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Current Hepatology Reports

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01-12-2016 | Portal Hypertension (K Brown, Section Editor)

Possible Treatment Strategies for Portal Hypertension in Liver Cirrhosis

Authors: Robert Schierwagen, Frank Erhard Uschner, Sabine Klein, Jonel Trebicka

Published in: Current Hepatology Reports | Issue 4/2016

Abstract

Purpose of the Review

Chronic liver injury leading to fibrosis and complicated by portal hypertension is an emerging burden for health systems worldwide, but current treatments are few and poorly effective. Therefore, this review aims to present diverse potential treatment approaches that are currently under investigation or on their way to clinical use.

Recent Findings

These options involve statins, the renin-angiotensin system and their downstream effectors, the anticoagulation system, farnesoid-x receptor agonism, and various other targets.

Summary

Since activated hepatic stellate cells play a pivotal role in both fibrogenesis and portal hypertension, most of these potential treatment approaches target directly or indirectly this profibrotic and procontractile cells in liver fibrosis with portal hypertension. Special focus should be paid to cell-specific treatments to minimize side effects and systemic complications in treatment of liver fibrosis and portal hypertension.

Friedman SL. Mechanisms of hepatic fibrogenesis. Gastroenterology. 2008;134:1655–69.CrossRefPubMedPubMedCentral

••Mederacke I, Hsu CC, Troeger JS, Huebener P, Mu X, Dapito DH, et al. Fate tracing reveals hepatic stellate cells as dominant contributors to liver fibrosis independent of its aetiology. Nat Commun. 2013;4:2823. This work demonstrates the prominent and pivotal role of activated hepatic stellate cells in liver fibrogenesis.

Baba TT, Ohara-Nemoto Y, Miyazaki T, Nemoto TK. Involvement of geranylgeranylation of Rho and Rac GTPases in adipogenic and RANKL expression, which was inhibited by simvastatin. Cell Biochem Funct. 2013;31:652–9.CrossRefPubMed

Veillard NR, Braunersreuther V, Arnaud C, Burger F, Pelli G, Steffens S, et al. Simvastatin modulates chemokine and chemokine receptor expression by geranylgeranyl isoprenoid pathway in human endothelial cells and macrophages. Atherosclerosis. 2006;188:51–8.CrossRefPubMed

Trebicka J, Hennenberg M, Laleman W, Shelest N, Biecker E, Schepke M, et al. Atorvastatin lowers portal pressure in cirrhotic rats by inhibition of RhoA/Rho-kinase and activation of endothelial nitric oxide synthase. Hepatology. 2007;46:242–53.CrossRefPubMed

Trebicka J, Hennenberg M, Odenthal M, Shir K, Klein S, Granzow M, et al. Atorvastatin attenuates hepatic fibrosis in rats after bile duct ligation via decreased turnover of hepatic stellate cells. J Hepatol. 2010;53:702–12.CrossRefPubMed

Klein S, Klösel J, Schierwagen R, Körner C, Granzow M, Huss S, et al. Atorvastatin inhibits proliferation and apoptosis, but induces senescence in hepatic myofibroblasts and thereby attenuates hepatic fibrosis in rats. Lab Investig. 2012;92:1440–50.CrossRefPubMed

Schierwagen R, Leeming DJ, Klein S, Granzow M, Nielsen MJ, Sauerbruch T, et al. Serum markers of the extracellular matrix remodeling reflect antifibrotic therapy in bile-duct ligated rats. Front Physiol. 2013;4:195.CrossRefPubMedPubMedCentral

•Marrone G, Russo L, Rosado E, Hide D, García-Cardeña G, García-Pagán JC, et al. The transcription factor KLF2 mediates hepatic endothelial protection and paracrine endothelial-stellate cell deactivation induced by statins. J Hepatol. 2013;58:98–103. An important work revealing that statins downregulate hepatic stellate cell activation by the intercellular communication between hepatic stellate cells and liver sinusoidal endothelial cells.

10.

Abraldes JG, Rodríguez-Vilarrupla A, Graupera M, Zafra C, García-Calderó H, García-Pagán JC, et al. Simvastatin treatment improves liver sinusoidal endothelial dysfunction in CCl4 cirrhotic rats. J Hepatol. 2007;46:1040–6.CrossRefPubMed

11.

