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Drug-induced Cholestatic Hepatitis

Drug Induced Cholangiolitic Hepatitis


Presentation

  • […] entitled “Severe sustained cholestatic hepatitis following temozolomide in a patient with glioblastoma multiforme: case study and review of data from the FDA adverse event reporting system,” recently published in Neuro-Oncology. 1 The authors first presented[neuro-oncology.oxfordjournals.org]
  • Main Article Content Luigi Anastasio * Valerio Manno Affiliation not present. Maria Carbone Affiliation not present. Nicola Lentini Affiliation not present. Sandro Baldari Affiliation not present. Lucia Sofia Affiliation not present.[italjmed.org]
  • It might be expected that the more severe cases presenting during the study period would not have been biopsied due to the presence of coagulopathy.[gut.bmj.com]
  • Younger patients present most commonly with a hepatocellular pattern of injury, whereas older patients mostly present with a cholestatic pattern of liver injury. 3 Some studies have found that women have a greater risk of developing DILI than men. 13[mdedge.com]
  • The possibility of pimozide-induced cholestatic hepatotoxicity presented here may help clinicians in this regard.[jpps.com.pk]
Pain
  • Evaluation of the patient's history reveals that the patient had been on paracetamol for postoperative pain within the 2 weeks between the craniotomy and discharge from the hospital (1000 mg 3 times per day).[neuro-oncology.oxfordjournals.org]
  • […] evidence B Inconsistent or limited-quality patient-oriented evidence C Consensus, usual practice, opinion, disease-oriented evidence, case series CASE › James A, age 68, presents to his family physician (FP) with anorexia, nausea, and vague upper abdominal pain[mdedge.com]
  • To investigate choledocolithiasis: Compatible clinical picture with epigastric or right upper quadrant pain, a history of biliary surgery and/or gallstones.[hepatitis.va.gov]
  • The pain usually lasts from one to several hours. Cancer Infections Birth defects, such as biliary atresia. It is the most common reason for liver transplants in children in the United States. Inflammation, which can cause scarring.[icdlist.com]
  • She denied fever, rash or abdominal pain. She also denied the use of alcohol or non-prescription medications, history of blood transfusion or foreign travel, exposure to toxins, or family history of liver disease.[nature.com]
Goiter
  • The examination found a syndrome of thyrotoxicosis, a vascular goiter with discrete bilateral exophthalmia. The TSHus level was less than 0.005 IU/L. There Figure 1. Ultrasound features showing heterogeneous hyper-vascular goiter. Table 1.[file.scirp.org]
  • Thyroid was soft and diffusely enlarged with grade 3 goiter and audible bruit. The liver and spleen were not palpable.[ijem.in]
  • ., 1484 Goiter, endemic, 1961: Nov., 1524 iatrogenic, 1961: Nov., 1524 toxic. See Hyperthyroidism.[kundoc.com]
Jaundice
  • Chlorpromazine jaundice had a very typical clinical signature of short incubation period (1 to 4 weeks), symptoms of pruritus and jaundice (the itching often arising before jaundice) and a benign, self limited course.[livertox.nih.gov]
  • Clinical manifestations of hepatic involvement were mainly dominated by jaundice. It was jaundice of the cholestatic type, not febrile. A painful sensitivity of the right hypochondrium was concomitant with jaundice in two of our patients.[file.scirp.org]
  • Just after two days of addition of pimozide to the ongoing therapy, jaundice and elevated liver enzymes were detected which may indicate a drug induced hepatitis.[jpps.com.pk]
  • The patient was then referred to a hepatologist for evaluation of worsening jaundice post-ERCP.[jmedicalcasereports.biomedcentral.com]
  • Keywords: Carbimazole, cholestatic jaundice, Graves′ disease, thyrotoxicosis How to cite this article: Kota SK, Meher LK, Kota SK, Jammula S, Modi KD. Carbimazole-induced cholestatic hepatitis in Graves' disease.[ijem.in]
Scleral Icterus
  • His pertinent physical exam findings were scleral icterus and jaundice all over the body and evidence of scratch marks and excoriations from itching but no abdominal distention and tenderness.[karger.com]
  • Physical examination was unremarkable other than mild scleral icterus. No hepatosplenomegaly or other stigmata of chronic liver disease was apparent.[gastroenterologyandhepatology.net]
Recurrent Jaundice
  • Oral contraceptives are contraindicated in patients with a history of recurrent jaundice of pregnancy.[clinicalgate.com]
Pruritus
  • References Bunchorntavakul C, Reddy KR: Pruritus in chronic cholestatic liver disease. Clin Liver Dis 2012;16: 331–346. Khandelwal M, Malet PF: Pruritus associated with cholestasis. A review of pathogenesis and management. Dig Dis Sci 1994;39: 1–8.[karger.com]
  • Patients should be specifically asked about the presence of pruritus. In general, pruritus presents earlier in cases of intrahepatic cholestasis.[hepatitis.va.gov]
  • Signs and symptoms [ edit ] Itchiness ( pruritus ). Pruritus is the primary symptom of cholestasis and is thought to be due to interactions of serum bile acids with opioidergic nerves.[en.wikipedia.org]
  • She continued taking methimazole for 4 days after the appearance of jaundice and presented to the hospital two weeks later because of persistent jaundice and pruritus.[livertox.nih.gov]
  • The hallmark clinical feature of intrahepatic cholestasis of pregnancy is pruritus.[clevelandclinicmeded.com]
Dark Urine
  • Dark urine [ citation needed ] Causes [ edit ] Possible causes: pregnancy androgens birth control pills antibiotics (such as TMP/SMX) abdominal mass (e.g. cancer ) biliary atresia and other pediatric liver diseases biliary trauma congenital anomalies[en.wikipedia.org]
  • Symptoms of both types of cholestasis include jaundice, pale and fatty stools, dark urine, and intense itching over the skin.[medical-dictionary.thefreedictionary.com]
  • Later, overt evidence of liver damage, such as jaundice, dark urine and an enlarged and tender liver, may develop. Two general pathogenic mechanisms are recognised: Predictable or direct: usually promptly follows an exposure to a new medication.[patient.info]
  • The pain was associated with yellow discoloration of the eyes, passage of dark urine, and generalized itching. He had no significant past medical, environmental, or social history.[jmedicalcasereports.biomedcentral.com]

