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Liver issues for the Rheumatologist

Liver issues for the Rheumatologist. David Wong, MD University of Toronto www.torontoliver.ca. Disclosures (last 1 year): Research Studies: BMS, Gilead, Johnson & Johnson, Vertex Advisory Boards: Merck, Vertex. Objectives.

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Liver issues for the Rheumatologist

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  1. Liver issues for the Rheumatologist David Wong, MD University of Toronto www.torontoliver.ca Disclosures (last 1 year): Research Studies: BMS, Gilead, Johnson & Johnson, Vertex Advisory Boards: Merck, Vertex

  2. Objectives To understand the sensitivity and specificity of Fibroscan and Fibrotest for liver monitoring in patients receiving MTX To understand which patients to refer to a specialist To consider which labs to monitor when screening for liver problems with DMARDS

  3. Drug induced liver injury (DILI) Acute injury Chronic injury Fatty liver Methotrexate Ductopenia Azathiprine, Gold salts Nodular regenerative hyperplasia Azathioprine • ALT/AST • NSAIDS • Sulfasalazine • ALP • NSAIDS • Sulfasalazine • Gold salts • Azathioprine

  4. Case of DILI • 52 year old woman with HIV • Hepatitis C genotype 3 • Poor adherence to meds, did not treat HCV • Previously FTC-TDF-LPV/r • Sep 2012 – disseminated MAC • CD4 40 (very low): Treat MAC first with antibiotics • Admit to Casey House to monitor treatment • Dec 2012 – start HIV medications • FTC-TDF-DRV/r • Jan 2012 – admitted with jaundice, ALT 200s, AST 300s • Stop HIV medications • Apr 2013 – re-started HIV medications • FTC-TDF-DRV/r • May 2013 – dying of liver failure

  5. When to worry about DILI? • ALT/AST • Height of elevation ~ degree of liver injury • Other considerations? • What is liver reserve? • Previously normal liver vs cirrhotic liver? • NB not everyone with HBV or HCV has cirrhosis • Hy’s law • Jaundice: case fatality rate 10%-50% • Re-introduction of medication can be diagnostic but deadly

  6. DILI Guruprasad P Aithal. Nat Rev Rheumatol. 2011;7:139

  7. Approach to DILI • Is there another cause for acute hepatitis? • Is there underlying cirrhosis? • How much liver fibrosis exists? • Is fibrosis progressive? • How high is ALT/AST • How badly do I need to use this drug? • Can I treat through this? • Jaundice is BAD

  8. HMO in Israel: Psoriasis and RA diagnosed Jan 1998-Jul 2007 • Alcohol • Fatty liver risks • Dyslipidemia • BMI, waist circumference • Fibrosis assessment H Amital et al. Rheumatology 2009;48(9):1107

  9. Methotrexate and the liver • Liver biopsy q1.5 grams? • Cirrhosis without abnormal liver enzymes • Monitoring of liver enzymes? • Role of ultrasound? Guruprasad P Aithal. Nat Rev Rheumatol. 2011;7:139

  10. Cases

  11. Methotrexate and the liverDILI vs fatty liver? Guruprasad P Aithal. Nat Rev Rheumatol. 2011;7:139

  12. How to prevent? JM Kremer et al. Arthritis Rheum 1994;37:316 HH Roenigk et al. J Am AcadDermatol 1998;38:478 C Paul et al. JEADV 2011;25 (Suppl 2)

  13. Objectives To understand the sensitivity and specificity of Fibroscan and Fibrotest for liver monitoring in patients receiving MTX To understand which patients to refer to a specialist To consider which labs to monitor when screening for liver problems with DMARDS

  14. Typical Referral • 52 year old man with psoriatic arthritis • MTX x 5 years • Liver biopsy? Fibroscan? • Assessment • Risks for fatty liver? • Diabetes, hypertriglyceridemia, central obesity • Alcohol • Risks for other liver disease • Viral hepatitis • Iron overload Celts

  15. Fibrosis Assessment • Fibroscan • Chest circumference • Are the ribs easily palpable • Is the rib space adequate • Fibrosis assessment in 3 minutes • Fibrotest • Cannot be done if hemolysis • Haptoglobin undetectable • Cost for some components • Fibrosis assessment in 1-4 weeks

