Table 1.
Clinical and molecular factors associated with ALD and NAFLD-related HCC.
| Group / Author |
Total n | Study type | Tissue assessed |
Parameter assessed |
Liver histology | ALD (n, % total) |
Characteristics associated with ALD-HCC |
NAFLD (n, % total) |
Characteristics associated with NAFLD-HCC |
Ref |
|---|---|---|---|---|---|---|---|---|---|---|
|
Predisposing
factors to HCC |
||||||||||
| Ascha et al | 510 | Retrospective cohort |
Clinical | 100% cirrhosis | 0 (0%) | NA | 195 (38%) | Age and any consumption of alcohol were risk factors for HCC |
32 | |
| Loomba et al | 23712 | Prospective cohort |
Clinical | NA | 2401 alcohol use (10%) |
BMI ≥30 was associated with increased risk of HCC |
NA | 33 | ||
| Tokushige et al | 14530 | Cross- sectional |
Clinical | NAFLD HCC: 62% cirrhosis ALD HCC: 78% cirrhosis |
991 (7%) | ALD HCC was associated with younger age and lower proportion of women. |
292 (2%) | Associated with metabolic syndrome and lower rates of cirrhosis. |
34 | |
| Raff et al | 480 | Retrospective cohort |
Clinical | NAFLD: 12% cirrhosis ALD: 46% cirrhosis |
165 (34%) | Diabetes associated with HCC development in ALD and NAFLD |
315 (66%) | See alcohol characteristics |
4 | |
| Mittal et al | 1500 | Retrospective cohort |
Clinical | NAFLD-HCC: 70% cirrhosis ALD-HCC: 89% cirrhosis |
1209 (81%) | Two times more ALD-HCC without cirrhosis than HCV- HCC. |
120 (8%) | Five times more NAFLD-HCC without cirrhosis than HCV-HCC. |
6 | |
| Kodama et al | 157 | Retrospective- prospective cohort |
Clinical | 100% cirrhosis | 85 (54%) | Diabetes. | 72 (46%) | Age, GGT and Child-Pugh score. |
9 | |
| Nahon et al | 301 | Prospective cohort |
Non- tumoral liver in subjects with HCC |
Liver iron deposition HFE mutations |
100% cirrhosis | 162 (54%) | Liver iron and HFE
C282Y mutations. |
NA | NA | 10 |
| Trepo et al | 2503 | Meta-analysis of individual participant data |
Blood |
PNPLA3 SNP (rs738409) |
100% cirrhosis | 1374 (55%) | rs738409 GG genotype |
2 (0.1%) | NA | 11 |
| Singal et al | 2937 | Meta-analysis | Blood |
PNPLA3 SNP (rs738409) |
NA | NA | rs738409 GG genotype |
NA | rs738409 GG genotype |
12 |
| Nischalke et al | 482 with ALD cirrhosis 382 controls Validation: 229 ALD cirrhosis |
Case-control | Blood |
PNPLA3 SNP (rs738409) NCAN (rs228603) |
100% cirrhosis | 356 (100%) | rs2228603 risk variant (CT/TT) and rs738409 risk variant (IM/MM) |
0 (0%) | 14 | |
| Ueyama et al | 389 | Retrospective cohort |
Blood | Multiple SNPs | 13% cirrhosis | 223 (57%) | rs738409 (PNPLA3) GG genotype |
35 | ||
| Charni et al | 496 | Cohort | Blood |
RANTES
promoter SNP (rs2107538) |
253 (51%) | rs2107538 risk variant associated with HCC occurrence MPO (rs2333227) and SOD2 (rs4880) SNP associated with risk of HCC and death |
0 (0%) | 16 | ||
| Nahon et al | 190 | Prospective cohort |
Blood | Multiple SNP | 100% cirrhosis | 191 (100%) | 0 (0%) | 15 | ||
|
Clinical and
Molecular Features of HCC |
||||||||||
| Lee et al | 512 | Retrospective cohort |
Clinical | 55 (11%) | 35 (7%) cryptogenic HCC |
Single nodule HCC, less portal vein invasion. No difference in survival. |
8 | |||
| Jeong et al | 91 HCC | Cohort | HCC | Gene expression |
50% cirrhosis | 7 (8%) | ALD-HCC enriched in gene expression cluster B |
NA | 18 | |
| Boyault et al | Derivation: 57 HCC Validation: 63 HCC |
Cohort | HCC | Gene expression |
NA | 41 (33%) | ALD-HCC enriched in HCC subtypes G3, G4 and G6 |
NA | NA | 19 |
| Schulze et al | 243 | Cohort | HCC | Mutational signatures based on exome sequencing |
49% cirrhosis | 100 (41%) | Mutational signature 3. CTNNB1 mutations. |
44 (18%) | NA | 21 |
|
Prognostic
factors after HCC diagnosis/ treatment |
||||||||||
| Siriwardana et al |
150 | Prospective cohort |
Clinical | 61 (41%) | Diffuse tumor nodules and macrovascular invasion more common. Worse survival of advanced HCC. |
89 (59%) cryptogenic HCC |
Single HCC more common. Improved survival in advanced HCC compared to ALD-HCC. |
24 | ||
| Takeuchi et al | 638 | Retrospective cohort |
Blood |
PNPLA3 SNP (rs738409) |
NA | 89 (14%) heavy drinkers |
Worse survival in ALD subjects with low BMI and rs738409 GG genotype rs738409 GG genotype associated with higher number of HCC lesions, higher HCC grade and worse survival in ALD and NAFLD subjects compared to other etiologies. |
70 (11%) | No association | 26 |
| Valenti et al | 460 HCC | Retrospective- prospective cohort |
Blood |
PNPLA3 SNP (rs738409) |
96% cirrhosis | 80 (17%) | 28 (6%) | See alcohol characteristics |
27 |
Studies with more than 100 ALD and/or NAFLD subjects were included.