A Case Report on Cholestatic Jaundice Secondary to Adverse Effect of Phaleria macrocarpa (Mahkota Dewa).

Drug induced cholestatic liver injury can posed a great diagnostic difficulty as a result of its long non-exhaustive list of potential offending causes which can be either prescribed or over-the-counter medications, such as medicinal herbs and remedies. Phaleria macrocarpa, or more commonly known as the 'God's crown' by the local people of South East Asia, is not listed as one of the causes. This medicinal plant extract has been increasingly used for traditional treatment for various ailments. Here, we report a case of a young man who has no known medical illness presented with cholestatic pattern of liver injury which caused by chronic ingestion of Phaleria macrocarpa. The objective of this case report is to share the uncommon side effect of taking this traditional product which may have been under-reported due to the unknown effect.

Voriconazole-Induced Hepatitis via Simvastatin- and Lansoprazole-Mediated Drug Interactions: A Case Report and Review of the Literature.

Therapeutic voriconazole concentrations have a narrow window of effectiveness before causing cholestatic hepatitis. After undergoing 1 year of voriconazole therapy for pulmonary aspergillosis, a 44-year-old man began treatment with 30 mg lansoprazole for gastroesophageal reflux symptoms. Within 5 days of starting treatment with lansoprazole, the patient presented with fatigue, jaundice, and cholestatic hepatitis. The hepatitis promptly resolved after stopping lansoprazole treatment. Sixteen months later, the patient was given simvastatin therapy, as recommended by the American Diabetes Association to prevent cardiovascular disease for patients with diabetes who are aged >40 years and have one additional risk factor. Within 2 weeks of taking simvastatin, a 3-hydroxy-3-methylglutaryl CoA reductase (statin) therapy, the patient redeveloped fatigue, jaundice, and cholestatic hepatitis. He described both episodes of fatigue and jaundice similarly in terms of onset and intensity. Voriconazole is metabolized by both CYP2C19 and CYP3A4 isoenzymes. Lansoprazole is an inhibitor of the CYP2C19 isoenzyme. Competition between voriconazole and lansoprazole likely led to increased voriconazole serum concentration and acute cholestatic hepatitis in this patient. Simvastatin inhibits the CYP3A4 isoenzyme. After the patient took 10 mg simvastatin daily for 2 weeks, cholestatic hepatitis occurred. The voriconazole concentration remained elevated (4.1 µg/ml) when measured 15 days after stopping simvastatin. The patient's Naranjo Adverse Drug Reaction Probability Scale score of 7 revealed that the cholestatic hepatitis was probably precipitated by lansoprazole. Likewise, the patient's Naranjo score of 9 also revealed that cholestatic hepatitis was attributable to a definite adverse drug reaction precipitated by the addition of simvastatin to the stable baseline regimen of voriconazole. In a single patient, two different inhibitors of the cytochrome P450 pathway stimulated voriconazole-induced cholestatic hepatitis. Although the major cytochrome P450 pathways for the metabolism and clearance of lansoprazole and simvastatin are different, they both likely contributed to the reduced hepatic clearance of voriconazole in this patient.

Amoxicillin-Clavulanate-Induced Liver Injury.

BACKGROUND AND AIMS: Amoxicillin-clavulanate (AC) is the most frequent cause of idiosyncratic drug-induced injury (DILI) in the US DILI Network (DILIN) registry. Here, we examined a large cohort of AC-DILI cases and compared features of AC-DILI to those of other drugs. METHODS: Subjects with suspected DILI were enrolled prospectively, and cases were adjudicated as previously described. Clinical variables and outcomes of patients with AC-DILI were compared to the overall DILIN cohort and to DILI caused by other antimicrobials. RESULTS: One hundred and seventeen subjects with AC-DILI were identified from the cohort (n = 1038) representing 11 % of all cases and 24 % of those due to antimicrobial agents (n = 479). Those with AC-DILI were older (60 vs. 48 years, P < 0.001). AC-DILI was more frequent in men than women (62 vs. 39 %) compared to the overall cohort (40 vs. 60 %, P < 0.001). The mean time to symptom onset was 31 days. The Tb, ALT, and ALP were 7 mg/dL, 478, and 325 U/L at onset. Nearly all liver biopsies showed prominent cholestatic features. Resolution of AC-DILI, defined by return of Tb to <2.5 mg/dL, occurred on average 55 days after the peak value. Three female subjects required liver transplantation, and none died due to DILI. CONCLUSION: AC-DILI causes a moderately severe, mixed hepatocellular-cholestatic injury, particularly in older men, unlike DILI in general, which predominates in women. Although often protracted, eventual apparent recovery is typical, particularly for men and usually in women, but three women required liver transplantation.

