Hepatitis C virus RNA kinetics during the initial 12 weeks treatment with pegylated interferon‐alpha 2a and ribavirin according to virological response

Carlsson, Thomas; Reichard, Olle; Norkrans, Gunnar; Bläckberg, Jonas; Sangfelt, Per; Wallmark, E.; Weiland, Ola

doi:10.1111/j.1365-2893.2005.00621.x

Cited by 34 publications

(32 citation statements)

References 31 publications

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“…However, the relatively low response rates for patients carrying genotype 1 virus remains a significant problem, especially in light of the costs and treatment-related toxicity. An improved prediction of SVR as well as non-SVR would therefore be important, and it has been proposed that the viral kinetics during treatment might be clinically useful for this purpose (1,2,4,5,16,18,20,22,25,26). For example, the magnitude of HCV RNA reduction after only one dose of interferon is clearly associated with an SVR (10,15), as is the rate of decline in viremia between day 7 and week 12 (second-phase slope) (1,8).…”

Section: Discussionmentioning

confidence: 99%

Response Prediction and Treatment Tailoring for Chronic Hepatitis C Virus Genotype 1 Infection

et al. 2007

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We monitored early viral response during the treatment of hepatitis C virus (HCV) infection with the aim of identifying predictors of treatment outcome. We studied 53 patients with genotype 1 infection who received 180 g/week pegylated interferon alfa-2a and 1,000 or 1,200 mg/day ribavirin depending on body weight and serially assessed HCV RNA in serum, using the Cobas TaqMan assay. Thirty-one patients (58%) achieved sustained viral response (SVR). SVR was obtained in 100% (10/10) of patients with pretreatment viremia concentrations below 400,000 IU/ml, in 100% (14/14) of patients with more than 1.5 log reduction of HCV RNA after 4 days of treatment, and in 95% (22/23) of patients with a rate of decline in viremia higher than 0.70 log units/week during the second phase. Non-SVR was seen in all patients with a second-phase decline rate lower than 0.35 log units/week. Patients with slopes between 0.50 and 0.80 log units/week achieved SVR (4/4) unless the treatment dose was modified (3/3). We conclude that the second-phase slope appears to be an accurate and useful predictor of treatment response. On the basis of these findings, we propose a model of tailored treatment which takes into account the second-phase slope and the amount of HCV RNA after 21 days of treatment.

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Section: Discussionmentioning

confidence: 99%

Response Prediction and Treatment Tailoring for Chronic Hepatitis C Virus Genotype 1 Infection

et al. 2007

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“…''Group 2'' consisted of 35 genotype 1-positive chronic HCV patients that were treated with peg-IFNa/ribavirin. Of these, 11 patients were treatment-naïve [Carlsson et al, 2005], while 24 had been treated before with IFNa/ ribavirin. Ten did not show any response (non-responders) to the first treatment and 14 relapsed after cessation of treatment.…”

Section: Patient Selection and Sample Collectionmentioning

confidence: 99%

Serum levels of anti‐NS4a and anti‐NS5a predict treatment response of patients with chronic hepatitis C

Desombere

Vlierberghe

Weiland

et al. 2007

Journal of Medical Virology

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In order to understand better the clinical significance and prognostic value of antibody responses to HCV proteins and in search for parameters that may allow the early identification of non-sustained responders to therapy, antibody levels were measured against NS3, NS4a and NS5a at baseline in the serum of 120 patients chronically infected with HCV of genotype 1 that were classified as sustained responders, relapsers, or non-responders to therapy. The capacity of these antibody tests to predict therapy-outcome was evaluated. While no differences were observed in the anti-NS3 responses in these different response groups, anti-NS4a and anti-NS5a antibodies were observed more frequently and at higher titres in sustained responders versus non-responders or non-sustained responders (=non-responders + relapsers). Based on this observation, a combination of test results consisting of 'the absence of NS4a (AA 1687-1718) antibody at baseline and the presence of HCV-RNA exceeding 10(5) IU/ml after 1 week of treatment' was identified which predicts non-sustained response to treatment with 100% certainty. Replacing the HCV-RNA decision limit by a HCV-core antigen level of >15 pg/ml resulted in the same predictive value. The proposed algorithm also holds for patients treated with peg-interferon and ribavirin. In conclusion, in patients with chronic HCV infection, the decision to continue or stop treatment can be made after 1 week of treatment with (peg)-interferon alpha and ribavirin.

