Psoriasis is a prevalent inflammatory disease that shares chronic inflammation pathways with the pathophysiology of metabolic syndrome (MetS), type-2 diabetes mellitus and atherosclerosis. A high prevalence of steatosis and advanced liver fibrosis has been described in psoriasis. The influence of MetS and its compounds, patatin-like phospholipase domain containing 3 and transmembrane 6 superfamily member 2 gene polymorphisms and the cumulative dose of methotrexate (MTX) in the progression of steatotic disease are still under debate. A suitable new classification for psoriasis-related liver disease, under the umbrella of steatotic liver disease (SLD), might be evaluated due to the potential impact of MTX on liver steatosis. Considering the interplay between the MetS, steatosis and MTX, a new definition for this complex disease might be discussed since it is not entirely addressed under the umbrella of SLD and metabolic-dysfunction associated SLD. Hence, shortly, a discussion could be raised on the feasible term "Met-Drug SLD", metabolic and drug-induced SLD, which comprises both metabolic dysfunction and drug-related SLD. This review aims to report the best evidence to accurately classify liver disease in psoriasis, considering the new definition of SLD, allowing appropriate management once it is carefully defined.

Background/Objectives: Psoriasis is a chronic immune-mediated skin disease associated with several metabolic comorbidities. Metabolic dysfunction-associated steatotic liver disease (MASLD) is also linked to psoriasis, but evidence regarding the severity of this association remains inconclusive. This meta-analysis aimed to investigate the relationship between MASLD and varying severities of psoriasis. Methods: We conducted an extensive search of four databases, MEDLINE, EMBASE, OSF, and ClinicalTrials.gov to identify relevant published articles assessing the risk of prevalent MASLD in patients with moderate-to-severe psoriasis up to April 2024. Effect estimates from each included study were combined together to calculate a pooled effect estimate for the meta-analysis using the generic inverse variance method of DerSimonian and Laird. Results: This meta-analysis included eight studies with a total of 109,806 participants. A 4.01-fold increased risk of prevalent MASLD was observed in patients with moderate-to-severe psoriasis compared to those without psoriasis (95% CI: 2.17, 7.77; I2 = 67%, p < 0.0001). The evidence supporting this outcome had low certainty. Conclusions: An incremental trend of MASLD was observed in patients with moderate-to-severe psoriasis. Routine screening for MASLD should be emphasized in this population.

Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide. In recent years, a new terminology and definition of metabolic dysfunction-associated fatty liver disease (MAFLD) has been proposed. Compared to the NAFLD definition, MAFLD better emphasizes the pathogenic role of metabolic dysfunction in the development and progression of this highly prevalent condition. Metabolic disorders, including overweight/obesity, type 2 diabetes mellitus (T2DM), atherogenic dyslipidemia and hypertension, are often associated with systemic organ dysfunctions, thereby suggesting that multiple organ damage can occur in MAFLD. Substantial epidemiological evidence indicates that MAFLD is not only associated with an increased risk of liver-related complications, but also increases the risk of developing several extra-hepatic diseases, including new-onset T2DM, adverse cardiovascular and renal outcomes, and some common endocrine diseases. We have summarized the current literature on the adverse effect of MAFLD on the development of multiple extrahepatic (cardiometabolic and endocrine) complications and examined the role of different metabolic pathways and organ systems in the progression of MAFLD, thus providing new insights into the role of MAFLD as a multisystem metabolic disorder. Our narrative review aimed to provide insights into potential mechanisms underlying the known associations between MAFLD and extrahepatic diseases, as part of MAFLD as a multisystem disease, in order to help focus areas for future drug development targeting not only liver disease but also the risk of extrahepatic complications.

Psoriasis was long regarded as an inflammatory disease limited to the skin. Data from dermatologic, rheumatologic and cardiologic research now show it to be a systemic disease, for which the term psoriatic disease is used.

This paper is based on a selective literature search with special attention to the findings of clinical trials and other current publications, as well as the recommendations of international guidelines.

Immunologically mediated inflammation of the skin, arteries, bones, and joints is a central feature of psoriatic disease. Other diseases that are known to be associated with psoriatic disease include hypertension, metabolic syndrome, and depression. The main risk factor for the development of psoriatic disease is obesity, which also increases the likelihood of psoriatic arthritis. The main known trigger factors are stress, infection, and, less commonly, medication. Psoriatic disease is characterized by complex genetics and by a characteristic pattern of inflammation that involves elements of both innate and acquired immunity and, in particular, the cytokines interleukin 17 and 23. The inflammatory processes underlying psoriatic disease can now be targeted with modern biologic and other therapies.

In view of the complexity of psoriatic disease, structured management is now recommended so that physicians and patients can work together to determine the optimal treatment strategy.

