Friedman SL. Leberfibrose – Vom Labor zum Krankenbett. J Hepatol. 2003;38(Suppl 1):S38-53.Schuppan D, Afdhal NH. Leberzirrhose. Lancet. 2008;371(9615): 838-51.Hernandez-Gea V, Friedman SL. Pathogenese der Leberfibrose. Annu Rev Pathol. 2011;6:425-56.Centers for Disease Control and Prevention. Summary Health Statistics Tables for U.S. Adults: National Health Interview Survey, 2017, Tabelle A-4b, A-4c. Verfügbar unter: https://ftp.cdc.gov/pub/Health_Statistics/NCHS/NHIS/SHS/2017_SHS_Table_A-4.pdf. Letzter Zugriff: 1. Mai 2019.Centers for Disease Control and Prevention. Deaths: Final data for 2016, tables 6, 7. Verfügbar unter: https://www.cdc.gov/nchs/fastats/liver-disease.htm. Last accessed: 1. Mai 2019.Patel K et al. Diagnosis of liver fibrosis: Gegenwart und Zukunft. Semin Liver Dis. 2015;35(2):166-83.Poynard T et al. A comparison of fibrosis progression in chronic liver diseases. J Hepatol. 2003;38(3): 257-65.Bonis PA et al. Is liver fibrosis reversible? N Engl J Med. 2001;344(6):452-4.Cholankeril G, Ahmed A. Alcoholic liver disease replaces hepatitis C virus infection as the leading indication for liver transplantation in the United States. Clin Gastroenterol Hepatol. 2018;16(8):1356-8.Wiegand J, Berg T. The etiology, diagnosis and prevention of liver cirrhosis: Teil 1 einer Serie zur Leberzirrhose. Dtsch Arztebl Int. 2013;110(6):85-91.Pirovino M et al. Cutaneous spider nevi in liver cirrhosis: Kapillarmikroskopische und hormonelle Untersuchungen. Klin Wochenschr. 1988;66(7):298-302.Cattau EL et al. The accuracy of the physical examination in the diagnosis of suspected ascites. JAMA. 1982;247(8):1164-6.Van Thiel DH et al. Liver disease and the hypothalamic pituitary gonadal axis. Semin Liver Dis. 1985;5(1):35-45.Williamson RM et al. Prevalence of and risk factors for hepatic steatosis and nonalcoholic fatty liver disease in people with type 2 diabetes: The Edinburgh type 2 diabetes study. Diabetes Care. 2011;34(5):1139-44.Peck-Radosavljevic M et al. Thrombopoietin induziert eine schnelle Auflösung der Thrombozytopenie nach orthotoper Lebertransplantation durch erhöhte Thrombozytenproduktion. Blood. 2000;95(3): 795-801.Schuppan D et al. Matrix as a modulator of hepatic fibrogenesis. Semin Liver Dis. 2001;21(3):351-72.Pinzani M. Pathophysiologie der Leberfibrose. Dig Dis. 2015;33(4):492-7.Gandhi CR. Hepatic stellate cell activation and pro-fibrogenic signals. J Hepatol. 2017;67(5):1104-5.Li D, Friedman SL. Liver fibrogenesis and the role of hepatic stellate cells: New insights and prospects for therapy. J Gastroenterol Hepatol. 1999;14(7):618-33.Tsuchida T, Friedman SL. Mechanismen der Aktivierung hepatischer Stellatzellen. Nat Rev Gastroenterol Hepatol. 2017;14(7):397-411.McGuire RF et al. Role of extracellular matrix in regulating fenestrations of sinusoidal endothelial cells isolated from normal rat liver. Hepatologie. 1992;15(6):989-97.Huang Y et al. Modulation of hepatic stellate cells and reversibility of hepatic fibrosis. Exp Cell Res. 2017;352(2):420-6.Rockey DC et al.; American Association for the Study of Liver Diseases. Liver Biopsy. Hepatologie. 2009;49(3):1017-44.Garcia-Tsao G et al. Now there are many (stages) where before there was one: Auf der Suche nach einer pathophysiologischen Klassifikation der Zirrhose. Hepatology. 2010;51(4):1445-9.Bonder A, Afdhal N. Utilization of FibroScan in clinical practice. Gurr Gastroenterol Rep. 2014;16(2):372.Tapper EB et al. FibroScan (vibration-controlled transient elastography): Wo steht es in der Praxis in den Vereinigten Staaten. Clin Gastroenterol Hepatol. 