1 / 26

Colangite Biliare Primitiva STRATIFICAZIONE DEL RISCHIO

Colangite Biliare Primitiva STRATIFICAZIONE DEL RISCHIO. Domenico ALVARO, MD Sapienza, University of Rome, Italy. PBC what to do after the diagnosis ? - Disease stage ! - Prognosis: risk stratification !. J. Hepatology 2017. Gut 2018. Hepatology 2018. DLD 2017. PBC Phenotype.

talib
Télécharger la présentation

Colangite Biliare Primitiva STRATIFICAZIONE DEL RISCHIO

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Colangite Biliare PrimitivaSTRATIFICAZIONE DEL RISCHIO Domenico ALVARO, MD Sapienza, University of Rome, Italy

  2. PBC what to do after the diagnosis ? - Disease stage ! - Prognosis: risk stratification !

  3. J. Hepatology 2017 Gut 2018 Hepatology 2018 DLD 2017

  4. PBC Phenotype Abbreviations AMA antimitochonaddrial antibody; ANA antinuclear antibody; ASMA, anti-smoth-muscle antibody; IBD, inflammotory bowel desease: MRCP, magnetic resonance cholangiography; PBC, primary biliary choalngitis. Trivedy PJ et al. Al.iment Pharmacol Ther 2012; 36:517-533.

  5. The Two Sides of PBC 50-60% ofourpts. 10-15% ofourpts. Abbreviations ANA antinuclear antibody; PBC, primary biliary choalngitis; UDCA, ursodeoxycholic acid.

  6. PBC: riskstratification ??? Rapid-progressive (young women, men, fatigue, UDCA-non-responders) Slow-progressive (elderly women, mild itch, UDCA-responders) Asymptomatic AMA+ ALP high Silent AMA+ ALP normal Portal hypertension-type progression (ACA-pos. ) Interface hepatitis/PBC-AIH overlap (non responder ) Hepatocellular failure-type progression (Anti-gp210 antibody pos.)

  7. PBC: riskstratification ! UDCA responders UDCA non responders VS

  8. PBC: the way to precision medicine • MAIN PRINCIPLES: • More proactive and predictive approach to medicine; • Risk stratification; • Individualization of treatment for each patient; • Prevention rather than the treatment of symptoms; ‘the right treatment, for the right person, at the right time’ !

  9. PBC: staging and prognostic indexes at the diagnosis ! RISK STRATIFICATION ! EASL guidelines 2017

  10. PBC: staging and prognostic indexes at the diagnosis ! • Anti-Sp100 and anti-gp210 ANA to be checked • since their prognostic significance !? • -Cirrhosis should be checked by US (PV doppler) • indirect signs ! • -Transient elastography to classify PBC patients • with or without severe fibrosis ! • - Alkalinephosphataseserumlevels ! • Category of evidence = II-2 • -Grade of evidence = A1

  11. Non-specific antinuclear antibodies (ANA) are found in at least 30% of PBC cases (85% AMA-neg. PBC) • ANA directed against nuclear body or envelope proteins such (anti-Sp100, anti-gp210) show a high specificity for PBC (>95%), but with low sensitivity ! EASL practice guidelines, J Hepatol 2009

  12. ANA PBC-specific (30% of PBC, > 95% of AMA-neg): • Anti-gp210 antibody: • PBC-specific anti-nuclear antibody, targets …nuclear pore complex (NPC); • Associated with more aggressive disease, more severe interface and lobular hepatitis, late stage PBC (Wesierska-Gadek 2006); • Marker of hepatocellular failure-type progression in PBC. • Anti sp100 antibody: • Found in many other autoimmune diseases, including systemic lupus erythematosus and systemic sclerosis (SSc); • Prognostic significance of sp100 antibodies unclear ! • Anti-centromere antibodies (ACA): • Characteristic of SSc but also found in PBC patients without coexistent SSc; • Predictive of portal hypertension-type disease progression, without synthetic failure (Gao et al. 2008); EASL practice guidelines, J Hepatol 2009

  13. PBC: UDCA-response + Liverstiffness ?! C. Corpechot

  14. 2015

  15. 15,875 PBC cohort (63.0±13.5 y, 78% female, 46% with cirrhosis); 6083 (38%) had ALP≥ 1.5×ULN Associated with : --more pruritus --more cirrhosis, + other autoimmune diseases Multivariate analysis: --presence of other autoimmune diseases --compensated or decompensated cirrhosis --being male …..higher risk of cirrhosis

  16. Asymptomatic primary biliary cirrhosis: a study of its natural history and prognosis. J Springer et al. American Journal of Gastroenterology 1999.

  17. PBC: riskstratification ! UDCA responders UDCA non responders VS

  18. PBC: UDCA responseasmainprognosticindex! * Dichotomous models, easy to use but: -only two levels of risk; -fail to quantify intermediate levels of risk; -ignore the relationship between risk and time They do not indicate whether the high-risk patient will need a LT tomorrow or fifteen years in the future !

  19. PBC: UDCA responseasmainprognosticindex! To properly inform treatment decisions, continuous risk index (or score) that quantifies the individual’s risk in relation to time are demanding …

  20. PBC: riskstratification ! UDCA responders UDCA non responders VS

  21. PBC: riskstratification ! UDCA responders UDCA non responders VS

  22. Costo UDCA = 180-220 euro/anno !

  23. 2703 PBC included in the UK-PBC cohort for derivation of the model 460 PBC in the external validation cohort: AUROC= 0.83 (95% CI 0·79–0·87)

  24. In 20 PBC liver biopsy UDCA response score associated with ductular reaction (r=–0·556, p=0·0130) and intermediate hepatocytes (probability of response was 0·90 if intermediate hepatocytes were absent vs 0·51 if present).

  25. Studi prospettici sui predittori istologici di risposta al trattamento e sulla progressione istologica di malattia in pazienti PBC trattati con UDCA+OCA sono indispensabili per stabilire quando cessare il trattamento o cambiare farmaco !

More Related