ABSTRACT: Obesity, kidney disease, and diabetes are common conditions that can affect outcomes of patients with chronic hepatitis C. The authors aimed to quantify the burden of these comorbid conditions among adults with chronic hepatitis C in the United States and to estimate the risk of death among people with chronic hepatitis C and comorbidities.The authors conducted cross-sectional and prospective analyses of 13,726 participants in the third National Health and Nutrition Examination Survey (NHANES III) and 23,691 participants of NHANES 1999-2012. Serum samples were analyzed for the presence of antibodies to hepatitis C virus (anti-HCV); in samples found to be positive for anti-HCV, the authors quantified HCV RNA (viral load). Individuals with anti-HCV and detectable HCV RNA were considered to have chronic hepatitis C. Comorbidities were defined using self-reported, physical examination, and laboratory data, as available. The authors used logistic models and predictive margins to estimate the adjusted prevalence of comorbidities in patients with chronic hepatitis C. The authors used Poisson regression models to estimate adjusted mortality rates based on chronic hepatitis C status, with or without comorbidities. Cox proportional hazards regression models to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of all-cause, cardiovascular, and cancer mortality according to chronic hepatitis C status, with and without comorbidities.Among persons with chronic hepatitis C, the demographic-adjusted prevalence estimate of diabetes was 17.9% (95% CI, 11.2%-27.5%) and of obesity was 20.9% (95% CI, 12.4%-29.5%). Overall, 69.6% of persons with chronic hepatitis C had at least 1 major cardiometabolic comorbidity (95% CI, 62.1%-76.2%). Only 38% of adults with chronic hepatitis C reported a diagnosis of liver disease. Chronic hepatitis C was associated with a substantially increased risk of death (HR, 2.45), especially in the presence of diabetes (HR, 3.24) or chronic kidney disease (HR, 4.39).In an analysis of NHANES data, the authors found that individuals with chronic hepatitis C have a high burden of major cardiometabolic comorbidities. Diabetes and chronic kidney disease, in particular, are associated with substantial excess mortality in persons with chronic hepatitis C.