••Marrone G, Maeso-Díaz R, García-Cardena G, Abraldes JG, García-Pagán JC, Bosch J, et al. KLF2 exerts antifibrotic and vasoprotective effects in cirrhotic rat livers: behind the molecular mechanisms of statins. Gut. 2015;64:1434–43. An important work that elucidates the molecular mechanisms how KLF2 effects liver fibrosis and portal hypertension.

12.

Trebicka J, Schierwagen R. Statins, Rho GTPases and KLF2: new mechanistic insight into liver fibrosis and portal hypertension. Gut. 2015;64:1349–50.CrossRefPubMed

13.

•Uschner FE, Ranabhat G, Choi SS, Granzow M, Klein S, Schierwagen R, et al. Statins activate the canonical hedgehog-signaling and aggravate non-cirrhotic portal hypertension, but inhibit the non-canonical hedgehog signaling and cirrhotic portal hypertension. Sci Rep. 2015;5:14573. One of several important studies which clarifies how statins improve liver fibrosis and portal hypertension.

14.

•Schierwagen R, Maybüchen L, Hittatiya K, Klein S, Uschner FE, Braga TT, et al. Statins improve NASH via inhibition of RhoA and Ras. Am J Physiol Gastrointest Liver Physiol. 2016; One of several important studies which clarifies how statins improve liver fibrosis in NASH.

15.

Park H-S, Jang JE, Ko MS, Woo SH, Kim BJ, Kim HS, et al. Statins increase mitochondrial and peroxisomal fatty acid oxidation in the liver and prevent non-alcoholic steatohepatitis in mice. Diabetes & Metabolism Journal [Internet]. 2016 (2016);40. Available from: /Synapse/10.4093/dmj.2016.40.e11

16.

Chong L-W, Hsu Y-C, Lee T-F, Lin Y, Chiu Y-T, Yang K-C, et al. Fluvastatin attenuates hepatic steatosis-induced fibrogenesis in rats through inhibiting paracrine effect of hepatocyte on hepatic stellate cells. BMC Gastroenterol. 2015;15:22.CrossRefPubMedPubMedCentral

17.

Nascimbeni M, Perié L, Chorro L, Diocou S, Kreitmann L, Louis S, et al. Plasmacytoid dendritic cells accumulate in spleens from chronically HIV-infected patients but barely participate in interferon-alpha expression. Blood. 2009;113:6112–9.CrossRefPubMed

18.

Dongiovanni P, Petta S, Mannisto V, Mancina RM, Pipitone R, Karja V, et al. Statin use and non-alcoholic steatohepatitis in at risk individuals. J Hepatol. 2015;63:705–12.CrossRefPubMed

19.

Blais P, Lin M, Kramer JR, El-Serag HB, Kanwal F. Statins are underutilized in patients with nonalcoholic fatty liver disease and dyslipidemia. Dig Dis Sci. 2016;61:1714–20.CrossRefPubMed

20.

Schierwagen R, Maybüchen L, Zimmer S, Hittatiya K, Bäck C, Klein S, et al. Seven weeks of Western diet in apolipoprotein-E-deficient mice induce metabolic syndrome and non-alcoholic steatohepatitis with liver fibrosis. Sci Rep. 2015;5:12931.CrossRefPubMedPubMedCentral

21.

Oliver NT, Hartman CM, Kramer JR, Chiao EY. Statin drugs decrease progression to cirrhosis in HIV/HCV co-infected individuals. AIDS. 2016

22.

Simon TG, King LY, Zheng H, Chung RT. Statin use is associated with a reduced risk of fibrosis progression in chronic hepatitis C. J Hepatol. 2015;62:18–23.CrossRefPubMed

23.

Simon TG, Bonilla H, Yan P, Chung RT, Butt AA. Atorvastatin and fluvastatin are associated with dose-dependent reductions in cirrhosis and hepatocellular carcinoma, among patients with hepatitis C virus: Results from ERCHIVES. Hepatology. 2016;64:47–57.CrossRefPubMed

24.

Butt AA, Yan P, Bonilla H, Abou-Samra A-B, Shaikh OS, Simon TG, et al. Effect of addition of statins to antiviral therapy in hepatitis C virus-infected persons: results from ERCHIVES. Hepatology. 2015;62:365–74.CrossRefPubMed

25.

Abraldes JG, Albillos A, Bañares R, Turnes J, González R, García–Pagán JC, et al. Simvastatin lowers portal pressure in patients with cirrhosis and portal hypertension: a randomized controlled trial. Gastroenterology. 2009;136:1651–8.CrossRefPubMed

26.

