Ifn Monotherapy In Acute Hepatitis C
Although the short courses of standard IFN monotherapy introduced in the 1980s by Hoofnagle et al, Davis et al, and Di Bisceglie et al led to sustained improvement in liver disease and loss of virus in less than 10% of patients, these therapies were the first to cure chronic viral hepatitis.
Jaeckel et al reported that treatment with IFN alfa-2b prevented chronic infection in 98% of a group of 44 German patients with acute hepatitis C. In this study, patients received 5 million U/day of IFN alfa-2b subcutaneously for 4 weeks and then three times per week for another 20 weeks the IFN alfa-2b was well tolerated in all patients but one.
Because it has the poorest safety profile of all the HCV antiviral agents, with few exceptions PEG-IFN is no longer recommended in combination regimens. Spontaneous resolution of acute HCV infection may occur in 15% to 50% of patients. Monitoring for spontaneous clearance for a minimum of 6 months before initiating any treatment is therefore recommended.
World Health Organization. Hepatitis C: fact sheet. Available at . Updated: October 2017 Accessed: January 23, 2018.
Frank C, Mohamed MK, Strickland GT, et al. The role of parenteral antischistosomal therapy in the spread of hepatitis C virus in Egypt. Lancet. 2000 Mar 11. 355:887-91. .
Kim A. Hepatitis C virus. Ann Intern Med. 2016 Sep 6. 165 :ITC33-ITC48. .
Svr Rates By Genotype
Based on five studies, pooled SVR rate for HCV-4 was 52.7% . Corresponding pooled SVR rates for HCV-1 and HCV-2/3 were 43.7% and 72.9% , respectively. Statistically significant heterogeneity was found in the analysis of each genotype and this may be attributed to variation in the patient characteristics and methodologies among the included studies.
Ombitasvir Paritaprevir And Ritonavir
Doctors may prescribe this combination of drugs to treat hepatitis C genotype 4. They may also prescribe ribavirin.
- Facts about Technivie include:
- Treatment time is 12 weeks.
- Dosage is a fixed-dose combination of 12.5 mg ombitasvir, 75 mg paritaprevir, and 50 mg ritonavir taken once daily.
- Common side effects include weakness, tiredness, nausea, and sleep problems.
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Treatment Of Hcv Genotype 3 Infection In Non
The combination of SOF plus RBV for 24 weeks was the first interferon-free therapy for patients with HCV genotype 3 infection approved by the FDA. International guidelines differ regarding the recommendations for this regimen. EASL guidelines do not recommend this therapeutic regimen for treatment-experienced cirrhotic patients. On the other hand, AASLD recommends SOF plus RBV as an alternative regimen for patients without cirrhosis with previous PegIFN/RBV failure or treatment-naive patients who are IFN-ineligible .
In naive non-cirrhotic patients with HCV genotype 3 infection, SOF plus RBV for 12 weeks resulted in an overall SVR of 61-68%. However, extending the treatment to 24 weeks led to an approximate 30% increase in SVR rates, ranging from 90 to 96% .
Two large clinical trials evaluated the efficacy of SOF plus RBV for 12 weeks in naive, non-cirrhotic patients infected with HCV genotype 3. The Fission trial included 145 patients, but only 89 achieved SVR . The Positron trial included 84 naive patients who were interferon-ineligible or intolerant, of which 57 reached SVR . The Boson clinical trial found higher SVR among naive and non-cirrhotic patients treated with SOF plus RBV for 16 weeks. Among 70 patients treated, 58 achieved SVR . Another arm of this study evaluated 72 naive non-cirrhotic patients treated for 24 weeks, with an overall SVR of 90% . SOF plus RBV for 24 weeks was also used in the Valence trial, which included 92 patients and 87 achieved SVR .
Epidemiology Of Hepatitis C Virus Genotypes And Genotypic Variations Around The World
HCV is divided into six distinct genotypes throughout the world with multiple subtypes in each genotype class. A genotype is a classification of HCV virus based on the genetic material in the RNA strands .
Figure 1.1.3. Genotypes of hepatitis C virus.
Genotypes 1, 2, and 3 have a worldwide distribution . Types HCV G1a and G1b predominate in Europe, North and South America, and Japan, accounting for about 60% of global infections. HCV G2 is common in Japan and China and is found in the United States and in northern, western, and southern Europe . HCV G3 is prevalent in Southeast Asia, India, and Australia and is variably distributed in Europe and the United States . HCV G4 is principally found in the Middle East, Egypt, and central Africa . HCV G5 is almost restricted to South Africa , and HCV G6 is found in specific regions in Asia .
