Patient Profile

Southern Perspective: Practical Solutions for Daily Management of HCV

It is an exciting time to be seeing patients with hepatitis C infection in the current era of direct-acting antiviral agents. To be able to offer a legitimate cure with almost no side effects and without the use of self-injections is quite remarkable. My hat is truly tipped to those scientists who participated in the development of such medications.

Many patients have been plagued with this disease for decades while witnessing friends and family members succumb to decompensated cirrhosis or liver cancer.

In Atlanta, most patients I see contracted hepatitis C through remote drug use or experimentation, blood transfusions before 1992, possible sexual exposure or indeterminate causes. Many veterans believe they may have contracted the virus while serving overseas in the Vietnam War. Most of the patients seen in our Atlanta clinic today are not actively using intravenous drugs.

Many patients that are evaluated for liver transplant with hepatitis C also have a history of significant alcohol intake. Some of the psychosocial issues affecting patients with both hepatitis C and heavy alcohol history may be more concerning than some of the same issues identified in a pretransplant patient with pure alcoholic liver disease.

Initial Treatment Options

For patients with genotype 1 HCV infection, we initially used the combination of simeprevir (Olysio, Janssen Therapeutics) and sofosbuvir (Sovaldi, Gilead Sciences) with or without ribavirin for 12 weeks fixed duration in all patients, both pre- and post-liver transplant. We used this combination in an off-label fashion until it was approved by the FDA. We observed few side effects and a high rate of sustained virologic response.

I was a bit surprised that the pendulum immediately swung toward ledipasvir/sofosbuvir (Harvoni, Gilead Sciences) when this drug became FDA approved. While the country seemed to follow suit, I was surprised at how quickly the simeprevir-sofosbuvir combination was essentially abandoned despite a nice track record. My feeling was that two drugs from two different drug companies made approval more difficult and possibly more expensive.

Ryan M. Ford

In regard to cost, I was not convinced that the 24-week duration of simeprevir-sofosbuvir was necessary in patients with cirrhosis. Because we had good success with a fixed 12-week duration, I felt you could likely save money by treating most patients for 12 weeks and then re-treating the few who did not achieve SVR with longer duration or a different regimen.

Whereas the once-a-day ledipasvir/sofosbuvir pill was quite attractive, I did — and still do — have some concerns about patients who fail on this drug, mainly because of NS5A resistance and the longer duration required to revert to wild-type virus after failure. That being said, one could argue that you could treat all genotype 1 patients with ledipasvir/sofosbuvir and then come up with a solid salvage regimen for those who fail (a small percentage most likely).

Recommendations, Interactions

I was glad to see the recent AASLD guidelines recommending that all patients with HCV (regardless of fibrosis stage) be treated and cured, albeit with some ranking based on priority. Though the cost of medications matters to an extent, the patient-doctor encounter should not be influenced by the pricing of drugs.

If two drugs are exactly the same, but one is much cheaper, then physicians should make the responsible decision to use the less expensive regimen. But if a patient comes to a clinic with a chronic viral infection that has been linked to cirrhosis, liver cancer, lymphoma, diabetes, fatigue, joint pains, kidney disease, non-liver cancer, vasculitis and even heart disease, there should be no waiting period to be prescribed a 3 to 6 month regimen with few to no side effects and be cured.

I certainly look forward to lower cost drugs and even shorter duration of therapy — perhaps even 8 weeks — but until that time comes, the government, third party payers and drug companies can discuss business ethics and pricing during their workday. If we can cure everyone with hepatitis C, the profits made by pharma would likely be dwarfed by the cost savings by avoiding cirrhosis, liver cancer and the extrahepatic manifestations of this disease.

As newer regimens and combinations become available, I will make my choice for each patient based on efficacy, safety, and ease of administration. Following the Hippocratic Oath, we must first do no harm.

