Treatment of hepatitis c genotype 3,cold sores home remedies from canada,energetic healings today,the gale encyclopedia of alternative medicine - 4 volume set - Reviews

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Describe the preferred therapy for retreatment of patients with HCV genotype 3 chronic infection who have failed prior therapy. Medications used to Treat Hepatitis C: The HCV Medications section on this web site provides detailed information for each of the FDA-approved medications listed in the treatment recommendations, including links to the full prescribing information and to patient assistance programs. ALLY-3:The phase 3 ALLY-3 trial enrolled 152 patients with genotype 3 infection (101 treatment-naive and 51 treatment experienced).
VALENCE: This phase 3 trial examined the efficacy of sofosbuvir and ribavirin in treatment-naive and treatment-experienced patients with genotype 2 or 3. FISSION: This phase 3 trial enrolled 499 treatment-naive patients with genotype 2 or 3 HCV infection and randomized treatment to 12 weeks of sofosbuvir plus ribavirin versus 24 weeks of peginterferon plus ribavirin. POSITRON: This phase 3 trial enrolled patients with genotype 2 or 3 infection who were (a) not willing to receive interferon, (b) not able to receive interferon, or (c) were intolerant to a previous course of interferon. PROTON: In this two cohort phase 2 trial, which enrolled treatment-naive patients with genotypes 1, 2, or 3 and no evidence of cirrhosis, a total of 25 patients in cohort B with genotype 2 (n =15) or genotype 3 (n =10) received a 12-week course of sofosbuvir, ribavirin, and peginterferon. Discussion In the United States, hepatitis C virus (HCV) genotypes 2 and 3 comprise approximately 25 to 30% of all HCV infections[1,2]. Rates of sustained virologic response among patients with genotype 2 or 3 hepatitis C infection, shown for each study arm and stratified by low or high baseline HCV viral level.
In the subset of HCV genotype 2 or 3 patients in this study, sustained virologic response rates were not significantly different amongst weight categories of patients who received weight-based ribavirin. Interferon alfa engages receptors on the surface of the hepatocyte, initiating intracellular signal transduction that prompts the transcription of multiple interferon-stimulated genes (ISGs) that encode proteins that can interfere at various stages of the hepatitis C viral life cycle. In the SPRINT-2 trial, previously untreated patients with genotype 1 HCV infection received treatment with peginterferon and ribavirin, with or without boceprevir. Discuss preferred therapies for initial treatment of patients with genotype 1a or 1b chronic HCV. List the preferred therapy for retreatment of patients with HCV genotype 1a or 1b chronic infection who have previously failed therapy.
Key Studies to Support Recommendations for Genotype 1: The following key studies support the recommendations for treatment of patients with chronic hepatitis C and genotype 1 infection who are treatment naive or who have previously received treatment and had virologic relapse with a regimen that included peginterferon and ribavirin.
A1444040: The AI444040 trial had multiple treatment arms of daclatasvir and sofosbuvir, with or without ribavirin.
ION-3: In this phase 3 trial, treatment-naive patients with genotype 1 HCV received fixed dose combination of ledipasvir-sofosbuvir, with or without ribavirin, for 8 or 12 weeks. SAPPHIRE-I: This phase 3 trial enrolled treatment-naive patients with genotype 1 HCV to receive a 12-week treatment course with ombitasvir-paritaprevir-ritonavir and dasabuvir plus ribavirin. PEARL-III and PEARL-IV: These phase 3 trials enrolled treatment-naive patients to receive a 12-week treatment course with ombitasvir-paritaprevir-ritonavir and dasabuvir with or without ribavirin.
TURQUOISE-II: This phase 3 trial enrolled treatment-naive and treatment-experienced patients with genotype 1 chronic HCV, including those with compensated cirrhosis, to receive a 12- or 24-week treatment course with ombitasvir-paritaprevir-ritonavir and dasabuvir plus ribavirin. OPTIMIST-1: In this randomized, phase 3, open-label trial, investigators compared an 8-week versus 12-week regimen of simeprevir plus sofosbuvir in HCV genotype 1, treatment-naive and treatment-experienced patients without cirrhosis.
