Table 4. Adjusted effect estimates for non-alcoholic fatty liver disease, non-alcoholic steato-hepatitis, advanced (stage F3) fibrosis and prevalent/incident chronic kidney disease, based on individual participant data meta-analysis from 20 studies (29,282 participants).
| Outcome | Cross-sectional Studies | Longitudinal Studies | ||||
| Covariate | Participants | OR (95% CI) | p-Value | Participants | HR (95% CI) | p-Value |
| CKD in NAFLD vs. non-NAFLD | ||||||
| Diabetes | 507 diabetic 3,031 non-diabetic | 2.62 (1.95–3.57) | 0.00001 | 2,046 diabetic, 39,365 non-diabetic | 1.99 (1.83–2.25) | 0.00001 |
| Age (y) a | 51 (18–89) | 2.39 (1.93–2.99) | 0.00003 | 38 (20–80) | 2.10 (1.74–2.63) | 0.000006 |
| BMI (kg/m2) a | 26 (16–71) | 2.21 (1.85–2.67) | 0.00006 | 24 (16–47) | 2.40 (1.94–2.99) | 0.00001 |
| Met sy | 885 with Met Sy, 2,654 without Met Sy | 2.43 (1.95–3.06) | 0.00001 | 3,758 with Met Sy, 19,226 without Met Sy | 2.13 (1.77–2.71) | 0.00009 |
| HTN | 1,061 with HTN, 2,477 without HTN) | 2.19 (1.78–2.61) | 0.00002 | 4,367 with HTN, 18,617 without HTN | 2.01 (1.69–2.77) | 0.00002 |
| Smoking | 1,168 smokers, 2,370 non-smokers | 2.11 (1.75–2.58) | 0.00005 | 9,653 smokers, 13,331 non-smokers | 2.28 (1.87–2.89) | 0.00008 |
| Ethnicity | 2,867 Asians, 1,071 non-Asian | 2.25 (1.87–2.70) | 0.00002 | 18,519 Asians, 6,937 non-Asians | 2.32 (1.32–4.10) | 0.00004 |
| Cirrhosis | 2,976 non-cirrhotic, 562 cirrhoticb | 2.34 (1.92–2.85) | 0.00001 | No cirrhotic participant | — | — |
| Waist (cm) a | 91 (54–153) | 2.63 (2.02–3.12) | 0.00007 | 89 (51–150) | 2.52 (2.00–3.02) | 0.00007 |
| HOMA-IR a | 1.8 (1.0–15.1) | 2.55 (2.00–2.98) | 0.00001 | 1.6 (0.6–10.3) | 2.12 (1.76–2.54) | 0.0009 |
| Duration of follow-up a | — | — | — | 5 (1–29) | 2.48 (1.98–2.97) | 0.0001 |
| All covariates | 3,538 individuals | 1.95 (1.55–2.71) | 0.00001 | 22,984 individuals | 1.91 (1.68–2.21 | 0.00001 |
| CKD in NASH vs. simple steatosis | ||||||
| Diabetes | 119 diabetic, 769 non-diabetic | 2.77 (1.81–4.24) | 0.0004 | 96 diabetic, 333 non-diabetic | 2.32 (1.55–3.48) | 0.00009 |
| Age (y) a | 46 (18–80) | 3.01 (2.50–3.72) | 0.00001 | 47 (18–67) | 2.61 (1.71–3.24) | 0.00004 |
| BMI (kg/m2) a | 33 (18–59) | 2.78 (2.09–3.24) | 0.0003 | 27 (18–47) | 2.32 (1.59–3.15) | 0.00006 |
| Met sy | 355 with Mey Sy, 532 without Met Sy | 2.66 (2.05–3.12) | 0.00008 | 136 with Met Sy, 293 without Met Sy | 2.71 (2.18–3.59) | 0.0001 |
| HTN | 408 with HTN, 479 without HTN | 2.59 (1.97–3.18) | 0.00002 | 172 with HTN, 257 without HTN | 2.58 (1.99–3.11) | 0.00007 |
| Smoking | 222 smokers, 665 non-smokers | 2.69 (1.63–3.82) | 0.00001 | 103 smokers, 326 non-smokers | 2.56 (1.54–3.13) | 0.0002 |
| Ethnicity | 263 Asians, 624 non-Asians | 3.14 (2.44–4.96) | 0.00001 | 102 Asians, 327 non-Asians | 2.37 (1.41–3.98) | 0.0001 |
