2. OCCUPATINAL LIVER DISEASE
دکتر سعید تیموری
متخصص طب کار وبیماریهای شغلی
مدیریت درمان تامین اجتماعی اصفهان
درمانگاه قدس عباس اباد

3. Route of Exposure
Inhalation
Ingestion
Percutaneous absorbtion

4. Liver Disorders Induced by physical agents
Hyperthermia (Heat stroke): Necrosis & cholestasis
Ionizing radiation (>3000 to 6000 rad): Hepatitis 2-6 Week later

5. Infectious Agents HAV HBV & HCV Cytomegalovirus Coxiella burnetti
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

6. 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

7. Morphologic patterns of liver injury
Sub acute TNT
Chronic
Cirrhosis TNT,PCBs,tetrachloroethane,Arsenic
Sclerosis Arsenic, vinyl chloride, thorium
Porphyria Dioxin
Neoplasia Arsenic , vinyl chloride
Steatosis DMF , CCL4
Granoluma Beryllium , copper

8. Screening tests Biochemical tests Tests of synthetic liver function
AST, ALT
ALP
LDH
Bilirubin
Urine bilirubin
Tests of synthetic liver function
Alb PT
Alpha fetoprotein
Ferritin
Clearance tests
Sulfobromophthalein
Indocyanine green
Antipyrine test
Aminopyrine breath test
Serum bile acid
Urinary D-glucaric acid

9. 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

10. 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

11. Medical Surveillance
Strategies for controlling occupational liver disease follow of primary and secondary prevention.
Primary preventive strategies attempt to identify and remove (or reduce) exposures.
Hepatotoxic exposures can be minimized by substitutingless toxic agents and by using engineering controls (e.g.,
improved ventilation) and personal protective equipment.

12. Medical Surveillance
Secondary preventive strategies involve the screening of workers actively exposed to known or suspected hepatotoxins.
This approach is appropriate when exposure is unpredictable or unavoidable .
Attempt to identifyhepatic disease at an early, reversible stage.

13. Screening tests
Despite high sensitivity and specificity in particular settings, all tests are potentially limited by low predictivevalue
AST,ALT, which are 90% accurate in the diagnosis of acute viral hepatitis, have a predictive value of less than 10% in screening for chronic liver disease in the general population..

14. Screening tests
Screening of healthy workers is recommended only when strongly suspected hepatotoxic agents.
(AST and ALT) remain the best practical choice at present.

15. Management of abnormal LFTs
In acute and subacut setting
Management of abnormal LFTs depends on the clinical presentation and exposure setting.
Transaminase levels are elevated several fold an monitored closely, early hepatic ultrasound to rule out biliary obstruction.

16. Management of abnormal LFTs
In chronic low-level exposures,
the relationship between elevated hepatic transaminase levels and specific exposures may be much more difficult to determine.
. Removal of the affected individual from work should be considered only after alternative etiologies, such as medications,non-occupational liver disorders, and excessive alcohol

17. Management of abnormal LFTs
There are no strict guidelines for the management of abnormal serum aminotransferase levels, which are often minimally elevated.
In situations in which significant exposure is unlikely and transaminase levels are between one and two times normal, repeat testing in 4 weeks has been advocated, with further investigation
reserved only for persistent elevations.

18. APPROACH Assess both occupational and non-occupational
significant alcohol use,viral hepatitis (A, B, and C), biliary disease, medications,blood transfusions, and hepatotoxic exposures from work,hobbies, the home, and second jobs
Potential hepatotoxic medications are numerou (e.g., acetaminophen,isoniazid, erythromycin, estrogens, phenytoin, and megavitamins such as vitamin A) and should be discontinued,
. The abnormal liver tests should berepeated in 2–4 weeks.
Metabolic etiologies including
diabetes mellitus, hemochromatosis, hypertriglyceridemia
and obesity should be considered.

19. APPROACH
2. Consider the AST/ALT ratio. Ratios less than one are suggestive of viral or toxic exposures rather than alcohol use.
3. Attempt to determine the presence of any known or suspected hepatotoxins in the workplace or environment.
Sources of such information may be obtained from MSDS

20. APPROACH 4. significant hepatotoxic exposure is identified
Individual should be removed from further exposure and his or her AST , ALT should be rechecked in 2–4 weeks.
Recovery suggests an occupational etiology,
but persistent elevations do not rule it out.
Such persons may return to work or the same environmental setting , appropriate controls or exposure modifications have been implemented
. Close follow-up,with continued monitoring of AST ,ALT levels, is necessary

21. APPROACH
5. Persistent elevation AST,ALT greater than twice normal for over 2 months further investigation; hepatologist .
Such individuals have an increased chronic active hepatitis, steatohepatitis, and fibrotic changes.
Hepatic ultrasonography, liver biopsy, or both,
may be indicated.
Findings of steatosis and necrosis are particularly suggestive of an occupational etiology.
Removal of the affected individual from hepatotoxic
exposures, even if they are only suspected.
Because various hepatotoxins may interact,alcohol use and potentially hepatotoxic medications should be minimized.

23. Heavy metal toxicity. THANKS YOUR ATTENTION
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

25. 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

28. 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).

29. 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.

30. 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.

31. 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. .

32. 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.

33. 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.

34. 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.

35. Fatty liver (steatosis)
pathology:alteration of hepatic fat metabolis
Hepatotoxins can block fat metabolism at accumulation of free fatty acids and triglycerides.

36. Liver specific enzymes Alb Alpha fetoprotein
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