Association of HIV, Hepatitis C Virus, and Liver Fibrosis Severity With the Enhanced Liver Fibrosis Score.

BACKGROUND: Liver disease is common during human immunodeficiency virus (HIV) infection, but valid serum fibrosis markers are lacking. We hypothesize that HIV monoinfection and HIV/hepatitis C virus (HCV) coinfection is associated with an enhanced liver fibrosis (ELF) score higher than that for uninfected controls and examine whether this association is affected by factors other than liver injury. METHODS: The association of HIV and HIV/HCV coinfection with the ELF score was evaluated using multivariable regression after controlling for transient elastography-measured liver stiffness and traditional and HIV-related factors in a cross-sectional analysis of 297 women. RESULTS: HIV/HCV-coinfected and HIV-monoinfected women had higher median ELF scores than controls (9.6, 8.5, and 8.2, respectively). After adjustment for demographic, behavioral, and metabolic factors and for inflammatory markers, HIV/HCV coinfection remained associated with a 9% higher ELF score (95% confidence interval [CI], 5%-13%), while the association of HIV monoinfection was substantially attenuated (1% higher ELF score; 95% CI, -2% to 4%). After further adjustment for liver stiffness, HIV/HCV coinfection remained associated with 6% higher levels (95% CI, 3%-10%). In HIV/HCV-coinfected and HIV-monoinfected women, higher liver stiffness values were associated with higher ELF scores, as were older age and a nadir CD4(+) T-cell count of <200 cells/mm(3). CONCLUSIONS: Our findings suggest that the ELF score can be used to assess liver fibrosis severity in HIV-infected women. However, higher ELF scores may reflect extrahepatic fibrosis in HIV-infected patients with a history of severe immunosuppression or advanced age.

Association of HIV, hepatitis C virus and liver fibrosis severity with interleukin-6 and C-reactive protein levels.

BACKGROUND: Hepatitis C virus (HCV) infection is associated with chronic inflammation; yet studies show greater interleukin (IL)-6, but lower C-reactive protein (CRP) levels. We determined whether liver fibrosis severity and HCV replication affect the ability of IL-6 to stimulate the production of CRP from the liver. METHODS: We used multivariable generalized linear regression to examine the association of HIV, HCV and transient elastography-measured liver stiffness with IL-6 and CRP in participants (164 HIV-monoinfected; 10 HCV-monoinfected; 73 HIV/HCV-coinfected; 59 neither infection) of the Women's Interagency HIV Study. Significant fibrosis was defined as liver stiffness greater than 7.1 kPa. RESULTS: IL-6 was positively correlated with CRP levels in all women, but CRP levels were lower in HCV-infected women (with and without HIV infection) at all levels of IL-6. HCV-infected women with fibrosis had nearly 2.7-fold higher IL-6 levels compared to controls [95% confidence interval (CI 146%, 447%]; HCV-infected women without fibrosis had IL-6 levels that were similar to controls. By contrast, CRP was 28% lower in HCV-infected women with fibrosis (95% CI -55%, 15%) and 47% lower in HCV-infected women without fibrosis (95% CI -68%, -12%). Among the HCV-infected women, higher HCV-RNA levels were associated with 9% lower CRP levels per doubling (95% CI -18%, 0%). CONCLUSION: Liver fibrosis severity is associated with greater IL-6 levels, but the stimulatory effect of IL-6 on CRP appears to be blunted by HCV replication rather than by liver fibrosis severity. Investigation of the potential CRP rebound after HCV-RNA eradication and persistent liver fibrosis on organ injury is needed.

The epidemiology of blastomycosis in Illinois and factors associated with death.

BACKGROUND: Blastomycosis is a systemic fungal disease that may be asymptomatic or progressive and may lead to death. METHODS: In response to a reported increase in the number of cases of blastomycosis in Illinois, surveillance data reported to the Illinois Department of Public Health from January 1993 to August 2003 were analyzed and the medical records of 4 patients who died were reviewed. RESULTS: Among the 500 cases reported, the median age of the patients was 43 years (range, 4-87 years), and 34 patients (7%) died. Higher rates of mortality were observed among persons who were black, who were > or =65 years of age, and who were male. The median time from onset of illness to diagnosis was 128 days (range, 12-489 days). Death was associated with a time from onset of illness to diagnosis of > or =128 days (OR, 2.1; 95% CI, 1.0-4.8). During the period from 1993 through 2002, the number of cases reported per year increased from 24 to 87 (P<.05). CONCLUSIONS: The incidence of blastomycosis has been increasing in Illinois. To reduce mortality related to delay in diagnosis and treatment, medical providers need to be educated about blastomycosis, with an emphasis on symptom recognition, methods of diagnosis, and appropriate antifungal treatment.