2015;13(1):27-36.Lucero C, Brown RS. Nichtinvasive Messungen der Leberfibrose und des Schweregrads der Lebererkrankung. Gastroenterol Hepatol (N Y). 2016;12(1):33-40.Martin J et al. Accuracy of ultrasound and noninvasive markers of fibrosis to identify patients with cirrhosis. Dig Dis Sci. 2015;60(6):1841-7.Amarapurkar D, Amarapurkar A. Indications of liver biopsy in the era of noninvasive assessment of liver fibrosis. J Clin Exp Hepatol. 2015;5(4):314-9.Chi H et al. Multiple biopsy passes and the risk of complications of percutaneous liver biopsy. Eur J Gastroenterol Hepatol. 2017;29(1): 36-41.Mikolasevic I et al. Transient elastography (FibroScan(®)) with controlled attenuation parameter in the assessment of liver steatosis and fibrosis in patients with nonalcoholic fatty liver disease – Where do we stand? World J Gastroenterol. 2016;22(32):7236-51.Wong GL. Update der Leberfibrose und Steatose mit transienter Elastographie (Fibroscan). Gastroenterol Rep (Oxf). 2013;1(1):19-26.Xiao H et al. Comparison of diagnostic accuracy of magnetic resonance elastography and Fibroscan for detecting liver fibrosis in chronic hepatitis B patients: A systematic review and meta-analysis. PLoS One. 2017;12(11):e0186660.Sharma S et al. Non-invasive diagnosis of advanced fibrosis and cirrhosis. World J Gastroenterol. 2014;20(45):16820-30.Jung KS, Kim SU. Klinische Anwendungen der transienten Elastographie. Clin Mol Hepatol. 2012;18(2):163-73.Hashemi SA et al. Assessment of transient elastography (FibroScan) for diagnosis of fibrosis in non-alcoholic fatty liver disease: A systematic review and meta-analysis. Caspian J Intern Med. 2016;7(4):242-52.Nahon P et al. Assessment of liver fibrosis using transient elastography in patients with alcoholic liver disease. J Hepatol. 2008;49(6):1062-8.Takahashi H et al. Evaluation of acoustic radiation force impulse elastography for fibrosis staging of chronic liver disease: A pilot study. Liver Int. 2010;30(4):538-45.Jiang T et al. Diagnostic accuracy of 2D-Shear wave elastography for liver fibrosis severity: A meta-analysis. PLoS One. 2016;11(6):e0157219.Li C et al. Diagnostic accuracy of real-time shear wave elastography for staging of liver fibrosis: A meta-analysis. Med Sci Monit. 2016;22: 1349-59.Piscaglia F et al. Ultrasound shear wave elastography for liver disease. Eine kritische Würdigung der vielen Akteure auf der Bühne. Ultraschall Med. 2016;37(1):1-5.Wagner M et al. Magnetic resonance elastography of the liver: Qualitativer und quantitativer Vergleich von Gradientenecho- und Spin-Echo-Echoplanar-Bildgebungssequenzen. Invest Radiol. 2016;51(9):575-81.Afify SM et al. Five fibrosis biomarkers together with serum ferritin level to diagnose liver fibrosis and cirrhosis. Clin Lab. 2018;64(10):1685-93.Wai CT et al. A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology. 2003;38(2):518-26.Teshale E et al. APRI and FIB-4 are good predictors of the stage of liver fibrosis in chronic hepatitis B: The chronic hepatitis cohort study (CHeCS). J Viral Hepat. 2014;21(12):917-20.Ahmed Z et al. Universal index for cirrhosis (UIC index): Die Entwicklung und Validierung eines neuartigen Index zur Vorhersage fortgeschrittener Lebererkrankungen. Hepat Med. 2018;10:133-8.Attallah AM et al. Fibro-Mark: A panel of laboratory parameters for predicting significant fibrosis in chronic hepatitis C patients. Br J Biomed Sci. 2018;75(1):19-23.Angulo P et al. The NAFLD fibrosis score: Ein nicht-invasives System zur Identifizierung der Leberfibrose bei Patienten mit NAFLD. Hepatology. 