63 research outputs found
Does the Addition of Lamivudine to Peginterferon a-2a sustain Response Rates in Patients with HBeAG Negative Hepatitis B?
No full textBACKGROUND HEPATITIS B e ANTIGEN (HBeAg)-NEGATIVE CHRONIC HEPATITIS B has a poor prognosis because sustained remission is hard to achieve with current treatments. The optimal therapy or combination of therapies for this condition has not been determined. OBJECTIVES To determine the efficacy and safety of peginterferon α-2a monotherapy, peg interferon α-2a in combination with lamivudine, and lamivudine monotherapy for the treatment of HBeAg-negative chronic hepatitis B
The treatment of hepatitis B e antigen-positive chronic hepatitis B with pegylated interferon
No full textInterferons were first used in the treatment of chronic hepatitis B two decades ago [1, 2 and 3] and eventually led to the registration of this drug in the treatment of chronic hepatitis B. The interferons act as immunomodulators having a number of effects on the immune system and also act as an antiviral agent by inducing oligoadenylate synthetase and other proteins which lead to cleavage of viral RNA. Although there was increasing efficacy with the dose of interferon achieving better results using 9 mIU per square metre of body surface area three times a week, the significant side effects caused withdrawal in many patients. There was a variety of other dose regimens including a daily dose of half the amount. The dose recommended was 2.5 mIU or 5 mIU per square metre three times a week. This translated into 4.5/5 or 9/10 mIU three times a week. Furthermore, the side effects, often described as an influenza-like illness of myalgia, fever and headache, occurred in most patients and there were a plethora of other side effects, including mood changes and even depression. The seroconversion rate in patients who had hepatitis B e antigen (HBeAg)-positive chronic hepatitis B ranged from 20 to 50% of patients who had a 6-month course of treatment. The introduction of lamivudine [4 and 5], the first antiviral agent to be licensed, had a dramatic impact on the treatment of chronic hepatitis B as it seemed not to have side effects. Virtually all patients had viral inhibition and a reduction in hepatitis B virus (HBV) DNA levels in blood, and a slower decrease in transaminases. Unfortunately, the rate of seroconversion was only about 20% in a year so that cessation of the drug led to relapse of chronic hepatitis B. As a result, many patients continued on lamivudine and seroconversion continued to occur, but at a lower rate and possibly no greater than that seen spontaneously. Unfortunately the development of lamivudine-resistant mutation in the YMDD domain of the polymerase gene at a rate of about 10–20% per annum proved a major stumbling block in the management of this disease with antiviral agents
Peginterferon-alpha 2a for the Treatment of Hepatitis B Infection
No full textChronic hepatitis B is one of the world's most common serious diseases with > 300 million patients worldwide. Currently recommended treatments include conventional interferon (IFN), lamivudine and adefovir. Recently, peginterferon-α (PEG-IFN-α, Pegasys®; Hoffmann-La Roche & Co.) has been approved for use in patients with chronic hepatitis B in the US, the EU, Switzerland, Turkey and in several countries in the Asia-Pacific region. Several trials have been carried out using PEG-IFN-α (40 kDa) compared with conventional IFN, lamivudine monotherapy and a combination of PEG-IFN-α and lamivudine in patients with hepatitis Be antigen- (HBeAg)positive chronic hepatitis B, and patients with HBeAg-negative chronic hepatitis B. PEG-IFN-α was shown to be superior to conventional IFN in HBeAg-positive disease and to lamivudine in both HBeAg-positive and HBeAg-negative chronic hepatitis B. Although there was greater suppression of virus while on therapy, the combination of lamivudine and PEG-IFN-α did not enhance sustained response at the end of the 24-week follow-up period, compared with PEG-IFN monotherapy. In addition, ∼ 3% of patients underwent hepatitis B surface antigen (HBsAg) seroconversion - the ultimate marker of therapeutic response, which is rarely seen following treatment with antiviral agents. The side effect profile was reasonable. PEG-IFN-α could become the treatment of choice in many patients with both HBeAg-positive and HBeAg-negative disease and, in those who fail to respond, consideration could then be given to the use of antiviral agents
Treatment with interferons (including pegylated interferons) in patients with hepatitis B
No full textStudies of 4 to 6 months of treatment with interferon for hepatitis B e antigen (HBeAg)-positive chronic hepatitis B virus (HBV) infection have shown clearance of HBeAg to be higher in treated patients than it is in controls by approximately 25%. These results are considerably better than those with antiviral agents. Therefore, the recent European Association for the Study of the Liver (EASL) Consensus Committee recommended the use of interferon alpha for this condition. Treatment with pegylated interferons in several trials has shown better results still. Lamivudine in combination with interferon, however, did not improve the results at 6 months after the end of therapy. In HBeAg-negative chronic HBV infection, pegylated interferon alpha is superior to lamivudine, and, again, combination with lamivudine does not improve the results. Side effects in all studies have been tolerable. Thus, these observations in chronic HBV infection, whether HBeAg-positive or HBeAg-negative, suggest an important, even primary, role for pegylated interferon therapy
The impact of peginterferon alfa-2a plus ribavirin combination therapy on health-related quality of life in chronic hepatitis C
No full textHepatitis C virus (HCV) is an important cause of
chronic liver disease worldwide. In the United States
alone, nearly 4 million individuals are infected with this
virus [1]. Currently, hepatitis C is responsible for an
estimated 8000â10,000 deaths annually [2], and without
effective intervention, that number is postulated to triplen the next 10â20 years [3]. Hepatitis C is now the leading
reason for liver transplantation in the United States [4].
