Table 1.
Summary of recent studies investigating the association between NAFLD and colorectal neoplasms.
| Author, Year | Country | Study Design | Study Population | Diagnosis of NAFLD and Colorectal Neoplasms | Main Findings |
|---|---|---|---|---|---|
| Hwang et al., 2010 [174] |
South Korea | Cross-sectional study | 2917 participants undergoing routine colonoscopy (556 subjects with adenomatous polyps and 2361 subjects without polyps) |
US and colonoscopy | NAFLD prevalence (adenomatous polyp group vs. control group): 41.5% vs. 30.2% (p < 0.001). NAFLD was associated with an increased risk of developing colorectal adenomatous polyps (OR, 1.28; 95% CI, 1.03–1.60; p = 0.029) |
| Touzin et al., 2011 [175] |
USA | Retrospective cohort study | 233 patients undergoing screening colonoscopy (94 patients with NAFLD and 139 patients without NAFLD) |
Liver biopsy + US, and colonoscopy |
Prevalence of colonic adenomas (NAFLD vs. control group): 24.4% vs. 25.1% (p = 1.00). Regarding the prevalence of adenomas, no difference was observed between the two groups |
| Wong et al., 2011 [176] |
China | Cross-sectional study | 380 community and consecutive patients undergoing screening colonoscopy (199 patients with NAFLD and 181 patients without NAFLD) |
Proton-magnetic resonance spectroscopy/ liver biopsy, and colonoscopy. |
Prevalence of colorectal adenomas (NAFLD vs. control group): 34.7% vs. 21.5% (p = 0.043). Prevalence of advanced colorectal neoplasms (NAFLD vs. control group): 18.6% vs. 5.5% (p = 0.002). Among the biopsy-proven NAFLD patients, the prevalence of (a) colorectal adenomas (NASH vs. NAFL group) was 51% vs. 25.6% (p = 0.005), and (b) advanced colorectal neoplasms (NASH vs. NAFL group) was 34.7% vs. 14.0% (p = 0.011). NASH was associated with colorectal adenomas (adjusted OR, 4.89; 95% CI, 2.04–11.70; p < 0.001) and advanced colorectal neoplasms (adjusted OR, 5.34; 95% CI, 1.92–14.84; p = 0.001) |
| Stadlmayr et al., 2011 [177] |
Austria | Cross-sectional study | 1211 patients undergoing screening colonoscopy (632 patients with NAFLD and 579 patients without NAFLD) | US and colonoscopy | Prevalence of colorectal lesions (NAFLD vs. control group): 34% vs. 21.7% (p < 0.001). Among men, (a) the prevalence of rectal adenomas (NAFLD vs. control group) was 11% vs. 3.4% (p = 0.004), and (b)CRC prevalence (NAFLD vs. control group) was 1.6% vs. 0.4% (p < 0.001). Hepatic steatosis was independently associated with an increased risk of developing colorectal adenomas (adjusted OR, 1.47; 95% CI, 1.079–2.003; p = 0.015) |
| Lee et al., 2012 [178] |
South Korea | Retrospective cohort study | 5517 females undergoing life insurance health examinations (831 participants with NAFLD and 4686 participants without NAFLD) |
US and colonoscopy | NAFLD was independently associated with an increased risk of developing colorectal adenomatous polyps (adjusted RR, 1.94; 95% CI, 1.11–3.40) and CRC (adjusted RR, 3.08; 95% CI, 1.02–9.34) |
| Min et al., 2012 [179] |
South Korea | Retrospective study | 227 CRC patients (59 patients with NAFLD and 168 patients without NAFLD) |
US and colonoscopy | The presence of NAFLD had no influence on the prognosis of CRC patients. There was no significant difference between CRC patients with and without NAFLD regarding the location and differentiation of tumors, CEA, and the total number of synchronous or advanced colorectal adenomas |
| Huang et al., 2013 [180] |
Taiwan | Retrospective cohort study | 1522 participants undergoing two consecutive colonoscopies (216 individuals with colorectal adenomas and 1306 individuals without colorectal adenomas after a negative baseline colonoscopy |
US and colonoscopy | NAFLD prevalence (adenoma vs. non-adenoma group): 55.6% vs. 38.8% (p < 0.05). NAFLD was an independent risk factor for developing colorectal adenomas after a negative baseline colonoscopy (adjusted OR, 1.45; 95% CI, 1.07–1.98; p = 0.016) |
| Lin et al., 2014 [181] |