2007;45(4):846-54.Raszeja-Wyszomirska J et al. Validation of the BARD scoring system in Polish patients with nonalcoholic fatty liver disease (NAFLD). BMC Gastroenterol. 2010;10:67.Poynard T et al. Applicability and precautions of use of liver injury biomarker FibroTest. A reappraisal at 7 years of age. BMC Gastroenterol. 2011;11:39.Salkic NN et al. FibroTest/Fibrosure for significant liver fibrosis and cirrhosis in chronic hepatitis B: A meta-analysis. Am J Gastroenterol. 2014;109(6):796-809.Kalantari H et al. Validation of hepascore as a predictor of liver fibrosis in patients with chronic hepatitis C infection. Hepat Res Treat. 2011;2011:972759.Huang Y et al. The ability of Hepascore to predict liver fibrosis in chronic liver disease: A meta-analysis. Liver Int. 2017;37(1):121-31.Zaman A et al. Assessment of FIBROSpect II to detect hepatic fibrosis in chronic hepatitis C patients. Am J Med. 2007;120(3):280.e9-14.Tama M et al. Overestimate of fibrosis by FIBROSpect® II in African Americans complicates the management of their chronic hepatitis C. J Clin Transl Hepatol. 2016;4(1):12-9.Mehta P et al. Diagnostic accuracy of serum hyaluronic acid, FIBROSpect II, and YKL-40 for discriminating fibrosis stages in chronic hepatitis C. Am J Gastroenterol. 2008;103(4):928-36.Wong GL et al. Non-invasive algorithm of enhanced liver fibrosis and liver stiffness measurement with transient elastography for advanced liver fibrosis in chronic hepatitis B. Aliment Pharmacol Ther. 2014;39(2):197-208.Marcellin P et al. Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: A 5-year open-label follow-up study. Lancet. 2013;381(9865):468-75.Byrne R et al. Tenofovir alafenamide in the treatment of chronic hepatitis B virus infection: Rationale und klinische Studienevidenz. Therap Adv Gastroenterol. 2018;11:1756284818786108.Schiff ER et al. Long-term treatment with entecavir induces reversal of advanced fibrosis or cirrhosis in patients with chronic hepatitis B. Clin Gastroenterol Hepatol. 2011;9(3):274-6.Dienstag JL et al. Histological outcome during long-term lamivudine therapy. Gastroenterology. 2003;124(1):105-17.Grgurevic I et al. Hepatitis C ist jetzt heilbar, aber was passiert danach mit Zirrhose und portaler Hypertension? Clin Exp Hepatol. 2017;3(4):181-6.Chan J et al. Direct-acting antiviral therapy for chronic HCV infection results in liver stiffness regression over 12 months post-treatment. Dig Dis Sci. 2018;63(2):486-92.Singh S et al. Comparative effectiveness of pharmacological interventions for nonalcoholic steatohepatitis: A systematic review and network meta-analysis. Hepatology. 2015;62(5):1417-32.Connolly JJ et al. Future pharmacotherapy for non-alcoholic steatohepatitis (NASH): Review of Phase 2 and 3 trials. J Clin Transl Hepatol. 2018;6(3):264-75.Singal AK et al. ACG clinical guideline: Alkoholische Lebererkrankung. Am J Gastroenterol. 2018;113(2):175-94.Borssén Å et al. Histological improvement of liver fibrosis in well-treated patients with autoimmune hepatitis: A cohort study. Medicine (Baltimore). 2017;96(34):e7708.Corpechot C et al. The effect of ursodeoxycholic acid therapy on liver fibrosis progression in primary biliary cirrhosis. Hepatology. 2000;32(6):1196-9.EAftSotLEa, Liver EAftSot. EASL clinical practice guidelines on nutrition in chronic liver disease. J Hepatol. 2019;70(1):172-93.Silva M et al. Nutrition in chronic liver disease. GE Port J Gastroenterol. 2015;22(6):268-76.Hickman IJ et al. Modest weight loss and physical activity in overweight patients with chronic liver disease results in sustained improvements in alanine aminotransferase, fasting insulin, and quality of life. Gut. 2004;53(3):413-9.Alter MJ. Impfung von Patienten mit chronischer Lebererkrankung. Gastroenterol Hepatol (N Y). 