Non-steroidal Anti-inflammatory Drugs Use and Risk of Upper Gastrointestinal Adverse Events in Cirrhotic Patients

Yen-Chieh Lee; Chia-Hsuin Chang; Jou-Wei Lin; Hsi-Chieh Chen; Min-Shung Lin; Mei-Shu Lai


Liver International. 2012;32(5):859-866. 

In This Article

Abstract and Introduction


Background/Aims The upper gastrointestinal (GI) toxicity associated with non-steroidal anti-inflammatory drugs (NSAID) use among cirrhotic patients remains unclear. The objective of this study was to evaluate the risk of upper GI adverse events associated with celecoxib and oral and parenteral non-selective NSAIDs in cirrhotic patients.
Methods All the patients aged ≥ 20 years with a diagnosis of cirrhosis hospitalized for variceal bleeding and non-variceal upper GI adverse events (oesophageal, gastric, duodenal ulcer, bleeding; gastritis and duodenitis) in 2006 were identified using ICD-9-CM diagnosis codes from inpatient claims from the Taiwan National Health Insurance Database. In the case-crossover study design, the case period was defined as 1–30 days and the control period as 31–60 days before the date of hospitalization. The information for individual NSAID use was obtained from the outpatient pharmacy prescription database. Adjusted self-matched odds ratios (OR) and their 95% confidence intervals (CI) were estimated with a conditional logistic regression model.
Results A total of 4876 cirrhotic patients were included. The adjusted OR (95% CI) was 1.44 (0.89–2.31) for celecoxib, 1.87 (1.66–2.11) for oral non-selective NSAIDs and 1.90 (1.55–2.32) for parenteral NSAIDs overall. Risks were similar for variceal and non-variceal events. Concomitant use of proton pump inhibitors and histamine-2 receptor antagonists tended to decrease the upper GI toxicity associated with non-selective NSAIDs and celecoxib.
Conclusion The use of nsNSAIDs but not celecoxib was associated with a two-fold increased risk of variceal and non-variceal upper GI events among cirrhotic patients.


Acute upper gastrointestinal (GI) bleeding is a common and potentially lethal complication in cirrhotic patients. Gastroesophageal variceal bleeding is the leading cause of haemorrhage from upper GI tract, accounting for 50–70% of all cases.[1–4] Despite improvement in preventive and therapeutic strategies in managing variceal haemorrhage in the past two decades with surgical, radiologic, endoscopic modality and medications, the risk of death is still around 20%.[5,6] In the US, variceal bleeding was found to be the most expensive of all digestive diseases and cause a high economic burden to the society.[7,8] Other common sources of bleeding include peptic ulcer, haemorrhagic gastritis, esophagitis, Mallory–Weiss syndrome and erosions.

Non-steroidal anti-inflammatory drugs (NSAIDs) are important causes of upper GI adverse events, including peptic ulcer, bleeding and perforation. Randomized trials suggest that cyclooxygenase-2 enzyme selective NSAIDs are associated with a decreased risk of upper GI adverse outcome as compared with non-selective non-steroidal anti-inflammatory drugs (nsNSAIDs).[9–11] Because cirrhotic patients were excluded from these trials and few observational studies specifically targeted at this high risk population, the upper GI toxicity associated with NSAID use among cirrhotic patients remains unclear. No study evaluated the harm on upper GI tract associated with selective NSAID use and possible protective role of proton pump inhibitors and histamine-2 receptor blockers in the patients with cirrhosis. Although most experts recommended avoidance of NSAID use in patient with compensated or decompensated cirrhosis, use of NSAIDs in this high risk population is not uncommon. As the predicted number of patients with chronic liver disease and cirrhosis will increase worldwide in the next decade,[12,13] systematic evaluation of the upper GI safety of NSAIDs among cirrhotic patients is needed to help physicians choose medications with an optimal risk-benefit ratio. Taiwan is an endemic area of viral hepatitis B with high prevalence, morbidity and mortality related to chronic liver disease. Therefore, we conducted a nationwide study to examine the risks of upper GI adverse events associated with use of individual oral and parenteral selective and non-selective NSAIDs among cirrhotic patients.