Evaluation and Staging of Liver Fibrosis

Transcription

1 Evaluation and Staging of Liver Fibrosis Marion G. Peters, MD John V. Carbone, MD, Endowed Chair Professor of Medicine Chief of Hepatology Research University of California San Francisco Recorded on April 29, 2013

2 Disclosure Information Dr Peters has reported the following financial relationships with commercial firms: Consultant: Merck & Co, Inc, Theravance, and Roche Data safety monitoring board: Biotron Scientific advisor: Clinical Care Options Her spouse is employed by Genentech (Roche) Slide 2 of 19

3 Outline 1 Indications for liver biopsy 2 Interpreting liver biopsy findings 3 Indirect and direct biomarkers 4 Imaging Slide 3 of 19

4 Slide 4 of 19 Indications for Liver Biopsy

5 Indications for Liver Biopsy YES Patient would only accept treatment if significant fibrosis Treatment different for patients with cirrhosis and labs and radiographic studies do not suggest cirrhosis Patient fails to achieve SVR and no recent biopsy available Chance of SVR low NO Patient wants treatment even if no fibrosis Patient does not want treatment Treatment contraindicated Cirrhosis on imaging or clinically New drugs results in high SVR for all Slide 5 of 19

6 Slide 6 of 19 Interpreting Liver Biopsy Findings

7 Fibrosis Progression: F0 F4 F1 F-0 is normal Few Septa Central Vein F2 F3 Portal Tract Fibrosis Cirrhosis F4 Slide 7 of 19 Numerous Septa

8 Sampling Error of Liver Biopsy Slide 8 of 19

9 Sampling Error of Liver Biopsy Fibrosis area: 65% Slide 9 of 19

10 Sampling Error of Liver Biopsy Fibrosis area: 65% Slide 10 of 19 Courtesy of M. Pinzani, Florence Fibrosis area: 15%!

11 Sampling Error of Liver Biopsy Fibrosis area: 65% Slide 11 of 19 Courtesy of M. Pinzani, Florence Fibrosis area: 15%!

12 Liver Biopsy Size in 355 Samples: The Smaller the Piece the Milder the Disease No. Portal Tracts Grade Stage Slide 12 of 19 Length of specimen > 3 cm 1.5 cm 1 cm complete 22.4 ± ± ± 1.2 Mild 49.7% 60.2% 86.6% Moderate 38.5% 39.1% 17.4% Severe 11.8% 0.6% 0 Mild (F0-1) 59% 68.3% 80.1% Moderate (F2) 29.8% 24.2% 14.9% Severe (F3-4) 11.2% 7.4% 4.9% Colloredo, J Hep, 2003

13 Liver Biopsy Value Still the best test to assess fibrosis in an individual patient in United States Only as good as the adequacy of the specimen More expensive than serum markers or elastography Requires expert for acquisition and pathology Less needed in viral hepatitis over time If therapy uncertain, biopsy is the best test to learn stage of disease Slide 13 of 19

14 Pros and Cons of Liver Biopsy Invasive, requires expertise, US guidance Risky: bleeding in 1 in 1000; pain Requires expert pathology assessment > 2 cm, > 6 portal tracts for diagnosis > 2 cm, >11 portal tracts for staging But assesses more than fibrosis Fat that can impact response to therapy Inflammation and location (eg, nonalcoholic fatty liver disease in hepatitis B virus) Other liver disease (autoimmune hepatitis, alcohol use) Slide 14 of 19

15 Fibrosis Is a Dynamic Process Not Reflected in Static Biopsy Sample Slide 15 of 19

16 Slide 16 of 19 Indirect and Direct Biomarkers

17 Fibrosis Is a Dynamic Process Not Reflected in Static Biopsy Sample Formation Degradation Slide 17 of 19

18 Blood tests Fibrotest AST-to-platelet ratio index Enhanced liver fibrosis Forns index FIBROSpect Fibrometer Hepascore FIB-4 (coinfected patients) Slide 18 of 19 Noninvasive Tests of Fibrosis Likely to Be an Alternative in the Future Reviewed in Nelson et al, Clin Gastroenterol Hepatol Liver Imaging Transient elastography Diffuse-weighted magnetic resonance imaging (MRI) MRI elastography MR spectroscopy

19 Fibrosis Tests Indirect Markers of liver injury ALT/AST Markers of hepatic function-indirect Prothrombin time, albumin, alfa 2 macroglobulin, haptoglobin, platelets Direct Markers of matrix production or degradation Procollagen, hyaluronic acid, tissue inhibitors of metalloproteinases, matrix metalloproteinases, Slide 19 of 19 YKL-40

20 Slide 20 of 19 Imaging

21 Slide 21 of 19 Hepatic Elastography

22 Elastography: Fibroscan 2.5 kpa Affected by weight, access of probe (2 cm), steatosis Slide 22 of 19

23 Summary Staging of Liver Disease Less important prior to hepatitis C virus (HCV) treatment as treatment success increases Noninvasive markers improving Transient elastography now approved in United States Ultrasound, computed tomography (CT), MRI useful in cirrhosis but not useful to stage disease Slide 23 of 19

24 End This presentation is brought to you by the International Antiviral Society-USA (IAS-USA) in collaboration with Hepatitis Web Study & the Hepatitis C Online Course Funded by a grant from the Centers for Disease Control and Prevention Slide 24 of 19