| Cirrhosis | No cirrhotic participant | — | — | No cirrhotic participant | — | — |
| Waist (cm) a | 110 (51–162) | 2.62 (2.01–3.31) | 0.0006 | 99 (70–115) | 2.76 (2.01–3.48) | 0.0003 |
| HOMA-IR a | 3.1 (0.3–28.1) | 2.54 (1.98–2.96) | 0.00002 | 2.7 (0.8–3.9) | 2.24 (1.55–2.46) | 0.00001 |
| Duration of follow-up a | — | — | — | 14 (3–30) | 2.31 (1.42–2.87) | 0.00007 |
| All covariates | 887 individuals | 2.42 (1.80–3.84) | 0.0001 | 429 individuals | 2.01 (1.40–2.98) | 0.0001 |
| CKD in advanced (stage F3) vs. non-advanced (stage F0–F2) fibrosis | ||||||
| Diabetes | 119 diabetic, 769 non-diabetic | 5.39 (3.66–8.20) | 0.0001 | 96 diabetic, 333 non-diabetic | 3.88 (2.97–5.23) | 0.00001 |
| Age (y) a | 46 (18–80) | 5.12 (3.71–6.99) | 0.00009 | 47 (18–67) | 3.91 (2.56–4.98) | 0.00007 |
| BMI (kg/m2) a | 33 (18–59) | 4.89 (3.94–5.98) | 0.00001 | 27 (18–47) | 3.45 (2.51–4.02) | 0.00004 |
| Met sy | 355 with Mey Sy, 532 without Met Sy | 5.00 (4.11–5.97) | 0.00007 | 136 with Met Sy, 293 without Met Sy | 3.28 (2.39–4.52) | 0.00006 |
| HTN | 408 with HTN, 479 without HTN | 4.98 (3.81–6.02) | 0.0003 | 172 with HTN, 257 without HTN | 4.11 (2.88–5.51) | 0.0001 |
| Smoking | 222 smokers, 665 non-smokers | 5.27 (3.94–6.42) | 0.00008 | 103 smokers, 326 non-smokers | 3.29 (2.24–4.43) | 0.00002 |
| Ethnicity | 263 Asians, 624 non-Asians | 5.18 (3.57–6.82) | 0.00001 | 102 Asians, 327 non-Asians | 3.70 (1.46–9.39) | 0.0006 |
| Cirrhosis | No cirrhotic participant | — | — | No cirrhotic participant | — | — |
| Waist (cm) a | 110 (51–162) | 5.39 (4.21–6.13) | 0.0006 | 99 (70–115) | 3.39 (2.12–4.51) | 0.00001 |
| HOMA-IR a | 3.1 (0.3–28.1) | 5.13 (4.01–6.29) | 0.00004 | 2.7 (0.8–3.9) | 3.70 (2.12–4.91) | 0.00003 |
| Duration of follow-up a | — | — | — | 14 (3–30) | 3.58 (2.46–5.89) | 0.0009 |
| All covariates | 887 individuals | 4.86 (3.54–6.69) | 0.00001 | 429 participants | 3.00 (2.08–4.33) | 0.0001 |
Data from all studies providing IPD were pooled together into a single dataset and effect estimates were calculated using multivariate logistic regression (cross-sectional studies) or Cox proportional hazard models (longitudinal studies). In these models, studies were incorporated as cluster and treated as random-effect, while covariates were treated as fixed-effect. The individual patient covariates entered in the models were: age, BMI, metabolic syndrome, hypertension, smoking status, diabetes, ethnicity (Asian versus non-Asian population), presence of cirrhosis, waist circumference, HOMA-IR index, duration of follow-up (for longitudinal studies). Finally, a fully adjusted model was run, with all covariates entered.
HTN, hypertension; Met Sy, metabolic syndrome; waist, waist circumference.
a
For continuous variables, median (range) of values is reported.
b
All cirrhotic individuals derive from the study by Park et al. [30].