Recently, it was concerning to hear the reports of bradycardia and death in some patients on DAAs and amiodarone. It lends itself to caution regarding potential drug-drug interactions when choosing an HCV regimen. This is quite important in the post-liver transplant setting, and I want to avoid having to change antirejection medication (eg, calcineurin inhibitors) dosing or frequency while treating HCV. I certainly believe in eradicating HCV infection post-liver transplant as soon as possible within the first year after transplant, but I do not see the need to treat patients in the early postoperative period unless they have fibrosing cholestatic HCV. By waiting several months after transplant, you can avoid some potential drug-drug interactions and confounding side effects.

Future Challenges, Current Practice

Future challenges include screening and identifying the many patients in the world who are wholly unaware of their HCV infection, and then linking them to proper care. I also have some concerns about viral resistance, especially when treating patients who are actively using IV drugs. I do believe there are regional differences of opinion on the matter of treating active drug users with these new expensive regimens.

There seems to be a fundamental difference between viewing the problem from an epidemiologic standpoint (eg, reduce incidence of new infections) and treating the patient in front of you (if I treat an active drug user, I risk relapse and potential viral resistance, issues like we have seen with HIV). My opinion would be to first treat the drug addiction, and then offer HCV treatment after a period of being clean. This is very similar to how alcoholics are treated when discussing the therapy of liver transplantation.

My current practice in treating genotypes 1 through 4 patients with HCV is to use sofosbuvir-based regimens. I believe that the nucleotide polymerase inhibitor is the strongest backbone to current therapy. I am excited to see more data on regimens to treat patients with genotype 3, and I have certainly seen several relapses after 24 weeks of sofosbuvir/ribavirin in such patients.

I try to treat all patients I encounter who have this chronic virus, although I do agree with recent guidelines suggesting that we assess potential lifespan based on non-HCV related morbidities. If insurance dictates a certain drug, as long as it is efficacious and safe (and preferably FDA-approved), I am willing to use it. If a drug combination has been on the market longer with good success, there needs to be a compelling reason to switch to a newer regimen without post marketing use and observation.

Sometimes national and international meetings concern me in the almost constant push just to present something new. It is hard for me to yearn for much more when we have SVR rates approaching 100%. The only thing that could derail the current zeal behind curing patients with HCV is to realize we could cause harm. – by Ryan Ford

It is an exciting time to be seeing patients with hepatitis C infection in the current era of direct-acting antiviral agents. To be able to offer a legitimate cure with almost no side effects and without the use of self-injections is quite remarkable. My hat is truly tipped to those scientists who participated in the development of such medications.

Many patients have been plagued with this disease for decades while witnessing friends and family members succumb to decompensated cirrhosis or liver cancer.

In Atlanta, most patients I see contracted hepatitis C through remote drug use or experimentation, blood transfusions before 1992, possible sexual exposure or indeterminate causes. Many veterans believe they may have contracted the virus while serving overseas in the Vietnam War. Most of the patients seen in our Atlanta clinic today are not actively using intravenous drugs.

Many patients that are evaluated for liver transplant with hepatitis C also have a history of significant alcohol intake. Some of the psychosocial issues affecting patients with both hepatitis C and heavy alcohol history may be more concerning than some of the same issues identified in a pretransplant patient with pure alcoholic liver disease.

Initial Treatment Options

For patients with genotype 1 HCV infection, we initially used the combination of simeprevir (Olysio, Janssen Therapeutics) and sofosbuvir (Sovaldi, Gilead Sciences) with or without ribavirin for 12 weeks fixed duration in all patients, both pre- and post-liver transplant. We used this combination in an off-label fashion until it was approved by the FDA. We observed few side effects and a high rate of sustained virologic response.

I was a bit surprised that the pendulum immediately swung toward ledipasvir/sofosbuvir (Harvoni, Gilead Sciences) when this drug became FDA approved. While the country seemed to follow suit, I was surprised at how quickly the simeprevir-sofosbuvir combination was essentially abandoned despite a nice track record. My feeling was that two drugs from two different drug companies made approval more difficult and possibly more expensive.

Ryan M. Ford

In regard to cost, I was not convinced that the 24-week duration of simeprevir-sofosbuvir was necessary in patients with cirrhosis. Because we had good success with a fixed 12-week duration, I felt you could likely save money by treating most patients for 12 weeks and then re-treating the few who did not achieve SVR with longer duration or a different regimen.

