Page 362 - Review of Medical Microbiology and Immunology ( PDFDrive )

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CHAPTER 41 Hepatitis Viruses
TABLE 41–6 Oral Drugs for Chronic HCV Infection
Hepatitis
B surface
Class of Drug
antigen
(HBsAg)
Sofosbuvir
RNA polymerase
Inhibits synthesis of
inhibitor
genome RNA; nucleoside
Delta virus
(uridine) analogue; chain
Capsid protein
terminating drug
(δ) antigen
Envelope
Inhibits synthesis of
RNA polymerase
Dasabuvir
lipid (from
inhibitor
genome RNA; non-
host cell)
nucleoside inhibitor FIGURE 41–5 Hepatitis D virus. Note that hepatitis B surface
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Ledipasvir,
Inhibits synthesis of
NS5A inhibitor
antigen (HBsAg) forms the outer envelope and the genome
genome RNA; blocks
Ombitasavir,
action of NS5A protein
consists of circular RNA. (Reproduced with permission from Ryan KJ,
that is a cofactor
required for RNA
New York, NY: McGraw-Hill; 2014.)
polymerase activity
Boceprevir,
Protease inhibitor
Inhibits cleavage of precur-
Important Properties & Replicative
sor polypeptide; blocks
Simeprevir,
production of functional
Cycle
HCV structural and non-
Telaprevir,
structural proteins
HDV is unusual in that it is a defective virus (i.e., it cannot
Paritaprevir
replicate by itself because it does not have the genes for its
envelope protein). HDV can replicate only in cells also
infected with HBV because HDV uses the surface antigen
for postexposure prophylaxis. There is no effective regimen
of HBV (HBsAg) as its envelope protein. HBV is therefore
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for prophylaxis following needle-stick injury; only moni-
the helper virus for HDV (Figure 41–5).
toring is recommended.
HDV is an enveloped virus with an RNA genome that
Blood found to contain antibody is discarded—a
procedure that has prevented virtually all cases of transfu-
circle. The RNA genome of HDV is very small and encodes
sion-acquired HCV infection since 1994, when screening
only one protein, the internal core protein called delta
began. Screening of individuals born in the United States
antigen. HDV genome RNA has no sequence homology to
between 1945 and 1965 for HCV antibody is recommended
HBV genome DNA. HDV has no virion polymerase; the
because they have a high rate of infection. Treatment of those
genome RNA is replicated and transcribed by the host cell
who are antibody-positive should reduce transmission.
RNA polymerase. HDV genome RNA is a “ribozyme” (i.e.,
Patients with chronic HCV infection should be advised
to reduce or eliminate their consumption of alcoholic bev-
that are employed during replication of the genome). HDV
erages to reduce the risk of hepatocellular carcinoma and
replicates in the nucleus, but the specifics of the replicative
cirrhosis. Patients with chronic HCV infection and cirrho- it has the ability to self-cleave and self-ligate—properties
cycle are complex and beyond the scope of this book.
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sis should be monitored with alpha-fetoprotein tests and
HDV has one serotype because HBsAg has only one
liver sonograms to detect carcinoma at an early stage.
serotype. There is no evidence for the existence of an ani-
Patients with liver failure due to HCV infection can receive
mal reservoir for HDV.
a liver transplant, but infection of the graft with HCV typi-
cally occurs.
Patients coinfected with HCV and HIV should be
HDV is transmitted by the same means as is HBV (i.e.,
prescribed highly active antiretroviral therapy (HAART)
sexually, by blood, and perinatally). In the United States,
with caution because recovery of cell-mediated immu-
most HDV infections occur in intravenous drug users who
nity can result in an exacerbation of hepatitis (immune
share needles. HDV infections occur worldwide, with a
reconstitution syndrome, IRIS). Consideration should
similar distribution to that of HBV infections.
be given to treat the HCV infection prior to starting
HAART.
Pathogenesis & Immunity
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It seems likely that the pathogenesis of hepatitis caused by
HDV and HBV is the same (i.e., the virus-infected hepa-
HEPATITIS D VIRUS (HDV, DELTA
tocytes are damaged by cytotoxic T cells). There is some
VIRUS)
IgG antibody against delta antigen is not detected for
Disease
long periods after infection; it is therefore uncertain
whether long-term immunity to HDV exists.
HDV causes hepatitis D (hepatitis delta).
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