China | Retrospective and consecutive cohort study | 2315 community subjects undergoing routine colonoscopy (263 patients with NAFLD and 2052 patients without NAFLD) | US and colonoscopy | Prevalence of colorectal lesions (NAFLD vs. control group): 90.9% vs. 93.3%. Prevalence of adenomatous polyps (NAFLD vs. control group): 44.5% vs. 55.7%. Prevalence of colorectal malignant neoplasms (NAFLD vs. control group): 29.3% vs. 18% (p < 0.05). NAFLD was an independent risk factor for developing colorectal malignant neoplasms (adjusted OR, 1.868; 95% CI, 1.360–2.567; p = 0.001) |
| You et al., 2015 [182] |
China | Retrospective cohort study | 1314 patients who underwent surgical resection of CRC (127 patients with NAFLD and 1187 patients without NAFLD) |
US, and pathological and colonoscopic sample analyses | There was no significant difference in DFS rates between the CRC patient groups with and without NAFLD (p = 0.267). After the adjustment for clinicopathologic covariates, the presence of NAFLD was an independent negative risk factor for OS (HR, 0.593; 95% CI, 0.442–0.921; p = 0.02), but not for DFS (p = 0.270) |
| Basyigit et al., 2015 [183] |
Turkey | Cross-sectional study | 127 consecutive patients undergoing colonoscopy (65 patients with NAFLD and 62 patients without NAFLD) | US and colonoscopy | CRC and colorectal adenomas’ prevalence was significantly higher in patients with insulin resistance (p = 0.005 and p = 0.008, respectively). CRC prevalence was significantly lower in NAFLD patients (p = 0.001). The risks of developing colorectal adenomas and cancer were significantly associated with the presence of insulin resistance (OR, 2.338; 95% CI, 1.080–4.993; p = 0.003 and OR, 5.023; 95% CI, 1.789–9.789; p = 0.001, respectively). CRC risk was increased in patients with insulin resistance but without NAFLD (OR, 5.218; 95% CI, 1.538–7.448; p = 0.017) |
| Bhatt et al., 2015 [184] |
USA | Retrospective cohort study | 591 patients who completed the liver transplant evaluation process (68 patients with NAFLD and 523 patients without NAFLD) |
Liver biopsy/clinical criteria assessment, and colonoscopy |
Prevalence of colorectal polyps (NAFLD vs. non-NAFLD group): 59% vs. 40% (p = 0.003). NAFLD was a significant predictor of finding a colorectal polyp (adjusted OR, 2.42; 95% CI, 1.42–4.11; p = 0.001). Prevalence of adenomatous polyps (NAFLD vs. non-NAFLD group): approximately 32% vs. 21% (p = 0.04). NAFLD was a significant predictor of finding colorectal adenomas (adjusted OR, 1.95; 95% CI, 1.09–3.48; p = 0.02) |
| Lee et al., 2016 [185] |
South Korea | Cross-sectional study | 44,220 participants undergoing colonoscopy and abdominal US as part of a health screening program (14,655 participants with NAFLD and 29,565 participants without NAFLD) |
US and colonoscopy | Adjusted ORs for colorectal neoplasms (patients with NAFLD vs. without NAFLD): 1.13; 95% CI, 1.04–1.24 for mild, 1.12; 95% CI, 0.94–1.33 for moderate, and 1.56; 95% CI, 0.98–2.47 for severe NAFLD (p for trend = 0.007). Adjusted ORs for non-advanced colorectal neoplasms (patients with NAFLD vs. without NAFLD): 1.12; 95% CI, 1.01–1.23 for mild, 1.10; 95% CI, 0.91–1.33 for moderate, and 1.65; 95% CI, 1.02–2.67 for severe NAFLD (p for trend = 0.02). Adjusted ORs for advanced colorectal neoplasms (patients with NAFLD vs. without NAFLD): 1.22; 95% CI, 0.98–1.53 for mild, 1.21; 95% CI, 0.78–1.89 for moderate, and 0.96; 95% CI, 0.23–3.98 for severe NAFLD (p for trend = 0.139). Colorectal neoplasm risk increased with worsening fatty liver severity |
| Pan et al., 2017 [186] |
China | Cross-sectional study | 1793 participants undergoing colonoscopy and abdominal US as part of health status check-up (573 participants with NAFLD and 1220 participants without NAFLD) |
US and colonoscopy | NAFLD was independently associated with an increased risk of developing colorectal neoplasms (adjusted OR, 2.11; 95% CI, 1.352–2.871; p = 0.001) and CRC (adjusted OR, 2.164; 95% CI, 1.289–3.217; p = 0.005) |
| Ahn et al., 2017 [187] |
South Korea | Cross-sectional study | 26,540 participants undergoing colonoscopy and abdominal US as part of a health check-up program (9501 participants with NAFLD and 17,039 participants without NAFLD) |
