Incidence Of Acute Liver Injury Research Articles

Impact of non-alcoholic fatty liver disease on coronavirus disease 2019: A systematic review.

Many studies have revealed a link between non-alcoholic fatty liver disease (NAFLD) and coronavirus disease 2019 (COVID-19), making understanding the relationship between these two conditions an absolute requirement. To provide a qualitative synthesis on the currently present data evaluating COVID-19 and NAFLD. This systematic review was conducted in accordance with the guidelines provided by preferred reporting items for systematic reviews and meta-analyses and the questionnaire utilized the population, intervention, comparison, and outcome framework. The search strategy was run on three separate databases, PubMed/MEDLINE, Scopus, and Cochrane Central, which were systematically searched from inception until March 2024 to select all relevant studies. In addition, ClinicalTrials.gov, Medrxiv.org, and Google Scholar were searched to identify grey literature. After retrieval of 11 studies, a total of 39282 patients data were pooled. Mortality was found in 11.5% and 9.4% of people in NAFLD and non-NAFLD groups. In all, 23.2% of NAFLD patients and 22% of non-NAFLD admissions diagnosed with COVID-19 were admitted to the intensive care unit, with days of stay varying. Ventilatory support ranged from 5% to 40.5% in the NAFLD cohort and from 3.1% to 20% in the non-NAFLD cohort. The incidence of acute liver injury showed significance. Clinical improvement on days 7 and 14 between the two classifications was significant. Hospitalization stay ranged from 9.6 days to 18.8 days and 7.3 days to 16.4 days in the aforementioned cohorts respectively, with 73.3% and 76.3% of patients being discharged. Readmission rates varied. Clinical outcomes except mortality consistently showed a worsening trend in patients with NAFLD and concomitant COVID-19. Further research in conducting prospective longitudinal studies is essential for a more powerful conclusion.

Impact of hepatic steatosis on risk of acute liver injury in people with chronic hepatitis B and SARS‐CoV‐2 infection

AbstractBackgroundSARS‐CoV‐2 infection was known to be associated with higher risk of liver impairment in people with chronic hepatitis B infection (CHB). However, evidence regarding the impact of concomitant hepatic steatosis (HS) on the risk of liver disease among people with CHB and SARS‐CoV‐2 infection is lacking. We investigated the impact of concomitant HS on people with CHB suffering from SARS‐CoV‐2 infection.MethodsThis retrospective cohort study was performed using an electronic health database for people in Hong Kong with CHB and confirmed SARS‐CoV‐2 infection between 21 January 2020 and 31 January 2023. People with HS diagnosis (HS + CHB + COVID‐19) were identified and matched 1:1 by propensity score with those without (CHB + COVID‐19). Each person was followed up until death, outcome event, or 31st January 2023. Study outcome was incidence of acute liver injury (ALI) within first 28 days since COVID‐19 diagnosis. Severity of ALI and comparison of ALI risk stratified by the presence of CHB infection and HS were also analysed. Incidence rate ratios (IRRs) were estimated by Poisson regression models.ResultsOf 52 259 COVID‐19 patients with CHB infection in the cohort, 15 391 people with HS + CHB + COVID‐19 and 15 391 people with CHB + COVID‐19 were included after matching. HS + CHB + COVID‐19 was associated with increased risk of ALI (IRR: 1.41, 95% CI:1.05–1.90, p = 0.023), compared to CHB + COVID‐19. Over 99% ALI cases were mild to moderate severity, and there were no differences in the severity of ALI between HS + CHB + COVID‐19 and CHB + COVID‐19 (p = 0.127).ConclusionsConcomitant HS was associated with increased risk of ALI among people with CHB infection suffering from SARS‐CoV‐2 infection.

Outcomes of two-stage type II hybrid aortic arch repair in elderly patients with acute type A aortic dissection

