PracticalDermatology

The liver is a highly complex organ, and its functioning can be impacted by a variety of diseases and their treatments. Psoriasis has been linked with advancing liver disease, and new guidelines issued jointly by the American Academy of Dermatology (AAD) and the National Psoriasis Foundation (NPF) provide a detailed discussion and recommendations about the potential impact of psoriasis and its treatments on liver health.¹ This includes methotrexate, an immunosuppressive agent that has been associated with chronic liver injury (i.e., inflammation and fat deposition), progressive fibrosis (liver scar formation), and the potential to progress to cirrhosis (advanced liver damage) and portal hypertension if left unchecked.²

This new recommendation points to the importance of non-invasive monitoring and the need to address liver damage among this patient population. In fact, non-alcoholic fatty liver disease (NAFLD), the accumulation of liver fat in people who drink little or no alcohol, occurs in approximately 47 percent of patients with psoriasis. The more progressive form of the disease, non-alcoholic steatohepatitis (NASH), is found in approximately one in five patients living with psoriasis.³

The challenge is that liver disease is often asymptomatic and, given the potential negative impact of methotrexate, cost effective and non-invasive approaches are needed to identify the presence of underlying liver disease.

Psoriasis-Liver Health Connection

The liver plays a fundamental part in the body’s overall regulation and good health. If left untreated, over time, liver injury can lead to cirrhosis, an advanced scarring of the liver that can lead to liver failure—the number one reason for liver transplants going forward, end-stage liver disease, or liver cancer due to cirrhosis. A multidisciplinary approach to managing NAFLD has proven to be effective in reducing elevated liver enzymes along with improving cholesterol levels, glucose control, and weight reduction.⁴

Psoriasis affects approximately two percent of the world’s population. The medications discussed in the AAD/NPF guidelines are still widely used. These therapies can benefit widespread psoriasis, have a comparatively low cost (in the case of older medications), have increased availability, and ease of administration.¹

The guidelines add to the growing evidence that direct assessments of liver health with a rapid, reliable, and non-invasive tool can serve as an essential part of overall health management. FibroScan (or Shearwave Elastography), for example, is a non-invasive exam performed at the point of care in the physician office that helps assess liver health, while determining the amount of liver fibrosis. It can play a role in identifying and monitoring liver health in people undergoing long term treatment with methotrexate, as well as those who are at risk for liver disease due to other reasons.

How Non-Invasive Liver Exams Work

During the exam, the patient lies comfortably on an exam table while the medical professional applies a water-based gel on the patient’s skin and places the non-invasive exam probe on the right side of the ribcage. The medical professional then takes 10 quick, painless measurements to generate immediate results for the physician to interpret. These consistent results (if the patients BMI is <35) enable physicians to make the most informed treatment decisions while providing patients with a quick, painless experience. It can also rule out the need for a painful, expensive liver biopsy or other invasive testing.

For those who suspect they may be at risk for liver disease, either because they meet the at-risk profile below or because they have psoriasis and have taken methotrexate for extended periods of time, it is in their best interest to ask their primary care physician about their liver health and if a non-invasive liver exam is appropriate.

Who is at Risk for Liver Disease?

NAFLD and NASH have been linked to obesity and associated with metabolic syndrome as the most common cause.⁵ Obesity in the US has doubled in the last decade, and health care providers are seeing a steady rise in fatty liver disease. Although children and young adults can get fatty liver disease, it is most common in middle age adults.

Risk factors include:

• Being overweight
• Having high blood fat levels, either triglycerides or LDL (“bad”) cholesterol
• Having diabetes or prediabetes
• Having high blood pressure.

Typically, fatty liver disease causes no symptoms. The first clue can show up in routine liver blood tests, and if elevated, should lead to further investigation. Imaging studies, like a regular ultrasound, could show that the liver has fat deposits. Some imaging tests (FibroScan or Shearwave Elastography) or MRI elastography scans can help diagnose the disease and identify how much scar tissue is present in the liver. But the only way to be certain that fatty liver disease is the only cause of liver damage is by ruling out other potential causes with careful history taking and chronic liver disease blood work. A liver biopsy might be needed, however the non-invasive scans have led to the decrease in liver biopsies over the years as technology has improved greatly. If a liver biopsy is needed, a gastroenterologist or hepatologist should determine if the procedure is necessary.

Psoriasis and Obesity

Obesity is not simply a matter of over-eating, but rather a complex disease that involves an excessive amount of body fat. To overcome the stigma of obesity, it is important to view this disease as a complex medical issue that increases the risk of heart disease, diabetes, high blood pressure, and certain cancers. Given its overwhelming prevalence–one in six adults in the US is affected–obesity is now recognized as a chronic disease by several organizations, including the American Medical Association.

The Centers for Disease Control and Prevention (CDC) defines chronic disease as conditions that last one year or more and require ongoing medical attention or limit activities of daily living, or both. Of the $3.3 trillion spent annually on medical care for chronic conditions, obesity alone is associated with $1.4 trillion.

Studies have shown that psoriasis is not merely a skin problem but also is linked with various comorbid conditions, especially obesity and metabolic syndrome. In one study, 70 percent of subjects with psoriasis were identified as having metabolic syndrome. Doctors gave all the patients skin evaluations to confirm psoriasis, and a liver ultrasound to detect signs of NAFLD.⁶

Forty-eight percent of patients were found to have excess abdominal fat, 96 percent had high cholesterol, 52.8 percent hyperglycemia, 53.6 percent hypertension, and 44 percent elevated levels of ALT, an enzyme measure of liver damage. Almost half the patients, 45.2 percent, had NAFLD. Those with NAFLD were younger and more obese than those with psoriasis alone. The NAFLD patients, mostly men, also had higher body-mass levels and more metabolic syndrome. In addition, NAFLD patients had higher fibrosis scores than non-NAFLD patients. None of the NAFLD patients had cirrhosis of the liver, however. Comorbidity of NAFLD was highly associated with psoriasis, which emphasized that both diseases may develop simultaneously.

