Reply
Authors: Jennifer C. Price, Phyllis C. Tien
Journal: Hepatology (2017)

Potential conflict of interest: Dr. Price owns stock and received grants from Merck. She advises Intercept. She received grants from Gilead. She owns stock in Bristol‐Myers Squibb, Johnson & Johnson, and AbbVie. Reply: We thank Drs. Pembroke and Sebastiani for their thoughtful comments on our article regarding hepatic steatosis (HS) in adults with and without hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections. They raise several important points. First, we found a lower prevalence of HS in the HIV and HCV‐infected individuals compared to other published reports. We agree that this may be due to the characteristics of our population, including the high proportion of women and African Americans. The writers also note that our HIV‐infected and HCV‐infected participants had lower body mass index compared to our uninfected participants. However, when we adjusted for visceral adipose tissue (which is thought to be a stronger predictor of HS), the association of HCV with less HS persisted. Thus, while body mass index and other participant characteristics are important to consider when comparing our findings to other studies, they do not explain the observed viral associations with HS within our cohort. It is also important to recognize that the studies cited by the writers used different modalities of detecting HS, which vary in their accuracy. Although liver biopsy is the gold standard, there is selection bias in who undergoes biopsy. We used magnetic resonance spectroscopy because magnetic resonance–based imaging has the highest accuracy in diagnosing and quantifying HS.1 However, we agree that our sample size is relatively small once categorized by infection status and that magnetic resonance spectroscopy is not feasible in large‐scale studies. Second, the writers posit that lower HS in the HCV‐infected participants may be explained by more fibrosis in this group. This is an important consideration, and we therefore exhaustively explored this possibility. While we were limited to using indirect serum markers of fibrosis, we ran separate models including aspartate aminotransferase‐to‐platelet ratio index, FIB‐4, and suspected cirrhosis and performed a sensitivity analysis excluding individuals with suspected cirrhosis. Nevertheless, there was no evidence that increasing fibrosis in the HCV‐infected groups could explain our results. In fact, we found that aspartate aminotransferase‐to‐platelet ratio index and FIB‐4 correlated with magnetic resonance spectroscopy–measured liver fat fraction, consistent with literature demonstrating that HS is a risk factor for greater fibrosis in HCV‐infected individuals.2 Indeed, the association of HCV with lower HS was actually strengthened when we adjusted for aspartate aminotransferase‐to‐platelet ratio index or FIB‐4. In conclusion, both the characteristics of the population and the method of detecting HS are important when interpreting HS prevalence, and we encourage caution when directly comparing results from different cohorts. We believe this highlights the importance of having appropriate comparators when evaluating the potential contributions of HIV and HCV to HS. Longitudinal studies are indeed warranted to elucidate the impact of HIV, HCV, and HCV eradication on HS incidence and progression.