Epidemiological data demonstrate strong associations between psoriasis and metabolic comorbidities, including obesity, hypertension, diabetes mellitus, dyslipidemia, and non-alcoholic fatty liver disease. The presence of metabolic comorbidities significantly influences the selection and effectiveness of pharmacological treatments. Some drugs should be prescribed with caution in patients with metabolic comorbidities because of an increased risk of adverse events, while others could have a reduced effectiveness. The aim of this narrative review is to highlight the challenges that healthcare professionals may face regarding the management of psoriasis in patients with metabolic comorbidities. In the first part of the article, the epidemiological association between psoriasis and metabolic comorbidities and their pathogenetic mechanisms is summarized. The second part describes the efficacy and safety profile of conventional and biologic drugs in patients with selected metabolic comorbidities including obesity, non-alcoholic fatty liver disease/hepatic steatosis, and diabetes. Finally, the role of pharmacological and non-pharmacological interventions, such as diet, alcohol abstinence, physical activity, and smoking avoidance is discussed. In conclusion, the choice of the best approach to manage patients with psoriasis with metabolic comorbidities should encompass both tailored pharmacological and individualized non-pharmacological interventions.

Patients with immune-mediated inflammatory diseases are prone to steatotic liver disease (SLD), which has been observed in patients with psoriasis and hidradenitis suppurativa. We aimed to assess whether systemic lupus erythematosus (SLE) was associated with SLD and to define factors associated with SLD in SLE. This was a cross-sectional study, we included 106 consecutive patients with SLE who were seen in the rheumatology clinic between June 2021 and March 2022 and we chose two sex-paired controls for each SLE. All the participants underwent FibroScan and anthropometric assessments. SLD was defined as a controlled attenuation parameter ≥ 275dB/m. Prevalence of SLD was lower in patients with SLE (21.7% vs 41.5%, p < 0.001). Patients with SLE and SLD had a lower frequency of hydroxychloroquine use (65% vs 84%, p = 0.04), and higher C3 levels [123mg/dl (IQR 102-136) vs 99mg/dl (IQR 78-121), p = 0.004]. Factors associated with SLD in SLE were body mass index (BMI), waist circumference, glucose, and C3; hydroxychloroquine use was a protective factor. On univariate analysis, SLE was associated with a reduced risk of SLD (OR 0.39, 95%CI 0.23-0.67); however, after adjusting for age, BMI, waist, glucose, triglycerides, high-density cholesterol, low-density cholesterol, leukocytes, and hydroxychloroquine, it was no longer associated (OR 0.43, 95%CI 0.10-1.91). In conclusion, the prevalence of SLD in patients with SLE was not higher than that in the general population, and SLE was not associated with SLD. The factors associated with SLD were anthropometric data, glucose, hydroxychloroquine, and C3 levels.

Psoriasis, a prevalent chronic inflammatory skin disorder affecting 2-3% of the global population, has transcended its dermatological confines, revealing a profound association with cardiovascular diseases (CVD). This comprehensive review explores the intricate interplay between psoriasis and cardiovascular system, delving into genetic links, immune pathways, and adipose tissue dysfunction beyond conventional CVD risk factors. The pathophysiological connections unveil unique signatures, distinct from other inflammatory skin conditions, in particular psoriasis-specific genetic polymorphisms in IL-23 and TNF-α have consistently been linked to CVD. The review navigates the complex landscape of psoriasis treatments, addressing challenges and future directions in particular relevance to CVDs in psoriasis. Therapeutic interventions, including TNF inhibitors (TNFi), present promise in reducing cardiovascular risks, and methotrexate could constitute a favourable choice. Conversely, the relationship between IL-12/23 inhibitors and cardiovascular risk remains uncertain, while recent evidence indicates that Janus kinase inhibitors may not carry CVD risks. Emerging evidence supports the safety and efficacy of IL-17 and IL-23 inhibitors in patients with CVDs, hinting at evolving therapeutic paradigms. Lifestyle modifications, statins, and emerging therapies offer preventive strategies. Dedicated screening guidelines for CVD risk assessment in psoriasis are however lacking. Further, the impact of different disease phenotypes and treatment hierarchies in cardiovascular outcomes remains elusive, demanding ongoing research at the intersection of dermatology, rheumatology, and cardiology. In conclusion, unraveling the intricate connections between psoriasis and CVD provides a foundation for a holistic approach to patient care. Collaboration between specialties, advancements in screening methodologies, and a nuanced understanding of treatment impacts are essential for comprehensive cardiovascular risk management in individuals with psoriasis.

This systematic review and meta-analysis aimed to report the evaluation of the prevalence and risk of nonalcoholic fatty liver disease (NAFLD) among adult psoriatic patients in a systematic review and meta-analysis.

