MTX hepatotoxicity in patients with psoriasis appears to increase with the total cumulative dose 6. There does not appear to be cross reactivity in hepatic side effects between methotrexate and other disease modifying antirheumatic drugs (DMARDs) such as leflunomide, hydroxychloroquine, azathioprine, etanercept, or infliximab. A third liver biopsy done after 4 years of therapy (total dose 2.2 g) again showed moderate activity, steatosis and mild fibrosis. PubMed Citation (Liver biopsy results on 88 patients with psoriasis treated with methotrexate found increase in fibrosis and cirrhosis after cumulative dose of 2 g; rates higher in alcoholics; fat was present in 64 of 14 untreated versus 61 of 41 treated non-users of alcohol; nuclear changes found in most treated patients; ALT and AST usually normal). Methotrexate is administered once weekly as a single dose or in divided doses given over a 24-hour period. 3 5 Many physicians use methotrexate for its steroid-sparing properties in patients with asthma and others who may have side effects related to corticosteroid use.6 The key to the success of methotrexate in treating any of these diseases (with the exception of ALL) is the recognition that low-dose therapy achieves efficacy while minimizing side effects. The dermatology literature, however, recommends a liver biopsy after a cumulative dose of 1.5 g in patients with psoriasis, including those who lack significant risk factors for hepatic disease.
Liver injury during cancer chemotherapy may not always reflect hepatotoxic anticancer drugs; the clinician must also consider reactions to antibiotics, analgesics, antiemetics, or other medications. Hepatotoxicity induced by 6-MP may occur in a variety of settings, especially when the dose of the drug exceeds the usual adult daily dose of 2 mg/kg (6-MP doses in children are prescribed on a mg/m2 basis), and may present as either hepatocellular or cholestatic liver disease 51, 52. Patients with RA or psoriasis who received cumulative doses of less than 2 g of MTX had a low incidence of hepatotoxicity, even though the average duration of therapy ranged from 28 to 48 months 75-78. As necessary, the total weekly dose can be increased up to 25 mg. Due to its potentially toxic effect on the liver, additional hepatotoxic medicinal products should not be taken during treatment with methotrexate unless clearly necessary and the consumption of alcohol should be avoided or greatly reduced (see section 4. A) Patients without risk factorsAccording to current medical standard of knowledge, liver biopsy is not necessary before a cumulative dose of 1.0-1.5 g is reached. Pregnant psoriatic patients must not receive methotrexate (see section 4.6). Absorption: In adults, oral absorption of methotrexate appears to be dose dependent. Impaired renal function as well as concurrent use of drugs such as weak organic acids that also undergo tubular secretion, can markedly increase methotrexate serum levels. The improvement in disease activity produced by methotrexate in clinical studies became maximal after 6 months of treatment and was maintained for a number of years.
An increased prevalence of metabolic syndrome including nonalcoholic fatty liver disease (NAFLD) was reported in psoriasis. The total cumulative dose of methotrexate over 1.5 g was seen in 39 (23.6) patients. 11 of psoriatic patients had significant liver fibrosis by high LSM. For patients at increased risk of hepatotoxicity, liver biopsy may be justified earlier during therapy.