Liver injury in inflammatory bowel disease: Long-term follow-up study of 786 patients

Gisbert, Javier P.; Luna, Marta; González-Lama, Yago; Pousa, Inés D.; Velasco, Marta; Moreno–Otero, Ricardo; Maté, José

doi:10.1002/ibd.20160

Cited by 112 publications

(101 citation statements)

References 53 publications

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“…A recent Spanish study detected abnormal liver enzyme levels in 15% and hepatotoxicity in 5% among 786 adult IBD patients prescribed with AZA. 10 The data were corroborated by a recent US study in which hepatotoxicity was observed in 4.6% of 173 AZA-treated adult IBD patients. 11 However, unlike myelosuppression, hepatotoxicity in AZA-prescribed patients was not correlated with thiopurine S-methyltransferase (TPMT) deficiency.…”

Section: Introductionsupporting

confidence: 56%

Improving pharmacovigilance in Europe: TPMT genotyping and phenotyping in the UK and Spain

et al. 2009

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Thiopurine S-methyltransferase (TPMT) is the rate-limiting step in the conversion of thiopurine drugs including azathioprine (AZA) to inactive metabolites. Heritable deficiency of TPMT activity increases risk for adverse events, most notably, myelosuppression leading to leukopenia and neutropenic sepsis. The reported European Commission study was undertaken to identify current evidence for the clinical utility of testing for TPMT status and extent of uptake, by either genotyping or phenotyping, in the clinical setting. Data presented here for the UK and Spain indicate that there has been a considerable increase in the uptake of TPMT testing in recent years. There are some data that support routine TPMT testing before AZA prescribing for reducing AZA-related adverse events. Key data include evidence in favor of TPMT testing in addition to the current practice of routine monitoring for reducing the number of AZA-related episodes of myelosuppression, averting deaths from neutropenic sepsis and improving health-related quality of life. Further data are needed for determining the cost-effectiveness of routine TPMT testing.

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Section: Introductionsupporting

confidence: 56%

Improving pharmacovigilance in Europe: TPMT genotyping and phenotyping in the UK and Spain

et al. 2009

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“…169 The use of AZA and 6-MP are associated with abnormal LFTs in patients with IBD. 57,170, A large study of IBD patients reported a 15% prevalence of abnormal LFTs, while fatty liver and drug-induced liver toxicity were the most common causes. 170 Hepatotoxicity usually manifests by elevation in aminotransferases, accompanied by flu-like symptoms.…”

Section: Drug-induced Hepatotoxicity Thiopurinesmentioning

confidence: 98%

Hepatopancreatobiliary manifestations and complications associated with inflammatory bowel disease

Navaneethan¹,

Shen²

2010

Inflammatory Bowel Diseases

178

127

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Diseases involving the hepatopancreatobiliary (HPB) system are frequently encountered in patients with inflammatory bowel disease (IBD). Hepatobiliary manifestations constitute some of the most common extraintestinal manifestations of IBD. They appear to occur with similar frequency in patients with Crohn's disease or ulcerative colitis. HPB manifestations may occur in following settings: 1) disease possibly associated with a shared pathogenetic mechanism with IBD including primary sclerosing cholangitis (PSC), small-duct PSC/pericholangitis and PSC/autoimmune hepatitis overlap, acute and chronic pancreatitis related to IBD; 2) diseases which parallel structural and physiological changes seen with IBD, including cholelithiasis, portal vein thrombosis, and hepatic abscess; and 3) diseases related to adverse effects associated with treatment of IBD, including drug-induced hepatitis, pancreatitis (purine-based agents), or liver cirrhosis (methotrexate), and reactivation of hepatitis B, and biologic agent-associated hepatosplenic lymphoma. Less common HPB manifestations that have been described in association with IBD include autoimmune pancreatitis (AIP), IgG4-associated cholangitis (IAC), primary biliary cirrhosis (PBC), fatty liver, granulomatous hepatitis, and amyloidosis. PSC is the most significant hepatobiliary manifestation associated with IBD and poses substantial challenges in management requiring a multidisciplinary approach. The natural disease course of PSC may progress to cirrhosis and ultimately require liver transplantation in spite of total proctocolectomy with ileal-pouch anal anastomosis. The association between AIP, IAC, and elevated serum IgG4 in patients with PSC is intriguing. The recently reported association between IAC and IBD may open the door to investigate these complex disorders. Further studies are warranted to help understand the pathogenesis of HPB manifestations associated with IBD, which would help clinicians better manage these patients. An interdisciplinary approach, involving gastroenterologists, hepatologists, and, in advanced cases, general, colorectal, and transplant surgeons is advocated.

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“…Mean values for LAEs were 178 IU for ALT, 117 IU for AST and bilirubin 1.1 (range 0.3-2.4 mg/dl); all abnormalities resolved after dose reduction or splitting the daily dose [31] . A longterm (five-year) follow up study of 786 IBD patients on thiopurine agents reported abnormal liver chemistries that required drug cessation in only 3.6% of all patients, suggesting that enzyme elevations are generally well tolerated or resolve spontaneously [32] . An idiosyncratic acute hypersensitivity reaction resulting in cholestatic hepatitis has also been reported with AZA [33][34][35] .…”

Section: Drug-induced Liver Injury Due To Agents Used Tomentioning

confidence: 99%

Hepatotoxicity of Agents Used in the Management of Inflammatory Bowel Disease

Khokhar

Lewis²

2010

Dig Dis

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Patients with inflammatory bowel disease (IBD) are at risk for hepatobiliary disease and toxicity, and the diagnosis of drug-induced liver disease in patients being treated for IBD can represent a clinical challenge. There are a number of disease states associated with IBD, which are primary sclerosing cholangitis, cholangiocarcinoma and autoimmune hepatitis. There is a wide spectrum of hepatic injury that can occur from the agents used to treat IBD, such as acute or chronic hepatic injury directly attributable to the drugs used to treat IBD (e.g. sulfasalazine, mesalamine, thiopurines, methotrexate, TNF antagonists, quinolone antibiotics); liver toxicity from drugs used to treat complications of immunomodulators and TNF antagonists (e.g. isoniazid for treatment of reactivation tuberculosis), and exacerbation of underlying chronic viral hepatitis with infliximab and other TNF antagonists. Thiopurines are also associated with the development of hepatic vascular lesions, such as nodular regenerative hyperplasia and peliosis hepatic. In addition, biologics can be associated with the reactivation of underlying chronic viral hepatitis, mandating universal screening prior to initiation of TNF-alpha antagonist therapy.

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Liver injury in inflammatory bowel disease: Long-term follow-up study of 786 patients

Cited by 112 publications

References 53 publications

Improving pharmacovigilance in Europe: TPMT genotyping and phenotyping in the UK and Spain

Improving pharmacovigilance in Europe: TPMT genotyping and phenotyping in the UK and Spain

Hepatopancreatobiliary manifestations and complications associated with inflammatory bowel disease

Hepatotoxicity of Agents Used in the Management of Inflammatory Bowel Disease

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