A comprehensive search was conducted across 4 databases of PubMed, Scopus, Cochrane Library, and Web of Science to collect relevant studies until November 30, 2023, without any restrictions for finding observational studies. The comprehensive meta-analysis version 3.0 software was used to calculate effect sizes, showing the event rate (ER), odds ratio (OR), and a 95% confidence interval (CI) to evaluate NAFLD risk or prevalence in psoriatic patients and controls or psoriatic patients alone. The quality scoring was performed by 1 author based on the Newcastle-Ottawa Scale tool. Publication bias, meta-regression analysis, and sensitivity analyses were performed. Additionally, Trial Sequential Analysis (TSA) was performed using TSA software.

A total of 581 records were identified among the databases and electronic sources. At last, 41 studies involving 607,781 individuals were included in the meta-analysis. The pooled ER of NAFLD among psoriatic patients was 29.5% (95%CI: 19.6%-41.7%) and I2 = 99.79%. The pooled OR of NAFLD in psoriatic patients compared to controls was 1.685 (95%CI: 1.382-2.055; P < .001) and I2 = 87.96%.

The study found a significant link between psoriasis and NAFLD, with psoriatic patients having a higher chance of developing NAFLD compared to the controls. The study calls for regular NAFLD screening in psoriatic patients to prevent liver complications.

There is an urgent need for noninvasive tests to identify patients with psoriasis at risk of significant liver fibrosis.

To externally validate the ability of the Steatosis-Associated Fibrosis Estimator (SAFE) score to detect significant liver fibrosis in patients with psoriasis using transient elastography (TE) as a reference.

We analysed data from 75 patients with psoriasis, including TE, SAFE score, Fibrosis-4 Index (FIB-4) and Nonalcoholic Fatty Liver Disease Fibrosis Score (NFS). Significant liver fibrosis was defined as TE values ≥ 7.1 kPa. Diagnostic accuracy was assessed using the area under the receiver operating characteristic curve (AUROC).

Fifteen patients (20%) exhibited significant liver fibrosis. The AUROCs for the SAFE and FIB-4 scores were 0.82 [95% confidence interval (CI) 0.67-0.97] and 0.62 (95% CI 0.45-0.79), respectively. The SAFE score outperformed the FIB-4 Index (P = 0.01) but was comparable with the NFS (P = 0.05) in predicting significant fibrosis. Using thresholds of < 0, 0 to < 100 and ≥ 100, the SAFE score categorized 36, 24 and 15 patients into low, intermediate and high-risk groups for significant fibrosis, respectively. The negative predictive value for excluding significant fibrosis with a SAFE score of < 0 was 94.4%, and the positive predictive value for diagnosing significant fibrosis with a SAFE score of > 100 was 53.3%. The duration of psoriasis, joint involvement and methotrexate treatment did not affect the diagnostic ability of the SAFE score whereas age of the patient did.

The SAFE score demonstrated good accuracy in assessing clinically significant fibrosis among patients with psoriasis. This score should prove valuable for risk stratification and patient management in dermatology practice.

Psoriasis is a chronic, immune-mediated, inflammatory disease that has a major impact on patients' quality of life. Common psoriasis-associated comorbidities include cardiovascular diseases, psoriatic arthritis, inflammatory bowel syndromes, type-2 diabetes, and metabolic syndrome. Nonalcoholic fatty liver disease (NAFLD) is affecting a substantial portion of the population and is closely linked with psoriasis. The interplay involves low-grade chronic inflammation, insulin resistance, and genetic factors. The review presents the pathophysiological connections between psoriasis and nonalcoholic fatty liver disease, emphasizing the role of cytokines, adipokines, and inflammatory cascades. The "hepato-dermal axis" is introduced, highlighting how psoriatic inflammation potentiates hepatic inflammation and vice versa. According to the new guidelines, the preliminary examination for individuals with psoriasis should encompass evaluations of transaminase levels and ultrasound scans as part of the initial assessment for this cohort. Considering the interplay, recent guidelines recommend screening for NAFLD in moderate-to-severe psoriasis cases. Treatment implications arise, particularly with medications impacting liver function. Understanding the intricate relationship between psoriasis and NAFLD provides valuable insights into shared pathogenetic mechanisms. This knowledge has significant clinical implications, guiding screening practices, treatment decisions, and the development of future therapeutic approaches for these chronic conditions.

Psoriasis is a frequent form of chronic inflammation in dermatology that is unmistakably linked to the metabolic syndrome (MetS) and its elements. This study was to explore the current status and new developments in the global research, and the holistic landscape of this field more intuitively through bibliometric analysis of scientific output and activity.

Publications regarding psoriasis and MetS were searched and chosen from the database of the Web of Science Core Collection. Excel 2019, VOSviewer, and CiteSpace software were utilized to conduct bibliometric analysis.

There were 1096 publications included. The scientific outputs in this field had increased from 2004 to 2022, and the expansion could continue in the following years. The United States contributed the most publications (241, 21.99%) and had the most citation frequency (13,489 times). The University of California System was the most productive affiliation. Girolomoni G., Armstrong A.W., Gisondi P. and Gelfand J.M. were key and influential researchers. Journal of the European Academy of Dermatology and Venereology published the greatest number of articles (65 articles). By analyzing keyword frequency and clustering, we have identified the following areas of research interest and frontiers: prevalence, risk, association, gene expression, waist circumference, adipose tissue inflammation, vascular inflammation, cardiovascular disease, psoriatic arthritis, and fibrosis.

