Acta Dermato-Venereologica Issue 8, 2017 97-8CompleteContent | Page 15

952 SHORT COMMUNICATION Transient Elastography May Improve Detection of Liver Fibrosis in Psoriasis Patients Treated with Methotrexate Toomas TALME 1 , Pernilla NIKAMO 1 , Peter ROSENBERG 2# and Mona STÅHLE 1# 1 Department of Dermatology & Venereology, Karolinska University Hospital Solna, SE-171 76 Stockholm, and 2 Department of Gastroenterology and Hepatology, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden. E-mail: [email protected] # These authors contributed equally to the article. Accepted Apr 18, 2017; Epub ahead of print Apr 19, 2017 Methotrexate (MTX) can provide remission and is re- commended as first-line systemic therapy for psoriasis (1). However, despite reasonable efficacy, its use is res- tricted by concerns regarding the risk of developing liver fibrosis (2). Liver biopsy, which is considered the gold standard for assessment of fibrosis, is invasive and has become less accepted for monitoring liver injury during long-term treatment with MTX (3, 4). Several scoring systems based on laboratory parameters have therefore been created to identify liver fibrosis (5–7). Serial mo- nitoring of the amino terminal of type III procollagen peptide (PIIINP) is proposed as an alternative for liver biopsy (8, 9). Several studies have shown that transient elastography (TE) may be useful for monitoring patients treated with MTX (10, 11). We have identified several cases of advan- ced liver fibrosis confirmed with liver biopsies despite normal levels of PIIINP. The aim of this case-control study in a cohort of patients with psoriasis treated with MTX was to compare TE measurements with serological markers for liver fibrosis. MATERIALS AND METHODS Consecutive psoriasis patients ≥ 18 years old requiring systemic treatment were recruited prospectively between 2012 and 2015. The study was approved by the regional ethics committee (Dnr: 294/576-32). Patients with hepatitis were excluded. Patients on MTX were stratified into 2 groups: treatment ≤ 24 months (range 1–24 months) (n = 47) and treatment > 24 months (range 25–432 months) (n = 122). Patients receiving biologicals as single systemic treatment, who had received MTX for a maximum of 6 months >4 years ago, served as controls (n = 32). Most patients were treated with 10–20 mg MTX once weekly. Liver fibrosis evaluation Liver stiffness measurements were performed using FibroScan 502 (Echosens, Paris, France) (12). Most patients were examined with the M-probe, but for obese patients the XL probe was used. Ten validated TE measurements and interquartile range (IQR) < 30% of median liver stiffness were deemed reliable. We used 6.5 kilopascal (kPa) (5.5 kPa with the XL–probe) as a cut-off value for mild fibrosis (grade 1–2), and 11.5 kPa (10 kPa XL–probe) for severe fibrosis (grade 3–4) and cirrhosis (13). The following laboratory parameters were determined in blood: aspartate transaminase (AST) (laboratory reference < 0.76 µkat/l), and alanine transaminase (ALT) (< 1.20 µkat/l), platelet count (165–387 × 10 9 /l) and PIIINP (300–800 IU/l). AST/ALT > 0.8 ratio was used as a cut-off for possible liver fibrosis and a ratio > 1.0 indicating cirrhosis (5). The AST to Platelet Ratio Index (APRI) doi: 10.2340/00015555-2677 Acta Derm Venereol 2017; 97: 952–954 score was calculated as AST (IU/l)/(upper limit of normal)/ platelet count (×10 9 /l)×100. Values for APRI > 0.7 were used to predict fibrosis and >1.0 to predict cirrhosis (6). The Fibrosis-4 (FIB-4) score was calculated as age × AST (IU/l)/platelet count (× 10 9 /l) × √ALT (IU/l) and a score > 1.45 was used to predict fibrosis and >3.25 to predict cirrhosis (7). Statistical analysis Results are expressed as odds ratio (OR), with 95% confidence interval (95% CI) and corresponding p-values. Significance was set at p-values below 0.05. Comparisons of quantitative data were made using Student’s t-test. When data did not exhibit a normal distribution Kruskal–Wallis rank sum test was used for testing 3 groups and Wilcoxon rank sum test with continuity correction was used for testing 2 groups. Normal distribution was tested with Shapiro–Wilk test of normality. A χ 2 test was used to check for differences between groups. Statistical analyses of confounders were performed with GLM in R program v 3.1.3 (http://www.r- project.org/). RESULTS A total of 201 consecutive psoriasis patients were inclu- ded in this study (Fig. S1 1 ). Demographic and clinical characteristics of the study population are shown in Table SI 1 . There was no statistical difference in median liver stiffness between the 3 groups. Of those who received MTX > 24 months, 46 out of 122 patients (37.7%) had a liver stiffness indicating mild liver fibrosis, and 11 pa- tients (9.0%) indicating severe fibrosis. In patients who received MTX ≤ 24 months 15 out of 47 (31.9%) had a liver stiffness indicating mild fibrosis, and 3 (6.4%) in- dicating severe fibrosis. In the control group 12 out of 32 patients (37.5%) had a liver stiffness indicating mild liver fibrosis, and 1 (3.1%) indicating severe fibrosis (Table SI 1 ). Statistical analysis showed that a body mass index (BMI) >30 and diabetes were the strongest predictors for liver fibrosis (Table I). There was no statistical difference in median values for APRI, AST/ALT– ratio or FIB-4 between the 3 groups. In patients with TE measurements indicating advanced fibrosis APRI > 0.7 was seen in 20%, AST/ ALT-ratio > 1.0 in 46.7% and FIB-4 > 1.45 in 66.7% of these cases. PIIINP was measured in 36 out of 47 patients treated with MTX ≤ 24 months and in 120 out of 122 patients treated with MTX > 24 months. Six https://www.medicaljournals.se/acta/content/abstract/10.2340/00015555-2677 1 This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta Journal Compilation © 2017 Acta Dermato-Venereologica.