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Nonalcoholic Fatty Liver Disease in Patients with Psoriasis: A Consequence of Systemic Inflammatory Burden?

This review explores the link between psoriasis and nonalcoholic fatty liver disease (NAFLD). It discusses the shared risk factors and the role of inflammation in driving the progression of both conditions. The importance of early diagnosis and referral to a hepatologist is highlighted.

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Nonalcoholic Fatty Liver Disease in Patients with Psoriasis: A Consequence of Systemic Inflammatory Burden?

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  1. Nonalcoholic fatty liver disease in patients with psoriasis: A consequence of systemic inflammatory burden? R. B. Prussick1,2 and L. Miele3,4 1Washington Dermatology Center, Rockville, MD, USA; 2Department of Dermatology, George Washington University, Washington DC, USA; 3Institute of Internal Medicine, Catholic University of Sacred Heart of Rome, Rome, Italy; 4Gastroenterological Area, Gastroenterology and Endocrine-Metabolic Sciences Department, Fondazione PoliclinicoUniversitario A. Gemelli, Rome, Italy British Journal of Dermatology. DOI: 10.1111/bjd.16239

  2. Introduction What’s already known? • The pathogenesis of psoriasis is not completely clear; however, genetic, immunologic, and environmental factors are thought to be involved1 • Chronic, low-grade inflammation is present in psoriasis and comorbidities such as NAFLD and metabolic syndrome2 • The prevalence of NAFLD is significantly higher in patients with psoriasis (17%−66%) than in healthy or matched controls (8%−35%)3-8 • NAFLD encompasses a spectrum of liver diseases ranging from steatosis (relatively benign) to NASH • Patients with psoriasis and NAFLD are significantly more likely than patients with NAFLD alone to have NASH4 • NASH can progress to advanced liver diseases, such as cirrhosis and hepatocellular carcinoma9,10 1. Griffiths CE and Barker JN. Lancet 2007;370:263-71; 2. Ganzetti G et al. World J Hepatol2015;7:315-26; 3. Gisondi P et al. J Hepatol2009;51:758-64; 4. Madanagobalane S and Anandan S. Australas J Dermatol2012;53:190-7; 5. van der Voort EA et al. J Am AcadDermatol2014;70:517-24; 6. Gisondi P et al. J EurAcadDermatolVenereol2016;30:282-7; 7. Abedini R et al. ClinExpDermatol2015;40:722-7; 8. Candia R et al. J EurAcadDermatolVenereol2015;29:656-62; 9. Anstee QM et al. Nat Rev GastroenterolHepatol2013;10:330-44; 10. Vernon G et al. Ailment PharmacolTher2011;34:274-85. NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis.

  3. Methods • This manuscript is a narrative review that summarizes the authors’ critical evaluation of literature related to psoriasis and comorbid NAFLD • Articles relevant to pathogenesis of NAFLD and/or psoriasis, diagnosis of NAFLD, and treatment of NAFLD in patients with psoriasis were analysed • The authors summarized their findings and provided pertinent commentary regarding the management of patients with psoriasis and NAFLD NAFLD, nonalcoholic fatty liver disease.

  4. A Link Between Psoriasis and NAFLD Significant associations and common risk factors between psoriasis and NAFLD • Release of inflammatory cytokines associated with metabolic syndrome and NAFLD drives further low-grade inflammation, leading to a vicious cycle that causes worsening of liver damage and progression of NAFLD1 • This inflammation may also drive the progression of psoriasis • Presence and severity of psoriasis correlate with prevalence, severity, and NAFLD risk2-7 • The odds ratio of NAFLD in patients with psoriasis versus healthy controls is 2.155 • Drugs that increase liver toxicity, such as methotrexate, can further drive progression of NAFLD 1. Meli R, et al. Front Immunol2014;5:177; 2. Gisondi P et al. J Hepatol2009;51:758-64; 3. Madanagobalane S and Anandan S. Australas J Dermatol2012;53:190-7; 4. Abedini R et al. ClinExpDermatol2015;40:722-7; 5. Candi R et al. J EurAcadDermatolVenereol2015;29:656-62; 6. Al-Mutairi N et al. J Dermatol2010;27:146-55; 7. Yang YW et al. Br J Dermatol2011;165:1037-43. NAFLD, nonalcoholic fatty liver disease; PsO, psoriasis.

  5. A Link Between Psoriasis and NAFLD (cont’d) • Adipose tissue produces adipokines, which play important roles in psoriasis and NAFLD pathogenesis1-6 • The liver responds to the production of adipokines by producing hepatokines6-8 • Adipokines and hepatokines affect lipid and glucose metabolism and promote NAFLD4 • Adipokines, such as leptin, adiponectin, and resistin, are important for energy balance, lipid and glucose metabolism, insulin sensitivity, blood pressure, and angiogenesis3,6 1. Ganzetti G et al. World J Hepatol2015;7:315-26; 2. Terra X et al. ClinEndocrinol (Oxf) 2012;77:691-8; 3. Kershaw EE and Flier JS. J ClinEndocrinolMetab2004;89:2548-56; 4. Ganzetti G et al. World J Cardiol2016;8:120-31; 5. Stojsavljević S et al. World J Gastroenterol2014;20:18070-91; 6. Panera N et al. Expert Rev Gastroenterol Hepatol2016;10:393-403; 7. Dushay J et al. Gastroenterology 2010;139:456-63; 8. Uysal S et al. Eur Rev Med PharmacolSci2014;18:3453-8. CRP, C-reactive protein; FGF21, fibroblast growth factor 21; IL, interleukin; NAFLD, nonalcoholic fatty liver disease; Th, T helper; TNF, tumor necrosis factor.

