• APRI
• FIB-4
• Fibroscan®
• methotrexate
• psoriasis
• transient elastography

• Methotrexate (MeSH ID D008727)
• drug monitoring (MeSH ID D016903)
• drug-related side effects and adverse reactions (MeSH ID D064420)
• skin diseases (MeSH ID D012871)

The use of methotrexate-acitretin (MTX-ACI) combination therapy in treating psoriasis has been limited due to concerns related to hepatic fibrosis. However, in vitro evidence revealed a protective effect of acitretin in methotrexate (MTX)-induced liver fibrosis.

This study aimed to compare the real-life incidence of hepatic fibrosis in patients with psoriasis receiving MTX-ACI and MTX monotherapy and to investigate factors associated with hepatic fibrosis in MTX-exposed patients.

A retrospective cohort study was conducted based on a real-life registry containing data on patients with psoriasis who were administered MTX-ACI or MTX between 2008 and 2019 and underwent transient elastography according to cumulative MTX dose of 1.0–1.5 g and/or 3.5–4.0 g. Time-to-event analysis was performed to determine the cumulative incidence, incidence rate, and factors potentially affecting the occurrence of hepatic fibrosis.

Of the 160 patients, 32 (20%) were treated with MTX-ACI, and 128 (80%) with MTX alone. Four patients (12.5%) in MTX-ACI group and 21 (16.4%) in MTX group developed hepatic fibrosis (p = 0.59). There was no statistically significant difference in cumulative incidence (16% in MTX-ACI vs 17% in MTX, p = 0.89) and incidence rate (37 cases per 1000 person-year in MTX-ACI vs 23 cases per 1000 person-year in MTX; hazard ratio [HR] = 1.07; p = 0.90) of hepatic fibrosis between the two groups. Diabetes and obesity were identified as significant factors associated with hepatic fibrosis (adjusted HR = 2.40, 95% confidence interval [CI]: 1.05–5.51; p = 0.04 and adjusted HR = 3.28, 95% CI: 1.18–9.16; p = 0.02, respectively) regardless of the cumulative MTX dose.

The incidence of hepatic fibrosis in a real-life clinical situation, determined by transient elastography in patients with psoriasis receiving MTX-ACI, was not increased compared to those receiving MTX monotherapy. Type 2 diabetes mellitus and obesity were identified as risk factors of hepatic fibrosis; hence, patients with these factors receiving long-term MTX therapy should be regularly monitored for this particular event.

• cirrhosis
• combination therapy
• drug
• liver fibrosis
• liver injury
• non-alcoholic steatohepatitis

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide and its incidence is definitely increasing. NAFLD is a metabolic disease with extensive multi-organ involvement, whose extra-hepatic manifestations include type 2 diabetes mellitus, cardiovascular disease, obstructive sleep apnea, chronic kidney disease, osteoporosis, and polycystic ovarian syndrome. Recently, further evidence has given attention to pathological correlations not strictly related to metabolic disease, also incorporating in this broad spectrum of systemic involvement hypothyroidism, psoriasis, male sexual dysfunction, periodontitis, and urolithiasis. The most common cause of mortality in NAFLD is represented by cardiovascular disease, followed by liver-related complications. Therefore, clinicians should learn to screen and initiate treatment for these extra-hepatic manifestations, in order to provide appropriate multidisciplinary assessments and rigorous surveillance. This review evaluates the current evidence regarding extra-hepatic associations of NAFLD, focusing on the pathogenic hypothesis and the clinical implications.

• cardiovascular risk
• comorbidities
• metabolic syndrome
• nonalcoholic fatty liver disease

• Autoimmune Diseases/chemically induced
• Autoimmune Diseases/epidemiology
• Autoimmune Diseases/pathology
• Chemical and Drug Induced Liver Injury/epidemiology
• Chemical and Drug Induced Liver Injury/pathology
• Cyclosporine/adverse effects
• Cyclosporine/therapeutic use
• Humans
• Inflammation/chemically induced
• Inflammation/epidemiology
• Liver/drug effects
• Liver/pathology
• Liver Diseases/epidemiology
• Liver Diseases/pathology
• Methotrexate/adverse effects
• Methotrexate/therapeutic use
• Psoriasis/complications
• Psoriasis/drug therapy
• Psoriasis/epidemiology
• Psoriasis/pathology

Psoriasis is a chronic inflammatory immune-mediated skin diseases which is frequently associated to comorbidities. Non-alcoholic fatty liver disease (NAFLD) is defined as an excessive accumulation of triglycerides in hepatocytes and includes a wide spectrum of liver conditions ranging from relatively benign steatosis to non-alcoholic steatohepatitis with fatty infiltration and lobular inflammation and to cirrhosis and end-stage liver disease. Actually, psoriasis is considered a systemic diseases associated to comorbidities, as metabolic syndrome and NAFLD is seen the hepatic manifestation of the metabolic syndrome. The possible link between psoriasis, obesity and metabolic syndrome, which are known risk factors for NAFLD has been recently documented focusing in the crucial role of the adipose tissue in the development of the inflammatory background sharing by the above entities. According to recent data, patients with psoriasis show a greater prevalence of NAFLD and metabolic syndrome than the general population. Moreover, patients with NAFLD and psoriasis are at higher risk of severe liver fibrosis than those with NAFLD and without psoriasis. The link between these pathological conditions appears to be a chronic low-grade inflammatory status. The aim of this review is to focus on the multiple aspects linking NAFLD and psoriasis, only apparently far diseases.

• Psoriasis
• Non-alcoholic fatty liver disease
• Adipose tissue
• Adipocytokines
• Biologic therapies
• Non-biologic therapies

Psoriasis is a chronic multifactorial disease affecting 2–4% of the general population. Due to its nature, psoriasis has a negative impact on the quality of life of patients. Therefore, the choice of an appropriate and individually tailored treatment controlling the symptoms of the disorder is necessary and continues to be a challenge for dermatologists. Therapeutic modalities in psoriasis should on the one hand be effective and on the other hand present a good safety profile. Methotrexate (MTX) is one of treatment options for psoriasis and can be administered both as monotherapy or in combination schemes. The paper presents the current state of knowledge about the possible treatment of psoriatic patients with MTX according to contemporary guidelines.

• methotrexate
• psoriasis
• treatment