Evaluation of possible chronic hepatotoxicity from methotrexate for psoriasis

Weinstein, Gerald D.

doi:10.1001/archderm.102.6.613

Cited by 18 publications

(4 citation statements)

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“…Methotrexate (MTX) is an antimetabolite drug that acts by inhibiting folate synthesis and while used to treat leukemia, lymphoma and solid organ tumors is also widely prescribed as a disease modifying anti‐rheumatic drug to treat various autoimmune conditions including rheumatoid arthritis and inflammatory bowel disease to name a few. While acute liver injury can occur with his doses of intravenous MTX , chronic treatment with MTX can lead to drug‐induced hepatic steatosis (DI‐HS) and/or chronic fibrosis which may progress to cirrhosis and portal hypertension . The prevalence of end‐stage liver disease due to MTX toxicity is exceedingly rare; a recent analysis of the OTPN/UNOS database by Dawwas and Aithal which found that 0.07% of patients listed for liver transplantation in the United States were listed for MTX‐related liver disease .…”

Section: Methodsmentioning

confidence: 99%

Chronic liver injury induced by drugs: a systematic review

Stine

Chalasani

2015

Liver International

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To examine the available literature and summarize what is known about chronic drug-induced liver injury. We reviewed PubMed/MEDLINE through March 2015. We developed a MEDLINE search strategy using PubMed medical subject heading terms chronic liver injury, hepatotoxicity, drug-induced liver injury, cirrhosis and chronic liver disease. We reviewed the reference list of included articles to identify articles missed in the database search. Chronic liver injury from drugs is more common than once thought with prevalence as high as 18% based on large national registries. Patients with cholestatic injury, age ≤65 years, and a long latency period (>365 days) are at increased risk. Of the most common drugs associated with drug-induced liver injury, antibiotics (amoxicillin-clavulanic acid, trimethoprim-sulfamethoxazole, azithromycin) are most likely to cause chronic injury. The presence of autoantibodies is common with chronic DILI, however, it is not diagnostic nor is it specific to autoimmune-like drug-induced liver injury. Immunosuppressive therapy may be necessary for individual cases of autoimmune-like drug-induced liver injury where cessation of the drug alone does not result in resolution of injury, however, the lowest dose should be used for the shortest duration with careful attention to the development of side effects. The effectiveness of treament of cholestatic liver injury with corticosteroids or ursodiol remains unclear. Cases of drug-induced fatty liver, nodular regenerative hyperplasia and peliosis hepatitis are less common subtypes of chronic drug-induced liver injury that deserve special consideration. A high degree of clinical suspicion is required for the diagnosis of chronic drug-induced liver injury and should be suspected in any patient with liver associated enzyme abnormalities that persist out past 6 months of initial presentation. Treatment with drug removal and/or immunosuppressive therapy appears to be effective for the majority of cases. More study into pharmacogenomics and personalized medicine may aid in predicting which patients will go on to develop chronic drug-induced liver injury.

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Section: Methodsmentioning

confidence: 99%

Chronic liver injury induced by drugs: a systematic review

Stine

Chalasani

2015

Liver International

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“…In patients undergoing treatment for chronic rheumatoid arthritis, or other rheumatologic disease, however these patients are at increased risk for fibrosis and cirrhosis. 8 …”

Section: Introductionmentioning

confidence: 99%

Chemotherapy induced liver abnormalities: an imaging perspective

et al. 2014

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Treating patients undergoing chemotherapy who display findings of liver toxicity, requires a solid understanding of these medications. It is important for any clinician to have an index of suspicion for liver toxicity and be able to recognize it, even on imaging. Cancer chemotherapy has evolved, and newer medications that target cell biology have a different pattern of liver toxicity and may differ from the more traditional cytotoxic agents. There are several hepatic conditions that can result and keen clinical as well as radiographic recognition are paramount. Conditions such as sinusoidal obstructive syndrome, steatosis, and pseudocirrhosis are more commonly associated with chemotherapy. These conditions can display clinical signs of acute hepatitis, liver cirrhosis, and even liver failure. It is important to anticipate and recognize these adverse reactions and thus appropriate clinical action can be taken. Often times, patients with these liver manifestations can be managed with supportive therapies, and liver toxicity may resolve after discontinuation of chemotherapy.

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“…A key difficulty with the literature is that studies were often conducted in the 1970s and 1980s, and almost exclusively in patients being treated with MTX for psoriasis, with fewer data on patients with RA. 10 11 20–22 They were frequently retrospective with small numbers, and some included pretreatment biopsies which demonstrate abnormalities pre-existent to MTX therapy. 10 Most importantly, however, MTX prescribing and monitoring practices differ markedly now from the time at which the studies were conducted.…”

Section: Discussionmentioning

confidence: 99%

“… 10 11 20–22 They were frequently retrospective with small numbers, and some included pretreatment biopsies which demonstrate abnormalities pre-existent to MTX therapy. 10 Most importantly, however, MTX prescribing and monitoring practices differ markedly now from the time at which the studies were conducted. Critically, liver biopsies are now rarely performed as part of routine monitoring, as there is considerable morbidity and mortality associated with the procedure.…”

Section: Discussionmentioning

confidence: 99%

Quantifying the hepatotoxic risk of alcohol consumption in patients with rheumatoid arthritis taking methotrexate

et al. 2017

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BackgroundPatients with rheumatoid arthritis (RA) who take methotrexate (MTX) are advised to limit their alcohol intake due to potential combined hepatotoxicity. However, data are limited to support this. The aim of this study was to quantify the risk of developing abnormal liver blood tests at different levels of alcohol consumption, using routinely collected data from primary care.MethodsPatients with RA in the Clinical Practice Research Datalink starting MTX between 1987 and 2016 were included. Hepatotoxicity was defined as transaminitis: alanine transaminase or aspartate aminotransferase more than three times the upper limit of normal. Crude rates of transaminitis were calculated per 1000 person-years, categorised by weekly alcohol consumption in units. Cox proportional hazard models tested the association between alcohol consumption and transaminitis univariately, then age and gender adjusted.Results11 839 patients were included, with 530 episodes of transaminitis occurring in 47 090 person-years follow-up. Increased weekly alcohol consumption as a continuous variable was associated with increased risk of transaminitis, adjusted HR (95% CI) per unit consumed 1.01 (1.00 to 1.02); consuming between 15 and 21 units was associated with a possible increased risk of hepatotoxicity, while drinking >21 units per week significantly increased rates of transaminitis, adjusted HR (95% CI) 1.85 (1.17 to 2.93).ConclusionsWeekly alcohol consumption of <14 units per week does not appear to be associated with an increased risk of transaminitis.

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Evaluation of possible chronic hepatotoxicity from methotrexate for psoriasis

Cited by 18 publications

References 0 publications

Chronic liver injury induced by drugs: a systematic review

Chronic liver injury induced by drugs: a systematic review

Chemotherapy induced liver abnormalities: an imaging perspective

Quantifying the hepatotoxic risk of alcohol consumption in patients with rheumatoid arthritis taking methotrexate

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