with hepatitis C infection and cirrhosis. Additionally, the paper focuses on the disease burden, epidemiology, diagnosis and the disease course from infection to treatment. We provide an overview of multiple studies for the treatment of chronic hepatitis C infection that have included patients with cirrhosis. We also discuss the advantages and disadvantages of treatment in cirrhotic patients and focus on the most up to date guidelines available for treatment. PMID:26207166

  7. Acute Kidney Injury in Patients with Cirrhosis

    PubMed Central

    Russ, Kirk B.; Stevens, Todd M; Singal, Ashwani K.

    2015-01-01

    Acute kidney injury (AKI) occurs commonly in patients with advanced cirrhosis and negatively impacts pre- and post-transplant outcomes. Physiologic changes that occur in patients with decompensated cirrhosis with ascites, place these patients at high risk of AKI. The most common causes of AKI in cirrhosis include prerenal injury, acute tubular necrosis (ATN), and the hepatorenal syndrome (HRS), accounting for more than 80% of AKI in this population. Distinguishing between these causes is particularly important for prognostication and treatment. Treatment of Type 1 HRS with vasoconstrictors and albumin improves short term survival and renal function in some patients while awaiting liver transplantation. Patients with HRS who fail to respond to medical therapy or those with severe renal failure of other etiology may require renal replacement therapy. Simultaneous liver kidney transplant (SLK) is needed in many of these patients to improve their post-transplant outcomes. However, the criteria to select patients who would benefit from SLK transplantation are based on consensus and lack strong evidence to support them. In this regard, novel serum and/or urinary biomarkers such as neutrophil gelatinase-associated lipocalin, interleukins-6 and 18, kidney injury molecule-1, fatty acid binding protein, and endothelin-1 are emerging with a potential for accurately differentiating common causes of AKI. Prospective studies are needed on the use of these biomarkers to predict accurately renal function recovery after liver transplantation alone in order to optimize personalized use of SLK. PMID:26623266

  8. Effect of Danshao Huaxian capsule on expression of matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 in fibrotic liver of rats

    PubMed Central

    Yang, Qin; Xie, Ru-Jia; Geng, Xiao-Xia; Luo, Xin-Hua; Han, Bing; Cheng, Ming-Liang

    2005-01-01

    AIM: To investigate the effects of Danshao Huaxian (DSHX) capsules, a preparation of traditional Chinese medicine, on the expression of matrix metalloproteinase-1 (MMP-1), and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the fibrous livers of rats. METHODS: Eighty male Wistar rats were randomly divided into normal control group (group A), CCl4-induced hepatic fibrosis group (group B), non-DSHX-treated group (group C), low dose-treated group (group D), and high dose-treated group (group E). Fibrous liver models in rats were induced by subcutaneous injection of CCl4, oral administration of alcohol and high-lipid/low-protein diet for 8 wk. After the models were established, the rats in groups D and E were orally given a low dose (0.5 g/kg) and a high dose (1.0 g/kg) of DSHX daily for 8 wk, respectively. Then, the liver indexes, serum hyaluronic acid (HA) and alanine aminotransferase (ALT) were examined. The degree of hepatic fibrosis was evaluated by optical microscopy. Hydroxyproline (Hyp) in the urine was determined, and the expression of MMP-1 and TIMP-1 was detected by immunohistochemical techniques. RESULTS: In groups D and E, the liver indexes, levels of serum HA and ALT reduced and development of hepatic fibrosis weakened significantly. The urinary Hyp and expression of MMP-1 in the liver tissues elevated, but the expression of TIMP-1 decreased obviously, as compared to groups B and C. CONCLUSION: DSHX enhances the expression of MMP-1 but decreases that of TIMP-1 in liver tissues of CCl4-induced hepatic fibrotic rats, which may result in its elevated activity that contributes to fighting against hepatic fibrosis. PMID:16124044

  9. Novel Therapies on Primary Biliary Cirrhosis.

    PubMed

    Czul, Frank; Levy, Cynthia

    2016-02-01

    All patients with primary biliary cirrhosis (PBC) and abnormal liver biochemistry should be considered for specific therapy. Ursodeoxycholic acid (UDCA) is the only FDA-approved drug for treating PBC. Approximately 40% of patients with PBC respond incompletely to treatment with UDCA, thus having increased risk of death or need for liver transplantation. No second-line therapies for patients with inadequate response to UDCA therapy have been approved. This review provides a current perspective on potential new approaches to treatment in PBC, and highlights some of the challenges we face in evaluating and effectively implementing those treatments. PMID:26593294

  10. Antitubercular therapy in patients with cirrhosis: Challenges and options

    PubMed Central

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

    2014-01-01

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

  11. Mesenchymal stem cell therapy for cirrhosis: Present and future perspectives

    PubMed Central

    Eom, Young Woo; Kim, Gaeun; Baik, Soon Koo

    2015-01-01

    Cirrhosis occurs as a result of various chronic liver injuries, which may be caused by viral infections, alcohol abuse and the administration of drugs and chemicals. Recently, bone marrow cells (BMCs), hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) have been used for developing treatments for cirrhosis. Clinical trials have investigated the therapeutic potential of BMCs, HSCs and MSCs for the treatment of cirrhosis based on their potential to differentiate into hepatocytes. Although the therapeutic mechanisms of BMC, HSC and MSC treatments are still not fully characterized, the evidence thus far has indicated that the potential therapeutic mechanisms of MSCs are clearer than those of BMCs or HSCs with respect to liver regenerative medicine. MSCs suppress inflammatory responses, reduce hepatocyte apoptosis, increase hepatocyte regeneration, reverse liver fibrosis and enhance liver functionality. This paper summarizes the clinical studies that have used BMCs, HSCs and MSCs in patients with liver failure or cirrhosis. We also present the potential therapeutic mechanisms of BMCs, HSCs and MSCs for the improvement of liver function. PMID:26420953

  12. Etiopathogenesis of primary biliary cirrhosis

    PubMed Central

    Lleo, Ana; Invernizzi, Pietro; Mackay, Ian R; Prince, Harry; Zhong, Ren-Qian; Gershwin, M Eric

    2008-01-01

    Primary biliary cirrhosis (PBC) is an autoimmune disease of the liver characterized by progressive bile duct destruction eventually leading to cirrhosis and liver failure. The serological hallmark of the disease is the presence of circulating antimitochondrial antibodies (AMA). These reflect the presence of autoreactive T and B cells to the culprit antigens, the E2 subunits of mitochondrial 2-oxo-acid dehydrogenase enzymes, chiefly pyruvate dehydrogenase (PDC-E2). The disease results from a combination of genetic and environmental risk factors. Genetic predisposition is indicated by the higher familial incidence of the disease particularly among siblings and the high concordance rate among monozygotic twins. Environmental triggering events appear crucial to disrupt a pre-existing unstable immune tolerance of genetic origin allowing, after a long latency, the emergence of clinical disease. Initiating mimotopes of the vulnerable epitope of the PDC-E2 autoantigen can be derived from microbes that utilize the PDC enzyme or, alternatively, environmental xenobiotics/chemical compounds that modify the structure of native proteins to make them immunogenic. A further alternative as a source of antigen is PDC-E2 derived from apoptotic cells. In the effector phase the biliary ductular cell, by reason of its proclivity to express the antigen PDC-E2 in the course of apoptosis, undergoes a multilineage immune attack comprised of CD4+ and CD8+ T cells and antibody. In this article, we critically review the available evidence on etiopathogenesis of PBC and present interpretations of complex data, new developments and theories, and nominate directions for future research. PMID:18528930

  13. Contribution and Mobilization of Mesenchymal Stem Cells in a mouse model of carbon tetrachloride-induced liver fibrosis.

    PubMed

    Liu, Yan; Yang, Xue; Jing, Yingying; Zhang, Shanshan; Zong, Chen; Jiang, Jinghua; Sun, Kai; Li, Rong; Gao, Lu; Zhao, Xue; Wu, Dong; Shi, Yufang; Han, Zhipeng; Wei, Lixin

    2015-01-01

    Hepatic fibrosis is associated with bone marrow derived mesenchymal stem cells (BM-MSCs). In this study, we aimed to determine what role MSCs play in the process and how they mobilize from bone marrow (BM). We employed a mouse model of carbon tetrachloride(CCl4)-induced liver fibrosis. Frozen section was used to detect MSCs recruited to mice and human fibrotic liver. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) was detected to assess liver function. It was found that MSCs of both exogenous and endogenous origin could aggravate liver fibrosis and attenuate liver damage as indicated by lower serum ALT and AST levels. Stromal cell-derived factor-1 (SDF-1?)/ CXCR4 was the most important chemotactic axis regulating MSCs migration from BM to fibrotic liver. Frozen section results showed that the migration did not start from the beginning of liver injury but occured when the expression balance of SDF-1? between liver and BM was disrupted, where SDF-1? expression in liver was higher than that in BM. Our findings provide further evidence to show the role of BM-MSCs in liver fibrosis and to elucidate the mechanism underlying MSCs mobilization in our early liver fibrosis mice model induced by CCl4. PMID:26643997

  14. Contribution and Mobilization of Mesenchymal Stem Cells in a mouse model of carbon tetrachloride-induced liver fibrosis

    PubMed Central

    Liu, Yan; Yang, Xue; Jing, Yingying; Zhang, Shanshan; Zong, Chen; Jiang, Jinghua; Sun, Kai; Li, Rong; Gao, Lu; Zhao, Xue; Wu, Dong; Shi, Yufang; Han, Zhipeng; Wei, Lixin

    2015-01-01

    Hepatic fibrosis is associated with bone marrow derived mesenchymal stem cells (BM-MSCs). In this study, we aimed to determine what role MSCs play in the process and how they mobilize from bone marrow (BM). We employed a mouse model of carbon tetrachloride(CCl4)-induced liver fibrosis. Frozen section was used to detect MSCs recruited to mice and human fibrotic liver. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) was detected to assess liver function. It was found that MSCs of both exogenous and endogenous origin could aggravate liver fibrosis and attenuate liver damage as indicated by lower serum ALT and AST levels. Stromal cell–derived factor-1 (SDF-1?)/ CXCR4 was the most important chemotactic axis regulating MSCs migration from BM to fibrotic liver. Frozen section results showed that the migration did not start from the beginning of liver injury but occured when the expression balance of SDF-1? between liver and BM was disrupted, where SDF-1? expression in liver was higher than that in BM. Our findings provide further evidence to show the role of BM-MSCs in liver fibrosis and to elucidate the mechanism underlying MSCs mobilization in our early liver fibrosis mice model induced by CCl4. PMID:26643997

  15. Ferulic acid protects against carbon tetrachloride-induced liver injury in mice.

    PubMed

    Kim, Hyo-Yeon; Park, Juhyun; Lee, Kwan-Hoo; Lee, Dong-Ung; Kwak, Jong-Hwan; Kim, Yeong Shik; Lee, Sun-Mee

    2011-04-11

    Ferulic acid (FA), isolated from the root of Scrophularia buergeriana, is a phenolic compound possessing antioxidant, anticancer, and antiinflammatory activities. Here, we have investigated the hepatoprotective effect of FA against carbon tetrachloride (CCl(4))-induced acute liver injury. Mice were treated intraperitoneally with vehicle or FA (20, 40, and 80mg/kg) 1h before and 2h after CCl(4) (20?l/kg) injection. The serum activities of aminotransferases and the hepatic level of malondialdehyde were significantly higher after CCl(4) treatment, while the concentration of reduced glutathione was lower. These changes were attenuated by FA. The serum level and mRNA expression of tumor necrosis factor-? significantly increased after CCl(4) treatment, and FA attenuated these increases. The levels of inducible nitric oxide synthase and cyclooxygenase-2 protein and mRNA expression after CCl(4) treatment were significantly higher and FA reduced these increases. CCl(4)-treated mice showed increased nuclear translocation of nuclear factor-?B (NF-?B), and decreased levels of inhibitors of NF-?B in cytosol. Also, CCl(4) significantly increased the level of phosphorylated JNK and p38 mitogen-activated protein (MAP) kinase, and nuclear translocation of activated c-Jun. FA significantly attenuated these changes. We also found that acute CCl(4) challenge induced TLR4, TLR2, and TLR9 protein and mRNA expression, and FA significantly inhibited TLR4 expression. These results suggest that FA protects from CCl(4)-induced acute liver injury through reduction of oxidative damage and inflammatory signaling pathways. PMID:21291945

  16. Asymmetric dimethylarginine as a mediator of vascular dysfunction in cirrhosis

    PubMed Central

    Lluch, Paloma; Segarra, Gloria; Medina, Pascual

    2015-01-01

    Cirrhosis is associated with marked abnormalities in the circulatory function that involve a reduction in systemic vascular resistance. An important cause of this vasodilatation is the increased production or activity of nitric oxide (NO) in the splanchnic circulation. During portal hypertension and cirrhosis an increased endothelial NO synthase (eNOS) activity is demonstrated in splanchnic vessels. In contrast, the activity of eNOS in the cirrhotic liver is decreased, which suggests a different regulation of eNOS in the liver and in the splanchnic vessels. Asymmetric dimethylarginine (ADMA) is an endogenous NO inhibitor and higher plasma levels of ADMA are related to increased cardiovascular risk in both the general population and among patients with cirrhosis. It has been demonstrated that the liver is a key player in the metabolism of ADMA. This observation was further supported by investigations in human patients, showing a close correlation between ADMA plasma levels and the degree of hepatic dysfunction. ADMA is degraded to citrulline and dimethylamine by dimethylarginine dimethylaminohydrolases (DDAHs). DDAHs are expressed as type 1 and 2 isoforms and are widely distributed in various organs and tissues, including the liver. In this review, we discuss experimental and clinical data that document the effects of dimethylarginines on vascular function in cirrhosis. Our increasing understanding of the routes of synthesis and metabolism of methylarginines is beginning to provide insights into novel mechanisms of liver disease and allowing us to identify potential therapeutic opportunities. PMID:26327755

  17. Antipyrine clearance and metabolite formation in patients with alcoholic cirrhosis.

    PubMed Central

    Teunissen, M W; Spoelstra, P; Koch, C W; Weeda, B; van Duyn, W; Janssens, A R; Breimer, D D

    1984-01-01

    The effect of liver cirrhosis on plasma clearance and metabolite profile of i.v. administered antipyrine was studied in 23 patients with alcoholic liver cirrhosis (age 37-70 years) and 17 healthy subjects (age 28-55 years). Liver volume was also measured and was found to be larger in patients than in controls, mean values being 1.86 and 1.36 l respectively. The elimination half-life of antipyrine in patients with alcoholic liver cirrhosis was significantly longer than in the healthy subjects (P less than 0.001). Mean values were 39.9 and 10.1 h respectively. Alcoholic liver cirrhosis had no effect on the apparent volume of distribution of antipyrine, but antipyrine plasma clearance was substantially reduced in the patients. Mean clearance values (ranges) were 13.5 (9.3-22.8) ml/min in the patients and 49.3 (31.1-103) ml/min in healthy subjects. Normalization of antipyrine plasma clearance for liver volume resulted in an only slightly increased distinction between patients and healthy subjects, mean values (ranges) being 7.8 (3.3-13.0) ml min(-1) 1(-1) and 36.1 (21.9-35.9) ml min(-1) 1(-1) respectively. The cumulative renal excretion of 4-hydroxyantipyrine (OHA) and norantipyrine (NORA) was significantly lower in patients with alcoholic liver cirrhosis than in healthy subjects, as was the total recovery of antipyrine and major metabolites from urine. Mean values were 15.0, 8.4 and 41.2% of dose in the patients respectively and 24.3, 25.8 and 68.9% of dose in the control subjects. Excreted amounts of total and unconjugated 3-hydroxymethylantipyrine (HMA) and of unchanged antipyrine were the same in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:6508980

  18. Thallium-201 per rectum for the diagnosis of cirrhosis in patients with asymptomatic chronic hepatitis

    SciTech Connect

    D'Arienzo, A.; Celentano, L.; Scuotto, A.; Di Siervi, P.; Lombardi, V.; Squame, G.; Mazzacca, G.

    1988-07-01

    In normal subjects, thallium-201, administered per rectum, is taken up mainly by the liver (heart/liver ratio in normal subjects: 0.04 to 0.12). It has been claimed that an increased heart/liver ratio is suggestive of portal-caval shunting and portal hypertension. To evaluate the possibility of using thallium-201 as a test to diagnose cirrhosis, we administered this substance per rectum to 33 patients with biochemical evidence, but no clinical symptoms, of liver disease. Laparoscopy and liver biopsy revealed chronic active hepatitis without cirrhosis in 18 patients, and chronic active hepatitis with cirrhosis in the others. The results of conventional liver function tests were similar in both groups. A significant difference, however, was found between the means of fasting serum bile acid concentrations (9.8 +/- 3.2 and 18.3 +/- 4.2 microM per liter) in chronic active hepatitis without cirrhosis and cirrhotic patients, and between the means of the heart/liver ratios 20 min after thallium-201 administration (heart/liver: 0.09 +/- 0.03 and 0.54 +/- 0.13, respectively). Unlike the serum bile acid concentration which gave some overlapping values, the thallium-201 test clearly distinguished the chronic active hepatitis without cirrhosis group from the cirrhotics. In the cirrhotic group, there was a significant correlation between the heart/liver ratio and signs of portal hypertension such as esophageal varices, increased diameter of the vena porta and hypersplenism. The thallium-201 test is therefore useful in discriminating between chronic active hepatitis with and without cirrhosis in clinically asymptomatic subjects with biochemical evidence of moderate liver function impairment. A heart/liver uptake ratio much higher than normal (above 0.30) strongly suggests the development of hepatic cirrhosis.

  19. Gut microbiota-related complications in cirrhosis

    PubMed Central

    Gómez-Hurtado, Isabel; Such, José; Sanz, Yolanda; Francés, Rubén

    2014-01-01

    Gut microbiota plays an important role in cirrhosis. The liver is constantly challenged with commensal bacteria and their products arriving through the portal vein in the so-called gut-liver axis. Bacterial translocation from the intestinal lumen through the intestinal wall and to mesenteric lymph nodes is facilitated by intestinal bacterial overgrowth, impairment in the permeability of the intestinal mucosal barrier, and deficiencies in local host immune defences. Deranged clearance of endogenous bacteria from portal and systemic circulation turns the gut into the major source of bacterial-related complications. Liver function may therefore be affected by alterations in the composition of the intestinal microbiota and a role for commensal flora has been evidenced in the pathogenesis of several complications arising in end-stage liver disease such as hepatic encephalopathy, splanchnic arterial vasodilatation and spontaneous bacterial peritonitis. The use of antibiotics is the main therapeutic pipeline in the management of these bacteria-related complications. However, other strategies aimed at preserving intestinal homeostasis through the use of pre-, pro- or symbiotic formulations are being studied in the last years. In this review, the role of intestinal microbiota in the development of the most frequent complications arising in cirrhosis and the different clinical and experimental studies conducted to prevent or improve these complications by modifying the gut microbiota composition are summarized. PMID:25400446

  20. Visual detection of serum asialohaptoglobin by plasmonic sandwich ELLSA - a new platform for cirrhosis diagnosis.

    PubMed

    Bose, Partha Pratim; Mandal, Gautam; Kumar, Dharmendra; Duseja, Ajay; Chatterjee, Bishnu Pada

    2016-01-01

    The cirrhotic condition of the liver has long been acknowledged as the preface to liver cancer. The desialylation status of the serum acute phase protein, haptoglobin, has been introduced as a new diagnostic analyte for liver cirrhosis. The reliability of this new diagnostic molecule has been evaluated in 30 liver cirrhosis patients having a history of earlier viral hepatitis C (HCV-LC). A novel enzyme linked lectinosorbent assay has been developed coupled with the plasmon mechanism of gold nanoparticle aggregation as the colorimetric read out which can visually distinguish the cirrhotic liver patients from the normal healthy and hepatitis C controls. The assay can be useful for rapid point-of-care detection, and even an untrained person can execute it without a specialized instrument. This method employs Sambucus nigra agglutinin (SNA) to detect the extent of ?-2,6 sialylation of serum haptoglobin, the new diagnostic molecule for liver cirrhosis. PMID:26568048

  1. BASIC--LIVER, PANCREAS, AND BILIARY Development of Nonalcoholic Steatohepatitis in Insulin-Resistant

    E-print Network

    Toledo, University of

    - crease in parallel to the increased prevalence of obesity.1 With NASH progressing to cirrhosis and the leading liver disease and cause of liver transplantation as a result of cirrhosis in Western countries and inflammation, leading to hep- atitis, apoptosis, fibrosis, and, ultimately, cirrhosis (sec- ond hit

  2. Spinal cord involvement in patients with cirrhosis

    PubMed Central

    Nardone, Raffaele; Höller, Yvonne; Storti, Monica; Lochner, Piergiorgio; Tezzon, Frediano; Golaszewski, Stefan; Brigo, Francesco; Trinka, Eugen

    2014-01-01

    A severe spinal cord involvement may rarely occur in patients with cirrhosis and other chronic liver diseases; this complication is usually associated with overt liver failure and surgical or spontaneous porto-systemic shunt. Hepatic myelopathy (HM) is characterized by progressive weakness and spasticity of the lower extremities, while sensory and sphincter disturbances have rarely been described and are usually less important. The diagnosis is assigned in the appropriate clinical setting on clinical grounds after the exclusion of other clinical entities leading to spastic paraparesis. Magnetic resonance imaging is often unremarkable; however, also intracerebral corticospinal tract abnormalities have been reported recently. The study of motor evoked potentials may disclose central conduction abnormalities even before HM is clinically manifest. HM responds poorly to blood ammonia-lowering and other conservative medical therapy. Liver transplantation represents a potentially definitive treatment for HM in patients with decompensated cirrhosis of Child-Pugh B and C grades. Other surgical treatment options in HM include surgical ligation, shunt reduction, or occlusion by interventional procedures. PMID:24627593

  3. doi:10.1016/j.ultrasmedbio.2008.03.002 ELASTOGRAPHY IN THE MANAGEMENT OF LIVER DISEASE

    E-print Network

    Parker, Kevin J.

    cirrhosis, a disease with serious medical implications. After the onset of cirrhosis, the probability is eliminated. Severe fibrosis (cirrhosis), how- ever, is likely to be irreversible and, in the extreme, results in liver failure. Furthermore, cirrhosis is associated with as much as a one hundred­fold increase

  4. Cirrhosis: A Patient's Guide

    MedlinePLUS

    ... bleeding from varices. Bilirubin: By-product of the body that is removed by the liver. A high level in the blood causes jaundice and is a sign that the liver is not working well. Child-Pugh (or CTP) score: A score that indicates how sick the liver ...

  5. The role of CYP2A5 in liver injury and fibrosis: chemical-specific difference.

    PubMed

    Hong, Feng; Si, Chuanping; Gao, Pengfei; Cederbaum, Arthur I; Xiong, Huabao; Lu, Yongke

    2016-01-01

    Liver injuries induced by carbon tetrachloride (CCL4) or thioacetamide (TAA) are dependent on cytochrome P450 2E1 (CYP2E1). CYP2A5 can be induced by TAA but not by CCL4. In this study, liver injury including fibrosis induced by CCL4 or TAA were investigated in wild-type (WT) mice and CYP2A5 knockout (cyp2a5 (-/-) ) mice as well as in CYP2E1 knockout (cyp2e1 (-/-) ) mice as a comparison. Acute and subchronic liver injuries including fibrosis were induced by CCL4 and TAA in WT mice but not in cyp2e1 (-/-) mice, confirming the indispensable role of CYP2E1 in CCL4 and TAA hepatotoxicity. WT mice and cyp2a5 (-/-) mice developed comparable acute liver injury induced by a single injection of CCL4 as well as subchronic liver injury including fibrosis induced by 1 month of repeated administration of CCL4, suggesting that CYP2A5 does not affect CCL4-induced liver injury and fibrosis. However, while 200 mg/kg TAA-induced acute liver injury was comparable in WT mice and cyp2a5 (-/-) mice, 75 and 100 mg/kg TAA-induced liver injury were more severe in cyp2a5 (-/-) mice than those found in WT mice. After multiple injections with 200 mg/kg TAA for 1 month, while subchronic liver injury as indicated by serum aminotransferases was comparable in WT mice and cyp2a5 (-/-) mice, liver fibrosis was more severe in cyp2a5 (-/-) mice than that found in WT mice. These results suggest that while both CCL4- and TAA-induced liver injuries and fibrosis are CYP2E1 dependent, under some conditions, CYP2A5 may protect against TAA-induced liver injury and fibrosis, but it does not affect CCL4 hepatotoxicity. PMID:26363552

  6. Antioxidant Bioactivity of Samsum Ant (Pachycondyla sennaarensis) Venom Protects against CCL4-Induced Nephrotoxicity in Mice

    PubMed Central

    Ebaid, Hossam; Al-Tamimi, Jameel; Hassan, Iftekhar; Alhazza, Ibrahim; Al-Khalifa, Mohamed

    2014-01-01

    To assess whether SAV could influence the effects of carbon tetrachloride (CCL4) exposure, mice were treated with SAV in doses of 100, 200, 300 and 400??g/kg body weight and the effects on oxidative status and kidney function were studied. Serum levels of creatinine, malondialdehyde (MDA), and blood urea, together with renal and hepatic levels of MDA, glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) were quantified in order to evaluate antioxidant activity. Results showed that the group injected with CCL4 exhibited significantly higher levels of oxidative stress markers, MDA, and significantly lower concentrations of GSH, SOD and catalase. SAV was found to significantly improve these oxidative markers, occasionally, in a dose-dependent manner. Furthermore, treatment with SAV was associated with the same behaviour in respect to kidney functions which had previously been impaired by CCL4. Histopathological examination demonstrated that SAV, in different groups, improved the renal tissue damage induced by CCL4 and histological scores confirmed that significant improvements were obtained after treatment with SAV, particularly with the lowest dose (100??g/kg body weight). In conclusion, SAV has the potential capability to restore oxidative stability and to improve kidney functions after CCL4 acute injury. PMID:24803985

  7. HEPATITIS B INFORMATION & VACCINATION WAIVER Hepatitis B is a serious infectious disease caused by a virus that attacks the liver. The hepatitis B virus

    E-print Network

    Chen, Shu-Ching

    by a virus that attacks the liver. The hepatitis B virus (HBV) can cause life-long infection that may lead to cirrhosis (scarring) of the liver, liver cancer, liver failure, or death. There is no cure for hepatitis B

  8. Liver Transplantation for Cholestatic Liver Diseases in Adults.

    PubMed

    Khungar, Vandana; Goldberg, David Seth

    2016-02-01

    Liver transplantation (LT) is an established lifesaving therapy for patients with cholestatic liver diseases, including primary cholestatic diseases, namely primary sclerosing cholangitis and primary biliary cirrhosis, as well as secondary forms of cholestatic liver disease, including those with cholestatic complications of LT needing a retransplant. Patients with cholestatic liver diseases can be transplanted for complications of end-stage liver disease or for disease-specific symptoms before the onset of end-stage liver disease. These patients should be regularly assessed. Patient survival after LT for cholestatic liver diseases is generally better than for other indications. PMID:26593299

  9. The interplay of the Notch signaling in hepatic stellate cells and macrophages determines the fate of liver fibrogenesis

    PubMed Central

    Bansal, Ruchi; van Baarlen, Joop; Storm, Gert; Prakash, Jai

    2015-01-01

    Hepatic stellate cells (HSCs) known as “master producers” and macrophages as “master regulators”, are the key cell types that strongly contribute to the progression of liver fibrosis. Since Notch signaling regulates multiple cellular processes, we aimed to study the role of Notch signaling in HSCs differentiation and macrophages polarization and to evaluate its implication in liver fibrogenesis. Notch pathway components were found to be significantly upregulated in TGF?-activated HSCs, inflammatory M1 macrophages, and in mouse and human fibrotic livers. Interestingly, inhibition of Notch using a selective ?-secretase inhibitor, Avagacestat, significantly inhibited TGF?-induced HSC activation and contractility, and suppressed M1 macrophages. Additionally, Avagacestat inhibited M1 driven-fibroblasts activation and fibroblasts-driven M1 polarization (nitric oxide release) in fibroblasts and macrophages co-culture, and conditioned medium studies. In vivo, post-disease treatment with Avagacestat significantly attenuated fibrogenesis in CCl4-induced liver fibrosis mouse model. These effects were attributed to the reduction in HSCs activation, and inhibition of inflammatory M1 macrophages and upregulation of suppressive M2 macrophages. These findings suggest that Notch signaling plays a crucial role in HSC activation and M1/M2 polarization of macrophages in liver fibrosis. These results provide new insights for the development of novel therapies against liver fibrosis through modulation of Notch signaling. PMID:26658360

  10. 28 CFR 79.27 - Indication of the presence of hepatitis B or cirrhosis.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... eligibility under this subpart for primary cancer of the liver, the claimant or eligible surviving beneficiary... six months before and six months after the date of diagnosis of primary cancer of the liver: (i) All... possessed by the state cancer or tumor registries, indicates the presence of hepatitis B or cirrhosis,...