Figure 1.1.4. Geographical distribution of hepatitis C virus genotypes.
Osi Obadahn, Sanaa M. Kamal, in, 2018
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Medications Used To Treat Hcv Genotype 2
The HCV Medications section on this website provides detailed information for each of the Food and Drug Administration -approved medications listed in the treatment recommendations, including links to the full prescribing information and to patient assistance programs. The direct-acting antiviral agents exert their action at specific steps in the HCV life cycle. There are three major classes of direct-acting antiviral medications: nonstructural proteins 3/4A protease inhibitors, NS5A inhibitors, and NS5B polymerase inhibitors the NS5B polymerase inhibitors include the nucleoside analogs and nonnucleoside analogs. Adherence with the treatment regimen is of paramount importance. Accordingly, patients should receive detailed counseling regarding the importance of adherence prior to starting therapy and clinicians should provide intensive follow-up during therapy.
Approach To Choosing Hcv Genotype 2 Treatment Regimen
For patients chronically infected with genotype 2 HCV, two key factors influence the choice and duration of therapy: cirrhosis status and prior treatment experience. In addition, the cost of the regimen, insurance coverage, concurrent medications, and patient and provider preference can play a major role in the regimen choice. The following treatment recommendations are based on the AASLD-IDSA HCV Guidance for initial treatment of adults with HCV genotype 2 and for retreatment of adults in whom prior therapy failed, including those with HCV genotype 2.
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Cautions Discusses Conditions That May Cause Diagnostic Confusion Including Improper Specimen Collection And Handling Inappropriate Test Selection And Interfering Substances
An “Undetected” or “Indeterminate” hepatitis C virus genotype result does not rule-out active HCV infection. Test results should be correlated with routine serologic and molecular-based testing, as well as clinical presentation. Specimens with indeterminate results will be automatically evaluated with the subsequent test HCVGR / Hepatitis C Virus Genotype Resolution, Serum.
Known cross-reactivity between the assay probes and various HCV genotypes limits the ability of this assay to identify multiple HCV genotypes present in a given specimen. Such cross-reactivity or the actual presence of multiple HCV genotypes in the same specimen may result in an “Indeterminate” or multiple/mixed genotype result.
Patients Who Have Previously Received Therapy
|Adverse event more frequent in triple therapy arm||Anemia, dysgeusia||Rash, anemia, pruritus, nausea, diarrhea|
- NA, not available PR, peginterferon plus ribavirin RCT, randomized, controlled trial SAE, serious adverse event SVR, sustained virological response.
- * A lead-in arm was included in the telaprevir retreatment trial but the FDA approved regimen did not include a lead-in strategy.
- â The BOC trial design included a 4-week lead-in phase of PegIFN and RBV and compared response-guided triple therapy and a fixed duration triple therapy given for 44 weeks to peginterferon and ribavirin therapy. BOC/RGT response-guided therapy patients who achieved an eRVR received an additional 24 weeks . If an eRVR was not achieved but HCV RNA became undetectable at week 12, BOC was stopped at week 32, and patients received an additional 12 weeks of SOC treatment . BOC/PR48: 4-week lead-in with peginterferon and ribavirin followed by a fixed duration of triple therapy for 44 weeks PR48: PegIFN and RBV administered for 48 weeks.
- â¡Telaprevir plus peginterferon and ribavirin administered with and without a 4 week SOC treatment lead in versus standard of care . T12PR48: TVR administered for 12 weeks followed by 36 weeks of peginterferon and ribavirin LI-T12/PR48: peginterferon and ribavirin for 4 weeks followed by TVR plus peginterferon and ribavirin for 12 weeks, followed by peginterferon and ribavirin for 32 weeks PR48: peginterferon and ribavirin administered for 48 weeks.
