Table 4.
Subgroup analysis of the association between circulating leptin levels and HCC risk
| Variable | Included studies | Test of association | Test of heterogeneity | ||||
|---|---|---|---|---|---|---|---|
| SMD | 95%CI | P-value* | Modal | P-value | I2 | ||
| HCC vs Healthy controls | |||||||
| Overall | [23–25, 30, 37, 40–42] | 4.32 | 2.41, 6.24 | 0.000 | RE | 0.000 | 98.4% |
| HCC(unreported reason) vs Healthy controls | [23, 24] | 5.58 | −5.11, 16.26 | 0.306 | RE | 0.000 | 98.8% |
| Viral cirrhotic HCC vs Healthy controls | [37, 41, 42] | 1.02 | − 0.78, 2.79 | 0.263 | RE | 0.000 | 94.1% |
| HCV-related HCC vs Healthy controls | [30, 37, 40] | 8.87 | − 1.08, 1.82 | 0.081 | RE | 0.000 | 98.7% |
| HCC vs Cirrhosis | |||||||
| Overall | [25–27, 30, 37, 40–42] | 1.85 | 0.70, 3.01 | 0.002 | RE | 0.000 | 97.0% |
| HCV-related cirrhotic HCC vs HCV-related cirrhosis | [26, 37] | 0.82 | 0.40, 1.24 | 0.000 | FE | 0.145 | 53.0% |
| HCV-related HCC vs HCV-related cirrhosis | [30, 40] | 8.71 | −3.84, 21.25 | 0.174 | RE | 0.000 | 99.2% |
| Viral cirrhotic HCC vs Viral cirrhosis | [27, 41, 42] | 0.13 | −0.11,0.37 | 0.302 | FE | 0.591 | 0 |
| HCC vs Chronic hepatitis | |||||||
| Overall | [28, 30, 32, 37, 41] | 0.94 | −0.15, 2.03 | 0.090 | RE | 0.000 | 94.9% |
| HCV-related HCC vs Chronic hepatitis C | [30, 32, 37] | 1.63 | −1.39, 4.65 | 0.290 | RE | 0.000 | 96.0% |
| Viral cirrhotic HCC vs Chronic hepatitis C | [37, 41] | −0.10 | − 0.51,0.32 | 0.643 | FE | 0.561 | 0 |
| Ethnicity | |||||||
| Asian | [25, 28, 32, 37, 42] | 0.10 | −0.50, 0.70 | 0.751 | RE | 0.000 | 85.6% |
| Caucasian | [24, 27, 30, 41] | 0.58 | −0.06, 1.22 | 0.077 | RE | 0.000 | 93.3% |
| African | [23, 26, 40] | 9.36 | −1.27, 19.99 | 0.084 | RE | 0.000 | 99.3% |
| Sample size | |||||||
| < 100 | [23, 25, 26, 32, 37, 42] | 1.57 | 0.22, 2.91 | 0.022 | RE | 0.000 | 95.8% |
| ≥ 100 | [24, 27, 28, 30, 40, 41] | 2.23 | 1.21, 3.26 | 0.000 | RE | 0.000 | 98.4% |
| Mean age | |||||||
| < 60 | [23, 25–28, 32, 37, 40] | 2.87 | 1.57, 4.17 | 0.000 | RE | 0.000 | 98.2% |
| ≥ 60 | [24, 30, 41, 42] | 0.76 | 0.03, 1.49 | 0.040 | RE | 0.000 | 93.7% |
| Study design | |||||||
| Case-control | [23, 25, 30, 37, 40, 41] | 3.81 | 1.83, 5.79 | 0.000 | RE | 0.000 | 97.5% |
| Nested Case-control | [24, 27, 28] | 0.14 | 0.01, 0.26 | 0.035 | FE | 0.777 | 0.0% |
| Assay method | |||||||
| ELISA | [23–28, 30, 37, 40, 41] | 2.13 | 1.27, 2.99 | 0.000 | RE | 0.000 | 97.9% |
| RIA | [32, 42] | 0.79 | 0.39, 1.19 | 0.000 | FE | 0.570 | 0.0% |
| Alanine aminotransferase | |||||||
| < 70 U/L | [23, 26, 28, 32, 37, 40] | 4.42 | 2.26, 6.50 | 0.000 | RE | 0.000 | 98.6% |
| ≥ 70 U/L | [25, 27, 30, 41, 42] | 0.43 | −0.38, 1.23 | 0.296 | RE | 0.000 | 94.4% |
| Albumin | |||||||
| < 3.5 g/dl | [25, 26, 30, 40, 42] | 3.47 | 1.28, 5.66 | 0.002 | RE | 0.000 | 98.7% |
| ≥ 3.5 g/dl | [27, 28, 32, 41] | 0.12 | −0.02, 0.26 | 0.091 | FE | 0.633 | 0.0% |
RE Random-effects model, FE Fixed-effects model, HCC Hepatocellular carcinoma, HCV hepatitis C virus
*Statistically significant results were shown in bold