IL28B genotype effects during early treatment with peginterferon and ribavirin in difficult-to-treat hepatitis C virus infection.

BACKGROUND: Mathematical models of hepatitis C virus (HCV) during therapy may elucidate mechanisms of action for antiviral therapy. In genome-wide association studies, IL28B gene polymorphisms are highly predictive of therapeutic clearance of HCV. METHODS: We collected sera from 20 chronically infected HCV participants at 13 points during the first 28 days of therapy. We assessed the presence of the C allele at single-nucleotide polymorphism rs12979860 using the ABI TaqMan allelic discrimination kit. We estimated dynamic parameters from the entire population using the Neumann model for HCV infection. Statistical methods for repeated nonlinear measures compared model parameters by established predictors of response. RESULTS: The frequencies of IL28B genotypes were 6 (C/C), 11 (C/T), and 3 (T/T). The mean log decline in HCV RNA from 0 to 48 hours was more rapid among C/C genotype participants compared with C/T or T/T genotype participants (1.4 vs 0.7; P = .07), and from 2 days to 14 days (1.6 vs 0.7; P = .04). In the multivariate model, the C/C genotype predicted a steeper second-phase decline when adjusted for race (P = .01). CONCLUSIONS: The presence of the C/C genotype at IL28B rs12979860 exerts its antiviral effect by increasing the infected hepatocyte death rate. This suggests that an immune-mediated mechanism is responsible.

Diagnosis of depression in former injection drug users with chronic hepatitis C.

GOALS: This study seeks to define the performance characteristics of 2 common depression screening tests and how psychiatric diagnoses affect adherence to treatment. BACKGROUND: Hepatitis C virus is common in former injection drug users (IDU). Many former IDUs have depression, which may complicate treatment, and are often denied therapy. STUDY: Ninety patients with chronic hepatitis C virus and reported IDU were recruited from a Hepatology Clinic in Seattle. Subjects completed the Beck Depression Inventory (BDI) and Patient Health Questionnaire-9 (PHQ-9) before antiviral therapy. A psychiatrist administered the Mini International Neuropsychiatric Interview as the "gold standard." Adherence was measured by self-report of missed doses. RESULTS: The BDI and PHQ-9 were highly correlated (r=0.75). Using a BDI score of ≥20 and a PHQ-9 score of ≥10, 39% and 52%, respectively, were misclassified as being depressed, as compared with the Mini International Neuropsychiatric Interview. Maximal sensitivity (85.7%) and specificity (82.6%) was achieved using a BDI score cutoff of 31, with an area under the curve of 0.82. For the PHQ-9, a cutoff of 14 yielded the best sensitivity (85.7%) and specificity (73.9%) with an area under the curve of 0.84. Adherence to at least 80% of medications was achieved by the majority. CONCLUSIONS: Subjects reported good adherence and outcomes despite a high level of psychiatric comorbidity. The BDI and PHQ-9 were highly correlated but both tended to overdiagnose depression. A high score on BDI or PHQ-9 should not be the sole basis for withholding treatment. These patients should be evaluated by a psychiatrist to make an informed decision.