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home - Liver - Miscellaneous - Chronic Drug Injury Written by Dr Sebastian Zeki

Recognises the importance of sepsis as a complication
Aware of the differential diagnosis and management of sepsis and its
possible sequelae

Knows the appropriate use of the appropriate antibiotics and their
complications Aware of prevention of nosocomial infection

Understands the principles and practice of diagnosis and treatment of

Prepared to involve and liaise with specialist sepsis support



Knows the importance of clinical nutrition and its disturbances in
patients with acute and chronic liver disease

Appreciates indications for enteral or parenteral support and
understanding of limitations of these interventions

Shows ability to make careful nutritional assessment
Can liaise with nutritional support team where appropriate


Understands prognostic scoring systems including Child - Pugh
MELD UKELD Maddrey and disease-specific scoring systems where
they exist

Builds the use of accredited quantitative scoring systems into routine
clinical liver practice clinical colleagues and junior staff

Shows consistent application of evidence-based in the
evaluation of liver disease and the determination of prognosis

Chronic Drug Injury

Fibrosis and cirrhosis This results from steatosis (amiodarone) or chronic hepatitis.The development of cirrhosis can occur asymptomatically (as with methotrexate or methyldopa). Written by Dr Sebastian Zeki Examples: amiodarone; amitriptyline; chloro-quine; perhexilene maleate; chlorphe-niramine; chlorproma-zine; thioridazine.Histology: lysosomes engorged with phos-pholipid, resulting in foamy hepatocytes.It is believed that an interaction between the phospholipid and the drug leads to the formation of a complex which prevents degra-dation of the phospho-lipid molecules..High incidence of cirrhosis Can also develop from: lesions of chronic intrahepatic cholestasis , chronic cholestasis (floxuridine), chronic congestive hepatopathy with sinusoidal obstruc-tion syndrome (azathioprine, mercaptopurine oral contraceptives) or hepatic vein thrombosis (oral contraceptives), and noncirrhotic portal hypertension (inorganic arsenic, copper sulfate, vinyl chloride, and vitamin A). Steatosis drug associations: parenteral nutrition.mercury.ethanol. Steatosis histologic changes:Mallorys hyaline.Neutrophilic inflamm-tion.Variable steatosis.Cirrhosis.Phospholipidosis may also be present. Causes:methyldopa; minocycline; nitrofurantoin; diclofenac; fenofibrate; papaverine; phenytoin, propylthioura-cil; germander; statins; PhospholipidosisPhospholipidosis is rare.It usually occuras after chronic ingestion.Clinical presentation includes hepatomegaly with or without hepatic insufficiency. Steatosis injuryMacrovesicular disease is less severe than microve-sicular steatosis.Patients presentwith hepatomegaly.Presentation is with a moderate ALT rise.Patients can be asympto-matic or get a steato-hepatitis with progres-sion to cirrhosis in weeks/ months. Viral hepatitis-like injuryThis presents as acute/chronic hepati-tis with type 2 AIH markers vs microso-mal cellular compo-nents.Examples include phenytoin; dihydrala-zine; ticrynafen.Patients can also get chronic hepatitis without AIH markers.This occurs with:Lisinopril, sulfona-mides, and trazodone.Patients can also get chronic toxicity with-out active necroin-flammatory disease.Eg: dantrolene, aspi-rin, and isoniazid. Autoimmune-like injuryIt resembles type I AIH. Drug Induced Chronic liver injury4 types of chronic hepatitis assoc. with drug-induced hepatotoxicity.As a general rule, these occur in patients taking the offending drug chronically.