OPTIMIST-2: This randomized, phase 3, open-label, single-arm trial examined the effectiveness and safety of a 12-week treatment course with simeprevir plus sofosbuvir in treatment-naive or treatment experienced patients with chronic HCV genotype 1 and compensated cirrhosis.
Factors to Consider Prior to Choosing Treatment Regimen: For patients with chronic hepatitis C genotype 1 infection who have treatment experience, the primary factors that determine the recommended regimen and duration of treatment are presence of cirrhosis, the prior regimen used when treatment failure occurred, and in some instances, genotype 1 subtype.
Accordingly, less extensive clinical trial data exists for genotype 3 than with genotype 1. The management of genotype 3 patients with decompensated cirrhosis, renal impairment, HIV coinfection, acute hepatitis C infection, or post-liver transplantation is not addressed in this lesson. The recommendations listed below are for patients with hepatitis C genotype 3 infection who are treatment naive. After very poor results were observed using a 12-week course for patients with genotype 3, the protocal was modified to so that patients with genotype 3 received 24 weeks of therapy. For patients with genotype 3 infection, 102 (56%) of 183 achieved an SVR12 with sofosbuvir plus ribavirin, compared with 110 (63%) of 176 of those treated with peginterferon plus ribavirin. Overall, 23 (92%) of the 25 patients with genotype 2 or 3 met criteria for SVR24; the results were not broken down by genotype 3 versus genotype 2.
In treatment-experienced genotype 3 patients, clinical experience combined with limited data from clinical trials to date have suggested the regimen of sofosbuvir plus ribavirin may be suboptimal, with an estimated response rate of 80% among cirrhotics with the 24-week regimen. The retreatment of genotype 3 patients with decompensated cirrhosis, renal impairment, HIV coinfection, acute hepatitis C infection, or post-liver transplantation is not addressed in this lesson. The recommendations listed below are for patients with hepatitis C genotype 3 infection who are treatment experienced and failed prior therapy with peginterferon and ribavirin.
Peginterferon-alpha 2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose.


Triple therapy with peginterferon and ribavirin plus telaprevir or boceprevir is recommended for genotype 1 infection (Figure 1. Enrollment included treatment-naive and treatment-experienced patients with genotype 1 and treatment-naive with genotype 2 or 3. Overall, treatment with simeprevir plus sofosbuvir resulted in an SVR12 in 86 (83%) of 103 patients. Patients with HCV genotype 3, when compared with HCV non-3 genotypes, have relatively faster rates of fibrosis progression, higher prevalence of severe (Grade 3) steatosis, and a higher incidence of hepatocellular carcinoma.
Among the treatment-naive patients with genotype 3 who received a 24-week treatment course of therapy, 99 (94%) of 105 achieved an SVR12; presence of cirrhosis did not significantly impact results for the treatment-naive genotype 3 patients with the 24-week treatment course. The results with a 12-week course of sofosbuvir plus ribavirin in genotype 3 patients were disappointing when compared with those observed in patients with genotype 2 infection.
For patients with genotype 3 infection, 60 (61%) of 98 achieved an SVR12 with sofosbuvir plus ribavirin. Six of the treatment arms involved treatment-naive patients with genotype 2 or 3 infection who received sofosbuvir monotherapy for 12 weeks, sofosbuvir plus ribavirin for 12 weeks, or sofosbuvir (12 weeks) plus ribavirin (8 to 12 weeks) plus peginterferon (4 to 12 weeks).
With most regimens, the baseline HCV RNA value does not influence the treatment choice or duration. The recommended four regimens for genotype 1a or 1b are listed in alphabetical order and are considered to have similar efficacy.
In Cohort 2, 40 (46%) of 87 patients were treatment naive and had advanced fibrosis (Metavir scores of F3-F4).
In the treatment-naive patients, the SVR12 rates with the 12-week regimen were superior to the 8-week regimen (97% versus 85%).