Acute type A aortic dissection (a-TAAD) is a severe disease characterized by high mortality, which can be fatal in elderly patients. The objective of this study was to investigate the safety and efficacy of two-stage type II hybrid aortic arch repair (HAR) in elderly patients with acute type A aortic dissection (a-TAAD). This was a single-center, retrospective study involving 119 patients with a-TAAD, including 82 males and 37 females, aged 22–81 years old. Eighty-eight patients underwent total aortic arch replacement (TAR) with frozen elephant trunk (FET) implantation (TAR with FET group) and 31 patients underwent two-stage type II HAR (HAR group). Propensity score matching was applied to adjust for preoperative data, and match 25 pairs. The preoperative, perioperative, postoperative and follow-up data were recorded. Fifteen patients died during the perioperative period; 13 cases were in the TAR with FET group and 2 cases were in the HAR group. The age, body mass index, cerebral infarction, renal insufficiency were significantly higher, and the 24-h fluid drainage, the incidence of acute liver injury, acute kidney injury and pulmonary infection were lower in the HAR group (all P < 0.05). Moreover, the mechanical ventilation time, intensive care unit time, hospital stay time were shorter in the HAR group (all P < 0.05). The follow-up period ranged from 12 to 54 months, with 7 deaths (9.3%) in the TAR with FET group and 2 deaths (6.9%) in the HAR group. The true lumen of the aortic arch and the middle descending thoracic aorta were larger and the false lumen thrombosis rates of the middle descending thoracic aorta and renal artery level were higher in the HAR group (all P < 0.05). Two-stage type II HAR is a safe and effective method for the treatment of elderly patients with a-TAAD. It may be a good choice for elderly patients with a-TAAD and comorbidities.

Retrospective evaluation of the clinical course and outcome of zinc toxicosis due to metallic foreign bodies in dogs (2005-2021): 55 cases.

To describe the overall clinical course of zinc toxicosis in dogs including source, time to source control, incidence of hemolytic anemia, acute liver injury (ALI), acute kidney injury (AKI), and pancreatitis. Retrospective case series from 2005 to 2021. Six university veterinary teaching hospitals. Fifty-five client-owned dogs with known zinc toxicosis due to metallic foreign body (MFB) ingestion. The most common source of zinc was US pennies minted after 1982 (67.3%). Forty-five of 55 (81.8%) dogs survived and 10 of 55 (18.2%) died or were euthanized. Median length of hospitalization for survivors and nonsurvivors was 3days. The most common clinical sequelae of zinc toxicosis were anemia (87%), ALI (82%), coagulopathy (71%), thrombocytopenia (30.5%), AKI (26.9%), and acute pancreatitis (5.5%). Most dogs (67.3%) required blood products and 83% of dogs achieved a stable HCT or PCV in a median of 24hours after MFB removal. The median duration of illness prior to presentation was 48hours for both survivors and nonsurvivors and there was no impact of time to presentation on the incidence of ALI, AKI, or pancreatitis. Zinc toxicosis secondary to MFB ingestion should be considered a differential diagnosis for dogs with gastrointestinal signs, hemolytic anemia, ALI, hemostatic abnormalities, AKI, and pancreatitis. AKI may be a more common sequela of zinc toxicosis than previously suspected. Acute pancreatitis is a rare but potentially serious sequela to zinc toxicosis.

Effectiveness and Safety of Lianhua Qingwen Capsules for COVID-19: A Propensity-Score Matched Cohort Study.

As a traditional Chinese medicine, Lianhua Qingwen capsules have been widely used to treat Coronavirus Disease 2019 (COVID-19). This study was aimed to demonstrate the association between treatment with Lianhua Qingwen capsules and the clinical outcomes of hospitalized patients with COVID-19. This retrospective study was conducted at four hospitals in Central China. Data of hospitalized COVID-19 patients were collected between December 19, 2019 and April 26, 2020. Based on whether Lianhua Qingwen capsules were used, patients were classified into Lianhua Qingwen and non-Lianhua Qingwen (control) groups. To control for confounding factors, we used conditional logistic regression in a propensity-score matched (PSM) cohort (1 : 1 balanced), as well as logistic regression without matching as sensitivity analysis. A total of 4918 patients were included, 2760 of whom received Lianhua Qingwen capsules and 2158 of whom did not. In the PSM model, after adjusting for confounders, the in-hospital mortality was similar between the Lianhua Qingwen group and the control group (6.8% vs. 3.3%, adjusted OR, 0.66 [95% CI, 0.38-1.15], p = 0.138). The negative conversion rate of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection was higher in the Lianhua Qingwen group (88.3% vs. 96.1%, adjusted OR, 4.02 [95% CI, 2.58-6.25], p < 0.001). The incidence of acute liver injury was comparable between the two groups (14.0% vs. 11.5%, adjusted OR: 0.85 [95% CI, 0.71-1.02], p = 0.083), and the incidence of acute kidney injury was lower in the Lianhua Qingwen group (5.3% vs. 3.0%, adjusted OR: 0.71 [95% CI, 0.50-1.00], p = 0.048). Treatment with Lianhua Qingwen capsules was not significantly associated with in-hospital mortality in COVID-19 patients. In the Lianhua Qingwen group, the negative conversion rate of SARS-CoV-2 infection was higher and the incidence of acute kidney injury was lower than in the control group.

