Knowledge of serum markers of liver decompensation would facilitate care of patients with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections. HCV load and anti-c33c and anti-NS5 levels did not distinguish 28 HCV- and HIV-positive predecompensation patients from 28 matched control patients, whereas more patients than controls had high anti-c100(p) and low anti-c22(p). In multivariate analysis, decompensation was associated with high anti-c100(p) titer (>/=1:4050; odds ratio [OR], 3. 4; 95% confidence interval [CI], 1.1-11.5) and low anti-c22(p) (<1:36,450; OR, 3.0; 95% CI, 1.0-10.2) and with antibody band strength at 1:50 dilution (anti-c100[p] OR, 7.0; 95% CI, 1. 7-48.9; anti-c22[p] OR, 7.1; 95% CI, 1.7-49.2). With high anti-c100(p) or low anti-c22(p), sensitivity for decompensation was 86%-96% and specificity was 21%-36%; with both markers, sensitivity was 29%-32% and specificity was 93%-96%. Although the mechanisms for these associations are unknown, if these findings are verified in other populations, anti-c100(p) and anti-c22(p) might be valuable surrogate markers for liver decompensation risk.