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‫دکتر سعید تیموری‬
‫متخصص طب کار وبیماریهای شغلی‬
‫مدیریت درمان تامین اجتماعی اصفهان‬
‫درمانگاه قدس عباس اباد‬
Route of Exposure

Inhalation

Ingestion

Percutaneous absorbtion
Liver Disorders Induced by
physical agents

Hyperthermia (Heat stroke):
& cholestasis
Necrosis

Ionizing radiation (>3000 to 6000 rad): Hepatitis
2-6 Week later
Aminotransferase (Transaminase)

AST & ALT: most useful indicators of hepatocellular
damage
High level:
 Viral, alcoholic, or ischemic hepatitis, extrahepatic
obstruction,
 False positive: erythromycin, aminosalicylic acid, DKA

A serum AST:ALT ratio <1 with trnsaminase level
< 300 IU/L may suggestive occupational liver
disease
Alkaline Phosphatase (ALP)

Several forms
 Bone, intestine, liver, kidney, placenta, leukocyte
 In the absence of bone disease or pregnancy, elevated levels of
ALP activity reflect impaired biliary tract functon.
Slight & moderate elevation
in parenchimal liver disorders such as hepatitis, cirrhosis
High elevation
 in extrahepatic biliary tract obstruction
 intrahepatic cholestasis (drug induced or PBC)
 more sensitive marker than bilirubin in biliary tract obstruction

To diffentiate hepatic origin from nonhepatic origin
 5’-nucleotidase or g-glutamyl- trasnspeptidase (GGT)
 isoenzyme assay; not practical
Morphologic patterns of
liver injury
Acute
Cytotoxic
Necrosis(Centrizonal)
CCL4,chloroform,TNT,PCB
Steatosis
C
CCL4,chloroform,P,DM hydrazine,styrene
Cholestatic
MDA,Rapeseed oil, aflatoxin
Acute Hepatic Injury

Carbon tetrachloride
 Dizziness, headache, visual disturbances,




confusion
Nausea, vomiting, abdominal pain, diarrhea
Palpable liver & spleen, jaundice, elevated
serum transaminase, prolonged PT
Renal failure
Hypoglycemia, encephalopathy, hemorrhage
Morphologic patterns of
liver injury
Sub acute
Chronic
Cirrhosis
Sclerosis
Porphyria
Neoplasia
Steatosis
Granoluma
TNT
TNT,PCBs,tetrachloroethane,Arsenic
Arsenic, vinyl chloride, thorium
Dioxin
Arsenic , vinyl chloride
DMF , CCL4
Beryllium , copper
Fatty liver (steatosis)
Steatosis is defined greater than 5%
hepatocytes containing fat.
 Steatosis occurs in diabetes mellitus,
hypertriglyceridemia, obesity
 There is multifactorial, thus industrial
hepatotoxins interact with underlying
metabolic disorders and other causes of
non-alcoholic steatohepatitis (NASH).

Fatty liver (steatosis)

pathology:alteration of hepatic fat
metabolis

Hepatotoxins can block fat metabolism
at accumulation of free fatty acids and
triglycerides.
Fatty liver (steatosis)

. Patients are usually asymptomatic.
Screening tests (AST, ALT) may not detect
 steatosis in the absence of inflammation
and necrosis.
 . Diagnosis is complicated by confounding
etiologies , including alcohol consumption,
obesity, diabetes, medications, and their
 interactions with suspected toxins.

Fatty liver (steatosis)
Necrosis, steatosis, and fibrosis can be
induced in animals by the chronic
administratio of carbon tetrachloride.
 Human studies that steatosis can occur
in the absence of elevated serum
hepatic transaminase levels.

Fatty liver (steatosis)
individuals with alcohol-induced
or metabolically induce significant
progression of steatosis to fibrosis
histologically, termed ‘steatocirrhosis’,
often in the absence of an inflammatory
response and associated transaminase
elevation.

Fatty liver (steatosis)
Diagnosis
 Laboratory tests may not be helpful
 because they frequently do not detect
steatosis in the absence of
inflammation.
 ultrasonography and CT scan can
suggest hepaticsteatosis.
 The definitive diagnosis a liver biopsy
specimen.

Fatty liver (steatosis)


When significant steatosis is found, should
attempt to differentiate occupational from other
known causes :
Medications associated with steatosis (such
as phenytoin tetracycline, isoniazid,
nitrofurantoin,

Hyperlipidemia, diabetes mellitus,obesity or
pregnancy, and substance abuse,.

Laboratory evaluation fasting blood sugar
and triglyceride levels. .
Fatty liver (steatosis)
Management
 The presence of steatosis without other
obvious etiologies, with exposure to
hepatotoxic , is suggest toxic exposure
should be minimized, and removal from
the workplace .
 Resolution elevation aminotransferas
elevels after removal from exposure
supports an occupational etiology.