This bibliometric analysis elucidates research domain of psoriasis and MetS, portraying present hotspots and future emerging trends. This field has generated significant interest and displays potential for further growth. The United States has made distinguished contributions, and currently dominates this field.

Cardiovascular comorbidity is a common companion of psoriasis and psoriatic arthritis (PsA). Recently, a significant link has been found between the HLA-Cw6 allele and a better cardiometabolic profile in these patients. We aimed to check this finding in our setting.

A cross-sectional observational study (n: 572 psoriasis patients, 30% with PsA) was conducted. Different study variables were collected in detail, as well as classic cardiometabolic risk factors. The distribution of the HLA-Cw6 allele and the IFIH1/MDA5 gene variants previously linked to disease risk were determined in the study cohort and stratified according to the cardiometabolic comorbidity. Linear and logistic regression models were constructed to analyze these associations.

The study cohort included 309 men and 263 women, with a mean age of 46.7 years (SD 14.5) and a mean disease duration of 19.4 years (SD 14.8). We confirmed the known association between HLA-Cw6 and type I psoriasis (familial, severe, and early onset). Psoriasis severity (OR: 2.14), female sex (OR: 1.63), and the IFIH1/MDA5 rs1990760 TT genotype (OR: 1.62) were significantly related to PsA, while HLA-Cw6 was protective (OR: 0.65). HLA-Cw6 carriers showed a lower waist perimeter, lower BMI, and lower risk of both hypertension (OR: 0.52, p < 0.001) and diabetes (OR: 0.36, p < 0.001), but these findings were no longer apparent upon adjusting the regression models. No IFIH1/MDA5 gene variant was associated with any cardiometabolic risk factor.

The influence of HLA-Cw6 on the cardiometabolic risk profile of psoriatic patients seems to be explained by other factors (age, sex, duration of the disease or arthritis) and not by this biomarker itself.

Psoriasis is a chronic disease of the skin with a prevalence of 2% in the general population. The high prevalence of psoriasis has prompted the study of its comorbidities in recent decades. We designed a study to determine the prevalence of psoriasis in a large-scale, population-based cohort, to exhaustively describe its comorbidities, and to analyze which diseases are associated with psoriasis.

Retrospective, observational study based on the clinical information contained in the electronic health records of the individuals in the EpiChron Cohort with a diagnosis of psoriasis (31,178 individuals) in 2019. We used logistic regression models and calculated the likelihood of the occurrence of each comorbidity based on the presence of psoriasis (p-value < 0.05).

The prevalence of psoriasis was 2.84%, and it was more prevalent in men (3.31% vs. 2.43%). The most frequent chronic comorbidities were disorders of lipid metabolism (35.87%), hypertension (35.50%), and other nutritional-endocrine-metabolic disorders (21.79%). The conditions most associated with psoriasis were (odds ratio; 95% confidence interval) tuberculosis (2.36; 1.24-4.49), cystic fibrosis (2.15; 1.25-3.69), amongst others. We did not find a significant association between psoriasis and hypertension or neoplasms (0.90; 0.86-0.95).

This study revealed significant associations between psoriasis and cardiac, psychological, and musculoskeletal comorbidities.

The prevalence of fibrosis and steatosis in patients with psoriasis, as determined by vibration-controlled transient elastography (VCTE), has not been evaluated in Turkiye to date. The present cross-sectional study aims to present the first systematic screening results, focusing on two primary objectives: 1) establishing the prevalence of fibrosis and steatosis, and 2) identifying independent predictors for liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) values in this patient population.

Patients were eligible for inclusion if they had a confirmed diagnosis of psoriasis by a qualified dermatologist based on characteristic signs and symptoms and histopathological examination, and had undergone VCTE for LSM and CAP measurements.

The diagnosis of severe fibrosis and cirrhosis - identified by LSM values of 10.0-13.9 and ≥14.0 kPa, respectively - was significantly prevalent (7.0% and 10.1%, respectively) among a sizeable cohort of relatively young Turkish patients with psoriasis (n=328; mean age: 49.5±12.7 years). Additionally, severe steatosis, as diagnosed by VCTE and characterized by a CAP value exceeding 290 dB/m, was identified in up to 43.3% of patients. Although body mass index (BMI) was the only variable found to be an independently associated with LSM, multivariable linear regression analysis failed to identify any statistically independent predictor of CAP values.

The prevalence of hepatic fibrosis and steatosis in Turkish patients with psoriasis is far from negligible, with BMI identified as an independent risk factor for fibrosis.

