The Critical Need for Identifying and Monitoring Liver Disease Early in Psoriasis

New guidelines¹ concerning the link between psoriasis and liver disease highlight the  importance of noninvasive monitoring and addressing liver damage among dermatology patients.² Issued jointly by the American Academy of Dermatology (AAD) and the National Psoriasis Foundation (NPF), these guidelines¹ focus on the potential impact on liver health from commonly prescribed medications for psoriasis, a skin disease that affects approximately 2% of the world’s population.³ In particular, methotrexate, an immunosuppressive agent, has been associated with chronic liver injury (ie, 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.⁴

This new guidance is an important alert for dermatologists as they address the growing epidemic of liver disease. Dermatologists should be aware that (1) nonalcoholic fatty liver disease (NAFLD), the accumulation of liver fat in people who drink little or no alcohol, occurs in approximately 47% of patients with psoriasis; and (2) the more progressive form of the disease, nonalcoholic steatohepatitis (NASH), is found in approximately one in five patients living with psoriasis.⁵ 

Left untreated, over time, liver disease can lead to a more serious stage called cirrhosis, an advanced scarring of the liver that can lead to liver failure (and the number one reason for liver transplants), end-stage liver disease, or liver cancer due to cirrhosis.

Additional AAD-NPF guidelines that focus on the management and treatment of psoriasis with consideration of comorbidities recommend that patients with psoriasis be educated on metabolic syndrome and its complications, which include fatty liver disease, and dermatologists should be aware of the role they can play in improving patient quality of life with pretreatment screening and on-treatment monitoring for liver disease.⁶ The challenge is that liver disease is often asymptomatic and, given the potential negative impact of methotrexate as well as the need to further study the relationship between hepatic disease and psoriasis, it is necessary to identify the presence of underlying liver disease. 

Psoriasis and Liver Health
The guidelines^1,6 add to the growing evidence that direct assessments of liver health with a rapid, reliable, and noninvasive tool can serve as an essential part of overall health management. While previous guidelines recommended a baseline liver biopsy, newer methods are becoming more effective. Vibration controlled transient elastography, for example, is a noninvasive test performed at the point of care in the physician office that helps assess liver health while determining the amount of liver fibrosis. This tool could play a role in identifying and monitoring liver health in people on long-term treatment with methotrexate, as well as those who are at risk for liver disease due to other reasons. 

For patients with psoriasis who may be at risk for liver disease, either because they meet the at-risk profile discussed below or have taken methotrexate for extended periods, it is in their best interest to monitor their liver health. The AAD-NPF guidelines recommend regular laboratory monitoring, including liver function tests and complete blood count, be performed before initiation of methotrexate therapy and every 3 to 6 months thereafter.¹ In addition, the guidelines provide two detailed algorithms for methotrexate hepatotoxicity screening based on the patient’s risk factors; abnormal results should be followed with repeat testing after 2 to 4 weeks, and persistent abnormalities should be referred to a gastroenterologist with consideration of alternative therapies.¹

Liver Disease Risk Factors 
NAFLD and NASH have been linked to obesity and associated with metabolic syndrome as the most common cause.⁷ Although children and young adults can get fatty liver disease, it is most common in middle-aged adults. Additional risk factors include obesity, diabetes or prediabetes, hyperlipidemia, and high blood pressure. All of these risk factors are common comorbidities of psoriasis.⁶

Typically, fatty liver disease has no symptoms. The first clue can show up in routine liver blood tests, and if abnormalities are detected, these should lead to further investigation. Imaging studies such as a regular ultrasound could show that the liver may have fat deposits; other imaging, including shearwave elastography or magnetic resonance imaging elastography scans, can help diagnose disease and identify how much scar tissue is present in the liver. However, the only way to be certain that fatty liver disease is the only cause of liver damage is to rule out other potential causes with careful history taking and continual liver disease blood work. A liver biopsy might be warranted in these instances, though noninvasive scans have led to a decrease in liver biopsies over the years as technology has improved greatly. If a patient’s blood work comes back elevated and liver disease is suspected, a gastroenterologist or hepatologist should help determine the next steps in the patient’s treatment plan with specialist consideration to preventing further liver damage. 

Addressing Obesity
Psoriasis is frequently associated with various comorbid conditions, particularly obesity and metabolic syndrome.^1,6 Obesity is a complex disease that involves an excessive amount of body fat that increases the risk of heart disease, diabetes, high blood pressure and certain cancers, and it has been associated with NAFLD. Given its overwhelming prevalence, one in six US adults, obesity is now recognized as a chronic disease by several organizations, including the American Medical Association.

In one study, 70% of patients with psoriasis were identified as having metabolic syndrome^.8 Of the 250 patients included, 48% of these patients had abdominal obesity, 96% had dyslipidemia, 52.8% had hyperglycemia, 53.6% had hypertension, and 44% had elevated alanine aminotransferase levels. Nearly half (n=113, 45.2%) had NAFLD.

This same study found that patients with psoriasis and NAFLD tended to be younger, male, and have a higher body mass index (BMI). Patients with psoriasis and NAFLD also had a higher Psoriasis Area and Severity Index than patients without NAFLD (P<.0001).⁸ Another study by Roberts et al⁵ found that NAFLD was highly prevalent, occurring in 47% of patients with psoriasis, and NASH was confirmed by biopsy in 22% of the study patients.

Treating Liver Disease
Most liver disease is preventable and, if caught early enough, reversible. 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. Furthermore, the upper limits of normal cutoffs for liver function testing by the major labs may be 50% higher than recommended by the American Gastroenterology Society.⁹

The most important part of treatment for NAFLD/NASH is weight loss. A loss of 3% to 5% of body weight can reduce the amount of fat on the liver, and a loss of 7% is believed to reduce inflammation.¹⁰ Patients should be counseled on gradual and sustainable weight loss, as fasting and extreme weight loss may worsen NAFLD.

A 2018 article published in Obesity found that of the 70% of patients who had spoken with their health care providers about their weight, only 55% received a formal diagnosis for obesity, and only 24% have been referred to weight loss follow-up care.¹¹ This further emphasizes the need for physicians to diagnose obesity and discuss weight loss solutions with their patients, taking a careful approach to patient-physician communications that considers the patient’s health literacy with regard to diet and exercise.

It is well known that mild to moderate physical activity can improve overall health. Recent research notes that this may include reducing liver fat through improved peripheral insulin resistance, increased fatty acid oxidation, decreased fatty acid synthesis, and reduced mitochondrial and hepatocellular damage.¹²

Diet is also a major factor in reducing BMI and improving overall health, and its effects on fatty liver disease have been studied extensively. Ford et al¹³ strongly recommended that overweight or obese patients with psoriasis follow a hypocaloric diet for dietary weight reduction. Another 2018 study examined the relationship between the Mediterranean anti-inflammatory diet and psoriasis severity, finding evidence that the Mediterranean diet, which has been associated with improvement in NAFLD,¹⁴ may correlate with a more mild disease severity.¹⁵ However, further study is needed to evaluate the best dietary recommendations for patients with psoriasis and NAFLD.

Conclusion
Dermatologists can play an important role in improving the overall health of their patients with psoriasis. Careful monitoring of liver function, through routine testing and noninvasive liver exams, can help determine a safe course of therapy for patients, encourage liver health, and impact lifestyle choices.

Dr Rahimi is a transplant hepatologist at Baylor University Medical Center in Dallas, TX, and assistant professor in the department of medicine at Texas A&M Health Science Center, College of Medicine, in Bryan, TX, and practices with Liver Consultants of Texas in Dallas.

Disclosure: The author reports no relevant financial relationships.

References
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