Cases Of Severe Liver Injury Research Articles

S3482 A Yellow Flower With Jaundice Power: A Case of Severe Liver Injury Attributed to Greater Celandine

S3482 A Yellow Flower With Jaundice Power: A Case of Severe Liver Injury Attributed to Greater Celandine

S2904 A Superfood With a Dark Side: A Case of Severe Liver Injury Due to Turmeric

S2904 A Superfood With a Dark Side: A Case of Severe Liver Injury Due to Turmeric

S3014 Hepatotoxic Effects of Whey Protein Supplementation

Introduction: Currently, more than 50% of Americans take dietary supplements. Whey is a commonly used protein supplement that is often viewed as safe, with only rare reports of drug-induced liver injury (DILI). Here, we report an unusual case of severe liver injury following whey protein consumption. Case Description/Methods: A 40-year-old female with obesity and well-controlled hypothyroidism presented with 3 days of nausea and painless jaundice. Her only home medication was levothyroxine. Two months prior, she began drinking whey protein shakes (each containing 20 grams of protein) twice daily to aid with weight loss. She denied use of alcohol, recreational drugs, herbal supplements, and recent medication changes. On physical exam, she was alert and oriented x4, with jaundice and scleral icterus present. Lab work was significant for ALT 2,502, AST 1,434, total bilirubin 11.0, INR 1.42, and platelets 217,000. Acetaminophen and salicylate levels were unremarkable. Her whey protein supplementation was immediately stopped and a workup for transaminitis was initiated. RUQ ultrasound was unremarkable. Evaluation for other causes of acute liver injury, including viral hepatitis (A, B, C, E), EBV, CMV, HIV, hemochromatosis, Wilson’s disease, and autoimmune hepatitis was unremarkable. A liver biopsy was performed, with pathology showing diffuse ballooning degeneration of hepatic parenchyma, numerous acidophil bodies, and dominant pericentral hepatocyte drop-out. A diagnosis of DILI (with predominant hepatocellular injury) was made. Following discontinuation of whey protein supplementation, the patient’s labs and clinical symptoms improved, and she was discharged home on hospital day 8. Discussion: This case highlights a rare occurrence of DILI secondary to whey protein consumption and emphasizes the importance of taking a thorough history when working up liver injury. Furthermore, in the treatment of DILI, we recommend cessation of all possible offending agents that were recently started, including supplements that are reputably marketed to be safe for consumption.

Gynura segetum-induced liver injury leading to acute liver failure: a case report and literature review

BackgroundGynura segetum (GS) is widely used in medical care and in community settings in China as the herbal remedy. It is widely thought to have antiphlogistic properties and pain relief in traditional Chinese medicine. It has been reported that GS can cause chronic drug-induced liver injury (DILI), manifested as hepatic sinusoid obstruction syndrome (HOSO). But case reports of acute DILI developing acute liver failure (ALF) due to GS are extremely rare.Case presentationWe report a case of a 63-year-old female patient with hepatolithiasis for more than 6 years. There were no deterioration of liver function and no history of viral liver disease, autoimmune liver disease, blood transfusion or surgical allergy before operation. ALF and grade II liver encephalopathy occurred after partial hepatectomy. To follow up the medical history, the patient has been taking GS (Tusanqi) for a year and a half. The causality assessment was done by the updated Roussel Uclaf Causality Assessment Method, and the possibility of DILI caused by GS as highly probable for the score was 6 points. Excluding other causes, a diagnosis of DILI-associated ALF was established. After symptomatic support and artificial liver support system (ALSS) treatment, the clinical symptoms and signs of the patients were significantly improved. After discharge, the liver function of the patients returned to normal.ConclusionsBased on this rare case of severe liver injury, we recommend that timely prevention, identification, and appropriate management of DILI is essential for patients with a history of taking GS and other hepatotoxic drugs, and careful monitoring of liver function for patients with DILI could avoid ALF as far as possible.