Psoriasis is an immune-mediated disease with a strong genetic component that brings many challenges to sick individuals, such as chronic illness, and which has multiple associated comorbidities like cardiovascular disease, metabolic syndrome, inflammatory bowel disease, and psychological disorders. Understanding the interplay between the innate and adaptative immune system has led to the discovery of specific cytokine circuits (Tumor Necrosis Factor-alpha (TNF-α), IL-23, IL-17), which has allowed scientists to discover new biomarkers that can be used as predictors of treatment response and pave the way for personalized treatments. In this review, we describe the footprint psoriasis leaves on the skin and beyond, key pathophysiological mechanisms, current available therapeutic options, and drawbacks faced by existing therapies, and we anticipate potential future perspectives that may improve the quality of life of affected individuals.

Non-alcoholic fatty liver disease (NAFLD) is a common concomitant condition in patients with inflammatory bowel disease (IBD). We aim to assess the magnitude of this association.

We searched MEDLINE, EMBASE and Scopus libraries for the period up to February 2023 to identify studies reporting cohorts of IBD patients in which NALFLD was evaluated.

Eighty-nine studies were analyzed. The overall prevalence of NAFLD was 24.4% (95%CI, 19.3-29.8) in IBD, 20.2% (18.3-22.3) in Crohn's disease and 18.5% (16.4-20.8) for ulcerative colitis. Higher prevalence was found in male compared to female patients, in full papers compared to abstracts, and in cross-sectional studies compared to prospective and retrospective ones. The prevalence of NAFLD in IBD has increased in studies published from 2015 onwards: 23.2% (21.5-24.9) vs. 17.8% (13.2-22.9). Diagnostic methods for NAFLD determined prevalence figures, being highest in patients assessed by controlled attenuation parameter (38.8%; 33.1-44.7) compared to ultrasonography (28.5%; 23.1-34.2) or other methods. The overall prevalence of fibrosis was 16.7% (12.2-21.7) but varied greatly according to the measurement method.

One-quarter of patients with IBD might present with NAFLD worldwide. This proportion was higher in recent studies and in those that used current diagnostic methods.

There are no published studies on the prevalence of non-alcoholic fatty liver disease (NAFLD) in patients with atopic dermatitis (AD).

To estimate the prevalence of NAFLD (assessed via liver ultrasonography) in adults with moderate-to-severe AD.

We performed a retrospective, cross-sectional, observational study including adult patients affected by moderate-to-severe AD, moderate-to-severe chronic plaque psoriasis, or a previous diagnosis of thin melanoma in situ (considered as the control group) who attended the Verona University Hospital between January 2022 and April 2023. Fatty liver was assessed via liver ultrasonography.

A total of 144 adults with AD, 466 with chronic plaque psoriasis, and 99 with thin melanoma were included. The prevalence rates of ultrasound-detected NAFLD among patients with in situ melanoma, those with moderate-to-severe AD, and those with moderate-to-severe chronic plaque psoriasis were 23.2% (23 out of 99), 24.1% (36 out of 144), and 49.8% (228 out of 466), respectively (p < 0.01). Logistic regression analysis revealed that being of male sex, a higher age, a higher body mass index, and psoriasis were independently associated with NAFLD, whereas AD was not.

Our findings show that the prevalence of ultrasound-detected NAFLD in patients with moderate-to-severe AD was comparable to that of patients with a previous diagnosis of in situ melanoma. It is plausible to hypothesize that the Th2-type inflammation typically characterizing AD is not a risk factor for NAFLD. Patients with moderate-to-severe psoriasis, but not those with AD, should be screened for NAFLD and other metabolic comorbidities.

Psoriasis is an important issue in daily dermatological practice. Not only is it an aesthetic defect but it is also a matter of decreased life quality and economic burden. However frequent, the pathogenesis of psoriasis remains uncertain despite numerous investigations. Gasdermins are a family of six proteins. Gasdermin D (GSDMD) is the best-studied from this group and is involved in the processes of inflammation, proliferation, and death of cells, especially pyroptosis. GSDMD has never been studied in psoriatic sera or urine before. Our study involved 60 patients with psoriasis and 30 volunteers without dermatoses as controls. Serum and urinary GSDMD concentrations were examined by ELISA. The tissue expression of GSDMD was assessed by immunohistochemistry. The serum-GSDMD concentration was insignificantly higher in the patients than controls. There were no differences in the urinary-GSDMD concentrations between the patients and controls. Strong tissue expression of GSDMD was significantly more prevalent in psoriatic plaque than in the non-lesional skin and healthy skin of the controls. There was no correlation between the serum-GSDMD concentrations and the psoriasis severity in PASI, age, or disease duration. Taking into consideration the documented role of gasdermins in cell proliferation and death, the increased expression of GSDMD in psoriatic skin may demonstrate the potential involvement of this protein in psoriasis pathogenesis. Neither serum, nor urinary GSDMD can be currently considered a psoriasis biomarker; however, future studies may change this perspective.

