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Risk of Liver Fibrosis in Patients With Psoriasis on Long-term Methotrexate: Role of Cumulative Dose and Comorbidities in 483 Patients

Groups and Associations Harshad Devarbhavi *, Govinda Narayanareddy Devamsh *, Anaberu Basavaraj Chiranth *, Mallikarjun Patil *, Rajvir Singh y, Ekta Parikh *, Syed Shafiq * * Department of Gastroenterology and Hepatology, St. John's Medical College Hospital, Bangalore, India and y Heart Hospital, Department of Cardiology, Hamad Medical Corporation, Doha, Qat
Journal of clinical and experimental hepatology 2025

 ethotrexate (MTX) is commonly used as an anti-
neoplastic agent in lymphomas and leukemia,
as well as a disease-modifying immunomodula-
tory agent in the treatment of psoriasis, rheumatoid arthri-
tis (RA), and inflammatory bowel disease. Since its first use
in 1972 for psoriasis, followed by RA in 1988, concerns
have remained over its potential to contribute to chronic
liver disease (CLD), including steatohepatitis, liver fibrosis,
and cirrhosis. 1 MTX dosage, duration, frequency of admin-
istration, and subtype of psoriatic disease have long been
suspected to contribute to CLD.2 Several dermatology so-
cieties recommend liver monitoring every three months, in-
cluding assessment of liver biochemistry and serum
aminoterminal propeptide of type III procollagen (PIIINP),
in patients with psoriasis receiving methotrexate. 3
Liver biopsy is the gold standard for evaluating liver in-
jury and fibrosis; however, the potential risks and costs
have led to a growing interest in the role of non-invasive
markers as surrogates for fibrosis and cirrhosis. 4 These in-
clude blood-based tests such as Fibrosis Index Based on 4
Factors (FIB-4) and enhanced liver fibrosis (ELF), and
ultrasound-based tests such as transient elastography
(TE) and shear wave elastography.
The relationship between liver fibrosis with psoriasis has
been mixed; one systematic review linked “any degree of fib-
rosis” with psoriasis;5,6 while others found a link between
fibrosis in psoriasis only in the presence of comorbidities
such as obesity, diabetes mellitus, insulin resistance, and
hyperlipidemia.7,8 These studies, however, were conducted
in a very homogenous, primarily Caucasian white popula-
tion, limiting the generalizability of these findings to other
racial and ethnic groups. As experts in liver fibrosis, hepa-
tologists are increasingly called upon to assist in the care
of patients with psoriasis with non-invasive modalities
such as Fibroscan and other modalities.
The primary objective was to determine the relationship
between MTX exposure and liver fibrosis in patients with
psoriasis. We also aimed to evaluate the role of risk factors
associated with psoriasis and liver fibrosis. Liver fibrosis
was measured TE and FIB- 4.
Keywords: liver stiffness, cirrhosis, fibroscan, diabetes mellitus, risk factors,
FIB4
Received: 18.4.2025; Accepted: 30.5.2025; Available online 6 June 2025
Address for correspondence: Department of Gastroenterology and Hepatology, St.
John's Medical College Hospital, Bangalore, India
E-mail: harshad.devarbhavi@gmail.com
Abbreviations: BMI: body mass index; CLD: chronic liver disease; DM: dia-
betes mellitus; FIB-4: Fibrosis-4 Index; LSM: liver stiffness measurement;
MASLD: metabolic dysfunction associated steatotic liver disease; MTX:
methotrexate; RA: rheumatoid arthritis; TE: transient elastography
https://doi.org/10.1016/j.jceh.2025.102606
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