••Abraldes JG, Villanueva C, Aracil C, Turnes J, Hernandez-Guerra M, Genesca J, et al. Addition of simvastatin to standard therapy for the prevention of variceal rebleeding does not reduce rebleeding but increases survival in patients with cirrhosis. Gastroenterology. 2016;150:1160–70.e3. An important work boostering the way of statins into clinics as a treatment option in liver fibrosis and portal hypertension.

27.

Abraldes JG, Burak KW. STAT order: Should patients with chronic liver disease be prescribed statins to prevent fibrosis progression and hepatocellular carcinoma? Hepatology. 2016;64:13–5.CrossRefPubMed

28.

••Granzow M, Schierwagen R, Klein S, Kowallick B, Huss S, Linhart M, et al. Angiotensin-II type 1 receptor-mediated Janus kinase 2 activation induces liver fibrosis. Hepatology. 2014;60:334–48. Important study outlining JAK2 as the effector of Arhgef1 and therefore as the link between AT1 receptor and RhoA/Rho-kinase signaling.CrossRefPubMed

29.

Bataller R, Sancho-Bru P, Ginès P, Lora JM, Al-Garawi A, Solé M, et al. Activated human hepatic stellate cells express the renin-angiotensin system and synthesize angiotensin II. Gastroenterology. 2003;125:117–25.CrossRefPubMed

30.

Paizis G, Cooper ME, Schembri JM, Tikellis C, Burrell LM, Angus PW. Up-regulation of components of the renin-angiotensin system in the bile duct-ligated rat liver. Gastroenterology. 2002;123:1667–76.CrossRefPubMed

31.

Sumners C, Horiuchi M, Widdop RE, McCarthy C, Unger T, Steckelings UM. Protective arms of the renin-angiotensin-system in neurological disease. Clin Exp Pharmacol Physiol. 2013;40:580–8.CrossRefPubMed

32.

Heller J, Shiozawa T, Trebicka J, Hennenberg M, Schepke M, Neef M, et al. Acute haemodynamic effects of losartan in anaesthetized cirrhotic rats. Eur J Clin Investig. 2003;33:1006–12.CrossRef

33.

Heller J, Trebicka J, Shiozawa T, Schepke M, Neef M, Hennenberg M, et al. Vascular, hemodynamic and renal effects of low-dose losartan in rats with secondary biliary cirrhosis. Liver Int. 2005;25:657–66.CrossRefPubMed

34.

Schepke M, Werner E, Biecker E, Schiedermaier P, Heller J, Neef M, et al. Hemodynamic effects of the angiotensin II receptor antagonist irbesartan in patients with cirrhosis and portal hypertension. Gastroenterology. 2001;121:389–95.CrossRefPubMed

35.

Guilluy C, Brégeon J, Toumaniantz G, Rolli-Derkinderen M, Retailleau K, Loufrani L, et al. The Rho exchange factor Arhgef1 mediates the effects of angiotensin II on vascular tone and blood pressure. Nat Med. 2010;16:183–90.CrossRefPubMed

36.

••Klein S, Rick J, Lehmann J, Schierwagen R, Schierwagen IG, Verbeke L, et al. Janus-kinase-2 relates directly to portal hypertension and to complications in rodent and human cirrhosis. Gut. 2015;gutjnl-2015-309600. An important work demonstrating the role of JAK2 signaling in portal hypertension with a strong translational focus.

37.

Wang D, Yin J, Dong R, Zhao J, Wang Q, Wang N, et al. Inhibition of Janus kinase-2 signalling pathway ameliorates portal hypertensive syndrome in partial portal hypertensive and liver cirrhosis rats. Dig Liver Dis. 2015;47:315–23.CrossRefPubMed

38.

Shaker ME, Hazem SH, Ashamallah SA. Inhibition of the JAK/STAT pathway by ruxolitinib ameliorates thioacetamide-induced hepatotoxicity. Food Chem. Toxicol. 2016

39.

••Grace JA, Klein S, Herath CB, Granzow M, Schierwagen R, Masing N, et al. Activation of the mas receptor by angiotensin-(1–7) in the renin–angiotensin system mediates mesenteric vasodilatation in cirrhosis. Gastroenterology. 2013;145:874–4.e5. An important work emphasizing the role of Mas receptor as the counterpart of the AT1 receptor in liver cirrhosis.

40.

Grace JA, Herath CB, Mak KY, Burrell LM, Angus PW. Update on new aspects of the renin–angiotensin system in liver disease: clinical implications and new therapeutic options. Clin Sci. 2012;123:225–39.CrossRefPubMed

41.