Dili is rare amongst patients without liver metastases receiving cancer treatment in Iceland: a population-based cohort study

Background There is limited information on the frequency of idiosyncratic drug-liver injury (DILI) among cancer patients. The aim of the study was to evaluate the frequency of DILI due to cancer treatment in a population-based setting. Material and methods All patients diagnosed with genitourinary cancer, breast cancer or metastatic malignant melanoma in 2007–2018 were matched with a database containing laboratory results for all major hospitals in Iceland. Medical chart review was performed for cases with ALT/AST ≥5× upper limit of normal (ULN), ALP ≥2× ULN or bilirubin ≥2× ULN. Patients with liver-, and/or bone metastases and isolated elevations of ALP and patients with other etiologies of liver enzyme elevations were excluded. Cases with a RUCAM score of probable or highly probable were included. Results Among 4956 patients, 840 patients had liver enzyme elevations. Overall, nine (0.2%) cases of DILI were identified, seven women (78%), median age 59 years (IQR 52–66). Four patients had kidney cancer, four breast cancer and one metastatic prostate cancer. In eight cases, a single agent was implicated: Pazopanib (n = 3), axitinib, docetaxel, gemcitabine, letrozole and paclitaxel. In all cases, the treatment was interrupted or discontinued due to the liver injury. No patient developed jaundice or liver failure and no death was linked to DILI. Time to normalization of liver enzymes was 17 days (IQR 25–120). Conclusion DILI was found to be rare and no cases of severe liver injury occurred. However, approximately 90% of patients switched to another treatment which might have affected prognosis.

Severe tyrosine-kinase inhibitor induced liver injury in metastatic renal cell carcinoma patients: two case reports assessed for causality using the updated RUCAM and review of the literature

BackgroundSunitinib and pazopanib are both oral small molecule multityrosine kinase inhibitors (MTKI) used in the treatment of renal cell carcinoma (RCC). Hepatotoxicity or “liver injury” is the most important adverse effect of pazopanib administration, but little is known about the underlying mechanism. Liver injury may also occur in patients treated with sunitinib, but severe toxicity is extremely rare. Herein we report two new cases of severe liver injury induced by MTKI. Both cases are unique and exceptional. We assessed both cases for drug-induced liver injury (DILI) using the updated score Roussel Uclaf causality assessment method (RUCAM). The literature on potential pathogenic mechanisms and precautionary measures is reviewed.Case presentationA case of a metastatic RCC (mRCC) patient treated with pazopanib who had manifestation of severe liver injury is presented. These manifestations consisted of grade 4 alanine aminotransferase (ALT) increase and grade 4 hyperbilirubinemia. Alternate causes of acute or chronic liver disease were excluded. The patient gradually recovered from the liver injury and refused any further therapy for mRCC. The patient was diagnosed with acute myeloid leukemia (AML) two years later and eventually succumbed to the disease. The second case describes a mRCC patient treated with sunitinib for 3,5 years and fatal liver failure after 2 weeks of clarithromycin co-medication for acute bronchitis.ConclusionsLiver injury has been commonly observed in TKI-treated patients with unpredictable course. Management requires regular routine liver enzyme-monitoring and the collaboration of medical oncologist and hepatologist. There is an unmet medical need for a risk stratification and definition of predictive biomarkers to identify potential genetic polymorphisms or other factors associated with TKI-induced liver injury. Any potential unrecommended concomitant therapy has to be avoided.

Impact of Non-Alcoholic Simple Fatty Liver Disease on Antituberculosis Drug-Induced Liver Injury.

ObjectiveTo observe the effect of non-alcoholic simple fatty liver disease on drug-induced liver injury caused by tuberculosis.MethodsWe retrospectively analyzed the incidence, characteristics, and risk factors of antituberculosis drug-induced liver injury in 104 patients with initial treatment of tuberculosis complicated with non-alcoholic simple fatty liver disease. The patients were divided into two groups according to whether there was liver injury or not. The differences in age, gender, body mass index (BMI), cholesterol, and triglycerides were studied between the two groups.ResultsAmong the 104 patients with initial treatment of tuberculosis complicated with non-alcoholic fatty liver disease, 24 (23%) patients developed a drug-induced liver injury. The remaining 80 (77%) patients did not develop drug-induced liver injury (χ2 = 60.308, P < 0.05). In the liver injury group, there were 20 cases of mild liver injury, two cases of moderate liver injury, two cases of severe liver injury, 22 cases of hepatocellular injury, two cases of cholestasis, and no cases of mixed liver injury. The time of abnormal liver function in antituberculosis treatment was 16.42 ± 9.18 days from the beginning of the antituberculosis treatment. There were no significant differences in gender, age, BMI, or triglyceride between the liver injury group and the non-liver injury group (χ2 = 2.063, t = 0.179, t = 0.703, t = 1.12, P > 0.05 in all), but there were significant differences in cholesterol (t = 3.08, P < 0.05). By logistic regression analysis, cholesterol was a high-risk factor for liver injury.ConclusionNon-alcoholic simple fatty liver disease may increase the risk of antituberculosis drug-induced liver injury.

