GuidelinesPerspective

AASLD/IDSA release updated HCV treatment guidelines

The AASLD and IDSA HCV Guidance Panel has released updated guidelines for the treatment of hepatitis C virus infection, according to newly published data in Hepatology.

“The goal of the hepatitis C guidance is to provide up-to-date recommendations for HCV care practitioners on the optimal screening, management, and treatment for adults with HCV infection in the United States, using a rigorous review process to evaluate the best available evidence,” the researchers wrote. “This review provides a condensed summary of recommendations from the guidance.”

Michael Saag

Michael S. Saag

The panel, which included HCV Next Editorial board members Arthur Y. Kim, MD, and Michael R. Charlton, MD, and HCV Next Co-Chief Editor Michael S. Saag, MD, used an evidence-based approach to review available information for the HCV guidance. Sources of information included peer-reviewed research; FDA research and safety information on products; manufacturer information; drug interaction data; prescribing information from FDA-approved products; and more.

Key recommendations were outlined in various topics: HCV testing and linkage to care, when and in whom to begin HCV therapy, the initial treatment of HCV, treating unique patient populations, HIV/HCV coinfection and acute HCV.

HCV testing and linkage to care

The panel recommends a one-time HCV test in people born between 1945 and 1965, as well as other people based on exposures, behaviors and conditions that may increase risk for contracting HCV. Every person that is recommended for HCV testing should be tested for anti-HCV using an FDA-approved test, according to the researchers, with positive results being confirmed through nucleic acid testing for HCV RNA. The panel also recommends annual testing be performed on men who have sex with men and people who inject drugs, as these populations are at increased risk.

Arthur Kim, MD

Arthur Y. Kim

Who should get HCV treatment and when

The panel recommends antiviral treatment for anyone diagnosed with chronic HCV infection, with the exception of people with limited life expectancy due to “non-hepatic causes.” If resources are limited for the patient to get treatment, the panel deems it “most appropriate to treat those at greatest risk of disease complications before treating those with less advanced disease,” according to the guidelines. To determine those at greatest risk for complications, the panel recommends noninvasive testing or liver biopsy for assessing hepatic fibrosis stage, which determines the urgency for treatment.

Initial treatment of HCV

Treatment-naive patients with HCV and different genotypes have posed a challenge. Some of the treatment recommendations from the panel for the various genotypes are: for treatment-naive patients with HCV genotype 1a, the panel recommends a daily fixed-dose combination of Harvoni (ledipasvir/sofosbuvir, Gilead Sciences) for 12 weeks, a daily fixed-dose combination of Viekira Pak (paritaprevir/ritonavir/ombitasvir/dasabuvir, AbbVie) and weight-based ribavirin (RBV) for 12 weeks in patients without cirrhosis or 24 weeks in patients with cirrhosis, among other treatments. For treatment-naive patients with HCV genotype 2, the panel recommends a daily regimen of Sovaldi (sofosbuvir, Gilead Sciences) and weight-based RBV for 12 weeks. For patients with HCV genotype 3, the panel recommends a daily sofosbuvir and weight-based RBV plus weekly pegylated-interferon (PEG-IFN) for 12 weeks for patients eligible to take PEG-IFN. For patients unable to take PEG-IFN, a daily sofosbuvir and weight-based RBV regimen for 24 weeks is recommended. See the list of guidelines for other genotypes and treatment recommendations.

Retreating patients who failed prior therapy

The panel recommends various regimens for treating this type of patient population, including ledipasvir/sofosbuvir and Olysio (simeprevir, Janssen Therapeutics) in combination with sofosbuvir. Treatments vary for patients with different genotypes, with and without cirrhosis, as well as patients who failed prior treatment with PEG-IFN and RBV.

