Editorial

The Unintended Consequences of Conservatism

The recent advances we have seen in HCV therapeutics with all-oral direct acting antiviral regimens are breathtaking. Today, we can cure well over 95% of patients with most genotypes and in most situations with an interferon-free regimen.

Michael Saag

Michael S. Saag

As these advances have just occurred within the past 5 years, with approvals as recently as 6 months ago, these regimens are so new that we do not yet have long-term outcomes. This has led to some experts in the field to believe that a sustained virologic response (SVR) obtained with these new all-oral, interferon-free DAAs is somehow different than an SVR achieved with interferon-based regimens.

In this issue of HCV Next, Kenneth Lin, MD, MPH, and colleagues claim, “Sustained virological response is not a cure.” They imply that we don’t know what the SVR cure means in this new era or that it may not yield the same clinical benefits as an SVR12 with interferon.

While I can appreciate the purity of the thought, conceptually proposed by Lin, it is difficult for me to accept this on a biological basis. We know that ongoing replication of hepatitis C is evil. It produces 100 billion to 1 trillion viruses a day and this onslaught of viremia leads to many, if not all, of the consequences of hepatitis C infection, including liver fibrosis and inflammatory-mediated diseases, such as advanced cardiovascular disease, increased risk of diabetes and other complications.

These complications of HCV are all improved, if not reversed, when the virus is cured. Therefore, I have trouble understanding why the elimination of HCV is a bad thing or a phenomenon to be doubted when we see the same benefits 10 years after interferon.

Why should we doubt that SVR due to DAA therapy is any different than an SVR obtained with interferon-based therapy?

Over time, we will have long-term “proof” of the benefits of DAA-derived SVR, but every clinician who has treated and cured a patient with hepatitis C using a DAA regimen notices the same improvement as they did when interferon led to “cure,” from a reversal of consequences of cryoglobulinemia to, in many cases, an improvement in fibrosis scores. It is hard to imagine that the “cure” from a DAA regimen is any different or less durable than interferon, and it is certainly better in terms of side effects while on treatment.

Finally, while I think in the corridors of academic hallways, we can wonder how applicable the findings or success of a DAA-based regimen might compare to the long-term success. But, to put this front and center as a major concern while patients are benefiting, creates unnecessary noise that interferes with the ability and enthusiasm of providers to treat patients.

We should be treating aggressively at this time now that finally we have the tools to do so with such widespread success. This is a potentially lethal virus that needs to be cured whenever possible.

Eventually, we will have the long-term data for which Lin yearns. Right now, though, the SVR rates are dramatically better than any we achieved with interferon-based therapies. And the patients in need of cure cannot afford the opportunity costs associated with waiting for long-term “proof” of what is obvious.

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

The recent advances we have seen in HCV therapeutics with all-oral direct acting antiviral regimens are breathtaking. Today, we can cure well over 95% of patients with most genotypes and in most situations with an interferon-free regimen.

Michael Saag

Michael S. Saag

As these advances have just occurred within the past 5 years, with approvals as recently as 6 months ago, these regimens are so new that we do not yet have long-term outcomes. This has led to some experts in the field to believe that a sustained virologic response (SVR) obtained with these new all-oral, interferon-free DAAs is somehow different than an SVR achieved with interferon-based regimens.

In this issue of HCV Next, Kenneth Lin, MD, MPH, and colleagues claim, “Sustained virological response is not a cure.” They imply that we don’t know what the SVR cure means in this new era or that it may not yield the same clinical benefits as an SVR12 with interferon.

While I can appreciate the purity of the thought, conceptually proposed by Lin, it is difficult for me to accept this on a biological basis. We know that ongoing replication of hepatitis C is evil. It produces 100 billion to 1 trillion viruses a day and this onslaught of viremia leads to many, if not all, of the consequences of hepatitis C infection, including liver fibrosis and inflammatory-mediated diseases, such as advanced cardiovascular disease, increased risk of diabetes and other complications.

These complications of HCV are all improved, if not reversed, when the virus is cured. Therefore, I have trouble understanding why the elimination of HCV is a bad thing or a phenomenon to be doubted when we see the same benefits 10 years after interferon.

Why should we doubt that SVR due to DAA therapy is any different than an SVR obtained with interferon-based therapy?

Over time, we will have long-term “proof” of the benefits of DAA-derived SVR, but every clinician who has treated and cured a patient with hepatitis C using a DAA regimen notices the same improvement as they did when interferon led to “cure,” from a reversal of consequences of cryoglobulinemia to, in many cases, an improvement in fibrosis scores. It is hard to imagine that the “cure” from a DAA regimen is any different or less durable than interferon, and it is certainly better in terms of side effects while on treatment.

Finally, while I think in the corridors of academic hallways, we can wonder how applicable the findings or success of a DAA-based regimen might compare to the long-term success. But, to put this front and center as a major concern while patients are benefiting, creates unnecessary noise that interferes with the ability and enthusiasm of providers to treat patients.

We should be treating aggressively at this time now that finally we have the tools to do so with such widespread success. This is a potentially lethal virus that needs to be cured whenever possible.

Eventually, we will have the long-term data for which Lin yearns. Right now, though, the SVR rates are dramatically better than any we achieved with interferon-based therapies. And the patients in need of cure cannot afford the opportunity costs associated with waiting for long-term “proof” of what is obvious.

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