  11. B-type natriuretic peptide and cirrhosis progression.

    PubMed

    Shi, L Y; Jin, R; Lin, C J; Wu, J S; Chen, X W; Yu, Z; Zhang, P C

    2015-01-01

    Brain natriuretic peptide (BNP) is used as a marker of cardiac dysfunction to predict heart failure mortality. The significance of the prognostic ability of BNP for liver cirrhosis remains unknown, although the levels of BNP seen in cirrhosis are high. We aimed to determine whether the BNP level is related to the stage of cirrhosis and could serve as a prognostic marker of cirrhosis (predict the 1-year all-cause mortality). We recruited 92 patients at different stages of cirrhosis and 81 controls matched by age and gender for this study. At admission, cardiac physical examination and BNP measurements were performed. Upon discharge, the 89 patients were followed up for 12 months. The median BNP levels of patients with cirrhosis were 167.0 pg/mL, which were significantly higher than those of the control group (167.0 vs 34.8 pg/mL, P = 0.001). Serum BNP levels were positively correlated with the Child score, the grade of esophageal varices, a history of spontaneous bacterial peritonitis, and the presence of ascites and collateral circulation. BNP levels above the median were associated with an increased occurrence of death within 12 months of discharge (log rank P = 0.025), as determined by univariate and multivariate Cox regression analyses. Esophageal varices, large/medium volume ascites, and BNP levels were related to the clinical outcome (P = 0.034, 0.030, and 0.025, respectively). Together, these results suggested that serum BNP levels are significantly correlated with the stage of cirrhosis, suggesting that BNP levels might serve as a significant predictor for 1-year all-cause mortality. PMID:26125712

  12. The investigation of glucose metabolism and insulin secretion in subjects of chronic hepatitis B with cirrhosis

    PubMed Central

    Guo, Chun-Hui; Sun, Ting-Ting; Weng, Xi-Ding; Zhang, Jian-Chun; Chen, Jian-Xin; Deng, Guo-Jiong

    2015-01-01

    Aims: To investigate the situations of abnormal glucose metabolism and dysfunction of pancreatic islet beta cells in subjects of chronic hepatitis B (CHB) with cirrhosis. Methods: 106 hepatitis B virus (HBV) positive subjects with liver cirrhosis as well as with different grade of Child-Pugh and 37 healthy subjects were included in this study. The oral glucose tolerance test (OGTT), C-peptide and insulin release test were detected. Plasma glucose and insulin levels were analyzed periodically for 2 h after oral glucose loading. Results: There was no significant difference in the level of fasting plasma glucose and C-peptide between cirrhosis group and control group (P>0.05). The levels of OGTT 2 h glucose, insulin and C peptide were significantly higher in cirrhosis group than control group (P<0.01). Peak plasma glucose levels were obtained at 60 min in normal group and cirrhosis group. The peak insulin and C-peptide response occurred at 60 min in normal group, whereas it was delayed to 120 min in cirrhosis group. There was a significant difference between two groups in the pattern of plasma glucose levels at corresponding time points (P<0.05). The OGTT 2 h glucose and insulin levels were positively correlated with Child-Pugh Score (r1 = 0.389, r2 = 0.508, P<0.01). Conclusion: These findings implied that there was a certain degree of insulin resistance and abnormal glucose metabolism in the patients with liver cirrhosis. PMID:26722544

  13. Coffee, alcohol and other beverages in relation to cirrhosis mortality: the Singapore Chinese Health Study

    PubMed Central

    Goh, George Boon-Bee; Chow, Wan-Cheng; Renwei-Wang; Yuan, Jian-Min; Koh, Woon-Puay

    2014-01-01

    Limited experimental and epidemiologic data suggest that coffee may reduce hepatic damage in chronic liver disease. The association between consumption of coffee and other beverages, and risk of cirrhosis mortality was evaluated in The Singapore Chinese Health Study. This is a prospective population-based cohort of 63,275 middle-aged and older Chinese subjects who provided data on diet, lifestyle and medical histories through in-person interviews using structured questionnaire at enrollment between 1993 and 1998. Mortality from cirrhosis in the cohort was ascertained through linkage analysis with nationwide death registry. After a mean follow-up of 14.7 years, 114 subjects died from cirrhosis; 33 of them from viral hepatitis B (29%), two from hepatitis C (2%), and 14 from alcohol-related cirrhosis (12%). Compared to non-drinkers, daily alcohol drinkers had a strong dose-dependent positive association between amount of alcohol and risk of cirrhosis mortality. Conversely, there was a strong dose-dependent inverse association between coffee intake and risk of non-viral hepatitis related cirrhosis mortality (p for trend=0.014). Compared to non-daily coffee drinkers, those who drank two or more cups per day had 66% reduction in mortality risk (HR=0.34, 95% CI=0.14–0.81). However, coffee intake was not associated with hepatitis B related cirrhosis mortality. The inverse relationship between caffeine intake and nonviral hepatitis-related cirrhosis mortality became null after adjustment for coffee drinking. The consumption of black tea, green tea, fruit juices or soft drinks was not associated with risk of cirrhosis death. Conclusion This study demonstrates the protective effect of coffee on non-viral hepatitis related cirrhosis mortality, and provides further impetus to evaluate coffee as a potential therapeutic agent in patients with cirrhosis. PMID:24753005

  14. Mutation of human keratin 18 in association with cryptogenic cirrhosis.

    PubMed Central

    Ku, N O; Wright, T L; Terrault, N A; Gish, R; Omary, M B

    1997-01-01

    Mutations in 11 of the more than 20 keratin intermediate filaments cause several epidermal and oral associated diseases. No disease-associated mutations have been described in keratin 8 or 18 (K8/18) which are the major keratin pair in simple-type epithelia, as found in the liver, pancreas, and intestine. However, transgenic mice that express mutant keratin 18 develop chronic hepatitis, and have an increased susceptibility to drug-induced hepatotoxicity. Also, ectopic expression of epidermal K14 in mouse liver results in chronic hepatitis, and disruption of mouse K8 leads to embryo lethality with extensive liver hemorrhage. We tested if patients with liver disease of unknown cause may harbor mutations in K18. We describe a his127-->leu (H127L) K18 mutation in a patient with cryptogenic cirrhosis that is germline transmitted. The K18 H127L isolated from the liver explant, or after expression in bacteria, showed an altered migration on two-dimensional gel analysis as compared with normal human liver or bacterially expressed K18. Electron microscopy of in vitro assembled K18 H127L and wild type K8 showed an assembly defect as compared with normal K8/18 assembly. Our results suggest that mutations in K18 may be predispose to, or result in cryptogenic cirrhosis in humans. PMID:9011570

  15. Therapeutic and clinical aspects of portal vein thrombosis in patients with cirrhosis

    PubMed Central

    Primignani, Massimo; Tosetti, Giulia; La Mura, Vincenzo

    2015-01-01

    Portal vein thrombosis (PVT) is a frequent complication in cirrhosis, particularly in advanced stages of the disease. As for general venous thromboembolism, risk factors for PVT are slow blood flow, vessel wall damage and hypercoagulability, all features of advanced cirrhosis. Actually, the old dogma of a hemorrhagic tendency in cirrhosis has been challenged by new laboratory tools and the clinical evidence that venous thrombosis also occurs in cirrhosis. The impaired hepatic synthesis of both pro- and anticoagulants leads to a rebalanced hemostasis, more liable to be tipped towards thrombosis or even bleeding. Conventional anticoagulant drugs (low molecular weight heparin or vitamin K antagonists) may be used in cirrhosis patients with PVT, particularly in those eligible for liver transplantation, to prevent thrombosis progression thus permitting/facilitating liver transplant. However, several doubts exist on the level of anticoagulation achieved as estimated by coagulation tests, on the efficacy of treatment monitoring and on the correct timing for discontinuation in non-transplant candidates, while in transplant candidates there is expert consensus on continuing anticoagulation until transplantation. The recent introduction of direct acting oral anticoagulant drugs (DOACs) in other clinical settings generates much interest on their possible application in patients with cirrhosis and PVT. However, DOACs were not evaluated yet in patients with liver disease and cannot be recommended for the present time. PMID:26689354

  16. Strategies for treating chronic HCV infection in patients with cirrhosis: latest evidence and clinical outcomes

    PubMed Central

    Wilder, Julius M.; Muir, Andrew J.

    2015-01-01

    The burden of chronic hepatitis C virus (HCV) infection is significant and growing. HCV is considered one of the leading causes of liver disease worldwide and the leading cause of liver transplantation globally. While those infected is estimated in the hundreds of millions, this is likely an underestimation because of the indolent nature of this disease when first contracted. Approximately 20% of patients with HCV infection will progress to advanced fibrosis and cirrhosis. Those that do are at risk of decompensated liver disease including GI bleeding, encephalopathy, severe lab abnormalities, and hepatocellular carcinoma. Those individuals with advanced fibrosis and cirrhosis have historically been difficult to treat. The backbone of previous HCV regimens was interferon (IFN). The outcomes for IFN based regimens were poor and resulted in increased adverse events among those with advanced fibrosis and cirrhosis. Now, in the era of new direct acting antiviral (DAA’s) medications, there is hope for curing chronic HCV in everyone, including those with advanced fibrosis and cirrhosis. This article provides a review on the most up to date data on the use of DAA’s in patients with advanced fibrosis and cirrhosis. We are at a point where HCV could be truly eradicated, but to do so will require ensuring there are effective and safe treatments for those with advanced fibrosis and cirrhosis. PMID:26568808

  17. Glycoprotein Nonmetastatic Melanoma B (Gpnmb)-Positive Macrophages Contribute to the Balance between Fibrosis and Fibrolysis during the Repair of Acute Liver Injury in Mice

    PubMed Central

    Kumagai, Kotaro; Tabu, Kazuaki; Sasaki, Fumisato; Takami, Yoichiro; Morinaga, Yuko; Mawatari, Seiichi; Hashimoto, Shinichi; Tanoue, Shiroh; Kanmura, Shuji; Tamai, Tsutomu; Moriuchi, Akihiro; Uto, Hirofumi; Tsubouchi, Hirohito; Ido, Akio

    2015-01-01

    Background and aims Glycoprotein nonmetastatic melanoma B (Gpnmb), a transmembrane glycoprotein that is expressed in macrophages, negatively regulates inflammation. We have reported that Gpnmb is strongly expressed in the livers of rats fed a choline-deficient, L-amino acid-defined (CDAA) diet. However, the role of macrophage-expressed Gpnmb in liver injury is still unknown. This study aimed to clarify the characteristics of infiltrating macrophages that express Gpnmb, and the involvement of Gpnmb in the repair process in response to liver injury. Methods C57BL/6J, DBA/2J [DBA] and DBA/2J-Gpnmb+ [DBA-g+] mice were treated with a single intraperitoneal injection of carbon tetrachloride (CCl4) at a dose of 1.0 mL/kg body weight. Mice were sacrificed at predetermined time points, followed by measurement of serum alanine aminotransferase (ALT) levels and histological examination. Expression of Gpnmb, pro-/anti-inflammatory cytokines, and profibrotic/antifibrotic factors were examined by quantitative RT-PCR and/or Western blotting. Immunohistochemistry, fluorescent immunostaining and flow cytometry were used to determine the expression of Gpnmb, CD68, CD11b and ?-SMA, phagocytic activity, and the presence of apoptotic bodies. We used quantitative RT-PCR and ELISA to examine TGF-? and MMP-13 expression and the concentrations and supernatants of isolated infiltrating hepatic macrophages transfected with siGpnmb. Results In C57BL/6J mice, serum ALT levels increased at two days after CCl4 injection and decreased at four days. Gpnmb expression in the liver was stimulated four days after CCl4 injection. Histological examination and flow cytometry showed that Gpnmb-positive cells were almost positive for CD68-positive macrophages, contained engulfed apoptotic bodies and exhibited enhanced phagocytic activity. Isolated infiltrating hepatic macrophages transfected with siGpnmb showed high MMP-13 secretion. There was no significant difference in the magnitude of CCl4-induced liver injury between DBA-g+ and DBA mice. However, hepatic MMP-13 expression, as well as ?-SMA expression and collagen production, increased significantly in DBA-g+ compared with DBA mice. Conclusions Gpnmb-positive macrophages infiltrate the liver during the recovery phase of CCl4induced acute liver injury and contribute to the balance between fibrosis and fibrolysis in the repair process following acute liver injury. PMID:26599547

  18. Chronic liver disease: evaluation by magnetic resonance

    SciTech Connect

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

    1984-01-01

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

  19. Endothelial dysfunction in cirrhosis: Role of inflammation and oxidative stress

    PubMed Central

    Vairappan, Balasubramaniyan

    2015-01-01

    This review describes the recent developments in the pathobiology of endothelial dysfunction (ED) in the context of cirrhosis with portal hypertension and defines novel strategies and potential targets for therapy. ED has prognostic implications by predicting unfavourable early hepatic events and mortality in patients with portal hypertension and advanced liver diseases. ED characterised by an impaired bioactivity of nitric oxide (NO) within the hepatic circulation and is mainly due to decreased bioavailability of NO and accelerated degradation of NO with reactive oxygen species. Furthermore, elevated inflammatory markers also inhibit NO synthesis and causes ED in cirrhotic liver. Therefore, improvement of NO availability in the hepatic circulation can be beneficial for the improvement of endothelial dysfunction and associated portal hypertension in patients with cirrhosis. Furthermore, therapeutic agents that are identified in increasing NO bioavailability through improvement of hepatic endothelial nitric oxide synthase (eNOS) activity and reduction in hepatic asymmetric dimethylarginine, an endogenous modulator of eNOS and a key mediator of elevated intrahepatic vascular tone in cirrhosis would be interesting therapeutic approaches in patients with endothelial dysfunction and portal hypertension in advanced liver diseases. PMID:25848469

  20. Nutrition in the management of cirrhosis and its neurological complications.

    PubMed

    Bémeur, Chantal; Butterworth, Roger F

    2014-06-01

    Malnutrition is a common feature of chronic liver diseases that is often associated with a poor prognosis including worsening of clinical outcome, neuropsychiatric complications as well as outcome following liver transplantation. Nutritional assessment in patients with cirrhosis is challenging owing to confounding factors related to liver failure. The objectives of nutritional intervention in cirrhotic patients are the support of liver regeneration, the prevention or correction of specific nutritional deficiencies and the prevention and/or treatment of the complications of liver disease per se and of liver transplantation. Nutritional recommendations target the optimal supply of adequate substrates related to requirements linked to energy, protein, carbohydrates, lipids, vitamins and minerals. Some issues relating to malnutrition in chronic liver disease remain to be addressed including the development of an appropriate well-validated nutritional assessment tool, the identification of mechanistic targets or therapy for sarcopenia, the development of nutritional recommendations for obese cirrhotic patients and liver-transplant recipients and the elucidation of the roles of vitamin A hepatotoxicity, as well as the impact of deficiencies in riboflavin and zinc on clinical outcomes. Early identification and treatment of malnutrition in chronic liver disease has the potential to lead to better disease outcome as well as prevention of the complications of chronic liver disease and improved transplant outcomes. PMID:25755550

  1. Serum levels of YKL-40 and PIIINP as prognostic markers in patients with alcoholic liver disease

    E-print Network

    Price, Paul A.

    with alcoholic hepatitis and/or cirrhosis had the highest levels. Serum YKL-40 was associated with the presence alcoholic hepatitis and liver fibrosis/cirrhosis [1,2]. Alcohol can lead to progressive perivenous injury. The increase in ECM deposited in the space of Disse leads to hepatic fibrosis and cirrhosis [4]. It has been

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

    PubMed

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

    2013-02-01

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

  3. Ethanol extract of Portulaca Oleracea L. reduced the carbon tetrachloride induced liver injury in mice involving enhancement of NF-?B activity.

    PubMed

    Shi, Hongguang; Liu, Xuefeng; Tang, Gusheng; Liu, Haiyan; Zhang, Yinghui; Zhang, Bo; Zhao, Xuezhi; Wang, Wanyin

    2014-01-01

    Acute hepatic injury causes high morbidity and mortality world-wide. Management of severe acute hepatic failure continues to be one of the most challenging problems in clinical medicine. In present study, carbon tetrachloride (CCl4) was used to induce acute liver damage in mice and the protective effects of ethanol extract of Portulaca Oleracea L. (PO) were examined. The aminotransferase activities were biochemical estimated and the liver damage was tested by morphological histological analysis and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. The role of PO on the activity of NF-?B was determined by luciferase reporter gene assay and immunohistochemistry. The level of p-p65 was tested by western blot. Our results showed that PO administration on mice would decrease the serum aminotransferase level and reduced the liver histological damage. We also found that nuclear translocation of p65 was enhanced in liver tissues of mice treated with PO compared with control animals. In addition, in cultured hepatic cells, PO increased the NF-?B luciferase reporter gene activity and upregulated the level of phosphorylation of p65, but had no effects on mice liver SOD activity and MDA level. Collectively, PO attenuated CCl4 induced mice liver damage by enhancement of NF-?B activity. PMID:25628785

  4. Ethanol extract of Portulaca Oleracea L. reduced the carbon tetrachloride induced liver injury in mice involving enhancement of NF-?B activity

    PubMed Central

    Shi, Hongguang; Liu, Xuefeng; Tang, Gusheng; Liu, Haiyan; Zhang, Yinghui; Zhang, Bo; Zhao, Xuezhi; Wang, Wanyin

    2014-01-01

    Acute hepatic injury causes high morbidity and mortality world-wide. Management of severe acute hepatic failure continues to be one of the most challenging problems in clinical medicine. In present study, carbon tetrachloride (CCl4) was used to induce acute liver damage in mice and the protective effects of ethanol extract of Portulaca Oleracea L. (PO) were examined. The aminotransferase activities were biochemical estimated and the liver damage was tested by morphological histological analysis and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. The role of PO on the activity of NF-?B was determined by luciferase reporter gene assay and immunohistochemistry. The level of p-p65 was tested by western blot. Our results showed that PO administration on mice would decrease the serum aminotransferase level and reduced the liver histological damage. We also found that nuclear translocation of p65 was enhanced in liver tissues of mice treated with PO compared with control animals. In addition, in cultured hepatic cells, PO increased the NF-?B luciferase reporter gene activity and upregulated the level of phosphorylation of p65, but had no effects on mice liver SOD activity and MDA level. Collectively, PO attenuated CCl4 induced mice liver damage by enhancement of NF-?B activity. PMID:25628785

  5. Early growth response (Egr)-1: A novel anti-fibrotic mediator in liver

    E-print Network

    Holt, Briana

    2014-12-31

    spent due to excessive alcohol consumption [1]. Alcoholic liver disease (ALD), which includes a spectrum of liver pathologies ranging from fatty liver, or steatosis, to steatohepatitis, fibrosis, and cirrhosis, accounts for 1 in 10 deaths in adults aged... 20-64 years and is increasing in prevalence [2]. While early stages of ALD can regress with abstinence from alcohol, cirrhosis, or end stage liver disease, can only be cured by liver transplantation. In an effort to discover earlier interventions...

  6. Environmental Factors in Primary Biliary Cirrhosis

    PubMed Central

    Juran, Brian D.; Lazaridis, Konstantinos N.

    2014-01-01

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

  7. Refractory pruritus in primary biliary cirrhosis

    PubMed Central

    Pinheiro, Nuno Cercas; Marinho, Rui Tato; Ramalho, Fernando; Velosa, José

    2013-01-01

    Pruritus is a major symptom of primary biliary cirrhosis, cholestatic autoimmune disease which affects mostly middle-age women. Often, it can be severe and refractory to multiple treatments, and mostly affecting the patient’s health-related quality of life. Intense pruritus can be itself an indication to liver transplantation, in extreme cases leading to suicide. Its physiopathology has not yet been fully elucidated, but recent studies added the elevation of autotaxin and lysophosphatidic acid to the group of classic mechanisms already linked to cholestatic pruritus. In this case report we illustrate how ultraviolet B phototherapy appears to successfully control severe pruritus and contribute to the healing of pruritic skin lesions caused by intense scratching. There is limited medical literature concerning this therapeutic approach on cholestatic pruritus, but we hope that further randomised controlled trials will successfully establish it as an effective treatment in the near future. PMID:24234429

  8. Adrenal insufficiency in patients with decompensated cirrhosis

    PubMed Central

    Karagiannis, Apostolos KA; Nakouti, Theodora; Pipili, Chrysoula; Cholongitas, Evangelos

    2015-01-01

    Adrenal reserve depletion and overstimulation of the hypothalamus-pituitary-adrenal (HPA) axis are causes for adrenal insufficiency (AI) in critically ill individuals. Cirrhosis is a predisposing condition for AI in cirrhotics as well. Both stable cirrhotics and liver transplant patients (early and later after transplantation) have been reported to present AI. The mechanisms leading to reduced cortisol production in cirrhotics are the combination of low cholesterol levels (the primary source of cortisol), the increased cytokines production that overstimulate and exhaust HPA axis and the destruction of adrenal glands due to coagulopathy. AI has been recorded in 10%-82% cirrhotics depending on the test used to evaluate adrenal function and in 9%-83% stable cirrhotics. The similarity of those proportions support the assumption that AI is an endogenous characteristic of liver disease. However, the lack of a gold standard method for AI assessment and the limitation of precise thresholds in cirrhotics make difficult the recording of the real prevalence of AI. This review aims to summarize the present data over AI in stable, critically ill cirrhotics and liver transplant recipients. Moreover, it provides information about the current knowledge in the used diagnostic tools and the possible effectiveness of corticosteroids administration in critically ill cirrhotics with AI. PMID:26052400

  9. Multimodal treatment of hepatocellular carcinoma on cirrhosis: an update.

    PubMed

    Vivarelli, Marco; Montalti, Roberto; Risaliti, Andrea

    2013-11-14

    Hepatocellular carcinoma (HCC) is the most frequent primary liver tumor, and overall, it is one of the most frequent cancers. The association of HCC with chronic liver disease, and cirrhosis in particular, is well known, making treatment complex and challenging. The treatment of HCC must take into account the presence and stage of chronic liver disease, with the aim of preserving hepatic function that is often already impaired, the stage of HCC and the clinical condition of the patient. The different treatment options include surgical resection, transplantation, local ablation, chemoembolization, radioembolization and molecular targeted therapies; these treatments can be combined in various ways to achieve different goals. Ideally, liver transplantation is best treatment for early stage HCC on cirrhosis because it removes both the tumor and the chronic disease that produced it; however, the application of this powerful tool is limited by the scarcity of donors. Downstaging and bridging are different strategies for the management of HCC patients who will undergo liver transplantation. Several professionals, including gastroenterologists, radiologists and surgeons, are involved in the choice of the most appropriate treatment for a single case, and a multidisciplinary approach is necessary to optimize the outcome. The purpose of this review is to provide a comprehensive description of the current treatment options for patients with HCC by analyzing the advantages, disadvantages and rationale for their use. PMID:24259963

  10. Multimodal treatment of hepatocellular carcinoma on cirrhosis: An update

    PubMed Central

    Vivarelli, Marco; Montalti, Roberto; Risaliti, Andrea

    2013-01-01

    Hepatocellular carcinoma (HCC) is the most frequent primary liver tumor, and overall, it is one of the most frequent cancers. The association of HCC with chronic liver disease, and cirrhosis in particular, is well known, making treatment complex and challenging. The treatment of HCC must take into account the presence and stage of chronic liver disease, with the aim of preserving hepatic function that is often already impaired, the stage of HCC and the clinical condition of the patient. The different treatment options include surgical resection, transplantation, local ablation, chemoembolization, radioembolization and molecular targeted therapies; these treatments can be combined in various ways to achieve different goals. Ideally, liver transplantation is best treatment for early stage HCC on cirrhosis because it removes both the tumor and the chronic disease that produced it; however, the application of this powerful tool is limited by the scarcity of donors. Downstaging and bridging are different strategies for the management of HCC patients who will undergo liver transplantation. Several professionals, including gastroenterologists, radiologists and surgeons, are involved in the choice of the most appropriate treatment for a single case, and a multidisciplinary approach is necessary to optimize the outcome. The purpose of this review is to provide a comprehensive description of the current treatment options for patients with HCC by analyzing the advantages, disadvantages and rationale for their use. PMID:24259963

