Risk Factors for Hepatocellular Carcinoma in the US
Risk Factors for Hepatocellular Carcinoma in the US
As shown in Table 1, 6,991 individuals with HCC and 255,702 control individuals were included in the analysis. The greatest percentage of persons with HCC were white (71%), followed by Asian (12%), black (8%), and Hispanic persons (4%). The majority of the cases (65.7%) were male; a proportion which did not vary greatly by racial/ethnic group.
Overall, 22.9% of the cases were positive for HCV, 6.9% were positive for HBV, 31.2% had prior alcohol-related liver disorders, 4.5% had rare genetic disorders, 61.5% had prior diagnoses of diabetes and/or obesity (hereafter referred to as diabetes/obesity) and 19.1% had no prior diagnosis of any of the above conditions ( Table 1). In contrast, 0.4% of the controls were positive for HCV, 0.1% were positive for HBV, 7.4% had prior alcohol-related liver disorders, 0.8% had rare genetic disorders, 34.7% had a prior diagnosis of diabetes/obesity and 60.5% had no prior diagnosis of any of the above conditions.
The prevalence of almost all conditions varied greatly by racial/ethnic group. For HCV, the highest rate was found among Asians (cases=37.1%, controls=1.7%) and the lowest rate, among white persons (cases=18.5%, controls=0.4%). For HBV, the highest rate was again among Asians (cases=30.3%, controls=1.5%) and the lowest rate among white persons (cases=2.8%, controls=0.1%). For alcohol-related liver disorders, the highest percentage was seen among Hispanics (cases=39.3%, controls=9.0%) and the lowest percentage was seen among Asians (cases=21.9%, controls=4.5%). For rare genetic disorders, the highest percentage of affected persons occurred among white persons (cases=5.0%, controls=0.7%) and the lowest percentage occurred among black persons (cases=<2.1%, controls=0.8%). Diabetes was relatively common in all groups, with percentages ranging from 68.9% of Hispanic cases and 50.7% of Hispanic controls to 58.7% of white cases and 31.0% of white controls. Percentages of persons who were obese varied more widely, with Hispanics having the highest percentages (cases=13.1%, controls=7.1%) and Asians having the lowest percentages (cases=2.5%, controls=2.8%). When diabetes and obesity were grouped together, the percentage of affected persons ranged from 71.5% of Hispanic cases and 52.4% of Hispanic controls to 61.0% of white cases and 32.8% of white controls.
Table 2 displays the OR of each risk factor overall and by gender. Among the total population, HCV had the largest OR at 39.9 (95% CI=36.3–43.8), followed by HBV (OR=11.17; 95% CI=9.18–13.59), alcohol-related disorders (OR=4.06, 95% CI=3.82–4.32), rare genetic disorders (OR=3.45, 95% CI=2.97–4.02), and finally diabetes/obesity (OR=2.47, 95% CI=2.34–2.61). ORs were also calculated after eliminating all risk factors that arose in the 12 months preceding the diagnosis of HCC. No appreciable change was noted in this sensitivity analyis (data not shown).
The PAF of each factor is also shown in Table 2. Overall, the greatest PAF was associated with diabetes/obesity (36.6%), followed by alcohol-related liver disorders (23.5%), HCV (22.4%), HBV (6.3%), and rare genetic disorders (3.2%). A comparison of PAFs in males and females found that the single greatest PAF in both genders was conferred by diabetes/obesity (male=36.4%, female=36.7%). Among males, alcohol-related liver disorders had the second greatest PAF (27.8%), followed by HCV (19.3%). Among females, the order of alcohol-related liver disorders and HCV was reversed with HCV having a PAF of 28.1% and alcohol-related liver disorders having a PAF of 15.4%. HBV had very similar PAFs in both genders (male=6.4%, female=6.1%). In contrast, rare genetic disorders had a substantially larger role among males (4.3%) than among females (0.9%). All factors together accounted for a larger proportion of HCC in males (65.6%) than in females (62.2%).
