Hepatic Side Research Articles

Incidence of Hyperbilirubinemia and Jaundice Due to Atazanavir in a Cohort of Hispanic Patients

Incidence of Hyperbilirubinemia and Jaundice Due to Atazanavir in a Cohort of Hispanic Patients

Non-Fatal and Fatal Liver Failure Associated with Valproic Acid

Little is known about hepatotoxicity associated with valproic acid (VPA), a widely used substance in neuropsychiatry.All reported cases to the German Federal Institute for Drugs and Medical Devices between 1993 and 2009 of VPA-induced serious hepatic side effects were evaluated.A total of 132 cases of serious VPA-associated liver failure were identified. Approximately one third (34.8%) occurred under VPA monotherapy, while the majority was seen with VPA plus co-medication, most frequently antiepileptics (34.8%) and benzodiazepines (16.7%). A subgroup of 34 cases (25.8%) had a fatal outcome, the largest number reported to date. Of these, 32.4% were under VPA monotherapy and 67.6% under VPA plus concomitant medication. Within the study period a significant increase in the total number of reported cases and the subgroup of fatal cases was found.This first pharmacovigilance study of VPA-associated liver failure indicates a higher rate of non-fatal and fatal liver failure when VPA is given with co-medication as compared to monotherapy. However, co-medication per se does not increase the risk of fatalities.

Adherence to Leukemia Maintenance Therapy: A Comparative Study Among Children, Adolescents, and Adults

This study describes patient adherence to leukemia maintenance therapy and the factors associated with nonadherence, with a particular focus on the different age groups concerned. Sixty-four in-depth interviews were performed in three centers among 31 parents of children, 12 parents of adolescents, 12 adolescents, and 9 adult patients. Adherence was determined through a multimethod approach based on patient and/or parent responses to three self-administered questions and patient and/or parent interviews. The results were compared with physician evaluation of adherence. Factors explaining nonadherence were investigated in the in-depth interviews and by statistical analysis of self-administered questionnaires. Intentional nonadherence occurred rarely (4/52 patients, 8%) following poor tolerance of the maintenance therapy. Despite a high motivation to follow the maintenance therapy, repeated forgetfulness (8/52, 15%) was not rare and rarely detected by physicians. Nonadherence increased with age, but also existed among children. Outings, the administration of therapy at bedtime, the lack of monitoring, a low socioeconomic status, and the hepatic side effects of the treatment were also associated with nonadherence. Declared nonadherence of leukemia maintenance therapy is not negligible and should be screened at follow-up consultations using three simple questions.

Treatment for Pulmonary Hypertension of Left Heart Disease

Pulmonary hypertension (PH) secondary to left heart disease is a largely underestimated target of therapy. Except for a specific focus on PH consequences in patients with advanced heart failure (HF) receiving a left ventricular mechanical assist device or candidates for transplantation, prevention and treatment of initial subclinical forms of PH are not considered a priority in the management of this chronic disease population. Nonetheless, there is recent growing evidence supporting a clinical and prognostic role of PH in the elderly and in HF with preserved ejection fraction (pEF). Studies have defined PH-HFpEF as a new entity typically defining the evolving nature of disease. Although the prevalence of PH in these populations is not well-defined, the potential for effective pharmacological approaches that might impact the natural history of the disease starting from earlier stages is promising. However, it should be recognized that pharmacological studies performed to date with traditional pulmonary vasodilators in cohorts with HF and left-sided PH have not been positive, primarily because of concomitant systemic hypotension and hepatic side effects. This evidence along with the lack of studies specifically performed in the elderly and HFpEF often lead Guidelines to give neutral recommendations or even arbitrary assumptions. Recent availability of selective well-tolerated pulmonary vasodilators, such as phosphodiesterase type 5 (PDE5) inhibitors, however, seem to offer a solid background for treating left-sided PH at both early and later stages of the disease process.

