Hepatitis C: A Beginner’s History Course

An introduction to the history of the discovery and treatment of hepatitis C

Hepatitis C virus
Hepatitis C virus. BSIP/Universal Images Group/Getty Images

Hepatitis C is a virus that can infect the liver and cause damage (hepatitis). The virus, known as HCV for Hepatitis C Virus, has no relationship to hepatitis A, B, D or E viruses.  We don’t know where the virus originated, but current theories are that it came out of Africa centuries ago.  In the United States, it wasn’t a major health issue until the 1970s when injection drug use and the frequent use of blood transfusions helped spread the disease.

There was no test for HCV at that time, so the blood banks could not screen blood for its presence. In fact, there were even doubts about its existence in the early 1970s. It wasn’t until really reliable tests for the known hepatitis A virus (HAV) and hepatitis B virus (HBV) in the mid- to late 1970s and early 1980s that it became convincingly demonstrated that another virus cause of hepatitis clearly existed. At that time, it was known as “non-A, non-B hepatitis” or NANB hepatitis. The virus was still not identified but surrogate testing of the blood supply was initiated using the ALT level (ALT link) and the presence of hepatitis B core antibody. At this time, nearly 10% of blood transfusions were contaminated with HCV and there were over 150,000 new cases of NANB hepatitis each year.  Finally, in 1989 the Chiron Corporation discovered the hepatitis C virus and developed a test to accurately identify those infected with the HCV.

  The test was an antibody assay which measured immunity to the HCV but did not measure the virus directly. A more specific recombinant immunoblot assay (RIBA) was subsequently developed which was more specific, but still only an immunological test.  In the early 1990s a commercial test to measure the virus itself was developed.

  It was a polymerase chain reaction (PCR) assay.  This development also opened the door to identification of several subtypes (or genotypes) of hepatitis C, which are numbered 1-6).

In the early 1980s, in spite of not having a way to confirm the presence of HCV, an interferon therapy was being developed for NANB hepatitis. Early studies with interferon demonstrated that it could improve the elevated ALT levels and improve liver biopsy findings, but unfortunately in only a small percentage of patients (approximately 6%). Interferon was not an ideal therapy since it needed to be administered by injection three times each week and was associated with severe side effects.   However, since some patients seemed to respond well with permanent normalization of liver tests, the duration of treatment was increased from 6 months to 12 months, and the response rate improved to around 12%.  By the mid-1990s, ribavirin was added to the interferon regimen in spite of the fact that it had little activity when given alone. The response rates almost doubled, but so too did the side effects.  Ribavirin caused significant anemia and occasional skin rash which meant that the therapy needed close monitoring and clinic visits.

 The development of pegylated interferon (interferon modified by the addition of a polyethylene glycol [PEG] side chain) allowed interferon injections to be reduced to once weekly with a modestly improved success rate of approximately 45-55%. Interestingly, patients infected with certain genotypes (2 or 3) had much better responses (75-85%) which could even be achieved with shorter durations of therapy. Furthermore, it became apparent that certain races had much better responses than others even given the same genotypes. Later, it was discovered that this difference in racial response was due to a genetically-associated handling of the interferon signal in the liver coded by a protein known as IL28B.

From 2000 to 2010, the therapy remained PEG-interferon and ribavirin but with many more subdivisions of response and treatment duration. Therapy became incredibly complicated.

Finally, in 2011, two direct-acting antiviral (DAA) agents were discovered and approved (Link DAA meds).  These were the HCV protease inhibitors telaprevir and boceprevir. They still needed to be administered with interferon and ribavirin, but the success rates improved to 68-75%. However, even more side effects were noted and this therapy could not be given to those with the most severe forms of hepatitis C. In 2013-14 it finally became able to treat hepatitis C without interferon with the approval of sofosbuvir and simeprevir (Link: guidelines).  Although quite costly (approximately $160,000 per course of treatment!) success rates improved to 90% and without significant side effects (Link: expense).   The past 2-3 years have seen an explosion of even newer oral treatments allowing even sorter durations of treatment to even as short as 8 weeks in some cases but with 95-100% cure rates (Link: cure).

It is truly remarkable to think that in just 25 years we have moved from the discovery of HCV in 1989 to the ability to cure almost everyone with the infection by 2014. The current issues facing hepatologists is how to further simplify therapy so that a single treatment will work equally for all genotypes, and also to decrease the cost of treatment so that it is more widely accessible.  Stay tuned! (Link: online resources)

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