1. Cirrhosis 18 November 2009 Thomas C Sodeman MD Associate Professor of Medicine Chief, Division of Gastroenterology

2. Cirrhosis Definition Diagnosis Pathogenesis Treatment Outlook

3. Cirrhosis Definition –Distortion of hepatic architecture by fibrosis and attempted regeneration that leads to loss of function, portal hypertension, and potential hepatocellular malignancy.

4. Cirrhosis http://www.hivandhepatitis.com/2006icr/ddw/images/cirrhosis-liver.jpg

5. Cirrhosis http://www.pathology.vcu.edu/education/gi/images/3.3h-b.jpg

6. Cirrhosis Causes –Alcohol –NASH –HBC, HCV, HDV –Iron, copper –Autoimmune –PSC, PBC, SSC –Vascular –  1-AT –Drugs –?

7. Cirrhosis Diagnosis –Clinical –Laboratory –Radiologic

8. Cirrhosis Diagnosis –Clinical Silent Ascites Encephalopathy Sleep-wake reversals Variceal bleeding Muscle wasting Gynecomastia Spiders

9. Cirrhosis

10. http://www.hepatitis.cl/images/varices.jpg

11. Cirrhosis http://www.medscape.com/content/2000/00/40/55/405535/art-mgi7381.lang.Fig2.jpg

12. Cirrhosis http://content.answers.com/main/content/wp/en/thumb/9/91/200px-IGV1.jpg

13. Cirrhosis Diagnosis –Laboratory Synthetic defect –Albumen, INR Thrombocytopenia Ammonia Bilirubin AST / ALT  FP

14. Cirrhosis Diagnosis –Radiologic –Can rule in but not rule out –Sensitivity and specificity of 80% –Splenomegaly, varices, ascites

15. Cirrhosis

22. Diagnosis –Biopsy 1% risk of complications Often understages Misdiagnosed in 10-30% Optimal biopsy 40 mm Average 16 mm

23. Cirrhosis Diagnosis –Noninvasive Fibroscan Fibrosure Actitest AST/platelet ratio ( AST / ULN)/PLT (10 9 /L)×100.

24. Cirrhosis Pathogenesis

25. Cirrhosis

26. Treatment –Treat underlying disease –Treat manifestations –Screen for problems Varices HCC –Transplantation

27. Cirrhosis Treatment –Treat underlying disease –HBV/HCV – slow progression –HHC – slow progression –AIH – slow progression –EtOH – slow progression

28. Cirrhosis Treatment –Treat manifestations Ascites Encephalopathy Varices

29. Cirrhosis

30. Treatment –Treat manifestations Ascites –Tap –SAAG >1.1 –Culture –Cytology –Albumen Lasix / aldactone Salt restriction 2g/day Tap / TIPS

31. Cirrhosis Treatment –Treat manifestations Ascites –SAAG –>1.1 Cirrhosis, CHF, Mets, FHF, Budd-Chiari –<1.1 Peritoneal Ca, TB, bile leak, nephrotic syndrome

32. Cirrhosis Treatment –Treat manifestations Ascites –Tap –1100 LVP –INR 8.7 –Plt 19 –No major complications Hepatology 2004: 40:484-488

33. Cirrhosis Treatment –Treat manifestations Ascites –“Failure” –High salt diet –IV fluids –NSAIDS Hepatology 2004: 40:484-488

34. Cirrhosis Treatment –Treat manifestations Ascites –SBP –>250 PMN –Cefotaxime –Quinolones Hepatology 2004: 40:484-488

35. Cirrhosis Treatment –Treat manifestations Hepatorenal syndrome GFR>1.5 or CrCl <40 No shock, infection, etc Urine protein <500 mg/day Hepatology 2004: 40:484-488

36. Cirrhosis Treatment –Treat manifestations Hepatorenal syndrome Current treatment –Preventive –Transplant –Midodrine / octreotide Hepatology 2004: 40:484-488

37. Cirrhosis Treatment –Treat manifestations Varices –Predict with thrombocytopenia –Grading I-IV –Bleeding risk with III IV –Screen »Repeat in 1-2 years if grade I or II »Repeat in 6 months if III IV

38. Cirrhosis Treatment –Treat manifestations Varices –Bleeding carries up to 50% mortality –Transfusion to Hb 8 –Octreotide –Intubation –Endoscopy –  blockers –Antibiotics for SBP

39. Cirrhosis Outlook –Bad –Mortality Compensated Decompensated –Variceal bleed 20% –Ascites 50% 2 year

40. Cirrhosis Outlook –Hepatocellular carcinoma Risk 1-5%/year Increased with: –Male –Iron –HBV –  1AT

41. Cirrhosis Outlook –Transplantation HCV/alcohol NASH HCC PBC/PSC

42. Cirrhosis Outlook –Transplantation MELD score MELD Score = 10 {0.957 Ln(Scr) + 0.378 Ln(Tbil) + 1.12 Ln(INR) + 0.643}

43. Cirrhosis Key points –Diagnosis Anything fixable? –Management of manifestations –Screening for problems –Transplantation