With nearly 50 years of use in the clinic, methotrexate has proven effective and relatively safe for the treatment of psoriasis in a significant proportion of patients. However, the drug has a known risk for liver toxicity in certain at-risk individuals as well as in patients who have received a cumulative dose of 3.5-4g of methotrexate. Traditionally, liver biopsy was the sole method available to assess possible liver damage. However, new minimally and non-invasive tools have emerged to screen for liver disease.
New Guidelines of Care for the Management of Psoriasis with Systemic Nonbiologic Therapies, jointly issued by the American Academy of Dermatology (AAD) and the National Psoriasis Foundation (NPF), cover a total of 12 non-biologic systemic treatments used (many off-label) for the treatment of psoriasis. Among those covered are older drugs like methotrexate and relative new-comer apremilast. One key change in the guidance is the recommendation of alternative methods for liver disease screening. Robert Rahimi, MD, a transplant hepatologist at Baylor Scott & White Health in Dallas, is a co-author of the new guidelines.
“Many years back, most patients that had about 3.5 to 4 grams of methotrexate after a few years of being on it would in general require a liver biopsy. That was standard of care. Now, there are blood tests that you can easily get,” Dr. Rahimi says. “The hope with the 2020 guidelines is if any dermatologists read it, then they will know we have these blood tests that we can check, and if they're abnormal, part of our algorithm is to send to a GI or liver specialist to do further workup.”
Along with Elliot B. Tapper, MD, Assistant Professor of Medicine at University of Michigan, Dr. Rahimi advised on the potential toxicities of various drugs.In the case of methotrexate, at-risk individuals could develop chronic liver injury, progressive fibrosis, cirrhosis, or portal hypertension.
Patients with a history of moderate to heavy alcohol use are susceptible to alcoholic fatty liver disease (AFLD), and liver damage may be augmented by methotrexate, Dr. Rahimi says. However, he notes, rates of non-alcoholic fatty liver disease (NAFLD) appear to be increasing in the general population in Western countries. “As we eat more in the Western World, we all tend to, in general, hold onto more weight. When we have a little more weight, some fat cells get swollen in the liver. NAFLD, over time, can lead to scarring of the liver, and scarring of the liver leads to what's called nonalcoholic steatohepatitis or NASH.” However, because these patients may be only light or moderate drinkers, prescribers may not think to screen them for liver disease. “That's an unrecognized diagnosis until someone checks their blood lab work,” Dr. Rahimi notes.
The new guidelines provide comprehensive listings of various liver disease risk factors and provide several simple algorithms to guide patient testing and monitoring.
Alternatives to biopsy include newer screenings, such as the FIB-4, which looks at multiple blood-based parameters, according to Dr. Rahimi. These include age, the AST (aspartate aminotransferase) levels, Alanine transaminase (ALT)levels, and platelets. A composite score is generated, which suggests the level of scarring or fibrosis the patient has. High scores on the FIB-4 may warrant referral for non-invasive liver imaging tests, such as a FibroScan or elastography.
Dr. Rahimi likens the test to an ultrasound, except the technology used is shear wave elastography. “It basically sends a signal through the liver, sort of like Doppler. And we get a result back through the probe; the stiffer the liver is (moderate to advanced scarring), the higher the number is reported in kilopascals, and the softer the liver is, the less liver scarring an individual has, so you get a smaller number,” he explains.
Blood tests plus bedside elastography supports staging of liver disease and may be used as a basis to either continue or discontinue methotrexate therapy. One caveat: the non-invasive liver scans become less reliable as patient BMI is greater than 35, and becomes even less sensitive as BMIreaches 40 or higher.
Other tests that may prove beneficial in assessing liver function and liver disease, according to Dr. Rahimi, are the FibroSure blood test, which assesses five serum biomarkers, as well as the age and gender of the patient, to determine a risk score as well as a necroinflammatory score—an assessment of inflammation in the liver. MRI elastography can also be used to further assess degree of liver disease if initially identified by these screenings.
“A lot of dermatologists are not expected to know these specific blood tests and imaging techniques exist, which can indirectly measure the stage of someone’s liver, that is fairly accurate,” Dr. Rahimi emphasizes. “You just have to know what test(s) to order—the FIB-4 or FibroSureblood test, and the elastography or FibroScan. It's usually in either GI clinics and/or hepatology clinics. Private practice GIs that deal specifically with mostly gastrointestinal disorders might not have access. It's usually in bigger centers that also do research.”