Review of Liver Enzymes Abnormalities in Patients with SARS-CoV-2 Infection

Background: Liver function derangements have been reported in COVID-19, but reported rates are variable. Treatment in intensive care units (ICU) has become a major challenge; therefore, early recognition of severe and critical cases is absolutely essential for timely triaging of patients. Objectives: to review incidence of acute liver injury in patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Patients and methods: obtaining clinical records and laboratory results prospectively from one hundred patients with PCR-confirmed or radiography-confirmed COVID-19, who are admitted to the isolation wards and emergency departments of three different hospitals in Baghdad from 1st of December 2020 to 31st of March 2021. Results: The mean age group of study sample was (61.2±12.36) years, males formed 59%. GI manifestations were recorded in 47% of total cases, and were statistically correlated with disease severity (P value 0.001). Wide range of LFT abnormalities are found in patients with COVID-19, but none of which showed statistical significance in relation to disease severity. When LFT results were reviewed in relation to previous comorbidities, GGT was found to be statistically correlated with the underlying CLD (P value 0.001), and ALP with both underlying CLD and DM (P values &lt;0.001 and 0.029, respectively) and even in the absence of underlying comorbidity (P value 0.006). Conclusion: Liver enzyme derangements are increasingly reported in patients with COVID-19, but are not necessarily correlate with disease severity. Cholestatic picture of liver enzyme derangement is a more commonly recorded manifestation.

Scavenging ROS to Alleviate Acute Liver Injury by ZnO-NiO@COOH.

Currently, the incidence of acute liver injury (ALI) is increasing year by year, and infection with coronavirus disease 2019 (COVID‐19) can also induce ALI, but there are still no targeted therapeutic drugs. ZnO–NiO particles is mainly used to clean up reactive oxygen species (ROS) in industrial wastewater, and it is insoluble in water. Its excellent properties are discovered and improved by adding shuttle‐based bonds to make it more water‐soluble. ZnO‐NiO@COOH particles are synthetically applied to treat ALI. The p‐n junction in ZnO–NiO@COOH increases the surface area and active sites, thereby creating large numbers of oxygen vacancies, which can quickly adsorb ROS. The content in tissues and serum levels of L‐glutathione (GSH) and the GSH/oxidized GSH ratio are measured to assess the capacity of ZnO–NiO@COOH particles to absorb ROS. The ZnO–NiO@COOH particles significantly reduce the expression levels of inflammatory factors (i.e., IL‐1, IL‐6, and TNF‐α), macrophage infiltration, and granulocyte activation. ZnO‐NiO@COOH rapidly adsorb ROS in a short period of time to block the generation of inflammatory storms and gain time for the follow‐up treatment of ALI, which has important clinical significance.

Correlation of Cardiopulmonary Bypass Time with the Incidence of Acute Liver Injury after Open Heart Surgery in Dr. Sardjito Hospital January 2019 - June 2020 Period

Correlation of Cardiopulmonary Bypass Time with the Incidence of Acute Liver Injury after Open Heart Surgery in Dr. Sardjito Hospital January 2019 - June 2020 Period

Review of Liver Enzymes Abnormalities in Patients with SARS-CoV-2 Infection

<i>Background</i>: Liver function derangements have been reported in COVID-19, but reported rates are variable. Treatment in intensive care units (ICU) has become a major challenge; therefore, early recognition of severe and critical cases is absolutely essential for timely triaging of patients. Objectives: to review incidence of acute liver injury in patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). <i>Patients and methods</i>: obtaining clinical records and laboratory results prospectively from one hundred patients with PCR-confirmed or radiography-confirmed COVID-19, who are admitted to the isolation wards and emergency departments of three different hospitals in Baghdad from 1st of December 2020 to 31st of March 2021. <i>Results</i>: The mean age group of study sample was (61.2±12.36) years, males formed 59%. GI manifestations were recorded in 47% of total cases, and were statistically correlated with disease severity (P value 0.001). Wide range of LFT abnormalities are found in patients with COVID-19, but none of which showed statistical significance in relation to disease severity. When LFT results were reviewed in relation to previous comorbidities, GGT was found to be statistically correlated with the underlying CLD (P value 0.001), and ALP with both underlying CLD and DM (P values <0.001 and 0.029, respectively) and even in the absence of underlying comorbidity (P value 0.006). <i>Conclusion</i>: Liver enzyme derangements are increasingly reported in patients with COVID-19, but are not necessarily correlate with disease severity. Cholestatic picture of liver enzyme derangement is a more commonly recorded manifestation.

