Pegylated interferon (peginterferon) alfa-2b plus ribavirin achieves a higher sustained response rate in patients with genotype 1 chronic hepatitis C virus (HCV) than standard combination therapy. This study evaluated HCV kinetics throughout therapy with 2 doses of peginterferon alfa-2b and ribavirin in 55 patients. Twenty-eight patients were randomized to receive a high once-weekly dose of peginterferon alfa-2b (3 g/kg for 1 week, 1.5 g/kg for 3 weeks, and 1.0 g/kg for 44 weeks), and 27 patients were randomized to receive a low dose (0.5 g/kg) for 48 weeks. Both groups also received 800 mg ribavirin daily. Mean baseline HCV RNA load, measured by reverse-transcription polymerase chain reaction, was similar in both groups (5.32 ؎ 0.86 log vs. 5.15 ؎ 1.04 log). The 3-g/kg dose of peginterferon alfa-2b inhibited HCV RNA more significantly than the 0.5-g/kg dose during the first 48 hours (2.08 ؎ 0.93 log vs. 1.09 ؎ 0.80 log; P < .001) and both increased at 72 hours (0.54 ؎ 0.73 log vs. 0.03 ؎ 0.36 log; P ؍ not significant [NS]), but the high dose showed a greater reduction at the end of the week (1.07 ؎ 0.99 log vs. 0.72 ؎ 0.73 log). Both doses showed a progressive, slower viral decrease throughout therapy; however, HCV RNA became undetectable faster and in more patients with the high dose (22% vs. 7% at week 4, 56% vs. 44% at week 12, 69% vs. 63% at week 24, and 71% vs. 61.5% at the end of therapy). In conclusion, peginterferon alfa-2b/ribavirin produces an initial rapid decline in HCV RNA levels, followed by a slower, progressive decrease, similar to the biphasic kinetic profile of standard combination therapy. Higher doses of peginterferon alfa-2b also accelerate viral clearance. (HEPATOLOGY 2002;35:930-936.) See Editorial on page 967 P egylated interferons (peginterferons) represent the most recent advance in the treatment of patients with chronic hepatitis C. Peginterferon alfa-2b consists of a conjugate of straight-chain polyethylene glycol (molecular weight, 12,000 daltons) and interferon alfa-2b in a 1:1 ratio. 1,2 The main effects of pegylated proteins are to delay clearance and prolong half-life, which allows for less-frequent dosing and may be associated with increased efficacy.Studies in humans have shown peginterferon to be safe and well tolerated. [1][2][3][4] The efficacy of peginterferon alfa-2b given once weekly has been evaluated in a large, multicenter study. This study showed that peginterferon alfa-2b increases the sustained virologic response rate to 25%, compared with the 12% rate observed with standard interferon therapy. 4 Even patients infected with genotype 1, who are least responsive to interferon therapy, experienced an increase in sustained virologic response when treated with peginterferon alfa-2b. 4,5 This response appeared to be dose dependent; 11% of patients with hepatitis C virus (HCV) genotype 1 treated with 0.5 g/kg peginterferon alfa-2b achieved sustained virologic
The purpose of this study was to assess the use of dried blood spot (DBS) samples for hepatitis B virus (HBV) DNA quantification, HBV genotyping, and detection of G1896A precore mutants and variants in the YMDD polymerase motif. We studied DBS and serum samples from 82 patients with chronic HBV infection (23 hepatitis B e antigen [HBeAg]-positive and 39 HBeAg-negative), 20 HBeAg-inactive carriers, and 15 HBeAg-negative patients under lamivudine therapy (selected from chronic HBV patients). DBS samples consisted of approximately 20 L of blood applied to 5-mm paper disks. HBV DNA quantification and HBV precore mutant detection were done using real-time polymerase chain reaction, HBV genotyping using restriction fragment length polymorphism, and YMDD variant detection by Inno-lipa assay. DBS and serum results were compared. HBV DNA was detected in a range of 10 2 -10 8 copies/mL, with low intra-assay and inter-assay variation (<10%). Median DBS HBV DNA (copies/mL) was: 3.7 ؋ 10 6 in HBeAg-positive, 6.2 ؋ 10 5 in HBeAg-negative, and 5.5 ؋ 10 2 in inactive carriers (P < .05). HBV DNA was positive in serum (median 5 ؋ 10 3 copies/mL) but negative in DBS for five inactive carriers. The correlation coefficient between HBV DNA concentration in DBS versus serum samples was r 2 ؍ 0.96 (P < .001). The sensitivity of HBV DNA detection in DBS samples was 1 log 10 lower than in serum samples. Concordance between DBS and serum for HBV genotyping, and for precore mutant and YMDD variant detection was optimal. DBS storage for 7 days at room temperature and 21 days at ؊20°C revealed no decrease in HBV DNA levels or integrity. In conclusion, the DBS sample is useful for HBV DNA quantification, genotyping, and detection of precore mutant and YMDD variants. All four determinations can be completed with a single drop of dried blood. ( V irological diagnosis and monitoring of hepatitis B virus (HBV) infection are based on serological assays that detect specific antibodies and that detect, quantify, or characterize HBV particles at the molecular level. Several authors have suggested that the study of virological characteristics such as HBV genotypes, molecular HBV variants, and quantification of HBV-DNA levels should be included as part of the laboratory testing for routine management of chronic hepatitis B (CHB) infection. 1-3 However, implementation of this policy requires access to specific laboratory equipment that may not be readily available in some settings.Dried blood spot (DBS) samples collected on filter paper have been used for genetic screening and diagnosis of several diseases. This approach is particularly useful for programs in which samples from many areas are sent to a central laboratory. 4 Since it was first introduced for the detection of RNA human immunodeficiency virus type 1 in 1991, polymerase chain reaction (PCR)-based DBS methods have proved particularly effective for the detection of proviral HIV-1 DNA and for viral sequencing. [5][6][7] In HBV infection, DBS samples have been used mainly for testing viral an...
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