Clinical studies have suggested a bidirectional association between non-alcoholic steatohepatitis (NASH) and psoriasis, affecting each other's development and severity. Here, we explored bidirectional causal linkages between NASH and psoriasis using a murine model.

NASH was induced in mice by streptozotocin injection at 2 days of age and by high-fat diet feeding (STAM™ model). Psoriasis was induced by topical application of imiquimod (IMQ) on the ear. The severities of liver damage and psoriatic skin changes were determined using histological analysis. Gene expression in the skin tissues was evaluated using quantitative PCR analysis. Serum cytokine levels were determined using enzyme-linked immunosorbent assay. To examine the innate immune responses of normal human epidermal keratinocytes (NHEKs), the cells were treated with interleukin (IL)-17A, tumor necrosis factor (TNF)-α, and AdipoRon, an adiponectin receptor agonist.

There were no differences in the degree of liver tissue damage (fat deposition, inflammation, and fibrosis) between NASH mice with and those without psoriasis. Conversely, the co-occurrence of NASH significantly augmented psoriatic skin changes, represented by epidermal hyperplasia, in psoriatic mice. Pro-inflammatory cytokines were expressed in the inflamed skin of psoriatic mice, and the expression of genes, especially Il23a, Il1b, Il36g, and Mip2, was significantly upregulated by the co-occurrence of NASH. The expression of keratinocyte activation marker genes Defb4b and Krt16 was also upregulated by the co-occurrence of NASH. The serum TNF-α and IL-17 levels were increased by the co-occurrence of NASH and psoriasis. The serum adiponectin levels decreased in NASH mice compared with that in non-NASH mice. In NHEK culture, TNF-α and IL-17A synergistically upregulated CXCL1, CXCL8, and IL1B expression. The upregulated pro-inflammatory gene expression was suppressed by AdipoRon treatment, reflecting the anti-inflammatory capacity of adiponectin.

The co-occurrence of NASH exacerbated psoriatic skin changes associated with increased serum inflammatory cytokine levels and decreased serum adiponectin levels. Combined with in vitro findings, increased inflammatory cytokine levels and decreased adiponectin levels likely promote innate immune responses in epidermal keratinocytes in psoriatic skin lesions. Overall, therapeutic intervention for co-occurring NASH is essential to achieve a favorable prognosis of psoriasis in clinical practice.

Psoriatic disease (PD) and non-alcoholic fatty liver disease (NAFLD) potentially share disease pathways given the numerous inflammatory pathways involved in both diseases and a higher prevalence of NAFLD in PD patients.  Metabolic syndrome and obesity are a key link between the two diseases, but even when controlling for this, associations between both diseases are still seen. Therapeutics that impact metabolic or inflammatory pathways may be impactful in both PD and NAFLD. In this review, we describe common inflammatory pathways contributing to both PD and NAFLD and critically review the potential impact of treatments for and on both diseases.

NAFLD has become a major public health problem for more than 2 decades with a growing prevalence in parallel with the epidemic of obesity and type 2 diabetes (T2D). The disease burden of NAFLD differs across geographical regions and ethnicities. Variations in prevalence of metabolic diseases, extent of urban-rural divide, dietary habits, lifestyles, and the prevalence of NAFLD risk and protective alleles can contribute to such differences. The rise in NAFLD has led to a remarkable increase in the number of cases of cirrhosis, hepatocellular carcinoma, hepatic decompensation, and liver-related mortality related to NAFLD. Moreover, NAFLD is associated with multiple extrahepatic manifestations. Most of them are risk factors for the progression of liver fibrosis and thus worsen the prognosis of NAFLD. All these comorbidities and complications affect the quality of life in subjects with NAFLD. Given the huge and growing size of the population with NAFLD, it is expected that patients, healthcare systems, and the economy will suffer from the ongoing burden related to NAFLD. In this review, we examine the disease burden of NAFLD across geographical areas and ethnicities, together with the distribution of some well-known genetic variants for NAFLD. We also describe some special populations including patients with T2D, lean patients, the pediatric population, and patients with concomitant liver diseases. We discuss extrahepatic outcomes, patient-reported outcomes, and economic burden related to NAFLD.

Advanced glycation end products (AGEs) are biologically active compounds formed physiologically throughout a sequence of chemical reactions, to generate highly oxidant-reactive aldehydes that combine covalently to proteins. They accumulate slowly in tissues during ageing but also in metabolic and selected inflammatory disorders. Accumulation of AGEs occurs more rapidly and intensely in the skin and serum of patients with type 2 diabetes, obesity, cardiovascular diseases, chronic renal insufficiency, and non-alcoholic fatty liver disease and also in the skin of patients with psoriasis. All of the above conditions are intimately associated with psoriasis. Interaction of AGEs with their receptors (RAGEs) stimulates cellular signaling with the formation of reactive oxygen species and activation of nuclear factor kappa light chain enhancer of activated B (NF-kB), which is a key regulator in the expression of inflammatory mediators and the production of oxidative stress. Thus, AGEs may play an interesting pathogenic role in the intersection of inflammatory and metabolic diseases, may represent a biomarker of inflammation and a potential target for novel therapeutic strategies. This is a narrative review with the objective to summarize current evidence on the role of AGEs in psoriasis.