Monitoring patients before, during and after antiviral therapy

The panel recommends all patients with HCV be evaluated prior to starting therapy, during treatment, and following discontinuation of treatment “in order to determine the severity of their liver disease and the efficacy and safety of their HCV treatment,” according to the research. Patients who fail to achieve sustained virologic response should undergo the following: a disease progression assessment every 6 to 12 months; ultrasound testing for HCC every 6 months in patients with advanced fibrosis; endoscopic surveillance in those with cirrhosis; among other recommendations. In patients who achieved SVR, the following is recommended: surveillance for HCC with twice-yearly abdominal imaging in those with fibrosis, patients without advanced fibrosis will no longer need to undergo additional follow-up, undergo an assessment for HCV recurrence or reinfection if the patient experiences some sort of hepatic dysfunction, among other recommendations.

Michael Charlton

Michael R. Charlton

Treating unique patient populations

The panel recommends patients with decompensated cirrhosis be referred to a medical practitioner who is highly experienced in the management of advanced liver disease and HCV treatment, according to the research. In treatment-naive and -experienced patients who experience recurrent HCV after liver transplantation, a recommended treatment regimen is a daily fixed-dose combination of ledipasvir/sofosbuvir with weight-based RBV for 12 weeks for patients with HCV genotype 1 or 4 infection in the allograft. Non genotype 1 patients who are treatment-naive and treatment-experienced with HCV genotype 2 in the allograft should

undergo a daily regimen of sofosbuvir and weight-based RBV for 24 weeks.

HIV/HCV co-infection

The panel states in the research: “HIV/HCV-co-infected persons should be treated and retreated the same as persons without HIV infection, after recognizing and managing interactions with antiretroviral medications. Antiretroviral treatment interruption to allow HCV therapy is not recommended. … Drug switches, when needed, should be done in collaboration with the HIV practitioner.”

Specific drug combinations (that may cause interactions) that providers should be mindful of in co-infected patients are ledipasvir, sofosbuvir and ledipasvir/sofosbuvir, PrOD, simeprevir and RBV.

Acute HCV infection

“Infection with HCV is considered to be acute during the first 6 months,” the researchers wrote. A few recommendation from the panel for diagnosing and treating acute HCV infection include: undergoing HCV antibody and HCV RNA testing when acute HCV infection is suspected, regular laboratory monitoring until alanine aminotransferase levels are normal and HCV RNA is undetectable, and counseling to prevent transmission and other “hepatotoxic insults.” – by Melinda Stevens

Disclosures: Please see the full study for a list of all authors’ relevant financial disclosures.

Editor's Note: This article has been corrected to reflect the correct manufacturer of simeprevir. 

 

The AASLD and IDSA HCV Guidance Panel has released updated guidelines for the treatment of hepatitis C virus infection, according to newly published data in Hepatology.

“The goal of the hepatitis C guidance is to provide up-to-date recommendations for HCV care practitioners on the optimal screening, management, and treatment for adults with HCV infection in the United States, using a rigorous review process to evaluate the best available evidence,” the researchers wrote. “This review provides a condensed summary of recommendations from the guidance.”

Michael Saag

Michael S. Saag

The panel, which included HCV Next Editorial board members Arthur Y. Kim, MD, and Michael R. Charlton, MD, and HCV Next Co-Chief Editor Michael S. Saag, MD, used an evidence-based approach to review available information for the HCV guidance. Sources of information included peer-reviewed research; FDA research and safety information on products; manufacturer information; drug interaction data; prescribing information from FDA-approved products; and more.

Key recommendations were outlined in various topics: HCV testing and linkage to care, when and in whom to begin HCV therapy, the initial treatment of HCV, treating unique patient populations, HIV/HCV coinfection and acute HCV.

HCV testing and linkage to care

The panel recommends a one-time HCV test in people born between 1945 and 1965, as well as other people based on exposures, behaviors and conditions that may increase risk for contracting HCV. Every person that is recommended for HCV testing should be tested for anti-HCV using an FDA-approved test, according to the researchers, with positive results being confirmed through nucleic acid testing for HCV RNA. The panel also recommends annual testing be performed on men who have sex with men and people who inject drugs, as these populations are at increased risk.