  11. Protective effect of aqueous extracts from Rhizopus oryzae on liver injury induced by carbon tetrachloride in rats.

    PubMed

    Suzuki, Takehito; Fukuoka, Hideo; Ushikoshi, Setsuo; Sato, Reiichiro; Morita, Hidetoshi; Takizawa, Tatsuya

    2015-05-01

    Hepatoprotective effects of Rhizopus?oryzae/?U-1 aqueous extract (RU) were demonstrated in carbon tetrachloride (CCl4 )-induced liver-injured rats. In order to investigate the RU effects, the rats were administered RU at a dose of 10 or 100?mg/kg of body weight for 10 days before induction of the liver injury by oral administration of CCl4 (125?mg/kg body weight). (i) Pretreatment with RU caused a significant decrease in serum lactate dehydrogenase (LDH), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities that were increased by the administration of CCl4 . (ii) RU pretreatment (100?mg/kg) increased 5-bromo-2'-deoxyuridine incorporation at 48?h after CCl4 treatment in hepatocytes. (iii) Histological hematoxylin and eosin staining of the liver showed that RU pretreatment reduced the damage induced by CCl4 administration. (iv) Reverse transcriptase PCR analysis showed RU retreatment caused a transient but significant increase in hepatocyte growth factor (HGF) and a sustained and significant increase in insulin-like growth factor-I (IGF-I) gene expression in hepatocytes injured by CCl4 treatment. From these results, we conclude that oral pre-administration of RU was effective to suppress liver injury induced by the subsequent oral CCl4 administration, and RU-induced increase in IGF-I and HGF gene expression may be, even in part, involved in biological actions of RU in rats. PMID:25496319

  12. Ultrasound elastography in liver.

    PubMed

    Frulio, N; Trillaud, H

    2013-05-01

    Conventional imaging techniques cannot provide information about tissue mechanical properties. Many injuries can cause changes in tissue stiffness, especially tumors and fibrosis. In recent years, various non-invasive ultrasound methods have been developed to study tissue elasticity for a large number of applications (breast, thyroid, prostate, kidneys, blood vessels, liver…). For non-invasive assessment of liver diseases, several ultrasound elastography techniques have been investigated: Transient elastography (the most extensively used), Real Time Elastography (RTE), Acoustic Radiation Force Impulse Imaging (ARFI) and more recently Shear Wave Elastography (SWE). Even if evaluation of liver fibrosis in chronic liver disease remains the principal application, there are many others applications for liver: predicting cirrhosis-related complications; monitoring antiviral treatments in chronic viral liver disease; characterizing liver tumors; monitoring local treatments, etc. The aim of this article is to report on the different hepatic ultrasound elastography techniques, their advantages and disadvantages, their diagnostic accuracy, their applications in clinical practice. PMID:23623211

  13. Osteoporosis in primary biliary cirrhosis revisited

    PubMed Central

    Newton, J; Francis, R; Prince, M; James, O; Bassendine, M; Rawlings, D; Jones, D

    2001-01-01

    BACKGROUND—Primary biliary cirrhosis (PBC) is increasingly being diagnosed in the earlier non-cholestatic stages of disease. Accepted wisdom has been that PBC is frequently complicated by osteoporosis. Whether this association holds true for the broader spectrum of PBC patients now recognised has not as yet been studied.?AIMS—To examine the extent to which osteoporosis occurs more commonly in PBC patients than in normal individuals of the same age and sex.?DESIGN—Retrospective review of a large cohort of well characterised PBC patients.?PATIENTS—A total of 272 PBC patients with definite or probable PBC followed up for a mean of 10.1 years (total follow up 2726 patient years) who had at least one bone mineral density measurement (BMD).?RESULTS—In this unselected group of PBC patients, mean Z scores (number of SDs from age and sex matched normal mean values) at the neck of femur (NOF) and lumbar spine (LS) at first BMD measurement (7 (6) years after PBC diagnosis) were ?0.1 (1.4) and 0.1 (1.4), respectively. At first BMD measurement, 18 PBC patients had Z scores less than ?2.0 and 85 had T scores less than ?2.5. No factors predictive of osteoporosis were found in affected patients. A total of 957 BMD measurements were performed (0.35 per patient year of follow up); 220 patients had two or more measurements. No patient went on to develop de novo osteoporosis during follow up. In the 51 patients (who were clinically representative of the whole group) who received no PBC or bone related treatment during follow up, %BMD changes per year at the NOF and LS were ?1.6 (3.2) and 0.1 (2.2), respectively. No variance in this "natural" rate of BMD measurement was seen in patients receiving PBC modulating agents (including prednisolone and UDCA) or osteoporosis prophylaxis/therapy. Significant improvement at the LS was seen in patients undergoing liver transplantation.?CONCLUSIONS—Osteoporosis is not a specific complication of PBC.???Keywords: liver cirrhosis; primary biliary cirrhosis; osteoporosis PMID:11454807

  14. Surgical treatment of hepatocellular carcinoma on cirrhosis: a Western experience.

    PubMed

    Mazziotti, A; Grazi, G L; Cavallari, A

    1998-08-01

    Recent improvements on the therapeutical management of hepatocellular carcinoma (HCC) on cirrhosis have led to further evaluate the role of surgery for this disease. In a 15-year period we have evaluated 532 cirrhotics with HCC on cirrhosis. Contraindications for surgery were founded in 170 (31.9%); 37 of them received a transarterial chemoembolization and 2 a percutaneous ethanol injection. Laparotomy was performed in 315 (59.2%) cases, but in 77 surgical treatment was contraindicated due to unexpected intraoperative findings. A liver resection was performed in 238 (44.7%) patients, representing the 26.1% of all liver resections performed at our Department. Seventy-eight (32.8%) were subsegmentectomies, 143 (60.1%) segmentectomies (including 1 to 3 anatomical segments) and 17 major hepatectomies. Overall 30-day mortality was 4.6%: 9.3% during years 83-91 and 0.8% during following years (P<0.005). Five-year actuarial survival rate was 41.3%. The remaining 47 (8.8%) patients were placed on the waiting list for orthotopic liver transplantation (OLT) and 41 already operated on. Operative mortality was 6.2% and 5-year actuarial survival rate 58.1%. The persistent shortage of organ donor represents the major factor limiting the application of liver transplantation for a larger number of patients carrying HCC on cirrhosis. Liver resection remains the option to be considered for all the patients with such a disease, even if in a large proportion of cases this procedure offers only a limited survival. PMID:9730389

  15. Questionnaire Based Assessment of Risk Factors for Primary Biliary Cirrhosis

    PubMed Central

    Lammert, Craig; Nguyen, Douglas L.; Juran, Brian D.; Schlicht, Erik; Larson, Joseph J.; Atkinson, Elizabeth J.; Lazaridis, Konstantinos N.

    2013-01-01

    Background Primary Biliary Cirrhosis is a cholestatic liver disease characterized by immune-mediated destruction of bile ducts. Its pathogenesis is largely unknown, although complex interactions between environment and genetic predisposition are proposed. Aims Identify disease risk factors using a detailed patient questionnaire and compare study findings to 3 published reports. Methods Questionnaire data were prospectively collected from 522 cases and 616 controls of the Mayo Clinic Primary Biliary Cirrhosis Genetic Epidemiology Registry. Case and control responses were compared using logistic regression, adjusting for recruitment age, sex, and education level. Results Cases reported ever regularly smoking cigarettes more frequently than controls (P < 0.001). History of urinary tract infection (UTI) was similar between groups; however, cases reported multiple UTIs more commonly than controls (P < 0.001). Frequency of other autoimmune disease was higher in cases than controls (P < 0.001). As well, prevalence of primary biliary cirrhosis among first-degree relatives was higher in case families than control families (P < 0.001). Conclusions Our study confirms prior reported risk factors associated with disease risk. Given the potential importance of gene and environment interactions, further examination of environmental risk factors considering genetic background may provide new insight into primary biliary cirrhosis pathogenesis. PMID:23490343

  16. Phycocyanobilin accelerates liver regeneration and reduces mortality rate in carbon tetrachloride-induced liver injury mice

    PubMed Central

    Liu, Jie; Zhang, Qing-Yu; Yu, Li-Ming; Liu, Bin; Li, Ming-Yi; Zhu, Run-Zhi

    2015-01-01

    AIM: To investigate the hepatoprotective effects of phycocyanobilin (PCB) in reducing hepatic injury and accelerating hepatocyte proliferation following carbon tetrachloride (CCl4) treatment. METHODS: C57BL/6 mice were orally administered PCB 100 mg/kg for 4 d after CCl4 injection, and then the serum and liver tissue of the mice were collected at days 1, 2, 3, 5 and 7 after CCl4 treatment. A series of evaluations were performed to identify the curative effects on liver injury and recovery. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin and superoxide dismutase (SOD) were detected to indirectly assess the anti-inflammatory effects of PCB. Meanwhile, we detected the expressions of hepatocyte growth factor, transforming growth factor alpha (TGF-?), TGF-?, tumor necrosis factor-alpha (TNF-?) and interleukin-6 (IL-6), the factors which are associated with inflammation and liver regeneration. The protein expressions of proliferating cell nuclear antigen (PCNA), TNF-? and cytochrome C were detected by western blot. Furthermore, the survival rates were analyzed of mice which were administered a lethal dose of CCl4 (2.6 mg/kg) with or without PCB. RESULTS: In our research, PCB showed a strongly anti-inflammatory effect on CCl4-induced liver injury in mice. The ALT was significantly decreased after CCl4 treatment from day 1 (P < 0.01) and the AST was significantly decreased from day 2 (P < 0.001). Both albumin and liver SOD were increased from day 2 (P < 0.001 and P < 0.01), but serum SOD levels did not show a significant increase (P > 0.05). PCB protected the structure of liver from the injury by CCl4. TUNEL assay showed that PCB dramatically reduced the number of apoptotic cells after CCl4 treatment compared to the control (101.0 ± 25.4 vs 25.7 ± 6.4, P < 0.01). The result of western blotting showed that PCB could increase PCNA expression, decrease TNF-? and cytochrome C expression. Furthermore, data shows that PCB could improve the survival rate of acute liver failure (ALF) mice which were injected with a lethal dose of CCl4 (60.0% vs 20.0%). CONCLUSION: Our study indicated that PCB could be an ideal candidate for reversing acute liver injury or ALF. PMID:25987768

  17. [Factors influencing development and progression of alcoholic liver disease].

    PubMed

    Abdelrahman, K; Marot, A; Deltenre, P

    2015-09-01

    Only a minority ot excessive drinkers develop cirrhosis. The main cofactors implicated in the pathophysiology of alcoholic liver disease are obesity, diabetes or the metabolic syndrome. Several genetic polymorphisms have been associated with a higher risk of alcoholic cirrhosis. Recent data indicate that gut microbiota could play a role in the pathogenesis of alcoholic liver disease. The aim of this review is to summarize the factors that influence development and progression of alcoholic liver disease. PMID:26502621

  18. Evidence for altered hepatic gluconeogenesis in patients with cirrhosis using in vivo 31-phosphorus magnetic resonance spectroscopy

    PubMed Central

    Changani, K; Jalan, R; Cox, I; Ala-Korpela, M; Bhakoo, K; Taylor-Robinson, S; Bell, J

    2001-01-01

    BACKGROUND AND AIMS—Alterations in gluconeogenesis in the diseased liver can be assessed non-invasively using magnetic resonance spectroscopy by measuring changes in phosphomonoester resonance which contains information regarding several metabolites, including the phosphorylated intermediates of the gluconeogenic pathway.?METHODS—31P magnetic resonance spectroscopy was used to determine changes in phosphomonoesters following bolus infusions of 2.8 mmol/kg L-alanine in five patients with functionally compensated cirrhosis and in five patients with functionally decompensated cirrhosis.?RESULTS—Compared with six healthy volunteers, baseline phosphomonoester values were elevated by 35% (p<0.05) in the compensated cirrhosis group and by 57% (p<0.01) in the decompensated cirrhosis group. Following alanine infusion, phosphomonoesters in healthy volunteers increased by 46% from baseline values (p<0.01), in patients with compensated cirrhosis by 27% (p<0.02) but those with decompensated cirrhosis showed no increase from baseline. There was a reduction in the percentage of inorganic phosphate signal in all subjects.?CONCLUSIONS—By analysing changes in phosphomonoester and inorganic phosphate resonances it is possible to discern clear metabolic differences between healthy volunteers and patients with cirrhosis of varying severity using magnetic resonance spectroscopy. Those patients with functionally decompensated cirrhosis have higher percentage baseline phosphomonoester values but the absence of phosphomonoester elevation following L-alanine infusion suggests that they are unable to mount a significant metabolic response with a progluconeogenic stimulus.???Keywords: gluconeogenesis; cirrhosis; alanine; ammonia; glucagon PMID:11559655

  19. Immune Components of Liver Damage Associated with Connective Tissue Diseases

    PubMed Central

    Serov, Youri A.; Alazmi, Mansour; Baba, Kamaldeen

    2014-01-01

    Autoimmune connective tissue diseases are associated with liver abnormalities and often have overlapping pathological and clinical manifestations. As a result, they can present great clinical challenges and evoke questions about diagnostic criteria for liver diseases. Moreover, discriminating between liver involvement as a manifestation of connective tissue disease and primary liver disease can be challenging since they share a similar immunological mechanism. Most patients with connective tissue diseases exhibit liver test abnormalities that likely result from coexisting, primary liver diseases, such as fatty liver disease, viral hepatitis, primary biliary cirrhosis, autoimmune hepatitis, and drug-related liver toxicity. Liver damage can be progressive, leading to cirrhosis, complications of portal hypertension, and liver-related death, and, therefore, must be accurately identified. In this review, we highlight the challenges facing the diagnosis of liver damage associated with connective tissue disease and identify immune mechanisms involved in liver damage associated with connective tissue diseases. PMID:26357616

  20. Benefits of nucleos(t)ide analog treatments for hepatitis B virus-related cirrhosis

    PubMed Central

    Honda, Koichi; Seike, Masataka; Murakami, Kazunari

    2015-01-01

    Chronic hepatitis B infection induces progressive liver disease. Before nucleos(t)ide analogs (NUCs) became established as a safe and effective treatment for hepatitis B, it was difficult to suppress the activity of the hepatitis B virus (HBV). Currently, many patients with hepatitis or cirrhosis associated with HBV are treated with NUCs for an extended period of time, and the effects, benefits, and limitations of these treatments have been apparent. This article reviews HBV-related cirrhosis, its natural course and survival, histological improvement after NUC treatments, treatment effects for decompensated cirrhosis, the incidence of hepatocellular carcinoma (HCC) after NUC treatments, and the efficacy of NUC treatments before and after the treatment of patients for HBV-related HCC. Of particular interest are the histological improvements, including regression of fibrosis, that have been achieved with NUC treatments. Liver function of patients with decompensated cirrhosis has significantly improved regardless of the type of NUC applied, and treatment with NUCs has reduced the incidence of HCC in cirrhotic patients. However, cirrhosis remains the strongest risk factor for HCC occurrence following NUC treatments, and the long-term cumulative incidence of HCC after NUC treatments remains high. When recurrence does occur, it is important to reconsider the treatment modality according to the degree of improved liver function that was achieved. PMID:26464756

  1. Protective Effects of Polydatin from Polygonum cuspidatum against Carbon Tetrachloride-Induced Liver Injury in Mice

    PubMed Central

    Zhang, Hong; Yu, Cheng-Hao; Jiang, Yi-Ping; Peng, Cheng; He, Kun; Tang, Jian-Yuan; Xin, Hai-Liang

    2012-01-01

    Polydatin is one of main compounds in Polygonum cuspidatum, a plant with both medicinal and nutritional value. The possible hepatoprotective effects of polydatin on acute liver injury mice induced by carbon tetrachloride (CCl4) and the mechanisms involved were investigated. Intraperitoneal injection of CCl4 (50 µl/kg) resulted in a significant increase in the levels of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and hepatic malondialdehyde (MDA), also a marked enhancement in the expression of hepatic tumor necrosis factor-alpha (TNF-?), interleukin-1 beta (IL-1?), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) and nuclearfactor-kappa B (NF-?B). On the other hand, decreased glutathione (GSH) content and activities of glutathione transferase (GST), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were observed following CCl4 exposure. Nevertheless, all of these phenotypes were evidently reversed by preadministration of polydatin for 5 continuous days. The mRNA and protein expression levels of hepatic growth factor-beta1 (TGF-?1) were enhanced further by polydatin. These results suggest that polydatin protects mice against CCl4-induced liver injury through antioxidant stress and antiinflammatory effects. Polydatin may be an effective hepatoprotective agent and a promising candidate for the treatment of oxidative stress- and inflammation-related diseases. PMID:23029551

  2. Changes in gut bacterial populations and their translocation into liver and ascites in alcoholic liver cirrhotics

    PubMed Central

    2014-01-01

    Background The liver is the first line of defence against continuously occurring influx of microbial-derived products and bacteria from the gut. Intestinal bacteria have been implicated in the pathogenesis of alcoholic liver cirrhosis. Escape of intestinal bacteria into the ascites is involved in the pathogenesis of spontaneous bacterial peritonitis, which is a common complication of liver cirrhosis. The association between faecal bacterial populations and alcoholic liver cirrhosis has not been resolved. Methods Relative ratios of major commensal bacterial communities (Bacteroides spp., Bifidobacterium spp., Clostridium leptum group, Enterobactericaea and Lactobacillus spp.) were determined in faecal samples from post mortem examinations performed on 42 males, including cirrhotic alcoholics (n?=?13), non-cirrhotic alcoholics (n?=?15), non-alcoholic controls (n?=?14) and in 7 healthy male volunteers using real-time quantitative PCR (RT-qPCR). Translocation of bacteria into liver in the autopsy cases and into the ascites of 12 volunteers with liver cirrhosis was also studied with RT-qPCR. CD14 immunostaining was performed for the autopsy liver samples. Results Relative ratios of faecal bacteria in autopsy controls were comparable to those of healthy volunteers. Cirrhotics had in median 27 times more bacterial DNA of Enterobactericaea in faeces compared to the healthy volunteers (p?=?0.011). Enterobactericaea were also the most common bacteria translocated into cirrhotic liver, although there were no statistically significant differences between the study groups. Of the ascites samples from the volunteers with liver cirrhosis, 50% contained bacterial DNA from Enterobactericaea, Clostridium leptum group or Lactobacillus spp.. The total bacterial DNA in autopsy liver was associated with the percentage of CD14 expression (p?=?0.045). CD14 expression percentage in cirrhotics was significantly higher than in the autopsy controls (p?=?0.004). Conclusions Our results suggest that translocation of intestinal bacteria into liver may be involved as a one factor in the pathogenesis of alcoholic liver cirrhosis. PMID:24564202

  3. Abstract --Nonalcoholic fatty liver disease (NAFLD) is estimated to have a 25-30% incidence among obese

    E-print Network

    Illinois at Urbana-Champaign, University of

    cirrhosis (one NASH outcome), even though pathology is the gold standard, existing techniques liver and hepatic cirrhosis (one NASH outcome), existing techniques are not currently able to detect,000 likely to have cirrhosis [2]. Early NAFLD consists of 5% or more intracellular lipid. NASH can result

  4. Monoethylglicinexylidide test: a prognostic indicator of survival in cirrhosis.

    PubMed

    Arrigoni, A; Gindro, T; Aimo, G; Cappello, N; Meloni, A; Benedetti, P; Molino, G P; Verme, G; Rizzetto, M

    1994-08-01

    The aim of this study was to assess the value of the monoethylglicinexylidide assay, a dynamic liver function test based on the determination of the serum concentration of lidocaine major metabolite, as a predictor of survival in cirrhosis. For this purpose, the predictive value of monoethylglicinexylidide was evaluated in comparison with the Pugh score, ascites, encephalopathy and a number of different biochemical parameters as collected from the prospective follow-up of 118 patients with cirrhosis. A stepwise regression analysis was performed on the variables of prognostic value according to the Cox model and with respect to 1-yr survival; because Pugh score and monoethylglicinexylidide were the sole variables selected, they were proved to supply independent prognostic information. The most reliable cutoff values for discrimination between death and survival were 25 ng/ml or less for monoethylglicinexylidide and less than 9 for the Pugh score. In 74 patients without overt signs of liver failure (i.e., Pugh < or = 9), monoethylglicinexylidide provided a wide range of results (i.e., 4 to 77 ng/ml), namely values ranging from very low to elevated. Of the 38 patients with satisfactory Pugh scores (< or = 9) but poor monoethylglicinexylidide values (< or = 25), 11 died during follow-up and 3 underwent liver transplantation, despite having shown no clinical signs of liver failure at entry. On the bases of discriminant levels, the monoethylglicinexylidide test is suitable for adoption as a reliable and sensitive indicator of survival in patients with cirrhosis because it supplies more accurate prognostic information compared with the Pugh score.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8045499

  5. Protective effect of a marine polyphenol, dieckol against carbon tetrachloride-induced acute liver damage in mouse.

    PubMed

    Kang, Min-Cheol; Kang, Sung-Myung; Ahn, Ginnae; Kim, Kil-Nam; Kang, Nalae; Samarakoon, Kalpa W; Oh, Myung-Cheol; Lee, Jung-Suck; Jeon, You-Jin

    2013-05-01

    In this study, the hepatoprotective effect of dieckol on carbon tetrachloride (CCl4) induced hepatic damages in ICR mice liver was investigated. Mice were randomly divided into 4 groups such as saline treated (negative control), CCl4 treated (positive control), CCl4+dieckol (5mg/kg mouse) and CCl4+dieckol (25mg/kg mouse), respectively. The body weights and survival rates of mice, followed by dieckol treatments were significantly increased compared to the positive control. The level of GOT, GPT and MDA in the serum of the dieckol treated groups were reduced dose dependently than the control, significantly. The antioxidant enzymes including CAT, and GSH-px levels were increased significantly compared to the positive control. However, no significant differences were observed on hepatic histophathological analysis in dieckol treated groups dose dependently. Down-regulation of Bax and up-regulation of Bcl-xl protein expressions were observed in liver tissues of the dieckol administered groups. These results suggested that, dieckol can be developed as a therapeutic agent for liver disease by oxidative stress. PMID:23528870

  6. Diagnosis of alcoholic cirrhosis with the right-to-left hepatic lobe ratio: concise communication

    SciTech Connect

    Shreiner, D.P.; Barlai-Kovach, M.

    1981-02-01

    Since scans of cirrhotic livers commonly show a reduction in size and colloid uptake of the right lobe, a quantitative measure of uptake was made using a minicomputer to determine total counts in regions of interest defined over each lobe. Right-to-left ratios were then compared in 103 patients. For normal paitents the mean ratio +- 1 s.d. was 2.85 +- 0.65, and the mean for patients with known cirrhosis was 1.08 +- 0.33. Patients with other liver diseases had ratios similar to the normal group. The normal range of the right-to-left lobe ratio was 1.55 to 4.15. The sensitivity of the ratio for alcoholic cirrhosis was 85.7% and the specificity was 100% in this patient population. The right-to-left lobe ratio was more sensitive and specific for alcoholic cirrhosis than any other criterion tested. An hypothesis is described to explain these results.

  7. Regulator of G-Protein Signaling-5 Is a Marker of Hepatic Stellate Cells and Expression Mediates Response to Liver Injury

    PubMed Central

    Bahrami, Arya J.; Gunaje, Jagadambika J.; Hayes, Brian J.; Riehle, Kimberly J.; Kenerson, Heidi L.; Yeung, Raymond S.; Stempien-Otero, April S.; Campbell, Jean S.; Mahoney, William M.