Acute bile nephropathy secondary to anabolic steroids.

Renal dysfunction in cholestatic liver disease is multifactorial. Acute kidney injury may develop secondary to renal vasoconstriction in the setting of peripheral vasodilation and relative hypovolemia, tubular obstruction by bile casts, and direct tubular toxicity from bile. Anabolic steroids are frequently used by athletes to boost endurance and increase muscle mass. These agents are a recently recognized cause of hepatotoxicity and jaundice and may lead to acute kidney injury. To increase awareness about this growing problem and to characterize the pathology of acute kidney injury in this setting, we report on a young male who developed acute kidney injury in the setting of severe cholestatic jaundice related to ingestion of anabolic steroids used for bodybuilding. Kidney biopsy showed bile casts within distal tubular lumina, filamentous bile inclusions within tubular cells, and signs of acute tubular injury. This report supports the recently re-emerged concept of bile nephropathy cholemic nephrosis.

Antimicrobial-related severe adverse events during treatment of bone and joint infection due to methicillin-susceptible Staphylococcus aureus.

Prolonged antimicrobial therapy is recommended for methicillin-susceptible Staphylococcus aureus (MSSA) bone and joint infections (BJI), but its safety profile and risk factors for severe adverse events (SAE) in clinical practice are unknown. We addressed these issues in a retrospective cohort study (2001 to 2011) analyzing antimicrobial-related SAE (defined according to the Common Terminology Criteria for Adverse Events) in 200 patients (male, 62%; median age, 60.8 years [interquartile range {IQR}, 45.5 to 74.2 years]) with MSSA BJI admitted to a reference regional center with acute (66%) or chronic arthritis (7.5%), osteomyelitis (9.5%), spondylodiscitis (16%), or orthopedic device-related infections (67%). These patients received antistaphylococcal therapy for a median of 26.6 weeks (IQR, 16.8 to 37.8 weeks). Thirty-eight SAE occurred in 30 patients (15%), with a median time delay of 34 days (IQR, 14.75 to 60.5 days), including 10 patients with hematologic reactions, 9 with cutaneomucosal reactions, 6 with acute renal injuries, 4 with hypokalemia, and 4 with cholestatic hepatitis. The most frequently implicated antimicrobials were antistaphylococcal penicillins (ASP) (13 SAE/145 patients), fluoroquinolones (12 SAE/187 patients), glycopeptides (9 SAE/101 patients), and rifampin (7 SAE/107 patients). Kaplan-Meier curves and stepwise binary logistic regression analyses were used to determine the risk factors for the occurrence of antimicrobial-related SAE. Age (odds ratio [OR], 1.479 for 10-year increase; 95% confidence interval [CI], 1.116 to 1.960; P = 0.006) appeared to be the only independent risk factor for SAE. In patients receiving ASP or rifampin, daily dose (OR, 1.028; 95% CI, 1.006 to 1.051; P = 0.014) and obesity (OR, 8.991; 95% CI, 1.453 to 55.627; P = 0.018) were associated with the occurrence of SAE. The high rate of SAE and their determinants highlighted the importance of the management and follow-up of BJI, with particular attention to be paid to older persons, especially for ASP dosage, and to rifampin dose adjustment in obese patients.

Severe cholestatic jaundice after a single administration of ajmaline; a case report and review of the literature.

BACKGROUND: Ajmaline is a pharmaceutical agent now administered globally for a variety of indications, particularly investigation of suspected Brugada syndrome. There have been previous reports suggesting that repetitive use of this agent may cause severe liver injury, but little evidence exists demonstrating the same effect after only a single administration. CASE PRESENTATION: A 33-year-old man of Libyan origin with no significant past medical history underwent an ajmaline provocation test for investigation of suspected Brugada syndrome. Three weeks later, he presented with painless cholestatic jaundice which peaked in severity at eleven weeks after the test. Blood tests confirmed no evidence of autoimmune or viral liver disease, whilst imaging confirmed the absence of biliary tract obstruction. A liver biopsy demonstrated centrilobular cholestasis and focal rosetting of hepatocytes, consistent with a cholestatic drug reaction. Over the course of the next few months, he began to improve clinically and biochemically, with complete resolution by one year post-exposure. CONCLUSION: Whilst ajmaline-related hepatotoxicity was well-recognised in the era in which the drug was administered as a regular medication, clinicians should be aware that ajmaline may induce severe cholestatic jaundice even after a single dose administration.

