Effect of human immunodeficiency virus infection on hepatitis C virus infection in hemophiliacs

Chronic liver disease due to hepatitis C virus (HCV) infection is a major problem in hemophiliacs. Recent reports suggested that hemophiliacs coinfected with hepatitis C virus and human immunodeficiency virus (HIV) have an increased incidence of liver failure but the mechanism of accelerated liver injury is not clear. We tested plasma from 100 hemophiliacs for anti-HCV by second generation ELISA, anti-HIV by EIA, and HCV RNA and HIV RNA by branched DNA and polymerase chain reaction assays to determine if hemophiliacs coinfected with HCV and HIV have higher HCV RNA levels and more active liver disease. Seventy-nine (79%) patients were anti-HCV positive, of whom 85% were HCV RNA positive. None of the anti-HCV-negative patients had detectable HCV RNA in plasma. Forty-two (42%) patients were anti-HIV positive, of whom 47% had detectable HIV RNA. All the anti-HIV-positive patients were also anti-HCV positive. The prevalence of both anti-HCV and anti-HIV increased significantly with age. There was no difference in HCV RNA levels between anti-HIV-positive and anti-HIV-negative patients (mean: 21±4 vs 18±5 Meq/ml), although HCV RNA levels were significantly higher in anti-HIV-positive patients with CD4 counts<200/mm 3 ( P =0.008). There was an inverse correlation between HCV RNA levels and CD4 counts but no correlation was found between HCV RNA and serum aminotransferase levels. We found a high prevalence of HCV and HIV coinfection in our hemophiliacs. Hepatitis C virus replication appears to be increased in patients with severe immunodeficiency secondary to progressive HIV infection. However, there was no correlation between HCV RNA and serum ALT level, suggesting that HCV is not directly cytopathic.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44427/1/10620_2005_Article_BF02088247.pd

A reflection on HIV/AIDS research after 25 years

Dr. Robert C. Gallo provides a personal reflection on the 25 year history of AIDS

Hypoxia Inducible Factor 1-Alpha (HIF-1 Alpha) Is Induced during Reperfusion after Renal Ischemia and Is Critical for Proximal Tubule Cell Survival

Acute tubular necrosis (ATN) caused by ischemia/reperfusion (I/R) during renal transplantation delays allograft function. Identification of factors that mediate protection and/or epithelium recovery could help to improve graft outcome. We studied the expression, regulation and role of hypoxia inducible factor 1-alpha (HIF-1 α), using in vitro and in vivo experimental models of I/R as well as human post-transplant renal biopsies. We found that HIF-1 α is stabilized in proximal tubule cells during ischemia and unexpectedly in late reperfusion, when oxygen tension is normal. Both inductions lead to gene expression in vitro and in vivo. In vitro interference of HIF-1 α promoted cell death and in vivo interference exacerbated tissue damage and renal dysfunction. In pos-transplant human biopsies, HIF-1 α was expressed only in proximal tubules which exhibited normal renal structure with a significant negative correlation with ATN grade. In summary, using experimental models and human biopsies, we identified a novel HIF-1 α induction during reperfusion with a potential critical role in renal transplant

Correlation between serum HCV RNA and aminotransferase levels in patients with chronic HCV infection

Cross-sectional studies on the correlation between serum hepatitis C virus (HCV) RNA and alanine aminotransferase (ALT) levels in patients with chronic hepatitis C have yielded conflicting results. We conducted a longitudinal study to examine the correlation between HCV viremia and serum ALT levels in individual patients over time. Serial samples (mean 9) from 25 patients with chronic HCV infection, including interferon-treated and untreated immunocompetent and immunosuppressed patients, collected over a period of 1–4.8 years (mean 2.6 years) were tested for HCV RNA and ALT levels using a highly reproducible quantitative (bDNA) assay. A significant correlation was found between serum HCV RNA and ALT levels in the patients who received IFN therapy, but no correlation was observed in the untreated patients. Among the untreated patients, the immunosuppressed patients had significantly higher HCV RNA levels (39±4 vs 3.6±8 Meq/ml, P <0.0001) but significantly lower ALT (56±11 vs 97±12 units/liter, P =0.03) levels when compared to the immunocompetent ones. In summary, we found no correlation between serum HCV RNA and ALT levels in chronic hepatitis C patients who are not receiving interferon therapy. Immunosuppression results in higher HCV RNA but lower ALT levels.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44425/1/10620_2005_Article_BF02071402.pd