Lessons from Lumiracoxib: Are cyclooxygenase‐2 inhibitors less hepatotoxic than non‐selective non‐steroidal anti‐inflammatory drugs?

Lessons from Lumiracoxib: Are cyclooxygenase‐2 inhibitors less hepatotoxic than non‐selective non‐steroidal anti‐inflammatory drugs?

Stem cells and other innovative intra-articular therapies for osteoarthritis: what does the future hold?

Osteoarthritis (OA), the most common type of arthritis in the world, is associated with suffering due to pain, productivity loss, decreased mobility and quality of life. Systemic therapies available for OA are mostly symptom modifying and have potential gastrointestinal, renal, hepatic, and cardiac side effects. BMC Musculoskeletal Disorders recently published a study showing evidence of reparative effects demonstrated by homing of intra-articularly injected autologous bone marrow stem cells in damaged cartilage in an animal model of OA, along with clinical and radiographic benefit. This finding adds to the growing literature showing the potential benefit of intra-articular (IA) bone marrow stem cells. Other emerging potential IA therapies include IL-1 receptor antagonists, conditioned autologous serum, botulinum toxin, and bone morphogenetic protein-7. For each of these therapies, trial data in humans have been published, but more studies are needed to establish that they are safe and effective. Several additional promising new OA treatments are on the horizon, but challenges remain to finding safe and effective local and systemic therapies for OA.Please see related article: http://www.biomedcentral.com/1471-2474/12/259

Melanoma diagnosed 27 years after a benoxaprofen-induced photosensitivity reaction

The propionic acid derivative Benoxaprofen was introduced for the treatment of rheumatic disorders in 1980. Its product license was then withdrawn 2 years later due to concerns over serious dermatologic, hepatic and renal side effects. Photosensitivity was the most common side effect with reported incidence of up to 50%. We present the first case report of a patient who presented with a melanoma diagnosed 27 years after a benoxaprofen-induced photosensitivity reaction. With an estimated 1.5 million patients previously on benoxaprofen, a large number of patients may potentially face increased risk of developing malignant melanoma. This case report can only suggest an association between solar injury secondary to benoxaprofen-related photosensitivity and subsequent melanoma. However the primary factor that improves survival from melanoma is early diagnosis, and so clinicians treating this group of patients should be aware of this risk. Although benoxaprofen is no longer in clinical use, the long-term sequelae to its photosensitizing effects may still be clinically important. Clinicians treating this group of patients should be vigilant, and consider a low threshold for diagnostic biopsy of suspicious skin lesions.

Macrophage depletion ameliorates kavalactone damage in the isolated perfused rat liver

Liver toxicity is a side effect observed with some herbal treatments, including Piper methysticum. The possible mechanisms responsible include inflammation subsequent to activation of liver macrophages and oxidative damage. Hepatotoxicity of the pharmacologically active component of Piper methysticum (kavalactones) was tested in isolated, perfused livers from rats which were pretreated with the macrophage intoxicant gadolinium chloride. Perfusions without kavalactones in gadolinium chloride pretreated and untreated livers were included as negative controls. Serial liver lobe biopsies were collected to measure temporal changes in available (reduced) hepatic glutathione. There were no statistically significant changes in reduced glutathione over the course of perfusion in any experimental group. Liver damage was observed using electron microscopy. Hepatic sinusoids displayed extensive damage to the endothelium in kavalactone-perfused, rat livers. This damage was significantly reduced by pre-treatment with gadolinium chloride. Hence liver macrophages may be a factor in liver injury induced by Piper methysticum. Characterisation and modulation of the liver macrophage response may enable the development of strategies to avoid these hepatic side effects.

