Hepatic effects of long-term methotrexate use in the treatment of inflammatory bowel disease

Te, Helen S.; Schiano, Thomas D.; Kuan, Shih Fan; Hanauer, Stephen B.; Conjeevaram, Hari S.; Baker, Alfred L.

doi:10.1111/j.1572-0241.2000.03287.x

Cited by 145 publications

(63 citation statements)

References 32 publications

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“…While most adverse events are the result of allergic reactions or intolerance, some are the result of the antimetabolic effects, similar to those seen in patients receiving chemotherapeutic agents [572]. Hepatic fibrosis and cirrhosis are rarely seen, leading to a withdrawal of the recommendation for a surveillance liver biopsy at 1.5 g cumulative dose [573], unless repeatedly elevated aminotransferases or decreased serum albumin are detected [574].…”

Section: Methotrexatementioning

confidence: 99%

Inflammatory Bowel Disease

Stenson

Hanauer

Cohen

2008

Textbook of Gastroenterology

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In the US, H. pylori vacA shows allelic variation in the signal sequence (which may be type sla, slb or s2) and the mid-region (type ml or m2). Previous PCR-based vacA mid-region typing classified most, but not all, Asian and South American strains tested as ml or m2. We now sought to investigate vacA mid-region diversity further.MotlmodL We studied 13 Japanese, 6 Chinese, 9 Thai, and 8 Peruvian H. pylori isolates. cagA was identified by colony hybridisation (CH), vacA signal sequence was typed by PCR, and vacA mid-region was typed proximally by CH and distally by PCR. Sections of the vacA mid-region from 8 strains were PCR-amplified, sequenced, and compared with known sequences from 8 other strains.Rcuts Of the 36 Asian and South American strains studied, 35 were cagA+ (the cagA-was Peruvian) and 35 were vacA sla (1 cagA + Peruvian was slb). vacA mid-regions from the 13 Japanese strains were not PCR-amplified by ml or m2-specific primers, but hybridised weakly with an ml probe. Sequence analysis of vacA from 1 Japanese strain revealed 91% nucleotide identity with the ml probe but only 71% identity with the m2 probe. The previously equivocal Thai and Peruvian strains also had ml-like mid-region sequences. A Chinese strain was ml in the proximal mid-region and m2 distally, showing a clear crossover site. Final mid-region types were: Japanese, all 13 ml; Chinese, 1 ml, 1 ml/m2, 4 m2; Thai, 3 ml, 6 m2; Peruvian 4 ml, 4 m2. Distal mid-region sequences of 16 strains, compared over 294 bp, clustered into 2 groups, ml and m2. Nucleotide identity between ml and m2 strains ranged from 73-78%. Within groups, m2 strains were less diverse than ml strains (m2 range 94-99.7%, ml 88-99.3%, p<0.001). Sequence analysis of 7 ml and 3 m2 strains over 1.1kb proximally showed maintenance of clustering outside the 294bp region C duions These Asian and South American strains are similar in terms of cagA status and vacA sla genotype, but fall into 2 vacA midregion groups. ml sequences are more diverse than m2, and thus may be phylogenetically older. The vacA sequence of 1 Chinese strain suggests recombination in vivo between ml and m2 alleles. Introduction: H.pylori antimicrobial susceptibility is an important determinant ofthe efficacy of eradication therapies'. The prevalence of antimicrobial resistance varies within the UK and may increase given the increased use of eradication therapy. This multicentre study assesses the prevalence and possible associations ofH.pylon antimicrobial resistance. Methods: H.pylon was isolated from antral biopsies of patients undergoing routine endoscopy and cultured according to standard microbiological methods. Antimicrobial resistance was determined using "E-tests" or disc tests (tinidazole only) with breakpoints defined by previous studies. Results: H.pyloni was isolated from 32% (1222/3823) of patients and antimicrobial susceptibility determined in 90% (1077/1222) Previous case-control studies of IBD have used hospital or community derived controls. There are obvious inherent biases in both metho...

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Section: Methotrexatementioning

confidence: 99%

Inflammatory Bowel Disease

Stenson

Hanauer

Cohen

2008

Textbook of Gastroenterology

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“…175 However, this compound had no effect on fibrogenesis in patients with primary biliary cirrhosis. 176,177 Metrothrexate is thought to have anti-inflammatory properties, but interestingly has typically been considered to be profibrogenic in the liver for patients receiving methotrexate for treatment of rheumatologic diseases 178 (although it is noteworthy that the risk of fibrosis progression may be less prominent than typically believed 178,179 ). Metrothrexate has been studied in patients with primary biliary cirrhosis.…”

Section: Miscellaneous Anti-inflammatory Drugsmentioning

confidence: 98%

Hepatic Fibrosis and Cirrhosis

Rockey¹,

Friedman²

2006

Zakim and Boyer's Hepatology

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“…The rheumatologic literature recommends liver biochemistry every 3 months, with persistent elevations in transaminases requiring a reduction in methotrexate dose and consideration for liver biopsy [34]. In contrast to patients with psoriasis or rheumatoid arthritis, surveillance liver biopsies are not currently warranted in the IBD population because cumulative methotrexate (> 1.5 g) does not to appear to predispose to signifi cant hepatotoxicity [35].…”

Section: Gastrointestinal and Hepaticmentioning

confidence: 99%

Managing the risks of IBD therapy

Seow

Silva²,

Kaplan³

et al. 2009

Curr Gastroenterol Rep

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Successful management of the patient with inflammatory bowel disease (IBD) involves not only the induction and maintenance of remission, but also the optimization of the benefit-to-risk equation to achieve the greatest gain in quality of life. These risks range from intolerance to prescribed medications to potentially life-threatening sequelae (eg, sepsis) of immune suppression. A proper awareness of risk on the part of the physician and education of the patient can lead to early detection and institution of an appropriate management plan, including risk management and, optimally, primary prevention (eg, prophylactic vaccination). One should take the opportunity regularly to reassess the utility and efficacy of existing therapy, with the provision of ineffective therapies mandating urgent review. Overall, optimal management of the patient with IBD requires open dialogue between clinician and patient so that both are cognizant of the goals, benefits, and potential risks of therapy.

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Hepatic effects of long-term methotrexate use in the treatment of inflammatory bowel disease

Abstract: Cumulative methotrexate doses up to 5410 mg given up to 281 wk in patients with inflammatory bowel disease are associated with little hepatotoxicity. Surveillance liver biopsies based on cumulative methotrexate doses are not warranted in these patients.

Cited by 145 publications

References 32 publications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Hepatic Fibrosis and Cirrhosis

Managing the risks of IBD therapy

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