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. 2021 Sep 11;11(9):618. doi: 10.3390/metabo11090618

Table 4.

Summary of the papers that examined cirrhotic, non-cirrhotic and various pre-cirrhotic stage occasion patients against each other. The arrows show (if applicable) whether a VOC level increased or decreased in the first group compared to the second group in the study design.

Author/Year Study Design Analytical Method VOCs Identified as Significant Discriminatory Performance
Alkhouri et al.
2015
20 advanced fibrosis vs. 41 mild fibrosis SIFT-MS Acetone ↓
Benzene ↓
Carbon disulphide ↓
Isoprene ↓
Pentane ↓
Ethane ↓
0.85 AUC
(Isoprene model)
Khalid et al.
2013
11 alcoholic cirrhotic with HE vs. 23 alcoholic cirrhotic without HE GC-MS Methyl-vinyl ketone ↓
Isothiocyanato-cyclohexane ↑
90% sensitivity
87% specificity
34 alcoholic cirrhotic vs. 13 non-alcoholic cirrhotic Undecane ↑
Unknown ↓
78.3% sensitivity
69.2% specificity
34 alcoholic cirrhotic vs. 7 harmful drinkers 1-methyl-4-(1-methyl-ethenyl)-benzene ↑
Unknown ↓
Unknown ↓
88% sensitivity
85% specificity
7 harmful drinkers vs. 15 healthy Octanal
2,6-dimethyl-7-octen-2-ol
Unknown
71% sensitivity
93% specificity
13 non-alcoholic cirrhotic vs. 15 healthy Methyl-vinyl ketone
1-methyl-2-(1-methyl-ethyl)-benzene (o-cymene)
Unknown
92% sensitivity
100% specificity
34 alcoholic cirrhotic vs. 15 healthy Heptane
1-methyl-2-(1-methyl-ethyl)-benzene
Phellandrene
2-methyl-hexane
97% sensitivity
93% specificity
O’Hara et al.
2016
11 cirrhotic HE vs. 11 cirrhotic without HE vs. 7 history of HE vs. 30 healthy PTR-MS Limonene ↑ Not reported
10 without HCC vs. 21 HCC vs. 30 healthy Limonene ↑ Not reported
Qin et al.
2010
30 HCC vs. 36 healthy GC-MS-SPME 3-hydroxy-2-butanone ↑
Styrene ↑
Decane ↑
83.3% sensitivity
91.7% specificity
30 HCC vs. 27 cirrhotic without HCC 3-hydroxy-2-butanone ↑
Styrene ↑
70% sensitivity
70.4% specificity
Ferrandino et al.
2020
32 cirrhotic without HCC vs. 12 cirrhotic with HCC vs. 40 healthy controls GC-MS Limonene ↑ 73% sensitivity
77% specificity
Miller-Atkins et al.
2020
† only the three most significant metabolite associations for each disease comparison are shown in the column of significant compounds
112 non-cirrhotic HCC vs. 54 healthy SIFT-MS (E)-2-nonene ↑
Ethane ↑
Benzene ↑
Hydrogen sulphide ↓
Healthy vs. all the rest
76% sensitivity
97% specificity
30 cirrhotic without HCC vs. 54 healthy Trimethyl-amine ↓
Propanol ↓
Cirrhotic vs. all the rest
40% sensitivity
96% specificity
49 PH vs. 54 healthy (E)-2-nonene ↑
Acetaldehyde ↑
Ethane ↑
Hydrogen sulphide ↓
HCC vs. all the rest
73% sensitivity
71% specificity
51 CRLM vs. 54 healthy (E)-2-nonene ↑
Acetaldehyde ↑
Triethyl-amine ↑
Acetone ↓
CRLM vs. all the rest
51% sensitivity
94% specificity
112 non-cirrhotic HCC vs. 30 cirrhotic Acetone ↓
Acetaldehyde ↓
Dimethyl-sulphide ↓
Ethanol ↑
PH vs. all the rest
58% sensitivity
93% specificity
Arasaradnam et al.
2016
22 non-cirrhotic HE vs. 20 healthy E-nose Not available 88% sensitivity
68% specificity
13 covert non-cirrhotic HE vs. 9 overt non-cirrhotic HE Not available 79% sensitivity
50% specificity
Solga et al.
2008
16 moderate to severe steatosis vs. 11 less steatosis GC Ethanol ↑
Acetone ↑
Not reported
24 NASH vs. 24 without NASH Acetone ↑ Not reported
Verdam et al.
2013
39 NASH vs. 26 without NASH GC-MS n-tridecane ↑
3-methyl-butanonitrile ↑
1-propanol ↑
90% sensitivity
69% specificity
Alkhouri et al.
2013
37 obese NAFLD vs. 23 obese without NAFLD SIFT-MS Isoprene ↑
Acetone ↑
Trimethylamine ↑
Acetaldehyde ↑
Pentane ↑
0.76 AUC
Millonig et al.
2010
37 cirrhotic vs. 35 healthy IMR-MS Ethanol ↑ 0.88 AUC
91 liver diseased vs. healthy Acetaldehyde ↑
Ethanol ↑
Isoprene ↑
0.94 AUC
34 NAFLD vs. healthy controls Acetaldehyde ↑ 0.96 AUC
20 AFLD vs. 35 healthy Acetaldehyde ↑
Isoprene ↑
0.97 AUC
20 AFLD vs. 34 NAFLD Isoprene ↑ 0.95 AUC
Letteron et al.
1993
89 alcohol abusers vs. 52 liver diseased vs. 42 healthy GC-FID Ethane ↑ Not reported
Hanouneh et al.
2014
80 liver diseased vs. 43 healthy SIFT-MS 2-propanol ↑
Acetaldehyde ↑
Acetone ↑
Ethanol ↑
Pentane ↑
Trimethylamine ↑
Not reported
40 cirrhotic AH vs. 40 cirrhotic AD Acetaldehyde ↑
Acetone ↑
Pentane ↑
Trimethylamine ↑
97% sensitivity
72% specificity
(Acetone-pentane-trimethylamine)