  6. Diagnosis of NAFLD • All patients with psoriasis should be screened for NAFLD at the time of diagnosis • NAFLD often presents asymptomatically or with nonspecific symptoms such as fatigue, malaise, and right upper-quadrant discomfort2 • Dermatologists are encouraged to refer patients to a hepatologist when NAFLD is suspected • A hepatologist should conduct a thorough history, a physical examination, and appropriate laboratory tests Recommended evaluations by a hepatologist for the diagnosis of NAFLD in psoriasis 1. European Association for the Study of the Liver (EASL). J Heptaol2016;64:1388-402; 2. Dowman JK et al. Ailment PharmacolTher2011;25:383-91. ALT, alanine aminotransferase; AST, aspartate aminotransferase; BMI, body mass index; CVD, cardiovascular disease; GGT, gamma-glutamyl transferase; HDL, high-density lipoprotein; HOMA, homeostatic model assessment; INR, international normalized ratio; LDL, low-density lipoprotein; NAFLD, nonalcoholic fatty liver disease; OGTT, oral glucose tolerance test; TSH, thyroid-stimulating hormone.

  7. Diagnosis of NAFLD • Probable diagnosis of NAFLD can be made if serum enzyme elevations are confirmed and other causes, such as hepatotoxic medications, excessive alcohol consumption, and hereditary disorders, are ruled out1,2 • Diagnosis of NAFLD is possible in the absence of elevated serum enzymes1 • A definitive diagnosis of NAFLD is made when diagnostic testing confirms the presence of fat in the liver2 • The only way to definitively confirm NASH is with a liver biopsy2 • Patients at high-risk for advanced liver fibrosis as indicated by obesity and diabetes and/or AST:ALT ratio ≥0.8 are candidates for liver biopsy1 1. Dowman JK et al. Aliment PharmacolTher2011;33:525-40; 2. European Association for the Study of the Liver (EASL). J Heptaol2016;64:1388-402. ALT; alanine aminotransferase; AST, aspartate aminotransferase; NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis.

  8. Treatment of NAFLD in Patients With Psoriasis • No specific guidelines exist for the treatment of psoriasis and comorbid NAFLD • Goals of NAFLD treatment are to prevent or reversehepatic injury and fibrosis1,2 • Pharmacological treatment should be limited to NASH, because patients with simple steatosis without fibrosis are at a low progression risk1,2 • Eating a healthy diet and increasing physical activity provide the best chance for long-term success and overall benefit3 • Prolongedactivity sessions (increased by ≥60 or maintained at 150 minutes per week) provide a significant benefit3 1. Chalasani N et al. Gastroenterology 2012;142:1592-609; 2. European Association for the Study of the Liver (EASL). J Heptaol2016;64:1388-402; 3. St George A et al. Hepatology 2009;50:68-76. NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis.

  9. Psoriasis Drugs and the Liver • Biologics can be appropriate treatments for patients with psoriasis and NAFLD • TNF-α inhibitors: • Drug-related livertoxicity was observed with infliximab1 • Etanercept may reduce the risk of hepatic fibrosis, but some patients experience increased weight/BMI/hip-to-waist ratio2,3 • Liver enzyme abnormalities have not been reported with adalimumab1 • IL-12/23 inhibitor: • Drug-related liver toxicity is mild and uncommon with ustekinumab4 • IL-17A inhibitors: • No clinically relevant changes in liver biochemical tests have been observed for secukinumab or ixekizumab5-7 • Apremilast, a small-molecule PDE4 inhibitor, may also be suitable for patients with psoriasis and NAFLD • No liver toxicity has been observed8 1. Nast A et al. J EurAcadDermatolVenereol2015;29:2277-94; 2. Campanati A et al. J Gastroenterol 2013;48:839-46; 3. Campanati A et al. Int J Dermatol2015;54:839-45; 4. Llamas-Velasco M et al. ActasDermosifiliogr2015;106:470-6; 5. Langley RG et al. N Engl J Med 2014;371:326-38; 6. Griffiths CE et al. Lancet 2015;386:541-51; 7. van de Kerkhof PC et al. J Am AcadDermatol2016;75:83-98 e4; 8. Gisondi P et al. J EurAcadDermatolVenereol2016;30:282-7. BMI, body mass index; IL, interleukin; NAFLD, nonalcoholic fatty liver disease; PDE4, phosphodiesterase 4; TNF, tumor necrosis factor.

  10. Discussion What does this study add? • Chronic, low-grade inflammation may clarify the association between psoriasis and NAFLD • Adipokines play important roles in psoriasis and NAFLD pathogenesis • All patients with psoriasis should be screened for NAFLD • Patients with suspected NAFLD should be referred to a hepatologist for further testing • Appropriate steps should be taken to choose suitable treatment and reduce risk for liver disease progression NAFLD, nonalcoholic fattyliverdisease.

  11. Conclusions • Psoriasis and its comorbiditiesnegatively impact health, quality of life, and overall well-being • Fatty liver disease often provides an indication of potential underlyingconditions, such as cardiovascular disease, metabolic syndrome, diabetes, obstructive sleep apnea, and obesity1 • Counselling patients on diet and lifestyle changes and tailoring treatment to meet patients’ needs is critical to improving patient outcomes • Large, prospective, controlled studies areneededto determine if newer biologic treatments can prevent progression of NAFLD in psoriasis 1. Prussick R et al. J ClinAesthetDermatol2015;8:43-5. NAFLD, nonalcoholic fattyliverdisease.

  12. Call for correspondence • Why not join the debate on this article through our correspondence section? • Rapid responses should not exceed 350 words, four references and one figure • Further details can be found here

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