•Klein S, Herath CB, Schierwagen R, Grace J, Haltenhof T, Uschner FE, et al. Hemodynamic effects of the non-peptidic angiotensin-(1–7) agonist AVE0991 in liver cirrhosis. PLoS ONE. 2015;10:e0138732. One of several important works about the beneficial effects of Mas receptor stimulation in liver cirrhosis decreasing portal pressure without systemic effects.CrossRefPubMedPubMedCentral

42.

Hennenberg M, Biecker E, Trebicka J, Jochem K, Zhou Q, Schmidt M, et al. Defective RhoA/Rho-kinase signaling contributes to vascular hypocontractility and vasodilation in cirrhotic rats. Gastroenterology. 2006;130:838–54.CrossRefPubMed

43.

Zhou H, Fang C, Zhang L, Deng Y, Wang M, Meng F. Fasudil hydrochloride hydrate, a Rho-kinase inhibitor, ameliorates hepatic fibrosis in rats with type 2 diabetes. Chin Med J. 2014;127:225–31.PubMed

44.

Futakuchi A, Inoue T, Fujimoto T, Inoue-Mochita M, Kawai M, Tanihara H. The effects of ripasudil (K-115), a Rho kinase inhibitor, on activation of human conjunctival fibroblasts. Exp Eye Res. 2016;149:107–15.CrossRefPubMed

45.

Zhou Q, Hennenberg M, Trebicka J, Jochem K, Leifeld L, Biecker E, et al. Intrahepatic upregulation of RhoA and Rho-kinase signalling contributes to increased hepatic vascular resistance in rats with secondary biliary cirrhosis. Gut. 2006;55:1296–305.CrossRefPubMedPubMedCentral

46.

Klein S, Van Beuge MM, Granzow M, Beljaars L, Schierwagen R, Kilic S, et al. HSC-specific inhibition of Rho-kinase reduces portal pressure in cirrhotic rats without major systemic effects. J Hepatol. 2012;57:1220–7.CrossRefPubMed

47.

van Beuge MM, Prakash J, Lacombe M, Gosens R, Post E, Reker-Smit C, et al. Reduction of fibrogenesis by selective delivery of a Rho kinase inhibitor to hepatic stellate cells in mice. J Pharmacol Exp Ther. 2011;337:628–35.CrossRefPubMed

48.

Caldwell SH, Hoffman M, Lisman T, Macik BG, Northup PG, Reddy KR, et al. Coagulation disorders and hemostasis in liver disease: pathophysiology and critical assessment of current management. Hepatology. 2006;44:1039–46.CrossRefPubMed

49.

Pradella P, Bonetto S, Turchetto S, Uxa L, Comar C, Zorat F, et al. Platelet production and destruction in liver cirrhosis. J Hepatol. 2011;54:894–900.CrossRefPubMed

50.

•Klein S, Herath CB, Schierwagen R, Grace J, Haltenhof T, Uschner FE, et al. Hemodynamic effects of the Non-peptidic angiotensin-(1–7) agonist AVE0991 in liver cirrhosis. PLoS ONE. 2015;10:e0138732. One of several studies indicating the beneficial effects of aspirin application for treatment of liver cirrhosis.

51.

••Yoshida S, Ikenaga N, Liu SB, Peng Z-W, Chung J, Sverdlov DY, et al. Extrahepatic platelet-derived growth factor-β, delivered by platelets, promotes activation of hepatic stellate cells and biliary fibrosis in mice. Gastroenterology. 2014;147:1378–92. An important work elucidating the role of platelets in hepatic stellate cell activation upon liver injury.

52.

Jiang ZG, Feldbrügge L, Tapper EB, Popov Y, Ghaziani T, Afdhal N, et al. Aspirin use is associated with lower indices of liver fibrosis among adults in the United States. Aliment Pharmacol Ther. 2016;43:734–43.CrossRefPubMed

53.

Villa E, Cammà C, Marietta M, Luongo M, Critelli R, Colopi S, et al. Enoxaparin prevents portal vein thrombosis and liver decompensation in patients with advanced cirrhosis. Gastroenterology. 2012;143:1253–60-4.CrossRefPubMed

54.

Yagüe S, Alvarez Arroyo V, Castilla A, González Pacheco FR, Llamas P, Caramelo C. Modulation of the effect of vascular endothelial growth factor on endothelial cells by heparin: critical role of nitric oxide-mediated mechanisms. J Nephrol. 2005;18:234–42.PubMed

55.