    2014-01-01

    Liver fibrosis is mediated by hepatic stellate cells (HSCs), which respond to a variety of cytokine and growth factors to moderate the response to injury and create extracellular matrix at the site of injury. G-protein coupled receptor (GPCR)-mediated signaling, via endothelin-1 (ET-1) and angiotensin II (AngII), increases HSC contraction, migration and fibrogenesis. Regulator of G-protein signaling-5 (RGS5), an inhibitor of vasoactive GPCR agonists, functions to control GPCR-mediated contraction and hypertrophy in pericytes and smooth muscle cells (SMCs). Therefore we hypothesized that RGS5 controls GPCR signaling in activated HSCs in the context of liver injury. In this study, we localize RGS5 to the HSCs and demonstrate that Rgs5 expression is regulated during carbon tetrachloride (CCl4)-induced acute and chronic liver injury in Rgs5LacZ/LacZ reporter mice. Furthermore, CCl4 treated RGS5-null mice develop increased hepatocyte damage and fibrosis in response to CCl4 and have increased expression of markers of HSC activation. Knockdown of Rgs5 enhances ET-1-mediated signaling in HSCs in vitro. Taken together, we demonstrate that RGS5 is a critical regulator of GPCR signaling in HSCs and regulates HSC activation and fibrogenesis in liver injury. PMID:25290689

  8. Development and characterization of sorafenib-loaded PLGA nanoparticles for the systemic treatment of liver fibrosis.

    PubMed

    Lin, Ts-Ting; Gao, Dong-Yu; Liu, Ya-Chi; Sung, Yun-Chieh; Wan, Dehui; Liu, Jia-Yu; Chiang, Tsaiyu; Wang, Liying; Chen, Yunching

    2016-01-10

    Sorafenib is a tyrosine kinase inhibitor that has recently been shown to be a potential antifibrotic agent. However, a narrow therapeutic window limits the clinical use and therapeutic efficacy of sorafenib. Herein, we have developed and optimized nanoparticle (NP) formulations prepared from a mixture of poly(ethylene glycol)-b-poly(lactic-co-glycolic acid) (PEG-PLGA) copolymers with poly(lactic-co-glycolic acid) (PLGA) for the systemic delivery of sorafenib into the fibrotic livers of CCl4-induced fibrosis mouse models. We characterized and compared the pharmaceutical and biological properties of two different PLGA nanoparticles (NPs) - PEG-PLGA NPs (PEG-PLGA/PLGA=10/0) and PEG-PLGA/PLGA NPs (PEG-PLGA/PLGA=5/5). Increasing the PLGA content in the PEG-PLGA/PLGA mixture led to increases in the particle size and drug encapsulation efficacy and a decrease in the drug release rate. Both PEG-PLGA and PEG-PLGA/PLGA NPs significantly prolonged the blood circulation of the cargo and increased the uptake by the fibrotic livers. The systemic administration of PEG-PLGA or PEG-PLGA/PLGA NPs containing sorafenib twice per week for a period of 4weeks efficiently ameliorated liver fibrosis, as indicated by decreased ?-smooth muscle actin (?-SMA) content and collagen production in the livers of CCl4-treated mice. Furthermore, sorafenib-loaded PLGA NPs significantly shrank the abnormal blood vessels and decreased microvascular density (MVD), leading to vessel normalization in the fibrotic livers. In conclusion, our results reflect the clinical potential of sorafenib-loaded PLGA NPs for the prevention and treatment of liver fibrosis. PMID:26551344

  9. Bone Marrow–Derived Stromal Cell Therapy in Cirrhosis: Clinical Evidence, Cellular Mechanisms, and Implications for the Treatment of Hepatocellular Carcinoma

    SciTech Connect

    Vainshtein, Jeffrey M.; Kabarriti, Rafi; Mehta, Keyur J.; Roy-Chowdhury, Jayanta; Guha, Chandan

    2014-07-15

    Current treatment options for hepatocellular carcinoma (HCC) are often limited by the presence of underlying liver disease. In patients with liver cirrhosis, surgery, chemotherapy, and radiation therapy all carry a high risk of hepatic complications, ranging from ascites to fulminant liver failure. For patients receiving radiation therapy, cirrhosis dramatically reduces the already limited radiation tolerance of the liver and represents the most important clinical risk factor for the development of radiation-induced liver disease. Although improvements in conformal radiation delivery techniques have improved our ability to safely irradiate confined areas of the liver to increasingly higher doses with excellent local disease control, patients with moderate-to-severe liver cirrhosis continue to face a shortage of treatment options for HCC. In recent years, evidence has emerged supporting the use of bone marrow–derived stromal cells (BMSCs) as a promising treatment for liver cirrhosis, with several clinical studies demonstrating sustained improvement in clinical parameters of liver function after autologous BMSC infusion. Three predominant populations of BMSCs, namely hematopoietic stem cells, mesenchymal stem cells, and endothelial progenitor cells, seem to have therapeutic potential in liver injury and cirrhosis. Preclinical studies of BMSC transplantation have identified a range of mechanisms through which these cells mediate their therapeutic effects, including hepatocyte transdifferentiation and fusion, paracrine stimulation of hepatocyte proliferation, inhibition of activated hepatic stellate cells, enhancement of fibrolytic matrix metalloproteinase activity, and neovascularization of regenerating liver. By bolstering liver function in patients with underlying Child's B or C cirrhosis, autologous BMSC infusion holds great promise as a therapy to improve the safety, efficacy, and utility of surgery, chemotherapy, and hepatic radiation therapy in the treatment of HCC.

  10. Application of metabonomics on an experimental model of fibrosis and cirrhosis induced by thioacetamide in rats

    SciTech Connect

    Constantinou, Maria A.; Theocharis, Stamatios E.; Mikros, Emmanuel . E-mail: mikros@pharm.uoa.gr

    2007-01-01

    Metabonomics has already been used to discriminate different pathological states in biological fields. The metabolic profiles of chronic experimental fibrosis and cirrhosis induction in rats were investigated using {sup 1}H NMR spectroscopy of liver extracts and serum combined with pattern recognition techniques. Rats were continuously administered with thioacetamide (TAA) in the drinking water (300 mg TAA/L), and sacrificed on 1st, 2nd, and 3rd month of treatment. {sup 1}H NMR spectra of aqueous and lipid liver extracts, together with serum were subjected to Principal Component Analysis (PCA). Liver portions were also subjected to histopathological examination and biochemical determination of malondialdehyde (MDA). Liver fibrosis and cirrhosis were progressively induced in TAA-treated rats, verified by the histopathological examination and the alterations of MDA levels. TAA administration revealed a number of changes in the {sup 1}H NMR spectra compared to control samples. The performance of PCA in liver extracts and serum, discriminated the control samples from the fibrotic and cirrhotic ones. Metabolic alterations revealed in NMR spectra during experimental liver fibrosis and cirrhosis induction, characterize the stage of fibrosis and could be illustrated by subsequent PCA of the spectra. Additionally, the PCA plots of the serum samples presented marked clustering during fibrosis progression and could be extended in clinical diagnosis for the management of cirrhotic patients.

  11. Estimation of the Scatterer Distribution of the Cirrhotic Liver using Ultrasonic Image

    NASA Astrophysics Data System (ADS)

    Yamaguchi, Tadashi; Hachiya, Hiroyuki

    1998-05-01

    In the B-mode image of the liver obtained by an ultrasonic imaging system, the speckled pattern changes with the progression of the disease such as liver cirrhosis.In this paper we present the statistical characteristics of the echo envelope of the liver, and the technique to extract information of the scatterer distribution from the normal and cirrhotic liver images using constant false alarm rate (CFAR) processing.We analyze the relationship between the extracted scatterer distribution and the stage of liver cirrhosis. The ratio of the area in which the amplitude of the processing signal is more than the threshold to the entire processed image area is related quantitatively to the stage of liver cirrhosis.It is found that the proposed technique is valid for the quantitative diagnosis of liver cirrhosis.

  12. Development of risky varices in alcoholic cirrhosis with a well-maintained nutritional status

    PubMed Central

    Enomoto, Hirayuki; Sakai, Yoshiyuki; Iwata, Yoshinori; Takata, Ryo; Aizawa, Nobuhiro; Ikeda, Naoto; Hasegawa, Kunihiro; Nakano, Chikage; Nishimura, Takashi; Yoh, Kazunori; Ishii, Akio; Takashima, Tomoyuki; Nishikawa, Hiroki; Iijima, Hiroko; Nishiguchi, Shuhei

    2015-01-01

    AIM: To compare the nutritional status between alcoholic compensated cirrhotic patients and hepatitis C virus (HCV)-related cirrhotic patients with portal hypertension. METHODS: A total of 21 patients with compensated cirrhosis (14 with HCV-related cirrhosis and seven with alcoholic cirrhosis) who had risky esophageal varices were investigated. In addition to physical variables, including the body mass index, triceps skinfold thickness, and arm-muscle circumference, the nutritional status was also assessed using the levels of pre-albumin (pre-ALB), retinol-binding protein (RBP) and non-protein respiratory quotient (NPRQ) measured with an indirect calorimeter. RESULTS: A general assessment for the nutritional status with physical examinations did not show a significant difference between HCV-related cirrhosis and alcoholic cirrhosis. However, the levels of pre-ALB and RBP in alcoholic compensated cirrhotic patients were significantly higher than those in HCV-related compensated cirrhotic patients. In addition, the frequency of having a normal nutritional status (NPRQ ? 0.85 and ALB value > 3.5 g/dL) in alcoholic compensated cirrhotic patients was significantly higher than that in HCV-related compensated cirrhotic patients. CONCLUSION: According to our small scale study, alcoholic compensated cirrhotic patients can develop severe portal hypertension even with a relatively well-maintained liver function and nutritional status compared with HCV-related cirrhosis. PMID:26413226

  13. [Treatment of alcoholic liver diseases. Abstinence, nutritional support, drug therapy, liver transplantation].

    PubMed

    Pár, A

    2000-04-16

    The review summarizes clinically established treatment forms of alcoholic liver disease in four main chapters: abstinence, nutritional supportation, drug therapy and liver transplantation are discussed. Drug therapy is described according to the three types of alcoholic hepatopathies (fatty liver, hepatitis and cirrhosis). Early diagnosis and treatment depending on the severity and stage of alcoholic liver disease are of importance for the attempts to retard progression and improve prognosis. PMID:10817009

  14. A New Modeling for the Changes in the Distribution of Scatterers in Cirrhotic Liver

    NASA Astrophysics Data System (ADS)

    Hara, Takashi; Hachiya, Hiroyuki

    2000-05-01

    The human liver is composed of small hexagonal structures called liver lobules. Cirrhosis destroys these liver lobules and replaces them with permanent connective tissue referred to as regenerative nodules. In this paper, we propose a new modeling technique for changes in the scatterer distribution in liver tissue considering the structure of liver lobules to obtain images of the cirrhotic liver over continuous stages. Using these images, we analyze the relationship between changes in characteristics of biological tissue and changes in B-mode images during progressive liver cirrhosis.

  15. Spontaneous bleeding or thrombosis in cirrhosis: What should be feared the most?

    PubMed Central

    Rodríguez-Castro, Kryssia Isabel; Antonello, Alessandro; Ferrarese, Alberto

    2015-01-01

    The more modern and accurate concept of a rebalanced hemostatic status in cirrhosis is slowly replacing the traditional belief of patients with cirrhosis being “auto-anticoagulated”, prone only to bleeding complications, and protected from thrombotic events. With greater attention to clinical thrombotic events, their impact on the natural history of cirrhosis, and with the emergence and increased use of point-of-care and global assays, it is now understood that cirrhosis results in profound hemostatic alterations that can lead to thrombosis as well as to bleeding complications. Although many clinical decisions are still based on traditional coagulation parameters such as prothrombin (PT), PT, and international normalized ratio, it is increasingly recognized that these tests do not adequately predict the risk of bleeding, nor they should guide pre-emptive interventions. Moreover, altered coagulation tests should not be considered as a contraindication to the use of anticoagulation, although this therapeutic or prophylactic approach is not at present routinely undertaken. Gastroesophageal variceal bleeding continues to be one of the most feared and deadly complications of cirrhosis and portal hypertension, but great progresses have been made in prevention and treatment strategies. Other bleeding sites that are frequently part of end-stage liver disease are similar to clinical manifestations of thrombocytopenia, with gum bleeding and epistaxis being very common but fortunately only rarely a cause of life-threatening bleeding. On the contrary, manifestations of coagulation factor deficiencies like soft tissue bleeding and hemartrosis are rare in patients with cirrhosis. As far as thrombotic complications are concerned, portal vein thrombosis is the most common event in patients with cirrhosis, but venous thromboembolism is not infrequent, and results in important morbidity and mortality in patients with cirrhosis, especially those with decompensated disease. Future studies and the more widespread use of point-of-care tests in evaluating hemostasis will aid the clinician in decision making when facing the patient with bleeding or with thrombotic complications, with both ends of a continuum being potentially fatal. PMID:26207163

  16. Spontaneous bleeding or thrombosis in cirrhosis: What should be feared the most?

    PubMed

    Rodríguez-Castro, Kryssia Isabel; Antonello, Alessandro; Ferrarese, Alberto

    2015-07-18

    The more modern and accurate concept of a rebalanced hemostatic status in cirrhosis is slowly replacing the traditional belief of patients with cirrhosis being "auto-anticoagulated", prone only to bleeding complications, and protected from thrombotic events. With greater attention to clinical thrombotic events, their impact on the natural history of cirrhosis, and with the emergence and increased use of point-of-care and global assays, it is now understood that cirrhosis results in profound hemostatic alterations that can lead to thrombosis as well as to bleeding complications. Although many clinical decisions are still based on traditional coagulation parameters such as prothrombin (PT), PT, and international normalized ratio, it is increasingly recognized that these tests do not adequately predict the risk of bleeding, nor they should guide pre-emptive interventions. Moreover, altered coagulation tests should not be considered as a contraindication to the use of anticoagulation, although this therapeutic or prophylactic approach is not at present routinely undertaken. Gastroesophageal variceal bleeding continues to be one of the most feared and deadly complications of cirrhosis and portal hypertension, but great progresses have been made in prevention and treatment strategies. Other bleeding sites that are frequently part of end-stage liver disease are similar to clinical manifestations of thrombocytopenia, with gum bleeding and epistaxis being very common but fortunately only rarely a cause of life-threatening bleeding. On the contrary, manifestations of coagulation factor deficiencies like soft tissue bleeding and hemartrosis are rare in patients with cirrhosis. As far as thrombotic complications are concerned, portal vein thrombosis is the most common event in patients with cirrhosis, but venous thromboembolism is not infrequent, and results in important morbidity and mortality in patients with cirrhosis, especially those with decompensated disease. Future studies and the more widespread use of point-of-care tests in evaluating hemostasis will aid the clinician in decision making when facing the patient with bleeding or with thrombotic complications, with both ends of a continuum being potentially fatal. PMID:26207163

  17. Coffee Consumption Decreases Risks for Hepatic Fibrosis and Cirrhosis: A Meta-Analysis

    PubMed Central

    Wu, Gang; Chen, Ling; Hu, Peng; Ren, Hong; Hu, Huaidong

    2015-01-01

    Background and Aim Previous studies have demonstrated that coffee consumption may be inversely correlated with hepatic fibrosis and cirrhosis. However, the reported results have been inconsistent. To summarize previous evidences quantitatively, a meta-analysis was performed. Methods The Medline, Web of Science, and Embase databases (from inception to June 2015) were searched to identify relevant trials that evaluated the effects of coffee consumption on hepatic fibrosis or cirrhosis. Odds ratios (ORs) of advanced hepatic fibrosis or cirrhosis for low or moderate, high, and any coffee consumption versus no consumption were pooled. Two cups per day was used as the cut-off level between low or moderate and high consumption. Results Sixteen studies were included, involving 3034 coffee consumers and 132076 people who do not consume coffee. The pooled results of the meta-analysis indicated that coffee consumers were less likely to develop cirrhosis compared with those who do not consume coffee, with a summary OR of 0.61 (95%CI: 0.45–0.84). For low or moderate coffee consumption versus no consumption, the pooled OR of hepatic cirrhosis was 0.66 (95%CI: 0.47–0.92). High coffee consumption could also significantly reduce the risk for hepatic cirrhosis when compared with no coffee consumption (OR = 0.53, 95%CI: 0.42–0.68). The effect of coffee consumption on hepatic fibrosis was summarized as well. The pooled OR of advanced hepatic fibrosis for coffee consumption versus no consumption was 0.73 (95%CI: 0.58–0.92). The protective effect of coffee on hepatic fibrosis and cirrhosis was also identified in subgroup meta-analyses of patients with alcoholic liver disease and chronic hepatitis C virus (HCV) infection. Conclusion Coffee consumption can significantly reduce the risk for hepatic fibrosis and cirrhosis. PMID:26556483

  18. Toxicological and biochemical studies on Schinus terebinthifolius concerning its curative and hepatoprotective effects against carbon tetrachloride-induced liver injury

    PubMed Central

    Abdou, Rania H.; Saleh, Sherif Y.; Khalil, Waleed F.

    2015-01-01

    Background: Recently, many efforts have been made to discover new products of natural origin which can limit the xenobiotic-induced hepatic injury. Carbon tetrachloride (CCl4) is a highly toxic chemical that is widely used to study hepatotoxicity in animal models. Objective: The present study was conducted to investigate the curative and protective effects of Schinus terbenthifolius ethanolic extract against CCl4 -induced acute hepatotoxicity in rats. Materials and Methods: S. terbenthifolius extract was orally administered in a dose of 350 mg dried extract/kg b.wt. before and after intoxication with CCl4 for curative and protective experiments, respectively. A group of hepatotoxicity indicative enzymes, oxidant-antioxidant capacity, DNA oxidation, and apoptosis markers were measured. Results: CCl4 increased liver enzyme leakage, oxidative stress, hepatic apoptosis, DNA oxidation, and inflammatory markers. Administration of S. terebinthifolius, either before or after CCl4 intoxication, significantly decreased elevated serum liver enzymes and reinstated the antioxidant capacity. Interestingly, S. terebinthifolius extract inhibited hepatocyte apoptosis as revealed by approximately 20 times down-regulation in caspase-3 expression when compared to CCl4 untreated group. On the other hand, there was neither protective nor curative effect of S. terebinthifolius against DNA damage caused by CCl4. Conclusion: The present study suggests that S. terebinthifolius extract could be a substantially promising hepatoprotective agent against CCl4 toxic effects and may be against other hepatotoxic chemical or drugs. PMID:26109780

  19. A 6 gene signature identifies the risk of developing cirrhosis in patients with chronic hepatitis B.

    PubMed

    Xu, Ming-Yi; Qu, Ying; Li, Zhenghong; Li, Fei; Xiao, Chun-Yang; Lu, Lun-Gen

    2016-01-01

    Clinical factors and liver biopsy cannot accurately predict the risk of developing cirrhosis in chronic hepatitis B (CHB).This study was to develop a predictive gene signature for cirrhosis in CHB patients. A total of 183 untreated CHB patients were enrolled. GeneChip, significant analysis of microarray (SAM) and prediction analysis of microarray (PAM) were used to select predictor genes (PGs) in liver tissues. The Cirrhosis Risk Score (CRS) was calculated based on 6 PG variables and the predictive value of CRS was evaluated. Firstly differentially expressed genes were filtered from a genome scan and SAM, and 87 significant genes were selected for the signature building. Secondly a signature consisting of 6 PGs (CD24, CXCL6, EHF, ITGBL1, LUM and SOX9) most predictive for cirrhosis risk in CHB patients was developed in the selection set (n=40) by use of PAM and PCR approach. Finally the CRS was calculated to estimate the risk of developing cirrhosis and then tested in validation cohort (n=143). The area under the ROC curves (AUROC) of the CRS was 0.944 and exceeded to 6 PGs and clinical factors. A low CRS cutoff of 6.43 to identify low-risk patients would misclassify only 8.16% of high-risk patients, while a high cutoff of 8.32 to identify high-risk patients would misclassify 0% of low-risk patients. So CRS is a better predictor than clinical factors in differentiating high-risk versus low-risk for cirrhosis and application of CRS in clinical practice could help to reduce the rate of liver biopsy in patients with CHB. PMID:26709788

  20. The influence of CCl4 biotransformation on the activation of rat liver phospholipase C in vitro.

    PubMed

    Coleman, J B; Condie, L W; Lamb, R G

    1988-09-15

    Carbon tetrachloride (CCl4) biotransformation and covalent binding was measured in 1000g liver fractions by determining the amount of 14CCl4 metabolites covalently bound to proteins and lipids at various (5-60 min) incubation times. Reactive intermediate binding to proteins and phospholipids peaked at 20 min, whereas CCl4 metabolites associated with neutral lipids (primarily diacylglycerol) were initially low (0-15 min) and then gradually increased from 20 to 60 min. The rise in labeled diacylglycerol was associated with a decrease in phospholipids containing covalently bound CCl4 metabolites, since CCl4 bioactivation increased phospholipase C (PLC) activity three- to fourfold. The major rise in PLC activity occurred after the plateau of CCl4 metabolite binding to cellular phospholipids. In contrast, when CCl4 bioactivation is absent, 0.5 mM CCl4 has little effect on PLC activity. At CCl4 concentrations of 1 mM and greater, the NADPH-dependent activation of PLC by CCl4 is reduced because CCl4 biotransformation is inhibited. Nevertheless, PLC is still activated by CCl4; however, PLC activation by high doses of CCl4 occurs by bioactivation-independent mechanisms. Therefore, there are two components of CCl4-induced PLC activation: one which is dependent on CCl4 biotransformation and one which is not. Under both conditions (+/- biotransformation), the activation of PLC may be a key event in CCl4 hepatotoxicity since PLC disrupts the functional and structural integrity of membranes by degrading membrane phospholipids. PMID:3420612

  1. Outcomes of patients with cirrhosis undergoing non-hepatic surgery: Risk assessment and management

    PubMed Central

    Millwala, Farida; Nguyen, Geoffrey C; Thuluvath, Paul J

    2007-01-01

    The reported mortality rates in patients with cirrhosis undergoing various non-transplant surgical procedures range from 8.3% to 25%. This wide range of mortality rates is related to severity of liver disease, type of surgery, demographics of patient population, expertise of the surgical, anesthesia and intensive care unit team and finally, reporting bias. In this article, we will review the pathophysiology, morbidity and mortality associated with non-hepatic surgery in patients with cirrhosis, and then recommend an algorithm for risk assessment and evidence based management strategy to optimize post-surgical outcomes. PMID:17696222

  2. Coinheritance of hereditary spherocytosis and reversibility of cirrhosis in a young female patient with hereditary hemochromatosis

    PubMed Central

    2009-01-01

    Here we report a 33-years-old woman with hereditary spherocytosis and hemochromatosis due to homozygosity for the C282Y mutation of the HFE gene. The coinheritance of both conditions led to severe iron overload and liver cirrhosis at young age. The patient was treated by repeated phlebotomy, and reversibility of cirrhosis was documented by transient elastography. This report discusses the pathophysiology of iron accumulation in patients with hemolytic anemia combined with HFE C282Y homozygosity. The case indicates that patients with hematological disorders characterized by increased erythropoetic activity should be screened for HFE mutations. PMID:19380292

  3. Neoplasms of the liver

    SciTech Connect

    Okuda, K.; Ishak, K.G.

    1987-01-01

    Primary Liver Cancer is perhaps the most prevalent malignancy in the world, particularly in South East Asia and Africa. After the discovery of hepatitis B virus as a cause of chronic liver disease often terminating cirrhosis and hepatocellular carcinoma, and, more recently, the integration of viral DNA into host chromosomal DNA, the progress made in this field has been remarkable. This book contains 35 chapters and covers all topical aspects, such as oncogenes, epidemiology, carcinogenic role of hepatitis viruses, histopathology, new imaging techniques and new treatment modalities that include ultrasound-guided intratumor injections of ethanol and targeting chemotherapy.

  4. Animal models of primary biliary cirrhosis.

    PubMed

    Katsumi, Tomohiro; Tomita, Kyoko; Leung, Patrick S C; Yang, Guo-Xiang; Gershwin, M Eric; Ueno, Yoshiyuki

    2015-06-01

    Primary biliary cirrhosis (PBC) is characterized histologically by the presence of chronic non-suppurative destructive cholangitis of the small interlobular bile duct, leading to chronic progressive cholestasis. Most PBC patients are asymptomatic and have a reasonable prognosis, but a few develop esophageal varices or jaundice, rapidly leading to liver failure within a short period. As multiple factors appear to be involved in the onset of PBC, its clinical course may be complicated. Therefore, the use of an animal model would be valuable for clarifying the pathogenesis of PBC. Here, we review recent data of selected PBC models, particularly spontaneous models, xenobiotic immunized models, and infection-triggered models. There are a number of spontaneous models: the NOD.c3c4, dominant-negative TGF-? receptor II, IL-2R?-/-, Scurfy, and Ae2a,b-/- mice. These animal models manifest distinct clinical and immunological features similar, but also often different, from those of human PBC. It is clear that a combination of genetic predisposition, environmental factors, and immunological dysfunction contribute to the pathogenesis of PBC. The diverse clinical course and complexity of the immunological mechanisms of PBC cannot be fully recapitulated solely any single animal model. The challenge remains to develop a progressive PBC disease model that exhibits fibrosis, and ultimately hepatic failure. PMID:25771770

  5. Update on the management of cirrhosis – focus on cost-effective preventative strategies

    PubMed Central

    Neff, Guy W; Kemmer, Nyingi; Duncan, Christopher; Alsina, Angel

    2013-01-01

    Cirrhosis is a chronic liver disease stage that encompasses a variety of etiologies resulting in liver damage. This damage may induce secondary complications such as portal hypertension, esophageal variceal bleeding, spontaneous bacterial peritonitis, and hepatic encephalopathy. Screening for and management of these complications incurs substantial health care costs; thus, determining the most economical and beneficial treatment strategies is essential. This article reviews the economic impact of a variety of prophylactic and treatment regimens employed for cirrhosis-related complications. Prophylactic use of ?-adrenergic blockers for portal hypertension and variceal bleeding appears to be cost-effective, but the most economical regimen for treatment of initial bleeding is unclear given that cost comparisons of pharmacologic and surgical regimens are lacking. In contrast, prophylaxis for spontaneous bacterial peritonitis cannot be recommended. Standard therapy for spontaneous bacterial peritonitis includes antibiotics, and the overall economic impact of these medications depends largely on their direct cost. However, the potential development of bacterial antibiotic resistance and resulting clinical failure should also be considered. Nonabsorbable disaccharides are standard therapies for hepatic encephalopathy; however, given their questionable efficacy, the nonsystemic antibiotic rifaximin may be a more cost-effective, long-term treatment for hepatic encephalopathy, despite its increased direct cost, because of its demonstrated efficacy and prevention of hospitalization. Further studies evaluating the cost burden of cirrhosis and cirrhosis-related complications, including screening costs, the cost of treatment and maintenance therapy, conveyance to liver transplantation, liver transplantation success, and health-related quality of life after transplantation, are essential for evaluation of the economic burden of hepatic encephalopathy and all cirrhosis-related complications. PMID:23626470

  6. Low 25-Hydroxyvitamin D Levels Are Associated with Infections and Mortality in Patients with Cirrhosis

    PubMed Central

    Finkelmeier, Fabian; Kronenberger, Bernd; Zeuzem, Stefan; Piiper, Albrecht; Waidmann, Oliver

    2015-01-01

    Background & Aims Vitamin D, best known to regulate bone mineralization, has numerous additional roles including regulation inflammatory pathways. Recently, an increased incidence of 25-hydroxyvitamin D3 (25(OH)D3) deficiency has been found in subjects suffering from liver diseases. We here investigated if low vitamin D levels might be associated with prognosis, inflammation and infectious complications in patients with cirrhosis. Methods We performed a prospective cohort study investigating the relation between 25(OH)D3 levels and stages of cirrhosis, mortality and complications of cirrhosis, including infections. Results 251 patients with cirrhosis were enrolled into the present prospective cohort study. 25(OH)D3 levels were quantified by radioimmunoassay from serum samples obtained at study inclusion. The mean follow-up time was 411 ± 397 days with a range of 1-1382 days. 30 (12.0%) patients underwent liver transplantation and 85 (33.8%) individuals died within the study. The mean serum 25(OH)D3 concentration was 8.93 ± 7.1 ng/ml with a range of 1.0 to 46.0 ng/ml. 25(OH)D3 levels differed significantly between Child Pugh scores and showed a negative correlation with the model of end stage liver disease (MELD) score. Patients with decompensated cirrhosis and infectious complications, had significantly lower 25(OH)D3 levels compared to subjects without complications. Low 25(OH)D3 was associated with mortality in uni- as well as multivariate Cox regression models. Conclusions 25(OH)D3 deficiency is associated with advanced liver disease and low 25(OH)D3 levels are an indicator for a poor outcome and are associated with infectious complications. PMID:26121590