An examination of PAFs by racial/ethnic group found noticeable differences among the groups ( Table 3). Among white persons, the factor with the greatest PAF (38.9%) was diabetes/obesity, followed by alcohol-related liver disorders (25.6%) and HCV (18.1%). Among black persons, the factor with the greatest PAF was HCV (34.9%), followed by alcohol-related liver disorders (18.5%) and diabetes/obesity (11.5%). Among Hispanics, diabetes/obesity had the greatest PAF (38.1%) followed by alcohol-related liver disorders (30.1%) and HCV (28.2%), while among Asians, the factors with the greatest PAFs were HCV (35.4%), diabetes/obesity (28.5%) and HBV (28.5%). The cumulative PAF of these factors was highest among Asians (70.1%), followed by Hispanics (69.7%), white persons (64.0%) and finally, black persons (52.4%).
A comparison by time period found that the PAFs of all factors increased in the interval between 1994–1999 and 2000–2007 ( Table 4). The combined PAFs of all factors increased from 54.3% in 1994–1999 to 65.7% in 2000–2007. The PAFs of HCV and HBV increased most substantially, with the PAF of HCV increasing from 13.3% to 25.3% and the PAF of HBV increasing from 3.1% to 7.2%. The PAFs of the other factors increased more modestly, with the PAF of alcohol-related liver disorders increasing from 21.4% to 23.0%, rare genetic disorders from 2.6% to 3.2% and diabetes/obesity from 30.0% to 35.6%. Although diabetes can be an independent risk factor for HCC, it can at times, also be the result of another HCC risk factor. Therefore, cumulative PAFs that did not include diabetes were also calculated for the two time periods of interest. For the period 1994–1999, the cumulative PAF for all factors except diabetes/obesity was 34.9% (31.9–37.9%). In the time period 2000–2007, the cumulative PAF for all risk factors except diabetes/obesity was 46.0% (44.5–47.5%) (data not shown).
Results
As shown in Table 1, 6,991 individuals with HCC and 255,702 control individuals were included in the analysis. The greatest percentage of persons with HCC were white (71%), followed by Asian (12%), black (8%), and Hispanic persons (4%). The majority of the cases (65.7%) were male; a proportion which did not vary greatly by racial/ethnic group.
Overall, 22.9% of the cases were positive for HCV, 6.9% were positive for HBV, 31.2% had prior alcohol-related liver disorders, 4.5% had rare genetic disorders, 61.5% had prior diagnoses of diabetes and/or obesity (hereafter referred to as diabetes/obesity) and 19.1% had no prior diagnosis of any of the above conditions ( Table 1). In contrast, 0.4% of the controls were positive for HCV, 0.1% were positive for HBV, 7.4% had prior alcohol-related liver disorders, 0.8% had rare genetic disorders, 34.7% had a prior diagnosis of diabetes/obesity and 60.5% had no prior diagnosis of any of the above conditions.
The prevalence of almost all conditions varied greatly by racial/ethnic group. For HCV, the highest rate was found among Asians (cases=37.1%, controls=1.7%) and the lowest rate, among white persons (cases=18.5%, controls=0.4%). For HBV, the highest rate was again among Asians (cases=30.3%, controls=1.5%) and the lowest rate among white persons (cases=2.8%, controls=0.1%). For alcohol-related liver disorders, the highest percentage was seen among Hispanics (cases=39.3%, controls=9.0%) and the lowest percentage was seen among Asians (cases=21.9%, controls=4.5%). For rare genetic disorders, the highest percentage of affected persons occurred among white persons (cases=5.0%, controls=0.7%) and the lowest percentage occurred among black persons (cases=<2.1%, controls=0.8%). Diabetes was relatively common in all groups, with percentages ranging from 68.9% of Hispanic cases and 50.7% of Hispanic controls to 58.7% of white cases and 31.0% of white controls. Percentages of persons who were obese varied more widely, with Hispanics having the highest percentages (cases=13.1%, controls=7.1%) and Asians having the lowest percentages (cases=2.5%, controls=2.8%). When diabetes and obesity were grouped together, the percentage of affected persons ranged from 71.5% of Hispanic cases and 52.4% of Hispanic controls to 61.0% of white cases and 32.8% of white controls.