Patients with chronic hepatitis C also have more impaired
health-related quality of life (HRQOL) than the general
population [5â9]. In addition, soon after the onset of treatment
with interferon monotherapy or interferon plus ribavirin,
patients report increased incidence and severity of fatigue,
pain, and mood changes that interfere with physical and
emotional well-being, work productivity, and activities of
daily living [5,10,11]. These changes in HRQOL might
adversely affect adherence and result in early discontinuation
of therapy. Previous research on hepatitisCtherapy has shown
that such declines in HRQOL increase the risk of premature
treatment discontinuation [12].
In a randomized clinical trial, peginterferon alfa-2a
has demonstrated increased efficacy (sustained virological
response rate after completion of treatment) in monotherapy
compared with conventional interferon alfa-2a
[13]. Analysis of HRQOL in that trial found that patients
in the peginterferon alfa-2a group reported significantly
less impairment of HRQOL during therapy than those in
the conventional interferon alfa-2a group [14]. The
current standard of care for patients with chronic
hepatitis C is combination therapy using interferon and
ribavirin [15â20]. In a recent multinational, randomized
trial, combination therapy with peginterferon alfa-2a plus
ribavirin demonstrated increased efficacy compared with
peginterferon alfa-2a alone (56 vs. 29%, P # 0:001) and
interferon alfa-2b plus ribavirin (56 vs. 44%, P # 0:001)
[21]. The study also found significantly lower rates of
influenza-like symptoms (fever, headache, myalgia, and
rigors) with peginterferon alfa-2a plus ribavirin vs.
interferon alfa-2b plus ribavirin [21]. Lower rates of
these adverse events may contribute to less impairment
of HRQOL during therapy with peginterferon alfa-2a
plus ribavirin vs. interferon alfa-2b plus ribavirin.
The present study examined differences in HRQOL
experienced by patients randomized to 48 weeks of treatment
with either peginterferon alfa-2a plus placebo, peginterferon
alfa-2a plus ribavirin, or interferon alfa-2b plus ribavirin. The
purpose of the studywas threefold. First, to determinewhether
peginterferon alfa-2a plus ribavirin was associated with less
impairment ofHRQOL and less fatigue burden than interferon
alfa-2b plus ribavirin. Second to test previous findings [5,7,12,
14] that successful treatment of HCV is associated with
significant improvements in patient quality of life. Third, to
compare the HRQOL experienced by patients in the
peginterferon alfa-2a plus placebo and peginterferon alfa-2a
plus ribavirin groups in order to examine the specific effects of
both peginterferon alfa-2a and ribavirin when used in
combination, on HRQOL
Symptom prevalence and clustering of symptoms in people living with chronic hepatitis C infection
No full textQuality of life has been shown to be poor among people living with chronic hepatitis C. However, it is not clear how this relates to the presence of symptoms and their severity. The aim of this study was to describe the typology of a broad array of symptoms that were attributed to hepatitis C virus (HCV) infection. Phase 1 used qualitative methods to identify symptoms. In Phase 2, 188 treatment-naïve people living with HCV participated in a quantitative survey. The most prevalent symptom was physical tiredness (86%) followed by irritability (75%), depression (70%), mental tiredness (70%), and abdominal pain (68%). Temporal clustering of symptoms was reported in 62% of participants. Principal components analysis identified four symptom clusters: neuropsychiatric (mental tiredness, poor concentration, forgetfulness, depression, irritability, physical tiredness, and sleep problems); gastrointestinal (day sweats, nausea, food intolerance, night sweats, abdominal pain, poor appetite, and diarrhea); algesic (joint pain, muscle pain, and general body pain); and dysesthetic (noise sensitivity, light sensitivity, skin problems, and headaches). These data demonstrate that symptoms are prevalent in treatment-naïve people with HCV and support the hypothesis that symptom clustering occurs
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