Hepatoprotective Potential of Pomegranate in Curbing the Incidence of Acute Liver Injury by Alleviating Oxidative Stress and Inflammatory Response.

Hepatitis is an inflammatory disease of the liver and is considered one of the leading causes of death worldwide. Due to its scavenging activity, Punica granatum may be used for the treatment and prevention of liver diseases. The current study investigated the protective mechanism underlying the effects of pomegranate against a rat model of carbon tetrachloride–induced liver injury. Intraperitoneal injection of CCl4 resulted in liver inflammation, oxidative stress, and accumulation of lipid in hepatocytes. CCl4 induced a downregulation of superoxide dismutase (SOD), glutathione (GSH), and melonaldehyde (MDA). Pomegranate protection was assessed in terms of biochemical parameters, histopathology, and immunohistochemistry. Promegranate administration decreased inflammation, elevated serum enzymes and ROS production, and countered the debilitating effects caused by CCl4. In addition, CCl4-induced histological changes were absent in the crude pomegranate extract group, which also enhanced the scavenging activity of reactive oxygen species by enhancing the antioxidant defense mechanism as confirmed by detecting MDA, SOD, and GSH expressions. The migration of CD68+ macrophages was halted at the injured area of the central vein and the number of macrophages was reduced to the normal control by the crude extract compared to the positive control silymarin group. Likewise, protective effects of ethylacetate and the aqueous fraction of the crude extract were also observed. However, the butanol and n-hexane fractions displayed increased levels of ALT, AST, and ALP as compared to silymarin. About 25% damage to hepatocytes was observed in the butanol and n-hexane group by histopathological examination, which is a little better compared to the CCl4-treated group. The crude extract and its ethyl acetate and aqueous fractions may be accountable for the hepatoprotective potential of Punica granatum, which was further confirmed by in vivo experiments. Together, these findings confirm that pomegranate exerts hepatoprotective activity against CCl4-induced oxidative stress and liver damage.

Comparing development of liver injury using the two versus three bag acetylcysteine regimen despite early treatment in paracetamol overdose

Introduction Some studies have reported that early administration of acetylcysteine using a 3-bag regimen may not fully prevent development of liver injury in some patients. We compared the incidence of acute liver injury (ALI) in patients receiving acetylcysteine within eight hours of ingestion between the two-bag acetylcysteine regimen (200 mg/kg over four hours, 100 mg/kg over 16 h) and the three-bag regimen (150 mg/kg over 1 h, 50 mg/kg over 4 h, 100 mg/kg over 16 h). Method This was a retrospective cohort study of the two-bag and three-bag acetylcysteine regimens from Monash Health, Victoria, Australia (2009–2020), compared to the three-bag acetylcysteine regimen data from the Canadian Acetaminophen Overdose Study (CAOS) database (1980–2005). The inclusion criteria included patients with an acute single ingestion of paracetamol; normal aminotransferases on presentation and acetylcysteine administered within eight hours post-overdose. The primary outcome was development of ALI (defined as: peak aminotransferase >150 IU/L). Results At Monash Health, 191 patients were treated with the two-bag acetylcysteine regimen, and 180 patients with the three-bag regimen. The CAOS cohort provided 515 patients treated with the three-bag regimen. ALI developed in 1.6% (3/191) of the two-bag Monash Health group, 2.2% (4/180) of the three-bag Monash Health group (difference −0.6%, p 0.7), and 2.9% (15/515) of the three-bag CAOS group (difference compared to two-bag −1.3%, p 0.4). Hepatotoxicity (ALT >1000) developed in 0.5% (1/191) of patients treated with the two-bag regimen, 1.7% (3/180) in the Monash Health three-bag regimen and 1% (5/515) of the three-bag CAOS group. There were no statistically significant differences between groups. Conclusions ALI and hepatotoxicity were observed in a small, comparable percentage of patients despite early acetylcysteine administration using the two-bag and three-bag regimens. Repeating blood tests at the end of acetylcysteine treatment will identify these patients and indicate those requiring continuation of acetylcysteine.