Dose Optimization of Deferasirox in Chelation Naïve Children with Thalassemia Major

Abstract 5294 Background:Deferasirox is a relatively new once-daily oral iron chelator widely used for patients with thalassemia major. Efficacy of deferasirox has been evaluated in pediatric and adult patients with thalassemia and transfusion-dependent anemias. Experience with deferasirox in pediatric patients with thalassemia major is mainly in heavily iron loaded patients with a history of prior iron chelation. There are no current reports available on its use in chelation naïve very young patients with thalassemia major. Material and Methods:Ten chelation naive children (mean age 17.7 ± 2.7 months), on hypertransfusion regimen at the Pediatric Thalassemia Day Care Center, Sultan Qaboos University Hospital, Muscat, Oman, were initiated on deferasirox at a dose of 20 mg/kg/day at serum ferritin levels >500 ng/ml at a minimum age of 14 months. Patients were monitored and evaluated for possible side effects. Complete blood count, renal function test, liver function test and urine dipstick were done monthly with serum ferritin analysis once every 2 months. Guided by serum ferritin level and safety markers (transaminases, serum creatinine, and clinical adverse effects), the dose of deferasirox was gradually increased to 40 mg/kg/day with increments of 5 mg/kg/day every 2 months, in order to maintain a safe serum ferritin level with no major hepatic or renal side effects. Results:After a median treatment duration of 13 months (2–38 months) with deferasirox at a mean dose of 33.22 ± 5.99 mg/kg/day, mean serum ferritin level is 985.8 ± 373.002 ng/ml, as compared to baseline level of 807.8 ± 182.766 ng/ml. The increase in mean serum ferritin is 178 ng/ml (95% confidence interval −9.72 to 365.72) which is statistically insignificant (p = 0.06, two sided paired t-test). Nausea and vomiting, abdominal pain, and rash were observed in 1 patient each. Increase in transaminases was mild (3 times upper limit of normal) and non-progressive in 3 of the patients. Two patients had single serum creatinine level increases >33% above baseline and >upper limit of normal, and one had 2 non-consecutive increases requiring dose modification. The adverse effects were mild and did not require drug interruption. None of the patients had leucopenia, neutropenia or thrombocytopenia. Compliance with chelation was optimal. Conclusions:Deferasirox is relatively well tolerated in very young chelation naïve patients with thalassemia major. Dose increments of 5 mg/kg/day at intervals of 2 months allowed the optimization of the drug to 40 mg/kg/day within 1 year of initiation of chelation with no major adverse effects. Inspite of initial rises in serum ferritin at doses < 25 mg/kg/day, serum ferritin levels showed a steady trend towards the end of 12 months of therapy, requiring the continuation of the drug at doses > 30 mg/kg/day to achieve safe ferritin levels. Appropriate drug dosing guided by serum ferritin levels and safety markers improve the efficacy of deferasirox.Table 1Demographic and patient characteristicsMean age of initiation of deferasirox ± SD, months17.7 ± 2.7Median age, range18 (14–22)Female: male, n6:4History of Hepatitis B/C, n0Splenectomy, n0Mean pre-transfusion hemoglobin ± SD, g/dl9.4 ± 0.33Mean number of transfusions prior to chelation ± SD11.8 ± 2.65Mean blood volume transfused prior to chelation ± SD, ml/kg/day0.50 ± 0.18Mean baseline serum ferritin ± SD, ng/ml807.8 ± 182.766Median baseline serum ferritin, range786 (567–1181)Mean baseline AST ± SD, IU/L32 ± 7.39Mean baseline ALT ± SD, U/L20.1 ± 6.04Mean duration of treatment with deferasirox ± SD, months17.7 ± 14.46Median duration, range13 (2–38)Mean dose of deferasirox, mg/kg/day33.22 ± 5.99Mean serum ferritin after treatment with deferasirox ± SD, ng/ml985.8 ± 373.002Median baseline serum ferritin after deferasirox, (range)874 (567–1602)Mean AST after deferasirox, ± SD,IU/L33.42 ± 6.86Mean ALT after deferasirox, ± SD, U/L24.4 ± 10.48Nausea, n1Vomiting, n1Abdominal pain, n1Rash, n1Increased serum creatinine, n3n = number of patients SD = Standard Deviation [Display omitted] Disclosures:Off Label Use: Deferasirox is a once-daily oral iron chelator used for patients with thalassemia major and other transfusion-dependent anemias. Experience with deferasirox in pediatric patients with thalassemia major is mainly in heavily iron loaded patients with a history of prior iron chelation. There are no current reports available on its use in chelation naïve patients with thalassemia major. We evaluated the efficacy of deferasirox in 10 very young chelation naïve children with thalassemia major.