  7. Aqueous Date Flesh or Pits Extract Attenuates Liver Fibrosis via Suppression of Hepatic Stellate Cell Activation and Reduction of Inflammatory Cytokines, Transforming Growth Factor-?1 and Angiogenic Markers in Carbon Tetrachloride-Intoxicated Rats

    PubMed Central

    Al-Rasheed, Nouf M.; Attia, Hala A.; Mohamad, Raeesa A.; Al-Rasheed, Nawal M.; Al-Amin, Maha A.; AL-Onazi, Asma

    2015-01-01

    Previous data indicated the protective effect of date fruit extract on oxidative damage in rat liver. However, the hepatoprotective effects via other mechanisms have not been investigated. This study was performed to evaluate the antifibrotic effect of date flesh extract (DFE) or date pits extract (DPE) via inactivation of hepatic stellate cells (HSCs), reducing the levels of inflammatory, fibrotic and angiogenic markers. Coffee was used as reference hepatoprotective agent. Liver fibrosis was induced by injection of CCl4 (0.4?mL/kg) three times weekly for 8 weeks. DFE, DPE (6?mL/kg), coffee (300?mg/kg), and combination of coffee + DFE and coffee + DPE were given to CCl4-intoxicated rats daily for 8 weeks. DFE, DPE, and their combination with coffee attenuated the elevated levels of inflammatory cytokines including tumor necrosis factor-?, interleukin-6, and interleukin-1?. The increased levels of transforming growth factor-?1 and collagen deposition in injured liver were alleviated by both extracts. CCl4-induced expression of ?-smooth muscle actin was suppressed indicating HSCs inactivation. Increased angiogenesis was ameliorated as revealed by reduced levels and expression of vascular endothelial growth factor and CD31. We concluded that DFE or DPE could protect liver via different mechanisms. The combination of coffee with DFE or DPE may enhance its antifibrotic effects. PMID:25945106

  8. The heart in liver transplantation.

    PubMed

    Ripoll, Cristina; Yotti, Raquel; Bermejo, Javier; Bañares, Rafael

    2011-04-01

    The heart and liver are organs that are closely related in both health and disease. Patients who undergo liver transplantation may suffer from heart disease that is: (a) related to the original cause of the liver disease such as hemochromatosis, (b) related to the liver disease itself, or (c) related to other associated conditions. Furthermore, liver transplantation is one of the most cardiovascular stressful events that a patient with cirrhosis may undergo. After liver transplantation, the progression of pre-existing or the development of new-onset cardiac disease may occur. This article reviews the relationship between the heart and liver transplantation in the pre-transplant, intra-operative, and post-transplant periods. PMID:21145840

  9. Lipids changes in liver cancer*

    PubMed Central

    Jiang, Jing-ting; Xu, Ning; Zhang, Xiao-ying; Wu, Chang-ping

    2007-01-01

    Liver is one of the most important organs in energy metabolism. Most plasma apolipoproteins and endogenous lipids and lipoproteins are synthesized in the liver. It depends on the integrity of liver cellular function, which ensures homeostasis of lipid and lipoprotein metabolism. When liver cancer occurs, these processes are impaired and the plasma lipid and lipoprotein patterns may be changed. Liver cancer is the fifth common malignant tumor worldwide, and is closely related to the infections of hepatitis B virus (HBV) and hepatitis C virus (HCV). HBV and HCV infections are quite common in China and other Southeast Asian countries. In addition, liver cancer is often followed by a procession of chronic hepatitis or cirrhosis, so that hepatic function is damaged obviously on these bases, which may significantly influence lipid and lipoprotein metabolism in vivo. In this review we summarize the clinical significance of lipid and lipoprotein metabolism under liver cancer. PMID:17565510

  10. Understanding and Treating Fatigue in Primary Biliary Cirrhosis and Primary Sclerosing Cholangitis.

    PubMed

    Jopson, Laura; Dyson, Jessica K; Jones, David E J

    2016-02-01

    Fatigue is a significant problem for patients with primary biliary cirrhosis and although experienced less by patients with primary sclerosing cholangitis, a minority still report significant fatigue. Fatigue is the symptom with the greatest impact on quality of life, particularly when associated with social dysfunction. The pathogenesis of fatigue in cholestatic liver disease is complex, poorly understood, and probably has central and peripheral components. Managing fatigue in cholestatic liver disease presents a challenge for clinicians given the complexity and its numerous associations. This article presents a structured approach to managing fatigue in cholestatic liver disease to improve fatigue severity and quality of life. PMID:26593295

  11. Host Genetics Predict Clinical Deterioration in HCV-Related Cirrhosis

    PubMed Central

    King, Lindsay Y.; Johnson, Kara B.; Zheng, Hui; Wei, Lan; Gudewicz, Thomas; Hoshida, Yujin; Corey, Kathleen E.; Ajayi, Tokunbo; Ufere, Nneka; Baumert, Thomas F.; Chan, Andrew T.; Tanabe, Kenneth K.; Fuchs, Bryan C.; Chung, Raymond T.

    2014-01-01

    Single nucleotide polymorphisms (SNPs) in the epidermal growth factor (EGF, rs4444903), patatin-like phospholipase domain-containing protein 3 (PNPLA3, rs738409) genes, and near the interleukin-28B (IL28B, rs12979860) gene are linked to treatment response, fibrosis, and hepatocellular carcinoma (HCC) in chronic hepatitis C. Whether these SNPs independently or in combination predict clinical deterioration in hepatitis C virus (HCV)-related cirrhosis is unknown. We genotyped SNPs in EGF, PNPLA3, and IL28B from liver tissue from 169 patients with biopsy-proven HCV cirrhosis. We estimated risk of clinical deterioration, defined as development of ascites, encephalopathy, variceal hemorrhage, HCC, or liver-related death using Cox proportional hazards modeling. During a median follow-up of 6.6 years, 66 of 169 patients experienced clinical deterioration. EGF non-AA, PNPLA3 non-CC, and IL28B non-CC genotypes were each associated with increased risk of clinical deterioration in age, sex, and race-adjusted analysis. Only EGF non-AA genotype was independently associated with increased risk of clinical deterioration (hazard ratio [HR] 2.87; 95% confidence interval [CI] 1.31–6.25) after additionally adjusting for bilirubin, albumin, and platelets. Compared to subjects who had 0–1 unfavorable genotypes, the HR for clinical deterioration was 1.79 (95%CI 0.96–3.35) for 2 unfavorable genotypes and 4.03 (95%CI 2.13–7.62) for unfavorable genotypes for all three loci (Ptrend<0.0001). In conclusion, among HCV cirrhotics, EGF non-AA genotype is independently associated with increased risk for clinical deterioration. Specific PNPLA3 and IL28B genotypes also appear to be associated with clinical deterioration. These SNPs have potential to identify patients with HCV-related cirrhosis who require more intensive monitoring for decompensation or future therapies preventing disease progression. PMID:25504078

  12. Primary biliary cirrhosis: Pathophysiology, clinical presentation and therapy

    PubMed Central

    Purohit, Treta; Cappell, Mitchell S

    2015-01-01

    Primary biliary cirrhosis (PBC) is an autoimmune, slowly progressive, cholestatic, liver disease characterized by a triad of chronic cholestasis, circulating anti-mitochondrial antibodies (AMA), and characteristic liver biopsy findings of nonsuppurative destructive cholangitis and interlobular bile duct destruction. About 10% of PBC patients, however, lack AMA. A variant, called PBC-autoimmune hepatitis (AIH) overlap, is characterized by the above findings of PBC together with findings of elevated serum alanine aminotransferase, elevated serum immunoglobulin G, and circulating anti-smooth muscle antibodies, with liver biopsy demonstrating periportal or periseptal, lymphocytic, piecemeal necrosis. PBC is hypothesized to be related to environmental exposure in genetically vulnerable individuals. It typically occurs in middle-aged females. Prominent clinical features include fatigue, pruritis, jaundice, xanthomas, osteoporosis, and dyslipidemia. The Mayo Risk score is the most widely used and best prognostic system. Ursodeoxycholic acid is the primary therapy. It works partly by reducing the concentration and injury from relatively toxic bile acids. PBC-AIH overlap syndrome is treated with ursodeoxycholic acid and corticosteroids, especially budesonide. Obeticholic acid and fibrate are promising new, but incompletely tested, therapies. Liver transplantation is the definitive therapy for advanced disease, with about 70% 10-year survival after transplantation. Management of pruritis includes local skin care, dermatologist referral, avoiding potential pruritogens, cholestyramine, and possibly opioid antagonists, sertraline, or rifaximin. Management of osteoporosis includes life-style modifications, administration of calcium and vitamin D, and alendronate. Statins are relatively safe to treat the osteopenia associated with PBC. Associated Sjogren’s syndrome is treated by artificial tears, cyclosporine ophthalmic emulsion to stimulate tear production; and saliva substitutes, cholinergic agents, and scrupulous oral and dental care. Complications of cirrhosis from advanced PBC include esophageal varices, ascites, spontaneous bacterial peritonitis, hepatorenal syndrome, and hepatoma formation. PMID:25954476

  13. Liver fibrosis in chronic viral hepatitis: An ultrasonographic study

    PubMed Central

    Zheng, Rong-Qin; Wang, Qing-Hui; Lu, Ming-De; Xie, Shi-Bin; Ren, Jie; Su, Zhong-Zhen; Cai, Yin-Ke; Yao, Ji-Lu

    2003-01-01

    AIM: To select valuable ultrasonographic predictors for the evaluation of hepatic inflammation and fibrosis degree in chronic hepatitis, and to study the value of ultrasonography in the evaluation of liver fibrosis and compensated liver cirrhosis in comparison with serology and histology. METHODS: Forty-four ultrasonographic variables were analyzed and screened using color Doppler ultrasound system in 225 patients with chronic viral hepatitis and compensated liver cirrhosis. The valuable ultrasonographic predictors were selected on the basis of a comparison with histopathological findings. The value of ultrasonography and serology in the evaluation of liver fibrosis degree and the diagnosis of compensated liver cirrhosis was also studied and compared. Meanwhile, the influencing factors on ultrasonographic diagnosis of compensated liver cirrhosis were also analyzed. RESULTS: By statistical analysis, the maximum velocity of portal vein and the degree of gall-bladder wall smoothness were selected as the valuable predictors for the inflammation grade (G), while liver surface, hepatic parenchymal echo pattern, and the wall thickness of gall-bladder were selected as the valuable predictors for the fibrosis stage (S). Three S-related independent ultrasonographyic predictors and three routine serum fibrosis markers (HA, HPCIII and CIV) were used to discriminate variables for the comparison of ultrasonography with serology. The diagnostic accuracy of ultrasonography in moderate fibrosis was higher than that of serology (P < 0.01), while there were no significant differences in the general diagnostic accuracy of fibrosis as well as between mild and severe fibrosis (P < 0.05). There were no significant differences between ultrasonography and serology in the diagnosis of compensated liver cirrhosis. However, the diagnostic accuracy of ultrasonography was higher in inactive liver cirrhosis and lower in active cirrhosis than that of serology (both P < 0.05). False positive and false negative results where found when the diagnosis of compensated liver cirrhosis was made by ultrasonography. CONCLUSION: There are different ultrasonographic predictors for the evaluation of hepatic inflammation grade and fibrosis stage of chronic hepatitis. Both ultrasonography and serology have their own advantages and disadvantages in the evaluation of liver fibrosis and compensated liver cirrhosis. Combined application of the two methods is hopeful to improve the diagnostic accuracy. PMID:14606081

  14. Systems biology analysis of omeprazole therapy in cirrhosis demonstrates significant shifts in gut microbiota composition and function

    PubMed Central

    Cox, I. Jane; Betrapally, Naga S.; Heuman, Douglas M.; Schubert, Mitchell L.; Ratneswaran, Maiyuran; Hylemon, Phillip B.; White, Melanie B.; Daita, Kalyani; Noble, Nicole A.; Sikaroodi, Masoumeh; Williams, Roger; Crossey, Mary M. E.; Taylor-Robinson, Simon D.; Gillevet, Patrick M.

    2014-01-01

    Proton pump inhibitors (PPI) have been associated with infectious complications in cirrhosis, but their impact on distal gut microbiota composition and function is unclear. We aimed to evaluate changes in stool microbiota composition and function in patients with cirrhosis and healthy controls after omeprazole therapy. Both 15 compensated cirrhotic patients and 15 age-matched controls underwent serum gastrin measurement, stool microbiota profiling with multitagged pyrosequencing, and urinary metabolic profiling with NMR spectroscopy to assess microbial cometabolites before/after a 14-day course of 40 mg/day omeprazole under constant diet conditions. Results before (pre) and after PPI were compared in both groups, compared with baseline by systems biology techniques. Adherence was >95% without changes in diet or MELD (model for end-stage liver disease) score during the study. Serum gastrin concentrations significantly increased after PPI in cirrhosis (pre 38.3 ± 35.8 vs. 115.6 ± 79.3 pg/ml P < 0.0001) and controls (pre 29.9 ± 14.5 vs. 116.0 ± 74.0 pg/ml, P = 0.001). A significant microbiota change was seen in both controls and cirrhosis after omeprazole (QIIME P < 0.0001). Relative Streptococcaceae abundance, normally abundant in saliva, significantly increased postomeprazole in controls (1 vs. 5%) and cirrhosis (0 vs. 9%) and was correlated with serum gastrin levels (r = 0.4, P = 0.005). We found significantly reduced hippurate in cirrhosis vs. controls both pre- and postomeprazole and increased lactate in both groups post vs. preomeprazole, whereas dimethylamine (DMA) decreased in cirrhosis only. On correlation network analysis, significant changes in linkages of bacteria with metabolites (hippurate/DMA/lactate) were found postomeprazole, compared with pre-PPI in cirrhosis patients. In conclusion, omeprazole is associated with a microbiota shift and functional change in the distal gut in patients with compensated cirrhosis that could set the stage for bacterial overgrowth. PMID:25258407

  15. Autoantibodies in autoimmune liver diseases.

    PubMed

    Sener, Asli Gamze

    2015-11-01

    Autoimmune hepatitis is a chronic hepatitis of unknown etiology characterized by clinical, histological, and immunological features, generally including circulating autoantibodies and a high total serum and/or gamma globulin. Liver-related autoantibodies are very significant for the correct diagnosis and classification of autoimmune liver diseases (AILD), namely autoimmune hepatitis types 1 and 2 (AIH-1 and 2), primary biliary cirrhosis (PBC), and the sclerosing cholangitis types in adults and children. This article intends to review recent studies that investigate autoantibodies in autoimmune liver diseases from a microbiological perspective. PMID:26359647

  16. Bacterial infections in cirrhosis: a position statement based on the EASL Special Conference 2013.

    PubMed

    Jalan, Rajiv; Fernandez, Javier; Wiest, Reiner; Schnabl, Bernd; Moreau, Richard; Angeli, Paolo; Stadlbauer, Vanessa; Gustot, Thierry; Bernardi, Mauro; Canton, Rafael; Albillos, Agustin; Lammert, Frank; Wilmer, Alexander; Mookerjee, Rajeshwar; Vila, Jordi; Garcia-Martinez, Rita; Wendon, Julia; Such, José; Cordoba, Juan; Sanyal, Arun; Garcia-Tsao, Guadalupe; Arroyo, Vicente; Burroughs, Andrew; Ginès, Pere

    2014-06-01

    Bacterial infections are very common and represent one of the most important reasons of progression of liver failure, development of liver-related complications, and mortality in patients with cirrhosis. In fact, bacterial infections may be a triggering factor for the occurrence of gastrointestinal bleeding, hypervolemic hyponatremia, hepatic encephalopathy, kidney failure, and development of acute-on-chronic liver failure. Moreover, infections are a very common cause of repeated hospitalizations, impaired health-related quality of life, and increased healthcare costs in cirrhosis. Bacterial infections develop as a consequence of immune dysfunction that occurs progressively during the course of cirrhosis. In a significant proportion of patients, infections are caused by gram-negative bacteria from intestinal origin, yet gram-positive bacteria are a frequent cause of infection, particularly in hospitalized patients. In recent years, infections caused by multidrug-resistant bacteria are becoming an important clinical problem in many countries. The reduction of the negative clinical impact of infections in patients with cirrhosis may be achieved by a combination of prophylactic measures, such as administration of antibiotics, to reduce the occurrence of infections in high-risk groups together with early identification and management of infection once it has developed. Investigation on the mechanisms of altered gut microflora, translocation of bacteria, and immune dysfunction may help develop more effective and safe methods of prevention compared to those that are currently available. Moreover, research on biomarkers of early infection may be useful in early diagnosis and treatment of infections. The current manuscript reports an in-depth review and a position statement on bacterial infections in cirrhosis. PMID:24530646

  17. Hypoxia and fatty liver.

    PubMed

    Suzuki, Tomohiro; Shinjo, Satoko; Arai, Takatomo; Kanai, Mai; Goda, Nobuhito

    2014-11-01

    The liver is a central organ that metabolizes excessive nutrients for storage in the form of glycogen and lipids and supplies energy-producing substrates to the peripheral tissues to maintain their function, even under starved conditions. These processes require a considerable amount of oxygen, which causes a steep oxygen gradient throughout the hepatic lobules. Alcohol consumption and/or excessive food intake can alter the hepatic metabolic balance drastically, which can precipitate fatty liver disease, a major cause of chronic liver diseases worldwide, ranging from simple steatosis, through steatohepatitis and hepatic fibrosis, to liver cirrhosis. Altered hepatic metabolism and tissue remodeling in fatty liver disease further disrupt hepatic oxygen homeostasis, resulting in severe liver hypoxia. As master regulators of adaptive responses to hypoxic stress, hypoxia-inducible factors (HIFs) modulate various cellular and organ functions, including erythropoiesis, angiogenesis, metabolic demand, and cell survival, by activating their target genes during fetal development and also in many disease conditions such as cancer, heart failure, and diabetes. In the past decade, it has become clear that HIFs serve as key factors in the regulation of lipid metabolism and fatty liver formation. This review discusses the molecular mechanisms by which hypoxia and HIFs regulate lipid metabolism in the development and progression of fatty liver disease. PMID:25386057

  18. Role of Gut Microbiota in Liver Disease.

    PubMed

    Brenner, David A; Paik, Yong-Han; Schnabl, Bernd

    2015-01-01

    Many lines of research have established a relationship between the gut microbiome and patients with liver disease. For example, patients with cirrhosis have increased bacteremia, increased blood levels of lipopolysaccharide, and increased intestinal permeability. Patients with cirrhosis have bacterial overgrowth in the small intestine. Selective intestinal decontamination with antibiotics is beneficial for patients with decompensated cirrhosis. In experimental models of chronic liver injury with fibrosis, several toll-like receptors (TLR) are required to make mice sensitive to liver fibrosis. The presumed ligand for the TLRs are bacterial products derived from the gut microbiome, and TLR knockout mice are resistant to liver inflammation and fibrosis. We and others have characterized the association between preclinical models of liver disease in mice with the microbial diversity in their gut microbiome. In each model, including intragastric alcohol, bile duct ligation, chronic carbon tetrachloride (CCl4), administration, and genetic obesity, there is a significant change in the gut microbiome from normal control mice. However, there is not a single clear bacterial strain or pattern that distinguish mice with liver injury from controlled mice. So how can the gut microbiota affect liver disease? We can identify at least 6 changes that would result in liver injury, inflammation, and/or fibrosis. These include: (1) changes in caloric yield of diet; (2) regulation of gut permeability to release bacterial products; (3) modulation of choline metabolism; (4) production of endogenous ethanol; (5) regulation of bile acid metabolism; and (6) regulation in lipid metabolism. PMID:26447960

  19. Effect of methanol extract of Dicranopteris linearis against carbon tetrachloride- induced acute liver injury in rats

    PubMed Central

    2014-01-01

    Background Dicranopteris linearis (family Gleicheniaceae) has been reported to possess anti-inflammatory and antioxidant activities but no attempt has been made to study its hepatoprotective potential. The aim of the present study was to determine the hepatoprotective effect of methanol extracts of D. linearis (MEDL) against carbon tetrachloride (CCl4)-induced acute liver injury in rats. Methods 6 groups (n?=?6) of rats received oral test solutions: 10% dimethyl sulfoxide (DMSO), 200 mg/kg silymarin, or MEDL (50, 250, and 500 mg/kg), once daily for 7 consecutive days, followed by hepatotoxicity induction with CCl4. Blood and liver were collected for biochemical and microscopic analysis. The extract was also subjected to antioxidant studies (e.g. 2, 2-diphenyl-1-picrylhydrazyl (DPPH)- and superoxide anion-radical scavenging assays, oxygen radical absorbance capacity (ORAC) test and total phenolic content (TPC) determination), phytochemical screening and HPLC analysis. Results Pretreatment with MEDL and silymarin significantly (P?liver tissues in groups pretreated with MEDL and silymarin showed mild necrosis and inflammation of the hepatocytes compared to the DMSO-pretreated group (negative control group). The MEDL showed higher DPPH- and superoxide anion-radical scavenging activity as well as high TPC and ORAC values indicating high antioxidant activity. Conclusions MEDL exerts hepatoprotective activity that could be partly contributed by its antioxidant activity and high phenolic content, and hence demands further investigation. PMID:24708543

  20. Cirrhosis

    MedlinePLUS

    ... priorities, and trends Funding Process Tips for applicants; human subjects research information; grant review and management resources; and commonly used funding mechanisms, including diversity and ...

  1. Hyponatremia in Hepatocellular Carcinoma Complicating with Cirrhosis

    PubMed Central

    Nishikawa, Hiroki; Kita, Ryuichi; Kimura, Toru; Ohara, Yoshiaki; Sakamoto, Azusa; Saito, Sumio; Nishijima, Norihiro; Nasu, Akihiro; Komekado, Hideyuki; Osaki, Yukio

    2015-01-01

    Background and aims: We aimed to investigate the effect of serum sodium level on survival in hepatocellular carcinoma (HCC) patients complicating with liver cirrhosis (LC). Methods: A total of 1170 HCC patients with LC were analysed. We classified these patients into three groups according to serum sodium level at HCC diagnosis: group A (n=96); serum sodium ?135 mmol/L, group B (n=520); 135 mmol/L < serum sodium ?140 mmol/L, group C (n=554); serum sodium >140 mmol/L. We compared the baseline characteristics and overall survival (OS) among these three groups. Furthermore, we examined the factors linked to OS using univariate and multivariate analyses. Results: In our results, decreased baseline serum sodium level was significantly associated with Child-Pugh classification and HCC stage along with several laboratory parameters in groups A, B and C. The median follow-up period was 1.1 years in group A, 2.4 years in group B and 3.3 years in group C. The 1-, 3- and 5-year cumulative OS rates in groups A, B and C were 64.8%, 46.9% and 25.7%, respectively, in group A, 85.5%, 60.5% and 41.1%, respectively, in group B and 90.7%, 66.6% and 48.2%, respectively, in group C (P<0.001). The multivariate analyses showed that Child-Pugh classification (P<0.001), HCC stage (P<0.001), serum sodium (P<0.001), aspartate aminotransferase ?57 IU/L (P=0.002), alkaline phosphatase ?348 IU/L (P<0.001), alpha-fetoprotein ?29.2 ng/mL (P=0.019) and des-?-carboxy prothrombin ?55 mAU/mL (P<0.001) were significant independent predictors linked to OS. Conclusion: Lower serum sodium concentration is a useful predictor in HCC patients complicating with LC. PMID:25874013

  2. Primary Biliary Cirrhosis and Primary Sclerosing Cholangitis: a Review Featuring a Women's Health Perspective

    PubMed Central

    Marchioni Beery, Renée M.; Vaziri, Haleh; Forouhar, Faripour

    2014-01-01

    Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are two major types of chronic cholestatic liver disease. Each disorder has distinguishing features and variable progression, but both may ultimately result in cirrhosis and hepatic failure. The following offers a review of PBC and PSC, beginning with a general overview of disease etiology, pathogenesis, diagnosis, clinical features, natural course, and treatment. In addition to commonly associated manifestations of fatigue, pruritus, and fat-soluble vitamin deficiency, select disease-related topics pertaining to women's health are discussed including metabolic bone disease, hyperlipidemia and cardiovascular risk, and pregnancy-related issues influencing maternal disease course and birth outcomes. This comprehensive review of PBC and PSC highlights some unique clinical considerations in the care of female patients with cholestatic liver disease. PMID:26357630

  3. Current research of hepatic cirrhosis in China

    PubMed Central

    Yao, Xi-Xian; Jiang, Shu-Lin; Yao, Dong-Mei

    2005-01-01

    Hepatic cirrhosis is a common disease that poses a serious threat to public health, and is characterized by chronic, progressive and diffuse hepatic lesions preceded by hepatic fibrosis regardless of the exact etiologies. In recent years, considerable achievements have been made in China in research of the etiopathogenesis, diagnosis and especially the treatment of hepatic fibrosis, resulting in much improved prognosis of hepatic fibrosis and cirrhosis. In this paper, the authors review the current status of research in hepatic fibrosis, cirrhosis and their major complications. PMID:15655809

  4. Potent antioxidant role of pirfenidone in experimental cirrhosis.

    PubMed

    Salazar-Montes, Adriana; Ruiz-Corro, Luis; López-Reyes, Alberto; Castrejón-Gómez, Eugenio; Armendáriz-Borunda, Juan

    2008-10-24

    Three important features must be considered when proposing therapeutic strategies in liver cirrhosis: inflammation, oxidative stress and fibrogenesis. Pirfenidone is a synthetic molecule which oxidative action has not been tested in cirrhosis. Cirrhosis was induced in rats by ligation of the common bile duct or carbon tetrachloride (CCl(4)) chronic intoxication and treated with pirfenidone or diphenyleneiodonium (a potent known antioxidant) for the last two weeks for bile duct ligation model or for the last three weeks for CCl(4) chronic intoxication. A 60% reduction in fibrosis index for bile duct ligation model and 42% for CCl(4) along with reduced inflammation was observed. Considerable reduction on hepatic enzymes and total and direct bilirubins were detected with pirfenidone in both models. Pirfenidone antioxidant capacity rendered a 28% and 30% reduction in nitrites and malonyldealdehide concentration in bile duct ligation and 52% and 38% in CCl(4). With respect to gene expression, fibrotic genes like transforming growth factor-beta (TGF-beta) and collagen Ialpha (Col-1alpha) were down-regulated by pirfenidone and increased expression of regenerative genes like hepatocyte growth factor (HGF) and c-met . Superoxide dismutase (SOD), catalase (CAT) and inducible nitric oxide synthase (iNOS) gene expression were importantly down-regulated where nuclear factor kappa B (NF-kappaB) binding activity also decreased with pirfenidone treatment. Also, SOD and CAT functional activity decreased after pirfenidone action. On the other hand, diphenyleneiodonium induced a drop in oxidative stress similar in extent to pirfenidone, but it was not as effective as pirfenidone in reducing fibrosis. In this work, we showed antioxidant properties of pirfenidone beyond its well-known antifibrotic effect. These features make pirfenidone an attractive drug for trying fibrotic diseases accompanied by oxidative stress processes. PMID:18652820

  5. Alcoholic liver disease: Treatment

    PubMed Central

    Suk, Ki Tae; Kim, Moon Young; Baik, Soon Koo

    2014-01-01

    The excess consumption of alcohol is associated with alcoholic liver diseases (ALD). ALD is a major healthcare problem, personal and social burden, and significant reason for economic loss worldwide. The ALD spectrum includes alcoholic fatty liver, alcoholic hepatitis, cirrhosis, and the development of hepatocellular carcinoma. The diagnosis of ALD is based on a combination of clinical features, including a history of significant alcohol intake, evidence of liver disease, and laboratory findings. Abstinence is the most important treatment for ALD and the treatment plan varies according to the stage of the disease. Various treatments including abstinence, nutritional therapy, pharmacological therapy, psychotherapy, and surgery are currently available. For severe alcoholic hepatitis, corticosteroid or pentoxifylline are recommended based on the guidelines. In addition, new therapeutic targets are being under investigation. PMID:25278689

  6. Examination of the Spatial Correlation of Statistics Information in the Ultrasonic Echo from Diseased Liver

    NASA Astrophysics Data System (ADS)

    Yamaguchi, Tadashi; Hachiya, Hiroyuki; Kamiyama, Naohisa; Moriyasu, Fuminori

    2002-05-01

    To realize a quantitative diagnosis of liver cirrhosis, we have been analyzing the characteristics of echo amplitude in B-mode images. Realizing the distinction between liver diseases such as liver cirrhosis and chronic hepatitis is required in the field of medical ultrasonics. In this study, we examine the spatial correlation, with the coefficient of correlation between the frames and the amplitude characteristics of each frame, using the volumetric data of RF echo signals from normal and diseased liver. It is found that there is a relationship between the tissue structure of liver and the spatial correlation of echo information.