[Methimazole-induced cholestatic jaundice in a hyperthyroid patient]. / Ictericia colestásica inducida por metimazol en una paciente con hipertiroidismo.

Hyperthyroidism is one of the most frequent endocrine disorders and its current treatment is based on drugs, surgery and radioactive iodine. Methimazole is the antithyroid drug of choice because of its potency and infrequent side effects, usuaIly mild. This medication is rarely associated with liver toxicity, usually manifested as cholestatic jaundice. Here we report the case of a 33-year-old woman treated at the University Hospital Fundación Santa Fe de Bogota, with hepatotoxicity induced by a methimazole-based treatment for Graves' disease. The pruritus and jaundice appeared after three weeks of therapy, viral hepatitis markers were negative, hepatobiliary ultrasonography was normal, and an increase of the levels of alkaline phosphatase, total bilirubin and aminotransferases was found The causal diagnosis of methimazole-induced hepatotoxicity was supported by the results of a liver biopsy. According to the CIOMS scale the score was 10, and the causal relationship of the hepatic adverse reaction by methimazole is highly probable. The clinical course was satisfactory when the medication was suspended, with clinical improvement at 5 days, and normalization of liver tests at 5 weeks. We discuss this case from a diagnostic and therapeutic approach.

An unusual evolution of thyroid function after therapeutic plasma exchange in Graves' disease with cholestatic jaundice: A case report.

RATIONALE: Methimazole (MMI) is the first-line agent in the treatment of hyperthyroidism. However, rare but severe cholestatic jaundice may occur. Therapeutic plasma exchange (TPE) may provide an alternative treatment for such patients and they received thyroidectomy/radioactive iodine ablation or continued oral anti hyperthyroidism medication immediately after TPE session in the reported literatures. The case reported here is, to our knowledge, the first to describe the long interval between anti hyperthyroidism therapy and TPE in such patients. PATIENT CONCERNS: A 49-year-old Chinese woman had developed worsening jaundice 3 weeks after receiving methimazole (20 mg/day) for the treatment of hyperthyroidism secondary to Graves' disease (GD). Additionally, she had a 2-year history of type 2 diabetes. DIAGNOSIS: Hyperthyroidism secondary to GD, MMI-induced severe cholestatic jaundice and type 2 diabetes. INTERVENTIONS: Methimazole was discontinued and the patient received 3 times of TPE, about 3-month glucocorticoid treatment, insulin administration accordingly and other conventional liver-protecting therapy. OUTCOMES: Her thyroid function was stabilized with small dose of thyroxine substitution and euthyroid status persisted after thyroxine discontinuation until hyperthyroidism recurred 7 months later while her cholestatic jaundice was eventually recovered by about 3-month glucocorticoid therapy. LESSONS: Due to the complex interplay between liver function and thyroid hormones, there may be unusual changes of thyroid function in GD patients with severe liver injury after TPE. By this case, we want to highlight the importance of a closely following up of thyroid function in order to deliver appropriate health suggestions for patients.

Cholestatic jaundice as a result of combination designer supplement ingestion.

OBJECTIVE: To report a case of cholestatic jaundice as a result of combination herbal and designer supplement use. CASE SUMMARY: A 50-year-old Hispanic male presented to the hospital with a 1-week history of significant painless jaundice; total bilirubin on admission was 29.4 mg/dL. He reported use of both herbal (creatine and whey protein) and designer (Incredible Bulk and Spartan 45) supplements concurrently for approximately 2 months. Upon admission, all supplements were discontinued and multiple laboratory and diagnostic tests were ordered. On day 6 of his hospital admission, a liver biopsy was performed, the results of which indicated drug-induced hepa to toxicity. On day 9 he was discharged with prescriptions for ursodeoxycholic acid and hydroxyzine. Three months post hospital discharge, the patient continued to be supplement-free and bilirubin had decreased substantially. DISCUSSION: Anabolic-androgenic steroids are capable of causing hepatotoxicity, and multiple cases reported in the literature support this. A case report described hepato toxicity secondary to both creatine and whey protein consumption, and several reports have described liver damage secondary to designer supplement use. To our knowledge, this is the first case to describe hepatotoxicity as a result of combination herbal and designer supplement use. The Roussel Uclaf Causality Assess ment Method (RUCAM) score for drug-induced hepatotoxicity indicated a highly probable correlation between the use of combination supplements and cholestatic jaundice. CONCLUSIONS: Health care professionals need to be aware of complications associated with designer supplement use and should be able to identify patients who would benefit from education on herbal and designer supplement use.

