Brief essay written for Dr. Gene Mesco, PhD's Anatomy & Physiology II course which I unofficially audited during the summer of 2014.

1. Hepatitis C:
A Brief Overview of HVC’s Viral Pathology
and the
Principal Challenges Remaining in the Iatrological Development
of
Efficacious Immunological Prophylaxis
Jackson David Reynolds
June 24, 2014
BIOL 2213K (Unofficial Audit)

2. Hepatitis C is a potentially symptomatically nefarious, hematologically
communicable disease that primarily results in the development of serious hepatological
pathologies. Infection is engendered by the hepatitis C virus [HCV], which, being an
RNA virus of the hepacivirus genus, allows for zoönotic transmission of the pathogen
between homo sapiens sapiens and the two presently extant chimpanzee species, Pan
troglodytes and Pan paniscus (Shors 535).
While acute infections affect roughly 15% of human patients (Maheshwari, et al.
321), this paper will focus solely on the clinical indicia of the chronic pathosis and the
challenges encountered in the ongoing endeavor to develop a non-therapeutic inoculative
agent.
Chronic hepatitis C infection, affecting more than 150 million individuals1
worldwide (Hanafiah, et al. 1333), frequently remains asymptomatic for decades, though
it usually ultimately results in a host of clinically significant and potentially debilitating
symptoms. These presentations range from the more benign fatigue/malaise to the
significantly more debilitating hepatic cirrhosis and malignancy, nonalcoholic
steatohepatitis, ascites, portal hypertension, esophageal/gastric varices, and chronic
hyperbilirubinemia. Interestingly, the majority of these pathologies are usually acquired
as sequelae to cirrhotically-induced hepatocyte damage (Ozaras and Tehan). While the
disease primarily assaults the structures of the liver, several extrahepatic conditions such
as thrombocytopenia, cardiomyopathy, autoimmune thyroiditis, type II cryoglobulinemia,
and the leukocyte-mediated destruction of exocrine tissue due to Sjögren's syndrome ,2
can also resultantly arise.
While available treatments include moderately effective antiviral drugs and a
prescribed total abstinence from dietary ethanol intake, cirrhosis and the extensive milieu
“Chronic” defined by the confirmed presence of clinically detectable viral replication for a period of at1
least 183 days.
Chronic Keratoconjunctivitis sicca and xerostomia frequently develop as symptomatic consecutions to the2
syndrome’s characteristic autoimmune attack on the lacrimal and salivary glands, respectively (Nocturne
and Mariette).

3. of its associated complications has made hepatitis C the chief indication for hepatic
transplantation across the board (Rosen 2429). Unfortunately, even surgically successful
whole-liver allotransplantations still exhibit a near 90% viral recurrence rate post-
operatively. Given such dishearteningly sepulchral statistics, it is clear that the advent of
an effective prophylactic agent would be hugely preferred to the markedly rebarbative
and incommodious aesculapian approaches presently employed.
While enormously successful vaccines for hepatitis A and B viruses have been in
widespread use for decades, the development of an inoculation for HCV has proven
appreciably more challenging. One reason for this is that, like the human
immunodeficiency virus [HIV] and other pathogens similar to it, HCV strains posses
astounding genetic heterogeneity. This, coupled with the virus’ extreme propensity for
expeditious mutation, makes it extraordinarily difficult to develop a vaccine that is both
broadly efficient while simultaneously being precisely effective on individual strains
(Randal 906). Even if an especially potent formulation does manage to confer immunity
from a large number of strains, due the aforementioned rapid mutative properties of the
virus, new, sufficiently dissimilar HCV genomes capable of producing infection will
quickly evolve, immediately weakening the protection provided by the inoculation, as the
genome-specific antigens in circulation will then serve to protect the immunized
individual against an increasingly smaller and smaller number of the extant strains. The
true magnitude of this problem becomes strikingly more apparent when it is taken into
consideration that the quantity of novel genomic profiles for HCV will not propagate
linearly, but rather in an exponential manner, making even the identification and
sequencing of the relentlessly evolving genomes a herculean task in and of itself.
Despite the staggering difficulties, however, progress has been, and continues to
be, made. Despite the fact that HCV cannot itself be laboratorially cultured, the same is
not true of its numerous proteases. Given the [relative] ease with which several HCV
proteases, specifically HCV NS3-4A Serine Protease, have been biochemically analyzed,
it seems likely that the first truly effective prophylactic for HCV will come in the form of
a vaccine-like agent that will systematically retard/inhibit the action of HCV’s requisite

4. proteases immediately upon hematologic invasion, in a fashion much similar to
antiretroviral protease inhibitors already in use to control established HIV/AIDS
infections in the long-term (Lin 169).

5. Works Cited
Hanafiah, Khayriyyah M., Justina Groeger, Abraham D. Flaxman, and Steven T.
Wiersma. "Global Epidemiology of Hepatitis C Virus Infection: New Estimates
of Age-specific Antibody to HCV Seroprevalence." Hepatology 57.4 (2014):
1333-342. Wiley Online Library. Web. 4 Feb. 2014. <http://
onlinelibrary.wiley.com/doi/10.1002/hep.26141/
abstract;jsessionid=D5F83B6AC69F5D3FDB402D4D1A291E1C.f03t04>.
Lin, Chao. "HCV NS3-4A Serine Protease." Hepatitis C Viruses: Genomes and
Molecular Biology. Norfolk, UK: Horizon Bioscience, 2006. 163-206.
PubMed. Horizon Bioscience. Web. 24 June 2014. <http://
www.ncbi.nlm.nih.gov/books/NBK1623/pdf/ch6.pdf>.
Maheshwari, Anurag, MD, Stuart Ray, MD, and Paul J. Thuluvath, FRCP. "Acute
Hepatitis C." The Lancet 372.9635 (2008): 321-32. The Lancet. The Lancet.
Web. 24 June 2014. <http://www.thelancet.com/journals/lancet/article/
PIIS0140-6736(08)61116-2/fulltext>.
Nocturne, Gaëtane, and Avier Mariette. "Advances in Understanding the Pathogenesis of
Primary Sjögren's Syndrome." Nature Reviews Rheumatology 9 (2013):
544-56. Nature Reviews. Nature, 16 July 2013. Web. 24 June 2014. <http://
www.nature.com/nrrheum/journal/v9/n9/abs/nrrheum.2013.110.html>.
Ozaras, Resat, and Veysal Tahan. "Acute Hepatitis C: Prevention and Treatment." Expert
Review of Anti-infective Therapy. Informa Healthcare, Apr. 2009. Web. 24 June
2014. <http://informahealthcare.com/doi/abs/10.1586/eri.09.8>.
Randal, Judith. "Hepatitis C Vaccine Hampered by Viral Complexity, Many Technical
Restraints." Journal of the National Cancer Institute 91.11 (1999): 906-08.
Oxford Journals. Web. 24 June 2014. <http://jnci.oxfordjournals.org/content/
91/11/906.long>.
Rosen, Hugo R., MD. "Chronic Hepatitis C Infection." New England Journal of Medicine
364 (2011): 2429-438. New England Journal of Medicine. Web. 24 June 2014.
<http://www.nejm.org/doi/full/10.1056/NEJMcp1006613>.

6. Shors, Teri, PhD. "Hepatitis Viruses." Understanding Viruses. Sudbury, MA: Jones and
Bartlett, 2009. 535. Google Play Books. Web. 24 June 2014. <http://
books.google.ca/books?
id=Uk8xP5LRHr4C&pg=PA535#v=onepage&q&f=false>.