Occupational exposure to vinyl chloride and liver diseases

Table 1 Studies investigating the association between occupational exposure and hepatocellular carcinoma in vinyl chloride workers

Ref. location	Study description	Disease assessment	Exposure assessment	Exposure categories	Number of cases	Relative risk (95%CI)	Notes
Ward et al[3] (2001), European cohort	Cohort study, 12700 workers	HCC, best evidence	Job exposure matrix: Cumulative exposure (ppm-years)	0-734	3	1.0	Trend test
				735-2379	2	3.02 (0.50-1.81)	P = 0.004
				2380-5188	1	2.47 (0.26-23.9)
				5189-7531	1	5.33 (0.54-52.8)
				≥ 7532	2	20.3 (2.98-138)
Mundt et al[9] (2017), United States cohort	Cohort study, 9951 workers	HCC, death certificates	Job exposure matrix: Cumulative exposure (ppm-years)	high cut-points:			30-yr lagged exp
				< 1021	8	1.0	1.0
				1021-3300	4	1.2 (0.4-3.8)	3.8 (1.4-10.4)
				3301-5685	7	7.2 (2.6-20.0)	8.9 (2.8-28.5)
				5686-10551	6	7.3 (2.5-21.1)	14.6 (4.7-45.1)
				≥ 10551	7	18.8 (6.8-51.9)	34.6 (10.3-115.8)
Fedeli et al[11] (2019), Italian plant	Cohort study, 1685 workers	HCC, histology or clinical records	Job exposure matrix: cumulative exposure (ppm-years)	0-734	12	1.00
				735-2379	4	1.72 (0.55-5.32)
				2380-5188	9	5.24 (2.20-12.5)
				≥ 5189	6	5.52 (2.03-14.9)
Wong et al[19] (2003), Taiwanese cohort	Nested case-control study: 18 cases, 68 referents	Liver cancer: 10 confirmed HCC, no angiosarcoma	Job title based on job history	Tank cleaning	18 liver cancers	3.6 (1.4-9.2)	Additional analyses on joint effects
				High exposure jobs		2.9 (1.1-7.3)
Mastrangelo et al[5] (2004), Italian plant	Nested case-control study: 13 cases, 139 referents	HCC, histology or clinical records	Job exposure matrix: Cumulative exposure (ppm-years)	Each 1000 ppm-years increase	13	1.71 (1.29-2.44) alcohol/virus adjusted	Additional analyses on joint effects

HCC: Hepatocellular carcinoma; CI: Confidence interval.

Table 2 Studies investigating the association between occupational exposure and liver fibrosis/liver cirrhosis in vinyl chloride workers

Ref. location	Study description	Disease assessment	Exposure assessment	Exposure categories	Number of cases	Relative risk (95%CI)	Notes
Maroni et al[23] (2003), Italy, four VC plants	Survey of 757 active workers	Liver ultrasonography: Periportal fibrosis	Job exposure matrix: Max Exposure (ppm)	0	Overall prevalence 16.0%	1.0	Adjusted for age, alcohol, body mass index, viral hepatitis
				1-10		1.55 (P = 0.276)
				50		1.54 (P = 0.405)
				200		4.12 (P = 0.005)
				500		2.47 (P = 0.064)
Hsiao et al[25] (2003), Taiwan, five VC plants	Survey of 347 active workers	Liver ultrasonography: Liver fibrosis including pre-cirrhosis and cirrhosis	Job exposure matrix: Cumulative exposure (ppm-years)	Low	3	1.0	Adjusted for age, alcohol, body mass index
				Moderate	5	4.6 (1.0–25.5)
				High (> 2400)	12	5.9 (1.7–28.2)
Mastrangelo et al[5] (2004), Italian plant	Nested case-control study: 40 Cases and 139 controls	Cirrhosis at histology and/or clinical records	Job exposure matrix: Cumulative exposure (ppm-years)	Each 1000 ppm-years increase	40	1.37 (1.13-1.69) alcohol/virus adjusted	Additional analyses on joint effects
Ward et al[3] (2001), European cohort	Cohort study, 12700 workers	Cause of death from death certificates	Job exposure matrix: Cumulative exposure (ppm-years)	< 524	8	1.0
				524-998	8	9.38 (3.52-25.0)
				999-3428	9	4.01 (1.55-10.4)
				3430-5148	8	9.77 (3.66-26.1)
				5149+	9	8.28 (3.15-21.8)
Mundt et al[9] (2017), United States cohort	Cohort study, 9951 workers	Cause of death from death certificates	Job exposure matrix: Cumulative exposure (ppm-years)	< 63	11	1.0
				63-286	19	1.8 (0.9-3.8)
				287-864	22	2.0 (1.0-4.1)
				865-2270	24	2.1 (1.0-4.3)
				2271+	21	1.7 (0.9-3.7)
Fedeli et al[11] (2019), Italian plant	Cohort study, 1685 workers	Deaths from cirrhosis + deaths from liver cancer with histological/clinical evidence of cirrhosis	Job exposure matrix: Cumulative exposure (ppm-years)	< 734	35	1.0
				734-2378	8	1.18 (0.55-2.55)
				2379-5187	12	2.43 (1.26-4.70)
				≥ 5188	8	2.60 (1.19-5.67)

VC: Vinyl chloride; CI: Confidence interval.