BRON VAN HEPATOLOGIE IN NL Heymans v.d.bergh 1914-1937 Utrecht L. Schalm, Brandt 1940-1980 Arnhem, Leerboek 1948 Que, Gips Groningen na 1968, P. Jansen vanaf 1993 Bilirubine dir.-indirect Bilirubine, Regeneratie, Hepatitis, LTX 1968 LTX, Hepatitis, Cholestase v.tongeren/ Yap Nijmegen vanaf 1975 S. Schalm R dam vanaf 1980 H.Janssen na 2006 P. Jansen, AMC na 2003, Oude Elferink Lever als syntheseontgiftingsorgaan HBV, HCV, Cholestase ERCP(Huybregtse) na 1975, Hepatitis, Cholestase
BRON VAN HEPATOLOGIE IN NL Heymans v.d.bergh 1914-1937 Utrecht L. Schalm, Brandt 1940-1980 Arnhem, Leerboek 1948 Que, Gips Groningen na 1968, P. Jansen vanaf 1993, Bilirubine dir.-indirect Bilirubine, Regeneratie, Hepatitis, LTX 1968 LTX, Hepatitis, Cholestase v.tongeren/ Yap Nijmegen vanaf 1975 S. Schalm R dam vanaf 1980 H.Janssen na 2006 P. Jansen, AMC na 2003, Oude Elferink Lever als syntheseontgiftingsorgaan HBV, HCV, Cholestase ERCP(Huybregtse) na 1975, Hepatitis, Cholestase
BRONNEN VAN HEPATOLOGIE IN NL Heymans v.d.bergh 1914-1937 Utrecht L. Schalm, Brandt 1940-1980 Arnhem, Leerboek 1948 Que, Gips Groningen na 1968, P. Jansen > 1993, Bilirubine dir.-indirect Bilirubine, Regeneratie, Hepatitis, LTX 1968 LTX, Hepatitis, Cholestase v.tongeren/ Yap Nijmegen vanaf 1975 S. Schalm R dam >1980 H.Janssen na 2006 P. Jansen(AMC) na 2003, R.Oude Elferink Lever als syntheseontgiftingsorgaan HBV, HCV, Cholestase ERCP(Huibregtse) na 1975, Hepatitis, Cholestase
ERCP HOOGSTE SCORE INNOVATIEVE TECHNOLOGIE >1970?
100 JAAR HEPATOLOGIE: ORGANISATIES Voor 1975 Na 1975 Oprichting EASL L. Schalm 1966 Marburg, DL EASL Congres Arnhem 1972 L. Schalm en Eerste vergadering Nederlandse Leverclub NVH 1977 NLS 1980, NLDS, MLDS 1995 Ned. Leverpat. Vereniging Nat. Hepatitis Centrum EASL Congressen: 1986 Groningen C. Gips 2000 Rotterdam S. Schalm 2013 A dam U. Beuers
100 JAAR HEPATOLOGIE: ORGANISATIES Voor 1975 Na 1975 Oprichting EASL L. Schalm 1966 Marburg, DL EASL Congres Arnhem 1972 L. Schalm en Eerste vergadering Nederlandse Leverclub NVH 1977 NLS 1980, NLDS, MLDS 1995 Ned. Leverpat. Vereniging Nat. Hepatitis Centrum EASL Congressen: 1986 Groningen C. Gips 2000 Rotterdam S. Schalm 2013 A dam U. Beuers
GALZOUTEN en GALVORMING: 1970-2013 Osmotisch gedreven proces? Galzoutafh. en onafh. fractie Specifieke transportsystemen >1990 Molecular cloning transporteiwitten >1995 FXR/LXR en FXR-agonisten >2000 (Cheno type 2 Diabetes en NASH) Bile Acids als hormonen voor receptor TGR5 >2010(energiebalans)
WHEN TRANSPORT SYSTEMS FAIL Hereditary Acquired Cholestatic syndromes Decreased transport proteins cholestasis and icterus
Hereditary Defects in Hepato-biliary Transport System Hepatocyte Sitosterolemia Bile duct Cystic fibrosis