Workup

  • His lab workup for liver failure was essentially negative including hepatitis panel, antimitochondrial antibody, α1-antitrypsin and α-fetoprotein levels.[karger.com]
  • A thorough investigative workup was negative for autoimmune and other viral causes of hepatitis.[bjmp.org]

Treatment

  • The treatment of this auto-immune disease rests on three alternative methods: medicinal, surgical, and isotopic. The medical treatment is the therapeutic method always advised in first line treatment.[file.scirp.org]
  • Atrial fibrillation, treatment, 1961: Nov., 1421 Atrial flutter, treatment, 1961: Nov., 1420; 1961![kundoc.com]
  • Treatment of GVHD consists of prophylactic measures and treatment of active disease. The most common prophylactic regimen is a combination of methotrexate and cyclosporine.[clevelandclinicmeded.com]
  • Links: links to example of drugs causing cholestasis cholestasis jaundice General Practice Notebook General Practice Notebook The information provided herein should not be used for diagnosis or treatment of any medical condition.[gpnotebook.co.uk]
  • Warren JE, Blaylock RC, Silver RM: Plasmapheresis for the treatment of intrahepatic cholestasis of pregnancy refractory to medical treatment. Am J Obstet Gynecol 2005;192: 2088–2089.[karger.com]

Prognosis

  • Prognosis is good. Notice the presence of fine yellow granular bile pigment in the cytoplasm of hepatocytes around the central vein (zone 3).[meddean.luc.edu]
  • The risk is higher in women. [ 6, 7 ] Prognosis Usually symptoms subside when the causative drug has been discontinued and drug-related hepatitis subsides within days or weeks after the offending drug is stopped.[patient.info]
  • Early indicators of prognosis in fulminant hepatic failure. Gastroenterol. 1989;97(2):439-495.[revistagastrocol.com]
  • The impact of eosinophilia and hepatic necrosis on prognosis in patients with drug-induced liver injury. Aliment Pharmacol Ther 2007;25:1411–1421. 36. Rochon J, Protiva P, Seeff LB et al.[gi.org]
  • Mushroom Poisoning: A Clinical Model of Toxin-Induced Centrilobular Necrosis Introduction Amanita: The Mushrooms The Toxins Amanita Poisoning: Manifestations Liver Lesions Prognosis Management Conclusions Acknowledgment References Chapter 35.[elsevier.com]