Does endoplasmic reticulum stress participate in APD-induced hepatic metabolic dysregulation?

Metabolic side effects caused by certain antipsychotic drugs (APDs), in particular clozapine and olanzapine, are now clinically well-documented. However, the potential mechanisms implicated in the metabolic disturbances of these drugs on peripheral tissues remain obscure. Here, we investigated the effects of five frequently prescribed APDs on the Sterol Regulatory Element Binding Protein (SREBP) transcription factor pathways which control lipogenesis and cholesterogenesis, using the Immortalized Human Hepatocyte cell model (IHH). First, clozapine, haloperidol, olanzapine and risperidone activated, at different levels, SREBP-1 activity reflected by an increased expression of SREBP-1 target genes involved in fatty acid biosynthesis (SREBP-1, FAS and/or SCD1) resulting in an accumulation of intracellular lipids. Second, clozapine and haloperidol also stimulated the SREBP-2 pathway associated with an increase in HMGCoAR expression. In contrast, quetiapine did not affect either the SREBP-1 or -2 pathways, but induced a slight accumulation of intracellular lipids. Interestingly, clozapine, haloperidol and olanzapine induced Endoplasmic Reticulum (ER) stress and, more precisely, initiation of the ER stress-activated eIF2α kinase (PERK) branch of the Unfolded Protein Response (UPR). Furthermore, treatment with thapsigargin, which increases intracellular calcium release, induced both ER stress and SREBP-1 and -2 pathway activation, whereas Ca 2+ chelation by BAPTA completely reversed the lipogenic effects and ER stress induction produced by clozapine. Based on these results, we propose that certain APDs induce ER stress via changes in Ca 2+ homeostasis in hepatocytes. This phenomenon potentially underlies a part of their known undesirable hepatic metabolic side effects. This article is part of a Special Issue entitled ‘Post-Traumatic Stress Disorder’.

Genetic polymorphisms of NAT2, CYP2E1 and GST enzymes and the occurrence of antituberculosis drug-induced hepatitis in Brazilian TB patients

Isoniazid (INH), one of the most important drugs used in antituberculosis (anti-TB) treatment, is also the major drug involved in hepatotoxicity. Differences in INH-induced toxicity have been attributed to genetic variability at several loci, such as NAT2, CYP2E1, GSTM1 and GSTT1, that code for drug-metabolising enzymes. Our goal was to examine the polymorphisms in these enzymes as susceptibility factors to anti-TB drug-induced hepatitis in Brazilian individuals. In a case-control design, 167 unrelated active tuberculosis patients from the University Hospital of the Federal University of Rio de Janeiro, Brazil, were enrolled in this study. Patients with a history of anti-TB drug-induced acute hepatitis (cases with an increase to 3 times the upper limit of normal serum transaminases and symptoms of hepatitis) and patients with no evidence of anti-TB hepatic side effects (controls) were genotyped for NAT2, CYP2E1, GSTM1 and GSTT1 polymorphisms. Slow acetylators had a higher incidence of hepatitis than intermediate/rapid acetylators [22% (18/82) vs. 9.8% (6/61), odds ratio (OR), 2.86, 95% confidence interval (CI), 1.06-7.68, p = 0.04). Logistic regression showed that slow acetylation status was the only independent risk factor (OR 3.59, 95% CI, 2.53-4.64, p = 0.02) for the occurrence of anti-TB drug-induced hepatitis during anti-TB treatment with INH-containing schemes in Brazilian individuals.

