Biomedical subjects
Publications and source records attributed to Silvia Garazzino.
The effect of HAART on HCV infection and HCV-RNA plasma levels is controversial. We describe a patient with HIV-HCV coinfection with persistent disappearance of HCV-RNA after immunological and virological response to HAART, and we briefly discuss similar cases reported in the literature.
OBJECTIVES: The optimal regimen for acute hepatitis C (AHC) is considered to be a 24 week treatment with interferon (IFN) alpha-2b. A 24 week treatment with pegylated IFN (PEG-IFN) alpha-2b is also effective. This study was designed to assess response rates to a 12 week regimen of PEG-IFN alpha-2b. PATIENTS AND METHODS: Patients with AHC were treated with PEG-IFN alpha-2b for 12 weeks in an open, non-randomized, prospective cohort study. Diagnosis of AHC was made with positive serum HCV RNA and elevated alanine aminotransferase (ALT) levels with a documented seroconversion or a known risk factor in the preceding 6 months. Treatment was administered within a median of 31 days (range 0-116) of the ALT level peak at a dosage varying from 1.06 to 1.66 microg/kg/week. The primary end-point was a sustained virological response (SVR). RESULTS: Nineteen patients were treated, of whom 11 patients (57.9%) had HCV genotype 1. Fourteen patients were asymptomatic. An SVR was achieved in 74% of patients and the SVR rate was 100 and 83.3%, respectively, in genotype 1 and non-1 infected patients treated with a dosage>or=1.33 microg/kg, compared with 40 and 50%, respectively, in those who received a lower dosage. An SVR was significantly associated by multivariate analysis only with PEG-IFN dosage>or=1.33 microg/kg/week. No significant association was found with any viral genotype. CONCLUSIONS: The rate of SVR was independent of the HCV genotype and was significantly associated by multivariate analysis only with the higher PEG-IFN dosage. Early identification and treatment of AHC is likely to decrease the burden of chronic hepatitis, especially when caused by HCV genotype 1.
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Interferon and pegylated interferon (peg-IFN) are highly effective in patients with acute hepatitis caused by hepatitis C virus (acute hepatitis C, AHC), but the optimal timing of treatment is still under debate. In this open-labelled, uncontrolled trial, 19 patients with AHC, including 12 intravenous drug users (IVDUs), were treated early in the course of the infection with peg-IFN-alpha2b for 12 weeks. Diagnosis was made according to standardized criteria. The HCV RNA decay was analysed during the first 4 weeks of treatment by quantitative branched-DNA and by qualitative RT-PCR. Of the patients, 11 (58%) had genotype 1. Sustained virological response (SVR) was achieved in 14 out of 19 patients (74%) and the mean time to achieve a negative RT-PCR for HCV RNA was 2.5 weeks. The SVR was associated by univariate analysis with peg-IFN dosage < or = 1.33 microg/kg/week (P = 0.026) and HCV RNA level at onset of therapy (P = 0.017). Using a logistic regression model, only peg-IFN dosage > or = 1.33 microg/kg/weekly was significantly associated with SVR (P = 0.0379, OR: 14.7; 95% CI: 1.16-185.2). The SVR was 100% and 83.3%, respectively, in genotype 1 and non-1 infected patients treated with a dosage equal to or higher than 1.33 microg/kg, compared with 40% and 50%, respectively, in those who received a lower dosage. Efforts should be made to propose a 12-week treatment with peg-IFN-alpha2b for AHC, and to maximize peg-IFN dosage. Early treatment is associated with early disappearance of HCV RNA.
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Abnormal liver function tests are frequently observed in HIV-infected individuals receiving nevirapine (NVP). Here we investigate the relationship between total and unbound plasma concentrations of NVP and the liver enzymes alanine aminotransferase (ALT) and gamma-glutamyl transferase (gammaGT). HIV-infected individuals [n = 85, 22 female, 34 hepatitis C or B virus (HCV or HBV(+))] receiving NVP (200 mg bd; median duration 66 weeks, range 3-189) and two nucleoside reverse transcriptase inhibitors (NRTIs) were enrolled into this study. Blood samples were taken at C(trough) (12 hr postdose) for measurement of NVP and liver function tests (ALT and gammaGT). Plasma protein bound and unbound drug was separated using ultrafiltration and NVP concentrations quantified using HPLC-MS/MS. A linear relationship was observed between total and unbound NVP C(trough) (r(2) = 0.77, p < 0.0001). Patients with elevated ALT (>37 IU/liter; n = 31) had higher NVP unbound C(trough) than those with ALT within the normal range (median 2268 vs. 1694 ng/ml, p = 0.04) but there was no difference in total C(trough). Logistic regression revealed no association between higher NVP C(trough) and ALT elevations. Significantly higher NVP total and unbound C(trough) were observed in patients with increased gammaGT (>40 IU/liter; n = 63; total 6747 vs. 4530 ng/ml, p = 0.001; unbound 2113 vs. 1557 ng/ml, p = 0.03). Significantly higher unbound NVP C(trough) was observed in HCV/HBV(+) (median 2275 vs. 1726 ng/ml, p = 0.02) and on bivariate analysis, higher NVP C(trough) was associated with HCV/HBV coinfection (chi(2) = 4.228; p = 0.04). Overall we found no strong association between NVP concentrations and hepatotoxicity. Although in this study NVP was well tolerated in HCV/HBV coinfected patients, higher plasma concentrations were observed.
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