Evaluation of liver function tests after coronary artery bypass surgery (CABG).

Background:Coronary artery bypass graft surgery (CABG) may have systemic effects on the body organs as liver. The purpose of present study was to evaluate changes in liver function tests(LFT) after on-pump CABG surgery and risk factors associated with LFT changes.Also, the incidence of acute liver injury after on-pump CABG is determined.Methods:385 patients who underwent on-pump CABG surgery were randomly selected.Preoperative and intraoperative risk factors were obtained from their medical records .Postoperative liver function tests at 24, 48 and 72 hours following surgery and discharge time were compared with the preoperative ones. A univariate linear regression analysis was used to assess the possible relationships between these changes and the preoperative and intraoperative risk factors.Results:Statisitcal analysis revealed direct and significant relationship between LFT changes and pump time, aortic cross-clamp clamp time and use of intra-aortic balloon pump(IABP). Also a medical history of previous myocardia infarction was significantly related to the changes in direct bilirubin in the first 48 hours following surgery.level of preoperative left ventricle ejection fraction,smoking and using opium had significant correlation with postoperative AST changes in different days.In 12.9% of patients, the aminotransferases levels increased to more than three folds over normal upper limit but the probability for incidence of acute ischemic liver injury (transient increase in aminotransferases to over 500IU/L) was 0.77%.Conclusion: Using techniques to reduce clamp and pump time when possible is important during CABG. Probable liver injuries post inserting IABP should be expected for appropriate monitoring and treatment.

Liver Injury in Liver Transplant Recipients With Coronavirus Disease 2019 (COVID-19): U.S. Multicenter Experience.

Background and AimsCoronavirus disease 2019 (COVID‐19) is associated with liver injury, but the prevalence and patterns of liver injury in liver transplantation (LT) recipients with COVID‐19 are open for study.Approach and ResultsWe conducted a multicenter study in the United States of 112 adult LT recipients with COVID‐19. Median age was 61 years (interquartile range, 20), 54.5% (n = 61) were male, and 39.3% (n = 44) Hispanic. Mortality rate was 22.3% (n = 25); 72.3% (n = 81) were hospitalized and 26.8% (n = 30) admitted to the intensive care unit (ICU). Analysis of peak values of alanine aminotransferase (ALT) during COVID‐19 showed moderate liver injury (ALT 2‐5× upper limit of normal [ULN]) in 22.2% (n = 18) and severe liver injury (ALT > 5× ULN) in 12.3% (n = 10). Compared to age‐ and sex‐matched nontransplant patients with chronic liver disease and COVID‐19 (n = 375), incidence of acute liver injury was lower in LT recipients (47.5% vs. 34.6%; P = 0.037). Variables associated with liver injury in LT recipients were younger age (P = 0.009; odds ratio [OR], 2.06; 95% confidence interval [CI], 1.20‐3.54), Hispanic ethnicity (P = 0.011; OR, 6.01; 95% CI, 1.51‐23.9), metabolic syndrome (P = 0.016; OR, 5.87; 95% CI, 1.38‐24.99), vasopressor use (P = 0.018; OR, 7.34; 95% CI, 1.39‐38.52), and antibiotic use (P = 0.046; OR, 6.93; 95% CI, 1.04‐46.26). Reduction in immunosuppression (49.4%) was not associated with liver injury (P = 0.156) or mortality (P = 0.084). Liver injury during COVID‐19 was significantly associated with mortality (P = 0.007; OR, 6.91; 95% CI, 1.68‐28.48) and ICU admission (P = 0.007; OR, 7.93; 95% CI, 1.75‐35.69) in LT recipients.ConclusionsLiver injury is associated with higher mortality and ICU admission in LT recipients with COVID‐19. Hence, monitoring liver enzymes closely can help in early identification of patients at risk for adverse outcomes. Reduction of immunosuppression during COVID‐19 did not increase risk for mortality or graft failure.

