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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.

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Colangite Biliare Primitiva STRATIFICAZIONE DEL RISCHIO

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  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 !

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