Zanubrutinib-induced liver injury: a case report and literature review

BackgroundZanubrutinib is a Bruton’s tyrosine kinase inhibitor that has been recently licensed in refractory mantle cell lymphoma and under assessment in phase 3 clinical trials for other B cell malignancies. To date, there are no reported cases of hepatotoxicity secondary to zanubrutinib. We report the first case of severe liver injury due to zanubrutinib.Case presentationA 56-year-old Caucasian male with a history of relapsed lymphoplasmacytic lymphoma was admitted to the hospital with new-onset jaundice, choluria, and pruritus for 10 days. He had been on zanubrutinib as part of a clinical trial for 30 months. His blood profile showed a severe hepatocellular injury with jaundice (alanine transaminase 2474 IU/L and total bilirubin 141 umol/L with mild coagulopathy). He had an extensive work-up including virology, autoimmune, and metabolic profiles in addition to abdominal ultrasound with no alternative explanation found for his liver injury. Zanubrutinib-induced liver injury was suspected, and causality assessment by the updated Roussel Uclaf Causality Assessment Method score showed a probable causal relationship with zanubrutinib. His liver histology was also consistent with drug-induced liver injury. His liver biochemistry improved following cessation of zanubrutinib and normalised after 8 weeks.ConclusionWe report the first case of severe liver injury secondary to zanubrutinib after 30 months of treatment. This case raises clinical awareness regarding zanubrutinib-induced liver toxicity and the importance of drug withdrawal in the event of liver injury.

Encorafenib/binimetinib induced severe liver injury in a melanoma patient: Case report and review of literature

Encorafenib/binimetinib combination is approved for BRAF mutated melanoma and is being increasing used. The landmark COLUMBUS trial reports <10% incidence of any liver related injury markers and no cases of severe liver injury from the regimen was noted. We report a 48-year-old male with severe life-threatening liver injury with the regimen. This injury was reproducible with re-introduction of the drug and vanished when the drugs were held. Dose reduction of encorafenib component of the combination allowed the regimen to be continued without liver damage. This highlights the only 2nd case reported with severe liver toxicity from the drug combination and proof-of-principle of using the lower dose in such scenario.

Tocilizumab for severe COVID-19 pneumonia.

We read with interest the study of Giovanni Guaraldi and colleagues1 on the use of tocilizumab in patients with COVID-19. We congratulate the authors for their effort to assess the effects of tocilizumab in patients with COVID-19, and for the promising results achieved. We wish to suggest a word of caution about the absence of association between the use of tocilizumab and liver injury in their study. Liver function test abnormalities occurred in up to 50% of patients treated with tocilizumab in registration trials, and cases of severe liver injury have been described after tocilizumab licensure.

Lomitapide and Mipomersen-Inhibiting Microsomal Triglyceride Transfer Protein (MTP) and apoB100 Synthesis.

The goal of this review is to evaluate the role of inhibiting the synthesis of lipoproteins when there is no or little residual LDL-receptor function as in patients with homozygous familial hypercholesterolaemia. Lomitapide is administered orally once a day while mipomersen is given by subcutaneous injection once a week. Lomitapide inhibits microsomal triglyceride transfer protein while mipomersen is an antisense oligonucleotide directed against apoB100. The pivotal registration trials for lomitapide and mipomersen were published in 2013 and 2010, respectively. More recently published data from extension trials and cohort studies provides additional information on long-term safety and efficacy. The mean LDL cholesterol reduction was 50% with lomitapide in its single-arm open-label registration trial. Mipomersen reduced LDL cholesterol by approximately 25% in its double-blind, placebo-controlled registration study. Both lomitapide and mipomersen therapy are associated with variable increases in hepatic fat content. The long-term safety of increased hepatic fat content in patients receiving these therapies is uncertain and requires further study. Both drugs may cause elevated transaminase in some patients, but no cases of severe liver injury have been reported. Lomitapide may also cause gastrointestinal discomfort and diarrhoea, especially if patients consume high-fat meals and patients are advised to follow a low-fat diet supplemented with essential fatty acids and fat-soluble vitamins. Mipomersen may cause injection-site and influenza-like reactions. The effect of lomitapide and mipomersen on cardiovascular outcomes has not been studied, but circumstantial evidence suggests that the LDL cholesterol lowering achieved with these two agents may reduce cardiovascular event rates.

