2. 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

6. 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

7. 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

10. 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

11. 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

12. 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 Morphologic patterns of liver injury

13. 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).

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

15. 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.

16. 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.

17. 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.

18. 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.

19. 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..

20. 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.

21. 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

22. 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

23. 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

24. 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 occasions at least 6 months apart  Risk of infection following percutaneous inj (HBeAg+&HBsAg+):22-31%

25. 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

26. Acute Hepatic Injury  Anesthetic gases  Bromobenzene  Carbon tetrabromide  Carbon tetrachloride  Chlorinated naphthalenes  Chloroform  Dichlorohydrin  Dimethylformamide  Phosphorus  2-Nitropropane  Tetrachloroethane  Trichloroethylene  Trinitrotoluene

27. HCV  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

28. Medical Surveillance  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

29.  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

30. 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

31. 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

32. Clinical Management of OCCUPATIONAL Liver Disease  Elevated serum transaminase level R/O nonoccupational causes Workplace Remove for 3-4 weeks Repeat

38. 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