Arthur Kim, MD

Arthur Y. Kim

Who should get HCV treatment and when

The panel recommends antiviral treatment for anyone diagnosed with chronic HCV infection, with the exception of people with limited life expectancy due to “non-hepatic causes.” If resources are limited for the patient to get treatment, the panel deems it “most appropriate to treat those at greatest risk of disease complications before treating those with less advanced disease,” according to the guidelines. To determine those at greatest risk for complications, the panel recommends noninvasive testing or liver biopsy for assessing hepatic fibrosis stage, which determines the urgency for treatment.

Initial treatment of HCV

Treatment-naive patients with HCV and different genotypes have posed a challenge. Some of the treatment recommendations from the panel for the various genotypes are: for treatment-naive patients with HCV genotype 1a, the panel recommends a daily fixed-dose combination of Harvoni (ledipasvir/sofosbuvir, Gilead Sciences) for 12 weeks, a daily fixed-dose combination of Viekira Pak (paritaprevir/ritonavir/ombitasvir/dasabuvir, AbbVie) and weight-based ribavirin (RBV) for 12 weeks in patients without cirrhosis or 24 weeks in patients with cirrhosis, among other treatments. For treatment-naive patients with HCV genotype 2, the panel recommends a daily regimen of Sovaldi (sofosbuvir, Gilead Sciences) and weight-based RBV for 12 weeks. For patients with HCV genotype 3, the panel recommends a daily sofosbuvir and weight-based RBV plus weekly pegylated-interferon (PEG-IFN) for 12 weeks for patients eligible to take PEG-IFN. For patients unable to take PEG-IFN, a daily sofosbuvir and weight-based RBV regimen for 24 weeks is recommended. See the list of guidelines for other genotypes and treatment recommendations.

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Retreating patients who failed prior therapy

The panel recommends various regimens for treating this type of patient population, including ledipasvir/sofosbuvir and Olysio (simeprevir, Janssen Therapeutics) in combination with sofosbuvir. Treatments vary for patients with different genotypes, with and without cirrhosis, as well as patients who failed prior treatment with PEG-IFN and RBV.

Monitoring patients before, during and after antiviral therapy

The panel recommends all patients with HCV be evaluated prior to starting therapy, during treatment, and following discontinuation of treatment “in order to determine the severity of their liver disease and the efficacy and safety of their HCV treatment,” according to the research. Patients who fail to achieve sustained virologic response should undergo the following: a disease progression assessment every 6 to 12 months; ultrasound testing for HCC every 6 months in patients with advanced fibrosis; endoscopic surveillance in those with cirrhosis; among other recommendations. In patients who achieved SVR, the following is recommended: surveillance for HCC with twice-yearly abdominal imaging in those with fibrosis, patients without advanced fibrosis will no longer need to undergo additional follow-up, undergo an assessment for HCV recurrence or reinfection if the patient experiences some sort of hepatic dysfunction, among other recommendations.

Michael Charlton

Michael R. Charlton

Treating unique patient populations

The panel recommends patients with decompensated cirrhosis be referred to a medical practitioner who is highly experienced in the management of advanced liver disease and HCV treatment, according to the research. In treatment-naive and -experienced patients who experience recurrent HCV after liver transplantation, a recommended treatment regimen is a daily fixed-dose combination of ledipasvir/sofosbuvir with weight-based RBV for 12 weeks for patients with HCV genotype 1 or 4 infection in the allograft. Non genotype 1 patients who are treatment-naive and treatment-experienced with HCV genotype 2 in the allograft should

undergo a daily regimen of sofosbuvir and weight-based RBV for 24 weeks.

HIV/HCV co-infection

The panel states in the research: “HIV/HCV-co-infected persons should be treated and retreated the same as persons without HIV infection, after recognizing and managing interactions with antiretroviral medications. Antiretroviral treatment interruption to allow HCV therapy is not recommended. … Drug switches, when needed, should be done in collaboration with the HIV practitioner.”

Specific drug combinations (that may cause interactions) that providers should be mindful of in co-infected patients are ledipasvir, sofosbuvir and ledipasvir/sofosbuvir, PrOD, simeprevir and RBV.

