Impact of HIV on liver fibrosis in men with hepatitis C infection and haemophilia

Abstract

Hepatitis C virus (HCV) is the major cause of liver disease in haemophilia. Few data exist on the proportion with liver fibrosis in this group after long-term HCV and HIV co-infection. We conducted a cross-sectional multi-centre study to determine the impact of HIV on the prevalence and risk factors for fibrosis in haemophilic men with chronic hepatitis C. Biopsies were independently scored by Ishak, Metavir and Knodell systems. Variables were tested for associations with fibrosis using logistic regression and receiver operating curves (ROC). Of 220 biopsied HCV(+) men, 23.6% had Metavir ≥ F3 fibrosis, with higher mean Metavir fibrosis scores among HIV/HCV co-infected than HCV mono-infected, 1.6 vs. 1.3 (P = 0.044). Variables significantly associated with fibrosis included AST, ALT, APRI score (AST/ULN × 100/platelet × 10(9) /L), alpha-fetoprotein (all P < 0.0001), platelets (P = 0.0003) and ferritin (P = 0.0008). In multiple logistic regression of serum markers, alpha-fetoprotein, APRI and ALT were significantly associated with ≥ F3 fibrosis [AUROC = 0.77 (95% CI 0.69, 0.86)]. Alpha-fetoprotein, APRI and ferritin were significant in HIV(-) [AUROC = 0.82 (95% CI 0.72, 0.92)], and alpha-fetoprotein and platelets in HIV(+) [AUROC = 0.77 (95% CI 0.65, 0.88]. In a multivariable model of demographic and clinical variables, transformed (natural logarithm) of alpha-fetoprotein (P = 0.0003), age (P = 0.006) and HCV treatment (P = 0.027) were significantly associated with fibrosis. Nearly one-fourth of haemophilic men have Metavir ≥ 3 fibrosis. The odds for developing fibrosis are increased in those with elevated alpha-fetoprotein, increasing age and past HCV treatment.

Conflict of interest statement

Conflict of interest disclosure: The authors declare no competing financial interests.

© 2010 Blackwell Publishing Ltd.

Figures

Figure 1. Metavir ≥ F3 Fibrosis in Hemophilic Men with Hepatitis C

Receiver Operating Characteristic (ROC) Curves of the APRI score for the detection of fibrosis, defined as Metavir ≥F3, are shown for all HCV(+) hemophilic men (Figure 1a), for HIV/HCV co-infected hemophilic men (Figure 1b); and for HCV mono-infected hemophilic men (Figure 1c). The AUROC for the whole group (Figure 1a), based on a model including variables significantly associated with fibrosis, i.e. APRI, ALT, and alfa-fetoprotein, was 0.77 (95%CI 0.69, 0.86). The AUROC for the HIV(+) group (Figure 1b), based on a model including platelet count and alpha-fetoprotein, was 0.77 (95%CI 0.65, 0.88). The AUROC for the HIV(−) group (Figure 1c), based on a model including APRI, ferritin, and alpha-fetoprotein, was 0.82 (95%CI 0.72, 0.92).

Figure 1. Metavir ≥ F3 Fibrosis in Hemophilic Men with Hepatitis C

Receiver Operating Characteristic (ROC) Curves of the APRI score for the detection of fibrosis, defined as Metavir ≥F3, are shown for all HCV(+) hemophilic men (Figure 1a), for HIV/HCV co-infected hemophilic men (Figure 1b); and for HCV mono-infected hemophilic men (Figure 1c). The AUROC for the whole group (Figure 1a), based on a model including variables significantly associated with fibrosis, i.e. APRI, ALT, and alfa-fetoprotein, was 0.77 (95%CI 0.69, 0.86). The AUROC for the HIV(+) group (Figure 1b), based on a model including platelet count and alpha-fetoprotein, was 0.77 (95%CI 0.65, 0.88). The AUROC for the HIV(−) group (Figure 1c), based on a model including APRI, ferritin, and alpha-fetoprotein, was 0.82 (95%CI 0.72, 0.92).

Figure 1. Metavir ≥ F3 Fibrosis in Hemophilic Men with Hepatitis C

Receiver Operating Characteristic (ROC) Curves of the APRI score for the detection of fibrosis, defined as Metavir ≥F3, are shown for all HCV(+) hemophilic men (Figure 1a), for HIV/HCV co-infected hemophilic men (Figure 1b); and for HCV mono-infected hemophilic men (Figure 1c). The AUROC for the whole group (Figure 1a), based on a model including variables significantly associated with fibrosis, i.e. APRI, ALT, and alfa-fetoprotein, was 0.77 (95%CI 0.69, 0.86). The AUROC for the HIV(+) group (Figure 1b), based on a model including platelet count and alpha-fetoprotein, was 0.77 (95%CI 0.65, 0.88). The AUROC for the HIV(−) group (Figure 1c), based on a model including APRI, ferritin, and alpha-fetoprotein, was 0.82 (95%CI 0.72, 0.92).