For the treatment-naive patients with genotype 3 infection, the superiority of the results with the 12-week regimen of sofosbuvir plus ribavirin plus peginterferon was maintained in patients with or without cirrhosis. With this 12-week treatment course, cirrhosis appeared to greatly impact the SVR12 response rates patients with genotype 3 infection: 3 (21%) of 14 in patients with cirrhosis obtained an SVR12 compared with 57 (68%) of 84 of those without cirrhosis. Forty (70%) of the 60 patients enrolled with genotype 2 or 3 infection had genotype 3 infection. Historically, genotype 1 hepatitis C has been considered the most difficult to treat hepatitis C genotype. For the treatment-naive genotype 1 patients treated with a 12-week course of daclatasvir plus sofosbuvir, with or without ribavirin, 80 (98%) of 82 achieved an SVR12. In the treatment-naive patients, the SVR12 rates were greater than 90% and similar with or without ribavirin and regardless of whether the patient received 12 or 24 weeks of therapy. This study demonstrates the all-oral 12-week regimen of simeprevir plus sofosbuvir is highly effective and well tolerated in treatment-naive and treatment-experienced HCV genotype 1 patients without cirrhosis. In the combined data for treatment-naive and treatment-experienced patients wtih genotype 1a infection, the SVR12 rates were higher in the group without the baseline Q80K mutation than those with the baseline Q80K mutation (92% versus 74%). It is important to note that pre-treatment resistance testing is now recommmended in cirrhotic patients who experienced treatment failure with a prior regimen that included any NS5a inhibitor, including daclatasvir plus sofosbuvir, ledipasvir-sofosbuvir, or ombitasvir-paritaprevir-ritonavir plus dasabuvir. Even with the introduction of newer direct-acting antiviral therapies available in 2015, treatment of genotype 3 has been difficult genotype to successfully treat, especially in patients with cirrhosis.
In contrast, the direct-acting antiviral agents, daclatasvir and sofosbuvir, have good activity against genotype 3. Excluding the sofosbuvir monotherapy arm (which did not perform well), the remaining 50 (100%) of 50 patients with genotype 2 or 3 achieved an SVR24. This discussion will review the current treatment of genotypes 2 and 3, as well as provide some background on clinical factors that may influence the management of patients with these genotypes. This study demonstrates that the all-oral 12-week regimen of simeprevir plus sofosbuvir is generally effective in treatment-naive patients with cirrhosis and HCV genotype 1, except that patients with genotype 1a and the baseline Q80K mutation have lower SVR rates.
The retreatment of genotype 1 patients with decompensated cirrhosis, renal impairment, HIV coinfection, acute hepatitis C infection, or post-liver transplantation is not addressed here. Clinical trials involving patients with genotype 2 or 3 infection have examined the efficacy of sofosbuvir plus weight-based ribavirin given for 12- to 16 weeks and have reported substantially lower SVR rates (30 to 60%) in patients with genotype 3 than with genotype 2 infection. The following discussion will summarize the medications used for treatment of hepatitis C, with an emphasis on mechanism of action, preparations and dosing, adverse effects, and appropriate use as part of combination therapy. In late 2013 and most of 2014, the standard of care for initial therapy of genotype 1 consisted of peginterferon plus ribavirin plus either sofosbuvir or simeprevir.
The following discussion regarding initial treatment and retreatment of patients with genotype 3 chronic hepatitis C assumes the patient and their clinician have already made the decision to initiate hepatitis C therapy.
The relatively lower SVR rates with genotype 3 can be improved by using a 12-week course of sofosbuvir plus ribavivirin plus peginterferon or extending the all-oral sofosbuvir plus ribavirin regimen to 24 weeks.
In 2015, the standard of care for genotype 1 consists of all-oral therapy; the new oral direct-acting antiviral agents used to treat HCV genotype 1 include daclatasvir, fixed-dose ledipasvir-sofosbuvir, fixed-dose ombitasvir-paritaprevir-ritonavir and dasabuvir, simeprevir, and sofosbuvir.