Impact of three-dimensional analysis of multidetector row computed tomography cholangioportography in operative planning for hilar cholangiocarcinoma

Background A detailed evaluation of portal triad structures, especially the biliary anatomy at the hepatic hilus, is essential to ensure curative resection for hilar cholangiocarcinoma. Methods Patients underwent 3-dimensional analysis using multidetector row computed tomography cholangioportography preoperatively. The number of bile duct orifices in the cut end of the hilar plate was estimated and compared with the actual number of bile ducts. Furthermore, the estimated length of the surgical margin and its relationship to the pathological margin status was evaluated. Results The number of bile duct orifices was correctly estimated in 14 of 19 patients. Of 18 hepatic ducts in which the estimated length of the hepatic side surgical margin was calculated 17 hepatic ducts (94.4%) were diagnosed pathologically as margin negative. Conclusions This investigatory technique has the advantages of precise visualization of anatomic structures and multidirectional assessment of biliary branches and vessels, allowing improved operative planning for the treatment of hilar cholangiocarcinoma.

Leukopenia due to anti-tuberculous chemotherapy including rifampicin and isoniazid

Leukopenia due to anti-tuberculous chemotherapy including rifampicin and isoniazid

Treating statin-intolerant patients

Statins are effective in reducing cardiovascular events and are safe for almost all patients. Nevertheless, intolerance to statins is frequently faced in clinical practice. This is mostly due to muscular symptoms (myalgia with or without increase of plasma creatinine kinase) and/or elevation of hepatic aminotransferases, which overall constitutes approximately two-thirds of reported adverse events during statin therapy. These side effects raise concerns in patients as well as in doctors and are likely to reduce patients’ adherence and, as a consequence, the cardiovascular benefit. Therefore, it is mandatory that clinicians improve their knowledge on the clinical aspects of muscular and hepatic side effects of statin therapy as well as their ability to manage patients with statin intolerance. Besides briefly examining the clinical aspects and the mechanisms that are proposed to be responsible for the most common statin-associated side effects, the main purpose of this article is to review the available approaches to manage statin-intolerant patients. The first step is to determine whether the adverse events are indeed related to statin therapy. If so, lowering the dosage or changing statin, alternate dosing options, or the use of nonstatin compounds may be practical strategies. The cholesterol-lowering potency as well as the usefulness of these different approaches in treating statin-intolerant patients will be examined based on currently available data. However, the cardiovascular benefit of these strategies has not been well established, so their use has to be guided by a careful clinical assessment of each patient.

P03-113 - Liver failure under valproic acid

Valproic acid (VPA, 2-propylvaleric acid) is originally an antiepileptic drug, which has been in use for more than 30 years in over 100 countries. The clinical application of VPA has expanded in the last years. Approval has been granted by the FDA for treatment of migraine and cluster headache in 1996, and for treatment of mania and long-term prophylaxis of bipolar affective disorder in 1995. In ongoing studies, VPA has been reported to inhibit growth of several types of cancer cells; in addition, effects on neurodegeneration, and on virus replication in HIV infection have been demonstrated potentially expanding the application of VPA in the future. Despite a good tolerability of the drug, reports of hepatotoxicty even in patients without risk factors become more frequent. We analysed all cases of VPA induced severe hepatic side effects reported to the german Federal Institute for Pharmaceuticals &amp; Medical Products (BfArM) between 1993 and 2009. A special intention was to detect correlations with present co-medication as a crucial factor in the break-down of hepatic function. As frequent co-medications in VPA-induced hepatic side effects benzodiazepines, and antiepileptics, especially carbamazepine, lamotrigine and topiramate were found. In addition, propofol as a co-medication was found in 4 lethal cases. Different pathomechanisms of VPA hepatotoxicity and a therapeutic approach with carnitine are discussed. Current international guidelines for prevention of VPA-induced liver failure are contrasted. Weekly control of liver enzymes in the first treatment weeks might help to detect VPA-induced hepatic side effects earlier.

