Break the Liver Biopsy Habit

Transcription

1 Break the Liver Biopsy Habit Dirk Elston MD Professor and Chairman Department of Dermatology and Dermatologic Surgery Medical University of South Carolina No conflict of interest

2 Father of one of my nurses: has insurance, but pays out of pocket for medications

3 Cleared 99% with MTX liquid 12.5 mg/week It costs him $8 per month, and he is delighted with the results He initially was afraid of MTX because he almost bled to death after a liver biopsy and wants to avoid another biopsy He was always told the biopsy was mandatory

4 What would you do? A. Treat with no lab work B. Follow LFTs C. Ultimatum: at 1.5 gm, no bx/no MTX D. Follow procollagen 3 terminal peptide E. Follow Fibrosure (NASH or HepC)

5 ACR vs AAD Recommendations are different Are liver biopsies necessary? At what dose? Only if LFTs are abnormal? Psoriasis are different from RA patients Higher doses and higher incidence of metabolic syndrome, obesity, ETOH use

6 MTX-induced fibrosis Not an inflammatory process Concurrent hepatitis may or may not exist LFTs measure inflammatory damage Fibrosure involves predictive modelling based on patient characteristics (many of which we already know for psoriasis patients)

7 Fibrosure (Fibrotest) Artificial intelligence algorithm using α2- macroglobulin, haptoglobin, apolipoprotein A1, bilirubin, γ-glutamyl transpeptidase (GGT), +/- ALT, with a patient s age and gender Reliable assessment of risk in HCV and NASH Should not be used for Gilbert disease, acute viral hepatitis, drug-induced hepatitis, genetic liver disease, autoimmune hepatitis, and/or extrahepatic cholestasis.

8 Hepatic fibrosis with MTX in RA Using AAD recommendations, 66 RA patients underwent 110 liver biopsies (ACR criteria would have resulted in 18 biopsies in 15 patients) Found 1 patient with cirrhosis who would have been missed with ACR criteria (NIDDM) Arthritis Rheum 1995; 38:1115-9

9 AAD vs ACR Recommendations Does this mean that 2% of cases of cirrhosis are missed in RA pts using ACR criteria? Would the percentage be higher for psoriasis patients given their higher overall risk? How many cases of cirrhosis are too many?

10 Danish Experience University of Aarhus Serial liver biopsies in 25 patients Subsequent specimens tended to be same or lower grade fibrosis 10 year follow-up One 84 year old woman died of liver failure despite normal LFTs for 8 years after last biopsy (normal) Dermatologica 1987; 107:418-9 Dermatology :343-6

11 Danish Experience University of Aarhus Change of practice - Procollagen3 terminal peptide measurement 10 year follow-up since introduction of P3P measurement No episodes of significant fibrosis or cirrhosis JAAD 2000; 42:531-4

12 Manchester Guidelines Test quarterly Normal: below values above 8 or one above 11: D/C or reduce dose Joint disease may cause high P3P unrelated to liver fibrosis

13 Transient Elastography and FibroTest Pulse-echoultrasonography to measure liver stiffness FibroTest (Fibrosure) is an indirect serum marker of hepatic fibrosis Serial procollagen 3 peptide (P3P) results were recorded The Use of Transient Elastography and FibroTest for Monitoring Hepatotoxicity in Patients Receiving Methotrexate for Psoriasis. JAMA Dermatol :856-62

14 Transient Elastography and FibroTest 77 patients (65% with valid TE assessment) 9 (18%) had an abnormal result Being overweight or obese increased the possibility of an invalid TE result and body mass index and age were correlated with abnormal TE results. Seventy-one patients received FibroTest 16% had an abnormal result

15 Transient Elastography and FibroTest No correlation between PIIINP levels and TE results or FibroTest results. Two patients had hepatic fibrosis The need for liver biopsy could be reduced if abnormalities in at least 2 tests (serial PIIINP, TE, or FibroTest) re required before biopsy is considered. 1 patient with grade 3a portal fibrosis: normal FibroTest 12 months post-mtx 1 with 3b sinusoidal fibrosis: invalid TE

16 Meta-analysis P3P (most extensively validated method) Sensitivity 77.3%, specificity 91.5% PPV and NPV depend on prevalence fibrosis FibroTest Sensitivity 83%, specificity 61% Fibroscan Sensitivity 50%, specificity 88% Recommended all 3 in combination J Eur Acad Dermatol Venereol May;25 Suppl 2:12-8. doi: /j x.

17 More Recent Meta-analysis Sensitivity and specificity 74% and 77% for P3P 60% and 80% for Fibroscan 55% and 49% for ultrasound 38% and 83% for LFTs Overall quality of data poor BJD 2014 Jun;170(6): doi: /bjd

18 Emerging Tests Urine markers N-cadherin, inter-alpha-trypsin inhibitor heavy chain H4, haptoglobin and serotransferrin found in urine of psoriasis patients with high cumulative MTX dose Validation needed Toxicol Lett Aug 29;221(3):

19 Eur Acad Dermatol Venereol Apr 15. doi: /jdv [Epub ahead of print] Worldwide survey 481 dermatologists from 63 countries Almost all monitored CBC, LFTs and renal function tests P3P and transient elastography used by a minority Many stopped the drug at 2 gm and expressed concern about safety

20 British Consultant Dermatologists Almost all monitored CBC, LFTs, RFTs 71% now measure P3P 12% reported patients with irreversible liver damage 49 deaths 18 myelosuppression 6 pulmonary fibrosis 2 liver failure Br J Dermatol Apr;158(4):

21 Conclusions It s time to break the liver biopsy habit The question is how to do it LFTs aren t very good P3P, FibroSure, and Fibroscan are better New tests are being developed Don t forget the risks of myelosuppression and pulmonary fibrosis