A higher correlation of HCV core antigen with CD4+ T cell counts compared with HCV RNA in HCV/HIV-1 coinfected patients

Abstract

Development of HCV infection is typically followed by chronic hepatitis C (CHC) in most patients, while spontaneous HCV viral clearance (SVC) occurs in only a minority of subjects. Compared with the widespread application of HCV RNA testing by quantitative RT-PCR technique, HCV core antigen detection may be an alternative indicator in the diagnosis of hepatitis C virus infections and in monitoring the status of infectious individuals. However, the correlation and differences between these two indicators in HCV infection need more investigation, especially in patients coinfected by HIV-1. In this study, a total of 354 anti-HCV and/or anti-HIV serum positive residents from a village of central China were enrolled. Besides HCV-related hepatopathic variables including clinical status, ALT, AST, anti-HCV Abs, as well as the altered CD4+/CD8+ T cell counts, HCV core antigen and HCV viral load were also measured. The concentration of serum HCV core antigen was highly correlated with level of HCV RNA in CHC patients with or without HIV-1 coinfection. Of note, HCV core antigen concentration was negatively correlated with CD4+ T cell count, while no correlation was found between HCV RNA level and CD4+ T cell count. Our findings suggested that quantitative detection of plasma HCV core antigen may be an alternative indicator of HCV RNA qPCR assay when evaluating the association between HCV replication and host immune status in HCV/HIV-1 coinfected patients.

Figure 1. The distributional characteristics of HCV- and/or HIV-infected patients involved in this study.

(A) 354 HCV seropositive or HIV-1 seropositive participants were divided into 5 different groups (HIV-noninfected CHC, HIV-infected CHC, HIV-noninfected SVC, HIV-infected SVC, HIV infection only) depending on existence of serum HIV-1/HCV antibodies and plasma HCV RNA. The proportions of each group in 354 subjects were indicated. (B) Comparison of the percentages of SVC subjects in HCV seropositive subjects between HIV-1 noninfected (black square) and HIV-1 infected (empty square) patients. (C) Percentage of HCV (black square) and HIV-1 (empty square) seropositive patients in whole 1252 residents. Pearson Chi-Square tests were performed for comparing the percentage between two different groups shown in (B) and (C). Triple asterisks (***) indicate P values below 0.001.

Figure 2. Serum ALT and AST enzymes were comparatively analyzed among five infected groups and healthy controls.

(A) ALT; (B) AST. The percentages of patients with positive ALT or AST values (more than 40 IU/ml) in each group were indicated in the middle beside each group. Median was also shown as a horizontal bar in each group. Group a (○), b(•), c(△), d(▴), e (▽) and f(▾) indicated participants of HIV-noninfected CHC, HIV-infected CHC, HIV-noninfected SVC, HIV-infected SVC, HIV-monoinfected patients and healthy controls respectively. Pearson Chi-Square tests (Yates' correction for continuity was used in certain situations) were performed for comparing the percentages with values above 40 IU/ml and Mann-Whitney U-tests were used for comparing the ALT/AST values between two different groups. Single asterisk (*) indicate P values below 0.05. Double asterisks (**) indicate P values below 0.01 and triple asterisks (***) indicate P values below 0.001.

Figure 3. S/CO ratio of anti-HCV antibody, plasma HCV viral load and concentration of plasma HCV core antigen were analyzed among five HCV- and/or HIV-infected groups and healthy controls.

(A) S/CO ratio of anti-HCV antibody. S/CO ratio was shown as a scatter dot plot graph. Values (S/CO) no less than 10 were considered as HCV antibody^high and percentages of patients with HCV antibody^high were indicated for each group. (B) CD4+ T cells counts in HIV-infected CHC subpopulations based on the level of anti-HCV antibody titer (S/CO). (C) Plasma HCV viral load in HIV-1-noninfected CHC and HIV-infected CHC patients. (D) Concentration of plasma HCV core antigen in HIV-noninfected CHC and HIV-infected CHC patients. Group a (○), b(•),c(△),d(▴),e (▽) and f(▾) indicated participants of HIV-noninfected CHC, HIV-infected CHC, HIV-noninfected SVC, HIV-infected SVC, HIV-monoinfected patients and healthy controls respectively. Median was shown as a horizontal bar in each group. Mann-Whitney U-tests were performed for statistical comparison between two different groups. Single asterisk (*) indicate P values below 0.05. Double asterisks (**) indicate P values below 0.01 and triple asterisks (***) indicate P values below 0.001.

Figure 4. (A) The concentration of HCV core antigen in serum were highly correlated with HCV RNA level in both HIV-noninfected CHC (△)and HIV-infected CHC (▽) patients and (B) ratio of serum HCV viral load to HCV core antigen concentration was significantly higher in HIV-noninfected CHC (a,△) than HIV-infected CHC (b,◊) patients.

Spearman's rank-correlation and Mann-Whitney U-tests were performed in (A) and (B) separately. Single asterisk (*) indicate P values below 0.05 and triple asterisks (***) indicate P values below 0.001.

Figure 5. Correlation analysis between anti-HCV Abs response (S/CO ratio)(A), or HCV viral load (B), or HCV core antigen concentration (C) and CD4+ T cell counts displayed in HIV-infected CHC patients with CD4+ T cell counts less than 1000/µl.

Spearman's rank-correlation were performed and double asterisks (**) indicated P values below 0.01.