Suspected drug-induced liver injury associated with iguratimod: a case report and review of the literature

BackgroundIguratimod is a novel anti-rheumatic drug with the capability of anti-cytokines as report goes. It has been reported that iguratimod is effective and safe for rheumatoid arthritis and other rheumatisms. As side effects, iguratimod can cause gastrointestinal reactions, dizziness, headache and itchy.Case presentationIn this case report, a 60-year-old female patient was admitted with suspected drug-induced liver injury (DILI) caused by iguratimod. The causality assessment was done by the updated RUCAM, and the possibility of the case in our paper diagnosed as highly probable for the score was 9 points. Iguratimod was discontinued immediately, and methylprednisolone was used for acute liver injury and Sjogren’s syndrome. The data showed the patient has improved gradually, and she was discharged on day 27. The true incidence of iguratimod-related hepatotoxicity and its pathogenic mechanism are largely unknown. It is difficult to recognize and diagnose DILI, and there is no standard for diagnosis of DILI. At the same time, the DILI is still lack of specific treatment.ConclusionsBased on this rare case of severe liver injury, we recommend careful monitoring of liver function throughout iguratimod treatment for diseases.

A Rare Case of Severe Liver Injury Related to Whey Protein Supplementation

A Rare Case of Severe Liver Injury Related to Whey Protein Supplementation

The Safety of Atomoxetine for the Treatment of Children and Adolescents with Attention-Deficit/Hyperactivity Disorder: A Comprehensive Review of Over a Decade of Research.

Atomoxetine is a noradrenergic reuptake inhibitor prescribed for attention-deficit/hyperactivity disorder (ADHD) that first gained approval in the USA in 2002 and has been authorized in 97 countries worldwide. The aim of this paper is to comprehensively review publications that addressed one or more of sevenmajor safety topics relevant to atomoxetine treatment of children and adolescents (aged≥6years) diagnosed with ADHD. While the review focuses on children and adolescents, publications in which data from patients aged>18years and from 6 to 18years were analyzed in the same dataset were included. Using a predefined search strategy, including agreement of two reviewers when selecting papers, reduced the potential for bias. Using this process, we identified 70 eligible papers (clinical trials, epidemiological studies, and case reports) across the seven topics. We also referred to the European Summary of Product Characteristics (SPC) and US label. We found 15 papers about suicidality, three about aggression/hostility, seven about psychosis/mania, six about seizures, seven about hepatic effects, 29 about cardiovascular effects, and 28 about growth and development. The main findings (i.e., those from the largest and most well-conducted studies/analyses) are as follows. A large register-based study of pediatric and adult patients (6818 received atomoxetine) calculated a hazard ratio of 0.96 for suicide-related events during treatment with atomoxetine, and a meta-analysis of 23 placebo-controlled studies (N=3883), published in 2014, found no completed suicides and no statistically significant association between atomoxetine and suicidality. The frequency of aggression/hostility was not statistically significantly higher with atomoxetine, e.g., experienced by 1.6% (N=21/1308) of atomoxetine-treated patients versus 1.1% (N=9/806) of placebo-treated patients in one meta-analysis. Symptoms of psychosis and mania were mainly observed in patients with comorbid bipolar disorder/depression. Based on spontaneous reports, during a 2-year period when 2.233 million adult and pediatric patients were exposed to atomoxetine, the reporting rate for seizures was 8 per 100,000 patients. In the manufacturer's database, atomoxetine was a "probable cause" of three hepatic adverse events (AEs) (all reversible hepatitis), and 133 hepatic AEs had possible confounding factors and were "possibly related" to atomoxetine, during 4years when atomoxetine exposure had reached about 4.3 million patients. Rare cases of severe liver injury are described in the US label and European SPC; a case requiring liver transplantation is described in the US label. In a comprehensive review of a clinical trials database (N=8417 received atomoxetine), most pediatric patients experienced modest increases in heart rate and blood pressure, and 8-12% experienced more pronounced changes (≥20bpm, ≥15 to 20mmHg). However, in three long-term analyses (≥2years), blood pressure was within age norms, and few patients discontinued due to cardiovascular AEs. As described in the European SPC, QT interval prolongation is uncommon, e.g., in an open-label study, 1.4% of 711 children and adolescents had prolonged QTc intervals (≥450 ms in males,≥470 ms in females) that were not clinically significant at≥3years of treatment with atomoxetine. The European SPC warns about potential QT interval prolongation in patients with a personal or family history, or if atomoxetine is administered with other drugs that potentially affect the QT interval. Decreases in growth (weight and height gain) occurred and were greatest in patients of above average weight and height, but appeared to recover over 2-5years of atomoxetine treatment. In conclusion, suicidality, aggression/hostility, psychosis, seizures, liver injuries, and prolonged QT interval are uncommon or rare in children and adolescents treated with atomoxetine, based on data from the predefined search and from the European SPC. Overall, the data that we assessed from our search do not suggest that associations exist between atomoxetine and suicidality or seizures. The data also suggest that an association may not exist between atomoxetine and aggression/hostility. While atomoxetine may affect the cardiovascular system, the data suggest these effects are not clinically significant in most patients. Reductions in growth appear to be reversible in the long term.