  7. Pleomorphic hepatocellular carcinoma following consumption of hypericum perforatum in alcoholic cirrhosis.

    PubMed

    Lampri, Evangeli S; Ioachim, Elli; Harissis, Haralampos; Balasi, Eufemia; Mitselou, Antigoni; Malamou-Mitsi, Vasiliki

    2014-02-28

    Hepatocellular carcinoma (HCC) often develops in patients with underlying liver disease, yet HCC with syncytial giant cells (SGCs) is extremely rare. Herein, we report a 55-year-old man with a 6-year history of alcoholic cirrhosis who during his regular checkup presented with marked elevation of alpha-fetoprotein. Clinical examination and imaging analyses revealed a tumor-like lesion in segment 4 of the liver, which was removed by limited wedge resection. Histological analysis by hematoxylin and eosin staining indicated pleomorphic and atypical nodules, with some SGCs, embedded within the boundaries of the neoplastic lesion. The adjacent liver parenchyma showed microvesicular steatosis, pericellular fibrosis, and moderate hemosiderin accumulation (grade 2, as determined by Prussian blue iron stain) in hepatocytes and Kupffer cells but no copper accumulation (as determined by orcein stain). Immunohistochemical analysis showed hepatocyte antigen-positive staining for the neoplastic cells and SGCs. The diagnosis was made for cirrhosis-related HCC with SGCs. The previous reports of pleomorphic HCC have featured osteoclast-like (i.e., mesenchymal type) giant cells, making this case of epithelial type giant cells very rare. The patient's 6-month history of hypericum perforatum/St John's wort self-medication may have prompted the cirrhosis or HCC progression or the unusual SGC manifestation. PMID:24587684

  8. Reprint of: Nutrition in the Management of Cirrhosis and its Neurological Complications.

    PubMed

    Bémeur, Chantal; Butterworth, Roger F

    2015-03-01

    Malnutrition is a common feature of chronic liver diseases that is often associated with a poor prognosis including worsening of clinical outcome, neuropsychiatric complications as well as outcome following liver transplantation. Nutritional assessment in patients with cirrhosis is challenging owing to confounding factors related to liver failure. The objectives of nutritional intervention in cirrhotic patients are the support of liver regeneration, the prevention or correction of specific nutritional deficiencies and the prevention and/or treatment of the complications of liver disease per se and of liver transplantation. Nutritional recommendations target the optimal supply of adequate substrates related to requirements linked to energy, protein, carbohydrates, lipids, vitamins and minerals. Some issues relating to malnutrition in chronic liver disease remain to be addressed including the development of an appropriate well-validated nutritional assessment tool, the identification of mechanistic targets or therapy for sarcopenia, the development of nutritional recommendations for obese cirrhotic patients and liver-transplant recipients and the elucidation of the roles of vitamin A hepatotoxicity, as well as the impact of deficiencies in riboflavin and zinc on clinical outcomes. Early identification and treatment of malnutrition in chronic liver disease has the potential to lead to better disease outcome as well as prevention of the complications of chronic liver disease and improved transplant outcomes. PMID:26041952

  9. Recurrence of autoimmune liver diseases after liver transplantation

    PubMed Central

    Faisal, Nabiha; Renner, Eberhard L

    2015-01-01

    Liver transplantation (LT) is the most effective treatment modality for end stage liver disease caused by many etiologies including autoimmune processes. That said, the need for transplantation for autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC), but not for primary sclerosing cholangitis (PSC), has decreased over the years due to the availability of effective medical treatment. Autoimmune liver diseases have superior transplant outcomes than those of other etiologies. While AIH and PBC can recur after LT, recurrence is of limited clinical significance in most, but not all cases. Recurrent PSC, however, often progresses over years to a stage requiring re-transplantation. The exact incidence and the predisposing factors of disease recurrence remain debated. Better understanding of the pathogenesis and the risk factors of recurrent autoimmune liver diseases is required to develop preventive measures. In this review, we discuss the current knowledge of incidence, diagnosis, risk factors, clinical course, and treatment of recurrent autoimmune liver disease (AIH, PBC, PSC) following LT. PMID:26689244

  10. Therapy. Statins and liver disease: from concern to 'wonder' drugs?

    PubMed

    Bosch, Jaume; Forns, Xavier

    2015-06-01

    The benefits of statins go beyond decreasing cholesterol levels; in liver disease, statins reduce the risk of progressive liver fibrosis and provide protection during infections and ischaemia–reperfusion injury. New evidence shows that statins improve response to interferon-based anti-HCV therapy, decrease progression to cirrhosis and likelihood of developing hepatocellular carcinoma. PMID:25963509

  11. Non-alcoholic Fatty Liver Disease (NAFLD) - A Review.

    PubMed

    Karim, M F; Al-Mahtab, M; Rahman, S; Debnath, C R

    2015-10-01

    Non-alcoholic fatty liver disease (NAFLD) is an emerging problem in Hepatology clinics. It is closely related to the increased frequency of overweight or obesity. It has recognised association with metabolic syndrome. Central obesity, diabetes mellitus, dyslipidemia are commonest risk factors. Association with hepatitis C genotype 3 is also recognised. NAFLD is an important cause of cyptogenic cirrhosis of liver. It affects all populations and all age groups. Most patients with NAFLD are asymptomatic or vague upper abdominal pain. Liver function tests are mostly normal or mild elevation of aminotranferases. Histological features almost identical to those of alcohol-induced liver damage and can range from mild steatosis to cirrhosis. Two hit hypothesis is prevailing theory for the development of NAFLD. Diagnosis is usually made by imaging tools like ultrasonogram which reveal a bright liver while liver biopsy is gold standard for diagnosis as well as differentiating simple fatty liver and non-alcoholic steatohepatitis (NASH). Prognosis is variable. Simple hepatic steatosis generally has a benign long-term prognosis. However, one to two third of NASH progress to fibrosis or cirrhosis and may have a similar prognosis as cirrhosis from other liver diseases. Treatment is mostly control of underlying disorders and dietary advice, exercise, insulin sensitizers, antioxidants, or cytoprotective agents. The prevalence of NAFLD is increasing. So it needs more research to address this problem. PMID:26620035

  12. Activity of MMP-2, MMP-8 and MMP-9 in serum as a marker of progression of alcoholic liver disease in people from Lublin Region, eastern Poland.

    PubMed

    Prystupa, Andrzej; Boguszewska-Czubara, Anna; Bojarska-Junak, Agnieszka; Toru?-Jurkowska, Anna; Roli?ski, Jacek; Za?uska, Wociech

    2015-01-01

    In alcoholic liver cirrhosis, normal liver cells are replaced by scar tissue (fibrosis). Liver fibrosis is a dynamic process in which activated hepatic stellate cells are involved in the synthesis of matrix proteins and the regulation of matrix degeneration. The aim of the presented study was to assess the usefulness of MMP-2, MMP-8 and MMP-9 as diagnostic markers of alcoholic liver disease. Sixty patients with alcoholic liver cirrhosis were randomly enrolled during hospitalization in departments of hospitals from the Lublin Region in eastern Poland. The stage of cirrhosis was estimated according to Child-Turcotte-Pugh criteria (Child-Pugh score) as P- Ch A, P-Ch B, P-Ch C. The control group consisted of 10 healthy persons without liver disease, who did not drink alcohol. Additionally, a group of alcoholics without liver cirrhosis was included in the study. Blood sample were obtained, and after centrifuge, serum was collected for further analysis. The activity of MMP-2, MMP-8 and MMP-9 in the blood plasma of the patients and the control group were measured by using the sandwich enzyme immunoassay technique with commercially available quantitative ELISA test kits. Activity of MMP-2, MMP-8 and MMP-9 in patients with liver cirrhosis were increased gradually according to Child-Pugh stages. The activity of MMP-2, MMP-8, MMP-9 were the highest in patients with liver cirrhosis stage C. MMP-2, MMP-8, MMP-9 concentrations in the people with liver cirrhosis (stage C) were significantly increased compared to controls. A significant difference were observed between activity MMP-2 in control group, alcoholics without liver cirrhosis, and those with liver cirrhosis (stages A, B, C according Child-Pugh score). MMP-2, MMP-8 and MMP-9 may be markers of alcoholic liver cirrhosis in the alcoholics. Elevated levels of MMP-2, MMP-8 and MMP-9 in the alcoholic patients indicated that cirrhosis has developed. The most sensitive is MMP-2, because the activity of this parameter is increased in all liver cirrhosis stages. MMP-8 and MMP-9 activity were significantly elevated only in serum patients with advanced liver cirrhosis, compared to controls. PMID:26094532

  13. Increased Porphyrins in Primary Liver Cancer Mainly Reflect a Parallel Liver Disease

    PubMed Central

    Kaczynski, Jerzy; Hansson, Göran; Wallerstedt, Sven

    2009-01-01

    Hepatic porphyries have been associated with an increased risk of primary liver cancer (PLC), which on the other hand may cause an increased porphyrin production. To evaluate the role of an underlying liver disorder we analyzed porphyrins in patients with hepatocellular carcinoma (HCC) (n = 65), cholangiocellular carcinoma (n = 3), or suspected PLC, which turned out to be metastases (n = 18) or a benign disorder (n = 11). None of the patients had a family history of porphyry or clinical signs of porphyry. Increased aminolevulinic acid or porphyrin values were common not only in patients with PLC (43%) but also in metastatic (50%) and benign (64%) liver disorders. The corresponding proportion for HCC patients with liver cirrhosis (55%) was higher (P < .05) than in those without cirrhosis (17%). We conclude that symptomatic porphyries are unusual in PLC, whereas elevated urinary and/or faecal porphyrins are common, primarily reflecting a parallel liver disease and not the PLC. PMID:19841684

  14. Presence of anti-mitochondrial antibodies and elevated serum immunoglobulin G levels: is this primary biliary cirrhosis-autoimmune hepatitis overlap syndrome?

    PubMed Central

    Muttaqillah, Najihan Abdul Samat; Abdul Wahab, Asrul; Ding, Chuan Hun; Mohammad, Marlyn; Biswas, Suvra; Rahman, Md. Mostafizur

    2015-01-01

    Primary biliary cirrhosis in combination with autoimmune hepatitis has been termed “overlap syndrome”, but its diagnosis is challenging. We report a case of a 43-year-old lady who presented with a six-month history of jaundice and pruritus. She subsequently developed gum bleeds. Laboratory investigations revealed hypochromic microcytic anemia, abnormal coagulation profiles, elevated serum alanine transferase and alkaline phosphatase levels, and raised serum IgG and IgM levels. Her serum was also positive for anti-nuclear and anti-mitochondrial antibodies. The findings from her abdominal CT scan were suggestive of early liver cirrhosis and the histopathological examination results of her liver biopsy were consistent with primary biliary cirrhosis. The patient was treated with ursodeoxycholic acid and her liver function test parameters normalized after six months.

  15. Obeticholic acid for the treatment of primary biliary cirrhosis.

    PubMed

    Trivedi, Palak J; Hirschfield, Gideon M; Gershwin, M Eric

    2016-01-01

    Primary biliary cirrhosis (PBC) is characterized by progressive nonsuppurative destruction of small bile ducts, resulting in intrahepatic cholestasis, fibrosis and ultimately end-stage liver disease. Timely intervention with ursodeoxycholic acid is associated with excellent survival, although approximately one-third of all patients fail to achieve biochemical response, signifying a critical need for additional therapeutic strategies. Obeticholic acid (OCA) is a potent ligand of the nuclear hormone receptor farnesoid X receptor (FXR). Activation of FXR inhibits bile acid synthesis and protects against toxic accumulation in models of cholestasis and facilitates hepatic regeneration in preclinical studies. Data from recent Phase II and III controlled trials suggest a therapeutic impact of OCA in PBC biochemical nonresponders, as evidenced by change in proven laboratory surrogates of long-term outcome. Dose-dependent pruritus is a common adverse effect, but may be overcome through dose-titration. Longer term studies are needed with focus on safety and long-term clinical efficacy. PMID:26549695

  16. Acute-on-Chronic Liver Failure

    PubMed Central

    Asrani, Sumeet K; O'Leary, Jacqueline G.

    2015-01-01

    For years, the natural history of patients with cirrhosis has been described as a period of stable compensated liver disease followed by a tumultuous progression in decompensated liver disease towards eventual liver transplantation or death. During this progression, the Model for End-Stage Liver Disease (MELD) has been the single best predictor of outcome. However over the last two decades, the concept of acute-on-chronic liver failure (ACLF) has been proposed as an alternate path in the natural history of cirrhosis. Unlike acute liver failure (ALF) that occurs in patients without underlying liver disease, ACLF occurs in patients with chronic liver disease and is characterized by a precipitating event (identified or surreptitious) often resulting in acute deterioration in liver function, multi-organ system failure, and high short-term mortality. The purpose of this review is to demonstrate the differing ways ACLF is characterized and define the natural course of patients with ACLF especially as it relates to management of cirrhotic patients on the transplant waiting list and its impact on liver transplantation outcomes. PMID:25017076

  17. Aflatoxin levels in chronic hepatitis B patients with cirrhosis or hepatocellular carcinoma in Bal?kesir, Turkey.

    PubMed

    Ayd?n, M; Ayd?n, S; Bacanl?, M; Ba?aran, N

    2015-11-01

    Aflatoxins, the secondary metabolites produced by species of naturally occurring Aspergilli, are commonly found in food such as cereals, dried fruits and juice, wine, beer and spices. They are hepatotoxic and are well known human carcinogens based on evidence from human studies. Aflatoxins are an environmental risk factor for the development of hepatocellular carcinoma (HCC). Chronic hepatitis B-infected patients are at increased risk of cirrhosis, hepatic failure and liver cancer. This study was designed to determine the serum aflatoxin B1 (AFB1 ), aflatoxin B2 (AFB2 ), aflatoxin G1 (AFG1 ) and aflatoxin G2 (AFG2 ) concentrations using high-pressure liquid chromatography (HPLC) in hepatitis B-infected patients with or without cirrhosis and liver cancer, alongside healthy controls in Bal?kesir, Turkey. The mean AFB1 and total AF levels in patients without liver cancer and cirrhosis were significantly higher than healthy controls. The mean AFB1 and total AF levels in patients with chronic hepatitis B and HCC were significantly higher than infected patients with or without cirrhosis. These results suggest that patients with chronic hepatitis B who are exposed to AFs are at increased risk for developing HCC, which might be prevented by reducing consumption of contaminated foods. PMID:25894298

  18. [Early neuropsychological changes in patients with nonalcoholic liver cirrhosis].

    PubMed

    Loguercio, C; Immirzi, M C; Perrone, L; Del Vecchio Blanco, C; Coltorti, M

    1990-01-01

    The presence of latent encephalopathy was assessed by means of various psychodiagnostic tests in 24 non-alcoholic cirrhotics. Twenty-four subjects hospitalized for chronic extrahepatic conditions served as the control group. The following tests were utilized: 1) semistructured individual clinical interviews; 2) Rorschach test; 3) Minnesota Multiphasic Personality Inventory; 4) Reitan's test; 5) spatial capability test (hand test); 6) reaction times to sound and light stimulation. Mood and behavioural modifications were frequently found in cirrhotics, probably as a consequence of the reaction to a chronic disease. Such abnormalities could, however, be differentiated from the early impairment of superior psychomotor functions which were present in nearly 50% of cirrhotics as latent encephalopathy. Results indicate that the use of the Reitan's test, can allow for a better management of cirrhotics even at non advanced stages of the disease and that more sophisticated tests failed to add further clues to diagnosis of latent encephalopathy. PMID:2089288

  19. FastStats: Chronic Liver Disease and Cirrhosis

    MedlinePLUS

    ... Address What's this? Submit What's this? Submit Button File Formats Help: How do I view different file formats (PDF, DOC, PPT, MPEG) on this site? Adobe PDF file Microsoft PowerPoint file Microsoft Word file Microsoft Excel ...

  20. Endoscopic treatment of esophageal varices in patients with liver cirrhosis

    PubMed Central

    Triantos, Christos; Kalafateli, Maria

    2014-01-01

    Variceal bleeding is a life-threatening complication of portal hypertension with a six-week mortality rate of approximately 20%. Patients with medium- or large-sized varices can be treated for primary prophylaxis of variceal bleeding using two strategies: non-selective beta-blockers (NSBBs) or endoscopic variceal ligation (EVL). Both treatments are equally effective. Patients with acute variceal bleeding are critically ill patients. The available data suggest that vasoactive drugs, combined with endoscopic therapy and antibiotics, are the best treatment strategy with EVL being the endoscopic procedure of choice. In cases of uncontrolled bleeding, transjugular intrahepatic portosystemic shunt (TIPS) with polytetrafluoroethylene (PTFE)-covered stents are recommended. Approximately 60% of the patients experience rebleeding, with a mortality rate of 30%. Secondary prophylaxis should start on day six following the initial bleeding episode. The combination of NSBBs and EVL is the recommended management, whereas TIPS with PTFE-covered stents are the preferred option in patients who fail endoscopic and pharmacologic treatment. Apart from injection sclerotherapy and EVL, other endoscopic procedures, including tissue adhesives, endoloops, endoscopic clipping and argon plasma coagulation, have been used in the management of esophageal varices. However, their efficacy and safety, compared to standard endoscopic treatment, remain to be further elucidated. There are safety issues accompanying endoscopic techniques with aspiration pneumonia occurring at a rate of approximately 2.5%. In conclusion, future research is needed to improve treatment strategies, including novel endoscopic techniques with better efficacy, lower cost, and fewer adverse events. PMID:25278695

  1. Acute Liver Failure After a Late TIPSS Revision

    SciTech Connect

    Radeleff, Boris Sommer, Christof-Matthias; Schawo, Simone; Lopez-Benitez, Ruben; Sauer, Peter; Schemmer, Peter; Kauffmann, Guenter W.; Richter, Goetz M.

    2008-01-15

    We report a rare case of late transjugular intrahepatic portosystemic stent shunt (TIPSS) occlusion due to progressive stent protrusion into the periportal liver parenchyma, which was a result of delayed liver shrinkage 2 years after TIPSS. The initial TIPSS procedure had been carried out in a 52-year-old man as a bridge for liver transplantation because of post-alcoholic liver cirrhosis. We describe the applied TIPSS recanalization and revision technique. Immediately after TIPSS revision acute liver failure developed, which required emergency liver transplantation.

  2. Surgery in a patient with liver disease.

    PubMed

    Rai, Rakesh; Nagral, Sanjay; Nagral, Aabha

    2012-09-01

    Surgery is often needed in patients with concurrent liver disease. The multiple physiological roles of the liver places these patients at an increased risk of morbidity and mortality. Diseases necessitating surgery like gallstones and hernia are more common in patients with cirrhosis. Assessment of severity of liver dysfunction before surgery is important and the risk benefit of the procedure needs to be carefully assessed. The disease severity may vary from mild transaminase rise to decompensated cirrhosis. Surgery should be avoided if possible in the emergency setting, in the setting of acute and alcoholic hepatitis, in a patient of cirrhosis who is child class C or has a MELD score more than 15 or any patient with significant extrahepatic organ dysfunction. In this subset of patients, all possible means to manage these patients conservatively should be attempted. Modified Child-Pugh scores and model for end-stage liver disease (MELD) scores can predict mortality after surgery fairly reliably including nonhepatic abdominal surgery. Pre-operative optimization would include control of ascites, correction of electrolyte imbalance, improving renal dysfunction, cardiorespiratory assessment, and correction of coagulation. Tests of global hemostasis like thromboelastography and thrombin generation time may be more predictive of the risk of bleeding compared with the conventional tests of coagulation in patients with cirrhosis. Correction of international normalized ratio with fresh frozen plasma does not necessarily mean reduction of bleeding risk and may increase the risk of volume overload and lung injury. International normalized ratio liver may better reflect the coagulation status. Recombinant factor VIIa in patients with cirrhosis needing surgery needs further study. Intra-operatively, safe anesthetic agents like isoflurane and propofol with avoidance of hypotension are advised. In general, nonsteroidal anti-inflammatory drug (NSAIDs) and benzodiazepines should not be used. Intra-abdominal surgery in a patient with cirrhosis becomes more challenging in the presence of ascites, portal hypertension, and hepatomegaly. Uncontrolled hemorrhage due to coagulopathy and portal hypertension, sepsis, renal dysfunction, and worsening of liver failure contribute to the morbidity and mortality in these patients. Steps to reduce ascitic leaks and infections need to be taken. Any patient with cirrhosis undergoing major surgery should be referred to a specialist center with experience in managing liver disease. PMID:25755440

  3. Role of Coagulation in Xenobiotic-Induced Liver Injury

    E-print Network

    Sullivan, Bradley P.

    2012-08-31

    ................. 73 4.4.8 TF and PAR-1 mRNAs are increased in livers of mice fed the ANIT diet and in patients with primary biliary cirrhosis and sclerosing cholangitis ....................................................................... 74 4.5 Discussion... cutting temperature compound PAI-1 Plasminogen activator inhibitor-1 PAR Protease activated receptor PBC Primary biliary cirrhosis PBS Phosphate buffered saline PCA Procoagulant activity Plg plasminogen p.o. per os (oral gavage) PSC...

  4. GWAS in Primary Biliary Cirrhosis

    PubMed Central

    Gulamhusein, Aliya F.; Juran, Brian D.

    2015-01-01

    Genome wide association studies (GWAS) have been a significant technological advance in our ability to evaluate the genetic architecture of complex diseases such as Primary Biliary Cirrhosis (PBC). To date, six large-scale studies have been performed which identified 27 non-HLA risk loci associated with PBC. The identified risk variants emphasize important disease concepts; namely, that disturbances in immunoregulatory pathways are important in the pathogenesis of PBC and that such perturbations are shared among a diverse number of autoimmune diseases – suggesting the risk architecture may confer a generalized propensity to autoimmunity not necessarily specific to PBC. Furthermore, the impact of non-HLA risk variants, particularly in genes involved with IL-12 signaling, and ethnic variation in conferring susceptibility to PBC have been highlighted. While GWAS have been a critical stepping-stone in understanding common genetic variation contributing to PBC, limitations pertaining to power, sample availability, and strong linkage disequilibrium across genes have left us with an incomplete understanding of the genetic underpinnings of disease pathogenesis. Future efforts to gain insight into this missing heritability, the genetic variation that contributes to important disease outcomes and the functional consequences of associated variants will be critical if practical clinical translation is to be realized. PMID:26676814

  5. Potential of human Induced Pluripotent Stem Cells in studies of liver disease

    E-print Network

    Sampaziotis, Fotios; Segeritz, Charis-Patricia; Vallier, Ludovic

    2015-02-10

    -Patricia Segeritz contributed equally to this work. 11   12   Key Words: Disease model, inherited metabolic disorders of the liver, 13   cholangiopathies, cirrhosis, toxicology studies. 14   15   2     Footnote Page 1   2   Contact information... to cirrhosis or in some cases 10   acute liver failure; while increased serum copper levels result in copper deposition 11   and toxicity, affecting multiple organs, mainly the brain, kidneys and cornea (39-40). 12   Current treatments with copper...

