Hepatitis C Report: Tuning in to a Silent Epidemic

April 5, 2017

Knowing the origin and causes could help clinicians better determine who to screen and treat.

The hepatitis C virus (HCV) is known as the “silent epidemic” because many patients are unaware of their infection status and many cases go unrecognized and untreated for many years. Gaining a better understanding of how patients were infected could help clinicians in determining who to screen and treat.

Adding to the Mystery[[{"type":"media","view_mode":"media_crop","fid":"58212","attributes":{"alt":"","class":"media-image media-image-right","id":"media_crop_8385496068081","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"7355","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"border-width: 0px; border-style: solid; margin: 5px; float: right; width: 247px; height: 242px;","title":" ","typeof":"foaf:Image"}}]]

The exact origin of the HCV is unknown, as are the mechanisms responsible for its pandemic spread in many parts of the world. Various dating and statistical methodologies have been employed to arrive at a “best guess” of HCV being several hundred years old, but the dramatic increase in the number of cases worldwide seems to have occurred after World War II.1

It has been speculated that nonhuman primates were somehow responsible for the spread of HCV to humans-similar to HIV-but no HCV or HCV-like viruses have been found in nonhuman primates. Adding to the mystery, nonprimate hepaciviruses (NPHVs) have been discovered in both horses and dogs.

In the few percent of horses found to be viremic with NPHV in a 2012 study,2 polymerase chain reaction–determined viral loads were comparable to what is observed in humans. The horses also showed some laboratory evidence of liver inflammation (elevated levels of γ-glutamyl transferase), but they did not appear to have any clinical symptoms referable to the liver.

In dogs, the NPHV was isolated from respiratory specimens in association with respiratory symptoms.3 In humans, HCV is not found in respiratory secretions, nor does it cause respiratory disease.

The Spread of a Blood-borne Virus

The HCV virus, a blood-borne virus, is inefficiently spread sexually in the absence of blood exposure. Much of the spread worldwide after World War II was a result of blood transfusions with HCV-contaminated blood or blood products, injection drug use and, in much of the world, the use of nonsterile medical equipment on multiple patients.

In the United States, about 1% of the population is infected with HCV, the third hepatitis virus discovered, after Hepatitis A virus (HAV) and hepatitis B virus (HBV). The existence of a “non-A, non-B” hepatitis virus associated with blood transfusions was known from the early 1970s. At that time, there were assays that detected HAV and HBV but not HCV.

Next: Transfusion and Chronic Liver Disease Links

Linked to Transfusion-related Cases and Chronic Liver Disease

A number of studies estimated that the non-A, non-B hepatitis virus was associated with almost 90% of transfusion-related cases. The virus also was linked to chronic liver disease in the hemophilia population.

Viral inactivation methods were not available as part of the production of factor concentrates until the late 1980s. This same non-A, non-B hepatitis virus also was linked to injection drug use around the world.

It was not until 1990 that an FDA-approved test for detecting antibodies to HCV became available. The development of this test followed the isolation in 1989 of genetic material from non-A, non-B hepatitis-infected blood that showed that the virus was in the Flaviviridae family. The virus now is assigned to the Hepacivirus genus within this family.

Multiple genotypes of HCV

There are multiple genotypes of HCV. In the United States, genotypes 1a (40%) and 1b (30%) predominate, followed by genotype 2 (15% to 20%), genotype 3 (10% to 12%), and genotypes 4–6 (about 1% each).4

Historically, genotype 1 has been considered the most difficult to treat, but multiple directly acting agents are available that result in “cure rates” (sustained virologic response rates) exceeding 90% to 95% after an average of 12 weeks of treatment.5

In the absence of treatment, 15% to 20% of HCV viremic patients progress to cirrhosis within 20 years of infection.6 End-stage liver disease or hepatocellular cancer or both subsequently occur in a high percentage of them.

The Changing Face of the Epidemic

Now that the blood supply in the Unites States is “safe,” the predominant mode of transmission of HCV is via injection drug use. Recent outbreaks of HCV in rural communities resulting from the injection of prescription narcotics illustrates the changing face of the epidemic and highlights the need for effective interventions.

In fact, some studies suggest that the best way to reverse the ongoing HCV epidemic in the United States is to target for treatment those at greatest risk for spreading HCV-injection drug users.7


Coming soon, the next part of this Special Report on Hepatitis C and Primary Care will focus on screening for HCV. Watch your email for eNewsletters from Patient Care and visit our homepage at www.patientcareonline.com to check for updates.


1. Simmonds P. The origin of hepatitis C virus. Curr Top Microbiol Immunol. 2013;369:1-15.

2. Lyons S, Kapoor A, Sharp C, et al. Nonprimate hepaciviruses in domestic horses, United kingdom. Emerg Infect Dis. 2012;18:1976-1982.

3. Kapoor A, Simmonds P, Gerold G, et al. Characterization of a canine homolog of hepatitis C virus. Proc Natl Acad Sci USA. 2011;108:11608-11613.

4. HCV Epidemiology in the United States. Hepatitis C Online.Accessed February 21, 2017.

5. Treatment of HCV Genotype 1. Hepatitis C Online. Accessed February 21, 2017.

6. Shire NJ, Sherman KE. Epidemiology of hepatitis C virus: a battle on new frontiers. Gastroenterol Clin N Am. 2015;44:699-716.

7. Martin NK, Vickerman P, Foster GR, et al. Can antiviral therapy for hepatitis C reduce the prevalence of HCV among injecting drug user populations? A modelling analysis of its prevention utility. J Hepatol. 2011;54:1137-1144.