Drug-Induced Liver Injury With Warzone: A War Against Drug Supplements?

Drug induced liver injury (DILI) is an important cause of hepatic injury and is a growing challenge given the increasing number of drugs. We describe a rare case of severe liver injury after the use of Warzone and Protex. A 29-year-old man with a history of depression and GERD presented with 2 weeks of progressive jaundice, pruritus and nausea after 3 weeks of initiating a body building supplement - Warzone (Trenavar, DMZ, Carbopol, Methystem, and Halodrol). Upon becoming jaundiced, Protex (milk thistle, n-acetyl cysteine, alpha lipoic acid and selenium) was self-initiated to support hepatic function. No family history of liver disease, recent travel or sick contacts. No alcohol use, illicit drug use, body piercing or tattoos. On exam, he was afebrile, hemodynamically stable, well appearing but icteric. No hepatosplenomegaly, encephalopathy or asterixis noted. Laboratory studies showed AST 183 U/L, ALT 524 U/L, total bilirubin 8.8 mg/dL (peaking at 52 mg/dL 4 weeks later), alkaline phosphatase 73 U/L and INR of 0.94. Hemogram, renal function, tests for autoimmune hepatitis, viral hepatitis, Wilson's disease, alpha 1 antitrypsin deficiency and hemochromatosis were unremarkable. Abdominal US and CT showed unremarkable liver and bile ducts, without stones or sludge. Liver biopsy showed marked cholestasis, moderate chronic inflammation with hepatocellular dropout consistent with DILI without any massive hepatocellular necrosis, interface hepatitis, macrovesicular steatosis, lymphoid aggregate, features of cholangitis or fibrosis. He was counseled to avoid supplements. Cholestyramine and ursodiol were initiated, with prednisolone 40 mg daily added 1 month later, as he continued to show cholestatic injury with rising bilirubin. With a 4 week taper of prednisolone, LFTs improved (AST 44 U/L, ALT 27 U/L, total bilirubin 38 mg/dL, and alkaline phosphatase 178 U/L). DILI is the leading cause of drug withdrawal from the United States market. The severity of liver injury due to androgenic or anabolic steroids ranges from minor transient serum enzyme elevations to profound prolonged cholestasis. Early recognition allows for prompt discontinuation of the inciting agent and treatment allowing for a successful recovery. Merely decreasing the dose of the offending agent or switching to another formulation is not appropriate and should be discouraged. Healthcare providers should be aware of the potential for liver injury due to supplements.

Acute Liver Injury during Co-treatment with Levetiracetam and Temozolomide

Drug-induced liver injury (DILI) accounts for approximately 10 percent of all cases of acute hepatitis. The patterns of acute injury include any form of hepatic injury, but the most common problems are cholestasis, hepatocellular damage, or a mixed type. DILI is often re- versible, and discontinuation of the offending agent usually results in a complete recovery; however, some cases may lead to chronic liver injury, cirrhosis, and even death. Temozolomide (TMZ) is an alkylating, anti-neoplastic agent used for the treatment of refractory anaplastic astrocytoma, newly-diagnosed Glioblastoma multiforme (GBM) and metastatic melanoma. Levetiracetam (LEV) is an established second-generation antiepileptic drug and is most com- monly approved as adjunctive treatment of partial-onset seizures with or without secondary generalization. When administered separately each of these drugs is considered to be relatively safe and only few cases of severe liver injury can be found throughout the literature; however, LEV and TMZ are commonly used together in the treatment of brain malignancies. We report three patients who presented with jaundice during treatment with TMZ and LEV, and propose a mechanism for liver sensitization by LEV for TMZ-induced injury.