Tasatargil A, Ogutman C, Golbasi I, Karasu E, Dalaklioglu S. Comparison of the vasodilatory effect of nadroparin, enoxaparin, dalteparin, and unfractioned heparin in human internal mammary artery. J Cardiovasc Pharmacol. 2005;45:550–4.CrossRefPubMed

56.

••Cerini F, Vilaseca M, Lafoz E, García-Irigoyen O, García-Calderó H, Tripathi DM, et al. Enoxaparin reduces hepatic vascular resistance and portal pressure in cirrhotic rats. J Hepatol. 2016;64:834–42. Important work which introduces new treatment options to reduce portal pressure by anticoagulant therapy.CrossRefPubMed

57.

Intagliata NM, Henry ZH, Maitland H, Shah NL, Argo CK, Northup PG, et al. Direct oral anticoagulants in cirrhosis patients pose similar risks of bleeding when compared to traditional anticoagulation. Dig Dis Sci. 2016;61:1721–7.CrossRefPubMed

58.

••Verbeke L, Farre R, Trebicka J, Komuta M, Roskams T, Klein S, et al. Obeticholic acid, a farnesoid-X receptor agonist, improves portal hypertension by two distinct pathways in cirrhotic rats. Hepatology. 2013. Important work which introduces new treatment options to reduce portal pressure by farnesoid-X receptor agonism

59.

•Mookerjee RP, Mehta G, Balasubramaniyan V, Mohamed FEZ, Davies N, Sharma V, et al. Hepatic dimethylarginine-dimethylaminohydrolase1 is reduced in cirrhosis and is a target for therapy in portal hypertension. J Hepatol. 2015;62:325–31. An important work elucidating how obeticholic acid restores endothelial function in liver cirrhosis.

60.

•Verbeke L, Mannaerts I, Schierwagen R, Govaere O, Klein S, Elst IV, et al. FXR agonist obeticholic acid reduces hepatic inflammation and fibrosis in a rat model of toxic cirrhosis. Scientific Reports. 2016. Important work demonstrating fibrosis reduction additional to lowering portal pressure by obeticholic acid treatment.

61.

••Verbeke L, Farre R, Verbinnen B, Covens K, Vanuytsel T, Verhaegen J, et al. The FXR agonist obeticholic acid prevents gut barrier dysfunction and bacterial translocation in cholestatic rats. Am J Pathol. 2015;185:409–19. One of several important works showing that obeticholic acid treatment ameliorates bacterial translocation and thereby beneficially influences liver cirrhosis.CrossRefPubMed

62.

••Úbeda M, Lario M, Muñoz L, Borrero M-J, Rodríguez-Serrano M, Sánchez-Díaz A-M, et al. Obeticholic acid reduces bacterial translocation and inhibits intestinal inflammation in cirrhotic rats. J Hepatol. 2016;64:1049–57. One of several important works showing that obeticholic acid treatment ameliorates bacterial translocation and thereby beneficially influences liver cirrhosis.

63.

Laleman W, Trebicka J, Verbeke L. Evolving insights in the pathophysiology of complications of cirrhosis: The Farnesoid-X receptor (FXR) to the rescue? Hepatology. 2016

64.

Garcia-Tsao G, Sanyal AJ, Grace ND, Carey W. Practice guidelines committee of the American association for the study of liver diseases, practice parameters committee of the American college of gastroenterology. Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis. Hepatology. 2007;46:922–38.CrossRefPubMed

65.

Trebicka J, Hennenberg M, Schulze Pröbsting A, Laleman W, Klein S, Granzow M, et al. Role of beta3-adrenoceptors for intrahepatic resistance and portal hypertension in liver cirrhosis. Hepatology. 2009;50:1924–35.CrossRefPubMed

66.

Vasina V, Giannone F, Domenicali M, Latorre R, Berzigotti A, Caraceni P, et al. Portal hypertension and liver cirrhosis in rats: effect of the β3-adrenoceptor agonist SR58611A. Br J Pharmacol. 2012;167:1137–47.CrossRefPubMedPubMedCentral

67.

Loureiro-Silva MR, Iwakiri Y, Abraldes JG, Haq O, Groszmann RJ. Increased phosphodiesterase-5 expression is involved in the decreased vasodilator response to nitric oxide in cirrhotic rat livers. J Hepatol. 2006;44:886–93.CrossRefPubMed

68.

