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The Gastroenterology Training Handbook
For Specialist Registrars
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Liver -
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Chronic Drug Injury
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Written by Dr Sebastian Zeki
MCQs for this page
What the Curriculum Says
Knowledge
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
Skills
Understands the principles and practice of diagnosis and treatment of
sepsis
Behaviours
Prepared to involve and liaise with specialist sepsis support
Also....
Knowledge
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
Skills
Shows ability to make careful nutritional assessment
Behaviours
Can liaise with nutritional support team where appropriate
Also...
Knowledge
Understands prognostic scoring systems including Child - Pugh
MELD UKELD Maddrey and disease-specific scoring systems where
they exist
Skills
Builds the use of accredited quantitative scoring systems into routine
clinical liver practice clinical colleagues and junior staff
Behaviours
Shows consistent application of evidence-based in the
evaluation of liver disease and the determination of prognosis
Chronic Drug Injury
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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:
diethylstilbestrol.
glucocorticoids.
griseofulvin.
methotrexate.
nifedipine.
tamoxifen.
total 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;
Phospholipidosis
Phospholipidosis is rare.
It usually occuras after
chronic ingestion.
Clinical presentation
includes hepatomegaly
with or without hepatic
insufficiency.
Steatosis injury
Macrovesicular 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
injury
This 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 injury
It resembles type
I AIH.
Drug Induced Chronic liver injury
4 types of chronic hepatitis assoc. with drug-induced hepatotoxicity.
As a general rule, these occur in patients taking the offending drug chronically.