A study based on the concept of the evolutionary profile of liver disease in HIV/HCV co-infection and HCV mono-infection was conducted. The purpose of this study was to evaluate hepatic fibrosis in HIV/HCV co-infected subjects as compared to HCV mono-infected using APRI score.
Subjects in the over-60 age group were the most infected with 63.6% of HIV/HCV co-infected subjects and 66.3% of HCV mono-infected subjects. These figures are different from those found in previous studies which found an average age of 48 [45–51] years old (14) and 38 [35–42] years old (15). Given the silent evolution of HCV infection over several years, these results may be explained by the fact that in our context, screening for HCV infection is not systematic among high-risk such as HIV infected patients.
Serum aminotransferases (AST and ALT) are critical in the biological evaluation and surveillance of viral hepatitis C. Their increase for more than six-months period is a sign of a transition to chronicity, and 60 to 90% of chronic hepatitis with elevated transaminases progress to fibrotic liver disease unlike individuals with normal transaminases (10). We found elevated mean AST level in HIV/HCV co-infected participants compared to HCV mono-infected (73.6 ± 45.8 IU/L versus 58.5 ± 39.3 IU/L). The increase in AST levels in our study population when compared to the normal AST value, which ranges between 5 to 40 IU/L in healthy individuals, could be explained by hepatic cytolysis since the liver is the main target organ for hepatic infections. Moreover, the increase in the rate of AST among HIV/HCV co-infected participants could also be linked to the increased replication of HCV-RNA activated by HIV infection; In fact, the interaction between HIV gp120 and CCR5/CXCR4 co-receptors on hepatocytes via TGF-β1 which is a key mediator in the process of liver fibrosis as it is one of the most profibrogenic cytokines (9). Our results are consistent with a previous study that found that HIV/HCV co-infected individuals have a high level of AST ranging from 31 to 75 IU/L (16).
The mean value of platelets in this study was 172 ± 67 × 103 IU/L; almost similar to a previous study which found an average of 175 ± 79 × 103 IU/L (16). The incidence of thrombocytopenia in HIV/HCV co-infected participants is 63.6% as compared to 38.4% in HCV mono-infected. This incidence could be explained by the peripheral destruction of platelets due to HIV infection following the existence of antiplatelet autoantibodies specifically directed against certain antigenic determinants of the platelet membrane. The existence of these antiplatelet autoantibodies usually results from a cross-reactive humoral reactivity between viral and platelet components, in particular gp120 and gp IIb/IIIa (17).
Using the Metavir system, 63.6% of our study participants co-infected with HIV/HCV had clinically significant fibrosis (F2, F3 and F4 stages) as compared to 39.5% mono-infected. These results are similar to previous studies that found F2, F3 and F4 stages in 59.8% of HIV/HCV co-infected individuals and 46.6% of mono-infected, respectively (18). This high rate of fibrosis is apparently link to the existence of a more active HCV infection supported by HIV-induced CD4+ T cell loss that disregulates T cell function leading to reduced anti-fibrotic activity of NK cells, resulting in accelerated progression of liver fibrosis in HIV/HCV co-infected participants.
The correlation coefficient (r) between the liver fibrosis score and the age of patients in our study population (r = 0,06 with p = 0,04) shows statistically significant association between the two variables. This result is consistent with a previous study that showed a significant acceleration of hepatic fibrosis after the age of 50 years regardless of the age of infection (19). Thus, age would be independently associated with the evolution of the liver fibrosis score.
Although the progression of significant fibrosis (F2, F3 and F4) is higher in men (47.6%) than in women (38.2%), we did not find a statistically significant association between these two variables (P = 0.11). On the other hand, a study has shown that women generally have a slower progression of significant fibrosis than men because estrogen has an inhibitory effect on fibrogenesis (19).
The decrease in CD4 count levels, due to HIV infection, leads to a reduction in the anti-fibrotic activity of NK cells, which leads to rapid progression of hepatic fibrosis in HIV/HCV co-infected individuals (9). The median CD4 count in this study was 536 cells/µL [IQR:169–709] which is similar to a previous study that found a median CD4 count of 584 cells/µL [IQR: 396–775] in HIV/HCV co-infection (14). All study participants (100%) with CD4 < 200 cells/µL had clinically significant fibrosis; therefore, supporting the fact that the decrease in CD4 count levels may activate viral replication C, resulting in increased destruction of liver cells leading to evolution of the fibrosis stage as shown in other studies (9). The association between the fibrosis score and CD4 count was not statistically significant (P = 0.58).
The evolution of HIV infection leads to a strong presence of lipo-saccharide proteins which activate hepatic stellar cells inducing the progression of hepatic fibrosis (10). Therefore, high viral load can lead to clinically significant fibrosis as exemplified in this study where all participants with detectable HIV viral load had clinically significant fibrosis versus 33.3% of participants with undetectable viral load; though we did not observe a statistically significant association between liver fibrosis score and HIV viral replication (P = 0,55). This result is similar to an earlier study that found no association between HIV viral load and APRI score in individuals co-infected with HIV/HCV (14).