Silodosinにより重篤な薬物性肝障害を惹起した1例

Silodosinにより重篤な薬物性肝障害を惹起した1例

Inhibition of cytochrome P450s enhances (+)‐usnic acid cytotoxicity in primary cultured rat hepatocytes

(+)-Usnic acid (UA) is consumed as a dietary supplement to promote weight loss; however, dietary supplements containing UA have been associated with clinical cases of severe liver injury. UA has been shown to be hepatotoxic in rats and is extensively metabolized by hepatic cytochrome P450s (CYPs); therefore, we examined if UA metabolism results in the formation of cytotoxic metabolites or if metabolism is a detoxification process in primary rat hepatocytes. When CYP activity was suppressed by the non-isoenzyme-selective inhibitor SKF-525A (20 μM), or the CYP1A inhibitor alpha-naphthoflavone (10 μM), or the CYP3A inhibitor ketoconazole (25 μM), the cytotoxicity of UA at 3~6 μM after 3~20 h of exposure was significantly increased as measured by lactate dehydrogenase (LDH) leakage. At 2 h after UA exposure, an earlier time point prior to LDH release, these CYP inhibitors potentiated UA-induced inhibition of cellular respiration as determined by the Clark type oxygen electrode. Cellular adenosine triphosphate (ATP) depletion by UA was also exacerbated by these CYP inhibitors. The CYP2B/2C inhibitor, ticlopidine at 20 μM, showed no effects in parallel experiments. These data demonstrate that UA is bio-transformed to less toxic metabolites in rat primary hepatocytes, probably mainly by CYP1A and 3A, but not 2B/2C. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

Two cases of food additive-induced severe liver damage associated with positive results on lymphocyte stimulation test and for antinuclear antibodies.

Two cases of severe liver injury and positive result for antinuclear antibodies induced by food additives are reported. The first patient reported long-term intake of Mabo Ramen(®) noodle soup, nutritional supplements, and over-the-counter drugs. Total bilirubin, aspartate aminotransferase, and alanine aminotransferase were 9.6mg/dL, 1,048, and 1,574IU/L, respectively. Antinuclear antibody was 80×. The drug-induced lymphocyte stimulation test (DLST) was positive for Mabo Ramen(®) and its additives such as Xanthan gum, guar gum, and Doubanjiang. Histologic examination of a liver biopsy specimen showed lymphocyte infiltration and necrosis. The autoimmune hepatitis score was 3. The second patient reported intake of dietary supplements, including Bimore C(®) and Chokora BB(®). Laboratory tests revealed that total bilirubin was 9.8mg/dL, aspartate aminotransferase was 1,130IU/L, and alanine aminotransferase was 1,094IU/L. Antinuclear antibody was 320×. Co-existing pancreatic damage was confirmed by the findings on abdominal CT and elevation of serum lipase, span-1, and DUPAN-2. DLSTs were positive for both supplements. These two supplements contained additives such as titanium oxide, magnesium stearate, and hydroxypropylcellulose. DLSTs for all three additives were positive. Histologic examination revealed periportal necrosis and lymphocyte infiltration of lobular and portal areas. These two cases demonstrate that repeating DLSTs is useful for identifying causative constituents in foods and supplements.

Severe acute liver injury associated with lumiracoxib

Significant elevations in liver transaminases were noted in some patients during pre-marketing clinical trials with lumiracoxib, a selective COX-2 inhibitor. It was withdrawn from the Australian market in August 2007, because of an association with severe liver injury. We describe in detail three cases of severe liver injury in patients taking lumiracoxib Three patients admitted to our hospital with severe liver injury and taking lumiracoxib are described in detail, together with information on a further six cases reported to the Australian Therapeutics Goods Administration (TGA), none of whom had pre-existing liver disease or obvious risk factors for liver disease. Liver histology showed severe hepatic necrosis. One patient required liver transplantation and another died. Autoantibodies were detected in all three patients. As with the other six cases reported to the TGA, all were females who had been taking lumiracoxib 200-400 mg daily, typically for a few months, for osteoarthritis. Lumiracoxib can be associated with severe liver injury. The presence of a variety of positive auto-antibodies suggests an altered immune response may be contributory.