Nonalcoholic fatty liver disease (NAFLD), affecting about 25% of general population and more than 50% of dysmetabolic patients, is an emerging cause of chronic liver disease and its complications. Recently, an international consensus of experts proposed to rename this disease as 'Metabolic dysfunction-Associated Fatty Liver Disease' (MAFLD) to focus on the bidirectional interplay between fatty liver and metabolic alterations and to stress the need of assessing fatty liver independently from alcohol consumption and other coexisting causes of liver disease. The peculiarity of NAFLD/MAFLD lies in the presence of a higher risk of not only - as expected - liver-related events but also of extrahepatic events, mostly cardiovascular and cancers. Available evidence suggests that these associations are not only the expression of sharing the same risk factors but shed light about the ability of NAFLD/MAFLD and particularly of its progressive form - nonalcoholic/metabolic dysfunction-associated steatohepatitis - to act as an independent risk factor via promotion of atherogenic dyslipidemia and a proinflammatory, profibrogenic, and procoagulant systemic environment. The present review summarizes available epidemiological and clinical evidence supporting the concept of NAFLD/MAFLD as a multisystemic disease, and highlights potential explanatory mechanisms underlying the association between NAFLD/MAFLD and extrahepatic disorders.

Patients with psoriasis are more likely than matched controls in the general population to have advanced liver fibrosis; however, our understanding of these patients is limited. There is currently no systematic evaluation of the prevalence and risk factors of liver fibrosis in psoriasis patients.

To evaluate the prevalence of psoriasis patients who are at high or low risk for advanced liver fibrosis and determine the risk factors for developing liver fibrosis.

Electronic searches were conducted using the PubMed, Embase, Scopus, and Cochrane Library databases from the dates of their inception till May 2022, using the PubMed, Embase, Scopus, and Cochrane Library databases. Any observational study describing the prevalence and/or risk factors for liver fibrosis in patients with psoriasis was included.

Patients with psoriasis at high risk for advanced liver fibrosis had a pooled prevalence of 9.66% [95% confidence interval (CI): 6.92-12.75%, I ² = 76.34%], whereas patients at low risk for advanced liver fibrosis had a pooled prevalence of 77.79% (95% CI: 73.23-82.05%, I ² = 85.72%). Studies that recruited methotrexate (MTX)-naïve patients found a lower prevalence of advanced liver fibrosis (4.44, 95% CI: 1.17-9.22%, I ² = 59.34%) than those that recruited MTX-user cohorts (12.25, 95% CI: 6.02-20.08%, I ² = 82.34%). Age, sex, BMI, PASI score, psoriasis duration, MTX cumulative dose, and the prevalence of obesity, MTX users, diabetes mellitus, hypertension, dyslipidemia, and metabolic syndrome were not identified as sources of heterogeneity by meta-regression analysis. The pooled odds ratios for age >50 years, BMI > 30, diabetes mellitus, hypertension, dyslipidemia, and metabolic syndrome were 2.20 (95% CI: 1.42-3.40, I ² = 0%), 3.67 (95% CI: 2.37-5.68, I ² = 48.8%), 6.23 (95% CI: 4.39-8.84, I ² = 42.4%), 2.82 (95% CI: 1.68-4.74, I ² = 0%), 3.08 (95% CI: 1.90-4.98, I ² = 0%), and 5.98 (95% CI: 3.63-9.83, I ² = 17%), respectively.

Approximately 10% of the population with psoriasis is at high risk for advanced liver fibrosis, while 78% are at low risk. Patients over the age of 50 with obesity, diabetes, hypertension, dyslipidemia, and/or metabolic syndrome have an increased risk of developing liver fibrosis, necessitating monitoring.

[https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022303886], identifier [CRD42022303886].

To date, evidences with high evidence-level evaluating the association between liver diseases and hidradenitis suppurativa was lacking. Given that inconsistency exists in some of the previous observational studies, evaluating the prevalence of liver diseases in HS patients could potentially serve as a reference of future guidelines for HS comorbidity screening. The aim of the current study was to evaluate potential association between hidradenitis suppurativa and liver diseases and provide integrated evidences.

A search in PubMed, Web of Science and Embase based on the syntaxes ''hidradenitis suppurativa'' or ''acne inversa'' with "comorbidities", "liver diseases", "fatty liver" or "hepatitis" was performed. Observational studies evaluating epidemiological association between hidradenitis suppurativa and the risk of all liver diseases, including specific diseases as non-alcoholic fatty liver disease, hepatitis B, hepatitis C were targeted to be extracted in this systematic review and meta-analysis.

