OCCUPATINAL LIVER DISEASE

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

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

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 • 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 • 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

20. 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.

21. 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

24. 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

27. 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).

28. 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.

29. 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.

30. 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. .

31. 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.

32. 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.

33. 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.

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

35. 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

41. 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