In a separate study, researchers found that NAFLD was highly prevalent among the cohort of patients with psoriasis, occurring in 47 percent of patients and biopsy confirmed NASH was 22 percent.⁷

Healthcare providers should be aware of this association because early evaluation and diagnosis of NAFLD in patients with psoriasis may play a vital role in alleviating the progression of liver disease.

Treating Liver Disease

Blood Test and Biopsy. Physicians can order a blood test to look for liver proteins released after a liver cell dies, which may suggest inflammation. Elevated liver enzymes alone do not correlate with NASH. What’s more, the upper limits of normal cutoffs for liver function testing by the major labs may be 50 percent higher than recommended by the American Gastroenterology Society.⁸

Today’s gold standard remains a liver sample, allowing doctors to see signs of scar tissue and ballooning under a microscope to determine how far the disease has progressed. This method, however, has been brought into question not only for its invasiveness and risk, but also for its inaccuracy.

Lifestyle Changes. Most liver disease is preventable and, if caught early enough, reversible. The first line of treatment for NAFLD/NASH is weight loss, done through a combination of calorie reduction, exercise, and healthy eating to reduce fat and inflammation in the liver. Losing just three to five percent of body weight can reduce fat, and losing seven percent can decrease inflammation as well. For those who are overweight or obese, doctors typically recommend a gradual seven to 10 percent loss of body weight over a one-year period because rapid weight loss through fasting can worsen NAFLD.

Too often, patients with obesity lack the health literacy and diagnoses necessary to motivate them to access long-term care solutions. One study found that of the 70 percent of patients who had spoken with their healthcare providers about their weight, only 55 percent received a formal diagnosis for obesity, and only 24 percent have been referred to weight loss follow-up care.⁹ These findings suggest that clinicians need to leverage better patient-provider communication surrounding a patient’s health status.

Supporting Patient Health Behavior. Data suggest mild to moderate activity, such as walking, can reduce liver fat, irrespective of diet. Various regimens of aerobic and resistance training have been shown to reduce hepatic fat content through improvements in insulin resistance, liver fatty acid metabolism, liver mitochondrial function, and activation of inflammatory cascades. These data provide justification for the current guidelines that recommend an exercise regimen that fits with the patient’s individual abilities and preferences, in order to facilitate long-term compliance with a more active lifestyle.

The best way to lose weight is by reducing the number of calories taken in, eating a healthy diet rich in fruits and vegetables, whole grains and low in saturated fats; limiting the amount of salt and sugar, particularly sugar-sweetened beverages, like soda, juices, sports drinks and sweetened tea; and exercising more. It’s also important to control diabetes and keep cholesterol down.

Uncontrolled studies have suggested that individuals with psoriasis or psoriatic arthritis may benefit from a diet supplemented with fish oil rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Diet recommendations include consumption of cold water fish (preferably wild fish, not farmed) such as salmon, herring, and mackerel; extra virgin olive oil; legumes; vegetables; fruits; and whole grains; and avoidance of alcohol, red meat, and dairy products. The effect of consumption of caffeine (including coffee, black tea, mate, and dark chocolate) remains to be determined.

Supporting Patients

To help support patients, non-invasive liver examinations are fast and painless. What’s more, results are immediately available for the physician to interpret to ease the patient’s mind about their liver health, detect liver conditions early and/or monitor the impact of lifestyle changes.

1. Menter A, Gelfand JM, Connor C, et al. Joint American Academy of Dermatology-National Psoriasis Foundation guidelines of care for the management of psoriasis with systemic nonbiologic therapies. J Am Acad Dermatol. 2020 Jun;82(6):1445-1486.

2. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012–. PMID: 31643176.

3. Roberts KK, Cochet AE, Lamb PB, et al. The prevalence of NAFLD and NASH among patients with psoriasis in a tertiary care dermatology and rheumatology clinic. Aliment Pharmacol Ther. 2015 Feb;41(3):293-300.

4. Cobbold JFL, Raveendran S, Peake CM, Anstee QM, Yee MS, Thursz MR. Piloting a multidisciplinary clinic for the management of non-alcoholic fatty liver disease: initial 5-year experience. Frontline Gastroenterol. 2013;4(4):263-269. doi:10.1136/flgastro-2013-100319

5. https://www.hopkinsmedicine.org/health/conditions-and-diseases/nonalcoholic-fatty-liver-disease, Accessed December 11, 2020

6. Narayanasamy K, Sanmarkan AD, Rajendran K, Annasamy C, Ramalingam S. Relationship between psoriasis and non-alcoholic fatty liver disease. Prz Gastroenterol. 2016;11(4):263-269. doi:10.5114/pg.2015.53376

7. Roberts KK, Cochet AE, Lamb PB, Brown PJ, Battafarano DF, Brunt EM, Harrison SA. The prevalence of NAFLD and NASH among patients with psoriasis in a tertiary care dermatology and rheumatology clinic. Aliment Pharmacol Ther. 2015 Feb;41(3):293-300.

8. Fracanzani AL, Valenti L, Bugianesi E, Andreoletti M, Colli A, Vanni E, Bertelli C, Fatta E, Bignamini D, Marchesini G, Fargion S. Risk of severe liver disease in nonalcoholic fatty liver disease with normal aminotransferase levels: a role for insulin resistance and diabetes. Hepatology. 2008 Sep;48(3):792-8.

9. https://patientengagementhit.com/news/better-patient-provider-communication-needed-for-obesity-care, Accessed December 11, 2020.