Infectious Agents
HAV
Nursery & kindergarten staff
Sewer workers
HBV & HCV
HCWs with blood and body fluid
contact
Cytomegalovirus
Pediatric health care workers
Coxiella burnetti
Animal care workers, farm
workers, slaughterhouse
workers
Leptospira
icterohaemorrhagiae
Sewer workers, farm workers
HAV

HCWs (Emergency rooms, surgery, laundry, children’s
psychiatry, dentists)
Transmission: fecal-oral, Blood (rare)
Incubation period: average 28-30 days
Abrupt onset with fever, malaise, anorexia, nausea,
abdominal discomfort, and jaundice
Greatest infectivity:2w before the onset of jaundice or liver
enzymes
Not chronic carrier
Dx: IgM anti HAV Ab

IgG confer enduring protection






HAV Prevention

a single IM dose of 0.02 ml/kg gamma globulin before
exposure (80-90%)

Routine Ig administration is not recommended for person
exposed to a fellow worker with hepatitis A

Close contacts should be given Ig

Vaccine: Travel or work in country with intermediate or high
endemicity, lab workers with exposure to live virus, animal
handlers

Employee with Hep A should be restricted from work until
symptoms subside or 1 W after the onset of jundice
HBV








A major cause of acute & chronic hepatitis, cirrhosis, hepatocellular
carcinoma
HCWs with blood or body fluid contact
Transmission: Blood or body fluid, not fecal-oral
Forms of illness:Acute,Inapparent sporadic episodes,Chronic carrier
Incubation period: 45-60 days
malaise, anorexia, nausea, abdominal pain, jaundice, skin rash, arthralgia,
arthritis
Chronic state: presence of HBsAg-positive serum on at least two occasion
at least 6 months apart
Risk of infection following percutaneous inj (HBeAg+&HBsAg+):22-31%
HBV Prevention

Individuals at risk for blood borne pathogen exposure should be
vaccinated

A three dose series: 95% protection

Not immune: >45y, obesity, smoking

Second three dose: 30-50% protection

Nonresponders to vaccination with HbsAg-negative: Ig

Employee whit Hep B & Liver dis should be advised to avoid
exposure to other potentially hepatotoxic agents such as ethanol or
workplace solvent
Acute Hepatic Injury







Anesthetic gases
Bromobenzene
Carbon tetrabromide
Carbon tetrachloride
Chlorinated
naphthalenes
Chloroform
Dichlorohydrin






Dimethylformamide
Phosphorus
2-Nitropropane
Tetrachloroethane
Trichloroethylene
Trinitrotoluene
HCV



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


Chronic: 70%
Transmission: Blood, IV drugs, (sexual, maternal ?)
Risk of infection following occupational percutaneous exp:1.8(0-7)%
80% anicteric & asymptomatic
Incubation period: 6-8 w
FHF is rare
CAH & cirrhosis: 60%
Major agent in the etiology of hepatocellular carcinoma
Dx: measurement of HCV RNA by PCR
Following percutaneous or mucosal occupational exposure, baseline
and follow-up HCV antibody measurements should be performed (6
w, 3 & 6 m)
Not vaccine is currently available
Medical Surveillance

Biochemical tests



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

Tests of synthetic liver function



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
AST, ALT
ALP
LDH
Bilirubin
Urine bilirubin
Alb
PT
Alpha fetoprotein
Ferritin
Clearance tests





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Sulfobromophthalein
Indocyanine green
Antipyrine test
Aminopyrine breath test
Serum bile acid
Urinary D-glucaric acid

SGGT
 More sensitive indicator but not specific

LDH
 Myocardium, skeletal muscle, brain, kidney, RBC

Liver specific enzymes

Alb
 Little value in differential diagnosis

Alpha fetoprotein
 70% positive in hepatocellular carcinoma
 Not utility in the occupational setting
Clinical Management of
OCCUPATIONAL Liver Disease

Occupational & medical Hx
 Exposure to hepatotoxins
 PMH of liver dis,medication
 Review of symptoms(CNS Toxicity due to solvent






exposure)
Travel to areas with endemic parasitic or viral disease
Steroid use,glue sniffing,recreational solvent use
Previous blood transfusion, tattoos, needle sticks, IV drug
…
Use of protective work practices
MSDS
Ask about other emploees
Clinical Management of
OCCUPATIONAL Liver Disease

Physical Examination
 Acute liver disease
RUQ tenderness
Hepatosplenomegaly
Jaundice
Chronic liver disease
Spider angioma
Palmar erythema
Testicular atrophy
Ascites
Gynecomastia

Clinical Management of
OCCUPATIONAL Liver Disease

Elevated serum transaminase level
 R/O nonoccupational causes
 Workplace
 Remove for 3-4 weeks
 Repeat
Heavy metal toxicity.
Arsenic ;Insecticide, Paris green
Sensory
> motor neuropathy, red hands, burning feet,
hyperhidrosis
 Lead
Paint, gas, batteries
Adults:
neuropathy, painful joints; children: cerebral
edema,
encephalopathy, low IQ
 Mercury Industrial, polluted fish
Severe
arm and leg pain, dementia with primarily
motor neuropathy
 Thallium
Insecticide, rat poison
Stocking-glove sensorimotorneuropathy, with
alopecia
THANKS YOUR ATTENTION