2012;8(2):120-2.Garcia-Tsao G. Current management of the complications of cirrhosis and portal hypertension: Varizenblutung, Aszites und spontane bakterielle Peritonitis. Dig Dis. 2016;34(4):382-6.Mittal S et al. Hepatocellular carcinoma in the absence of cirrhosis in United States veterans is associated with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2016;14(1):124-31.e1.Chayanupatkul M et al. Hepatocellular carcinoma in the absence of cirrhosis in patients with chronic hepatitis B virus infection. J Hepatol. 2017;66(2):355-62.Axley P et al. Patients with stage 3 compared to stage 4 liver fibrosis have lower frequency of and longer time to liver disease complications. PLoS One. 2018;13(5):e0197117.Sauerbruch T et al. Managing portal hypertension in patients with liver cirrhosis. F1000Res. 2018;7.Trautwein C et al. Hepatic fibrosis: Concept to treatment. J Hepatol. 2015;62(1 Suppl):S15-24.Perry CM, Simpson D. Tenofovir disoproxil fumarate: Bei chronischer Hepatitis B. Drugs. 2009;69(16): 2245-56.Jang JW et al. Long-term effect of antiviral therapy on disease course after decompensation in patients with hepatitis B virus-related cirrhosis. Hepatology. 2015;61(6):1809-20.Tsuboi Y et al. Common clinicopathological features of the patients with chronic hepatitis B virus infection who developed hepatocellular carcinoma after seroconversion to anti-HBs–A consideration of the pathogenesis of HBV-induced hepatocellular carcinoma and a strategy to inhibit it. Hepatogastroenterologie. 2006;53(67):110-4.Poynard T et al. Impact of pegylated interferon alfa-2b and ribavirin on liver fibrosis in patients with chronic hepatitis C. Gastroenterology. 2002;122(5):1303-13.Jakobsen JC et al. Direct-acting antivirals for chronic hepatitis C. Cochrane Database Syst Rev. 2017;9:CD012143.Dolmazashvili E et al. Regression of liver fibrosis over a 24-week period after completing direct-acting antiviral therapy in patients with chronic hepatitis C receiving care within the national hepatitis C elimination program in Georgia: Ergebnisse der HEPA-Erfahrung der hepatologischen Klinik. Eur J Gastroenterol Hepatol. 2017;29(11):1223-30.Lledó GM et al. Regression of liver fibrosis after curing chronic hepatitis C with oral antivirals in patients with and without HIV coinfection. AIDS. 2018;32(16):2347-52.D’Ambrosio R et al. The diagnostic accuracy of Fibroscan for cirrhosis is influenced by liver morphometry in HCV patients with a sustained virological response. J Hepatol. 2013;59(2):251-6.Axley P et al. Hepatitis C virus and hepatocellular carcinoma: A narrative review. J Clin Transl Hepatol. 2018;6(1):79-84.Ravi S et al. Ungewöhnlich hohe Raten von hepatozellulären Karzinomen nach Behandlung mit direkt wirkender antiviraler Therapie bei Hepatitis-C-bedingter Zirrhose. Gastroenterology. 2017;152(4):911-2.Flemming JA et al. Reduction in liver transplant wait-listing in the era of direct-acting antiviral therapy. Hepatology. 2017;65(3):804-12.Belli LS et al.; The European Liver and Intestine Transplant Association (ELITA). Impact of DAAs on liver transplantation: Major effects on the evolution of indications and results. Eine ELITA-Studie auf der Grundlage des ELTR-Registers. J Hepatol. 2018;69(4):810-7.Sanyal AJ; Association AG. AGA technical review on nonalcoholic fatty liver disease. Gastroenterology. 2002;123(5):1705-25.Vilar-Gomez E et al. Weight loss through lifestyle modification significantly reduces features of nonalcoholic steatohepatitis. Gastroenterology. 