Impact of fluoxetine on liver damage in rats

Fluoxetine (Flux) is a fluorine-containing drug that selectively inhibits serotonin reuptake. It is widely prescribed as a treatment for depression disorders. Hepatic side effects have been reported during Flux therapy. These reports led us to investigate the involvement of oxidative stress mechanisms in liver injury caused by Flux. It has been shown that exposure to fluoride (F-) induces excessive production of free radicals and affects the antioxidant defense system. Based on this knowledge, we examined the F- concentration in serum and urine during administration of Flux.In our study, the effects of one month of Flux treatment on lipid and protein peroxidation, the concentration of uric acid in the liver and the activity of transaminases and transferases in the serum were investigated in rats. Eighteen adult male Wistar rats were divided into three equal groups of six animals each: (I) controls who drank tap water and received 1 ml of tap water intragastrically; (II) animals that received 8mg Flux/kg bw/day intragastrically; and (III) animals that received 24mg Flux/kg bw/day intragastrically. Flux treatment increased of the levels of carbonyl groups, thiobarbituric acid reactive species (TBARS) and the uric acid content in the liver. The activities of alanine transaminase (ALT), aspartate transaminase (AST) and glutathione-S transferase (GST) increased in the serum of the treated groups. The Flux levels in the plasma of the treated rats increased significantly in a dose-dependent manner. We observed no changes in the concentration of fluoride in either the serum or the urine of treated rats compared to the control group.In conclusion, our study indicates that Flux induces liver damage and mediates free radical reactions. Our data also indicate that Flux does not release F - during metabolism and does not affect physiological levels of F - in the serum or urine.

Zukunft der Therapie mit Methotrexat und anderen Folatinhibitoren

Because of its good effectiveness and tolerability, methotrexate (MTX) has been the most important DMARD for the treatment of rheumatoid arthritis (RA) worldwide for many years. Thus the treatment of this disease is strongly based on the principle of folate inhibition. Recent years have brought new insights into the pharmacology and mechanisms of action of MTX. As a result, it now appears possible to further develop folate inhibitors to increase effectiveness and specificity. Polyglutamation of the drug, a metabolic step which appears to play a role both in terms of therapeutic effects and hepatic side effects, might be a possible starting point. Moreover, methods of targeted drug delivery intended to increase drug accumulation at the site of inflammation can increase the effectiveness of treatment and reduce toxicity. Albumin-coupled and liposomally-conjugated MTX, both of which inhibit inflammation in animal models more potently than MTX, are undergoing preclinical evaluation. It was recognized that activated synovial macrophages upregulate folate receptor ß (FR-ß) expression and that MTX can become active by this pathway. This finding makes it possible to develop new FR-ß-specific folate inhibitors with specificity for this pathophysiologically important cell population.

Liver diseases associated with anti-tumor necrosis factor-alpha (TNF-α) use for inflammatory bowel disease

The conventional treatment of inflammatory bowel disease (IBD) has focused on nonspecifically targeting mucosal inflammation. In the last decade, with the advent of novel biological agents that directly inhibit proinflammatory cytokines, such as tumor necrosis factor alpha (TNF-α), rapid progress has been made in clinical management of complex and challenging patients with IBD. However, there remain many unanswered questions about the short and long-term side effects; this article focuses on hepatic complications. This review aims to provide a concise update to gastroenterologists on the well-known, as well as the potential rare consequences of anti-TNFα therapy on the liver and recommendations for clinical management. We performed a focused literature review for reports of the effect of anti-TNF therapy on preexisting liver disease as well as de novo hepatitis and drug-induced hepatotoxicity. Search terms used included anti-TNF therapy, biologics, liver disease, inflammatory bowel disease, hepatitis, hepatotoxicity, opportunistic infections,, and hepatitis virus reactivation. There are multiple potential effects of anti-TNF therapy on the liver during treatment of patients with IBD. Often treatment may be complicated by preexisting chronic liver disease. Clinicians should be aware of potential hepatic side effects and appropriate management options.

