The aminopyrine breath test, an inadequate early indicator of methotrexate-induced liver disease in patients with psoriasis.

The aminopyrine breath test has been shown to be a sensitive noninvasive indicator of liver cell dysfunction. In a search for a noninvasive method of monitoring the effects of methotrexate therapy, we have investigated the use of the aminopyrine breath test in patients receiving methotrexate for the treatment of severe psoriasis. The [14C]-aminopyrine breath test was performed in 20 normal control subjects, 32 patients with psoriasis receiving methotrexate therapy, and 8 patients with histologically confirmed cirrhosis of differing etiology. Eighteen patients on methotrexate had liver biopsies classified as grade I changes, 6 patients as grade II, and 8 patients as grade III. The normal value for the breath test was 11.0 +/- 1.6% (mean +/- 1 SD). The mean [14C]-CO2 excretion (8.3 +/- 4.4%) of the 8 patients with grade III liver disease was significantly different from the control subjects (p less than 0.02), and those with grade I liver changes (p less than 0.04). The aminopyrine breath test was only able to detect the later severe stages of methotrexate hepatotoxicity, grade III, when fibrosis occurs, before established cirrhosis was present. Our data suggests that the aminopyrine breath test is not a sensitive indicator for the detection of early methotrexate-induced hepatotoxicity, (stages I and II), but will detect the precirrhotic stage III change. Consequently, we recommend that a liver biopsy should be performed annually in all psoriatic patients receiving methotrexate, to detect histological damage, especially when the aminopyrine breath test score falls below the 95% confidence limits of normal.