2015;149(2):367-78.Axley P et al. Text messaging approach improves weight loss in patients with nonalcoholic fatty liver disease: A randomized study. Liver Int. 2018;38(5):924-31.Wong VW et al. Community-based lifestyle modification programme for non-alcoholic fatty liver disease: A randomized controlled trial. J Hepatol. 2013;59(3):536-42.Hagström H et al. Fibrosis stage but not NASH predicts mortality and time to development of severe liver disease in biopsy-proven NAFLD. J Hepatol. 2017;67(6):1265-73.Dulai PS et al. Increased risk of mortality by fibrosis stage in nonalcoholic fatty liver disease: Systematic review and meta-analysis. Hepatology (Baltimore, Md). 2017;65(5):1557-65.Mutsaers HA et al. Chronic kidney disease and fibrosis: The role of uremic retention solutes. Front Med (Lausanne). 2015;2:60.Boettcher E et al. Meta-Analyse: Pioglitazon verbessert Leberhistologie und Fibrose bei Patienten mit nicht-alkoholischer Steatohepatitis. Aliment Pharmacol Ther. 2012;35(1):66-75.Intercept Pharmaceuticals. Randomisierte globale Phase-3-Studie zur Bewertung der Auswirkungen der Behandlung mit Obeticholsäure auf NASH mit Fibrose (REGENERATE). NCT02548351. https://clinicaltrials.gov/ct2/show/NCT02548351.National Institue of Diabetes and Digestive and Kidney Diseases (NIDDK). The farnesoid X receptor (FXR) ligand obericholic acid in NASH treatment Trial(FLINT) (FLINT). NCT01265498. https://clinicaltrials.gov/ct2/show/NCT01265498.Tobira Therapeutics Inc. AURORA: Phase-3-Studie zur Wirksamkeit und Sicherheit von CVC zur Behandlung der Leberfibrose bei Erwachsenen mit NASJ. NCT03028740. https://clinicaltrials.gov/ct2/show/NCT03028740.Genfit. Phase-3-Studie zur Untersuchung der Wirksamkeit und Sicherheit von Elafibranor gegenüber Placebo bei Patienten mit nichtalkoholischer Steatohepatitis (NASH) (RESOLVE-IT). NCT02704403. https://clinicaltrials.gov/ct2/show/NCT02704403.Gilead Wissenschaft. Sicherheit, Verträglichkeit und Wirksamkeit von GS-4997 allein oder in Kombination mit Simtuzumab (SIM) bei Erwachsenen mit nichtalkoholischer Steatohepatitis (NASH) und Fibrosestadien F2-F3. NCT02466516. https://clinicaltrials.gov/ct2/show/NCT02466516.Gilead Sciences. Sicherheit und Wirksamkeit von Selonsertib bei Erwachsenen mit nichtalkoholischer Steatohepatitis (NASH) und überbrückender (F3) Fibrose (STELLAR3). NCT03053050. https://clinicaltrials.gov/ct2/show/NCT03053050.Gilead Wissenschaft. Sicherheit und Wirksamkeit von Selonsertib bei Erwachsenen mit kompensierter Zirrhose aufgrund von nichtalkoholischer Steatohepatitis (NASH) (STELLAR 4). NCT03053063. https://clinicaltrials.gov/ct2/show/NCT03053063.Gilead Wissenschaft. Sicherheit und Wirksamkeit von Selonsertib, Firsocostat, Cilofexor und Kombinationen bei Teilnehmern mit überbrückender Fibrose oder kompensierter Zirrhose aufgrund von nichtalkoholischer Steatohepatitis (NASH) (ATLAS). NCT03449446. https://clinicaltrials.gov/ct2/show/NCT03449446.Bergheim I et al. Treatment of alcoholic liver disease. Dig Dis. 2005;23(3-4):275-84.Chang Y et al. Nonheavy drinking and worsening of noninvasive fibrosis markers in nonalcoholic fatty liver disease: A cohort study. Hepatology. 2019;69(1):64-75.Thursz MR et al. Prednisolon oder Pentoxifyllin bei alkoholischer Hepatitis. N Engl J Med. 2015;373(3):282-3.O’Shea RS et al.; Practice Guideline Committee of the American Association for the Study of Liver Diseases; Practice Parameters Committee of the American College of Gastroenterology. Alcoholic liver disease. Hepatology. 