Etravirine in the Treatment of HIV-1: A Clinical Overview for Healthcare Professionals

Current HIV treatment guidelines emphasize the importance of using an active antiretroviral therapy regimen that produces full virologic suppression and immunologic competence, while at the same time providing patients with a favorable safety profile and limited risk for development of drug resistance. Etravirine (TMC125), a recently approved, non-nucleoside reverse transcriptase inhibitor (NNRTI), has shown durable, superior virologic efficacy over placebo in the Phase III, randomized, double-blind DUET trials in 1,203 treatment-experienced, NNRTI-resistant, HIV-1-infected patients. Statistical significance of responses with etravirine over placebo was maintained through Week 24, 48 and 96, regardless of baseline demographics, baseline disease characteristics or the background regimen used. Etravirine has demonstrated a favorable safety and tolerability profile; the incidence of treatment-emergent adverse events was comparable with placebo in the DUET trials, with the exception of rash. The tolerability profile of etravirine also appears to be favorable in terms of neuropsychiatric and hepatic side effects. The pharmacokinetic profile of twice-daily etravirine minimizes the potential for clinically relevant drug-drug interactions and allows for its use in combination with a wide range of other agents. In addition, etravirine has a high genetic barrier to the development of resistance, further enhancing potential benefit in patients infected with NNRTI-resistant virus. The clinical efficacy and favorable safety profile of etravirine, together with its pharmacokinetic profile and high genetic barrier to resistance, make it a valuable treatment option for a wide range of treatment-experienced HIV-1-infected patients.

Trenbolone Acetate Use Causing Acute Hepatitis

Purpose: Athletes continuously seek ways to improve performance in their sport and can be drawn to the use of anabolic steroids in order to obtain this goal. They tend to ignore the potentially life-threatening side effects of these drugs and consequently put their overall physical well-being at risk. We describe a case of an amateur body builder who took trenbolone acetate and subsequently developed acute hepatitis. Case: A 40-year-old male amateur bodybuilder took trenbolone acetate by injection for one year and developed jaundice. He had a seven-week history of generalized fatigue, diarrhea with light colored stools, dark urine, and right upper quadrant pain. He denied alcohol use or family history of liver disease. Physical examination showed scleral icterus with a palpable liver 3 centimeters below the costal margin. Laboratory results were significant for Aspartate aminotransferase of 121 IU/L, alanine aminotransferase of 199 IU/L, total bilirubin of 17.4 mg/dL, direct bilirubin of 9.9 mg/dL, albumin of 2.8 mg/dL, total cholesterol of 508 mg/dL, LDL of 389 mg/dL, and HDL of 10 mg/dL. Coagulation profile was normal. Ultrasonography showed a contracted gallbladder with thickened walls and no evidence of intra- or extra-hepatic ductal dilatation. Liver biopsy showed moderately severe parenchymal and canalicular cholestasis with minimal portal inflammation consistent with drug-induced cholestatic hepatitis. Discussion: Hepatic complications associated with anabolic steroid use include hepatocellular and intrahepatic cholestasis. Aminotransferases are usually less than 100 IU\L and serum alkaline phosphatase levels may be mildly elevated. HDL can be decreased and LDL can be increased, which can put these patients at risk for cardiovascular disease. Hepatocellular adenomas and peliosis hepatis have been described. Most of these effects can be reversed upon cessation of the steroids; however there have been fatalities. By methylating testosterone, it undergoes less first pass hepatic metabolism and it's oral bioavailability improves. Trenbolone acetate is a steroid approved for use in veterinary practice as a means of maintaining cattle weight in the days prior to slaughter. It is not approved, nor studied in humans, and its hepatic side effect profile is unknown. Our case reminds health care professionals about the abuse potential of anabolic steroids and the systemic side effects they can cause.