Whereas the once-a-day ledipasvir/sofosbuvir pill was quite attractive, I did — and still do — have some concerns about patients who fail on this drug, mainly because of NS5A resistance and the longer duration required to revert to wild-type virus after failure. That being said, one could argue that you could treat all genotype 1 patients with ledipasvir/sofosbuvir and then come up with a solid salvage regimen for those who fail (a small percentage most likely).

Recommendations, Interactions

I was glad to see the recent AASLD guidelines recommending that all patients with HCV (regardless of fibrosis stage) be treated and cured, albeit with some ranking based on priority. Though the cost of medications matters to an extent, the patient-doctor encounter should not be influenced by the pricing of drugs.

If two drugs are exactly the same, but one is much cheaper, then physicians should make the responsible decision to use the less expensive regimen. But if a patient comes to a clinic with a chronic viral infection that has been linked to cirrhosis, liver cancer, lymphoma, diabetes, fatigue, joint pains, kidney disease, non-liver cancer, vasculitis and even heart disease, there should be no waiting period to be prescribed a 3 to 6 month regimen with few to no side effects and be cured.

I certainly look forward to lower cost drugs and even shorter duration of therapy — perhaps even 8 weeks — but until that time comes, the government, third party payers and drug companies can discuss business ethics and pricing during their workday. If we can cure everyone with hepatitis C, the profits made by pharma would likely be dwarfed by the cost savings by avoiding cirrhosis, liver cancer and the extrahepatic manifestations of this disease.

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As newer regimens and combinations become available, I will make my choice for each patient based on efficacy, safety, and ease of administration. Following the Hippocratic Oath, we must first do no harm.

Recently, it was concerning to hear the reports of bradycardia and death in some patients on DAAs and amiodarone. It lends itself to caution regarding potential drug-drug interactions when choosing an HCV regimen. This is quite important in the post-liver transplant setting, and I want to avoid having to change antirejection medication (eg, calcineurin inhibitors) dosing or frequency while treating HCV. I certainly believe in eradicating HCV infection post-liver transplant as soon as possible within the first year after transplant, but I do not see the need to treat patients in the early postoperative period unless they have fibrosing cholestatic HCV. By waiting several months after transplant, you can avoid some potential drug-drug interactions and confounding side effects.

Future Challenges, Current Practice

Future challenges include screening and identifying the many patients in the world who are wholly unaware of their HCV infection, and then linking them to proper care. I also have some concerns about viral resistance, especially when treating patients who are actively using IV drugs. I do believe there are regional differences of opinion on the matter of treating active drug users with these new expensive regimens.

There seems to be a fundamental difference between viewing the problem from an epidemiologic standpoint (eg, reduce incidence of new infections) and treating the patient in front of you (if I treat an active drug user, I risk relapse and potential viral resistance, issues like we have seen with HIV). My opinion would be to first treat the drug addiction, and then offer HCV treatment after a period of being clean. This is very similar to how alcoholics are treated when discussing the therapy of liver transplantation.

My current practice in treating genotypes 1 through 4 patients with HCV is to use sofosbuvir-based regimens. I believe that the nucleotide polymerase inhibitor is the strongest backbone to current therapy. I am excited to see more data on regimens to treat patients with genotype 3, and I have certainly seen several relapses after 24 weeks of sofosbuvir/ribavirin in such patients.

I try to treat all patients I encounter who have this chronic virus, although I do agree with recent guidelines suggesting that we assess potential lifespan based on non-HCV related morbidities. If insurance dictates a certain drug, as long as it is efficacious and safe (and preferably FDA-approved), I am willing to use it. If a drug combination has been on the market longer with good success, there needs to be a compelling reason to switch to a newer regimen without post marketing use and observation.

Sometimes national and international meetings concern me in the almost constant push just to present something new. It is hard for me to yearn for much more when we have SVR rates approaching 100%. The only thing that could derail the current zeal behind curing patients with HCV is to realize we could cause harm. – by Ryan Ford