Etiology

  • Liver biopsy is generally not indicated in acute cholestatic injury unless the etiology continues to be uncertain despite all pertinent investigations.[hepatitis.va.gov]
  • TERMINOLOGY Abbreviations • Cholestatic drug-induced liver injury (DILI), primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC) ETIOLOGY/PATHOGENESIS 4 General Categories • Based on symptom duration and histologic pattern of injury Pure[basicmedicalkey.com]
  • […] drug exposure varies from hours to months Clinical manifestations range from asymptomatic deranged liver function to fulminant hepatic failure and death Mimic all forms of acute, chronic, vascular or neoplastic liver diseases that are caused by other etiologies[pathologyoutlines.com]
  • This categorization allows testing for competing etiologies in a systematic approach.[gi.org]
  • It is important to consider ACE-I as an etiology for drug-induced liver injury (DILI) since continuation of the ACE-I beyond onset of hepatitis is fatal 1.[bjmp.org]

Epidemiology

  • Hepatotoxicity of Herbals and Dietary Supplements Introduction Epidemiology of and Expenditure on Herbals and Dietary Supplements Origin and Production of Herbals and Botanicals for Medicinal Purposes Regulation of Dietary Supplements The Use of Herbal[elsevier.com]
  • About 10% of cases are idiosyncratic. [ 1 ] Epidemiology A very large number of drugs have been implicated as a potential cause of drug-induced hepatitis but with variable risk of both frequency and severity.[patient.info]
  • ., Ndongo, S. and Pouye, A. (2016) Epidemiological, Clinical, Therapeutic and Evolutionary Aspects of Graves’ Disease in Internal Medicine at the CHU Le Dantec Dakar (Senegal). Pan African Medical Journal, 25, 6. 5.[file.scirp.org]
  • Epidemiology of idiosyncratic drug-induced liver injury. Semin Liver Dis. 2009;29:337-347. 5. Larson AM. Drug-induced liver injury. UptoDate. www.uptodate.com/contents/drug-induced-liver-injury. Accessed July 8, 2016. 6.[uspharmacist.com]
  • Larrey D (2002) Epidemiology and individual susceptibility to adverse drug reactions affecting the liver. Semin Liver Dis 22: 145-156. Leise MD, Poterucha JJ, Talwalkar JA (2014) Drug-induced liver injury. Mayo ClinProc 89: 95-106.[omicsonline.org]
Sex distribution
Age distribution

Pathophysiology

  • Definition / general Drug / toxin reactions can be intrinsic or predictable, where they are dose dependent (e.g. acetaminophen ); or idiosyncratic and unpredictable, where they are dose independent (e.g. isoniazid) Pathophysiology Underlying mechanisms[pathologyoutlines.com]
  • Approximately 80% of patients with PSC have inflammatory bowel disease, more commonly ulcerative colitis than Crohn’s disease. 21 Pathophysiology and Natural History The pathophysiology of PSC is unclear, but there is evidence suggesting an autoimmune[clevelandclinicmeded.com]
  • Hepatocanalicular transport defects: pathophysiologic mechanisms of rare diseases. Gastroenterology. 2006;130(3):908–25. Jacquemin E. Progressive familial intrahepatic cholestasis. Genetic basis and treatment. Clin Liver Dis. 2000;4(4):753–63.[revistagastrocol.com]
  • Oxidant Stress, Antioxidant Defense, and Liver Injury Introduction The Major Reactive Oxygen and Nitrogen Species in the Liver and their Sources Pathophysiological Consequences of Oxidative Stress Antioxidants Drug-Induced Oxidative Stress in the Liver[elsevier.com]
  • Pathophysiology Hepatic drug transport has been shown to be involved in the pathophysiology of cholestatic effects from drugs.[ 15, 16 ] In the liver, transport at the apical membrane into hepatocytes involves the organic anion transporting polypeptide[onlinelibrary.wiley.com]

Prevention

  • Monitoring for and recognition of drug-induced hepatotoxicity may prevent some cases of acute hepatic failure.[nejm.org]
  • CONCLUSION Early diagnosis of drug induced liver disease and identification of the drug may prevent more severe even fatal outcomes.[jpps.com.pk]
  • After the procedure we started oral flecainide (300 mg/d) for long-termtherapy as relapse prevention, as the patient’s hemodynamics was impaired due to VT-storm. Hereafter no recurrence of ventricular tachycardia was observed.[archivesofmedicine.com]
  • Please read the Tylenol Liver Damage article for a detailed discussion of the symptoms, mechanisms of acetaminophen toxicity, treatment (early use of N-acetylcysteine), and prevention.[medicinenet.com]
  • Hepatitis E Whether IG prevents hepatitis E remains undetermined.[clinicalgate.com]

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