US and colonoscopy | Prevalence of colorectal tumors (NAFLD vs. non-NAFLD group): 38% vs. 28.9% (p < 0.001). Prevalence of advanced colorectal neoplasia (NAFLD vs. non-NAFLD group): 2.8% vs. 1.9% (p < 0.001). NAFLD was independently associated with an increased risk of developing any colorectal neoplasia (adjusted OR, 1.10; 95% CI, 1.03–1.17; p = 0.002), but not advanced colorectal neoplasia (adjusted OR, 1.21; 95% CI, 0.99–1.47; p = 0.053) |
| Chen et al., 2017 [188] |
China | Cross-sectional study | 3686 individuals undergoing abdominal US and colonoscopy as part of routine health check-up (779 individuals with NAFLD and 2907 individuals without NAFLD) |
US and colonoscopy | NAFLD was independently associated with an increased risk of developing colorectal polyps (adjusted OR, 1.26; 95% CI, 1.05–1.51; p < 0.05) and colorectal adenomas (adjusted OR, 1.28; 95% CI, 1.01–1.64; p < 0.05). Significant association was found between NAFLD and colorectal adenomas in males (adjusted OR, 1.53; 95% CI, 1.18–2.00; p < 0.05), but not in females. NAFLD was also associated with multiple colorectal adenomas (OR, 1.82; 95% CI, 1.29–2.55; p = 0.001), distal adenomas (OR, 1.63; 95% CI, 1.11–2.39; p = 0.013) and bilateral adenomas (OR, 1.89; 95% CI, 1.23–2.91; p = 0.004) |
| Yang et al., 2017 [189] |
South Korea | Retrospective cohort study | 1023 patients undergoing surveillance colonoscopy after index colonoscopy (unmatched population: 441 patients with NAFLD and 582 patients without NAFLD; propensity score matched population: 441 patients with NAFLD and 441 patients without NAFLD) | US or CT scan, and colonoscopy |
Overall colorectal neoplasm occurrence at 3 years after index colonoscopy (NAFLD vs. non-NAFLD group): 9.1% vs. 5% Overall colorectal neoplasm occurrence at 5 years after index colonoscopy (NAFLD vs. non-NAFLD group): 35.2% vs. 25.3% (p = 0.01). NAFLD was independently associated with an increased risk of developing colorectal neoplasms (adjusted HR, 1.31; 95% CI, 1.01–1.71; p = 0.05) and multiple (≥3) adenomas (adjusted HR, 2.49; 95% CI, 1.20–5.20; p = 0.02), but not advanced colorectal neoplasms (adjusted HR, 1.07; 95% CI, 0.51–2.26; p = 0.85) |
| Kim et al., 2017 [190] |
South Korea | Cohort study | 25,947 subjects undergoing screening colonoscopy as part of a health check-up program (8721 subjects with NAFLD and 17,226 subjects without NAFLD) | US and colonoscopy | NAFLD was significantly associated with CRC in males (adjusted HR, 2.01; 95% CI, 1.10–3.68; p = 0.02), but not in females (p = 0.41). The severity of NAFLD was not associated with CRC risk |
| Ze et al., 2018 [191] |
South Korea | Retrospective observational study | 2976 consecutive subjects undergoing abdominal US and colonoscopy as part of a health check-up program (1512 subjects with NAFLD and 1464 subjects without NAFLD) | US and colonoscopy | Fatty liver index ≥ 30 was associated with an increased risk of developing colorectal adenomas (OR, 1.269; 95% CI, 1.06–1.49; p = 0.008) |
| Chen et al., 2018 [192] |
China | Cross-sectional study | 764 CRC patients who were primarily treated by surgical resection (316 patients with NAFLD and 448 patients without NAFLD) |
US and pathological sample analyses |
Significant NAFLD was an independent risk factor for CRC-specific mortality in females. Significant NAFLD and metabolic syndrome has a synergistic effect on promoting mortality among CRC patients |
| Kim et al., 2019 [193] |
South Korea | Cross-sectional study | 6332 subjects undergoing abdominal US and 1st-time colonoscopy as part of a health screening program (2395 subjects with NAFLD and 3937 subjects without NAFLD) | US and colonoscopy | Prevalence of colorectal adenomas (NAFLD vs. non-NAFLD group): 33.3% vs. 23.8% (p < 0.001). Prevalence of advanced adenomas (NAFLD vs. non-NAFLD group): 5.3% vs. 2.4% (p < 0.001). Prevalence of multiple colorectal adenomas (NAFLD vs. non-NAFLD group): 5.8% vs. 3% (p < 0.001). NAFLD was independently associated with the risk of developing colorectal adenomas (adjusted OR, 1.15; 95% CI, 1.02–1.30; p = 0.027), advanced adenomas (adjusted OR, 1.50; 95% CI, 1.12–2.01; p = 0.006), and multiple adenomas (adjusted OR, 1.32; 95% CI, 1.01–1.73; p = 0.006) |