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“…In general, we follow the evolving treatment guidelines for CHC as recommended by various authoritative groups [4,5], including making decisions about how long treatment should be continued based on initial reductions in HCV-RNA and how well therapy is being tolerated at the end of 3 months in compliant patients [32,33]. Each patient was asked to consider their treatment options, including expectant management.…”

Section: Design and Collection Of Datamentioning

confidence: 99%

Reasons Why Patients Infected with Chronic Hepatitis C Virus Choose to Defer Treatment: Do They Alter Their Decision with Time?

Khokhar

Lewis

2007

Dig Dis Sci

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This study was designed to determine the percentage of treatment-naïve patients infected with chronic hepatitis C virus who make an informed choice to forego (defer) treatment with pegylated interferon regimens in the absence of any medical, psychosocial, or other contraindications, and to reassess their decision by using a questionnaire at least 1 year later. Patient charts dating from 2001 were retrieved and retrospectively analyzed for the following data: patient age, gender, race, hepatitis C viral load, genotype, liver biopsy results, hepatic imaging results, peak alanine aminotransferase (ALT) levels, comorbid conditions, source of infection, estimated duration of infection, and reasons given by the patient for declining pegylated interferon-based treatment at the time of their consultation. A questionnaire survey sought to determine their satisfaction with their initial decision. Of 446 patient charts reviewed, 280 patients were treatment-naïve and were judged to have no contraindications to receiving interferon-based therapy. Of these, 115 (41%) opted to defer treatment and are the subject of this analysis. Women declining therapy outnumbered men by approximately 3 to 2. Middle-aged patients (45-55 years) were most likely to choose expectant therapy compared with older or younger individuals. The proportion of African American patients who deferred therapy (48%) was higher than non-African American patients (36.6%). More than 90% of the patients choosing to be followed were genotype 1. Peak ALT values were normal in 37% and<2X upper limits of normal (ULN) in another 40%. The estimated duration of chronic hepatitis C infection was >16 years in approximately three-quarters of individuals. The most common source of their infection was intravenous drug use followed by transfusion-related. The most common reason for opting not to receive treatment, given by nearly two-thirds of patients, was the asymptomatic nature of their infection coupled with their concern about side effects of the medications. Approximately 10% had unfavorable social situations, including a lack of support or health insurance, that precluded receiving therapy (despite the availability of indigent care programs offered by the pharmaceutical manufacturers). Only five patients (4.3%) cited doubts about efficacy as the main reason that they did not want to be treated. The questionnaire survey at 1 year found that 79% of the patients confirmed their ongoing satisfaction with their initial decision to decline treatment, and another 10.6% indicated that they were still "moderately satisfied" with their decision and unlikely to change it in the near-future. Only six patients (7%) voiced their current dissatisfaction with expectant management and expressed the desire to have a follow-up discussion about treatment options. Of the remaining three patients (3.5%), two had already started treatment and one was deceased (of non-liver-related causes). A significant proportion of patients infected with hepatitis C virus who are otherwise eligible for the...

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Hepatitis C virus RNA kinetics during the initial 12 weeks treatment with pegylated interferon‐alpha 2a and ribavirin according to virological response

Cited by 34 publications

References 31 publications

Response Prediction and Treatment Tailoring for Chronic Hepatitis C Virus Genotype 1 Infection

Response Prediction and Treatment Tailoring for Chronic Hepatitis C Virus Genotype 1 Infection

Serum levels of anti‐NS4a and anti‐NS5a predict treatment response of patients with chronic hepatitis C

Reasons Why Patients Infected with Chronic Hepatitis C Virus Choose to Defer Treatment: Do They Alter Their Decision with Time?

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