Acute HCV infection

“Infection with HCV is considered to be acute during the first 6 months,” the researchers wrote. A few recommendation from the panel for diagnosing and treating acute HCV infection include: undergoing HCV antibody and HCV RNA testing when acute HCV infection is suspected, regular laboratory monitoring until alanine aminotransferase levels are normal and HCV RNA is undetectable, and counseling to prevent transmission and other “hepatotoxic insults.” – by Melinda Stevens

Disclosures: Please see the full study for a list of all authors’ relevant financial disclosures.

Editor's Note: This article has been corrected to reflect the correct manufacturer of simeprevir. 

 

    Perspective
    Michael S. Saag

    Michael S. Saag

    The guidelines for hepatitis C were updated twice in the month of August.

    The first update incorporated the approval of daclatasvir (Daklinza, Bristol-Myers Squibb) in the United States and, based on that approval, modified treatment recommendations for most of the treatment groups. This update came on the heels of a June 2015 update that incorporated the recently presented data from the European Association for the Study of the Liver (EASL) meeting in Vienna.

    The largest impact of the daclatasvir approval is on the treatment of genotype 3. It was becoming clear that with many of the available direct-acting agents showed great activity against genotype 1a and 1b and to some degree, genotype 4, genotype 3 was becoming the one particular area where our options were more limited. Based on data presented at EASL, there was even a suggestion that a PEG-IFN-based regimen for certain patients with genotype 3 might be the best option. With the approval of daclatasvir, an all-oral regimen consisting of sofosbuvir (Sovaldi, Gilead Sciences) and daclatasvir now is a viable option for patients and practitioners.

    There’s a fair degree of data to support the use of daclatasvir and sofosbuvir in the treatment of other genotypes as well, and the guidelines have added daclatasvir as a treatment option to genotype 1 and 2, though there were not enough data to recommend daclatasvir for genotype 4.

    Daclatasvir has been available in Europe for well over a year and a half, so these new additions to the HCV guidelines apply mostly to those of us in the United States, though they do codify for those who use the drug in Europe.

    Another new formulation of some of the AbbVie drugs, consisting of parataprevir/ritonavir plus ombitasvir (Technivie), also was recently approved, but there was no need to modify the HCV Guidelines, per se, since these two drugs were already a recommended regimen for genotype 4.

    The second update to the guidelines that came out on August 20 was a cost effectiveness section. It should be clear that the purpose of publishing this particular section was to provide information to providers regarding cost effectiveness, including definition of terms and methodologies. There’s a lot of discussion in the lay literature and patients often ask questions about cost effectiveness. Sometimes providers are approached by payers to comment on cost effectiveness when we try to advocate for access to certain drugs and the payers claim that the regimen is not cost effective.

    The guidelines committee felt it was important to get information out there so providers would understand the principles of cost effectiveness and be conversant on the topic. The new section contains a table that defines commonly used acronyms, such as QALY and ICER.

    The cost effectiveness update basically is a primer for those who haven’t thought much about cost effectiveness literature, straightens out the terminology and explains how these data are generated. It then reviews some of the cost effectiveness data that exists for different genotypes and approved therapies.

    It’s important to underscore, however, that cost data and cost effectiveness data are not used by the guidelines committee to make recommendations on treatment.

    Treatment recommendations are made in isolation of cost or cost effectiveness.  Recommendations are made as if a panel member answering a phone call from a colleague with a consult on a patient, asking “What would you recommend I do for this patient?”

    These updates continue to exemplify the incredible value of having the guidelines exist as a “living document” online. At this point, if you’re giving a talk or writing a review of current treatments of hepatitis C, your recommendations run the risk of being highly out of date at the time of your talk or publication of your paper.

    The best thing to do is to reference the HCV Guidelines webpage because the guidelines are updated so frequently and rapidly. For example, when AbbVie released their 3D drugs in December, the guidelines were updated within 5 days of FDA approval. Within 2 weeks of daclatasvir approval, the guidelines were updated again.

    This is part of the mission of the guidelines panel and, so far, the group has achieved its mission in remarkable fashion.

    • Michael S. Saag, MD
    • Co-Chief Medical Editor, HCV Next