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Understanding Mutations Of Hepatitis C Genotypes
In addition to the different hepatitis C genotypes and subtypes, there are also quasispecies of the virus. After HCV infects the liver, the virus is constantly reproducing or making copies of itself. This happens on an almost unimaginable scale, with trillions of individual viruses replicating every day. As viruses replicate, some of the copies they make contain errors or mutations in their genetic code. Sometimes, a mutation results in a quasispecies of HCV that is successful at evading the bodys immune system. The immune system is constantly trying to catch up with the HCV virus as it produces slightly different versions of itself. Once the body has successfully eradicated an HCV quasispecies, another takes its place. Experts believe that this process of mutation and quasispecies development is the reason why so many people who are infected with HCV develop chronic disease and why infection is so difficult to cure. This also may be why it is so difficult to develop a vaccine against HCV.3
Sofosbuvir Plus Daclatasvir With Or Without Rbv
The combination SOF plus DCV for 12 weeks is recommended by EASL and AASLD for the treatment of patients with HCV genotype 3 infection . In non-cirrhotic patients with HCV genotype 3 infection, whether naive or treatment-experienced, SOF plus DCV with or without RBV for 12 or 24 weeks resulted in an overall SVR of 80100% .
Among naive or treatment-experienced patients without cirrhosis, treatment with SOF plus DCV for 12 weeks resulted in an overall SVR of 9497% . Two studies evaluated SOF plus DCV for 12 weeks in naive or treatment-experienced non-cirrhotic patients with HCV genotype 3 infection . ALLY-3, a phase III clinical trial, included 75 naive and 34 previously treatment-experienced patients and SVR rates were, respectively, 97% and 94% . An observational study included 25 naive and treatment-experienced patients, 24 of whom achieved SVR .
A single study, ALLY-3+, evaluated the addition of RBV to SOF plus DCV for 12 or 16 weeks for HCV genotype 3 naive or treatment-experienced patients without cirrhosis, including 14 patients with advanced fibrosis, but without cirrhosis. Six patients were treated for 12 weeks and 8 patients were treated for 16 weeks with SOF plus DCV and RBV, with all of them achieving SVR12 in both the 12- and 16-week treatment arms plus sofosbuvir plus ribavirin for 12 or 16 weeks in HCV genotype 3-infected patients with advanced fibrosis or cirrhosis: The ALLY-3+ phase 3 study. AASLD Liver Meeting 2015. San Francisco, November 1317, 2015.).
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Comparison Of Svr In Hcv Genotype 6 Group Versus Hcv Genotype 1 Or Genotype 3 Group
The 7 included studies involving 1415 patients reported the rate of SVR in patients with genotype 6 HCV infection versus patients with genotype 1 HCV infection. As the heterogeneity among these studies was significant , the random-effect method was applied to calculate the overall effects. The SVR was similar between the HCV-6 group and the HCV-1 group .4). In addition, the sensitivity analysis was performed through the sequential omission of every study the results showed that the significance of the ORs was not influenced excessively.
Meta-analysis of sustained virological Response in patients with chronic genotype 6 hepatitis C virus infection versus patients with chronic genotype 1 HCV infection. CI = confidence interval.
The 3 included studies involving 252 patients reported the rate of SVR in HCV-6 versus HCV-3 patients. The between-study heterogeneity was not significant when the 3 studies were pooled into a meta-analysis , the fixed-effect method was applied to calculate the overall effects. The rate of SVR was similar between the patients with genotype 6 HCV infection and the patients with genotype 3 HCV infection .
Sofosbuvir Velpatasvir And Voxilapresvir
This drug combination is similar to Epclusa but also includes a drug called voxilapresvir.
Facts about Vosevi include:
- Treatment time is 12 weeks for people without cirrhosis or compensated cirrhosis .
- Dosage is fixed at 400 mg of sofosbuvir, 100 mg of velpatasvir, and 100 mg of voxilapresvir once per day with food.
- Common side effects include tiredness, a headache, diarrhea, and nausea.
Doctors often recommend Vosevi for people who have had previous treatment for hepatitis C that did not work.
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Clinical Significance Of Hepatitis C Genotypes
Genotype generally has not been found in epidemiological studies to play a large rolein liver disease progression due to HCV. Rather, genotype is of clinical importanceprincipally as a factor in selecting the appropriate HCV medications for treatment. Please see the HCV Treatment Considerations for more information.
What Are Hepatitis C Genotypes
Hepatitis C is split into six unique genotypes all over the world these genotypes have along with several subtypes. However, it is labelled into 1 to 6 types. In these days many people are infected with genotype 1. People are infected by anyone genotype, each contains the combination of their relevant viruses which known as quasi-species. There is alternative medical treatment avail for hepatitis c virus. Different genotypes react differently so it is very important to know about Hepatitis C genotype before treatment. For this, testing will be processed with a blood test. Doctor offer drug treatment based on the type of HCV genotype infected on your body. To cure HCV different treatment is undertaken for a specific person. Genotype is consisting of nucleic acid which presents on the DNA molecule. Exclusive techniques are used for different phenotypes. It is various forms or alleles. On the treatment, doctors understand current immune and process treatment faster.