Role of plasma exchange in autoimmune hyperthyroidism complicated by severe tiamazol-induced cholestatic jaundice.

Therapeutic plasma exchange (TPE) is an alternative treatment for hyperthyroidism, resulting in a rapid decline in plasma thyroid hormones and anti-thyroid antibodies. TPE has also been used both in primary liver disease and in drug-induced cholestasis. Data on thyrotoxic patients with severe hepatic complications are scarce. Cholestasis induced by imidazol-derived anti-thyroid drugs is extremely rare. The use of TPE for treating this complication was not previously reported. We report the experience of one such patient with a favorable response to TPE. A 45-year-old male patient with Graves' disease, presented with severe jaundice and extremely high serum bilirubin levels due to hepatotoxicity induced by tiamazol. Through extensive investigation primary liver disease, including viral, metabolic, neoplastic and autoimmune disease, as a cause of cholestasis were all ruled out. The patient underwent total of 6 TPEs which in combination with low dose of glucocorticoids and standard supportive measures, resulted in normalization of thyroid hormones and normal liver function tests. TPE provided a safe, rapid and effective treatment of severe drug-induced cholestasis and auto immune hyperthyroidism. From this case we conclude that TPE should be considered as a valuable alternative therapeutic option in thyrotoxic patients with severe complications. Guidelines and indication criteria for TPE treatment in patients with hyperthyroidism are still lacking.

[Rizatriptan-induced liver toxicity. Report of a case]. / Hepatotoxicidad de rizatriptán. Descripción de un caso clínico.

Triptans are a class of drugs with proven efficacy in the acute treatment of migraine headache. The first component of these drugs was sumatriptan, with various derivatives subsequently emerging. Until now, there has only been one reported case of liver toxicity with zolmitriptan. We now present a case of hepatotoxicity related to another drug in this group: rizatriptan.

Case report: Severe cholestatic jaundice associated with hyperthyroidism treated with methimazole.

RATIONALE: We present a case of a 43-year-old female patient diagnosed with hyperthyroidism. This study aims to demonstrate the rare association between hyperthyroidism and severe cholestatic jaundice, and the effectiveness of methimazole treatment. PATIENT CONCERNS: The patient developed severe jaundice, a typically mild symptom in most hyperthyroidism cases. DIAGNOSIS: The severe jaundice was suspected to be a result of cholestasis induced by hyperthyroidism, with other potential causes such as drug-induced or autoimmune liver dysfunction being ruled out. OUTCOMES: The patient was effectively treated with methimazole. Outcomes: Treatment with methimazole alleviated the severe cholestatic jaundice and restored normal thyroid function. LESSONS: The specific mechanism of cholestasis as a secondary complication of hyperthyroidism remains unclear, and there are no specific biochemical markers for cholestasis caused by this hormonal disease. This case underscores the possibility of severe jaundice as a clinical manifestation of hyperthyroidism, and highlights antithyroid drug treatment as an effective strategy for managing severe cholestatic jaundice.

Thalidomide-induced acute cholestatic hepatitis: case report and review of the literature.

Drug-induced liver injury (DILI) is a leading cause of liver failure and an important safety issue in drug development. Thalidomide is nowadays used for the treatment of several conditions including multiple myeloma (MM). Several adverse effects have been described but liver toxicity was seldom reported. We describe a case of thalidomide-induced hepatitis in a man treated for MM. The clinical setting and temporal association between the start of the drug and liver injury allowed the assumption of the causative role of thalidomide. As its clinical indications expand we wish to increase awareness of a new potential side effect of thalidomide. A short review on thalidomide-induced liver injury is also presented.

The effect of obstructive jaundice on the sensitivity of intravenous anesthetic of remimazolam: study protocol for a controlled multicenter trial.

BACKGROUND: It is well known that obstructive jaundice could affect the pharmacodynamics of some anesthetics, and the sensitivity of some anesthetics would increase among icteric patients. Remimazolam is a new ultra-short-acting intravenous benzodiazepine sedative/anesthetic, which is a high-selective and affinity ligand for the benzodiazepine site on the GABAA receptor. However, no study has reported the pharmacodynamics of remimazolam in patients with obstructive jaundice. We hypothesize that obstructive jaundice affects the pharmacodynamics of remimazolam, and the sensitivity of remimazolam increases among icteric patients. METHODS/DESIGN: The study will be performed as a prospective, controlled, multicenter trial. The study design is a comparison of remimazolam requirements to reach a bispectral index of 50 in patients with obstructive jaundice versus non-jaundiced patients with chronic cholecystitisor intrahepatic bile duct stones. Remimazolam was infused at 6 mg/kg/h until this endpoint was reached. DISCUSSION: Remimazolam could be suitable for anesthesia of patients with obstructive jaundice, because remimazolam is not biotransformed in the liver. Hyperbilirubinemia has been well-described to have toxic effects on the brain, which causes the increasing of sensitivity to some anesthetics, such as desflurane, isoflurane, and etomidate. Furthermore, remimazolam and etomidate have the same mechanism of action when exerting an anesthetic effect. We aim to demonstrate that obstructive jaundice affects the pharmacodynamics of remimazolam, and the dose of remimazolam when administered to patients with obstructive jaundice should be modified. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100043585 . Registered on 23 February 2021.