All of these agents, except for daclatasvir, are FDA approved for the treatment of genotype 1 HCV. Early data suggest some polymerase inhibitors have greater activity across all genotypes and may have a role in the treatment of genotype 2 or 3 infection[8]. Further subset analysis revealed that patients with genotype 2 or 3 infection who had higher viral loads or advanced liver fibrosis did not benefit from a more intensive regimen.
These symptoms typically become more pronounced during the few days immediately following the injection, although usually resolve completely after 4 to 6 weeks of treatment. Although current guidelines recommend 24 weeks as optimal therapy for genotypes 2 and 3, these same guidelines acknowledge that shorter duration of therapy may be considered in those who attain a rapid virologic response[4].
Persons with a history of psychiatric illness may have enhanced susceptibility for developing depressive symptoms while on interferon treatment[10]. Neurovegetative symptoms that may include fatigue, sleep disturbance, and psychomotor slowing can also occur during treatment. These neuropsychiatric symptoms tend to become more pronounced as treatment duration extends[9].
Weight-based ribavirin may also benefit this subset of patients with genotypes 2 or 3 infection who do not achieve a RVR.
One retrospective analysis of genotype 2 or 3 patients who did not achieve an RVR found a trend toward higher SVR rates among those who received 48 weeks of weight-based ribavirin compared with those in other treatment categories (24 weeks of weight-based ribavirin, 24 weeks of fixed-dose ribavirin, or 48 weeks of fixed-dose ribavirin)[22]. Among those that attained a rapid virologic response, SVR rates were similar (83 to 86%) between genotype 2 and 3 patients, regardless of duration of therapy (12 to 16 weeks or 24 weeks) or baseline HCV RNA levels. These data suggest that patient with genotype 3 may benefit from a longer duration of therapy, particularly if other poor prognostic factors, such as high baseline viral level and lack of RVR, exist. This has led to the identification of a subset of patients with genotype 1 HCV infection (those with the IL28B CC genotype) who have higher SVR rates with interferon-based therapy (compared to those with the IL28B CT or TT alleles)[25]. In contrast, the association between the IL28B polymorphism and SVR does not appear to be a consistent finding for patients with genotype 2 or 3 infection; the influence of this genetic variation on SVR appears to be more attenuated in this population. A more recent study noted that the IL28B CC genotype was an independent predictor of SVR primarily in patients with genotype 2 or 3 infection who did not achieve an RVR[26]. Further data may help clarify how these predictors of SVR can be used to individualize HCV therapy in patients with genotype 2 or 3. Assessment of hepatitis C virus RNA and genotype from 6807 patients with chronic hepatitis C in the United States. Patients with chronic hepatitis C who are of reproductive age should be advised to use two forms of contraception during treatment and at least 6 months following the end of therapy[11,12]. Hemolytic anemia is one of the main toxicities of ribavirin and occurs within 1 to 2 weeks of treatment and may be accompanied by a rise in indirect bilirubin.
Hemoglobin or hematocrit should be checked before starting treatment as well as at weeks 2 and 4 and every 4 to 8 weeks thereafter as indicated.
The ultimate duration of triple therapy for either drug depends on a variety of patient factors, including the initial HCV response to treatment, presence of cirrhosis, and past treatment history.
Individualized treatment with combination of Peg-interferon alpha 2b and ribavirin in patients infected with HCV genotype 3.
Peginterferon alfa-2b plus ribavirin for treatment of chronic hepatitis C in previously untreated patients infected with HCV genotypes 2 or 3.
An update on treatment of genotype 1 chronic hepatitis C virus infection: 2011 practice guideline by the American Association for the Study of Liver Diseases. An IL28B polymorphism determines treatment response of hepatitis C virus genotype 2 or 3 patients who do not achieve a rapid virologic response. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Interferon-induced depression in chronic hepatitis C: a systematic review and meta-analysis.
Relationship between adherence to hepatitis C virus therapy and virologic outcomes: a cohort study. Protease inhibitors for the treatment of chronic hepatitis C genotype-1 infection: the new standard of care. A practical guide for the use of boceprevir and telaprevir for the treatment of hepatitis C.



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