  16. Acting on Fibrosis Assessment • Concordant results • F0-2: continue treatment • F3-4: change treatment • Discordant results • Ultrasound • Liver biopsy

  17. Hepatitis BWorldwide Problem

  18. Natural History of Hepatitis BImportance of immune control HJ Yim and AS Lok. Hepatology 2006;43:S173

  19. HBV investigations HBsAg anti-HBs, anti-HBc 1. Screen for HBV HBsAg-POS Infected HBsAg-NEG Not-Infected 1a. Need for vaccine Anti-HBc POS Prior infection Anti-HBc NEG, Anti-HBs NEG No infection, vaccinate High Risk Refer! Low Risk Monitor ALT Check HBsAg if ALT  Advanced liver fibrosis? Platelets < 160 Age > 40

  20. Hepatitis C in OntarioModeled prevalence MOHLTC integrated Public Health Information System, 4/12/2011

  21. Challenges in HCV treatmentSVR>90%, minimal side effects • New agents screened against HCV G1b • Not as effective against G1a • Most do not work for non-1 • Genotype 3? • Other challenges • Cirrhosis • Monotherapy not sufficient • Treatment experience • Interferon sensitivity (IL28b) • Ribavirin resistance?

  22. ABT orals + RBV in non-cirrhotics (naïve and nulls) • ABT-450/r PI • ABT-267 NS5a inhibitor • ABT-333 NN NS5b inhibitor • N=451 treated 12-24 weeks • Going ahead with 12 weeks • Degree of Difficulty • Excludes cirrhotics • Includes 1a (66%), non-CC (81%) KV Kowdley et al. A3. EASL 2013

  23. SVR24 Naïve N=159 Null N=88 % SVR24 81 50 124 42 44 33 33 66 45 3 78 108 35 113 115 56 55 22 41 85 1b >7 log <7 log CC Male Female 1a F0-F1 Non-CC 1b >7 log <7 log F2-F3 CC Male Female 1a F0-F1 Non-CC F2-F3 KV Kowdley et al. A3. EASL 2013

  24. Salvage for BOC/TPV failuresSOF+DCV+/-RBV x 24 weeks • SOF - PolI • Declatasvir (DCV) – NS5A inhibitor • Degree of Difficulty • Excludes cirrhotics • Includes treatment failures (nulls) • Excludes early DC due to AE • 1a: 76-85%, non-CC: 95-100% MS Sulkowski et al. A1417. EASL 2013

  25. SVR12 1 missed is SVR24 % SVR 21 20 21 20 21 20 21 20 21 20 MS Sulkowski et al. A1417. EASL 2013

  26. Hepatitis C diagnosis • Anti-HCV antibody: exposed • HCV PCR: needed to confirm infection • HCV not greatly affected by immunosuppression • HCV curable

  27. Summary • Immunosuppression • Hepatitis B • Vasculitis • Hepatitis C >> Hepatitis B

  28. Objectives To understand the sensitivity and specificity of Fibroscan and Fibrotest for liver monitoring in patients receiving MTX To understand which patients to refer to a specialist To consider which labs to monitor when screening for liver problems with DMARDS

  29. Recommendations for Methotrexate or Imuran Baseline Monitoring Labs ALT, AST, ALP Look for rising numbers over the first year that continue to go up rather than just fluctuate CBC Look for falling patelet count to < 150 Very concerned if Plts < 150 and falling by >15% over 2 years • History • Metabolic syndrome • Did you ever drink on a regular or daily basis? • Other history of liver disease • Labs • ALT, AST, ALP, CBC • Ultrasound if abnormal tests • Especially if Plts < 150 • HBsAg

  30. What to do for your cirrhotics • Plts < 150: suspect cirrhosis • Plts < 100: likely will have varices • Plts < 70: higher risk of renal failure (hepatorenal syndrome) • No NSAIDS (even with PPI) • Tylenol <3-4g/day is much safer • Coffee may be good • Alcohol in moderation may be good

  31. Questions?

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