Risk of oral antifungal agent‐induced liver injury in Taiwanese

Oral antifungal agent-induced liver injury is a common safety concern that may lead to patients' hesitation in treating fungal infections such as onychomycosis. This study evaluated risk of drug-induced liver injury (DILI) caused by oral antifungal agents in Taiwanese populations. A population-based study was conducted by analyzing who used oral antifungal agents from 2002 to 2008 from the Taiwan National Health Insurance Database. A comparison control group was randomly extracted from the remainder of the original cohort. Of the 90,847 oral antifungal agents users, 52 patients had DILI. Twenty-eight DILI cases used ketoconazole, 12 fluconazole, eight griseofulvin, three itraconazole and two terbinafine. The incidence rates (IR) of DILI per 10,000 persons were 31.6, 4.9, 4.3, 3.6 and 1.6 for fluconazole, ketoconazole, griseofulvin, itraconazole and terbinafine, respectively. Longer exposure duration increased the risk of DILI, with IR for exposure duration ≥ 60 defined daily dose (DDD) of 170.9, 62.5, and 36.1 per 10,000 persons for ketoconazole, itraconazole and terbinafine, respectively. Patients taking antifungal agents had higher incidences of developing DILI compared with those in the control group after adjusting for age, gender and co-morbidities (relative risk 2.38, P < 0.001). All of the six patients with fatal DILI used fluconazole. Old age and fluconazole increased the risk of oral antifungal-induced fatal DILI. Oral antifungal agents are associated with low incidence of acute liver injury, but which may be fatal, especially for the elderly. Longer treatment duration may increase the risk of antifungal agent-induced liver injury, especially ketoconazole.

Orlistat and the risk of acute liver injury: self controlled case series study in UK Clinical Practice Research Datalink

Objective To measure the association between orlistat and acute liver injury.Design Self controlled case series study.Setting Population based primary care setting, United Kingdom.Participants 94 695 patients receiving orlistat and registered...

Risk of acute liver injury associated with the use of drugs: a multicentre population survey

Acute liver injury of uncertain aetiology is often drug related and quantitative information about the associated risk is scarce. To estimate the risk of acute liver injury associated with the use of drugs. In a population survey study, 126 cases of acute liver injury were prospectively assembled from January 1993 to December 1999, in patients over 15 years of age, in 12 hospitals in Barcelona (Spain). We estimated the relative risk for each drug as the ratio between the incidence of acute liver injury among the exposed population to the drug and the incidence of acute liver injury among those not exposed to it. Drug consumption data were used to estimate the exposed population. Isoniazid, pyrazinamide, rifampicin, amoxicillin with clavulanic acid, erythromicin, chlorpromazine, nimesulide, and ticlopidine presented the highest risk (point relative risk > 25). Amoxicillin, metoclopramide, captopril and enalapril, furosemide, hydrochlorothiazide, fluoxetine, paroxetine, diazepam, alprazolam, lorazepam, metamizole, low-dose acetylsalicylic acid and salbutamol showed the lowest risk (point relative risk < 5). This study provides a risk estimation of serious liver disease for various drugs that will be useful in its diagnosis and management, and when comparing with the drug therapeutic benefit in each indication. Some observed associations would be worth specific studies.

Acute liver injury associated with nonsteroidal anti-inflammatory drugs and the role of risk factors.

Hospitalizations for acute liver injury in the absence of a viral infection or any other well-defined pathologic finding that could have caused it is rare. In this study, we included both outpatients and hospitalized patients with acute liver injury to estimate the risk of clinically important acute liver injury associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and to study the role of certain risk factors. This was a retrospective cohort study with secondary case-control analysis. The study included 536 general practitioners' practices in England and Wales for the period October 1987 through August 1991. A total of 625,307 persons who received more than 2 million prescriptions for one of 12 NSAIDs were followed up to estimate the risk of newly diagnosed acute liver injury. There were 23 cases of acute liver injury. The incidence of acute liver injury was 3.7 per 100,000 NSAID users or 1.1 per 100,000 NSAID prescriptions. None of the cases had a fatal outcome. Sulindac was the only NSAID with a substantially greater risk than that for the overall NSAID group. Users of NSAIDs who had rheumatoid arthritis had a 10-fold increased risk of acute liver injury compared with NSAID-treated patients with osteoarthritis. Concomitant exposure to other hepatotoxic medications also increased the risk. Transient minor increases in liver test values were not a useful predictor of diagnosed NSAID-associated acute liver injury. Although NSAIDs have been found to be associated with acute liver injury in a small number of persons, the risk is sufficiently small as to be of minimal concern for most NSAIDs.