LAUSR

Monitoring methotrexate associated liver toxicity in patients with psoriasis is challenging due to the co-presence of non-alcoholic fatty liver disease (NAFLD) in an estimated 59% of all patients. NAFLD relates to the accumulation of fat in the liver and is a manifestation of metabolic syndrome. It can progress to non-alcoholic steatohepatitis (NASH). Liver dysfunction is monitored through liver transaminase tests, serum aminoterminal peptide of procollagen 3 (P3NP) and transient elastography. P3NP is a peptide released as a by-product of collagen synthesis and is an indirect marker of liver fibrosis. Transient elastography is a form of shear wave ultrasonography, endorsed by the Australasian Psoriasis Collaboration that measures liver stiffness. Liver biopsies are no longer routinely done. We reviewed the results of 4 years of monitoring of transient elastography from 2015 to 2019. Data collected included body mass index (BMI), P3NP, alanine transaminase (ALT), presence of co-morbidities (hypertension, diabetes and psoriatic arthritis), current and cumulative methotrexate doses, along with transient elastography scores. Scores were graded as normal (F0/F1 transient elastography = 0–7), mild fibrosis (F1/F2 transient elastography = 7.1–9), moderate fibrosis (F2/F3 transient elastography = 9.1–12) or severe fibrosis/cirrhosis (F4 transient elastography > 12). A valid transient elastography result required an interquartile range (IQR) not to exceed 30% of the median value. The success rate had to be at least 60%. All FibroScan tests were performed by the same nurse practitioner in accordance with the manufacturer’s standard operating procedure. The chi-square test or Fisher exact test was used to compare data, as appropriate. We used SPSS program version 20.0, and a P value < 0.05 was considered as significant. A total of 213 patients on methotrexate had transient elastography performed. Of these, 105 were being treated for psoriasis and 108 (50.7%) were being treated for other skin conditions, mostly atopic dermatitis; 38 (36.2%) had an invalid reading. Only 66 patients met criteria for inclusion within the study. Patient characteristics are summarised in Table 1, and comparative findings are summarised in Table 2. Just over half the 66 patients were female (51.5%). The mean weekly dose of methotrexate was 18.1 mg; mean cumulative dose 5.2 g; mean duration of therapy 72.5 months. Thirty-two (48.5%) patients had cumulative methotrexate dose >3.5 g. Only two patients underwent liver biopsy. Fifty-six per cent of patients had a normal transient elastography readings (F0/F1); 9.1% had mild fibrosis (F1/F2), 12.1% moderate fibrosis (F2/F3) and 22.7% had severe fibrosis/cirrhosis (F4). Two of the 15 patients with severe fibrosis (F4) had NASH liver cirrhosis (one diagnosed by liver biopsy and the other by liver ultrasound combined with laboratory studies); one had liver cirrhosis secondary to alcohol and haemochromatosis (diagnosed by liver biopsy); twelve had NAFLD. Review by gastroenterology showed no cases of cirrhosis primarily due to methotrexate. In total, 12 of 66 (18%) patients stopped methotrexate. P3NP levels were elevated (>4.2 μg/L) in 29 patients (43.9%). Four of 15 patients with severe fibrosis (F4) had normal P3NP levels. Nonetheless, an elevated P3NP (4.1 2 vs 5.2 1.9; P < 0.001) was associated with higher transient elastography scores. Transaminase (ALT) levels (normal range 0 45 u/L) were elevated in 20 (30.3%) patients, and was not statistically related to the transient elastography score. A higher BMI (30.3 5.6 vs 34.3 8.2; P = 0.026) and diabetes (5.4 vs 24.1%, P = 0.032) were associated with an