Obstructive Jaundice Due to Duodenal Ulcer Induced by Lenvatinib Therapy for Hepatocellular Carcinoma.

An 82-year-old man with hepatocellular carcinoma presented with upper abdominal pain, vomiting, and jaundice. He had been taking a standard lenvatinib dose for three months. Although acute cholangitis was suggested, imaging studies failed to detect the biliary obstruction site. An endoscopic examination following discontinuation of lenvatinib and aspirin revealed multiple duodenal ulcers, one of which was formed on the ampulla of Vater and causing cholestasis. Endoscopic biliary drainage and antibiotics improved concomitant Enterobacter cloacae bacteremia. Ulcer healing was confirmed after rabeprazole was replaced with vonoprazan and misoprostol. Our case shows that lenvatinib can induce duodenal ulcers resulting in obstructive jaundice.

[Hepatic lesions induced by systemic chemotherapy for digestive cancer]. / Lésions hépatiques induites par la chimiothérapie systémique pour cancer d'origine digestive.

The anticancerous chemotherapies are often responsible for toxic injury of the nontumoral liver. Two types of histological lesions were recently reported during the treatment of digestive cancers: the sinusoidal obstruction syndrome (SOS); or veno-occlusive disease associated with the use of oxaliplatine, and steatohepatitis associated with the use of irinotecan. The SOS is a cause of increased postoperative morbidity, particularly during major hepatectomy or when more than six cycles of chemotherapy are administered. Steatohepatitis increases the postoperative morbidity and mortality. The new targeted molecules do not seem to modify the postoperative course. Hepatic injury and postoperative complications associated with chemotherapies used in the treatment of digestive cancers are summarized in this review.

Hydralazine-induced cholestatic hepatitis.

Hydralazine has been widely used for treating hypertension, particularly in patients with renal failure. We report a case on a patient in whom we believe the drug was implicated in an otherwise unexplained disturbance of liver function. A 63-year-old African-American female with medical history of hypertension and end-stage renal disease (on hemodialysis) was admitted to the hospital with epigastric pain and jaundice. The symptoms started about 1 week ago. Initial laboratory tests showed abnormal liver enzymes with elevated conjugated bilirubin and alkaline phosphatase suggestive of cholestatic jaundice. Amylase and lipase were normal. Abdominal ultrasound showed normal caliber common bile duct without evidence of obstruction. Abdominal CT scan does not show any evidence of intra- or extrahepatic biliary ductal dilatation, and no mass lesions were seen in the pancreas. Further blood chemistry showed worsening of liver enzymes and increased bilirubin over the next 2-3 days. Magnetic resonance cholangiopancreatography failed to show any evidence of intra- or extrahepatic biliary ductal dilatation. No other laboratory evidence of cholestatic jaundice was found. Before proceeding for invasive diagnostic procedure, that is, endoscopic retrograde cholangiopancreatography, the patient's drug history was reviewed. She was on hydralazine 75 mg 3 times per day, started 5 months ago. At that time, her liver function tests were normal. As we could not find any other cause of cholestatic jaundice, we attributed this as a side effect of hydralazine. A trial was given by stopping the hydralazine. It was seen that there was significant improvement in the liver function enzymes over the next week. Complete clinical and biochemical recovery occurred over the next 4 weeks. Liver injury after long-term therapy with hydralazine and after short-term therapy with hydralazine (2-10 days) has been described. Hydralazine-induced hepatotoxicity may manifest as hypersensitivity-type injury, mixed hepatocellular injury, acute hepatitis, cholestatic jaundice, or centrilobular necrosis. The Hydralazine-induced cholestatic liver injury seems to be fully reversible. Complete clinical and biochemical recovery occurs after discontinuation of the drug. Also, the differential diagnosis of any patient with hepatocellular injury should include medications. This will prevent unnecessary diagnostic tests.