Our study sample (89% consent rate) included 330 chronically HCV+ male veterans between ages 50 and 59 years old, with 59% of African American and 41% of non-Hispanic White race/ethnicity. () Multiple medical and behavioral comorbidities were highly prevalent in this population including diabetes (26%) and obesity (31%). Almost all participants (93%) reported exposure to at least one known risk factor for HCV transmission as well as correspondent ages for exposure, with the most frequently reported risk factors injection drug use (58%), blood transfusion pre-1992 (9%), intranasal cocaine use (8%), and tattoos (12%). The estimated maximum median duration of HCV infection was 32.0 years. Prevalence of cirrhosis (F4) was non-significantly modestly higher in Whites compared to African-Americans (29% vs. 35%, respectively). Only two participants (0.6%) were on antiviral therapy, with both study-confirmed viremic. Overall, <5% of our participants had ever been on HCV antiviral therapy, which was discontinued after several months because of non-response, side-effects, or non-compliance.
Background characteristics of 330 male study participants with chronic hepatitis C.
Unadjusted median fibrosis progression rates (FPR) across ordered levels of sociodemographic, clinical and anthropometric variables are presented separately for Whites and African-Americans in Supplementary Table 1
. In White HCV+ males, increasing BMI category was associated with significant increased median FPR (ptrend
=0.03). There were also suggestive but non-significant trends for increasing % body fat (FPR=0.077, 0.088, and 0.092 for lowest, middle, and highest tertile of % body fat, respectively, ptrend
=0.12), and with increasing duration of overweight/obese or BMI≥25 (FPR=0.066, 0.088, and 0.097 for never overweight/obese, overweight/obese for last year, and overweight/obese for at least the last five years, respectively, ptrend
=0.08). In univariate analysis in African-American HCV+ males, there were also significant increases in median FPR across increasing levels of % body fat and duration of BMI≥25 (overweight/obese) (ptrend
= 0.04 and 0.02, respectively). However, in contrast to White males where median FPR was the same in non-diabetics regardless of whether they had IR or not, in African-Americans males the median FPR was significantly higher in non-diabetics with IR compared to non-diabetics without IR (FPR=0.100 vs. 0.077 for IR+ and IR-, respectively).
Multiple differences in risk of high FPR were also observed in race-stratified multivariate analyses that adjusted for age and chronic alcohol abuse. () In HCV+ White males, there were no statistically significant associations between any individually assessed anthropometric measure and risk of high FPR. The single anthropometric measurement which approached significance was the 133% decreased high FPR risk in White males in the highest tertile of lean trunk mass (ORadj=0.43, 95% CI 0.17–1.09, p=0.08). There was also increased high FPR risk with increased BMI (ORadj=1.48 and 1.51 for overweight and obese in comparison to normal weight, respectively), and with increased % body fat (ORadj=1.27 and 1.60 for those in middle and highest compared to those in the lowest tertile, respectively), though these effects were non-significant. These results differ from those in African-American males where lean body mass in the upper tertile (total, trunk, arm and leg) was uniformly associated with ≥70% increased risk of high FPR, though individual effects were non-significant. Although the excess risk conveyed by overweight and obesity were similar in African-Americans and Whites in race-stratified multivariate analyses, both % body fat and body fat mass were more strongly associated with FPR risk in African-Americans only.
Fibrosis Progression Rate (FPR) Upper Tertile: Multivariate logistic regression models evaluating association between individual anthropometric measurements and high FPR risk in chronically HCV-infected male veterans.^
Prevalence of advanced inflammatory grade (A2-A3) was significantly greater in Whites compared to African-Americans (43% vs. 36%, respectively). In univariate analysis, White HCV+ veterans with advanced inflammation were significantly more likely to have BMI≥30 (53% vs. 32%, p<0.01), to have been overweight/obese for the last five or more years (66% vs. 48%, p=0.047), and to have both a personal and parental history of overweight/obesity (29% vs. 20%, p=0.04) than White HCV+ veterans with mild hepatic inflammation (A0-A1/A2). (Supplementary Table 2
) These results differed from the univariate associations in African-Americans where the likelihood of obesity or of having a combined personal and parental history of overweight/obesity was similar in African-American advanced inflammation cases and African-American mild inflammation controls (24% vs. 23%, p=0.75 for obesity and 23% vs. 19%, p=0.79 for personal/parental adiposity, respectively). Further, in contrast to Whites where the prevalence of diagnosed diabetes was the same (27%) in White advanced inflammation cases and White mild disease controls, the prevalence of diabetes in chronically HCV-infected African-American male veterans was significantly higher in those with advanced compared to those with mild hepatic inflammation (34% vs. 19%, p=0.01). Race-stratified multivariate models for the association between each individual anthropometric measurement and risk of advanced hepatic inflammation (A2-A3) are reported in . In White HCV+ males after adjusting for age and chronic alcohol abuse, the strongest effect was the significant 231% increased advanced inflammation risk in the obese in comparison to those with normal BMI, with a non-significant 96% excess risk in the overweight compared to those with normal BMI. A combined parental as well as personal history of overweight/obesity was also associated with an over 3-fold significant excess risk of advanced inflammation compared to those with absence of both personal and parental adiposity history (ORadj
=3.08, =0.04), an effect slightly higher than that conveyed by only personal history of adiposity (ORadj
=2.93, p=0.03). Results differed in African-American HCV+ males where there was no significant excess inflammation risk associated with either overweight or obesity in multivariate analysis (ORadj
=1.10 and 1.21, respectively). Additionally, neither increased body fat mass nor % body fat was strongly or consistently associated with increased hepatic inflammation risk. Diabetes was the strongest predictor of advanced inflammation risk in African-American males (ORadj
=3.01, p<0.001), an effect larger than observed in Whites (OR=1.41, p=0.43).
Activity (FibroSURE-ActiTest A2-A3 vs. A0-A1/A2): Multivariate logistic regression models evaluating association between individual anthropometric measurements and advanced inflammation risk in chronically HCV-infected male veterans.^
In a sensitivity analyses where advanced fibrosis as defined as F3/F4-F4, the ethnic divergence where increased lean mass was associated with high FPR risk in African-Americans and decreased risk in Whites, was replicated (e.g., ORadjTrunkMassUpperTertile=0.44, 95% CI 0.32–1.03, p=0.06 and ORadjTrunkMassUpperTertile=1.70, 95% CI 0.60–2.90, p=0.18 in White and African-American HCV+ males, respectively). (data not shown)
We also conducted parallel exploratory multivariate analyses that adjusted for race/ethnicity (as opposed to race-stratified analyses presented in and ). Race-adjusted point estimates did not adequately reflect those for one and often both subgroups obtained in race-stratified multivariate analysis in many instances. For example, White males with BMI≥30 (obese) compared to BMI<25 (normal) had 3.3-fold excess risk of advanced hepatic inflammation in race-stratified multivariate analysis (), but only a 1.9-fold excess risk in race-adjusted analysis. (data not shown)
Overall, most bioimpedance measurements of adiposity were significantly correlated with BMI and WHR, with a similar magnitude and direction of these associations in Whites and African-Americans (e.g., Kendall’s tau=0.755 and 0.796 for African Americans and Whites, respectively). (data not shown) The single largest interethnic difference in correlation with BMI was the 7.5% greater correlation between BMI and % body fat among Whites compared to African-Americans. The single largest interethnic difference in correlation between WHR and a BIA adiposity measure was also with % body fat (Kendall’s tau=.301 and 0.168 for African-American and White males, respectively).