Is Curing Hepatitis C With Medications Possible?

What defines a cure?

Studio shot of various pills in bottle
Jamie Grill/Getty

 The term ‘cure’ is such a powerful word with such important implications that liver specialists and virologists avoided using it for decades to describe one outcome of hepatitis C therapy (Amer Liver Foundation) (WebMD). The hepatitis C virus is virus that needs to continue to replicate in the liver to survive. There is no ability of HCV to become dormant or go into a state of suspended animation.

Therefore, if HCV is suppressed with treatment for a sufficient period of time, the virus cannot survive.  However, merely becoming undetectable in the blood does not mean that the virus is completely suppressed in the liver. We now realize that there is 1000-1,000,000 times more virus in the liver than in the blood.  This means that treatment needs to be continued long enough to drop the virus level until it is undetectable in the liver (which is normally an approximation) for an unknown period of time.  It seems from many of the recent studies with new, very potent HCV medicines, that the shortest duration of therapy which can cure some patients with hepatitis C is at least 6 weeks. A longer duration is required in those with certain difficult-to-treat genotypes (e.g. genotype 3) (Genotypes) and in those with cirrhosis.  Almost every patient who initiates treatment with these newer therapies becomes virus-undetectable in the blood within two weeks provided they take the medications as directed.

Resistance to hepatitis C medications can occur, but is uncommon if a combination of two or medicines are used together. Additional information is available at the American Liver Foundation (ALF)

In the very early days, before the virus itself was able to be assessed, the outcome of interferon therapy was described using the response of the blood ALT level (ALT article).

The response to therapy was either nonresponse (no change in ALT level); partial response (a reduction but not normalization of the ALT); a relapse (normalization of ALT during therapy but increase again when therapy discontinued); and a complete response in which the ALT remains normal six months or more after stopping therapy. We now know that many of those with a complete response likely had the virus eradicated. 

Once we were able to measure the hepatitis C viral RNA (HCV RNA) as a reflection of active virus in the blood, and hence continued viral replication in the liver, this became the standard to determine therapeutic outcome.  Many of the original terms remained, but sustained viral response (SVR) took the place of complete response (HCVguidelines). Unfortunately, in those early days the testing to measure HCV RNA was crude and relatively insensitive by today’s standards.  Thus, although we suspected that some or all patients with SVR might be free of the virus, we could not be absolutely positive.

  Hence, we continued to avoid the term ‘cure’.

Using newer techniques termed polymerase chain reactions (PCR), laboratories could detect miniscule amounts of virus in the blood and liver. This now allowed accurate determination of virus levels (https://www.hcv.com/curing/goal). Long term follow-up studies of patients who achieved SVR were then undertaken. It was discovered that 98-99% of those who had achieved SVR still had undetectable virus 4-5 years later.  Furthermore, liver biopsies performed at these later time points demonstrated normalization of liver inflammation and regression of scarring (fibrosis). It was also possible to show that there was no longer any detectable virus in the liver years after completion of therapy. Finally, it has been demonstrated that those with eradication of virus have a significantly lower risk of developing cirrhosis or liver cancer. 

Therefore, if there is no virus in the blood, no virus in the liver and there is regression of liver inflammation and scarring five years after treatment, this fulfills my definition of what a ‘cure’ should represent.

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