Table 5.
Overview of epidemiological studies on the association between exposure to aflatoxin and liver disease
| Reference country | Study type (duration) | N | Age (years) (mean ± SD) | Biomarker (matrix) | Method (LOD/LOQ) | Levels of exposure | Outcome |
|---|---|---|---|---|---|---|---|
|
Afum et al. (2016) Ghana |
Case–control | 38 cases; 102 HBV/HCV +ve controls; 136 –ve controls | > 18 | Urinary AFM1 | HPLC‐FD (LOD = 0.5 pg/mg creatinine) |
68.5 pg/mg creatinine (cases) 67 pg/mg (−ve con) 65.3 pg/mg (+ve con) |
Liver disease |
| Anitha et al. (2014) India | Case–control |
138 cases 108 controls |
> 18 | AF‐alb (s) | ELISA (LOD ?) |
Con 19.25 pg/mg albumin Child's class A 18.1 pg/mg Child's class B 71.25 pg/mgChild's class C 575 pg/mg |
Decompensated liver disease |
|
Chen et al. (2007) Taiwan |
Case–control | 72 cirrhosis, 13 HCC, 229 controls | 66.9 ± 9.7 | AF‐alb (s) | ELISA (LOD 39.8 ng/mL) | 10.5 (ALD) vs. 5.5 (CON) ng/mg alb | ALD |
|
Chu et al., (2017) Taiwan |
Nested case–control |
232 cirrhosis cases 262 HCC cases 577 controls |
R: 30–65 | AF‐alb (s) | ELISA (LOD 2 fmol/mg albumin) |
Median of 21.5 fmol/mg (equivalent to about 9.8 pg/mg) in controls Median for cases not given |
Cirrhosis and HCC in HBV carriers |
| Chu et al. (2018), Taiwan | Nested case–control |
506 cases 2,636 controls |
R: 30–65 | AF‐alb (s) | ELISA (LOD 2 fmol/mg albumin) | Median of 21.5 fmol/mg (equivalent to about 9.8 pg/mg) in controls | HCC in HCV carriers |
|
Habibi et al. (2018) Iran |
Case–control |
41 cases 41 controls |
57.5 ± 10.8 (cases) 44.8 ± 15.1 (controls) |
AF‐alb (s) | ELISA (LOD 0.054 pg/mL serum) |
Cases: Median 3.87 pg/mL, IQR 3.46 Controls: Median 2.63 pg/mL, IQR 3.14c |
HCC |
|
Jolly et al. (2007) Ghana |
Cross‐sectional | 162 | 40.8 (R: 19–86) | AF‐alb (s) | Radioimmunoassay | Mean 0.89 ± 0.46 pmol/mg albumin (equivalent to 407 ± 211 pg/mg albumin) | Liver disease |
|
Kuniholm et al. (2008) Gambia |
Case–control |
97 cases 397 controls |
Controls 44.8 ± 15.2 Cases 42.5 ± 14.1 |
TP53 249ser | FFQ for aflatoxin exposure | NA | Cirrhosis |
|
Liu et al. (2008) China |
Case–control |
71 cases 695 controls |
36.6 ± 15.6 (controls). Not given for cases | AF‐alb (p) | ELISA (LOQ 10 fmol/mg albumin) |
Cases: mean 15.11 pmol/mL plasma Control: mean 10.02 pmol/mL plasmad |
HCC |
|
Lu et al. (2010) China |
Longitudinal (21 years) | 515 HBV +ve (123 went on to develop HCC) | R: 20–60 at recruitment | AFM1 (24 h u) Collected monthly for 8 months at outset | HPLCb following immunoaffinity column concentration (LOD 0.5 ng/mL) |
Mean of 48.46 ng/mL and a median of 24.90 ng/mL, range 5.7–243 ng/mL among AFM1 +ve samples Association with HCC based on +ve vs. −ve AFM1 results |
HCC |
|
Lu et al. (2012) China |
Longitudinal (23 years) |
148 Absolute number of cases not given |
R: 20–60 at recruitment |
AFM1 (24 h u) Collected monthly for 8 months at outset |
HPLCb following immunoaffinity column concentration (LOD 0.5 ng/mL) |
Mean of 48.46 ng/mL and a median of 24.90 ng/mL, range 5.7–243 ng/mL among AFM1 +ve samples Association with HCC based on +ve vs −ve AFM1 results |
HCC |
|
Manda et al. (2018) Côte d'Ivoire |
Case–control |
33 HCC 66 controls (33 HBV +ve & 33 HBV −ve) |
49.84 ± 15.34 (R: 24–77) | AFB1‐lys (s) | HPLC‐FD (LOQ 2.3 pg/mg albumin) | Mean of 36.57 pg/mg albumin in HCC patients, 34.95 pg/mg albumin in HBV patients and 25.63 pg/mg albumin in blood donors | Liver disease |
|
Mohd‐Redzwan et al. (2014) Malaysia |
Cross‐sectional | 71 aflatoxin exposed subjectsa | 34.34 ± 9.7 (R: 23–57) |
AFB1‐lys (s) AF metabolites (u) |
HPLC‐FD (LOQ 0.17 ng/mL) | Mean 6.85 +/−3.2 pg/mg | Liver disease |
|
Wu et al. (2009a) Taiwan |
Nested case–control | 241 cases and 1,052 controls from an initial cohort of 24,000 | 53.8 ± 7.9 |
AF‐alb (s) AF metabolites (u) |
ELISA (LOD 0.01 fmol/μg) ELISA (LOD 1 fmol/mL urine) |
Mean 59.8 fmol/mg albumin (equivalent to about 27 pg/mg) Mean 55.2 fmol/mL urine |
HCC |
|
Zheng et al. (2017) China |
Case–control |
214 cases 214 controls |
50.7 ± 9.7 (cases) 51.2 ± 9.9 (controls) |
AF‐alb (s) AF‐N7‐gua (u) |
ELISA (LOD 0.1 ng/mL) ELISA (LOD 0.1 ng/mL) |
Median; Cases 146.23 pg/mg albumin, controls 74.42 pg/mg albumin Median; cases 0.17 ng/mg creatinine controls 0.14 ng/mg creatinine |
HCC |
+ve: positive; −ve: negative; AF‐alb: aflatoxin albumin adduct; AFB1‐lys: aflatoxin B1 lysine adduct; AF‐N7‐gua: aflatoxin‐N7‐guanine; ALD: advanced liver disease; ELISA: enzyme‐linked immunosorbent assay; FD: fluorescence detection; FFQ: food frequency questionnaire; HBV: hepatitis B virus; HCC: hepatocellular carcinoma; HCV: hepatitis C virus; HPLC: high‐performance liquid chromatography; LOD: limit of detection; LOQ: limit of quantification; IQR: interquartile range; p: plasma; R: range; s: serum; SD: standard deviation; u: urine.
Identified by screening for AFM1 in urine.
Detector not reported.
Concentration reported as pg/mL serum without correcting for albumin levels which may be different depending on health status.
No correction by the authors for the albumin level which was about 10% higher in controls than in cases. Consequently, the CONTAM Panel could not convert the concentration into pg/mg albumin.