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International Journal of Anesthesiology & Pain Medicine
ISSN: 2471-982X
Volume 4
March 26-28, 2018
Vienna, Austria
Pain Management 2018
Internal Medicine 2018
Page 19
JOINT EVENT
7
t h
E d i t i o n o f I n t e r n a t i o n a l C o n f e r e n c e o n
Internal Medicine and Patient Care
&
6
t h
E d i t i o n o f I n t e r n a t i o n a l C o n f e r e n c e o n
Pain Management
H
epatitis C (HCV) is a global infection due to
Hepacivirus
,
a member of the Flaviviridae family. Parenteral routes
including blood transfusion, injecting drug and exposure to
medical procedures usually transmit infection; however, the
virus can be transmitted maternally and in some patients, no
known risk factor is identifiable. Over 170 million persons
worldwide are infected and chronic infection leads to cirrhosis,
hepatocellular carcinoma and increased all-cause mortality. The
majority of infected patients maintain a chronic infection leading
to several hepatic and non-hepatic complications. Linked to
progressive infection is the presence of significant fibrosis
within the liver and several risk factors predict which patients are
likely to develop complications such as cirrhosis, hepatocellular
carcinoma (HCC), and increased all-cause mortality. HCC is the
fifth most common cancer in males, seventh in females and
is a major cause of cancer related death. Eighty-five percent
of cases occur in the developing world and HCV is a leading
predisposition. The pathogenesis of HCV relatedHCC is complex
and unlike hepatitis B virus, HCV does not integrate into the host
genome. However, HCV does dysregulate cellular proliferation
and differentiation pathways, creates chronic inflammation
and inhibits tumor suppressor gene activity. Our laboratory has
focused on two aspects of HCC carcinogenesis, namely cancer
like stem cells and chronic inflammation. Hepatoma cells
expressing a HCV subgenomic replicon express several cancers
like stem cell markers, especially doublecortin-like kinase
(DCLK1), a microtubule kinase that is a putative marker for
intestinal and pancreatic cancers. Expression of DCLK-1 is linked
to HCV replication and tumorigenesis in xenograft models, and
DCLK-1 is identifiable in tissue and plasma derived from patients
with HCV associated cirrhosis and HCC. SiRNA knockdown of
DCLK-1 inhibits tumor growth in animal models suggesting that
DCKL-1 might be a therapeutic marker. Additionally, total RNA
analysis of FCA4 cells, which also express a HCV subgenomic
replicon, reveals upregulation of DCLK-1 and a number of pro-
inflammatory markers including S100A9 and SMARCA. These
cells generate tumors in xenograft models that express DCLK-
1, AFP and S100A9 and siRNA knockdown of DCLK-1 abrogates
tumorigenesis and S100A9 expression. Over the last several
years, there has been significant progress in the treatment of
HCV infection. New, pan-genotypic direct antiviral agents (DAA)
have vastly improved our treatment strategies not only achieving
cure in a large percentage of patients, but also showing promise
in reducing the complications of HCV infection.
Biography
Michael S. Bronze, M.D. was appointed Professor and Chairman, Depart-
ment of Medicine, University of Oklahoma Health Sciences Center effec-
tive July 1, 2000. He was named the Stewart G. Wolf Professor in Internal
Medicine in 2004 and David Ross Boyd Professor in 2011. He is board
certified in Internal Medicine and Infectious Diseases. He completed his
medical school training at the University of Tennessee, Memphis in 1982.
His internship and residency were completed at the University of Tennes-
see, Memphis and served and additional year as Chief Medical Resident.
Michael-Bronze@ouhsc.eduImpact of hepatitis C virus: update on
pathogenesis of complications and treatment
strategies
Michael S Bronze
University of Oklahoma Health Sciences Center, USA
Michael S Bronze, Int J Anesth Pain Med 2018, Volume 4
DOI: 10.21767/2471-982X-C1-001