2010;51(1): 307-28.Singal AK et al. Antioxidants as therapeutic agents for liver disease. Liver Int. 2011;31(10):1432-48.Pharmicell Co., Ltd. Langzeit-Follow-up-Studie von Livercellgram bei alkoholischen LC-Patienten, die die Phase-2-Studie von Livercellgram abgeschlossen haben. NCT02806011. https://clinicaltrials.gov/ct2/show/NCT02806011.Peeraphatdit TB et al. Exploring new treatment paradigms for alcoholic hepatitis by extrapolating from NASH and cholestasis. J Hepatol. 2018;69(2):275-7.Kang YJ, Zhou Z. Zinc prevention and treatment of alcoholic liver disease. Mol Aspects Med. 2005;26(4-5): 391-404.Shah VH. Management der alkoholischen Lebererkrankung. Clin Mol Hepatol. 2015;21(3):212-9.Thompson J et al. Extracorporeal cellular therapy (ELAD) in severe alcoholic hepatitis: A multinational, prospective, controlled, randomized trial. Liver Transpl. 2018;24(3):380-93.Loomba R et al. The ASK1 inhibitor selonsertib in patients with nonalcoholic steatohepatitis: A randomized, phase 2 trial. Hepatology. 2017. .Caballería J et al. Metadoxine accelerates fatty liver recovery in alcoholic patients: Results of a randomized double-blind, placebo-control trial. Spanische Gruppe für das Studium der alkoholischen Fettleber. J Hepatol. 1998;28(1):54-60.Singh V et al. Granulocyte colony-stimulating factor in severe alcoholic hepatitis: A randomized pilot study. Am J Gastroenterol. 2014;109(9): 1417-23.Gao B, Shah VH. Combination therapy: Neue Hoffnung für die alkoholische Hepatitis? Clin Res Hepatol Gastroenterol. 2015;39 Suppl 1:S7-S11.Li F et al. Probiotics and alcoholic liver disease: Behandlung und mögliche Mechanismen. Gastroenterol Res Pract. 2016;2016:5491465.Hospital Universitari Vall d’Hebron Research Institute. Auswirkungen von Rifaximin bei Patienten mit akuter alkoholischer Hepatitis (RIFA-AAH). NCT02116556. https://clinicaltrials.gov/ct2/show/NCT02116556.Gilead Sciences. Selonsertib in Kombination mit Prednisolon versus Prednisolon allein bei Teilnehmern mit schwerer alkoholischer Hepatitis (AH). NCT02854631. https://clinicaltrials.gov/ct2/show/NCT02854631.Higuera-de la Tijera F et al. Metadoxine improves the three- and six-month survival rates in patients with severe alcoholic hepatitis. World J Gastroenterol. 2015;21(16):4975-85.Postgraduate Institute of Medical Education and Research. GCSF bei alkoholischer Hepatitis. NCT03703674. https://clinicaltrials.gov/ct2/show/NCT03703674.Mayo Klinik. Einsatz von F-652 bei Patienten mit alkoholischer Hepatitis (TREAT 008). NCT02655510. https://clinicaltrials.gov/ct2/show/NCT02655510.Manns MP et al. Diagnosis and management of autoimmune hepatitis. Hepatology. 2010;51(6):2193-213.Heathcote EJ. Management der primär biliären Zirrhose. Die Praxisrichtlinien der American Association for the Study of Liver Diseases. Hepatology. 2000;31(4):1005-13.Bellentani S et al. Ursodiol in the long-term treatment of chronic hepatitis: Eine doppelblinde multizentrische klinische Studie. J Hepatol. 1993;19(3):459-64.Lee J et al. Transplantation trends in primary biliary cirrhosis. Clin Gastroenterol Hepatol. 2007;5(11):1313-5.Nevens F et al. A placebo-controlled trial of obeticholic acid in primary biliary cholangitis. N Engl J Med. 2016;375(7):631-43.Intercept Pharmaceuticals. Phase-4-Studie mit Obeticholsäure zur Bewertung der klinischen Ergebnisse bei Patienten mit primär biliärer Cholangitis (COBALT). NCT02308111. https://clinicaltrials.gov/ct2/show/NCT02308111.Schon HT et al. Pharmacological intervention in hepatic stellate cell activation and hepatic fibrosis. Front Pharmacol. 2016;7:33.