| Hamaguchi et al., 2019 [194] | Japan | Cohort study | 15,926 individuals participating in a health check-up program (3211 individuals with NAFLD and 12,715 individuals without NAFLD) |
US and colonoscopy | CRC incidence rate: 0.37 per 1000 person years in the non-NAFLD group without obesity; 0.72 in the non-NAFLD group with obesity; 0.41 in the NAFLD group without obesity; 1.49 in the NAFLD group with obesity. NAFLD with obesity was independently associated with an increased CRC risk (adjusted HR, 2.96; 95% CI, 1.44–6.09; p = 0.003) |
| Li et al., 2019 [195] |
China | Retrospective cohort study | 1089 subjects undergoing colonoscopy (502 subjects with NAFLD and 587 subjects without NAFLD) |
US + CAP score using FibroScan probes, and colonoscopy |
NAFLD was independently associated with an increased risk of developing colorectal adenomas (OR, 1.425; 95% CI, 1.112–2.042; p = 0.018). NAFLD was associated with an increased adenoma risk in males (OR, 1.473; 95% CI, 1.003–2.162; p = 0.048), but not in females (OR, 1.316; 95% CI, 0.817–2.12; p = 0.259). NAFLD and metabolic syndrome were significantly associated with a high risk of developing adenomas |
| Cho et al., 2019 [196] |
South Korea | Prospective cohort study | 476 patients undergoing screening colonoscopy (379 patients with NAFLD and 97 patients without NAFLD) | Liver biopsy and colonoscopy |
NAFL was independently associated with an increased risk of developing adenomatous polyps (adjusted OR, 2.76; 95% CI, 1.51–5.06; p = 0.001). NASH was independently associated with an increased risk of developing colorectal adenomatous polyps (adjusted OR, 2.08; 95% CI, 1.12–3.86; p = 0.02) and advanced colorectal neoplasms (adjusted OR, 2.81; 95% CI, 1.01–7.87; p = 0.049) |
| Allen et al., 2019 [197] |
USA | Cohort study | 19,163 subjects (4722 subjects with NAFLD and 14,441 age- and sex-matched referent individuals) |
NAFLD and cancer was defined utilizing a code-based algorithm (using the NAFLD-specific HICDA, ICD-9-CM and ICD-10-CM codes) | NAFLD was associated with an increased colon cancer risk (IRR, 1.8; 95% CI, 1.1–2.8) |
| Lee et al., 2020 [198] |
South Korea | Retrospective cohort study | 8,120,674 subjects who received healthcare checkups (936,159 adults with NAFLD and 7,184,515 adults without NAFLD) |
FLI, and endoscopy + ICD-10 codes | NAFLD (FLI ≥ 60) was significantly associated with the risk of developing colon cancer (HR, 1.23; 95% CI, 1.19–1.26) and an increased risk of all-cause mortality in CRC patients (HR, 1.16; 95% CI, 1.10–1.22) |
| Blackett et al., 2020 [199] | USA | Cross-sectional study | 369 patients who underwent liver biopsy and screening or surveillance colonoscopy (123 subjects with NAFLD and 246 matched controls without NAFLD) |
Liver biopsy and colonoscopy |
Prevalence of colorectal adenomas (NAFLD vs. control group): 40.7% vs. 28.1% (OR, 1.87; 95% CI, 1.15–3.03; p = 0.01). NAFLD was independently associated with an increased risk of detecting colorectal adenomas (adjusted OR, 1.74; 95% CI, 1.05–2.88; p = 0.032), but not advanced neoplastic lesions (adjusted OR, 2.2; 95% CI, 0.93–5.18; p = 0.07). The risk of developing colorectal adenomas was not associated with the severity (steatohepatitis vs. no steatohepatitis) of NAFLD (adjusted OR, 2.47; 95% CI, 0.67–9.1; p = 0.17) |
| Lesmana et al., 2020 [200] | Indonesia | Retrospective database study | 138 subjects undergoing elective colonoscopy (68 subjects with NAFLD and 70 subjects without NAFLD) |
US and colonoscopy | Prevalence of colon polyps (NAFLD vs. control group): 44.1% vs. 27.1% (p = 0.037). NAFLD was associated with an increased risk of developing any colon polyp |
| Yu et al., 2020 [201] |
China | Cross-sectional study | 1538 patients with colorectal polyps undergoing abdominal US (550 patients with NAFLD and 988 patients without NAFLD) |