Primary Biliary Cirrhosis, an enigmatic disease: 1970? 2013? Chronic cholestatic liver disease Anti-mitochondrial antibody Non-suppurative destructive cholangitis Females >> males
DUTCH MULTICENTRE PBC COHORT STUDY >300 patients 44 hospitals ALL TREATED WITH UDCA Med. follow-up >6 yrs Prospective study
HEPATOLOGY: < 1985 LARGE SYNDROMES DIAGNOSIS THERAPY CIRRHOSIS ASCITES Bacterial Peritonitis Variceal Bleeding Encephalopathy HCC CLINICAL Child Score BIOPSY CLINICAL, US? PUNCTION Endoscopy EEG, NH3 AFP, US? Radiology Eliminate causes LTX Spironol. Paracentesis, Shunt ANTIBIOTICS Scleroth, Balloon Lactulose, Neomycin Surgery
AU-ANTIGEEN POS. CAH-PAT.(1969)
Hepatology < 1985 Etiology Marker Therapy Hepatitis B Non-A, non-b hepatitis Auto Immune Hepatitis Prim Biliary Cirrhosis Prim Sclerosing Cholangitis HBsAg, eag, HBVDNA - - ALT- IgG, ANA- SMA AF- IgM, AMA - Cholangiography - IFN Pred-Aza
HEPATOLOGY: 2013 LARGE SYNDROMES CIRRHOSIS Markers US-Fibroscan MELD, Child Score Therapy Eliminate causes LTX ASCITES Clinical- US Spironol. TIPS Variceal Bleed HCC Endoscopy Contrast US, CT-MRI Banding, TIPS Perc. Tumor Ablation, Surgery, LTX
HEPATOLOGY IN 2013 Etiology Marker Therapy HEPATITIS B HBsAg, eag, HBVDNA, HBV-genotype Interferon, Lamivudine, Entecavir, Tenofovir HEPATITIS C antihcv, HCVRNA, HCV-genotype, IL-28 Interferon, Ribavirine, Telapravir, TMC435 Auto Immune Hepatitis ALT- IgG, ANA-SMA Prednison, Azathioprine Prim Biliary Cirrhosis AF- IgM, AMA UDCA Prim Sclerosing Chol AF - Cholangiography - Hemochromatose Ferritin, Fe, Transferrin C282Y Phlebotomy
HEALTH GAIN IN HEPATOLOGY OVER 50 YEARS: WHAT DID WE LEARN? In 2013 LARGE HEALTH GAIN SMALL HEALTH GAIN Removing cause disease Regression Liver Fibrosis after biliary drainage or antiviral Rx/ Survival benefit after antiviral Rx/ in HBV and HCV Treatment of Complications Cirrhosis B-Blokkers in Var. Bleeding TIPS in survival Treatment UDCA PBC / PSC? Survival after LTX
The Rise of Modern Hepatology(naar S.Schalm) continued innovation from 1980-2013 Illustrious innovations from Clinical science: HBIg for HBV LTx, Ribavirin for HCV, TIPS, Perc Tumor Ablation, LTx Illustrious innovations from Industry: HCV / HCVRNA, entecavir / tenofovir for HBV, STAT-C for HCV, fibroscan, V-scan? Also illustrious innovations from Genomics & Epidemiology?: Genomics: C282Y for hemochromatosis, markers in cholestasis? Epidemiology: only systematic studies & limited T1/2 of Truth?
Real Challenge for the Netherlands >2013 PREVENTION OF COMPLICATIONS by taking away primary cause: NASH, HBV, HCV, PBC, PSC in The Netherlands mortality due to hepatitis b can be reduced by 80% if 6000 patients at high risk are identified and treated with a 3rd generation antihepatitis B drug *. More emphasis on CLINICAL RESEARCH! * Toy M et al: Potential impact of therapy in chronic hepatitis B Hepatology 2009 30