Rheumatoid Arthritis: Treatment [151-201]: 151. Should we be Looking More Carefully for Methotrexate Induced Liver Disease?

Background: UK guidelines and a `Rheumatology' editorial suggest that liver function tests (LFTs) alone remain a satisfactory method for methotrexate (MTX) monitoring in rheumatoid arthritis (RA). Recent literature also suggests no difference in hepatotoxity between MTX treated RA and psoriatic arthritis (PsA) patients. We describe 3 cases of liver fibrosis / cirrhosis missed by conventional monitoring. Methods: Case 1: 71 yr old female, RA 35 yrs. Presented 2005. Previous breast cancer. Alcohol < 1 unit/week. Rx MTX for 20 years, up to 25mg weekly. Leflunomide (Lef) 10 mg od added 3 mths previously. LFTs normal, P3NP 6.6. 2005-6 RA well controlled, normal LFTs. Repeat P3NP 2006 11.7. Liver ultrasound (US): normal echogenicity and hepatic and portal vein flow. Attempts to stop Lef were unsuccessful and led to use of rescue depomedrone. Developed diabetes. Sept 2007 LFTs normal, albumin 35. Feb 2008: admitted with ascites, ALT 41, albumin 31, bilirubin 24. CT liver normal, US suggested fatty change with normal portal flow. Biopsy showed established cirrhosis on a background of steatohepatitis. MTX and Lef stopped. June 2008: fatal pneumonia. Case 2: 69 yr old male. RA 2007; previous type II diabetes Rx insulin. On simvastatin. Alcohol < 1 unit/week. eGFR 60. LFTs normal. Rx MTX 12.5 mg/week + folic acid. July 2008 ALT 83: MTX ↓ 10 mg, Oct 2008 ALT 89: MTX ↓7.5 mg. Nov 2008 ALT 69. Dec 2008 - Aug 2009 ALT 70, 91, 67, 65, 52 (ie < x2 normal). Aug 2009 ALT 38, alb 27. Sept 2008 ALT 85, albumin 22, INR 1.7.US: shrunken liver. Full liver screen negative. Developed spontaneous bacterial peritonitis. Died Sept 2009. Results: Case 3: 63 yr old female, presented 1999. PsA diagnosed 1993, Rx MTX 7.5mg weekly. Alcohol < 1 unit/week. 1996 ‘routine’ liver biopsy performed (i.e. after 3 yrs MTX), result missing. 1997 US liver normal. Jan 1999: AST 69. Previous liver biopsy retrieved: steatosis + perivascular fibrosis. MTX stopped. LFTs normalized and remain normal. Conclusions: The risk of liver damage in some MTX treated RA and PsA patients may be higher than we think. Patients remain on MTX long term, may resume excess alcohol consumption and may develop concommitant non alcoholic fatty liver disease and steatohepatitis (NAFLD, NASH) during the course of their illness. Polypharmacy (case 1) and diabetes (cases 1 and 2) may be further risk factors. Normal LFTs and US may offer false reasurance. However, minor elevations of liver enzymes may point towards ongoing fibrosis (Case 2). P3NP is used in psoriasis but not in RA because of the confounding factors of disease activity and joint erosion. However, normal values may give some reassurance. US is unreliable as a guide to fibrosis, but more sensitive scans, including Fibroscan, offer promise. Our cases suggest that there may be at risk MTX treated RA and PsA patients who require more detailed liver monitoring. Disclosure statement: All authors have declared no conflicts of interest.