Korean J Occup Environ Med.  2012 Sep;24(3):304-310.

A Suspicious Case of Chloroform Induced Acute Toxic Hepatitis in Laboratory Worker

• Lee DG
• Lee CH
• Jang KH
• Chae HJ
• Moon JD

Abstract

OBJECTIVES
To report upon a case of toxic hepatitis in a worker exposed to chloroform.
METHODS
A 28-year-old female who had worked as chemical analysis engineer in a laboratory using chloroform was hospitalized due to nausea, vomiting and generalized weakness. The authors evaluated her using blood tests, abdominal CT scan and her occupational history.
RESULTS
The blood tests revealed acute toxic hepatitis. Other causes of hepatitis such as viral, drug induced or alcoholic hepatitis could be excluded. But autoimmune hepatitis couldn't be totally ruled out(ANA (++), IgG(serum) 1780 mg/dL). After admission, her symptoms improved and her liver enzyme levels(AST and ALT) were markedly reduced. She returned to her workplace after discharge. Afterwards, however, her liver enzyme levels increased again one week after returning to her workplace. Subsequent to a job change, her liver enzyme levels reduced and normalized after eight weeks. The airbone laboratory chloroform ranged from 3.155 to 9.037 ppm.
CONCLUSIONS
The authors presume that this patient's liver injury was related to an interaction of chloroform toxicity and a predisposition to autoimmune hepatitis. The rapid improvement of the clinical symptoms and the progressive normalization of the liver function tests once the chloroform exposure eliminated supports the diagnosis.

Keyword

Toxic hepatitis; Chloroform

MeSH Terms

Adult
Chloroform
Drug-Induced Liver Injury
Female
Hematologic Tests
Hepatitis
Hepatitis, Alcoholic
Hepatitis, Autoimmune
Humans
Liver
Liver Function Tests
Nausea
Vomiting
Chloroform

Figure

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  Fig. 1 Preprocessing(25 minutes).

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  Fig. 2 Vial setting(8 minutes).

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  Fig. 3 Analytical instrument(290 minutes).

Reference

1. NIOSH. Pocket Guide to Chemical Hazards. 1997. 64–65.

2. Michael G. Chemical Hazards. Occupational and Environmental Health. 2006. 5th ed. Philadelphia: Lippincott Williams & Wilkins Pub;293–306.

3. Linda M, Fraizer G, Deborah BF. Adverse Health Effects. Occupational and Environmental Health. 2006. 5th ed. Philadelphia: Lippincott Williams & Wilkins Pub;630–633.

4. Jung KC. Industrial Poisoning Handbook. 1995. Seoul: Shinkwang Company;208–211. 496–498. (Korean).

5. American Conference of Governmental Industrial Hygienists(ACGIH). Cincinnati, OH 45240-1634 2007. Documentation of the TLV's and BEI's with other world wide occupational exposure values. CD-ROM.

6. McMartin DN, O'Connor JA, Kaminsky LS. Effects of differential changes in rat hepatic and renal cytochrome P-450 concentrations on hepatotoxicity and nephrotoxicity of chloroform. Res Commun Chem Pathol Pharmacol. 1981. 31:99–110.

7. Branchflower RV, Schulick RD, George JW, Pohl LR. Comparison of the effects of methyl n-butyl ketone and phenobarbital on rat liver cytochrome P-450 and the metabolism of chloroform to phosgene. Toxicol Appl Pharmacol. 1983. 71:414–421.

8. Harris RN, Ratnayake JH, Garry VF, Anders MW. Interactive hepatotoxicity of chloroform and carbon tetrachloride. Toxicol Appl Pharmacol. 1982. 63:281–289.

9. Hewitt WR, Miyajima H, Cote MG, Plaa GL. Acute alteration of chloroform-induced hepato- and nephrotoxicity by mirex and kepone. Toxicol Appl Pharmacol. 1979. 48:509–527.

10. Brown BR, Sipes IG, Sagalyn AM. Mechanism of acute hepatic toxicity : chloroform, halothane and glutathione. Anesthesiology. 1974. 41:554–561.

11. Cowlen MS, Hewitt WR, Schroeder F. Mechanism in 2-hexanone potentiation of chloroform hepatotoxicity. Toxicol Lett. 1984. 22:293–299.