  6. Serum Sphingolipid Variations Associate with Hepatic Decompensation and Survival in Patients with Cirrhosis

    PubMed Central

    Grammatikos, Georgios; Ferreiròs, Nerea; Waidmann, Oliver; Bon, Dimitra; Schroeter, Sirkka; Koch, Alexander; Herrmann, Eva; Zeuzem, Stefan; Kronenberger, Bernd; Pfeilschifter, Josef

    2015-01-01

    Background Sphingolipids constitute bioactive molecules with functional implications in liver homeostasis. Particularly, ablation of very long chain ceramides in a knockout mouse model has been shown to cause a severe hepatopathy. Methods We aimed to evaluate the serum sphingolipid profile of 244 patients with cirrhosis prospectively followed for a median period of 228±217 days via mass spectrometry. Results We thereby observed a significant decrease of long and very long chain ceramides, particularly of C24ceramide, in patients with increasing severity of cirrhosis (p<0.001). Additionally, hydropic decompensation, defined by clinical presentation of ascites formation, was significantly correlated to low C24ceramide levels (p<0.001) while a significant association to hepatic decompensation and poor overall survival was observed for low serum concentrations of C24ceramide (p<0.001) as well. Multivariate analysis further identified low serum C24ceramide to be independently associated to overall survival (standard beta = -0.001, p = 0.022). Conclusions In our current analysis serum levels of very long chain ceramides show a significant reciprocal correlation to disease severity and hepatic decompensation and are independently associated with overall survival in patients with cirrhosis. Serum sphingolipid metabolites and particularly C24ceramide may constitute novel molecular targets of disease severity, hepatic decompensation and overall prognosis in cirrhosis and should be further evaluated in basic research studies. PMID:26382760

  7. Peripheral Blood Stem Cell Transplantation Improves Liver Functional Reserve

    PubMed Central

    Cai, Ting; Deng, Qinzhi; Zhang, Shun; Hu, Airong; Gong, Qinghai; Zhang, Xingfen

    2015-01-01

    Background Currently available treatment options for decompensated hepatitis B-induced liver cirrhosis are limited and largely ineffective. Recently, stem cell transplantation has emerged as a promising treatment for cirrhosis. The aim of this study was to determine whether autologous peripheral blood stem cell transplantation can improve liver functional reserve in patients with hepatitis B-induced cirrhosis. Material/Methods In this study, 51 patients with hepatitis B-induced liver cirrhosis were assigned to the treatment group (n=23) or the control group (n=28). The treatment group underwent autologous peripheral blood stem cell transplantation in addition to comprehensive medical treatment, and the control group received comprehensive medical treatment alone. Liver functional reserve was monitored for 48 weeks after autologous peripheral blood stem cell transplantation. Results After transplantation, most patients showed improvements in symptoms such as fatigue, anorexia, and abdominal distension. The retention rate of indocyanine green at 15 minutes, a common indicator of liver functional reserve, declined from 41.99±4.68 at baseline to 37.79±3.75 by 48 weeks after transplantation, showing significant improvement. Conclusions Autologous peripheral blood stem cell transplantation can improve several markers of liver health and liver functional reserve and is a promising prospect for clinical application. PMID:25970080

  8. Is There a Role for Probiotics in Liver Disease?

    PubMed Central

    Lo, Robert S.; Austin, Andrew S.; Freeman, Jan G.

    2014-01-01

    Intestinal microbiota plays an important role in health and disease. Alteration in its healthy homeostasis may result in the development of numerous liver disorders including complications of liver cirrhosis. On the other hand, restoration and modulation of intestinal flora through the use of probiotics is potentially an emerging therapeutic strategy. There is mounting evidence that probiotics are effective in the treatment of covert and overt hepatic encephalopathy, as well as in the prevention of recurrence of encephalopathy. The beneficial effect of probiotics also extends to liver function in cirrhosis, nonalcoholic fatty liver disease, and alcoholic liver disease. On the other hand, data associating probiotics and portal hypertension is scanty and conflicting. Probiotic therapy has also not been shown to prevent primary or secondary spontaneous bacterial peritonitis. Larger clinical studies are required before probiotics can be recommended as a treatment modality in liver diseases. PMID:25436233

  9. Hepatitis C and liver transplantation

    NASA Astrophysics Data System (ADS)

    Brown, Robert S.

    2005-08-01

    Liver transplantation is a life-saving therapy to correct liver failure, portal hypertension and hepatocellular carcinoma arising from hepatitis C infection. But despite the successful use of living donors and improvements in immunosuppression and antiviral therapy, organ demand continues to outstrip supply and recurrent hepatitis C with accelerated progression to cirrhosis of the graft is a frequent cause of graft loss and the need for retransplantation. Appropriate selection of candidates and timing of transplantation, coupled with better pre- and post-transplant antiviral therapy, are needed to improve outcomes.

  10. Liver fibrosis markers of nonalcoholic steatohepatitis

    PubMed Central

    Enomoto, Hirayuki; Bando, Yukihiro; Nakamura, Hideji; Nishiguchi, Shuhei; Koga, Masafumi

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) is one of the major causes of chronic liver injury. NAFLD includes a wide range of clinical conditions from simple steatosis to nonalcoholic steatohepatitis (NASH), advanced fibrosis, and liver cirrhosis. The histological findings of NASH indicate hepatic steatosis and inflammation with characteristic hepatocyte injury (e.g., ballooning degeneration), as is observed in the patients with alcoholic liver disease. NASH is considered to be a potentially health-threatening disease that can progress to cirrhosis. A liver biopsy remains the most reliable diagnostic method to appropriately diagnose NASH, evaluate the severity of liver fibrosis, and determine the prognosis and optimal treatment. However, this invasive technique is associated with several limitations in routine use, and a number of biomarkers have been developed in order to predict the degree of liver fibrosis. In the present article, we review the current status of noninvasive biomarkers available to estimate liver fibrosis in the patients with NASH. We also discuss our recent findings on the use of the glycated albumin-to-glycated hemoglobin ratio, which is a new index that correlates to various chronic liver diseases, including NASH. PMID:26139988

  11. Initiation of Liver Transplantation in Bangladesh: Report on the First Two Successful Cases

    PubMed Central

    Gupta, Subash; Zafar, S.M.A.; Rashid, Mamunur; Husain, Muhd. Mustaque; Rabbi, Hashim; Ahmed, A.H.M. Tanvir; Akhtar, K.M.; Alam, Hasina

    2014-01-01

    ABSTRACT Liver transplantation (LT) is the treatment of choice for patients with end-stage liver disease (ESLD). Chronic liver disease due to many causes is prevalent in a significant percentage of the Bangladeshi population. Until recently, liver transplantation facilities were not available, and ESLD patients were dying without treatment. Liver transplantation is a complex procedure that requires integrated and organized approach by a multidisciplinary team. The initiation of liver transplantation in Bangladesh has faced many difficulties. These difficulties have been encountered and overcome in phases. We have successfully performed the first two living-donor liver transplantations (LDLTs) in Bangladesh. The recipient of the first LDLT was a 42-year man with cryptogenic cirrhosis, and the second one was a male of 35 years, suffering from HBV cirrhosis. Both the recipients and donors are doing well and relishing the prospect of a normal life. These two successful liver transplantations are milestones in the development of liver transplantation services in Bangladesh. PMID:25895203

  12. A genome-wide association study confirms PNPLA3 and identifies TM6SF2 and MBOAT7 as risk loci for alcohol-related cirrhosis.

    PubMed

    Buch, Stephan; Stickel, Felix; Trépo, Eric; Way, Michael; Herrmann, Alexander; Nischalke, Hans Dieter; Brosch, Mario; Rosendahl, Jonas; Berg, Thomas; Ridinger, Monika; Rietschel, Marcella; McQuillin, Andrew; Frank, Josef; Kiefer, Falk; Schreiber, Stefan; Lieb, Wolfgang; Soyka, Michael; Semmo, Nasser; Aigner, Elmar; Datz, Christian; Schmelz, Renate; Brückner, Stefan; Zeissig, Sebastian; Stephan, Anna-Magdalena; Wodarz, Norbert; Devière, Jacques; Clumeck, Nicolas; Sarrazin, Christoph; Lammert, Frank; Gustot, Thierry; Deltenre, Pierre; Völzke, Henry; Lerch, Markus M; Mayerle, Julia; Eyer, Florian; Schafmayer, Clemens; Cichon, Sven; Nöthen, Markus M; Nothnagel, Michael; Ellinghaus, David; Huse, Klaus; Franke, Andre; Zopf, Steffen; Hellerbrand, Claus; Moreno, Christophe; Franchimont, Denis; Morgan, Marsha Y; Hampe, Jochen

    2015-12-01

    Alcohol misuse is the leading cause of cirrhosis and the second most common indication for liver transplantation in the Western world. We performed a genome-wide association study for alcohol-related cirrhosis in individuals of European descent (712 cases and 1,426 controls) with subsequent validation in two independent European cohorts (1,148 cases and 922 controls). We identified variants in the MBOAT7 (P = 1.03 × 10(-9)) and TM6SF2 (P = 7.89 × 10(-10)) genes as new risk loci and confirmed rs738409 in PNPLA3 as an important risk locus for alcohol-related cirrhosis (P = 1.54 × 10(-48)) at a genome-wide level of significance. These three loci have a role in lipid processing, suggesting that lipid turnover is important in the pathogenesis of alcohol-related cirrhosis. PMID:26482880

  13. Comprehensive Care of Patients with Chronic Liver Disease.

    PubMed

    James, Jocelyn; Liou, Iris W

    2015-09-01

    Chronic liver disease results from a wide range of conditions, for which individual management is beyond the scope of this article. General education, counseling, and harm reduction practices are important to the primary care of these patients, as are monitoring for cirrhosis and management of its complications. For patients with advanced liver disease, comprehensive care includes considering referral for liver transplantation, educating and empowering patients to prioritize goals of care, and optimizing symptom relief. PMID:26320039

  14. microRNA-29b prevents liver fibrosis by attenuating hepatic stellate cell activation and inducing apoptosis through targeting PI3K/AKT pathway

    PubMed Central

    Wang, Jia; Chu, Eagle S.H.; Chen, Hai-Yong; Man, Kwan; Go, Minnie Y.Y.; Huang, Xiao Ru; Lan, Hui Yao; Sung, Joseph J.Y.; Yu, Jun

    2015-01-01

    microRNA-29b (miR-29b) is known to be associated with TGF-?-mediated fibrosis, but the mechanistic action of miR-29b in liver fibrosis remains unclear and is warranted for investigation. We found that miR-29b was significantly downregulated in human and mice fibrotic liver tissues and in primary activated HSCs. miR-29b downregulation was directly mediated by Smad3 through binding to the promoter of miR-29b in hepatic stellate cell (HSC) line LX1, whilst miR-29b could in turn suppress Smad3 expression. miR-29b transduction in the liver of mice prevented CCl4 induced-fibrogenesis, concomitant with decreased expression of ?-SMA, collagen I and TIMP-1. Ectopic expression of miR-29b in activated HSCs (LX-1, HSC-T6) inhibited cell viability and colony formation, and caused cell cycle arrest in G1 phase by downregulating cyclin D1 and p21cip1. Further, miR-29b induced apoptosis in HSCs mediated by caspase-9 and PARP. miR-29b inhibited its downstream effectors of PIK3R1 and AKT3 through direct targeting their 3?UTR regions. Moreover, knockdown of PIK3R1 or AKT3 suppressed ?-SMA and collagen I and induced apoptosis in both HSCs and in mice. In conclusion, miR-29b prevents liver fibrogenesis by inhibiting HSC activation and inducing HSC apoptosis through inhibiting PI3K/AKT pathway. These results provide novel mechanistic insights for the anti-fibrotic effect of miR-29b. PMID:25356754

  15. Liver metastases

    MedlinePLUS

    Metastases to the liver; Metastatic liver cancer; Liver cancer - metastatic ... Almost any cancer can spread to the liver. Cancers that can spread to the liver include: Breast cancer Colorectal cancer Esophageal ...

  16. Liver Cancer

    MedlinePLUS

    ... body digest food, store energy, and remove poisons. Primary liver cancer starts in the liver. Metastatic liver ... and spreads to your liver. Risk factors for primary liver cancer include Having hepatitis B or C ...

  17. Very low calorie ketogenic weight reduction diet in patients with cirrhosis: a case series

    PubMed Central

    Temmerman, J C; Friedman, A N

    2013-01-01

    Weight reduction may be necessary in patients with end-stage liver disease (ESLD) before liver transplantation. Although very low calorie diets (VLCDs) are a highly effective weight loss strategy, they risk inducing protein-calorie malnutrition, sarcopenia and hepatic encephalopathy in ESLD patients. We report for the first time on the use of VCLDs in ESLD. Two severely obese individuals with ESLD underwent a modified VLCD to become eligible for liver transplantation. Patients consumed four protein supplements and one lean meal daily, equivalent to 800?kilocalories (kcal) and were closely monitored during the diet period. Subject 1, a 46-year-old male with alcoholic cirrhosis, lost 44.1?kg after 28 weeks on a modified VLCD. Liver function and MELD (model for end-stage liver disease) scores improved and he currently does not require listing for transplantation. Subject 2, a 64-year-old female with non-alcoholic steatohepatitis, lost 39.7?kg after a 30-week modified VLCD. She is awaiting liver transplantation listing with a stable MELD score. VLCDs were well tolerated by both patients without adverse effects. In conclusion, under close medical supervision VLCDs in patients with ESLD can be safe and effective in reducing weight, facilitating liver transplantation listing, and possibly improving liver damage. PMID:24247485

  18. Analysis of LIF-Raman spectroscopy for the diagnosis of normal and liver diseases

    NASA Astrophysics Data System (ADS)

    Li, Xiaozhou; Yang, Tianyue; Yu, Ting; Sun, Ruomin; Li, Siqi

    2011-07-01

    In this paper, 514.5nm argon ion laser induced human serum Raman and auto-fluorescence spectra of normal, liver cirrhosis and liver cancer were measured and analyzed. The spectral differences between these three types of serums were observed and given brief explanations. Three parameters ?, ? and ?? were introduced to describe characteristics of each type of spectrum. Experimental results showed that these parameters might be applicable for discrimination of normal, liver cirrhosis and liver cancer, which will provide some reference values to explore the method of laser spectral diagnosis of cancer.

  19. Iron homeostasis in the liver

    PubMed Central

    Anderson, Erik R; Shah, Yatrik M

    2014-01-01

    Iron is an essential nutrient that is tightly regulated. A principal function of the liver is the regulation of iron homeostasis. The liver senses changes in systemic iron requirements and can regulate iron concentrations in a robust and rapid manner. The last 10 years have led to the discovery of several regulatory mechanisms in the liver which control the production of iron regulatory genes, storage capacity, and iron mobilization. Dysregulation of these functions leads to an imbalance of iron, which is the primary causes of iron-related disorders. Anemia and iron overload are two of the most prevalent disorders worldwide and affect over a billion people. Several mutations in liver-derived genes have been identified, demonstrating the central role of the liver in iron homeostasis. During conditions of excess iron, the liver increases iron storage and protects other tissues, namely the heart and pancreas from iron-induced cellular damage. However, a chronic increase in liver iron stores results in excess reactive oxygen species production and liver injury. Excess liver iron is one of the major mechanisms leading to increased steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. PMID:23720289

  20. Intravenous and intrapulmonary administration of honey solution to healthy sheep: effects on blood sugar, renal and liver function tests, bone marrow function, lipid profile, and carbon tetrachloride-induced liver injury.

    PubMed

    Al-Waili, Noori S

    2003-01-01

    Safety of intravenous (i.v.) or intrapulmonary administration of different concentrations of honey and their effects on blood sugar, renal and liver function tests, bone marrow function, lipid profile, and carbon tetrachloride (CCl(4))-induced liver damage were studied. Healthy sheep of either sex, 6-8 months old, were assigned randomly into the following groups: sheep received i.v. infusion of 5% honey in normal saline at 10-day intervals for 50 days and were compared with sheep that received 5% dextrose; sheep received higher doses of honey (50 g of honey) by i.v. infusion daily for 10 days; sheep received four higher doses of honey (80 g each dose) for 2 weeks; sheep received subcutaneous injection of CCl(4) after four doses of i.v. infusion of 80 g of honey, and estimations of serum gamma-glutamyl transpeptidase (SGGT), serum glutamic oxaloacetic transaminase (SGOT), and serum glutamate pyruvate transaminase (SGPT) were performed daily for 10 days postinjection; sheep received i.v. infusion of 40 g of honey, and blood sugar estimation was performed for 3 h at 30-min intervals after infusion and compared with sheep that received 5% dextrose; sheep received rapid i.v. injection of 40% honey or 40% dextrose, and blood sugar was estimated before and after injection; sheep received various concentrations of honey in distilled water (0.5 mL/1.5 mL, 0.75 mL/1.75 mL and 1.2 mL/2.2 mL), and blood sugar estimation was performed before and after inhalation. Results showed that i.v. or intrapulmonary administration of honey did not cause any adverse effect. Intravenous delivery of honey by slow infusion caused improvement of renal and hepatic function, bone marrow function, and lipid profile. It reduced SGOT, SGPT, triglyceride, cholesterol, blood urea nitrogen, and blood sugar and elevated serum protein, serum albumin, hemoglobin, white blood cell, and neutrophil percentage. Similar results were obtained with the use of higher doses of honey. CCl(4) caused mild elevation of SGPT and SGGT and lowering of SGOT in sheep that received repeated i.v. administration of honey before administration of CCl(4), whereas in control sheep CCl(4) caused significant elevation of all the liver enzymes. Intravenous infusion of 40 g of honey caused elevation of blood sugar for 90 min postinfusion, whereas it decreased blood sugar at 2 and 3 h postinfusion as compared with fasting blood sugar. Dextrose caused significant elevation of blood sugar at all time intervals. Similar results were obtained with the use of 10% dextrose or 80 g of honey. Addition of honey to dextrose caused less hyperglycemia as compared with dextrose alone. Acute injection of 20 mL of 40% dextrose significantly elevated blood sugar for 3 h postinjection, whereas little elevation in blood sugar was obtained after injection of 40% honey; the difference between honey and dextrose was significant. Inhalation of honey caused significant lowering of blood sugar during and after inhalation as compared with fasting blood sugar and water inhalation. The effect was greater with a higher concentration of inhaled honey. It might be concluded that slow i.v. infusion or rapid i.v. injection of honey in different concentrations was safe and could lower blood sugar and improve renal, hepatic, and bone marrow functions and lipid profile. Intravenous honey had a hepatoprotective effect against CCl(4)-induced liver injury. Inhaled honey was safe and reduced blood sugar significantly. PMID:14585190

  1. Angiogenesis and liver fibrosis

    PubMed Central

    Elpek, Gülsüm Özlem

    2015-01-01

    Recent data indicate that hepatic angiogenesis, regardless of the etiology, takes place in chronic liver diseases (CLDs) that are characterized by inflammation and progressive fibrosis. Because anti-angiogenic therapy has been found to be efficient in the prevention of fibrosis in experimental models of CLDs, it is suggested that blocking angiogenesis could be a promising therapeutic option in patients with advanced fibrosis. Consequently, efforts are being directed to revealing the mechanisms involved in angiogenesis during the progression of liver fibrosis. Literature evidences indicate that hepatic angiogenesis and fibrosis are closely related in both clinical and experimental conditions. Hypoxia is a major inducer of angiogenesis together with inflammation and hepatic stellate cells. These profibrogenic cells stand at the intersection between inflammation, angiogenesis and fibrosis and play also a pivotal role in angiogenesis. This review mainly focuses to give a clear view on the relevant features that communicate angiogenesis with progression of fibrosis in CLDs towards the-end point of cirrhosis that may be translated into future therapies. The pathogenesis of hepatic angiogenesis associated with portal hypertension, viral hepatitis, non-alcoholic fatty liver disease and alcoholic liver disease are also discussed to emphasize the various mechanisms involved in angiogenesis during liver fibrogenesis. PMID:25848465

  2. Renal failure in cirrhosis: Emerging concepts

    PubMed Central

    Bittencourt, Paulo Lisboa; Farias, Alberto Queiroz; Terra, Carlos

    2015-01-01

    Acute renal failure, now termed acute kidney injury (AKI), is frequently found in patients with cirrhosis. The occurrence of AKI, irrespective of the underlying cause, is associated with reduced in-hospital, 3-mo and 1-year survival. Hepatorenal syndrome is associated with the worst outcome among AKI patients with cirrhosis. Several definitions for AKI that have been proposed are outlined and evaluated in this paper. Among these, the International Club for Ascites-AKI criteria substantially strengthen the quality of early diagnosis and intervention according to underlying cause of AKI. PMID:26413223

  3. Native fluorescence characterization of human liver abnormalities

    NASA Astrophysics Data System (ADS)

    Ganesan, Singaravelu; Madhuri, S.; Aruna, Prakasa R.; Suchitra, S.; Srinivasan, T. G.

    1999-05-01

    Fluorescence spectroscopy of intrinsic biomolecules has been extensively used in biology and medicine for the past several decades. In the present study, we report the native fluorescence characteristics of blood plasma from normal human subjects and patients with different liver abnormalities such as hepatitis, leptospirosis, jaundice, cirrhosis and liver cell failure. Native fluorescence spectra of blood plasma -- acetone extract were measured at 405 nm excitation. The average spectrum of normal blood plasma has a prominent emission peak around 464 nm whereas in the case of liver diseased subjects, the primary peak is red shifted with respect to normal. In addition, liver diseased cases show distinct secondary emission peak around 615 nm, which may be attributed to the presence of endogenous porphyrins. The red shift of the prominent emission peak with respect to normal is found to be maximum for hepatitis and minimum for cirrhosis whereas the secondary emission peak around 615 nm was found to be more prominent in the case of cirrhosis than the rest. The ratio parameter I465/I615 is found to be statistically significant (p less than 0.001) in discriminating liver abnormalities from normal.

  4. Management of thrombocytopenia in advanced liver disease

    PubMed Central

    Gangireddy, VGR; Kanneganti, PC; Sridhar, S; Talla, S; Coleman, T

    2014-01-01

    Thrombocytopenia (defined as a platelet count <150×109/L) is a well-known complication in patients with liver cirrhosis and has been observed in 76% to 85% of patients. Significant thrombocytopenia (platelet count <50×109/L to 75×109/L) occurs in approximately 13% of patients with cirrhosis. Thrombocytopenia can negatively impact the care of patients with severe liver disease by potentially interfering with diagnostic and therapeutic procedures. Multiple factors can contribute to the development of thrombocytopenia including splenic platelet sequestration, immunological processes, bone marrow suppression by chronic viral infection, and reduced levels or activity of the hematopoietic growth factor thrombopoietin. The present review focuses on the etiologies and management options for severe thrombocytopenia in the setting of advanced liver disease. PMID:25222481

  5. Clinical Use of Diuretics in Heart Failure, Cirrhosis, and Nephrotic Syndrome

    PubMed Central

    Qavi, Ahmed Hassaan; Kamal, Rida; Schrier, Robert W.

    2015-01-01

    Diuretics play significant role in pharmacology and treatment options in medicine. This paper aims to review and evaluate the clinical use of diuretics in conditions that lead to fluid overload in the body such as cardiac failure, cirrhosis, and nephrotic syndrome. To know the principles of treatment it is essential to understand the underlying pathophysiological mechanisms that cause the need of diuresis in the human body. Various classes of diuretics exist, each having a unique mode of action. A systemic approach for management is recommended based on the current guidelines, starting from thiazides and proceeding to loop diuretics. The first condition for discussion in the paper is cardiac failure. Treatment of ascites in liver cirrhosis with spironolactone as the primary agent is highlighted with further therapeutic options. Lastly, management choices for nephrotic syndrome are discussed and recommended beginning from basic sodium restriction to combined diuretic therapies. Major side effects are discussed. PMID:26294976

  6. Primary structure of the human M2 mitochondrial autoantigen of primary biliary cirrhosis: Dihydrolipoamide acetyltransferase

    SciTech Connect

    Coppel, R.L.; McNeilage, L.J.; Surh, C.D.; Van De Water, J.; Spithill, T.W.; Whittingham, S.; Gershwin, M.E. )

    1988-10-01

    Primary biliary cirrhosis is a chronic, destructive autoimmune liver disease of humans. Patient sera are characterized by a high frequency of autoantibodies to a M{sub r} 70,000 mitochondrial antigen a component of the M2 antigen complex. The authors have identified a human cDNA clone encoding the complete amino acid sequence of this autoantigen. The predicted structure has significant similarity with the dihydrolipoamide acetyltransferase of the Escherichia coli pyruvate dehydrogenase multienzyme complex. The human sequence preserves the Glu-Thr-Asp-Lys-Ala motif of the lipoyl-binding site and has two potential binding sites. Expressed fragments of the cDNA react strongly with sera from patients with primary biliary cirrhosis but not with sera from patients with autoimmune chronic active hepatitis or sera from healthy subjects.

  7. Optical analysis of cirrhotic liver by near infrared time resolved spectroscopy

    NASA Astrophysics Data System (ADS)

    Nishio, Toshihiro; Kitai, Toshiyuki; Miwa, Mitsuharu; Takahashi, Rei; Yamaoka, Yoshio

    1999-10-01

    The severity of liver cirrhosis was related with the optical properties of liver tissue. Various grades of liver cirrhosis were produced in rats by intraperitoneal injection of thioacetamide (TAA) for different periods: 4 weeks, 8 weeks, 12 weeks, and 16 weeks. Optical properties of the liver, absorption, coefficient ((mu) a) and scattering coefficient (microsecond(s) '), were measured by near-infrared time- resolved spectroscopy. Histological examination confirmed cirrhotic changes in the liver, which were more severe in rats with TAA administration for longer periods. The (mu) a increased in 4- and 8-week rats, and then decreased in 12- and 16-week rats. The (mu) a of blood-free liver decreased as liver cirrhosis progressed. The hemoglobin content in the liver calculated from the (mu) a values increased in 4- and 8-week rats and decreased in 12- and 16-week rats. The microsecond(s) ' decreased in the cirrhotic liver, probably reflecting the decrease in the mitochondria content. It was shown that (mu) a and microsecond(s) ' determination is useful to assess the severity of liver cirrhosis.