US and colonoscopy | No significant difference regarding the location and morphology of colorectal polyps between the NAFLD and control groups (p > 0.05). NAFLD was significantly associated with colorectal polyps, especially, in patients with multiple polyps, those with a large size and with villous features (p < 0.05) |
| Zhang et al., 2021 [202] |
China | Retrospective cohort study | 8351 NAFLD patients (5308 patients with prior colonoscopy and 3043 patients without prior colonoscopy) |
- CRC was identified based on ICD-9-CM diagnosis codes or procedure codes for CRC treatment |
Compared to the general population, NAFLD patients who did not undergo colonoscopy had higher incidence rate of CRC (SIR, 2.20; 95% CI, 1.64–2.88; p < 0.001). NAFLD patients who underwent colonoscopy had lower incidence rate of CRC (SIR, 0.54; 95% CI, 0.37–0.75; p < 0.001). After adjustment for demographic and metabolic factors, NAFLD patients with a high fibrosis-4 score (>2.67) had higher risk of developing CRC |
| Fukunaga et al., 2021 [203] | Japan | Cross-sectional study | 124 consecutive health check-up examinees undergoing colonoscopy (58 examinees with NAFLD and 66 examinees without NAFLD; 63 examinees with MAFLD and 61 examinees without MAFLD) |
US and colonoscopy | MAFLD was independently associated with colorectal adenomas (OR, 3.191; 95% CI, 1.494–7.070; p = 0.003). Non-obese MAFLD was also associated with colorectal adenomas (OR, 3.351; 95% CI, 1.589–7.262; p ≤ 0.001) |
| Kim et al., 2021 [204] |
South Korea | Cohort study | 6182 subjects undergoing abdominal US, endoscopic removal of ≥1 adenomas at the index colonoscopy and a follow-up surveillance colonoscopy (2642 subjects with NAFLD and 3540 subjects without NAFLD) | US and colonoscopy | NAFLD was independently associated with an increased risk of developing metachronous overall colorectal neoplasia in both males (adjusted HR, 1.17; 95% CI, 1.06–1.29) and females (adjusted HR, 1.63; 95% CI, 1.27–2.07). NAFLD was also independently associated with an increased risk of developing metachronous advanced colorectal neoplasia in females (adjusted HR, 2.61; 95% CI, 1.27–5.37) |
| Seo et al., 2021 [205] |
South Korea | Retrospective cohort study | A total of 3441 subjects participating in a health check-up program (1127 subjects with MAFLD and 2314 without MAFLD). 3044 subjects were included in the NAFLD analysis (1143 subjects with NAFLD and 1901 subjects without NAFLD) |
US and colonoscopy | NAFLD and MAFLD were significantly associated with an increased risk of developing colorectal adenomas in females (adjusted OR, 1.43; 95% CI, 1.01–2.03; p = 0.046 and OR, 1.55; 95% CI, 1.09–2.20; p = 0.015, respectively). NAFLD and MAFLD with an advanced fibrosis index score were also associated with an increased risk of developing adenomas (OR, 1.38; 95% CI, 1.04–1.83; p = 0.027, and OR, 1.45; 95% CI, 1.13–1.96; p = 0.004, respectively) |
| Lee et al., 2022 [206] |
South Korea | Cohort study | 8,933,017 participants undergoing routine National Health Insurance Service health examinations (2,517,330 participants with NAFLD and 6,415,687 participants without NAFLD; 3,337,122 participants with MAFLD and 5,595,895 participants without MAFLD) |
FLI, and ICD-10 diagnosis codes |
The presence of fatty liver disease was significantly associated with an increased CRC risk. The CRC risk was higher in MAFLD patients with liver fibrosis |
NAFLD: non-alcoholic fatty liver disease; US: ultrasonography; OR: odds ratio; CI: confidence interval; NASH: non-alcoholic steatohepatitis; CRC: colorectal cancer; RR: relative risk; CEA: carcinoembryonic antigen; DFS: disease-free survival; OS: overall survival; HR: hazard ratio; CT: computed tomography; CAP: controlled attenuation parameter; HICDA: Hospital International Classification of Diseases Adapted; ICD: International Classification of Diseases; CM: clinical modification; IRR: incidence rate ratio; FLI: fatty liver index; SIR: standardized incidence ratio; MAFLD: metabolic dysfunction-associated fatty liver disease.