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09 RA DengueInducedHepaticInjury12 PDF
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the virus to the receptor on the host levels of endoplasmic reticulum showed varying degrees of liver
cells but the nature of the receptor stress induce apoptosis and similar damage, mostly showing sinusoidal
is yet to be determined. 6 mec hani sm has been pr opo sed c o n g e st i o n pr e d o mi n a n t l y i n
At present, the exact mechanism in other members of f lavivi rus midzonal and centrilobular area
of i nt er ac ti on between dengue genus.12 Transcription factor NF-κB with no evidence of significant
virus a nd hepatoc yte is poorly activation has been implicated in fibrosis. 18
defi ned. The inter ac ti on va ri es the induction of apoptosis.13 TRAIL
with different serotypes. Glucose (Tumor Necrosis Factor-Related Clinical and Laboratory
regulated protein 78 (GRP78) was Apoptosis-I nducing Ligand) Profile
reported to be used by DEN-2 to expression has been suggested to
be partly responsible for causing Dengue fever indicates a poor
gai n entr y int o HepG2 c ell s (a
apoptosis.14 Councilman bodies are pr og n o si s i f l i ver a nd c entr a l
human hepatoblastoma cell line).7
the remnants of cells undergoing nervous system are involved at
High affinity Laminin receptor was
apoptosis. the same time. Dengue can also
reported to be used by DEN-1 to
result into fulminant hepatitis.
enter liver cells. 8 Heparan sulfate Diff er e nt i mmune r esponses
Common features suggesting
pl ays a n i mpor tant r ol e i n the ar e se en i n de ngue i nf ec ti on s
liver involvement are the
entry of all dengue serotypes into resulting in liver dysfunction of
presence of hepatomegaly and
HepG2 cells. 8 However, the degree which the phenomena of antibody
elevated liver enzymes. Va r i ou s
of interaction varies. dependent enhancement explain
sy mpt o ms seen ar e a bdomi nal
The susceptibility of a cell to the cause of more severe disease on
pai n, anor exia, and vomiting. 19
infection depends on two factors. second infection. Effective CD4 and
Clinically jaundice can be seen.
These a re: 1) the abi li ty of the CD8 cells play important role in
Hepatomegaly is seen in both
virus to enter the cell, and 2) the clearance of acute dengue infection.
dengue fever (DF) and DHF but,
factors within the cell that enable Ser otype specific and ser otype
it is more common in DF. 2 1
the virus to replicate successfully. cross reactive memory cells are
Also, hepatomegaly is seen more
It is modulated by virus serotype, formed after primary infection. On
commonly in children than adults.20
strain, and cell type. For example, secondary exposure, most serotype
Rarely, acalculous cholecystitis
HepG2 cells in G2 phase of the cell cross reactive CD4+ and CD8+ cells
has been reported and one must
cycle have a higher susceptibility to increase the severity of infection
watch for impending gall bladder
infection and a higher replication by producing various cytokines.
gangrene. 22 Table 1 illustrates
rate. 9 Children have most of their During the first three days of illness,
various studies showing deranged
cells in G2 phase of the cell cycle; serum c oncentrations of TNFα,
liver function. Liver enzymes are
which may justify as to why they IL-2, IL-6, and INF-ϒ are highest
raised in 30% of the cases.23 Wong
a re mor e susc epti bl e to sever e while IL-5, IL-10 appear later. 15
et al reported that AST
forms of dengue. 9 The other cellular Level s of R ANTES (R egul at ed
abnormality was higher as
proteins reported to be used by Upon Activation, Normal T cell
compared to ALT.24 Souza et al
viruses to enter the cells are DC- Ex pressed and Secreted), a CC
also reported a similar trend of
Specific ICAM- 3 Grabbing Non- chemokine has chemotactic activity
AST/ALT elevation in dengue.4 A
integrin (DC-SIGN),used by the for T c ell s, monoc ytes, natural
similar study from Taiwan by Kuo
virus to gain entry into monocyte- killer cells, and eosinophils; have
et al also showed 90% abnormality
d e r i ve d d en d r i t i c c el l s , 1 0 a n d been r epor te d to be hi gher i n
in AST levels.3 Damaged myocytes
the Fc_ receptor used in cases of dengue infection.16
release AST which could explain
secondary infection to gain entry Pathological changes include- hi gher l evel s of AS T than ALT
into monocytes.11 microvesicular steatosis, in dengue at earlier stage. AST
The Final outcome of dengue hepatocellular necrosis, K u p f f e r i s a l so re l ea se d f r om h e a r t,
induced infection of hepatocytes c el l h y per pl a si a and striated muscle, erythrocytes, etc.,
is apoptosis. Several mechanisms d e s t r u c ti o n , C o u n c i l ma n apart from the liver, whilst ALT
are involved. These include direct bodies and cellular infiltrates at primarily is hepatic in origin. 4 1
cytopa thic eff ec ts of the vir us, the portal tract. 1 7 Dengue virus Various studies have shown that
mitochondrial dysfunction due to c auses hepatoc el l ula r nec r osi s AST and ALT values were higher
low flow hypoxia, and the influence mo s tl y i n t he mi dz on al a r ea s in severe forms of dengue. 4 ,21 ,2 3
of cellular and humoral immune and sometimes the centrilobular Gender vise, transami niti s was
factors in the liver. The process of area. Presence of coagulopathy seen more in males than in females
apoptosis in hepatocytes is different a n d t hr o mb o c y t o pe ni a ma ke s i n a st udy f r o m Vene zuel a i n
in a way that it is independent i t di f fi c ul t to obt ai n sa mpl e s. dengue 3 ser otype. 2 5 But Suoza
of p53. Several mechanisms are R ec ent l y, a uto psy ser i es f r o m et al reported liver damage more
involved in apoptosis. Increased d e n g u e pa t i e n t s i n M ya n ma r in females in a large study from
78 Journal of The Association of Physicians of India ■ Vol. 65 ■ December 2017
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