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Hepatitis C And Health
How can health-care personnel avoid exposure to HCV?
Avoiding occupational exposure to blood is the primary way to prevent transmission of bloodborne illnesses among health-care personnel. To promote blood safety in the workplace, health-care personnel should consult infectious-disease control guidance from the National Institute for Occupational Safety and Health and from CDC. Depending on the medical procedure involved, Standard Precautions may include the appropriate use of personal protective equipment .
What is the risk of acquiring hepatitis C after being accidentally exposed to HCV-contaminated blood or body fluids in the workplace?
Although sharps injuries have decreased in recent decades due to improved prevention measures, they continue to occur, placing health-care personnel at risk for several bloodborne pathogens like hepatitis C. A recent analysis of several studies revealed an overall 0.2% risk for infection among those exposed to HCV-antibody-positive blood through needlestick or sharps injuries . Updated guidelines for management and treatment of hepatitis Cexternal icon are available to provide guidance for health-care personnel who become infected via exposure to contaminated blood at the workplace.
Other than needlesticks, do other exposures place health-care personnel at risk for hepatitis C?
Should HCV-infected health-care personnel be restricted in their work?
How Is Genotype Determined
A simple blood test can be used to determine your hepatitis C genotype. The test doesnt have to be repeated because once someone has been infected with HCV, the genotype remains the same. It is possible to be infected by more than one HCV genotype. However, this occurs rarely.
Learn more about recommended treatment based on HCV genotype.
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Guided Treatment Of Hepatitis C Virus
The appropriate duration of treatment for HCV infection varies depending on the HCV strain that infects the patient. HCV genotypes 2 and 3 respond much better to standard treatment regimens. Thus, only 24 weeks of therapy are needed to achieve maximum benefit, compared to 48 weeks in persons infected with other HCV genotypes. In current clinical practice, treatment is offered to all patients with HCV infection except those with decompensated cirrhosis, where treatment may lead to worsening of the patients condition. Once treatment is initiated, the most reliable means to determine efficacy is to evaluate the response by measuring HCV RNA. Successful treatment is associated with at least two different phases of viral clearance. The first phase, which occurs rapidly over the course of days, is thought to reflect HCV RNA clearance from a circulating pool through the antiviral effect of interferon. In the second phase of clearance, infected liver cells undergo cell turnover and are replaced by uninfected cells. The second phase of clearance is more variable in duration. First-phase clearance is less specific for detecting success of antiviral treatment therefore, it is necessary to evaluate whether second-phase clearance has occurred.
Ahmed Abdel Aziz, in, 2018
What Tests Are Needed For Knowing My Genotype
When screening for HCV, a patient takes several tests to make a diagnosis .
Once a patient has been diagnosed with HCV, the doctor will run viral load level and genotype tests before starting treatment. Knowing a patients genotype determines the best treatment regimen.
Genotype tests use blood taken from fingersticks or simple blood draws. A patient might need to return to the doctors office to confirm whether the infection is chronic or to confirm whether they have been cured of the virus.
Genotypes 1a and 1b may require a patient to take additional blood tests to determine whether the virus has any resistance .
HCV treatment is now simpler, safer, and more effective, and diagnostics, including HCV genotyping, need to become simpler and less expensive.
The medications are available depending on the payer or what is available in a country or region.
What Is Genotype 2 Hepatitis C Virus
The symptoms of the genotype are basically the same as those associated with the other HCV genotypes. It is also contracted in the same ways by coming into contact with contaminated blood like in blood transfusions. However, genotype 2, along with genotype 3, is generally easier to treat than genotype 1.
Genotype 2 hepatitis C has traditionally been treated with two drugs: interferon and ribavirin. Interferon is administered via injection. Frequency of these injections varies, usually from one to three times per week. Ribavirin is taken in pill form, usually twice daily. Together, the two drugs make up the usual combination treatment. However, additional medications have become available for hepatitis C such as sofosbuvir. It’s important to keep in mind that the specific drug treatment for hepatitis C depends on the genotype, as well as its severity and complications. Therefore, the treatment should be decided through a careful and informed consideration with one’s doctor.
Unfortunately, the drugs used to treat genotype 2, as well as other hepatitis C genotypes, can cause side effects. Patients may experience flu-like symptoms and low red or white blood cell counts. Irritability and depression may occur as well.