Table 2 displays the OR of each risk factor overall and by gender. Among the total population, HCV had the largest OR at 39.9 (95% CI=36.3–43.8), followed by HBV (OR=11.17; 95% CI=9.18–13.59), alcohol-related disorders (OR=4.06, 95% CI=3.82–4.32), rare genetic disorders (OR=3.45, 95% CI=2.97–4.02), and finally diabetes/obesity (OR=2.47, 95% CI=2.34–2.61). ORs were also calculated after eliminating all risk factors that arose in the 12 months preceding the diagnosis of HCC. No appreciable change was noted in this sensitivity analyis (data not shown).
The PAF of each factor is also shown in Table 2. Overall, the greatest PAF was associated with diabetes/obesity (36.6%), followed by alcohol-related liver disorders (23.5%), HCV (22.4%), HBV (6.3%), and rare genetic disorders (3.2%). A comparison of PAFs in males and females found that the single greatest PAF in both genders was conferred by diabetes/obesity (male=36.4%, female=36.7%). Among males, alcohol-related liver disorders had the second greatest PAF (27.8%), followed by HCV (19.3%). Among females, the order of alcohol-related liver disorders and HCV was reversed with HCV having a PAF of 28.1% and alcohol-related liver disorders having a PAF of 15.4%. HBV had very similar PAFs in both genders (male=6.4%, female=6.1%). In contrast, rare genetic disorders had a substantially larger role among males (4.3%) than among females (0.9%). All factors together accounted for a larger proportion of HCC in males (65.6%) than in females (62.2%).
An examination of PAFs by racial/ethnic group found noticeable differences among the groups ( Table 3). Among white persons, the factor with the greatest PAF (38.9%) was diabetes/obesity, followed by alcohol-related liver disorders (25.6%) and HCV (18.1%). Among black persons, the factor with the greatest PAF was HCV (34.9%), followed by alcohol-related liver disorders (18.5%) and diabetes/obesity (11.5%). Among Hispanics, diabetes/obesity had the greatest PAF (38.1%) followed by alcohol-related liver disorders (30.1%) and HCV (28.2%), while among Asians, the factors with the greatest PAFs were HCV (35.4%), diabetes/obesity (28.5%) and HBV (28.5%). The cumulative PAF of these factors was highest among Asians (70.1%), followed by Hispanics (69.7%), white persons (64.0%) and finally, black persons (52.4%).
A comparison by time period found that the PAFs of all factors increased in the interval between 1994–1999 and 2000–2007 ( Table 4). The combined PAFs of all factors increased from 54.3% in 1994–1999 to 65.7% in 2000–2007. The PAFs of HCV and HBV increased most substantially, with the PAF of HCV increasing from 13.3% to 25.3% and the PAF of HBV increasing from 3.1% to 7.2%. The PAFs of the other factors increased more modestly, with the PAF of alcohol-related liver disorders increasing from 21.4% to 23.0%, rare genetic disorders from 2.6% to 3.2% and diabetes/obesity from 30.0% to 35.6%. Although diabetes can be an independent risk factor for HCC, it can at times, also be the result of another HCC risk factor. Therefore, cumulative PAFs that did not include diabetes were also calculated for the two time periods of interest. For the period 1994–1999, the cumulative PAF for all factors except diabetes/obesity was 34.9% (31.9–37.9%). In the time period 2000–2007, the cumulative PAF for all risk factors except diabetes/obesity was 46.0% (44.5–47.5%) (data not shown).
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