Accuracy of simple biochemical tests in identifying liver fibrosis in patients co-infected with human immunodeficiency virus and hepatitis C virus.

BACKGROUND & AIMS: We assessed the ability of 3 simple biochemical tests to stage liver fibrosis in patients co-infected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV). METHODS: We analyzed liver biopsy samples from 324 consecutive HIV/HCV-positive patients (72% men; mean age, 38 y; mean CD4+ T-cell counts, 548 cells/mm(3)). Scheuer fibrosis scores were as follows: 30% had F0, 22% had F1, 19% had F2, 23% had F3, and 6% had F4. Logistic regression analyses were used to predict the probability of significant (>or=F2) or advanced (>or=F3) fibrosis, based on numeric scores from the APRI, FORNS, or FIB-4 tests (alone and in combination). Area under the receiver operating characteristic curves were analyzed to assess diagnostic performance. RESULTS: Area under the receiver operating characteristic curves analyses indicated that the 3 tests had similar abilities to identify F2 and F3; the ability of APRI, FORNS, and FIB-4 were as follows: F2 or greater: 0.72, 0.67, and 0.72, respectively; F3 or greater: 0.75, 0.73, and 0.78, respectively. The accuracy of each test in predicting which samples were F3 or greater was significantly higher than for F2 or greater (APRI, FORNS, and FIB-4: >or=F3: 75%, 76%, and 76%, respectively; >or=F2: 66%, 62%, and 68%, respectively). By using the lowest cut-off values for all 3 tests, F3 or greater was ruled out with sensitivity and negative predictive values of 79% to 94% and 87% to 91%, respectively, and 47% to 70% accuracy. Advanced liver fibrosis (>or=F3) was identified using the highest cut-off value, with specificity and positive predictive values of 90% to 96% and 63% to 73%, respectively, and 75% to 77% accuracy. CONCLUSIONS: Simple biochemical tests accurately predicted liver fibrosis in more than half the HIV/HCV co-infected patients. The absence and presence of liver fibrosis are predicted fairly using the lowest and highest cut-off levels, respectively.

Ghrelin, glucose homeostasis, and carotid intima media thickness in kidney transplantation.

BACKGROUND: Abnormalities in glucose homeostasis (AGH) frequently occur in kidney transplantation and favor vascular lesions. The purpose of this study was to analyze whether C-reactive protein (CRP), adiponectin, and ghrelin are markers of AGH and indicators of carotid atherosclerosis in kidney transplant patients with fasting plasma glucose below 126 mg/dL. METHODS: This was a cross-sectional study of 85 kidney transplant patients (59 men; mean age: 52.4 +/- 11.6 years; median posttransplant follow-up 31 (range 3-61) months). All patients underwent an oral glucose tolerance test. Abnormalities in glucose homeostasis were diagnosed following American Diabetes Association criteria. CRP, adiponectin, and ghrelin levels were determined. Doppler ultrasound of the carotid artery was performed to determine intima media thickness (IMT) and atheromatous plaque. RESULTS: A total of 50.5% of patients had AGH (12.9% were diagnosed with new-onset diabetes mellitus after transplantation and 37.7% had impaired glucose tolerance or impaired fasting glucose), whereas 49.4% were normoglycemic. Patients with AGH were older (P=0.002), had greater carotid IMT (P=0.022), and lower ghrelin concentrations (P=0.017) than normoglycemic patients. Logistic regression analyses showed ghrelin to be an independent marker for AGH (P=0.012) and AGH to be related to greater IMT (P=0.041). No differences in adiponectin or CRP were found in relation to AGH or atherosclerosis; however, there was a positive correlation between adiponectin levels and prednisone dose (r=0.240; P=0.044). CONCLUSIONS: A total of 50.5% of the study patients had abnormalities in glucose homeostasis. Patients with AGH had a higher percentage of preclinical atherosclerosis (greater carotid IMT). Ghrelin is an independent marker for abnormalities in glucose homeostasis.

Advanced liver fibrosis in HIV/HCV-coinfected patients on antiretroviral therapy.

HIV infection is believed to adversely affect the progression of hepatitis C virus (HCV)-related liver disease. However, information regarding HIV and HCV coinfection in the era of highly active antiretroviral therapy (HAART) is scarce. A cross-sectional study in 75 HCV/HIV-coinfected patients (most of them on HAART) and 75 HCV-monoinfected patients paired by age, sex, and date of liver biopsy analyzed the association of HIV infection with advanced liver fibrosis (Knodell fibrosis stages 3 + 4). The median CD4 cell count in HIV-coinfected patients was 546 cells/microl; 78.7% had an HIV-1 viral load <1000 copies/ml and 88% were on antiretroviral therapy. The percentage of patients harboring genotype 4 and with a higher HCV viral load was greater in the HIV-coinfected group. HCV/HIV-coinfected patients had more advanced liver fibrosis (Knodell fibrosis stages 3 + 4) than HCV-monoinfected patients (46.7% vs. 12%, p < 0.0001). In the univariate analysis, the factors associated with advanced liver disease were male sex (OR: 2.7, 95% CI: 1.05-7.1), history of injecting drug use (OR: 4.6, 95% CI: 2.0-10.2), HIV infection (OR: 6.4, 95% CI: 2.7-14.7), and previous exposure to therapy with protease inhibitors (OR: 3.0, 95% CI:1.4-6.3). In the multivariate analysis; only male sex (OR: 3.17, 95% CI: 1.152-8.773) and HIV infection (OR: 6.85, 95% CI: 2.93-16.005) were associated with advanced liver fibrosis. HIV infection is associated with advanced liver fibrosis. HIV/HCV-coinfected individuals on HAART are at risk of developing end-stage liver disease despite virological success and immunological reconstitution.

Effect of liver fibrosis on long-term mortality in HIV/hepatitis C virus-coinfected individuals who are evaluated to receive interferon therapies in the highly active antiretroviral therapy era.

The factors associated with overall mortality and liver decompensation in HIV and hepatitis C virus (HCV)-coinfected patients who are evaluated to receive HCV antiviral therapy with a known liver histological fibrosis stage were evaluated in a prospective cohort study. A total of 387 consecutive HIV/HCV-coinfected patients attending an outpatient clinical unit between January 1997 and December 2007 who fulfilled criteria to be treated with interferon and to whom liver biopsy was performed were included and followed every 6 months from time of liver biopsy to death or to December 2008. The follow-up period was 6.2 years (IQR: 3.5-9.2). The median age at time of liver biopsy was 38 years. This included 73% men; 28% had advanced liver fibrosis (F3-F4) and a CD4 cell count of 556 cells/mm(3), 72% had HIV RNA <400 copies/ml and a mean CD4 nadir of 207 cell/mm(3), 21% had a previous diagnosis of AIDS, and 92% were on antiretroviral therapy. During follow-up 48% underwent HCV antiviral therapy, with a sustained virological response in 33%. The overall mortality rate and the incidence of liver decompensation or liver-related death were 1.17 and 0.72 per 100 patients-year, respectively. End stage liver disease (9/28 patients) and non-AIDS-related cancer (6/28) were the main causes of death. F3-F4 (HR: 3.74, 95% CI: 1.69-8.26, p=0.001) and previous AIDS diagnosis (HR: 3.04, 95% CI: 1.36-6.81) were the factors independently associated with death. Mortality rates in patients who received and who did not receive HCV antiviral therapy were 0.44 and 2.04 per 100 patients-year, respectively (p=0.003). In addition to the low mortality rate observed, HIV/HCV-coinfected patients with poor predictors of survival are candidates for intensive clinical management.