Drug induced Liver Injury
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1. Epidemiology
2. Diagnosis
2.1. 1. Evidence of Liver Injury with drug exposure at appropriate time.
2.2. 2. Exclusion of Alternate Causes
2.2.1. Non-invasive liver screen
2.2.2. Liver imaging
2.2.3. Possibly Liver biopsy
2.3. 3. Resolution on Withdrawl
3. Clinical Picture
3.1. Asymptomatic LFT abnormalities
3.2. Cholestasis w/ pruritis
3.3. Acute illness with jaundice similar to viral
3.4. Acute liver failure
4. Treatment
4.1. 1. Discontinue offending drug
4.2. 2. Observation
4.3. 3. Supportive Care
4.3.1. anti-emetic
4.3.2. anti-pruritic
5. Patterns of Injury
5.1. Acute Hepatic Necrosis
5.1.1. Rapid Onset
5.1.2. Nausea, weakness, abdominal pain
5.1.3. Progresses to liver failure and multi-organ failure
5.1.4. Paracetemol; cocaine; mdma; IV amiodarone; methotrexate; terbutaline; phosphorous
5.2. Hepatocellular Hepatitis
5.2.1. 2-24 weeks
5.2.2. elevated ALT/AST
5.2.3. wide range from asymptomatic to severe
5.2.4. Isoniazid; pyrazinamide; disulfiram; fenofibrate; aspirin; allopurinol; amiodarone; HAART; ketoconazole; lisinopril; losartan; NSAIDs; statins; tetracyclines; ephedra; grater celandine; green tea; other herbals
5.3. Cholestatic Hepatitis
5.3.1. Typicall 2-12 weeks
5.3.2. elevated ALKP; variable elevation of ALT/AST
5.3.3. Fatigue and Nausea progressingto dark urine, pruritis and jaundice
5.3.4. May lead to vanishing bile duct syndrome
5.3.5. Co-amoxiclav; penicillins; rifampin; cephalosporins; sulfonylureas; many others
5.4. Mixed Hepatitis
5.4.1. Typicall 2-12 weeks
5.4.2. Prominant ALKP elevation, ALT/AST elevation
5.4.3. Immunoallergic features
5.4.4. Recovery usually more prolonged
5.4.5. may lead to vanishing bile duct syndrome
5.4.6. Anticonvulsants; azathioprine; enalapril; clindamycin; nitrofurantoin; sulphonamides; trazodone; verapamil; NSAIDS
5.5. Bland Cholestasis
5.5.1. Typically 4-24 weeks
5.5.2. Pruritis followd by dark urine and jaundice
5.5.3. Clasically caused by androgenic steroids adn oestrogens as well as azathioprine and 6MP
5.5.4. Jaundice may be deep and prolonged
5.6. Acute Fatty Liver with Lactic Acidosis
5.6.1. 7 days - 3 months
5.6.2. Prodromal nausea, anorexia and abdominal discomfort
5.6.3. Progresses to drowsiness/coma
5.6.4. Jaundice usually mild
5.6.5. ASA (Reye's syndrome)
5.6.6. Didanosine, stavudine, zidovudine
5.7. Non-Alcoholic Fatty Liver Disease
5.7.1. May be months
5.7.2. Usually asymptomatic
5.7.3. Steroids, antidepressents, tamoxifen, amiodarone, methotrexate
5.8. Sinusoidal Obstruction
5.8.1. Acute, subacute and chronic forms
5.8.2. Related to Cancer chemotherapy
5.8.3. Abdominal pain, swelling, ascites and oedema
5.8.4. Can progress to liver failure
5.8.5. Less common with less toxic chemotherapy regimes
5.8.6. Busulfan; cyclophosphamide; melphalan; cabroplatin; cisplatin; oxalipltin; azathioprine; 6MP; bush tea
5.8.7. Defibrotide recommended for prevention and treatment
5.9. Nodular Regenerative Hyperplasia
5.9.1. Non-cirrhotic portal hypertension, ofte presenting with ascites ro varices
5.9.2. Latency fo years
5.9.3. Liver enzymes frequently normal
5.9.4. Azathioprine; 6MP; didanosine; stavudine; Vit A
5.10. Hepatocellular Tumors
5.10.1. Focal nodular hyperplasia/ adenoma - oestrogens
5.10.2. HCC - androgens
6. Drug Induced Liver Injury with immune Features
6.1. Immunoallergic Hepatitis
6.1.1. Fever, rash, eosinophlia, facial oedema
6.1.2. Short latency
6.1.3. anticonvulsants; pencillines; mcrolidea; fluoroquinolones; celecoxib; allopurinol; nevirapine; efavirinz
6.1.4. Severest form in DRESS Syndrome
6.1.5. DRESS with hepatitis has poor prognosis
6.2. Drug Induced Autoimmune Hepatitis
6.2.1. Raised IgG, positive auto-antibodies (SMA, ANA, LKM)
6.2.2. Nitrofurantoin; minocycline; hydralazine; methyldopa; interferon; infliximab; etanercept
6.2.3. Spectrum of severeity can present with jaundice and liver failure