A recent large single center study (Pusateri AJ et al. JPGN 2015; 60: 592-97) provides some very practical information regarding elevated liver enzymes in the setting of inflammatory bowel disease (IBD). Because there are some serious liver diseases associated with IBD and due to the potential for liver toxicity from many of the medications, bumps in liver enzymes need to be carefully considered.
This retrospective study with 514 patients indicates that 77% of these elevations are transient. Table 1 lists the definitions (chronicity, severity) and patterns that were analyzed. Transient elevations were broken down into brief (<30 days), prolonged <180 days, chronic >180 days and either intermittent or continuously abnormal. The three types were the following:
- Hepatic: elevated ALT and/or AST; normal alkaline phosphatase (AP), GGT, and direct bilirubin (DB)
- Cholestatic: elevated AP, GGT, and/or DB; normal ALT and AST
Severity or degree was classified as follows:
- 1 –peak liver enzyme 0-1 x ULN
- 2 –peak liver enzyme >1-2 x ULN
- 3 –peak liver enzyme >2-4 x ULN
- 4 –peak liver enzyme >4 x ULN
- 219 of 514 patients had 1 or more episode of abnormal liver enzymes; five patients with preexisting liver disease were excluded from the analysis.
- Of 214 patients (152 with Crohn’s disease [CD], 62 with Ulcerative colitis [UC]) with abnormalities, 69% had a hepatitic pattern, 8% had a cholestatic pattern, and 23% had a mixed pattern. There was no association between the pattern and the final diagnosis (eg. idiopathic vs defined etiology)
- Only 128 had adequate data to assess chronicity. In this group, 77% had transient elevations (CD 75%, UC 80%)
- 87% of elevations were considered idiopathic. 65% of patients with idiopathic elevation had levels < 2 times ULN.
- Among patients with levels <2 times ULN, 95.3% had an idiopathic etiology.
- Among patients with levels >4 times ULN, 63% had a benign idiopathic etiology
- Figure 1 provides a pie chart of diagnoses. Among the 12.6% with a specific etiology for elevated liver tests, drug toxicity was the most common reason: 51.9% were considered due to 6-MP therapy, 3.7% due to methotrexate, 3.7% due to acetaminophen.
- Other identified causes among the 12.6% with a defined etiology included NAFLD in 11.1%, infections (CMV,EBV, Histoplasmosis) in 14.8%, cholelithiasis in 3.7%, autoimmune hepatitis in 3.7%, primary sclerosing cholangitis/overlap in 3.7%, and vascular malformation in 3.7%.
As with any retrospective study, there are a number of limitations, especially underdiagnosis given a lack of uniform approach to evaluation. That being said, all patients had a minimum follow-up of at least nine months and most patients with prolonged liver enzyme elevation would have been examined closely.
Bottomline: This study provides reassurance that liver enzyme elevations are common in children with IBD, occurring in >40% of patients over 3 years at this center; most often these elevations are benign and transient.
Related blog posts:
- Screening for subclinical PSC in IBD? | gutsandgrowth
- Liver Disease Associated with Inflammatory Bowel Disease …
- Advice on drug-induced liver injury (DILI) | gutsandgrowth
- Liver toxicity -where to look online | gutsandgrowth
- Liver Injury from Anti-TNF Agents | gutsandgrowth
- Methotrexate and liver toxicity | gutsandgrowth