  8. Hepatocarcinogenesis in non-alcoholic fatty liver disease in Japan.

    PubMed

    Tokushige, Katsutoshi; Hashimoto, Etsuko; Kodama, Kazuhiko

    2013-12-01

    In Japan, there has been a gradual increase in cases of non-viral chronic liver diseases, including non-alcoholic fatty liver disease (NAFLD), occurring with hepatocellular carcinoma (HCC). First, a national survey investigating the etiology of HCC in Japan was performed. Among HCCs based on non-viral disease, alcoholic liver disease with HCC accounted for 7.2% of all HCCs, followed by chronic liver disease of unknown etiology with HCC (5.1%) and NAFLD with HCC (2.0%). The clinical characteristics of these three HCC groups were clearly different. In our second analysis, the HCC development rates among liver cirrhosis with NAFLD, alcoholic cirrhosis, and cirrhosis with hepatitis C virus (HCV) were compared. HCC development rates were 11.3%/5 years in NAFLD cirrhosis, 30.5%/5 years in HCV cirrhosis, and 12.5%/5 years in alcoholic cirrhosis, suggesting that the hepatocarcinogenesis in NAFLD and alcoholic liver disease were similar but were lower than that in HCV. Using Cox hazards analysis, older age, higher serum ?-glutamyl transpeptidase level, and higher Child-Pugh score as risk factors of HCC were identified. Finally, clinical data of NAFLD-HCC with the data for HCC with HCV (HCV-HCC) were compared. The percentage of NAFLD-HCC patients with des-gamma-carboxy prothrombin-positive was higher than that with ?-fetoprotein-positive. The 5-year survival and recurrence rates for NAFLD-HCC were almost similar to those for HCV-HCC. In Asian countries, the prevalence of NAFLD is increasing. Therefore, elucidating the pathogenesis and clinical features of HCC in patients with NAFLD is indeed an urgent problem. PMID:24251711

  9. Diagnosis and Management of Alcoholic Liver Disease

    PubMed Central

    Dugum, Mohannad; McCullough, Arthur

    2015-01-01

    Alcohol is a leading cause of liver disease and is associated with significant morbidity and mortality. Several factors, including the amount and duration of alcohol consumption, affect the development and progression of alcoholic liver disease (ALD). ALD represents a spectrum of liver pathology ranging from fatty change to fibrosis to cirrhosis. Early diagnosis of ALD is important to encourage alcohol abstinence, minimize the progression of liver fibrosis, and manage cirrhosis-related complications including hepatocellular carcinoma. A number of questionnaires and laboratory tests are available to screen for alcohol intake. Liver biopsy remains the gold-standard diagnostic tool for ALD, but noninvasive accurate alternatives, including a number of biochemical tests as well as liver stiffness measurement, are increasingly being utilized in the evaluation of patients with suspected ALD. The management of ALD depends largely on complete abstinence from alcohol. Supportive care should focus on treating alcohol withdrawal and providing enteral nutrition while managing the complications of liver failure. Alcoholic hepatitis (AH) is a devastating acute form of ALD that requires early recognition and specialized tertiary medical care. Assessment of AH severity using defined scoring systems is important to allocate resources and initiate appropriate therapy. Corticosteroids or pentoxifylline are commonly used in treating AH but provide a limited survival benefit. Liver transplantation represents the ultimate therapy for patients with alcoholic cirrhosis, with most transplant centers mandating a 6 month period of abstinence from alcohol before listing. Early liver transplantation is also emerging as a therapeutic measure in specifically selected patients with severe AH. A number of novel targeted therapies for ALD are currently being evaluated in clinical trials. PMID:26356792

  10. Hepatoprotective effect of commercial herbal extracts on carbon tetrachloride-induced liver damage in Wistar rats

    PubMed Central

    Cordero-Pérez, Paula; Torres-González, Liliana; Aguirre-Garza, Marcelino; Camara-Lemarroy, Carlos; Guzmán-de la Garza, Francisco; Alarcón-Galván, Gabriela; Zapata-Chavira, Homero; de Jesús Sotelo-Gallegos, Ma.; Nadjedja Torres-Esquivel, Cipactli; Sánchez-Fresno, Ethel; Cantú-Sepúlveda, Daniel; González-Saldivar, Gerardo; Bernal-Ramirez, Judith; E. Muñoz-Espinosa, Linda

    2013-01-01

    Background: Various hepatoprotective herbal products from plants are available in Mexico, where up to 85% of patients with liver disease use some form of complementary and alternative medicine. However, only few studies have reported on the biological evaluation of these products. Objective: Using a model of carbon tetrachloride (CCl4)-induced hepatotoxicity in rats, we evaluated the effects of commercial herbal extracts used most commonly in the metropolitan area of Monterrey, Mexico. Materials and Methods: The commercial products were identified through surveys in public areas. The effect of these products given with or without CCl4 in rats was evaluated by measuring the serum concentrations of aspartate amino transferase (AST) and alanine amino transferase (ALT), and histopathological analysis. Legalon® was used as the standard drug. Results: The most commonly used herbal products were Hepatisan® capsules, Boldo capsules, Hepavida® capsules, Boldo infusion, and milk thistle herbal supplement (80% silymarin). None of the products tested was hepatotoxic according to transaminase and histological analyses. AST and ALT activities were significantly lower in the Hepavida+CCl4-treated group as compared with the CCl4-only group. AST and ALT activities in the silymarin, Hepatisan, and Boldo tea groups were similar to those in the CCl4 group. The CCl4 group displayed submassive confluent necrosis and mixed inflammatory infiltration. Both the Hepatisan+CCl4 and Boldo tea+CCl4 groups exhibited ballooning degeneration, inflammatory infiltration, and lytic necrosis. The silymarin+CCl4 group exhibited microvesicular steatosis. The Hepavida+CCl4- and Legalon+CCL4-treated groups had lower percentages of necrotic cells as compared with the CCl4-treated group; this treatment was hepatoprotective against necrosis. Conclusion: Only Hepavida had a hepatoprotective effect. PMID:23900881

  11. The effect of the respiratory cycle on liver stiffness values as measured by transient elastography.

    PubMed

    Yun, M H; Seo, Y S; Kang, H S; Lee, K G; Kim, J H; An, H; Yim, H J; Keum, B; Jeen, Y T; Lee, H S; Chun, H J; Um, S H; Kim, C D; Ryu, H S

    2011-09-01

    The findings of several studies suggest that liver stiffness values can be affected by the degree of intrahepatic congestion respiration influence intrahepatic blood volume and may affect liver stiffness. We evaluated the influence of respiration on liver stiffness. Transient elastography (TE) was performed at the end of inspiration and at the end of expiration in patients with chronic liver disease. The median values obtained during the inspiration set and during the expiration set were defined as inspiratory and expiratory liver stiffness, respectively. A total of 123 patients with chronic liver disease were enrolled (mean age 49years; 64.2% men). Liver cirrhosis coexisted in 29 patients (23.6%). Expiratory liver stiffness was significantly higher than inspiratory liver stiffness (8.7 vs 7.9kPa, P=0.001), while the expiratory interquartile range/median ratio (IQR ratio) did not differ from the inspiratory IQR ratio. Expiratory liver stiffness was significantly higher than inspiratory liver stiffness in 49 (39.8%) patients (HE group), expiratory liver stiffness was significantly lower than inspiratory stiffness in 15 (12.2%) patients, and there was no difference in 59 (48.0%) patients. Liver cirrhosis was more frequent in those who had a lower liver stiffness reading in expiration, and only the absence of liver cirrhosis was significantly associated with a higher reading in expiration in multivariate analysis. In conclusion, liver stiffness was significantly elevated during expiration especially in patients without liver cirrhosis. The effect of respiration should be kept in mind during TE readings. PMID:21029256

  12. Fibrogenesis in alcoholic liver disease

    PubMed Central

    Fujii, Hideki; Kawada, Norifumi

    2014-01-01

    Alcoholic liver disease (ALD) is a major cause of morbidity and mortality worldwide. In developed countries, ALD is a major cause of end-stage liver disease that requires transplantation. The spectrum of ALD includes simple steatosis, alcoholic hepatitis, ?brosis, cirrhosis, and hepatocellular carcinoma. Alcohol abstinence is the most effective therapy for ALD. However, targeted therapies are urgently needed for patients with severe ALD (i.e., alcoholic hepatitis) or those who do not abstain from alcohol. The lack of studies and the availability of animal models that do not reflect all the features of this disease in humans inhibit the development of new drugs for ALD. In ALD-associated fibrosis, hepatic stellate cells are the principal cell type responsible for extracellular matrix production. Although the mechanisms underlying fibrosis in ALD are largely similar to those observed in other chronic liver diseases, oxidative stress, methionine metabolism abnormalities, hepatocyte apoptosis, and endotoxin lipopolysaccharides that activate Kupffer cells may play unique roles in disease-related fibrogenesis. Lipogenesis during the early stages of ALD has recently been implicated as a risk factor for the progression of cirrhosis. Other topics include osteopontin, interleukin-1 signaling, and genetic polymorphism. In this review, we discuss the basic pathogenesis of ALD and focus on liver fibrogenesis. PMID:25009376

  13. Development of a New Diagnostic System for Human Liver Diseases Based on Conventional Ultrasonic Diagnostic Equipment

    NASA Astrophysics Data System (ADS)

    Kikuchi, Tsuneo; Nakazawa, Toshihiro; Harada, Akimitsu; Sato, Hiroaki; Maruyama, Yukio; Sato, Sojun

    2001-05-01

    In this paper, the authors present the experimental results of using a quantitative ultrasonic diagnosis technique for human liver diseases using the fractal dimension (FD) of the shape of the power spectra (PS) of RF signals. We have developed an experimental system based on a conventional ultrasonic diagnostic system. As a result, we show that normal livers, fatty livers and liver cirrhosis can be identified using the FD values.

  14. Thalidomide Accelerates the Degradation of Extracellular Matrix in Rat Hepatic Cirrhosis via Down-Regulation of Transforming Growth Factor-?1

    PubMed Central

    Meng, Qingshun; Liu, Jie; Wang, Chuanfang

    2015-01-01

    Purpose The degradation of the extracellular matrix has been shown to play an important role in the treatment of hepatic cirrhosis. In this study, the effect of thalidomide on the degradation of extracellular matrix was evaluated in a rat model of hepatic cirrhosis. Materials and Methods Cirrhosis was induced in Wistar rats by intraperitoneal injection of carbon tetrachloride (CCl4) three times weekly for 8 weeks. Then CCl4 was discontinued and thalidomide (100 mg/kg) or its vehicle was administered daily by gavage for 6 weeks. Serum hyaluronic acid, laminin, procollagen type III, and collagen type IV were examined by using a radioimmunoassay. Matrix metalloproteinase-13 (MMP-13), tissue inhibitor of metalloproteinase-1 (TIMP-1), and ?-smooth muscle actin (?-SMA) protein in the liver, transforming growth factor ?1 (TGF-?1) protein in cytoplasm by using immunohistochemistry and Western blot analysis, and MMP-13, TIMP-1, and TGF-?1 mRNA levels in the liver were studied using reverse transcriptase polymerase chain reaction. Results Liver histopathology was significantly better in rats given thalidomide than in the untreated model group. The levels of TIMP-1 and TGF-?1 mRNA and protein expressions were decreased significantly and MMP-13 mRNA and protein in the liver were significantly elevated in the thalidomide-treated group. Conclusion Thalidomide may exert its effects on the regulation of MMP-13 and TIMP-1 via inhibition of the TGF-?1 signaling pathway, which enhances the degradation of extracellular matrix and accelerates the regression of hepatic cirrhosis in rats. PMID:26446639

  15. Nonalcoholic fatty liver disease.

    PubMed

    Alfire, Marcos E; Treem, William R

    2006-04-01

    NAFLD likely is the most common liver disease in children and is responsible for significant progression to cirrhosis, portal hypertension, and the need for liver transplantation in adults and even in some adolescents. Early diagnosis and lifestyle interventions appear to be our best hope for controlling progression of disease. The pediatrician is responsible for screening all obese children with measurement of aminotransferases. Those with elevated enzymes (particularly ALT) for longer than 3 months, in the absence of markers of hepatitis B or C, autoimmune chronic active hepatitis, Wilson's disease, hemochromatosis, or alpha-1-antitrypsin deficiency, should follow up with an abdominal ultrasound. In patients with a BMI in the morbidly obese range, an ultrasound to search for a diffusely echogenic liver should be performed even if the liver enzymes are normal. Findings suggestive of NAFLD should prompt the institution of appropriate dietary and exercise regimens. If these are unsuccessful after a 3-month trial, the patient should be referred to a pediatric gastroenterologist and hepatologist for further work-up and treatment, preferably in the context of a controlled therapeutic trial. Only by aggressively engaging this current epidemic will we be able to decrease the mounting human cost of NAFLD. PMID:16637558

  16. Liver Biopsy

    MedlinePLUS

    A liver biopsy is a medical procedure performed in order to obtain a small sample of the liver. This is ... small scar. The most common reasons for a liver biopsy include the evaluation of: ? Jaundice ? Liver inflammation (hepatitis) ? ...

  17. BIOCONJUGATION OF OLIGONUCLEOTIDES FOR TREATING LIVER FIBROSIS

    PubMed Central

    Ye, Zhaoyang; Hajj Houssein, Houssam S.; Mahato, Ram I.

    2009-01-01

    Liver fibrosis results from chronic liver injury due to hepatitis B and C, excessive alcohol ingestion, and metal ion overload. Fibrosis culminates in cirrhosis and results in liver failure. Therefore, a potent antifibrotic therapy is in urgent need to reverse scarring and eliminate progression to cirrhosis. Although activated hepatic stellate cells (HSCs) remains the principle cell type responsible for liver fibrosis, perivascular fibroblasts of portal and central veins as well as periductular fibroblasts are other sources of fibrogenic cells. This review will critically discuss various treatment strategies for liver fibrosis, including prevention of liver injury, reduction of inflammation, inhibition of HSC activation, degradation of scar matrix, and inhibition of aberrant collagen synthesis. Oligonucleotides (ODNs) are short, single-stranded nucleic acids, which disrupt expression of target protein by binding to complementary mRNA or forming triplex with genomic DNA. Triplex forming oligonucleotides (TFOs) provide an attractive strategy for treating liver fibrosis. A series of TFOs have been developed for inhibiting the transcription of ?1(I) collagen gene, which opens a new area for antifibrotic drugs. There will be in depth discussion on the use of TFOs and how different bioconjugation strategies can be utilized for their site-specific delivery to HSCs or hepatocytes for enhanced antifibrotic activities. Various insights developed in individual strategy and the need for multipronged approaches will also be discussed. PMID:18154454

  18. Aquaporin-1 Facilitates Angiogenic Invasion in the Pathologic Neovasculature that Accompanies Cirrhosis

    PubMed Central

    Huebert, Robert C.; Vasdev, Meher M.; Shergill, Uday; Das, Amitava; Huang, Bing Q.; Charlton MR, Michael R.; LaRusso, Nicholas F.; Shah, Vijay H.

    2010-01-01

    Increasing evidence suggests that hepatic fibrosis and pathologic angiogenesis are inter-dependent processes that occur in parallel. Endothelial cell invasion is requisite for angiogenesis and thus studies of the mechanisms governing liver endothelial cell (LEC) invasion during cirrhosis are of great importance. Emerging research implicates amoeboid-type motility and membrane blebbing as features that may facilitate invasion through matrix-rich microenvironments. Aquaporins (AQPs) are integral membrane water channels, recognized for their importance in epithelial secretion and absorption. However, recent studies also suggest links between water transport and cell motility / invasion. Therefore, the purpose of this study was to test the hypothesis that AQP-1 is involved in amoeboid motility and angiogenic invasion during cirrhosis. AQP-1 expression and localization was examined in normal and cirrhotic liver tissues derived from human and mouse. AQP-1 levels were modulated in LEC using retroviral overexpression or siRNA knockdown and functional effects on invasion, membrane blebbing dynamics, and osmotic water permeability were assayed. Results demonstrate that AQP-1 is up-regulated in the small, angiogenic, neo-vasculature within the fibrotic septa of cirrhotic liver. AQP-1 overexpression promotes FGF-induced dynamic membrane blebbing in LEC which is sufficient to augment invasion through extracellular matrix. Additionally, AQP-1 localizes to plasma membrane blebs where it increases osmotic water permeability and locally facilitates the rapid, trans-membrane flux of water. CONCLUSION AQP-1 enhances osmotic water permeability and FGF-induced dynamic membrane blebbing in LEC and thereby drives invasion and pathologic angiogenesis during cirrhosis PMID:20578142

  19. Thioacetamide-induced cirrhosis in selenium-adequate mice displays rapid and persistent abnormity of hepatic selenoenzymes which are mute to selenium supplementation

    SciTech Connect

    Zhang Jinsong Wang Huali; Yu Hanqing

    2007-10-01

    Selenium reduction in cirrhosis is frequently reported. The known beneficial effect of selenium supplementation on cirrhosis is probably obtained from nutritionally selenium-deficient subjects. Whether selenium supplementation truly improves cirrhosis in general needs additional experimental investigation. Thioacetamide was used to induce cirrhosis in selenium-adequate and -deficient mice. Selenoenzyme activity and selenium content were measured and the influence of selenium supplementation was evaluated. In Se-adequate mice, thioacetamide-mediated rapid onset of hepatic oxidative stress resulted in an increase in thioredoxin reductase activity and a decrease in both glutathione peroxidase activity and selenium content. The inverse activity of selenoenzymes (i.e. TrxR activity goes up and GPx activity goes down) was persistent and mute to selenium supplementation during the progress of cirrhosis; accordingly, cirrhosis was not improved by selenium supplementation in any period. On the other hand, selenium supplementation to selenium-deficient mice always more efficiently increased hepatic glutathione peroxidase activity and selenium content compared with those treated with thioacetamide, indicating that thioacetamide impairs the liver bioavailability of selenium. Although thioacetamide profoundly affects hepatic selenium status in selenium-adequate mice, selenium supplementation does not modify the changes. Selenium supplementation to cirrhotic subjects with a background of nutritional selenium deficiency can improve selenium status but cannot restore hepatic glutathione peroxidase and selenium to normal levels.

  20. Cartilage oligomeric matrix protein: A novel non-invasive marker for assessing cirrhosis and risk of hepatocellular carcinoma

    PubMed Central

    Norman, Gary L; Gatselis, Nikolaos K; Shums, Zakera; Liaskos, Christos; Bogdanos, Dimitrios P; Koukoulis, George K; Dalekos, George N

    2015-01-01

    AIM: To assess serum cartilage oligomeric matrix protein (COMP) as a marker of cirrhosis and risk of progression to hepatocellular carcinoma (HCC). METHODS: A COMP enzyme-linked immunosorbent assay was used to test 187 patients with chronic liver diseases at the time point of first evaluation. The selected patients included 72 with chronic hepatitis B infection, 75 with chronic hepatitis C infection, 22 with primary biliary cirrhosis, 7 with autoimmune hepatitis type 1, and 11 with alcoholic liver disease. Demographic, biochemical, histological and clinical characteristics of the patients were recorded at the first evaluation. One hundred and forty-seven patients were followed for a median [interquartile range (IQR)] duration of 96.5 (102) mo. The clinical, biochemical and histological data, as well as the development of cirrhosis, HCC according to internationally accepted criteria and in case of death, a liver-related cause during the follow-up period, were recorded at the electronic database of our clinic. COMP determination was also performed in 43 healthy individuals who served as the control study group. RESULTS: COMP positivity (> 15 U/L) was detected in 22%-36% among chronic liver disease groups. Strikingly, almost 83% of COMP-positive patients were cirrhotic at baseline, independently of cause of liver disease. Among the patients who developed HCC during follow-up, 73.7% (14/19) were COMP positive at baseline. COMP positivity was significantly associated with older age (P < 0.001), advanced fibrosis (P = 0.001) and necroinflammatory activity (P = 0.001), higher aspartate aminotransferase (P < 0.001), alanine aminotransferase (P < 0.02), ?-glutamyl transpeptidase (P = 0.003), alkaline phosphatase (P = 0.001), bilirubin (P < 0.05), international normalized ratio (P = 0.002) and alpha-fetoprotein levels (P < 0.02), and lower albumin (P < 0.001), and platelet count (P = 0.008). COMP levels [median (IQR)] were significantly higher in cirrhotics compared to non-cirrhotics [13.8 (7.9) U/L vs 9.8 (4.6) U/L, respectively; P < 0.001]. On multivariate logistic regression analysis, COMP-positivity was independently associated only with cirrhosis (OR = 4.40, 95%CI: 1.33-14.69, P = 0.015). Kaplan-Meier analysis showed that COMP positivity was significantly associated with HCC development (P = 0.007) and higher incidence of liver-related death (P < 0.001). CONCLUSION: Elevated COMP levels are strongly associated with cirrhosis and HCC progression. Serum COMP is a new promising non-invasive biomarker for HCC risk assessment in surveillance programs. PMID:26207169

  1. Detection of liver cancer and abnormal liver tissue by Raman spectroscopy and fluorescence

    NASA Astrophysics Data System (ADS)

    Li, Xiaozhou; Ding, Jianhua; Zhang, Xiujun; Lin, Junxiu; Wang, Deli

    2005-01-01

    In this paper, laser induced human serum Raman spectra of liver cancer are measured. The spectra differences in serum from normal people and liver disease patients are analyzed. For the typical spectrum of normal serum, there are three sharp Raman peaks and relative intensity of Raman peaks excited by 514.5nm is higher than that excited by 488.0nm. For the Raman spectrum of liver cancer serum there are no peaks or very weak Raman peaks at the same positions. Results from more than two hundred case measurements show that clinical diagnostic accuracy is 92.86%. And then, the liver fibrosis and liver cirrhosis are studied applying the technology of LIF. To liver cirrhosis, the shape of Raman peak is similar to normal and fluorescence spectrum is similar to that of liver cancer from statistic data. The experiment indicates that there is notable fluorescence difference between the abnormal and normal liver tissue and have blue shift in fluorescence peak. Except for human serum, we use rats serum for researching either. Compared with results of path al examination, we analyze the spectra of normal cases, hepatic fibrosis and hepatocirrhosis respectively in an attempt to find some difference between them. Red shift of fluorescence peak is observed with disease evolution using 514.5nm excitation of an Ar-ion laser. However, no distinct changes happen with 488.0nm excitation. These results have important reference values to explore the method of laser spectrum diagnosis.

  2. Connective tissue diseases and the liver.

    PubMed

    Youssef, Wael I; Tavill, Anthony S

    2002-10-01

    Connective tissue diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis, Sjögren's syndrome, and scleroderma are systemic disorders that may have an autoimmune basis. The system manifestations vary, and there is frequent overlap among the syndromes. Liver involvement in patients with connective tissue diseases has been well documented but is generally considered rare. Although advanced liver disease with cirrhosis and liver failure is rare in patients with connective tissue diseases, clinical and biochemical evidence of associated liver abnormalities is common. Previous treatment with potentially hepatotoxic drugs or coincident viral hepatitis has usually been implicated as the main causes of liver disease in patients with connective tissue diseases. However, even after careful exclusion of these etiologies, the question remains whether to classify the patient as having a primary liver disease with associated autoimmune, clinical, and laboratory features or as having liver disease as a manifestation of generalized connective tissue disease. The main example of this pathogenetic dilemma is autoimmune hepatitis and SLE-associated hepatitis, which have been regarded as two different entities, although they have features in common of autoimmune syndromes. Several clinical and histopathologic features have been used to discriminate autoimmune hepatitis from SLE, a relevant diagnostic exercise because complications and therapy are quite different. Although hepatic steatosis and abnormal results on biochemical liver function tests are the most common hepatic abnormalities associated with connective tissue diseases, other less frequent abnormalities have been noted, such as nodular regenerative hyperplasia, portal vein obliteration and portal hypertension, features of primary biliary cirrhosis, and rarely portal fibrosis with abnormal lobular architecture. Vascular disorders of the liver also have been described, such as Budd-Chiari syndrome. Histologic assessment may reveal a variety of subclinical liver diseases. The aim of this contribution is to review the current published data regarding liver involvement in connective tissue diseases. PMID:12352299

  3. Infliximab as a treatment option for patients with rheumatoid arthritis and primary biliary cirrhosis.

    PubMed

    Dimopoulou, Despoina; Dimitroulas, Theodoros; Akriviadis, Evangelos; Garyfallos, Alexandros

    2015-11-01

    Rheumatoid arthritis (RA) is a chronic inflammatory systemic disease which commonly requires treatment with biologic agents targeting various inflammatory pathways. Tumor necrosis factor alpha is a proinflammatory cytokine which plays a pivotal role not only in the pathogenesis of RA but also in other autoimmune diseases such as primary biliary cirrhosis. The co-existence of more than one autoimmune disorder in the same individual is very challenging in the daily practice as therapy strategies applicable to one disease setting may cause clinical and/or biochemical relapse of the other clinical entity. As a result, treatment options able to control different diseases are highly desirable among rheumatologists and other specialties. In that respect, we present a case of a 61-year-old female patient with RA and concomitant primary biliary cirrhosis with poor clinical response to conventional disease-modifying drugs for RA. The introduction of tumor necrosis factor alpha antagonist infliximab led to significant clinical improvement of RA and to stabilization of liver function. In this case review study, we discuss aspects of pathophysiology of primary biliary cirrhosis associated with tumor necrosis alpha and we review the available data of similar published cases. PMID:26411882

  4. Radionuclide demonstration of intrapulmonary shunting in cirrhosis

    SciTech Connect

    Bank, E.R.; Thrall, J.H.; Dantzker, D.R.

    1983-05-01

    The association of hepatic cirrhosis and severe arterial hypoxemia has been well described. Although alterations in ventilatory function may partially account for the hypoxemia, the principal mechanism is thought to be a microangiopathic change in the pulmonary vasculature resulting in intrapulmonary arteriovenous shunting with resultant systemic desaturation. Whole-body radionuclide scans with technetium-99m macroaggregated albumin labeling have been diagnostic of right-to-left shunting by their demonstration of tracer accumulation within the extrapulmonary circulation. A case of severe pulmonary arteriovenous shunting in an alcoholic patient in whom hepatic disease had not been of apparent clinical significance before radionuclide scanning is reported. He did not have cuntaeous angiomata as have all other patients with alcoholic cirrhosis and hypoxemia.

  5. Radionuclide demonstration of intrapulmonary shunting in cirrhosis

    SciTech Connect

    Bank, E.R.; Thrall, J.H.; Dantzker, D.R.

    1983-05-01

    The association of hepatic cirrhosis and severe arterial hypoxemia has been well described. Although alterations in ventilatory function may partially account for the hypoxemia, the principal mechanism is thought to be a microangiopathic change in the pulmonary arteriovenous shunting with resultant systemic desaturation. Whole-body radionuclide scans with technetium-99m macroaggrregated albumin (/sup 99m/Tc MAA) labeling have been diagnostic of right-to-left shunting by their demonstration of tracer accumulation within the extrapulmonary circulation. A case of severe pulmonary arteriovenous shunting in an alcoholic patient in whom hepatic disease had not been of apparent clinical significance before radionuclide scanning is reported. He did not have cutaneous angiomata as have all other patients with alcoholic cirrhosis and hypoxemia.

  6. Targeted recombinant fusion proteins of IFN? and mimetic IFN? with PDGF?R bicyclic peptide inhibits liver fibrogenesis in vivo.

    PubMed

    Bansal, Ruchi; Prakash, Jai; De Ruiter, Marieke; Poelstra, Klaas

    2014-01-01

    Hepatic stellate cells (HSCs), foll