Significance of liver biopsy for the evaluation of methotrexate-induced liver damage in patients with rheumatoid arthritis

Abstract

It is well recognized that long-term administration of methotrexate (MTX) in patients with rheumatoid arthritis (RA) can induce liver fibrosis via a steatohepatitis-like inflammatory process. Several non-invasive tests have been investigated as alternatives to liver biopsy, which is, however, still recognized as a final diagnostic modality to detect the MTX-induced liver damage. To clarify whether there is a significant discrepancy between clinical estimations and pathologic findings of this hepatic condition, we performed a following comparative study. Four RA patients (4 women, age 67-80 yr) with MTX-induced liver damage were reviewed. The severity of hepatic damage estimated clinically was compared with histopathologic findings. Consequently, the liver biopsies showed the relatively earlier stages of and milder degrees of hepatic damages than the clinical estimations. The histopathologic findings were more reliable and useful than any other clinical examinations, to plan and modify the treatment strategies, especially in cases of liver damages with multiple etiologies besides MTX. These findings suggest that liver biopsy is an unavoidable examination to assess precisely MTX-induced liver damage. Non-invasive tests may be useful to monitor the hepatic condition of RA patients receiving MTX but do not constitute an acceptable alternative to liver biopsy.

Keywords: Methotrexate; biopsy; liver fibrosis; rheumatoid arthritis; steatohepatitis.

Figure 1

Computed tomography findings of the four cases. A. Case 1. Atrophy of liver, splenomegaly, and ascites suggest cirrhosis. B. Case 2. Findings almost identical with Case 1 suggest cirrhosis. C. Case 3. The low-density of liver indicates fatty change. D. Case 4. No significant change is seen in the liver.

Figure 2

Histological findings of liver biopsies of the four cases. A. Case 1. Faint steatosis, hepatocyte ballooning, portal inflammation, and bridging fibrosis (portal-to-portal) are seen, but regenerative nodules of cirrhosis are absent. B. Case 2. Findings are almost identical with Case 1. C. Case 3. Marked macrosteatosis, hepatocyte ballooning, portal and lobular inflammation, and perivenular fibrosis with bridging are seen. The findings are similar to alcoholic and nonalcoholic steatohepatitis. D. Case 4. Steatosis, hepatocyte ballooning, and bridging fibrosis are seen, but interface hepatitis is absent. These findings are not consistent with autoimmune hepatitis. (Upper rows, hematoxylin-eosin; lower rows, Azan-Mallory stain; original magnification, ×20).