Within the initial 702 records, there were finally 8 real-world observational studies extracted. Results suggest that patients with HS are associated with all liver diseases (OR= 1.50; 95% CI, 1.27, 1.76), non-alcoholic fatty liver disease (OR= 1.78; 95% CI, 1.28, 2.48) and hepatitis B (OR=1.48; 95% CI, 1.12, 1.94), but not hepatitis C (OR= 1.27; 95% CI, 0.78, 2.07). HS patients were associated with significantly increased risk of liver diseases, especially the risk of non-alcoholic fatty liver disease and hepatitis B.

Clinicians should be alert to the clinical relationship while caring people with hidradenitis suppurativa and the screening of liver function should be recommended to HS patients.

https://www.crd.york.ac.uk/prospero/, identifier CRD42022296034.

Liver disease is one of the most important causes of morbidity and mortality worldwide whose prevalence is dramatically increasing. The first sign of hepatic damage is inflammation which could be accompanied by the accumulation of fat called non-alcoholic fatty liver disease (NAFLD), causing damage in the hepatocytes. This stage can progress to fibrosis where the accumulation of fibrotic tissue replaces healthy tissue reducing liver function. The next stage is cirrhosis, a late phase of fibrosis where a high percentage of liver tissue has been replaced by fibrotic tissue and liver functionality is substantially impaired. There is a close interplay of cardiovascular disease (CVD) and hepatic alterations, where different mechanisms mediating this relation between the liver and systemic vasculature have been described. In chronic inflammatory diseases such as rheumatoid arthritis (RA) and psoriatic arthritis (PsA), in which the CVD risk is high, hepatic alterations seem to be more prevalent compared to the general population and other rheumatic disorders. The pathogenic mechanisms involved in the development of this comorbidity are still unraveled, although chronic inflammation, autoimmunity, treatments, and metabolic deregulation seem to have an important role. In this review, we will discuss the involvement of liver disease in the cardiovascular risk associated with inflammatory arthritis, the pathogenic mechanisms, and the recognized factors involved. Likewise, monitoring of the liver disease risk in routine clinical practice through both, classical and novel techniques and indexes will be exposed. Finally, we will examine the latest controversies that have been raised about the effects of the current therapies used to control the inflammation in RA and PsA, in the liver damage of those patients, such as methotrexate, leflunomide or biologics.

Psoriasis patients are at increased risk of harmful alcohol use and alcohol dependency with many deleterious effects. Increasing alcohol use is associated with worsening psoriasis severity, is a risk factor for poor response to systemic treatments and may impact on comorbidities such as psoriatic arthritis, cardiovascular disease, cancer and liver disease. Harmful alcohol use and alcohol dependency can be defined by the updated ICD-11 coding system and screening can be completed using many tools including the Cut down, Annoyed, Guilty, Eye-Opener (CAGE), Alcohol Use Disorders Identification Test (AUDIT) and Michigan Alcohol Screening Test (MAST) questionnaires. Dermatologists may be able to complete brief interventions encouraging alcohol reduction in psoriasis patients. Psoriasis patients may respond to messages of gain with reduced psoriasis severity and loss with reduced cardiovascular risk. It is important for dermatologists to discuss alcohol with all psoriasis patients, to be aware of the impact of alcohol in psoriasis and to familiarise themselves with screening tools, brief intervention and local services available to patients who require specialist input for harmful alcohol use or alcohol dependency.

Fibrosis is the only histological feature reflecting the severity and prognosis of nonalcoholic steatohepatitis (NASH). We aim to explore novel genes associated with fibrosis progression in NASH.

Two human RNA-seq datasets were downloaded from the public database. Weighted gene co-expression network analysis (WGCNA) was used to identify their co-expressed modules and further bioinformatics analysis was performed to identify hub genes within the modules. Finally, based on two single-cell RNA-seq datasets from mice and one microarray dataset from human, we further observed the expression of hub genes in different cell clusters and liver tissues.

7 hub genes (SPP1, PROM1, SOX9, EPCAM, THY1, CD34 and MCAM) associated with fibrosis progression were identified. Single-cell RNA-seq analysis revealed that those hub genes were expressed by different cell clusters such as cholangiocytes, natural killer (NK) cells, and hepatic stellate cells (HSCs). We also found that SPP1 and CD34 serve as markers of different HSCs clusters, which are associated with inflammatory response and fibrogenesis, respectively. Further study suggested that SPP1, SOX9, MCAM and THY1 might be related to NASH-associated hepatocellular carcinoma (HCC). Receiver operating characteristic (ROC) analysis showed that the high expression of these genes could well predict the occurrence of HCC. At the same time, there were significant differences in metabolism-related pathway changes between different HCC subtypes, and SOX9 may be involved in these changes.

The present study identified novel genes associated with NASH fibrosis and explored their effects on fibrosis from a single-cell perspective that might provide new ideas for the early diagnosis, monitoring, evaluation, and prediction of fibrosis progression in NASH.