“Given the prevalence of nonalcoholic fatty liver disease in patients with psoriasis, we propose that NASH FibroSure can be used as a stand-alone test to monitor the progression of hepatic fibrosis in patients with psoriasis receiving long-term methotrexate therapy." — Bruce Bauer, et al., JAMA Dermatology
Psoriasis patients who are on long-term methotrexate therapy are regularly screened for hepatic fibrosis, most often with a liver biopsy — sometimes multiple times.
Now, a new study in JAMA Dermatology raises the possibility of adopting the nonalcoholic steatohepatitis (NASH) FibroSure test to detect hepatic fibrosis in psoriasis patients, which may minimize the number of liver biopsies these patients need.
“Given the prevalence of nonalcoholic fatty liver disease in patients with psoriasis, we propose that NASH FibroSure can be used as a stand-alone test to monitor the progression of hepatic fibrosis in patients with psoriasis receiving long-term methotrexate therapy,” wrote Bruce Bauer, et al. in the October issue of JAMA Dermatology.
While there are a number of noninvasive tests used to monitor the risk of hepatic fibrosis in patients with nonalcoholic fatty liver disease, a diagnosis most often involves a liver biopsy — an invasive procedure prone to sampling errors and various interpretations by pathologists. While no alternative tests can replace the need for a liver biopsy, they could possibly reduce the number of needed biopsies.
Other tests that are used to monitor fibrosis in psoriasis patients receiving methotrexate therapy include a procollagen III amino terminal peptide, which is a serologic marker of collagen turnover. Or, panels of serum biomarkers and patient biometrics that are used to score the risk of hepatic fibrosis. In 2014, Lynch et al. reported in JAMA Dermatology that the combined use of procollagen III amino terminal peptide levels, transient elastography, and FibroTest/FibroSure could successfully be used to monitor methotrexate-induced hepatotoxic effects. NASH FibroSure is similar to FibroTest, but it was designed only for patients with nonalcoholic fatty liver disease.
The ultrasound test transient elastography measures liver stiffness. It is reported to have a high degree of sensitivity at 84.8% and specificity at 93.6% for the detection of fibrosis, but it has difficulty discerning mild from advanced fibrosis. However, with a failure rate of 50%, the test doesn’t work as well for patients with a BMI of 30 or higher.
NASH FibroSure differs in that it includes height and weight in the patient, thereby accounting for the contribution of BMI to the progression of steatosis to fibrosis. It has a sensitivity of 83% and a specificity of 78% in detecting the risk of significant fibrosis. It has a sensitivity of 71% and a specificity of 72% in flagging the risk of significant cant steatosis in patients with nonalcoholic fatty liver disease. The test employs 10 biochemical markers in combination with age, sex, height and weight.
The retrospective analysis in JAMA included 129 psoriasis patients who had at least one NASH FibroSure test during methotrexate treatment from January 2007 to December 2013. Of these, 69 patients (53.5%) had a baseline test before starting methotrexate, of whom 78.3% had elevated steatosis scores and 26.1% had elevated fibrosis scores.
Of the 107 patients who had a NASH FibroSure test conducted any time during therapy, there was a statistically significant association between the cumulative methotrexate dose and a higher NASH FibroSure hepatic fibrosis score in women, but not in men.
NASH FibroSure accounts for height and weight, including the contribution of the body mass index (BMI) in progressing steatosis to fibrosis. In this study, obesity was found to be significantly correlated to elevated fibrosis scores and cumulative methotrexate dose.
“To our knowledge, our study is the first to evaluate the utility of this test in monitoring the progression of fibrosis scores among patients with psoriasis with elevated BMI, including obesity,” the authors wrote.
In women, there was a statistically significant correlation between a BMI of at least 28 and worsening fibrosis scores. Conversely, there was no meaningful association between the combination of patients older than 65 years and worsening of hepatic fibrosis scores with cumulative MTX dose.
Despite the encouraging study results, the NASH FibroSure test is not a true measure of fibrosis, but rather a mathematical model to generate a risk score for hepatic fibrosis. Other than in two patients, liver biopsies and imaging were not performed in order to validate the fibrosis scores.
Because the study was retrospective, medication adherence could not be determined. But the authors advocate discontinuing methotrexate in males who exhibit deteriorating fibrosis scores.
Going forward, the authors would like a prospective, randomized, multi-institutional analysis of NASH FibroSure and liver biopsies in psoriasis patients who are receiving MTX compared to other treatments.
Bauer B, Chyou PH, Stratman EJ, Green C. “Noninvasive testing for nonalcoholic steatohepatitis and hepatic fibrosis in patients with psoriasis receiving long-term methotrexate sodium therapy,” JAMA Dermatology. Aug. 23, 2017. DOI:10.1001/jamadermatol.2017.2083