12. Lavigne JG, Marchand C. The role of metabolism in chloroform hepatocyto-toxicity. Toxicol Appl Pharmacol. 1974. 29:312–326.

13. Bomski HA, Sobdewska A, Strakowski A. Toxic damage of the liver by chloroform in chemical industry workers. Int Arch Arbeitsmed. 1967. 24:127–134.

14. Bai C, Canfield PJ, Stacey NH. Individual serum bile acids as early indicators of carbon tetrachloride- and chloroform-induced liver injury. Toxicology. 1992. 75:221–234.

15. Hakim A, Jain AK, Jain R. Chloroform ingestion causing toxic hepatitis. J Assoc Physicians India. 1992. 40:477.

16. Jules LD. Toxic and Drug-Induced Hepatitis. Harrison's Principles Internal Medicine. 2008. 17th ed. New York: McGraw-Hill company;1949–1955.

17. Jon R, Leslie M. Occupational illnesses. Current Occupational and Environmental Medicine. 2007. 4th ed. New York: McGraw-Hill company;175–184.

18. Robert JH. Liver Toxicology. Current Occupational and Environmental Medicine. 2007. 4th ed. New York: McGraw-Hill company;345–349.

19. Seo JC, Jeon WJ, Park SS, Kim SH, Lee KM, Chae HB. Clinical experience of 48 acute toxic hepatitis patients. Korean J Hepatol. 2006. 12:74–81. (Korean).

20. Jaeschke H, Gores GJ, Cederbaum AI, Hinson JA, Pessayre D, Lemasters JJ. Mechanisms of hepatotoxicity. Toxicol Sci. 2002. 65:166–176.

21. Lee WM. Drug-induced hepatotoxicity. N Engl J Med. 2003. 349:474–485.

22. Robin MA, Le Roy M, Descatoire V, Pessayre D. Plasma membrane cytochrome P450 as neoantigens and autoimmune targets in drug-induced hepatitis. J Hepatol. 1997. 26:23–30.

23. Larson JL, Wolf DC, Morgan KT, Mery S, Butterworth BE. The toxicity of one week exposures to inhaled chloroform in female B6C3F1 mice and male F-344 rats. Fundam Appl Toxicol. 1994. 22:431–446.

24. Phoon WH, Goh KT, Lee LT, Tan KT, Kwok SF. Toxic jaundice from occupational exposure to chloroform. Med J Malaysia. 1983. 38:31–34.

25. Kutob SD, Plaa GL. The effect of acute ethanol intoxication on chloroform-induced liver damage. J Pharmacol Exp Ther. 1962. 135:245–251.

26. Sato A, Nakajima T, Koyama Y. Effects of chronic ethanol consumption on hepatic metabolism of aromatic and chlorinated hydrocarbons in rats. Br J Ind Med. 1980. 37:382–386.

27. Sato A, Najajiwa T, Koyama Y. Dose-related effect of a single dose of ethanol on the metabolism in rat liver of some aromatic and chlorinated hydrocarbons. Toxicol Appl Pharmacol. 1981. 60:8–15.

28. Hewitt LA, Palmason C, Masson S, Plaa GL. Evidence for the involvement of organelles in the mechanism of ketone-potentiated chloroform-induced hepatotoxicity. Liver. 1990. 10:35–48.

29. Manns MP, Strassburg CP. Autoimmune hepatitis : clinical challengers. Gastroenterology. 2001. 120:1502–1517.

30. Kim YS. Recent diagnosis and treatment of autoimmune hepatitis. Korean J Hepatol. 2009. 15:7–20. (Korean).

31. Jules L. Dienstag. Chronic Hepatitis. Harrison's Principles Internal Medicine. 2008. 17th ed. New York: McGraw-Hill company;1966–1969.

32. Robin MA, Le Roy M, Descatoire V, Pessayre D. Plasma membrane cytochrome P450 as neoantigens and autoimmune targets in drug-induced hepatitis. J Hepatol. 1997. 26:23–30.

33. Czaja AJ, Dos Santos RM, Porto A, Santrach PJ, Moore SB. Immune phenotype of chronic liver disease. Dig Dis Sci. 1998. 43:2149–2155.