Choi S-M, Shin J-H, Kim J-M, Lee C-H, Kang K-K, Ahn B-O, et al. Effect of udenafil on portal venous pressure and hepatic fibrosis in rats. Arzneimittelforschung. 2011;59:641–6.CrossRef

69.

Kreisel W, Deibert P, Kupcinskas L, Sumskiene J, Appenrodt B, Roth S, et al. The phosphodiesterase-5-inhibitor udenafil lowers portal pressure in compensated preascitic liver cirrhosis. A dose-finding phase-II-study. Dig Liver Dis. 2015;47:144–50.CrossRefPubMed

70.

Jiang JX, Chen X, Serizawa N, Szyndralewiez C, Page P, Schröder K, et al. Liver fibrosis and hepatocyte apoptosis are attenuated by GKT137831, a novel NOX4/NOX1 inhibitor in vivo. Free Radic Biol Med. 2012;53:289–96.CrossRefPubMedPubMedCentral

71.

García-Calderó H, Rodríguez-Vilarrupla A, Gracia-Sancho J, Diví M, Laviña B, Bosch J, et al. Tempol administration, a superoxide dismutase mimetic, reduces hepatic vascular resistance and portal pressure in cirrhotic rats. J Hepatol. 2011;54:660–5.CrossRefPubMed

72.

Gonzalez-Paredes FJ, Hernández Mesa G, Morales Arraez D, Marcelino Reyes R, Abrante B, Diaz-Flores F, et al. Contribution of cyclooxygenase end products and oxidative stress to intrahepatic endothelial dysfunction in early non-alcoholic fatty liver disease. PLoS ONE. 2016;11:e0156650.CrossRefPubMedPubMedCentral

73.

Wu J, Saleh MA, Kirabo A, Itani HA, Montaniel KRC, Xiao L, et al. Immune activation caused by vascular oxidation promotes fibrosis and hypertension. J Clin Invest. 2016;126:50–67.CrossRefPubMed

74.

De Gottardi A, Berzigotti A, Seijo S, D’Amico M, Thormann W, Abraldes JG, et al. Postprandial effects of dark chocolate on portal hypertension in patients with cirrhosis: results of a phase 2, double-blind, randomized controlled trial. Am J Clin Nutr. 2012;96:584–90.CrossRefPubMed

75.

••Loffredo L, Del Ben M, Perri L, Carnevale R, Nocella C, Catasca E, et al. Effects of dark chocolate on NOX-2-generated oxidative stress in patients with non-alcoholic steatohepatitis. Aliment Pharmacol Ther. 2016;44:279–86. Important work demonstrating beneficial effects of controlled dark chocolate consumption in non-alcoholic steatohepatitis.

76.

••Tripathi DM, Erice E, Lafoz E, García-Calderó H, Sarin SK, Bosch J, et al. Metformin reduces hepatic resistance and portal pressure in cirrhotic rats. Am J Physiol - Gastrointest Liver Physiol. 2015;309:G301–9. An important work introducing metformin as a therapeutic option for treatment of portal pressure in liver cirrhosis.

77.

Ma S-J, Zheng Y-X, Zhou P-C, Xiao Y-N, Tan H-Z. Metformin use improves survival of diabetic liver cancer patients: systematic review and meta-analysis. Oncotarget. 2016

78.

Doyle M-A, Singer J, Lee T, Muir M, Cooper C. Improving treatment and liver fibrosis outcomes with metformin in HCV-HIV co-infected and HCV mono-infected patients with insulin resistance: study protocol for a randomized controlled trial. Trials. 2016;17:331.CrossRefPubMedPubMedCentral

79.

•Li T, Eheim AL, Klein S, Uschner FE, Smith AC, Brandon-Warner E, et al. Novel role of nuclear receptor rev-erbα in hepatic stellate cell activation: potential therapeutic target for liver injury. Hepatology. 2014;59:2383–96. Important study which offers a novel treatment target to reduce hepatic stellate cell activation in liver fibrosis.CrossRefPubMed

Title: Possible Treatment Strategies for Portal Hypertension in Liver Cirrhosis
Authors: Robert Schierwagen
Frank Erhard Uschner
Sabine Klein
Jonel Trebicka
Publication date: 01-12-2016
Publisher: Springer US
Published in: Current Hepatology Reports / Issue 4/2016
Electronic ISSN: 2195-9595
DOI: https://doi.org/10.1007/s11901-016-0321-y

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